LMTK2 and CRB1 are two novel risk genes for Alzheimer's disease in Han Chinese.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with a substantial genetic background. However, its underlying genetic architecture remains to be elucidated.

Methods: In this study, we performed whole-exome sequencing in 282 familial and/or early-onset AD patients and 1086 cognitively normal controls in the Han Chinse populations.

LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis.

Background: Laminin subunit beta 1 (LAMB1) has regulatory functions on the proliferation, attachment, and migration of tumor cells, with increased levels linked to different cancers.

Objective: This study aims at investigating the effects and mechanisms of LAMB1 in glioma.

Methods And Material: Glioma cell models with LAMB1 overexpression or downregulation were constructed.

Causal Relationship Between the Abuse of Cholesterol-Lowering Medication, Blood Pressure Medication, Insulin, and Exogenous Hormones and Cerebral Infarction.

Background: Cholesterol-lowering medications, blood pressure medication, insulin, and exogenous hormones (including hormone replacement therapy, oral contraceptives, and minipills) are commonly utilized in clinical practice. Recent studies indicate that the use of these medications may significantly influence the occurrence and progression of cerebral infarction. This study aims to investigate the relationship between these medications and cerebral infarction using Mendelian randomization (MR) analysis, with the goal of offering valuable insights for the clinical management of cerebral infarction.

Streptococcus agalactiae infection of a reconstructed human respiratory epithelium revealed infection and host response characteristics by different serotypes.

Background: Streptococcus agalactiae poses a significant threat to neonatal health, causing morbidity and mortality when transmitted from the maternal vagina to the newborn's respiratory tract. Among its various strains, serotype III is predominant in severe neonatal infections in Asia. However, the mechanisms of pathogenesis and host responses underlying serotype-specific disease outcomes remain poorly understood.

Ocular Mucous Membrane Pemphigoid Demonstrates a Distinct Autoantibody Profile from Those of Other Autoimmune Blistering Diseases: A Preliminary Study.

: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate.

IgG autoantibodies in bullous pemphigoid directly induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes.

Unlabelled: While autoantibodies in bullous pemphigoid (BP) are known to activate the innate immune response, their direct effect on keratinocytes, and the contribution of BP-IgG autoantibody-dependent keratinocyte responses to BP pathology is largely unknown. Herein, we performed multiplex immunoassays and bulk RNA-seq on primary keratinocytes treated with IgG from BP patients or controls. We identified a pro-inflammatory and proteolytic response with release of several cytokines (IL-6, IL-24, TGF-β1), chemokines (CXCL16, CTACK, MIP-3β, RANTES), C1s, DPP4, and MMP-9.

Integrated Single-Cell Analysis Reveals Spatially and Temporally Dynamic Heterogeneity in Fibroblast States during Wound Healing.

Wound healing is a dynamic process over temporal and spatial scales. Key to repair outcomes are fibroblasts; yet, how they modulate healing across time and in different wound regions remains incompletely understood. By integrating single-cell RNA-sequencing datasets of mouse skin and wounds, we infer that fibroblasts are the most transcriptionally dynamic skin-resident cells, evolving during postnatal skin maturation and rapidly after injury toward distinct late scar states.

A missing jigsaw within the hygiene hypothesis: Low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection.

The rising occurrence of allergic asthma in early life across industrialized countries suggests that environmental factors play a crucial role in determining asthma susceptibility and severity. While prior exposure to microbial lipopolysaccharides (LPSs) has been found to offer protection against allergic asthma, infants residing in urban environments are increasingly exposed to environmental pollutants. Utilizing limulus lysate test screens and virtual screening models, we identified pollutants that can modulate LPS bioactivity.

Current status and influencing factors of policy identification in health impact assessment: a case study of Zhejiang Province.

Background: Health impact assessment (HIA) is a procedure, method and tool for evaluating the potential health impacts of policies, plans and construction projects, as well as the distribution of these impacts on population. Majority of international studies on health impact assessment have focussed on conceptual papers or case evaluations, neglecting participants' views on policies.

Methods: A semi-structured interview with 30 health impact assessment experts was employed in this study, and the Nvivo software was utilized to analyse factors that influence policy identification.

A Roadmap for a Consensus Human Skin Cell Atlas and Single-Cell Data Standardization.

Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite.

Effects of Social Networks on Job Performance of Individuals among the Hypertension Management Teams in Rural China.

Background: Limited studies have explored the relationship among cross-organizational and multidisciplinary medical staff.

Aim: The present study conducted an in-depth examination and validation of the influence of complex cross-organization and multidisciplinary social networks on the job performance of team members.

Method: Multi-level hierarchical regression analysis was used to assess the impact of the centrality and the characteristics of structural holes in social networks (i.

Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity.

Bifurcation analysis in a Holling-Tanner predator-prey model with strong Allee effect.

In this paper, we analyze the bifurcation of a Holling-Tanner predator-prey model with strong Allee effect. We confirm that the degenerate equilibrium of system can be a cusp of codimension 2 or 3. As the values of parameters vary, we show that some bifurcations will appear in system.

Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development.

COVID-19 pandemic continues to spread throughout the world with an urgent demand for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a bacterial vector COVID-19 vaccine (aPA-RBD) that carries the gene for the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Live-attenuated strains of (aPA) were constructed which express the recombinant RBD and effectively deliver RBD protein into various antigen presenting cells through bacterial type 3 secretion system (T3SS) .

Significance of differential expression of OLFM4 in the development of endometrial adenocarcinoma.

The incidence of endometrial adenocarcinoma (EA) has increased worldwide in recent years due to the widespread use of estrogen therapy and the overall increase in life expectancy. However, we know of no sensitive molecular index that can be used to predict the onset of EA, evaluate the therapeutic effects of treatment agents, or provide prognostic benefit in post-treatment follow-up. To explore the correlation between human olfactomedin 4 (OLFM4) and the clinicopathologic parameters of EA, and to determine the precise involvement of OLFM4 as a related factor in the occurrence and development of EA.

Clinical characteristics and genotype-phenotype correlation analysis of familial Alzheimer's disease patients with pathogenic/likely pathogenic amyloid protein precursor mutations.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with aging, environmental, and genetic factors. Amyloid protein precursor () is a known pathogenic gene for familial Alzheimer's disease (FAD), and now more than 70 mutations have been reported, but the genotype-phenotype correlation remains unclear. In this study, we collected clinical data from patients carrying APP mutations defined as pathogenic/likely pathogenic according to the American college of medical genetics and genomics (ACMG) guidelines.

The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case-control study in Chinese population.

Aim: The associations of non-pathogenic variants of APP, PSEN1, and PSEN2 with Alzheimer's disease (AD) remain unclear. This study is aimed at determining the role of these variants in AD.

Methods: Our study recruited 1154 AD patients and 2403 controls.

Engineering Immunomodulatory Biomaterials to Drive Skin Wounds toward Regenerative Healing.

The healing of human skin wounds is designed for a rapid fibroproliferative response at the expense of tissue complexity and is therefore prone to scar formation. Moreover, wound healing often goes awry when excessive inflammation leads to chronic nonhealing wounds or when excessive repair results in uncontrolled tissue fibrosis. The immune system plays a central role in orchestrating wound healing, and, thus, controlling immune cell activities holds great potential for reducing scars and enhancing regeneration.

CYLD variants identified in Alzheimer's disease and frontotemporal dementia patients.

Objectives: CYLD was a novel causative gene for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis. Given the clinical and pathological overlap of FTD and Alzheimer's disease (AD), it is necessary to screen CYLD in AD patients and FTD patients in the Chinese population.

Methods: In our study, using a targeted sequencing panel, we sequenced the CYLD gene in a large cohort of 2485 participants in the Chinese population, including 1008 AD patients, 105 FTD patients, and 1372 controls.