Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

[Purpose]To analyze the trend of incidence rates of gallbladder cancer in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of gallbladder cancer from 1972 to 2021 were collected from the Qidong Tumour Registry database,the crude incidence rate(CR),age-standardized rate by Chinese standard population(ASRC),age-standardized rate by world standard population(ASRW)of gallbladder cancer were calculated.Trend analysis was per-formed using Joinpoint 4.9.1.0 software to calculate the average annual percentage change(AAPC)of gallbladder cancer incidence rates,and time trend analysis was performed on the overall inci-dence rate by sex and age.[Results]A total of 1 369 cases of gallbladder cancer occurred in Qi-dong City from 1972 to 2021,accounting for 0.93％of all malignant tumors.The overall CR of gallbladder cancer was 2.44/105 in 50 years,ASRC was 0.88/105 and ASRW was 1.45/105.The truncated rate of 35～64 years old was 1.98/105,the cumulative incidence of gallbladder cancer at 0～74 years old was 0.16％,and the risk of cumulative incidence of gallbladder cancer was 0.16％.CR was slightly higher in women than that in men,but after standardization it was slightly higher in men than that in women.The sex ratio of CR,ASRC and ASRW was 0.89,1.07 and 1.06,respectively.With the increase of age,the incidence of gallbladder cancer was also increased.The age of onset was slightly increased in last 50 years.In last 50 years,there was an upward trend in the overall incidence of gallbladder cancer,the incidence both for men and women,and the inci-dence of each age group.[Conclusion]The incidence of gallbladder cancer in Qidong City has increased considerably during the past 50 years,and continuing attention should be paid to the prevention and treatment of gallbladder cancer especially for the key populations.

[Purpose]To analyze the survival rate of breast cancer in Qidong City of Jiangsu Province from 1972 to 2019 and to predict the trend in the next 10 years.[Methods]The data of breast cancer collected from Qidong Cancer Registry from 1972 to 2019 were extracted.Observed survival rate(OSR),relative survival rate(RSR),age-adjusted relative survival(ARS)and average annual percentage change(AAPC)of breast cancer were calculated.ARIMA model was used to predict the trend of breast cancer survival rate.[Results]The 5-year RSR increased from 57.30％during 1972-1977 to 89.01％during 2014-2019,and the uptrend of RSR in the 8 periods was statistically significant(P＜0.001).The 5-year ARS increased from 48.12％during 1972-1977 to 85.64％during 2014-2019 with an AAPC of 1.85％(t=10.113,P＜0.001).The 5-year RSR during 1972-2019 for males was 85.22％,and for females was 74.51％.For females,the 5-year RSR in-creased from 56.44％during 1972-1977 to 88.93％during 2014-2019 with an AAPC of 1.29％(t=13.087,P＜0.001),and the 5-year ARS increased from 46.14％during 1972-1977 to 85.23％during 2014-2019 with an AAPC of 1.90％(t=10.369,P＜0.001).The 5-year RSR in the age groups of 25～34,35～44,45～54,55～64,65～74,and over 75 years old were 66.91％,74.69％,76.97％,75.52％,73.44％and 66.40％,respectively;the corresponding AAPCs of 5-RSR in above age groups were 1.02％(t=3.816,P=0.009),1.03％(t=4.936,P=0.003),1.23％(t=5.826,P=0.001),1.86％(t=5.997,P=0.001),2.13％(t=10.245,P＜0.001),and 1.44％(t=6.405,P=0.001),respectively.ARIMA modeling of survival trend prediction showed that 5-RSR and 5-ARS for breast cancer will be ascended to 98.76％and 98.33％by 2028,respectively.[Conclusion]The overall survival rate of registered breast cancer cases in Qidong City has been greatly improved and will be further improved in the future,more attention should be paid to the prevention and treatment of breast cancer.

Objective:To develop a double-antibody sandwich ELISA for detecting soluble advanced oxidation protein products(AOPPs).Methods:BALB/c mice were immunized with sodium hypochlorite-oxidized mouse albumin to generate AOPPs-specific monoclonal antibodies(mAbs).Specificity of the mAbs was assessed using indirect ELISA and Western blot.Competitive ELISA was employed to determine if the epitope recognized by newly prepared mAb was consistent with that recognized by mAb 3F2,which developed in our previous work.The sandwich ELISA was then established,and its specificity and sensitivity were compared with the chloramine-T method,the repeatability of double-mAb sandwich ELISA was verified.Results:A mAb AP-4C5 with specific AOPPs recognition was obtained,two sandwich ELISA were developed for the specific detection of soluble AOPPs.Double-mAb sandwich ELISA,using mAb 3F2 as the capture antibody and mAb AP-4C5 as the detection antibody,detected AOPPs in range of 0.25～2 μg/ml(R2=0.991 80).PcAb-mAb sandwich ELISA,using goat anti-HSA polyclonal antibody as the capture antibody and AP-4C5 as detection antibody,detected AOPPs in range of 1.5～25 μg/ml(R2=0.968 75).The double-mAb sandwich ELISA was found to be more sensitive and specific compared to chloramine-T method.Double-mAb sandwich ELISA has good reproducibility(intra-assay CV:3.23％～4.51％,inter-assay CV:3.08％～5.29％).Conclusion:Two kinds of sandwich ELISA for detecting soluble AOPPs have been estab-lished,which hold promise for the detection of clinical samples and understanding of the pathogenic mechanisms of AOPPs.

