Multiplicity Control in Oncology Clinical Trials With a Binary Surrogate Endpoint-Based Drop-The-Losers Design.

Typical phase 1 oncology studies identify the maximum tolerated dose as the "optimal" dose for subsequent phases. With the advancement of molecular targeted agents and immunotherapies, however, evaluating two or more doses has become increasingly critical for dose selection. Such evaluation is often done in phase 2 studies in a randomized manner.

PPARγ acetylation governs mammary adenocarcinoma tumor growth via acetylated residues that determine DNA sequence-specific binding.

Peroxisome proliferator-activated receptor γ (PPARγ), which is expressed in a variety of malignancies, governs biological functions through transcriptional programs. Defining the molecular mechanisms governing the selection of canonical versus non-canonical PPARγ binding sequences may provide the opportunity to design regulators with distinct functions and side effects. Acetylation at K268/293 in mouse Pparγ2 participates in the regulation of adipose tissue differentiation, and the conserved lysine residues (K154/155) in mouse Pparγ1 governs lipogenesis in breast cancer cells.

Treatment Comparison for a Single Arm Study Utilizing External Control: Performing Inference when Imputing Potential Outcomes.

Non-randomized comparative studies are often used to compare treatment effects between an investigational product and a control when randomization is not feasible or difficult in practice. A typical situation is that the product is investigated in a single-arm study, and the control data are collected in an external data source. For such a situation, we propose an alternative approach to draw inference on the treatment effect difference.

A Novel Field Resistance Mechanism: Two Structural Variations in FgOs1 Confer Ultrahigh Fludioxonil Resistance in without Disrupting FgOs1 Transcription or Translation.

, the causal agent of Fusarium head blight (FHB), reduces the wheat yield and quality. Fludioxonil, a phenylpyrrole fungicide, is registered in China for FHB control. In 2024, two structurally resistant variants in FgOs1 were identified from field isolates ZJ-44 and ZJ-78 in Hangzhou, Zhejiang, China.

X-ray stimulates NQO1-dependent cascade reactions to induce strong immunogenicity for MRI-guided cancer radio-chemodynamic-immunotherapy.

Immunogenicity activation is vital for radioimmunotherapy, but the short-term oxidative damage caused by precise radiation planning limits this effect. Chemodynamic therapy (CDT) with prolonged generation of hydroxyl radical (•OH) can initiate immunogenicity in combination with X-rays, however, its performance is constrained by tumor insufficient H2O2. Here, we propose to construct β-lapachone-based nanoparticles (β-Lap/Fe NPs) which initiate cascade reactions to generate high levels •OH for an extended period in tumor following X-ray irradiation.

Integrative Analysis of Plasma Proteomics and Transcriptomics Reveals Potential Therapeutic Targets for Psoriasis.

(PsO) is an immune-mediated inflammatory disease that imposes a significant burden on patients. Many patients experience relapse or inadequate responses, and PsO subtypes also lack effective therapies, highlighting the need for new therapeutic targets. We performed a proteome-wide Mendelian randomization (MR) to explore potential therapeutic targets for PsO.

Identification of novel biomarkers related to pathogenesis and treatment of psoriasis based on integrated analysis of weighted gene co-expression network analysis and LASSO.

Background: Psoriasis is an inflammatory skin disease, and current treatments have their own limitations, including moderate treatment effectiveness, poor compliance, and potential safety risks, etc. Therefore, the primary focus of this study is to explore novel molecular targets and improve the diagnosis and treatment of psoriasis patients.

Method: In this study, comprehensive bioinformatics analysis was performed on the expression profiles of tissue samples from patients with psoriasis in the clinical trial of TYK2/JAK1 inhibitor treatment (NCT02310750).

Hyperspectral Fluorescence Imaging with a New Polarity-Ultrasensitive Fluorescent Probe.

Hyperspectral fluorescence imaging (HSFI) could simultaneously offer morphological visualization and microenvironmental information through fluorescence wavelength-shifting of microenvironmental-sensitive fluorescent probes, yet its advancement is directly hindered by the scarcity of probes with sufficient spectral sensitivity. Herein, this study focuses on the development of an innovative fluorescent probe that exhibits heightened spectral sensitivity to microenvironmental changes and its advanced HSFI application. First, the comprehensive investigation of various donor-π-acceptor molecules uncovers the critical role of π-spacer on the wavelength sensitivity to microenvironment polarity.

Light-driven sp-C bond interconversion in black phosphorus/graphdiyne nanozyme for enhanced peroxidase-like activity and dual-mode detection of Vibrio vulnificus.

