Spatial confinement: An effective strategy to improve H2O and SO2 resistance of the expandable graphite-modified TiO2-supported Pt nanocatalysts for CO oxidation.

The expandable graphite (EG) modified TiO2 nanocomposites were prepared by the high shear method using the TiO2 nanoparticles (NPs) and EG as precursors, in which the amount of EG doped in TiO2 was 10 wt.%. Followed by the impregnation method, adjusting the pH of the solution to 10, and using the electrostatic adsorption to achieve spatial confinement, the Pt elements were mainly distributed on the exposed TiO2, thus generating the Pt/10EG-TiO2-10 catalyst. The best CO oxidation activity with the excellent resistance to H2O and SO2 was obtained over the Pt/10EG-TiO2-10 catalyst: CO conversion after 36 hr of the reaction was ca. 85% under the harsh condition of 10 vol.% H2O and 100 ppm SO2 at a high gaseous hourly space velocity (GHSV) of 400,000 hr-1. Physicochemical properties of the catalysts were characterized by various techniques. The results showed that the electrostatic adsorption, which riveted the Pt elements mainly on the exposed TiO2 of the support surface, reduced the dispersion of Pt NPs on EG and achieved the effective dispersion of Pt NPs, hence significantly improving CO oxidation activity over the Pt/10EG-TiO2-10 catalyst. The 10 wt.% EG doped in TiO2 caused the TiO2 support to form a more hydrophobic surface, which reduced the adsorption of H2O and SO2 on the catalyst, greatly inhibited deposition of the TiOSO4 and formation of the PtSO4 species as well as suppressed the oxidation of SO2, thus resulting in an improvement in the resistance to H2O and SO2 of the Pt/10EG-TiO2-10 catalyst.

Efficacy and safety of ramucirumab in gastric or gastroesophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Ramucirumab is considered a potential treatment for gastric or gastroesophageal cancer; however, its safety has not been evaluated. This meta-analysis aimed to evaluate the efficacy and safety of ramucirumab for treating gastric or gastroesophageal cancer. METHODS: The databases of PubMed, Embase, and Cochrane Library were searched through October 2023. The search focused on randomized controlled trials (RCTs) comparing ramucirumab (with or without chemotherapy) to a placebo (with or without chemotherapy) in patients with gastric or gastroesophageal cancer. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were pooled. RESULTS: Seven RCTs with a total of 2613 patients were included. Compared with placebo (with or without chemotherapy), ramucirumab (with or without chemotherapy) significantly improved OS (HR: 0.90, 95% CI: 0.82-0.99, p = 0.030), PFS (HR: 0.74, 95% CI: 0.60-0.90, p = 0.003), ORR (OR: 1.39, 95% CI: 1.15-1.67, p < 0.001), and DCR (OR: 1.91, 95% CI: 1.38-2.63, p < 0.001). However, ramucirumab (with or without chemotherapy) also increased the incidence of decreased appetite (OR: 1.29, 95% CI: 1.09-1.53, p = 0.004), diarrhea (OR: 1.39, 95% CI: 1.01-1.91, p = 0.05), hypertension (OR: 3.13, 95% CI: 2.03-4.83, p < 0.00001), and bleeding or hemorrhage (OR: 2.34, 95% CI: 1.93-2.85, p < 0.00001). CONCLUSIONS: Ramucirumab (with or without chemotherapy) can improve OS, PFS, ORR and DCR in patients with gastric or gastroesophageal cancer. However, it may also increase the incidence of specific AEs.

Physical Compatibility of Reduced Glutathione for Injection With 44 Intravenous Drugs During Simulated Y-site Administration.

PURPOSE: Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes. METHODS: Simulated Y-site administration was conducted in vitro by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values. FINDINGS: GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours. IMPLICATIONS: This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.

Recent Advances of Organic-inorganic Hybrid Fluorescent Hyperbranched Polymer: Synthesis, Performance Regulation Strategies and Applications.

The organic-inorganic hybrid fluorescent hyperbranched polymer, including hyperbranched polysiloxane and hyperbranched polyborate, have attracted much attention due to their excellent optical properties and wide range of applications. Hyperbranched polysiloxane and polyborates, prepared by introducing Si or B elements into organic polymer chains at the molecular level through rational molecular design and novel synthesis methods, exhibit outstanding photophysical properties as an indispensable branch of organic-inorganic hybrid fluorescent materials. Herein, this review article highlights the recent research progress on hyperbranched polysiloxanes and hyperbranched polyborates, including strategies for regulating their emission wavelengths, quantum yields, and fluorescence lifetimes, potential emission mechanisms, and various applications. Finally, some challenges and promising future directions in the field of organic-inorganic hybrid fluorescent polymers are summarized.

