Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form.

Methods: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan).

Artemisinin alleviates Parkinson's disease by targeting Adcy5-Gch1 axis to trigger a cascade generation of BH4 and dopamine in rats.

Background: Parkinson's disease is a highly prevalent neurodegenerative disorder. Hyposecretion of dopamine (DA) is the end result in the pathology of Parkinson's disease. Unfortunately, safe and efficient therapeutic drugs are deficient.

Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response.

Purpose: Cancer remains a major global cause of death, with rising incidence influenced by environmental factors. The THOC5 gene, part of the THO complex, has emerged as a potential regulator in cancer biology. This study investigates THOC5 expression across various cancers, its role in prognosis, and its potential therapeutic implications, particularly in liver hepatocellular carcinoma (LIHC).

Heavy Metals Toxicity: Mechanism, Health Effects, and Therapeutic Interventions.

Heavy metals (HMs), such as chromium, arsenic, cadmium, mercury, and lead, constitute a class of environmental pollutants with significant toxicity that pose a serious threat to human health. This review provides a comprehensive overview of the biochemical properties of HMs, and their effects at the cellular, molecular, and genetic levels. HMs exert their toxic effects by interfering with various intracellular biochemical processes, including enzyme activity, protein synthesis, and energy metabolism.

Variations in the lipid of dry-cured mutton ham during storage: UPLC-MS-MS-based lipidomic analysis.

Dry-cured mutton ham is prone to quality deterioration during storage due to excessive lipid oxidation. Therefore, to control the ham quality, it is essential to comprehensively understand the lipid changes occurring in the storage. In this study, the variations and primary metabolic pathways of ham lipids during storage were investigated utilizing the lipid metabolomics.

Metallothionein and neurodegenerative diseases.

Neurodegenerative diseases, which mainly include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, and Huntington's disease, are a group of disorders characterized by loss of neurons in the brain and spinal cord. However, the underlying pathogenetic mechanisms of these disorders remain unclear. The metal ion hypothesis is considered a possible cause of a variety of neurodegenerative diseases.

Large-scale plasma proteomics uncovers preclinical molecular signatures of Parkinson's disease and overlap with other neurodegenerative disorders.

Parkinson's disease (PD) remains incurable, with a long preclinical phase currently undetectable by existing methods. In the largest proteomic study in neurodegenerative diseases to date, we analyzed blood samples from ~74,000 individuals across discovery and validation cohorts. In the EPIC4PD discovery case-cohort, large-scale profiling of 7,285 proteins (SomaScan-7K) in 4,538 initially unaffected participants (574 incident cases) identified 17 proteins that predict PD up to 28 years before diagnosis.

Integrative analysis of polyamine metabolism-related genes in gliomas: implications for prognosis and therapy.

Introduction: Tumor transformation and progression are accompanied by multiple carcinogenic pathways that dysregulate polyamine demand and metabolism. The importance of polyamines has demonstrated that their metabolism is a potential therapeutic strategy. Yet, few prognostic models based on polyamine metabolism-related gene risk have been developed for gliomas.

Artesunate alleviates Parkinson's disease by targeting astrocyte MT2A to attenuate dopamine neuronal cuproptosis.

Parkinson's disease (PD) is the second most common prevalent neurodegenerative disease. Recent studies revealed that dysregulation of copper homeostasis was associated with the progression of PD. However, safe and efficient therapeutic drugs were deficient.

Preparation of high-quality pure titanium SLA surface and evaluation of its physicochemical and biological properties - in vitro experiments.

Objectives: This study aimed to prepare high-quality sandblasted large-grit acid-etched surfaces of pure titanium and to evaluate their physicochemical and biological properties.

Methods: We investigated the acid-etching parameters of pure titanium under two sandblasting conditions, focusing on acid concentration, temperature, and time, utilizing an orthogonal experimental design. The optimal conditions for each sandblasted titanium surface were determined through range analysis, enabling the production of high-quality sandblasted large-grit acid-etched surfaces.

Multiomics analysis revealed the regulatory role of chenodeoxycholic acid in fatty acid metabolism and lipid homeostasis.

Objective: This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives.

Methods: Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA's mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics.

Screening and validation of long non-coding RNAs associated with colorectal cancer based on random forest and LASSO regression algorithm.

Objective: Colorectal cancer (CRC) ranks as the third most prevalent contributor to global disease burden and represents the second highest mortality rate among all malignancies worldwide. Long non-coding RNAs (lncRNAs) are a new class of regulatory RNAs, which play a crucial role in the occurrence and development of colorectal cancer. Therefore, it is potentially important to use bioinformatics and machine learning methods to study novel biomarkers for CRC.

Identification of druggable genetic targets for prostate cancer risk based on mendelian randomization and single-cell RNA sequencing.

Purpose: This study aimed to identify genetic targets linked to prostate cancer risk using advanced genetic analysis techniques.

Objective: The goal was to conduct a comprehensive analysis using Mendelian Randomization (MR), colocalization, and single-cell RNA sequencing to identify druggable genes as potential therapeutic targets or diagnostic markers.

Methods: The study involved selecting 2608 druggable genes by intersecting expression Quantitative Trait Loci (eQTLs) with druggable genome databases.

Protein palmitoylation: biological functions, disease, and therapeutic targets.

