Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective To analyze mosquito species composition and prevalence of pathogens carried by mosquitoes in Jiangsu Province from 2020 to 2024 and to provide a scientific basis for the prevention and control of mosquito-borne diseases. Methods Mosquitoes were collected using CO2-baited traps. The presence of mosquito-borne pathogens including dengue virus, Japanese encephalitis virus, yellow fever virus, West Nile virus, Chikungunya virus, and Sindbis virus was tested using commercial kits for fluorescence-based quantitative PCR. Results The most prevalent mosquito species found across different regions of Jiangsu Province were Culex pipiens pallens and Cx. tritaeniorhynchus, accounting for 81.35% to 93.01% of the total, followed by Armigeres subalbatus and Anopheles sinensis, which comprised 5.89% to 15.85% of the total. The densities of other monitored mosquito species were relatively low. Pathogen detection revealed that, only Cx. tritaeniorhynchus tested positive for Japanese encephalitis virus nucleic acid, whereas the remaining four mosquito species tested negative for the nucleic acids of all other six pathogens. The overall positivity rate of Japanese encephalitis virus (JEV) in Cx. tritaeniorhynchus showed an initially increasing trend followed by a decrease and a subsequent increase. The peak detection rate occurred in 2021 (11.93%), with a much lower positive rate of 0.80% in 2023. Genotyping result revealed that all JEV strains in Jiangsu Province belonged to the G1 genotype and were genetically closest to the strain Shangdong08DY.29 (MN072875.1). Conclusions The incidence of Japanese encephalitis virus carried by mosquito, especially Cx. tritaeniorhynchus, in Jiangsu Province shows an upward trend, requiring sustained surveillance. A variety of monitoring method should be adopted to survey mosquitoes across different habitats, ensuring the accuracy and comprehensiveness of the monitoring result.

Objective To investigate the species composition, distribution, density, and pathogen-carrying status of host-seeking ticks in urban environments of Jiangsu Province, and to provide a scientific basis for the prevention and control of tick-borne diseases in urban settings. Methods From April to September 2023, a survey on host-seeking ticks was conducted in three types of habitats (city parks, residential areas, and street greenbelts) across 54 counties (cities, districts) of 13 prefecture-level cities in Jiangsu Province by using the flagging method. RStudio 4.4.3 (Windows version) was employed to perform chi-square test analysis on the species composition of ticks across different months, and Friedman test (for multiple paired samples) was applied to analyze monthly changes in the average tick density index among different habitats. Quantitative real-time PCR was performed to detect pathogens in the captured ticks. Results A total of 863 host-seeking ticks were captured from 54 habitats in 24 counties (cities, districts) of 11 prefecture-level cities (Nanjing, Wuxi, Changzhou, Suzhou, Nantong, Huai'an, Yancheng, Yangzhou, Zhenjiang, Taizhou, and Suqian) in Jiangsu Province, whereas no ticks were captured in Xuzhou and Lianyungang. The collected ticks belonged to three species, with Haemaphysalis longicornis being the dominant species (accounting for 82.62%), followed by Haemaphysalis flava and Hae. phasiana. The average density index of ticks in positive habitats was 3.20 ticks/ (flag·100 m). In terms of tick density among prefecture-level cities, Wuxi had the highest density[13.55 ticks/(flag·100 m)], whereas Nanjing and Taizhou had the lowest[both,0.20 ticks/(flag·100 m)]. With respect to the types of positive habitats,46 positive city parks,7 positive residential areas, and 1 positive street greenbelt were found, with the average tick density index being 3.46, 1.86, and 3.60 ticks/flag · 100 m, respectively. No statistically significant differences were observed in the monthly variations in the average tick density index among different habitats (P＞0.05). Pathogen detection showed no Bandavirus dabieense, Rickettsia, or Borrelia burgdorferi in the collected ticks. Conclusions Host-seeking ticks have established populations in urban environments across most prefecture-level cities in Jiangsu Province, with Hae. longicornis identified as the dominant species. City parks serve as the primary breeding habitats for these ticks. Strengthening tick surveillance and control measures in densely populated and frequently visited areas, such as city parks and residential neighborhoods, is crucial for the effective prevention and control of urban tick-borne diseases.

ObjectiveTo investigate the effect and mechanism of cordycepin in inhibiting fat infiltration after rotator cuff injuries in rats by regulating the Wnt/β-catenin signaling pathway， providing a theoretical basis for clinical treatment of rotator cuff injuries. MethodsFifty SPF-grade female SD rats were used in this study， with 10 randomly selected as the blank group. A rotator cuff injury repair model was established by supraspinatus tendon and suprascapular nerve compression. The successfully modeled rats were randomized into model and low-dose （20 mg·kg^-1）， medium-dose （40 mg·kg^-1）， and high-dose （80 mg·kg^-1） cordycepin groups. After 6 weeks of treatment， the gait analysis was performed to assess the limb function in rats. Oil red O staining and Masson staining were employed to observe pathological changes in the muscle tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum. Immunohistochemistry （IHC） was employed to detect the expression of peroxisome proliferator-activated receptor γ （PPARγ） and CCAAT/enhancer-binding protein α （C/EBPα）， which are markers of adipogenesis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of Wnt3a， Wnt10b， and β-catenin. ResultsCompared with the blank group， the model group showed decreases in stride length and paw print area （P<0.01）， an increase in ratio of wet muscle mass reduction and a decrease in muscle fiber cross-sectional area （P<0.05）， and decreased ratios of fat infiltration area and collagen fiber area （P<0.01）. Additionally， the model group showed elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， up-regulated protein levels of PPARγ and C/EBPα （P<0.01）， and down-regulated mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. Compared with the model group， the low-， medium-， and high-dose cordycepin groups showed increases in stride length and paw print area （P<0.01）， a decrease in ratio of wet muscle mass reduction and an increase in muscle fiber cross-sectional area （P<0.05）， and increases in ratios of fat infiltration area and collagen fiber area （P<0.05， P<0.01）. In addition， cordycepin lowered the serum levels of IL-1β， IL-6， and TNF-α （P<0.05， P<0.01）， down-regulated the protein levels of PPARγ and C/EBPα （P<0.01）， and up-regulated the mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. ConclusionCordycepin can improve the limb function， alleviate rotator cuff muscle atrophy， fat infiltration， and fibrosis， and inhibit inflammation in rats by regulating the Wnt/β-catenin signaling pathway.

