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.

The abnormal accumulation, structural change, and spread of tau protein in the brain are now considered important factors in the progression of Alzheimer’s disease (AD) and many other tau-related neurodegenerative diseases. Clinical and pathological studies have shown that the amount and distribution of abnormal tau protein are closely related to synaptic damage, neuronal loss, and cognitive decline. Therefore, tau protein has become an important target for disease-modifying therapy. However, tau is difficult to target because it has no fixed structure, lacks a clear active site, undergoes many post-translational modifications, and forms different abnormal structures in different diseases and disease stages. Therefore, the effective and selective removal of harmful tau species is both a major opportunity and a major challenge in drug discovery for neurodegenerative diseases. Proteolysis-targeting chimeras (PROTACs) offer a new strategy to deal with this problem. Unlike traditional inhibitors, PROTACs do not simply block protein function. Instead, they bring the target protein close to an E3 ubiquitin ligase, which leads to ubiquitination and degradation of the target protein by the proteasome. This event-driven mechanism may be especially useful for disease-related proteins such as tau protein, which are hard to inhibit with traditional small molecules. In recent years, tau protein-targeting PROTACs and related degradation strategies have shown promising effects in cell and animal models. These effects include reducing abnormal tau protein levels, lowering synaptic toxicity, regulating disease-related signaling pathways, and improving behavioral or cognitive outcomes. These studies support targeted tau protein degradation as a promising therapeutic approach, although many problems still need to be solved before clinical use. In this review, we summarize recent progress in the development of tau protein-targeting PROTACs and discuss the main factors that affect their design and activity. We focus on the choice of tau protein-binding ligands, their binding sites, and their ability to recognize abnormal tau protein rather than normal tau protein. We also discuss the selection of E3 ligase recruiters, linker length and structure, ternary complex formation, and structure-activity relationships that influence degradation potency and selectivity. In addition, we introduce new strategies beyond traditional proteasomal degradation, including the regulation of tau protein phosphorylation and autophagy-based clearance. These approaches may be more suitable for different tau species or different stages of disease. A major challenge for tau protein-targeting PROTACs is delivery to the central nervous system. Many PROTACs have high molecular mass, large polar surface area, flexible structures, and may be removed by efflux transporters. As a result, they often have poor ability to cross the blood-brain barrier and may not reach enough free drug levels in the brain. Therefore, the therapeutic potential of tau protein-targeting PROTACs depends not only on their ability to degrade tau protein in vitro, but also on whether they can achieve long-lasting, selective, and safe target engagement in important brain regions after practical administration. Future studies should focus on improving selectivity for abnormal tau protein, understanding E3 ligase function in neural cells, designing brain-penetrant molecules, developing better delivery methods, and testing these drugs in models that better reflect human disease. Overall, tau protein-targeting PROTACs are a promising and fast-developing strategy for treating tau-related diseases. However, their successful clinical translation will require progress in chemical biology, medicinal chemistry, neuroscience, drug delivery, and translational medicine.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective To observe the value of machine learning(ML)model based on chest non-contrast CT(NCCT)radiomics for diagnosing metabolic syndrome(MetS)in males.Methods A total of 792 males who would undergo chest NCCT and bone density CT examination for physical check-up were prospectively enrolled and divided into training set(n=554,including 171 cases of MetS)and validation set(n=238,including 70 cases of MetS)at the ratio of 7∶3.Chest NCCT was performed,ROI of liver,intra-abdominal fat and skeletal muscle were delineated,and visceral fat area(VFA)at L2-3 intervertebral disc level was measured.Then radiomic signature(RS)of liver,intra-abdominal fat and skeletal muscle were established,and ML models were constructed using logistic regression(LR),random forests(RF)and extreme gradient boosting(XGBoost)algorithms,respectively,and their diagnostic performance were observed.Results Significant difference of age was found between MetS and non-MetS males in training set(P=0.010),while of RS scores were noticed in both training set and validation set(all P＜0.001).Combined ML models were constructed with age and RS.The area under the curve(AUC)of combined LR,RF and XGBoost models for diagnosing male MetS in training set was 0.899,0.996 and 0.943,while that in validation set was 0.861,0.860 and 0.876,respectively.Combined XGBoost model had the best performance.Conclusion XGBoost model based on chest NCCT radiomics was helpful for diagnosing male MetS.Combining with age could further improve its efficacy.

