Hjorthkragelund2292

Urolithin A (Uro-A), a metabolite of ellagitannins in mammals' intestinal tract, displays broad biological properties in preclinical models, including anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the clinical application of Uro-A is restricted because of its low aqueous solubility and short elimination half-life. Our purpose was to develop a delivery system to improve the bioavailability and anti-tumor efficacy of Uro-A. To achieve this goal, urolithin A-loaded PEGylated liposomes (Uro-A-PEG-LPs) were prepared for the first time and its physicochemical properties and anti-tumor efficacy in vitro were evaluated. The morphology of Uro-A-PEG-LPs displayed a uniform sphere under transmission electron microscope. The particle size, polydispersity index, zeta potential, and encapsulation efficiency of Uro-A-PEG-LPs were 122.8 ± 7.4 nm, 0.25 ± 0.16, - 25.5 ± 2.3 mV, and 94.6 ± 1.6%, respectively. Moreover, Uro-A-PEG-LPs possessed higher stability and could be stably stored at 4°C for a long time. In vitro release characteristics indicated that Uro-A-PEG-LPs possessed superior sustained release properties. The results of confocal laser scanning microscopy experiment showed that the coumarin 6-loaded PEGylated liposomes (C6-PEG-LPs) have superior cellular uptake than that of conventional liposomes. In addition, in vitro tests demonstrated that Uro-A-PEG-LPs elevated cytotoxicity and pro-apoptotic effect in human hepatoma cells comparing with free Uro-A. Furthermore, the results of pharmacokinetic experiments showed that the t1/2, AUC0-t, and MRT0-t of Uro-A-PEG-LPs increased to 4.58-fold, 2.33-fold, and 2.43-fold than those of free Uro-A solution, respectively. Collectively, these manifested that PEGylated liposomes might be a potential delivery system for Uro-A to prolonging in vivo circulation time, promoting cellular uptake, and enhancing its anti-tumor efficacy.In Kerala and other South Indian States, the ayurvedic by-products are widely available which can adequately be incorporated into pig diets. The objective of this study was to determine the effect of dietary incorporation of cooked barley residue and spent grapes on feed intake, growth performance, and nutrient utilization in sows and their piglets. Using completely randomized design (CRD), fifteen (15) Large White Yorkshire (LWY) pregnant sows with an average body weight of 180.53 kg, 3 weeks before the estimated date of farrowing, were randomly allotted to one of three treatment groups. The dietary treatment groups consisted of T1 (control), fed with a ration containing maize and soya bean meal of 18% CP and 3265 kcal/kg ME, T2 with a ration containing cooked barley residue replacing 25% maize in control, and T3 with a ration containing spent grapes replacing 25% maize in control ration. Data on average daily feed intake (ADFI), fortnightly bodyweight of sows and their piglets were recorded for 63 days. Also, the average daily gain (ADG), feed conversion ratio (FCR), and cost of feed per kg of weight gain of the piglets were calculated. The result showed no significant (P > 0.05) dietary treatment effects on average weekly dry matter intake and fortnightly average body weight gain among the sows in all the three groups. Piglets showed no significant difference (P > 0.05) in total dry matter intake (DMI), total body weight gain, ADG, and FCR among the three groups during the entire study period. No variations were observed for the apparent digestibility of nitrogen-free extract and the availability of magnesium in the three rations. The cost of feed per kg weight gain was lower in piglets belonging to T2 and T3 than the control (T1), though not significant statistically (P > 0.05). It is, therefore, concluded that cooked barley residue and spent grapes could be included up to 25% in the ration of sow and their piglets by partially replacing maize without affecting their overall performances.

Myasthenia gravis (MG) is an autoimmune neuromuscular disease whose treatment encompasses acetylcholinesterase inhibitors, oral steroids, and other immunosuppressants. Kaposi's sarcoma (KS) is a lymphangioproliferative disease associated with human herpesvirus 8 (HHV-8) infection and immunodeficiency or immunosuppression, mainly corticosteroids.

We present two cases of MG patients treated with oral steroids who developed KS. Patient 1 was diagnosed with three oral KS lesions. Prednisone was discontinued with lesion regression and stabilization, while azathioprine and pyridostigmine prompted control of MG. Patient 2 developed KS lesions on the trunk and lower limbs while taking prednisone and azathioprine. Steroid tapering was started but new oral and lymph nodal lesions appeared. Paclitaxel therapy was introduced and the patient experienced pulmonary embolism and developed sensitive neuropathy. Complete remission of KS lesions was achieved and maintained with azathioprine and pyridostigmine as MG medications.

KS is an uncommon but clinically relevant adverse event (AE) often induced by steroid therapy. It can be controlled by steroid withdrawal but could necessitate chemotherapy, which associates with further potential AEs. Skin evaluation should be performed in all patients with chronic steroid therapy. Steroid-sparing strategies, including new drugs, could reduce KS and other steroid-related comorbidities. HHV-8 testing should be considered before starting chronic immunosuppression.

