Background Differentiating Parkinson's disease (PD) from Atypical Parkinsonian Syndromes (APS) is challenging due to overlapping speech impairments. This study addresses the gap in utilizing speech biomarkers for early differentiation in Mandarin speakers. Objective To identify distinct acoustic phenotypes in PD and APS and develop machine learning models for differential diagnosis and severity monitoring. Methods Speech samples from sustained vowels (nine Mandarin core vowels) and diadochokinesis tasks were collected from 34 PD, 25 APS (13 multiple system atrophy, 12 progressive supranuclear palsy), and 30 healthy controls. Acoustic parameters including Fundamental Frequency, Jitter, Shimmer, Noise-to-Harmonics Ratio, Vowel Space Area, Vowel Articulation Index, and diadochokinesis rate were extracted. Principal component analysis followed by linear discriminant analysis was used for classification. An XGBoost model predicted dysarthria severity based on UPDRS‑III subscores. Results APS patients showed more severe impairments (reduced Fundamental Frequency, elevated Jitter and Shimmer, decreased sound pressure level, increased noise-to-harmonics ratio for /ər/) compared to PD and healthy controls. PD patients primarily showed milder articulatory deficits (reduced Vowel Space Area and Vowel Articulation Index) and slower diadochokinesis rate. Cognitive impairment correlated with worse vocal instability in both groups. The linear discriminant analysis model achieved a mean accuracy of 0.83 ± 0.09 (10-fold cross-validation) and 0.93 on an independent test set. For PD vs. APS differentiation, area under the curve was 0.8389 ± 0.1693. XGBoost predicted dysarthria severity with area under the curve of 0.75 (PD) and 0.85 (APS). Conclusion Mandarin speech biomarkers combined with machine learning enable accurate differentiation of PD, APS, and healthy controls, as a potential non-invasive adjunctive tool for early diagnosis and severity monitoring.

Parkinson's disease (PD) is an intractable progressive neurodegenerative disease with poor prognosis in elder patients, which is largely attribute to the deficiency of ultimate pathogenesis. Longitudinal studies have indicated a pivotal role of natural killer (NK) cells, yet the systematic and detailed information of circulating NK cells in PD is largely unknowable. To explore the role of NK cells in PD, we isolated mononuclear cells from peripheral blood (PBMCs) by Ficoll-based density gradient centrifugation, and detected the content of total resident NK cells in healthy donors (HD-NKs) and PD patients (PD-NKs) and the concomitant subsets by flow cytometry (FCM) assay. Then, we took advantage of our well-established "3ILs"-based strategy for ex vivo NK cell expansion and activation, and followed by cellular viability and cytotoxicity assessment. By conducting RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses, we compared the transcriptomic signatures of expanded HD-NKs and PD-NKs. Compared to HD-NKs, PD-NKs showed increase in resident NK cells but minimal differences in expanded NK cells, together with diversity in the subpopulations of NK cells (CD16+, NKG2D+, NKp46+). Interestingly, PD-NKs revealed a moderate higher percentage of apoptotic cells and cytotoxicity upon the co-cultured Nalm6 and U937 tumor cell lines. Despite with high conservations in gene expression pattern and genetic variations, PD-NKs revealed multifaceted diversity in gene set-associated immune response and metabolism. Overall, our data revealed the multidimensional biological and transcriptomic signatures of resident and expanded NK cells generated from peripheral blood of PD patients and HDs. Our findings would provide new references for the further development of NK cell-based biomarkers for PD diagnosis and novel immunotherapy for neurodegenerative diseases.

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.