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective To explore the impact of the TINCR-MAF:MAFB transcription factor network on the expression of proliferation and differentiation-related genes in keratinocytes,to verify the role of this network in the occurrence and development of psoriasis and its potential mechanisms.Methods Employed RNA interference technology to knock down TINCR gene expression,and the proliferation ability of keratinocytes was assessed using the CCK-8 method.Additionally,qRT-PCR and Western blot analyses were conducted to evaluate the RNA and protein expression levels of TINCR,MAFB,and KLF4 genes.Immunohistochemical methods were used to detect the expression of KLF4 protein in psoriasis tissues.Results After TINCR gene siRNA interference,the proliferation ability of keratinocytes significantly decreased at 24,48,and 72 hours(P<0.001),indicating that the TINCR gene plays a critical role in cell proliferation.The results of qRT-PCR and Western blot analyses showed that the RNA and protein expression levels of TINCR,MAFB,and KLF4 genes were significantly reduced(P<0.001),suggesting that TINCR may influence the differentiation of keratinocytes by regulating the expression of MAFB transcription factor and KLF4 differentiation-related genes.Furthermore,immunohistochemical results indicated that the expression of KLF4 protein was significantly elevated in psoriasis tissues compared to normal skin tissues,suggesting that KLF4 plays an important role in the pathogenesis of psoriasis.Conclusions The TINCR-MAF:MAFB transcription factor network may participate in the occurrence and development of psoriasis by affecting the proliferation and differentiation of keratinocytes.This finding provides a new perspective on the pathogenesis of psoriasis and potential targets for future therapeutic strategies.

Objectives:To evaluate the hemodynamic impact of different bypass grafting methods on the left anterior descending(LAD)artery using computational fluid dynamics,providing a theoretical basis for optimizing coronary artery bypass grafting.Methods:A patient-specific 3D coronary model was constructed using SimVascular software,including an in-situ internal mammary artery graft(model 1)and three free grafts of varying diameters(model 2:2 mm internal mammary artery free graft;model 3 and model 4:3 mm and 4 mm great saphenous vein free grafts).The hemodynamic parameters of the native artery and grafts were compared among the four bypass grafting models.Results:All four bypass grafting models supply sufficient blood flow for the severely stenosed LAD.LAD flow was slightly lower in the model 1.Free internal mammary artery grafts showed higher flow and wall shear stress.4 mm great saphenous vein free grafts presented with maximum flow but lowest shear stress,3 mm great saphenous vein free grafts offered better hemodynamic stability.Conclusions:Computational fluid dynamics analysis indicates that free internal mammary grafts could provide superior hemodynamics,while larger grafts result in lower shear stress,which might affect long-term graft patency.These findings thus provide experimental evidences useful for optimizing LAD bypass strategies.

Objective To assess the accuracy and consistency of point-of-care testing(POCT)technology in detecting D-dimer(DDI),Procalcitonin(PCT),and N-terminal pro B-type natriuretic peptide(NT-proBNP)in whole blood samples,as well as to validate its feasibility for rapid clinical diagnosis.Methods From July 8 to August 22,2022,a total of 104 paired DDI whole blood and plasma samples,496 paired PCT whole blood and serum samples,and 77 paired NT-proBNP whole blood and serum samples were collected.The consistency and accuracy of test results between whole blood and plasma/serum samples were assessed using the Mann-Whitney U test,regression analysis,relative sensitivity,relative specificity,Youden's index,and Kappa value.Results The test results of DDI,PCT,and NT-proBNP in whole blood and plasma/serum samples demonstrated excellent consistency,with correlation coefficients of r2=0.951 2,r2=0.942 8,and r2=0.991 6,respectively,and all P-values exceeding 0.05.At the medical decision levels,for DDI(0.55 μg/mL),the relative sensitivity,rela-tive specificity,Youden index,and Kappa value were 94.3%,94.1%,0.88,and 0.87,respectively.For PCT(0.5 ng/mL and 2.0 ng/mL),the relative sensitivities were 97.4%and 89.0%,the relative specificities were 95.8%and 98.3%,the Youden indices were 0.93 and 0.87,and the Kappa values were 0.93 and 0.89,respectively.For NT-proBNP(125 pg/mL),the relative sensitivity was 94.1%,the relative specificity was 100%,the Youden index was 0.94,and the Kappa value was 0.87.These findings confirm the high accuracy of whole blood sample testing and the strong concordance between the two methods.Conclusions This study confirmed the efficacy of POCT technology for detecting DDI,PCT,and NT-proBNP in whole blood samples.The results showed a high level of consistency compared to traditional plasma/serum methods,thereby reinforcing the clinical applicability of POCT for rapid diagnosis.

Exosome, as the critical communication carrier secreted by cells, has been demonstrated to carry non-coding RNA (ncRNA) that participate in regulating the onset and progression of various female reproductive system diseases. In this review, the roles of exosome ncRNA (such as microRNA, long ncRNA, and circular RNA) in non-tumor diseases of the female reproductive system were reviewed, including premature ovarian failure, polycystic ovary syndrome, and endometriosis, as well as in female reproductive system tumor diseases such as ovarian cancer, cervical cancer, and endometrial cancer. The theoretical basis and broad application prospects for the development of non-invasive diagnostic markers, prognostic evaluation tools, and potential therapeutic targets based on exosome ncRNA were provided.