Alzheimer’s disease (AD) is a common neurodegenerative condition characterized by amyloid-β protein (Aβ) deposition, which is central to its pathological changes. Oxidative stress also plays an important role in its pathogenesis. Visinin-like protein 3 (VILIP3), a neuronal calcium sensor protein, is abnormally expressed in the brains of patients with AD; however, the exact mechanism remains unclear. This study investigated the role of abnormal VILIP3 expression in AD pathogenesis and its underlying mechanisms. We used 5×FAD mice as an in vivo model of AD and Aβ1−42-treated SH-SY5Y cells to construct an in vitro model. Changes in VILIP3 expression were assessed in both models. VILIP3 was overexpressed in the hippocampus of 5×FAD mice and SH-SY5Y cells using adeno-associated virus (AAV) or plasmid transfection. Cognitive function, Aβ deposition, neuronal damage, synaptic plasticity, apoptosis, oxidative stress, and other relevant indices were evaluated. VILIP3 was expressed at lower levels in AD model mice and cells than in controls. Overexpression of VILIP3 ameliorated cognitive deficits, reduced Aβ deposition and neuronal loss in 5×FAD mice, and attenuated oxidative stress levels and apoptosis in 5×FAD mice and Aβ1−42-treated SH-SY5Y cells. Furthermore, VILIP3 activated nuclear factor E2-related factor 2 (Nrf2) and increased the expression of downstream antioxidant genes. The amelioration of apoptosis and oxidative stress by VILIP3 was blocked by Nrf2-specific inhibitors. VILIP3 mitigates oxidative stress and apoptosis by activating the Nrf2 signaling pathway, thereby alleviating neuropathological damage and cognitive dysfunction in AD.

Background Alzheimer's disease (AD) has been recognized as the most common neurodegenerative disease. Despite immunodysregulation being involved in AD pathogenesis, the systematic and detailed dissection of the cellular and transcriptomic characteristics of natural killer cells (NKs) in peripheral blood of AD patients is largely obscure. Objective To investigate the cytophenotypic and transcriptomic features of NKs in peripheral blood of AD patients. Methods We used flow cytometry assay, co-culturing, RNA-SEQ, multifaceted bioinformatics analyses (e.g., GSEA, GO, KEGG, PCA), and ELISA and qRT-PCR analysis for the comparison of the cytophenotypic and transcriptomic signatures of heathy donors-NKs (HD-NKs) and AD-NKs. Results Compared with HD-NKs, AD-NKs showed increase in the content of NKs in peripheral blood mononuclear cells (PBMCs). After a 14-day ex vivo expansion and activation, the content of AD-NKs also revealed a significant increase. Expanded AD-NKs exhibited higher cellular viability and cytotoxicity than HD-NKs. Both HD-NKs and AD-NKs revealed conservations in gene expression profiling and genetic variations, yet with multifaceted variations in diverse gene sets and the concomitant biological processes (e.g., nerve structural organization, negative regulation of immune, Wnt signaling pathway, cytotoxicity against tumor cell lines). Compared to HD-NKs, AD-NKs revealed abnormally high levels of neuroinflammation-related gene expression and cytokine secretion. Conclusions Collectively, our data indicated the similarities and variations between HD-NKs and AD-NKs both at the cellular and transcriptomic levels, which would supply new references for further dissecting the pathogenesis of AD from the aspect of NKs and benefiting the development of novel therapeutic regimens in the future.

The role of inflammation in the etiology and progression of Alzheimer's disease (AD) has attracted increasing attention; however, the effect of peripheral adaptive immune cells and IL-24 expression on amnestic mild cognitive impairment (aMCI)/AD remains unclear. We detected a reduction in CD4+ central memory T cells (TCM) and an increase in effector memory T cells (TEM) in AD compared with aMCI and controls. CD4+ T cells from patients with AD showed enhanced proliferation, reduced secretion levels of IL-24, and increased secretion levels of IFN-γ and TNF-α. The decrease in IL-24 expression in patients with AD was positively associated with cognition. IL-24 overexpression significantly ameliorated the cognitive deficits, neuropathological injury, and cytotoxicity in AD in vivo and in vitro, potentially through PERK-eIF2α pathway inhibition. Altogether, T cell subset analyses supported a shift towards senescence of the adaptive immune system in AD. IL-24 is a new therapeutic target and strategy for AD.

