Addition of metronidazole to standard-of-care perioperative prophylaxis at the time of hysterectomy for gynecologic malignancies.

Objective: The purpose of this study was to evaluate whether the combination of cefazolin or a second-generation cephalosporin plus metronidazole is associated with a reduced risk of surgical site infection in women undergoing hysterectomy for gynecologic cancer compared to using cefazolin or a second-generation cephalosporin alone.

Methods: This was a retrospective cohort study of patients who underwent hysterectomy at a single institution between January 2020 and June 2022. The primary outcome was surgical site infection.

Plasma Glial Fibrillary Acidic Protein Correlates With Brain Metal Burden in Wilson's Disease.

Objective: Neuroinflammation driven by extracellular copper contributes to neuronal damage in Wilson's disease (WD). This study investigated the relationship between brain metal burden and peripheral neuroinflammation markers in WD.

Methods: We conducted a cross-sectional study involving 89 participants, including patients with WD (n = 63), asymptomatic ATP7B heterozygous carriers (n = 12), and age/sex-matched controls (n = 14).

Engineered Substrate-Free Small Molecules for Enhanced Raman Scattering and Photothermal Conversion Efficiency.

Raman spectroscopy with surface-enhanced Raman scattering (SERS) through metal substrates is a highly precise bioimaging technique. Alternatively, recently discovered small molecules to enhance the Raman signal intensities through their self-stacking, termed stacking-induced intermolecular charge transfer-enhanced Raman scattering (SICTERS), offer ultrasensitive in vivo Raman imaging free of substrates. Molecular engineering to increase the SICTERS intensity and to tune photothermal conversion efficiency of these molecules is critical for furthering their biomedical application but not yet feasible.

Deciphering Pharmacological Targets of Plumbagin in Cisplatin-resistant Ovarian Cancer Model using in vitro and in silico Approaches.

Introduction: Ovarian cancer (OC) is a malignancy of the female reproductive system for which cisplatin chemotherapy is one of the first-line treatments. Despite the initial response to chemotherapy, such patients eventually develop resistance, which poses a major obstacle to treatment, along with potential side effects. Phytochemicals function as chemosensitizers, offering novel therapies in OC patients by targeting drug resistance, and are perceived to be less toxic.

The impact of donor and recipient age on post-transplantation clonality in murine haematopoiesis.

The sustained production of blood and immune cells is driven by a pool of hematopoietic stem cells (HSCs) and their offspring. Due to the intrinsic heterogeneity of HSCs, the composition of emergent clones changes over time, leading to a reduced clonality in aging mice and humans. Theoretical analyses suggest that clonal conversion rates and clonal complexity depend not only on HSC heterogeneity, but also on additional stress conditions.

SLB-msSIM: A Spectral Library-Based Multiplex Segmented SIM Platform for Single-Cell Proteomic Analysis.

Mass spectrometry (MS)-based single-cell proteomics, while highly challenging, offers unique potential for a wide range of applications to interrogate cellular heterogeneity, trajectories, and phenotypes at a functional level. We report here the development of the spectral library-based multiplex segmented selected ion monitoring (SLB-msSIM) method, a conceptually unique approach with significantly enhanced sensitivity and robustness for single-cell analysis. The single-cell MS data is acquired by a multiplex segmented selected ion monitoring (msSIM) technique, which sequentially applies multiple isolation cycles with the quadrupole using a wide isolation window in each cycle to accumulate and store precursor ions in the C-trap for a single scan in the Orbitrap.

A human-mouse atlas of intrarenal myeloid cells identifies conserved disease-associated macrophages in lupus nephritis.

Monocytes and macrophages in patients with lupus nephritis exhibit altered behavior compared with healthy kidneys. How to optimally use mouse models to develop treatments targeting these cells is poorly understood. This study compared intrarenal myeloid cells in four mouse models and 155 lupus nephritis patients using single-cell profiling, spatial transcriptomics, and functional studies.

Efficacy and Safety of Curcumin as an Adjuvant to Standard Chemotherapy in Advanced and Metastatic Breast Cancer Patients: A Randomized Controlled Study.

The potential of the phytoconstituent, curcumin, as an adjuvant to chemoradiotherapy has been investigated because of its ameliorating effects, including the sensitization of cancer and cancer stem cells. Curcumin, a strong antioxidant with pharmacologically non-toxic effects, can be used as an adjuvant with enhanced bioavailability and administered along with chemotherapy to achieve better treatment outcomes. The present study was carried out with a total of 120 women with locally advanced/metastatic breast cancer, who were randomized to receive standard chemotherapy alone or chemotherapy with oral curcumin, a 500 mg capsule (1 g/day) containing 95% curcuminoid and 1% piperine given for 12 to 24 weeks.

Progressive changes in phenotype, transcriptome and proliferation capacity characterise continued maturation and migration of intestinal cDCs in homeostasis.

Conventional dendritic cells (cDCs) are important antigen presenting cells which link innate and adaptive immunity by transferring antigenic information from peripheral organs to T cells in lymph nodes (LNs). However, despite their central function in the induction of adaptive immune responses, the kinetics and molecular regulation of the cDC life cycle and migration remain poorly understood. Using a variety of in vivo techniques, we examine the kinetics of cDC turnover in the intestine and address the molecular changes throughout the various stages of the cDC life cycle - from tissue entry and differentiation to CCR7 upregulation and subsequent migration into draining LNs.

CNO induced Ca store and glutamate-dependent nonspecific Ca signalling in DREADD-free brain slices.

DREADD (design receptors exclusively activated by designer drugs) is a widely used powerful tool designed to study specific cellular functions. However, off-target effects of chemogenetic activators, including clozapine N-oxide (CNO) and deschloroclozapine (DCZ), have been reported. In our study, we demonstrated the direct off-target effects of CNO and DCZ on basal Ca levels in the locus coeruleus nucleus in both neurons and astrocytes by combining viral microinjection, Ca imaging and electrophysiology.

Epidemiology and diagnostic challenges in neuromyelitis optica spectrum disorder in Taiwan: a hospital-based surveillance accompanied by a nationwide study.

Neuromyelitis optica spectrum disorder is a rare autoimmune inflammatory demyelinating disease that must be differentiated from multiple sclerosis. The impact of misclassification on these patients in Taiwan remains unclear. We conducted a hospital-based retrospective cohort study of neuromyelitis optica spectrum disorder patients using the Chang Gung Research Database from 2005 to 2021.

Large-scale network topography of stroke predicts functional outcome after mechanical thrombectomy.

Mechanical thrombectomy effectively restores blood flow in patients with acute ischaemic stroke caused by large vessel occlusion. While mechanical thrombectomy has improved functional outcomes, 35%-60% of patients still experience residual disabilities. Typically, patients are selected for mechanical thrombectomy based on degree of hypoperfusion around the core measured on a vascular atlas.

Early pharmacological blockade of the CXCL12-CXCR4 axis attenuates vertebral hypercalcification in a zebrafish model of pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE), caused by pathogenic variants in , is characterized by pathological ectopic calcification with poorly understood mechanisms and no effective therapies. To address this, we developed the first zebrafish model of human PXE by introducing the pathogenic point mutation ( , F2 generation) using the highly efficient zhyA3A-CBE5 cytosine base editor. Three mutant types (Type1-Type3, T1-T3) stratified by calcification severity, exhibited reduced levels of the calcification inhibitors vitamin K1 (VK1) and carboxylated matrix Gla protein (cMGP), which were inversely correlated with the severity of calcification.

A cytotoxic peptide-drug conjugate for tumor-specific delivery of co-injected molecules.

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents.

Synaptic accumulation of GluN2B-containing NMDA receptors mediates the effects of BDNF-TrkB signalling on synaptic plasticity and in hyperexcitability during status epilepticus.

