The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development ...and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs.
The primary aim of this study is to discern the association between specific clinical parameters and low muscle mass (LMM). We endeavor to elucidate the determinants of LMM and the predictive potency ...of individual factors.
In this retrospective cross-sectional study, we encompassed 450 older adult Chinese participants (252 males and 198 females). Muscle mass quantifications were performed using bioelectrical impedance analysis. Comprehensive data encompassing demographic details (age, sex, height, and weight) and laboratory results (complete blood count, thyroid function, liver function, and renal function) were systematically recorded. Logistic regression models, coupled with receiver operating characteristic curve analytics, were employed to ascertain the variables influencing LMM and to evaluate the predictive validity of each parameter on LMM.
Upon confounding adjustment for age, gender, body mass index (BMI), and free thyroxine (FT4) persisted as a determinant of LMM. Specifically, individuals with an FT4 exceeding 1.105 ng/dL exhibited a 1.803-fold increased propensity for LMM relative to those with FT4 values below the specified threshold. Incorporating age, gender, BMI, and FT4 in the diagnostic algorithm enhanced the precision of LMM. The results differ between men and women. In the male population, we can still observe that FT4 has a certain value in the diagnosis of LMM, but this phenomenon is not found in the female population.
Elevated FT4 concentrations, albeit within clinically accepted limits, are inversely associated with muscle mass. As such, FT4 could be postulated as a potential biomarker for LMM in geriatric individuals, especially in the male group.
Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoofed animals such as pigs, cattle, and sheep. The disease is caused by the foot-and-mouth disease virus (FMDV) which ...has a non-enveloped virion with icosahedral symmetry that encapsulates a positive-sense, single-stranded RNA genome of ∼8.4 kb. FMDV infection causes obvious immunosuppressive effects on the host. In recent years, studies on the immunosuppressive mechanism of FMDV have become a popular topic. In addition, studies have shown that many FMDV proteins are involved in the regulation of host innate immunity and have revealed mechanisms by which FMDV proteins mediate host innate immunity. In this review, advances in studies on the mechanisms of interaction between FMDV proteins and host innate immunity are summarized to provide a comprehensive understanding of FMDV pathogenesis and the theoretical basis for FMD prevention and control.
The gut microbiota is widely regarded as a "metabolic organ" that could generate myriad metabolites to regulate human metabolism. As the microbiota metabolites, bile acids (BAs) have recently been ...identified as the critical endocrine molecules that mediate the cross-talk between the host and intestinal microbiota. This study provided a comprehensive insight into the gut microbiota and BA research through bibliometric analysis from 2003 to 2022. The publications on this subject showed a dramatic upward trend. Although the USA and China have produced the most publications, the USA plays a dominant role in this expanding field. Specifically, the University of Copenhagen was the most productive institution. Key research hotspots are the gut-liver axis, short-chain fatty acids (SCFAs), cardiovascular disease (CVD), colorectal cancer (CRC), and the farnesoid x receptor (FXR). The molecular mechanisms and potential applications of the gut microbiota and BAs in cardiometabolic disorders and gastrointestinal cancers have significant potential for further research.The gut microbiota is widely regarded as a "metabolic organ" that could generate myriad metabolites to regulate human metabolism. As the microbiota metabolites, bile acids (BAs) have recently been identified as the critical endocrine molecules that mediate the cross-talk between the host and intestinal microbiota. This study provided a comprehensive insight into the gut microbiota and BA research through bibliometric analysis from 2003 to 2022. The publications on this subject showed a dramatic upward trend. Although the USA and China have produced the most publications, the USA plays a dominant role in this expanding field. Specifically, the University of Copenhagen was the most productive institution. Key research hotspots are the gut-liver axis, short-chain fatty acids (SCFAs), cardiovascular disease (CVD), colorectal cancer (CRC), and the farnesoid x receptor (FXR). The molecular mechanisms and potential applications of the gut microbiota and BAs in cardiometabolic disorders and gastrointestinal cancers have significant potential for further research.
