Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

ObjectiveTo investigate whether Bushen Huoxue prescription improves embryo implantation through regulating exosomal miRNA to enhance maternal-fetal interface communication based on Bushen Huoxue therapy. MethodsIn the animal experiment， all the rats （except for the blank group） were administered hydroxyurea （450 mg·kg^-1） via gavage for 10 d， as well as epinephrine （0.3 mg·kg^-1） and mifepristone （5.5 mg·kg^-1） via subcutaneous injection for 7 d to establish an implantation disorder model of kidney deficiency and blood stasis type. The Bushen Huoxue prescription （BSHX） groups were administered the prescription at different doses （7.30 g·kg^-1 for the high-dose group， 3.65 g·kg^-1 for the medium-dose group， and 1.83 g·kg^-1 for the low-dose group） via gavage. The dydrogesterone group was administered the corresponding medicine （2.63 mg·kg^-1） via gavage. After intervention for 10 days， uterine histopathological changes were observed via hematoxylin-eosin （HE） staining. Mucin （MUC1）， forkhead box protein O1 （FoxO1）， and homeobox A10 （HoxA10） expression levels were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Cell experiment selected primary endometrial epithelial cells （EEC） and trophoblast cells （TC） as research subjects. Exosome-free medicated serum was prepared by ultracentrifugation and cultured in complete medium. Exosomes were isolated from cell supernatants by ultracentrifugation for cross-co-culture. After 48 h， migration and invasion abilities were assessed by scratch and Transwell assays. Sequencing was then performed on EEC-origin exosomal miRNA. ResultsThe model rats exhibited thin endometrium， along with reduced blood vessels， glandules， and pinopode numbers. BSHX improved endometrial morphology and increased pinopode numbers. MUC1， FoxO1， and HoxA10 expressions were downregulated in the model rats， while these parameters were upregulated after BSHX medium- and high-dose intervention. In the cell experiment， after exosome-free medicated serum intervention for 24 h， migration and invasion abilities were enhanced in the BSHX groups （P<0.01）. In EEC-origin exosomal miRNA sequencing， gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses revealed enrichment in biological processes （gastrulation， neuronal differentiation， alongside cell development and regeneration）， involving the mitogen-activated protein kinase （MAPK）， FoxO1， Wnt， mammalian target of rapamycin （mTOR）， and tumor necrosis factor （TNF） signaling pathways. ConclusionBSHX promotes embryo implantation by improving endometrial receptivity via regulating exosomal miRNA. These findings provide potential targets for exosomal miRNA-based assisted reproductive strategies and a novel theoretical basis for infertility treatment by traditional Chinese medicine.

During long-duration manned space missions, the complex and extreme space environment exerts significant impacts on astronauts' physiological, psychological, and cognitive functions, thereby posing direct risks to mission safety and operational efficiency. As a key bridge between the brain and external devices, brain-computer interface (BCI) technology enables precise acquisition and interpretation of neural signals, offering a novel paradigm for human-machine collaboration in manned spaceflight. Non-invasive BCI technology shows broad application prospects across astronaut selection, mission training, in-orbit task execution, and post-mission rehabilitation. During mission preparation, multimodal signal assessment and neurofeedback training based on BCI can effectively enhance cognitive performance and psychological resilience. During mission execution, BCI can provide real-time monitoring of physiological and psychological states and enable intention-based device control, thereby improving operational efficiency and safety. In the post-mission rehabilitation phase, non-invasive BCI combined with neuromodulation may improve emotional and cognitive functions, support motor and cognitive recovery, and contribute to long-term health management. However, the application of BCI in space still faces challenges, including insufficient signal robustness, limited system adaptability, and suboptimal data processing efficiency. Looking forward, integrating multimodal physiological sensors with deep learning algorithms to achieve accurate monitoring and individualized intervention, and combining BCI with virtual reality and robotics to develop intelligent human-machine collaboration models, will provide more efficient support for space missions.
Brain-Computer Interfaces ; Humans ; Space Flight ; Astronauts/psychology* ; Neurofeedback ; Cognition ; Electroencephalography ; Man-Machine Systems

JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

Objective To investigate the correlation between serum levels of long non-coding RNA(Ln-cRNA)-prostate androgen regulated transcript 1(PART1),LncRNA-nucleolar ribonucleic acid host gene 14(SNHG14)and disease stage,cognitive impairment and motor function in patients with Parkinson's disease(PD).Methods A total of 100 PD patients(PD group)who admitted to the Department of Neurology in the hospital from January 2021 to December 2023 and 100 healthy subjects(control group)who underwent the physical examination during the same period of time were selected.According to Hoehn-Yahr staging,PD pa-tients were divided into early stage group(grade 1.0-2.5,20 cases),middle stage group(grade 3.0,48 ca-ses)and late stage group(grade 4.0-5.0,32 cases).According to the Montreal Cognitive Assessment(Mo-CA)score,the patients were divided into normal cognitive group(MoCA score≥26 points,33 cases),PD-mild cognitive impairment group(MoCA score 21-＜26 points,46 cases)and PD dementia group(MoCA score＜21 points,21 cases).According to the Unified Parkinson's Disease Rating Scale(UPDRS)-Ⅲ score,the pa-tients were divided into mild dyskinesia group(0-15 points,29 cases),moderate dyskinesia group(＞15-40 points,46 cases)and severe dyskinesia group(＞40-56 points,25 cases).Real-time fluorescence quantitative PCR was used to detect serum LncRNA-PART1 and LncRNA-SNHG14 levels.Spearman method was used to analyze the correlation between serum LncRNA-PART1,LncRNA-SNHG14 levels and Hoehn-Yahr staging,MoCA score and UPDRS-Ⅲ score in PD patients.Results The level of serum LncRNA-PART1 in PD group was lower than that in control group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in control group(P＜0.05).The serum levels of LncRNA-PART1 in the middle stage group and late stage groups were lower than those in the early stage group(P＜0.05),and the levels of LncRNA-SNHG14 were higher than those in the early stage group(P＜0.05).In addition,the serum level of LncRNA-PART1 in the late stage group was lower than that in the middle stage group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in the middle stage group(P＜0.05).The serum LncRNA-PART1 levels in the PD-mild cognitive impairment group and PD dementia group were lower than those in the normal cognitive group(P＜0.05),while the LncRNA-SNHG14 levels were higher than those in the normal cognitive group(P＜0.05).Additionally,the serum LncRNA-PART1 level in the PD dementia group was lower than that in the PD-mild cognitive impairment(P＜0.05),while the LncRNA-SNHG14 level was higher than that in the PD-mild cog-nitive impairment group(P＜0.05).The serum levels of LncRNA-PART1 in the moderate dyskinesia group and severe dyskinesia group were lower than those in the mild dyskinesia group(P＜0.05),and the levels ofLncRNA-SNHG14 were higher than that in the mild dyskinesia group(P＜0.05).In addition,the serum level of LncRNA-PART1 in the severe dyskinesia group was lower than that in the moderate dyskinesia group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in the moderate dyskinesia group(P＜0.05).Spearman method results showed that serum LncRNA-PART1 level was negatively correlated with Hoehn-Yahr staging and UPDRS-Ⅲ score in PD patients,and positively correlated with MoCA score(P＜0.05).The level of serum LncRNA-SNHG14 was positively correlated with Hoehn-Yahr staging and UPDRS-Ⅲ score in PD patients,and negatively correlated with MoCA score(P＜0.05).Conclusion The level of ser-um LncRNA-PART1 in PD patients is decreased,and the level of LncRNA-SNHG14 is increased,both of them are related to the disease stage,cognitive impairment and motor function of PD patients,which may be-come evaluation indicators for PD progression.

Objective: Based on spinopelvic parameters and biomechanical principles, the pedicle-facet joint (PFJ) morphological characteristics of isthmic and degenerative spondylolisthesis were analyzed, and the mechanism of their onset and progression was discussed. Methods: This retrospective cross-sectional study included 194 patients with L5 spondylolysis or L5–S1 low-grade isthmic spondylolisthesis (IS group), 172 patients with L4–5 degenerative spondylolisthesis (DS group), and 366 patients with nonlumbar spondylolysis (NL group). The spinopelvic parameters and PFJ morphological parameters of the patients were measured, the differences in these parameters among and within the 3 groups were compared, and the correlations were analyzed. Results: Sacral slope (SS) and lumbar lordosis (LL) were the highest in the IS group, the second highest in the DS group, and the lowest in the NL group. Among the 3 groups, the L4 facet joint angle (FJA) was the largest in the IS group, the second largest in the NL group, and the smallest in the DS group. The L4 pedicle-facet joint angle (PFA) was the largest in the DS group, the second largest in the IS group, and the smallest in the NL group. Pearson correlation analysis showed that within each group, SS and LL were negatively correlated with FJA and positively correlated with PFA. Conclusion This study found a correlation between the PFJ morphological characteristics of patients with lumbar spondylolisthesis and spinopelvic parameters, suggesting that the morphological characteristics of PFJs may be caused by varying stresses under different spinopelvic morphologies.