Objective To analyze the difference of rotator cuff muscle group fat content by MR proton density fat fraction(PDFF)tech-nology,and to explore the correlation between these variations and the severity grading of supraspinatus tendon injury.Methods Ninety-three patients with supraspinatus tendon injury were retrospectively selected and divided into the tendinitis group(grade Ⅰ),the partial tear group(grade Ⅱ),and the complete tear group(grade Ⅲ).The fat fraction(FF)values of the three groups of rotator cuff mus-cle group were measured using the PDFF technology,and the differences in FF values among the rotator cuff muscle group in the three groups were compared.The risk factors of the grading of supraspinatus tendon injury and the correlation between FF values and the severity grading of supraspinatus tendon injury were analyzed.Results The differences in the FF values of the supraspinatus and infraspinatus muscles among the three groups were statistically significant(P＜0.01).The FF values of both the supraspinatus and infraspinatus muscles were identified as significant factors associated with the severity grading of supraspinatus tendon injury.Further-more,the FF values of the supraspinatus and infraspinatus muscles were positively correlated with the severity grading of supraspina-tus tendon injury(r=0.576,P＜0.01;r=0.510,P＜0.01).Conclusion MR PDFF technology can effectively evaluate the extent of fat infiltration in the rotator cuff muscle group after supraspinatus tendon injury.Specifically,the FF values of the supraspinatus and infraspinatus muscles serve as reliable quantitative indicators for classifying supraspinatus tendon injury.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Objective To analyze the characteristics of MR amide proton transfer(APT)imaging and enhancement signals in benign and malignant muscular soft tissue tumors and to explore the value of MR APT imaging,contrast enhancement techniques,and their combined application in the differential diagnosis of benign and malignant muscular soft tissue tumors.Methods A retrospective analysis was conducted on 34 patients with muscular soft tissue tumors confirmed by pathology,including 13 malignant and 21 benign.All patients underwent both MR with contrast enhancement and APT imaging examinations before surgery.APT values were obtained through post-processing on an image workstation.The enhancement signal characteristics and APT values were compared between benign and malignant muscular soft tissue tumors.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of the two techniques alone and in combination for differentiating between benign and malignant muscular soft tissue tumors.Results There were significant differences in enhancement signal characteristics on MR and APT values between benign and malignant muscular soft tissue tumors(P<0.05).The enhancement signal of malignant tumors was more heterogeneous,with higher enhancement degree than benign tumors;the APT value of benign tumors was(2.20±0.93)%,and the APT value of malignant tumors was(3.52±0.83)%,the ROC curve analysis determined a cutoff APT value of 2.82%for malignant tumors,with a diagnostic specificity of 90.5%and sensitivity of 76.9%.The area under the curve(AUC)for MR with contrast enhancement,APT imaging,and the combination of the two techniques were 0.694,0.857 and 0.894,respectively.No significant differences were found in the diagnostic efficacy between MR with contrast enhancement and APT imaging(Z=1.587,P=0.112 6)or between APT imaging and the combination of the two tech-niques(Z=1.217,P=0.223 4),but there was significant difference between MR with contrast enhancement and the combination of the two techniques(Z=2.428,P=0.015 2).Moreover,the combination of the two techniques showed the overall highest diag-nostic efficacy.Conclusion The combined application of MR APT imaging and contrast enhancement techniques is more beneficial for the qualitative diagnosis of muscular soft tissue tumors.

Objective:To evaluate the short-and medium-term therapeutic efficacy of shockwave balloon therapy for TASCⅡ C/D femoropopliteal artery atherosclerosis obliteration.Methods:This retrospective cohort study included 25 patients who received shockwave balloon therapy in five vascular centers from August 2022 to June 2023. All patients were diagnosed with TASC Ⅱ C/D femoropopliteal arteriosclerosis obliterans (13 cases of type C and 12 cases of type D), and underwent intravascular shock wave lithotripsy (IVL) to treat calcified lesions. The immediate effectiveness (residual stenosis<30% and no flow-limiting dissection), safety (whether there were adverse vascular events during the operation) and the rate of salvage stent implantation were recorded. The observation indexes of patients before operation, early postoperative period (immediately after operation or before discharge) and postoperative follow-up period (3, 6, 12 months after operation) were collected. The observation indexes included ankle-brachial index (ABI), Rutherford classification, and minimum lumen diameter (MLD). Repeated measures ANOVA was used to evaluate the changes of observation indexes in the early postoperative and follow-up stages compared with those before operation; Kaplan-Meier survival analysis was used to evaluate the one-stage patency rate at follow-up and the target lesion revascularization rate free from clinical drive.Results:The immediate effectiveness of surgery was 100% in all patients, with no vascular related adverse events occurred, and no remedial stent implantation was performed. The ABI, Rutherford grade and MLD of the patients in the early postoperative period and each follow-up stage were improved compared with those before operation, with statistically significant differences ( P<0.05). Kaplan-Meier survival analysis showed that the primary patency rate at 12 months after surgery was 0.78 (95% CI 0.64-0.84), and the revascularization rate of target lesions free from clinical drive was 0.87 (95% CI 0.85-0.95). Conclusion:Shockwave balloon therapy for complex calcified femoropopliteal artery lesions is safe and reliable, with satisfactory short-and medium-term efficacy.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.