The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

Objective:To analyze the disease burden and changing trend of pancreatic cancer in our country from 1990 to 2021, and predict the incidence and mortality trends of pancreatic cancer from 2022 to 2036.Methods:Utilizing the data from the Global Burden of Disease 2021 Study, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life rate (DALY) of pancreatic cancer in our country from 1990 to 2021 were evaluated. DALY is calculated by adding the number of years of life lost due to pancreatic cancer to the years of life lost due to disability. The Joinpoint model was used to calculate the average annual percentage change (AAPC), the age-period-cohort model was applied to control the influence of age, period and birth cohort, and the Bayesian age-period-cohort model was used to predict the incidence and mortality trends of pancreatic cancer in our country from 2022 to 2036.Results:Compared with 1990, the data of ASIR, ASMR and age-standardized disability-adjusted life years (DALY) rates of pancreatic cancer in our country in 2021 all increased, and the increase in men was more significant than that in women. The peaks of morbidity and mortality in 1990 and 2021 were both occurred in the elderly. The incidence rate, mortality rate and changes of men in all age groups were higher than those of women. The changes in the age-standardized DALY rate were mainly reflected in the male population. The first peaks of the age-standardized DALY rate in 1990 and 2021 both occurred at the age of 70-74, and the second peak of the age-standardized DALY rate in 2021 shifted to the age of 85-89. The peak rate of age-standardized DALY in females is earlier than that in males. The AAPC of ASIR and ASMR for all genders of pancreatic cancer in our country from 1990 to 2021 was 0.72 (95% CI: 0.50-0.94, P<0.001) and 0.56 (95% CI: 0.31-0.82, P<0.001), respectively, and the difference was statistically significant. In our country men with pancreatic cancer, ASIR (AAPC=0.89, 95% CI: 0.68-1.10, P<0.001) and ASMR (AAPC=0.71, 95% CI: 0.49-0.93, P<0.001) were compared with ASIR (AAPC=0.48, 95% CI: ) in women. 0.22-0.73, P<0.001) and ASMR (AAPC=0.33, 95% CI: 0.08-0.58, P=0.010) increased rapidly, and the difference was statistically significant. The ASDR of all genders showed an upward trend (AAPC=0.36, 95% CI: 0.18-0.54, P<0.001), and the difference was statistically significant. The incidence rate and mortality rate of all genders are on the rise. When the age of the population is over 60 years old, the incidence and mortality of specific diseases show an upward trend with the delay of the birth cohort. It is expected that from 2022 to 2036, the ASIR and ASMR of both men and women will increase annuallyand eventually double. Conclusion:From 1990 to 2021, the burden of pancreatic cancer in our country has generally shown an increasing trend, and it is expected that the disease burden will further increase in the future.

Objective:To investigate the association between the metabolic score for visceral fat(METS-VF)and sarcopenia in older adults in China.Methods:A retrospective cohort study was conducted.A total of 1 262 participants aged ≥60 years old who did not diagnose with sarcopenia in 2011 and had complete follow-up data in 2015 were selected from the China health and retirement longitudinal survey(CHARLS). Participants were divided into the low METS-VF group (n=621)and the high METS-VF group (n=641), and then the corrleation between METS-VF and sarcopenia was analyzed.Results:The inverse probability of treatment weighting(IPTW)was used to balance all covariates between the low METS-VF group and high METS-VF group.The results showed that 30 participants in the low METS-VF group and 47 participants in the high METS-VF group were diagnosed with sarcopenia, with prevalence rates of 4.83%(30/621)and 7.33%(47/641), respectively.The difference in the prevalence of sarcopenia between the two groups was statistically significant after IPTW ( χ2=3.934, P=0.048, SMD=0.150). Logistic regression analysis showed that, after adjusting for various confounders, high METS-VF was significantly associated with an increased risk of sarcopenia in older adults( OR=2.130, 95% CI: 1.294~3.572, P=0.003). Subgroup analyses further indicated that individuals without cardiovascular disease had a relatively higher risk of sarcopenia( P for interaction=0.032). Conclusions:METS-VF is associated with an increased risk of sarcopenia in older adults in China, and its predictive and diagnostic value warrants further investigation.

Objective:To investigate the association between the metabolic score for visceral fat(METS-VF)and sarcopenia in older adults in China.Methods:A retrospective cohort study was conducted.A total of 1 262 participants aged ≥60 years old who did not diagnose with sarcopenia in 2011 and had complete follow-up data in 2015 were selected from the China health and retirement longitudinal survey(CHARLS). Participants were divided into the low METS-VF group (n=621)and the high METS-VF group (n=641), and then the corrleation between METS-VF and sarcopenia was analyzed.Results:The inverse probability of treatment weighting(IPTW)was used to balance all covariates between the low METS-VF group and high METS-VF group.The results showed that 30 participants in the low METS-VF group and 47 participants in the high METS-VF group were diagnosed with sarcopenia, with prevalence rates of 4.83%(30/621)and 7.33%(47/641), respectively.The difference in the prevalence of sarcopenia between the two groups was statistically significant after IPTW ( χ2=3.934, P=0.048, SMD=0.150). Logistic regression analysis showed that, after adjusting for various confounders, high METS-VF was significantly associated with an increased risk of sarcopenia in older adults( OR=2.130, 95% CI: 1.294~3.572, P=0.003). Subgroup analyses further indicated that individuals without cardiovascular disease had a relatively higher risk of sarcopenia( P for interaction=0.032). Conclusions:METS-VF is associated with an increased risk of sarcopenia in older adults in China, and its predictive and diagnostic value warrants further investigation.

Objective:To analyze the disease burden and changing trend of pancreatic cancer in our country from 1990 to 2021, and predict the incidence and mortality trends of pancreatic cancer from 2022 to 2036.Methods:Utilizing the data from the Global Burden of Disease 2021 Study, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life rate (DALY) of pancreatic cancer in our country from 1990 to 2021 were evaluated. DALY is calculated by adding the number of years of life lost due to pancreatic cancer to the years of life lost due to disability. The Joinpoint model was used to calculate the average annual percentage change (AAPC), the age-period-cohort model was applied to control the influence of age, period and birth cohort, and the Bayesian age-period-cohort model was used to predict the incidence and mortality trends of pancreatic cancer in our country from 2022 to 2036.Results:Compared with 1990, the data of ASIR, ASMR and age-standardized disability-adjusted life years (DALY) rates of pancreatic cancer in our country in 2021 all increased, and the increase in men was more significant than that in women. The peaks of morbidity and mortality in 1990 and 2021 were both occurred in the elderly. The incidence rate, mortality rate and changes of men in all age groups were higher than those of women. The changes in the age-standardized DALY rate were mainly reflected in the male population. The first peaks of the age-standardized DALY rate in 1990 and 2021 both occurred at the age of 70-74, and the second peak of the age-standardized DALY rate in 2021 shifted to the age of 85-89. The peak rate of age-standardized DALY in females is earlier than that in males. The AAPC of ASIR and ASMR for all genders of pancreatic cancer in our country from 1990 to 2021 was 0.72 (95% CI: 0.50-0.94, P<0.001) and 0.56 (95% CI: 0.31-0.82, P<0.001), respectively, and the difference was statistically significant. In our country men with pancreatic cancer, ASIR (AAPC=0.89, 95% CI: 0.68-1.10, P<0.001) and ASMR (AAPC=0.71, 95% CI: 0.49-0.93, P<0.001) were compared with ASIR (AAPC=0.48, 95% CI: ) in women. 0.22-0.73, P<0.001) and ASMR (AAPC=0.33, 95% CI: 0.08-0.58, P=0.010) increased rapidly, and the difference was statistically significant. The ASDR of all genders showed an upward trend (AAPC=0.36, 95% CI: 0.18-0.54, P<0.001), and the difference was statistically significant. The incidence rate and mortality rate of all genders are on the rise. When the age of the population is over 60 years old, the incidence and mortality of specific diseases show an upward trend with the delay of the birth cohort. It is expected that from 2022 to 2036, the ASIR and ASMR of both men and women will increase annuallyand eventually double. Conclusion:From 1990 to 2021, the burden of pancreatic cancer in our country has generally shown an increasing trend, and it is expected that the disease burden will further increase in the future.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Lung cancer is characterized by high incidence and mortality rates and invasiveness, and its occurrence and development are influenced by various factors. Mitochondria, as ubiquitous organelles in the human body, regulate cellular processes, such as metabolism, signal transduction, oxidative stress, and genomic instability, thereby affecting the initiation and progression of lung cancer. This article summarizes the recent research progress on mitochondrial-targeted drugs, mitochondrial transfer, and mitochondrial gene therapy for lung cancer treatment. This work also discusses the principles and prospects of mitochondrial therapy to provide new insights for lung cancer treatment.

Background and objective Both of lung cancer incidence and mortality rank first among all cancers in China.Previous lung cancer screening trials were mostly selective screening for high-risk groups such as smokers.Non-smoking women accounted for a considerable proportion of lung cancer cases in Asia.This study aimed to evaluate the outcome of community-based mass screening in Guangzhou and identify the high-risk factors for lung cancer.Methods Residents aged 40-74 years in Guangzhou were screened with low-dose computed tomography(LDCT)for lung cancer and the pulmonary nodules were classified and managed according to China National Lung Cancer Screening Guideline with Low-dose Computed Tomography(2018 version).The detection rate of positive nodules was calculated.Before the LDCT examination,residents were required to complete a"lung cancer risk factors questionnaire".The risk factors of the questionnaire were analyzed by least absolute shrinkage and selection operator(LASSO)penalized Logistic regression analysis.Results A total of 6256 residents were included in this study.1228 positive nodules(19.63％)and 117 lung cancers were confirmed,including 6 cases of Tis,103 cases of stage Ⅰ(accounting for 88.03％of lung cancer).The results of LASSO penalized Logistic regression analysis indicated that age ≥50 yr(OR=1.07,95％CI:1.06-1.07),history of cancer(OR=3.29,95％CI:3.22-3.37),textile industry(OR=1.10,95％CI:1.08-1.13),use coal for cooking in childhood(OR=1.14,95％CI:1.13-1.16)and food al-lergy(OR=1.10,95％CI:1.07-1.13)were risk factors of lung cancer for female in this district.Conclusion This study highlighted that numerous early stages of lung cancer cases were detected by LDCT,which could be applied to screen-ing of lung cancer in women.Besides,age ≥50 yr,personal history of cancer,textile industry and use coal for cooking in childhood are risk factors for women in this district,which suggested that it's high time to raise the awareness of early lung cancer screening in this group.