Sodium ; Wastewater ; Potassium ; Diet ; Blood Pressure ; China ; Sodium, Dietary ; Sodium Chloride, Dietary

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Objective To investigate the effect of phlorofucofuroeckol A(PFFE-A)on the proliferation and invasion of colorectal carcinoma cells and its regulation of transforming growth factor-β1(TGF-β1)and mothers against decapentaplegic hom-olog 2/3(Smad2/3)signaling pathway.Methods The cells were processed as follows:the cells were intervened with low,medium and high doses of 50,100,and 150 μmol·L-1 of PFFE-A,respectively and cells in the normal control group were also established.5-Ethynyl-2'-deoxyuridine(EdU)staining was used to detect the cell proliferation.The transwell chamber was used to detect the invasion ability.A xenograft colon cancer nude mice model was used to detect the growth and metastasis ability of the cells in vivo.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of epithelial-to-mes-enchymal transition(EMT)related genes.Western blotting was used to detect the expression levels of TGF-β1 and p-Smad2/3 in cells.Results Compared with normal control group,the proliferation rate,the number of invaded cells,the tumor mass,the pro-portion of tumor metastasis,the expression of N-cadherin mRNA,the expression of TGF-β1 and p-Smad2/3 were significantly de-creased(P＜0.05),and the mRNA expression of E-cadherin was significantly increased(P＜0.05).All were presented with a sig-nificant dose-dependent(P＜0.05).Conclusion PFFE-A could inhibit the EMT process of tumor cells,inhibit the prolifera-tion and invasion of HT29 cells in vitro,and down-regulate the growth and metastasis of HT29 cells in vivo,which may be achieved by down-regulating TGF-β1/Smad2/3 signaling pathway.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

Infrared spectroscopy technology has many advantages such as high efficiency and non-destructiveness,and has an important research and application value in the field of petroleum pollutant classification and detection.In this study,a petroleum pollutant classification method by combing the discrete wavelet transform(DWT)algorithm and a one-dimensional convolutional neural network based on the Inception module(Inception-1D-CNN)was proposed.Firstly,the DWT algorithm was used to denoise the original infrared spectral data to eliminate the interference information caused by experimental environment,instrument error and manual operation.Then,the inception-1D-CNN model was used to obtain multi-scale infrared spectroscopy feature information,and then classify the petroleum pollutants.Experimental results showed that compared with preprocessing methods such as standard normal variable(SNV),adaptive iteratively reweighted penalized least squares(AirPLS),and Savitzky-Golay smoothing(S-G),the prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 3×1 was 86.6%,which was 6.6%,6.6%and 3.3%higher,respectively.The prediction accuracy of DWT algorithm combined with 1D-CNN model with a convolutional kernel size of 5×1 was 93.3%,which was 10.0%,7.0%and 3.3%higher,respectively.The prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 7×1 was 90.0%,which was 6.7%,10.0%and 3.4%higher,respectively.The prediction accuracy of the DWT algorithm combined with the inception-1D-CNN model was 100.0%,which was 10.0%,10.0%and 3.4%higher,respectively.Therefore,the DWT algorithm combined with the inception-1D-CNN model could accurately classify and predict petroleum pollutants,and provided a certain basis for the subsequent treatment of oil spills on the sea surface.

Snake bites are characterized by acute onset,rapid changes in condition,and high disability and mortality rates.The effects of snake venom on the human body are divided into systemic and local toxic effects.The popu-larity of antivenom has greatly reduced the mortality of snake bites,but local tissue damage and permanent dysfunction are still problems to be solved urgently.Studies have found that snake venom metalloproteinases,hyaluronidases,phospholi-pases and other venoms participate in a variety of local pathological effects by interfering with the degradation and remodel-ing of extracellular matrix(ECM).This article reviews the mechanism of ECM in the development of local tissue damage caused by snake bites,in order to find effective therapeutic targets and provide reference and ideas for the clinical research and prevention of local tissue damage caused by snake bites.

The UK screening and treatment of retinopathy of prematurity(ROP)updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists,following the standards of the National Institute for Health and Care Excellence.They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022,and formally published in Early Human Development in March 2023.The guidelines provide evidence-based recommendations for the screening and treatment of ROP.The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks.The treatment section covers treatment indications,timing,methods,and follow-up visits of ROP.This article interprets the guidelines and compares them with ROP guidelines/consensus in China,providing a reference for domestic peers.