Epidemiological and clinical characteristics of imported cases of COVID-19: a multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to expand. Herein, we report the epidemiological and clinical features of 478 patients with confirmed COVID-19 from a multicenter study conducted in four cities in China excluding Wuhan. METHODS: A total of 478 patients transferred by emergency medical services to designated hospitals in four major cities in China (Beijing, Chongqing, Jinan, and Nanning) were enrolled. We compared the characteristics of imported and indigenous cases and calculated the frequencies of fatal, severe, mild, and asymptomatic disease. The results were used to generate a pyramid of COVID-19 severity. RESULTS: The mean age of patients with COVID-19 was 46.9 years and 49.8% were male. The most common symptoms at onset were fever (69.7%), cough (47.5%), fatigue (24.5%), dyspnea (8.4%), and headache (7.9%). Most cases (313, 65.5%) were indigenous, while 165 (34.5%) were imported. Imported cases dominated during the early stages of the pandemic, but decreased from 1 February 2020 as indigenous cases rose sharply. Compared with indigenous cases, imported cases differed significantly in terms of sex (P = 0.002), severity of disease (P = 0.006), occurrence of fever (P < 0.001), family clustering (P < 0.001), history of contact (P < 0.001), and primary outcome (P < 0.001). CONCLUSIONS: Within the population studied, imported cases had distinct characteristics from those of indigenous cases, with lower fatality rates and higher discharge rates. New infections shifted from imported cases to local infection gradually, and overall infections have declined to a low level. We suggest that preventing import of cases and controlling spread within local areas can help prevent SARS-CoV-2 infection spread.

Clinical and Demographic Characteristics of Cluster Cases and Sporadic Cases of Coronavirus Disease 2019 (COVID-19) in 141 Patients in the Main District of Chongqing, China, Between January and February 2020.

BACKGROUND In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, China. Patients with COVID-19 were also identified in Chongqing. This study aimed to investigate the clinical and demographic characteristics of cluster cases and sporadic cases of COVID-19 in 141 patients in the main district of Chongqing during one month, between January and February 2020. MATERIAL AND METHODS A retrospective study included 141 patients with a diagnosis of COVID-19. The diagnosis was confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2. The patients were divided into cluster cases (n=90) and sporadic cases (n=51). Demographic and clinical characteristics were compared between the two study groups and included the presence of comorbidities, the presenting symptoms, chest computed tomography (CT) imaging findings, and laboratory findings. RESULTS The mean age of the 141 patients diagnosed with COVID-19 was 47.3 years, and the most common presenting symptom was a persistent cough (48.9%). The 90 cluster cases (63.8%) were older than the sporadic cases, and cross-infection from family gathering occurred in 82.2%, and cough was more common than fever, and there was an increased prevalence of asymptomatic, mild, and moderate cases. Cluster cases showed fewer typical manifestations of COVID-19 on chest CT. However, the laboratory findings between the cluster and sporadic cases showed no significant differences. CONCLUSIONS There were demographic and clinical differences between cluster cases and sporadic cases of COVID-19 in the main district of Chongqing during the month between January to February 2020.

Epidemiological and clinical characteristics of 136 cases of COVID-19 in main district of Chongqing.

BACKGROUND: We did a comprehensive exploration of the epidemiological and clinical characteristics of 136 patients with confirmed COVID-19 in main district of Chongqing which was adjacent to the west of Hubei province. METHODS: This study was conducted on 136 patients with COVID-19 in main district of Chongqing from Jan 25 to Feb 20, 2020. Data of patients included demographic, epidemiological, clinical features, chest radiographs of imported cases, local cases, second-generation cases and third-generation cases. Student's t-test was adopted for quantitative variables while Pearson Chi-squared test or Fisher's exact test for categorical variables. RESULTS: The median age was 47 years and common symptoms of illness were cough (50.7%), fever (47.1%) and fatigue (14.0%). The time from contact symptomatic case to illness was 7.7 days, and 88 patients (64.7%) were cluster cases, radiological evidence found bilateral lung involvement was common (57.4%).Compared with the imported cases, the local cases were significantly older, the proportion of men is lower. There was higher proportion of cluster cases in local cases. Unlike imported cases, which fever was the dominant symptom, the local cases have more cough patients, with a significant higher proportion of asymptomatic patients. The third-generation cases have a significant higher proportion of asymptomatic patients. CONCLUSION: We concluded the epidemiological and clinical characteristics of the cases andsuggested to take more comprehensive measures for screening patients, especially for elderly person, avoid family gatherings, and implement more closely surveillance of suspect patients and their close contacts.

