Apolipoprotein E is a prognostic factor for pancreatic cancer and associates with immune infiltration.

BACKGROUND: The expression level of apolipoprotein E (APOE) in pancreatic ductal adenocarcinoma (PDAC) and its effect on the prognosis of PDAC patients are not clear. The effect of APOE on the immune status of patients with PDAC has not been elucidated. METHODS: We obtained pancreatic cancer data from the TCGA and GETx databases. Patients with PDAC who underwent pancreatic surgery at the Second Affiliated Hospital of Jiaxing University between 2012 and 2021 were included. Clinical pathological data were recorded, plasma APOE levels were measured, and tissue samples were collected. A tissue microarray was generated using the collected tissue samples. APOE and CD4 staining was performed to determine immunoreactive scores (IRSs). The expression of APOE in the plasma and tumour tissues of pancreatic cancer patients was analysed and compared. The correlations between plasma APOE levels, tissue APOE levels and clinicopathological characteristics were analysed. Survival prognosis was analysed using Kaplan-Meier survival analysis and Cox multivariate regression analysis. The correlations between APOE expression levels and immune biomarkers and immune cells were further analysed. Single-cell analysis of APOE distribution in various cells was performed on the TISCH website. RESULTS: APOE was highly expressed in the tumour tissue of pancreatic cancer patients, and high plasma APOE levels were associated with poor prognosis. Females, patients with high-grade disease and patients with pancreatic head carcinoma had high plasma APOE levels. High APOE expression in tumour tissues was associated with good prognosis. Mononuclear macrophages in the pancreatic cancer microenvironment primarily expressed APOE. APOE levels positively correlated with immune biomarkers, such as CD8A, PDCD1, GZMA, CXCL10, and CXCL9, in the tumour microenvironment. APOE promoted CD4 + T cell or dendritic cell infiltration in the tumour microenvironment. CONCLUSIONS: APOE may affect the occurrence and development of pancreatic cancer by regulating the infiltration of immune cells in the tumour microenvironment.

Spatial multi-omics at subcellular resolution via high-throughput in situ pairwise sequencing.

Technology for spatial multi-omics aids the discovery of new insights into cellular functions and disease mechanisms. Here we report the development and applicability of multi-omics in situ pairwise sequencing (MiP-seq), a method for the simultaneous detection of DNAs, RNAs, proteins and biomolecules at subcellular resolution. Compared with other in situ sequencing methods, MiP-seq enhances decoding capacity and reduces sequencing and imaging costs while maintaining the efficacy of detection of gene mutations, allele-specific expression and RNA modifications. MiP-seq can be integrated with in vivo calcium imaging and Raman imaging, which enabled us to generate a spatial multi-omics atlas of mouse brain tissues and to correlate gene expression with neuronal activity and cellular biochemical fingerprints. We also report a sequential dilution strategy for resolving optically crowded signals during in situ sequencing. High-throughput in situ pairwise sequencing may facilitate the multidimensional analysis of molecular and functional maps of tissues.

Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis.

The essence of difference between hemostasis and thrombosis is that the clotting reaction is a highly fine-tuned process. Vascular protein disulfide isomerase (PDI) represents a critical mechanism regulating the functions of hemostatic proteins. Herein we show that histidine-rich glycoprotein (HRG) is a substrate of PDI. Reduction of HRG by PDI enhances the procoagulant and anticoagulant activities of HRG by neutralization of endothelial heparan sulfate (HS) and inhibition of factor XII (FXIIa) activity, respectively. Murine HRG deficiency (Hrg-/-) leads to delayed onset but enhanced formation of thrombus compared to WT. However, in the combined FXII deficiency (F12-/-) and HRG deficiency (by siRNA or Hrg-/-), there is further thrombosis reduction compared to F12-/- alone, confirming HRG's procoagulant activity independent of FXIIa. Mutation of target disulfides of PDI leads to a gain-of-function mutant of HRG that promotes its activities during coagulation. Thus, PDI-HRG pathway fine-tunes thrombosis by promoting its rapid initiation via neutralization of HS and preventing excessive propagation via inhibition of FXIIa.

Anti-sulfatide antibody-related Guillain-Barré syndrome presenting with overlapping syndromes or severe pyramidal tract damage: a case report and literature review.

Introduction: Anti-sulfatide antibodies are key biomarkers for the diagnosis of Guillain-Barré syndrome (GBS). However, case reports on anti-sulfatide antibody-related GBS are rare, particularly for atypical cases. Case description case 1: A 63 years-old man presented with limb numbness and diplopia persisting for 2 weeks, with marked deterioration over the previous 4 days. His medical history included cerebral infarction, diabetes, and coronary atherosclerotic cardiomyopathy. Physical examination revealed limited movement in his left eye and diminished sensation in his extremities. Initial treatments included antiplatelet agents, cholesterol-lowering drugs, hypoglycemic agents, and medications to improve cerebral circulation. Despite this, his condition worsened, resulting in bilateral facial paralysis, delirium, ataxia, and decreased lower limb muscle strength. Treatment with intravenous high-dose immunoglobulin and dexamethasone resulted in gradual improvement. A 1 month follow-up revealed significant neurological sequelae. Case description case 2: A 53 years-old woman was admitted for adenomyosis and subsequently experienced sudden limb weakness, numbness, and pain that progressively worsened, presenting with diminished sensation and muscle strength in all limbs. High-dose intravenous immunoglobulin, vitamin B1, and mecobalamin were administered. At the 1 month follow-up, the patient still experienced limb numbness and difficulty walking. In both patients, albuminocytologic dissociation was found on cerebrospinal fluid (CSF) analysis, positive anti-sulfatide antibodies were detected in the CSF, and electromyography indicated peripheral nerve damage. Conclusion: Anti-sulfatide antibody-related GBS can present with Miller-Fisher syndrome, brainstem encephalitis, or a combination of the two, along with severe pyramidal tract damage and residual neurological sequelae, thereby expanding the clinical profile of this GBS subtype. Anti-sulfatide antibodies are a crucial diagnostic biomarker. Further exploration of the pathophysiological mechanisms is necessary for precise treatment and improved prognosis.

Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. METHODS: BBR was orally administered at doses of 100 mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice. RESULTS: We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1ß, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota. CONCLUSIONS: BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.

Correction: Exploring the Mpemba effect: a universal ice pressing enables porous ceramics.

Correction for 'Exploring the Mpemba effect: a universal ice pressing enables porous ceramics' by Xiaodan Yang et al., Mater. Horiz., 2024, DOI: https://doi.org/10.1039/d3mh01869e.

Exploring the Mpemba effect: a universal ice pressing enables porous ceramics.

Piezoceramics with global porosity and local compaction are highly desired to exploit the combination of mechanical and electrical properties. However, achieving such a functional combination is challenging because of the lack of techniques for applying uniform pressure inside porous ceramic green parts. Nature provides many examples of generating strong forces inside the macro and micro channels via the state transformation of water. Inspired by these phenomena, we present a technique of "ice and fire", that is, water freezing (ice pressing) and high-temperature sintering (fire), to produce ideal porous piezoceramics. We introduce a new compaction method called the "ice pressing method", which manipulates liquid phase transition for compaction. This method has several advantages, including uniform pressure distribution, a wide pressure range, high effectiveness, and selective freezing. It can generate an ultrahigh pressure of up to 180 MPa on the piezoceramic green skeletons in minutes while retaining their functional pore structures. By exploiting the Mpemba phenomenon, we further accelerate the compaction procedure by 11%. The first ice-pressed and second fire-consolidated lead zirconate titanate (PZT) ceramics are highly densified and exhibit an outstanding piezoelectric response (d33 = 531 pC N-1), comparable to conventional pressed bulk counterparts and 10-20 times higher than those of unpressed materials. The novel ice pressing method breaks the limitation of lacking a compaction technique for porous ceramics. The versatile and effective ice pressing method is a green and low-cost route promoting applications in sensors, acoustics, water filtration, catalyst substrates, and energy harvesting.

Effect of Trichinella spiralis-Derived Antigens on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice.

Nonalcoholic fatty liver disease (NAFLD) is a liver disease characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. No approved effective therapeutic medicine is available to date for NAFLD. Helminth therapy is believed to be a novel direction and therapeutic strategy for NAFLD. Our previous study showed that Trichinella spiralis-derived antigens (TsAg) had the potential for partially alleviating obesity via regulating gut microbiota. However, the effect of TsAg on NAFLD remains unclear. In this study, high-fat diet (HFD)-induced model mice were treated with TsAg and microbiota transplantation experiments, and alterations in the pathogenesis of nonalcoholic liver disease were assessed. The results showed that TsAg markedly reduced hepatic steatosis, improved insulin resistance, and regulated the abnormal expression of hepatic lipid-related genes. Of note, TsAg ameliorated hepatic inflammation by decreasing pro-inflammatory TNF-α and IL-1ß, suppressing hepatic macrophage infiltration, as well as promoting M2 macrophage polarization. Moreover, TsAg reversed gut dysbiosis, as especially indicated by an increase in beneficial bacteria (e.g., Akkermansiaceae and Rikenellaceae). Furthermore, our study found that TsAg reduced LPS hepatic translocation and hepatic TLR4/NF-κB signaling, which further contributed to inhibiting hepatic inflammation. In addition, TsAg inhibited hepatic oxidative stress involving Nrf2/NQO-1 signaling. Microbiota transplantation showed that TsAg-altered microbiota is sufficient to confer protection against NAFLD in HFD-induced mice. Overall, these findings suggest that TsAg involving gut-liver axis and Nrf2/NQO-1 signaling is a novel promising candidate for NAFLD treatment. TsAg restores intestinal microbiota and intestinal barrier to inhibit bacteria and LPS translocation into the liver, contributing to reduce inflammation, oxidative stress, and hepatic steatosis in the liver of NAFLD mice. The effects were attributed to, at least in part, the inactivation of NF-κB pathway and the activation of Nrf-2/NQO-1 pathway. This study provides new insights for understanding immune modulation by T. spiralis-derived products as well as the potential application of TsAg as a modality for NAFLD.

Serine protease inhibitor from the muscle larval Trichinella spiralis ameliorates non-alcoholic fatty liver disease in mice via anti-inflammatory properties and gut-liver crosstalk.

Trichinella spiralis is recognized for its ability to regulate host immune responses. The serine protease inhibitor of T. spiralis (Ts-SPI) participates in T. spiralis-mediated immunoregulatory effects. Studies have shown that helminth therapy exhibits therapeutic effects on metabolic diseases. In addition, we previously found that T. spiralis-derived crude antigens could alleviate diet-induced obesity. Thus, Ts-SPI was hypothesized to alleviate non-alcoholic fatty liver disease (NAFLD). Herein, recombinant Ts-SPI (rTs-SPI) was prepared from the muscle larvae T. spiralis. The relative molecular mass of rTs-SPI was approximately 35,000 Da, and western blot analysis indicated good immunoreactivity. rTs-SPI ameliorated hepatic steatosis, inflammation, and pyroptosis in NAFLD mice, which validated the hypothesis. rTs-SPI also reduced macrophage infiltration, significantly expanded Foxp3+ Treg population, and inactivated TLR4/NF-κB/NLRP3 signaling in the liver. Furthermore, rTs-SPI treatment significantly shifted the gut microbiome structure, with a remarkable increase in beneficial bacteria and reduction in harmful bacteria to improve gut barrier integrity. Finally, Abx-treated mice and FMT confirmed that gut-liver crosstalk contributed to NAFLD improvement after rTs-SPI treatment. Taken together, Taken together, these findings suggest that rTs-SPI exerts therapeutic effects in NAFLD via anti-inflammatory activity and gut-liver crosstalk.

Unlocking the Design Paradigm of In-Plane Heterojunction with Built-in Bifunctional Anion Vacancy for Unexpectedly Fast Sodium Storage.

