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Abstract Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into NAD + within the body after ingestion. NMN plays a pivotal role in several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. NMN has emerged as a key focus of research in the fields of biomedicine, health care, and food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights into the pathogenesis of age- and aging-related diseases. Given the sustained global research interest in NMN and the substantial market expectations for the future, here, we comprehensively review the milestones in research on NMN biotherapy over the past 10 years. Additionally, we highlight the current research on NMN in the field of digestive system diseases, identifying existing problems and challenges in the field of NMN research. The overarching aim of this review is to provide references and insights for the further exploration of NMN within the spectrum of digestive system diseases.

Abstract Consensus plays a crucial role in blockchain technology, with the delegated proof of stake (DPoS) consensus mechanism commonly utilized in both public and hybrid chains. However, the current DPoS mechanism faces challenges such as low node engagement in voting and potential security risks posed by malicious nodes. In response, we propose the DL-DPoS (deep link–delegated proof of stake) mechanism, which builds upon the DPoS framework. The DL-DPoS incorporates the LINK incentive mechanism to encourage inactive nodes to participate in voting and leader selection. Furthermore, a comprehensive credit scoring system based on wealth, performance, and stability is introduced to enhance the security of elected nodes. The verification process is optimized to involve all nodes except the leader node, and mechanisms are in place to handle malicious attacks by degrading or removing offending nodes and redistributing their responsibilities to the LINK group. Performance testing of the DL-DPoS mechanism, conducted through blockchain simulation tests using the GO language, shows a 23% increase in throughput compared to DPoS, with over 95% node participation and improved distribution of rights and equity. These results indicate the enhanced performance, security, and stability of the DL-DPoS consensus mechanism.

Abstract Background Dietary assessment methods have limitations in capturing real-time eating behaviour accurately. Equipped with automated dietary-data-collection capabilities, the “intelligent ordering system” (IOS) has potential applicability in obtaining long-term consecutive, relatively detailed on-campus dietary records among university students with little resource consumption. We investigated (1) the relative validity of IOS-derived nutrient/food intakes compared to those from the 7-day food diary (7DFD); (2) whether including a supplemental food frequency questionnaire (SFFQ) improves IOS accuracy; and (3) sex differences in IOS dietary intake estimation. Methods Medical students (n = 221; age = 22.2 ± 2.4 years; 38.5% male and 61.5% female) completed the 7DFD and SFFQ. During the consecutive 7-day survey period, students weighed and photographed each meal before and after consumption. Then, students reviewed their 3-month diet and completed the SFFQ, which includes eight underprovided school-canteen food items (e.g., dairy, fruits, nuts). Meanwhile, 9385 IOS dietary data entries were collected. We used Spearman coefficients and linear regression models to estimate the associations among the different dietary intake assessment methods. Individual- and group-level agreement was assessed using the Wilcoxon signed-rank test, cross-classification, and Bland‒Altman analysis. Results IOS mean daily energy, protein, fat, and carbohydrate intake estimations were significantly lower (-15-20%) than those of the 7DFD. The correlation coefficients varied from 0.52 (for added sugar) to 0.88 (for soybeans and nuts), with fruits (0.37) and dairy products (0.29) showing weaker correlations. Sixty-two (milk and dairy products) to 97% (soybeans and nuts) of participants were classified into the same or adjacent dietary intake distribution quartile using both methods. The energy and macronutrient intake differences between the IOS + SFFQ and 7DFD groups decreased substantially. The separate fruit intake measurements from each assessment method did not significantly differ from each other (p > 0.05). IOS and IOS + SFFQ regression models generally yielded higher R2 values for males than for females. Conclusion Despite estimation differences, the IOS can be reliable for medical student dietary habit assessment. The SFFQ is useful for measuring consumption of foods that are typically unavailable in school cafeterias, improving the overall dietary evaluation accuracy. The IOS assessment was more accurate for males than for females.

Abstract The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.

Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear.Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored.Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133+ subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells. Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis.Conclusions: Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified.Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids.Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa.Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Abstract Wearing face masks is the best way to stop the spread of respiratory infections. However, if masks are not sterilized, changing them too frequently can actually increase the risk of cross‐contamination. Herein, the construction of an antipathogen photocatalytic mask with carbon vacancy‐modified carbon nitride nanosheets (g‐C3N4‐VC Ns) coated on the non‐woven fabrics of the out layer of the mask, offering effective and long‐term protection against damaging pathogens when exposed to light is reported. The introduced carbon vacancies are found capable of creating energy‐disordered sites and inducing energetic electric force to overcome the Coulomb interactions between electron‐hole pairs, thus promoting the electron‐hole separation to achieve a high generation of reactive oxygen species (ROS). Thanks to its high activity in generating ROS upon exposure to light, the as‐prepared photocatalytic mask shows high pathogen sterilization performance. This, in turn, prolongs the mask's protective lifetime, decreases the need for regular replacement, and decreases medical waste production. The work demonstrated here opens new viewpoints in designing pathogens biocidal protective devices for health protection, offering significant promise in specific environment self‐protection.

Summary: Background: Atrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive. Methods: Atrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3−/− mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms. Findings: The expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes. Interpretation: Our data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM. Funding: This study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).

Abstract Background No effective therapies for pulmonary fibrosis (PF) exist because of the unclear molecular pathogenesis and the lack of effective therapeutic targets. Zinc finger protein 451 (ZNF451), a transcriptional regulator, plays crucial roles in the pathogenesis of several diseases. However, its expression pattern and function in PF remain unknown. This study was designed to investigate the role of ZNF451 in the pathogenesis of lung fibrosis. Methods GEO dataset analysis, RT‒PCR, and immunoblot assays were used to examine the expression of ZNF451 in PF; ZNF451 knockout mice and ZNF451-overexpressing lentivirus were used to determine the importance of ZNF451 in PF progression; and migration assays, immunofluorescence staining, and RNA-seq analysis were used for mechanistic studies. Results ZNF451 is downregulated and negatively associated with disease severity in PF. Compared with wild-type (WT) mice, ZNF451 knockout mice exhibited much more serious PF changes. However, ZNF451 overexpression protects mice from BLM-induced pulmonary fibrosis. Mechanistically, ZNF451 downregulation triggers fibroblast activation by increasing the expression of PDGFB and subsequently activating PI3K/Akt signaling. Conclusion These findings uncover a critical role of ZNF451 in PF progression and introduce a novel regulatory mechanism of ZNF451 in fibroblast activation. Our study suggests that ZNF451 serves as a potential therapeutic target for PF and that strategies aimed at increasing ZNF451 expression may be promising therapeutic approaches for PF.

Network neuroscience, especially causal brain network, has facilitated drug-resistant epilepsy (DRE) studies, while surgical success rate in patients with DRE is still limited, varying from 30% $\sim ~70$ %. Predicting surgical outcomes can provide additional guidance to adjust treatment plans in time for poorly predicted curative effects. In this retrospective study, we aim to systematically explore biomarkers for surgical outcomes by causal brain network methods and multicenter datasets. Electrocorticogram (ECoG) recordings from 17 DRE patients with 58 seizures were included. Ictal ECoG within clinically annotated epileptogenic zone (EZ) and non-epileptogenic zone (NEZ) were separately computed using six different algorithms to construct causal brain networks. All the brain network results were divided into two groups, successful and failed surgeries. Statistical results based on the Mann-Whitney-U-test show that: causal connectivity of $\alpha $ -frequency band ( $8~\sim ~13$ Hz) in EZ calculated by convergent cross mapping (CCM) gains the most significant differences between the surgical success and failure groups, with a P value of 7.85e-08 and Cohen’s d effect size of 0.77. CCM-defined EZ brain network can also distinguish the successful and failed surgeries considering clinical covariates (clinical centers, DRE types) with ${P}\lt {0}.{001}$ . Based on the brain network features, machine learning models were developed to predict the surgical outcomes. Among them, the SVM classifier with Gaussian kernel function and Bayesian optimization demonstrates the highest average accuracy of 84.48% by 5-fold cross-validation, further indicating that the CCM-defined EZ brain network is a reliable biomarker for predicting DRE surgical outcomes.

Measuring causal brain network is a significant topic for exploring complex brain functions. While various data-driven algorithms have been proposed, they still have some drawbacks such as ignoring time non-separability, cumbersome parameter settings, and poor robustness. To solve these deficiencies, we developed a novel framework: “time-shift permutation cross-mapping, TPCM,” integrating steps of: (1) delayed improved phase-space reconstruction (DIPSR), (2) rank transformation of embedding vectors’ distances, (3) cross-mapping with a fitting estimation, and (4) causality quantification using multi-delays. Based on the synthetic models and comparison with baseline methods, numerical validation results demonstrate that TPCM significantly improves the robustness for data length with or without noise interference, and achieves the best quantification accuracy in detecting time delay and coupling strength, with the highest determination coefficient ( ${R}^{{2}}={0}.{96}\text {)}$ of fitting verse coupling parameters. The developed TPCM was finally applied to ictal electrocorticogram (ECoG) analysis of patients with drug-resistant epilepsy (DRE). A total of 17 patients with DRE were included into the retrospective study. For 8 patients undergoing successful surgeries, the causal coupling strength ( $0.58~\pm ~0.20$ ) within epileptogenic zone network is significantly higher than those suffering failed surgeries ( $0.38~\pm ~0.16$ ) with ${P}\lt {0}. {001}$ through Mann-Whitney-U-test. Therefore, the epileptic brain network measured by TPCM is a credible biomarker for predicting surgical outcomes. These findings additionally confirm TPCM’s superior performance and promising potential to advance precision medicine for neurological disorders.

Introduction Cigarette smoking may impact the progression of idiopathic pulmonary fibrosis (IPF), and the intensity of smoking presents a dose-response association with IPF. Methods We retrospectively analyzed IPF patients diagnosed in our hospital from 2014 to 2018 and performed follow-up to confirm survival status and duration, and determine the effect of smoking on the prognosis of IPF. We retrieved information on IPF from a bioinformatics database to identify the differential expression of lncRNAs and proteins in smokers. Therefore, we explored and verified the mechanism by which cigarette smoke exposure (CSE) regulates LINC00665/XBP-1 involvement in pulmonary fibrosis through cell experiments. We clarified the mechanism between LINC00665 and XBP-1 through cellular and molecular experiments, and verified the inhibitory effect of silencing LINC00665 on pulmonary fibrosis by using a bleomycin (BLM)-induced pulmonary fibrosis model. Results We found that smokers with IPF had a poor prognosis compared with non-smokers. Both the expression of LINC00665 and XBP-1 in IPF lung tissue and smoker lung tissue were significantly upregulated, moreover, LINC00665 was higher in smoker IPF lung tissue than in smoker healthy people. Exposure to CSE could upregulate LINC00665/XBP-1 in lung fibroblast-to-myofibroblast transition. Cellular and molecular experiments showed that LINC00665 regulates the expression of XBP-1 by targeting miR-214-3p. LINC00665 expression, was significantly upregulated in BLM-induced mouse lung fibrosis tissues, and LINC00665 knockdown inhibited fibrogenesis in BLM-induced lung fibrosis. Conclusions Our study found that the high expression of LINC00665 is involved in the pathogenesis of smoker IPF and that CSE may positively regulate LINC00665/ XBP-1 to participate in lung fibroblast-to-myofibroblast transition. These findings help elucidate the pathogenesis of smoker IPF and may contribute to the development of new targeted drugs for IPF therapy.

Abstract Since November 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the worldwide pandemic of the coronavirus disease 2019 (COVID-19), the impact of which is huge to the lives of world populations. Many studies suggested that such situation will continue due to the endless mutations in SARS-CoV-2 genome that result in complexity of the efforts for the control of SARS-CoV-2, since the special enrichment of nucleotide substitution C>U in SARS-CoV-2 sequences were discovered mainly due to the editing by human host factors APOBEC3 genes. The observation of SARS-CoV-2 variants Beta (B.1.351) and Omicron (B.1.1.529) firstly spreading in South Africa promoted us to hypothesize that genetic variants of APOBEC3 special in African populations may be attributed to the higher mutation rate of SARS-CoV-2 variants in Africa. Current study was conducted to search for functional variants of APOBEC3 genes associate with COVID-19 hospitalization in African population. By integrating data from the 1000 Genomes Project, Genotype-Tissue Expression (GTEx), and Host Genetics Initiative (HGI) of COVID-19, we identified potential functional SNPs close to APOBEC3 genes that are associated with COVID-19 hospitalization in African but not with other populations. Our study provides new insights on the potential contribution of APOBEC3 genes on the evolution of SARS-CoV-2 mutations in African population, but further replication is needed to confirm our results.

