Unraveling Microplastic Effects on Gut Microbiota across Various Animals Using Machine Learning.

Microplastics, rapidly expanding and durable pollutant, have been shown to significantly impact gut microbiota across a spectrum of animal species. However, comprehensive analyses comparing microplastic effects on gut microbiota among these species are still limited, and the critical factors driving these effects remain to be clarified. To address these issues, we compiled 1352 gut microbiota samples from six animal categories, employing machine learning to conduct an in-depth meta-analysis.

Nucleoside Reverse Transcriptase Inhibitors Are the Major Class of HIV Antiretroviral Therapeutics That Induce Neuropathic Pain in Mice.

The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated.

Hospital-Treated Infectious Diseases, Infection Burden, and Risk of Lung Cancer: An Observational and Mendelian Randomization Study.

Background: Although infections play a role in the development of lung cancer, the longitudinal association between infection and the risk of lung cancer is disputed, and data relating to pathogen types and infection sites are sparse.

Research Question: How do infections affect subsequent lung cancer risk, and is the impact limited to specific microbes rather than infection burden?

Study Design And Methods: Data on > 900 infectious diseases were gathered from the UK Biobank study. Short- and long-term effects of infections were assessed by using time-varying Cox proportional hazards models.

Hospital-treated infectious diseases, genetic susceptibility and risk of type 2 diabetes: A population-based longitudinal study.

Background: The longitudinal association between infectious diseases and the risk of type 2 diabetes (T2D) remains unclear.

Methods: Based on the UK Biobank, the prospective cohort study included a total of 396,080 participants without diabetes at baseline. We determined the types and sites of infectious diseases and incident T2D using the International Classification of Diseases 10th Revision codes (ICD-10).

Deciphering the pathogenic risks of microplastics as emerging particulate organic matter in aquatic ecosystem.

Microplastics are accumulating rapidly in aquatic ecosystems, providing habitats for pathogens and vectors for antibiotic resistance genes (ARGs), potentially increasing pathogenic risks. However, few studies have considered microplastics as particulate organic matter (POM) to elucidate their pathogenic risks and underlying mechanisms. Here, we performed microcosm experiments with microplastics and natural POM (leaves, algae, soil), thoroughly investigating their distinct effects on the community compositions, functional profiles, opportunistic pathogens, and ARGs in Particle-Associated (PA) and Free-Living (FL) bacterial communities.

Identifications of novel host cell factors that interact with the receptor-binding domain of the SARS-CoV-2 spike protein.

SARS-CoV-2 entry into host cells is facilitated by the interaction between the receptor-binding domain of its spike protein (CoV2-RBD) and host cell receptor, ACE2, promoting viral membrane fusion. The virus also uses endocytic pathways for entry, but the mediating host factors remain largely unknown. It is also unknown whether mutations in the RBD of SARS-CoV-2 variants promote interactions with additional host factors to promote viral entry.

Association of hospital-treated infectious diseases and infection burden with cardiovascular diseases and life expectancy.

Background: The association of a broad spectrum of infectious diseases with cardiovascular outcomes remains unclear.

Objectives: We aim to provide the cardiovascular risk profiles associated with a wide range of infectious diseases and explore the extent to which infections reduce life expectancy.

Methods: We ascertained exposure to 900+ infectious diseases before cardiovascular disease (CVD) onset in 453,102 participants from the UK Biobank study.

Neural Circuitry Polarization in the Spinal Dorsal Horn (SDH): A Novel Form of Dysregulated Circuitry Plasticity during Pain Pathogenesis.

Pathological pain emerges from nociceptive system dysfunction, resulting in heightened pain circuit activity. Various forms of circuitry plasticity, such as central sensitization, synaptic plasticity, homeostatic plasticity, and excitation/inhibition balance, contribute to the malfunction of neural circuits during pain pathogenesis. Recently, a new form of plasticity in the spinal dorsal horn (SDH), named neural circuit polarization (NCP), was discovered in pain models induced by HIV-1 gp120 and chronic morphine administration.

Employing bimodal representations to predict DNA bendability within a self-supervised pre-trained framework.

The bendability of genomic DNA, which measures the DNA looping rate, is crucial for numerous biological processes of DNA. Recently, an advanced high-throughput technique known as 'loop-seq' has made it possible to measure the inherent cyclizability of DNA fragments. However, quantifying the bendability of large-scale DNA is costly, laborious, and time-consuming.

Fatty acid binding protein 5 inhibition attenuates pronociceptive cytokine/chemokine expression and suppresses osteoarthritis pain: A comparative human and rat study.

Objective: Osteoarthritis (OA) is often accompanied by debilitating pain that is refractory to available analgesics due in part to the complexity of signaling molecules that drive OA pain and our inability to target these in parallel. Fatty acid binding protein 5 (FABP5) is a lipid chaperone that regulates inflammatory pain; however, its contribution to OA pain has not been characterized.

Design: This combined clinical and pre-clinical study utilized synovial tissues obtained from subjects with end-stage OA and rats with monoiodoacetate-induced OA.

Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain.

Chronic pain is a prevalent neurological complication among individuals living with human immunodeficiency virus (PLHIV) in the post-combination antiretroviral therapy (cART) era. These individuals experience malfunction in various cellular and molecular pathways involved in pain transmission and modulation, including the neuropathology of the peripheral sensory neurons and neurodegeneration and neuroinflammation in the spinal dorsal horn. However, the underlying etiologies and mechanisms leading to pain pathogenesis are complex and not fully understood.

Association Between Glucosamine Use and the Risk of Incident Heart Failure: The UK Biobank Cohort Study and Mendelian Randomization Analysis.

Objective: To evaluate the association between regular glucosamine intake and heart failure (HF) and to explore whether the association is mediated by relevant cardiovascular disease.

Patients And Methods: We included 479,650 participants with data available for supplement use and without HF at baseline from the UK Biobank study. Using 12 single-nucleotide polymorphisms linked to HF, a weighted genetic risk score was calculated.

Safety, Pharmacokinetics, and Antifibrotic Activity of CC-90001 (BMS-986360), a c-Jun N-Terminal Kinase Inhibitor, in Pulmonary Fibrosis.

Approved treatments for idiopathic pulmonary fibrosis have tolerability concerns and limited efficacy. CC-90001, a c-Jun N-terminal kinase inhibitor, is under investigation as a therapy for fibrotic diseases. A Phase 1b safety, pharmacokinetics, and pharmacodynamics study of oral CC-90001 (100, 200, or 400 mg) administered once daily for 12 weeks was conducted in patients with pulmonary fibrosis (NCT02510937).

The antitumor effect of mycelia extract of the medicinal macrofungus Inonotus hispidus on HeLa cells via the mitochondrial-mediated pathway.

Ethnopharmacological Relevance: Inonotus hispidus (I. hispidus), known as shaggy bracket, has been used extensively in China and some East Asian countries as a traditional medicinal macrofungus to treat difficult diseases, such as diabetes, gout, and arthritis. Modern pharmacological research has shown that I.

Association of regular glucosamine use with incident dementia: evidence from a longitudinal cohort and Mendelian randomization study.

Background: Emerging data suggests the neuroprotective and anti-neuroinflammatory effects of glucosamine. We aimed to examine the association between regular glucosamine use and risk of incident dementia, including dementia subtypes.

Methods: We conducted large-scale observational and two-sample Mendelian randomization (MR) analyses.

Spinal astrocytic MeCP2 regulates Kir4.1 for the maintenance of chronic hyperalgesia in neuropathic pain.

Astrocyte activation in the spinal dorsal horn may play an important role in the development of chronic neuropathic pain, but the mechanisms involved in astrocyte activation and their modulatory effects remain unknown. The inward rectifying potassium channel protein 4.1 (Kir4.

SARS-CoV-2 Spike Protein Post-Translational Modification Landscape and Its Impact on Protein Structure and Function via Computational Prediction.

To elucidate the role of post-translational modifications (PTMs) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein's structure and virulence, we generated a high-resolution map of 87 PTMs using liquid chromatography with tandem mass spectrometry data on the extracted spike protein from SARS-CoV-2 virions and then reconstituted its structure heterogeneity caused by PTMs. Nonetheless, Alphafold2, a high-accuracy artificial intelligence tool to perform protein structure prediction, relies solely on primary amino acid sequence, whereas the impact of PTM, which often modulates critical protein structure and function, is much ignored. To overcome this challenge, we proposed the mutagenesis approach-an in silico, site-directed amino acid substitution to mimic the influence of PTMs on protein structure due to altered physicochemical properties in the post-translationally modified amino acids-and then reconstituted the spike protein's structure from the substituted sequences by Alphafold2.

Transcriptomics combined with metabolomics unveiled the key genes and metabolites of mycelium growth in .

Morels () are one of the most popular edible fungi in the world, especially known for their rich nutrition and delicious taste. Earlier research indicates that the production of fruiting bodies can be affected by the growth of mycelium. To investigate the molecular mechanisms underlying mycelium growth in , we performed transcriptome analysis and metabolomics analysis of three growth stages of the hypha of .

An atlas of bacterial two-component systems reveals function and plasticity in signal transduction.

Two-component systems (TCSs) consist of the biggest group of signal transduction pathways in biology. Although TCSs play key roles in sensing signals to sustain survival and virulence, the genome-wide regulatory variability and conservation and synergistic actions of global TCSs in response to external stimulus are still uncharacterized. Here, we integrate 120 transcriptome sequencing datasets and 38 chromatin immunoprecipitation sequencing datasets of the model phytopathogen Pseudomonas syringae to illustrate how bacterial TCSs dynamically govern their regulatory roles under changing environments.

Soil microbial diversity and functional capacity associated with the production of edible mushroom in croplands.

In recent years, a rare edible mushroom has become popular. has the characteristics of easy cultivation, low cost, high output value, and low labor requirement, making its economic benefits significantly superior to those of other planting industries. Accumulating research demonstrates that cultivating edible fungus is advantageous for farming soil.

Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling.

Opioids are the frontline analgesics for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression.

Whole-genome assembly and analysis of a medicinal fungus: .

() is a medicinal macrofungus that plays a key role in anti-tumor and antioxidant functions. To further understand and enhance the value of , we performed whole-genome sequencing and an analysis of its strain for the first time. was sequenced using the Illumina NovaSeq high-throughput sequencing platform.