MicroRNA-205-5p: A potential therapeutic target for influenza A.

We are committed to finding host targets for influenza A therapeutics. The nucleoprotein (NP) plays an important role in influenza A virus replication and is an indispensable part of viral transcription and replication. Exploring endogenous substances that can modulate NP is critical for finding host targets. MicroRNAs (miRNAs, miR) are a novel class of powerful, endogenous gene expression regulators. Herein, we used miRanda to analyse the base complementarity between the NP gene and the 14 host miRNAs reported previously by us. MiRanda predicted that miR-431-5p, miR-744-3p and miR-205-5p could complement the NP gene. To understand the effect of these miRNAs on NP expression, we co-transfected 293 T cells with NP gene sequence containing above miRNAs binding site or full sequence of NP gene (transfected into pmirGlo or pcDNA3.1 vectors, respectively), and mimics of miR-205-5p, miR-431-5p and miR-744-3p. Dual luciferase reporter gene or Western blotting assays confirmed that miR-205-5p and miR-431-5p inhibit NP expression by binding with the miRNA binding site of NP gene. Further, we infected Mouse Lung Epithelial (MLE-12) cells overexpressing miR-205-5p and miR-431-5p with influenza A virus and performed Western blotting to examine NP expression. We found that NP expression was significantly reduced in MLE-12 cells overexpressing miR-205-5p during influenza A infection. The miR-205-5p overexpression-induced inhibition of influenza A replication could be attributed to the inhibition of NP expression. Further, we administered oseltamivir and Jinchai Antiviral Capsules (JC, an anti-influenza Chinese medicine) to influenza A virus-infected MLE-12 cells and mice. We found that miR-205-5p was significantly decreased increased in infected cells and lung tissues, and oseltamivir and JC could up-regulate miR-205-5p. In conclusion, we provide new evidence that miR-205-5p plays a role in regulating viral NP protein expression in combating influenza A and may be a potential target for influenza A therapy.

Cantharidin induces senescence via inhibition of AMP-activated protein kinase and activation of NLRP3 inflammasome in H9c2 cardiomyocytes.

Cantharidin is a natural compound with cardiotoxicity. Cellular senescence and senescence-associated secretory phenotype (SASP) are implicated in chemotherapy-associated cardiotoxicity. We here investigated how cantharidin induced cardiomyocyte senescence. H9c2 cells were treated with cantharidin. Senescence, mitochondrial functions, SASP, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling and AMP-activated protein kinase (AMPK) phosphorylation were examined. Cantharidin inhibited viability and increased expression of senescence-associated ß--galactosidase (SA-ß-Gal), p16 and p21 in H9c2 cells, suggesting occurrence of senescence. Cantharidin impaired mitochondrial functions evidenced by reduction in basal respiration, ATP levels and spare respiratory capacity. Cantharidin also decreased mitochondrial DNA copy number and down-regulated mRNA levels of cytochrome c oxidase-I, -II and -III. Moreover, cantharidin suppressed activity of mitochondria complex-I and -II. Examinations of SASP showed that cantharidin promoted expression and secretion of SASP cytokines interleukin-1ß-, -6 and -8 and tumor necrosis factor-α, associated with activation of NLRP3/caspase-1 pathway. Finally, cantharidin suppressed AMPK phosphorylation. AMPK activator GSK621 abrogated the up-regulation of SA-ß--Gal, p16 and p21 and counteracted the activation of NLRP3 and caspase-1 in cantharidin-challenged H9c2 cells. In conclusion, cantharidin stimulated senescence and SASP in cardiomyocytes through activation of NLRP3 inflammasome and inhibition of AMPK, providing novel molecular insights into cantharidin-induced cardiotoxicity.

[Effect of polysaccharides from seeds of Vaccaria segetalis in alleviating urinary tract infection induced bladder injury by inhibiting NLRP3 inflammasome].

