Comprehensive Proteomic Analysis of Dysferlinopathy Unveiling Molecular Mechanisms and Biomarkers Linked to Pathological Progression.

AIMS: Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies. METHODS: We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy. RESULTS: A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays. CONCLUSIONS: Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors.

AVM: A Manually Curated Database of Aerosol-transmitted Virus Mutations, Human Diseases, and Drugs.

Aerosol-transmitted viruses possess strong infectivity and can spread over long distances, earning the difficult-to-control title. They cause various human diseases and pose serious threats to human health. Mutations can increase the transmissibility and virulence of the strains, reducing the protection provided by vaccines and weakening the efficacy of antiviral drugs. In this study, we established a manually curated database (termed AVM) to store information on aerosol-transmitted viral mutations (VMs). The current version of the AVM contains 42,041 VMs (including 2613 immune escape mutations), 45 clinical information datasets, and 407 drugs/antibodies/vaccines. Additionally, we recorded 88 human diseases associated with viruses and found that the same virus can target multiple organs in the body, leading to diverse diseases. Furthermore, the AVM database offers a straightforward user interface for browsing, retrieving, and downloading information. This database is a comprehensive resource that can provide timely and valuable information on the transmission, treatment, and diseases caused by aerosol-transmitted viruses (http://www.bio-bigdata.center/AVM).

Mitigation of biocorrosion of X80 carbon steel by a shale microbiome biofilm using a green biocide enhanced by d-amino acids.

Microbiologically influenced corrosion (MIC) in shale gas field is a major threat with the hydraulic fracturing fluid injected into the subsurface. In this study, the microbiome collected from a shale gas produced water sample was extracted and cultivated in ATCC 1249 medium modified with 10 g/L NaCl anaerobically at 30 °C. d-amino acids, which were reported as biocide enhancers, were found to enhance 2,2-dibromo-3-nitrilopropionamide (DBNPA) biocide on the mitigation of shale microbiome MIC on X80 carbon steel. The combination of 50 ppm (w/w) d-leucine + 50 ppm d-alanine + 1 ppm d-tyrosine had the best enhancement effect on 50 ppm DBNPA with 84 % less weight loss, and 67 % lower corrosion current density (icorr) compared to 50 ppm DBNPA alone. The corrosion data were consistent with the enhanced biofilm inhibition observation. The experimental data also indicated that d-tyrosine used alone at a low dosage of 1 ppm enhanced DBNPA considerably, with 44 % less weight loss and 47 % less icorr. The electrochemical results showed the positive response of shale gas microbiome biofilm to the injected magnetite nanoparticles indicating the extracellular electron transfer might be a main mechanism for its corrosion.

Interaction of biochar with extracellular polymers of resistant bacteria restrains Pb(II) adsorption onto their composite: Macro and micro scale investigations.

Pb(II) sequestration in extracellular polymers-biochar composites (EPS-BC) was explored using macroscopic models and microscopic technology. The results showed that the actual adsorption capacity of EPS-BC was 52.2% lower than the calculated capacity based on adsorption onto pure components due to the interaction of polysaccharide and amide group in extracellular polymers with biochar, which masked the reactive sites related to Pb(II) in EPS-BC. The bond of Pb-O (40.8%) and Pb-OOC (31.5%) mainly contributed to Pb(II) speciation on the EPS-BC surfaces. Furthermore, each Pb atom coordinated with 6O atoms in the first shell and with 0.5C atoms in the second shell, indicating that the carboxyl group in composite was complexed with Pb(II) as a monodentate inner-sphere structure. The findings provide an in-depth understanding of the adsorption mechanism of heavy metals by extracellular polymers coupled with biochar at molecular scale, guiding bioremediation with respect to heavy metal contamination.

Hyaluronic acid-zein shell-core biopolymer nanoparticles enhance hepatocellular carcinoma therapy of celastrol via CD44-mediated cellular uptake.

