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Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

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BACKGROUND: Exposure to fine or respirable particulate matter has been linked to an elevated risk of gestational diabetes mellitus (GDM). However, the association between exposure to particulate matter with an aerodynamic diameter ≤ 1 µm (PM1) and GDM has not been explored. METHODS: We conducted a cohort study involving 60,173 pregnant women from nine hospitals in Beijing, China, from February 2015 to April 2021. Daily concentrations of PM1 and ozone were obtained from a validated spatiotemporal artificial intelligence model. We used a modified Poisson regression combined with distributed lag models to estimate the association between weekly-specific PM1 exposure and the risk of GDM after adjusting for individual-level covariates. RESULTS: Among the 51,299 pregnant women included in the final analysis, 4008 were diagnosed with GDM. Maternal exposure to PM1 during preconception and gestational periods was generally associated with an increased risk of GDM. The most pronounced associations were identified during the 12th week before pregnancy, the 5th-8th weeks of the first trimester, and the 23rd-24th weeks of the second trimester. Each 10 µg/m3 increase in PM1 was associated with a relative risk of GDM of 1.65 (95 % CI: 1.59, 1.72) during the preconception period, 1.67 (95 % CI: 1.61, 1.73) in the first trimester, 1.52 (95 % CI: 1.47, 1.58) in the second trimester, and 2.54 (95 % CI: 2.45, 2.63) when considering the first and second trimester combined. CONCLUSIONS: Exposure to PM1 before and during pregnancy was associated with an increased risk of GDM, particularly during the 12 weeks before pregnancy and gestational weeks 5-8 and 23-24.

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Background: Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Henoch-Schönlein Purpura (HSP) and whether it can be mediated by immune cells is still unknown. Methods: We performed a two-sample Mendelian randomization study using an inverse variance weighted (IVW) method to examine the causal role of GM on HSP and the mediation effect of immune cells between the association of GM and HSP. Results: We demonstrated the causal relationships between 14 axas and 6 pathways with HSP. Additionally, we identified 9 immune cell characteristics associated with HSP. Importantly, through mediation MR analysis, we identified several immune cell characteristics that mediate the impact of GM on HSP. For instance, Genus_Blautia affects HSP via Monocyte (HLA DR on CD14+ CD16- monocyte) and Monocyte (HLA DR on monocyte). The proportion of mediation effects further elucidated the complex dynamics between GM exposure, immune markers, and their combined impact on HSP. Conclusion: The study suggested a causal relationship between GM and HSP, which may be mediated by immune cells.

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Coordinated cytoskeleton-mitochondria organization during myogenesis is crucial for muscle development and function. Our understanding of the underlying regulatory mechanisms remains inadequate. Here, we identified a novel muscle-enriched protein, PRR33, which is upregulated during myogenesis and acts as a promyogenic factor. Depletion of Prr33 in C2C12 represses myoblast differentiation. Genetic deletion of Prr33 in mice reduces myofiber size and decreases muscle strength. The Prr33 mutant mice also exhibit impaired myogenesis and defects in muscle regeneration in response to injury. Interactome and transcriptome analyses reveal that PRR33 regulates cytoskeleton and mitochondrial function. Remarkably, PRR33 interacts with DESMIN, a key regulator of cytoskeleton-mitochondria organization in muscle cells. Abrogation of PRR33 in myocytes substantially abolishes the interaction of DESMIN filaments with mitochondria, leading to abnormal intracellular accumulation of DESMIN and mitochondrial disorganization/dysfunction in myofibers. Together, our findings demonstrate that PRR33 and DESMIN constitute an important regulatory module coordinating mitochondrial organization with muscle differentiation.

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The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.

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Plasmonic metal nanostructures can simultaneously scatter and absorb light, with resonance wavelength and strength depending on their morphology and composition. This work demonstrates that unique dichroic effects and high-contrast colour-switching can be achieved by leveraging the resonant scattering and absorption of light by plasmonic nanostructures and the specular reflection of the resulting transmitted light. Using core/shell nanostructures comprising a metal core and a dielectric shell, we show that their spray coating on reflective substrates produces dichroic films that can display colour switching at different viewing angles. The high-contrast colour switching, high flexibility in designing multicolour patterns, and convenience for large-scale production promise their wide range of applications, including anticounterfeiting, mechanochromic sensing, colour display, and printing.

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AIM: To evaluate the clinical efficacy of small-diameter acellular porcine corneal stroma (SAPS) for the treatment of peripheral corneal ulceration (PCU). METHODS: This retrospective clinical study included 18 patients (18 eyes) with PCU between April 2018 and December 2020. All patients had PCU and underwent lamellar keratoplasty with SAPS. Observation indicators included preoperative and postoperative best-corrected visual acuity (BCVA) and transparency of SAPS. The infection control rate in the surgical eye-lesion area was also calculated. RESULTS: Eighteen patients underwent lamellar keratoplasty with SAPS to treat PCU. None of the patients experienced rejection after 6mo (18/18) and 12mo (16/16) of follow-up. The BCVA (0.47±0.30) at the 6mo follow-up after operation was significantly improved compared with the baseline (0.99±0.80), and the difference was statistically significant (Z=-3.415, P<0.05). The BCVA at the 12mo follow-up after operation was not statistically significant compared to the 6mo (Z=0, P=1). With time, the SAPS graft gradually became transparent. At the 6mo (18/18) and 12mo (16/16) follow-up, none of the patients had recurrent corneal infection. CONCLUSION: SAPS is clinically effective in the treatment of PCU, improving the patient's BCVA and reducing the incidence of rejection after keratoplasty.

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The endoplasmic reticulum (ER) is connected to mitochondria through mitochondria-associated ER membranes (MAMs). MAMs provide a framework for crosstalk between the ER and mitochondria, playing a crucial role in regulating cellular calcium balance, lipid metabolism, and cell death. Dysregulation of MAMs is involved in the development of chronic liver disease (CLD). In CLD, changes in MAMs structure and function occur due to factors such as cellular stress, inflammation, and oxidative stress, leading to abnormal interactions between mitochondria and the ER, resulting in liver cell injury, fibrosis, and impaired liver function. Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD. This paper reviews the literature on the association between mitochondria and the ER, as well as the intervention of traditional Chinese medicine in regulating CLD.

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The aim is to investigate the relationship between serum coagulation parameters (PT, APTT, D-D and FDP) before hospitalization and recurrence of chronic subdural hematoma (CSDH). 236 patients with CSDH who were diagnosed for the first time and had complete medical records were followed up for at least 90 days. Fifty patients (21.2%) had relapsed. Univariate analysis was conducted including general data, imaging data and test results. Serum coagulation parameters (PT, APTT, D-D and FDP) were detected for all CSDH patients. The study identified several factors that exhibited a significant correlation with chronic subdural hematoma (CSDH) recurrence. These factors included advanced age (p = 0.01), hypertension (p = 0.04), liver disease (p = 0.01), anticoagulant drug use (p = 0.01), antiplatelet drug use (p = 0.02), bilateral hematoma (p = 0.02), and single-layer hematoma (p = 0.01). In addition, the presence of fibrin/fibrinogen degradation products (FDP) exceeding 5 mg/L demonstrated a significant relationship with CSDH recurrence (P < 0.05). Notably, the combined assessment of D-dimer (D-D) and FDP exhibited a significant difference, particularly regarding recurrence within 30 days after surgery (P < 0.05). The simultaneous elevation of serum FDP and D-D levels upon admission represents a potentially novel predictor for CSDH recurrence. This finding is particularly relevant for patients who experience recurrence within 30 days following surgical intervention. Older individuals with CSDH who undergo trepanation and drainage should be closely monitored due to their relatively higher recurrence rate.

