Demethylzeylasteral induces PD-L1 ubiquitin-proteasome degradation and promotes antitumor immunity targeting USP22.

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells.

Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.

Immune checkpoint inhibitors (ICIs) are drugs that inhibit immune checkpoint (ICP) molecules to restore the antitumor activity of immune cells and eliminate tumor cells. Due to the limitations and certain side effects of current ICIs, such as programmed death protein-1, programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibodies, there is an urgent need to find new drugs with ICP inhibitory effects. In this study, a network-based computational framework called multi-network algorithm-driven drug repositioning targeting ICP (Mnet-DRI) is developed to accurately repurpose novel ICIs from ≈3000 Food and Drug Administration-approved or investigational drugs.

Determination and Ecological Risk Assessment of Quinolone Antibiotics in Drinking and Environmental Waters Using Fully Automated Disk-Based SPE Coupled with UPLC-MS/MS.

Quinolone antibiotics (QNs) contamination in the aquatic environment is a global public health issue considering their resistance and mobility. In this study, a simple, efficient, and sensitive method was developed for the accurate quantification of fifteen QNs in water using automated disk-based solid-phase extraction (SPE) coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). By utilizing a 3M SDB-XC disk to enrich QNs from a 1000 mL water sample, the detection limits were improved to 0.

Functional analysis of and under low-phosphate stress in maize.

Unlabelled: The PHOSPHATE STARVATION RESPONSE REGULATOR (PHR) plays a crucial regulatory role in plants during the process of responding to phosphate starvation. In this study, we combined reverse genetics and biotechnology to investigate the function of and , including proteins containing the Myb_DNA_banding and Myb_CC-LHEQLE structural domains, in maize seedlings. Phylogenetic analysis revealed that and have high homology with and , and share the characteristic features of nuclear localisation and transcriptional self-activation.

Occurrence and risk assessment of quinolones and sulfonamides in freshwater aquaculture ponds in Northeast Zhejiang, China.

Antibiotics play an essential role in the aquaculture industry, but their overuse and weak degradability inevitably lead to light to severe residues in natural and aquaculture environments. Most studies were interested in the occurrence, distribution, and ecological risks of a limited number of antibiotics in natural environments (rivers, lakes, and coastal regions) with a minor focus on antibiotic presence in either water, sediments, or organisms in aquaculture environments located in specific regions. In this study, we conducted a comprehensive investigation into the occurrence and distribution of up to 32 antibiotics [including 15 quinolones (QNs) and 17 sulfonamides (SAs)] in organisms and their corresponding environmental matrices from 26 freshwater aquaculture ponds in Northeast Zhejiang, China.

Determination of Volatile Halogenated Hydrocarbons in Drinking and Environmental Waters by Headspace Gas Chromatography.

Volatile halogenated hydrocarbons (VHHs) are annually produced and released into the environment, posing a threat to public health. In this study, a simple, rapid, sensitive and automated method based on headspace and gas chromatography (GC) with electron-capture detection was described for the determination of VHHs in different concentration levels in water samples. The proposed headspace GC method was initially optimized, and the optimum experimental conditions found were 10-mL water sample containing 20% w/v sodium chloride placed in a 20-mL vial and stirred at 60°C for 35 min, and then 14 VHHs were well separated on DB-35 MS capillary column with a split ratio of 12.

Rapid Determination of Tetracyclines in Drinking and Environmental Waters Using Fully Automatic Solid-Phase Extraction with Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

The abuse and irrational use of tetracyclines (TCs) in human medicine and animal husbandry has become a serious concern, affecting the ecological environment and human health. The aim of this study was to develop a sensitive and selective method using fully automatic solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the determination of twelve TCs in water. Four isotope-labeled internal standards for TCs were used to correct matrix effects.

Formic acid enhances whole-plant mulberry silage fermentation by boosting lactic acid production and inhibiting harmful bacteria.

Mulberry has also been regarded as a valuable source of forage for ruminants. This study was developed to investigate the impact of four additives and combinations thereof on fermentation quality and bacterial communities associated with whole-plant mulberry silage. Control fresh material (FM) was left untreated, while other groups were treated with glucose (G, 20 g/kg FM), a mixture of and (L, 10 CFU/g FM), formic acid (A, 5 mL/kg FM), salts including sodium benzoate and potassium sorbate (S, 1.

Rate dependent neural responses of interaural-time-difference cues in fine-structure and envelope.

Advancements in cochlear implants (CIs) have led to a significant increase in bilateral CI users, especially among children. Yet, most bilateral CI users do not fully achieve the intended binaural benefit due to potential limitations in signal processing and/or surgical implant positioning. One crucial auditory cue that normal hearing (NH) listeners can benefit from is the interaural time difference (ITD), .

Volatile fatty acids production from kitchen waste slurry using anaerobic membrane bioreactor via alkaline fermentation with high salinity: Evaluation on process performance and microbial succession.

In this study, a pilot-scale anaerobic membrane bioreactor (AnMBR) was developed to continuously produce volatile fatty acids (VFAs) from kitchen waste slurry under an alkaline condition. The alkaline fermentation effectively suppressed methanogenesis, thus achieving high VFAs production of 60.3 g/L.

Pinoresinol diglucoside mitigates dexamethasone-induced osteoporosis and chondrodysplasia in zebrafish.

Background: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly.

Objective: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia.

Methods: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone.

Simultaneous preconcentration and quantification of ultra-trace tin and lead species in seawater by online SPE coupled with HPLC-ICP-MS.

Background: Tin and lead contamination is a global threat to marine ecosystems considering their species-specific toxicity, bioavailability and mobility. Hence simultaneous measurement of multiple tin and lead compounds at μg L to pg L levels in environmental water is always an indispensable but challengeable task. High performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) is one of the most widely used choices for this purpose because of good sensitivity, strong separation power and good compatibility.

Simultaneous quantification of tin and lead species in Antarctic krill and fish by interfacing high-performance liquid chromatography with inductively coupled plasma mass spectrometry based on strong cation-exchange and Amphion columns.

Tin and lead are a global concern considering their species-dependent toxicity, bioavailability and transformation. Simultaneous speciation analysis of tin and lead is challenging for a large food capacity containing unstable species. Herein, we developed two sensitive methods for rapid quantification of tin and lead species in Antarctic seafood by high-performance liquid chromatography and inductively coupled plasma mass spectrometry based on strong cation-exchange and Amphion columns.

Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3.

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockade has become a mainstay of cancer immunotherapy. Targeting the PD-1/PD-L1 axis with small molecules is an attractive approach to enhance antitumor immunity. Here, we identified a natural marine product, benzosceptrin C (BC), that enhances the cytotoxicity of T cells to cancer cells by reducing the abundance of PD-L1.

Dietary of different forms of on growth performance and intestinal bacterial communities in piglets.

The present study was aimed at elucidating the effects of feeding different forms of (Hu) on performance and bacterial communities in piglets. A total of 160 piglets were divided into four groups: (1) a control (CG, basal diet); (2) a basal diet with Hu pulp (HS), basal diet + Hu pulp; (3) a basal diet with Hu juice (HSJ), basal diet + Hu juice; and (4) a basal diet with Hu residue (HSR), basal diet + Hu residue. Results showed that HS, HSJ, and HSR supplementation led to rich average daily gain () and poor feed conversion ratio () during 28 to 70 d of age, increased 120 d body weight (), average daily feed intake () and ADG and decreased FCR during 71 to 120 d of age.

Target-triggered dual signal amplification based on HCR-enhanced nanozyme activity for the sensitive visual detection of .

