Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

Objective To observe changes in genetic material in the peripheral blood of pediatric patients with vascular malformations after interventional procedures. Methods A total of 108 children with vascular malformations who underwent interventional procedures at Shandong University Affiliated Children’s Hospital between February 2021 and January 2024 were selected as the research subjects. Clinical data and peripheral venous blood samples before and after the interventional procedures were collected from the children. Two biological indicators, γ-H2AX and peripheral blood lymphocyte chromosomal aberration (CA), were used to determine the levels of genetic material damage in children with vascular malformations before and after interventional procedures. Results The median age of the children was 7 years and the median body weight was 27 kg. The median dose-area product (DAP) was 24.20 Gy·cm² and the median DAP/kg was 1.04 Gy·cm²/kg. The incidence rates of both γ-H2AX foci and CA in children with vascular malformations significantly increased after the interventional procedures (Z = 5.924, P < 0.001; Z = 8.515, P < 0.001). The incidence of postoperative CA in 7 children were significantly higher than that in others, approaching or exceeding 4%. The incidence rates of postoperative γ-H2AX foci and CA in children with DAP/kg ≥ 1 Gy·cm²/kg were significantly higher than those in children with DAP/kg < 1 Gy·cm²/kg (U = 7.586, P = 0.031; U = 6.835, P = 0.009). No significant differences were observed in the incidence rates of postoperative γ-H2AX foci and CA among subgroups based on age, body weight, or surgical site. A positive correlation was observed between the difference in the incidence rates of γ-H2AX foci before and after the procedure and DAP/kg (R = 0.493, P = 0.027). Conclusion Ionizing radiation exposure during interventional procedures can increase peripheral blood genetic material damage levels in children with vascular malformations, and the damage levels show a correlation with the radiation dose, with some children being abnormally sensitive. Further research is needed to explore the influencing factors for genetic material damage in children with vascular malformations after interventional procedures, which is of great significance for reducing long-term cancer risks and achieving personalized treatment strategies.

Objective:To analysis of the latent profiles and influencing factors of body image in patients with postoperative oral cancer.Methods:From July 2024 to March 2025, a total of 332 patients with primary oral cancer confirmed by pathology, aged ≥18 years, and undergoing oral cancer surgery at Hunan Cancer Hospital were selected using simple random sampling and cluster sampling. Among them, 25 were female and 307 were male. The body image scale and the Rosenberg self-esteem scale were used to investigate the patients. The main indicators included the total scale scores and scores on various dimensions of body image, such as appearance evaluation and health focus, with particular attention to satisfaction with facial appearance and oral function.The correlation between self-esteem and body image was analyzed, and differences in scores were compared based on gender, age, self-esteem level, and surgical procedure.Results:Among the 332 patients, 93.4% (310/332) were married, and 6.6% (22/332) were unmarried, divorced, or widowed. A total of 84.3% (280/332) underwent flap transplantation surgery, while 15.7% (52/332) did not. The body image distress in the 332 patients could be categorized into a body image adaptation group [80.12% (266/332)] and a body image disorder group [19.88% (66/332)]. Unmarried/divorced/widowed status ( P=0.020), undergoing flap transplantation ( P=0.006), and self-esteem level ( P<0.001) were identified as influencing factors for postoperative body image disorder in oral cancer patients. Conclusions:Given the varying levels of body image concerns among oral cancer patients, healthcare providers can implement targeted, personalized nursing interventions based on their distinct categories and influencing factors.

Objective:To develop a method of employing flow cytometry to directly detect the γ-H2AX expression levels in peripheral blood lymphocytes of mice through fixation and lysis and to evaluate the feasibility of applying this method to research on the radiation-related biological effects and the efficacy evaluation of radioprotective drugs.Methods:A total of 41 male C57BL/6J mice were used. First, 21 mice were randomly divided into 7 groups according to different radiation doses (0, 1, 2, 4, 6, 8, and 10 Gy) with 3 mice in each group. Blood samples were collected from the tail vein of mice at 1, 4, 8, and 24 h after irradiation and immediately fixed with formaldehyde. Red blood cells (RBC) were lysed with Triton X-100, and γ-H2AX was labeled with specific antibodies. DRAQ5 dye was used to further exclude debris and anucleate cells. The mean fluorescence intensity of γ-H2AX in lymphocyte populations was directly analyzed by flow cytometry through forward and side scatter, and dose-effect curves after irradiation were established. Then, the other 20 mice were divided into radiation alone groups and radiation combined with WR-2721 administration groups at 4 and 6 Gy, respectively, with 5 mice in each group. Blood samples were collected from the tail vein of mice at 1, 4, 8, and 24 h after irradiation to detect the average fluorescence intensity of γ-H2AX in lymphocytes, which was used to evaluate the degree of DNA damage in mice and the therapeutic effect of WR-2721.Results:The expression of γ-H2AX in peripheral blood lymphocytes of mice significantly increased with the increase of radiation doses, and reached a peak at 1-2 h and then decreased. The dose-effect relationship was significant ( R2 = 0.9914). At 24 h after 4 and 6 Gy irradiation, compared with the radiation alone groups, the average fluorescence intensity of γ-H2AX in the radiation combined with WR-2721 administration groups was lower (144.8 ± 8.0 and 109.5 ± 9.7, vs. 178.0 ± 18.5 and 136.6 ± 5.4), with statistically significant difference ( t = 3.78, 5.48, P < 0.05). The average fluorescence intensity of γ-H2AX at 24 h after irradiation was consistent with the lowest values of the three blood cell lines at 7 or 14 d after irradiation. Conclusions:The application of flow cytometry with a fixation/dissolution protocol to directly detect the mean fluorescence intensity of γ-H2AX in peripheral blood lymphocytes of mice has significant application value in radiation biology effect research, radiation protection drug screening, and efficacy evaluation.

