Explore the vast range of titles available.

Liver diseases caused by viral infection, alcohol abuse and metabolic disorders can progress to end‐stage liver failure, liver cirrhosis and liver cancer, which are a growing cause of death worldwide. Although liver transplantation and hepatocyte transplantation are useful strategies to promote liver regeneration, they are limited by scarce sources of organs and hepatocytes. Mesenchymal stem cells (MSCs) restore liver injury after hepatogenic differentiation and exert immunomodulatory, anti‐inflammatory, antifibrotic, antioxidative stress and antiapoptotic effects on liver cells in vivo. After isolation and culture in vitro, MSCs are faced with nutrient and oxygen deprivation, and external growth factors maintain MSC capacities for further applications. In addition, MSCs are placed in a harsh microenvironment, and anoikis and inflammation after transplantation in vivo significantly decrease their regenerative capacity. Pre‐treatment with chemical agents, hypoxia, an inflammatory microenvironment and gene modification can protect MSCs against injury, and pre‐treated MSCs show improved hepatogenic differentiation, homing capacity, survival and paracrine effects in vitro and in vivo in regard to attenuating liver injury. In this review, we mainly focus on pre‐treatments and the underlying mechanisms for improving the therapeutic effects of MSCs in various liver diseases. Thus, we provide evidence for the development of MSC‐based cell therapy to prevent acute or chronic liver injury. Mesenchymal stem cells have potential as a therapeutic to prolong the survival of patients with end‐stage liver diseases in the near future.

ObjectiveTo characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile.DesignWe collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity.ResultsOral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery.ConclusionThis study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.

Acetaminophen (APAP)-induced injury is a common clinical phenomenon that not only occurs in a dose-dependent manner but also occurs in some idiosyncratic individuals in a dose-independent manner. APAP overdose generally results in acute liver injury via the initiation of oxidative stress, endoplasmic reticulum (ER) stress, autophagy, liver inflammation, and microcirculatory dysfunction. Liver transplantation is the only effective strategy for treating APAP-induced liver failure, but liver transplantation is inhibited by scarce availability of donor liver grafts, acute graft rejection, lifelong immunosuppression, and unbearable costs. Currently, N -acetylcysteine (NAC) effectively restores liver functions early after APAP intake, but it does not protect against APAP-induced injury at the late stage. An increasing number of animal studies have demonstrated that mesenchymal stem cells (MSCs) significantly attenuate acute liver injury through their migratory capacity, hepatogenic differentiation, immunoregulatory capacity, and paracrine effects in acute liver failure (ALF). In this review, we comprehensively discuss the mechanisms of APAP overdose-induced liver injury and current therapies for treating APAP-induced liver injury. We then comprehensively summarize recent studies about transplantation of MSC and MSC derivatives for treating APAP-induced liver injury. We firmly believe that MSCs and their derivatives will effectively promote liver regeneration and liver injury repair in APAP overdose-treated animals and patients. To this end, MSC-based therapies may serve as an effective strategy for patients who are waiting for liver transplantation during the early and late stages of APAP-induced ALF in the near future.

Marine engineering thick plates are essential structural materials for large vessels and offshore platforms, and optimizing their manufacturing processes is critical for advancing marine equipment. This study examined the microstructural and property variations in 120 mm-thick S460 plates fabricated by thermo-mechanical controlled processing (TMCP). A finite element model was developed to simulate the cooling phase, enabling the prediction of the internal cooling path in the thick plate. An optimized cooling scheme was proposed, which was validated against the model and implemented. The following key results were obtained: (1) Under the initial cooling parameters (initial temperature: 715 °C, duration: 130 s), the 60 mm depth toughness was severely compromised, as evidenced by a low −40 °C impact energy of 59 J, significantly lower than values observed at the10 mm and 30 mm depth positions. Microstructural analysis revealed that the 60 mm depth region was dominated by ferritic bainite and pearlite, with a pearlite content of 8.7%. Numerical simulations further indicated a 60 mm depth cooling rate of 1.10 °C/s under these conditions. (2) Model predictions confirmed the original 60 mm depth cooling rate of 1.10 °C/s. The optimized process increased the initial cooling temperature to 725 °C and extended the cooling time to 160 s, achieving an enhanced 60 mm depth cooling rate of 1.36 °C/s. (3) The optimized process remarkably improved the 60 mm depth impact energy to 144 J, achieving near-complete elimination of pearlite, increased granular bainite content, refined M-A constituent size, and enhanced density of high-angle grain boundaries. This study demonstrates that enhancing internal temperature gradients and prolonging cooling durations can effectively inhibit microstructural degradation in 60 mm depth regions of thick plates, providing both theoretical foundations and practical methodologies for optimizing TMCP processes of extra-thick steel plates.

