Assessing the mediating role of family resilience between caregiver burden and caregiver capacity: a cross-sectional study among Chinese stroke survivors and family caregivers in a real-world setting.

OBJECTIVES: To investigate the relationships among caregiver burden, family resilience, and caregiver capacity in the care of stroke survivors. We hypothesised that family resilience would mediate the relationship between caregiver burden and caregiver capacity. DESIGN: A cross-sectional study design was used. SETTING: The study was conducted in a tertiary care setting in Ningbo City, Zhejiang Province, China. PARTICIPANTS: The study involved 413 stroke survivors and their primary caregivers. OUTCOME MEASURES: The primary caregivers completed the Shortened Chinese Version of the Family Resilience Assessment Scale, Zarit Caregiver Burden Interview and Family Caregiver Task Inventor and provided their sociodemographic information. Stroke survivors were assessed for activities of daily living, and their sociodemographic information was provided. Data were analysed, controlling for sociodemographic variables and focusing on the mediating effect of family resilience. RESULTS: Caregiver burden was influenced by the activities of daily living of stroke survivors, caregiver age and caregiver health status (p<0.05). Higher caregiver burden was associated with lower family resilience (p<0.01). Lower caregiver capacity corresponded to heavier caregiver burden (p<0.01). Family resilience mediated the relationship between caregiver burden and caregiver capacity (b=0.1568; 95% CI: 0.1063 to 0.2385). CONCLUSIONS: Enhancing family resilience can reduce caregiver burden and improve caregiver capacity in stroke care. These findings underscore the importance of developing interventions focused on nursing skills and family resilience.

One-Component Cationic Lipids for Systemic mRNA Delivery to Splenic T Cells.

Unlocking the full potential of mRNA immunotherapy necessitates targeted delivery to specific cell subsets in the spleen. Four-component lipid nanoparticles (LNPs) utilized in numerous clinical trials are primarily limited in hepatocyte and muscular targeting, highlighting the imperative demand for targeted and simplified non-liver mRNA delivery systems. Herein, we report the rational design of one-component ionizable cationic lipids to selectively deliver mRNA to the spleen and T cells with high efficacy. Unlike the tertiary amine-based ionizable lipids involved in LNPs, the proposed cationic lipids rich in secondary amines can efficiently deliver mRNA both in vitro and in vivo as the standalone carriers. Furthermore, these vectors facilitate efficacious mRNA delivery to the T cell subsets following intravenous administration, demonstrating substantial potential for advancing immunotherapy applications. This straightforward strategy extends the utility of lipid family for extrahepatic mRNA delivery, offering new insights into vector development beyond LNPs to further the field of precise mRNA therapy.

FGF4 protects the liver from immune-mediated injury by activating CaMKKß-PINK1 signal pathway to inhibit hepatocellular apoptosis.

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine; however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca2+/calmodulin-dependent protein kinasekinase 2 (CaMKKß) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

Insight into the probability of ethoxy(pentafluoro)cyclotriphosphazene (PFPN) as the functional electrolyte additive in lithium-sulfur batteries.

Enhancing the flame retardancy of electrolytes and the stability of lithium anodes is of great significance to improve the safety performance of lithium-sulfur (Li-S) batteries. It is well known that the most commonly used ether based electrolyte solvents in Li-S batteries have a lower flash point and higher volatility than the ester electrolyte solvents in Li-ion batteries. Hence, lithium-sulfur batteries have greater safety risks than lithium-ion batteries. Herein, ethoxy(pentafluoro)cyclotriphosphazene (PFPN), which is commonly used as a flame retardant for ester electrolytes in lithium-ion batteries, is utilized as both a film-forming electrolyte additive and a flame retardant additive for the ether electrolyte to investigated its applicability in Li-S batteries. It is found that the ether electrolyte containing PFPN not only has good flame retardant properties and a wide potential window of about 5 V, but also can form a stable SEI film on the surface of a lithium anode. As a result, with the ether-based electrolyte containing 10 wt% PFPN, Li-Cu and Li-S batteries all delivered a stable cycling performance with a high coulombic Efficiency and a long-lifespan performance, which were all superior to the batteries using the ether-based electrolyte without PFPN. This study demonstrates an effective solution to solve the problems of flammable ether-based electrolytes and reactive lithium anodes, and it may contribute to the development of safe Li-S batteries.