KS is an uncommon but clinically relevant adverse event (AE) often induced by steroid therapy. It can be controlled by steroid withdrawal but could necessitate chemotherapy, which associates with further potential AEs. Skin evaluation should be performed in all patients with chronic steroid therapy. Steroid-sparing strategies, including new drugs, could reduce KS and other steroid-related comorbidities. HHV-8 testing should be considered before starting chronic immunosuppression.Macrophages are a vital component of the tumour microenvironment and crucial mediators of tumour progression. In the last decade, significant strides have been made in understanding the crucial functional roles played by macrophages in the development of the plasma cell (PC) malignancy, multiple myeloma (MM). Whilst the interaction between MM PC and stromal cells within the bone marrow (BM) microenvironment has been extensively studied, we are only just starting to appreciate the multifaceted roles played by macrophages in disease progression. Accumulating evidence demonstrates that macrophage infiltration is associated with poor overall survival in MM. Indeed, macrophages influence numerous pathways critical for the initiation and progression of MM, including homing of malignant cells to BM, tumour cell growth and survival, drug resistance, angiogenesis and immune suppression. As such, therapeutic strategies aimed at targeting macrophages within the BM niche have promise in the clinical setting. This review will discuss the functions elicited by macrophages throughout different stages of MM and provide a comprehensive evaluation of potential macrophage-targeted therapies.Neuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease-along with the relative paucity of recurrent somatic mutations-reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.The bisegmented genome of a novel double-stranded (ds) RNA mycovirus, named "Aspergillus nidulans partitivirus 1" (AnPV1), isolated from the fungus Aspergillus nidulans strain HJ5-47, was sequenced and analyzed. AnPV1 contains two segments, AnPV1-1 and AnPV1-2. AnPV1-1 has 1837 bp with an open reading frame (ORF) that potentially encodes a putative RNA-dependent RNA polymerase (RdRp) of 572 amino acids (aa). AnPV1-2 has 1583 bp with an ORF encoding a putative capsid protein (CP) of 488 aa. Phylogenetic analyses indicated that AnPV1 and related viruses clustered in a group that could represent a new unclassified genus in the family Partitiviridae.

Concerns about rising health care costs require rigorous economic study to inform clinical and policy decision-making. Micro-costing is a cost estimation methodology employing detailed resource utilization and unit cost data to generate precise estimates of economic costs. Micro-costing studies have not been critically appraised.

Critical appraisal of micro-costing studies in English. Studies fully or predominantly employing micro-costing were appraised for methodological and reporting quality through economic evaluation guidelines (Evers, Drummond, Consolidated Health Economic Evaluation Reporting Standards (CHEERS), Fukuda and Imanaka checklists). Following the Panel on Cost Effectiveness in Health and Medicine, micro-costing studies were defined as involving "direct enumeration and costing out of every input consumed in the treatment of a particular patient."

Full or predominant micro-costing studiesincluded neoplasms (18.5%), infectious and parasitic diseases (17.9%), and diseases of circulatory systems (10.8%) as the most studied diseases. 36.9% were in the United States and 34.9% were in Europe. 33.8% did not report analytic perspective, 32.8% did not report price year, 3.6% did not inflation adjust cost data, and 44.1% did not specify inflation adjustment. 86.2% did not separately report unit costs and resource utilization quantity, 14.9 and 19.5% did not provide sufficient detail to assess appropriateness of measured physical units or valued costs.

Micro-costing studies vary widely in methodological and reporting quality, highlighting the need to standardize methods and reporting of micro-costing studies and develop tools for their evaluation.

Micro-costing studies vary widely in methodological and reporting quality, highlighting the need to standardize methods and reporting of micro-costing studies and develop tools for their evaluation.

Esophageal squamous cell carcinoma (ESCC) is featured by early metastasis and late diagnosis. MicroRNA-301 (miR-301) is known to participate in diverse cancers. Nevertheless, effects of miR-301 on ESCC remain unexplored. Thus, we aim to explore the role of miR-301 in ESCC progression.

Expression of miR-301 and phosphatase and tensin homologue (PTEN) in ESCC tissues and cell lines was assessed. Next, the screened cells were treated with altered miR-301 or PTEN oligonucleotide and plasmid, and then, the colony formation ability, cell viability, migration, invasion, cell cycle distribution and apoptosis of ESCC cells were assessed. Moreover, tumor growth and microvessel density (MVD) were also assessed, and the targeting relationship between miR-301 and PTEN was affirmed.

MiR-301 was upregulated, and PTEN was downregulated in ESCC tissues and cells. KYSE30 cells and Eca109 cells were selected for functional assays. In KYSE30 cells, inhibited miR-301 or overexpressed PTEN suppressed cell malignant behaviors, and silenced PTEN eliminated the impact of miR-301 inhibition on ESCC progression. In Eca109 cells, miR-301 overexpressionor PTEN inhibition promoted cell malignant behaviors, and PTEN overexpression reversed the effects of miR-301 elevation on ESCC progression. The in vivo assay revealed that miR-301 inhibition or PTEN overexpression repressed ESCC tumor growth and MVD, and miR-301 elevation or PTEN reduction had contrary effects. Moreover, PTEN was targeted by miR-301.

Taken together, results in our study revealed that miR-301 affected cell growth, metastasis and angiogenesis via regulating PTEN expression in ESCC.

Taken together, results in our study revealed that miR-301 affected cell growth, metastasis and angiogenesis via regulating PTEN expression in ESCC.Gastric-type adenocarcinoma (GAS) of the cervix is a human papilloma virus (HPV)-independent, aggressive, and chemo-resistant adenocarcinoma. However, although the histopathological features of GAS have been extensively investigated, squamous differentiation has not been mentioned. This study aimed to elucidate the frequency of GAS with squamous differentiation and describe their clinicopathological characteristics. We retrospectively evaluated 78 patients with GAS (n = 13) and adenosquamous carcinoma (n = 65) diagnosed between 2000 and 2020. Two patients with GAS with squamous differentiation were identified. Both tumors showed advanced stage (pT2bN1) and had predominant GAS and merged squamous cell carcinoma components without p16-block positivity and HPV DNA. Gastric-type adenocarcinoma in situ was confirmed in both cases. Some cases of GAS could show squamous differentiation mimicking the usual, HPV-associated, adenosquamous carcinoma. GAS with squamous differentiation is recognized as an HPV-independent cancer.Uterine leiomyosarcoma (ULMS) with osteoclast-like giant cells (OLGCs) has been reported as a rare phenomenon in ULMS, and its clinico-pathological features and tumorigenesis remain unclear. We recently reported high expression of receptor activator of nuclear factor κB ligand (RANKL) in ULMS with OLGCs. As osteoblasts produce RANKL, in this study, we analyzed the expression of Runt-related transcription factor 2 (RUNX2), a critical transcription factor for osteoblasts, and osteoclast-related proteins in three cases of ULMS with OLGCs as well as five conventional ULMSs and nine leiomyomas. Immunohistochemistry and real-time reverse transcription quantitative polymerase chain reaction analyses showed high expression of RUNX2 and RANKL in ULMS with OLGCs. In these cases, macrophages expressed receptor activator of nuclear factor κB (RANK), and OLGCs expressed osteoclast-related proteins (nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and cathepsin K). Accumulation sites of cathepsin K-positive OLGCs showed hemorrhagic appearance and degraded type IV collagen. We reviewed reported cases of ULMS with OLGCs, including ours, and found that they presented an aggressive course even at stage I. Furthermore, metastatic lesions showed similar histological features to those of OLGC association in ULMS. Here, we show that tumor cells in ULMS with OLGCs highly express RUNX2 and RANKL and that osteoclastic differentiation of macrophages occurs in the tumor tissue.Intraarticular nodular fasciitis arising in the joint synovium is an uncommon lesion. Most cases have been reported in the knee and rarely in other joints. A USP6 gene fusion has so far been documented in only four cases of intraarticular nodular fasciitis, three were located in the knee and one in the proximal interphalangeal joint. In all three cases located in the knee, MYH9 was detected as a USP6 fusion partner. We analysed three cases of intraarticular nodular fasciitis for the presence of USP6 fusion by targeted RNA sequencing. Two cases were located in the hip (a 25-year-old female and 48-year-old male) and one in the shoulder (a 38-year-old male). We detected a MYH9-USP6 fusion in the two hip cases and a COL1A1-USP6 fusion in the shoulder case. Our findings provide additional evidence that intraarticular nodular fasciitis is a form of nodular fasciitis arising in the joint synovium, harbouring a USP6 fusion. Although a MYH9-USP6 fusion seems to predominate in intraarticular nodular fasciitis, other fusion partners of the USP6 gene may also be involved. Detection of a USP6 fusion by targeted RNA sequencing may assist in confirming the diagnosis in selected cases.Tumor budding, defined as a single cancer cell or clusters of fewer than five cancer cells observed at the tumor invasion front, has been reported to be associated with poor prognosis in various types of cancers. However, limited information regarding the pathological and prognostic significance of tumor budding in upper urinary tract urothelial carcinoma (UUTUC) is available. We investigated 135 consecutive patients with newly diagnosed invasive UUTUCs (73 with renal pelvic cancers and 62 with ureteral cancers) treated with nephroureterectomy or partial ureterectomy between 1999 and 2018 in our hospital. Under a × 200 magnification, tumors with 10 or more budding foci were defined as "high tumor budding". The median follow-up period was 53.6 months. Among the 135 patients, 41 (30%; 16 with renal pelvic cancers and 25 with ureteral cancers) showed high tumor budding. High tumor budding was related to adjuvant chemotherapy status, higher pathological T stage, lymphovascular invasion, lymph node metastasis, tumor location, concomitant variant histology, and non-papillary gross finding. The multivariate Cox analysis revealed that LVI and high tumor budding were independent predictors for extraurothelial recurrence (P = 0.039 and 0.014, hazard ratio = 2.50 and 2.88, respectively), and high tumor budding was an independent predictor for overall survival (P = 0.024, hazard ratio = 2.33). Tumor budding can be easily introduced in clinical practice with no need for immunohistochemical analysis, may be an important clinicopathological factor of UUTUC, and is suggested to be useful as a novel predictive prognostic factor of patients with invasive UUTUC.Analysis of breast cancer prognostic and predictive factors is still nowadays poorly accurate and standardized. The advent of multi-gene expression profiles (MGEPs) has improved the prediction of breast cancer outcome, particularly regarding early luminal breast cancers (LBCs). The availability in our Institute of EndoPredict® (EP), a last-generation prognostic gene signature assay, has prompted us to study a series of LBCs, firstly verifying its reproducibility on six routine representative cases, either presenting non-optimal preanalytical conditions or different tumor samples from the same patient; secondly, correlating EP results on 8 retrospectively recruited samples with patients' follow-up; thirdly, applying prospectively EP on 100 routinely diagnosed cases, assessing the oncologists' and pathologists' attitude toward it. The complete reproducibility of EP on all the samples investigated in the first phase allowed to state that EP overcomes the detrimental effects of an inaccurate pre-analytic phase, determining the most appropriate prognostic and predictive parameters of breast cancer. The second phase confirmed EP as a fundamental tool in guiding therapeutic decision, improving the classical bio-pathological characterization and recovering 38% patients' inadequately managed. Finally, the study disclosed how oncologists sometimes inadequately requested EP, but also how it allows a better stratification of breast cancer otherwise considered poorly aggressive and not requiring an EP test, such as G1 neoplasms or tubular histotype. In conclusion, the introduction of EP test in an Anatomic Pathology Department emerges as a useful tool in routine breast cancer diagnosis, both for the characterization of individual cases and, as a result, for more appropriate therapeutic choices.Discontinuous tumor involvement (DTI) is a not uncommon finding in the tumor in prostate needle core biopsies undertaken for diagnosis of prostate cancer (PCa). The objective of this review is to establish a clear definition of DTI in order to provide a standardized method of measurement which reliably reflects pathologic features and disease progression following radical prostatectomy (RP). A systematic literature search was performed using PubMed up to March 2020 to identify studies of PCa patients which included needle biopsies containing DTI and matched subsequent RP treatment with or without follow-up information. The methodology and quality of reporting of DTI are reviewed, compared, and summarized. DTI is a frequent finding in diagnostic biopsy for PCa (up to 30%). Six studies were compared by methods of measurement used for predicting pathologic features and outcomes which are observed in subsequent RP. In most cases with DTI (> 90%), intervening benign tissue in the tumor core was less than 5 mm. DTIserved in these two methods of measurement. DTI in core biopsies may represent undersampling of a larger irregular nodule but likely does not result from multifocality and is similarly unlikely to represent multiclonality. Linear measurement of DTI was more accurately predictive of post-RP pathologic findings and oncologic prognosis. This method should be applied for patient selection for AS.Guidance regarding the effect of codeine and its metabolites on foetal development is limited by small studies and inconsistent findings. The primary objective was to use physiologically based pharmacokinetic modelling to investigate the impact of gestational stage and maternal CYP2D6 phenotype on foetal morphine exposure following codeine administration. Full body physiologically based pharmacokinetic models were developed and verified for codeine and morphine using Simcyp (version 19.1). The impact of gestational age and maternal CYP2D6 phenotype on foetal and maternal morphine and codeine exposure following oral codeine administration was modelled in a cohort of 250 pregnant females and foetuses at gestational weeks 0 (mothers only), 6, 12, 24 and 36. Consistent with the known effect on codeine metabolism, a clinically meaningful (> 1.65-fold) increase in foetal morphine AUC was observed in the CYP2D6 UM phenotype cohort compared to the CYP2D6 EM and PM phenotype cohorts. The mean (95% CI) foetal morphine AUC in the CYP2D6 UM cohort of 0.988 (0.902 to 1.073) ng/mL.h was 1.8-fold higher than the CYP2D6 EM cohort of 0.546 (0.492 to 0.600) ng/mL.h (p  less then  0.001). Despite a 2.8-fold increase in maternal CYP2D6 protein abundance between gestational weeks 6 and 36, the mean foetal morphine AUC in the CYP2D6 EM and UM phenotype cohorts reduced by 1.55- and 1.75-fold, respectively, over this period. Maternal CYP2D6 phenotype is a significant determinant of foetal morphine AUC. Simulations suggest that the greatest risk with respect to foetal morphine exposure is during the first trimester of pregnancy, particularly in CYP2D6 UM phenotype mothers.