Ecological cultivation is an important way for the sustainable production of traditional Chinese medicine in the context of the carbon peaking and carbon neutrality goals. Facility cultivation and simulative habitat cultivation modes have been developed and applied to develop the endangered Dendrobium huoshanense on the basis of protection. However, the differences in the greenhouse gas emissions and global warming potential of these cultivation modes remain unexplored, which limits the accurate assessment of carbon-friendly ecological cultivation modes of D. huoshanense. Greenhouse gas emission flux monitoring based on the static chamber method provides an effective way to solve this problem. Therefore, this study conducted a field experiment in the facility cultivation and simulative habitat cultivation modes at a D. huoshanense cultivation base in Dabie Mountains, Anhui Province. From April 2023 to March 2024, samples of greenhouse gases were collected every month, and the concentrations of CO_2, CH_4, and N_2O of the samples were then detected by gas chromatography. The greenhouse gas emission fluxes, cumulative emissions, and global warming potential were further calculated, and the following results were obtained.(1)The two cultivation modes of D. huoshanense showed significant differences in greenhouse gas emission fluxes, especially the CO_2 emission flux, with a pattern of facility cultivation>simulative habitat cultivation [(35.60±11.70)mg·m~(-2)·h~(-1) vs(2.10±4.59)mg·m~(-2)·h~(-1)].(2) The annual cumulative CO_2 emission flux in the case of facility cultivation was significantly higher than that of simulative habitat cultivation[(3 077.00±842.00)kg·hm~(-2) vs(221.00±332.00)kg·hm~(-2)], while no significant difference was found in annual cumulative CH_4 and N_2O emission fluxes.(3) The facility cultivation mode had a significantly higher global warming potential than the simulative habitat cultivation mode [(3 053.00±847.00)kg·hm~(-2) vs(196.00±362.00)kg·hm~(-2)]. Overall, the simulative habitat cultivation of D. huoshanense has obvious carbon-friendly characteristics compared with facility cultivation, which is in line with the concept of ecological cultivation of medicinal plants. This study is of great reference significance for the implementation and promotion of the ecological cultivation mode of D. huoshanense under carbon peaking and carbon neutrality goals.
Dendrobium/chemistry* ; Greenhouse Gases/metabolism* ; Carbon/analysis* ; Ecosystem ; Carbon Dioxide/metabolism* ; China ; Global Warming

Neonates are susceptible to respiratory viral infections, with outbreaks reported in areas with a high population of neonates, such as postpartum care centers and neonatal wards. While specific antiviral drugs are currently available for influenza, symptomatic supportive treatment remains the primary approach for respiratory syncytial virus (RSV), making prevention particularly important. The article closely follows the "Expert recommendations for the prevention of common respiratory viral infections in neonates" and provides an in-depth interpretation of recent breakthroughs in RSV prevention. It discusses the physiological and immunological characteristics of neonates, the disease burden and transmission routes of RSV infection, the main clinical manifestations and long-term effects of RSV infection in neonates, as well as specific preventive measures against RSV and practical recommendations and prevention experiences for RSV from abroad to lay a foundation for RSV prevention and control in neonates in China.
Humans ; Respiratory Syncytial Virus Infections/transmission* ; Infant, Newborn ; Respiratory Tract Infections/prevention & control*

OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Osteopontin(OPN)is a multifunctional protein,widely distributed in a variety of cells,tissues,organs and body fluids.This protein has a classical RGD domain and can bind to a variety of integrins and CD44 receptors,thereby participating in various pathological processes in the body,such as infection,allergic reaction,autoimmune and tissue damage.Recently,many studies have revealed that OPN is highly expressed in the central nervous system(CNS)and plays different regulatory roles in CNS diseases,that is,OPN can play a pro-inflammatory role in some conditions to stimulate neurotoxicity,while it can play a neuroprotective role in other conditions.While there has been growing interest in the biological role of OPN in the CNS,a comprehensive review is currently lacking.The purpose of this paper is to provide an overview of the expression and function of OPN in the CNS,with a focus on microglia,astrocytes,and neurons.