Combined delivery of IL12 and an IL18 mutant without IL18BP-binding activity by an adenoviral vector enhances tumor specific immunity.

Cytokines play pivotal roles in anticancer immune response. We previously reported that adenovirus armed with an IL18 variant (DR18) that overcomes IL18BP neutralizing effect displayed powerful therapeutic effects in local and distant tumors when delivered intratumorally. Here, we tested a combined delivery of IL12 and DR18 in tumor models since IL12 and IL18 are known to act synergistically in potentiating IFNγ production and antitumor immunity.

Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study.

The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment.

Single-cell transcriptomics of bronchoalveolar lavage during PRRSV infection with different virulence.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the global swine industry due to its high genetic diversity and different virulence levels, which complicate disease management and vaccine development. This study evaluated longitudinal changes in the immune cell composition of bronchoalveolar lavage fluid and the clinical outcomes across PRRSV strains with varying virulence, using techniques including single-cell transcriptomics. In highly virulent infection, faster viral replication results in an earlier peak lung-damage time point, marked by significant interstitial pneumonia, a significant decrease in macrophages, and an influx of lymphocytes.

Renal and Peripheral Blood Transcriptome Signatures That Predict Treatment Response in Proliferative Lupus Nephritis-A Prospective Study.

Mechanisms contributing to non-response to treatment in lupus nephritis (LN) are unclear. We characterised the transcriptome of paired peripheral blood mononuclear cells (PBMCs) and renal tissues in LN before and after cyclophosphamide (CYC) treatment and identified markers that predicted treatment response. Total RNA isolated from paired PBMCs (n = 32) and renal tissues (n = 25) of 16 proliferative LN before CYC treatment, 6 months post-treatment, and during renal flare, was sequenced on Illumina Novaseq-6000 platform.

Gas chromatography-mass spectrometry metabolic profiling and sensory evaluation of greenhouse mangoes (Mangifera indica L. 'Irwin') over multiple harvest seasons.

Compared to outdoor mango cultivation in the tropics, greenhouse cultivation in temperate regions is less reported due to its short history and small scale. Here, we evaluated for the first time the taste-focused quality of greenhouse-grown mangoes (Irwin) by GC-MS metabolic profiling and sensory evaluation for over three years (2021-2023). The relative standard deviation in sensory evaluation scores was approximately 15 % each year.

Thyroid Endocrine Disrupting Potential of Fluoxetine in Zebrafish Larvae.

Fluoxetine (FLX), a typical selective serotonin reuptake inhibitors, has been frequently detected in aquatic environment and wild fish. However, little is known about its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 1, 3, 10, and 30 μg/L of FLX for 6 days.

Guanine-Assisted Contrived Low Pt-Integrated MoC/C for Hydrogen Evolution Reaction.

Due to the high cost of the available Pt electrocatalysts, the large-scale water electrolysis production of hydrogen has been hindered. Hydrogen generation via electrochemical water splitting is a renewable energy essential to a sustainable society, creating a distinct material interface that shows Pt-like properties with long-term stability crucial to hydrogen evolution reactions (HERs). Here, we synthesized the guanine-assisted facile synthesis of 1 wt % Pt/MoC/C having a layered type morphology via solid state calcined process followed by chemical reduction.

Screening a 681-membered yeast collection for the secretion of proteins with antifungal activity.

Fungal pathogens pose a threat to human health and food security. Few antifungals are available and resistance to all has been reported. Novel strategies to control plant and human pathogens as well as food spoilers are urgently required.

IN SILICO AND IN VITRO ASSESSMENT OF ANTI-Leishmania infantum ACTIVITY OF A NOVEL CYCLOHEXYL-1,2,4-OXADIAZOLE DERIVATIVE.

Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affecting underdeveloped countries. In Brazil, the available treatments are pentavalent antimonials and Amphotericin B, which are outdated, toxic, require prolonged parenteral administration and have limited efficacy.

Therapeutics of bitter plants from Northeast region of India and their pharmacological and phytochemical perspectives.

Natural resources have been used for food and medicine since the beginning of human civilization, and they have always been a low-cost, easily accessible source for individuals. Northeast region of India (NER) represents a significant portion of India's flora and fauna. Marginality, fragility, inaccessibility, ethnicity, and cultural diversity thrived in the region, resulting in the richest reservoir of genetic variation of bioresources.

Computational identification and experimental validation of novel microRNAs along with their targets through RT-PCR approach.

Various metabolic and cell signaling processes impact the functions of sugarcane plant cells. MicroRNAs (miRNAs) play critical regulatory roles in enhancing yield and providing protection against various stressors. This study seeks to identify and partially characterize several novel miRNAs in sugarcane using tools, while also offering a preliminary assessment of their functions.

Microbial synthesis of m-tyrosine via whole-cell biocatalysis.

Meta-tyrosine (m-tyrosine), a nonproteinogenic amino acid, has shown significant potential for applications as an herbicide in agriculture and for various medical uses. However, the natural abundance of m-tyrosine is very low, limiting its widespread use. In this study, we successfully achieved microbial production of m-tyrosine by establishing the in vivo enzyme activity of phenylalanine 3-hydroxylase (PacX from Streptomyces coeruleoribudus) in E.

Norharmane prevents muscle aging via activation of SKN-1/NRF2 stress response pathways.