To study the mechanism of polysaccharides from seeds of Vaccaria segetalis( PSV) in the treatment of bacterial cystitis through the NLRP3 inflammasome pathway. The rat model of urinary tract infection was used and treated with PSV,and the urine and bladders were collected. The level of interleukin-10( IL-10) in rat urine was detected by enzyme linked immunosorbent assay( ELISA). Western blot and immunofluorescence staining were used to detect the expressions of sonic hedgehog( SHH) and NLRP3 inflammasome [NOD-like receptor thermoprotein domain 3( NLRP3),apoptosis associated speck like protein( ASC) and pro-caspase-1]. The expression of Toll-like receptor pathway was detected by RT-PCR. The death of 5637 cells induced by uropathogenic Escherichia coli( UPEC) and lactate dehydrogenase( LDH) release were evaluated using live/dead staining. The results showed that in the rat bladder,the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors were significantly up-regulated,and NLRP3 inflammasomes were significantly activated by UPEC infection. The administration with PSV could significantly increase the concentration of IL-10 in urine,inhibit the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors in bladder,and inhibit the activation of NLRP3 inflammasomes. A large number of 5637 cells were dead after UPEC infection and caused LDH production. PSV could significantly inhibit the death of 5637 cells and the release of LDH. In conclusion,PSV could inhibit the expression and activation of NLRP3 inflammasomes by inhibiting the Toll-like receptor pathway,thereby mitigating the bladder injury.

[Material basis and mechanism of Xiao'er Resuqing Oral Liquid on hand, foot and mouth disease based on network pharmacology and molecular docking].

This paper aimed to investigate the active components and molecular mechanism of Xiao'er Resuqing Oral Liquid on hand, foot and mouth disease(HFMD) based on network pharmacology and molecular docking methods. The potential active components of 8 herbs in Xiao'er Resuqing Oral Liquid were selected through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), Batman database and relevant literature consultation. Then related targets for the medicine were analyzed through PubChem and Swiss Target Prediction database, while related targets for HFMD were analyzed through GeneCards platform. The common targets for medicine and disease were put into STRING database to obtain the potential targets of Xiao'er Resuqing Oral Liquid for treatment of HFMD. The Cytoscape software was used to establish the "herbs-components-targets-disease" network. The protein-protein interaction(PPI) network was constructed based on STRING platform and Cytoscape software to screen the core targets. Based on Metascape platform, GO function enrichment analysis and KEGG signal pathway enrichment analysis were carried out. The main active components and potential key targets of Xiao'er Resuqing Oral Liquid were verified by molecular docking with Autodock vina 1.1.2 software. A total of 118 potential active components and 123 potential targets for treatment of HFMD were collected. PPI network indicated a total of 23 key targets, such as AKT1, MAPK1, IL6, VEGFA, EGFR, TNF, HRAS, CCND1, and CXCL8. GO function enrichment analysis results showed that there were 381 GO biological processes, 127 GO cellular components, and 117 GO molecular functions(P<0.01). KEGG enrichment analysis showed that 116 signal pathways were obtained(P<0.01), and the results showed that it was mainly associated with TNF signal pathway, IL-17 signal pathway, inflammatory mediator regulation of TRP channels, and cytokine-cytokine receptor interaction. Molecular docking results showed that the main active components all had a high binding ability with the main potential key targets. This study preliminarily investigated the multi-pathways, multi-targets and multi-components molecular mechanism of Xiao'er Resuqing Oral Liquid for treatment of HFMD, providing theoretical references for further researches on its active components and action mechanism.

[Meta-analysis on effectiveness and safety of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection].