Effectiveness of various interventions for non-traumatic osteonecrosis: a pairwise and network meta-analysis.

Background: Osteonecrosis of the femoral head (ONFH) is acknowledged as a prevalent, challenging orthopedic condition for patients. Purpose: This study aimed to evaluate the efficacy of various interventions for non-traumatic ONFH and provide guidance for clinical decision-makers. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023 for relevant randomized controlled trials evaluating treatments for femoral head necrosis, without language restrictions. Quality evaluation was performed using the Cochrane risk-of-bias assessment tool, and analysis was performed using Stata 15.1. Results: Eleven randomized controlled trials were included in this study. The meta-analysis results revealed that CellTherapy [MD= -3.46, 95%CI= (-5.06, -1.85)], InjectableMed [MD= -3.68, 95%CI= (-6.11, -1.21)], ESWT [MD= -2.84, 95%CI= (-4.23, -1.45)], ESWT+InjectableMed [MD= -3.86, 95%CI= (-6.22, -1.53)] were significantly more effective in improving VAS pain score than CD+PTRI, as well as CD+BG+CellTherapy, and CD+BG. Furthermore, CD+BG+CellTherapy was better than CD+BG [MD= -0.97, 95%CI= (-1.71, -0.19)]. The SUCRA ranking for HHS score indicated that CellTherapy (77%) has the best effectiveness rate, followed by ESWT+InjectableMed (72.2%), ESWT (58.3%), InjectableMed (50%), CD+PTRI (31.4%), and CD+BG (11%). In terms of WOMAC and Lequesne scores, the meta-analysis showed no statistically significant differences between the experimental group CD+BG+CellTherapy and the control group CD+BG. Conclusion: CellTherapy and non-surgical ESWT combined with medication or CellTherapy have the best effect on ONFH. Surgical CD+BG combined with CellTherapy is more effective than CD+BG alone. ESWT+InjectableMed is recommended for short-term or acute onset patients, while ESWT is recommended for long-term patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024540122.

Analysis of changes in nutritional compounds of dried yellow chili after different processing treatments.

Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.

Spatial disparities and dynamic evolution of professional public health resource supply level in Beijing, China.

BACKGROUND: This study aims to explore the development status of the supply level of professional public health resources in Beijing Municipality, analyze the areal differences and spatial distribution characteristics of the supply level in 16 districts, and provide a scientific basis for promoting the balanced development of the supply level of professional public health resources in each district of Beijing Municipality. METHODS: Based on panel data from Statistical Yearbook of Health Work in Beijing Municipality and Health and Family Planning Work in Beijing Municipality from 2014 to 2022. Using the entropy method to measure the supply level of professional public health resources in Beijing, employing the Dagum Gini coefficient and Kernel density estimation method to analyze the spatial differentiation characteristics and dynamic evolution process of the supply level, and using heat maps to display the spatial distribution of the supply level in various districts of Beijing. RESULTS: The Dagum Gini coefficient of the supply level of professional public health resources in Beijing Municipality decreased continuously from 0.3419 in 2014 to 0.29736 in 2020, then gradually increased, showing a trend of initially decreasing and then increasing overall spatial differences. The spatial differences mainly stem from differences between areas. The kernel density curve shows that the supply level of professional public health resources in Beijing Municipality gradually increased, slightly decreased after 2021, and did not form a situation of two or multi-level differentiation. CONCLUSION: From 2014 to 2022, the supply level of professional public health resources in Beijing Municipality showed an overall upward trend, but attention should be paid to the decline after 2021; spatial differences initially decreased and then increased, and the differences between areas is the main source of the overall difference in Beijing. Therefore, the Beijing Municipal Government should focus on narrowing the differences between areas, determine the allocation and management of public health resources based on the actual situation of core areas, promote coordinated development within and outside areas, and thus enhance the supply level of professional public health resources.

Ultrasensitive Electrochemiluminescence Biosensor with ZIF-67@MXene as an Efficient Co-Reaction Accelerator and Plasmonic Nanozyme as a Smart Signal Amplification Probe.