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The drug encapsulation efficiency, release rate and time, sustained release, and stimulus-response of carriers are very important for drug delivery. However, these always cannot obtained for the carrier with a single component. To improve the comprehensive performance of chitosan-based carriers for 5-Fu delivery, diatomite-incorporated hydroxypropyl cellulose/chitosan (DE/HPC/CS) composite aerogel microspheres were fabricated for the release of 5-fluorouracil (5-Fu), and the release performance was regulated with the content of diatomite, pH value, and external coating material. Firstly, the 5-Fu loaded DE/HPC/CS composite aerogel microspheres and Eudragit L100 coated microspheres were prepared with cross-linking followed by freeze-drying, and characterized by SEM, EDS, FTIR, XRD, DSC, TG, and swelling. The obtained aerogel microspheres have a diameter of about 0.5 mm, the weight percentage of F and Si elements on the surface are 0.55 % and 0.78 % respectively. The glass transition temperature increased from 179 °C to 181 °C and 185 °C with the incorporation of DE and coating of Eudragit, and the equilibrium swelling percentage of DE/HPC/CS (1.5:3:2) carriers are 101.52 %, 45.27 %, 67.32 % at pH 1.2, 5.0, 7.4, respectively. Then, the effect of DE content on the drug loading efficiency of DE/HPC/CS@5-Fu was investigated, with the increase of DE content, the highest encapsulation efficiency was 82.6 %. Finally, the release behavior of DE incorporated and Eudragit L100 Coated microspheres were investigated under different pH values, and evaluated with four kinetic models. The results revealed that the release rate of 5-Fu decreased with the increase of DE content, sustained release with extending time and pH-responsive were observed for the Eudragit-coated aerogel microspheres.

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Polar metals have recently garnered increasing interest because of their promising functionalities. Here we report the experimental realization of an intrinsic coexisting ferromagnetism, polar distortion and metallicity in quasi-two-dimensional Ca3Co3O8. This material crystallizes with alternating stacking of oxygen tetrahedral CoO4 monolayers and octahedral CoO6 bilayers. The ferromagnetic metallic state is confined within the quasi-two-dimensional CoO6 layers, and the broken inversion symmetry arises simultaneously from the Co displacements. The breaking of both spatial-inversion and time-reversal symmetries, along with their strong coupling, gives rise to an intrinsic magnetochiral anisotropy with exotic magnetic field-free non-reciprocal electrical resistivity. An extraordinarily robust topological Hall effect persists over a broad temperature-magnetic field phase space, arising from dipole-induced Rashba spin-orbit coupling. Our work not only provides a rich platform to explore the coupling between polarity and magnetism in a metallic system, with extensive potential applications, but also defines a novel design strategy to access exotic correlated electronic states.

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BACKGROUND: With the increasing prevalence of colorectal cancer (CRC), optimizing perioperative management is of paramount importance. This study investigates the potential of stellate ganglion block (SGB), known for its stress response-mediating effects, in improving postoperative recovery. We postulate that preoperative SGB may enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. METHODS: We conducted a randomized controlled trial of 57 patients undergoing laparoscopic colorectal cancer surgery at a single center. Patients, aged 18-70 years, were randomly assigned to receive either preoperative SGB or standard care. SGB group patients received 10 mL of 0.2% ropivacaine under ultrasound guidance prior to surgery. Primary outcome was time to flatus, with secondary outcomes encompassing time to defecation, lying in bed time, visual analog scale (VAS) pain score, hospital stays, patient costs, intraoperative and postoperative complications, and 3-year mortality. A per-protocol analysis was used. RESULTS: Twenty-nine patients in the SGB group and 28 patients in the control group were analyzed. The SGB group exhibited a significantly shorter time to flatus (mean [SD] hour, 20.52 [9.18] vs. 27.93 [11.69]; p = 0.012), accompanied by decreased plasma cortisol levels (mean [SD], postoperatively, 4.01 [3.42] vs 7.75 [3.13], p = 0.02). Notably, postoperative pain was effectively managed, evident by lower VAS scores at 6 h post-surgery in SGB-treated patients (mean [SD], 4.70 [0.91] vs 5.35 [1.32]; p = 0.040). Furthermore, patients in the SGB group experienced reduced hospital stay length (mean [SD], day, 6.61 [1.57] vs 8.72 [5.13], p = 0.042). CONCLUSIONS: Preoperative SGB emerges as a promising approach to enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. CLINICAL TRIAL REGISTRATION: ChiCTR1900028404, Principal investigator: Xia Feng, Date of registration: 12/20/2019.

