ObjectiveTo construct a stable monoclonal human embryonic kidney 293 （HEK293） cell line expressing recombinant human coagulation factor Ⅶ （rhFⅦ） and evaluate the expression level and procoagulant bioactivity of rhFⅦ. MethodsThe plasmid pCDNA3.1-EGFP-FⅦ was transfected into HEK293 cells to verify the effectiveness of the transfection system. The plasmid pCDNA3.1-FⅦ was transfected into HEK293 cells， and monoclonal stable transfected cell lines were selected using geneticin （G418）. The transcription of the FⅦ gene was identified by reverse transcription polymerase chain reaction （RT-PCR）. The expression level of rhFⅦ in the supernatant of the monoclonal stable transfected cell line was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. The concentration of rhFⅦ was determined by enzyme-linked immunosorbent assay （ELISA）， and the procoagulant activity of rhFⅦ was measured by human coagulation factor Ⅶ potency assay. ResultsHEK293 cells transfected with pcDNA3.1-EGFP-FⅦ showed green fluorescence， indicating that rhFⅦ was successfully expressed in the supernatant of HEK293 cells after transient transfection with pcDNA3.1-FⅦ. The monoclonal stable transfected cell line was obtained by G418 screening. RT-PCR identified that the FⅦ gene was integrated into the genome of the monoclonal stable transfected cell line. The cell viability was good as detected by Cell Counting Kit-8， and a single band of rhFⅦ was obtained by purification of the cell supernatant. The highest rhFⅦ expression was （1.27±0.09） mg/L， and the highest procoagulant activity was （380.29±13.80）%. ConclusionThe monoclonal HEK293 cell lines which can express rhFⅦ protein efficiently and stably with excellent procoagulant bioactivity is successfully screened.

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.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

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

Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

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