To systematically review the effectiveness and safety of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection and conduct Meta-analysis. We electronically retrieved databases, including PubMed, Web of Science, VIP, WanFang and CNKI, for published articles of randomized controlled trials(RCTs) of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection from inception to April 2019. According to the inclusion and exclusion criteria, two reviewers independently screened out literatures, extracted data and assessed the risk of bias in included studies. Then, Meta-analysis were conducted by Stata 15.0 software. A total of 16 RCTs involving 1 924 patients with upper respiratory infection were included. The results of Meta-analysis showed that the improvement of clinical symptoms, such as fever subsided time(WMD=-3.66, 95%CI[-4.61,-2.72], P<0.001), cough time(WMD=-1.89, 95%CI[-2.51,-1.27], P<0.001), time of runny noses(WMD=-4.60, 95%CI[-5.85,-3.34], P<0.001) and time of sore throat(WMD=-2.62, 95%CI[-3.54,-1.70], P<0.001). Meanwhile, the results of Meta-analysis showed the improvement of laboratory indications, including TNF-α(WMD=-2.68, 95%CI[-2.98,-1.58], P<0.001) and IL-6(WMD=-2.26, 95%CI[-3.36,-2.36], P<0.01). The current evidence shows that Pudilan Xiaoyan Oral Liquid may significantly improve the effectiveness and safety. According to the limited quality of included studies, the above conclusion needs be to verified with more high-quality studies.

[Study on therapeutic effect of Chaiyin Particles on combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome based on regulation of immune function].

According to the classification of traditional Chinese medicine syndromes of coronavirus disease 2019 by the national competent authority, this study determined that human coronavirus 229 E(HCoV-229 E) was infected in a mouse model of cold and dampness syndrome, so as to build the human coronavirus pneumonia with pestilence attacking lung syndrome model. The model can simulate the traditional Chinese medicine treatment of common disease syndromes in Coronavirus Disease 2019 Diagnosis and Treatment Program(the sixth edition for trial). Specific steps were as follows. ABALB/c mouse model of cold and dampness syndrome was established, based on which, HCoV-229 E virus was infected; then the experiment was divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), high-dose Chaiyin Particles group(8.8 g·kg~(-1)·d~(-1)), and low-dose Chaiyin Particles group(4.4 g·kg~(-1)·d~(-1)). On the day of infection, Chaiyin Particles was given for three consecutive days. Lung tissues were collected the day after the last dose, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted, and the HCoV-229 E virus load was detected by Real-time fluorescent quantitative RT-PCR. Blood leukocytes were separated, and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted, and IL-6, IL-10, TNF-α and IFN-γ contents were detected by ELISA. High and low-dose Chaiyin Particles significantly reduced the lung index(P<0.01) of mice of human coronavirus pneumonia with pestilence attacking the lung syndrome, and the inhibition rates were 61.02% and 55.45%, respectively. Compared with the model control group, high and low-dose Chaiyin Particles significantly increased cross blood CD4~+ T lymphocytes, CD8~+T lymphocytes and total B lymphocyte percentage(P<0.05, P<0.01), and reduced IL-10, TNF-α and IFN-γ levels in lungs(P<0.01). In vitro results showed that TC_(50), TC_0, IC_(50) and TI of Chaiyin Particles were 4.46 mg·mL~(-1), 3.13 mg·mL~(-1), 1.12 mg·mL~(-1) and 4. The control group of in vitro culture cells had no HCoV-229 E virus nucleic acid expression. The expression of HCoV-229 E virus nucleic acid in the virus control group was 1.48×10~7 copies/mL, and Chaiyin Particles significantly reduced HCoV-229 E expression at doses of 3.13 and 1.56 mg·mL~(-1), and the expression of HCoV-229 E nucleic acid was 9.47×10~5 and 9.47×10~6 copies/mL, respectively. Chaiyin Particles has a better effect on the mouse model with human coronavirus pneumonia with pestilence attacking the lung syndrome, and could play a role by enhancing immunity, and reducing inflammatory factor expression.

[Application of Reyanning Mixture in evaluating combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome].