Lung function, cognitive ability, and lifestyle are key factors affecting the health of older adults, especially in predicting frailty. However, the relationship between lung function and frailty is unclear, particularly in Chinese middle-aged and elderly populations, and clinical frailty assessment methods lack standardization. This study aimed to develop a frailty risk prediction model by analyzing lung function, cognitive ability, and lifestyle factors, providing a basis for early frailty screening and intervention. Data from the baseline wave (2011-2012) of the China Health and Retirement Longitudinal Study were used, including 6065 individuals aged ≥ 45 years. Peak expiratory flow (PEF) was measured using standardized procedures. The percentage of predicted PEF (PEFpred%) was calculated as (measured PEF/predicted PEF) × 100%, where predicted values were estimated based on age-, sex-, and height-adjusted reference equations derived from a Chinese population. Frailty was assessed through a questionnaire, and relevant covariates were recorded. Multilevel logistic regression analyzed the relationship between PEFpred% and frailty, with Bootstrap methods evaluating the mediating role of cognitive function. Least absolute shrinkage and selection operator regression and cross-validation were used to identify key predictors for the frailty risk model, evaluated by receiver operating characteristic and calibration curves. The mean age of the participants was 58.3 years, with 51% female. Twenty-three point five percent had a PEFpred% <60%. Higher PEFpred% was associated with lower frailty risk. Dose-response analysis showed a nonlinear relationship, with significant risk increases when PEFpred% was < 80.03%. Cognitive function partially mediated the relationship, explaining 20.11% of the effect. The model based on PEFpred%, cognitive function, and other variables showed good performance: area under the curve was 0.796 in the training set and 0.775 in the validation set. PEFpred% is a useful predictor of frailty risk in Chinese middle-aged and elderly individuals, with cognitive function playing a key mediating role. The frailty risk prediction model demonstrates good performance and warrants further clinical validation.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by gradual cognitive decline. Early-onset Alzheimer’s disease (EOAD) is defined as AD occurring before age 65. The main pathogenic gene variants associated with EOAD include PSEN1, PSEN2, and APP. IDE gene has been identified as a risk factor in the pathogenesis of AD. In this study, we report a 33-year-old male with mutations in the PSEN2 gene (c.640G > T, p.V214L) and IDE gene (c.782G > A, p.R261Q). PSEN2 V214L has been reported in five previous cases, and no reported cases have carried IDE R261Q. He had progressive memory decline, his sister carried the same gene mutations but had no clinical manifestations. Neuroimaging revealed mild cortical atrophy. The concentration of Aβ42 in cerebrospinal fluid (CSF) was obviously decreased. In silico predictive models suggested that these mutations are damaging. Our findings indicate that mutations in the PSEN2 and IDE genes may disrupt the normal functioning of their respective proteins, contributing to the pathogenesis of AD.

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.

Junctional adhesion molecule 3 (JAM3) can be used as a prognostic marker in multiple cancer types. However, the potential prognostic role of JAM3 in gastric cancer (GC) remains unclear. The purpose of this research was to gauge JAM3 expression and methylation as potential biomarkers for GC patient survival. Through bioinformatics research, we analyzed JAM3 expression, methylation, prognosis, and immune cell infiltrations. JAM3 methylation acts as a negative regulator of JAM3, leading to reduced expression of JAM3 in GC tissues relative to normal tissues. Patients with GC who expressed little JAM3 have a better chance of living a long time free of the disease, according to the Cancer Genome Atlas (TCGA) database. Through univariate and multivariate Cox regression analysis, inadequate JAM3 expression was labeled as an isolated indicator for overall survival (OS). The GSE84437 dataset was also used to confirm JAM3 prognostic role in GC, with consistent findings. A meta-analysis also found that low levels of JAM3 expression were significantly associated with longer OS. Finally, there was a strong correlation between JAM3 expression and a subset of immune cells. According to the TCGA database, low JAM3 expression could predict favorable OS and progression-free-survival (PFS) in GC patients ( P < .05). The univariate and multivariate Cox regression demonstrated that low JAM3 expression was independent biomarker for OS ( P < .05). Moreover, GSE84437 dataset was utilized to verify the prognostic role of JAM3 in GC, and the similar results were reached ( P < .05). A meta-analysis revealed that low JAM3 expression was closely relevant to better OS. Finally, JAM3 expression exhibited a close correlation with some immune cells ( P < .05). JAM3 might be a viable predictive biomarker and likely plays a crucial part in immune cell infiltration in individuals with GC.

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.

Diabetic kidney disease (DKD), a common cause of end-stage renal disease, is a serious complication that develops with the progression of chronic diabetes. Its main clinical manifestations are persistent proteinuria and/or a progressive decline in the estimated glomerular filtration rate. Podocytes, terminally differentiated glomerular visceral epithelial cells, constitute the glomerular filtration barrier together with the basement membrane and endothelial cells, and the structural and functional barrier integrity is closely related to proteinuria. In recent years, an increasing number of studies have confirmed that podocyte injury is the central target of the occurrence and development of DKD, and research on exosomes in podocyte injury associated with DKD has also made great progress. The aim of this review is to comprehensively describe the potential diagnostic value of exosomes in podocyte injury associated with DKD, analyze the mechanism by which exosomes realize the communication between podocytes and other types of cells and discuss the possibility of exosomes as targeted therapy drug carriers to provide new targets for and insights into delaying the progression of and treating DKD.