Gut microbiota make up the largest microecosystem in the human body and are closely related to chronic metabolic diseases. Herein, 520 fecal samples are collected from different regions of China, the gut microbiome in chronic kidney disease (CKD) is characterized, and CKD classifiers based on microbial markers are constructed. Compared with healthy controls (HC, n = 210), gut microbial diversity is significantly decreased in CKD (n = 110), and the microbial community is remarkably distinguished from HC. Genera Klebsiella and Enterobacteriaceae are enriched, while Blautia and Roseburia are reduced in CKD. Fifty predicted microbial functions including tryptophan and phenylalanine metabolisms increase, while 36 functions including arginine and proline metabolisms decrease in CKD. Notably, five optimal microbial markers are identified using the random forest model. The area under the curve (AUC) reaches 0.9887 in the discovery cohort and 0.9512 in the validation cohort (49 CKD vs 63 HC). Importantly, the AUC reaches 0.8986 in the extra diagnosis cohort from Hangzhou. Moreover, Thalassospira and Akkermansia are increased with CKD progression. Thirteen operational taxonomy units are correlated with six clinical indicators of CKD. In conclusion, this study comprehensively characterizes gut microbiome in non‐dialysis CKD and demonstrates the potential of microbial markers as non‐invasive diagnostic tools for CKD in different regions of China. Compared with healthy controls, gut microbial diversity in CKD is significantly reduced, Klebsiella and Akkermansia are significantly increased, Roseburia and Faecalibacterium are significantly reduced, and the predictive function of gut microbiota such as ascorbate metabolism and lipopolysaccharide biosynthesis is significantly enhanced. Akkermansia increases along with the progression of CKD, which is positively correlated with serum creatinine and blood urea nitrogen, and negatively correlated with estimated glomerular filtration rate, and could be used as a therapeutic target to improve the prognosis of CKD. Importantly, gut microbial markers have strong diagnostic potential for CKD and achieve cross‐regional validation, which can be used as a non‐invasive diagnostic tool for CKD.

Hospital-acquired infection (HAI) and antimicrobial resistance (AMR) represent major challenges in healthcare system. Despite numerous studies have assessed environmental and patient samples, very few studies have explored the microbiome and resistome profiles of medical staff including nursing workers. This cross-sectional study was performed in a tertiary hospital in China and involved 25 nurses (NSs), 25 nursing workers (NWs), and 55 non-medical control (NC). Stool samples from all participants and hand samples (i.e., the microbiome sample from hand skin, which were collected by swabbing both hands with a sponge-swab soaked with neutralized buffer and centrifuging the liquid buffer) from NSs and NWs were collected for metagenomic analysis. Metagenomic analysis revealed that medical staff exhibited lower abundances of beneficial species such as Blautia , and Bifidobacterium in the gut microbiome. However, an important potential pathogen, Staphylococcus haemolyticus , was enriched in the hands of NWs, suggesting a considerable prevalence of pathogenesis and multi-drug resistance. Accordantly, ARG analysis revealed worse hand hygiene among NWs than among NSs, characterized by a higher diversity of ARGs and a higher abundance of ARGs conferring multi-drug resistance including mdtF , acrB , AcrF and evgS . This study provides a comprehensive overview of the microbial and ARG profiles in the gut and hands of NSs and NWs. The higher abundance of potential pathogens and diverse multi-drug resistant ARGs in NWs hands indicates insufficient hand hygiene and a higher risk of HAI in this subgroup. This study is the first to highlight the critical need to improve hand hygiene among NWs, thus mitigating the risks of AMR and HAI.

This study explores finite-time synchronization (FTS) in fractional-order quaternion-valued neural networks (FQVNNs) characterized by discontinuous activation functions and uncertainties in parameters. Initially, leveraging the properties of the Mittag-Leffler function along with fractional-order (F-O) delayed differential inequalities, a novel finite-time stability theorem for F-O systems is established, building upon previous research findings. Next, based on norm definitions, two state feedback controllers employing quaternion 1-norm and quaternion 2-norm are devised to ensure FTS for the system under consideration. Following this, by utilizing differential inclusion theory, examining the quaternion sign function, employing advanced inequality methods, applying principles of F-O differential equations, and using the Lyapunov functional approach, new criteria for achieving FTS in FQVNNs are formulated. Additionally, precise estimates for the settling time are presented. In conclusion, two carefully designed numerical examples are included to corroborate the theoretical results derived.

