Capsaicin reduces blood glucose and prevents prostate growth by regulating androgen, RAGE/IGF-1/Akt, TGF-ß/Smad signalling pathway and reversing epithelial-mesenchymal transition in streptozotocin-induced diabetic mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-ß1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-ß/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.

EQ-5D-5L population norms for China derived from a national health survey.

OBJECTIVES: To develop the EQ-5D-5L (5L) population norms for China; and to assess the relationship between various factors and 5L data. METHODS: The study used data derived from the Psychology and Behavior Investigation of Chinese Residents, a national sample survey of 21,909 representative participants aged 12 years and above. Participants' health-related quality of life (HRQoL) was measured by the 5L. Their socioeconomic characteristics, behavioral factors, and health conditions were also obtained from the survey. Norm scores were generated and compared for different socioeconomic variables. Multiple linear and logistic regressions were used to assess the relationships of the three kinds of variables with the 5L utility, visual analogue scale (VAS) scores and 5L health problems. RESULTS: The mean (SD) age of participants was 39.4 (18.9) years, and 50.0% of the participants were female. The mean (SD) utility and VAS scores were 0.940 (0.138) and 73.4 (21.6), respectively. Participants reported considerably more problems in anxiety/depression (26.2%) and pain/discomfort (22.2%) dimensions. The gender difference in HRQoL is attenuated. The participants older than 75 years suffered from a sharp decline in HRQoL; the participants in Shanghai and Tibet provinces reported lower utility and VAS scores and more health problems. Those who were younger, with better socioeconomic status and healthier lifestyles, and without diseases tended to report higher utility and VAS scores and fewer health problems. CONCLUSIONS: The study derived the 5L population norms for China based on a representative population sample.

Thermally Evaporated Metal Halide Perovskites and Their Analogues: Film Fabrication, Applications and Beyond.

Metal halide perovskites emerge as promising semiconductors for optoelectronic devices due to ease of fabrication, attractive photophysical properties, their low cost, highly tunable material properties, and high performance. High-quality thin films of metal halide perovskites are the basis of most of these applications including solar cells, light-emitting diodes, photodetectors, and electronic memristors. A typical fabrication method for perovskite thin films is the solution method, which has several limitations in device reproducibility, adverse environmental impact, and utilization of raw materials. Thermal evaporation holds great promise in addressing these bottlenecks in fabricating high-quality halide perovskite thin films. It also has high compatibility with mass-production platforms that are well-established in industries. This review first introduces the basics of the thermal evaporation method with a particular focus on the critical parameters influencing the thin film deposition. The research progress of the fabrication of metal halide perovskite thin films is further summarized by different thermal evaporation approaches and their applications in solar cells and other optoelectronic devices. Finally, research challenges and future opportunities for both fundamental research and commercialization are discussed.

Anthraquinone-based covalent organic framework as a recyclable direct hydrogen atom transfer photocatalyst for C-H functionalization.

Photocatalytic direct hydrogen atom transfer (d-HAT) is a synthetically important strategy to convert C-H bonds to useful C-X bonds. Herein we report the synthesis of an anthraquinone-based two-dimensional covalent organic framework, DAAQ-COF, as a recyclable d-HAT photocatalyst for C-H functionalization. Powder X-ray diffraction, N2 sorption isotherms, solid-state NMR spectra, infrared spectra, and thermogravimetric analysis characterized DAAQ-COF as a crystalline, porous COF with a stable ketoenamine linkage and strong absorption in the visible region. Under visible light irradiation, DAAQ-COF is photo-excited to cleave C(sp3)-H or C(sp2)-H bonds via HAT to generate reactive carbon radicals, which add to different radical acceptors to achieve C-N or C-C coupling reactions. DAAQ-COF is easily recovered from the reaction mixture via centrifugation or filtration and used in six consecutive reaction runs without any decrease in catalytic efficiency. The ease of catalyst separation allows sequential conversion of the C-N coupling intermediate to synthetically useful amide, ester, or thioester products. Photophysical and isotope labelling experiments support the d-HAT mechanism of DAAQ-COF-catalyzed C-H bond functionalization.