Dehydrative alkynylation of 3-hydroxyisoindolinones with terminal alkynes for the synthesis of 3-alkynylated 3,3-disubstituted isoindolinones.

A brand-new procedure for the synthesis of 3-alkynylated 3,3-disubstituted isoindolinones has been disclosed via a HOTf or Fe(OTf)3-catalyzed dehydrative alkynylation of 3-hydroxyisoindolinones with terminal alkynes. Aryl, alkenyl and alkyl terminal alkynes are suitable to couple with a broad range of 3-hydroxyisoindolinones to afford the desired products in moderate to good yields. This protocol features the use of an inexpensive catalyst, mild reaction conditions, broad substrate scope and easy elaboration of the products.

Label-free and portable detection of HIV-DNA by a handheld luminometer.

BACKGROUND: The human immunodeficiency virus (HIV) remains a major worldwide health problem. Nowadays, many methods have been developed for quantitative detecting human immunodeficiency virus DNA (HIV-DNA), such as fluorescence and colorimetry. However, these methods still have the disadvantages of being expensive and requiring professional technicians. Early diagnosis of pathogens is increasingly dependent on portable instruments and simple point-of-care testing (POCT). Therefore, it is meaningful and necessary to develop portable and cheap methods for detecting disease markers. RESULTS: In this work, a label-free chemiluminescence (CL) method was developed for detecting HIV-DNA via a handheld luminometer. To achieve label-free target detection, the CL catalyst, G-triplex-hemin DNAzyme (G3-hemin DNAzyme), was in-situ assembled in the presence of HIV-DNA. For improving sensitivity, HIV-DNA induced the cyclic strand displacement reaction (SDR), which can form three G3-hemin DNAzymes in one cycle. So, the chemiluminescence reaction between luminol and H2O2 was highly effectively catalyzed, and the CL intensity was linearly related with the concentration of HIV-DNA in the range of 0.05-10 nM with a detection limit of 29.0 pM. Due to the high specificity of hairpin DNA, single-base mismatch can be discriminated, which ensured the specific detection of HIV-DNA. SIGNIFICANCE: In-situ formation of G3-hemin DNAzyme led to label-free and selective detection without complex synthesis and functionalization. Therefore, it offers a cheap, selective, sensitive and portable method for detecting disease-related genes, which is promising for POCT of clinical diagnosis in resource-limited settings.

[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

The smallest Schwarzite carbon with only heptagonal carbon rings.

Carbon materials with full sp2-hybridized buckling is a major challenge pervading fundamental nanoscience and nanotechnology research. Carbon atoms that are sp2 hybridized prefer to form hexagonal rings, such as in carbon nanotubes and graphene, which are low-dimensional materials. The incorporation of heptagonal, octagonal, and/or larger rings into a hexagonal sp2 carbon meshwork has been identified as a strategy for assembling three-dimensional (3D) sp2 carbon crystals, and one of the typical representatives are Schwarzite carbons, which possess a negative surface Gaussian curvature as well as unique physical properties. Herein, a 3D Schwarzite carbon consisting of only sp2-buckled heptagonal carbon rings, which is referred to as Hepta-carbon, is proposed based on first-principles calculations. Hepta-carbon is mechanically and thermodynamically stable, and energetically more favourable than experimental graphdiyne, fullerene C20 and most Schwarzite carbons under ambient conditions. Molecular dynamics simulations indicate that Hepta-carbon exhibits high-temperature thermostability up to 1500 K. Band structure and mechanical property simulations indicate that Hepta-carbon is a semi-metallic material with electron conduction and exhibits impressive mechanical properties such as high strength with quasi-isotropy, high incompressibility similar to diamonds, elastic deformation behaviour under uniaxial stress, and high ductility. Hepta-carbon presents a porous network with a low mass density of 1.84 g cm-3 and connected channels with diameters of 3.3-6.1 Å. Theoretical simulations of gas adsorption energy demonstrate that Hepta-carbon can effectively adsorb and stabilize greenhouse gases, including N2O, CO2, CH4, and SF6.

Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue.

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

Qualitative research on the cognition of breastfeeding knowledge in primiparas during pregnancy.

BACKGROUND: In view of the lack of attention and predictability in postpartum breastfeeding in primiparas, health education on breastfeeding during pregnancy should be carried out to publicize the benefits of breastfeeding. OBJECTIVE: To investigate how well the primiparas during pregnancy are known of breastfeeding knowledge, and to provide a basis for developing health education measures for them. METHODS: With the adoption of the objective sampling method and the principle of saturation, 10 primiparas in the obstetrics outpatient department of the Hunan Provincial People's Hospital were selected as the study participants. Semi-structured in-depth interviews combined with the observation method were used for data collection. The interview data were analyzed and the theme was refined by Colaizzi's seven-step method. RESULTS: The results of the four themes of the cognition of breastfeeding knowledge among primiparas were as follows: Lack of knowledge and curiosity about breastfeeding in some women, lack of access to correct breastfeeding knowledge, insufficient support from family members for postpartum breastfeeding, and lack of approach to solve problems during breastfeeding among primiparas. CONCLUSION: Due to the current problems of the cognition of breastfeeding knowledge in primiparas, it was imperative to build a health education model suitable for primiparas to improve this knowledge.

Multifunctional Manganese-Nucleotide Laccase-Mimicking Nanozyme for Degradation of Organic Pollutants and Visual Assay of Epinephrine via Smartphone.

As a natural green catalyst, laccase has extensive application in the fields of environmental monitoring and pollutant degradation. However, susceptibility to environmental influences and poor reusability seriously hinder its application. To address these concerns, for the first time, manganese ion replaced copper ion as the active center to coordinate with guanosine monophosphate (GMP) for synthesizing mimic laccase with high catalytic activity. Compared with natural laccase, the laccase-like nanozyme (Mn-GMPNS) demonstrated superior thermal stability, acid-base resistance, salt tolerance, reusability, and substrate universality. Benefiting from the high catalytic activity of Mn-GMPNS, epinephrine, a significant neurotransmitter and hormone associated with numerous diseases, was visually detected within 10 min and a portable assay by smartphone. More encouragingly, Mn-GMPNS can efficiently degrade dye pollutants, achieving a decolorization rate over 70% within 30 min. Thus, the coordination between manganese ion and nucleotide demonstrated the potential in rational design of nanozymes with high catalytic activity, low cost, good stability, and good biocompatibility.

Simultaneous determination of iguratimod and its metabolite in rat plasma using a UPLC-MS/MS method: Application for drug-drug interaction.

This aim of the work was to establish an acceptable sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentrations of iguratimod (IGR) and its metabolite M2 in rats, and to further investigate the effect of fluconazole on the pharmacokinetics of IGR and M2. The mobile phase consisted of acetonitrile and water with 0.1% formic acid, was used to separate IGR, M2 and internal standard (IS) fedratinib on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) with the flow rate of 0.4 mL/min. Positive ion mode and multiple reaction monitoring (MRM) were used to construct the quantitative analysis. The calibration standard of IGR and M2 covered 2-10000 and 1-1000 ng/mL respectively, with the lower limit of quantification (LLOQ) as 2 ng/mL and 1 ng/mL respectively. In addition, selectivity, recovery, accuracy, precision, matrix effect and stability of the method validation program were well accepted in this work. Subsequently, this approach was used to assess the effect of fluconazole on the pharmacokinetics of IGR and M2 in rats. In the presence of 20 mg/kg fluconazole (experimental group), we found the main pharmacokinetic parameters were significantly altered when compared with 2.5 mg/kg IGR alone (control group). Among them, AUC(0-∞) and Cmax of IGR in the experimental group was 1.43 and 1.08 times higher than that of the control group, respectively. Moreover, we also found that the other main pharmacokinetic parameters of M2 had no significant changes, except t1/2z and Tmax. In conclusion, fluconazole significantly altered the main pharmacokinetics of IGR and M2 in rats. It implys that we should pay more attention to the adverse reaction of IGR when the concomitant use of fluconazole and IGR occur in the future clinical practice.

