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Surface soil moisture (SSM) plays an important role in agricultural and environmental systems. With the continuous improvement in the availability of remote sensing data, satellite technology has experienced widespread development in the monitoring of large-scale SSM. Synthetic Aperture Radar (SAR) and optical remote sensing data have been extensively utilized due to their complementary advantages in this field. However, the limited information from single-band SARs or single optical remote sensing data has restricted the accuracy of SSM retrieval, posing challenges for precise SSM monitoring. In contrast, multi-source and multi-band remote sensing data contain richer and more comprehensive surface information. Therefore, a method of combining multi-band SAR data and employing machine learning models for SSM inversion was proposed. C-band Sentinel-1 SAR data, X-band TerraSAR data, and Sentinel-2 optical data were used in this study. Six commonly used feature parameters were extracted from these data. Three machine learning methods suitable for small-sample training, including Genetic Algorithms Back Propagation (GA-BP), support vector regression (SVR), and Random Forest (RF), were employed to construct the SSM inversion models. The differences in SSM retrieval accuracy were compared when two different bands of SAR data were combined with optical data separately and when three types of data were used together. The results show that the best inversion performance was achieved when all three types of remote sensing data were used simultaneously. Additionally, compared to the C-band SAR data, the X-band SAR data exhibited superior performance. Ultimately, the RF model achieved the best accuracy, with a determinable coefficient of 0.9186, a root mean square error of 0.0153 cm3/cm3, and a mean absolute error of 0.0122 cm3/cm3. The results indicate that utilizing multi-band remote sensing data for SSM inversion offers significant advantages, providing a new perspective for the precise monitoring of SSM.

Tumor-associated macrophages (TAMs) are present in almost all solid tumor tissues. 16They play critical roles in immune regulation, tumor angiogenesis, tumor stem cell activation, tumor invasion and metastasis, and resistance to therapy. However, it is unclear how TAMs perform these functions. With the application of single-cell RNA sequencing (scRNA-seq), it has become possible to identify TAM subpopulations associated with distinct functions. In this review, we discuss four novel TAM subpopulations in distinct solid tumors based on core gene signatures by scRNA-seq, including FCN1+, SPP1+, C1Q+ and CCL18+ TAMs. Functional enrichment and gene expression in scRNA-seq data from different solid tumor tissues found that FCN1+ TAMs may induce inflammation; SPP1+ TAMs are potentially involved in metastasis, angiogenesis, and cancer cell stem cell activation, whereas C1Q+ TAMs participate in immune regulation and suppression; And CCL18+ cells are terminal immunosuppressive macrophages that not only have a stronger immunosuppressive function but also enhance tumor metastasis. SPP1+ and C1Q+ TAM subpopulations can be further divided into distinct populations with different functions. Meanwhile, we will also present emerging evidence highlighting the separating macrophage subpopulations associated with distinct functions. However, there exist the potential disconnects between cell types and subpopulations identified by scRNA-seq and their actual function.

Background: Mitochondria are dynamic organelles, and mitochondrial dynamics are important for the maintenance of mitochondrial inheritance and function. Recently, an increasing number of studies have shown that mitochondrial dynamics play an important role in the occurrence and development of hepatocellular carcinoma (HCC). However, bibliometric analyses of mitochondrial dynamics in HCC are scarce. Therefore, we conducted a bibliometric analysis to explore the current global research status and trends in mitochondrial dynamics and HCC. Methods: Global publications on mitochondrial dynamics and HCC published between 2007 and May 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using Bibliometrix, VOSviewer, and CiteSpace to analyze the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results: A total of 518 publications were retrieved fromthe WoSCC database. China and The Fourth Military Medical University were the most productive countries and institutions. Zorzano, A published the most literature whereas Chen, HC was the author with the highest number of co-citations. Plos One was the most popular journal, whereas the Journal of Biological Chemistry had the highest number of co-citations. The most frequently used keyword was “mitochondria”. Further analysis of the references and keywords showed that the molecular mechanisms linking them to drug therapy targets should be the focus of future studies. Conclusions: Research on mitochondrial dynamics in HCC has received much attention, and many studies have been published. However, research on mitochondrial dynamics and HCC has been limited by insufficient regional development imbalances and global cooperation. Nevertheless, future research on mitochondrial dynamics and HCC is promising, especially regarding the molecular mechanisms of mitochondrial fission and fusion and how to link the currently known molecular mechanisms with drug therapy targets for HCC.

ABSTRACTAspartic acid (Asp) isomerization is a spontaneous non-enzymatic post-translation modification causing a change in the structure of the protein backbone, which is commonly observed in therapeutic antibodies during manufacturing and storage. The Asps in Asp–Gly (DG), Asp–Ser (DS), and Asp–Thr (DT) motifs in the structurally flexible regions, such as complementarity-determining regions (CDRs) in antibodies, are often found to have high rate of isomerization, and they are considered “hot spots” in antibodies. In contrast, the Asp-His (DH) motif is usually considered a silent spot with low isomerization propensity. However, in monoclonal antibody mAb-a, the isomerization rate of an Asp residue, Asp55, in the aspartic acid-histidine-lysine (DHK) motif present in CDRH2 was found to be unexpectedly high. By determining the conformation of DHK motif in the crystal structure of mAb-a, we found that the Cgamma of the Asp side chain carbonyl group and the back bone amide nitrogen of successor His were in proximal contact, which facilitates the formation of succinimide intermediate, and the +2 Lys played an important role in stabilizing such conformation. The contributing roles of the His and Lys residues in DHK motif were also verified using a series of synthetic peptides. This study identified a novel Asp isomerization hot spot, DHK, and the structural-based molecular mechanism was revealed. When 20% Asp55 isomerization in this DHK motif occurred in mAb-a, antigen binding activity reduced to 54%, but the pharmacokinetics in rat was not affected significantly. Although Asp isomerization of DHK motif in CDR does not appear to have a negative impact on PK, DHK motifs in the CDRs of antibody therapeutics should be removed, considering the high propensity of isomerization and impact on antibody activity and stability.

Background: IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method: We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result: A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt. Conclusion: This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.

