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ate the Framework, evaluate PCCS for dementia, explore determinants, and develop strategies to implement and scale-up PCCS approaches. Such studies should explore how to tailor PCCS needs and preferences based on input from persons with dementia, and by sex/gender and other intersectional factors such as ethnicity or culture.
Despite the paucity of research on PCCS for dementia, synthesis of knowledge from diverse studies into a Framework provides interim guidance for those planning or evaluating dementia services in outpatient, home or community settings. Further research is needed to elaborate the Framework, evaluate PCCS for dementia, explore determinants, and develop strategies to implement and scale-up PCCS approaches. Such studies should explore how to tailor PCCS needs and preferences based on input from persons with dementia, and by sex/gender and other intersectional factors such as ethnicity or culture.
Cyanobacteria receive huge interest as green catalysts. While exploiting energy from sunlight, they co-utilize sugar and CO
. This photomixotrophic mode enables fast growth and high cell densities, opening perspectives for sustainable biomanufacturing. The model cyanobacterium Synechocystis sp. PCC 6803 possesses a complex architecture of glycolytic routes for glucose breakdown that are intertwined with the CO
-fixing Calvin-Benson-Bassham (CBB) cycle. To date, the contribution of these pathways to photomixotrophic metabolism has remained unclear.
Here, we developed a comprehensive approach for
C metabolic flux analysis of Synechocystis sp. PCC 6803 during steady state photomixotrophic growth. Under these conditions, the Entner-Doudoroff (ED) and phosphoketolase (PK) pathways were found inactive but the microbe used the phosphoglucoisomerase (PGI) (63.1%) and the oxidative pentose phosphate pathway (OPP) shunts (9.3%) to fuel the CBB cycle. buy Finerenone Mutants that lacked the ED pathway, the PK pathway, or phosphatory intermediates or alternatively, that EDA possesses additional so far unknown functions. These ideas require further experiments.
The developed approach, based on parallel 13C tracer studies with GC-MS analysis of amino acids, sugars, and sugar derivatives, optionally adding NMR data from amino acids, is valuable to study fluxes in photomixotrophic microbes to detail. In photomixotrophic cells, PGI and OPP form glycolytic shunts that merge at switch points and result in synergistic fueling of the CBB cycle for maximized CO2 fixation. However, redirected fluxes in an ED shunt-deficient mutant and the impossibility to delete this shunt in a GAPDH2 knockout mutant, indicate that either minor fluxes (below the resolution limit of 13C flux analysis) might exist that could provide catalytic amounts of regulatory intermediates or alternatively, that EDA possesses additional so far unknown functions. These ideas require further experiments.Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.
Steatotic livers tolerate ischemia-reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown.
A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos.
We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effeh might be a promising strategy to treat IRI in steatotic grafts.
Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts.
During fermentation, industrial microorganisms encounter multiple stresses that inhibit cell growth and decrease fermentation yields, in particular acid stress, which is due to the accumulation of acidic metabolites in the fermentation medium. Although the addition of a base to the medium can counteract the effect of acid accumulation, the engineering of acid-tolerant strains is considered a more intelligent and cost-effective solution. While synthetic biology theoretically provides a novel approach for devising such tolerance modules, in practice it is difficult to assemble stress-tolerance modules from hundreds of stress-related genes.
In this study, we designed a set of synthetic acid-tolerance modules for fine-tuning the expression of multi-component gene blocks comprising a member of the proton-consuming acid resistance system (gadE), a periplasmic chaperone (hdeB), and reactive oxygen species (ROS) scavengers (sodB and katE). Directed evolution was used to construct an acid-responsive asr promoter lchieving synthetic modules of interest, particularly in improving the robustness and productivity of industrial strains.