The Effect of ICOS Polymorphism Interactions with HBV Mutations on HBV Subtype Infection Outcomes.

INTRODUCTION AND AIM: Hepatitis B virus (HBV) infection remains a public health problem worldwide. In addition, HBV infection results are influenced by various virological, immunological, and genetic factors. Inducible T-cell costimulator (ICOS) polymorphisms involving chronic HBV infection have been confirmed in previous studies. This study was to explore the effects of ICOS single nucleotide polymorphisms in HBV subtypes and their interactions with viral mutations on HBV infection outcomes. MATERIAL AND METHODS: A total of 1,636 Han Chinese individuals were recruited, including 47 asymptomatic HBV carriers (ASC), 353 chronic hepatitis B (CHB) patients, 327 HBV-related liver cirrhosis (LC) patients, 193 HBV-related hepatocellular carcinoma (HCC) patients, 464 patients with spontaneous recovery from HBV infection (SR), and 252 healthy controls (HC). DNA samples from these subjects were genotyped for four ICOS SNPs (rs11883722, rs10932029, rs1559931, and rs4675379). Direct sequencing was used to determine the HBV mutations in the enhancer II, basal core promoter, and pre-core regions. RESULTS: We found that the genotype "TC" of ICOS rs10932029 SNP was associated with decreased HBV-related LC risk in the genotype C group. Additionally, the A1762T, G1764A and A1762T/G1764A mutations were associated with an increased risk of LC in the genotype C group. Further study indicated that interactions between ICOS rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations significantly decreased the LC risk in the genotype C group. CONCLUSION: The rs10932029 genotype "TC" might be an LC-protective factor for HBV genotype C infection. The interactions between the rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations could decrease the risk of LC.

Retinoid X Receptor α-Dependent HBV Minichromosome Remodeling and Viral Replication.

BACKGROUND AND AIM: The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. MATERIAL AND METHODS: This study investigated RXRα involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXRα, histones, and chromatin-modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. RESULTS: RXRα Was found to directly bind to HBV cccDNA; recruitment of RXRα to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXRα overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. CONCLUSIONS: Our results confirmed the regulation of RXRα on HBV replication in vitro and demonstrated the modulation of RXRα on HBV cccDNA epigenetics. These findings provide a profound theoretical and experimental basis for late-model antiviral treatment acting on the HBV cccDNA and minichromosome.

Association of HLA-DQ and IFNL4 polymorphisms with susceptibility to hepatitis B virus infection and clearance.

UNLABELLED:  Background and aim. Leukocyte antigen DQ (HLA-DQ) and interferon-λ4 (IFNL4) gene polymorphisms were associated with susceptibility to chronic hepatitis B and C virus infection. This study further confirmed that variants of these genes were associated with susceptibility and spontaneous clearance of HBV infection in a Chinese population. MATERIAL AND METHODS: A total of 1,069 subjects were recruited and divided into three groups i.e. 397 with CLD (HBV-related chronic liver disease), 434 with SC (spontaneous clearance), and 238 HC (healthy controls). HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917SNPs were genotyped using the Sequenom MassARRAY MALDI-TOF system. RESULTS: HLA-DQ rs9275319 showed a significant association with HBV infection (allele model, OR, 0.514; 95% CI, 0.359-0.738, adjusted p = 0.0003) and with natural clearance (allele model, OR, 1.659; 95% CI, 1.197-2.300, adjusted. However, there was no association between IFNL4 polymorphism and HBV susceptibility or natural clearance (all p > 0.05). The multifactor dimensionality reduction (MDR) test with permutation correction showed that a three-way interaction between IFNL4 and HLA-DQ SNPs was identified for HBV susceptibility (permutation p = 0.009 for the best factor model) and clearance (permutation p = 0.014 for the best factor model). CONCLUSIONS: The data from the current study provided additional evidence for an SNP-SNP interaction between HLA-DQ and IFNL4 in regulation to HBV infection and natural clearance.

Effects of interaction between genetic variants in human leukocyte antigen DQ and granulysin genes in Chinese Han subjects infected with hepatitis B virus.