In this work, p-double network (p-DN) hydrogels were formed by the interpenetration of poly(2-acrylamide-2-methylpropanesulfonic acid-copolymer- acrylamide) microgel and polyacrylamide. The initial ...viscosity of prepolymer solution before hydrogel polymerization, mechanical properties, temperature and salt resistance of the hydrogels were studied. The results showed that the initial viscosity of the prepolymer was less than 30 mP·s, and the p-DN hydrogel not only exhibited high compressive stress (37.80 MPa), but the compressive strength of p-DN hydrogel could also reach 23.45 MPa after heating at 90 °C, and the compressive strength of p-DN hydrogel could reach 13.32 MPa after soaking for 24 h in the solution of 5W mineralization. In addition, the cyclic loading behavior of hydrogel was studied. The dissipation energy of p-DN hydrogel under 80% strain was 7.89 MJ/m
, which effectively dissipated energy. Meanwhile, p-DN hydrogel maintained its original form while breaking the pressure greater than 30 MPa, indicating excellent plugging performance.
Polycystin-1 (PC1) and -2 (PC2), products of the PKD1 and PKD2 genes, are mutated in autosomal dominant polycystic kidney disease (ADPKD). They localize to the primary cilia; however, their ciliary ...function is in dispute. Loss of either the primary cilia or PC1 or PC2 causes cyst formation. However, loss of both cilia and PC1 or PC2 inhibits cyst growth via an unknown pathway. To help define a pathway, we studied cilium length in human and mouse kidneys. We found cilia are elongated in kidneys from patients with ADPKD and from both Pkd1 and Pkd2 knockout mice. Cilia elongate following polycystin inactivation. The role of intraflagellar transport proteins in Pkd1-deficient mice is also unknown. We found that inactivation of Ift88 (a gene expressing a core component of intraflagellar transport) in Pkd1 knockout mice, as well as in a new Pkd2 knockout mouse, shortened the elongated cilia, impeded kidney and liver cystogenesis, and reduced cell proliferation. Multi-stage in vivo analysis of signaling pathways revealed β-catenin activation as a prominent, early, and sustained event in disease onset and progression in Pkd2 single knockout but not in Pkd2.Ift88 double knockout mouse kidneys. Additionally, AMPK, mTOR and ERK pathways were altered in Pkd2 single knockout mice but only AMPK and mTOR pathway alteration were rescued in Pkd2.Ift88 double knockout mice. Thus, our findings advocate an essential role of polycystins in the structure and function of the primary cilia and implicate β-catenin as a key inducer of cystogenesis downstream of the primary cilia. Our data suggest that modulating cilium length and/or its associated signaling events may offer novel therapeutic approaches for ADPKD.
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Abstract Objectives General practitioners are trained to care for patients with a high level of responsibility and professional competency. However, there are few reports on the physical and mental ...health status of general practitioners (GPs) in China, particularly regarding help seeking and self-treatment. The primary aims of this study were to explore GPs’ expectations of their own family doctors and their reflection on role positioning, and to explore the objective factors that hinder the system of family doctors. Study design Cross-sectional study. Methods We conducted an online survey of Chinese GPs. Descriptive statistics were used to summarize the findings. Results More than half of the participants (57.20%) reported that their health was normal over the past year. A total of 420 participants (23.35%) reported having chronic diseases. For sleep duration, 1205 participants (66.98%) reported sleeping 6–8 h per day; 473 participants (26.29%) reported chronic insomnia. Two hundred thirty-one participants (12.84%) had possible depression. A total of 595 (33.07%) participants reported that they had contracted a fixed family doctor. In terms of preventing themselves from contracting for a family doctor, the following factors were identified: lack of sufficient time (54.81%), could solve obstacles themselves (50.97%), and embarrassment (24.24%). The proportion of the contract group (12.44%) taking personal relationship as a consideration was higher than that of the non-contract group (7.64%) (χ2 = 10.934 P = 0.01). Most participants (79.90%) in the non-signed group reported never having seen a family doctor. In terms of obstacles, more than half of the signed group thought that they could solve obstacles themselves, while the non-signed group (39.20%) was less confident in the ability of family doctors than the signed group (29.75%) (χ2 = 15.436, P < 0.01). Conclusions GPs work under great pressure and lack of self-care awareness, resulting in an increased prevalence of health conditions. Most GPs did not have a regular family doctor. Having a family doctor with a fixed contract is more conducive to the scientific management of their health and provides a reasonable solution to health problems. The main factors hindering GPs from choosing a family doctor were time consumption, abilities to solve obstacles themselves, and trust in the abilities of GPs. Therefore, simplifying the process of family doctor visits, Changing the GPs' medical cognition, and strengthening the policy of GP training would be conducive to promoting a family doctor system that enhances hierarchical diagnosis and treatment. International collaboration could integrate GP health support into global healthcare system.
The efficacy of hepatitis B vaccination in adults was evaluated by comparison of the positive seroprotection rates and the hepatitis B surface antibody (anti-HBs) geometric mean titers (GMTs) between ...intensive intervention areas and non-intensive intervention areas after 8 years post-vaccination in the Zhejiang province. Seven cities (towns) in Zhejiang province were selected as intensive intervention areas, and adults in the demonstration areas receive hepatitis B vaccine voluntarily and for free. Other areas were non-intensive intervention areas. A total of 3587 participants received the full vaccination course (three doses), and blood samples were withdrawn 8 years after the first vaccination comprised the immunized group, and 2000 participants constituted the control group. The anti-HBs positive seroprotection rates of the immunized and control groups were 65.0% and 53.0%, respectively. The anti-HBs GMT of the subjects in the immunized group was 26.30 mIU/mL compared to 9.33 mIU/mL in the control group (P < .001). Significant differences were detected in the 24-35-, 36-45-, and 46-55-year-old subgroups in the positive seroprotection rates and the anti-HBs GMTs (P < .001) between the immunized and control groups. Moreover, significant differences were found in the anti-HBs GMT in the 46-55-year-old subgroup between the two groups (P = .02), while no differences were observed in the positive seroprotection rate (P = .428). In conclusion, adults who did not receive the hepatitis B vaccine in infancy and had negative serological markers of hepatitis B, especially adults <47-years-old, need vaccination.
Abstract
Background
Long non-coding RNA growth arrest specific 5 (GAS5) is a regulator in non-small cell lung cancer (NSCLC) progression. Nonetheless, the mechanism by which GAS5 exerts its ...biological function in NSCLC cells remains unclear.
Methods
GAS5, miR-221-3p relative expression levels in NSCLC tissues and cells were examined by qPCR. After gain-of-function and loss-of-function models were established, the viability of H1299 and A549 cells were examined by CCK-8 and EdU assays. Cell migration and invasion were examined by the Transwell experiment. The binding sequence of GAS5 for miR-221-3p was confirmed by the dual-luciferase reporter gene experiment. The regulatory function of GAS5 and miR-221-3p on IRF2 was investigated by Western blot.
Results
GAS5 expression was down-modulated in NSCLC tissues and cell lines. GAS5 overexpression restrained the proliferation, migration and invasion of NSCLC cells, while miR-221-3p, which was targeted and negatively modulated by GAS5, worked oppositely. Restoration of miR-221-3p markedly reversed the effects of GAS5 on NSCLC cells. Additionally, GAS5 increased IRF2 expression in NSCLC cells by repressing miR-221-3p.
Conclusions
GAS5 blocks the progression of NSCLC partly via increasing IRF2 expression level via repressing miR-221-3p.
The SSS (sea surface salinity) is an important factor affecting global climate changes, sea dynamic environments, global water cycles, marine ecological environments, and ocean carbon cycles. ...Satellite remote sensing is a practical way to observe SSS from space, and the key to retrieving SSS satellite products is to establish an accurate sea surface brightness temperature forward model. However, the calculation results of different forward models, which are composed of different relative permittivity models and SSR (sea surface roughness) brightness temperature increment models, are different, and the impact of this calculation difference has exceeded the accuracy requirement of the SSS inversion, and the existing SSR brightness temperature increment models, which primarily include empirical models and theoretical models, cannot match all the relative permittivity models. In order to address this problem, this paper proposes a universal DNN (deep neural network) model architecture and corresponding training scheme, and provides different SSR brightness temperature increment models for different relative permittivity models utilizing DNN based on offshore experiment data, and compares them with the existing models. The results show that the DNN models perform significantly better than the existing models, and that their calculation accuracy is close to the detection accuracy of a radiometer. Therefore, this study effectively solves the problem of SSR brightness temperature correction under different relative permittivity models, and provides a theoretical support for high-precision SSS inversion research.
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