Enfortumab vedotin plus pembrolizumab for previously untreated locally advanced or metastatic urothelial carcinoma: a cost-effectiveness analysis.

Background: Both the antibody-drug conjugate (ADC) enfortumab vedotin (EV) and programmed death-1 inhibitor pembrolizumab have been shown to provide survival benefits in patients previously treated with locally advanced or metastatic urothelial carcinoma (la/mUC). Cost-effectiveness is necessary to consider whether the increased efficacy of the two therapies will lead to higher prices for first-line treatment of previously untreated la/mUC.

Objectives: To guide the choice of EV plus pembrolizumab or chemotherapy for patients with previously untreated la/mUC.

Recent Advances in the Synthesis of Cyclic Sulfone Compounds with Potential Biological Activity.

In recent years, cyclic sulfone compounds, a subset of biologically active heterocyclic compounds, have gained considerable attention due to their potential in the development of novel active pharmaceutical ingredients. This review focuses on identifying simple, mild, environmentally friendly, and efficient synthesis methods. Various catalytic approaches for the synthesis of cyclic sulfone compounds are systematically reviewed, highlighting their advantages and potential applications in pharmaceutical development.

The Promising Potency of Sodium-Glucose Cotransporter 2 Inhibitors in the Prevention of and as Treatment for Cognitive Impairment Among Type 2 Diabetes Patients.

Type 2 diabetes mellitus (T2DM), accounting for the majority of diabetes mellitus prevalence, is associated with an increased risk of cognition decline and deterioration of cognition function in diabetic patients. The sodium-glucose cotransporter 2 (SGLT2), located in the renal proximal tubule, plays a role in urine glucose reabsorption. SGLT2 inhibitors (SGLT2i), have shown potential benefits beyond cardiac and renal improvement in preventing and treating cognitive impairment (CI), including mild cognitive impairment, Alzheimer's disease and vascular dementia in T2DM patients.

Unveiling anharmonic scattering in van der Waals semiconductor GaPS through Raman spectroscopy and theoretical calculation.

The van der Waals thiophosphate GaPS presents additional opportunities for gallium-based semiconductors, but limited research on phonon interactions has hindered optimization on thermal properties. This research undertakes a comprehensive investigation into the anharmonic phonon scattering within GaPS. The findings reveal pronounced anharmonic scattering, with both cubic and quartic phonon scatterings significantly influencing phonon redshift and broadening.

Ordered Photoexfoliation for Polypseudorotaxane Nanosheets.

Two-dimensional layered structural materials exhibit a wide range of properties due to their ultrahigh specific surface area. However, achieving ordered exfoliation to obtain uniform two-dimensional structures remains challenging. In this study, we developed a supramolecular system by covalently bonding hexathiobenzene (HB) into β-cyclodextrin to create a light-responsive moiety, followed by coassembly with bipyridine and nickel ions to form a polypseudorotaxane (PR) system, which enables an light-induced exfoliation strategy for two-dimensional materials.

Experiments to simulate the salinisation process of loess under a dynamic water cycle.

Addressing loess salinisation is a crucial element in preserving ecological stability and fostering sustainable development in the northwest Loess Plateau. To investigate the impacts of salt solution on the properties of loess, independently designed salt solution-loess dynamic cyclic erosion equipment was used to soak the loess. Then, numerous tests were performed to analyse the variability of the effects of salt solution concentrations (SSC) and type, as well as the duration of soaking time, on these physico-mechanical properties.

Emergence and clinical challenges of ST11-K64 carbapenem-resistant Klebsiella pneumoniae: molecular insights and implications for antimicrobial resistance and virulence in Southwest China.

Background: In clinical practice, the emergence of ST11-K64 carbapenem-resistant Klebsiella pneumoniae (ST11-K64 CRKP) has become increasingly alarming. Despite this trend, limited research has been conducted to elucidate the clinical and molecular characteristics of these strains.

Objectives: This study aimed to comprehensively investigate the clinical characteristics, antimicrobial resistance patterns, resistance and virulence-associated genes, and molecular epidemiology of ST11-K64 CRKP in Southwest China.

