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Background: Osteoarthritis (OA) is a leading cause of disability globally, affecting over 500 million individuals worldwide. However, accurate and early diagnosis of OA is challenging to achieve. Immune-related genes play an essential role in OA development. Therefore, the objective of this study was to develop a diagnostic model for OA based on immune-related genes identified in synovial membrane. Methods: The gene expression profile of OA were downloaded based on four datasets. The significantly differentially expressed genes (DEGs) between OA and control groups were selected. The differential immune cells were analyzed, followed by immune-related DEGs screening. WGCNA was used to screen module genes and these genes were further selected through optimization algorithm. Then, nomogram model was constructed. Chemical drug small molecule related to OA was predicted. Finally, expression levels of several key genes were validated by qRT-PCR through construction of OA rat models. Results: The total 656 DEGs were obtained. Eight immune cells were significantly differential between two groups, and 317 immune-related DEGs were obtained. WGCNA identified three modules. The genes in modules were significantly involved in 15 pathways, involving in 65 genes. Then 12 DEGs were screened as the final optimal combination of DEGs, such as CEBPB, CXCL1, JUND, GABARAPL2 and PDGFC. The Nomogram model was also constructed. Furthermore, the chemical small molecules, such as acetaminophen, aspirin, and caffeine were predicted. The expression levels of CEBPB, CXCL1, GABARAPL2 and PDGFC were validated in OA rat models. Conclusion: A diagnostic model based on twelve immune related genes was constructed. These model genes, such as CEBPB, CXCL1, GABARAPL2, and PDGFC, may serve as diagnostic biomarkers and immunotherapeutic targets.

In the macrophage-specific mTORC1 signaling activation model, the synovial macrophages polarized toward M1, thus aggravating synovitis and progression of OA. Therefore, intra-articular injection of rapamycin, a classical mTORC1 inhibitor, may show great potential for alleviating synovitis and delaying cartilage destruction in osteoarthritis (OA). However, the durable retention of drugs in the joint cavity is still a critical issue to be addressed. Herein, we crosslinked the Poloxamer 407 and hyaluronic acid (P-HA) to prepare an injectable and thermo-responsive drug delivery system to durably retain rapamycin and dramatically magnify their therapeutic effects in OA management. The prepared P-HA hydrogel showed excellent biocompatibility with chondrocytes and fibroblasts, as well as possessed sustained rapamycin release profiles for 14 days. Intra-articular injection of this rapamycin-incorporated P-HA hydrogel indicated a positively effect on inducing the polarization of synovial macrophages from M1 to M2 phenotype and reducing synovial inflammation in OA. This strategy significantly decreased the pro-inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) and increased the anti-inflammatory cytokine (e.g., IL-10) expression in the synovial tissues and synovial fluid. As a result, intra-articular injection of rapamycin-incorporated P-HA hydrogel significantly prevented cartilage destruction by inducing cartilage matrix formation, which suggesting a great potential for the management of OA.

BackgroundWhen the coronavirus disease 2019 (COVID-19) erupted in Yangzhou, China, at the end of July 2021, medical workers in Yangzhou immediately joined the frontline for the fight against the pandemic. This study aimed to identify the mental health and fatigue experienced by the medical workers in Yangzhou during the COVID-19 outbreak.MethodsWe included 233 medical workers who participated in the front-line work for more than 1 month through the questionnaire, including doctors, nurses, medical technicians and medical students. The generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 (PHQ-9), and Fatigue self-assessment scale (FSAS) were administered to the participants and their responses were evaluated.ResultsA total of 233 eligible questionnaires were received. Among them, 130 people (57.08%) were probably anxious and 141 (60.52%) people were clinically depressed. Poor sleep was considered an independent risk factor for anxiety (OR = 7.164, 95% CI: 3.365 15.251, p = 0.000) and depression (OR = 6.899, 95% CI: 3.392 14.030, p = 0.000). A high PHQ-9 score was considered an independent risk factor for general fatigue (OR = 1.697, 95% CI: 1.481 1.944, p = 0.000). Mental fatigue (OR = 1.092, 95% CI: 1.027 1.161, p = 0.005) and fatigue response to sleep/rest (OR = 1.043, 95% CI: 1.011 1.076 p = 0.008) were considered independent risk factors for general fatigue.ConclusionPoor quality of sleep led to probable anxiety, depression, and general fatigue. Mental fatigue and fatigue response to sleep/rest were independent risk factors for depression, which merits attention for battling COVID-19.

Working memory impairment is a common cognitive dysfunction after traumatic brain injury (TBI), which severely affects the quality of life of patients. Acetylcholine is a neurotransmitter which is closely related to cognitive functions. In addition, epigenetic modifications are also related to cognitive functions. A neurorehabilitation strategy, enriched environment (EE) intervention, has been widely used to improve cognitive impairment. However, studies of the mechanism of EE on cholinergic system and epigenetic modifications in mouse with TBI have not been reported yet. In this paper, a mouse model with traumatic frontal lobe injury was established, and the mechanism on EE for the mice with TBI was explored. It was found that EE could improve Y-maze performance of mice with TBI, the function of cholinergic system, and the imbalance of acetylation homeostasis in the prefrontal cortex of contralateral side of TBI. In addition, EE also could increase the level of CREB binding protein and histones H3 acetylation at ChAT gene promoter region in the prefrontal cortex of contralateral side of TBI. These indicate that EE has an important effect on the improvement of working memory impairment and the underlying mechanism may involve in histones H3 acetylation at ChAT gene promoter regions in the prefrontal cortex.

Objective To investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice. Methods A total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD) lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test. Results The 12-month-old aged mice were divided into a normal gait group (n = 75) and an abnormal gait group (n = 25). Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV) in stride length, two with base of support (BOS) deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was significantly higher in the abnormal gait group as compared to that in the normal gait group (x = 21.986, P

The structure and crystal quality of GaN using Rutherford Backscattering Spectrometry and Channeling were studied. The samples were grown on sapphire by metal-organic vapor-phase epitaxy. The H+, He+, N+ with different ion energies and doses were implanted into GaN. Post-implantation annealing were investigated. We observed 7–8 orders increasing of resistivity by Hall measurements after specific temperature annealing, and the optimized annealing temperature is approximately 200–400 °C for H+, He+ and N+ respectively. Even after 600–700 °C annealing, the resistivity is still very high. We think vacancies and radioactive damage by implantation are responsible for resistivity changes in GaN samples. [Copyright &y& Elsevier]