Single nucleotide polymorphisms (SNPs) of HLA-DQ and granulysin (GNLY) are reportedly associated with HBV infection. The aim of this study was to investigate the effects of interactions between SNPs in HLA-DQ and GNLY on the outcome of hepatitis B virus (HBV) infection in Chinese Han subjects. HLA-DQ (rs9275572) and GNLY (rs1866139 and rs11127) were genotyped in 310 subjects with HBV-related chronic liver disease, 295 in whom spontaneous clearance of HBV had occurred and 316 who had not been exposed to HBV. HLA-DQ rs9275572 was significantly correlated with HBV clearance (dominant genetic model: OR, 1.84; 95% CI, 1.30-2.61; adjusted P = 0.001). There was no statistical association of GNLY rs1866139 and rs11127with HBV infection outcomes. However, significant sex-specific associations with HBV susceptibility were observed in men who carried rs1866139 CG or rs11127 TC and in women who carried rs1866139 GG or rs11127 CC. The findings were the same in the validation cohort, which was composed of 829 subjects. Based on a multifactor dimensionality reduction test with permutation correction, a three-way interaction between SNPs in HLA-DQ and GNLY was identified in terms of HBV clearance. In conclusion, additional evidence for an association of HLA-DQ and GNLY SNPs with HBV infection outcomes has been identified and a SNP-SNP interaction between HLA-DQ and GNLY on HBV clearance observed.

The underlying mechanism and targeted therapy strategy of miRNAs cross-regulating EMT process through multiple signaling pathways in hepatocellular carcinoma.

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/ß-catenin pathway, PTEN/PI3K/AKT pathway, TGF-ß 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.

Paclitaxel-induced Immune Dysfunction and Activation of Transcription Factor AP-1 Facilitate Hepatitis B Virus Replication.

Background and Aims: Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified as a potential trigger for HBV reactivation. This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo, which may inform new strategies for HBV antiviral treatment. Methods: The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay, dual-luciferase reporter assay, quantitative real-time PCR, chromatin immunoprecipitation, and immunohistochemical staining. Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice. Results: PTX enhanced the levels of HBV 3.5-kb mRNA, HBV DNA, HBeAg, and HBsAg both in vitro and in vivo. PTX also promoted the activity of the HBV core promoter and transcription factor AP-1. Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation. Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17, NF-κB, and MAPK signaling pathways, with the pivotal common key molecule being AP-1. The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota. Conclusions: PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1. These findings propose a novel molecular mechanism, underscoring the critical role of AP-1 in PTX-induced HBV reactivation.

Enhanced delivery of CRISPR/Cas9 system based on biomimetic nanoparticles for hepatitis B virus therapy.

The persistent presence of covalently closed circular DNA (cccDNA) in hepatocyte nuclei poses a significant obstacle to achieving a comprehensive cure for hepatitis B virus (HBV). Current applications of CRISPR/Cas9 for targeting and eliminating cccDNA have been confined to in vitro studies due to challenges in stable cccDNA expression in animal models and the limited non-immunogenicity of delivery systems. This study addresses these limitations by introducing a novel non-viral gene delivery system utilizing Gemini Surfactant (GS). The developed system creates stable and targeted CRISPR/Cas9 nanodrugs with a negatively charged surface through modification with red blood cell membranes (RBCM) or hepatocyte membranes (HCM), resulting in GS-pDNA@Cas9-CMs complexes. These GS-pDNA complexes demonstrated complete formation at a 4:1 w/w ratio. The in vitro transfection efficiency of GS-pDNA-HCM reached 54.61%, showing homotypic targeting and excellent safety. Additionally, the study identified the most effective single-guide RNA (sgRNA) from six sequences delivered by GS-pDNA@Cas9-HCM. Using GS-pDNA@Cas9-HCM, a significant reduction of 96.47% in in vitro HBV cccDNA and a 52.34% reduction in in vivo HBV cccDNA were observed, along with a notable decrease in other HBV-related markers. The investigation of GS complex uptake by AML-12 cells under varied time and temperature conditions revealed clathrin-mediated endocytosis (CME) for GS-pDNA and caveolin-mediated endocytosis (CVME) for GS-pDNA-HCM and GS-pDNA-RBCM. In summary, this research presents biomimetic gene-editing nanovectors based on GS (GS-pDNA@Cas9-CMs) and explores their precise and targeted clearance of cccDNA using CRISPR/Cas9, demonstrating good biocompatibility both in vitro and in vivo. This innovative approach provides a promising therapeutic strategy for advancing the cure of HBV.

Dynamics of lamivudine-resistant hepatitis B virus strains in patients with entecavir rescue therapy.

