Strandoutzen8330
Drought is the main factor restricting peanut growth, but the molecular mechanism underlying peanut drought tolerance remains unclear. Herein, the seedling stage of drought-resistant peanut cultivar J11 was subjected to drought stress, and its proteomic profile was systematically analysed by isobaric tags for relative and absolute quantification (iTRAQ), the results of which were further complemented with our previous transcriptome results. A total of 4,018 proteins were identified by proteomic analysis, which revealed that the expression levels of 69 proteins were altered under drought stress. Among the differentially expressed proteins (DEPs), 50 were upregulated, and 19 were downregulated. The most enriched metabolic pathways for these DEPs were those involving phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction. The proteomic data and previous transcriptome results revealed 44 groups of genes/proteins with the same expression trend, including a LEA (Late embryogenesis abundant) gene, AhLEA2. Our present study showed that overexpression of the AhLEA2 gene enhanced the drought resistance of transgenic Arabidopsis plants, and the activities of related antioxidant enzymes in the transgenic plants significantly changed. The AhLEA2 gene was found to be located in the cytoplasm and cell membrane by subcellular localization experiments. This work systematically analysed the differentially expressed proteins in peanut in response to drought stress, providing important candidates for further functional analysis of the stress response of peanut. Our results also indicated that AhLEA2 plays an important role in the peanut response to drought stress.Alteration in glycosylation pattern of MUC1 mucin tandem repeats during carcinomas has been shown to negatively affect adhesive properties of malignant cells and enhance tumor invasiveness and metastasis. In addition, MUC1 overexpression is closely interrelated with angiogenesis, making it a great target for immunotherapy. Alongside, easier interaction of nanobodies (single-domain antibodies) with their antigens, compared to conventional antibodies, is usually associated with superior desirable results. Herein, we evaluated the preclinical efficacy of a recombinant nanobody against MUC1 tandem repeats in suppressing tumor growth, angiogenesis, invasion and metastasis. Expressed nanobody demonstrated specificity only toward MUC1-overexpressing cancer cells and could internalize in cancer cell lines. The IC50 values (the concentration at which the nanobody exerted half of its maximal inhibitory effect) of the anti-MUC1 nanobody against MUC1-positive human cancer cell lines ranged from 1.2 to 14.3 nM. Similar concentrations could also effectively induce apoptosis in MUC1-positive cancer cells but not in normal cells or MUC1-negative human cancer cells. Immunohistochemical staining of spontaneously developed mouse breast tumors prior to in vivo studies confirmed cross-reactivity of nanobody with mouse MUC1 despite large structural dissimilarities between mouse and human MUC1 tandem repeats. In vivo, a dose of 3µg nanobody per gram of body weight in tumor-bearing mice could attenuate tumor progression and suppress excessive circulating levels of IL-1a, IL-2, IL-10, IL-12 and IL-17A pro-inflammatory cytokines. Also, a significant decline in expression of Ki-67, MMP9 and VEGFR2 biomarkers, as well as vasculogenesis, was evident in immunohistochemically stained tumor sections of anti-MUC1 nanobody-treated mice. In conclusion, the anti-MUC1 tandem repeat nanobody of the present study could effectively overcome tumor growth, invasion and metastasis.De novo thymidylate synthesis is a crucial pathway for normal and cancer cells. Deoxythymidine monophosphate (dTMP) is synthesized by the combined action of three enzymes serine hydroxymethyltransferase (SHMT), dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), with the latter two being targets of widely used chemotherapeutics such as antifolates and 5-fluorouracil. These proteins translocate to the nucleus after SUMOylation and are suggested to assemble in this compartment into the thymidylate synthesis complex (dTMP-SC). We report the intracellular dynamics of the complex in cancer cells by in situ proximity ligation assay, showing that it is also detected in the cytoplasm. This result indicates that the role of the dTMP-SC assembly may go beyond dTMP synthesis. We have successfully assembled the dTMP synthesis complex in vitro, employing tetrameric SHMT1 and a bifunctional chimeric enzyme comprising human TYMS and DHFR. We show that the SHMT1 tetrameric state is required for efficient complex assembly, indicating that this aggregation state is evolutionarily selected in eukaryotes to optimize protein-protein interactions. Saracatinib Lastly, our results on the activity of the complete thymidylate cycle in vitro, may provide a useful tool to develop drugs targeting the entire complex instead of the individual components.Effective endosomal escape after cellular uptake represents a major challenge in the field of nanodelivery, as the majority of drug payloads must localize to subcellular compartments other than the endosomes in order to exert activity. In nature, viruses can readily deliver their genetic material to the cytosol of host cells by triggering membrane fusion after endocytosis. For the influenza A virus, the hemagglutinin (HA) protein found on its surface fuses the viral envelope with surrounding membrane at endosomal pH values. Here, biomimetic nanoparticles capable of endosomal escape were fabricated using a membrane coating derived from cells engineered to express HA on their surface. When evaluated in vitro, these virus-mimicking nanoparticles were able to deliver an mRNA payload to the cytosolic compartment of target cells, resulting in the successful expression of the encoded protein. When the mRNA-loaded nanoparticles were administered in vivo, protein expression levels were significantly increased in both local and systemic delivery scenarios. We therefore conclude that utilizing genetic engineering approaches to express viral fusion proteins on the surface of cell membrane-coated nanoparticles is a viable strategy for modulating the intracellular localization of encapsulated cargoes.
As the pursuit for a safe and effective device for laser hair removal continues, the use of simultaneous multiple wavelengths in a single device requires further exploration.
To evaluate the safety and efficacy of a novel multi-wavelength laser device for hair removal.
This retrospective cohort study included adult participants of both sexes with Fitzpatrick skin types of III and IV. Hairy sites were treated by a multiple wavelength (810nm, 940nm, and 1064nm) laser device (Primelase, Coccoon medical, Barcelona, Spain). Laser parameters included fluence of 14-20J/cm
, pulse duration of 7-30ms, and spot size of 20*9mm
. Participants underwent up to 7 treatments at 6-8weeks intervals and were followed for 6months after the last treatment session. "Before" and "after" clinical photographs were acquired and were used to evaluate efficacy by 2 independent dermatologists. They employed the Global Aesthetic Improvement Scale (GAIS; scale of 0 [no improvement] to 4 [excellent improvement; Over 75% hair reduction]). Participants' satisfaction was rated on a scale of 1 (not satisfied) to 5 (very satisfied). Pain perception and adverse events were recorded as well.
Eighteen participants (6men, 12 women) were included with a total of 49 treatment sites. Mean hair reduction was 3.6 out of 4 in the GAIS. Participants' satisfaction rate was high (mean 4.5). Beside mild transient discomfort during the procedure, no adverse events were recorded.
The use of a multiple wavelengths' laser device is safe and effective for hair removal.
The use of a multiple wavelengths' laser device is safe and effective for hair removal.
To identify barriers and enablers to COVID-19 vaccination in renal transplant recipients who are undecided about vaccination.
An online survey was distributed to 876 adult kidney transplant recipients at a tertiary referral service, who had not been vaccinated against COVID-19. The survey assessed willingness to be vaccinated, attitudes toward COVID-19 vaccines, and barriers and enablers to proceeding with vaccination.
The survey response rate was 54% (473/876). Three hundred and forty-six (73.1%) participants planned to receive vaccination (yes group), 105 (22.2%) were undecided, and 22 (4.7%) refused vaccination. The undecided group were younger but were not different in other demographic characteristics to the yes group. The undecided group were less positive toward (34.29% vs. 91.3%, p<.001) and more concerned about (93.3% vs. 25.1%, p<.001) vaccination than the yes group. Their concerns related to vaccine safety (including harm to their transplant), poor efficacy, and a lack of rigorous testiinformation provided by their transplant specialist/team. These simple interventions can be readily implemented to optimize vaccine uptake.Gottfried Huttner, formerly Professor of Inorganic Chemistry at Heidelberg University, passed away on July 21, 2021. With his pioneering contributions, he sustainably enriched the fields of X-ray crystallography, organometallic chemistry and main group chemistry. He will be remembered as an outstanding researcher and charismatic teacher.Chronic wounds present a major disease burden in people with recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering skin disorder caused by mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils at the dermal-epidermal junction. Treatment of RDEB wounds is mostly symptomatic, and there is considerable unmet need in trying to improve and accelerate wound healing. In this study, we defined transcriptomic profiles and gene pathways in RDEB wounds and compared these to intact skin in RDEB and healthy control subjects. We then used a reverse transcriptomics approach to discover drugs or compounds, which might restore RDEB wound profiles towards intact skin. Differential expression analysis identified >2000 differences between RDEB wounds and intact skin, with RDEB wounds displaying aberrant cytokine-cytokine interactions, Toll-like receptor signalling, and JAK-STAT signalling pathways. In-silico prediction for compounds that reverse gene expression signatures highlighted methotrexate as a leading candidate. Overall, this study provides insight into the molecular profiles of RDEB wounds and underscores the possible clinical value of reverse transcriptomics data analysis in RDEB, and the potential of this approach in discovering or repurposing drugs for other diseases.Tacrolimus has a narrow therapeutic index and large individual differences in pharmacokinetics. The distribution of tacrolimus in ascitic fluid and its influence on whole-blood tacrolimus were unclear. In this study, a sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was established and validated for the quantification of tacrolimus in the ascitic fluid of liver transplant recipients. Chromatographic separation was achieved on an Agilent ZORBAX Eclipse Plus Phenyl-Hexyl column (2.1 × 100 mm, 3.5 μm). Mass spectrometry was performed in multiple reaction monitoring conditions of transitions m/z 821.4→768.5 for tacrolimus. The concentrations of tacrolimus in the ascitic fluid range from 0.2 to 3.0 ng/mL, accounting for 1.19-31.87% of whole-blood tacrolimus concentrations. A linear mixed model showed a statistically significant positive correlation between the steady-state trough blood concentration of tacrolimus and the corresponding amount of tacrolimus excreted in the ascitic fluid for 24 consecutive hours, especially after normalization by daily dose per unit body weight.
