Clinical Manifestations.

Background: Accumulating evidence has shown the neuroprotective effects of estrogen on cognition function, for example delaying the cognitive deterioration in patients with Alzheimer's disease (AD). However, the clinical usage of estrogen in AD remains controversial. The cytochrome P450 aromatase encoded by CYP19A1, is a key enzyme catalyzing the C19 androgen conversion to C18 estrogen, which induces testosterone to estradiol and androstenedione to estrone.

MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.

Individuals with genetic elimination of (mixed lineage kinase domain like pseudokinase) exhibit an increased susceptibility to neurodegenerative diseases like Alzheimer disease (AD). However, the mechanism is not yet fully understood. Here, we observed significant compromise in macroautophagy/autophagy in the brains of knockout (KO) mice, as evidenced by the downregulation of BECN1/Beclin1 and ULK1 (unc-51 like autophagy activating kinase 1).

Exosomes from Hypoxia Preconditioned Muscle-Derived Stem Cells Enhance Cell-Free Corpus Cavernosa Angiogenesis and Reproductive Function Recovery.

Tissue engineering for penile corpora cavernosa defects requires microvascular system reconstruction.GelMA hydrogels show promise for tissue regeneration. However, using stem cells faces challenges such as immune rejection, limited proliferation and differentiation, and biosafety concerns.

Core planar cell polarity genes and in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear.

Association of genetic variation in with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the gene.

Enhancing the efficacy of vaccinia-based oncolytic virotherapy by inhibiting CXCR2-mediated MDSC trafficking.

Oncolytic virotherapy is an innovative approach for cancer treatment. However, recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment (TME) after oncolysis-mediated local inflammation leads to tumor resistance to the therapy. Using the murine malignant mesothelioma model, we demonstrated that the in situ vaccinia virotherapy recruited primarily polymorphonuclear MDSCs (PMN-MDSCs) into the TME, where they exhibited strong suppression of cytotoxic T lymphocytes in a reactive oxygen species-dependent way.

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable.

MicroRNA-128 suppresses tau phosphorylation and reduces amyloid-beta accumulation by inhibiting the expression of GSK3β, APPBP2, and mTOR in Alzheimer's disease.

Introduction And Aims: Alzheimer's disease (AD) is characterized by the abnormal accumulation of hyperphosphorylated tau proteins and amyloid-beta (Aβ) peptides. Recent studies have shown that many microRNAs (miRNAs) are dysregulated in AD, and modulation of these miRNAs can influence the development of tau and Aβ pathology. The brain-specific miRNA miR-128, encoded by MIR128-1 and MIR128-2, is important for brain development and dysregulated in AD.

Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids.

Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids.

Isoformic PD-1-mediated immunosuppression underlies resistance to PD-1 blockade in hepatocellular carcinoma patients.

Objective: Immune checkpoint blockade (ICB) has improved cancer treatment, yet why most hepatocellular carcinoma (HCC) patients are resistant to PD-1 ICB remains elusive. Here, we elucidated the role of a programmed cell death protein 1 (PD-1) isoform, Δ42PD-1, in HCC progression and resistance to nivolumab ICB.

Design: We investigated 74 HCC patients in three cohorts, including 41 untreated, 28 treated with nivolumab and 5 treated with pembrolizumab.

Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity.

Background: Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive.

Methods: We investigated a total of 137 APs infected with SARS-CoV-2.

Distribution and inter-regional relationship of amyloid-beta plaque deposition in a 5xFAD mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia. Although previous studies have selectively investigated the localization of amyloid-beta (Aβ) deposition in certain brain regions, a comprehensive characterization of the rostro-caudal distribution of Aβ plaques in the brain and their inter-regional correlation remain unexplored. Our results demonstrated remarkable working and spatial memory deficits in 9-month-old 5xFAD mice compared to wildtype mice.

Autophagy in Alzheimer's disease pathogenesis: Therapeutic potential and future perspectives.

Alzheimer's disease (AD) is a complex neurodegenerative disease in the elderly and the most common cause of human dementia. AD is characterized by accumulation of abnormal protein aggregates including amyloid plaques (composed of beta-amyloid (Aβ) peptides) and neurofibrillary tangles (formed by hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc.

Identification of Copy Number Variants in a Southern Chinese Cohort of Patients with Congenital Scoliosis.

Congenital scoliosis (CS) is a lateral curvature of the spine resulting from congenital vertebral malformations (CVMs) and affects 0.5-1/1000 live births. The copy number variant (CNV) at chromosome 16p11.

Amyloid-β toxicity modulates tau phosphorylation through the PAX6 signalling pathway.

The molecular link between amyloid-β plaques and neurofibrillary tangles, the two pathological hallmarks of Alzheimer's disease, is still unclear. Increasing evidence suggests that amyloid-β peptide activates multiple regulators of cell cycle pathways, including transcription factors CDKs and E2F1, leading to hyperphosphorylation of tau protein. However, the exact pathways downstream of amyloid-β-induced cell cycle imbalance are unknown.

Asymmetric left-right hippocampal glutamatergic modulation of cognitive control in ApoE-isoform subjects is unrelated to neuroinflammation.

The glutamatergic cycle is essential in modulating memory processing by the hippocampal circuitry. Our combined proton magnetic resonance spectroscopy ( H-MRS) and task-based functional magnetic resonance imaging (fMRI) study (using face-name paired-associates encoding and retrieval task) of a cognitively normal cohort of 67 healthy adults (18 ApoE4 carriers and 49 non-ApoE4 carriers) found altered patterns of relationships between glutamatergic-modulated synaptic signalling and neuronal activity or functional hyperaemia in the ApoE4 isoforms. Our study highlighted the asymmetric left-right hippocampal glutamatergic system in modulating neuronal activities in ApoE4 carriers versus non-carriers.

DAGM: A novel modelling framework to assess the risk of HER2-negative breast cancer based on germline rare coding mutations.

Background: Breast cancers can be divided into HER2-negative and HER2-positive subtypes according to different status of HER2 gene. Despite extensive studies connecting germline mutations with possible risk of HER2-negative breast cancer, the main category of breast cancer, it remains challenging to obtain accurate risk assessment and to understand the potential underlying mechanisms.

Methods: We developed a novel framework named Damage Assessment of Genomic Mutations (DAGM), which projects rare coding mutations and gene expressions into Activity Profiles of Signalling Pathways (APSPs).

Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer's Disease Mouse Model.

Several genetic studies have identified a rare variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a risk factor for Alzheimer's disease (AD). However, findings on the effects of TREM2 on Aβ deposition are quite inconsistent in animal studies, requiring further investigation. In this study, we investigated whether elevation of TREM2 mitigates Aβ pathology in TgCRND8 mice.

Small-World Networks and Their Relationship With Hippocampal Glutamine/Glutamate Concentration in Healthy Adults With Varying Genetic Risk for Alzheimer's Disease.

Background: Apolipoprotein E ɛ4 allele (ApoE4) is the most common gene polymorphism related to Alzheimer's disease (AD). Impaired synaptic dysfunction occurs in ApoE4 carriers before any clinical symptoms. It remains unknown whether ApoE4 status affects the hippocampal neuromodulation, which further influences brain network topology.

Exploring the multifunctional role of melatonin in regulating autophagy and sleep to mitigate Alzheimer's disease neuropathology.

Melatonin (MLT) is a neurohormone that is regulated by the circadian clock and plays multifunctional roles in numerous neurodegenerative disorders, such as Alzheimer's disease (AD). AD is the most common form of dementia and is associated with the degradation of axons and synapses resulting in memory loss and cognitive impairment. Despite extensive research, there is still no effective cure or specific treatment to prevent the progression of AD.

Proper positioning of mice for Cobb angle radiographic measurements.

Background: There is no recommended standard for positioning of a mouse for radiographic assessment of the spine. This is necessary to have reproducible radiographic data and avoid false positive results. The objective of this study was to investigate the impact of various postures on Cobb angle measurements and to set up a positioning standard for imaging mouse spines.