Abstract We report a rare case of Sjogren’s syndrome complicated with Birt-Hogg-Dubé syndrome (BHDS) not previously mentioned in the literature. Further, there is insufficient evidence linking the two diseases. Here, we review existing diagnostic algorithms for diagnosing diffuse cystic lung disease and provide new insights. The patient initially complained of thirst and dry eyes for ten years, and gradually developed shortness of breath. After admission, physical examination showed five missing teeth, decreased respiratory sounds in both lower lungs, and Velcro rales. Computed tomography showed multiple thin-walled cystic lesions in both lungs. Initial xerophthalmia and labial gland biopsy seemed to reveal a pulmonary cystic change associated with Sjogren’s syndrome. Before discharge, a rash suspected to indicate a fibrofollicular tumor in the neck was observed, and then FLCN variant has been found. The challenges how to clarify the diagnosis of DCLD causes are discussed.

Abstract Interstitial lung diseases (ILDs), or diffuse pulmonary lung disease, are a subset of lung diseases that primarily affect lung alveoli and the space around interstitial tissue and bronchioles. It clinically manifests as progressive dyspnea, and patients often exhibit a varied decrease in pulmonary diffusion function. Recently, variants in telomere biology-related genes have been identified as genetic lesions of ILDs. Here, we enrolled 82 patients with interstitial pneumonia from 2017 to 2021 in our hospital to explore the candidate gene mutations of these patients via whole-exome sequencing. After data filtering, a novel heterozygous mutation (NM_025099: p.Gly131Arg) of CTC1 was identified in two affected family members. As a component of CST (CTC1-STN1-TEN1) complex, CTC1 is responsible for maintaining telomeric structure integrity and has also been identified as a candidate gene for IPF, a special kind of chronic ILD with insidious onset. Simultaneously, real-time PCR revealed that two affected family members presented with short telomere lengths, which further confirmed the effect of the mutation in the CTC1 gene. Our study not only expanded the mutation spectrum of CTC1 and provided epidemiological data on ILDs caused by CTC1 mutations but also further confirmed the relationship between heterozygous mutations in CTC1 and ILDs, which may further contribute to understanding the mechanisms underlying ILDs.

Abstract High‐performance polymers have proliferated in modern society across a variety of industries because of their low density, good chemical stability, and superior mechanical properties. However, while polymers are widely applied, frequent fire disasters induced by their intrinsic flammability have caused massive impacts on human beings, the economy, and the environment. Supramolecular chemistry has recently been intensively researched to provide fire retardancy for polymers via the physical barrier and char‐catalyzing effects of supramolecular aggregates. In parallel, the noncovalent interactions between supramolecular and polymer chains, such as hydrogen bonding, π–π interactions, metal–ligand coordination, and synergistic interactions, can endow the matrix with enhanced mechanical strength. This makes it possible to integrate physical–chemical properties and noncovalent interactions into one supramolecular aggregate‐based high‐performance polymeric system on demand. However, fulfilling these promises needs more research. Here, we provide an overview of the latest research advances of fire‐retardant and high‐strength polymer materials based on supramolecular structures and interactions of aggregates. This work reviews their conceptual design, characterization, modification principles, performances, applications, and mechanisms. Finally, development challenges and perspectives on future research are also discussed.

The consistent notion holds that hepatocellular carcinoma (HCC) initiation, progression, and clinical treatment failure treatment failure are affected by the accumulation of various genetic and epigenetic alterations. MicroRNAs (miRNAs) play an irreplaceable role in a variety of physiological and pathological states. meanwhile, epithelial-mesenchymal transition (EMT) is a crucial biological process that controls the development of HCC. miRNAs regulate the intermediation state of EMTor mesenchymal-epithelial transition (MTE)thereby regulating HCC progression. Notably, miRNAs regulate key HCC-related molecular pathways, including the Wnt/β-catenin pathway, PTEN/PI3K/AKT pathway, TGF-β pathway, and RAS/MAPK pathway. Therefore, we comprehensively reviewed how miRNAs produce EMT effects by multiple signaling pathways and their potential significance in the pathogenesis and treatment response of HCC. emphasizing their molecular pathways and progression in HCC initiation. Additionally, we also pay attention to regulatory mechanisms that are partially independent of signaling pathways. Finally, we summarize and propose miRNA-targeted therapy and diagnosis and defense strategies forHCC. The identification of the mechanism leading to the activation of EMT programs during HCC disease processes also provides a new protocol for the plasticity of distinct cellular phenotypes and possible therapeutic interventions. Consequently, we summarize the latest progress in this direction, with a promising path for further insight into this fast-moving field.

Background: Sarcopenia frequently complicates cirrhosis and leads to substantial mortality. Infection is a complication of cirrhosis that results in high mortality. Both sarcopenia and infection are accompanied by systemic inflammation and adversely affect the prognosis of cirrhosis. This article was designed to decipher the association of sarcopenia with infection occurrence, and to ascertain the risk factors for the 90-day death rate in hospitalized cirrhotic patients with infection. Methods: A total of 808 cirrhotic patients (373 with infection and 435 without) who had undergone abdominal CT from 2017 to 2021 were recruited for this retrospective single-center research. The skeletal muscle index was assessed at the level of the third lumbar vertebra (L3 SMI). The optimal cutoff value of the CAIL3 model (CTP score, AKI, INR, and L3 SMI) for the prediction of the 90-day death rate was authenticated with receiver operating characteristic (ROC) analysis. Results: L3 SMI was considered to be the independent risk factor for infection in cirrhotic patients and 90-day death rate in these patients with infection (HR 2.840 95% CI 2.076–3.886, p

Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. Epigenetics, which involves the regulation of host gene expression without changing the nucleotide sequence, provides an exact direction for us to understand how the environment, lifestyle factors, and other risk factors contribute to obesity. DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. In this review, we examined recent advancements in research, focusing on the involvement of intestinal microbiota and DNA methylation in the etiology and progression of obesity, as well as potential interactions between the two factors, providing novel perspectives and avenues for further elucidating the pathogenesis, prevention, and treatment of obesity.