Sarcopenia, the age-related decline in muscle mass and function, is a significant contributor to increased frailty and mortality in the elderly. Currently, no FDA-approved treatment exists for sarcopenia. Here, we identified norharmane (NR), a β-carboline alkaloid, as a potential therapeutic agent for mitigating muscle aging.

Bioorganic compounds in quorum sensing disruption: strategies, Mechanisms, and future prospects.

Recent research has shed light on the complex world of bacterial communication through quorum sensing. This sophisticated intercellular signalling mechanism, driven by auto-inducers, regulates crucial bacterial community behaviours such as biofilm formation, expression of virulence factors, and resistance mechanisms. The increasing threat of antibiotic resistance, coupled with quorum sensing mediated response, necessitates alternative strategies to combat bacterial infections.

Spatiotemporal distribution of marine aerosols and gaseous species over the North Pacific Ocean.

Observational studies of marine aerosols are essential for understanding the global aerosol budget and its environmental impacts. This study presents simultaneous in-situ measurements of major ionic components (Cl, NO, SO, NH, K, Ca, Na, and Mg) in aerosols and gaseous species (HCl, HNO, HONO, SO, and NH) over the North Pacific Ocean from July 4 to 15 and September 19 to October 3, 2022. Using high temporal resolution instruments aboard the Republic of Korea's icebreaker research vessel Araon, this study aimed to (1) report the spatial and temporal distributions of aerosols and gaseous species, (2) estimate the source contributions of continental anthropogenic pollutants, and (3) assess the influence of aerosol chemical composition and gaseous species on aerosol acidity and water content.

Novel bioactive peptides alleviate Western diet-induced MAFLD in C57BL/6J mice by inhibiting NLRP3 inflammasome activation and pyroptosis via TLR4/NF-κB and Keap1/Nrf2/HO-1 signaling pathways.

Metabolic-associated fatty liver disease (MAFLD) has emerged as a leading chronic liver disease. This condition is characterized by an abnormal accumulation of fat within liver and can progress from simple steatosis to more severe stages involving chronic inflammation and oxidative stress. In this study, we investigated the potential therapeutic effects and underlying mechanism of novel bioactive peptides (EWYF and EWFY) on Western diet-induced MAFLD in C57BL/6J mice.

Detecting IDH and TERTp mutations in diffuse gliomas using H-MRS with attention deep-shallow networks.

Background: Preoperative and noninvasive detection of isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutations in glioma is critical for prognosis and treatment planning. This study aims to develop deep learning classifiers to identify IDH and TERTp mutations using proton magnetic resonance spectroscopy (H-MRS) and a one-dimensional convolutional neural network (1D-CNN) architecture.

Methods: This study included H-MRS data from 225 adult patients with hemispheric diffuse glioma (117 IDH mutants and 108 IDH wild-type; 99 TERTp mutants and 100 TERTp wild-type).

MCC950 mitigates SIRT3-NLRP3-driven inflammation and rescues post-stroke neurogenesis.

Sustained activation of the SIRT3-NLRP3 inflammasome has been associated with worse outcomes after ischemic stroke. The objective of this study was to examine the potential mechanism by which the SIRT3-NLRP3 inflammasome affects neural stem and progenitor cells (NSPCs) after transient middle cerebral artery occlusion (tMCAO) in rats. Following tMCAO, significantly elevated levels of NLRP3, ASC, cleaved caspase 1, IL-1β, and IL-18 were observed in the ischemic subventricular zone.

A case-control genome-wide association study of estimated breeding values for resistance to gastrointestinal nematodes in two local dairy sheep breeds.

In sheep, gastrointestinal nematodes (GINs) can cause disease, reduced feed intake, and nutritional deficiencies. To counteract GINs, anthelmintics are widely used although it is well known they may enter the environment impacting ecosystems. In addition, anthelmintics resistance has rapidly developed and consequently, alternative approaches are crucial for profitable and sustainable sheep production.

Patch-based dual-domain photon-counting CT data correction with residual-based WGAN-ViT.

Objective: X-ray photon-counting detectors (PCDs) have recently gained popularity due to their capabilities in energy discrimination power, noise suppression, and resolution refinement. The latest extremity photon-counting computed tomography (PCCT) scanner leverages these advantages for tissue characterization, material decomposition, beam hardening correction, and metal artifact reduction. However, technical challenges such as charge splitting and pulse pileup can distort the energy spectrum and compromise image quality.

Directed Evolution's Selective Use of Quantum Tunneling in Designed Enzymes─A Combined Theoretical and Experimental Study.

Natural enzymes are powerful catalysts, reducing the apparent activation energy for reactions and enabling chemistry to proceed as much as 10 times faster than the corresponding solution reaction. It has been suggested for some time that, in some cases, quantum tunneling can contribute to this rate enhancement by offering pathways through a barrier inaccessible to activated events. A central question of interest to both physical chemists and biochemists is the extent to which evolution introduces mechanisms below the barrier, or tunneling mechanisms.

Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy.

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances in biotechnology have revealed the potential of bacteria and their derivatives as drug delivery systems for tumor therapy by leveraging their biological properties. Engineered bacteria, including , , and , along with their derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), and bacterial spores (BSPs)─can be loaded with a variety of antitumor agents, enabling precise targeting and sustained drug release within the tumor microenvironment (TME).

Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.

Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.