Psychometric performance of EQ-5D-5L and SF-6Dv2 in patients with lymphoma in China.

AIM: To assess and compare the measurement properties of EQ-5D-5L and SF-6Dv2 among lymphoma patients in China. METHODS: A face-to-face survey of Chinese lymphoma patients was conducted at baseline (all types) and follow-up (diffuse large B-cell). EQ-5D-5L and SF-6Dv2 health utility scores (HUSs) were calculated using the respective Chinese value sets. Ceiling effect was assessed by calculating the percentage of respondents reporting the optimal health state. Convergent validity of EQ-5D-5L and SF-6Dv2 was assessed using the Spearman rank correlation coefficient (r) with QLQ-C30 as a calibration standard. Known-groups validity of the two HUSs was evaluated by comparing their scores of patients with different conditions; and their sensitivity was further assessed in the known-groups using relative efficiency (RE). Test-retest reliability and responsiveness was tested using ICC and standardized response mean (SRM), respectively. RESULTS: Altogether 200 patients were enrolled at baseline and 78 were followed up. No ceiling effect was found for SF-6Dv2 compared to 24.5% for EQ-5D-5L. Correlation between the two HUSs and with QLQ-C30 score was strong (r > 0.5). Each dimension of EQ-5D-5L and SF-6Dv2 had moderate or greater correlations with similar dimensions of QLQ-C30 (r > 0.35). Both EQ-5D-5L and SF-6Dv2 could only a minority known-groups, and the latter may have better sensitivity. EQ-5D-5L had better test-retest reliability (ICC = 0.939); while both of them were responsive to patients with worsened and improved clinical status. CONCLUSIONS: EQ-5D-5L and SF-6Dv2 were found to have good convergent validity and responsiveness, while EQ-5D-5L had better test-retest reliability and higher ceiling effect. Not enough evidence indicates which of the two measures has better known-group validity and sensitivity.

Enhancing Skin Injury Repair: Combined Application of PF-127 Hydrogel and hADSC-Exos Containing miR-148a-3p.

The use of exosomes to relieve skin injuries has received considerable attention. The PluronicF-127 hydrogel (PF-127 hydrogel) is a novel biomaterial that can be used to carry biomolecules. This study sought to investigate the impact of exosomes originating from human mesenchymal stem cells (MSCs) developed from adipose tissue (hADSC-Exos) combined with a PF-127 hydrogel on tissue repair and explore the underlying mechanism using in vitro and in vivo experiments. miR-148a-3p is the most expressed microRNA (miRNA) in hADSC-Exos. We found that exosomes combined with the PF-127 hydrogel had a better efficacy than exosomes alone; moreover, miR-148a-3p knockdown lowered its efficacy. In vitro, we observed a significant increase in the tumor-like ability of HUVECs after exosome treatment, which was attenuated after miR-148a-3p knockdown. Furthermore, the effects of miR-148a-3p on hADSC-Exos were achieved through the prevention of PTEN and the triggering of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. In conclusion, our results demonstrated that hADSC-Exos can promote angiogenesis and skin wound healing by delivering miR-148a-3p and have a better effect when combined with the PF-127 hydrogel, which may be an alternative strategy to promote wound healing.

Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy.

Background: Adipose mesenchymal stem cell-derived exosomes (ADSC-Exos) have great potential in the field of tissue repair and regenerative medicine, particularly in cases of refractory diabetic wounds. Interestingly, autophagy plays a role in wound healing, and recent research has demonstrated that exosomes are closely associated with intracellular autophagy in biogenesis and molecular signaling mechanisms. Therefore, this study aimed to investigate whether ADSC-Exos promote the repair of diabetic wounds by regulating autophagy to provide a new method and theoretical basis for the treatment of diabetic wounds. Methods: Western blot analysis and autophagy double-labelled adenovirus were used to monitor changes in autophagy flow in human immortalized keratinocyte cell line (HaCaT) cells. ADSC-Exos were generated from ADSC supernatants via ultracentrifugation. The effectiveness of ADSC-Exos on HaCaT cells was assessed using a live-cell imaging system, cell counting kit-8 and cell scratch assays. The cells were treated with the autophagy inhibitor bafilomycin A1 to evaluate the effects of autophagy on cell function. The recovery of diabetic wounds after ADSC-Exo treatment was determined by calculating the healing rates and performing histological analysis. High-throughput transcriptome sequencing was used to analyze changes in mRNA expression after the treatment of HaCaT cells with ADSC-Exos. Results: ADSC-Exos activated autophagy in HaCaT cells, which was inhibited by high glucose levels, and potentiated their cellular functions. Moreover, ADSC-Exos in combination with the autophagy inhibitor bafilomycin A1 showed that autophagy defects further impaired the biological function of epidermal cells under high-glucose conditions and partially weakened the healing effect of ADSC-Exos. Using a diabetes wound model, we found that ADSC-Exos promoted skin wound healing in diabetic mice, as evidenced by increased epidermal autophagy and rapid re-epithelialization. Finally, sequencing results showed that increased expression of autophagy-related genes nicotinamide phosphoribosyltransferase (NAMPT), CD46, vesicle-associated membrane protein 7 (VAMP7), VAMP3 and eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) may contribute to the underlying mechanism of ADSC-Exo action. Conclusions: This study elucidated the molecular mechanism through which ADCS-Exos regulate autophagy in skin epithelial cells, thereby providing a new theoretical basis for the treatment and repair of skin epithelial damage by ADSC-Exos.

Metabolic reprogramming in skin wound healing.

Metabolic reprogramming refers to the ability of a cell to alter its metabolism in response to different stimuli and forms of pressure. It helps cells resist external stress and provides them with new functions. Skin wound healing involves the metabolic reprogramming of nutrients, such as glucose, lipids, and amino acids, which play vital roles in the proliferation, differentiation, and migration of multiple cell types. During the glucose metabolic process in wounds, glucose transporters and key enzymes cause elevated metabolite levels. Glucose-mediated oxidative stress drives the proinflammatory response and promotes wound healing. Reprogramming lipid metabolism increases the number of fibroblasts and decreases the number of macrophages. It enhances local neovascularization and improves fibrin stability to promote extracellular matrix remodelling, accelerates wound healing, and reduces scar formation. Reprogramming amino acid metabolism affects wound re-epithelialization, collagen deposition, and angiogenesis. However, comprehensive reviews on the role of metabolic reprogramming in skin wound healing are lacking. Therefore, we have systematically reviewed the metabolic reprogramming of glucose, lipids, and amino acids during skin wound healing. Notably, we identified their targets with potential therapeutic value and elucidated their mechanisms of action.

Bacteria-loaded biochar for the immobilization of cadmium in an alkaline-polluted soil.

The combination of biochar and bacteria is a promising strategy for the remediation of Cd-polluted soils. However, the synergistic mechanisms of biochar and bacteria for Cd immobilization remain unclear. In this study, the experiments were conducted to evaluate the effects of the combination of biochar and Pseudomonas sp. AN-B15, on Cd immobilization, soil enzyme activity, and soil microbiome. The results showed that biochar could directly reduce the motility of Cd through adsorption and formation of CdCO3 precipitates, thereby protecting bacteria from Cd toxicity in the solution. In addition, bacterial growth further induces the formation of CdCO3 and CdS and enhances Cd adsorption by bacterial cells, resulting in a higher Cd removal rate. Thus, bacterial inoculation significantly enhances Cd removal in the presence of biochar in the solution. Moreover, soil incubation experiments showed that bacteria-loaded biochar significantly reduced soil exchangeable Cd in comparison with other treatments by impacting soil microbiome. In particular, bacteria-loaded biochar increased the relative abundance of Bacillus, Lysobacter, and Pontibacter, causing an increase in pH, urease, and arylsulfatase, thereby passivating soil exchangeable Cd and improving soil environmental quality in the natural alkaline Cd-contaminated soil. Overall, this study provides a systematic understanding of the synergistic mechanisms of biochar and bacteria for Cd immobilization in soil and new insights into the selection of functional strain for the efficient remediation of the contaminated environments by bacterial biochar composite.

Low-intensity pulsed ultrasound enhances neurite growth in serum-starved human neuroblastoma cells.

Introduction: Low-intensity pulsed ultrasound (LIPUS) is a recognized tool for promoting nerve regeneration and repair; however, the intracellular mechanisms of LIPUS stimulation remain underexplored. Method: The present study delves into the effects of varying LIPUS parameters, namely duty cycle, spatial average-temporal average (SATA) intensity, and ultrasound amplitude, on the therapeutic efficacy using SK-N-SH cells cultured in serum-starved conditions. Four distinct LIPUS settings were employed: (A) 50 mW/cm2, 40%, (B) 25 mW/cm2, 10%, (C) 50 mW/cm2, 20%, and (D) 25 mW/cm2, 10%. Results: Immunochemistry analysis exhibited neurite outgrowth promotion in all LIPUS-treated groups except for Group D. Further, LIPUS treatment was found to successfully promote brain-derived neurotrophic factor (BDNF) expression and enhance the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) signaling pathways, as evidenced by western blot analysis. Discussion: The study suggests that the parameter combination of LIPUS determines the therapeutic efficacy of LIPUS. Future investigations should aim to optimize these parameters for different cell types and settings and delve deeper into the cellular response mechanism to LIPUS treatment. Such advancements may aid in tailoring LIPUS treatment strategies to specific therapeutic needs.

Soil heavy metal source apportionment and environmental differentiation study in Dulan County, Qinghai Province, using geodetector analysis.

Elucidating material sources and investigating the impact of various environmental factors on material source accumulation are important for the environmental restoration of the Qinghai-Tibet Plateau. This study was conducted within the Borhan Buda Mountain Range of Dulan County, Qinghai Province, China, where 6274 surface soil samples were collected. The geoaccumulation index was employed to assess the levels of heavy metals, including As, Cr, Cu, Hg, Ni, Pb, Sb, Sn, and Zn, in the soil. A comprehensive approach combining principal component analysis (PCA) and geodetector analysis was employed to assess the spatial variation in soil heavy metal origins and the factors that influence them. The findings indicate that the mean concentrations of Pb exceed the background values for the soil in Qinghai Province, with Hg exhibiting low pollution, whereas the other elements showed no contamination. PCA indicated that the soil elements in the Borhan Buda Mountain Range were influenced by four sources, all attributed to the geological background. Geodetector analysis of the factor contributions suggested that geological factors had the strongest explanatory power for the four material sources. Furthermore, the risk detection results demonstrated significant variations in the material source contributions among most subregions when considering three environmental factors in pairs. Interaction detection revealed that the combined influence of two environmental factors on material source contributions was greater than that of the individual factors. Additionally, ecological detection demonstrated significant differences in material source contributions one, two, and three between land cover types and geological backgrounds, whereas no significant differences were observed in material source four between land cover types and geological backgrounds. This study offers valuable insights into the sources of soil elements in Dulan County and the influence of environmental factors on these sources, thereby contributing an essential knowledge base for the protection and management of soil heavy metals in the region.

Characterization of a Human Gastrointestinal Stromal Tumor Cell Line Established by SV40LT-Mediated Immortalization.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the digestive tract and originate from the interstitial cells of Cajal (ICC), which is the pacemaker for peristaltic movement in the gastrointestinal tract. Existing GIST cell lines are widely used as cell models for in vitro experimental studies because the mutation sites are known. However, the immortalization methods of these cell lines are unknown, and no Chinese patient-derived GIST cell lines have been documented. Here, we transfected simian virus 40 large T antigen (SV40LT) into primary GIST cells to establish an immortalized human GIST cell line (ImGIST) for the first time. The ImGIST cells had neuronal cell-like irregular radioactive growth and retained the fusion growth characteristics of GIST cells. They stably expressed signature proteins, maintained the biological and genomic characteristics of normal primary GIST cells, and responded well to imatinib, suggesting that ImGIST could be a potential in vitro model for research in GIST to explore the molecular pathogenesis, drug resistance mechanisms, and the development of new adjuvant therapeutic options.

Responses of the microbial community and the production of extracellular polymeric substances to sulfamethazine shocks in a novel two-stage biological contact oxidation system.

Introduction: The biological contact oxidation reactor is an effective technology for the treatment of antibiotic wastewater, but there has been little research investigating its performance on the sulfamethazine wastewater treatment. Methods: In this study, a novel two-stage biological contact oxidation reactor was used for the first time to explore the impact of sulfamethazine (SMZ) on the performance, microbial community, extracellular polymeric substances (EPS), and antibiotic-resistant genes (ARGs). Results: The chemical oxygen demand (COD) and ammonia nitrogen (NH4+-N) removal efficiencies kept stable at 86.93% and 83.97% with 0.1-1 mg/L SMZ addition and were inhibited at 3 mg/L SMZ. The presence of SMZ could affect the production and chemical composition of EPS in the biofilm, especially for the pronounced increase in TB-PN yield in response against the threat of SMZ. Metagenomics sequencing demonstrated that SMZ could impact on the microbial community, a high abundance of Candidatus_Promineofilum, unclassified_c__Anaerolineae, and unclassified_c__Betaproteobacteria were positively correlated to SMZ, especially for Candidatus_Promineofilum. Discussion: Candidatus_Promineofilum not only had the ability of EPS secretion, but also was significantly associated with the primary SMZ resistance genes of sul1 and sul2, which developed resistance against SMZ pressure through the mechanism of targeted gene changes, further provided a useful and easy-implement technology for sulfamethazine wastewater treatment.

Mendelian randomization analysis revealed a gut microbiota-mammary axis in breast cancer.

Background: Observational epidemiological studies suggested an association between the gut microbiota and breast cancer, but it remains unclear whether the gut microbiota causally influences the risk of breast cancer. We employed two-sample Mendelian randomization (MR) analysis to investigate this association. Methods: We used summary statistics of the gut microbiome from a genome-wide association study (GWAS) of 18,340 individuals in the MiBioGen study. GWAS summary statistics for overall breast cancer risk and hormone receptor subtype-specific analyses were obtained from the UK Biobank and FinnGen databases, totaling 400,000 individuals. The inverse variance-weighted (IVW) MR method was used to examine the causal relationship between the gut microbiome and breast cancer and its subtypes. Sensitivity analyses were conducted using maximum likelihood, MR-Egger, and MR pleiotropic residual sums and outliers methods. Results: The IVW estimates indicated that an increased abundance of Genus_Sellimonas is causally associated with an increased risk of ER+ breast cancer [odds ratio (OR) = 1.09, p = 1.72E-04, false discovery rate (FDR) = 0.02], whereas an increased abundance of Genus_Adlercreutzia was protective against ER+ breast cancer (OR = 0.88, p = 6.62E-04, FDR = 0.04). For Her2+ breast cancer, an increased abundance of Genus_Ruminococcus2 was associated with a decreased risk (OR = 0.77, p = 4.91E-04, FDR = 0.04), whereas an increased abundance of Genus_Erysipelatoclostridium was associated with an increased risk (OR = 1.25, p = 6.58E-04, FDR = 0.04). No evidence of heterogeneity or horizontal pleiotropy was found. Conclusion: Our study revealed a gut microbiota-mammary axis, providing important data supporting the potential use of the gut microbiome as a candidate target for breast cancer prevention, diagnosis, and treatment.

Thermus thermophilus Argonaute-based signal amplifier for highly sensitive and specific microRNA detection.

The prokaryote-derived gene defense system as a new generation of nucleic acid detection tool exhibits impressive performance in the field of molecular diagnosis. Prokaryotic Argonaute (Ago) is a CRISPR-associated protein that is guided by a short DNA (gDNA) and then efficiently cleaves gDNA-complementary nucleic acids and presents unique characteristics that are different from the CRISPR/Cas system. However, the application of Ago in biosensing is still relatively scarce, and many properties of Ago need to be further clarified. In this study, we aim to systematically explore the properties of Thermus thermophilus Argonaute (TtAgo), including the dependence of TtAgo activity on guide DNA (gDNA) length, substrates' length, and the position of gDNA complementary region on the substrate. Based on these properties, we constructed an exonuclease III-assisted target-recycled amplification system (exoAgo) for sensitive miRNA detection. The result showed that exoAgo can be used for miRNA profiling with a detection limit of 12.2 pM and single-base-resolution and keep good performance for the detection of complex samples, which indicates that Ago has great application potential in the detection of nucleic acids. In conclusion, this study will provide guidance for further development and utilization of Ago in the field of biosensing.

Iron in multiple sclerosis - Neuropathology, immunology, and real-world considerations.

Iron is an essential element involved in a multitude of bodily processes. It is tightly regulated, as elevated deposition in tissues is associated with diseases such as multiple sclerosis (MS). Iron accumulation in the central nervous system (CNS) of MS patients is linked to neurotoxicity through mechanisms including oxidative stress, glutamate excitotoxicity, misfolding of proteins, and ferroptosis. In the past decade, the combination of MRI and histopathology has enhanced our understanding of iron deposition in MS pathophysiology, including in the pro-inflammatory and neurotoxicity of iron-laden rims of chronic active lesions. In this regard, iron accumulation may not only have an impact on different CNS-resident cells but may also promote the innate and adaptive immune dysfunctions in MS. Although there are discordant results, most studies indicate lower levels of iron but higher amounts of the iron storage molecule ferritin in the circulation of people with MS. Considering the importance of iron, there is a need for evidence-guided recommendation for dietary intake in people living with MS. Potential novel therapeutic approaches include the regulation of iron levels using next generation iron chelators, as well as therapies to interfere with toxic consequences of iron overload including antioxidants in MS.

Mechanoregulatory Cholesterol Oxidase-Functionalized Nanoscale Metal-Organic Framework Stimulates Pyroptosis and Reinvigorates T Cells.

Cancer cells alter mechanical tension in their cell membranes. New interventions to regulate cell membrane tension present a potential strategy for cancer therapy. Herein, the increase of cell membrane tension by cholesterol oxidase (COD) via cholesterol depletion in vitro and the design of a COD-functionalized nanoscale metal-organic framework, Hf-TBP/COD, for cholesterol depletion and mechanoregulation of tumors in vivo, are reported. COD is found to deplete cholesterol and disrupt the mechanical properties of lipid bilayers, leading to decreased cell proliferation, migration, and tolerance to oxidative stress. Hf-TBP/COD increases mechanical tension of plasma membranes and osmotic fragility of cancer cells, which induces influx of calcium ions, inhibits cell migration, increases rupturing propensity for effective caspase-1 mediated pyroptosis, and decreases tolerance to oxidative stress. In the tumor microenvironment, Hf-TBP/COD downregulates multiple immunosuppressive checkpoints to reinvigorate T cells and enhance T cell infiltration. Compared to Hf-TBP, Hf-TBP/COD improves anti-tumor immune response and tumor growth inhibition from 54.3% and 79.8% to 91.7% and 95% in a subcutaneous triple-negative breast cancer model and a colon cancer model, respectively.