In the previous research, our laboratory established a mouse model combining disease with syndrome of human coronavi-rus pneumonia with pestilence attacking the lung syndrome, based on the national traditional Chinese medicine clinical classification of Novel Coronavirus Infected Pneumonia Diagnosis and Treatment Plan. In this study, a mouse model combining disease with syndrome of human coronavirus pneumonia with pestilence attacking the lung syndrome was used to evaluate the effectiveness of Reyanning Mixture to provide animal experimental support for clinical application. Mice were divided into normal group, 229 E infection group, cold-dampness group, cold-dampness+229 E infection group(the model group), Reyanning high and low dose groups. The cold-dampness group, cold-dampness+229 E infection group, two Reyanning groups were given cold and damp stimulation for 7 days. On the 5 th day, the 229 E infection group, cold-dampness+229 E infection group, and two Reyanning groups were infected with HCoV-229 E virus. Reyanning was administered for 3 days, starting from the day of infection. Blood was collected on the 4 th day and the lung tissue was dissected to calculate the lung index and inhibition rate; flow cytometry was used to detect the percentage of T and B lymphocytes in peripheral blood; RT-PCR was used to detect the nucleic acid virus load in lung tissue; ELISA was used to detect motilin and gastrin in serum, and inflammatory factors TNF-α, IFN-γ, IL-6, IL-10 in lung tissue proteins. Reyanning Mixture could reduce the lung index(P<0.01) of coronavirus pneumonia mice with pestilence attacking the lung; it could significantly increase the percentage of CD8~+ T lymphocytes and CD4~+ T lymphocytes in peripheral blood of model mice(P<0.05, P<0.01). The low dose of Reyanning could effectively increase the percentage of total B lymphocytes(P<0.05), reduce virus load in lung tissue of model mice(P<0.01), reduce the levels of TNF-α, IFN-γ, IL-6, IL-10 in the lung tissue of model mice(P<0.01), reduce the content of motilin in the serum of model mice(P<0.01). Reyanning Mixture convey a better effect in treating coronavirus pneumonia mice with pestilence attacking the lung. It manifested obvious effects in improving lung lesions, enhancing the gastrointestinal function of mice, improving the autoimmune function of mice, and reducing the expression of inflammatory factors in vivo, which could provide evidences for clinical research.

[Therapeutic effect of Compound Qinlan Oral Liquid on treating combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome].

The aim of this paper was to investigate the therapeutic effect of Compound Qinlan Oral Liquid recommended by Provincial Novel Coronary Virus Pneumonia Treatment Scheme on the treatment of BALB/c mice with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome and to explore its clinical application in the treatment of novel coronavirus pneumonia, and to provide laboratory data support for clinical Chinese medicine. According to the classification of syndromes of novel coronavirus pneumonia by the national competent department of traditional Chinese medicine, this study determined that human coronavirus 229 E(HCoV-229 E)-infected mouse model of cold and dampness syndrome can be used to study human coronavirus pneumonia combined with pestilence attacking the lung syndrome model. This model is suitable for simulating traditional Chinese medicine treatment of common disease syndromes in Novel Coronavirus Pneumonia Diagnosis and Treatment program(trial implementation of the sixth edition). Specific steps are as follows. BALB/c mice of cold and dampness syndrome is infected with HCoV-229 E virus, and were divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), and Compound Qilan Oral Liquid high dose group(22 mL·kg~(-1)·d~(-1)) and low dose group(11 mL·kg~(-1)·d~(-1)). On the day of infection, the Compound Qilan Oral Liquid was administered for three consecutive days. On the last dosing day, the lung tissue was dissected, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted and the HCoV-229 E virus load was detected by RT-PCR. Blood leukocytes were separated and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted and the contents of IL-6, IL-10, TNF-α and IFN-γ were detected by ELISA. Serum was separated and the contents of gastrin(GAS) and motilin(MTL) were detected by ELISA. Histopathological analysis was performed with lung tissue. The high and low doses of Compound Qinlan Oral Liquid significantly reduced the lung index(P<0.01) of mice with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome, and the inhibition rates were 59.01% and 47.72%, respectively. Compared with the model control group, the high and low doses of Compound Qinlan Oral Liquid significantly reduced lung tissue viral load(P<0.01), increased cross blood CD4~+ T lymphocytes, CD8~+ T lymphocytes and total B lymphocyte percentage(P<0.01), reduced serum motilin content(P<0.01), reduced IL-6, IL-10, TNF-α and IFN-γ levels in lungs(P<0.01) and reduced lung tissue inflammation. Compound Qinlan Oral Liquid has a better effect on the mouse model with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome, which may attribute to its function of in virus replication inhibition, gastrointestinal function improvement, immunity enhancement, and inflammatory factor reduction.

