UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing.

The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods.

GLUT1 as a generic biomarker enables near-infrared fluorescence molecular imaging guided precise intraoperative tumor detection in breast cancer.

Purpose: Precise tumor excision is important but challenging in breast-conserving surgery (BCS). Tumor-specific fluorescence imaging may be used for intraoperative tumor detection and, therefore, to guide precise tumor excision. The aims of this study are to develop a glucose transporter 1 (GLUT1)-targeted near-infrared fluorescence tracer and evaluate its accuracy for breast cancer detection using fresh surgical breast specimens.

Association of composite dietary antioxidant index with mortality risk among adults with chronic kidney disease in NHANES.

At present, the relationship between the intake of antioxidants in food and the mortality rate of patients with chronic kidney disease (CKD), especially the association with the mortality rate of specific causes, is not clear. This study included 6379 adult CKD patients from the National Health and Nutrition Examination Survey (2001-2018). Use the Cox proportional hazards model, restricted cubic spline (RCS) model, and stratified and sensitivity analysis to evaluate the relationship between the Composite Dietary Antioxidant Index (CDAI) and mortality in patients with chronic kidney disease.

Human epididymis protein 4-annexin II binding promotes aberrant epithelial-fibroblast crosstalk in pulmonary fibrosis.

Invasive lung myofibroblasts are the main cause of tissue remodeling in idiopathic pulmonary fibrosis (IPF). A key mechanism contributing to this important feature is aberrant crosstalk between the abnormal/injured lung epithelium and pulmonary fibroblasts. Here, we demonstrate that lungs from patients with IPF and from mice with bleomycin (BLM)-induced pulmonary fibrosis (PF) are characterized by the induction of human epididymis protein 4 (HE4) overexpression in epithelial cells.

Frequency-specific and state-dependent neural responses to brain stimulation.

Non-invasive brain stimulation is promising for treating many neuropsychiatric and neurological conditions. It could be optimized by understanding its intracranial responses in different brain regions. We implanted multi-site intracranial electrodes and systematically assessed the acute responses in these regions to transcranial alternating current stimulation (tACS) at different frequencies.

Identifying a non-conserved site for achieving allosteric covalent inhibition of CECR2.

The bromodomain (BRD) represents a highly conserved structural module that provides BRD proteins with fundamental functionality in modulating protein-protein interactions involved in diverse biological processes such as chromatin-mediated gene transcription, DNA recombination, replication and repair. Consequently, dysregulation of BRD proteins has been implicated in the pathogenesis of numerous human diseases. In recent years, considerable scientific endeavors have focused on unraveling the molecular mechanisms underlying BRDs and developing inhibitors that target these domains.

Peptidoglycan isolated from the fruit of Lycium barbarum alleviates liver fibrosis in mice by regulating the TGF-β/Smad7 signaling and gut microbiota.

The hepatoprotective effect of the fruit of Lycium barbarum has been documented in China over millennia. Lycium barbarum polysaccharides (LBPs) were the first macromolecules reported to mitigate liver fibrosis in carbon tetrachloride (CCl)-treated mice. Herein, a neutral peptidoglycan, named as LBPW, was extracted from the fruit of Lycium barbarum.

Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis.

S-palmitoylation is a reversible and widespread post-translational modification, but its role in the regulation of ferroptosis has been poorly understood. Here, we elucidate that GPX4, an essential regulator of ferroptosis, is reversibly palmitoylated on cysteine 66. The acyltransferase ZDHHC20 palmitoylates GPX4 and increases its protein stability.

Efficient recognition of Parkinson's disease mice on stepping characters with CNN.

Parkinson's disease (PD), as the second most prevalent neurodegenerative disorder worldwide, impacts the quality of life for over 12 million patients. This study aims to enhance the accuracy of early diagnosis of PD through non-invasive methods, with the goal of enabling earlier intervention in the disease process. To this end, we constructed an open-field environment using flexible sensors under dark conditions, conducting experiments on a mouse model of Parkinson's disease alongside a normal control group.