Transition metal chalcogenide (TMD) electrodes in sodium-ion batteries exhibit intrinsic shortcomings such as sluggish reaction kinetics, unstable conversion thermodynamics, and substantial volumetric strain effects, which lead to electrochemical failure. This report unlocks a design paradigm of VSe2- x /C in-plane heterojunction with built-in anion vacancy, achieved through an in situ functionalization and self-limited growth approach. Theoretical and experimental investigations reveal the bifunctional role of the Se vacancy in enhancing the ion diffusion kinetics and the structural thermodynamics of Nax VSe2 active phases. Moreover, this in-plane heterostructure facilitates complete face contact between the two components and tight interfacial conductive contact between the conversion phases, resulting in enhanced reaction reversibility. The VSe2- x /C heterojunction electrode exhibits remarkable sodium-ion storage performance, retaining specific capacities of 448.7 and 424.9 mAh g-1 after 1000 cycles at current densities of 5 and 10 A g-1 , respectively. Moreover, it exhibits a high specific capacity of 353.1 mAh g-1 even under the demanding condition of 100 A g-1 , surpassing most previous achievements. The proposed strategy can be extended to other V5 S8- x and V2 O5- x -based heterojunctions, marking a conceptual breakthrough in advanced electrode design for constructing high-performance sodium-ion batteries.

Protective effect of electroacupuncture at ST36 against damage of intestinal mucosa, oxidative stress and apoptosis induced by 5-FU chemotherapy in mice with colon cancer. / 电针"足三里"å‡è½»å¤§è‚ ç™Œå°é¼ åŒ–ç–—åŽè‚ é»è†œæŸä¼¤åŠå ¶å¯¹æ°§åŒ–åº”æ¿€å’Œç»†èƒžå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on intestinal mucosal damage, intestinal mucosal oxidative stress injury and apoptosis induced by 5-fluorouraeil (5-FU) chemotherapy in colorectal cancer-bearing mice. METHODS: Thirty male BALB/c mice were randomly divided into normal control, colorectal cancer (CT26), 5-FU, non-acupoint and ST36 groups, with 6 mice in each group. Except for those of the normal control group, mice of the remaining 4 groups received subcutaneous implantation of colorectal CT26 cell suspension (0.1 mL) in the right armpit for establishing colorectal cancer model. Rats of the 5-FU group, non-acupoint group and ST36 group were given with 5 mg/mL 5-FU solution once every 3 days for a total of 21 days. For mice of the non-acupoint group and ST36 group, EA (2 Hz, 1-2 mA) was applied to bilateral ST36 or non-acupoints (the bilateral sunken spots about 3 mm to the midpoint between the tail root and the anus) for 5 min after each intraperitoneal infusion of 5-FU, once every 3 days, for a total of 21 days. After the intervention, the diarrhea index was assessed. The length of colon (from the endpoint of cecum to the anal orifice) was measured. Histopathological changes of colonic mucosa were observed by H.E. staining, and the length of colonic villi was measured. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of colonic tissue were detected by thibabituric acid, xanthine oxidase and colorimetric method, respectively. The rate of cell apoptosis in the colonic tissue was measured by TUNEL assay. The positive expressions of Bax and Bcl-2 in colonic tissue were determined by immunohistochemistry. RESULTS: The CT26 model group didn't show any significant changes in the diarrhea index, colon length, colon villus length, MDA content, SOD and GSH-Px activities, colonic cell apoptosis rate, and Bax and Bcl-2 expression levels when compared with the normal group. Compared with the CT26 group, the 5-FU group had a remarkable increase in the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level (P<0.01, P<0.05), and a marked decrease in the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level (P<0.01), suggesting the side effects of administration of 5-FU. Compared with the 5-FU group, the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level were markedly decreased (P<0.05, P<0.01) and those of the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level were obviously increased (P<0.01) in the ST36 group. Compared with the 5-FU group, the non-acupoint group also had an increase in the colon villus length, SOD and GSH-Px activities (P<0.01, P<0.05) and a decrease in the cell apoptosis rate (P<0.01). CONCLUSIONS: EA at ST36 has a positive effect in reducing intestinal mucosal damage induced by 5-FU chemotherapy in cancer-bearing mice, which may be related to its function in relieving oxidative stress injury and inhibiting apoptosis of colonic tissue.

One-wire reconfigurable and damage-tolerant sensor matrix inspired by the auditory tonotopy.

Sensor matrices are essential in various fields including robotics, aviation, health care, and industrial machinery. However, conventional sensor matrix systems often face challenges such as limited reconfigurability, complex wiring, and poor robustness. To address these issues, we introduce a one-wire reconfigurable sensor matrix that is capable of conforming to three-dimensional curved surfaces and resistant to cross-talk and fractures. Our frequency-located technology, inspired by the auditory tonotopy, reduces the number of output wires from row × column to a single wire by superimposing the signals of all sensor units with unique frequency identities. The sensor units are connected through a shared redundant network, giving great freedom for reconfiguration and facilitating quick repairs. The one-wire frequency-located technology is demonstrated in two applications-a pressure sensor matrix and a pressure-temperature multimodal sensor matrix. In addition, we also show its potential in monitoring strain distribution in an airplane wing, emphasizing its advantages in simplified wiring and improved robustness.

miRNA transcriptomics analysis shows miR-483-5p and miR-503-5p targeted miRNA in extracellular vesicles from severe acute pancreatitis-associated lung injury patients.

AIM: This study sought to identify potential biomarkers and miRNA-mRNA networks within extracellular vesicles (EVs) for detecting severe acute pancreatitis-associated lung injury (SAPALI). METHODS: Blood-derived EVs were isolated, and their miRNA transcriptomic profiles were comprehensively analyzed using miRBase v.21 database along with miRDeep2 tool to predict novel miRNAs. DEGseq R package was deployed for the identification of differentially expressed miRNAs (DEMs). Protein-protein interaction (PPI) networks were assembled using STRING and Cytoscape. A lung injury model was established using Lipopolysaccharide (LPS)-induced BEAS-2B cells, chosen for their respiratory epithelial origin and pertinent association with lung injury. The expression levels of targeted miRNA and associated proteins, TLR4, NF-κB mRNA were quantified via RT-PCR and Western Blot. Levels of IL-6, IL-1ß, TNF-α, and ROS were measured using designated kits. Dual-luciferase reporter assay was conducted to examine the interaction between miRNA and proteins. RESULTS: The comparisons between the SAPALI and the control group revealed 10 DEM, including miR-503-5p and miR-483-5p. The cytoHubba plugin in Cytoscape identified three principal miRNA-mRNA interactions: miR-483-5p with PTK2 and HDAC2; miR-28-5p with MAPK1, TP53BP1, SEMA3A; and miR-503-5p with PPP1CB, SEMA6D, EPHB2, UNC5B. The SAPALI model exhibited elevated miR-503-5p, HDAC2 and inflammatory markers, with a decline UNC5B, miR-483-5p and miR-28-5p. Transfection with miR-503-5p and miR-483-5p inhibitors increased the levels of their supposed binding proteins but not miR-28-5p inhibitor. The Dual-luciferase reporter gene assay identified the interaction of miR-503-5p with UNC5B, and miR-483-5p with HDAC2, but not miR-28-5p with TP53BP1. CONCLUSIONS: Our study maps miRNA-mRNA interactions in SAPALI, identifying miR-503-5p and miR-483-5p as critical regulatory miRNAs.

Investigation on Awareness of Cognitive Impairment Diseases Among Surgical Practitioners.

Objective: In this study, we assessed the awareness of cognitive dysfunction and the reasons for the lack of awareness among surgical practitioners in Jiaxing. Methods: Questionnaires were distributed to surgical practitioners covering all Class III and Class II hospitals in Jiaxing. Respondents were asked to make selections regarding the demographic data, clinical attitudes and practices of cognitive dysfunction based on Alzheimer's Disease Assessment Scale (ADKS) of the Chinese version. Results: A total of 180 questionnaires were distributed, 12 of which were incomplete, with 168 being included for analysis. The respondents were generally under 50 years of age (150, 89.3%), predominantly males (146, 86.9%), and surgeons (153, 91.1%). They generally had a bachelor's or master's degrees (165, 98.2%), and served in Class III hospitals (127, 75.6%). The title of the practitioner was found to impact their attention toward their patients' cognitive status during preoperative preparation (P<0.05). Titles and hospital levels were found to influence decisions of surgical practitioners to invite specialist physicians for consultation and assessment when a patient was identified to have cognitive dysfunction (P<0.05). Most surgical practitioners had little knowledge or training about Alzheimer's disease and cognitive dysfunction. Among the 168 respondents, the mean ADKS score was 20.14±2.40, and the awareness rate was 67.1%, indicating that the surgical practitioner's title influenced ADKS score (P<0.001). Conclusion: Surgical practitioners, especially young physicians and those in Class II hospitals, had lower awareness of cognitive dysfunction, with low ADKS scores; therefore, they needed to be further trained to recognize cognitive dysfunction.

A Newly Synbiotic Combination Alleviates Obesity by Modulating the Gut Microbiota-Fat Axis and Inhibiting the Hepatic TLR4/NF-κB Signaling Pathway.

SCOPE: Obesity has been recognized as a worldwide public health crisis, this is accompanied by dysregulation of the intestinal microbiota and upregulation of liver steatosis and adipose inflammation. Synbiotic as a novel alternative therapy for obesity have recently gained much attention. METHODS: This study innovatively research the anti-obesity properties of a newly synbiotic composed of Lactobacillus acidophilus, Bifidobacterium infantis and konjac glucomannan oligosaccharides. RESULTS: The synbiotic treatment can reduce body weight, fat mass, blood sugar, liver steatosis and adipose inflammation in obesity mice fed by high-fat diet (HFD). Meanwhile, synbiotic treatment activated brown adipose tissue and improve energy, glucose and lipid metabolism. In addition, synbiotic treatment not solely enhanced the protection of intestinal barrier, but also ameliorated gut microbiota dysbiosis directly by enhancing beneficial microbes and reducing potentially harmful bacteria. Furthermore, the microbiome phenotype and functional prediction showed that synbiotic treatment can improve the gut microbiota functions involving inflammatory state, immune response, metabolism and pathopoiesia. CONCLUSION: The synbiotic may be an effective candidate treatment strategy for the clinical prevention and treatment of obesity and other associated metabolic diseases such as hyperlipidemia, nonalcoholic fatty liver diseases by alleviating inflammatory response, regulating energy metabolism and maintaining the balance of intestinal microecology.

In situ enrichment of sulphate-reducing microbial communities with different carbon sources stimulating the acid mine drainage sediments.

The applications of sulphate-reducing microorganisms (SRMs) in acid mine drainage (AMD) treatment systems have received extensive attention due to their ability to reduce sulphate and stabilize metal(loid)s. Despite great phylogenetic diversity of SRMs, only a few have been used in AMD treatment bioreactors. In situ enrichment could be an efficient approach to select new effective SRMs for AMD treatment. Here, we performed in situ enrichment of SRMs in highly stratified AMD sediment cores using different kinds of carbon source mixture. The dsrAB (dissimilatory sulfite reductase) genes affiliated with nine phyla (two archaeal and seven bacterial phyla) and 26 genera were enriched. Remarkably, those genes affiliated with Aciduliprofundum and Vulcanisaeta were enriched in situ in AMD-related environments for the first time, and their relative abundances were negatively correlated with pH. Furthermore, 107 dsrAB-containing metagenome-assembled genomes (MAGs) were recovered from metagenomic datasets, with 14 phyla (two archaeal and 12 bacterial phyla) and 15 genera. The relative abundances of MAGs were positively correlated with total carbon and sulphate contents. Our findings expanded the diversity of SRMs that can be enriched in AMD sediment, and revealed the physiochemical properties that might affect the growth of SRMs, which provided guidance for AMD treatment bioreators.

Agricultural non-point source pollution and rural transformation in a plain river network: Insights from Jiaxing city, China.

Recently, agricultural non-point source pollution (ANPSP) has gained increasing attention in China. However, using a uniform paradigm to analyze ANPSP in all regions is difficult, considering their geographical, economic, and policy differences. In this study, we adopted the inventory analysis method to estimate the ANPSP of Jiaxing City, Zhejiang Province as a representative region of the plain river network area from 2001 to 2020 and analyzed it in the framework of policies and rural transformation development (RTD). The ANPSP showed an overall decreasing trend over 20 years. Compared to 2001, total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) decreased by 33.93%, 25.77%, and 43.94%, respectively, in 2020. COD accounted for the largest annual average (67.02%), whereas TP contributed the most to the equivalent emissions (50.9%). The highest contribution of TN, TP, and COD, which fluctuated and decreased over the past 20 years, originated from livestock and poultry farming. However, the contribution of TN and TP from aquaculture increased. The overall trend of RTD and ANPSP showed an inverted "U" shape with time, and the evolution of both showed similar stage characteristics. With the gradual stabilization of RTD, ANPSP successively went through three stages: high-level stabilization (2001-2009), rapid-decreasing (2010-2014), and low-level stabilization (2015-2020). Additionally, the relationships between pollution loads from different agricultural sources and indicators of different dimensions of RTD varied. These findings provide a reference for the governance and planning of ANPSP in the plain river network area and a new perspective for investigating the relationship between rural development and the environment.

Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota.

Alcoholic liver disease (ALD) is a globally prevalent liver-related disorder characterized by severe oxidative stress and inflammatory liver damage, for which no effective treatment is currently available. Hydrogen gas (H2) has been demonstrated to be an efficient antioxidant in various diseases in animals as well as humans. However, the protective effects of H2 on ALD and its underlying mechanisms remain to be elucidated. The present study demonstrated that H2 inhalation ameliorated liver injury, and attenuated liver oxidative stress, inflammation, and steatosis in an ALD mouse model. Moreover, H2 inhalation improved gut microbiota, including increasing the abundance of Lachnospiraceae and Clostridia, and decreasing the abundance of Prevotellaceae and Muribaculaceae, and also improved intestinal barrier integrity. Mechanistically, H2 inhalation blocked activation of the LPS/TLR4/NF-κB pathway in liver. Notably, it was further demonstrated that the reshaped gut microbiota may accelerate alcohol metabolism, regulate lipid homeostasis and maintain immune balance by bacterial functional potential prediction (PICRUSt). Fecal microbiota transplantation from mice that had undergone H2 inhalation significantly alleviated acute alcoholic liver injury. In summary, the present study showed that H2 inhalation alleviated liver injury by reducing oxidative stress and inflammation, while also improving intestinal flora and enhancing the intestinal barrier. H2 inhalation may serve as an effective intervention for preventing and treating ALD in a clinical context.

PCSK6 mediates Th1 differentiation and promotes chronic colitis progression and mucosal barrier injury via STAT1.

This study was aimed at investigating the expression and role of proprotein convertase subtilisin/kexin type (PCSK6) in inflammatory bowel disease (IBD). DSS induced mouse colitis and mucosal barrier injury, down-regulation of TJ proteins, improvement of permeability, and increases of the proportions of Th1 and M1 macrophages. After PCSK6 knockdown, the colitis in KO mice was improved relative to WT mice, the TJ protein levels increased, and the proportions of Th1 and M1 macrophages decreased. STAT1 inhibitor treatment also inhibited chronic colitis in mice. As revealed by in-vitro experiments, PCSK6 overexpression promoted the transformation of Th0 into Th1, while PCSK6 silencing suppressed the transfection. COPI assay results revealed the presence of targeted binding relation between PCSK6 and STAT1. PCSK6 binds to STAT1 to promote STAT1 phosphorylation and regulate Th1 cell differentiation, thus promoting the M1 polarization of macrophages and aggravating colitis progression. PCSK6 is promising as the new target for the treatment of colitis.

Single-cell analysis of peripheral blood from high-altitude pulmonary hypertension patients identifies a distinct monocyte phenotype.

Immune and inflammatory responses have an important function in the pathophysiology of pulmonary hypertension (PH). However, little is known about the immune landscape in peripheral circulation in patients with high-altitude pulmonary hypertension (HAPH). We apply single-cell transcriptomics to characterize the monocytes that are significantly enriched in the peripheral blood mononuclear cells (PBMC) of HAPH patients. We discover an increase in C1 (non-classical) and C2 (intermediate) monocytes in PBMCs and a decrease in hypoxia-inducible transcription factor-1α (HIF-1α) in all monocyte subsets associated with HAPH. In addition, we demonstrate that similar immune adaptations may exist in HAPH and PH. Overall, we characterize an immune cell atlas of the peripheral blood in HAPH patients. Our data provide evidence that specific monocyte subsets and HIF-1α downregulation might be implicated in the pathogenesis of HAPH.