Comparison of Participation in Strength Activity Among People With and Without Disabilities: 2013-2017 Behavioral Risk Factor Surveillance System.

BACKGROUND: The current physical activity guidelines recommend engagement in strength activities at least 2 days per week. Currently, there is a lack of literature examining strength activities among people with disabilities. The purpose of this study is to estimate and compare the prevalence of engagement in strength activities and adherence to strength activity guidelines among adults with and without disabilities in the United States. METHODS: A total of 1,005,644 adults (18-80 y old) with and without disabilities from the 2013 to 2017 Behavioral Risk Factor Surveillance System were included in this secondary data analysis. Descriptive analyses were performed to describe the prevalence of strength activity behaviors of adults with and without disabilities. Logistic and Poisson regression models were performed to evaluate the relative contribution of disability status on strength activity behaviors. RESULTS: A higher proportion of participants without disabilities (46.42%, 95% CI, 46.18-46.65) reported engaging in strength activities compared with participants with disabilities (30.68%, 95% CI, 30.29-31.08; P < .01). Participants with disabilities were less likely to engage in strength activities (odds ratio = 0.51, 95% CI, 0.50-0.52; adjusted odds ratio = 0.75, 95% CI, 0.73-0.77) and meet strength activity guidelines (odds ratio = 0.56, 95% CI, 0.54-0.57; adjusted odds ratio = 0.75, 95% CI, 0.73-0.77) than participants without disabilities. CONCLUSION: Experiencing a disability is associated with lower engagement in strength activities; thus, it is important to identify effective and efficient approaches to promoting strength activities among people with disabilities.

Mobile-Delivered Mindfulness Intervention on Anxiety Level Among College Athletes: Randomized Controlled Trial.

BACKGROUND: College athletes are a group often affected by anxiety. Few interventional studies have been conducted to address the anxiety issues in this population. OBJECTIVE: We conducted a mobile-delivered mindfulness intervention among college athletes to study its feasibility and efficacy in lowering their anxiety level and improving their mindfulness (measured by the Five Facet Mindfulness Questionnaire [FFMQ]). METHODS: In April 2019, we recruited 290 college athletes from a public university in Shanghai, China, and 288 of them were randomized into an intervention group and a control group (closed trial), with the former (n=150) receiving a therapist-guided, smartphone-delivered mindfulness-based intervention and the latter receiving mental health promotion messages (n=138). We offered in-person instructions during the orientation session for the intervention group in a classroom, with the therapist interacting with the participants on the smartphone platform later during the intervention. We used generalized linear modeling and the intent-to-treat approach to compare the 2 groups' outcomes in dispositional anxiety, precompetition anxiety, and anxiety during competition, plus the 5 dimensions of mindfulness (measured by the FFMQ). RESULTS: Our intent-to-treat analysis and generalized linear modeling found no significant difference in dispositional anxiety, precompetition anxiety, or anxiety during competition. Only the "observation" facet of mindfulness measures had a notable difference between the changes experienced by the 2 groups, whereby the intervention group had a net gain of .214 yet fell short of reaching statistical significance (P=.09). Participants who specialized in group sports had a higher level of anxiety (ß=.19; SE=.08), a lower level of "nonjudgemental inner experience" in FFMQ (ß=-.07; SE=.03), and a lower level of "nonreactivity" (ß=-.138; SE=.052) than those specializing in individual sports. CONCLUSIONS: No significant reduction in anxiety was detected in this study. Based on the participant feedback, the time availability for mindfulness practice and session attendance for these student athletes in an elite college could have compromised the intervention's effectiveness. Future interventions among this population could explore a more student-friendly time schedule (eg, avoid final exam time) or attempt to improve cognitive and scholastic outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024449; https://www.chictr.org.cn/showproj.html?proj=40865.

TRIM29 modulates proteins involved in PTEN/AKT/mTOR and JAK2/STAT3 signaling pathway and suppresses the progression of hepatocellular carcinoma.

Tripartite motif-containing 29 (TRIM29), also known as the ataxia telangiectasia group D-complementing (ATDC) gene, has been reported to play an oncogenic or tumor suppressive role in developing different tumors. So far, its expression and biological functions in hepatocellular carcinoma (HCC) remain unclear. We investigated TRIM29 expression pattern in human HCC samples using quantitative RT-PCR and immunohistochemistry. Relationships between TRIM29 expression level, clinical prognostic indicators, overall survival (OS), and disease-free survival (DFS) were evaluated by Kaplan-Meier analysis and Cox proportional hazards model. A series of in vitro experiments and a xenograft tumor model were conducted to detect the functions of TRIM29 in HCC cells. RNA sequencing, western blotting, and immunochemical staining were performed to assess the molecular regulation of TRIM29 in HCC. We found that the mRNA and protein levels of TRIM29 were significantly reduced in HCC samples, compared with adjacent noncancerous tissues, and were negatively correlated with poor differentiation of HCC tissues. Survival analysis confirmed that lower TRIM29 expression significantly correlated with shorter OS and DFS of HCC patients. TRIM29 overexpression remarkably inhibited cell proliferation, migration, and EMT in HCC cells, whereas knockdown of TRIM29 reversed these effects. Moreover, deactivation of the PTEN/AKT/mTOR and JAK2/STAT3 pathways might be involved in the tumor suppressive role of TRIM29 in HCC. Our findings indicate that TRIM29 in HCC exerts its tumor suppressive effects through inhibition of the PTEN/AKT/mTOR and JAK2/STAT3 signaling pathways and may be used as a potential biomarker for survival in patients with HCC.

A network pharmacology approach to reveal the key ingredients in Scrophulariae Radix (SR) and their effects against Alzheimer's disease.

Background: Scrophulariae Radix (SR) is a commonly used medicinal plant. Alzheimer's disease (AD) is a neurodegenerative disease for which there is no effective treatment. This study aims to initially clarify the potential mechanism of SR in the treatment of AD based on network pharmacology and molecular docking techniques. Methods: The principal components and corresponding protein targets of SR were conducted by HPLC analysis and searched on TCMSP. AD targets were searched on DrugBank, Chemogenomics, TTD, OMIM and GeneCards databases. The compound-target network was constructed by Cytoscape3.8.2. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a PPI network. We further performed GO and KEGG enrichment analysis on the targets. Meanwhile, molecular docking study and cell experiments were approved for the core target and the active compound. Results: Through multidatabase retrieval and integration, it was found that 17 components of SR could exert anti-AD effects against 40 targets. KEGG enrichment analysis indicated that Alzheimer's disease (hsa05010) was one of the most significant AD enrichment signalling pathways. Combined with the gene expression profile information in the AlzData database, 15 targets were found to be associated with tau or beta-amyloid protein (Aß). GO analysis indicated that the primary molecular functions of SR in the treatment of AD were neurotransmitter receptor activity (GO:0007268), postsynaptic neurotransmitter receptor activity (GO:0070997), and acetylcholine receptor activity (GO:0050435). Moreover, we explored the anti-AD effects of SR extract and ursolic acid (UA) using SH-SY5Y cells. Treatment of SH-SY5Y cells with 20 µM UA significantly reduced the oxidative damage to these neuronal cells. Conclusion: This study reveals the active ingredients and potential molecular mechanism of SR in the treatment of AD, and provides a theoretical basis for further basic research and clinical application.

Experimental evidence for cancer resistance in a bat species.

Mammals exhibit different rates of cancer, with long-lived species generally showing greater resistance. Although bats have been suggested to be resistant to cancer due to their longevity, this has yet to be systematically examined. Here, we investigate cancer resistance across seven bat species by activating oncogenic genes in their primary cells. Both in vitro and in vivo experiments suggest that Myotis pilosus (MPI) is particularly resistant to cancer. The transcriptomic and functional analyses reveal that the downregulation of three genes (HIF1A, COPS5, and RPS3) largely contributes to cancer resistance in MPI. Further, we identify the loss of a potential enhancer containing the HIF1A binding site upstream of COPS5 in MPI, resulting in the downregulation of COPS5. These findings not only provide direct experimental evidence for cancer resistance in a bat species but also offer insights into the natural mechanisms of cancer resistance in mammals.

DsbA-L ameliorates renal aging and renal fibrosis by maintaining mitochondrial homeostasis.

Renal fibrosis is the final pathological change in renal disease, and aging is closely related to renal fibrosis. Mitochondrial dysfunction has been reported to play an important role in aging, but the exact mechanism remains unclear. Disulfide-bond A oxidoreductase-like protein (DsbA-L) is mainly located in mitochondria and plays an important role in regulating mitochondrial function and endoplasmic reticulum (ER) stress. However, the role of DsbA-L in renal aging has not been reported. In this study, we showed a reduction in DsbA-L expression, the disruption of mitochondrial function and an increase in fibrosis in the kidneys of 12- and 24-month-old mice compared to young mice. Furthermore, the deterioration of mitochondrial dysfunction and fibrosis were observed in DsbA-L-/- mice with D-gal-induced accelerated aging. Transcriptome analysis revealed a decrease in Flt4 expression and inhibition of the PI3K-AKT signaling pathway in DsbA-L-/- mice compared to control mice. Accelerated renal aging could be alleviated by an AKT agonist (SC79) or a mitochondrial protector (MitoQ) in mice with D-gal-induced aging. In vitro, overexpression of DsbA-L in HK-2 cells restored the expression of Flt4, AKT pathway factors, SP1 and PGC-1α and alleviated mitochondrial damage and cell senescence. These beneficial effects were partially blocked by inhibiting Flt4. Finally, activating the AKT pathway or improving mitochondrial function with chemical reagents could alleviate cell senescence. Our results indicate that the DsbA-L/AKT/PGC-1α signaling pathway could be a therapeutic target for age-related renal fibrosis and is associated with mitochondrial dysfunction.

Exopolysaccharides of Paenibacillus polymyxa: A review.

Paenibacillus polymyxa (P. polymyxa) is a member of the genus Paenibacillus, which is a rod-shaped, spore-forming gram-positive bacterium. P. polymyxa is a source of many metabolically active substances, including polypeptides, volatile organic compounds, phytohormone, hydrolytic enzymes, exopolysaccharide (EPS), etc. Due to the wide range of compounds that it produces, P. polymyxa has been extensively studied as a plant growth promoting bacterium which provides a direct benefit to plants through the improvement of N fixation from the atmosphere and enhancement of the solubilization of phosphorus and the uptake of iron in the soil, and phytohormones production. Among the metabolites from P. polymyxa, EPS exhibits many activities, for example, antioxidant, immunomodulating, anti-tumor and many others. EPS has various applications in food, agriculture, environmental protection. Particularly, in the field of sustainable agriculture, P. polymyxa EPS can be served as a biofilm to colonize microbes, and also can act as a nutrient sink on the roots of plants in the rhizosphere. Therefore, this paper would provide a comprehensive review of the advancements of diverse aspects of EPS from P. polymyxa, including the production, extraction, structure, biosynthesis, bioactivity and applications, etc. It would provide a direction for future research on P. polymyxa EPS.