Exploring novel electrochemiluminescence (ECL) co-reaction accelerators to construct ultrasensitive sensing systems is a prominent focus for developing advanced ECL sensors. However, challenges still remain in finding highly efficient accelerators and understanding their promoting mechanisms. In this paper, ZIF-67@MXene nanosheet composites, with highly conductive in-plane structure and confined-stable pore/channel, are designed to act as high-efficient co-reaction accelerators and achieve a significant enhancement in the luminol-H2O2 based ECL system. Mechanism investigation suggests that hydroxyl radicals (·OH) and singlet oxygen (1O2) can be selectively and preferentially generated on ZIF-67@MXene due to the stable and efficient absorption of ·OH and 1O2, leading to a remarkable enhancement in the ECL efficiency of luminol (830%). Finally, by designing a plasmonic NH2-MIL-88@Pd nanozyme, an "on-off" switch immunosensor is constructed for the detection of prostate-specific antigen (PSA). Based on the multiple signal amplification effect, the linear detection range for PSA is expanded by three orders of magnitude. The detection limit is also improved from 1.44 × 10-11 to 9.1 × 10-13 g mL-1. This work proposes an effective method for the preparation of highly efficient co-reaction accelerators and provides a new strategy for the sensitive detection of cancer markers.

Design, synthesis, and preclinical evaluation of 11C/18F-labeled inhibitors for RIPK1 PET imaging.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a promising target for the diagnosis and treatment of various diseases, especially neurodegenerative disorders. Developing PET imaging probes targeting RIPK1 is beneficial for visualizing the connections between RIPK1 and diseases, as well as for related drug development. In this study, we report the design and synthesis of a series of novel RIPK1 inhibitors. Three potent inhibitors, 7i, 7k, and 8a, with good cell anti-necroptosis potency and physicochemical properties, were identified and selected for PET imaging probe development. Subsequently, three PET imaging radioligands ([11C]7k, [18F]7i, and [18F]8a) were successfully synthesized. In mouse PET imaging studies, all three radioligands showed good brain uptake. Among them, probe [18F]8a exhibited good binding specificity in both in vitro autoradiography and in vivo PET imaging studies. Additionally, [18F]8a demonstrated good in vivo metabolic stability. This work highlights the potential of probe [18F]8a for imaging brain RIPK1 in live animals, laying the groundwork for the future development of RIPK1 PET radioligands.

Revealing the lethal effects of Pasteurella multocida toxin on multiple organ systems.

Pasteurella multocida toxin (PMT) is one of the most important virulence factors of Pasteurella multocida type D. Pasteurella multocida infection has caused enormous economic losses in the pig farming industry. Although it is well known that this bacterial infection causes progressive atrophic rhinitis, its effects on other organ tissues in pigs are unclear. In this study, PMT was expressed and purified, and the cytotoxic effects of PMT on four types of swine cells, LLC-PK1, PAM, IPEC, and ST, were investigated. LLC-PK1 exhibited the highest sensitivity to the cytotoxic effects of PMT. Our studies revealed that a PMT concentration of 0.1 µg/kg can lead to weight loss, whereas a PMT concentration of 0.5 µg/kg can lead to death in mice. PMT causes damage to the intestines, kidneys, lungs, livers, and spleens of mice. Furthermore, PMT caused acute death in pigs at treatment concentrations greater than 5 µg/kg; at PMT concentration of 2.5 µg/kg, weight loss occurred until death. PMT mainly caused damage to the hearts, lungs, livers, spleens and kidneys of pigs. The organ coefficient showed that damage to the heart and kidneys was the most severe and caused the renal pelvis and renal pyramid to dissolve and become cavitated. Pathology revealed hemorrhage in the lungs, liver, and spleen, and the kidneys were swollen and vacuolated, which was consistent with the damaged target organs in the mice. In conclusion, these findings demonstrate that PMT is extremely toxic in vitro and in vivo, causing damage to various organs of the body, especially the kidneys and lungs. This study provides a theoretical basis for the in-depth exploration of the cytotoxic effects of PMT on target organs.

Risk prediction model for in-stent restenosis following PCI: a systematic review.