Generation of live mice from haploid ESCs with germline-DMR deletions or switch.

Genomic imprinting is required for sexual reproduction and embryonic development of mammals, in which, differentially methylated regions (DMRs) regulate the parent-specific monoallelic expression of imprinted genes. Numerous studies on imprinted genes have highlighted their critical roles in development. However, what imprinting network is essential for development is still unclear.

A dual role of Cohesin in DNA DSB repair.

Cells undergo tens of thousands of DNA-damaging events each day. Defects in repairing double-stranded breaks (DSBs) can lead to genomic instability, contributing to cancer, genetic disorders, immunological diseases, and developmental defects. Cohesin, a multi-subunit protein complex, plays a crucial role in both chromosome organization and DNA repair by creating architectural loops through chromatin extrusion.

A high-valence bismuth(V) nanoplatform triggers cancer cell death and anti-tumor immune responses with exogenous excitation-free endogenous HO- and O-independent ROS generation.

Reactive oxygen species with evoked immunotherapy holds tremendous promise for cancer treatment but has limitations due to its dependence on exogenous excitation and/or endogenous HO and O. Here we report a versatile oxidizing pentavalent bismuth(V) nanoplatform (NaBiO-PEG) can generate reactive oxygen species in an excitation-free and HO- and O-independent manner. Upon exposure to the tumor microenvironment, NaBiO-PEG undergoes continuous H-accelerated hydrolysis with •OH and O generation through electron transfer-mediated Bi-to-Bi conversion and lattice oxygen transformation.

Spatiotemporal transcriptome and metabolome landscapes of cotton fiber during initiation and early development.

Cotton fibers are single cells that develop from the epidermal cells in the outer integument of developing seeds. The processes regulating fiber cell development have been extensively studied; however, the spatiotemporal transcriptome and metabolome profiles during the early stages of fiber development remain largely unknown. In this study, we profile the dynamics of transcriptome and metabolome during the early stages of cotton fiber cell development using a combination of spatial transcriptomic, single-cell transcriptomic, and spatial metabolomic analyses.

A single residue switch mediates the broad neutralization of Rotaviruses.

Broadly neutralizing antibodies (bNAbs) could offer escape-tolerant and lasting protection against viral infections and therefore guide development of broad-spectrum vaccines. The increasing challenge posed by viral evolution and immune evasion intensifies the importance of the discovery of bNAbs and their underlying neutralization mechanism. Here, focusing on the pivotal viral protein VP4 of rotavirus (RV), we identify a potent bNAb, 7H13, exhibiting broad-spectrum neutralization across diverse RV genotypes and demonstrating strong prevention of virus infection in female mice.

Iatrogenic diversion of inferior vena cava to the left atrium presented as persistent hypoxemia: Case series.

Rationale: The transcatheter closure and atrioseptopexy are the main treatment methods for atrial septal defect (ASD). However, persistent hypoxemia due to iatrogenic diversion of inferior vena cava (IVC) to the left atrium (LA) is reported as a rare complication after ASD closure. Contrast echocardiology is a reliable and powerful tool to detect iatrogenic diversion and identify the etiology accurately.

Extensive small cell lung cancer treated by integrated traditional Chinese and Western medicine: A case report.

Rationale: Patients with extensive small cell lung cancer (SCLC) generally have a dismal survival rate and are conventionally treated with chemotherapy. This study aimed to explore an alternative treatment approach by combining traditional Chinese medicine (TCM) with radiotherapy and chemotherapy.

Patient Concerns: A 68-year-old male was diagnosed with extensive-stage SCLC.

Ahmed glaucoma valve implantation for congenital ectropion uveae with glaucoma: A case report.

Rationale: Congenital ectropion uveae (CEU) is a rare, nonprogressive anomaly characterized by the proliferation of the iris pigment epithelium on the anterior surface of the iris, often associated with glaucoma. Due to its rarity and complexity, standardized glaucoma surgical management is limited. To our knowledge, the application of glaucoma drainage devices in CEU is rarely documented.

Controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: study protocol for a randomised controlled trial.

Introduction: Multimodal anticancer therapies greatly damage the fertility of breast cancer patients, which raises urgent demand for fertility preservation. The standard options for fertility preservation are oocyte and embryo cryopreservation; both require controlled ovarian hyperstimulation (COH). However, there are safety concerns regarding breast cancer relapse due to the elevated serum estradiol levels during COH.

Genetic features and pharmacological rescue of novel Kv7.2 variants in patients with epilepsy.

Background: Increasing evidence indicates a robust correlation between epilepsy and variants of the Kv7.2 () channel, which is critically involved in directing M-currents and regulating neuronal excitability within the nervous system. With the advancement of next-generation sequencing, the identification of variants has surged.

Intrinsic dual-emitting Si dots for high-precision and broad-range pH detection.

Background: High-precision and broad-range pH detection is critical for health status assessment, such as signal transduction, enzyme activity, endocytosis, and cell proliferation and apoptosis. Although pH-responsive ratiometric fluorescent probes offer an effective pH monitoring strategy, their preparation often requires multi-step modification and decreases fluorescence efficiency and stability. Herein, we developed a simple method to prepare fluorescent Si dots with dual emission centers for high-precision and broad-range pH monitoring, and the detection of urease based on pH-responsive Si dots and pH monitoring in living cell was further explored.

Novel Nitrogen Hybrid F Sensors Based on ESIPT Mechanism Achieving Super Low Detection Limits.

Two novel nitrogen hybrid fluorescent sensors based on the ESIPT mechanism were successfully synthesized for the detection of fluoride ions (F), and they exhibit high sensitivity and selectivity with a fast response. The detection limits even reach the parts per billion level. With the addition of F, both sensors showed a ratiometric fluorescence change with a large Stokes shift.

A novel small molecule NJH-13 induces pyroptosis via the Ca driven AKT-FOXO1-GSDME signaling pathway in NSCLC by targeting TRPV5.

Introduction: Pyroptosis represents a mode of programmed necrotic cell death (PCD), mediated by members of gasdermin family (GSDMs), such as GSDME. It is emerging as a promising approach for combating cancer. Notably, GSDME is the key modulator for the switch between apoptosis and pyroptosis in cells.

AlphaFold-Based AI Docking Reveals AMPK/SIRT1-TFEB Pathway Modulation by Traditional Chinese Medicine in Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD) is a chronic, progressive disorder characterized by hepatic steatosis and excessive lipid accumulation. Its high global adult prevalence (approximately 50.7%), however, FDA-approved therapeutic drugs remains lacking.

Cotargeting of thioredoxin 1 and glutamate-cysteine ligase in both imatinib-sensitive and imatinib-resistant CML cells.

Chronic myeloid leukemia (CML) is a type of malignancy characterized by harboring the oncogene Bcr-Abl, which encodes the constitutively activated tyrosine kinase BCR-ABL. Although tyrosine kinase inhibitors targeting BCR-ABL have revolutionized CML therapy, native and acquired drug resistance commonly remains a great challenge. Thioredoxin 1 (Trx1) and glutamate-cysteine ligase (GCL), which are two major antioxidants that maintain cellular redox homeostasis, are potential targets for cancer therapy and overcoming drug resistance.

Naotaifang formula regulates Drp1-induced remodeling of mitochondrial dynamics following cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) has emerged as a hindrance for rehabilitation of ischemic stroke patients. Naotaifang (NTF) exhibits beneficial efficacy in alleviating inflammation and ferroptosis in vitro during CIRI. While the potential role of NTF in regulating mitochondrial dynamics in CIRI are not elucidated.