3D printed patient-specific anatomical models have been applied clinically to orthopaedic care for surgical planning and patient education. The estimated cost and print time per model for 3D printers have not yet been compared with clinically representative models across multiple printing technologies. This study investigates six commercially-available 3D printers Prusa i3 MK3S, Formlabs Form 2, Formlabs Form 3, LulzBot TAZ 6, Stratasys F370, and Stratasys J750 Digital Anatomy.

Seven representative orthopaedic standard tessellation models derived from CT scans were imported into the respective slicing software for each 3D printer. For each printer and corresponding print setting, the slicing software provides a print time and material use estimate. Material quantity was used to calculate estimated model cost. Print settings investigated were infill percentage, layer height, and model orientation on the print bed. The slicing software investigated are Cura LulzBot Edition 3.6.20, GrabCAD Print 1.43, PreForhis study have the potential for clinical utility. Print time and print cost are dependent on orientation of anatomy and the printers and settings selected. Cost-effective clinical 3D printing of anatomic models should consider an appropriate printer for the complexity of the anatomy and the experience of the printer technicians.

All investigated 3D printers in this study have the potential for clinical utility. Print time and print cost are dependent on orientation of anatomy and the printers and settings selected. Cost-effective clinical 3D printing of anatomic models should consider an appropriate printer for the complexity of the anatomy and the experience of the printer technicians.In the rodent brain, the central processing of ecologically relevant chemical stimuli involves many different areas located at various levels within the neuraxis the main and accessory olfactory bulbs, some nuclei in the amygdala, the hypothalamus, and brainstem. These areas allow the integration of the chemosensory stimuli with other sensory information and the selection of the appropriate neurohormonal and behavioral response. This review is a brief introduction to the processing of intraspecific chemosensory stimuli beyond the secondary projection, focusing on the activity of the relevant amygdala and hypothalamic nuclei, namely the medial amygdala and ventromedial hypothalamus. These areas are involved in the appropriate interpretation of chemosensory information and drive the selection of the proper response, which may be behavioral or hormonal and may affect the neural activity of other areas in the telencephalon and brainstem.Recent data support the notion that the processing of intraspecific chemical signals is not unique to one chemosensory system and some molecules may activate both the main and the accessory olfactory system. Moreover, both these systems have mixed projections and cooperate for the correct identification of the stimuli and selection of relevant responses.The necklace glomeruli are a loosely defined group of glomeruli encircling the caudal main olfactory bulb in rodents. Initially defined by the expression of various immunohistochemical markers, they are now better understood in the context of the specialized chemosensory neurons of the main olfactory epithelium and Grueneberg ganglion that innervate them. It has become clear that the necklace region of the rodent main olfactory bulb is composed of multiple distinct groups of glomeruli, defined at least in part by their afferent inputs. In this review, we will explore the necklace glomeruli and the chemosensory neurons that innervate them.The role of granule cells in olfactory processing is surrounded by several enigmatic observations, such as the purpose of reciprocal spines and the mechanisms for GABA release, the apparently low firing activity and recurrent inhibitory drive of granule cells, the missing proof for functional reciprocal connectivity, and the apparently negligible contribution to lateral inhibition. Here, we summarize recent results with regard to both the mechanisms of GABA release and the behavioral relevance of granule cell activity during odor discrimination. We outline a novel hypothesis that has the potential to resolve most of these enigmas and allows further predictions on the function of granule cells in odor processing. Briefly, recent findings imply that GABA release from the reciprocal spine requires a local spine action potential and the cooperative action of NMDA receptors and high voltage-activated Ca2+ channels. Thus, lateral inhibition is conditional on activity in the principal neurons connected to a granule cell and tightly intertwined with recurrent inhibition. This notion allows us to infer that lateral inhibition between principal neurons occurs "on demand," i.e., selectively on coactive mitral and tufted cells, and thus can provide directed, dynamically switched lateral inhibition in a sensory system with 1000 input channels organized in glomerular columns. The mechanistic underpinnings of this hypothesis concur with findings from odor discrimination behavior in mice with synaptic proteins deleted in granule cells. In summary, our hypothesis explains the unusual microcircuit of the granule cell reciprocal spine as a means of olfactory combinatorial coding.The olfactory system translates chemical signals into neuronal signals that inform behavioral decisions of the animal. Odors are cues for source identity, but if monitored long enough, they can also be used to localize the source. Odor representations should therefore be robust to changing conditions and flexible in order to drive an appropriate behavior. In this review, we aim at discussing the main computations that allow robust and flexible encoding of odor information in the olfactory neural pathway.In numerous mammalian species, the nose harbors several compartments populated by chemosensory cells. Among them, the Grueneberg ganglion (GG) located in the anterior nasal region comprises sensory neurons activated by given substances. In rodents, in which the GG has been best studied, these chemical cues mainly include heterocyclic compounds released by predators or by conspecifics. Since some of these substances evoke fear- or stress-associated responses, the GG is considered as a detector for alerting semiochemicals. In fact, certain behavioral and physiological reactions to alarm pheromones and predator-secreted kairomones are attenuated in the absence of a functional GG. Intriguingly, GG neurons are also stimulated by cool temperatures. Moreover, ambient temperatures modulate olfactory responsiveness in the GG, indicating that cross-talks exist between the transduction pathways mediating chemo- and thermosensory signaling in this organ. In this context, exploring the relevant molecular cascades has demonstrated that some chemosensory transduction elements are also crucial for thermosensory signaling in the GG. Finally, for further processing of sensory information, axons of GG neurons project to the olfactory bulb of the brain where they innervate distinct glomerular structures belonging to the enigmatic necklace glomeruli. In this review, the stimuli activating GG neurons as well as the underlying transduction pathways are summarized. Because these stimuli do not exclusively activate GG neurons but also other sensory cells, the biological relevance of the GG is discussed, with a special focus on the role of the GG in detecting alarm signals.The ability of the olfactory system to detect and discriminate a broad spectrum of odor molecules with extraordinary sensitivity relies on a wide range of odorant receptors and on the distinct architecture of neuronal circuits in olfactory brain areas. More than 1000 odorant receptors, distributed almost randomly in the olfactory epithelium, are plotted out in two mirror-symmetric maps of glomeruli in the olfactory bulb, the first relay station of the olfactory system. How does such a precise spatial arrangement of glomeruli emerge from a random distribution of receptor neurons? Remarkably, the identity of odorant receptors defines not only the molecular receptive range of sensory neurons but also their glomerular target. Despite their key role, odorant receptors are not the only determinant, since the specificity of neuronal connections emerges from a complex interplay between several molecular cues and electrical activity. This review provides an overview of the mechanisms underlying olfactory circuit formation. In particular, recent findings on the role of odorant receptors in regulating axon targeting and of spontaneous activity in the development and maintenance of synaptic connections are discussed.Osteoarthritis (OA) is the most common joint disease with an unsatisfactory therapy outcome and characterized by the degradation of articular cartilage and synovial inflammation. Here, we isolated bone marrow mesenchymal stem cells (BMSCs) from rat's bone marrow and BMSC-derived exosome (BMSCs-Exo) from BMSCs successfully. MiR-135b was proved to be highly expressed in TGF-β1-stimulated BMSC-derived exosomes (BMSCs-ExoTGF-β1). Then, our results demonstrated that BMSCs-ExoTGF-β1 reduced OA-induced upregulation of pro-inflammatory factors in rat's serum and damage in cartilage tissues, which was then reversed by miR-135b decreasing. Subsequently, we found that the OA-resulted M1 polarization of synovial macrophages (SMs) was repressed by BMSCs-ExoTGF-β1, this effect of BMSCs-ExoTGF-β1 was limited by miR-135b decreasing. We also proved that M2 polarization of SMs can be induced by miR-135b mimics. Furthermore, we found that the promotory effect of miR-135b and BMSCs-ExoTGF-β1 on M2 SMs polarization was reversed by increasing of MAPK6. Overall, our data showed that BMSCs-ExoTGF-β1 attenuated cartilage damage in OA rats through carrying highly expressed miR-135b. Mechanistically, miR-135b promoted M2 polarization of SMs through targeting MAPK6, thus improving cartilage damage. Our study provided a novel regulatory mechanism of BMSCs-Exo in OA development and revealed a new potential treatment target of OA.The nasal cavity of tetrapods has become phylogenetically adapted to the environment in terms of function, respiration, and olfaction. In addition, the nasal cavity of sea turtles plays an important role in seawater flow and water olfaction, unlike that of terrestrial species. Here, we describe the functional, morphological, and histological characteristics of the nasal cavity, and the odorant receptors encoded in the genome of sea turtles. The nasal cavity of sea turtles is well-suited to its complicated functions, and it significantly differs from those of other animals, including terrestrial and semi-aquatic turtles.In teleost fish, specialized oxygen (O2) chemoreceptors, called neuroepithelial cells (NECs), are found in the gill epithelium in adults. During development, NECs are present in the skin before the formation of functional gills. NECs are known for retaining the monoamine neurotransmitter, serotonin (5-HT) and are conventionally identified through immunoreactivity with antibodies against 5-HT or synaptic vesicle protein (SV2). However, identification of NECs in live tissue and isolated cell preparations has been challenging due to the lack of a specific marker. The present study explored the use of the transgenic zebrafish, ETvmat2GFP, which expresses green fluorescent protein (GFP) under the control of the vesicular monoamine transporter 2 (vmat2) regulatory element, to identify NECs. Using immunohistochemistry and confocal microscopy, we confirmed that the endogenous GFP in ETvmat2GFP labelled serotonergic NECs in the skin of larvae and in the gills of adults. NECs of the gill filaments expressed a higher level of endogenous GFP compared with other cells. The endogenous GFP also labelled intrabranchial neurons of the gill filaments. Flow cytometric analysis demonstrated that filamental NECs could be distinguished from other dissociated gill cells based on high GFP expression alone. Acclimation to 2 weeks of severe hypoxia (PO2 = 35 mmHg) induced an increase in filamental NEC frequency, size and GFP gene expression. Here we present for the first time a transgenic tool that labels O2 chemoreceptors in an aquatic vertebrate and its use in high-throughput experimentation.Appropriate perception and representation of sensory stimuli pose an everyday challenge to the brain. In order to represent the wide and unpredictable array of environmental stimuli, principle neurons of associative learning regions receive sparse, combinatorial sensory inputs. Despite the broad role of such networks in sensory neural circuits, the developmental mechanisms underlying their emergence are not well understood. As mammalian sensory coding regions are numerically complex and lack the accessibility of simpler invertebrate systems, we chose to focus this review on the numerically simpler, yet functionally similar, Drosophila mushroom body calyx. We bring together current knowledge about the cellular and molecular mechanisms orchestrating calyx development, in addition to drawing insights from literature regarding construction of sparse wiring in the mammalian cerebellum. From this, we formulate hypotheses to guide our future understanding of the development of this critical perceptual center.Alcoholic fermentation is a crucial step of winemaking, during which yeasts convert sugars to alcohol and also produce or biotransform numerous flavour compounds. In this context, nutrients are essential compounds to support yeast growth and ultimately ensure complete fermentation, as well as optimized production of flavour compounds over that of off-flavour compounds. In particular, the vitamin thiamine not only plays an essential cofactor role for several enzymes involved in various metabolic pathways, including those leading to the production of wine-relevant flavour compounds, but also aids yeast survival via thiamine-dependent stress protection functions. Most yeast species are able to both assimilate exogenous thiamine into the cell and synthesize thiamine de novo. However, the mechanism and level of thiamine