Biomarkers.

Background: Not all people with neuropathological evidence of Alzheimer's disease (AD) manifest clinical symptoms in life (cognitive resilience). We aimed to identify genetic and epigenetic signatures of cognitive resilience, utilizing data from brain donors with neuropathological evidence of AD who were either symptomatic or asymptomatic in life.

Method: Among brain donors with neuropathologically-confirmed AD (364 asymptomatic/cognitively resilient and 490 symptomatic) from the Boston University AD Research Center, Framingham Heart Study-where we generated our own data-as well as the Religious Orders Study and Rush Memory and Aging Project, we utilized genome-wide genetic array data, genome-wide DNA methylation array data and RNA sequencing data.

Transcriptome Signatures for Cognitive Resilience Among Individuals with Pathologically Confirmed Alzheimer Disease.

Introduction: Limited success to date in development of drugs that target hallmark Alzheimer disease (AD) proteins as a means to slow AD-related cognitive decline has sparked interest in approaches focused on cognitive resilience. We sought to identify transcriptome signatures among brain donors with neuropathologically confirmed AD that distinguish those with cognitive impairment from those that were cognitively intact.

Methods: We compared gene expression patterns in brain tissue from donors in four cohorts who were cognitively and pathologically normal (controls), met clinical and pathological criteria for AD (SymAD), or were cognitively normal prior to death despite pathological evidence of AD (cognitively resilient or AsymAD).

Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease.

Psychological stress contributes to cardiovascular disease (CVD) and sudden cardiac death, yet its molecular basis remains obscure. RNA binding protein RBM24 plays a critical role in cardiac development, rhythm regulation, and cellular stress. Here, we show that psychological stress activates RBM24 S181 phosphorylation through eIF4E2-GSK3β signaling, which causally links psychological stress to CVD by promoting APOE translation (apolipoprotein E).

Single-Cell Multi-Omics Analysis of In Vitro Post-Ovulatory-Aged Oocytes Revealed Aging-Dependent Protein Degradation.

Once ovulated, the oocyte has to be fertilized in a short time window or it will undergo post-ovulation aging (POA), whose underlying mechanisms are still not elucidated. Here, we optimized single-cell proteomics methods and performed single-cell transcriptomic, proteomic, and phosphoproteomic analysis of fresh, POA, and melatonin-treated POA oocytes. POA oocytes showed downregulation of most differentially expressed proteins, with little correlation with mRNA expression, and the protein changes can be rescued by melatonin treatment.

The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis and clinical assessment: an updated meta-analysis of randomized trials.

Background: Coronavirus disease 2019 (COVID-19), a disease that affected tens of millions of people, upended the lives of countless individuals around the globe. The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were the most frequently cited as potential treatments and preventatives against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary aim of this investigation was to scrutinize the effectiveness and safety of HCQ for COVID-19 prevention and to present powerful evidence and reference for clinical practice.

Recycling drinking water treatment sludge in construction and building materials: A review.

Drinking water treatment sludge (DWTS) is a by-product of water treatment, and it is difficult to recycle to high value and poses potential environmental risks. Recycling DWTS into cement-based materials is an effective measure to achieve its high-volume utilization and reduce its environmental load. DWTS is rich in silica-alumina phases and has potential pozzolanic activity after drying, grinding and calcination, giving it similar properties to traditional supplementary cementitious materials.

TransGCN: a semi-supervised graph convolution network-based framework to infer protein translocations in spatio-temporal proteomics.

Protein subcellular localization (PSL) is very important in order to understand its functions, and its movement between subcellular niches within cells plays fundamental roles in biological process regulation. Mass spectrometry-based spatio-temporal proteomics technologies can help provide new insights of protein translocation, but bring the challenge in identifying reliable protein translocation events due to the noise interference and insufficient data mining. We propose a semi-supervised graph convolution network (GCN)-based framework termed TransGCN that infers protein translocation events from spatio-temporal proteomics.

scapGNN: A graph neural network-based framework for active pathway and gene module inference from single-cell multi-omics data.

Although advances in single-cell technologies have enabled the characterization of multiple omics profiles in individual cells, extracting functional and mechanistic insights from such information remains a major challenge. Here, we present scapGNN, a graph neural network (GNN)-based framework that creatively transforms sparse single-cell profile data into the stable gene-cell association network for inferring single-cell pathway activity scores and identifying cell phenotype-associated gene modules from single-cell multi-omics data. Systematic benchmarking demonstrated that scapGNN was more accurate, robust, and scalable than state-of-the-art methods in various downstream single-cell analyses such as cell denoising, batch effect removal, cell clustering, cell trajectory inference, and pathway or gene module identification.

Bio-Inspired Proprioceptive Touch of a Soft Finger with Inner-Finger Kinesthetic Perception.

In-hand object pose estimation is challenging for humans and robots due to occlusion caused by the hand and object. This paper proposes a soft finger that integrates inner vision with kinesthetic sensing to estimate object pose inspired by human fingers. The soft finger has a flexible skeleton and skin that adapts to different objects, and the skeleton deformations during interaction provide contact information obtained by the image from the inner camera.

Widespread Involvement of Acetylation in the Retinal Metabolism of Form-Deprivation Myopia in Guinea Pigs.

Myopia has become the major cause of visual impairment worldwide. Although the pathogenesis of myopia remains controversial, proteomic studies suggest that dysregulation of retinal metabolism is potentially involved in the pathology of myopia. Lysine acetylation of proteins plays a key role in regulating cellular metabolism, but little is known about its role in the form-deprived myopic retina.

Enhanced extracellular production of raw starch-degrading α-amylase in Bacillus subtilis through expression regulatory element modification and fermentation optimization.

Background: Raw starch-degrading α-amylase (RSDA) can hydrolyze raw starch at moderate temperatures, thus contributing to savings in starch processing costs. However, the low production level of RSDA limits its industrial application. Therefore, improving the extracellular expression of RSDA in Bacillus subtilis, a commonly used industrial expression host, has great value.

Successful treatment of near-fatal asthma with ECMO: A case report and literature review.

Near-fatal asthma (NFA) can lead to severe hypercapnia and sudden cardiac arrest; however, it can be reversed by extracorporeal membrane oxygenation (ECMO). We report a case of a 37-year-old male diagnosed with NFA. After fluid rehydaration, spasmolysis, and treatment with glucocorticoid and mechanical ventilation, the patient's condition improved temporarily.

DeepSP: A Deep Learning Framework for Spatial Proteomics.

The study of protein subcellular localization (PSL) is a fundamental step toward understanding the mechanism of protein function. The recent development of mass spectrometry (MS)-based spatial proteomics to quantify the distribution of proteins across subcellular fractions provides us a high-throughput approach to predict unknown PSLs based on known PSLs. However, the accuracy of PSL annotations in spatial proteomics is limited by the performance of existing PSL predictors based on traditional machine learning algorithms.

Successful treatment of veno-arterial extracorporeal membrane oxygenation complicated with left ventricular thrombus by intravenous thrombolysis: A case report.

Background: Left ventricular thrombus is a rare condition, for which appropriate treatments are not extensively studied. Although it can be treated by thrombectomy, such surgery can be difficult and risky, and not every patient can tolerate the surgery.

Case Summary: We report a case of a middle-aged man receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction who developed left ventricular thrombus despite systemic anticoagulation.

HLA-DR mucosal-associated invariant T cells predict poor prognosis in patients with sepsis: A prospective observational study.

Mucosal-associated invariant T (MAIT) cells are important in antibacterial immune responses; however, during sepsis, they are few in number and exhibit highly activated phenotypes. The relationship between MAIT cells in peripheral blood and the prognosis of sepsis is not well understood. Thus, this study aimed to examine the levels and phenotypes of MAIT cells in early sepsis, evaluate their clinical relevance, and investigate their association with patient prognosis.

Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

Background: Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized.

Comparison of Efficacy and Safety of Different Doses of Dexmedetomidine for Epidural Labor Analgesia.

Objective: To explore the efficacy and safety of different doses of dexmedetomidine (DEX) for epidural labor analgesia (ELA).

Methods: From June 2021 to June 2022, 147 parturients who underwent ELA in our hospital were selected and divided into low- (0.5 g/kg DEX), medium- (0.

Pleiotropy analysis between lobar intracerebral hemorrhage and CSF β-amyloid highlights new and established associations.

Background And Aims: Combining biologically related traits in genome-wide association studies (GWAS) increases the power for genetic discovery. Given the established relationship between lobar intracerebral hemorrhage (ICH) and cerebral amyloid angiopathy (CAA), and between the latter and levels of cerebrospinal fluid amyloid-β 42 (CSF-Aβ42), we leveraged genetic predisposition for lower CSF-Aβ42 levels as a proxy phenotype for CAA to identify new genes associated with lobar ICH.

Methods: We used publicly available GWAS data for CSF-Aβ42 levels (n = 3146) and for lobar ICH (n = 2094).

Repetitive head impacts and chronic traumatic encephalopathy are associated with TDP-43 inclusions and hippocampal sclerosis.

Hippocampal sclerosis (HS) is associated with advanced age as well as transactive response DNA-binding protein with 43 kDa (TDP-43) deposits. Both hippocampal sclerosis and TDP-43 proteinopathy have also been described in chronic traumatic encephalopathy (CTE), a neurodegenerative disease linked to exposure to repetitive head impacts (RHI). However, the prevalence of HS in CTE, the pattern of TDP-43 pathology, and associations of HS and TDP-43 with RHI are unknown.

Genome-Wide Pleiotropy Study Identifies Association of with Age-Related Macular Degeneration and COVID-19 Infection Outcomes.

Age-related macular degeneration (AMD) has been implicated as a risk factor for severe consequences from COVID-19. We evaluated the genetic architecture shared between AMD and COVID-19 (critical illness, hospitalization, and infections) using analyses of genetic correlations and pleiotropy (i.e.