The development of high-performance nanozymes is often hindered by intrinsic activity limitations that restrict biosensing sensitivity. In this study, a black phosphorus/graphdiyne (BP/GDY) heterostructure nanozyme was engineered to overcome these challenges, exhibiting significantly enhanced peroxidase (POD)-like activity under light irradiation. Compared to pristine GDY and BP, the BP/GDY nanozyme demonstrated 11.

Insight into the Origin of Strong Metal-Support Interaction Obtained on an Inverse TiO/Au/AlO Quasi-Model Catalyst.

Strong metal-support interaction (SMSI) is one of the most important phenomena in the history of heterogeneous catalysis and has gained renewed attention in the past decade due to the emergence of various new types of SMSI. However, the origin of SMSI still remains in debate. Both minimizing surface energy and electron transfer have been regarded as the origin of SMSI because these two are hard to decouple in traditional supported metal catalysts.

Potential interactions between STING pathway and the complement system in immune regulation.

Introduction: The innate immune system's complement system and cGAS-STING pathway play crucial roles in pathogen defense and immune response modulation. Complement's role in cancer is multifaceted, affecting myeloid cells and T cell activities, while intracellular complement (complosome) participates in cellular processes like metabolism and autophagy. STING's activation influences tumor dynamics through NF-κB pathway interactions, enhancing or suppressing tumor responses.

Study on the dissolution and degradation patterns of cellulose in phosphonate-based ionic liquids and the construction of ternary phase diagrams.

The growing demand for sustainable materials necessitates green solvents for cellulose fiber production. This study addresses the unclear mechanisms of phosphonate-based ionic liquids (ILs) in cellulose dissolution and regeneration, which limit their industrial application. Five phosphonate-based ILs were synthesized and characterized: 1-butyl-3-methylimidazolium methylphosphonate ([Bmim]MP), 1-ethyl-3-methylimidazolium dimethylphosphate ([Emim]DMP), 1-ethyl-3-methylimidazolium ethylphosphonate ([Emim]EP), 1-ethyl-3-methylimidazolium methylphosphonate ([Emim]MP), and 1,3-dimethylimidazolium methylphosphonate ([Mmim]MP).

Exploring the therapeutic mechanism of Miao nationality medicine Qijiao Shengbai capsule on leukopenia based on multi-omics, network pharmacology and experimental verification.

Introduction: Leukopenia is caused by numerous factors, and modern drug therapies have obvious side effects, Qijiao Shengbai Capsule (QJSB) is a compound prescription developed from Miao medicine, widely used in clinical treatment of leukopenia. However, its mechanism of action for treating leukopenia remains unclear.

Objectives: This study aims to investigate the active ingredients, effects and underlying mechanism of QJSB on leukopenia.

Single-Atom Mediated d-Band Engineering of Platinum Nanocatalysts for High-Efficiency Acidic Hydrogen Evolution.

The rational construction of single-atom-mediated Pt catalysts with optimized electronic structures and robust stability remains a grand challenge for hydrogen evolution reaction (HER). Herein, spatial confinement coupled with a d-band engineering strategy is pioneered to fabricate cobalt single-atom coordinated Pt nanocatalysts (Pt@Co-SAs/NC), achieving exceptional HER activity with ultralow Pt loading (0.94 wt%).

Mechanistic insight into sp-hybridized carbon-induced dual electronic 'push effect' in Pt/graphdiyne/graphene for boosting oxidase-like activity.

Efficient oxidase-mediated oxidation is pivotal for environmental remediation and energy conversion application, yet natural enzymes require artificial alternatives due to inherent instability. Cofactors are essential in natural oxidase catalysis, interacting with the active centre to induce an electronic 'push effect' that propels the catalytic process. While efforts to mimic cofactors in nanozyme often involve sophisticated designs and complex synthesis.

Fitness and Resistance Mechanism of from Fields to Demethylation Inhibitor (DMI) Fungicides in China.

Tebuconazole and prothioconazole are triazole sterol demethylation inhibitor (DMI) fungicides widely used for controlling head blight (FHB) in the world. In 2023, 3714 isolates were collected from fields of 8 provinces in China, among which 116 (3.12%) isolates and 82 (2.

Factors Influencing Resistivity Inversion for CO Geological Storage Zones: A Quantitative Study.

This study establishes a homogeneous half-space and a horizontally layered two-layer background stratigraphy model using cross-borehole electrical resistivity tomography (ERT) based on an incomplete Gauss-Newton (IGN) method to investigate the resistivity inversion characteristics of CO storage zones. The effects of storage zone volume (VCO2), storage zone resistivity (ρCO2), background formation resistivity (ρf), and CO diffusion on inversion results were systematically analyzed, and the mechanisms underlying the influence of different parameters on inversion imaging were explored. The results indicate that an increase in the VCO2 significantly affects the inverted resistivity.

Exploring the Potential Link Between Autoimmune Diseases and Pan-Cancer: A Multidatabase Mendelian Randomization Analysis.

The relationship between autoimmune diseases (AIDs) and cancer is unclear and this study aimed to investigate the relationship between AIDs and cancer at the genetic level using Mendelian randomization (MR). The study employed two-sample MR and meta-analysis to investigate the association between AIDs and 33 types of cancer, following STROBE-MR guidelines. Single nucleotide polymorphisms (SNPs) associated with AIDs were used as instrumental variables, with data from FinnGen, UK Biobank, and other databases.

Rapid and sensitive Mycoplasma detection in antibody bioprocessing via RPA-CRISPR/Cas12a.

Mycoplasma species are prevalent microbial contaminants in the production of biological products, such as monoclonal antibodies, posing significant threats to the safety and efficacy of these products. Current regulatory guidelines as well as pharmacopoeias mandate the demonstration of the absence of Mycoplasma in the cell culture and further downstream processing to ensure product safety. Despite recent advancements in sensitive detection techniques for Mycoplasma in eucaryotic expression systems, these methods remain complex and time-consuming.

Rational development of Nile red derivatives with significantly improved specificity and photostability for advanced fluorescence imaging of lipid droplets.

Since the first report of Nile Red as a fluorescent probe for lipid droplets (LDs) imaging was published in 1985, this fluorescent probe has been widely used for nearly 40 years, and so far, it is still one of the most commonly used probes for LDs imaging. Although Nile Red has achieved continuous success, it has gradually emerged two major limitations (poor LDs specificity and low photostability) which directly limit the study of LDs via advanced fluorescence imaging techniques. In this context, we have developed a new synthetic route to conveniently prepare a series of Nile Red derivatives (NR-1 to NR-15).

Dual-Bessel-Beam Stimulated Emission Depletion Microscopy for Super-resolution Volumetric Projection Imaging of Lipid Droplet Dynamics.

Volumetric imaging efficiently captures comprehensive spatial structures and dynamic function information on organisms in biomedical research. However, optical diffraction limit restricts the visualization of fine structure details at nanoscale. To address this limitation, we developed dual-Bessel-beam stimulated emission depletion (DB-STED) microscopy to enhance the information throughput and lateral resolution.

Using Propensity Score Weighting to Enhance the Operating Characteristics of Power Prior in Leveraging External Data to Augment a Traditional Clinical Study.

The method of power prior has long been used as a tool for leveraging external data to augment a traditional clinical study. More recently, it has been found that integrating propensity scoring into its application has the potential for improved operating characteristics. In this paper, we introduce a new propensity score-integrated power prior strategy which uses propensity score weighting and is distinctive from other such proposals in the literature.

Fuzzy control algorithm of cleaning parameters of street sweeper based on road garbage volume grading.

The research examines the challenges city street sweepers face, which struggles to adapt cleaning settings based on varying road garbage volume, resulting in inefficient cleaning and high energy consumption. The study proposes a fuzzy control algorithm for adjusting the cleaning parameters of street sweepers based on road garbage volume grading. It starts by utilizing the YOLO (You Only Look Once) v5 deep learning model for target detection and garbage classification on road surfaces.

NebulaPlate: a droplet microfluidic platform to analyze platelet aggregation.

The accurate assessment of platelet activity is crucial in clinical practice and scientific research owing to the pivotal role of platelets in the progression of cardiovascular conditions, such as arterial thrombotic diseases. However, conventional platelet activity assessment methods are currently limited by their requirement of substantial blood samples and inadequate high-throughput capabilities, and therapeutic resistance induced by antiplatelet agents impedes treatment efficacy. In this study, we developed a microdroplet-based platelet function detection method, referred to as NebulaPlate, to achieve miniaturized and robust platelet activity assessment, thereby overcoming current challenges.

Effects of different organic materials and reduced nitrogen fertilizer application on sorghum yield and soil nutrients.

Rapeseed and sorghum, important economic crops in China, generate abundant straw resources. However, studies examining the effects of straw return combined with reduced nitrogen fertilization on soil quality are still insufficient to meet the precise fertilization needs, necessitating further research. This study employed two treatments: rapeseed straw plus sorghum straw (LT) and rapeseed green manure plus sorghum straw (YGT) returned to the soil.