Activity tolerance

BACKGROUND: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT4 ] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery. METHODS: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.1 mg/100 ​mL or 0...

BACKGROUND AND AIMS: The pivotal phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis. This analysis assessed ozanimod during TN and the ongoing open-label extension (OLE) in patients with active disease who were naive to advanced therapies (ATs). METHODS: TN was a randomized, double-blind, placebo-controlled trial consisting of a 10-week induction period and 42-week maintenance period...

Cadmium (Cd) is an extremely toxic heavy metal that can originate from industrial activities and accumulate in agricultural soils. This study investigates the potential of biologically synthesized silicon oxide nanoparticles (Bio-SiNPs) in alleviating Cd toxicity in bayberry plants. Bio-SiNPs were synthesized using the bacterial strain Chryseobacterium sp. RTN3 and thoroughly characterized using advanced techniques. A pot experiment results demonstrated that Cd stress substantially reduced leaves biomass, photosynthesis efficiency, antioxidant enzyme activity, and induced oxidative damage in bayberry (Myrica rubra) plants...

Antimicrobial peptides (AMPs), which have a low probability of developing resistance, are considered the most promising antimicrobial agents for combating antibiotic resistance. Feleucin-K3 is an amphiphilic cationic AMP that exhibits broad-spectrum antimicrobial activity. In our previous research, the first phenylalanine residue was identified as the critical position affecting its biological activity. Here, a series of Feleucin-K3 analogs containing hydrophobic D-amino acids were developed, leveraging the low sensitivity of proteases to unnatural amino acids and the regulatory effect of hydrophobicity on antimicrobial activity...

Crop plants face complex tropospheric ozone (O3 ) stress, emphasizing the need for a food security-focused management strategy. While research extensively explores O3 's harmful effects, this study delves into the combined impacts of O3 and CO2 . This study investigates the contrasting responses of O3 -sensitive (PBW-550) and O3 -resistant (HUW-55) wheat cultivars, towards elevated ozone (eO3 ) and elevated carbon dioxide (eCO2 ), both individually and in combination. The output of the present study confirms the positive effect of eCO2 on wheat cultivars exposed to eO3 stress, with more prominent effects on O3 -sensitive cultivar PBW-550, as compared to the O3 -resistant HUW-55...

Climate change is predicted to change not only the temperature of many freshwater systems but also flow dynamics. Understanding how fishes will fare in the future requires knowing how they will respond to both extended variations of temperature and flow. Arctic charr have had their thermal tolerance measured, but never with respect to flow. Additionally, this circumpolar species has multiple populations exhibiting dramatic phenotypic plasticity which may mean that regional differences in thermal tolerance are unaccounted for...

PURPOSE: While cytotoxic chemotherapy is standard first-line treatment for patients with metastatic soft tissue sarcoma (STS), clinical outcomes remain suboptimal. Our prior study showed lurbinectedin plus doxorubicin is well-tolerated with promising clinical activity in STS. We designed this phase 1b trial to optimize dosing as the basis for a randomized trial in leiomyosarcoma (LMS) and to further explore the safety profile and efficacy signal. PATIENTS AND METHODS: Patients had advanced/metastatic STS and no prior anthracycline/lurbinectedin/trabectedin...

Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4-dione derivatives ( MY1-41 ) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds ( MY1-41 ) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC50 ) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 μM, compared with that of the positive control lithocholic acid (IC50 = 9.62 ± 0.14 μM)...

Alternative energy sources are required due to the decline in fossil fuel resources. Therefore, devices that utilize hydrovoltaic technology and light energy have drawn widespread attention because they are emission-free and solar energy is inexhaustible. However, previous investigations mainly focused on accelerating the water evaporation rate at the electrode interface. Here, a cooperative photoelectrochemical effect on a hydrovoltaic chip is achieved using NH2 -MIL-125-modified TiO2 nanotube arrays (NTs)...

IMPORTANCE: Options for adults with relapsed or refractory B-cell acute lymphoblastic leukemia or lymphoma (B-ALL) are limited, and new approaches are needed. Inotuzumab ozogamicin (InO) has been combined with low-intensity chemotherapy, with modest improvements over historical controls, and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) treatment is safe and active for newly diagnosed ALL. OBJECTIVE: To assess the safety and clinical activity of DA-EPOCH and InO in adults with relapsed or refractory B-ALL...

Herein, we report a viable protocol to access furo[3,2- c ]chromen-4-ones by engaging easily accessible 4-hydroxy coumarins as a three-atom CCO unit and thioamides as a C2 coupling partner, mediated by phenyliodine(III) diacetate (PIDA) at room temperature in a highly efficient and pot-/step-economical manner. This strategy not only avoids potential toxicity and tiresome workup conditions, but also features operational simplicity, a broad substrate scope, good functional group tolerance, high yields, easy scalability and exclusive selectivity...

The development of cost-effective and high-performance non-noble metal catalysts for the oxygen reduction reaction (ORR) holds substantial promise for real-world applications. Introducing a secondary metal to design bimetallic sites enables effective modulation of a metal-nitrogen-carbon (M-N-C) catalyst's electronic structure, providing new opportunities for enhancing ORR activity and stability. Here, we successfully synthesized an innovative hierarchical porous carbon material with dual sites of Zn and Mg (Zn/Mg-N-C) using polymeric ionic liquids (PILs) as precursors and SBA-15 as a template through a bottom-up approach...

BACKGROUND: Preterm infants (born before 37 weeks' gestation) are often unable to co-ordinate sucking, swallowing, and breathing for oral feeding because of their immaturity. In such cases, initial nutrition is provided by orogastric or nasogastric tube feeding. Feeding intolerance is common and can delay attainment of full enteral and sucking feeds, prolonging the need for nutritional support and the hospital stay. Smell and taste play an important role in the activation of physiological pre-absorptive processes that contribute to food digestion and absorption...

Cr(VI) has been a carcinogen for organisms and a hazard to human health throughout the food chain. To explore a cost-effective and efficient method for removing Cr(VI), a Cr-resistant strain named LBA108 was isolated from the soil of a molybdenum-lead mining area. It was identified as Microbacterium through biochemical tests and 16S rDNA sequence analysis. Following 48 hours of incubation in LB culture medium containing 60 mg L-1 Cr(VI), the LBA108 strain exhibited reduction and adsorption rates for Cr(VI) at 96...

DNA replication faces challenges from DNA lesions originated from endogenous or exogenous sources of stress, leading to the accumulation of single-stranded DNA (ssDNA) that triggers the activation of the ATR checkpoint response. To complete genome replication in the presence of damaged DNA, cells employ DNA damage tolerance mechanisms that operate not only at stalled replication forks but also at ssDNA gaps originated by repriming of DNA synthesis downstream of lesions. Here, we demonstrate that human cells accumulate post-replicative ssDNA gaps following replicative stress induction...

Most malaria ( Plasmodium spp.) parasite species undergo asexual replication synchronously within the red blood cells of their vertebrate host. Rhythmicity in this intraerythrocytic developmental cycle (IDC) enables parasites to maximise exploitation of the host and align transmission activities with the time of day that mosquito vectors blood feed. The IDC is also responsible for the major pathologies associated with malaria, and plasticity in the parasite's rhythm can confer tolerance to antimalarial drugs...

INTRODUCTION: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance...

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 μg/mL) and lowest (10,000 μg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis...

BACKGROUND: Blocking the CD47 "don't eat me"-signal on tumor cells with monoclonal antibodies or fusion proteins has shown limited clinical activity in hematologic malignancies and solid tumors thus far. Main side effects are associated with non-tumor targeted binding to CD47 particularly on blood cells. METHODS: We present here the generation and preclinical development of NILK-2401, a CEACAM5×CD47 bispecific antibody (BsAb) composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format)...

Climate change results in continuous warming of the planet, threatening sustainable crop production around the world. Amaranth is an abiotic stress-tolerant, climate-resilient, C4 leafy orphan vegetable that has grown rapidly with great divergence and potential usage. The C4 photosynthesis allows amaranth to be grown as a sustainable future food crop across the world. Most amaranth species grow as weeds in many parts of the world, however, a few amaranth species can be also found in cultivated form. Weed species can be used as a folk medicine to relieve pain or reduce fever thanks to their antipyretic and analgesic properties...