The Efficacy and Safety of Durvalumab and Tremelimumab with Concomitant Treatment for MSS/pMMR Metastatic Colorectal Cancer: A Single Arm Meta-Analysis.

Objectives: To address the issue that most microsatellite-stable (MSS) and proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) patients have minimal response to immunotherapy, this meta-analysis evaluated the efficacy and safety of durvalumab and tremelimumab with concomitant treatment in treating MSS/pMMR metastatic colorectal cancer.

Methods: All included trials were prospective studies with a median patient age of 63 years, of which 94.2% were MSS/pMMR mCRC patients, with a male to female ratio of 1.

End-to-End Deep Learning Prediction of Neoadjuvant Chemotherapy Response in Osteosarcoma Patients Using Routine MRI.

This study aims to develop an end-to-end deep learning (DL) model to predict neoadjuvant chemotherapy (NACT) response in osteosarcoma (OS) patients using routine magnetic resonance imaging (MRI). We retrospectively analyzed data from 112 patients with histologically confirmed OS who underwent NACT prior to surgery. Multi-sequence MRI data (including T2-weighted and contrast-enhanced T1-weighted images) and physician annotations were utilized to construct an end-to-end DL model.

Structural basis for human NKCC1 inhibition by loop diuretic drugs.

Na-K-Cl cotransporters functions as an anion importers, regulating trans-epithelial chloride secretion, cell volume, and renal salt reabsorption. Loop diuretics, including furosemide, bumetanide, and torsemide, antagonize both NKCC1 and NKCC2, and are first-line medicines for the treatment of edema and hypertension. NKCC1 activation by the molecular crowding sensing WNK kinases is critical if cells are to combat shrinkage during hypertonic stress; however, how phosphorylation accelerates NKCC1 ion transport remains unclear.

Ubiquitin-specific protease 7 exacerbates acute pancreatitis progression by enhancing ATF4-mediated autophagy.

Acute pancreatitis (AP) is a serious inflammatory disease with high incidence rate and mortality. It was confirmed that overactivation of autophagy in acinar cells can increase the risk of AP. Nevertheless, the regulatory mechanism of autophagy in AP is unclear.

Prediction model and real-time diagnostics of hydraulic fracturing pressure for highly deviated wells in deep oil and gas reservoirs.

It is a common occurrence in the fracture processes of deep carbonate reservoirs that the fracturing construction pressure during hydraulic fracturing operation exceeds 80 MPa. The maximum pumping pressure is determined by the rated pressure of the pumping pipe equipment and the reservoir characteristics, which confine the fracture to the target area. When the pump pressure exceeds the safety limit, hydraulic fracturing has to reduce the construction displacement to prevent potential accidents caused by overpressure.

A practical methodology for incorporating volume-translated equation of states in isochoric-isothermal phase equilibrium calculations for liquid phase pressure prediction.

Accurately predicting the phase behavior and properties of reservoir fluid plays an essential role in the simulation of petroleum recovery processes. Similar to the inaccurate liquid-density prediction issue in the isobaric-isothermal (PT) phase equilibrium calculations, an inaccurate pressure prediction issue can also be observed in isothermal-isochoric (VT) phase equilibrium calculations which involves a liquid phase. In this work, a practical methodology is proposed to incorporate a volume-translated equation of state in VT phase equilibrium calculations for more accurate pressure predictions.

A copy number variation detection method based on OCSVM algorithm using multi strategies integration.

Copy number variation (CNV) is an important part of human genetic variations, which is associated with various kinds of diseases. To tackle the limitations of traditional CNV detection methods, such as restricted detection types, high error rates, and challenges in precisely identifying the location of variant breakpoints, a new method called MSCNV (copy number variations detection method for multi-strategies integration based on a one-class support vector machine model) is proposed. MSCNV establishes a multi-signal channel that integrates three strategies: read depth, split read, and read pair.

Impacts of climate change on the suitable habitat of Angelica sinensis and analysis of its drivers in China.

Climate change is shifting optimal habitats for medicinal plants, potentially compromising the efficacy and therapeutic value of herbal remedies. Global warming and increased extreme weather events threaten the sustainability and pharmaceutical integrity of Angelica sinensis (Oliv.) Diels (A.

