METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

Cost-of-illness of gastroenteritis caused by rotavirus in Chinese children less than 5 years.

Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.

A signal amplification for Trp isomers electrochemical recognition based on PEDOT:PSS and CS/PAA multilayers.

In this work, enhanced tryptophan (Trp) isomers recognition was successfully demonstrated on (CS/PAA)3.5@PEDOT:PSS/GCE, a multilayer chiral sensor with good stability and reproducibility. The (CS/PAA)n multilayers chiral interface was first fabricated via alternating self-assembly of chiral chitosan (CS) and achiral polyacrylic acid (PAA). Conductive PEDOT:PSS was then compounded with (CS/PAA)n multilayers to obtain the chiral sensor for the electrochemical recognition of Trp isomers. The structure of the sensor and its chirality properties for Trp isomers were characterized by fourier transform infrared spectroscopy (FT-IR)，scanning electron microscopy (SEM) and electrochemical methods. The SEM images showed uniform distribution of PEDOT:PSS in the multilayer films, which changed the internal structure of the (CS/PAA)3.5. Consequently, (CS/PAA)3.5@PEDOT:PSS multilayers rendered more chiral centers in addition to improved good conductivity, which significantly amplified the oxidation peak current ratio of D-Trp to L-Trp (ID/IL) up to 6.71 at 25 °C. In addition, a linear relationship was observed between the peak current and Trp enantiomer concentration in the range of 0.002-0.15 mM, and the detection limits of D-Trp and L-Trp were 0.33 and 0.67 µM, respectively. More importantly, the percentage of D-Trp in non-racemic Trp enantiomers mixture solutions were successfully determined on the chiral interface, showing its effectiveness and promising potential in practical applications.

Molecular epidemiology analysis of symptomatic and asymptomatic norovirus infections in Chinese infants.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

Roles of RNA m6A modification in nonalcoholic fatty liver disease.

NAFLD is a series of liver disorders, and it has become the most prevalent hepatic disease to date. However, there are no approved and effective pharmaceuticals for NAFLD owing to a poor understanding of its pathological mechanisms. While emerging studies have demonstrated that m6A modification is highly associated with NAFLD. In this review, we summarize the general profile of NAFLD and m6A modification, and the role of m6A regulators including erasers, writers, and readers in NAFLD. Finally, we also highlight the clinical significance of m6A in NAFLD.

Genetic characterization of two G8P[8] rotavirus strains isolated in Guangzhou, China, in 2020/21: evidence of genome reassortment.

BACKGROUND: The G8 rotavirus genotype has been detected frequently in children in many countries and even became the predominant strain in sub-Saharan African countries, while there are currently no reports from China. In this study we described the genetic characteristics and evolutionary relationship between rotavirus strains from Guangzhou in China and the epidemic rotavirus strains derived from GenBank, 2020-2021. METHODS: Virus isolation and subsequent next-generation sequencing were performed for confirmed G8P[8] specimens. The genetic characteristics and evolutionary relationship were analyzed in comparison with epidemic rotavirus sequences obtained from GenBank. RESULTS: The two Guangzhou G8 strains were DS-1-like with the closest genetic distance to strains circulating in Southeast Asia. The VP7 genes of the two strains were derived from a human, not an animal G8 rotavirus. Large genetic distances in several genes suggested that the Guangzhou strains may not have been transmitted directly from Southeast Asian countries, but have emerged following reassortment events. CONCLUSIONS: We report the whole genome sequence information of G8P[8] rotaviruses recently detected in China; their clinical and epidemiological significance remains to be explored further.

microRNA-506 regulates proliferation, migration and invasion in hepatocellular carcinoma by targeting F-spondin 1 (SPON1).

Our previous study indicates microRNA-506 (miR-506) is downregulated in hepatocellular carcinoma (HCC). In the current study, we investigate the effects of miR-506 on proliferation, migration and invasion in HCC. We report that enforced expression of miR-506 inhibits proliferation, migration and invasion in vitro, and suppresses tumor growth in vivo. Conversely, suppression of miR-506 exhibits promoting effects on proliferation, migration and invasion in vitro, and on tumor growth in vivo. In addition, miR-506 binds to the 3'UTR of F-spondin 1(SPON1), and enforced expression of miR-506 decreases accumulation of SPON1. Moreover, enforced expression of SPON1 and suppression of SPON1 alleviates effects of miR-506 mimics and inhibitors on proliferation, migration and invasion in vitro, respectively. In conclusion, microRNA-506 regulates proliferation, migration and invasion in HCC by targeting SPON1.