accumulation depend on several factors. This review provides an in-depth overview of thiamine utilization and metabolism in the model yeast species Saccharomyces cerevisiae, as well as the current knowledge on (1) the intracellular functions of thiamine, (2) the balance between and regulation of uptake and synthesis of thiamine and (3) the multitude of factors influencing thiamine availability and utilization. For the latter, a particular emphasis is placed on conditions occurring during wine fermentation. The adequacy of thiamine concentration in grape must to ensure successful fermentation is discussed together with the effect of thiamine concentration on fermentation kinetics and on wine sensory properties. This knowledge may serve as a resource to optimise thiamine concentrations for optimal industrial application of yeasts. KEY POINTS • Thiamine uptake is preferred over biosynthesis and is transcriptionally repressed. • Multiple factors affect thiamine synthesis, availability and uptake for wine yeast. • Thiamine availability impacts fermentation kinetics and wine's sensory properties.Levan, a type of β (2→6)-linked fructan, is a promising biopolymer with distinct properties and extensive applications in the fields of food, pharmaceutical, cosmetics, etc. However, the commercial availability of levan is still limited due to the relatively high production costs. Here, a new Paenibacillus sp. strain FP01 was isolated and identified as an efficient fructan producer with high yield (around 89.5 g/L fructan was obtained under 180 g/L sucrose) and conversation rate (49.7%). The fructan named Plev was structurally characterized as a linear levan-type fructan with a molecular mass of 3.11 × 106 Da. Aqueous solutions of Plev exhibited a non-Newtonian behavior at concentrations 3-5%. Heating and chilling had no obvious effects on apparent viscosities of Plev solutions. Plev also had good rheological stabilities toward pH (3-11) and metal salts (Na+, K+, Ca2+, Mg2+). Microbiome and metabolome analysis showed that Plev intervention increased the abundance of beneficial bacteria and elevated the levels of short-chain fatty acids (SCFAs) in feces of mice. Taken together, Plev could be considered a potential thickener and prebiotic supplement in food industry.Key points• Paenibacillus sp. strain FP01 was identified as a high-efficient levan producer.• The levan Plev from FP01 exhibited good rheological properties and stabilities.• The in vivo prebiotic activities of linear levan were revealed.Diosgenin is a plant-derived secondary metabolite mainly present in the members of the plant family Dioscoreaceae. It is a pharmaceutically important compound because of its anti-cancerous, anti-diabetic, anticoagulant, anti-thrombosis, anti-inflammatory, anti-viral, anti-ageing and other properties. Biotechnology provides an opportunity to genetically manipulate cells, tissues, organs or the whole organisms by propagating them in vitro in order to harvest the bioactive compounds. Diosgenin production from botanical sources is being improved by in vitro techniques which include elicitation, genetic transformations and bioconversions. Various techniques have been developed to obtain compounds for drug detection including separation from plants and other natural sources, molecular modelling, synthetic chemistry and combinatorial chemistry. Development in molecular markers determines genetic relationship, genetic linkage map construction, genetic diversity and identification. For rapid clonal propagation and ex situ conservation, the in vitro tools involving plant cell, tissue and organ culture have been well documented for plant-derived diosgenin production. The present review encompasses the wide application of the biotechnological techniques for diosgenin production via elucidating its biosynthetic pathway, in vitro production and mass propagation and elicitation. In addition, molecular marker-mediated diversity assessment of diosgenin containing plant species is also discussed. The review also presents the recent literature to explore the limitations of the relevant studies and future direction of research on production of diosgenin from Dioscorea spp. KEY POINTS • Critical and updated assessment on sustainable production of diosgenin from Dioscorea spp. • In vitro propagation of Dioscorea spp. and elicitation of diosgenin production. • Diversity assessment of Dioscorea spp. using molecular markers.Gut microbiota have been implicated in the development of cancer. Colorectal and gastric cancers, the major gastrointestinal tract cancers, are closely connected with the gut microbiome. Nevertheless, the characteristics of gut microbiota composition that correlate with gastric cancer are unclear. In this study, we investigated gut microbiota alterations during the progression of gastric cancer to identify the most relevant taxa associated with gastric cancer and evaluated the potential of the microbiome as an indicator for the diagnosis of gastric cancer. Compared with the healthy group, gut microbiota composition and diversity shifted in patients with gastric cancer. Different bacteria were used to design a random forest model, which provided an area under the curve value of 0.91. Verification samples achieved a true positive rate of 0.83 in gastric cancer. Principal component analysis showed that gastritis shares some microbiome characteristics of gastric cancer. Chemotherapy reduced the elevated bacteria levels in gastric cancer by more than half. More importantly, we found that the genera Lactobacillus and Megasphaera were associated with gastric cancer.Key Points• Gut microbiota has high sensitivity and specificity in distinguishing patients with gastric cancer from healthy individuals, indicating that gut microbiota is a potential noninvasive tool for the diagnosis of gastric cancer.• Gastritis shares some microbiota features with gastric cancer, and chemotherapy reduces the microbial abundance and diversity in gastric cancer patients.• Two bacterial taxa, namely, Lactobacillus and Megasphaera, are predictive markers for gastric cancer.Bacterial communities play an important role in the biogeochemical cycle in reservoir ecosystems. However, the dynamic changes in both planktonic and sediment bacterial communities in a highly regulated dam reservoir remain unclear. This study investigated the temporal distribution patterns of bacterial communities in a transition section of the Three Gorges Reservoir (TGR) using Illumina MiSeq sequencing. Results suggested that in comparison to the planktonic bacteria, sediment bacteria contributed more to the reservoir microbial communities, accounting for 97% of the 7434 OTUs. The Shannon diversity index in the water (3.22~5.68) was generally lower than that in the sediment (6.72~7.56). In the high water level period (January and March), Proteobacteria, Actinobacteria, Cyanobacteria, and Firmicutes were the most abundant phyla, whereas in the low water level period (May, July, and September), the dominant phyla were Proteobacteria, Actinobacteria, and Bacteroidetes. Sediment