BACKGROUND: Existing measures of frailty developed in community dwelling older adults may mis-classify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung trans-plantation with improved performance characteristics.METHODS: We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms. We applied a 4-step established approach (identify frailty domain variable bivariate associations with the outcome of waitlist delisting or death; build models sequentially incorporating variables from each frailty domain cluster; retain variables that improved model performance ability by c-statistic or AIC) to develop 3 candidate "Lung Transplant Frailty Scale (LT-FS)" measures: 1 incorporating readily available clinical data; 1 adding muscle mass, and 1 adding muscle mass and research-grade Biomarkers. We compared construct and predictive validity of LT-FS models to the SPPB and FFP by ANOVA, ANCOVA, and Cox proportional-hazard modeling. RESULTS: In 342 lung transplant candidates, LT-FS models exhibited superior construct and predictive validity compared to the SPPB and FFP. The addition of muscle mass and Biomarkers improved model performance. Frailty by all measures was associated with waitlist disability, poorer HRQL, and waitlist delisting/death. LT-FS models exhibited stronger associations with waitlist delisting/death than SPPB or FFP (C-statistic range: 0.73-0.78 vs. 0.57 and 0.55 for SPPB and FFP, respectively). Compared to SPPB and FFP, LT-FS models were generally more strongly associated with delisting/death and improved delisting/death net reclassification, with greater improvements with increasing LT-FS model complexity (range: 0.11-0.34). For example, LT-FS-Body Composition hazard ratio for delisting/death: 6.0 (95%CI: 2.5, 14.2), SPPB HR: 2.5 (95%CI: 1.1, 5.8), FFP HR: 4.3 (95%CI: 1.8, 10.1). Pre -trans-plant LT-FS frailty, but not SPPB or FFP, was associated with mortality after transplant. CONCLUSIONS: The LT-FS is a disease-specific physical frailty measure with face and construct valid-ity that has superior predictive validity over established measures. J Heart Lung Transplant 2023;42:892-904 & COPY; 2023 International Society for Heart and Lung Transplantation. All rights reserved.

Chinese universities have been conducting a variety of sexuality education programs, including a sexuality curriculum (SC) to increase sexual and reproductive health (SRH) knowledge and improve sexual attitudes and practices among college students. However, little is known regarding the effect of SC on students' sexual attitudes and behaviors. The purpose of this study was to evaluate the effect of SC on SRH knowledge, sexual attitudes, and practices among college students of Shandong University. To assess these issues, an online cross-sectional survey was conducted via a WeChat applet. Four hundred and forty-nine freshmen were recruited from Shandong University, including 209 students with SC and 240 students without SC. We assessed their SRH knowledge, sexual attitude, and practice. We found that 15.8% engaged in sexual activities, while 59.2% had viewed nonscientific books or videos describing sexual behavior within the past 2 weeks. Regarding the initial source of their SRH information, 65.9% taught themselves through reading or viewing SRH content in the media, and 46.8% participated in school lectures on SRH, while only 31.2% of the participants discussed SRH matters with their parents. As compared with students without SC, students with SC had significantly greater total scores with regard to reproductive health knowledge (P < 0.001) and sexual health knowledge (P < 0.001). Students without SC showed a significant degree of prejudice against sexually transmitted disease patients and were more resistant to interact with acquaintances infected with human immunodeficiency virus (P < 0.001). Exposure to a school-based SC had a beneficial effect on increasing the SRH knowledge of these students as well as mitigating risky sexual attitudes and behaviors.NEW & NOTEWORTHY To assess the SRH knowledge, sexual attitudes, and practices in freshmen of Shandong University and assess the effect of SC, an online cross-sectional survey was conducted via a WeChat applet. Our findings indicate that these freshmen demonstrate a high prevalence of being sexually active and exposure to a school-based SC had a beneficial effect on increasing the SRH knowledge of these students as well as mitigating risky sexual attitudes and behaviors.

Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.

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.