Changing Geographic Patterns and Risk Factors for Avian Influenza A(H7N9) Infections in Humans, China.

The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016-2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far.

Shufeng Jiedu Capsules Alleviate Lipopolysaccharide-Induced Acute Lung Inflammatory Injury via Activation of GPR18 by Verbenalin.

BACKGROUND/AIMS: Acute respiratory tract infection (ARTI) is the most common reason for outpatient physician office visits. Although powerful and significant in the treatment of infections, antibiotics used for ARTI inappropriately have been an important contributor to antibiotic resistance. We previously reported that Shufeng Jiedu Capsule (SJC) can effectively amplify anti-inflammatory signaling during infection. In this study, we aimed to systematically explore its composition and the mechanism of its effects in ARTI. METHODS: Pseudomonas aeruginosa (PAK) strain was used to generate a mouse model of ARTI, which were then treated with different drugs or compounds to determine the corresponding anti-inflammatory roles. High-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry. was conducted to detect the chemical compounds in SJC. RNAs from the lung tissues of mice were prepared for microarray analysis to reveal globally altered genes and the pathways involved after SJC treatment. RESULTS: SJC significantly inhibited the expression and secretion of inflammatory factors from PAK-induced mouse lung tissues or lipopolysaccharide-induced peritoneal macrophages. Verbenalin, one of the bioactive compounds identified in SJC, also showed notable anti-inflammatory effects. Microarray data revealed numerous differentially expressed genes among the different treatment groups; here, we focused on studying the role of GPR18. We found that the anti-inflammatory role of verbenalin was attenuated in GPR18 knockout mice compared with wild-type mice, although no statistically significant difference was observed in the untreated PAK-induced mice types. CONCLUSION: Our data not only showed the chemical composition of SJC, but also demonstrated that verbenalin was a significant anti-inflammatory compound, which may function through GPR18.

Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

Opportunities and challenges for human papillomavirus vaccination in China.

Current estimates of the HPV infection rate in China vary by geographic region (9.6-23.6%), with two age peaks in prevalence in women ≤20-25 years of age and 50-60 years of age. HPV-16, 52 and 58 are the most commonly-detected HPV genotypes in the Chinese population. In China, five HPV vaccines are licensed and several others are undergoing clinical trials. Multiple RCTs have shown the efficacy and safety of the bvHPV (Cervarix), Escherichia coli-produced bvHPV (Cecolin), Pichia pastoris-produced bvHPV (Walrinvax), qvHPV (Gardasil) and 9vHPV (Gardasil-9) vaccines in Chinese populations, including two studies showing long-term efficacy (≥8 years) for the bvHPV and qvHPV vaccines. Real-world data from China are scarce. Although modeling studies in China show HPV vaccination is cost-effective, uptake and population coverage are relatively low. Various policies have been implemented to raise awareness and increase vaccine coverage, with the long-term aim of eliminating cervical cancer in China.

Comprehensive pan-cancer analysis of 33 human cancers reveals immunotherapeutic value of focal adhesion tyrosine kinase.

The immune environment in tumors is the key factor affecting the survival and immunotherapeutic response of patients. This research aimed to explore the underlying association between focal adhesion tyrosine kinase (FAK/PTK2) and cancer immunotherapy in 33 human cancers. Gene expression data and clinical features of 33 cancers were retrieved from the Cancer Genome Atlas Database. The immunotherapy cohorts included GSE67501, GSE78220, and IMVIGOR210, which were derived from the comprehensive gene expression database or from previous studies. Clinical parameters including patient age, gender, survival rate, and tumor stage were analyzed to evaluate the prognostic value of FAK/PTK2. FAK/PTK2 activity was detected by single-sample gene set enrichment analysis and used to compare the difference between FAK/PTK2 transcriptome and protein expression levels. To better understand the role of FAK/PTK2 in cancer immunotherapy, we analyzed its correlations with tumor microenvironment and with immune processes/elements (e.g., immune cell infiltration, immunosuppressants, and stimulants) and major histocompatible complexes. Potential pathways associated with FAK/PTK2 signaling in cancers were also explored. Correlations between FAK/PTK2 and 2 immunotherapeutic biomarkers (tumor mutation load and microsatellite instability) were studied. Finally, the 3 independent immunotherapy cohorts were used to study the relationship between FAK/PTK2 and immunotherapeutic response. Although FAK/PTK2 is not closely associated with age (13/33), gender (5/33), or tumor stage (5/33) in any of the studied human cancers, it has potential prognostic value for predicting patient survival. Consistency between FAK/PTK2 activity and expression exists in some cancers (3/33). Generally, FAK/PTK2 is robustly correlated with immune cell infiltration, immune modulators, and immunotherapeutic markers. Moreover, high FAK/PTK2 expression is significantly related to immune-relevant pathways. However, FAK/PTK2 is not significantly correlated with the immunotherapeutic response. Research on the immunotherapeutic value of FAK/PTK2 in 33 human cancers provides evidence regarding the function of FAK/PTK2 and its role in clinical treatment. However, given the use of a bioinformatics approach, our results are preliminary and require further validation.

Unveiling the mechanism of high sugar diet induced advanced glycosylation end products damage skin structure via extracellular matrix-receptor interaction pathway.

BACKGROUND: AGEs accumulate in the skin as a result of a high-sugar diet and play an important role in the skin aging process. OBJECTIVES: The aim of this study was to characterize the mechanism underlying the effect of a high-sugar diet on skin aging damage at a holistic level. METHODS: We established a high-sugar diet mouse model to compare and analyze differences in physiological indexes. The effect of a high-sugar diet on skin aging damage was analyzed by means of a transcriptome study and staining of pathological sections. Furthermore, the differences in the protein expression of AGEs and ECM components between the HSD and control groups were further verified by immunohistochemistry. RESULTS: The skin in the HSD group mice tended toward a red, yellow, dark, and deep color. In addition, the epidermis was irregular with anomalous phenomena, the epidermis was thinned, and the dermis lost its normal structure and showed vacuolated changes. Transcriptomics results revealed significant downregulation of the ECM-receptor interaction pathway, significant upregulation of the expression of AGEs and significant downregulation of the expression levels of COLI, FN1, LM5, and TNC, among others ECM proteins and ECM receptors. CONCLUSIONS: High-sugar diets cause skin aging damage by inducing the accumulation of AGEs, disrupting the expression of ECM proteins and their receptors, and downregulating the ECM-receptor interaction pathway, which affects cellular behavioral functions such as cell proliferation, migration, and adhesion, as well as normal skin tissue structure.

Feasibility and reproducibility of cardiovascular magnetic resonance-feature tracking for quantitative right atrial function in dilated cardiomyopathy patients.