Abstract Background Adipose tissue-derived stem cell (ADSC) transplantation has been shown to be effective for the management of severe liver disorders. Preactivation of ADSCs enhanced their therapeutic efficacy. However, these effects have not yet been examined in relation to cholestatic liver injury. Methods In the present study, a cholestatic liver injury model was established by bile duct ligation (BDL) in male C57BL/6 mice. Human ADSCs (hADSCs) with or without tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) pretreatment were administrated into the mice via tail vein injections. The efficacy of hADSCs on BDL-induced liver injury was assessed by histological staining, real-time quantitative PCR (RT-qPCR), Western blot, and enzyme-linked immune sorbent assay (ELISA). In vitro, the effects of hADSC conditioned medium on the activation of hepatic stellate cells (HSCs) were investigated. Small interfering RNA (siRNA) was used to knock down cyclooxygenase-2 (COX-2) in hADSCs. Results TNF-α/IL-1β preconditioning could downregulate immunogenic gene expression and enhance the engraftment efficiency of hADSCs. Compared to control hADSCs (C-hADSCs), TNF-α/IL-1β-pretreated hADSCs (P-hADSCs) significantly alleviated BDL-induced liver injury, as demonstrated by reduced hepatic cell death, attenuated infiltration of Ly6G + neutrophils, and decreased expression of pro-inflammatory cytokines TNF-α, IL-1β, C-X-C motif chemokine ligand 1 (CXCL1), and C-X-C motif chemokine ligand 2 (CXCL2). Moreover, P-hADSCs significantly delayed the development of BDL-induced liver fibrosis. In vitro, conditioned medium from P-hADSCs significantly inhibited HSC activation compared to that from C-hADSCs. Mechanistically, TNF-α/IL-1β upregulated COX-2 expression and increased prostaglandin E2 (PGE2) secretion. The blockage of COX-2 by siRNA transfection reversed the benefits of P-hADSCs for PGE2 production, HSC activation, and liver fibrosis progression. Conclusion In conclusion, our results suggest that TNF-α/IL-1β pretreatment enhances the efficacy of hADSCs in mice with cholestatic liver injury, partially through the COX-2/PGE2 pathway.

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

Improving the net carbon sink efficiency of mariculture is one of the important ways for China to achieve the goal of carbon neutrality. This paper used the super efficiency SBM model to calculate the net carbon sink efficiency of mariculture in 9 coastal provinces of China from 2008 to 2019, and analyzed its global and local spatial auto-correlation. Then, the dynamic spatial durbin model was used to explore the influencing factors of the net carbon sink efficiency of mariculture and its spatial spillover effect. The results showed that: (1) The net carbon sink efficiency of mariculture in China was generally high and rising, but there were obvious regional differences. (2) From the global perspective, the net carbon sink efficiency of mariculture between provinces had a spatial positive correlation, and the agglomeration effect was significant, but the degree of spatial agglomeration gradually weakened with the passage of time; from the local perspective, the spatial evolution path of net carbon sink efficiency in some provinces had not changed during the study period, showing a certain path dependence. (3) Science and technology promotion and yield structure had a promoting effect on the net carbon sink efficiency of mariculture, while economic scale and professional personnel investment intensity had an inhibitory effect; from the perspective of spatial spillover effect, professional personnel investment intensity,science and technology promotion and yield structure had positive spillover effect on the net carbon sink efficiency of adjacent areas, while economic scale had negative spillover effect.

Rare sugars are a kind of prebiotics with special chemical structure and bioactivities such as regulate intestinal flora, inhibit pathogen, resist oxidation, improve immunity, antitumor and so on. Rare sugars were widely used in the production of health food, infant formula food, dairy products as well as functional drinks. Nowadays, series progress has been made in the discovering of novel rare sugar, structural analysis, optimization of producing process, enzyme engineering, metabolic engineering and Izumoring strategy research. This paper reviews and prospects above advances, focuses on the research progress of bioactivity and biotransformation of rare sugars, and discusses their industrial application potential, existing problems and solutions, to provide a theoretical basis for the development, function mining and industrial production and utilization of rare sugars.

Chiral α-acylated N-heterocycles are commonly found in pharmaceutical drugs, natural products, and catalysts for asymmetric synthesis. Here, the authors describe a cooperative nickel/photoredox catalysis strategy for the site- and enantioselective cross-coupling of saturated azacycles and carboxylic acids to access such valuable heterocyclic molecules.

Background & Aims: Klebsiella pneumoniae (KLP), a Gram-negative bacterium belonging to the family of Enterobacteriaceae, is a common cause of antimicrobial-resistant opportunistic infections in hospitalized patients. KLP can colonize in the human gastrointestinal tract, especially in patients with inflammatory bowel diseases. However, effects of KLP on the onset and development of inflammatory bowel disease remain unclear. Methods: We analyzed the relationship between Mayo indexes of ulcerative colitis and KLP using quantitative reverse-transcription polymerase chain reaction and endoscopy. Using caspase-1/11-/-, NLRP3-/-, NLRC4-/-, interleukin (IL)18-/-, and IL22-/- mice, we showed that KLP could induce colitis through caspase-11–mediated release of mature IL18. Through in vitro gut organoid culture, we determined the mechanism for KLP to induce colitis. Results: We first found that there was a positive relationship between the Mayo indexes of ulcerative colitis and KLP. Then, we isolated a strain of KLP, named Klebsiella pneumoniae J (KLPJ), from the colon tissues of patients with colitis. This strain of bacteria could induce the production of mature IL18 in colon epithelial cells and gut organoids, and also induce colitis and promote dextran sodium sulfate–mediated colitis. Using caspase-1/11-/-, NLRP3-/-, NLRC4-/-, IL18-/-, and IL22-/- mice, we showed that KLPJ-mediated colitis occurred through activation of caspase-11, and was dependent on IL18 and partly on IL22. Our data also showed that lipopolysaccharide from KLPJ could bind with caspase-11 to induce mature IL18 in mouse and human colon organoids. Conclusions: KLPJ from the colon tissues of patients with ulcerative colitis can colonize the colon, activate caspase-11 inflammasomes, and contribute to intestinal inflammation.

Hexafluoropropylene oxide dimer acid (HFPO-DA) is widely used as a substitute for perfluorooctanoic acid (PFOA). HFPO-DA exhibits high water solubility and low adsorption potential, conferring significant fluidity in aquatic environments. Given that the toxicity of HFPO-DA is similar to PFOA, it is necessary to control its content in aquatic environments. Electrochemical and thermally-activated persulfates have been successfully used to degrade HFPO-DA, but UV-activated persulfates cannot degrade the compound. Given that research on degradation mechanisms is still incomplete and lacks kinetic research, the mechanism and kinetic calculations of oxidative degradation were studied in detail using DFT calculations. And the toxicity of HFPO-DA degradation intermediates and products was evaluated to reveal the feasibility of using advanced oxidation process (AOP) technology based on persulfate to degrade HFPO-DA in wastewater. The results showed that the committed step of HFPO-DA degradation was initiated by the electron transfer reaction of SO4•- radicals. This reaction is not spontaneous at room temperature and requires sufficient electrical or thermal energy to be absorbed from the external environment. The perfluoroalcohol produced during this reaction can subsequently undergo four possible reactions: H atom abstraction from alcohol groups by an OH radical; H atom abstraction by SO4•-; direct HF removal; and HF removal with water as the catalyst. The final degradation products of HFPO-DA mainly include CO2, CF3CF2COOH, CF3COOH, FCOOH and HF, which has been identified through previous experimental analysis. Ecotoxicity assessment indicates that degradation does not produce highly toxic intermediates, and that the final products are non-toxic, supporting the feasibility of persulfate-based AOP technologies.

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new “valve-off” starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R•), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R• facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic in vivo and in vitro results suggested that this radical-enhanced “valve-off” strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.

