E3 ubiquitin ligase SYVN1 as a promising therapeutic target for diverse human diseases.

Numerous studies conducted in recent years indicate that mammalian E3 ubiquitin ligases serve as key regulators in the maintenance of cellular homeostasis by targeting the ubiquitination of substrate proteins and activating downstream signaling pathways. SYVN1, an E3 ubiquitin ligase, is characterized by its significant functions in regulating various biological processes, including molecular mechanisms related to gene expression, signaling pathways, and cell death, among others. Consequently, SYVN1 plays a crucial role in both normal human physiology and the pathogenesis of various diseases, such as oncogenesis, cardiovascular disorders, immune regulation, skeletal anomalies, and neurological diseases.

Self-monitoring of blood pressure following a stroke or transient ischaemic attack (TASMIN5S): a randomised controlled trial.

Background: Blood pressure (BP) control following stroke is important but currently sub-optimal. This trial aimed to determine whether self-monitoring of hypertension with telemonitoring and a treatment escalation protocol, results in lower BP than usual care in people with previous stroke or transient ischaemic attack (TIA).

Methods: Unblinded randomised controlled trial, comparing a BP telemonitoring-based intervention with control (usual care) for hypertension management in 12 primary care practices in England.

A new species of the genus Boulenophrys from South China (Anura, Megophryidae).

In this study, a new species of the genus Boulenophrys is described from northwestern Guangdong, within the Nanling Moutains. The new species can be distinguished from all known congeners by a combination of morphological characteristics and the mitochondrial genetic divergence. The new species is found to breed in winter season which was not common in most amphibian groups but also present in some Boulenophrys congeners.

Comparison of the smiley face rod method versus intervertebral fusion for the treatment of L5 spondylolysis in adults.

Purpose: For patients who suffered from L5 spondylolysis and fail to improve using conservative treatment, the best surgical strategy remains controversial. This study compares the efficacy of the treatment of L5 spondylolysis using the smiley face rod (SFR) method versus intervertebral fusion (IF).

Methods: We analyzed 38 patients with L5 spondylolysis who underwent surgery in our department between January 2017 and June 2019.

Transcriptome-wide mapping of internal mRNA N-methylguanosine in sporulated and unsporulated oocysts of Eimeria tenella reveals stage-specific signatures.

Background: Growing evidence indicates that N-methylguanosine (mG) modification plays critical roles in epigenetic regulation. However, no data regarding mG modification are currently available in Eimeria tenella, a highly virulent species causing coccidiosis in chickens.

Methods: In the present study, we explore the distribution of internal messenger RNA (mRNA) mG modification in sporulated and unsporulated oocysts of E.

Dental pulp stem cells promote genioglossus repair and systemic amelioration in chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model.

Quantitative proteomics and multi-omics analysis identifies potential biomarkers and the underlying pathological molecular networks in Chinese patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach.

Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment.

Background: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection.

mRNA 5-methylcytosine in Eimeria tenella oocysts: An abundant post-transcriptional modification associated with broad-ranging biological processes.

Eimeria tenella is the major causative agent of chicken coccidiosis. 5-Methylcytosine (mC) is a type of RNA chemical modifications reported to regulate diverse biological processes. However, the distribution and biological functions of mC in E.

Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes.

Background: Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited.

Methods: In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged ≥18 years in the community with a positive test for SARS-CoV-2 and symptoms lasting ≤14 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions.

Nurse-delivered sleep restriction therapy to improve insomnia disorder in primary care: the HABIT RCT.

Background: Insomnia is a prevalent and distressing sleep disorder. Multicomponent cognitive-behavioural therapy is the recommended first-line treatment, but access remains extremely limited, particularly in primary care where insomnia is managed. One principal component of cognitive-behavioural therapy is a behavioural treatment called sleep restriction therapy, which could potentially be delivered as a brief single-component intervention by generalists in primary care.

User engagement in clinical trials of digital mental health interventions: a systematic review.

Introduction: Digital mental health interventions (DMHIs) overcome traditional barriers enabling wider access to mental health support and allowing individuals to manage their treatment. How individuals engage with DMHIs impacts the intervention effect. This review determined whether the impact of user engagement was assessed in the intervention effect in Randomised Controlled Trials (RCTs) evaluating DMHIs targeting common mental disorders (CMDs).

Recent advances in oxidative dearomatization involving C-H bonds for constructing value-added oxindoles.

Exploring three-dimensional chemical space is an important research objective of organic synthetic chemistry. Oxidative dearomatization (ODA) is one of the most important and powerful tools for realizing this goal, because it changes and removes aromatic structures from aromatic compounds to increase levels of saturation and stereoisomerism by direct addition reactions between functional groups with aromatic cores under oxidative conditions. As a hot topic in indole chemistry, the synthetic value of the oxidative dearomatization of indoles has been well recognized and has witnessed rapid development recently, since it could provide convenient and unprecedented access to fabricate high-value-added three-dimensional oxindole skeletons, such as C-quaternary indolones, polycycloindolones and spiroindolones, and be widely applied to the total synthesis of these oxindole alkaloids.

Effect of antihypertensive deprescribing on hospitalisation and mortality: long-term follow-up of the OPTiMISE randomised controlled trial.

Background: Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3 months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality.

New Flavan Derivatives from the Leaves and Stems of Cassia Nodosa.

Three new flavan derivatives including two methylene-linked flavan-3-ol dimers, bis(8-epiafzelechinyl)methane (1), and 8,8-(epiafzelechin-afzelechin)methane (2), a flavan-3-ol monomer, (-)-3-O-acetyl-epiafzelechin (3) and four known related compounds (4-7) were isolated from the leaves and stems of Cassia nodosa. Their structures were elucidated by extensive spectroscopic analyses and CD data. The isolates were evaluated for their antioxidant, α-glucosidase inhibitory, cytotoxic and neuroinflammatory activities, and compound 3 exhibited remarkable radical scavenging activities in both the DPPH and ABTS models with IC values of 2.

FOUND Trial: randomised controlled trial study protocol for case finding of obstructive sleep apnoea in primary care using a novel device.

Introduction: Obstructive sleep apnoea (OSA) is a common, but underdiagnosed, sleep disorder. If untreated, it leads to poor health outcomes, including Alzheimer's disease, cancer, cardiovascular disease and all-cause mortality. Our aim is to determine the feasibility and cost-effectiveness of moving the testing for OSA into general practice and how general practitioner (GP)-based screening affects overall detection rates.

Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

Objectives: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes.

Methods: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count.

Ivermectin for COVID-19 in adults in the community (PRINCIPLE): An open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes.

Background: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials.

Methods: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days.