The accumulation of amyloid β (Aβ) protein, derived from the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) by inducing neuronal cell injury. This study investigated the specific functions of ubiquitin-specific protease 1-associated factor 1 (UAF1) in mediating the neurotoxic effects triggered on Aβ. To model AD-related neuronal injury in vitro and in vitro, SH-SY5Y cells exposed to Aβ25-35 and APPswe/PS1dE9 (APP/PS1) transgenic mice were utilized. Compared with control mice, UAF1 levels were significantly elevated in the hippocampus of experimental mice. In vitro experiments showed that UAF1 knockdown reduced Aβ-induced apoptosis and enhanced cell viability. Furthermore, UAF1 knockdown markedly suppressed Aβ25-35 -induced pyroptosis in SH-SY5Y cells and reduced the production of IL-1β and IL-18 through the nucleotide-binding domain and leucine-rich repeat containing family pyrin domain-containing 3 (NLRP3)/Gasdermin D pathway. Mechanistic analyses revealed that UAF1 directly binds to NLRP3 to mediate its effects. In vivo, UAF1 knockdown mitigated cognitive deficits, decreased APP expression, Aβ plaque deposition, and reduced hyperphosphorylated Tau levels. These findings underscore the critical role of UAF1 in regulating neuronal apoptosis and pyroptosis, thereby highlighting its potential as a promising therapeutic target for AD.

Despite the considerable progress in mesenchymal stem/stromal cells (MSCs)-based novel intervention of multiple sclerosis (MS), yet the disease-modifying effect of VCAM-1- MSCs and novel VCAM-1+ counterpart is largely obscure. In this study, we took advantage of the EAE mouse model and VCAM-1+ human umbilical cord-derived MSCs (hUC-MSCs) for the evaluation of the therapeutic effect of systematic MSCs infusion. On the one hand, we compared the protective effect of VCAM-1- and VCAM-1+ hUC-MSCs against the clinical symptoms, demyelination, active glia cells and neuroinflammation in EAE mice by conducting multifaceted detections upon spinal cord and brain tissues. On the other hand, we conducted RNA-sequencing (RNA-SEQ) and multidimensional bioinformatics analyses for the evaluation of the transcriptomic features of spinal cord tissue in EAE mice after systematic hUC-MSCs infusion. Compared to those with VCAM-1- hUC-MSCs injection, VCAM-1+ mice showed further remission in clinical manifestations, and in particular, the inflammatory infiltration and active glial cells. Mice in all groups revealed conservations in overall gene expression profiling and somatic mutation spectrum. The differentially expressed genes (DEGs) between EAE mice and those with hUC-MSCs infusion were mainly involved in neuroinflammation and inflammatory response. Our findings indicated the feasibility of VCAM-1+ hUC-MSCs for multiple sclerosis treatment, which would supply new references for the development of novel VCAM-1+ MSCs-based cytotherapy in future.

Objective People with visual impairment have more functional limitations associated with subjective cognitive decline (SCD), and those with SCD are extremely susceptible to transitioning to irreversible cognitive impairment. This study aimed to explore if visual impairment is a significant predictor of SCD compared with other socioeconomic and health factors associated with SCD.Design Cross-sectional study.Setting and participants The investigation aimed to assess the factors influencing SCD among 428 participants aged 60 and above in Zhaoyuan, China.Primary outcome measures The primary outcome variable was SCD, measured by the Chinese version of SCD questionnaire. Multiple logistic regression and propensity score matching (PSM) were used to analyse the influence of visual impairment on the subjective cognition of the elderly.32.2% of the elderly were experiencing SCD. Older adults with SCD showed a higher prevalence of visual impairment (72.5%) than the elderly without SCD (58.6%) (P=0.006). Multivariate logistic regression analysis showed that bad self-reported health status, lack of physical exercise and visual impairment were the risk factors for SCD in older adults, while more than 9 years of education was a protective factor. In addition, PSM model showed that after eliminating the dominant biases caused by the individual observable heterogeneity of older adults with and without visual impairment, the risk of SCD in the elderly with visual impairment was increased by 13.6%–14.5% and the difference was statistically significant (P<0.05).Conclusions It was found that older adults experiencing visual impairments are at an elevated risk of developing SCD compared with their counterparts without such impairments. Additionally, visual impairment remains a significant risk factor for SCD in the elderly, even adjusting for potential biases arising from individual observable heterogeneity.