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Deposition of potentially toxic elements (PTEs) in soils due to different types of mining activities has been an increasingly important concern worldwide. Quantitative differences of soil PTEs contamination and related health risk among typical mines remain unclear. Herein, data from 110 coal mines and 168 metal mines across China were analyzed based on 265 published literatures to evaluate pollution characteristics, spatial distribution, and probabilistic health risks of soil PTEs. The results showed that PTE levels in soil from both mine types significantly exceeded background values. The geoaccumulation index (Igeo) revealed metal-mine soil pollution levels exceeded those of coal mines, with average Igeo values for Cd, Hg, As, Pb, Cu, and Zn being 3.02-15.60 times higher. Spearman correlation and redundancy analysis identified natural and anthropogenic factors affecting soil PTE contamination in both mine types. Mining activities posed a significant carcinogenic risk, with metal-mine soils showing a total carcinogenic risk an order of magnitude higher than in coal-mine soils. This study provides policymakers a quantitative foundation for developing differentiated strategies for sustainable remediation and risk-based management of PTEs in typical mining soils.

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Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases (CVDs), such as diabetic cardiomyopathy, ischemia/reperfusion injury, myocardial infarction, heart failure and hypertension. Noncoding RNAs (ncRNAs) are important regulatory factors. Many Chinese medicine (CM) compounds, including their effective components, can regulate pyroptosis and exert myocardium-protecting effects. The mechanisms underlying this protection include inhibition of inflammasome protein expression, Toll-like receptor 4-NF-κB signal pathway activation, oxidative stress, endoplasmic reticulum stress (ERS), and mixed lineage kinase 3 expression and the regulation of silent information regulator 1. The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM. Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

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Background: Ovarian cancer (OV) is characteristic of high incidence rate and fatality rate in the malignant tumors of female reproductive system. Researches on pathogenesis and therapeutic targets for OV need to be continued. This study mainly analyzed the immune-related pathogenesis and discovered the key immunotherapy targets for OV. Methods: WGCNA was used for excavating hub gene modules and hub genes related to the immunity of OV. Enrichment analysis was aimed to analyze the related pathways of hub gene modules. Biological experiments were used for exploring the effect of hub genes on SKOV3 cells. Results: We identified two hub gene modules related to the immunoscore of OV and found that these genes in the modules were related to the extracellular matrix and viral infections. At the same time, we also discovered six hub genes related to the immunity of OV. Among them, KIF26B and CREB3L1 can affect the proliferation, migration, and invasion of SKOV3 cells by the Wnt/ß-catenin pathway. Conclusions: The local infection or inflammation of ovarian may affect the immunity of OV. KIF26B and CREB3L1 are expected to be potential targets for the immunotherapy of OV.

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Toxocariasis is an important zoonotic parasitic disease. Toxocaris canis adults live and reproduce in the intestinal tract of dogs and other canine hosts, and the infectious eggs are continuously excreted in feces, which causes environmental contamination and has an important public health significance. In this study, TMT proteomic and untargeted metabolomic methods were used to explore the physiological and pathological effects on the intestinal tract of dogs which infected with T. canis, and a series of bioinformatics analyses were conducted to identify differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs). The proteomics results showed that 198 DEPs were mainly enriched in the immune system and signal transduction pathway, and involved in the regulation of the occurrence and development of cancer and infectious diseases. T. canis could disrupt intestinal permeability by increasing the expression of proteins such as zinc finger protein DZIP1L and myosin heavy chain 10. Additionally, T. canis infection could also inhibit the host immune response by decreasing the expression of MHC-II, NF-κB, DLA and other immune-related molecules. While, the metabolomics results revealed that the expression of oxoglutaric acid, glutamate, d-aspartate, arginine, taurochenodeoxycholic acid and taurocholic acid which participated in tricarboxylic acid (TCA) cycle, glycolysis/gluconeogenesis, bile secretion, biosynthesis of amino acids pathway were significantly decreased. The correlation results of proteomics and metabolomics showed that DEPs and DEMs were mainly co-enriched in bile secretion pathway to regulate intestinal peristalsis. Analyzing DEPs and DEMs will not only provide insights into the mechanisms of host parasite interaction, but also aid in identifying potential targets for therapy and diagnosis, thus setting the groundwork for effectively preventing and managing toxocariasis.