Introduction: The morbidity and mortality rates of coronary heart disease are significant, with PCI being the primary treatment. The high incidence of ISR following PCI poses a challenge to its effectiveness. Currently, there are numerous studies on ISR risk prediction models after PCI, but the quality varies and there is still a lack of systematic evaluation and analysis. Methods: To systematically retrieve and evaluate the risk prediction models for ISR after PCI. A comprehensive search was conducted across 9 databases from inception to March 1, 2024. The screening of literature and extraction of data were independently carried out by two investigators, utilizing the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS). Additionally, the risk of bias and applicability were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Results: A total of 17 studies with 29 models were included, with a sample size of 175-10,004 cases, and the incidence of outcome events was 5.79%-58.86%. The area under the receiver operating characteristic curve was 0.530-0.953. The top 5 predictors with high frequency were diabetes, number of diseased vessels, age, LDL-C and stent diameter. Bias risk assessment into the research of the risk of higher bias the applicability of the four study better. Discussion: The overall risk of bias in the current ISR risk prediction model post-PCI is deemed high. Moving forward, it is imperative to enhance study design and specify the reporting process, optimize and validate the model, and enhance its performance.

The Interplay between nighttime/midday sleep duration and the number of new-onset chronic diseases: A decade-long prospective study in China.

OBJECTIVE: To investigate the interplay between individual nighttime and midday sleep duration and the number of new-onset chronic diseases and determine the optimal sleep duration associated with lowest number of new-onset chronic diseases. METHODS: We used data from the China Health and Retirement Longitudinal Study (CHARLS) covering a decade and involving 10,828 participants. A random intercept cross-lagged model was used to explore the interplay between nighttime/midday sleep durations and new-onset chronic diseases at both the within-individual and between-individual levels, followed by a dose-response analysis at the between-individual level to determine the optimal sleep duration. New-onset chronic diseases include 14 types of self-reported diseases diagnosed by doctors. RESULTS: Within-individual analysis revealed that increased nighttime/midday sleep duration led to a higher number of new-onset chronic diseases, and an increased number of new-onset chronic diseases resulted in decreased nighttime sleep duration. Between nighttime and midday sleep, one type of sleep duration increase was likely to lead to an increase in another type. Between-individual analysis found a nonlinear relationship between the number of new-onset chronic diseases and nighttime sleep duration, identifying the optimal nighttime sleep duration as 7.46 h. CONCLUSIONS: These findings elucidate the interplay between sleep duration and number of new-onset chronic diseases and underscore the need for public awareness and comprehensive interventions. Future studies should focus on refining sleep monitoring and exploring the sleep-chronic diseases nexus in greater depth.

Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD. METHODS: Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1ß, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment. RESULTS: High levels of TRAIL, CXCL12, and IL-1ß were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003-2.495; CXCL12: OR, 3.610; 95% CI, 1.011-12.889; IL-1ß: OR, 4.500; 95% CI, 1.129-17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538-0.976; MaR1: OR, 0.985; 95% CI, 0.970-0.999; LXA4: OR, 0.849; 95% CI, 0.727-0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1ß, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05). CONCLUSION: Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.

Sparassis latifolia polysaccharide alleviated lipid metabolism abnormalities in kidney of lead-exposed mice by regulating oxidative stress-mediated inflammation and autophagy based on multi-omics.

Lead is a common environmental pollutant which can accumulate in the kidney and cause renal injury. However, regulatory effects and mechanisms of Sparassis latifolia polysaccharide (SLP) on lipid metabolism abnormality in kidney exposed to lead are not clarified. In this study, mice were used to construct an animal model to observe the histopathological changes in kidney, measure lead content, damage indicators, differentially expressed metabolites (DEMs) and genes (DEGs) in key signaling pathways that cause lipid metabolism abnormalities based on lipidomics and transcriptomics, which were later validated using qPCR and western blotting. Co-treatment of Pb and N-acetylcysteine (NAC) were used to verify the link between SLP and oxidative stress. Our results indicated that treatment with SLP identified 276 DEMs (including metabolism of glycerophospholipid, sphingolipid, glycerolipid and fatty acid) and 177 DEGs (including genes related to oxidative stress, inflammation, autophagy and lipid metabolism). Notably, regulatory effects of SLP on abnormal lipid metabolism in kidney were mainly associated with oxidative stress, inflammation and autophagy; SLP could regulate abnormal lipid metabolism in kidney by reducing oxidative stress and affecting its downstream-regulated autophagy and inflammatory to alleviate renal injury caused by lead exposure. This study provides a theoretical basis for SLP intervention in lead injury.

Alternative splicing of ALDOA confers tamoxifen resistance in breast cancer.