Protein palmitoylation, a reversible post-translational lipid modification, is catalyzed by the ZDHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases, regulating protein localization, accumulation, secretion, and function. Neurological disorders encompass a spectrum of diseases that affect both the central and peripheral nervous system. Recently, accumulating studies have revealed that pathological protein associated with neurological diseases, such as β-amyloid, α-synuclein, and Huntingtin, could undergo palmitoylation, highlighting the crucial roles of protein palmitoylation in the onset and development of neurological diseases.

Resetting the Hsc70-mediated lysosomal degradation of PD-L1 via a supramolecular meso peptide for the restoration of acquired anti-tumor T cell immunity.

The reduction of cellular PD-L1 abundance through lysosomal degradation is recognized as essential for effective and sustained targeting of PD-L1-dependent immune evasion in cancer. While Hsc70 can interact with PD-L1 to promote its lysosomal degradation, the overexpression of CMTM6 competitively inhibits this interaction, leading to the blockade of PD-L1 lysosomal degradation. To overcome this issue, a meso chimeric peptide PDL1 was designed to specifically bind the PD-1 binding domain of PD-L1 instead of the Hsc70/CMTM6 binding domain, while also binding to Hsc70 to facilitate the dragging of PD-L1 into Hsc70-mediated chaperone-mediated autophagy (CMA), thereby achieving lysosomal degradation.

Identification and validation of Atp5f1c in CD4 T cell as a hub protein in Parkinson's disease.

Parkinson's disease (PD) is an age-related and progressive neurodegenerative disease. Growing evidences indicate that CD4 T cell dysfunction plays an essential role in the progress of PD. Here, in LPS-induced PD mice, we isolated midbrain CD4 T cell and peripheral CD4 T cell to perform proteomics, and then screened a total of 167 co-expression proteins via integrated bioinformatics analysis.

RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system.

Background: Neurodegenerative diseases (NDs) constitute a significant public health challenge, as they are increasingly contributing to global mortality and morbidity, particularly among the elderly population. Pathogenesis of NDs is intricate and multifactorial. Recently, post-transcriptional modifications (PTMs) of RNA, with a particular focus on mRNA methylation, have been gaining increasing attention.

Network pharmacology, transcriptomics, and biological validation reveal a lipid secretion inhibitory and anti-inflammatory mechanism of tanreqing gel in the treatment of acne.

Ethnopharmacological Relevance: Acne vulgaris is a common skin disease affecting the pilosebaceous unit, in which abnormal sebum secretion and inflammation play crucial roles. The traditional Chinese medicine Tanreqing has been utilized in dermatology to effectively treat various diseases. However, its effects and underlying mechanisms in acne vulgaris remain unclear.

Satellite-Based Monitoring of Methane Emissions from China's Rice Hub.

Rice cultivation is one of the major anthropogenic methane sources in China and globally. However, accurately quantifying regional rice methane emissions is often challenging due to highly heterogeneous emission fluxes and limited measurement data. This study attempts to address this issue by quantifying regional methane emissions from rice cultivation with a high-resolution inversion of satellite methane observations from the Tropospheric Monitoring Instrument (TROPOMI).

Invasive aspergillosis complicated in a patient with non-small cell lung cancer harboring fusion during treatment with RET-TKIs: a case report and literature review.

Pralsetinib and selpercatinib have been approved as specific tyrosine kinase inhibitors (TKIs) for the treatment of patients with non-small cell lung cancer (NSCLC) harboring rearranged during transfection () fusion and mutation. However, adverse events associated with pralsetinib and selpercatinib are not fully understood, especially in the real world. In this case, invasive aspergillosis that appeared concurrent with RET-TKI targeted therapy is proposed to be an additional adverse drug reaction (ADR) that was not mentioned in previous reports.

Associations of milk, dairy products, calcium and vitamin D intake with risk of developing Parkinson´s disease within the EPIC4ND cohort.

Literature indicates a potential association between dairy consumption and risk of Parkinson´s disease (PD), especially among men, yet the results remain inconclusive. We investigated this association in a large prospective European cohort. Dietary and non-dietary data was collected from 183,225 participants of the EPIC-for-Neurodegenerative-Diseases (EPIC4ND) cohort, a sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

The RING-type E3 ligase RIE1 sustains leaf longevity by specifically targeting AtACS7 to fine-tune ethylene production in .

Ethylene is widely recognized as a positive regulator of leaf senescence. However, how plants coordinate the biosynthesis of ethylene to meet the requirements of senescence progression has not been determined. The rate-limiting enzyme in the ethylene biosynthesis pathway is ACC synthase.

Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study.

Background: Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota-derived metabolites in PD were small-scale and post-diagnosis, raising concerns about reverse causality.

Objectives: Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.

Microbial community composition and co-occurrence network analysis of the rhizosphere soil of the main constructive tree species in Helan Mountain of Northwest China.

To understand the microbial diversity and community composition within the main constructive tree species, Picea crassifolia, Betula platyphylla, and Pinus tabuliformis, in Helan Mountain and their response to changes in soil physicochemical factors, a high throughput sequencing technology was used to analyze the bacterial and fungal diversity and community structure. RDA (Redundancy Analysis) and Pearson correlation analysis were used to explore the influence of soil physicochemical factors on microbial community construction, and co-occurrence network analysis was conducted on the microbial communities. The results showed that the fungal and bacterial diversity was highest in B.