Enhanced phosphorus weathering contributed to Late Miocene cooling.

Late Miocene climate evolution provides an opportunity to assess Earth's climate sensitivity to carbon cycle perturbation under warmer-than-modern conditions. Despite its relevance for understanding the climate system, the driving mechanisms underlying profound climate and carbon cycle changes - including the enigmatic Late Miocene cooling from 7 to 5.4 million years ago - remain unclear.

Enantioselective reductive cross-couplings to forge C(sp)-C(sp) bonds by merging electrochemistry with nickel catalysis.

Motivated by the inherent benefits of synergistically combining electrochemical methodologies with nickel catalysis, we present here a Ni-catalyzed enantioselective electroreductive cross-coupling of benzyl chlorides with aryl halides, yielding chiral 1,1-diaryl compounds with good to excellent enantioselectivity. This catalytic reaction can not only be applied to aryl chlorides/bromides, which are challenging to access by other means, but also to benzyl chlorides containing silicon groups. Additionally, the absence of a sacrificial anode lays a foundation for scalability.

Quantification and optimization of platinum-molybdenum carbide interfacial sites to enhance low-temperature water-gas shift reaction.

Pt/α-MoC catalysts exhibit exceptional activity in low-temperature water-gas shift reactions. However, quantitatively identifying and fine-tuning the active sites has remained a significant challenge. In this study, we reveal that fully exposed monolayer Pt nanoclusters on molybdenum carbides demonstrate mass activity that exceeds that of bulk molybdenum carbide catalysts by one to two orders of magnitude at 100-200 °C for low-temperature water-gas shift reactions.

Coupling CuO clusters and imine-linked COFs on microfiltration membranes for fast and robust water sterilization.

As bacterial contamination crises escalate, the development of advanced membranes possessing both high flux and antibacterial properties is of paramount significance for enhancing water sterilization efficiency. Herein, an ultrathin layer of TbPa (an imine-linked covalent organic framework) and nanosized CuO clusters, sequentially deposited onto polyethersulfone membranes, demonstrate exceptional water flux performance, reaching a permeance level of 16000 LHM bar. The deposited TbPa, generating uniformly distributed reduction sites under illumination, facilitates the uniform formation of CuO clusters.

Skull bone marrow and skull meninges channels: redefining the landscape of central nervous system immune surveillance.

The understanding of neuroimmune function has evolved from concepts of immune privilege and protection to a new stage of immune interaction. The discovery of skull meninges channels (SMCs) has opened new avenues for understanding central nervous system (CNS) immunity. Here, we characterize skull bone marrow and SMCs by detailing the anatomical structures adjacent to the skull, the differences between skull and peripheral bone marrow, mainstream animal processing methods, and the role of skull bone marrow in monitoring various CNS diseases.

Design, Structure Optimization, and Preclinical Characterization of JAB-21822, a Covalent Inhibitor of KRAS.

KRAS is the most frequently mutated driver oncogene in human cancer, and KRAS mutation is commonly found in non-small-cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). Inhibitors that covalently modify the mutated codon 12 cysteine have completed proof-of-concept studies in the clinic. Here, we describe structure-based design and cocrystal-aided drug optimization of a series of compounds with the 1,8-naphthyridine-3-carbonitrile scaffold.

Bias-Induced Ga-O-Ir Interface Breaks the Limits of Adsorption-Energy Scaling Relationships for High-Performing Proton Exchange Membrane Electrolyzers.

Rationally manipulating the in-situ formed catalytically active surface of catalysts remains a significant challenge for achieving highly efficient water electrolysis. Herein, we present a bias-induced activation strategy to modulate in-situ Ga leaching and trigger the dynamic surface restructuring of lamellar Ir@Ga2O3 for the electrochemical oxygen evolution reaction. The in-situ reconstructed Ga-O-Ir interface sustains high water oxidation rates at OER overpotentials.

Prediction-based rapid force control of a single-acting pneumatic cylinder under hysteresis nonlinearity.

Hysteresis characteristics widely affects the performance and reliability of pneumatic systems across various industrial applications. Addressing this challenge can significantly enhance system efficiency and precision. This paper aims to develop a rapid and accurate method for controlling the actuating force of a Single-Acting Pneumatic Cylinder (SAPC), considering hysteresis characteristic.

Brain-Computer Interface and Electrochemical Sensor Based on Boron-Nitrogen Co-Doped Graphene-Diamond Microelectrode for EEG and Dopamine Detection.

The simultaneous detection of electroencephalography (EEG) signals and neurotransmitter levels plays an important role as biomarkers for the assessment and monitoring of emotions and cognition. This paper describes the development of boron and nitrogen codoped graphene-diamond (BNGrD) microelectrodes with a diameter of only 200 μm for sensing EEG signals and dopamine (DA) levels, which have been developed for the first time. The optimized BNGrD microelectrode responded sensitively to both EEG and DA signals, with a signal-to-noise ratio of 9 dB for spontaneous EEG signals and a limit of detection as low as 124 nM for DA.

Diverse pathways for the treatment of Parkinson's disease: Integration and development of traditional and emerging therapies.

Parkinson's disease (PD) is the second most common central neurodegenerative disease in the world after Alzheimer's disease (AD), which mainly occurs in middle-aged and elderly people, and is increasing with the aging of the population. With the increasing incidence of PD, it is particularly important to explore its pathology and provide effective interventions and treatments. The pathogenesis of PD involves a variety of factors such as genetics, environment, and age, and is not yet fully understood.

Deep eutectic solvent-mediated extraction of lignin: A novel strategy for producing high-quality biopolymers in controlled-release mulching applications.

Microplastic contamination of low-density polyethylene mulch and nutrient loss from fertilizers present significant challenges in the crop-growing. In this study, the focus was on creating a biodegradable film that combines the advantages of plastic film, thermal insulation and water retention, as well as the controlled release of fertilizer. A key innovation was the efficient introduction of low molecular weight and low dispersibility of poplar lignin into chitosan and polyvinyl alcohol matrices.

Flame retardancy and durability of cotton fabric modified with high-efficiency diboraspiro rings groups flame retardant.

The synthesis of highly efficient and environmentally friendly flame retardants through the synergistic interaction of boron, phosphorus and nitrogen is becoming a new research direction. In this study, N-DBSPA, a flame retardant with high flame retardancy, high thermal stability and high efficiency, was prepared by the reaction between pentaerythritol borate and amino trimethylene phosphate, and the limiting oxygen index (LOI) of the modified cotton fabric increased from 18 % to 44.7 % at a weight gain (WG) of 20.

Targeted Gut Microbiome Therapy: Applications and Prospects of Probiotics, Fecal Microbiota Transplantation and Natural Products in the Management of Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM.

Exploring the genetic causal inference between plasma lipidome and hemorrhagic stroke.

Objectives: Recent research indicates that the plasma lipidome composition may undergo alterations following hemorrhagic stroke. Nevertheless, the causal inference between plasma lipidome and hemorrhagic stroke remains elusive.

Materials And Methods: Exposure data were achieved from a recent Genome-wide Association Study (GWAS) study of 179 lipid species involving 7,174 individuals, while the outcome data were obtained from the FinnGen consortium (R10), including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and non-traumatic intracranial hemorrhage (nITH).

Lung-targeted delivery of PTEN mRNA combined with anti-PD-1-mediated immunotherapy for In Situ lung cancer treatment.

mRNA-based protein replacement therapy has become one of the most widely applied forms of mRNA therapy, with lipid nanoparticles (LNPs) being extensively studied as efficient delivery platforms for mRNA. However, existing LNPs tend to accumulate in the liver or kidneys after intravenous injection, highlighting the need to develop vectors capable of targeting specific organs. In this study, we synthesized a small library of ionizable lipids and identified PPz-2R as a promising candidate, exhibiting lung-targeting capabilities, high mRNA transfection efficiency, and good stability through structure-activity relationship studies.

Regulatory networks of bZIPs in drought, salt and cold stress response and signaling.

Abiotic stresses adversely impact plants survival and growth, which in turn affect plants especially crop yields worldwide. To cope with these stresses, plant responses depend on the activation of molecular networks cascades, including stress perception, signal transduction, and the expression of specific stress-related genes. Plant bZIP (basic leucine zipper) transcription factors are important regulators that respond to diverse abiotic stresses.