Primary graft dysfunction (PGD) limits clinical benefit after lung transplantation, a life-prolonging therapy for patients with end-stage disease. PGD is the clinical syndrome resulting from pulmonary ischemia-reperfusion injury (IRI), driven by innate immune inflammation. We recently demonstrated a key role for NK cells in the airways of mouse models and human tissue samples of IRI. Here, we used 2 mouse models paired with human lung transplant samples to investigate the mechanisms whereby NK cells migrate to the airways to mediate lung injury. We demonstrate that chemokine receptor ligand transcripts and proteins are increased in mouse and human disease. CCR5 ligand transcripts were correlated with NK cell gene signatures independently of NK cell CCR5 ligand secretion. NK cells expressing CCR5 were increased in the lung and airways during IRI and had increased markers of tissue residency and maturation. Allosteric CCR5 drug blockade reduced the migration of NK cells to the site of injury. CCR5 blockade also blunted quantitative measures of experimental IRI. Additionally, in human lung transplant bronchoalveolar lavage samples, we found that CCR5 ligand was associated with increased patient morbidity and that the CCR5 receptor was increased in expression on human NK cells following PGD. These data support a potential mechanism for NK cell migration during lung injury and identify a plausible preventative treatment for PGD.

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.

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes and is a chronic progressive condition. It is also a common cause of end-stage renal disease (ESRD), which is characterized by proteinuria or a progressive decline in the glomerular filtration rate. Due to their dependence on high-energy and aerobic metabolism, renal tubules are more susceptible to the metabolic disturbances associated with DKD, leading to inflammation and fibrosis. Consequently, tubular injury has become a recent research focus, and significant advancements have been made in studying the role of extracellular vesicles in DKD-associated tubular injury. This review aimed to elucidate the mechanisms and potential applications of different types of extracellular vesicles in tubular injury in DKD to provide new insights for the prevention and treatment of DKD.

Objectives:During COVID-19 pandemic in 2020, China, some public health measures of forced lockdown, closure of school and public meeting places, staying at home, transportation stop, masks wearing, hands washing, environmental disinfection were taken on to control epidemic transmission, these measures have made indirect affect on the other infectious diseases incidence.Study design:During COVID-19 pandemic in 2020, we retrospectively analyzed and compared reported cases of other infectious diseases,in order to found what impact of measures in controlling COVID-19 pandemic on the other infectious diseases in China.Methods:We retrospectively analyzed and compared reported cases of measles, pertussis, scarlet fever, seasonal influenza, mumps, HFMD each month in 2018, 2019 and 2020 from the National Health Commission, PRC.Results:Cases of measles, pertussis, scarlet fever, seasonal influenza, mumps and HFMD in January 2020 were not declined, or even increased compare to 2018 and 2019, but from February to December 2020, began to drop significantly compare with the cases of 2018 and 2019. However, seasonal influenza cases in 2020 were more than in 2018.Conclusion:It shown that how important scientific measures are taken to cut off COVID-19 pandemic transmission, However, these taken measures have led to indirect impact on the diffusion of other infectious diseases, led to measles, pertussis, scarlet fever, seasonal influenza, mumps, HFMD declined.

Inadequate trophoblastic infiltration and resulting placental hypoxia and inflammation comprise the core pathological basis of preeclampsia (PE). Maternally expressed gene 3 (MEG3) is known to be involved in the pathogenesis of preeclampsia by inhibiting the migration and invasion of trophoblasts and promoting their apoptosis. Nevertheless, the specific underlying downstream molecular mechanism of MEG3 is less well characterized. In this study, we detected lower expression levels of MEG3 and β-Catenin and higher expression of nod-like receptor pyrin domain-containing 3 (NLRP3) in placental tissues of pregnant women with severe preeclampsia (sPE) than in normal pregnancies. Elevated serum levels of IL-1β and TNF-α were also observed in the sPE group. Then, we established a hypoxia/reoxygenation (H/R) model to mimic preeclampsia. Similar results with sPE group were found in the H/R group compared with the control group. In addition, suppressive trophoblast proliferation, migration and invasion and increases in the apoptotic rate and inflammation were also detected in the H/R group. Notably, overexpressing MEG3 markedly improved trophoblast dysfunction and inflammation caused by H/R. However, the effects of MEG3 on trophoblasts, whether upregulated or downregulated, can be reversed by DKK-1 (Wnt/β-Catenin inhibitor) and MCC950 (NLRP3 inhibitor). The current study revealed that MEG3 regulates trophoblast function and inflammation through the Wnt/β-Catenin/NLRP3 axis and provided new insights into the pathogenesis of preeclampsia.