Background: The importance of right heart assessment in dilated cardiomyopathy (DCM) is increasingly recognized. The development of cardiovascular magnetic resonance-feature tracking (CMR-FT) has provided a novel approach to quantify myocardial deformation and evaluate cardiac function. In this study, we aimed to evaluate the feasibility and reproducibility of CMR-FT for the quantitative derivation of right atrial (RA) strain and strain rate (SR) in patients with DCM. Methods: A total of 68 DCM patients (84% male; aged 50.6±13.2 years) and 58 healthy controls (81% male; aged 48.4±11.2 years) were retrospectively enrolled from September 2018 to August 2022 at the First Affiliated Hospital of Zhejiang Chinese Medical University and Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine. RA reservoir, conduit, and booster strain (εs, εe, and εa) and peak positive, peak early negative, and peak late negative SR (SRs, SRe, and SRa) were measured using CMR-FT and compared between 2 groups using Student's t-test. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: Compared to healthy controls, DCM patients showed significantly lower RA strain (εs: 19.7%±9.0% vs. 44.4%±9.7%; εe: 7.9%±5.3% vs. 25.8%±8.6%; εa: 11.8%±6.2% vs. 18.6%±5.1%, all P<0.001) and SR (SRs: 1.17±0.48 vs. 1.92±0.62 s-1; SRe: -0.85±0.56 vs. -1.94±0.63 s-1; SRa: -1.39±0.71 vs. -2.01±0.65 s-1, all P<0.001). There was no significant difference in RA maximum volume index between the 2 groups. Simple linear regression analysis demonstrated a significant correlation between N-terminal B-type natriuretic peptide (NT-proBNP), RA emptying fraction passive (RAEF passive), and RA εe [(NT-proBNP and εe): r=-0.48, P<0.001, 95% confidence interval (CI): -0.64 to -0.26; and (RAEF passive and εe): r=0.41, P=0.001, 95% CI: 0.22 to 0.56, respectively] in DCM patients. Intra- and inter-observer reproducibility was excellent (all ICCs >0.85) for RA deformation measurements. Conclusions: CMR-FT is a promising, noninvasive approach for the quantitative assessment of RA phasic function in patients with DCM. DCM patients exhibit impaired RA reservoir, conduit, and booster pump function prior to visible RA enlargement.

Hypoxia inhibits ferritinophagy-mediated ferroptosis in esophageal squamous cell carcinoma via the USP2-NCOA4 axis.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive system. Hypoxia is a crucial player in tumor ferroptosis resistance. However, the molecular mechanism of hypoxia-mediated ferroptosis resistance in ESCC remains unclear. Here, USP2 expression was decreased in ESCC cell lines subjected to hypoxia treatment and was lowly expressed in clinical ESCC specimens. Ubiquitin-specific protease 2 (USP2) depletion facilitated cell growth, which was blocked in USP2-overexpressing cells. Moreover, USP2 silencing enhanced the iron ion concentration and lipid peroxidation accumulation as well as suppressed ferroptosis, while upregulating USP2 promoted ferroptotic cell death in ESCC cells. Furthermore, knockout of USP2 in ESCC models discloses the essential role of USP2 in promoting ESCC tumorigenesis and inhibiting ferroptosis. In contrast, overexpression of USP2 contributes to antitumor effect and ferroptosis events in vivo. Specifically, USP2 stably bound to and suppressed the degradation of nuclear receptor coactivator 4 (NCOA4) by eliminating the Lys48-linked chain, which in turn triggered ferritinophagy and ferroptosis in ESCC cells. Our findings suggest that USP2 plays a crucial role in iron metabolism and ferroptosis and that the USP2/NCOA4 axis is a promising therapeutic target for the management of ESCC.

Antiviral activity of Jinchai capsule against influenza virus.

OBJECTIVE: To evaluate the effect on influenza virus of Jinchai, a capsule made of Traditional Chinese Medicine. METHODS: Madin-darby canine kidney (MDCK) cells were infected with the FM1 strain of influenza virus A (subtype H1N1) in vitro. They were used to explore how Jinchai affected cell adsorption, cell membrane fusion, transcription and replication of the influenza virus. Hemagglutinin (HA) protein, intracellular pH, and influenza virus protein acid (PA) polymerase subunit were detected with confocal microscopy and real-time fluorescent quantitative polymerase chain reaction. RESULTS: Jinchai significantly reduced the expression of HA and PA polymerase subunit mRNA in infected MDCK cells. Jinchai also significantly decreased intracellular pH in infected cells. CONCLUSIONS: Jinchai had strong anti-influenza activity against the influenza virus. It weakened the ability of the influenza virus to adsorb to cell wall and fuse with cell membranes in the early infection stage, and inhibited the transcription and replication of the virus.

The influencing factor model and empirical research of TikTok charity live streaming impact users' online charitable donation.