Agricultural water resources are water resources that can be used for agricultural production, including surface water, groundwater, and soil water. The sustainable use of water resources is of great significance to agriculture and rural economy. In the context of climate change and the increasing crisis of water resources, how to effectively use forest resources and other natural resources to achieve sustainable management of agricultural water ecosystems has become an increasingly urgent issue. Therefore, this paper proposed a real-time self-organization algorithm for forest cultivation, tea planting, and tea processing for sustainable ecosystem management of agricultural water resources. This paper described the sustainable ecosystem of agricultural water resources, carried out optimization analysis on tea planting and processing technology using the genetic optimization algorithm based on decision tree, and then carried out an experimental analysis on a tea garden. It can be seen from the data that the average monthly temperature of the tea garden cultivated by the algorithm in this paper was between 13.4 and 20.5 °C and the average annual temperature was 16.16 °C. However, the average monthly temperature of the traditional cultivation method was between 11.5 and 16.8 °C and the average annual temperature was 13.64 °C. HIGHLIGHTS A real-time self-organization algorithm for forest cultivation, tea planting, and tea processing is proposed for sustainable ecosystem management of agricultural water resources.; Optimization analysis on tea planting and processing technology is carried out using the genetic optimization algorithm based on a decision tree.; Experimental analysis is carried out on a tea garden.;

The principal pathogen responsible for chronic urinary tract infections, immunocompromised hosts, and cystic fibrosis patients is Pseudomonas aeruginosa, which is difficult to eradicate. Due to the extensive use of antibiotics, multidrug-resistant P. aeruginosa has evolved, complicating clinical therapy. Therefore, a rapid and efficient approach for detecting P. aeruginosa strains and their resistance genes is necessary for early clinical diagnosis and appropriate treatment. This study combines recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats-association protein 13a (CRISPR-Cas13a) to establish a one-tube and two-step reaction systems for detecting the mexX gene in P. aeruginosa. The test times for one-tube and two-step RPA-Cas13a methods were 5 and 40 min (including a 30 min RPA amplification reaction), respectively. Both methods outperform Quantitative Real-time Polymerase Chain Reactions (qRT-PCR) and traditional PCR. The limit of detection (LoD) of P. aeruginosa genome in one-tube and two-step RPA-Cas13a is 10 aM and 1 aM, respectively. Meanwhile, the designed primers have a high specificity for P. aeruginosa mexX gene. These two methods were also verified with actual samples isolated from industrial settings and demonstrated great accuracy. Furthermore, the results of the two-step RPA-Cas13a assay could also be visualized using a commercial lateral flow dipstick with a LoD of 10 fM, which is a useful adjunt to the gold-standard qRT-PCR assay in field detection. Taken together, the procedure developed in this study using RPA and CRISPR-Cas13a provides a simple and fast way for detecting resistance genes.

Background Acute myocardial infarction (AMI) is one of the most important causes of mortality among patients with cardiovascular disease. Ginsenoside Rh2 plays a protective role in cardiovascular diseases. Furthermore, pyroptosis reportedly participates in regulating the occurrence and development of AMI. However, whether ginsenoside Rh2 contributes to mitigating AMI by regulating cardiomyocyte pyroptosis remains unknown. Methods In the present study, we established an AMI model in rats. Next, we determined the effects of ginsenoside Rh2 on AMI by examining the myocardial infarct area, while regulation of myocardial pyroptosis was determined by assessing related factors. We established a cardiomyocyte model using hypoxia/reoxygenation (H/R) treatment. The expression of pyroptosis-related factors was determined following ginsenoside Rh2 treatment. In addition, we evaluated the correlation between ginsenoside Rh2 and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway at the mechanistic level. Results Herein, we observed that ginsenoside Rh2 alleviated AMI in rats and cells. Notably, the expression levels of inflammatory factors were reduced in AMI rats and cells. Furthermore, AMI rats and cells exhibited high expression levels of cleaved caspase-1 and gasdermin D, which were downregulated following treatment with ginsenoside Rh2. Further analysis revealed that ginsenoside Rh2 could inhibit cardiomyocyte pyroptosis by regulating the PI3K/AKT signaling pathway. Conclusions Collectively, the findings of the present study demonstrated that ginsenoside Rh2 regulates pyroptosis in cardiomyocytes to alleviate AMI in vivo and in vitro, thereby affording a novel therapeutic approach to treat AMI.

Background Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis in head and neck squamous cell carcinoma (HNSCC) is still unclear. Methods Herein, we analyzed the expression level of FTH1 in HNSCC using TCGA database, and FTH1 protein in HNSCC tissues and cell lines was determined by immunohistochemistry (IHC) and western blotting, respectively. Then, its prognostic value and relationship with clinical parameters were investigated in HNSCC patients. Additionally, the biological function of FTH1 in HNSCC was explored. Results The current study showed that FTH1 is significantly overexpressed in HNSCC tissues and related to poor prognosis and lymph node metastasis of HNSCC. FTH1 knockdown could suppress the metastasis and epithelial-mesenchymal transition (EMT) process of HNSCC. Conclusion Our findings indicate that FTH1 plays a critical role in the progression and metastasis of HNSCC and can serve as a promising prognostic factor and therapeutic target in HNSCC.

Abstract This cohort study aimed to identify the characteristics and risk factors of adult idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) and further explore the prognostic factors of IIM-ILD. We extracted data regarding 539 patients with laboratory-confirmed idiopathic inflammatory myopathy (IIM) with or without interstitial lung disease (ILD) from the Second Xiangya Hospital of Central South University between January 2016 and December 2021. The regression analysis was conducted to identify the possible risk factors for ILD as well as mortality. Of 539 IIM patients, 343 (64.6%) were diagnosed with IIM-ILD. The median (IQR) baseline neutrophil-to-lymphocyte ratio (NLR), C-reactive protein to albumin ratio (CAR) and ferritin were 4.1371 (2.6994–6.8143), 0.1685 (0.0641–0.5456) and 393.6 (210.6–532.2), respectively. Risk factors associated with IIM-ILD were older age (p = 0.002), arthralgia (p = 0.014), lung infection (p = 0.027), hemoglobin (p = 0.022), high CAR (p = 0.014), anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive (p

Traditional hydrodynamic models face the significant challenge of balancing the demands of long prediction spans and precise boundary conditions, large computational areas, and low computational costs when attempting to rapidly and accurately predict the nonlinear spatial and temporal characteristics of fluids at the basin scale. To tackle this obstacle, this study constructed a novel deep learning framework with a hydrodynamic model for the rapid spatiotemporal prediction of hydrodynamics at the basin scale, named U-Net-ConvLSTM. A validated high-fidelity hydrodynamic mechanistic model was utilized to build a 20-year hydrodynamic indicator dataset of the middle and lower reaches of the Han River for the training and validation of U-Net-ConvLSTM. The findings indicate that the R2 value of the model surpassed 0.99 when comparing the single-step prediction results with the target values. Additionally, the required computing time fell by 62.08% compared with the hydrodynamic model. The ablation tests demonstrate that the U-Net-ConvLSTM framework outperforms other frameworks in terms of accuracy for basin-scale hydrodynamic prediction. In the multi-step-ahead prediction scenarios, the prediction interval increased from 1 day to 5 days, while consistently maintaining an R2 value above 0.7, which demonstrates the effectiveness of the model in the missing boundary conditions scenario. In summary, the U-Net-ConvLSTM framework is capable of making precise spatiotemporal predictions in hydrodynamics, which may be considered a high-performance computational solution for predicting hydrodynamics at the basin scale.

The coordinated control and management of water resources, the water environment, and water ecology are essential for optimizing the management of water resources, improving the water environment, rehabilitating water ecosystems, and achieving sustainable development. Most studies conducted to investigate the water carrying capacity have focused primarily on water resources or water environment. However, it is challenging to conduct such research in areas where the interactions between water resources, the environment, and ecology are intricate. In this study, an evaluation indicator system for the water resources - water environment - water ecology carrying capacity (WCC) was constructed, and a coupling coordination model and GeoDetector were employed to systematically analyze the coupling coordination indices (CCI) among the water resource carrying capacity (WRECC), water environment carrying capacity (WENCC), and water ecology carrying capacity (WECCC), as well as the main influencing factors in the Three Gorges Reservoir Area (TGRA) from 2005 to 2018. The results showed that the numbers of counties and districts with a high CCI class gradually increased over this period. The percentage of Class V fluctuated from 0% to 7.7%, and the stability of the water system steadily increased. Spatially, the overall distribution pattern gradually increased from southwest to northeast, and both the single and interactive effects of anthropogenic factors on water systems gradually increased. The CCI was predominantly affected by factors such as the amount of surface water resources per capita, indices of water conservation, forest coverage, discharge of domestic sewage per capita, and water replenishment of the ecosystem. These results show that coordination between the WCC components should be strengthened to further improve water use and domestic water treatment efficiency. To achieve superior-class, effective, and environmentally friendly scientific governance, the productivity of water resources should be increased in areas where the disparity between water availability and the demand for socioeconomic development is severe, and sewage treatment processes should be closely regulated. It is also important to combine resource development and utilization with water ecological protection and management.

ABSTRACT Yersinia pestis is the etiological agent of plague. Marmota himalayana of the Qinghai-Tibetan plateau is the primary host of flea-borne Y. pestis. This study is the report of isolation of Mu-like bacteriophages of Y. pestis from M. himalayana. The isolation and characterization of four Mu-like phages of Y. pestis were reported, which were named as vB_YpM_3, vB_YpM_5, vB_YpM_6, and vB_YpM_23 according to their morphology. Comparative genome analysis revealed that vB_YpM_3, vB_YpM_5, vB_YpM_6, and vB_YpM_23 are phylogenetically closest to Escherichia coli phages Mu, D108 and Shigella flexneri phage SfMu. The role of LPS core structure of Y. pestis in the phages’ receptor was pinpointed. All the phages exhibit “temperature dependent infection,” which is independent of the growth temperature of the host bacteria and dependent of the temperature of phage infection. The phages lyse the host bacteria at 37°C, but enter the lysogenic cycle and become prophages in the chromosome of the host bacteria at 26°C. IMPORTANCE Mu-like bacteriophages of Y. pestis were isolated from M. himalayana of the Qinghai-Tibetan plateau in China. These bacteriophages have a unique temperature dependent life cycle, follow a lytic cycle at the temperature of warm-blooded mammals (37°С), and enter the lysogenic cycle at the temperature of its flea-vector (26°С). A switch from the lysogenic to the lytic cycle occurred when lysogenic bacteria were incubated from lower temperature to higher temperature (initially incubating at 26°C and shifting to 37°C). It is speculated that the temperature dependent lifestyle of bacteriophages may affect the population dynamics and pathogenicity of Y. pestis.

Ionic liquids (ILs) are excellent solvents for cellulose, but the dissolution mechanism is not deeply understood. In the present study, cellobiose was used as a model of cellulose, and the imidazolium halide-based ILs with the same cation of 1-butyl-3-methylimidazolium (Bmim+) including BmimCl, BmimBr, and BmimI were used as solvents. The interaction mechanism between the ILs and cellobiose was analyzed by carbon-13 nuclear magnetic resonance (13C NMR). The results showed that the strength of hydrogen bonds formed between the hydroxyl groups of cellobiose and the ILs was greatly affected by the position of hydroxyl groups and the electro-negativity and size of the anions. Compared with the secondary alcoholic hydroxyl groups, the primary alcoholic hydroxyl groups (C6–OH and C12–OH) on the glucopyranose rings of cellobiose more easily formed hydrogen bonds with the ILs. The strength of hydrogen bonds formed between the protons on the imidazolium cation and cellobiose varied with the positions of the protons. The formation of hydrogen bonds between the halogen anions and cellobiose was the main reason for the dissolution of cellobiose in the ILs. The ability of the three ILs to form hydrogen bonds with cellobiose followed the order: BmimCl > BmimBr > BmimI.

Abstract Background Despite the increasing number of cases of scrub typhus and its expanding geographical distribution in China, its potential distribution in Fujian Province, which is endemic for the disease, has yet to be investigated. Methods A negative binomial regression model for panel data mainly comprising meteorological, socioeconomic and land cover variables was used to determine the risk factors for the occurrence of scrub typhus. Maximum entropy modeling was used to identify the key predictive variables of scrub typhus and their ranges, map the suitability of different environments for the disease, and estimate the proportion of the population at different levels of infection risk. Results The final multivariate negative binomial regression model for panel data showed that the annual mean normalized difference vegetation index had the strongest correlation with the number of scrub typhus cases. With each 0.1% rise in shrubland and 1% rise in barren land there was a 75.0% and 37.0% increase in monthly scrub typhus cases, respectively. In contrast, each unit rise in mean wind speed in the previous 2 months and each 1% increase in water bodies corresponded to a decrease of 40.0% and 4.0% in monthly scrub typhus cases, respectively. The predictions of the maximum entropy model were robust, and the average area under the curve value was as high as 0.864. The best predictive variables for scrub typhus occurrence were population density, annual mean normalized difference vegetation index, and land cover types. The projected potentially most suitable areas for scrub typhus were widely distributed across the eastern coastal area of Fujian Province, with highly suitable and moderately suitable areas accounting for 16.14% and 9.42%, respectively. Of the total human population of the province, 81.63% reside in highly suitable areas for scrub typhus. Conclusions These findings could help deepen our understanding of the risk factors of scrub typhus, and provide information for public health authorities in Fujian Province to develop more effective surveillance and control strategies in identified high risk areas in Fujian Province.

With the development of smart cities and smart electric vehicles (EVs), the problem of improving the performance of Vehicular Ad-hoc Networks (VANETs) is gradually being emphasized. To improve the network performance of VANETs, some scholars have considered parked vehicles as roadside units, but have not paid attention to the energy consumption characteristics of vehicles, especially electric vehicles. Therefore, in this paper, we propose a QL-mRSU series artificial intelligence energy saving method to optimize the energy consumption of parked electric vehicles during communication. The method is based on electric vehicle self-organizing networks (E-VANETs), which dynamically cluster electric vehicles parked in parking lots by parameters such as traffic flow, number of service demands, and charging index in reinforcement learning, select the most suitable vehicles as mobile roadside units (mRSUs), and adjust the working mode according to environmental changes such as the number of service demands to achieve the effects of self-learning and energy saving. The simulation experimental results show that compared with other energy-based routing algorithms, the method is able to make optimal choices through self-learning with guaranteed communication quality and is more adaptable to traffic flow changes on the road, thus ensuring the stability of energy-saving efficiency. In addition, the method significantly improves the energy structure of electric vehicle parking clusters.

The coal gangue hill is formed by the accumulation of waste in the coal mining process. A large amount of heat energy accumulates inside it, which makes it prone to spontaneous combustion, seriously pollutes the environment and wastes resources. In this paper, taking a gangue hill in a mining area as an example, a gravity heat pipe device is used to extract heat from the deep part of the gangue hill, and a mathematical model for heat extraction is established. And through experiments to explore the cooling effect of coal gangue at different depths, it is concluded that the cooling range of gravity heat pipe can reach about 15%. At the same time, to avoid the waste of geothermal resources, this paper uses the extracted heat twice and designs a thermoelectric power generation system based on the gravity heat pipe device to realize the purpose of resource utilization of the underground heat energy of coal gangue hills. The experimental results show that the thermoelectric conversion efficiency can reach 7.39%, and after the addition of the soaking plate, the thermoelectric efficiency is increased to 9.02%, which has a very important reference significance for promoting the treatment of coal gangue hills and the recovery and utilization of low-temperature geothermal heat.

Coal gangue is industrial waste formed during coal production. Due to the accumulation of a large amount of heat inside, it is prone to spontaneous combustion. At present, the use of heat pipes to extract heat from coal gangue has become a relatively effective method, but the extracted heat has not been used rationally, causing damage to the natural environment. This paper proposes to use this part of thermal energy for thermoelectric conversion to realize thermoelectric generation, and on the basis of the experiment platform, and the factors that affect the maximum output power such as the arrangement mode, hierarchical structure and cold end heat dissipation mode of the thermoelectric module are studied. The paper also presents a thermoelectric conversion structure of “pipe in pipe”, which reduces heat loss, increases the contact area between the heat pipe and the thermoelectric generation sheet, and improves the energy conversion efficiency and reduces energy waste, thus the output power of thermoelectric conversion increases. The use of thermoelectric conversion to convert waste heat energy into electrical energy is of great significance to the secondary use of energy.

Abstract Background An outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, affected nine adult males in the southwest area of Xi’an in November 2020 was analyzed in this study. Methods Clinical and epidemiological data of HFRS patients in this outbreak were retrospectively analyzed. The whole genome of a hantavirus named 201120HV03xa (hv03xa for short) isolated from Apodemus agrarius captured in the construction site was sequenced and analyzed. In addition, nine HFRS patients were monitored for the IgG antibody against the HV N protein at 6 and 12 months, respectively. Results In this study, inhalation of aerosolized excreta and contaminated food may be the main source of infection. Genome analysis and phylogenetic analysis showed that hv03xa is a reassortment strain of HTNV, having an S segment related to A16 of HTN 4, an M segment related to Q37 and Q10 of HTN 4, and an L segment related to prototype strain 76–118 of HTN 7. Potential recombination was detected in the S segment of hv03xa strain. The anti-HV-IgG level of all the patients persist for at least one year after infection. Conclusions This report documented an HFRS outbreak in Xi’an, China, which provided the basic data for epidemiological surveillance of endemic HTNV infection and facilitated to predict disease risk and implement prevention measures.

Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not clear yet. Here, we find SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. SARS-CoV-2 ORF3a promotes the degradation of NRF2 through recruiting Keap1, thereby attenuating cellular resistance to oxidative stress and facilitated cells to ferroptotic cell death. Our study uncovers that SARS-CoV-2 ORF3a functions as a positive regulator of ferroptosis, which might explain SARS-CoV-2-induced damage in multiple organs in COVID-19 patients and imply the potential of ferroptosis inhibition in COVID-19 treatment.

Fibrotic diseases result in organ remodelling and dysfunctional failure and account for one-third of all deaths worldwide. There are no ideal treatments that can halt or reverse progressive organ fibrosis, moreover, organ transplantation is complicated by problems with a limited supply of donor organs and graft rejection. The development of new approaches, especially induced pluripotent stem cell (iPSC)-based therapy, is becoming a hot topic due to their ability to self-renew and differentiate into different cell types that may replace the fibrotic organs. In the past decade, studies have differentiated iPSCs into fibrosis-relevant cell types which were demonstrated to have anti-fibrotic effects that may have the potential to inform new effective precision treatments for organ-specific fibrosis. In this review, we summarize the potential of iPSC-based cellular approaches as therapeutic avenues for treating organ fibrosis, the advantages and disadvantages of iPSCs compared with other types of stem cell-based therapies, as well as the challenges and future outlook in this field.

Terraces play a crucial role in regulating the water cycle. The management and restoration of, and the conservation strategies and plans for basins rely heavily on the assessment of alterations in hydrological characteristics, whether natural or man-made, within these basin systems. This study centers on evaluating the impact of terraces on temporal variations in the hydrological regime within the Laixi River basin, within the context of climate variability. To achieve this, we employed a hydrological model and applied the Indicators of Hydrologic Alteration and Range of Variability Approach (IHA–RVA). The results show that, under the influence of terraces, the annual flow exhibited an overall decreasing trend. There was a noticeable decrease in streamflow from March to July, while from October to December, there was a clear upward trend, with increases ranging from 4.76% to 8.10% at the Guanshenxindi (GSXD) and Watershed outlet (WO) cross-sections. The indicators related to the minimum flow showed an overall increasing trend, whereas all indicators related to the maximum flow exhibited a clear decreasing trend. Both high and low flow pulse counts decreased, while high and low pulse durations increased overall. The overall trend of flow reversal counts also showed a decrease. All hydrological indicators exhibited low levels of alteration, with hydrologic alteration values lower than 33.33%. However, the influence of terraces on the upstream hydrological conditions was more pronounced than their downstream effect. The terraces in the study area have played a beneficial role in the flood regulation, drought mitigation, and water resource conservation of the Laixi River. They have contributed to stabilizing the daily average flow during high flow periods and have had a positive impact on the ecological base flow during low flow periods, thereby improving the aquatic ecological environment. This study provides theoretical support for river regulation within the framework of soil and water conservation measures.

Abstract Background Patient subgroups are important for easily understanding a disease and for providing precise yet personalized treatment through multiple omics dataset integration. Multiomics datasets are produced daily. Thus, the fusion of heterogeneous big data into intrinsic structures is an urgent problem. Novel mathematical methods are needed to process these data in a straightforward way. Results We developed a novel method for subgrouping patients with distinct survival rates via the integration of multiple omics datasets and by using principal component analysis to reduce the high data dimensionality. Then, we constructed similarity graphs for patients, merged the graphs in a subspace, and analyzed them on a Grassmann manifold. The proposed method could identify patient subgroups that had not been reported previously by selecting the most critical information during the merging at each level of the omics dataset. Our method was tested on empirical multiomics datasets from The Cancer Genome Atlas. Conclusion Through the integration of microRNA, gene expression, and DNA methylation data, our method accurately identified patient subgroups and achieved superior performance compared with popular methods.

Large amounts of insecticides bring selection pressure and then develop insecticide resistance in Aedes albopictus. This study demonstrated for the first time the effect of pyrethroid exposure on the internal microbiota in Ae. albopictus. 36, 48, 57 strains of virgin adult Ae. albopictus were exposed to the pyrethroids deltamethrin (Dme group), β-cypermethrin (Bcy group), and cis-permethrin (Cper group), respectively, with n-hexane exposure (Hex group) as the controls (n = 36). The internal microbiota community and functions were analyzed based on the metagenomic analysis. The analysis of similarity (ANOSIM) results showed that the Hex/Bcy (p = 0.001), Hex/Cper (p = 0.006), Hex/Dme (p = 0.001) groups were well separated, and the internal microbes of Ae. albopictus vary in the composition and functions depending on the type of pyrethroid insecticide they are applied. Four short chain fatty acid-producing genera, Butyricimonas, Prevotellaceae, Anaerococcus, Pseudorhodobacter were specifically absent in the pyrethroid-exposed mosquitoes. Morganella and Streptomyces were significantly enriched in cis-permethrin-exposed mosquitoes. Wolbachia and Chryseobacterium showed significant enrichment in β-cypermethrin-exposed mosquitoes. Pseudomonas was significantly abundant in deltamethrin-exposed mosquitoes. The significant proliferation of these bacteria may be closely related to insecticide metabolism. Our study recapitulated a specifically enhanced metabolic networks relevant to the exposure to cis-permethrin and β-cypermethrin, respectively. Benzaldehyde dehydrogenase (EC 1.2.1.28), key enzyme in aromatic compounds metabolism, was detected enhanced in cis-permethrin and β-cypermethrin exposed mosquitoes. The internal microbiota metabolism of aromatic compounds may be important influencing factors for pyrethroid resistance. Future work will be needed to elucidate the specific mechanisms by which mosquito microbiota influences host resistance and vector ability.

Measurement(s) Human Brainwave • spoken language Technology Type(s) EEG collector • audio recorder Sample Characteristic - Organism Homo Sapiens Sample Characteristic - Location China

Abstract We use the Japan Meteorological Agency (JMA) earthquake catalogue from January, 2001 to February, 2021 to investigate the spatiotemporal foreshock occurrence for shallow (within 30 km depth) onshore earthquakes (Mj3.0 to 7.2). We find clear peaks for the numbers of small earthquakes within 10 days and 3 km prior to the larger earthquakes, which are considered as our definition of foreshocks. After removing the aftershocks, earthquake swarms and possible triggered earthquakes by the 2011 Mw9.0 Tohoku-oki earthquake, we find that for the 2066 earthquakes (mainshocks), 783 (38%) have one or more foreshocks. There is a decreasing trend of foreshock occurrence rate with mainshock depth. Also, normal faulting earthquakes have higher foreshock occurrence rate than reverse faulting earthquakes. We calculate the earthquake occurrence rate as a function of the magnitudes of foreshocks and mainshocks, and we have found no clear trend between the magnitudes of foreshocks and mainshocks. Graphical Abstract

Background: /Objective: The treatment of bone defect has always been a difficult problem in orthopedic clinic. The search for alternative biodegradable implants is a hot topic. The development of biodegradable magnesium scaffolds for the treatment of bone defects has long been a goal of the public. Methods: In this study, we proposed a porous magnesium scaffold prepared by 3D gel printing and surface modification with an additional calcium phosphate coating and use of its strength, degradability and slow degradation rate in a bone graft substitute material. The porous magnesium granular scaffold was prepared by 3D gel printing technology and modified by DCPD (Dibasic Calcium Phosphate Dihydrate) coating. The biocompatibility, degradation rate, and osteogenic ability of the scaffold were evaluated in vitro and in vivo. Results: The biocompatibility, in vivo degradation and bone defect healing response of the implants were investigated. Porous magnesium scaffolds were successfully prepared, and the strength of sintered scaffolds reached 5.38 ​MPa. The degradation rates of scaffolds were significantly reduced after coating with DCPD. The cell compatibility evaluation showed that DCPD-coated Mg scaffold was suitable for cell proliferation. In vivo biosafety monitoring showed that scaffold implantation did not cause an increase in Mg ion concentration in vivo, and no toxic damage was detected in the liver or kidney. Micro-CT and pathological results showed that a large amount of new bone was formed at 6 weeks. At 12 weeks, approximately 52% of the scaffold volume remained. At 24 weeks, osteogenesis, which was stimulated by some residual scaffold, still can be observed. In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives. Conclusion: In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives. The Translational potential of this article: The translational potential of this article is to make use of the advantages of 3D gel printing technology with higher efficiency and lower cost compared with SLM and SLS technologies, and use pure magnesium powder as raw material to prepare degradable porous magnesium metal scaffolds, opening up a new technical route for the preparation of degradable porous magnesium scaffolds which are made for bone defect regeneration in the future.