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Root metabolites and soil microbial community structure in the rhizosphere play critical roles in crop growth. Here, we assessed the efficiency of conventional and tissue culture propagation methods in modulating the soil health and microbiota in the rhizosphere of sugarcane (Saccharum officinarum L.) plants. The seeding canes were obtained using newly planted and two-year ratooned canes propagated by conventional (CSN and CSR) or tissue culture (TCN and TCR) methods. Changes in soil fertility, root metabolites and soil microbial community structure in the rhizosphere of sugarcane plants obtained using these canes were assessed. The activities of soil ß-glucosidase and aminopeptidase, soil microbial biomass nitrogen, and abundances of soil beneficial microbes, both at phyla and genera levels, were significantly higher in the rhizosphere of sugarcane plants in TCN and TCR treatments than those in that of plants in CSN and CSR treatments. Furthermore, flavonoid and flavonol biosynthesis and alanine, aspartate and glutamate metabolism were significantly upregulated in the roots of TCR and TCN plants compared with those in the roots of CSN and CSR plants. These results suggest that the tissue culture propagation method is a sustainable method for sugarcane cultivation to improve soil fertility and health in sugarcane rhizosphere.

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The N6-methyladenosine (m6A) methyltransferase METTL3 has been demonstrated to function in mediating m6A modification, but its role in ischemic stroke (IS) has not been fully elucidated. This study aimed to explore the downstream mechanism of METTL3-mediated m6A modification in IS. GSE16561 and GSE22255 were downloaded from the Gene Expression Omnibus database for analysis of differentially expressed genes (DEGs), and it was found that METTL3 mRNA was downregulated in IS. Then quantitative real-time polymerase chain reaction was used to verify the downregulation of METTL3 mRNA in the peripheral blood of IS patients and the cortexes of transient middle cerebral artery occlusion mice. By combining DEGs with the m6A-downregulated genes in GSE142386 which performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) on METTL3-deficient and control endothelial cells, a total of 131 genes were identified as the METTL3-mediated m6A-modified genes in IS. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the genes were mainly involved in cytokine-cytokine receptor interaction, MAPK signaling pathway and NF-kappa B signaling pathway. CTSS and SBK1 were further screened as the key METTL3-mediated m6A-modified genes by random forest model and PCR validation. The ROC curve analysis showed that the combination with CTSS and SBK1 was of good diagnostic value for IS, with the AUC of 0.810, sensitivity of 0.780, and specificity of 0.773. Overall, we found that METTL3-mediated m6A modification may influence the occurrence and development of IS by participating in inflammation-related biological processes, and two key m6A-modified genes mediated by METTL3 (CTSS and SBK1) can be used as diagnostic biomarkers for IS.

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The aim of the present study was to elucidate the role and downstream mechanism of long non­coding RNA (lncRNA) metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) in the process of cervical cancer cell pyroptosis. The effect of inhibiting lncRNA MALAT1 on cervical cancer cells was determined using primary cells isolated from patients and U14 cervical tumor­bearing nude mice. The level of lncRNA MALAT1 expression and cell viability were determined for relationship analysis. Pyroptosis was then investigated in HeLa cells with lncRNA MALAT1 knockdown or overexpression with or without lipopolysaccharide (LPS) treatment. Bioinformatics tools were used to identify downstream factors of lncRNA MALAT1, which were subsequently verified by gain­ or loss­of­function analyses in the process of cervical cancer cell pyroptosis. It was observed that the level of lncRNA MALAT1 was markedly higher in cervical carcinoma cells compared with expression in paracarcinoma cells, and knockdown of lncRNA MALAT1 induced cervical cancer cell death through pyroptosis. By contrast, overexpression of lncRNA MALAT1 blocked LPS­induced pyroptosis. These results, combined with bioinformatics statistical tools, demonstrated that the microRNA (miR)­124/sirtuin 1 (SIRT1) axis may affect the progression of cervical cancer at least partly by mediating the effect of lncRNA MALAT1 on the pyroptosis of cervical cancer cells. In conclusion, the lncRNA MALAT1/miR­124/SIRT1 regulatory axis in cervical cancer cells may mediate pyroptosis and may provide potential targets against the progression of cervical cancer.

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