Low concentrations or limited residence times in tumor tissues, making celastrol (Cel) difficult to exert significant therapeutic effects. Thus, we developed Zein/hyaluronic acid core-shell nanoparticles (Cel/Zein@HA NPs) for active targeted delivery of Cel via CD44 receptor over-expression on cancer cells, which may strengthen the therapeutic efficacy of Cel and improve delivery targeting. Cel-loaded Zein nanoparticles (core), are elegantly enveloped by a hydrophilic HA coating that forms the shell, resulting in significantly improved encapsulation efficiency and ensured good stability. The cellular uptake of Cel/Zein@HA NPs in HepG2 cells was 1.57-fold higher than nontargeting Cel/Zein NPs. Near-infrared fluorescence imaging confirmed the accumulation of Cel/Zein@HA NPs in H22 liver cancer tumors in mice, resulting in effective antitumor effects and good biosafety. Besides, in vitro and in vivo experiments showed that compared with Cel/Zein NPs, Cel/Zein@HA NPs had more efficient inhibitory effect on tumor proliferation and lower systemic toxicity. Further studies revealed that Cel/Zein@HA NPs induced apoptosis in hepatocellular carcinoma cells by modulating Bax and Bcl-2 expression, while also inhibiting tumor angiogenesis by decreasing CD31 and VEGF levels. Overall, this study presents a promising strategy for enhancing targeted liver cancer therapy through the utilization of biopolymer nanoparticle-based nano-pharmaceuticals that facilitate CD44-mediated cellular uptake.

Regulation of hippocampal miRNA expression by intestinal flora in anxiety-like mice.

This study investigated the possible interaction between gut flora and miRNAs and the effect of both on anxiety disorders. The model group was induced with chronic restraint stress (CRS) and each group was tested for anxiety-like behaviour by open field test and elevated plus maze test. Meanwhile, the gut flora was analysed by 16S rRNA high-throughput sequencing. The miRNAs in hippocampus were analysed by high-throughput sequencing, and the key miRNAs were obtained by using the method of bioinformatics analysis. PCR was used to verify the significantly related key miRNAs. Spearman correlation analysis was used to explore the correlation between behaviour, key miRNAs and differential gut microbiota. The 16S rRNA high-throughput sequencing result showed that the gut flora was dysregulated in the model group. In particular, Verrucomicrobia, Akkermansia, Anaerostipes, Ralstonia, Burkholderia and Anaeroplasma were correlated with behaviour. The results of miRNA high-throughput sequencing analysis and bioinformatics analysis showed that 7 key miRNAs influenced the pathogenesis of anxiety, and qRT-PCR results were consistent with the high-throughput sequencing results. Mmu-miR-543-3p and mmu-miR-26a-5p were positively correlated with Verrucomicrobia, Akkermansia and Anaerostipes. Therefore, we infer that chronic stress caused the decrease of Akkermansia abundance, which may aggravate the decrease of mmu-miR-543-3p and mmu-miR-26a-5p expression, leading to the increase of SLC1A2 expression. In conclusion, gut flora has played an important influence on anxiety with changes in miRNAs.

Enthalpy Change of V-Ti Interface as an Indicator of High Catalytic Activity.

Vanadium-supported TiO2 is one of the most widely used catalysts. In previous reports, most researchers focused on the performance of a formed catalyst and almost no work was devoted to understanding the activation process from a precursor to a catalyst. In this work, differential scanning calorimetry was used to calculate the enthalpy change (ΔH, kJ·mol-1) during the transition from a precursor to a catalyst. When the V-loading amount was increased from 0.1 to 5 wt %, more polymeric V were formed and ΔH of V-supported anatase was decreased from 10.13 to 4.13 kJ·mol-1. At the same loading amount of 1 wt %, anatase showed a higher ΔH value of 8.71 kJ·mol-1 than rutile and brookite. When the ratio of the {001} facet was increased in the anatase, ΔH was increased to 9.65 kJ·mol-1. A theoretical calculation proved that V embedding into {001} facet resulted in a bigger energy difference in comparison to {101} and {100} facets. A bigger ΔH stood for forming a more active V species during catalyst preparation, which further stood for a higher turnover frequency (TOF, s-1) during the catalysis. The anatase with the biggest ratio of the {001} facet resulted in the biggest ΔH as well as the largest TOF. These results help to understand the interaction between loaded active species and catalyst support, which is in favor of designing an effective catalyst.

A Risk Correlative Model for Sleep Disorders in Chinese Older Adults Based on Blood Micronutrient Levels: A Matched Case-Control Study.

