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.

Objective To observe the value of pituitary radiomics and MRI features combined model for predicting growth hormone(GH)status in pediatric short stature.Methods Totally 300 children with short stature were enrolled as training set,while other 73 cases were taken as external validation set.Based on growth hormone stimulation test,the children were divided into GH deficiency(GHD)group(n=228)and non-GHD group(n=145).The training set included 196 cases in GHD subgroup and 104 cases in non-GHD subgroup,while the validation set included 32 cases in GHD subgroup and 41 cases in non-GHD subgroup.Radiomics features of pituitary were extracted from T1WI.The key features were selected using least absolute shrinkage and selection operator(LASSO)regression,and machine learning models were subsequently constructed using support vector machine(SVM),logistic regression(LR),naive Bayes(NB)and K-nearest neighbor(KNN),respectively.Then combined models were constructed combining with MRI features,and the efficacy of each model was evaluated.Results The area under the curve(AUC)of SVM,LR,NB,and KNN radiomics model for predicting GH status in pediatric short stature was 0.860,0.831,0.838 and 0.901 in training set,0.788,0.829,0.823 and 0.770 in validation set,while of the relative combined SVM,LR,NB and KNN model was 0.924,0.903,0.859 and 0.920 in training set,and 0.827,0.881,0.836 and 0.718 in validation set.LRcombined model had the best overall performance,with sensitivity of 84.94％,specificity of 80.56％and accuracy of 83.61％in training set,and 80.95％,72.22％and 80.00％in validation set,respectively.Conclusion Pituitary radiomics and MRI features combined model could effectively predict GH status in pediatric short stature.

Objective To screen antidepressant-active compounds from Polygonati Rhizoma and explore their effects and possible mechanisms against depression induced by simulated weightlessness.Methods A systems pharmacology approach was used to screen potential antidepressant-active compounds and their targets from Polygonati Rhizoma.The hindlimb unloading(HLU)rat model was employed for the study.Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups:control group(administered 0.5%carboxymethylcellulose by gavage),HLU group(hindlimb unloading),and HLU+treatment group(hindlimb unloading+active compound gavage),with 8 rats in each group.After 28 days of hindlimb unloading,depressive-like behaviors in rats were evaluated using the forced swimming test and tail suspension test.Hippocampal morphology was examined with H&E staining,and GO and KEGG enrichment analyses were conducted on the targets of active compounds.Results A total of 38 active compounds were screened from Polygonati Rhizoma,among which apigenin had an oral bioavailability of 23.06%and a drug-likeness score of 0.21.Compound-target network analysis indicated that apigenin had the highest degree and betweenness centrality values,suggesting it might be the key active component with antidepressant potential in Polygonati Rhizoma.In the forced swimming and tail suspension tests,rats in the HLU group showed a significant increase in immobility time compared to the control group,indicating successful establishment of the depression model.However,compared to the HLU group,rats in the HLU plus apigenin group exhibited significantly reduced immobility time.The H&E staining results of hippocampal tissue showed a significant reduction in the number of hippocampal neurons,along with numerous shrunken neurons and small vacuoles in nerve fibers in the HLU group.In contrast,the treatment group exhibited an increased number of hippocampal neurons,with improved cellular morphology.Target enrichment analysis indicated that apigenin targets were mainly involved in the regulation of apoptosis and cancer-related signaling pathways.Conclusion Apigenin significantly improved depressive-like behaviors in rats subjected to hindlimb unloading,and it has a protective effect on hippocampal tissue.It may provide a new natural active compound for the treatment of depression caused by spaceflight-induced weightlessness.

Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P＜0.05,P＜0.01).The levels of WBC and NE in the model-A increased significantly(P＜0.01).The level of LY in model-B decreased significantly(P＜0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P＜0.01).The levels of IL-6 in model-A and model-B were significantly increased(P＜0.05,P＜0.01).The collagen volume fraction of model-A and model-B were significantly increased(P＜0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P＜0.01),and the expression levels of IκBα/β-actin were significantly decreased(P＜0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P＜0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.

Objective To explore the effects of dodecanoylcarnitine(DA)and myristoleic acid(MA)on the function of mouse alveolar epithelial cell line MLE-12 and their underlying mechanisms.Methods An inflammatory model was established by stimulating MLE-12 cells with IL-4.The expression levels of DA,MA,and sphingosine-1-phosphate(S1P)in the cell supernatant were detected by ELISA.MLE-12 cells were separately intervened with DA and MA.RT-PCR and flow cytometry were used to detect the expression changes of inflammatory factors IL-6 and tumor necrosis factor-α(TNF-α)and the level of intracellular reactive oxygen species(ROS).Additionally,Western blot was performed to detect the expression of key proteins such as p38 mitogen-activated protein kinase(p-38 MAPK)and src homology 2 domain-containing phosphatase 1(SHP-1).To explore the role of S1PR2 in the effects of DA and MA,MLE-12 cells were pretreated with the S1PR2 inhibitor JTE-013,and the above experiments were repeated.Results IL-4 stimulation significantly upregulated the levels of DA,MA,and S1P in MLE-12 cells(P<0.05).DA/MA treatment groups exhibited significantly increased expression of IL-6 and TNF-α compared with the control group(P<0.05),along with elevated ROS levels(P<0.05).Western blot analysis revealed that DA/MA promoted SHP-1 dephosphorylation and phosphorylated p38 MAPK activation in MLE-12 cells.Notably,JTE-013 pre-treatment completely reversed these effects(P<0.05).Conclusion Asthma-related metabolites DA and MA exacerbate the inflammatory and oxidative stress responses of MLE-12 cells by activating the S1PR2 receptor,promoting the dephosphorylation of SHP-1 and the activation of the p-p38 MAPK pathway.This study reveals the core regulatory role of S1PR2 in this pathway as well.

Objective To investigate the effects of Phellinus baumii polyphenol(PBP)on head and neck squamous cell carcinoma(HNSCC)and analyze the potential mechanism based on network pharmacology and in vitro experiments.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),DrugBank,GeneCards,Comparative Toxicogenomics Database(CTD)and Online Mendelian Inheritance in Man(OMIM)database were used to screen the active components of PBP and potential targets of PBP on HNSCC.The potential target interaction network was constructed using String database,and the core targets were screened by two-step topology analysis.Enrichment analysis of potential targets was performed using the DAVID database.Human HNSCC cell lines SCC-15 and SCC-25 were cultured in vitro using PBP intervention of 0,25,50 mg/L,respectively.The cell proliferation and colony formation ability were detected by cell counting reagent(CCK-8)and colony formation assay.Western blot assay was used to detect the expression of PBP core target protein in 2 cell lines.Results A total of 280 targets were identified for 17 active components of PBP,264 of which were HNSCC-related genes.Two-step topology analysis showed that hypoxia inducible factor 1 subunit alpha(HIF1A),tumor protein p53(TP53),AKT serine/threonine kinase 1(AKT1),signal transducer and activator of transcription 3(STAT3),cyclin A2(CCNA2)and JUN proto-oncogene(JUN)were the core targets.The enrichment results suggested that PBP may play a role in HNSCC through various pathways.In vitro experiment results showed that with the increase of PBP intervention concentration,the proliferation ability and colony formation ability of SCC-15 and SCC-25 cells were significantly decreased(P＜0.05),while the protein expression levels of STAT3,AKT1 and CCNA2 were decreased(P＜0.05).Conclusion PBP can inhibit the progression of HNSCC by multi-target and multi-pathway.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant