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Despite the growing availability of effective COVID-19 vaccines in rural communities in the United States, widespread vaccine hesitancy delays COVID-19 vaccine coverage in rural communities and threatens to worsen pre-pandemic rural–urban disparities in other vaccination rates, including influenza and routine pediatric immunizations. Therefore, there is an urgent need to develop communication-based interventions to improve vaccine confidence in rural America. This study demonstrates the efficacy of a community-engaged approach to developing social media campaign messages in promoting COVID-19 vaccine uptake and pro-vaccine social diffusion among rural adults. Using a community-engaged approach, we developed social media campaign videos varying in (a) featured messengers (clinicians versus community leaders) and (b) the presence of personal testimonials. We conducted a national online experiment (N = 1,364 rural adults) in spring 2022. We found that videos featuring clinicians serving rural communities and their testimonials increased (a) vaccination intentions in the unvaccinated group (4-point scale, b = 0.23, p =.015) and (b) intention to discuss the messages with others (4-point scale, b = 0.14, p =.037), share the message (4-point scale, b = 0.15, p =.026), and promote the vaccines to others (9-point scale, b = 0.48, p =.013). Results suggest that vaccine promotional social media campaigns targeting rural populations can benefit from including clinician testimonials.

Mutation of SERPINC1 is related to the incidence of Inherited antithrombin (AT) deficiency. In this study, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a patient with a mutation of SERPINC1 c.236G>A (p.R79H). The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Besides, it has a normal female karyotype and could differentiate into all three germ layers in vitro.

Abstract Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide due to the lack of early diagnostic markers and specific drugs. Previous studies have shown the association of LUAD growth with aberrant alternative splicing (AS). Herein, clinical data of 535 tumor tissues and 59 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. Each sample was analyzed using the ESTIMATE algorithm; a comparison between higher and lower score groups (stromal or immune) was made to determine the overall- and progression-free survival-related differentially expressed AS (DEAS) events. We then performed unsupervised clustering of these DEASs, followed by determining their relationship with survival rate, immune cells, and the tumor microenvironment (TME). Next, two prognostic signatures were developed using bioinformatics tools to explore the prognosis of cases with LUAD. Five OS- and six PFS-associated DEAS events were implemented to establish a prognostic risk score model. When compared to the high-risk group (HRG), the PFS and OS of the low-risk group (LRG) were found to be considerable. Additionally, a better prognosis was found considerably associated with the ESTIMATE score of the patients as well as immune cells infiltration. Our analysis of AS events in LUAD not only helps to clarify the tumorigenesis mechanism of AS but also provides ideas for revealing potential prognostic biomarkers and therapeutic targets.

BackgroundHomozygous or compound heterozygous mutations in the high-temperature requirement A serine protease 1 gene (HTRA1) elicits cerebral autosomal recessive arteriopathy with subcortical infarcts and white matter lesions (CARASIL). The relationship between some heterozygous mutations, most of which are missense ones, and the occurrence of cerebral small vessel diseases (CSVD) has been reported. Recently, heterozygous HTRA1 nonsense mutations have been recognized to be pathogenic.Case presentationWe described two Chinese patients diagnosed with HTRA1-CSVD accompanied by heterozygous nonsense mutations. Their first clinical manifestations were symptoms due to ischemic stroke, and brain Magnetic Resonance Imaging (MRI) showed diffuse white matter lesions (WMLs) and microbleeds in both of them. Genetic sequencing revealed two novel heterozygous nonsense mutations: c.1096G>T (p.E366X) and c.151G>T (p.E51X).ConclusionThis case report expands the clinical, radiographic, and genetic spectrum of HTRA1-CSVD. Attention should be paid to young patients with ischemic stroke as the first clinical manifestation. Genetic screening for such sporadic CSVD is recommended, even if the symptoms are atypical.

Abstract Background Although the medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. In recent years, studies have found that four-transmembrane superfamily proteins are involved in multiple stages of tumorigenesis and development, but their expression and function in tumors have not been systematically studied. Methods We used the Oncomine database to analyze the mRNA expression levels of TSPAN family in various cancers. Then differentially expressed genes were screened out and verified by liver cancer, colorectal cancer, and gastric cancer cells by q-PCR and Western blot analysis. CCK8 and EDU analysis are used to detect cell proliferation, Cell wound scrape assay and Cell invasion assay are used to analyze cell invasion and metastasis. Nude tumor formation test used to verify the tumor suppressive effect of TSPAN7 in vivo. Results Differential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, TSPAN30. TSPAN7 is the only four-transmembrane protein with reduced expression in three types of digestive tract tumors, so we chose TSPAN7 to be selected for cellular and molecular level verification. We found that compared with normal cells, the expression of TSPAN7 in liver cancer cells was significantly reduced, while the expression of gastric and colon cancer was not significantly different from that of normal cells. In addition, we also found that the high expression of Tspan7 not only inhibited the proliferation of HCC-LM3 cells, but also inhibited its invasion and metastasis. Conclusions Our study evaluated the expression and function of the TSPANs family in digestive cancers and explored TSPAN7 in hepatoma cells in detail. We found some members of the TSPAN family show significant expression differences between cancer and normal tissues, of which TSPAN7 may be a potential biomarker for liver cancer.

Abstract Objects Abnormal blood pressure (BP) regulation is a feature of autonomic dysfunction in Parkinson's disease (PD) patients. The present study was to analyze the BP alterations by 24‐h ambulatory BP monitoring in PD patients with different disease stages and subtypes. Methods 32 consecutive patients PD patients and 43 control patients in our hospital from 2017 to 2020 were included. The circadian BP rhythm was divided into three types according to the 24‐h ambulatory BP monitoring. Dipping was defined as an average systolic BP (SBP) reduction during night‐time of 10%–19%. Reverse dipping was defined as an average increase in night‐time SBP values. The differences of the circadian BP rhythm and BP variability (BPV) were analyzed between PD group and the control group, the early PD group and the advanced PD group, as well as the tremor‐dominant group and the nontremor‐dominant group. Results There was statistical difference in circadian BP rhythm between PD group and control group (p

To investigate the associations between soluble Lectin-like Oxidized Low-density lipoprotein receptor-1 (sLOX-1) and clinical prognosis, especially infarct volume in patients with acute atherosclerosis-related ischemic stroke. We recruited acute ischemic stroke patients within 3 days after onset. Patients were stratified into 3 groups by sLOX-1 level. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI by ITK-SNAP software. The clinical prognosis was evaluated by DWI volume, clinical response at discharge, and functional outcome at 90 days. Spearman rank correlation analysis was used to examine associations between circulating sLOX-1 levels and infarct volumes. Logistic regression was used to explore the relationship between sLOX-1 levels and clinical prognosis. A total of 207 patients were included in our study. The median DWI volume in the lowest sLOX-1 tertile was 1.98 cm 3 , smaller than 4.26 cm 3 in the highest sLOX-1 group. The Spearman rank correlation coefficient between sLOX-1 levels and DWI volume was 0.47 ( P

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, which usually manifests as abdominal pain, diarrhea and hematochezia. The disease often recurs and is difficult to cure. At present, the pathogenesis is not clear, but it is believed that the disease is caused by a complex interaction among immunity, heredity, environment and intestinal microflora disorders. MicroRNA (miRNA) is endogenous single-stranded non-coding RNA of 17–25 nucleotides (nts). They target the 3'Untranslated Region of a target gene and inhibit or degrade the target gene according to the extent of complementary bases. As important gene expression regulators, miRNAs are involved in regulating the expression of most human genes, and play an important role in the pathogenesis of many autoimmune diseases including UC. Studies in recent years have illustrated that abnormal expression of miRNA occurs very early in disease pathogenesis. Moreover, this abnormal expression is highly related to disease activity of UC and colitis-associated cancer, and involves virtually all key UC-related mechanisms, such as immunity and intestinal microbiota dysregulation. Recently, it was discovered that miRNA is highly stable outside the cell in the form of microvesicles, exosomes or apoptotic vesicles, which raises the possibility that miRNA may serve as a novel diagnostic marker for UC. In this review, we summarize the biosynthetic pathway and the function of miRNA, and summarize the usefulness of miRNA for diagnosis, monitoring and prognosis of UC. Then, we described four types of miRNAs involved in regulating the mechanisms of UC occurrence and development: 1) miRNAs are involved in regulating immune cells; 2) affect the intestinal epithelial cells barrier; 3) regulate the homeostasis between gut microbiota and the host; and 4) participate in the formation of tumor in UC. Altogether, we aim to emphasize the close relationship between miRNA and UC as well as to propose that the field has value for developing potential biomarkers as well as therapeutic targets for UC.

OBJECTIVE:We examined the demographic and clinical profiles of Parkinson's disease in Shanghai, China, to assist in disease management and provide comparative data on Parkinson's disease prevalence, phenotype, and progression among different regions and ethnic groups.METHODS:A door-to-door survey and follow-up clinical examinations identified 180 community-dwelling Han-Chinese Parkinson's disease patients (104 males, 76 females).RESULTS:The average age at onset was 65.16±9.60 years. The most common initial symptom was tremor (112 patients, 62.22%), followed by rigidity (38, 21.11%), bradykinesia (28, 15.56%) and tremor plus rigidity (2, 1.11%). Tremor as the initial symptom usually began in a single limb (83.04% of patients). The average duration from onset to mild Parkinson's disease (Hoehn-Yahr phase 1-2) was 52.74±45.64 months. Progression from mild to moderate/severe Parkinson's disease (phase≥3) was significantly slower (87.07±58.72 months; p

The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson’s disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

BACKGROUND: Motor imagery training is a promising rehabilitation strategy for stroke patients. However, few studies had focused on the neural mechanisms in time course of its cognitive process. This study investigated the cognitive alterations after left hemispheric ischemic stroke during motor imagery task. METHODOLOGY/PRINCIPAL FINDINGS: Eleven patients with ischemic stroke in left hemisphere and eleven age-matched control subjects participated in mental rotation task (MRT) of hand pictures. Behavior performance, event-related potential (ERP) and event-related (de)synchronization (ERD/ERS) in beta band were analyzed to investigate the cortical activation. We found that: (1) The response time increased with orientation angles in both groups, called "angle effect", however, stoke patients' responses were impaired with significantly longer response time and lower accuracy rate; (2) In early visual perceptual cognitive process, stroke patients showed hypo-activations in frontal and central brain areas in aspects of both P200 and ERD; (3) During mental rotation process, P300 amplitude in control subjects decreased while angle increased, called "amplitude modulation effect", which was not observed in stroke patients. Spatially, patients showed significant lateralization of P300 with activation only in contralesional (right) parietal cortex while control subjects showed P300 in both parietal lobes. Stroke patients also showed an overall cortical hypo-activation of ERD during this sub-stage; (4) In the response sub-stage, control subjects showed higher ERD values with more activated cortical areas particularly in the right hemisphere while angle increased, named "angle effect", which was not observed in stroke patients. In addition, stroke patients showed significant lower ERD for affected hand (right) response than that for unaffected hand. CONCLUSIONS/SIGNIFICANCE: Cortical activation was altered differently in each cognitive sub-stage of motor imagery after left hemispheric ischemic stroke. These results will help to understand the underlying neural mechanisms of mental rotation following stroke and may shed light on rehabilitation based on motor imagery training.