PKR Inhibitor C16 Regulates HIV-gp120 Induced Neuronal Injury and Cognitive Impairment in Vivo and in Vitro Models.

To study the neuronal protective effect and its potential mechanism of C16 against gp120-induced cognitive impairment in vitro and in vivo. The NORT method was used to evaluate the short-term memory abilities of rats, the morphological changes in hippocampus were observed by Nissl staining. Cell viability and damage degree were detected by MTT and LDH.

Proteomic characterization of molecular mechanisms of paraquat-induced lung injury in a mouse model.

Background: We sought to explore the molecular mechanisms underpinning acute lung injury (ALI) caused by poisoning with paraquat (PQ).

Methods: Selection mice were intraperitoneally injected with PQ at 40 mg/kg, whereas controls were injected with sterile saline. On days 2, 7, and 14 after administration, mice were anesthetized and sacrificed, and lung tissue was removed.

Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs.

Norepinephrine (NE) released from locus coeruleus (LC) noradrenergic (NAergic) neurons plays a pivotal role in the regulation of olfactory behaviors. However, the precise circuits and receptor mechanisms underlying this function are not well understood. Here, in DBH-Cre mice model, we show that LC NAergic neurons project directly to both anterior piriform cortex (aPC) and the olfactory bulb (OB).

HDAC6 deacetylates TRIM56 to negatively regulate cGAS-STING-mediated type I interferon responses.

Histone deacetylase HDAC6 has been implicated in regulating antiviral innate immunity. However, its precise function in response to DNA virus infection remains elusive. Herein, we find that HDAC6 deficiency promotes the activation of cGAS-STING signaling and type I interferon (IFN) production, both in vitro and in vivo, resulting in a decrease in HSV-1 infection.

Prevalence and Risk Factors of Covert Brain Infarction: a Community-based Cross-sectional Study.

Background: Covert brain infarction (CBI) is common and poses a potential and non-negligible burden of disease worldwide. The prevalence and risk factors for CBI have been reported inconsistently in previous studies.

Aims: This study aims to ascertain the prevalence and risk factors of CBI and its imaging phenotypes in community-dwelling adults.

An oral vaccine based on the Ad5 vector with a double-stranded RNA adjuvant protects mice against respiratory syncytial virus.

A safe and effective vaccine is urgently needed to prevent acute respiratory infections caused by respiratory syncytial virus (RSV). Oral administration offers several advantages, including ease of delivery, minimal stress for vaccine recipients, and greater safety than the systemic injection. In this study, we developed an oral vaccine candidate based on the human adenovirus serotype 5 (Ad5) vector, Ad5-PreF-DS2, encoding a prefusion protein of RSV with a dsRNA as an endogenous adjuvant.

The impact of digital infrastructure on air quality: Mediating role of public environmental attention and industrial development.

The digital economy has significantly enhanced economic quality, and studying its implications on the environment can provide empirical support for policies that foster environment-economy coordination. This paper examines the impact of digital infrastructure on air quality, focusing on the mechanisms of public environmental attention and industrial development. It further analyzes heterogeneity in urban locations, degree of urbanization, and environmental regulation intensity.

GaN/CuI heterostructure ultraviolet photovoltaic detector for low-power optical communication.

In this work, a planar structured GaN/CuI heterojunction ultraviolet photodetector (UVPD) with a self-powered manner was constructed by the spin-coating method. Both UVA and UVC waveband lights were precisely detected by this designed GaN/CuI PD. Irradiated upon 365 nm UVA light, our PD device performed decent self-powered photoresponse properties with a photo-to-dark current ratio (PDCR) of 1.

Development and validation of an explainable model of brain injury in premature infants: A prospective cohort study.

Background: Preterm brain injury (PBI) is a prevalent complication in preterm infants, leading to the destruction of critical structural and functional brain connections and placing a significant burden on families. The timely detection of PBI is of paramount importance for the prevention and treatment of the condition. However, the absence of specific clinical manifestations in the early stages of PBI renders it susceptible to misdiagnosis and missed diagnoses.