IntroductionObesity and related metabolic issues are a growing global health concern. Recently, the discovery of new probiotics with anti-obesity properties has gained interest.MethodsIn this study, four Faecalibacte-rium prausnitzii strains were isolated from healthy human feces and evaluated on a high-fat diet-induced mouse model for 12 weeks.ResultsThe F. prausnitzii strains reduced body weight gain, liver and fat weights, and calorie intake while improving lipid and glucose metabolism in the liver and adipose tissue, as evidenced by regulating lipid metabolism-associated gene expression, including ACC1, FAS, SREBP1c, leptin, and adiponectin. Moreover, the F. prausnitzii strains inhibited low-grade inflammation, restored gut integrity, and ameliorated hepatic function and insulin resistance. Interestingly, the F. prausnitzii strains modulated gut and neural hormone secretion and reduced appetite by affecting the gut-brain axis. Supplementation with F. prausnitzii strains noticeably changed the gut microbiota composition.DiscussionIn summary, the novel isolated F. prausnitzii strains have therapeutic effects on obesity and associated metabolic disorders through modulation of the gut-brain axis. Additionally, the effectiveness of different strains might not be achieved through identical mechanisms. Therefore, the present findings provide a reliable clue for developing novel therapeutic probiotics against obesity and associated metabolic disorders.

The motivation–direction model has served as the primary framework for understanding frontal cortical activity. However, research on the link between approach/avoidance motivation and left/right frontal cortical activity has produced inconsistent findings. Recent studies suggest that regulatory systems may offer a more accurate explanation than the motivational direction model. Despite being regulatory systems, the relationship between regulatory focus and frontal cortical activity has received limited attention. Only one experimental study has explored this connection through correlational analysis, yet it lacks causal evidence. The present study aimed to address this gap by manipulating regulatory focus and measuring frontal cortical activity in 36 college students. Our results revealed that induced promotion focus led to increased left frontal cortical activity, whereas induced prevention focus led to increased right frontal cortical activity. These findings enhance our physiological understanding of regulatory focus and offer a deeper explanation of how regulatory focus influences alterations in psychology and behavior.

Natural phytochemicals are well known to protect against numerous metabolic disorders. Anthocyanins are vacuolar pigments belonging to the parent class of flavonoids. They are well known for their potent antioxidant and gut microbiome-modulating properties, primarily responsible for minimizing the risk of cardiovascular diseases, diabetes, obesity, neurodegenerative diseases, cancer, and several other diseases associated with metabolic syndromes. Berries are the primary source of anthocyanin in the diet. The color and stability of anthocyanins are substantially influenced by external environmental conditions, constraining their applications in foods. Furthermore, the significantly low bioavailability of anthocyanins greatly diminishes the extent of the actual health benefits linked to these bioactive compounds. Multiple strategies have been successfully developed and utilized to enhance the stability and bioavailability of anthocyanins. This review provides a comprehensive view of the recent advancements in chemistry, biosynthesis, dietary sources, stabilization, bioavailability, industrial applications, and health benefits of anthocyanins. Finally, we summarize the prospects and challenges of applications of anthocyanin in foods.

Persulfate-based advanced oxidation process has been proven to be a promising method for the toxic pesticide chlorpyrifos (CPY) degradation in wastewater treatment. However, due to the limitation for the short-lived intermediates detection, a comprehensive understanding for the degradation pathway remains unclear. To address this issue, density functional theory was used to analyze the degradation mechanism of CPY at the M06-2X/6-311++G(3df,3pd)//M06-2X/6-31+G(d,p) level, and computational toxicology methods were employed to explore the toxicity of CPY and its degradation products. Results show that hydroxyl radicals (·OH) and sulfate radicals (SO4•−) initiate the degradation reactions by adding to the P=S bond and abstracting the H atom on the ethyl group, rather than undergoing α-elimination of the pyridine ring in the persulfate oxidation process. Moreover, the addition products were attracted and degraded by breaking the P–O bond, while the abstraction products were degraded through dealkylation reactions. The transformation products, including 3,5,6-trichloro-2-pyridynol, O,O-diethyl phosphorothioate, chlorpyrifos oxon, and acetaldehyde, obtained through theoretical calculations have been detected in previous experimental studies. The reaction rate constants of CPY with ·OH and SO4•− were 6.32 × 108 and 9.14 × 108 M−1·s−1 at room temperature, respectively, which was consistent with the experimental values of 4.42 × 109 and 4.5 × 109 M−1 s−1. Toxicity evaluation results indicated that the acute and chronic toxicity to aquatic organisms gradually decreased during the degradation process. However, some products still possess toxic or highly toxic levels, which may pose risks to human health. These research findings contribute to understanding the transformation behavior and risk assessment of CPY in practical wastewater treatment.

Egg white proteins pose notable limitations in emulsion applications due to their inadequate wettability and interfacial instability. Polyphenol-driven alterations in proteins serve as an effective strategy for optimizing their properties. Herein, covalent and non-covalent complexes of egg white proteins-proanthocyanins were synthesized. The analysis of structural alterations, amino acid side chains and wettability was performed. The superior wettability (80.00° ± 2.23°) and rigid structure (2.95 GPa) of covalent complexes established favorable conditions for their utilization in emulsions. Furthermore, stability evaluation, digestion kinetics, free fatty acid (FFA) release kinetics, and correlation analysis were explored to unravel the impact of covalent and non-covalent modification on emulsion stability, dynamic digestion process, and interlinkages. Emulsion stabilized by covalent complex exhibited exceptional stabilization properties, and FFA release kinetics followed both first-order and Korsmeyer–Peppas models. This study offers valuable insights into the application of complexes of proteins-polyphenols in emulsion systems and introduces an innovative approach for analyzing the dynamics of the emulsion digestion process.

Abstract Background Stomach adenocarcinomas (STAD) are the most common malignancy of the human digestive system and represent the fourth leading cause of cancer-related deaths. As early-stage STAD are generally mild or asymptomatic, patients with advanced STAD have short overall survival. Early diagnosis of STAD has a considerable influence on clinical outcomes. Methods The mRNA expression data and clinical indicators of STAD and normal tissues were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The gene expression differences were analyzed by R packages, and gene function enrichment analysis was performed. Kaplan–Meier method and univariate Cox proportional risk regression analysis were used to screen differential expressed genes (DEGs) related to survival of STAD patients. Multivariate Cox proportional risk regression analysis was used to further screen and determine the prognostic DEGs in STAD patients, and to construct a multigene prognostic prediction signature. The accuracy of predictive signature was tested by receiver operating characteristic (ROC) curve software package, and the nomogram of patients with STAD was drawn. Cox regression was used to investigate the correlation between multigene prognostic signature and clinical factors. The predictive performance of this model was compared with two other models proposed in previous studies using KM survival analysis, ROC curve analysis, Harrell consistency index and decision curve analysis (DCA). qRT-PCR and Western blot were used to verify the expression levels of prognostic genes. The pathways and functions of possible involvement of features were predicted using the GSEA method. Results A total of 569 early-stage specific DEGs were retrieved from TCGA-STAD dataset, including 229 up-regulated genes and 340 down-regulated genes. Enrichment analysis showed that the early-stage specific DEGs were associated with cytokine–cytokine receptor interaction, neuroactive ligand–receptor interaction, and calcium signaling pathway. Multiple Cox regression algorithm was used to identify 10 early-stage specific DEGs associated with overall survival (P

Bile acids (BAs) as cholesterol-derived molecules play an essential role in some physiological processes such as nutrient absorption, glucose homeostasis and regulation of energy expenditure. They are synthesized in the liver as primary BAs such as cholic acid (CA), chenodeoxycholic acid (CDCA) and conjugated forms. A variety of secondary BAs such as deoxycholic acid (DCA) and lithocholic acid (LCA) and their derivatives is synthesized in the intestine through the involvement of various microorganisms. In addition to essential physiological functions, BAs and their metabolites are also involved in the differentiation and functions of innate and adaptive immune cells such as macrophages (Macs), dendritic cells (DCs), myeloid derived suppressive cells (MDSCs), regulatory T cells (Treg), Breg cells, T helper (Th)17 cells, CD4 Th1 and Th2 cells, CD8 cells, B cells and NKT cells. Dysregulation of the BAs and their metabolites also affects development of some diseases such as inflammatory bowel diseases. We here summarize recent advances in how BAs and their metabolites maintain gut and systemic homeostasis, including the metabolism of the BAs and their derivatives, the role of BAs and their metabolites in the differentiation and function of immune cells, and the effects of BAs and their metabolites on immune-associated disorders.

The endoplasmic reticulum protein TECRL promotes mitochondrial function in cardiomyocytes and its knockout in mice leads to cardiac dysfunction, decreased mitochondria function, and elevated levels of reactive oxygen species.

Abstract Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics, and currently used drugs cannot reverse the disease progress. Worse still, there are still challenges to be addressed to fully decipher the intricated pathogenesis. Thus, specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed. In this work, multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents. By utilizing an unbiased and time-resolved analysis of the transcriptome, proteome and phosphoproteome of a silicosis mouse model, we have verified the significant differences in transcript, protein, kinase activity and signaling pathway level during silicosis progression, in which the importance of essential biological processes such as macrophage activation, chemotaxis, immune cell recruitment and chronic inflammation were emphasized. Notably, the phosphorylation of EGFR (p-EGFR) and SYK (p-SYK) were identified as potential therapeutic targets in the progression of silicosis. To inhibit and validate these targets, we tested fostamatinib (targeting SYK) and Gefitinib (targeting EGFR), and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis. Overall, our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis.

Abstract Background The use of beneficial microorganisms as an alternative for pest control has gained increasing attention. The objective of this study was to screen beneficial rhizosphere bacteria with the ability to enhance tomato anti-herbivore resistance. Results Rhizosphere bacteria in tomato field from Fuqing, one of the four locations where rhizosphere bacteria were collected in Fujian, China, enhanced tomato resistance against the tobacco cutworm Spodoptera litura, an important polyphagous pest. Inoculation with the isolate T6–4 obtained from the rhizosphere of tomato field in Fuqing reduced leaf damage and weight gain of S. litura larvae fed on the leaves of inoculated tomato plants by 27% in relative to control. Analysis of 16S rRNA gene sequence identities indicated that the isolate T6–4 was closely related to Stenotrophomonas rhizophila supported with 99.37% sequence similarity. In the presence of S. litura infestation, inoculation with the bacterium led to increases by a 66.9% increase in protease inhibitor activity, 53% in peroxidase activity and 80% in polyphenol oxidase activity in the leaves of inoculated plants as compared to the un-inoculated control. Moreover, the expression levels of defense-related genes encoding allene oxide cyclase (AOC), allene oxide synthase (AOS), lipoxygenase D (LOXD) and proteinase inhibitor (PI-II) in tomato leaves were induced 2.2-, 1.7-, 1.4- and 2.7-fold, respectively by T6–4 inoculation. Conclusion These results showed that the tomato rhizosphere soils harbor beneficial bacteria that can systemically induce jasmonate-dependent anti-herbivore resistance in tomato plants.

While rare, SARS-CoV-2-infected children can develop severe COVID-19 (ARDS) or inflammatory syndrome (MIS-C). Here, the authors use proteomics to characterize hundreds of blood proteins and identify key biological pathways that differentiate MIS-C and ARDS.

Abstract Background Epilepsy is one of the most common chronic neurological diseases that adversely impact the quality of life of patients and their families. The “Quality of Life of Childhood Epilepsy Questionnaire” (hereinafter referred to as “QOLCE-16”) is a 16-item measure that was designed to assess health-related quality of life (HRQOL) among children with epilepsy. The purpose of the study was to translate and evaluate the psychometric properties of the QOLCE-16. Methods The 10 steps of Principles of Good Practices for translation and cultural adaptation of measures were adopted to translate the QOLCE-16 into Chinese. After that, item analysis, floor effect and ceiling effect, internal consistency, test–retest reliabilities, content validity and construct validity were conducted to test its applicability in children with epilepsy in China. A total of 435 native Chinese-speaking parents with children who had epilepsy from one children’s hospital were invited to take part in the study, including a cognitive interview sample of 5 and a validation sample of 430. Results A total of 414 objects were enrolled in our study for psychometric testing. The results of the item analysis revealed QOLCE-16-C to have good discrimination, the floor effect and ceiling effect were 0.2% and 1.0% respectively, and each item was significantly related to the total scale (P

Abstract Blindness caused by corneal damage affects millions of people worldwide, and this number continues to rise. However, rapid epithelization and a stable epithelium process are the two biggest challenges for traditional corneal materials. These processes are related to corneal curvature, which is an important factor in determination of the corneal healing process and epithelial behavior during corneal damage. In this study, smooth 3D‐printed convex corneal implants based on gelatin methacrylate and collagen are generated. As epithelium distribution and adhesion vary in different regions of the natural cornea, this work separates the surfaces into four regions and studies how cells sense topological cues on curvature. It is found that rabbit corneal epithelial cells (RCECs) seeded on steeper slope gradient surfaces on convex structures result in more aligned cell organization and tighter cell‐substrate adhesion, which can also be verified through finite element simulation and signaling pathway analysis. In vivo transplantation of convex implants result in a better fit with adjacent tissue and stronger cell adhesion than flat implants, thereby accelerating corneal epithelialization and promoting collagen fibers and neural regeneration within 180 days. Taken together, printed convex corneal implants that facilitate corneal regeneration may offer a translational strategy for the treatment of corneal damage.

Stachyose is a well-known gut microbiota-oriented prebiotic that could directly reach colon and influence the intestinal microenvironment. Through an in vitro fermentation on fecal microbiota from a drug-naive new-onset and a perennial patient, we for the first time revealed a novel function of stachyose on promoting the microbial transformation from tryptophan to indole catabolites (i.e., indole-3-propionic acid, indole-3-lactic acid and indole-3-carboxaldehyde), which has shown to improve intestinal functions and glucose metabolism. Stachyose increased Bifidobacterium and Lactobacillus genera, while reducing Lactococcus and Streptococcus. Similar regulatory effects on microbial transformation of tryptophan and its related microbiota were confirmed in C57BL/6 mice with high-fat-diet induced impaired fasting glucose and gut dysbacteria. Additionally, stachyose up-regulated microbiota related metabolites with ameliorative effects on type 2 diabetes, i.e., hyocholic acid and conjugated linoleic acid in vitro. Our study proves benefits of stachyose for management of type 2 diabetes via regulating microbial metabolism of tryptophan.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high morbidity and fatality rate. Traditional diagnostic methods for HCC are primarily based on clinical presentation, imaging features, and histopathology. With the rapid development of artificial intelligence (AI), which is increasingly used in the diagnosis, treatment, and prognosis prediction of HCC, an automated approach to HCC status classification is promising. AI integrates labeled clinical data, trains on new data of the same type, and performs interpretation tasks. Several studies have shown that AI techniques can help clinicians and radiologists be more efficient and reduce the misdiagnosis rate. However, the coverage of AI technologies leads to difficulty in which the type of AI technology is preferred to choose for a given problem and situation. Solving this concern, it can significantly reduce the time required to determine the required healthcare approach and provide more precise and personalized solutions for different problems. In our review of research work, we summarize existing research works, compare and classify the main results of these according to the specified data, information, knowledge, wisdom (DIKW) framework.

Abstract Halogen perovskite, a novel semiconductor material that has gained momentum in the energy sector, has also emerged in the field of electromagnetic wave (EMW) protection. Inorganic halogen perovskites are expected to perform well owing to their excellent stability and dielectric properties. In this study, a CsPbBr3/Carbon nanotubes (CNTs) composite is designed using a convenient antisolvent method. In addition to an ultrawide absorption bandwidth (5.56 GHz) and ultrahigh absorption strength (|Reflection loss| = 51.74 dB), the composite shows excellent thermal stability and environmental tolerance. In an air environment, its EMW‐absorbing performance can be maintained at a high level at a temperature below 400 °C. CNTs build an efficient conductive network between CsPbBr3 to enhance the conduction loss of the composite, while it brings more defects and vacancies to the surface of CsPbBr3 to form electrical polarization centers which improving the polarization loss of the composite. This is the first study of the application of inorganic halogen perovskites in the field of EMW absorption. The excellent EMW‐absorbing performance and stability of CsPbBr3/CNTs demonstrate the great potential of inorganic halogen perovskites in the field of EMW absorption and provide a valuable reference and feasible strategy for regulating and controlling the EMW‐absorbing performance of perovskite materials.

Background The etiology of inflammatory bowel disease (IBD) remains unclear. However, intestinal metabolism is known to be critical in the pathogenesis of IBD. Bile acid is one of the main intestinal metabolites, and its role in the pathogenesis of IBD is worthy of investigation. This study investigated the role of deoxycholic acid (DCA), a bile acid, in the pathogenesis of IBD. Methods Peripheral serum metabolomics, fecal metabolomics, and microbiome analyses were performed on patients with IBD and healthy controls. Flow cytometry, real-time quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence analysis were used to evaluate cytokines in the inflamed colonic mucosa and immune cells and tuft cells in the intestine of mice with dextran sulfate sodium (DSS)-induced colitis. Results In total, 156 patients with IBD and 58 healthy controls were enrolled. DCA levels in the serum and feces of patients with IBD were significantly decreased compared to the controls. This decrease was associated with a decrease in the abundance of intestinal flora, including Firmicutes, Clostridia, Ruminnococcaceae, and Lachnospiraceae. Additionally, interleukin (IL)-1β levels in the serum of patients with active Crohn’s disease were significantly increased compared with the healthy controls. Moreover, in DCA-treated DSS-induced mice, the expression of IL-1β and the proportion of CD3+ and CD4+ T cells increased while the number of intestinal tuft cells decreased, compared with the DSS group. Conclusion In IBD patients, the decreased DCA levels in serum and fecal samples are associated with disturbances in gut microflora diversity and abundance. Possible mechanisms by which DCA affects immunity in DSS-induced murine colitis include increasing IL-1β secretion, reducing the number of tuft cells in the mucosa, and activating CD4+ and CD3+ T cells to exaggerate immune responses, consequently worsening intestinal inflammation.

Objective To explore the impact of the COVID-19 epidemic on platelets supply management and its countermeasures. Methods Relevant data on platelets collection, supply, daily inventory and adjustment were collected through the blood information management system of our blood center after the outbreak of the epidemic in Xi′an (from December 9, 2021 to February 2, 2022), and then compared with the data during the corresponding period of last year (from December 9, 2020 to February 2, 2021). Results In this study, in the first half month of the epidemic, the collection and supply of platelets were slightly higher than the same period of the previous year. After the first-level response to the epidemic was initiated, the collection and issuing of platelets decreased significantly compared with the same period of the previous year. Half a month after the home isolation had been gradually lifted, the collection and issuing of platelets increased significantly as compared with the home isolation period. Otherwise, the collection and issuing of platelets had been increased as compared with the same period of the previous year. Conclusion After the outbreak of the epidemic, the timely adjustment of platelet collection strategy as well as the launch of emergency plan for platelets collection and supply during the first-level response to the epidemic effectively ensured the supply of clinical platelets in Xi′an during the period of home isolation.

Abstract Background IL-35–producing Bregs and Treg cells critically regulate chronic illnesses worldwide via mechanisms related to disrupting the gut microbiota composition. However, whether the gut microbiota regulates these IL-35+ cells remains elusive. We herein investigated the regulatory effects of the gut microbiota on IL-35+ cells by using genetically modified mouse models of obesity. Results We first found that gut Reg4 promoted resistance to high-fat diet-induced obesity. Using 16S rRNA sequencing combined with LC-MS (liquid chromatography–mass spectrometry)/MS, we demonstrated that gut Reg4 associated with bacteria such as Lactobacillus promoted the generation of IL-35+ B cells through 3-idoleacetic acid (IAA) in the presence of LPS. HuREG4 IECtg mice fed a high-fat diet exhibited marked IL-35+ cell accumulation in not only their adipose tissues but also their colons, whereas decreased IL-35+ cell accumulation was observed in the adipose and colon tissues of Reg4 knockout (KO) mice. We also found that Reg4 mediated HFD-induced obesity resistance via IL-35. Lower levels of IAA were also detected in the peripheral blood of individuals with obesity compared with nonobese subjects. Mechanistically, IAA together with LPS mediated IL-35+ B cells through PXR and TLR4. KO of PXR or TLR4 impaired the generation of IL-35+ B cells. Conclusion Together, IAA and LPS induce the generation of IL-35+ B cells through PXR and TLR4. Video Abstract

Fan, Hou et al. investigate the role of phosphodiesterase (PDE) 4 and the PDE4-cAMP-PKA pathway on hypertension, reporting that PDE4D is upregulated in hypertension induced by angiotensin II. The authors also show that Pde4d knockout in mouse SMCs attenuates Ang II-induced hypertension and implicate AMPK signalling and MYPT1-MLC phosphorylation in Ang II-induced SMC contraction.

The reservoir space, types and distribution characteristics of karst carbonate gas reservoirs in the fourth member of Sinian Dengying Formation (Deng 4 Member) in central Sichuan Basin are analyzed based on the drilling, logging and seismic data. A development model of karst reservoirs is constructed to support the high-efficiency development of gas pools. The research shows that the reservoirs in Deng 4 Member have mainly small-scale karst vugs and fractures as storage space, and can be divided into three types, fracture-vug, pore-vug and pore types. The development patterns of the karst reservoirs are determined. On the plane, the karst layers increase from 65 m to 170 m in thickness from the karst platform to the karst slope, and the high-quality reservoirs increase from 25.0 m to 42.2 m in thickness; vertically, the reservoirs at the top of Deng 4 Member appear in multiple layers, and show along-bedding and along fracture dissolution characteristics. The reservoirs at the bottom are characterized by the dissolution parallel to the water level during the karstification period, and have 3–5 large-scale fracture-cave systems. Based on the reservoir development characteristics and the genetic mechanism, three types of reservoir development models of karst reservoir are established, i.e., bed-dissolved body, fracture- dissolved body and paleohorizon-dissolved body. The construction of karst reservoir development models and seismic response characteristics of the three types of reservoirs can provide parameter for well placement and trajectory design, and substantially improve productivity and development indices of individual wells and gas reservoirs. The designed production capacity of the gas reservoir has enhanced from the initial 3.6 billion to 6 billion cubic meters, making the profit of the reservoir development increase noticeably.

Abstract Background Although approximately 50% of Chinese with type 2 diabetes mellitus (T2DM) patients have vitamin D deficiency, studies regarding vitamin D supplementation on insulin resistance (IR) have mainly focused on non-Asians. Endurance exercise training (ET) enhances insulin-mediated glucose metabolism, which plays a critical role in T2DM prevention and control. However, the combined effects of vitamin D supplementation and ET on IR in T2DM patients are unclear. The objectives of this study is to investigate the synergistic effect of vitamin D supplementation combined with exercise training intervention on IR in T2DM patients. Methods and analysis We propose a 3-month randomized controlled trial among 60 T2DM patients aged 40–65, newly diagnosed with T2DM ≤ 1 year, and with stable HbA1c level (≤ 8.0%) in the past 3 months. The participants will be randomly allocated to the vitamin D group, vitamin D combined with exercise training group, exercise training group, and control group (CG) using a computer-generated random number sequence. At baseline, participants will undergo a medical review, anthropometric measurements, dual X-ray absorptiometry, a 75-g oral glucose tolerance test (OGTT), ankle-brachial index measurements, and physical fitness measurements and will complete related lifestyle questionnaires. Fasting blood lipid and glucose levels were also measured. In a 3-month intervention period, vitamin D intervention group will receive a dose of 1000 IU daily; exercise group will perform a 1-h endurance exercise 3 times per week (maximal heart rate, 60–80%), and the control group will receive apparently identical tablets. Additionally, all participants will be advised to maintain their normal diet and physical activities during the intervention. All measurements will be repeated at 3-month follow-up after the intervention with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion. Secondary outcome measures will compare the changes in anthropometry, ankle-brachial index, and physical fitness factors (e.g., peak oxygen uptake, hand grip strength). Data will be managed and analyzed using the Statistical Package for the Social Sciences. Discussion This is the first study to conduct a randomized trial to clearly determine the independent and combined effects of vitamin D supplementation and endurance exercise trial on IR in Chinese T2DM patients as measured by OGTT. The findings from the proposed study will not only provide new evidences that vitamin D supplementation plays an important role in IR management but also develop a simple and efficient method to improve IR-associated metabolic diseases for T2DM patients. Trial registration Chinese Clinical Trial Registry ChiCTR1800015383 , Registered on 28 March 2018

Objectives: To explore the differences in the cortical morphometric similarity network (MSN) between COVID-19 survivors and healthy controls, and the correlation between these differences and behavioral features and transcriptional signatures. Materials & methods: 39 COVID-19 survivors and 39 age-, sex- and education years-matched healthy controls (HCs) were included. All participants underwent MRI and behavioral assessments (PCL-17, GAD-7, PHQ-9). MSN analysis was used to compute COVID-19 survivors vs. HCs differences across brain regions. Correlation analysis was used to determine the associations between regional MSN differences and behavioral assessments, and determine the spatial similarities between regional MSN differences and risk genes transcriptional activity. Results: COVID-19 survivors exhibited decreased regional MSN in insula, precuneus, transverse temporal, entorhinal, para-hippocampal, rostral middle frontal and supramarginal cortices, and increased regional MSN in pars triangularis, lateral orbitofrontal, superior frontal, superior parietal, postcentral, and inferior temporal cortices. Regional MSN value of lateral orbitofrontal cortex was positively associated with GAD-7 and PHQ-9 scores, and rostral middle frontal was negatively related to PHQ-9 scores. The analysis of spatial similarities showed that seven risk genes (MFGE8, MOB2, NUP62, PMPCA, SDSL, TMEM178B, and ZBTB11) were related to regional MSN values. Conclusion: The MSN differences were associated with behavioral and transcriptional signatures, early psychological counseling or intervention may be required to COVID-19 survivors. Our study provided a new insight into understanding the altered coordination of structure in COVID-19 and may offer a new endophenotype to further investigate the brain substrate.

The well-established semantic fluency test measures the ability to produce a sequence of spoken words from a particular category within a limited period of time. Like patients with Parkinson’s disease (PD), patients with progressive supranuclear palsy (PSP) tend to produce fewer correct words than age-matched healthy adults. This study further examined the difference between patients with PSP and PD in their semantic fluency performance using a graph theory-based approach. Twenty-nine patients with PSP Richardson’s syndrome (PSP-RS), thirty-eight patients with PD, and fifty-one healthy controls (HC) were recruited. All participants completed a standard semantic fluency test (animals). Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. The speech graphs of the PSP-RS group showed higher density, shorter diameter, and shorter average shortest path than those of the PD and HC groups. It indicates that the PSP-RS group produced smaller and denser speech graphs than the PD and HC groups. In the PSP-RS group, moreover, the average shortest paths of the speech graphs correlated with the severity of motor symptoms. This study shows the potential of the graph theory-based approach in distinguishing the semantic fluency performance of nondemented patients with PSP-RS and PD.

Since the accurate early gas well production regime is related to the production period and final productivity, it is crucial to make better use of early flow stage production data for gas well productivity evaluation. Absolute open flow potential (AOF) and estimated ultimate recovery (EUR) are essential parameters for evaluating the productivity of shale gas wells. This study establishes new AOF calculation methods for the early production stage. The analytical model can calculate the AOF only by using stable pressure and production data in the flowback stage, which greatly improves the efficiency of productivity evaluation. Three methods have, respectively, calculated the productivity of the shale gas wells above 3500 m in the Luzhou block. The results show that well L2-3 has the highest AOF, averaging 278.1×104 m3/d, whereas well Y2-8 has the lowest AOF, averaging 100.2×104 m3/d. Different AOF calculation methods are identified for gas wells in different stages of production. For gas wells in the initial unstable flow stage, a pseudogas production index method is recommended. A water production index analysis method, with lower evaluation results, is proposed for gas wells in the flowback stage. A modern production decline analysis method is found to be preferred for calculating the EUR of deep shale gas wells. Well L2-3 has the highest average EUR of 1.26×108 m3, whereas well Y2-8 has the lowest average EUR of 0.42×108 m3. The Blasingame method is recommended for medium-to-high-production gas wells, whereas a normalized pressure integral method is suggested for low-production wells. A strong exponential quantitative link between the AOF and the EUR shows that a fracture system’s initial productivity has a significant impact on a well’s EUR. The findings of this study enrich the productivity evaluation system, increase the accuracy of productivity evaluation results, and provide theoretical support for deep shale gas wells.

ABSTRACT Antibiotic resistance genes (ARGs) pose a serious threat to public health and ecological security in the 21st century. However, the resistome only accounts for a tiny fraction of metagenomic content, which makes it difficult to investigate low-abundance ARGs in various environmental settings. Thus, a highly sensitive, accurate, and comprehensive method is needed to describe ARG profiles in complex metagenomic samples. In this study, we established a high-throughput sequencing method based on targeted amplification, which could simultaneously detect ARGs (n = 251), mobile genetic element genes (n = 8), and metal resistance genes (n = 19) in metagenomes. The performance of amplicon sequencing was compared with traditional metagenomic shotgun sequencing (MetaSeq). A total of 1421 primer pairs were designed, achieving extremely high coverage of target genes. The amplicon sequencing significantly improved the recovery of target ARGs (~9 × 104-fold), with higher sensitivity and diversity, less cost, and computation burden. Furthermore, targeted enrichment allows deep scanning of single nucleotide polymorphisms (SNPs), and elevated SNPs detection was shown in this study. We further performed this approach for 48 environmental samples (37 feces, 20 soils, and 7 sewage) and 16 clinical samples. All samples tested in this study showed high diversity and recovery of targeted genes. Our results demonstrated that the approach could be applied to various metagenomic samples and served as an efficient tool in the surveillance and evolution assessment of ARGs. Access to the resistome using the enrichment method validated in this study enabled the capture of low-abundance resistomes while being less costly and time-consuming, which can greatly advance our understanding of local and global resistome dynamics. IMPORTANCE ARGs, an increasing global threat to human health, can be transferred into health-related microorganisms in the environment by horizontal gene transfer, posing a serious threat to public health. Advancing profiling methods are needed for monitoring and predicting the potential risks of ARGs in metagenomes. Our study described a customized amplicon sequencing assay that could enable a high-throughput, targeted, in-depth analysis of ARGs and detect a low-abundance portion of resistomes. This method could serve as an efficient tool to assess the variation and evolution of specific ARGs in the clinical and natural environment.

IntroductionFermented egg-milk peptides (FEMPs) could enhance the colon-intestinal barrier and upgrade the expression of zonula occludens-1 and mucin 2. Besides, the underlying biological mechanism and the targets FEMPs could regulate were analyzed in our study.MethodsHerein, the immunofluorescence technique and western blot were utilized to evaluate the repair of the intestinal barrier. Network pharmacology analysis and bioinformatics methods were performed to investigate the targets and pathways affected by FEMPs.Results and discussionAnimal experiments showed that FEMPs could restore intestinal damage and enhance the expression of two key proteins. The pharmacological results revealed that FEMPs could regulate targets related to kinase activity, such as AKT, CASP, RAF, and GSK. The above targets could interact with each other. GO analysis indicated that the targets regulated by FEMPs could participate in the kinase activity of the metabolic process. KEGG enrichment revealed that the core targets were enriched in pathways related to cell apoptosis and other important procedures. Molecular docking demonstrated that FEMPs could bind to the key target AKT via hydrogen bond interactions. Our study combined the experiment in vivo with the method in silico and investigated the interaction between peptides and targets in a pattern of multi-targets and multi-pathways, which offered a new perspective on the functional validation and potential application of bioactive peptides.

Antimicrobial proteins possess a broad spectrum of bactericidal activity and play an important role in shaping the composition of gut microbiota, which is related to multiple diseases such as metabolic syndrome. However, it is incompletely known for the regulation of defensin expression in the gut Paneth cells. Here, we found that FABP4 in the Paneth cells of gut epithelial cells and organoids can downregulate the expression of defensins. FABP4fl/flpvillinCreT mice were highly resistance to Salmonella Typhimurium (S.T) infection and had increased bactericidal ability to pathogens. The FABP4-mediated downregulation of defensins is through degrading PPARγ after K48 ubiquitination. We also demonstrate that high-fat diet (HFD)-mediated downregulation of defensins is through inducing a robust FABP4 in Paneth cells. Firmicutes/Bacteroidetes (F/B) ratio in FABP4fl/flpvillinCreT mice is lower than control mice, which is opposite to that in mice fed HFD, indicating that FABP4 in the Paneth cells could reprogram gut microbiota. Interestingly, FABP4-mediated downregulation of defensins in Paneth cells not only happens in mice but also in human. A better understanding of the regulation of defensins, especially HFD-mediated downregulation of defensin in Paneth cells will provide insights into factor(s) underlying modern diseases.Abbreviations: FABP4: Fatty acid binding protein 4; S. T: Salmonella Typhimurium; HFD: High-fat diet; Defa: α-defensin; 930 HD5: Human α-defensin 5; HD6: Human α-defensin 6; F/B: Firmicutes/Bacteroidetes; SFB: Segmental filamentous bacteria; AMPs: Antimicrobial peptides; PPARγ: Peroxisome proliferator-activated receptor γ; P-PPAR: Phosphorylated PPAR; Dhx15: DEAD-box helicase 15; 935 EGF: Epidermal growth factor; ENR: Noggin and R-spondin 1; CFU: Colony forming unit; Lyz1: Lysozyme 1; Saa1: Serum amyoid A 1; Pla2g2a: Phospholipase A2, group IIA; MMP-7: Matrix metalloproteinase; AU-PAGE: Acid-urea polyacrylamide gel electrophoresis; PA: Palmitic 940 acid; GPR40: G-protein-coupled receptor; GF: Germ-free; EGF: Epidermal growth factor; LP: Lamina propria; KO: Knock out; WT: Wild-type.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiomyopathy, which is one of the most common reasons for cardiac arrest in children or adolescents. It is characterized by ventricular hypertrophy (usually left ventricle), small ventricular cavity, and reduced ventricular diastolic compliance found by echocardiography in the absence of abnormal load (such as hypertension or aortic stenosis). HCM is usually caused by mutations in genes encoding sarcomere or sarcomere-related genes. Whole exome sequencing (WES) is performed to identify probable causative genes. Through WES, we identified LIM domain-binding protein 3 (LDB3) mutations (R547Q and P323S) respectively in an 11-year-old HCM girl and a 6-year-old HCM boy. Neural network analyses showed that the LDB3 (R547Q and P323S) mutation decreased its protein stability, with confidence scores of −0.9211 and −0.8967. The STRUM server also confirmed that the mutation decreased its protein stability. Thus, LDB3 mutation may be associated with heritable HCM. To our knowledge, this is the first time to report LDB3 heterozygous variants (R547Q and P323S) responsible for heritable HCM.

