Basic Considerations for Data Pooling Strategy in Multi-Regional Clinical Trials (MRCTs).

The National Medical Products Administration of China has been implementing ICH E17, which describes the general principles for planning and designing of multi-regional clinical trials (MRCTs), yet there are several ambiguities in the execution and conduct remains in China or East Asia. In specific, pooling strategy, effect modifiers (EMs), statistical analysis, sample size allocation and their impact in alignment with global trial remains a challenge. In this paper, we explore on the criteria mentioned above under the context of China.

Separating nanobubble nucleation for transfer-resistance-free electrocatalysis.

Electrocatalytic gas-evolving reactions often result in bubble-covered surfaces, impeding the mass transfer to active sites. Such an issue will be worsened in practical high-current-density conditions and can cause sudden cell failure. Herein, we develop an on-chip microcell-based total-internal-reflection-fluorescence-microscopy to enable operando imaging of bubbles at sub-50 nm and dynamic probing of their nucleation during hydrogen evolution reaction.

Insights into excitonic behavior in single-atom covalent organic frameworks for efficient photo-Fenton-like pollutant degradation.

The generation of radicals through photo-Fenton-like reactions demonstrates significant potential for remediating emerging organic contaminants (EOCs) in complex aqueous environments. However, the excitonic effect, induced by Coulomb interactions between photoexcited electrons and holes, reduces carrier utilization efficiency in these systems. In this study, we develop Cu single-atom-loaded covalent organic frameworks (Cu/COFs) as models to modulate excitonic effects.

Basic Considerations for the Consistency Evaluation Based on ICH E17 Guideline.

In the International Council for Harmonisation (ICH) guidance on General Principles for Planning and Design of Multi-Regional Clinical Trials (E17), it is important to evaluate the consistency of treatment effect across regions in a multi-regional clinical trial (MRCT). In this paper, we elaborated on some basic considerations to evaluate consistency. We first list the design considerations, and then provide consistency evaluation and interpretation on pharmacokinetics, pharmacodynamics, efficacy, safety, and benefit-risk.

Multiomic characterization, immunological and prognostic potential of SMAD3 in pan-cancer and validation in LIHC.

SMAD3, a protein-coding gene, assumes a pivotal role within the transforming growth factor-beta (TGF-β) signaling pathway. Notably, aberrant SMAD3 expression has been linked to various malignancies. Nevertheless, an extensive examination of the comprehensive pan-cancer impact on SMAD3's diagnostic, prognostic, and immunological predictive utility has yet to be undertaken.

Supervillin-Mediated ZO-1 Downregulation Facilitates Migration of Cisplatin-Resistant HCT116 Colorectal Cancer Cells.

Supervillin (SVIL), the biggest member of the villin/gelsolin superfamily, has recently been reported to promote the metastasis of hepatocellular carcinoma by stimulating epithelial-mesenchymal transition (EMT). However, little is known about the roles of SVIL in the migration of colorectal cancer cells. Here, we investigated the effects of SVIL on the migration of cisplatin-resistant colorectal cancer cells.

Longitudinal trajectories of digital upper limb biomarkers for multiple sclerosis.

Background: Upper limb dysfunction is a common debilitating feature of relapsing-remitting multiple sclerosis (RRMS). We aimed to examine the longitudinal trajectory of the iPad®-based Manual Dexterity Test (MDT) and predictors of change over time.

Methods: We prospectively enrolled RRMS patients (limited to Expanded Disability Status Scale (EDSS) < 4).

Association between high-density lipoprotein cholesterol and risk of abdominal aortic aneurysm among males and females aged 60 years and over.

Objective: Whether high-density lipoprotein cholesterol (HDL-C) has a protective role against abdominal aortic aneurysm (AAA) development in both older males and females remains uncertain. This study aims to assess the sex-specific association between HDL-C and incident AAA in older adults from the UK Biobank.

Methods: This cohort study included 86,184 males and 95,682 females aged ≥60 years from the UK biobank.

Screening, identification, and application of aptamers against allergens in food matrices.

Food allergies have become one of the most pressing issues in food safety and public health globally along with their incidence increasing in recent years. The reliable recognition of allergens from different sources, especially food-hidden allergens, is essential for preventing and controlling food allergies. Recently, aptamers, as emerging recognition elements, have gained considerable attention in food allergy, especially in the detection of food allergens.

Study on the Role of microRNA-138-5p Through Sorbin and SH3 Domain-Containing Protein 2 in Breast Cancer.

Breast cancer (BRCA) is one of the major threats to women's health worldwide. This study focuses on the roles of sorbin and SH3 domain-containing protein 2 (SORBS2) protein and microRNA-138-5p in the progression of BRCA, analyzing their regulatory effects on cancer cell proliferation, cell cycle, and migration ability. Using bioinformatics tools and experimental methods, the study found that SORBS2 is commonly underexpressed in BRCA.

Electrocatalytic nitrate reduction using iron single atoms for sustainable ammonium supplies to increase rice yield.

Increasing food production and ensuring drinking water safety have always been a focus of attention, especially for people in underdeveloped regions of the world. Traditional excessive fertilizer applications have increased crop yield but also caused groundwater nitrate pollution. Agricultural irrigating water is an important reservoir for nitrogen (N) (e.

Evaluating KLHDC8A as a biomarker for glioma: impact on survival and proliferation through the Wnt/β-catenin pathway.

Glioma is one of the most common malignant tumors and shows a high metastasis rate and poor prognosis. KLHDC8A has been implicated in several cancers, but its role in glioma and its potential as a biomarker remain unclear. We conducted a pan-cancer analysis of KLHDC8A using multiple databases and assessed its expression levels, survival associations, and diagnostic utility.

Neuropathic Pain Induced by Spinal Cord Injury from the Glia Perspective and Its Treatment.

Regional neuropathic pain syndromes above, at, or below the site of spinal damage arise after spinal cord injury (SCI) and are believed to entail distinct pathways; nevertheless, they may share shared defective glial systems. Neuropathic pain after SCI is caused by glial cells, ectopic firing of neurons endings and their intra- and extracellular signaling mechanisms. One such mechanism occurs when stimuli that were previously non-noxious become so after the injury.

Real-time visualization of "small Molecules-ssDNA" complexes for aptamer screening based on online competition CE-SELEX.

Capillary electrophoresis-based systematic evolution of ligands by exponential enrichment (CE-SELEX) is one of the most efficient techniques for aptamers screening. However, CE-SELEX is generally considered challenging for small molecule targets due to a slight charge-to-mass ratio (z/m) difference that fails to create a clear separation between small molecule-ssDNA complexes and ssDNA libraries, thus heavily restricting the screening target scopes. Herein, a novel online competition CE-SELEX (ocCE-SELEX) strategy was introduced for real-time visualization of "small molecules-ssDNA" complexes to screen aptamers for small molecule targets in free solution.

Processing and properties of graphene-reinforced polylactic acid nanocomposites for bioelectronic and tissue regenerative functions.

An in-situ polymer-solution-processing approach enables the efficient production of uniform graphene-reinforced polylactic acid (G-PLA) nanocomposites with notable physical and biomedical properties. The approach effectively enhances the interfacial bonding between graphene and PLA by creating graphene dangling bonds and defects during exfoliation. As a result, an 182 % increase in Young's modulus and an 85 % increase in tensile strength can be achieved in G-PLA.

Computed tomography enterography-based deep learning radiomics to predict stratified healing in patients with Crohn's disease: a multicenter study.

Objectives: This study developed a deep learning radiomics (DLR) model utilizing baseline computed tomography enterography (CTE) to non-invasively predict stratified healing in Crohn's disease (CD) patients following infliximab (IFX) treatment.

Methods: The study included 246 CD patients diagnosed at three hospitals. From the first two hospitals, 202 patients were randomly divided into a training cohort (n = 141) and a testing cohort (n = 61) in a 7:3 ratio.

Aptamer-functionalized magnetic blade spray coupled with a nucleic acid dye-based mass tag strategy for miniature mass spectrometry analysis of endoglin.

Ambient ionization mass spectrometry (AIMS) allows rapid analysis of targets, while its overall selectivity is somewhat limited due to the lack of chromatographic separation. Recently, magnetic blade spray (MBS) has enhanced AIMS by incorporating immunomagnetic beads instead of the traditional coated blade spray (CBS) coating, thereby improving selectivity and sensitivity by targeted analyte detection and reducing background interference. In this study, an aptamer-functionalized and nucleic acid dye (GelRed)-loaded MS probe (AGMP) was developed and employed with MBS-based miniature mass spectrometer.

The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study.

Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort.

Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort.

LRRC45 accelerates bladder cancer development and ferroptosis inhibition via stabilizing NRF2 by competitively KEAP1 interaction.

Centrosomal dysregulation is closely linked to the genesis and progression of tumors. A comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data has revealed that leucine-rich repeat-containing protein 45 (LRRC45), a centrosome linker protein crucial for maintaining centrosome cohesion and a member of the leucine-rich repeat-containing proteins (LRRCs) family, is significantly upregulated in bladder cancer. Notably, the elevated expression levels of LRRC45 were strongly correlated with a poor prognosis in patients.

Chitosan-Modified Hydrogel Microsphere Encapsulating Zinc-Doped Bioactive Glasses for Spinal Cord Injury Repair by Suppressing Inflammation and Promoting Angiogenesis.

Spinal cord injury (SCI) is a common nerve injury caused by external force, resulting in sensory and motor impairments. Previous studies demonstrated that inhibiting the neuroinflammation promoted SCI repair. However, these approaches are low efficient, and lack targeting specificity, and even require repeated and high doses of systemic administration.

Matrix Background Screening of an ssDNA Aptamer and Its Identification Against Lactopontin.

Lactopontin (LPN) is a highly phosphorylated O-glycosylated acidic protein closely associated with infant gut, brain, and immune development, and its recognition is urgent due to its rising application in fortified dairy products and infant formula. In this study, an ssDNA aptamer against LPN was obtained, among which two kinds of matrix-background-assisted systematic evolution of ligands via exponential enrichment (SELEX) approaches were performed and compared. The direct approach was to utilize the sample matrix as the mixing-incubation background between the ssDNA library and LPN that can theoretically increase screening pressure and simulate practical application scenarios.

2-Bromopalmitate-Induced Intestinal Flora Changes and Testicular Dysfunction in Mice.

2-Bromopalmitate (2-BP) is a palmitoylation inhibitor that can prevent the binding of palmitic acid to proteins, thereby exhibiting significant effects in promoting inflammation and regulating the immune system. However, limited research has been conducted regarding the direct effects of 2-BP on the animal organism. Therefore, we probed mice injected with 2-BP for altered expression of inflammatory genes, with a focus on demonstrating changes in the intestinal flora as well as damage to the reproductive system.