Objective: To investigate the relationship between 24 hour activity behaviors and fine motor development in preschool children, and to simulate the effects of reallocating time among different activity behaviors on fine motor development using isotemporal substitution analysis. Methods: From March to July 2022, a stratified cluster random sampling method was used to recruit 447 preschool children aged 3-6 years (254 boys and 193 girls) from Pingxiang City, Jiangxi Province. The 24 hour activity behaviors in preschool children were measured using ActiGraph wGT3-BT accelerometers and subjective sleep reports. Fine motor development was assessed using the Gesell Developmental Schedules. A component linear regression model was employed to analyze the impact of 24 hour activity behaviors on the development of fine motor activities, and the potential effects of adjusting activity behaviors were simulated through an isochoric substitution model. Results: The daily durations of sedentary behavior (SB) was ( 572.92 ±102.96) min (accounting for 39.79% of 24 h), the duration of light physical activity (LPA) was (131.21± 38.11 ) min ( 9.11% ), the duration of moderate to vigorous physical activity (MVPA) was (65.61±22.21) min (4.56%), and sleep duration was (670.65±57.58) min (46.82%). Sleep composition was positively associated with fine motor development ( β =2.74), while MVPA ( β =-0.84) and SB ( β =-1.93) compositions were negatively associated with fine motor development (all P <0.01). Isochoric substitution analysis showed that sleep had positive effects on the development of fine motor skills when replacing other activity behaviors (all P < 0.05), with the substitution effect for MVPA being the most significant and gradually increasing with the duration of substitution (60 min: β =28.66); sleep replacement of SB and LPA also showed positive effects (60 min: β =4.25, 2.00) (all P < 0.05). On the contrary, the substitution of sleep with MVPA showed negative effects (60 min: β =-7.86), and the substitution of LPA and SB with MVPA also showed negative effects (60 min: β =-5.65, -3.40) (all P <0.05). Conclusions The overall composition of 24 hour activity behaviors is associated with fine motor development in preschool children, with sleep playing a crucial role. Ensuring adequate sleep and optimizing the structure of activity behaviors may effectively promote the development of fine motor skills in preschool children.

Immune-stimulating antibody drug conjugate (ISAC) can not only effectively solve the defects of stimulator of interferon genes (STING) agonists by coupling antibodies with STING agonists through the targeting of antibodies, but also play a synergistic role with antibodies to further improve the efficacy of STING agonists. This review first provides a concise overview of the current research landscape of ISACs and STING agonists, systematically elaborates on evolving trends in STING agonist development, and subsequently summarizes the mechanistic advances in STING ISAC research. Special emphasis is placed on representative STING ISAC candidates in preclinical/clinical development. Finally, the future directions of STING ISACs are critically discussed with perspectives and recommendations, aiming to provide theoretical insights and practical guidance for future investigations.