Abstract Background There are differences in survival between high-and low-grade Upper Tract Urothelial Carcinoma (UTUC). Our study aimed to develop a nomogram to predict overall survival (OS) of patients with high- and low-grade UTUC after tumor resection, and to explore the difference between high- and low-grade patients. Methods Patients confirmed to have UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. The UTUCs were identified and classified as high- and low-grade, and 1-, 3- and 5-year nomograms were established. The nomogram was then validated using the Chinese multicenter dataset (patients diagnosed in Shandong, China between January 2010 and October 2020). Results In the high-grade UTUC patients, nine important factors related to survival after tumor resection were identified to construct nomogram. The C index of training dataset was 0.740 (95% confidence interval [CI]: 0.727–0.754), showing good calibration. The C index of internal validation dataset was 0.729(95% CI:0.707–0.750). On the other hand, Two independent predictors were identified to construct nomogram of low-grade UTUC. The C index was 0.714 (95% CI: 0.671–0.758) for the training set,0.731(95% CI:0.670–0.791) for the internal validation dataset. Encouragingly, the nomogram was clinically useful and had a good discriminative ability to identify patients at high risk. Conclusion We constructed a nomogram and a corresponding risk classification system predicting the OS of patients with an initial diagnosis of high-and low-grade UTUC.

Cloning quantitative trait loci (QTL) in crops is often slow and laborious. Here, the authors describe RapMap, a method to rapidly clone multiple QTL based on F2 gradient populations coupled with a co-segregation standard, and show how it can be used to identify genes controlling grain size in rice.

Abstract We present predictions for hadronic decays of the Higgs boson at next-to-next-to-leading order (NNLO) in QCD matched with parton shower based on the POWHEG framework. Those include decays into bottom quarks with full bottom-quark mass dependence, light quarks, and gluons in the heavy top quark effective theory. Our calculations describe exclusive decays of the Higgs boson with leading logarithmic accuracy in the Sudakov region and next-to-leading order (NLO) accuracy matched with parton shower in the three-jet region, with normalizations fixed to the partial width at NNLO. We estimated remaining perturbative uncertainties taking typical event shape variables as an example and demonstrated the need of future improvements on both parton shower and matrix element calculations. The calculations can be used immediately in evaluations of the physics performances of detector designs for future Higgs factories.

Background: Exercise can modulate gut microbiota and lower the risk of cardiovascular disease (CVD). However, the association between exercise-induced changes in gut microbiota and CVD risk have not been investigated.Objective: This study determined the effects of exercise training on CVD risk and gut microbiota in physically active elderly women and whether exercise-induced gut microbiota changes were associated with CVD risk.Methods: An 8-week randomized controlled trial was conducted with 14 elderly women assigned to exercise group (n = 8) or control group (n = 6). Physical function, sarcopenic obesity, and metabolic syndrome were evaluated as components of CVD risk. Gut microbiota composition was determined using 16S rRNA gene sequencing. Repeated-measures analysis of variance was used to examine intra-group and inter-group differences.Results: A significant group × time interaction was observed for chair sit-and-reach (F = 8.262, p = 0.014), single-leg standing with eyes closed (F = 7.340, p = 0.019), waist circumference (F = 6.254, p = 0.028), and body fat mass (F = 12.263, p = 0.004), for which the exercise group showed improved trends. The exercise group exhibited significant improvements in skeletal muscle mass (p = 0.041) and fasting blood glucose (p = 0.017). Regarding gut microbiota, a significant interaction was observed for the class Betaproteobacteria (F = 6.822, p = 0.023) and genus Holdemania (F = 4.852, p = 0.048).Conclusion: The 8-week exercise training improved physical function, lowered CVD risk, and modulated relative abundance of gut microbiota associated with CVD in physically active elderly women.

ABSTRACT Antimicrobial resistance (AMR) seriously threatens public health by reducing antibiotic effectiveness in curing bacterial infections. Atmospheric particulate matter (APM) is a common environmental hazard that affects human health by causing various diseases and disseminating bacterial pathogenesis, of which pathogenic bacteria and AMR are essential parts. The properties of APM microbiomes and resistomes, along with their shaping factors and mutual relationships, need further examination. To address this, we analyzed APMs collected from 13 cities within four clusters (North and South China, Inner Mongolia, and Tibet). Significant regionalization was found for both the microbiomes (P < 0.001) and core resistomes (P < 0.001) for APMs, with statistical analyses showing significant differences in different regions. Principal coordinate analysis (PCoA) and accompanying ANOSIM analyses showed that microbiomes and core resistomes followed the same regional subclustering hierarchy patterns. This finding, together with response analysis of APM microbiomes and core resistomes to environmental parameters that showed similar response patterns, as well as Procrustes analysis (M2 = 0.963, P < 0.05) between APM microbiomes and core resistomes, strongly suggested that APM microbiomes and core resistomes are correlated. Co-occurrence network analysis further revealed key taxa and antimicrobial resistance determinants in the interactions between APM microbiomes and core resistomes. Thus, it was concluded that APM microbiome and resistome compositions were highly regional, that environmental pollutants and APM levels impacted APM microbiomes and resistomes, and that microbiomes and resistomes in APMs are significantly correlated (P < 0.05). IMPORTANCE Bacteria associated with atmospheric particulate matter (APMs) can transmit over long distances. A large portion of these bacteria can potentially threaten human health. The antimicrobial resistance (AMR) of pathogenic bacteria carried by APMs prevents curing from infections. Therefore, both the pathogenic bacteria in APMs and their AMR are receiving more attention. The literature suggests a knowledge gap that exists for bacterial AMR and bacterial pathogenesis in APMs, including their distribution patterns, mutual relationships, and factors influencing their compositions. This work aimed to bridge this knowledge gap by studying APM samples collected from 13 cities. The results demonstrated that both bacteria and antibiotic resistance determinants were highly regional and that their composition patterns were significantly correlated, and influenced by the same group of environmental factors. This study thus determined the relationship between the two important aspects of bacterial pathogenesis in APMs and represents significant progress in understanding bacterial pathogenesis in APMs.

This study aimed to assess the effects of a 12-week vitamin D and endurance exercise intervention on bone health, body composition and physical performance among patients with type 2 diabetes. Totally, 61 patients were randomly assigned to vitamin D (VDG), exercise (EG), vitamin D and exercise intervention (VEG), and control (CG) groups. Bone health (bone mineral density, BMD; bone mineral content, BMC), body composition and physical performance were measured before and after the intervention. Dual energy X-ray absorptiometry was used to assess bone health and body composition. There were no additive effects of vitamin D beyond exercise were observed. Vitamin D supplementation had significant effects on maintaining bone health compared with their counterpart Total (BMC, EG + CG: 2,719.9 ± 70.0 vs. 2,670.1 ± 65.6; VDG + VEG: 2,610.9 ± 88.2 vs. 2,605.3 ± 84.8; trunk BMC, 870.2 ± 26.8 vs. 836.3 ± 23.7; 824.8 ± 29.5 vs. 822.1 ± 27.8; spine BMD, 1.15 ± 0.03 vs. 1.11 ± 0.02; 1.09 ± 0.03 vs. 1.09 ± 0.02) were observed. Exercise had a main effect on the reduction of total and trunk BF%. Patients in EG had a decreased BMC, while it was alleviated in VEG after intervention. Although no additive effect of vitamin D supplementation beyond exercise training, the supplementation had a potential effect on the prevention of bone loss induced by exercise only.