The "live streaming + charity" model is a new model for China's philanthropy, accelerating the new development of China's philanthropy, but there is still a relative paucity of research in the academic community on how charity live streaming affects online charitable donations. In this sense, this study aims to identify the construction of a model of the factors influencing charity live streaming on online charitable donations. This study selected TikTok Live, based on the UTAUT model, combining perceived risk and perceived interactivity, recovered 607 valid questionnaires, and concluded and structural equation modeling to construct an influence factor model to analyze their correlation. The results show that users' performance expectancy, effort expectancy, perceived interactivity, facilitating conditions, and social influence are significantly positively correlated with online charitable donations, and perceived risk does not negatively affect users' intentions to make online charitable donations. Our findings can provide a basis for live-streaming platforms and relevant social organizations and government departments to develop charity communication strategies.

Necrotic related-lncRNAs: Prediction of prognosis and differentiation between cold and hot tumors in head and neck squamous cell carcinoma.

Treatment of head and neck squamous cell carcinoma (HNSCC) is a substantial clinical challenge due to the high local recurrence rate and chemotherapeutic resistance. This project seeks to identify new potential biomarkers of prognosis prediction and precision medicine to improve this condition. A synthetic data matrix for RNA transcriptome datasets and relevant clinical information on HNSCC and normal tissues was downloaded from the Genotypic Tissue Expression Project and The Cancer Genome Atlas (TCGA). The necrosis-associated long-chain noncoding RNAs (lncRNAs) were identified by Pearson correlation analysis. Then 8-necrotic-lncRNA models in the training, testing and entire sets were established through univariate Cox (uni-Cox) regression and Lasso-Cox regression. Finally, the prognostic ability of the 8-necrotic-lncRNA model was evaluated via survival analysis, nomogram, Cox regression, clinicopathological correlation analysis, and receiver operating characteristic (ROC) curve. Gene enrichment analysis, principal component analysis, immune analysis and prediction of risk group semi-maximum inhibitory concentration (IC50) were also conducted. Correlations between characteristic risk score and immune cell infiltration, immune checkpoint molecules, somatic gene mutations, and anti-cancer drug sensitivity were analyzed. Eight necrosis-associated lncRNAs (AC099850.3, AC243829.2, AL139095.4, SAP30L-AS1, C5orf66-AS1, LIN02084, LIN00996, MIR4435-2HG) were developed to improve the prognosis prediction of HNSCC patients. The risk score distribution, survival status, survival time, and relevant expression standards of these lncRNAs were compared between low- and high-risk groups in the training, testing and entire sets. Kaplan-Meier analysis showed the low-risk patients had significantly better prognosis. The ROC curves revealed the model had an acceptable predictive value in the TCGA training and testing sets. Cox regression and stratified survival analysis indicated that the 8 necrosis-associated lncRNAs were risk factors independent of various clinical parameters. We recombined the patients into 2 clusters through Consensus ClusterPlus R package according to the expressions of necrotic lncRNAs. Significant differences were found in immune cell infiltration, immune checkpoint molecules, and IC50 between clusters, suggesting these characteristics can be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. This risk model may serve as a prognostic signature and provide clues for individualized immunotherapy for HNSCC patients.

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma.

Aging is highly associated with tumor formation and progression. However, little research has explored the association of aging-related lncRNAs (ARLs) with the prognosis and tumor immune microenvironment (TIME) of head and neck squamous cell carcinoma (HNSCC). RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas. In the training group, we used Pearson correlation, univariate Cox regression, least absolute shrinkage/selection operator regression analyses, and multivariate Cox regression to build a prognostic model. In the test group, we evaluated the model. Multivariate Cox regression was done to screen out independent prognostic factors, with which we constructed a nomogram. Afterward, we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics. Gene set enrichment analysis, immune correlation analysis, and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno- and chemo-therapeutic responses. The most important LINC00861 in the model was examined in HNE1, CNE1, and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid. In addition, CCK-8, Edu, and SA-ß-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells. The signature based on nine ARLs has a good predictive value in survival time, immune infiltration, immune checkpoint expression, and sensitivity to multiple drugs. LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells, and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines. This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC. LINC00861 is a protective factor for the development of HNSCC.