The cancer-associated alternative splicing (AS) events generate cancer-related transcripts which are involved in uncontrolled cell proliferation and drug resistance. However, the key AS variants implicated in tamoxifen (TAM) resistance in breast cancer remain elusive. In the current study, we investigated the landscape of AS events in nine pairs of primary and relapse breast tumors from patients receiving TAM-based therapy. We unrevealed a notable association between the inclusion of exon 7.2 in the 5'untranslated region (5'UTR) of ALDOA mRNA and TAM resistance. Mechanistically, the inclusion of ALDOA exon 7.2 enhances the translation efficiency of the transcript, resulting in increased ALDOA protein expression, mTOR pathway activity, and the promotion of TAM resistance in breast cancer cells. Moreover, the inclusion of exon 7.2 in ALDOA mRNA is mediated by MSI1 via direct interaction. In addition, elevated inclusion of ALDOA exon 7.2 or expression of MSI1 is associated with an unfavorable prognosis in patients undergoing endocrine therapy. Notably, treatment with Aldometanib, an ALDOA inhibitor, effectively restrains the growth of TAM-resistant breast cancer cells in vitro and in vivo. The present study unveils the pivotal role of an AS event in ALDOA, under the regulation of MSI1, in driving TAM resistance in breast cancer. Therefore, this study provides a promising therapeutic avenue targeting ALDOA to combat TAM resistance.

Ling-gui-zhu-gan granules reduces obesity and ameliorates metabolic disorders by inducing white adipose tissue browning in obese mice.

Background: Ling-gui-zhu-gan (LGZG) formula has been demonstrated to effectively ameliorate the clinical symptoms of patients with obesity or metabolic syndrome. This study aimed to explore both the effect and the underlying mechanisms of LGZG against obesity. Methods: Male C57BL/6N mice were randomized into four groups (n = 8): normal control (NC), obese (OB), metformin (Met), and LGZG. After 8 weeks of gavage administration, the pharmacological effects of LGZG on obesity and metabolism were investigated using biochemical parameters, histomorphological examination, and lipidomics techniques. Pivotal factors associated with white adipose tissue browning were evaluated using quantitative real-time polymerase chain reaction and western blotting. Results: The results revealed that LGZG reduced the levels of obesity markers, including body weights, body fat mass and food intake in obese mice. Further evaluations highlighted that LGZG restored glucose homeostasis and significantly improved insulin sensitivity in obese mice. Importantly, LGZG could adjust serum lipid profiles and regulate the lipidomic spectrum of intestinal contents, with noticeable shifts in the levels of certain lipids, particularly diacylglycerols and monoacylglycerols. Histopathological examinations of LGZG-treated mice also revealed more favorable adipose tissue structures than their obese counterparts. Furthermore, we found that LGZG upregulated the expression of several key thermogenesis-related factors, such as UCP1, PRDM16, PGC-1α, PPARα, PPARγ, CTBP1, and CTBP2 in white adipose tissues. Conclusion: Our findings position LGZG as a novel strategy for preventing obesity and improving metabolic health.

Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys.

DNA methylation plays a crucial role in environmental adaptations. Here, using whole-genome bisulfite sequencing, we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed monkey ( Rhinopithecus bieti) and the closely related golden snub-nosed monkey ( R. roxellana). Our findings indicated a slight increase in overall DNA methylation levels in golden snub-nosed monkeys compared to Yunnan snub-nosed monkeys, suggesting a higher prevalence of hypermethylated genomic regions in the former. Comparative genomic methylation analysis demonstrated that genes associated with differentially methylated regions were involved in membrane fusion, vesicular formation and trafficking, hemoglobin function, cell cycle regulation, and neuronal differentiation. These results suggest that the high-altitude-related epigenetic modifications are extensive, involving a complete adaptation process from the inhibition of single Ca 2+ channel proteins to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation. Functional assays demonstrated that overexpression or down-regulation of candidate genes, such as SNX10, TIMELESS, and CACYBP, influenced cell viability under stress conditions. Overall, this research suggests that comparing DNA methylation across closely related species can identify novel candidate genomic regions and genes associated with local adaptations, thereby deepening our understanding of the mechanisms underlying environmental adaptations.

Comparative pharmacokinetic study of Anisodamine Hydrobromide tablets and injection in septic acute lung injury rats.

