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.

Incretin-based drugs have demonstrated significant clinical value in weight management and the treatment of metabolic diseases by mimicking or enhancing endogenous incretin signaling. These agents primarily target multiple receptors including glucagon-like peptide-1， glucose-dependent insulinotropic polypeptide， and glucagon， exerting weight-reducing effects through multiple mechanisms such as central appetite regulation， gastrointestinal function modulation， and peripheral metabolic improvement， while further ameliorating blood glucose， blood lipids， fatty liver， and cardiorenal metabolic risks. This review focuses on incretin-based drugs， systematically summarizing the key clinical application points and relevant research progress of domestically marketed and investigational candidate drugs in the field of weight reduction. Available evidence indicates that semaglutide and tirzepatide demonstrate substantial weight reduction with multiple metabolic benefits； domestic innovative drugs represented by mazdutide and ecnoglutide also exhibit favorable weight-reducing effects and safety profiles. Regarding safety， these agents are generally well-tolerated， with the most common adverse reactions being mild-to-moderate gastrointestinal events， while potential risks including gallbladder events， pancreatitis， and mood changes require attention. In special populations， individualized assessment is warranted for use in children， elderly people， and pregnant women. Future research should focus on the screening of predictive biomarkers for efficacy， the development of long-acting oral formulations， and the accumulation of long-term safety follow-up data.

The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions,which range from parasite infections and fibrosis to autoimmune diseases.In particular,HF is believed to play an excellent anticancer role by suppressing the proliferation,adhesion,metastasis,and invasion of cancers.This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF.In the studies covered in this review,the anticancer molecular mechanisms of HF mainly included transforming growth factor-β(TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2(Nrf2),serine/threonine kinase proteins(Akt)/mechanistic target of rapa-mycin complex 1(mTORC1)/wingless/integrated(Wnt)/β-catenin,the exosomal microRNA-31(miR-31)/histone deacetylase 2(HDAC2)signaling pathway,and the interaction of the extracellular matrix(ECM)and immune cells.Notably,HF,as a novel type of adenosine triphosphate(ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase(ProRS)and amino acid starvation therapy(AAS)to suppress the formation of ribosome,further exerts a significant effect on the tumor microenvironment(TME).Additionally,the combination of HF with other drugs or therapies obtained universal attention.Our results showed that HF has significant potential for clinical cancer treatment.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

OBJECTIVE: To provide the experience and demonstration for the transformation of acupuncture-moxibustion techniques standards from Chinese national standards to international standards. METHODS: Questionnaire research, literature research, semi-structured interviews and expert consultation were used. RESULTS: The safety of acupuncture-moxibustion techniques was evaluated through literature research, and based on the results of the questionnaire survey, expert interviews, and expert consultation, 11 main bodies and structure of the former Chinese national standard, Technical Benchmark of Acupuncture and Moxibustion: General Rules for Drafting, were adjusted and optimized in accordance with the requirements of international standard (including the language, normative references, purpose, scope, applicable environment, target population, work team, terms and definitions, general principles and basic requirements, structural elements and text structure, and compilation process); and the first international standard, World Federation of Acupuncture-Moxibustion Societis (WFAS) Technical Benchmark of Acupuncture and Moxibustion: General Rules for Drafting was formulated to specify the general rules for drafting. CONCLUSION The 3 key questions, "international compatibility", "technical operability" and "safety" should be solved technically on the basis of explicit international requirements. It is the core technical issue during transforming the national standards of technical benchmark of acupuncture and moxibustion into international standards.
Moxibustion/methods* ; Acupuncture Therapy/methods* ; Humans ; Translational Research, Biomedical/standards* ; Surveys and Questionnaires ; China ; Benchmarking/standards*

This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals ; Humans ; Autophagy/drug effects* ; Reishi/chemistry* ; Mice ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Neoplasms/genetics* ; Hepatoblastoma/genetics* ; Polysaccharides/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Male ; Cell Proliferation/drug effects* ; Hep G2 Cells

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from parasite infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included transforming growth factor-β (TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2 (Nrf2), serine/threonine kinase proteins (Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated (Wnt)/β-catenin, the exosomal microRNA-31 (miR-31)/histone deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence