Isatidis root polysaccharides ameliorates post-weaning diarrhea by promoting intestinal health and modulating the gut microbiota in piglets.

This study aimed to investigate the effects of dietary isatidis root polysaccharide (IRP) on diarrhea, immunity, and intestinal health in weanling piglets. Forty healthy piglets were randomly assigned to five groups receiving varying dosages of IRP. The findings indicated that different concentrations of IRP significantly reduced diarrhea scores ( < 0.

Treating myocardial infarction via a nano-ultrasonic contrast agent-mediated high-efficiency drug delivery system targeting macrophages.

Following myocardial infarction (MI), the accumulation of CD86-positive macrophages in the ischemic injury zone leads to secondary myocardial damage. Precise pharmacological intervention targeting this process remains challenging. This study engineered a nanotherapeutic delivery system with CD86-positive macrophage-specific targeting and ultrasound-responsive release capabilities.

Dual efficacy of tocilizumab in managing PD-1 inhibitors-induced myocardial inflammatory injury and suppressing tumor growth with PD-1 inhibitors: a preclinical study.

The combined use of tocilizumab (TCZ) and immune checkpoint inhibitors (ICIs) in cancer treatment is gaining attention, but preclinical studies are lacking. Our study aims to investigate the synergistic anti-tumor effect of TCZ combined with ICIs and its role in treating immune-related adverse events (irAEs). The clinical significance of high interleukin-6 (IL-6) expression in tumor patients was analyzed from the Cancer Genome Atlas (TCGA) database.

Identification, Biocontrol and Plant Growth Promotion Potential of Endophytic Streptomyces sp. a13.

Medicinal plants often harbour various endophytic actinomycetia, which are well known for their potent antimicrobial properties and plant growth-promoting traits. In this study, we isolated an endophytic actinomycetia, A13, from the leaves of tea clone P312 from the MEG Tea Estate, Meghalaya, India. The isolate A13 was identified as Streptomyces sp.

Detecting somatic variants in purified brain DNA obtained from surgically implanted depth electrodes in epilepsy.

Objective: Somatic variants causing epilepsy are challenging to detect, as they are only present in a subset of brain cells (e.g., mosaic), resulting in low variant allele frequencies.

Basic Science and Pathogenesis.

Background: Whilst numerous studies have explored the relationship between Alzheimer's disease (AD) and diabetes, there remains significant conflicting evidence as to their relationship. Some studies suggest an increased likelihood of developing AD in individuals with diabetes, especially type 2 diabetes (T2D) and that both diseases share pathological features. In contrast, other studies indicate that T2D is more aligned with vascular cognitive impairment and dementia and associated cerebrovascular/white matter pathology.

Basic Science and Pathogenesis.

Background: Published data have highlighted associations between Alzheimer's disease (AD) susceptibility loci and AD-related brain changes. The amyloid imaging to prevent AD (AMYPAD) consortium is a European collaboration consisting of several parent cohorts, four of which had raw genotype array data available. We sought to integrate and harmonise the genetic data, calculate AD polygenic risk scores (PRS), and investigate their association with global amyloid deposition.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) missing heritability remains extensive despite numerous genetic risk loci identified by genome-wide association or sequencing studies. This has been attributed, at least partially, to mechanisms not currently investigated by traditional single-marker/gene approaches. Polygenic Risk Scores (PRS) aggregate sparse genetic information across the genome to identify individual genetic risk profiles for disease prediction and patient risk stratification.

Basic Science and Pathogenesis.

Background: Polygenic Risk Scores (PRS) are important in predicting disease risk and are usually rely on markers selected by thresholding p-values from genome-wide association studies (GWAS). In traditional approaches, one single model is built to calculate risk scores, employing effect size to determine additive risk. However, this traditional method overlooks potential interactions between genetic loci resulting in reduced prediction power.

Basic Science and Pathogenesis.

Background: Murine studies have identified blood proteins that influence brain aging, but translating these findings to humans remains challenging. We used an innovative approach to investigate whether genetically predicted blood levels of proteins linked to brain aging in animal models are associated with cognitive performance in individuals at risk of Alzheimer's disease (AD) [Figure 1].

Method: Through systematic review, we identified 13 circulating proteins with an aging/rejuvenating effect on the mouse brain.

Integrated Analysis of Methylome and Transcriptome Responses to Exercise Training in Children with Overweight/Obesity.

We examined the effects of a 20-week exercise intervention on whole-blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.

dEREGulated pathways: Unraveling the role of epiregulin in skin, kidney and lung fibrosis.

The epidermal growth factor receptor (EGFR) signaling pathway is an evolutionary conserved mechanism to control cell behavior during tissue development and homeostasis. Deregulation of this pathway has been associated with abnormal cell behavior, including hyperproliferation, senescence, and an inflammatory cell phenotype, thereby contributing to pathologies across a variety of organs, including kidney, skin, and lung. To date, there are seven distinct EGFR ligands described.

Basic Science and Pathogenesis.

Background: There is currently an unmet need for novel accessible biomarkers that capture the complex and heterogenous pathophysiology of Alzheimer's disease (AD). Over the past decade, the systems-based multi-omic approaches employed by the Accelerating Medicines Partnership in AD (AMP-AD) have resulted in the identification of promising peripheral markers of disease heterogeneity. This scientific review will highlight these advances with a particular focus on the consortium's successes in peripheral protein biomarker discovery in cerebrospinal fluid (CSF) and plasma.

Basic Science and Pathogenesis.

Achieving greater diversity and inclusion in global dementia research requires the inclusion of underrepresented geographic, ethnic and regional populations such as indigenous Africans. The ADSP is a collaborative global initiative that includes sample collection across diverse populations, data generation including whole genome sequencing in over 120,000 individuals and multi-omics, the collating of rich phenotypic information, data harmonization, and unified data management and quality control. These datasets are being analyzed to accelerate our understanding of AD neurobiology with implications for better risk prediction and discovery of novel precision diagnostics and therapeutics.

Basic Science and Pathogenesis.

Background: Neuroinflammation plays a critical role in Alzheimer's disease pathogenesis. Neurons are anatomically divided in subcellular compartments (axons, soma, and synapses), which may be distinctly impacted by neuroinflammation. This study aims to examine cellular compartment-specific proteomic signatures in excitatory neurons following a systemic neuroinflammatory stress.

Basic Science and Pathogenesis.

Background: Observational studies have suggested a co-occurring relationship between Alzheimer's disease (AD) and asthma. However, the aetiology and biological mechanisms underlying AD and its potential association with asthma, an autoimmune condition, remain unclear.

Method: We examine the genetic relationship between AD and asthma by analysing large-scale genome-wide association study (GWAS) summary data from international research consortia and groups.

KPRR: a novel machine learning approach for effectively capturing nonadditive effects in genomic prediction.

Nonadditive genetic effects pose significant challenges to traditional genomic selection methods for quantitative traits. Machine learning approaches, particularly kernel-based methods, offer promising solutions to overcome these limitations. In this study, we developed a novel machine learning method, KPRR, which integrated a polynomial kernel into ridge regression to effectively capture nonadditive genetic effects.

Genetic variability in snake venom and its implications for antivenom development in sub-Saharan Africa.

Snake venom, a complex mixture of proteins, has attracted human attention for centuries due to its associated mortality, morbidity and other therapeutic properties. In sub-Saharan Africa (SSA), where snakebites pose a significant health risk, understanding the genetic variability of snake venoms is crucial for developing effective antivenoms. The wide geographic distribution of venomous snake species in SSA countries demonstrates the need to develop specific and broad antivenoms.

Incidental Detection of Maternal Cancer Following Cell-Free DNA Screening for Fetal Aneuploidies.

Background: Prenatal cell-free DNA (cfDNA) screening is a success story of clinical genomics that has translated to and transformed obstetric care. It is a highly sensitive and specific method of screening for the most common fetal aneuploidies, including trisomies 13, 18, and 21. While primarily designed to detect fetal chromosomal abnormalities, the test also analyzes maternal cfDNA, which can complicate interpretation of results.

Mind the Gap: A Neural Network Framework for Imputing Genotypes in Non-Model Species.

Reduced representation sequencing (RRS) has proven to be a cost-effective solution for sequencing subsets of the genome in non-model species for large-scale studies. However, the targeted nature of RRS approaches commonly introduces large amounts of missing data, leading to reduced statistical power and biased estimates in downstream analyses. Genotype imputation, the statistical inference of missing sites across the genome, is a powerful alternative to overcome the caveats associated with missing sites.

The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists.

Unlabelled: Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations.

FTO rs1121980 polymorphism contributes to coronary artery disease susceptibility in a Chinese Han population.

Background: The fat mass and obesity-associated protein (FTO) has been showed to be involved in the pathogenesis and progression of coronary artery disease (CAD). However, the effects of FTO variants on CAD risk remain poorly understood. We herein genotyped three SNPs (rs1121980, rs72803657, and rs4783818) in FTO to investigate the influence of FTO polymorphisms on individual susceptibility to CAD.

OrchidBase 6.0: increasing the number of Cymbidium (Orchidaceae) genomes and new bioinformatic tools for orchid genome analysis.

Background: Orchids are well-known for their rich diversity of species as well as wide range habitats. Their floral structures are so unique in angiosperms that many of orchids are economically and culturally important in human society. Orchids pollination strategy and evolutionary trajectory are also fantastic human for centuries.

An ultra-conserved poison exon in the Tra2b gene encoding a splicing activator is essential for male fertility and meiotic cell division.

The cellular concentrations of splicing factors (SFs) are critical for controlling alternative splicing. Most serine and arginine-enriched (SR) protein SFs regulate their own concentration via a homeostatic feedback mechanism that involves regulation of inclusion of non-coding 'poison exons' (PEs) that target transcripts for nonsense-mediated decay. The importance of SR protein PE splicing during animal development is largely unknown despite PE ultra-conservation across animal genomes.

Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.