samples were dominated by Proteobacteria, Chloroflexi, and Acidobacteria. Principal coordinate analysis of the bacterioplankton communities showed greater sensitivity to monthly changes than that of the sediment bacterial communities. Network analysis suggested that in comparison to planktonic bacterial communities, sediment bacterial communities were more complex and stable. The linear relationship between the CH4/CO2 ratio, water level, and relative abundance of methanotrophs highlighted the potential methane-oxidizing process in the mid-part of the TGR. Moreover, the potential impact of dam regulation on the bacterial communities was revealed by the significant relationship between abundant phyla and the inflow of the TGR. KEY POINTS • Bacterioplankton communities showed great sensitivity to monthly changes. • Potential methane-oxidizing process was revealed in this representative area. • Water inflow regulated by dam has significant effects on dominant bacterioplankton.Seaweeds have received considerable attention as sources of dietary fiber and biomass for manufacturing valuable products. The major polysaccharides of red seaweeds include agar and porphyran. In a marine environment, marine bacteria utilize agar and porphyran through the agarase and porphyranase genes encoded in their genomes. Most of these enzymes identified and characterized so far originate from marine bacteria. Recently, Bacteroides plebeius, a human gut bacterium isolated from seaweed-eating Japanese individuals, was revealed to contain a polysaccharide utilization locus (PUL) targeting the porphyran and agarose of red seaweeds. For example, B. plebeius contains an endo-type β-agarase, BpGH16A, belonging to glycoside hydrolase family 16. BpGH16A cleaves the β-1,4-glycosidic linkages of agarose and produces neoagarooligosccharides from agarose. Since it is crucial to study the characteristics of BpGH16A to understand the depolymerization pathway of red seaweed polysaccharides by B. plebeius in the human gut and to industrially apply the enzyme for the depolymerization of agar, we characterized BpGH16A for the first time. According to our results, BpGH16A is an extracellular endo-type β-agarase with an optimal temperature of 40 °C and an optimal pH of 7.0, which correspond to the temperature and pH of the human colon. BpGH16A depolymerizes agarose into neoagarotetraose (as the main product) and neoagarobiose (as the minor product). Thus, BpGH16A is suggested to be an important enzyme that initiates the depolymerization of red seaweed agarose or agar in the human gut by B. plebeius. KEY POINTS • Bacteroides plebeius is a human gut bacterium isolated from seaweed-eating humans. • BpGH16A is an extracellular endo-type β-agarase with optimal conditions of 40 °C and pH 7.0. • BpGH16A depolymerizes agarose into neoagarotetraose and neoagarobiose.Vibrio parahaemolyticus is one of the major pathogens responsible for vibriosis and zoonotic infections in teleosts, marine invertebrates, and also humans through consumption of contaminated or unprocessed seafood. Emergence of resistance against current accessible antibiotics and spread to the food chain and environment necessitate the development of safe and effective subunit vaccine against this bacterium. Many bacteria including V. parahaemolyticus produce extracellular curli fibrils, heteropolymeric filaments of major and minor subunit, which have been implicated in adhesion, biofilm formation, and virulence. Adhesins are the primary contact points with the host which help in establishing infection and colonization. CsgA, an adhesin, is the major structural component of the curli fiber that forms homopolymers of several hundred units. Due to their exposure on the cell surface, the curli fibers are recognized by the host's immune system, would generate high immune response, and therefore can serve as effeutinating antibodies. • Immunization with the rVpCsgA protected mice against V. parahaemolyticus challenge.While we have a basic understanding of the functioning of the gene when coding sequences of specific proteins, we feel the lack of information on the role that DNA has on specific diseases or functions of thousands of proteins that are produced. Bioinformatics combines the methods used in the collection, storage, identification, analysis, and correlation of this huge and complex information. All this work produces an "ocean" of information that can only be "sailed" with the help of computerized methods. The goal is to provide scientists with the right means to explain normal biological processes, dysfunctions of these processes which give rise to disease and approaches that allow the discovery of new medical cures. Recently, sequencing platforms, a large scale of genomes and transcriptomes, have created new challenges not only to the genomics but especially for bioinformatics. The intent of this article is to compile a list of tools and information resources used by scientists to treat information from the massive sequencing of recent platforms to new generations and the applications of this information in different areas of life sciences including medicine. KEY POINTS • Biological data mining • Omic approaches • From genotype to phenotype.Recent attempts to create synthetic Escherichia coli methylotrophs identified that de novo biosynthesis of amino acids, in the presence of methanol, presents significant challenges in achieving autonomous methylotrophic growth. Previously engineered methanol-dependent strains required co-utilization of stoichiometric amounts of co-substrates and methanol. As such, these strains could not be evolved to grow on methanol alone. In this work, we have explored an alternative approach to enable biosynthesis of all amino acids from methanol-derived carbon in minimal media without stoichiometric coupling. First, we identified that biosynthesis of threonine was limiting the growth of our methylotrophic E. coli. To address this, we performed adaptive laboratory evolution to generate a strain that grew efficiently in minimal medium with methanol and threonine. Methanol assimilation and growth of the evolved strain were analyzed, and, interestingly, we found that the evolved strain synthesized all amino acids, including threonine, from methanol-derived carbon. The evolved strain was then further engineered through overexpression of an optimized threonine biosynthetic pathway. We show that the resulting methylotrophic E. coli strain has a methanol-dependent growth phenotype with homoserine as co-substrate. In contrast to previous methanol-dependent strains, co-utilization of homoserine is not stoichiometrically linked to methanol assimilation. As such, future engineering of this strain and successive adaptive evolution could enable autonomous growth on methanol as the sole carbon source. KEY POINTS • Adaptive evolution of E. coli enables biosynthesis of all amino acids from methanol. • Overexpression of threonine biosynthesis pathway improves methanol assimilation. • Methanol-dependent growth is seen in minimal media with homoserine as co-substrate.