Target Discovery Driven by Chemical Biology and Computational Biology.

Target identification is crucial for drug screening and development because it can reveal the mechanism of drug action and ensure the reliability and accuracy of the results. Chemical biology, an interdisciplinary field combining chemistry and biology, can assist in this process by studying the interactions between active molecular compounds and proteins and their physiological effects. It can also help predict potential drug targets or candidates, develop new biomarker assays and diagnostic reagents, and evaluate the selectivity and range of active compounds to reduce the risk of off-target effects.

E3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.

The carboxyl terminus of Hsc70-interacting protein (CHIP) is pivotal for managing misfolded and aggregated proteins via chaperone networks and degradation pathways. In a preclinical rodent model of CHIP-related ataxia, we observed that CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), whose role in this context remains poorly understood. Here, we investigated the molecular mechanisms underlying the role of PDE9A in CHIP-related ataxia and demonstrated that CHIP binds to PDE9A, facilitating its polyubiquitination and autophagic degradation.

DNMT3b-mediated CpA methylation facilitates REST binding and gene silencing and exacerbates hippocampal demyelination in diabetic mice.

The remyelination process within the diabetes mellitus (DM) brain is inhibited, and dynamic interactions between DNA methylation and transcription factors are critical for this process. Repressor element-1 silencing transcription factor (REST) is a major regulator of oligodendrocyte differentiation, and the role of REST on DM remyelination remains to be investigated. Here, we investigated the effects of REST and DNA methylation on DM remyelination and explored the underlying mechanisms.

Risk Factors for Postoperative Urinary Tract Infections in Paediatric Hydronephrosis: A Retrospective Analysis.

Background: Paediatric hydronephrosis frequently necessitates surgical intervention. However, postoperative urinary tract infections (UTIs) are common and challenging. This retrospective cohort study aimed to identify UTI risk factors following an operation for paediatric hydronephrosis.

Mechanistic study of SCOOPs recognition by MIK2-BAK1 complex reveals the role of N-glycans in plant ligand-receptor-coreceptor complex formation.

Ligand-induced receptor and co-receptor heterodimerization is a common mechanism in receptor kinase (RK) signalling activation. SERINE-RICH ENDOGENOUS PEPTIDEs (SCOOPs) mediate the complex formation of Arabidopsis RK MIK2 and co-receptor BAK1, triggering immune responses. Through structural, biochemical and genetic analyses, we demonstrate that SCOOPs use their SxS motif and adjacent residues to bind MIK2 and the carboxy-terminal GGR residues to link MIK2 to BAK1.

Effects and Safety of Monoamine Oxidase-B Inhibitors for Early Parkinson's Disease: A Network Meta-Analysis.

Introduction: The objective of this study was to evaluate the effects and safety of monoamine oxidase-B inhibitors (MAO-B inhibitors) for early Parkinson's disease (PD).

Methods: All studies that assessed the efficacy of MAO-B inhibitors in patients with early PD were searched. Publications were screened, and data were extracted according to predefined criteria.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population.

Digital biomarkers for precision diagnosis and monitoring in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder with high prevalence among the elderly, primarily manifested by progressive decline in motor function. The aging global demographic and increased life expectancy have led to a rapid surge in PD cases, imposing a significant societal burden. PD along with other neurodegenerative diseases has garnered increasing attention from the scientific community.

Value of different preoperative bone evaluation methods in predicting intraoperative screw insertion torque: a prospective clinical comparative trial.

Background Context: Establishing good screw-bone structural stability is conducive to reducing the risk of postoperative screw loosening. Screw insertion torque is an objective index for evaluating screw-bone structural stability. Therefore, accurate prediction of screw insertion torque can improve the preoperative evaluation of patients, optimize the surgical plan, and improve the surgical effect.

Microalgae Film-Derived Water Evaporation-Induced Electricity Generator with Negative Carbon Emission.

Water evaporation-induced electricity generators (WEGs) are regarded as one of the most promising solutions for addressing the increasingly severe environmental pollution and energy crisis. Owing to the potential carbon emission in the preparation process of WEGs, whether WEG represents a clean electricity generation technology is open to question. Here, a brand-new strategy is proposed for manufacturing negative carbon emission WEG (CWEG).

Interaction between the SFTSV envelope glycoprotein Gn and STING inhibits the formation of the STING-TBK1 complex and suppresses the NF-κB signaling pathway.

Unlabelled: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus with high pathogenicity. There has been a gradual increase in the number of reported cases in recent years, with high morbidity and mortality rates. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays an important role in the innate immune defense activated by viral infection; however, the role of the cGAS-STING signaling pathway during SFTSV infection is still unclear.

Association between inflammatory bowel disease and Parkinson's disease: a prospective cohort study of 468,556 UK biobank participants.

Introduction: Inflammatory Bowel Disease (IBD) and Parkinson's disease (PD) are both chronic, progressive disorders. As such, given the inconclusive results of extensive research on the association between IBD and PD, our study intends to examine this relationship further using the UK Biobank database.

Methods: We conducted a prospective cohort study using the Cox proportional hazards model, analyzing data from the UK Biobank to investigate the relationship between IBD and PD, following subjects until PD diagnosis, loss to follow up, death or study termination on 30 June, 2023.

Prediabetes and the incidence of Parkinson's disease: A meta-analysis.

Diabetes has been associated with an elevated risk of Parkinson's disease (PD), yet the relationship between prediabetes (PreD) and the incidence of PD in the adult population remains unclear. Therefore, a systematic review and meta-analysis was conducted to evaluate if PreD is also associated with a higher risk of PD. We conducted comprehensive searches of the PubMed, Embase, and Web of Science databases to identify relevant observational studies with longitudinal follow-up.

Study on brain damage patterns of COVID-19 patients based on EEG signals.

Objective: The coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the SARA-CoV-2, characterized by high infectivity and incidence. Clinical data indicates that COVID-19 significantly damages patients' perception, motor function, and cognitive function. However, the electrophysiological mechanism by which the disease affects the patient's nervous system is not yet clear.

Facilitation effect of token syllable frequency in Chinese spoken word production.

Syllable frequency effects in spoken word production have been interpreted as evidence that speakers store syllable-sized motor programmes for phonetic encoding in alphabetic languages such as English or Dutch. However, the cognitive mechanism underlying the syllable frequency effect in Chinese spoken word production remains unknown. To investigate the locus of the syllable frequency effect in spoken Chinese, this study used a picture-word interference (PWI) task in which participants were asked to name the picture while ignoring the distractor word.

Diagnostic performance of metagenomic next-generation sequencing and conventional microbial culture for spinal infection: a retrospective comparative study.

Purpose: The study evaluated the diagnostic performance of metagenomic next-generation sequencing (mNGS) as a diagnostic test for biopsy samples from patients with suspected spinal infection (SI) and compared the diagnostic performance of mNGS with that of microbial culture.

Methods: All patients diagnosed with clinical suspicion of SI were enrolled, and data were collected through a retrospective chart review of patient records. Biopsy specimens obtained from each patient were tested via mNGS and microbial culture.

Enterovirus D68 infection upregulates SOCS3 expression to inhibit JAK-STAT3 signaling and antagonize the innate interferon response of the host.

Enterovirus D68 (EV-D68) can cause respiratory diseases and acute flaccid paralysis, posing a great threat to public health. Interferons are cytokines secreted by host cells that have broad-spectrum antiviral effects, inducing the expression of hundreds of interferon-stimulated genes (ISGs). EV-D68 activates ISG expression early in infection, but at a later stage, the virus suppresses ISG expression, a strategy evolved by EV-D68 to antagonize interferons.

Ageing of grammatical advance planning in spoken sentence production: an eye movement study.

This study used an image-description paradigm with concurrent eye movement recordings to investigate differences of grammatical advance planning between young and older speakers in spoken sentence production. Participants were asked to produce sentences with simple or complex initial phrase structures (IPS) in Experiment 1 while producing individual words in Experiment 2. Young and older speakers showed comparable speaking latencies in sentence production task, whereas older speakers showed longer latencies than young speakers in word production task.