Background: Brain-derived neurotrophic factor (BDNF) is a key mediator of synaptic plasticity and memory formation in the hippocampus. However, the BDNF-induced alterations in the glutamate receptors coupled to the plasticity of glutamatergic synapses in the hippocampus have not been elucidated. In this work we investigated the putative role of GluN2B-containing NMDA receptors in the plasticity of glutamatergic synapses induced by BDNF.

Danhong Injection targets CaMKII through Dihydrotanshinone I to alleviate cardiomyocyte death and inflammation in viral myocarditis.

Viral myocarditis, an inflammatory heart disorder caused by viral infections, often leads to poor outcomes due to the lack of effective prevention and treatment strategies. Despite the characteristic feature of cardiomyocyte death in this condition, the underlying mechanisms and potential therapeutic approaches remain poorly understood. Traditional Chinese medicine (TCM), despite its extensive history in treating various diseases, has not yet been approved for the treatment of viral myocarditis.

Multi-omics identification of quantitative trait loci associated with vascular pathogenesis and diagnostic potential in chronic venous disease.

Chronic venous disease (CVD) is a prevalent vascular disorder with a poorly characterized genetic basis. In this study, we employed an integrative omics strategy combining genome-wide association studies (GWAS), expression quantitative trait loci (eQTL) mapping, endothelial cell functional assays, and transcriptomic correlation analysis to elucidate the molecular architecture of CVD. A GWAS conducted in a Taiwanese population identified two CVD-associated single nucleotide polymorphisms: VSTM2L rs1998049 and DPYSL2 rs1442887.

Aptamer-based targeted drug delivery and disease therapy in preclinical and clinical applications.

The advent of precision medicine has created an urgent need for advanced drug-targeting strategies and refined drug delivery systems. Aptamers, characterized by their exceptional affinity and specificity, low molecular weight, negligible immunogenicity, remarkable stability, cost-effectiveness, and structural versatility, are emerging as promising candidates in targeted therapeutics, both in preclinical research and clinical applications. This review provides a comprehensive analysis of the latest advancements in aptamer-based therapeutic strategies, encompassing three key application domains: direct therapeutic agents, targeted ligand engineering, and controlled drug release.

Generation and characterization of a patient-derived iPSC line, CSSi022-A (15666), with a pathogenic MFN2 mutation causing Charcot-Marie-Tooth disease type 2A.

Charcot-Marie-Tooth disease type 2A (CMT2A; OMIM 609260) is a rare sensorimotor neuropathy caused by mutations in the MFN2 gene (1p36.22). We successfully reprogrammed fibroblasts from an 8-year-old girl carrying a de novo MFN2 mutation into induced pluripotent stem cells using non-integrative vectors.

DNA-Programmable Protein Degradation: Dynamic Control of Proteolysis-Targeting Chimera Activity via DNA Hybridization and Strand Displacement.

Targeted protein degradation is a powerful therapeutic approach: expanding the druggable proteome, providing enhanced selectivity, and having the ability to overcome conventional resistance mechanisms. A major class of such molecules is proteolysis-targeting chimeras (PROTACs). PROTACs are catalytic heterobifunctional small molecules that simultaneously bind a protein of interest (POI) and an E3 ligase.

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low- frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).

Stereo-seq V2: Spatial mapping of total RNA on FFPE sections with high resolution.

Performing total RNA profiling on formalin-fixed, paraffin-embedded (FFPE) samples, the predominant sample conservation method in clinical practice, remains challenging for current spatial transcriptomics techniques. Here, we introduce Stereo-seq V2, which employs random primers to capture and sequence RNAs in situ on FFPE sections and provides single-cell resolution. The random-priming-based strategy offers unbiased transcript capturing and uniform gene body coverage, which increase the sensitivity to marker genes, the efficiency of non-polyadenylation (poly(A)) RNA profiling, and immune repertoire coverage.