BACKGROUND: The physical abilities of older adults decline with age, making them more susceptible to micronutrient deficiency, which may affect their sleep quality. OBJECTIVES: This study aimed to construct a risk correlative model for sleep disorders in Chinese older adults based on blood micronutrient levels. METHODS: In this matched case-control study, we recruited 124 participants with sleep disorders and 124 matched controls from the Tianjin Elderly Nutrition and Cognition cohort in China. Micronutrient levels in whole blood were measured using the dried blood spot technique. We compared the differences in micronutrient levels between the two groups and also constructed a receiver operating characteristic (ROC) model and nomogram for sleep disorders. RESULTS: In comparison to the control group, the sleep disorders group showed lower levels of blood vitamin A, vitamin E (VE), folate, magnesium, copper, iron, and selenium (Se) in the univariate analysis (p < 0.05). The ROC curve analysis indicated that the combination of VE + folate + Se may have an excellent diagnostic effect on sleep disorders, with an area under the curve of 0.964. This VE + folate + Se was integrated into a nomogram model to demonstrate their relationship with sleep disorders. The consistency index of the model was 0.88, suggesting that the model assessed sleep disorders well. CONCLUSIONS: The sleep disorders risk correlative model constructed by the levels of VE, folate, and Se in whole blood might show good performance in assessing the risk of sleep disorders in older adults.

Ultra-rapid detection of nuclear protein of severe fever with thrombocytopenia syndrome virus by colloidal gold immunochromatography assay.

In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie bandavirus (DBV), was first discovered in Henan, China. It is a tick-borne zoonotic virus with a fatality rate ranging from 6% to 30%. Currently, we lack safe and effective vaccines or antiviral drugs to treat SFTSV infection. Therefore, the development of a specific, sensitive, and cost-effective detection method is crucial. Using inactivated SFTSV and recombinant SFTSV nucleocapsid protein (SFTSV-NP), we repeatedly immunized mice with different adjuvants and obtained two monoclonal antibodies against SFTSV-NP, which were used to develop a colloidal gold immunochromatographic assay (ICA) rapid test kit for SFTSV. Compared with nucleic acid testing (gold standard), the ICA test strips are 97.67% accurate in testing clinical serum samples (36 cases of clinical serum samples and seven cases of whole blood samples). The test kit was 100% accurate in detecting different SFTSV strains. No false-positive results were generated when detecting other arboviruses. Therefore, our developed SFTSV test kit conveniently, rapidly, and effectively detects SFTSV.

Exploring the key flavor compounds and aroma profiles in traditionally fermented golden pompano (Trachinotus ovatus): Perspective from molecular sensory science.

Fermented golden pompano (Trachinotus ovatus) has a distinctive flavor, but the key flavor compounds and aroma profiles remains unclear. Thus, a molecular sensory science approach was used to investigate flavor and key aromatic compounds. The fermentation process enhanced the overall flavor, as evidenced by sensory evaluation and electronic nose (E-nose) analyses. A total of 48 aroma compounds were identified at different fermentation stages. Among them, 11 key aroma compounds were identified by flavor dilution (FD) factors ≥8 and odor activity values (OAVs) ≥ 1. Aroma recombination model successfully reproduces the characteristic floral and fruity aromas of fermented golden pompano. Omission experiments identified hexanal, decanal, 1-octen-3-ol, limonene, and isovaleric acid as significant contributors to the overall aroma profile. This study elucidates flavor dynamic modulation and key aromatic compounds during golden pompano fermentation, to provide a theoretical reference for the targeting process regulation of the product.

TMEM56 deficiency impairs the haem metabolism and cell cycle progression during human erythropoiesis.

TMEM56, a gene coding a transmembrane protein, is abundantly expressed in erythroid cells. Despite this, its role in erythropoiesis has not been well characterized. In this study, we sought to clarify the function of TMEM56 in erythroid development, focusing specifically on its involvement in haem biosynthesis and cell cycle progression. To do this, we used CD34+ haematopoietic stem cells derived from umbilical cord blood and differentiated them into erythroid cells in an ex vivo model. Our results indicate that the loss of TMEM56 disrupts haem biosynthesis and impairs erythroid differentiation. Furthermore, deletion of Tmem56 in the erythroid lineage in murine models using erythropoietin receptor (EpoR)-Cre revealed defects in erythroid progenitors within the bone marrow under both normal conditions and during haemolytic anaemia. These observations underscore the regulatory role of TMEM56 in maintaining erythroid lineage homeostasis. Taken together, our results unveil a previously unrecognized function of TMEM56 in erythroid differentiation and suggest its potential as an unfounded target for therapeutic strategies in the treatment of erythropoietic disorders.

CircSEC24B activates autophagy and induces chemoresistance of colorectal cancer via OTUB1-mediated deubiquitination of SRPX2.