Alzheimer's disease (AD) is a prevalent irreversible neurodegenerative condition marked by gradual cognitive deterioration and neuronal loss. The mammalian Ste20-like kinase (MST1)–Hippo pathway is pivotal in regulating cell apoptosis, immune response, mitochondrial function, and oxidative stress. However, the association between MST1 and mitochondrial function in AD remains unknown. Therefore, this study investigates the effect of MST1 on neuronal damage and cognitive impairment by regulating mitochondrial homeostasis in AD. In this study, 4- and 7-month-old 5xFAD mice were selected to simulate the early and middle stages of AD, respectively; age-matched wild-type mice served as controls for comparative analysis. Adeno-associated virus (AAV) was injected into the hippocampus of mice. Four weeks post-injection, cognitive function, neuronal damage indicators, and mitochondrial morphology, dynamics, oxidative stress, ATP, and apoptosis-related indicators were evaluated. Additionally, RNA-sequencing was performed on the hippocampal tissue of 5xFAD mice and MST1-knockdown 5xFAD mice. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on differentially expressed genes to elucidate the potential mechanism of MST1. In vitro studies were performed to investigate the effects of MST1 on SH-SY5Y model cell viability and mitochondrial function and validate the potential underlying molecular mechanisms. MST1 overexpression accelerated neuronal degeneration and cognitive deficits in vivo while promoting oxidative stress and mitochondrial damage. Similarly, in vitro, MST1 overexpression facilitated apoptosis and mitochondrial dysfunction. MST1 knockdown and chemical inactivation reduced cognitive decline, mitochondrial dysfunction, and neuronal degeneration. Mechanistically, MST1 regulated the transcription of mitochondrial genes, including MT-ND4L, MT-ATP6, and MT-CO2, by binding to PGC1α. Moreover, MST1 influenced cellular oxidative stress through the PI3K-Akt-ROS pathway, ultimately disrupting mitochondrial homeostasis and mediating cell damage. Cumulatively, these results suggest that MST1 primarily regulates mitochondrial DNA transcription levels by interacting with PGC1α and modulates cellular oxidative stress through the PI3K-Akt-ROS pathway, disrupting mitochondrial homeostasis. This discovery can be exploited to potentially enhance mitochondrial energy metabolism pathways by targeting MST1, offering novel potential therapeutic targets for treating AD.

Introduction: This study aimed to investigate the impact of miR-137-3p on the pathogenesis of Alzheimer's disease (AD) and develop a pioneering in vivo delivery method for its therapeutic potential. Methods: This study was initiated by quantifying the levels of miR-137-3p in both human neuroblastoma cells and a mouse model of AD. Our focus was on elucidating its effects on microtubule (MT) stability, tau protein hyperphosphorylation, synaptic damage, and other hallmark features of AD. To circumvent the risks associated with direct brain injections, a novel drug delivery system was engineered, employing lipid nanoparticles (LNPs) functionalized with rabies virus glycoprotein to facilitate the transcytosis of miR-137-3p across the blood-brain barrier and target its delivery directly to neurons. Results: The results confirmed miR-137-3p deficiency in both AD cells and animal models. A protective effect of miR-137-3p on MT stability in the AD model was first observed in SH-SY5Y. We validated that the delivery system could effectively penetrate the blood-brain barrier and target neurons, resulting in a significant increase in miR-137-3p levels in the hippocampus of APP/PS1 mice. Glycogen synthase kinase-3 beta expression in the hippocampus of AD mice was inhibited, suggesting successful treatment of AD in this animal model. Discussion: This study verified a new mechanism of action of miR-137-3p in AD pathogenesis in cells. By developing an LNPs-based miR-137-3p delivery system, this study offers a novel avenue for treating AD, highlighting miR-137-3p as a key factor in AD pathogenesis and its therapeutic application.

Focusing on older people with and without an intimate partner, this study aimed to evaluate the prevalence of low life satisfaction in both groups, as well as the potential risk factors.

Introduction: The purpose of this study was to analyze IL-33 maybe as a biomarker especially with respect to intrathecal immunoglobulin G (IgG) synthesis which was involved in the immune-mediated process in the demyelinating disease of the central nervous system. Methods: We aimed to determine the risk association of the serum and CSF levels of IL-33 in aquaporin-4 (AQP4)+neuromyelitis optica spectrum disorder (NMOSD) patients and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) patients compared with the control group. Levels of inflammatory (IL-2, IL-4, IL-6, and IL-10) markers and QAlb, the IgG index, and 24-h IgG synthesis rate were assessed in 28 AQP4+NMOSD patients and 11 MOGAD patients. Disease severity was assessed using the Expanded Disability Status Scale (EDSS). Results: The level of IL-33 in serum decreased first but then increased gradually in AQP4+NMOSD and MOGAD. The serum level of IL-2, IL-4, and IL-10 increased more significantly and decreased more rapidly after methylprednisolone treatment. The level of IL-33 in CSF increased progressively in AQP4+NMOSD and MOGAD, especially in MOGAD. The QAlb levels were increased significantly in the CSF of MOGAD patients and AQP4+NMOSD patients on the acute stage of the disease. The IgG index and 24-h IgG synthesis rate were also increased significantly in the CSF of two groups similarly. Conclusions: Thus, we concluded that IL-33 may induce dysfunction of the blood-brain barrier and lead to intrathecal synthesis of immunoglobulin in the AQP4+NMOSD and MOGAD, especially in MOGAD. It maybe as a biomarker, at least in part, was involved in the demyelinating diseases of the central nervous system.

Introduction: Dendritic cells (DCs) play critical roles in the pathogenesis of myasthenia gravis (MG), and a series of DC-based experimental strategies for MG have recently been developed. However, the definite roles of different DC subsets in the mechanism of MG have scarcely been covered by previous studies. The present study aimed to investigate the levels of three main DC subsets, plasmacytoid DCs (pDCs) (CD303 positive) and two distinct subsets of conventional DCs (cDCs), namely CD1c+ cDCs and CD141+ cDCs, in MG patients and analyze related clinical features. Methods: From January 2016 to December 2020, 160 newly diagnosed MG patients and matched healthy controls (n = 160) were included in the study, and their clinical data were collected. The blood samples from MG patients before treatment and controls were collected for flow cytometry analysis. A total of 14 MG thymoma, 24 control thymoma, and 3 thymic cysts were used to immunostain the DC subsets. Results: The flow cytometry analysis showed a significantly higher frequency of circulating pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients than in healthy controls (p < 0.001 for all). Patients with early-onset MG (<50 years old) had a lower frequency of circulating pDCs but a higher frequency of circulating CD1c+ cDCs than those with late-onset MG (≥50 years old) (p = 0.014 and p = 0.025, respectively). The frequency of circulating pDCs was positively associated with the clinical severity of late-onset MG patients (r = 0.613, p < 0.001). 64.3% (9/14) of MG thymoma is of type B2 under the World Health Organization classification, which is higher than that in control thymoma (33.3%, 8/24) (p = 0.019). For type B2 thymoma, there were significantly more pDCs but fewer CD1c+ cDCs in MG thymoma than in the controls. Conclusion: The distribution of aberrant pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients displayed age- and thymoma-related differences, which may contribute to the impaired immune tolerance and lead to the onset of MG.

Mesenchymal stem/stromal cells (MSCs) are spindle-like heterogeneous cell populations with advantageous bidirectional immunomodulatory and hematopoietic support effects. Vascular cellular adhesion molecule-1 (VCAM-1) + MSCs have been reported to exhibit immunoregulatory and proangiogenic capacities. Here, we studied the effects of VCAM-1 + human umbilical cord (hUC)-MSCs on neuroprotection against cerebral infarction. Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO), and VCAM-1 − and VCAM-1 + hUC-MSCs were intravenously injected into the rat 4 h post-MCAO surgery. Thereafter, modified neurological severity scores (mNSS) were determined, and the Morris water maze test, 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin (H&E), Nissl, TUNEL staining, and qRT-PCR were conducted. Following induction of oxygen–glucose deprivation/reoxygenation (OGD/R), SH-SY5Y cells were co-cultured with VCAM-1 − and VCAM-1 + hUC-MSCs. CCK-8, flow cytometry, ELISA, and western blot analyses were performed in vitro. Compared with VCAM-1 − hUC-MSCs, administration of VCAM-1 + hUC-MSCs revealed improved therapeutic efficacy against cerebral infarction in rats, as confirmed by lower mNSS scores and infarct volumes, as well as improved learning and memory capacities. In addition, VCAM-1 + hUC-MSCs exhibited improved efficacy against neurological defects in rats with cerebral infarction, accompanied by inhibition of the NLRP3-mediated inflammatory response. VCAM-1 + hUC-MSC co-culture improved the viability and diminished NLRP3-mediated inflammatory response in OGD/R-treated SH-SY5Y cells. Moreover, NLRP3 overexpression in SH-SY5Y cells prevented the beneficial effects of VCAM-1 + hUC-MSC co-culture. Overall, our findings demonstrated the relevance of VCAM-1 + hUC-MSC-based cytotherapy for preclinical neuroprotection against cerebral infarction.

Alzheimer's disease (AD) is currently an incurable neurodegenerative disorder and is the most common etiological cause of dementia. Consequently, it has severe burden on its patients and on their caregivers and represents a global health concern. Clinical investigations have indicated that a dysregulation of peripheral T cell immune homeostasis may be involved in the pathogenesis of AD, as well as in the early stages of AD, characterized by mild cognitive impairment (MCI). However, the characteristics and concomitant feasibility of the use of T-cell receptor (TCR) typing for disease diagnosis remains largely unknown. We employed a high-throughput sequencing and multidimensional bioinformatics analyses for the identification of TCR repertoires present in peripheral blood samples of 10 patients with amnestic MCI (aMCI), 10 patients with AD, and 10 healthy controls (HCs). Based on the characteristics of the TCR repertoires in the amount and diversity of combinations of V-J, the spectrum of immune defense, and differentially expressed genes (DEGs), single and specific TCR profiles were observed in the patient samples of aMCI and AD compared to profiles of HCs. In particular, the diversity of TCR clonotypes manifested a pattern of "decreased first and then increased" pattern during the progression from aMCI to AD, a pattern that was not observed in HC samples. Additionally, a total of 46 and 35 amino acid CDR3 sequences with consistent and reverse expressive abundance with diversity of TCR clonotypes were identified, respectively. Taken together, we provide novel and essential preliminary evidence demonstrating the presence of diversity of T cell repertoires from differentially expressed V-J gene segments and amino acid clonotypes using peripheral blood samples from patients with AD, aMCI, and from HC. Such findings have the potential to reveal potential mechanisms through which aMCI progresses to AD and provide a reference for the future development of immune-related diagnoses and therapies for AD.

Alzheimer's disease (AD) is a chronic neurological disease characterized by memory loss and progressive cognitive impairment. The characteristic AD pathologies include extracellular senile plaques formed by β‑amyloid protein deposition, neurofibrillary tangles formed by hyper‑phosphorylation of τ protein and neuronal loss caused by glial cell proliferation. However, the pathogenesis of AD is still unclear. Dysregulation of RNA methylation is associated with biological processes, including neurodevelopment and neurodegenerative disease. N6‑methyladenosine (m6A) is the main modification in eukaryotic RNA and may be associated with the pathophysiology of AD. Circular RNA (circRNA) is a new type of evolutionarily conserved non‑coding RNA without 5'‑cap and 3'‑polyadenylic acid tail. circRNA undergoes m6A RNA methylation and may be involved in the pathogenesis of AD. In the present study, high‑throughput sequencing was performed to assess the degree of circRNA m6A methylation in APP/PS1 AD and C57BL/6 mice. These results suggested that circRNA m6A methylation in AD mice was markedly altered compared to the control group. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to predict associated pathways; genes with different circRNA m6A methylation in AD mice were associated with 'axon guidance', 'long‑term potentiation', 'glutamatergic synapse', 'cholinergic synapse', 'GABAergic synapse' and 'long‑term depression'. Methylated RNA immunoprecipitation reverse transcription‑quantitative PCR demonstrated that among the eight selected circRNA m6A genes, there were five genes that demonstrated significantly increased methylation and three demonstrated significantly decreased methylation. In summary, the present study indicated that circRNA m6A methylation may be associated with pathogenesis of AD.