The detection of foodborne pathogens is crucial for food hygiene regulation and disease diagnosis. Colorimetry has become one of the main analytical methods in studying foodborne pathogens due to its advantages of visualization, low cost, simple operation, and no complex instrument. However, the low sensitivity limits its applications in early identification and on-site detection for trace analytes.

Functional analysis of reveals its role in responses to low-phosphorus stress and regulation of grain yield in maize.

A previous metabolomic and genome-wide association analysis of maize screened a glucose-6-phosphate 1-epimerase () gene, which responds to low-phosphorus (LP) stress and regulates yield in maize's recombinant inbred lines (RILs). However, the relationship of with phosphorus and yield remained elusive. This study aimed to elucidate the underlying response mechanism of the gene to LP stress and its consequential impact on maize yield.

Benzophenone induces cardiac developmental toxicity in zebrafish embryos by upregulating Wnt signaling.

Benzophenone (BP) is found in many popular consumer products, such as cosmetics. BP potential toxicity to humans and aquatic organisms has emerged as an increased concern. In current study, we utilized a zebrafish model to assess BP-induced developmental cardiotoxicity.

Cysteamine hydrochloride affects ocular development and triggers associated inflammation in zebrafish.

The increasing use of cosmetics has raised widespread concerns regarding their ingredients. Cysteamine hydrochloride (CSH) is a newly identified allergenic component in cosmetics, and therefore its potential toxicity needs further elucidation. Here, we investigated the in vivo toxicity of CSH during ocular development utilizing a zebrafish model.

An Automated Solid-Phase Extraction-UPLC-MS/MS Method for Simultaneous Determination of Sulfonamide Antimicrobials in Environmental Water.

The large-scale use of sulfonamide antimicrobials in human and veterinary medicine has seriously endangered the ecological environment and human health. The objective of this study was to develop and validate a simple and robust method for the simultaneous determination of seventeen sulfonamides in water using ultra-high performance liquid chromatography-tandem mass spectrometry coupled with fully automated solid-phase extraction. Seventeen isotope-labeled internal standards for sulfonamides were used to correct matrix effects.

Joint concanavalin A-aptamer enabled dual recognition for anti-interference visual detection of Salmonella typhimurium in complex food matrices.

Given that food poisoning and infectious diseases caused by Salmonella typhimurium (S. typhimurium) draw intensive public health concerns, developing rapid, accurate, and cost-effective approaches to detect the pathogen is of crucial importance. Herein, we proposed a concanavalin A (Con A)-aptamer joint strategy to realize dual recognition for the strongly specific, visual, and highly sensitive determination of S.

Pexidartinib hydrochloride exposure induces developmental toxicity and immunotoxicity in zebrafish embryos via activation of Wnt signaling.

Pexidartinib, a macrophage colony-stimulating factor receptor (CSF-1R) inhibitor, is indicated for the treatment of tendon sheath giant cell tumor (TGCT). However, few studies on the toxicity mechanisms of pexidartinib for embryonic development. In this study, the effects of pexidartinib on embryonic development and immunotoxicity in zebrafish were investigated.

Hepatic lipid metabolism disorders and immunotoxicity induced by cysteamine in early developmental stages of zebrafish.

Cysteamine, a sulfhydryl compound, is an intermediate in the metabolism of coenzyme A to taurine in living organisms. However, the potential side effects of cysteamine such as hepatotoxicity in pediatric patients have been reported in some studies. To evaluate the impact of cysteamine on infants and children, larval zebrafish (a vertebrate model) were exposed to 0.

Ainsliadimer A induces ROS-mediated apoptosis in colorectal cancer cells via directly targeting peroxiredoxin 1 and 2.

The peroxiredoxin (PRDX) family is a class of antioxidant enzymes with peroxidase activity. Human PRDXs currently have six members (PRDX1-6), which are gradually becoming potential therapeutic targets for major diseases such as cancer. In this study, we reported ainsliadimer A (AIN), a sesquiterpene lactone dimer with antitumor activity.