Circular RNAs (circRNAs) are a type of regulatory RNA that feature covalently closed single-stranded loops. Evidence suggested that circRNAs play important roles in the progression and development of various cancers. However, the impact of circRNA on autophagy-mediated progression of colorectal cancer (CRC) remains unclear. The objective of this project was to investigate the influence of circSEC24B on autophagy and its underlying mechanisms in CRC. To validate the presence and circular structure of circSEC24B in CRC cells and tissues, PCR and Sanger sequencing techniques were employed. Drug resistance and invasive phenotype of CRC cells were evaluated using CCK8, transwell, and Edu assays. Gain- and loss-of-function experiments were conducted to assess the effects of circSEC24B and its protein partner on the growth, invasion, and metastasis of CRC cells in vitro and in vivo. Interactions between circSEC24B, OTUB1, and SRPX2 were analyzed through immunofluorescence, RNA-pulldown, and RIP assays. Mass spectrometry analysis was used to identify potential binding proteins of circRNA in CRC cells. Vectors were constructed to investigate the specific structural domain of the deubiquitinating enzyme OTUB1 that binds to circSEC24B. Results showed that circSEC24B expression was increased in CRC tissues and cell lines, and it enhanced CRC cell proliferation and autophagy levels. Mechanistically, circSEC24B promoted CRC cell proliferation by regulating the protein stability of SRPX2. Specifically, circSEC24B acted as a scaffold, facilitating the binding of OTUB1 to SRPX2 and thereby enhancing its protein stability. Additionally, evidence suggested that OTUB1 regulated SRPX2 expression through an acetylation-dependent mechanism. In conclusion, this study demonstrated that circSEC24B activated autophagy and induced chemoresistance in CRC by promoting the deubiquitination of SRPX2, mediated by the deubiquitinating enzyme OTUB1.

Abnormally High Expression of DNAJB6 Accelerates Malignant Progression of Lung Adenocarcinoma.

DNAJB6, a major member of the DNAJ/HSP40 family, plays an important role in tumor development. We explored the effect of DNAJB6 expression on the prognosis of patients and its biological role in lung adenocarcinoma (LUAD). mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA). Enriched pathways were determined by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A nomogram incorporating DNAJB6 and three clinical features was constructed to predict the survival rate. DNAJB6 expression and function in LUAD were explored using immunohistochemistry, Western blotting, proliferation, cell cycle analysis, RNA sequencing, and xenograft tumor assays. DNAJB6 mRNA levels were elevated in the LUAD-TCGA dataset. DNAJB6 protein levels were higher in LUAD tumor tissues than in normal tissues. A high DNAJB6 level was an independent risk factor for poor prognosis in patients with LUAD. The proportion of tumor-infiltrating immune cells significantly differed between high and low DNAJB6 expression. DNAJB6 was associated with cell cycle pathways; therefore, its knockdown induced G2/M cell cycle arrest and inhibited LUAD cell proliferation. This is the first report of the DNAJB6 requirement for LUAD cell proliferation and its potentially crucial role in LUAD prognosis.

Methods established for the detection of mineral levels in whole blood by the dried blood spot technique.

Mineral are intimately related to human health and disease, and detection of mineral content in the body is of great significance for the diagnosis and prevention of diseases. In this study, we validated the method developed to detect magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) levels in dried blood spots (DBS). In accordance with the requirements of the guidelines for the Bioanalytical Method Validation Guidance for Industry, we evaluate the linearity, sensitivity, precision, accuracy and selectivity of the developed methods. In addition, Mg, Cu, Fe, Zn and Se were quantified in 195 older adults using DBS technique, and its accuracy was assessed by comparing the results to those detected by inductively coupled plasma-mass spectrometry (ICP-MS). The method has excellent sensitivity and linear range to cover the concentration range of mineral elements in the general population with the required precision, accuracy and selectivity. The correlation coefficients of Mg, Cu, Fe, Zn and Se levels in blood detected by the DBS technique and ICP-MS were 0.638, 0.823, 0.463, 0.728 and 0.751, respectively (all P < 0.05), which indicated that there was a strong correlation between the detection results of the two methods. More than 95 % of the sample results in the Bland-Altman consistency test were within the acceptable limits of agreement (LOA) range, indicating that they had good consistency. DBS technique has good accuracy and reliability in detecting blood mineral levels in the elderly, suggesting potential in the quantification of mineral level in blood.

Effect of High-Pressure Processing Treatment on the Physicochemical Properties and Volatile Flavor of Mercenaria mercenaria Meat.

High-pressure processing (HPP) technology can significantly improve the texture and flavor of Mercenaria mercenaria. This study aimed to investigate the effect of HPP treatment with varying levels of pressure (100, 200, 300, 400, 500, and 600 MPa) and a holding time of 8 min at 20 °C on the physicochemical properties and volatile flavors of M. mercenaria. The significant changes in hardness, resilience, and water holding capacity occurred with increasing pressure (p < 0.05), resulting in improved meat quality. Scanning electron microscopy (SEM) was utilized to observe the decomposition of muscle fibers in M. mercenaria due to varying pressures, which explains the differences in texture of M. mercenaria. Different pressure treatments also had an influence on the volatile flavor of M. mercenaria, and the quantities of low-molecular-weight aldehydes (hexanal, heptanal, and nonanal) with a fishy taste decreased dramatically following 400 and 500 MPa HPP treatments. Furthermore, the level of 2-Methylbutyraldehyde, which is related to sweetness, increased significantly following 400 MPa HPP treatment. The study found that 400 MPa HPP treatment resulted in minor nutrient losses and enhanced sensory quality. The results of this study provide a theoretical basis for the application of HPP treatment to M. mercenaria.

Causal Association Between Sedentary Behaviors and Health Outcomes: A Systematic Review and Meta-Analysis of Mendelian Randomization Studies.

BACKGROUND: Different types of sedentary behavior are associated with several health outcomes, but the causality of these associations remains unclear. OBJECTIVES: To conduct a systematic review and meta-analysis of Mendelian randomization (MR) studies investigating the associations between sedentary behaviors and health outcomes. METHODS: A systematic search on PubMed, Embase, Web of Science, Scopus, and PsycINFO up to August 2023 was conducted to identify eligible MR studies. We selected studies that assessed associations of genetically determined sedentary behaviors and health outcomes. A meta-analysis was conducted to examine the causal associations when two or more MR studies were available. We graded the evidence level of each MR association based on the results of the main method and sensitivity analyses in MR studies. RESULTS: A total of 31 studies with 168 MR associations between six types of sedentary behavior and 47 health outcomes were included. Results from meta-analyses suggested a total of 47 significant causal associations between sedentary behaviors and health outcomes. Notably, more leisure TV watching is robustly correlated with increased risks of myocardial infarction, coronary artery disease, all-cause ischemic stroke, and type 2 diabetes. Conversely, robust inverse associations were observed between leisure computer use and risks of rheumatoid arthritis, Alzheimer's disease, and gastroesophageal reflux disease. CONCLUSION: These findings suggest that different types of sedentary behavior have distinct causal effects on health outcomes. Therefore, interventions should focus not only on reducing sedentary time but also on promoting healthier types of sedentary behavior. PROSPERO REGISTRATION: CRD42023453828.

The predictive value of serum fibrinogen and platelet distribution width for long-term cardiac death in acute myocardial infarction patients.

Background: Acute myocardial infarction (AMI) is the most severe manifestation of coronary heart disease (CHD), and timely and effective opening of the culprit vessels has been effective in reducing its mortality, but long-term death still threatens the life of patients. Therefore, finding biomarkers to predict death post-myocardial infarction (MI) is crucial. The aim of our study is to find biomarkers that predicted long-term death in Chinese AMI patients. Methods: This retrospective analysis included patients with AMI from 1 January 2017 to 30 September 2019. All patients were followed up at least 4 years. Propensity score matching was used to mitigate the influence of nonrandom selection in MI-survival and MI-death groups. Cox analysis was applied for analyzing the risk factors of death post-MI. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of biomarkers. Results: Of the 1,059 AMI patients analyzed, 130 died during follow-up. After propensity matching, there were 116 patients in each of the two groups. In addition to the traditional risk factors for long-term death post-MI, two important risk factors platelet distribution width (PDW) [hazard ratio (HR) =1.210, 95% confidence interval (CI): 1.080-1.356, P=0.001] and fibrinogen (HR =1.218, 95% CI: 1.027-1.444, P=0.02) were found. The area under the curve (AUC) of PDW and fibrinogen was 0.604 (P=0.007) and 0.684 (P<0.001) respectively. The optimal thresholds were 13.05% and 3.562 g/L respectively. Conclusions: PDW and fibrinogen seem to be useful as biomarkers for long-term death prediction post-MI. The current research provides new insight into the prevention and treatment of death in Chinese patients post-MI.

Regulatory Effects of Maternal Intake of Microbial-Derived Antioxidants on Colonization of Microbiota in Breastmilk and That of Intestinal Microbiota in Offspring.

In this study, sixteen Sprague Dawley (SD) female rats and eight SD male rats were co-housed to mate. Pregnant SD female rats were fed with a control diet or an MA diet. Breast milk, maternal ileum, and intestinal samples of the offspring were collected at the day of birth and ten days afterwards. The results showed that the impact of MA was more obvious on the microbiota of mature milk (p = 0.066) than on that of colostrum. In addition, MA additive did not significantly affect maternal ileal microbiota, but affected offsprings' colonic microbiota significantly ten days after birth (p = 0.035). From the day of giving birth to ten days afterwards, in addition to the increase in microbial richness and diversity, at genus level, the dominant bacteria of breastmilk changed from Pseudomonas veronii to Bacillus and Lactococcus. Different from breastmilk microbiota, ten days after giving birth, the maternal ileal microbiota and the offsprings' intestinal microbiota were dominated by Lactobacillus. Instead of ileal microbiota, offsprings' colonic microbiota is a key action site of maternal MA additive. Therefore, the current findings have significant implications for the development of maternal feed aimed at modulating the intestinal microbiota of offspring, ultimately leading to improved health outcomes for both mothers and their offspring.

SOX9 promotes hypoxic pulmonary hypertension through stabilization of DPP4 in pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by pulmonary vascular remodeling (PVR), primarily due to the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This study aimed to investigate the role and molecular mechanism of SOX9 in hypoxic PH in rats. The findings revealed that SOX9 was upregulated in the pulmonary arteries and PASMCs of hypoxia-exposed rats. SOX9 knockdown inhibited hypoxia-induced proliferation and migration of PASMCs, reduced PVR, and subsequently alleviated hypoxia-induced PH in rats, suggesting that SOX9 plays a critical role in PH. Further investigation demonstrated that SOX9 interacted with DPP4, preventing its ubiquitin degradation in hypoxia-exposed PASMCs. DPP4 knockdown inhibited hypoxia-induced PASMC proliferation and migration, and administration of the DPP4 inhibitor sitagliptin (5 mg/kg) significantly reduced PVR and alleviated hypoxia-induced PH in rats, indicating that SOX9 contributes to PH by stabilizing DPP4. The results also showed that hypoxia induced YAP1 expression and dephosphorylation, leading to YAP1 nuclear localization. YAP1 knockdown promoted the degradation of HIF-1α in hypoxia-exposed PASMCs and inhibited hypoxia-induced proliferation and migration of PASMCs. Additionally, HIF-1α, as a transcription factor, promoted SOX9 expression by binding to the SOX9 promoter in hypoxia-exposed PASMCs. In conclusion, hypoxia promotes the proliferation and migration of PASMCs through the regulation of the YAP1/HIF-1α/SOX9/DPP4 signaling pathway, leading to PH in rats. These findings suggest that SOX9 may serve as a potential prognostic marker and therapeutic target for PH.

Interface Energy-Level Reorganization for Efficient Perovskite γ-Ray Detectors.

Metal halide perovskites are promising candidates for γ-ray spectrum detectors. However, achieving high-resolution energy spectra in single-photon pulse-height analysis mode remains challenging, due to the inevitable leakage currents degrade the recognizable fingerprint energies which is critical for resolving γ-ray spectroscopy. We demonstrate under high bias voltage, a deficient contact barrier can lead to excessive surface charge injection, thereby increasing leakage current from electrodes to perovskites. Hence, we conceive to employ surface ligand engineering on perovskite single crystals to manipulate energy levels to suppress leakage current. In particular, anchoring a strong dipole ligand onto the perovskite induced surface charge-density displacement, leading to a downward band bending and heightened the corresponding contact barrier. Consequently, the strategy minimized the detectors'leakage current by an order of magnitude, to as low as 44 nA cm-2. The resulting detectors show a significant improvement in energy resolution, 3.9% for 22Na 511 keV γ-rays has been achieved at room temperature. The resulting detector further resolves each fingerprint energy for 152Eu γ-spectrum, representing one of the best γ-rays perovskite detectors reported to date. Moreover, the detectors exhibited stabilized energy resolution without any degradation under a continuous electric field for over 300 minutes, representing the longest longevity reported to date.