Our results demonstrate a promising synthetic-biology strategy to enhance the growth robustness and productivity of E. coli upon the mildly acidic conditions, in both a general lab strain MG1655 and an industrial lysine-producing strain SCEcL3, by using the stress-responsive synthetic acid-tolerance modules comprising a limited number of genes. This study provides a reliable and efficient method for achieving synthetic modules of interest, particularly in improving the robustness and productivity of industrial strains.Lorlatinib is a promising third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that has been approved for treating ALK-positive non-small-cell lung cancer (NSCLC) patients with previous ALK-TKI treatment failures. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A more comprehensive understanding of the acquired resistance mechanisms to lorlatinib will enable the development of more efficacious therapeutic strategies. The efficacy of chloroquine (CQ) in combination with lorlatinib in ALK-positive NSCLC cells in vitro and in vivo was assessed using CCK-8, colony formation, immunofluorescence staining, flow cytometry analysis, western blot analysis, and xenograft implantation. Here, we show that lorlatinib induced apoptosis and protective autophagy in ALK-positive NSCLC cells. However, the protective autophagy can gradually lead to decreased cytotoxicity of loratinib in ALK-positive NSCLC cells. Meanwhile, we found that the combination of lorlatinib and CQ, an inhibitor of autophagy, inhibited autophagy and promoted apoptosis both in vitro and in vivo, which sensitized cells to lorlatinib through the dephosphorylation of Foxo3a and promoted nuclear translocation, then activation of Foxo3a/Bim axis. Taken together, our results suggest that inhibition of protective autophagy might be a therapeutic target for delaying the occurrence of acquired resistance to lorlatinib in ALK-positive NSCLC patients.
Psoriasis (PS) is difficult to cure with a high incidence. Therefore, the quality of life (QOL) of people with Psoriasis has caused widespread concern. Universal scales respond poorly to subtle changes caused by specific diseases, which makes it challenging to fully understand the impact of QOL in patients with psoriasis. In view of the deficiencies of the universal scale and the lack of a specific scale suitable for Chinese cultural background, this study aims to develop the psoriasis scale among the system of QOL instruments for chronic diseases QLICD-PS (V2.0).
The scale QLICD-PS (V2.0) was developed based on the procedural decision-making approach and the experience of establishing scales at home and abroad. 122 patients with psoriasis were participated in measuring QOL 3 times before and after treatments. The reliability was assessed by test-retest reliability (Pearson's correlation coefficients) and also internal consistency (Cronbach's alpha coefficients). Qualitative analysis was adopted to evalua were statistically significant with SRM being 0.5, showing moderate responsiveness.
As the first psoriasis-specific QOL scale developed by the modular approach in Chinese, the QLICD-PS showed good reliability, validity and responsiveness, and could be used to measure the QOL of Patients with psoriasis specifically and sufficiently.
As the first psoriasis-specific QOL scale developed by the modular approach in Chinese, the QLICD-PS showed good reliability, validity and responsiveness, and could be used to measure the QOL of Patients with psoriasis specifically and sufficiently.
Key to the US refugee resettlement effort is the role of non-governmental organizations (NGOs) who receive, place, and provide transitional programs and referrals to new and recently resettled refugees. Yet only one rapid assessment study thus far examined the impact of COVID-19 on service delivery systems of US refugee resettlement agencies. This exploratory study describes the capability and preparedness of US refugee resettlement agencies to provide services and care to clients during the COVID-19 pandemic.
Using both telephone interviews and an internet survey, we assessed the impact of COVID-19 on service delivery, agency capacity, and preparedness of 101 US refugee resettlement agencies. Descriptive statistics were used to describe the dataset, while chi-square (χ
) tests were used to examine relationships by resettlement agency size (number of employees in each agency).
Despite a temporary pause on refugee admissions, restrictive stay-at-home orders, and refugee travel restrictions, the majorityce or operations.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. Deregulation of mRNA translation is a frequent feature of cancer. Eukaryotic translation initiation factor 3 subunit B (EIF3B) has been reported as an oncogene; however, its role in HNSCC has yet to be fully elucidated.
In this study, the clinical significance of EIF3B expression was analyzed based on TCGA datasets. Then, EIF3B expression was knocked down and its role in HNSCC was revealed. To explore the molecular mechanisms of EIF3B, we applied RNA sequencing and proteomics and acquired deregulated pathways. RNA immunoprecipitation (RIP) sequencing was conducted to reveal the target mRNAs of EIF3B, and TCGA datasets were used to validate potential targets of EIF3B.
Elevated expression of EIF3B was observed in the HNSCC cancer samples. The expression of EIF3B was significantly correlated with the patient's sex, age, HPV infection status, T stage, N stage, perineural invasion status and survival status. EIF3B serves as a marker of an unfavorable HNSCC prognosis.