Genome of root celery and population genomic analysis reveal the complex breeding history of celery.

Celery (Apium graveolens L.) is an important vegetable crop in the Apiaceae family. It comprises three botanical varieties: common celery with solid and succulent petioles, celeriac or root celery with enlarged and fleshy hypocotyls and smallage or leaf celery with slender, leafy and usually hollow petioles.

Pan-cancer single cell and spatial transcriptomics analysis deciphers the molecular landscapes of senescence related cancer-associated fibroblasts and reveals its predictive value in neuroblastoma via integrated multi-omics analysis and machine learning.

Introduction: Cancer-associated fibroblasts (CAFs) are a diverse group of cells that significantly contribute to reshaping the tumor microenvironment (TME), and no research has systematically explored the molecular landscapes of senescence related CAFs (senes CAF) in NB.

Methods: We utilized pan-cancer single cell and spatial transcriptomics analysis to identify the subpopulation of senes CAFs via senescence related genes, exploring its spatial distribution characteristics. Harnessing the maker genes with prognostic significance, we delineated the molecular landscapes of senes CAFs in bulk-seq data.

METTL3-mediated m6A modification of EGR1 mRNA promotes T2DM vasculopathy.

Vascular endothelial dysfunction is one of the leading causes of developing vascular lesions in Type 2 diabetes mellitus (T2DM). In the development of vascular lesions, when endothelial cells are stimulated by hyperglycemia, inflammation and other external conditions, endothelial cell dysfunction will occur, which promotes endothelial cells to lose its typical phenotype and gain mesenchymal characteristics, with the occurrence of endothelial-to-mesenchymal transition (EndMT). At the same time promote endothelial cell proliferation and migration, induce vascular injury.

Clinical Efficacy and Safety of Vancomycin Based on Unbound Vancomycin Concentration Monitoring.

Objective: To monitor total trough concentration (Cmin_total) and unbound trough concentration (Cmin_free) of vancomycin in clinical samples and analyze the factors influencing them, and to assess their correlation with clinical efficacy and acute kidney injury (AKI).

Methods: Plasma samples were processed by protein precipitation, followed by hollow-fiber centrifugal ultrafiltration to separate unbound vancomycin from plasma. Thereafter, Cmin_total and Cmin_free were determined using high-performance liquid chromatography.

Short-chain fatty acids and cancer.

Short-chain fatty acids (SCFAs), derived from the diet and the microbiota, serve as crucial links between the diet, gut microbiota, metabolism, immunity, and cancer. They function as energy sources through β-oxidation and regulate macromolecular synthesis, G protein-coupled receptor (GPCR) and histone deacetylase (HDAC) activities, protein modifications, signaling pathways, and gene expression in cells within the tumor microenvironment, particularly in tumor and immune cells. The critical role of SCFAs in maintaining normal homeostasis and influencing tumor progression highlights the potential of targeting SCFA-mediated cellular processes for cancer prevention and treatment.

Characteristics of gut microbiota of premature infants in the early postnatal period and their relationship with intraventricular hemorrhage.

Background: Studies have shown correlations between gut microbiota and neurocognitive function, but little was known about the early postnatal gut microbiota and intraventricular hemorrhage (IVH). We aimed to explore the characteristics of gut microbiota in premature infants and their relationship with IVH, further exploring potential therapeutic targets.

Methods: Premature infants delivered at Peking University First Hospital from February 2023 to August 2023 were recruited as a cohort.

Establishment of a Reverse Genetics System for Rotavirus Vaccine Strain LLR and Developing Vaccine Candidates Carrying VP7 Gene Cloned From Human Strains Circulating in China.

Human rotavirus A (RVA) causes acute gastroenteritis in infants and young children. The LLR RVA vaccine, which licensed in 2000 and widely used in China, significantly reduced rotavirus disease burden in China. With the changing of RV circulating strains and the emergence of new genotypes, the LLR vaccine against RVGE needed to be upgraded.