Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Humans ; Bone Remodeling ; Cell Differentiation ; Osteogenesis ; Semaphorin-3A/pharmacology* ; Trigeminal Ganglion/metabolism*

Objective To study the antifungal activity of N2 derivatives. Methods The anti-fungal activity of N2 compounds was investigated by micro-liquid dilution. Then the activity of N2 compounds on hyphal and biofilm formation was investigated. Results N2 compounds had significant antifungal activity against Candida albicans. It also expressed actively inhibitory effect on hyphal and biofilm formation. The mechanism of its fungicidal function was to damage the structure of candida albicans’ cell membrane and cell wall. Conclusion The results showed that N2 had obvious antifungal activity against Candida albicans., which provided a new idea for the development of antifungal drugs and the solution of antifungal drugs resistance.

Objective: To determine the spatiotemporal distribution of Schistosoma (S.) japonicum infections in humans, livestock, and Oncomelania (O.) hupensis across the endemic foci of China. Methods: Based on multi-stage continuous downscaling of sentinel monitoring, county-based schistosomiasis surveillance data were captured from the national schistosomiasis surveillance sites of China from 2005 to 2019. The data included S. japonicum infections in humans, livestock, and O. hupensis. The spatiotemporal trends for schistosomiasis were detected using a Joinpoint regression model, with a standard deviational ellipse (SDE) tool, which determined the central tendency and dispersion in the spatial distribution of schistosomiasis. Further, more spatiotemporal clusters of S. japonicum infections in humans, livestock, and O. hupensis were evaluated by the Poisson model. Results: The prevalence of S. japonicum human infections decreased from 2.06% to zero based on data of the national schistosomiasis surveillance sites of China from 2005 to 2019, with a reduction from 9.42% to zero for the prevalence of S. japonicum infections in livestock, and from 0.26% to zero for the prevalence of S. japonicum infections in O. hupensis. Analysis using an SDE tool showed that schistosomiasis-affected regions were reduced yearly from 2005 to 2014 in the endemic provinces of Hunan, Hubei, Jiangxi, and Anhui, as well as in the Poyang and Dongting Lake regions. Poisson model revealed 11 clusters of S. japonicum human infections, six clusters of S. japonicum infections in livestock, and nine clusters of S. japonicum infections in O. hupensis. The clusters of human infection were highly consistent with clusters of S. japonicum infections in livestock and O. hupensis. They were in the 5 provinces of Hunan, Hubei, Jiangxi, Anhui, and Jiangsu, as well as along the middle and lower reaches of the Yangtze River. Humans, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the north of the Hunan Province, south of the Hubei Province, north of the Jiangxi Province, and southwestern portion of Anhui Province. In the 2 mountainous provinces of Sichuan and Yunnan, human, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the northwestern portion of the Yunnan Province, the Daliangshan area in the south of Sichuan Province, and the hilly regions in the middle of Sichuan Province. Conclusions: A remarkable decline in the disease prevalence of S. japonicum infection was observed in endemic schistosomiasis in China between 2005 and 2019. However, there remains a long-term risk of transmission in local areas, with the highest-risk areas primarily in Poyang Lake and Dongting Lake regions, requiring to focus on vigilance against the rebound of the epidemic. Development of high-sensitivity detection methods and integrating the transmission links such as human and livestock infection, wild animal infection, and O. hupensis into the surveillance-response system will ensure the elimination of schistosomiasis in China by 2030.

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Objective To predict and assess biomechanical responses and injury mechanisms of the thorax and abdomen for small-sized females in vehicle collisions. Methods The accurate geometric model of the thorax and abdomen was constructed based on CT images of Chinese 5th percentile female volunteers. A thoracic-abdominal finite element model of Chinese 5th percentile female with detailed anatomical structure was developed by using the corresponding software. The model was validated by reconstructing three groups of cadaver experiments (namely, test of blunt anteroposterior impact on the thorax, test of bar anteroposterior impact on the abdomen, test of blunt lateral impact on the chest and abdomen). Results The force-deformation curves and injury biomechanical responses of the organs from the simulations were consistent with the cadaver experiment results, which validated effectiveness of the model. Conclusions The model can be used for studying injury mechanisms of the thorax and abdomen for small-sized female, as well as developing small-sized occupant restraint systems and analyzing the forensic cases, which lays foundation for developing the whole body finite element model of Chinese 5th percentile female.

Objective:By calculating the efficiency of the scientific research laboratory, which reflects the level of the scientific research input and output capacity, provide reference for the evaluation and decision-making of its scientific research sustainable development capacity.Methods:20 scientific research laboratories in a hospital were selected as the research subjects, annual input data were used as the input index. Weighted quantitative scores of the performance of each laboratory in research capacity and contribution, research team construction, discipline development and personnel training, operation management, papers and monographs, patents and transfer, awards, graduate-student training, standards and norms, and academic conferences. All these factors mentioned above were used as output indicators. Then Analytic Hierarchy Process (AHP) and Data Envelopment Analysis (DEA) are used to evaluate the scientific efficiency of each laboratory.Results:The performance of the laboratory is weak in the aspects of patent transfer, awards, standardization. The technical efficiency of laboratory 20 is the lowest, and the scale efficiency of laboratory 12 is the lowest.Conclusions:Scientific Research Laboratories should enhance the effectiveness through input adjustment and output enhancement, meanwhile each laboratory should pay attention to the transformation of scientific achievements and also the optimization of construction system.

Objective To study the effect of neck restrain on traumatic brain injury during airbag inflation in traffic accidents. Methods Based on the previously validated 3-year-old child head finite element (FE) model, the impact on out-of-position (OOP) child occupant during airbag inflation was simulated by FE method, so as to investigate the effects of neck restraint on intracranial response and injury mechanism in traffic accidents. Results The head kinematics with neck restrain was different from that without neck restrain under the impact of airbag inflation. The neck restraint would obviously decrease the maximum Von Mises stress of pediatric brain. When airbag-head distance was 20 cm or 25 cm, the neck restraint would obviously decrease the maximum intracranial pressure. Conclusions Neck restraint had a relatively large influence on pediatric intracranial response. When the FE method is used to predict pediatric craniocerebral injury, consideration of neck restrain on child brain response is necessary.

Modern vehicle safety design and safety regulations are mostly based on 50th percentile populations. However, with the increase of obese populations, it is very important to investigate the injury mechanism and protection of obese occupant. Methods such as traffic accidents statistics, cadaver experiments, multi-body modeling and finite element modeling, are currently used to study the injury mechanism of obese occupants. Different hypotheses including cushion effect, body geometrical effect and mass increasing effect have been put forward to explain the effect of obesity on occupant injury mechanism, which means that its mechanism is still uncertain. The impact injury mechanisms of obese occupant were comprehensively summarized. Furthermore, the problems confronted by the research of current obese occupant impact injury and future investigations were proposed in this study.

Objective To explore the effects of different skull-brain interfaces and mesh density of the cerebrospinal fluid (CSF) on dynamic responses of the brain. Methods The impact kinematics on cadaver head under rotation and translation impacts were reconstructed based on the 50th percentile adult head finite element model. The interfaces between skull and CSF, CSF and brain were modeled with different types of interfaces, which were set as sharing nodes, tied, frictionless sliding, so as to investigate the effect of different interface types on dynamic responses of the brain. Then, the interfaces between CSF, skull and brain were set as sharing nodes, while CSF was divided into single-layer and tri-layer of hexahedral element with the constant thickness of CSF, to study influences of CSF with different mesh density layers on dynamic responses of the brain. Results The intracranial pressure was highly sensitive to the interface types, while the brain response seemed to be relatively insensitive to the variation in CSF layers. Conclusions The research findings provide theoretical references for the construction of CSF and the selection of skull-brain contact interface of the head finite element model.

Objective To compare and analyze the effect of membrane element and spring element on biomechanical responses of cervical ligaments. Methods Based on the existing 6-year-old pediatric neck finite element model, the ligaments were simulated by membrane element and spring element, respectively. Then dynamic tensile test of C4-5 vertebrae and tensile test of full cervical spine were conducted. The membrane element model was also used to simulate the bending test, and the simulation results were analyzed. Results In dynamic tensile test of C4-5 vertebral segment, the final failure force of membrane element simulation test and spring element simulation test was 1 207 N and 842 N, respectively, and their difference from the cadaver experiment was 0.6% and 30.6%, respectively. In full cervical tensile test, the difference of peak force from membrane element simulation test and cadaver experiment was 1.8%. The peak force of spring element simulation test was 484 N, and the difference from simulation test and cadaver experiment was large. The simulation result of membrane element bending test was good. Conclusions The spring element had some limitations in force simulation. The membrane element had higher biofidelity and could reflect the biomechanical response of the ligaments.