阿尔茨海默病( AD)是以进行性记忆力下降和其他认知功能障碍为特征的一种慢性神经退行性疾病,是导致痴呆的最常见病因.2017年世界卫生组织报告显示,全球约有5000 万痴呆患者,预计到2050年,全世界痴呆患者将超 1. 31 亿,其中约60％ ～70％为 AD 患者﹝1﹞.

Mitochondrial dysfunction plays a key role in the pathogenesis of Alzheimer's disease (AD). The translocase of the outer membrane (TOM) complex controls the input of mitochondrial precursor proteins to maintain mitochondrial function under pathophysiological conditions. However, its role in AD development remains unclear. TOM70 is an important translocase present in the TOM complex. In the current study, we found that TOM70 levels were reduced in the peripheral blood and hippocampus of the APP/PS1 mice. In addition, we examined the whole-blood mRNA levels of TOM70 in patients with AD, dementia with Lewy bodies (DLB), and post-stroke dementia (PSD). Our study revealed that the mRNA level of TOM70 was decreased in the blood samples of patients with AD, which was also correlated with the progression of clinical stages. Therefore, we proposed that the expression of TOM70 could be a promising biomarker for AD diagnosis and monitoring of disease progression.

Our previous study showed that interferon gamma (IFN-γ) might enhance the immunosuppressive properties of mesenchymal stem cells (MSCs) by upregulating the expression of indoleamine 2,3-dioxygenease. Therefore, we treated experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis (MS), with IFN-γ-primed human umbilical cord MSCs (IFN-γ-hUCMSCs). This study aimed to investigate the potential therapeutic effects of IFN-γ-hUCMSCs transplantation and to identify the biological pathways involved in EAE mice. Firstly, the body weights and clinical scores of EAE mice were recorded before and after treatment. Then, the inflammatory cytokine levels in splenic cell supernatants were quantified by enzyme-linked immunosorbent assay. Finally, the mRNA expression levels of signal transducer and activator of transduction 3 (STAT3), retinoic acid-related orphan receptor gamma t (ROR-γt), and forkhead box P3 (Foxp3) were detected by quantitative reverse transcription polymerase chain reaction. We observed that IFN-γ-hUCMSCs transplantation significantly alleviated body weight loss and decreased the clinical scores of mice. Additionally, IFN-γ-hUCMSCs transplantation could regulate the production of inflammatory cytokines, interleukin (IL)-10 and IL-17, thereby showing more potent treatment efficacy than human umbilical cord MSCs (hUCMSCs) transplantation (p < 0.05). Compared with the EAE group, the expressions of STAT3 and ROR-γt in the transplantation groups were significantly decreased, but the expression of Foxp3 was significantly upregulated in the IFN-γ-hUCMSCs transplantation group compared to that in the hUCMSCs transplantation group. We assumed that IFN-γ-hUCMSCs may affect the balance of T helper 17 (Th17) cells/regulatory T cells (Tregs) through the Foxp3/ROR-γt/STAT3 signaling pathway to reduce the inflammatory response, thereby improving the clinical symptoms of EAE mice. Our study demonstrated that transplantation of IFN-γ-hUCMSCs could reduce inflammation in EAE mice via the Foxp3/ROR-γt/STAT3 signaling pathway, highlighting the therapeutic effects of IFN-γ-hUCMSCs in patients with MS.

BackgroundWith promotion of COVID-19 vaccinations, there has been a corresponding vaccine hesitancy, of which older adolescents and young adults represent groups of particular concern. In this report, we investigated the prevalence and reasons for vaccine hesitancy, as well as potential risk factors, within older adolescents and young adults in China.MethodsTo assess these issues, an online survey was administered over the period from March 14 to April 15, 2021. Older adolescents (16–17 years old) and young adults (18–21 years old) were recruited nationwide from Wechat groups and results from a total of 2,414 respondents were analyzed. Socio-demographic variables, vaccine hesitancy, psychological distress, abnormal illness behavior, global well-being and social support were analyzed in this report.ResultsCompared to young adults (n = 1,405), older adolescents (n = 1,009) showed higher prevalence rates of COVID-19 vaccine hesitancy (16.5 vs. 7.9%, p < 0.001). History of physical diseases (p = 0.007) and abnormal illness behavior (p = 0.001) were risk factors for vaccine hesitancy among older adolescents, while only a good self-reported health status (p = 0.048) was a risk factor for young adults. Concerns over COVID-19 vaccine side effects (67.1%) and beliefs of invulnerability regarding infection risk (41.9%) were the most prevalent reasons for vaccine hesitancy. Providing evidence on the vaccine reduction of COVID-19 infection risk (67.5%), ensuring vaccine safety (56.7%) and the low risk of side effects (52.7%) were the most effective persuasions for promoting vaccinations.ConclusionIn China, older adolescents showed a higher prevalence for vaccine hesitancy than that of young adults. Abnormal illness behavior and history of physical diseases were risk factors for vaccine hesitancy among these older adolescents, while social support represents an important factor which could help to alleviate this hesitancy.

Objective:To discuss the clinical features, diagnosis and treatment of linear scleroderma (LS).Methods:A case of LS diagnosed in the Second Hospital of Shandong University in October 20, 2020, was reported and the clinical features and pathological documentation of the disease reported in the literature were reviewed.Results:A 24-year-old woman presented cicatricial alopecia on the left frontoparietal area and facial atrophy for about 10 years. Two years before, she began to suffer ptosis and neurological complaints. Clinical features of different stages of the disease are presented. All 15 patients reported in the literature were analyzed, with a median of 22 years and a male to female ratio of 9∶6. There were 4 cases of linear scleroderma with ipsilateral drooping eyelids and lateral contraction, 3 cases of linear scleroderma with demyelinating lesions, combined with lateral contraction, 3 cases of linear scleroderma combined with lateral atrophy, and 1 case of linear scleroderma with ipsilateral facial spasm. Two cases were with the chest sclerosing spot. Two cases of linear scleroderma were with epileptic seizure and white matter demyelination lesion. Six cases were treated with hormone, 2 cases were treated with methotrexate. One case was treated with both hormone and methotrexate. One case was treated with botulinum toxin. Three cases were treated with surgical correction of eyelid ptosis. One case was treated with ultraviolet A1 radiation phototherapy and 1 case was treated with vitamin therapy.Conclusions:Patients with scleroderma may have ipsilateral facial atrophy, blepharoptosis and facial spasm. Some patients involving the nervous system may have epilepsy and myelitis. And demyelinating lesions can be seen in magnetic resonance imaging. Localized scleroderma may develop into systemic scleroderma. Therefore, it is recommended to combine immunosuppressants as soon as possible to control the development of the disease if necessary.

Abstract Alzheimer's disease is the most common form of dementia in older people. The pathogenesis of AD is still uncertain, although it appears autophagy abnormalities are involved. In recent years, epigenetics, including RNA N6-methyladenosine (m6A) methylation, has been shown to be involved in the pathogenesis of neurodegeneration. However, how RNA methylation may be involved in the pathogenesis of AD is still unclear. Our previous RNA m6A methylation high-throughput sequencing analysis found that some hippocampal genes showed elevated methylation in AD mouse models, but that some genes showed declining methylation. Genes showing different methylation patterns tended to be related to autophagy. The focus of this study is to examine possible mechanisms by which m6A RNA methylation may be involved in AD. SH-SY5Y cells treated with Aβ25−35 were used as AD models, and untreated SH-SY5Y cells were used as controls. We first detected the expression of methylase in the two groups of cells. The results showed that the protein expression of METTL3 in the AD cell group was higher than that in the control group, while FTO expression showed no statistically significant differences. We then used lentivirus-mediated METTL3 RNA knockouts to observe the expression of Parkin protein in each group of cells. Results showed that expression of the Parkin protein in the AD cell group was increased compared to the control group, while the expression levels of Parkin protein in AD cells with METTL3 RNA knockout decreased. Additionally, mitochondrial structural changes were observed using transmission electron microscopy. These results showed that the mitochondrial structure in an AD cell model with METTL3 RNA knockout was improved compared to the AD cell model alone. Taken together, our findings suggest that RNA m6A methylation is involved in the AD process.