Vitamin C as a treatment for organ failure in sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with a high morbidity and mortality rate. Exogenous vitamin C supplementation is a potential therapeutic option for the treatment of multi-organ dysfunction in sepsis due to the significantly lower levels of vitamin C in the circulating blood of sepsis patients compared to healthy subjects and the importance of vitamin C in many of the physiological processes of sepsis. Vitamin C may influence the function of numerous organs and systems, including the heart, lungs, kidneys, brain, and immune defences, by reducing oxidative stress, inhibiting inflammatory factor surges, regulating the synthesis of various mediators and hormones, and enhancing immune cell function. With the development of multiple clinical randomized controlled trials, the outcomes of vitamin C treatment for critically ill patients have been discussed anew. This review's objectives are to provide an overview of how vitamin C affects various organ functions in sepsis and to illustrate how it affects each organ. Understanding the pharmacological mechanism of vitamin C and the organ damage caused by sepsis may help to clarify the conditions and clinical applications of vitamin C.

Generation and Stabilization of a Dinickel Catalyst in a Metal-Organic Framework for Selective Hydrogenation Reactions.

Although many monometallic active sites have been installed in metal-organic frameworks (MOFs) for catalytic reactions, there are no effective strategies to generate bimetallic catalysts in MOFs. Here we report the synthesis of a robust, efficient, and reusable MOF catalyst, MOF-NiH, by adaptively generating and stabilizing dinickel active sites using the bipyridine groups in MOF-253 with the formula of Al(OH)(2,2'-bipyridine-5,5'-dicarboxylate) for Z-selective semihydrogenation of alkynes and selective hydrogenation of C=C bonds in α,ß-unsaturated aldehydes and ketones. Spectroscopic studies established the dinickel complex (bpy⋅- )NiII (µ2 -H)2 NiII (bpy⋅- ) as the active catalyst. MOF-NiH efficiently catalyzed selective hydrogenation reactions with turnover numbers of up to 192 and could be used in five cycles of hydrogenation reactions without catalyst leaching or significant decrease of catalytic activities. The present work uncovers a synthetic strategy toward solution-inaccessible Earth-abundant bimetallic MOF catalysts for sustainable catalysis.

Wistar-Kyoto rats and chronically stressed Wistar rats present similar depression- and anxiety-like behaviors but different corticosterone and endocannabinoid system modulation.

The interplay of social, psychological, and biological stresses can trigger mental health conditions such as major depressive disorder (MDD), adjustment disorder, and posttraumatic stress disorder (PTSD). The endocannabinoid system (ECS), comprising endocannabinoids and cannabinoid receptors, is the critical pathway that mediates responses to stress stimuli. This study aimed to investigate the ECS's impact on responding to chronic social instability stress (SIS). Wistar (WIS) rats and an endogenously depressed rat model, Wistar-Kyoto (WKY), were used to evaluate depression- and anxiety-like behavioral responses, cognitive function, hormone levels, and ECS function. The animals in the stress group (WIS-STS and WKY-STS) were exposed to TMT (predator odor) for 10 mins (two exposures in total: one in light cycle and one in dark cycle) and daily roommate changes (30 days in total), while the control group (CTL) rats were exposed to a sham odor stimulus (distilled water) and did not undergo roommate changes. The results in the open field test suggest that WKY rats had significantly lower locomotor activity than WIS rats. In contrast, WKY rats and chronically stressed WIS rats presented similar depression- and anxiety-like behaviors and impaired cognitive function in the elevated plus maze, forced swimming test, and novel objective recognition test. However, chronic SIS did not exacerbate these behavioral changes in WKY rats. ELISA and Western blot analysis indicated that chronic SIS did not induce further upregulation of endocannabinoids and CB1R downregulation in WKY rats compared to WIS rats. In addition, the Luminex assay revealed that WKY rats showed a higher resilience on the HPA-axis modulation towards chronic SIS, distinguished by the hyperactivity of the HPA-axis modulation in WIS rats. Overall, the study revealed that the chronic SIS animal model (stressed WIS rats) and an animal model of endogenous depression (WKY rats) can generate similar behavioral changes in anxious behavior, behavioral despair, and cognitive impairment. Both animal models present hyperactivity of the ACTH modulation and ECS activity, while WKY rats are more resilient on CORT modulation towards chronic SIS.