Aim: We aimed to establish a sensitive LC-MS/MS method to analyze the pharmacokinetics of Ani HBr tablets and injection. Methods: Around 10 mmNH4Ac containing 0.1% formic acid and acetonitrile were used as the mobile phase. Acute lung injury in septic and normal rats, respectively, were administered Ani HBr tablets at doses of 12.5, 25 and 50 mg/kg and injection at doses of 4, 8 and 16 mg/kg, followed by extraction of the drugs from plasma using ethyl acetate for subsequent analysis. Results & conclusion: The method met the requirements for biological analysis. Ani HBr tablets absorbed slowly in rats with disease, tail vein administration was a more promising approach for treating septic acute lung injury.

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ZFC3H1 as an Indicator of Poor Prognosis in Hepatocellular Carcinoma: Bioinformatic Analysis and Experimental Verification.

BACKGROUND: Zinc finger C3H1-type containing (ZFC3H1) might regulate RNA processes. However, research lacks the prognostic value of ZFC3H1 in hepatocellular carcinoma (HCC). METHODS: The study analyzed ZFC3H1 expression in HCC cells and its correlation with patient prognosis using transcriptomics, immunohistochemistry, and quantitative real-time reverse transcription PCR, as well as single-cell RNA expression data. Additionally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to investigate the potential ZFC3H1-related cellular functions and signaling pathways. The impact of ZFC3H1 expression on the tumor microenvironment and tumor mutational burden (TMB) was assessed using the ESTIMATE algorithm. Cell-based assays, including cell counting kit 8, proliferation, colony formation, cell cycle, wound healing, and Transwell assays, were conducted to evaluate the influence of ZFC3H1 on hepatocellular carcinoma proliferation and migration. RESULTS: ZFC3H1 is upregulated in HCC and linked to tumor progression. High ZFC3H1 expression is a prognostic risk factor for HCC, according to Kaplan-Meier and Cox regression analyses. ESTIMATE analysis suggested that ZFC3H1 reduces immune cell infiltration and increases the TMB. Patients with low ZFC3H1 expression might respond better to immunotherapy. High ZFC3H1 expression is associated with increased half-maximal inhibitory concentration (IC50) of sorafenib. Functional experiments demonstrated that reducing ZFC3H1 expression inhibited HCC cell proliferation and migration. CONCLUSION: ZFC3H1 is upregulated in HCC, promoting the proliferation and migration of liver cancer cells, impacting the prognosis of HCC patients and the effectiveness of immunotherapy. ZFC3H1 might serve as a therapeutic target and biomarker for HCC.

Predictors of COVID-19 severity in autoimmune disease patients: A retrospective study during full epidemic decontrol in China.

BACKGROUND: Early identification of risk factors for adverse COVID-19 progression in patients with autoimmune diseases is crucial for patient management, but data on the Chinese population are scarce. OBJECTIVES: The purpose of this study was to identify predictors of severe COVID-19 in patients using blood cell ratios, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and other inflammatory markers. METHODS: A retrospective study of 855 patients (746 females; median age 49 years) with autoimmune diseases and concurrent COVID-19 was conducted from December 2022 to February 2023 at the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University. Disease severity was assessed according to the 8th edition of the National Health Commission of the People's Republic of China's COVID-19 Diagnosis and Treatment Guidelines. The clinical classification criteria group mild and moderate cases as nonsevere cases and severe and critical cases as severe cases. A multivariate logistic regression model was established to evaluate the relationships between COVID-19 severity and demographic characteristics, comorbidities, medication use, and laboratory findings. RESULTS: The PLR, NLR, and SII were significantly greater in the severe COVID-19 group than in the nonsevere group (all P < 0.05). In addition to classical independent clinical risk factors, increases in the PLR (OR: 1.004, 95 % CI: 1.001∼1.007, p = 0.001), NLR (OR: 1.180, 95 % CI: 1.041∼1.337, p = 0.010), and SII (OR: 0.999, 95 % CI: 0.998∼1.000, p = 0.005) were identified as risk factors for severe COVID-19 in patients with autoimmune diseases. After adjusting for clinical risk factors, the PLR (AUC: 0.592 vs. 0.865; P < 0.05), NLR (AUC: 0.670 vs. 0.866; P < 0.05), and SII (AUC: 0.616 vs. 0.864; P < 0.05) demonstrated higher predictive values. CONCLUSION: Early prediction of severe COVID-19 in patients with autoimmune diseases can be achieved using the NLR, PLR, and SII.