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

Objective To explore the predictive value of fat attenuation index(FAI)and fibrous plaque index(FPI)for the prognosis of patients with acute coronary syndrome(ACS).Methods A retrospective cohort study was conducted on 334 ACS patients undergoing percutaneous coronary intervention(PCI)in the First Affiliated Hospital of Army Military Medical University and Yongchuan Hospital of Chongqing Medical University from March 2021 to July 2023.All patients received coronary computed tomography angiography(CCTA)to measure FAI and FPI.According to the occurrence of major adverse cardiovascular events(MACE)with 1 year of follow-up,they were divided into MACE group(n=108)and non-MACE group(n=226).The baseline data,CCTA data and results of laboratory tests were collected and compared between the 2 groups.Multivariate logistic regression analysis was used to analyze the relationship of FAI and FPI with the prognosis of ACS patients,and ROC curve was drawn to evaluate its predictive efficiency.Results Among the 334 ACS patients,108(32.34%)experienced MACE.When compared with the non-MACE group,the MACE group exhibited significantly larger proportions of diabetes(72.22%vs 31.86%)and left main coronary artery disease(18.52%vs 7.08%),but lower success rate of operation(79.63%vs 93.81%,P<0.05).Radiologic results showed that the proportion of severe stenosis(20.37%vs 10.62%),FAI(-80.12±6.41 HU vs-72.34±7.09 HU)and FPI(0.58±0.41 vs 0.26±0.12)were obviously increased in the MACE group than the non-MACE group(P<0.05).Laboratory tests indicated that there were statistical differences between the 2 groups in high-density lipoprotein-cholesterol(HDL-C,1.20±0.15 vs 1.09±0.16 mmol/L),miR-126(0.91±0.12 vs 0.96±0.15)and SST2(38.45±5.67 vs 34.30±4.89 ng/mL,P<0.05).Multivariate Logistic regression analysis revealed that FAI(OR=1.200,95%CI:1.136～1.268),FPI(OR=63.157,95%CI:14.126～282.374),moderate stenosis(OR=1.332,95%CI:1.024～1.859),severe stenosis(OR=1.480,95%CI:1.074～2.039),miR-126(OR=0.007,95%CI:0.001～0.077),and sST2(OR=1.192,95%CI:1.113～1.277)were independent predictors of MACE(P<0.05).ROC curve analysis displayed that stenosis degree(AUC=0.622,95%CI:0.561～0.683,P=0.001),FAI(AUC=0.790,95%CI:0.741～0.839,P=0.001)and FPI(AUC=0.700,95%CI:0.638～0.761,P=0.001),miR-126(AUC=0.646,95%CI:0.584～0.707,P=0.001),sST2(AUC=0.700,95%CI:0.638～0.761,P=0.001)had certain predictive values for ACS prognosis.Conclusion Coronary FAI and FPI can be used as independent prognostic indicators of ACS patients,and their numerical changes are closely related to plaque stability and inflammatory state.

Cosmetics may be an important source of human exposure to per-and polyfluoroalkyl substances(PFASs),posing risks to human health.In this study,a nontarget screening method for PFASs in cosmetics was developed using ultra-high performance liquid chromatography-high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)based on the Kendrick mass defect(KMD).The sample was extracted by ultrasonic assisted extraction prior to being analyzed by UHPLC-Q-Orbitrap HRMS.Acquisition of HRMS data was achieved in both full scan and data-dependent(Full MS/dd MS2)mode.The data collected by HRMS were imported into an in-lab built R script for processing.Samples retained the mass spectra peaks with KMD values in the range of 0.85-1 or 0-0.15 for in-and out-of-library matching;when KMD deviation(δKMD)<0.001 and CF 2 mass error(δMS)<15 ppm,it was considered as a potential PFASs homologues.According to matches of parent ions(MS),fragment ions(MS2)and retention time(RT)with the in-house built PFASs database,the screened and identified potential PFASs were categorized to 5 confidence levels(CL1-CL5).A total of 15 kinds of PFASs homologues with confidence level of CL3 and above were screened from 13 cosmetics products and 8 cosmetic raw materials,including perfluoroalkyl alcohol,hydroperfluoroalkyl sulfonic acid,chloroperfluoroalkyl sulfonic acid,etc.with concentrations ranging from 1.9 ng/g to 98.1 ng/g.The nontarget screening method could be used to screen and identify PFASs homologues feasibly and therefore provided data basis for management and control of PFASs addition in cosmetics.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.