Background Polycyclic aromatic hydrocarbons (PAHs) are widely known atmospheric pollutants, which can cause serious harm to human body and ecological environment. Objective To analyze the concentrations and sources of PAHs in atmospheric PM_2.5 in Zhifu District and Longkou City during the heating period in Yantai. Methods Two monitoring sites in Zhifu District and Longkou City of Yantai were selected, and PM_2.5 sample collection was carried out from April 2023 to March 2024. Gas chromatography-mass spectrometry was applied to analyze the concentrations of PAHs in atmospheric PM_2.5 during the heating period (from November 2023 to March 2024) and the non-heating period (from April to October 2023). The concentrations of PAHs in the two periods were compared and the sources of PAHs during the heating period were analyzed by characteristic ratio method. Results During the heating period, the total concentration ranges of PAHs in atmospheric PM_2.5 at the monitoring sites in Zhifu District and Longkou City of Yantai were (1.59-23.70) ng·m⁻³ and (2.08-149.72) ng·m⁻³ respectively, and the medians (M) and the 25th and 75th percentiles (P₂₅, P₇₅) were 4.99 (2.61, 8.09) ng·m⁻³ and 15.46 (8.15, 29.05) ng·m⁻³ respectively. The PAHs concentrations in Longkou City were significantly higher than those in Zhifu District in all months (P<0.05). The highest median total concentrations of PAHs in both sites were reported in January (8.14 ng·m⁻³ and 81.56 ng·m⁻³ respectively). In the non-heating period, the M (P₂₅, P₇₅) of the total PAHs concentrations at the two sites were 1.59 (1.59, 2.78) ng·m⁻³ and 4.11 (2.94, 7.97) ng·m⁻³ respectively, much lower than those in the heating period (P<0.01). The order of composition of PAHs by ring number in PM_2.5 at both sites was 4-ring> 5-ring> 6-ring, with the 4-ring contributing the largest proportion (65.33% and 46.39% respectively). Fluoranthene had the highest concentration among PAHs at both sites, with concentrations M (P₂₅, P₇₅) of 1.29 (0.51, 1.78) ng·m⁻³ and 2.32 (1.30, 3.82) ng·m⁻³ respectively. The characteristic ratios of fluoranthene/(fluoranthene + pyrene), fluoranthene/pyrene, benzo[a]anthracene/(benzo[a]anthracene + chrysene), pyrene/benzo[a]pyrene, benzo[a]pyrene/(benzo[a]pyrene + chrysene), benzo[a]pyrene/benzo[g,h,i]pyrene, and indeno[1,2,3-c,d]pyrene/(indeno[1,2,3-c,d]pyrene + benzo[g,h,i]pyrene) in Zhifu District were 0.62, 1.65, 0.41, 4.48, 0.50, 0.93 and 0.47 respectively, and those in Longkou were 0.57, 1.35, 0.40, 2.89, 0.29, 0.79 and 0.47 respectively. The results showed that PAHs pollutants were generated by combination of coal combustion, vehicle exhaust emissions and gasoline combustion. Conclusion During the heating period in Yantai area, the total concentration of PAHs in atmospheric PM_2.5 is significantly higher than that in the non-heating period. Among them, during the heating period, the pollution level in Longkou City is significantly higher than that in Zhifu District. The local PAHs may be sourced from mixed pollution, and the main sources include gasoline, and coal combustion and vehicle exhaust emissions.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Aging and cancer share overlapping characteristics, referred to as meta-hallmarks, which elucidate the convergent, antagonistic, or contradictory relationships between aging and cancer. Likewise, as a key characteristic of aging, senescent cells share some meta-hallmarks with tumor cells. These hallmarks include apoptosis resistance, metabolic alterations, secretory phenotypes, epigenetic reprogramming, and immune surveillance, all of which play pivotal roles in both tumorigenesis and senescence. Moreover, senolytic drugs, which are a class of agents selectively designed to eliminate senescent cells, have emerged as promising therapeutic agents in oncology and aging-related diseases. Since the discovery of the first senolytic drug in 2015, a diverse array of such agents has been developed. Notably, most senolytic drugs are repurposed from existing anti-tumor therapies, leveraging their shared mechanisms with senescent cells and tumor cells. Thus, this review examines the similarities between senescent cells and tumor cells, providing a better understanding of the meta-hallmarks. Besides, we categorize existing senolytic drugs based upon meta-hallmarks and elucidate the potential molecular mechanisms underlying their effects. By integrating insights from cancer and senescence research, this work aims to inspire innovative strategies for senolytic drug discovery.

Tooth autotransplantation is a restoration technology that grafts the patient's own teeth to the missing tooth area, usually by using the third molar to replace a nonnormally functioning molar for the purpose of "turning waste into treasure". Robotic surgical assistance has been widely used in the fields of breast cancer, liver cancer, and orthopedics; however, its application in the dental field, particularly in tooth autotransplantation, remains relatively rare. This paper reports a case of tooth autotransplantation with the assistance of a domestic autonomous oral surgery robot, providing a reference for the application of robotic surgery assistance in tooth autotransplantation.
Humans ; Molar, Third/transplantation* ; Robotic Surgical Procedures/methods* ; Transplantation, Autologous

Objective To study the shielding effect of water body on γ spectrometer during underwater measurements.Methods A mathematical model of water immersion was constructed for the 3-inch(ф76.2 mm×76.2 mm)lanthanum bromide detector.The totipotent peak count rate of 10 typical γ characteristic energies under different radius water sphere conditions was calculated by MCNP software,and the relationship was established.Results The effective radii of γ photons of different energies based on the 3-inch lanthanum bromide detector was obtained.The relation of energy and effective radius was established,and the effective radius of Tl-208@2614keV was 102.99 cm.Conclusion The quantitative relationship between photons of different energies of a typical 3-inch lanthanum bromide detector and effective radius had been established theoretically,which provides a theoretical basis for measuring and analyzing radioactive water body by γ spectrometer.

Objective To study the shielding effect of water body on γ spectrometer during underwater measurements.Methods A mathematical model of water immersion was constructed for the 3-inch(ф76.2 mm×76.2 mm)lanthanum bromide detector.The totipotent peak count rate of 10 typical γ characteristic energies under different radius water sphere conditions was calculated by MCNP software,and the relationship was established.Results The effective radii of γ photons of different energies based on the 3-inch lanthanum bromide detector was obtained.The relation of energy and effective radius was established,and the effective radius of Tl-208@2614keV was 102.99 cm.Conclusion The quantitative relationship between photons of different energies of a typical 3-inch lanthanum bromide detector and effective radius had been established theoretically,which provides a theoretical basis for measuring and analyzing radioactive water body by γ spectrometer.