Abstract Low cement castables (LCCs) containing different types of drying agents (polymer fibers and EMSIL‐DRY™) have been studied both in laboratory‐ and industrial‐scale. Our study shows that the type of drying agent has a profound impact on the flow/workability of the fresh castables and that EMSIL‐DRY™ ensures the best workability. The thermal behavior of 300 mm cubes (approximately 80 kg) was studied using a unique macro‐thermo‐balance (macro‐TGA). Compared to the polymer fibers, EMSIL‐DRY™ reduces the temperature level for maximum dewatering rate and will effectively help prevent explosions during heat‐up. The LCC with EMSIL‐DRY™ showed excellent explosion resistance, as demonstrated by the production of a perfect 400 kg block that was fired to 850°C at a rate of 75°C/h.

Abstract Background Golgi phosphoprotein 3 (GOLPH3) has been frequently reported as an oncoprotein in a variety of tumors. However, its role in the cancer-associated intercellular signaling communication has not yet been explored. This study aimed at exploring whether GOLPH3 regulates angiogenesis and sorafenib resistance via exosomal mechanisms in hepatocellular carcinoma (HCC). Methods In vivo assays were performed to elucidate the function of GOLPH3 in HCC. Exosomes of HCC cells were isolated by differential centrifugation, and then measured and quantified using nanoparticle tracking analysis (NTA), BCA assay, western blot (WB), and transmission electron microscopy (TEM). Differentially expressed miRNAs in exosome were analyzed and verified through small RNA sequencing (sRNA-seq) and reverse-transcription polymerase chain reaction (RT-PCR). In addition, a series of in vitro assays were performed to determine the function of exosomes and miR-494-3p in HCC. The candidate target gene of miR-494-3p was identified by bioinformatics prediction and dual-luciferase reporter assay. Results Downregulation of GOLPH3 expression could suppress angiogenesis and enhance sorafenib sensitivity in HCC. Exosomes derived from GOLPH3 overexpression HCC cells promoted the angiogenesis ability of HUVECs and induced sorafenib resistance in HCC cells. A total of 13 differentially expressed miRNAs between negative control and GOLPH3 knockdown group were found in exosomes. However, GOLPH3 was only associated with miR-494-3p expression level in exosomes derived from HCC cells without affecting total cellular miR-494-3p content. Results confirmed that exosomal miR-494-3p promotes angiogenesis of HUVECs and sorafenib resistance in HCC cells through directly targeting PTEN. Conclusions HCC cells with high expression levels of GOLPH3 could promote angiogenesis and sorafenib resistance by enhancing exosomal miR-494-3p secretion to recipient HUVECs and HCC cells, respectively.

Pulmonary fibrosis is characterized by stiffening of the extracellular matrix. Fibroblasts migrate in the direction of greater stiffness, a phenomenon termed durotaxis. The mechanically guided fibroblast migration could be a crucial step in the progression of lung fibrosis. In this study, we found primary human lung fibroblasts sense increasing matrix stiffness with a change of mitochondrial dynamics in favor of mitochondrial fission and increased production of ATP. Mitochondria polarize in the direction of a physiologically relevant stiffness gradient, with conspicuous localization to the leading edge, primarily lamellipodia and filopodia, of migrating lung fibroblasts. Matrix stiffness–regulated mitochondrial fission and durotactic lung fibroblast migration are mediated by a dynamin-related protein 1/mitochondrial fission factor–dependent (DRP1/MFF-dependent) pathway. Importantly, we found that the DRP1/MFF pathway is activated in fibrotic lung myofibroblasts in both human IPF and bleomycin-induced mouse lung fibrosis. These findings suggest that energy-producing mitochondria need to be sectioned via fission and repositioned in durotactic lung fibroblasts to meet the higher energy demand. This represents a potentially new mechanism through which mitochondria may contribute to the progression of fibrotic lung diseases. Inhibition of durotactic migration of lung fibroblasts may play an important role in preventing the progression of human idiopathic pulmonary fibrosis.

AimThere are no prospective longitudinal studies on the association between well-controlled gestational diabetes mellitus (GDM) without pharmacologic therapy and the physical growth of offspring in infancy. We aimed to identify the trajectories in physical growth (from 0–12 months of age) in the offspring of mothers with well-controlled GDM without pharmacologic therapy in a prospective cohort in China.MethodsThis study included 236 offspring of mothers with GDM and 369 offspring of mothers without GDM. Mothers with GDM were not on pharmacologic therapy. The length and weight of infants were measured at 0, 1, 3, 6, and 12 months. Linear mixed-effect models and linear mixed-effect models were applied.ResultsThe fully adjusted model showed that the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and BMI-for-age z-score (BMIZ) were similar at birth for the GDM and control groups. However, subsequent increases in WAZ and BMIZ for the GDM group lagged the increases for the control group at the subsequent periods of observation, 0–1, 0–6, and 0–12 months.ConclusionsWell-controlled GDM without pharmacologic therapy may normalize physical growth of offspring at birth and decelerate their weight gain in infancy. Whether glycemic control can mitigate the long-term effects of GDM on the growth trajectory in offspring remains unclear.

Study region: Middle and lower Hanjiang River (MLHR) basin, China. Study focus: Changes in streamflow are often due to intertwined factors like climatic variability, land use change, and hydraulic constructions, whose relative impact is however poorly understood. In this study, we disentangled these effects by comparing real data and modelled scenarios of catchment behaviour. Modelled scenarios employ the soil and water assessment tool (SWAT), whereas the scenario comparison uses the Indicators of Hydrologic Alteration (IHA). New hydrological insights for the region: Our analyses show that (1) watershed inlet was the major factor altered the streamflow regime at the watershed outlet, which pointed us to consider only the relative catchment contribution in further analyses. (2) Climate variability was the main driver of the net changes in natural hydrological regime, which downplayed the effect of land use change on streamflow variability. (3) The streamflow regulation associated to the progressive increase in reservoirs and their operation significantly altered the flow pattern, causing a general decrease in average streamflow, an attenuation of extreme events indicators, and an alteration of the pulse pattern with more frequent but shorter pulses. (4) The average water withdrawals at MLHR were estimated, which were 8.03 × 109 m3/year. Overall, this research provides a path to assess the hydrologic impact of cascading reservoirs at the basin level under climate variability and land use change elsewhere.