Warming climate and water withdrawals threaten river flow connectivity in China.

River flow connectivity, the continuity of fluvial discharge in space and time, provides a crucial lifeline for most biotic communities on Earth. Yet there is still limited understanding of the impacts of climate change and human water withdrawal on river connectivity. Here, we assess the river flow connectivity of 217,001 river reaches in mainland China from 1961 to 2020 and the impact of different climate warming trends and water withdrawals for different sectors.

Bispecific killer cell engager-secreting CAR-T cells redirect natural killer specificity to enhance antitumour responses.

T cells and natural killer (NK) cells collaborate to maintain immune homeostasis. Current cancer immunotherapies predominantly rely on the individual application of these cells. Here we use bicistronic vectors to co-express chimeric antigen receptors (CARs) and secreted immune cell engagers (ICEs), leveraging the combined therapeutic potential of both effector cell types.

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.

Characterization of Mechanical Property Evolution and Durability Life Prediction of Engineered Cementitious Composites Under Frozen State.

Engineered cementitious composites (ECCs) exhibit superior mechanical properties (MPs) and excellent crack control capabilities, making them widely used in practical engineering applications. However, the MPs of ECCs in frozen states (FSs), particularly their flexural properties (FPs), still need to be better understood. MP tests were designed for frozen ECC samples to investigate the service performance of ECCs in an FS.

Uncovering host response in adults with severe community-acquired pneumonia: a proteomics and metabolomics perspective study.

Background: Community-acquired pneumonia (CAP) represents a significant public health concern due to its widespread prevalence and substantial healthcare costs. This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP.

Methods: We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP.

A retrospective study to predict failure of high-flow oxygen therapy for acute hypoxic respiratory failure.

Objective: This study aimed to analyze the characteristics of patients who fail high-flow nasal cannula(HFNC) therapy for acute hypoxemic respiratory failure(AHRF) and to identify predictors of treatment failure.

Methods: This single-center, retrospective, observational study analyzed clinical data from 388 patients with AHRF. Patients were divided into two groups: the HFNC success group (HFNC-S, n = 256) and the HFNC failure group (HFNC-F, n = 132).

Remote Ischemic Postconditioning Protects the Neurovascular Units in MCAO/R Rats through HIF-1α-Mediated Pathway.

Remote ischemic postconditioning (RIPostC), administered after the onset of local ischemia, has been shown to have beneficial effects on neurological, vascular, and motor functions in animal models. However, the precise mechanisms and interactions underlying these functional improvements remain unclear. Our study aimed to determine whether RIPostC exerts protective effects on the neurovascular units (NVU) and to investigate whether this protection is mediated by hypoxia-inducible factor-1α (HIF-1α).

Remote Ischemic Postconditioning Improve Cerebral Ischemia-Reperfusion Injury Induced Cognitive Dysfunction through Suppressing Mitochondrial Apoptosis in Hippocampus via TK/BK/B2R-Mediated PI3K/AKT.

Remote ischemic postconditioning (RIPostC) is known to improve motor function recovery in animal models, but its efficacy in alleviating cognitive impairment caused by ischemic stroke remains unclear. This study aims to investigate the beneficial role of RIPostC in recovering cognitive impairment induced by cerebral ischemia-reperfusion injury (CIRI). Building upon our previous research findings, we proved that the TK/BK/B2R pathway is crucial for understanding the crosstalk between cognitive impairment and RIPostC.

Myeloid-Driven Immune Suppression Subverts Neutralizing Antibodies and T Cell Immunity in Severe COVID-19.

The objective of this study was to better understand immune failure mechanisms during severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 infection, which are critical for developing targeted vaccines and effective treatments. We collected 34 cases representing different disease severities and performed high-quality single-cell TCR/BCR sequencing to analyze the peripheral immune cell profiles. Additionally, we assessed antibody-neutralizing activity through in vitro experiments.

Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis.

Background: Clinical implications of metagenomics next-generation sequencing (mNGS) in sepsis have not been fully evaluated. This study aimed to determine the diagnostic, therapeutic, and prognostic impacts of mNGS in sepsis.

Methods: This multicenter prospective study was conducted at 19 sites in China from 2020 to 2021, and 859 adult patients hospitalized with sepsis were enrolled.

Germline variants analysis of Chinese breast cancer patients reveals numerous alterations in homologous recombination genes.

Purpose: We aimed to identify the pathogenic variants of homologous recombination (HR) genes and analyze the correlation between the pathogenic variants and clinical characteristics in Chinese breast cancer patients.

Methods: A cohort of 178 breast cancer patients participated in this study. We assessed genomic alterations using a 23-gene panel, which includes most of the HR-related genes and DNA mismatch repair (MMR) gene, through next-generation sequencing.

Fabrication of micro-wire stent electrode as a minimally invasive endovascular neural interface for vascular electrocorticography using laser ablation method.

. Minimally invasive endovascular stent electrode is a currently emerging technology in neural engineering with minimal damage to the neural tissue. However, the typical stent electrode still requires resistive welding and is relatively large, limiting its application mainly on the large animal or thick vessels.