Entecavir rescue therapy is frequently used in patients with lamivudine-resistant hepatitis B virus (HBV) strains. The aim of this study was to investigate evolutionary patterns of HBV quasispecies during entecavir rescue therapy and evaluate their impacts on therapeutic efficacy. We enrolled 21 chronic hepatitis B patients who failed to respond to lamivudine therapy and were switched to entecavir treatment. Measurement of serum HBV DNA and sequence analysis of HBV reverse transcriptase were done up to 144 weeks. Four patients of this series showed a reversion to wild-type HBV after entecavir treatment and in three of them, a complete viral response (<2.6 log10 copies/ml) was achieved. An additional five patients developed entecavir genotypic resistance, with prior occurrence of lamivudine-resistant mutation (L180 M ± M204 V/I). A viral breakthrough was observed in four of the five patients with entecavir-resistant mutants. The remaining 12 patients of this series showed dominance of lamivudine-resistant mutants throughout the entecavir rescue therapy, and five of them achieved a complete viral response at the end of follow-up. The average HBV DNA level was significantly lower in patients with a reversion to wild-type HBV than in those without it (P < 0.05). In conclusion, reversion to wild-type HBV is a favorable indicator for response to entecavir rescue therapy in lamivudine-refractory patients with chronic hepatitis B. The presence of lamivudine-resistant mutations contributes to the development of entecavir resistance.

Fractional derivative modeling for sediment suspension in ice-covered channels.

Characterizing the anomalous diffusion behavior of sediment transport is a key factor in calculating sediment concentration. This study attempts to seek an equation that captures the nonlocal movement feature of the transport of an ensemble of sediment particles on ice-covered channels with a steady uniform flow field. Given that the fractional advection-dispersion equation with a noninteger order on the space term is nonlocal and able to describe the long-distance transport, a mathematical model with the Caputo fractional derivative is proposed to estimate the vertical diffusion of suspended sediment particles in the ice-covered channel. Results show that the fractional derivative model has a good predictive ability to the suspended sediment concentration as compared to the measurements. Especially in regions close to the undersurface of the ice cover, the proposed model matches better with experiments than the existing analytical model. Sensitivity analyses indicate that the strength of the turbulent diffusion effect dominates the uniformity of the sediment concentration profile. Besides, the sediment concentration is more sensitive to the variation of the boundary roughness than to the change of the sediment settling velocity. It should be noted that the sediment concentration reduces with the decrease of the order of the fractional derivative, which differs from the findings in previous studies.

Numerical Simulation Study on Spatial Diffusion Behavior of Non-Point Source Fugitive Dust under Different Enclosure Heights.

Non-point source fugitive dust produced during municipal road construction is one of the main ambient air pollutants gravely threatening the life and health of construction workers and residents around construction areas. In this study, a gas-solid two-phase flow model is used to simulate the diffusion behavior of non-point source dust with different enclosure heights under wind loads. Moreover, the inhibitory effect of the enclosure on the diffusion of non-point source dust from construction to residential areas is analyzed. The results show that the physical blocking and reflux effects of the enclosure can effectively restrain dust diffusion. When the enclosure height is 3-3.5 m, the concentration of particulate matter in most sections of residential areas can be reduced to less than 40 µg/m3. Moreover, when the wind speed is 1-5 m/s and the enclosure height is 2-3.5 m, the diffusion height of non-point source dust particles above the enclosure is concentrated in the range 1.5-2 m. This study provides a scientific basis for setting the heights of enclosures and atomization sprinklers at construction sites. Further, effective measures are proposed to reduce the impact of non-point source dust on the air environment of residential areas and health of residents.

GATA4 Forms a Positive Feedback Loop with CDX2 to Transactivate MUC2 in Bile Acids-Induced Gastric Intestinal Metaplasia.

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.

Activin and Hepatocyte Growth Factor Promotes Colorectal Cancer Stemness and Metastasis through FOXM1/SOX2/CXCR4 Signaling.

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.

Phenotypic assay of a hepatitis B virus strain carrying an rtS246T variant using a new strategy.

Phenotypic assays of hepatitis B virus (HBV) play an important role in research related to the problem of drug resistance that emerges during long-term nucleot(s)ide therapy in patients with chronic hepatitis B. Most of the phenotypic assay systems that are available currently rely on the transfection of recombinant replication-competent HBV DNA into hepatoma cell lines. Cloning clinical HBV isolates using conventional digestion-and-ligation techniques to generate replication-competent recombinants can be very difficult because of the sequence heterogeneity and unique structure of the HBV genome. In this study, a new strategy for constructing an HBV 1.1× recombinant was developed. The core of this strategy is the "fragment substitution reaction" (FSR). FSR allows PCR fragments to be cloned without digestion or ligation, providing a new tool for cloning fragments or genomes amplified from serum HBV DNA, and therefore making the assay of HBV phenotypes more convenient. Using this strategy, a phenotypic assay was performed on an HBV strain carrying an rtS246T variant isolated from a patient with chronic hepatitis B that was only responsive partially to entecavir therapy. The results indicated that this strain is sensitive to entecavir in vitro.

Effect of Municipal Solid Waste Incineration Fly Ash on the Mechanical Properties and Microstructure of Geopolymer Concrete.

Geopolymers are environmentally friendly materials made from industrial solid waste with high silicon and aluminum contents, and municipal solid waste incineration fly ash (MFA) contains active ingredients such as Si, Al and Ca. According to this fact, a green and low-carbon geopolymer concrete was prepared using MFA as a partial replacement for metakaolin in this study. The mechanical properties of the MFA geopolymer concrete (MFA-GPC) were investigated through a series of experiments, including a compressive strength test, splitting tensile strength test, elastic modulus test and three-point bending fracture test. The effect of the MFA replacement ratio on the microstructure of MFA-GPC was investigated by SEM test, XRD analysis and FTIR analysis. MFA replacement ratios incorporated in GPC were 5%, 10%, 15%, 20%, 25%, 30%, 35% and 40% by replacing metakaolin with equal quality in this study. In addition, toxic leaching tests of MFA and MFA-GPC were performed by ICP-AES to evaluate the safety of MFA-GPC. The results indicated that the mechanical properties of MFA-GPC decreased with the increase of the MFA replacement ratio. Compared with the reference group of GPC without MFA, the maximum reduction rates of the cubic compressive strength, splitting tensile strength, axial compressive strength, elastic modulus, initiation fracture toughness, unstable fracture toughness and fracture energy of MFA-GPC were 83%, 81%, 78%, 93%, 77%, 73% and 61%, respectively. The microstructure of MFA-GPC was porous and carbonized; however, the type of hydrated gel products was still a calcium silicoaluminate-based silicoaluminate gel. Moreover, the leaching content of heavy metals from MFA-GPC was lower than that of the standard limit. In general, the appropriate amount of MFA can be used to prepare GPC, and its mechanical properties can meet the engineering requirements, but the amount of MFA should not be too high.

Mechanical Properties of Polyvinyl Alcohol Fiber-Reinforced Cementitious Composites after High-Temperature Exposure.

The mechanical properties of cementitious composites before and after exposure to high temperature are affected by calcium-silicate-hydrate (C-S-H) gels. To evaluate the effects of high temperature, plyvinyl alcohol (PVA) fiber content, and the cooling method on properties of cementitious composites, physical, mechanical, and microscopic tests were performed in this study. The target temperatures were 25, 100, 200, 300, 400, 600, and 800 °C. The PVA fiber contents were 0.0, 0.3, 0.6, 0.9, 1.2, and 1.5 vol%. The high-temperature resistance of PVA fiber-reinforced cementitious composite (PVA-FRCC) specimens was investigated through changes in their appearance, mass loss, compressive strength, splitting tensile strength, flexural strength, and microstructure. The results showed that PVA fibers reduced the probability of explosion spalling in the PVA-FRCC specimens exposed to high temperatures. The mass loss rate of samples exposed to temperatures below 200 °C was small and lower than 5%, whereas a significant mass loss was observed at 200 °C to 800 °C. A small rise in the cubic compressive and splitting tensile strengths of samples was found at 400 °C and 300 °C, respectively. Below 400 °C, the fibers were beneficial to the mechanical strength of the PVA-FRCC specimens. Nevertheless, when the temperature was heated above 400 °C, melted fibers created many pores and channels, which caused a decrease in the strength of the specimens. The method of cooling with water could aggravate the damage to the cementitious composites exposed to temperatures above 200 °C. High temperature could lead to the decomposition of the C-S-H gels of the PVA-FRCC samples, which makes C-S-H gels lose their bonding ability. From the perspective of the microstructure, the structure of PVA-FRCC samples exposed to 600 °C and 800 °C became loose and the number of microcracks increased, which confirmed the reduction in macro-mechanical properties.

Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the liver and is often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, and other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD in 2020 as metabolic (dysfunction) associated with fatty liver disease (MAFLD). The changes in diet and lifestyle are recognized the non-drug treatment strategies; however, due to the complex pathogenesis of NAFLD, the current drug therapies are mainly focused on its pathogenic factors, key links of pathogenesis, and related metabolic disorders as targets. There is still a lack of specific drugs. In clinical studies, the common NAFLD treatments include the regulation of glucose and lipid metabolism to protect the liver and anti-inflammation. The NAFLD treatments based on the enterohepatic axis, targeting gut microbiota, are gradually emerging, and various new metabolism-regulating drugs are also under clinical development. Therefore, this review article has comprehensively discussed the research advancements in NAFLD treatment in recent years.

Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis.

Background: Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified. Methods: HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF. Results: Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-κB pathway. Conclusions: Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP.