Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists.

Peptide drugs targeting class B1 G-protein-coupled receptors (GPCRs) can treat multiple diseases; however, there remains substantial interest in the development of orally delivered non-peptide drugs. Here, we reveal unexpected overlap between signaling and regulation of the glucagon-like peptide-1 (GLP-1) receptor by the non-peptide agonist PF 06882961 and GLP-1 that was not observed for another compound, CHU-128. Compounds from these patent series, including PF 06882961, are currently in clinical trials for treatment of type 2 diabetes. High-resolution cryoelectron microscopy (cryo-EM) structures reveal that the binding sites for PF 06882961 and GLP-1 substantially overlap, whereas CHU-128 adopts a unique binding mode with a more open receptor conformation at the extracellular face. Structural differences involving extensive water-mediated hydrogen bond networks could be correlated to functional data to understand how PF 06882961, but not CHU-128, can closely mimic the pharmacological properties of GLP-1. These findings will facilitate rational structure-based discovery of non-peptide agonists targeting class B GPCRs.

CATAD: exploring topologically associating domains from an insight of core-attachment structure.

Identifying topologically associating domains (TADs), which are considered as the basic units of chromosome structure and function, can facilitate the exploration of the 3D-structure of chromosomes. Methods have been proposed to identify TADs by detecting the boundaries of TADs or identifying the closely interacted regions as TADs, while the possible inner structure of TADs is seldom investigated. In this study, we assume that a TAD is composed of a core and its surrounding attachments, and propose a method, named CATAD, to identify TADs based on the core-attachment structure model. In CATAD, the cores of TADs are identified based on the local density and cosine similarity, and the surrounding attachments are determined based on boundary insulation. CATAD was applied to the Hi-C data of two human cell lines and two mouse cell lines, and the results show that the boundaries of TADs identified by CATAD are significantly enriched by structural proteins, histone modifications, transcription start sites and enzymes. Furthermore, CATAD outperforms other methods in many cases, in terms of the average peak, boundary tagged ratio and fold change. In addition, CATAD is robust and rarely affected by the different resolutions of Hi-C matrices. Conclusively, identifying TADs based on the core-attachment structure is useful, which may inspire researchers to explore TADs from the angles of possible spatial structures and formation process.

Chromatin remodeling complexes regulate genome architecture in Arabidopsis.

In eukaryotes, three-dimensional (3D) chromatin architecture maintains genome stability and is important in regulating gene transcription. However, little is known about the mechanisms by which diverse ATP-dependent chromatin remodeling complexes regulate the 3D chromatin structure in plants. We examined the 3D chromatin structure within the ATPase subunit of the SWI/SNF, ISWI, INO80, and CHD remodeling complexes in wild-type (WT) and mutant Arabidopsis thaliana plants by combining high-throughput sequencing with in situ Hi-C, the enrichment of histone marks, nucleosome density, and gene expression. We found that compartment regions switched and compartmental strength was significantly weakened in all four enzyme mutants. Chromatin remodeling complexes differentially regulated the nucleosome distribution pattern and density within the switching compartments. Alterations of nucleosome distribution pattern and density were associated with a reduction in H3K27me3 levels in the chromatin remodeling enzyme mutants and led to compartment switching. Our data show that chromatin remodeling complexes regulate the linear nucleosome distribution pattern and density to promote H3K27me3 deposition, which in turn regulates 3D chromatin structure.

Identification of alternative protein targets of glutamate-ureido-lysine associated with PSMA tracer uptake in prostate cancer cells.

Prostate-specific membrane antigen (PSMA) is highly overexpressed in most prostate cancers and is clinically visualized using PSMA-specific probes incorporating glutamate-ureido-lysine (GUL). PSMA is effectively absent from certain high-mortality, treatment-resistant subsets of prostate cancers, such as neuroendocrine prostate cancer (NEPC); however, GUL-based PSMA tracers are still reported to have the potential to identify NEPC metastatic tumors. These probes may bind unknown proteins associated with PSMA-suppressed cancers. We have identified the up-regulation of PSMA-like aminopeptidase NAALADaseL and the metabotropic glutamate receptors (mGluRs) in PSMA-suppressed prostate cancers and find that their expression levels inversely correlate with PSMA expression and are associated with GUL-based radiotracer uptake. Furthermore, we identify that NAALADaseL and mGluR expression correlates with a unique cell cycle signature. This provides an opportunity for the future study of the biology of NEPC and potential therapeutic directions. Computationally predicting that GUL-based probes bind well to these targets, we designed and synthesized a fluorescent PSMA tracer to investigate these proteins in vitro, where it shows excellent affinity for PSMA, NAALADaseL, and specific mGluRs associated with poor prognosis.

Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.

3D-Printed Biomimetic Structural Colors.

Resolution control and expansibility have always been challenges to the fabrication of structural color materials. Here, a facile strategy to print cholesteric liquid crystal elastomers (CLCEs) into complex structural color patterns with variable resolution and enhanced expansibility is reported. A volatile solvent is introduced into the synthesized CLC oligomers, modifying its rheological properties and allowing direct-ink-writing (DIW) under mild conditions. The combination of printing shear flow and anisotropic deswelling of ink drives the CLC molecules into an ordered cholesteric arrangement. The authors meticulously investigate the influence of printing parameters to achieve resolution control over a wide range, allowing for the printing of multi-sized 1D or 2D patterns with constant quality. Furthermore, such solvent-cast direct-ink-writing (DIW) strategy is highly expandable and can be integrated easily into the DIW of bionic robots. Multi-responsive bionic butterfly and flower are printed with biomimetic in both locomotion and coloration. Such designs dramatically reduced the processing difficulty of precise full-color printing and expanded the capability of structural color materials to collaborate with other systems.

SPLDExtraTrees: robust machine learning approach for predicting kinase inhibitor resistance.

Drug resistance is a major threat to the global health and a significant concern throughout the clinical treatment of diseases and drug development. The mutation in proteins that is related to drug binding is a common cause for adaptive drug resistance. Therefore, quantitative estimations of how mutations would affect the interaction between a drug and the target protein would be of vital significance for the drug development and the clinical practice. Computational methods that rely on molecular dynamics simulations, Rosetta protocols, as well as machine learning methods have been proven to be capable of predicting ligand affinity changes upon protein mutation. However, the severely limited sample size and heavy noise induced overfitting and generalization issues have impeded wide adoption of machine learning for studying drug resistance. In this paper, we propose a robust machine learning method, termed SPLDExtraTrees, which can accurately predict ligand binding affinity changes upon protein mutation and identify resistance-causing mutations. Especially, the proposed method ranks training data following a specific scheme that starts with easy-to-learn samples and gradually incorporates harder and diverse samples into the training, and then iterates between sample weight recalculations and model updates. In addition, we calculate additional physics-based structural features to provide the machine learning model with the valuable domain knowledge on proteins for these data-limited predictive tasks. The experiments substantiate the capability of the proposed method for predicting kinase inhibitor resistance under three scenarios and achieve predictive accuracy comparable with that of molecular dynamics and Rosetta methods with much less computational costs.

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines.

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with messenger RNA (mRNA) vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT, Moderna), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using liquid chromatography coupled to tandem mass spectrometry. Antibody-dependent-cellular-phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured by flow cytometry. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD was significantly lower in AstraZeneca-vaccinated individuals. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.

Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Tislelizumab and radiation therapy in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type: a phase II study protocol.

Low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type has a favorable outcome with radiation therapy alone, and the addition of chemotherapy shows no survival benefit. Nonetheless, a proportion of patients will relapse or progress, with a dismal outcome, highlighting the need for a novel therapeutic strategy. Promising preliminary findings indicate the efficacy of PD-1/PD-L1 inhibitors in extranodal natural killer/T-cell lymphoma, nasal type, with good toxicity profiles. Here we describe the design of a phase II study (CLCG-NKT-2101), which is evaluating the safety and efficacy of adding anti-PD-1 antibody to the current radiation therapy regimen in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type patients. Tislelizumab will be added in an inductive and concurrent way to radiation therapy. The primary end point will be the complete response rate after induction immunotherapy. Clinical trial registration: ClinicalTrials.gov (NCT05149170).

Multicenter phase II study of moderate low-dose radiotherapy in indolent non-Hodgkin lymphoma: CLCG-iNHL-01 protocol.

Background: Radiotherapy is an effective treatment for indolent non-Hodgkin lymphoma (iNHL); however, the optimal radiotherapy dose remains to be determined. We hypothesize that a suitable dose may exist between 4 and 24 Gy. Methods: This prospective multicenter phase II trial intends to recruit 73 sites of iNHL patients, who will receive involved-site radiotherapy of 12 Gy in four fractions. The primary objective is the 6-month clinical complete response rate. Tumor tissue, blood and conjunctival specimens will be collected to identify potential predictive biomarkers. Discussion: The CLCG-iNHL-01 trial will evaluate the efficacy and toxicity of 12 Gy in patients with iNHL and provide information on a novel hypofractionation regimen of low-dose radiotherapy. Clinical Trial Registration: NCT05543070 (ClinicalTrials.gov).

Interventions to improve social network in older people with sensory impairment: a systematic review.

BACKGROUND: Sensory impairment significantly reduces speech discrimination and perception ability, presenting a challenge to effective communication. It can lead to social withdrawal and a reduced social network which can lead to cognitive impairment, seriously affecting the quality of life of older people. However, it is unclear which intervention components are effective to improving social network in older people with sensory impairment. OBJECTIVE: The aim of this systematic review was to summarize interventions designed to improve social network in older people with sensory impairment. METHODS: We searched seven databases from inception to December 1, 2023. Eligible studies included randomized clinical trials (RCT) and quasi-experimental studies of interventions for older people with sensory impairment aimed at improving social networks. Two reviewers searched databases, extracted data, and assessed the quality of the included studies independently. RESULTS: Nine studies including five RCTs and four quasi-experimental studies were selected, enrolling 721 older people with sensory impairment. Methodological quality of the studies was modest. Eight studies demonstrated a positive impact of the interventions used in older people with sensory impairment. The detailed effective intervention components may include communication strategies, resources for older people and their significant others, exercise or tech-back of communication, sensory device fitting, and use and maintenance of sensory devices. CONCLUSION: There are few interventions available for improving social network in older people with sensory impairment. Most interventions mainly focus on communication education and care, and sensory device fitting and education. To improve the social network in older people with sensory impairment, it is necessary to develop more effective, multidisciplinary collaborative effective interventions and conduct more high-quality original studies.

Highly extensile approach for comminuted ulna coronoid process fractures with mini-plate fixation: a case series of 31 patients.

BACKGROUND: For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up. METHODS: Thirty-one patients diagnosed with coronoid fractures accompanied with a "terrible triad" or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded. RESULTS: The mean follow-up time was 26.7 months (range, 14-60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey's criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification. CONCLUSION: An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.

Graphene Oxide-Enhanced and Dynamically Crosslinked Bio-Elastomer for Poly(lactic acid) Modification.

Being a bio-sourced and biodegradable polymer, polylactic acid (PLA) has been considered as one of the most promising substitutes for petroleum-based plastics. However, its wide application is greatly limited by its very poor ductility, which has driven PLA-toughening modifications to be a topic of increasing research interest in the past decade. Toughening enhancement is achieved often at the cost of a large sacrifice in strength, with the toughness-strength trade-off having remained as one of the main bottlenecks of PLA modification. In the present study, a bio-elastomeric material of epoxidized soybean oil (ESO) crosslinked with sebacic acid (SA) and enhanced by graphene oxide (GO) nanoparticles (NPs) was employed to toughen PLA with the purpose of simultaneously preserving strength and achieving additional functions. The even dispersion of GO NPs in ESO was aided by ultrasonication and guaranteed during the following ESO-SA crosslinking with GO participating in the carboxyl-epoxy reaction with both ESO and SA, resulting in a nanoparticle-enhanced and dynamically crosslinked elastomer (GESO) via a ß-hydroxy ester. GESO was then melt-blended with PLA, with the interfacial reaction between ESO and PLA offering good compatibility. The blend morphology, and thermal and mechanical properties, etc., were evaluated and GESO was found to significantly toughen PLA while preserving its strength, with the GO loading optimized at ~0.67 wt%, which gave an elongation at break of ~274.5% and impact strength of ~10.2 kJ/m2, being 31 times and 2.5 times higher than pure PLA, respectively. Moreover, thanks to the presence of dynamic crosslinks and GO NPs, the PLA-GESO blends exhibited excellent shape memory effect and antistatic properties.

A Dataset on Population Activity Patterns in Typical Regions of North China.

This data article describes the "Typical Regional Activity Patterns" (TRAP) dataset, which is based on the Tackling Key Problems in Air Pollution Control Program. In order to explore the interaction between air pollution and physical activity, we collected activity patterns of 9,221 residents with different occupations and lifestyles for three consecutive days in typical regions (Jinan and Baoding) where air pollutant concentrations were higher than those in neighboring areas. The TRAP dataset consists of two aspects of information: demographic indicators (personal information, occupation, personal habits, and living situation) and physical activity pattern data (activity location and intensity); additionally, the exposure measures of physical activity patterns are included, which data users can match to various endpoints for their specific purpose. This dataset provides evidence for exploring the attributes of activity patterns of residents in northern China and for interdisciplinary researchers to develop strategies and measures for health education and health promotion.

Self-neglect as a mediator between family functioning and healthy aging in older adults living alone in rural China: A cross-sectional study.

OBJECTIVE: This study aims to investigate the mediating role of self-neglect among older adults in the relationship between family functioning and healthy aging. METHODS: A questionnaire survey was conducted between June and September 2023, involving 255 older adults living alone in rural China. The healthy ageing, self-neglect, and family functioning was assessed using the Healthy Aging Instrument;the Elderly Self-neglect Assessment (Rural);and Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) scale. RESULTS: Positive correlations were found between family functioning and healthy aging (r = 0.363, p < 0.05). Moreover, self-neglect was identified as a significant mediator, explaining 40.84 % of the total effect. CONCLUSION: Among older adults living alone in rural China, family functioning is significantly associated with healthy aging, with self-neglect mediating this relationship. These findings suggest that community-based interventions aimed at improving family functioning and addressing self-neglect behaviors might be beneficial for promoting healthy aging in this population.

Social participation in older people with hearing impairment in Chinese community: A latent profile analysis.

OBJECTIVES: Hearing impairment may lead to increased communication difficulties for older people, making their social participation less optimistic. However, there is little research on the social participation of older people with hearing impairment, especially based on the characteristics of their social participation. This study aimed to identify different social participation profiles in older people with hearing impairment and to explore sociodemographic characteristics, disease-related characteristics and psychosocial factors with different social participation profiles. METHODS: A cross-sectional study of 300 older people with hearing impairment using the sociodemographic questionnaire, the Impact on Participation and Autonomy Questionnaire, the Lubben Social Network Scale-6, Medical Outcomes Study Social Support Survey and Geriatric Depression Scale-15 from May to August 2023 in a community of Beijing, China. Latent profile analysis was used to analyse the latent profiles of social participation in elderly with hearing impairment. Multiple logistic regression was used to explore the predictors of different profiles. RESULTS: The social participation of older people with hearing impairment in the community can be classified into three potential profiles: Profile 1 - high social participation group (76.05 %), Profile 2 - moderate social participation group (17.34 %), Profile 3 - low social participation group (6.61 %). Age, types of chronic diseases, self-reported health, severity of hearing impairment, social network, social support and depression were predictors of different profiles. CONCLUSIONS: Nurses should pay attention to the characteristics, depression, social network and support of older people with different hearing impairment to improve social participation in different profiles. IMPLICATIONS AND RECOMMENDATIONS: This was the first study exploring latent profiles of social participation in older people with hearing impairment. Insights from this study are useful for gerontological nursing to distinguish different profiles and further identify the characteristics of different profiles in older people with hearing impairment by characterizing the level of social participation in the community and better implement interventions according to profiles.

Social network and related factors in older people with sensory impairment in the community: Using principal component analysis.

AIM: Older people with sensory impairment are more likely to have smaller and weaker social network due to their reduced ability, which lowers their quality of life. However, there is little research on the social network in older people with sensory impairment, especially the related factors. The aim of the study was to explore the related factors of social network and to provide evidence for the improvement of social network to promote successful aging in older people with sensory impairment. METHODS: A cross-sectional study was conducted among 374 participants for hearing and vision assessment and questionnaire survey in a community, Beijing. Data were collected and analyzed by principal component analysis (PCA) and multiple logistic regression using IBM SPSS 25.0 software. RESULTS: PCA showed that there were six risk factors whose eigenvalues >1 were extracted, with a total variance of 56.555%. Multiple logistic regression analysis of principal component indicated that five factors including physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor, were statistically significant (p < 0.05). CONCLUSIONS: The social network of older people with sensory impairment is relatively poor. Physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor may be related factors. Medical staff should pay attention to physical, psychological and social characteristics of older people, especially with sensory impairment, to carry out necessary measures to improve social network and avoid social isolation.

Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury.

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.