Background Carbapenem-resistant Enterobacteriaceae (CRE) infections have become a global health threat. Controlling CRE transmission in hospitals is increasingly dependent on the use of disinfectants to restrict the risk of infection. Here, the susceptibility of patient-derived carbapenem resistant Klebsiella pneumoniae (CRKP) and Escherichia coli (CREC) strains against three common disinfectants and the determinants of resistance to disinfectants were investigated. Methods The minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of three common chemical disinfectants: chlorhexidine, trichloroisocyanuric (TCCA) acid and Povidone iodine (PVP-I) against 50 CRE strains were measured. The drug-resistance genes - qacEΔ1 , qacA/B and cepA -were determined using polymerase chain reaction. Results A total of 36 CRKP and 14 CREC strains were collected in our hospital from 2016 to 2018. The MIC ranges of 36 CRKP strains against chlorhexidine, TCCA and PVP-I were 8~512 mg/L, 64~128 mg/L and 8~128 mg/L, respectively. For 14 CREC strains, the MIC ranges against chlorhexidine, TCCA and PVP-I were 4~128 mg/L, 64~128 mg/L and 4~128 mg/L, respectively. Moreover, against chlorhexidine and PVP-I, the MIC 90 of 36 CRKP strains was higher than that of 50 CSKP strains. The qacE△1 gene was detected in 15 isolates among 36 CRKP strains (41.7%), and 8 isolates among 14 CREC strains (57.1%); while the qacA/B gene was not detected. Specifically, the cepA gene was much more prevalent than the qacEΔ1 ; it reached over 80% among CRKP strains. Compared to the CSKP strains, the presence of the qacEΔ1 and cepA genes was significantly higher among the CRKP strains ( p < 0.05 ). Conclusion CRE strains collected from patients in our hospital exhibit various degree of resistance to the commonly used chemical disinfectants. It is of great help to keep monitoring the tendency of the reduced susceptibility of the pan-resistant strains against disinfectants, in order to effectively control and prevent the spread of the super resistant bacteria.

Oral microbiota is related to the severity and recovery of SARS-CoV-2 infection. This study aims to predict clinical classification after SARS-CoV-2 infection using oral microbiota before infection. Herein, we collected tongue-coating samples before infection and then monitored clinical information after infection. Oral microbiota was detected by MiSeq sequencing. We randomly assigned participants from Zhengzhou into discovery and validation cohorts to develop a predictive model and conducted cross-region verification using Xinyang and Hangzhou cohorts. Sixteen asymptomatic patients (AP), 257 mild patients (MP), 106 common patients (CP), and 7 severe patients (SP) were enrolled. Oral microbiota diversity was decreased in CP versus MP. At genus level, 11 microorganisms, including Rothia and Gemella , were increased, while 5 microorganisms, including Selenomonas and Lachnoanaerobaculum , were decreased in CP versus MP. Moreover, the classifier based on 15 optimal markers showed high prediction efficiency in discovery cohort (area under the curve [AUC]: 98.35%), validation cohort (AUC: 81.91%), Xinyang cohort (AUC: 74.34%), and Hangzhou cohort (AUC: 94.44%). Interestingly, a higher abundance of Selenomonas was associated with milder clinical symptoms. In conclusion, our study established a good model to predict clinical classification after SARS-CoV-2 infection using oral microbiota before infection, providing a novel strategy for precise prevention and treatment.

As there is a small amount of deformation in the center during the rolling process of ultra-heavy plates, it is extremely easy to cause poor mechanical properties in the center. Increasing the deformation in the center is the most feasible method to eliminate the deformation effects in the cross-section of ultra-heavy plates. In this study, the gradient temperature rolling (GTR) process is compared with the traditional uniform temperature rolling (UTR) process. It is found that the GTR process can significantly increase the deformation in the center and thereby refine the grains. The room temperature tensile test and instrumented Charpy impact test are used to test the strength at room temperature and impact energy at low temperature. Combined with the obtained impact load/energy displacement curve, the deformation and damage process under impact load are analyzed. The microstructure morphology and impact fracture obtained by different rolling processes in the center are analyzed by experimental methods such as OM, SEM, EBSD, etc. The prior austenite grain (PAG) boundary morphology is analyzed and the densities of grain boundaries are statistically quantified. The results showed that the strength, plasticity, and low-temperature toughness of the GTR process are improved compared to the UTR process, with increased dislocation density in the center microstructure, the density of PAG boundaries, and the density of packet boundaries. The size of the PAG in the center is refined by ~49%, the density of PAG boundaries increased by ~140%, the density of high-angle packet boundaries increased by ~39%, and the density of low-angle packet boundaries increased by ~49%. The crack propagation in the instrumented Charpy impact test of the GTR process showed stable expansion, indicating a ductile fracture compared to the semi-brittle fracture of the UTR process. The densities of PAG boundaries and high-angle packet boundaries are the most important factors affecting the strength and low-temperature toughness.