Co-blocking TIGIT and PVRIG Using a Novel Bispecific Antibody Enhances Antitumor Immunity.

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) and poliovirus receptor-related immunoglobulin domain (PVRIG) are immune checkpoints co-expressed on activated T and NK cells, contributing to tumor immune evasion. Simultaneous blockade of these pathways may enhance therapeutic efficacy, positioning them as promising dual targets for cancer immunotherapy. This study aimed to develop a bispecific antibody (BsAb) to co-target TIGIT and PVRIG.

Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management.

Background: Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

Purpose: This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

Bidirectional interaction between IL and 17A/IL-17RA pathway dysregulation and α-synuclein in the pathogenesis of Parkinson's disease.

Parkinson's disease (PD) pathogenesis is characterized by α-synuclein (α-syn) pathology, which is influenced by various factors such as neuroinflammation and senescence. Increasing evidence has suggested a pivotal role for Interleukin-17A(IL-17A) and Interleukin-17 Receptor A (IL-17RA) in PD, yet the trigger and impact of IL-17A/IL-17RA activation in PD remains elusive. This study observed an age-related increase in IL-17A and IL-17RA in the human central nervous system, accompanied by increased α-syn and senescence biomarkers.

Prenylated Dihydroflavonol from Regulate the Polarization and Phagocytosis of Macrophages In Vitro.

As an important member of innate immunity, macrophages show remarkable plasticity and heterogeneity, and play an important role in immune regulation, tissue development, homeostasis of the internal environment and injury repair. However, the excessive activation of macrophages is closely related to the occurrence and development of many diseases. The prenylated flavonoid structure is one of the characteristic structures isolated from , with anti-inflammatory, anti-tumor, anti-allergy and other effects.

Harnessing Competitive Interactions to Regulate Supramolecular "Micelle-Droplet-Fiber" Transition and Reversibility in Water.

The supramolecular assembly of proteins into irreversible fibrils is often associated with diseases in which aberrant phase transitions occur. Due to the complexity of biological systems and their surrounding environments, the mechanism underlying phase separation-mediated supramolecular assembly is poorly understood, making the reversal of so-called irreversible fibrillization a significant challenge. Therefore, it is crucial to develop simple model systems that provide insights into the mechanistic process of monomers to phase-separated droplets and ordered supramolecular assemblies.

[Resveratrol enhances the local antioxidant ability of the ovary in rats with polycystic ovary syndrome].

Objective: To investigate the effects of resveratrol (RSV) on ovarian morphology, plasma anti-Müllerian hormone (AMH) and insulin-like growth factor 1 levels (IGF-1), and oxidative stress parameters in rats with polycystic ovary syndrome (PCOS).

Methods: Forty-six rats were randomly divided into a normal control (n = 12), a PCOS model control (n = 12), a rosiglitazone (RSG, n = 11), and an RSV group (n = 11). The PCOS model was established in the latter three groups by rejection of epidehydroandrosterone.

Molecularly Engineered Supramolecular Thermoresponsive Hydrogels with Tunable Mechanical and Dynamic Properties.

Synthetic supramolecular polymers and hydrogels in water are emerging as promising biomaterials due to their modularity and intrinsic dynamics. Here, we introduce temperature sensitivity into the nonfunctionalized benzene-1,3,5-tricarboxamide () supramolecular system by incorporating a poly(-isopropylacrylamide)-functionalized ( moiety, enabling 3D cell encapsulation applications. The viscous and structural properties in the solution state as well as the mechanical and dynamic features in the gel state of mixtures were investigated and modulated.

Integrative multi-omics analysis unravels the host response landscape and reveals a serum protein panel for early prognosis prediction for ARDS.

Background: The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified.

Methods: We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm.

Physiological and transcriptomic analyses provide preliminary insights into the autotoxicity of .

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Generation of a human iPSC line from a Parkinson's disease patient with a novel CHCHD2 mutation (p.R145Q).

Mutations in CHCHD2 have been reported to be associated with familial Parkinson's disease (PD). We generated a human induced pluripotent stem cell (hiPSC) line by reprogramming dermal fibroblasts from a PD patient harboring a novel CHCHD2 mutation (c.434G > A, p.

Superparamagnetic Iron Oxide Nanoparticles Reprogram the Tumor Microenvironment and Reduce Lung Cancer Regrowth after Crizotinib Treatment.

ALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates. Growing evidence suggests that the combination of drug and immune therapies greatly improves patient survival; however, due to the low immunogenicity of the tumors, ALK-positive patients do not respond to currently available immunotherapies. Tumor-associated macrophages (TAMs) play a crucial role in facilitating lung cancer growth by suppressing tumoricidal immune activation and absorbing chemotherapeutics.

Deconvolving Passive and Active Targeting of Liposomes Bearing LDL Receptor Binding Peptides Using the Zebrafish Embryo Model.

Improving target versus off-target ratio in nanomedicine remains a major challenge for increasing drug bioavailability and reducing toxicity. Active targeting using ligands on nanoparticle surfaces is a key approach but has limited clinical success. A potential issue is the integration of targeting ligands also changes the physicochemical properties of nanoparticles (passive targeting).