Effects of quercetagetin on the growth performance, nutrient digestibility, slaughter performance, meat quality, and antioxidant capacity of broiler chickens.

This study investigated the effects of quercetagetin (QG) on growth performance, nutrient digestibility, meat quality, and antioxidant capacity of broilers. Four hundred 1-day-old Cobb broilers were randomly divided into five diets, each with eight replicates and 10 birds per replicate. The diets included a basal diet, and four diets with 25, 50, 100, and 200 mg/kg QG supplemented in basal diet.

Immune-Mediated Liver Effects Associated With Administration of a Human Anti-IL-21 Receptor Antibody (ATR-107) in Rats.

The toxicity of ATR-107, a human anti-interleukin-21 receptor (IL-21R) monoclonal antibody (mAb), was evaluated in CD-1 mice and cynomolgus monkeys after single-dose intravenous (IV) administration, and in Sprague-Dawley (SD) rats and cynomolgus monkeys after weekly IV and subcutaneous (SC) administration in 13-week toxicity studies that included recovery. Adverse liver necrosis, diffuse bridging fibrosis, and higher liver enzymes occurred in rats in the low-dose IV group (10 mg/kg), but not at 50 or 250 mg/kg IV, and not following SC administration despite overlapping systemic ATR-107 exposures. Similar findings were not seen in mice or cynomolgus monkeys.

Integration of single-cell sequencing with machine learning and Mendelian randomization analysis identifies the NAP1L1 gene as a predictive biomarker for Alzheimer's disease.

Background: The most effective approach to managing Alzheimer's disease (AD) lies in identifying reliable biomarkers for AD to forecast the disease in advance, followed by timely early intervention for patients.

Methods: Transcriptomic data on peripheral blood mononuclear cells (PBMCs) from patients with AD and the control group were collected, and preliminary data processing was completed using standardized analytical methods. PBMCs were initially segmented into distinct subpopulations, and the divisions were progressively refined until the most significantly altered cell populations were identified.

Deciphering mitochondrial dysfunction: Pathophysiological mechanisms in vascular cognitive impairment.

Vascular cognitive impairment (VCI) encompasses a range of cognitive deficits arising from vascular pathology. The pathophysiological mechanisms underlying VCI remain incompletely understood; however, chronic cerebral hypoperfusion (CCH) is widely acknowledged as a principal pathological contributor. Mitochondria, crucial for cellular energy production and intracellular signaling, can lead to numerous neurological impairments when dysfunctional.

Enzymolytic soybean meal-impact on growth performance, nutrient digestibility, antioxidative capacity, and intestinal health of weaned piglets.

Enzymolytic soybean meal (ESBM) enriches free amino acids and small peptides, while mitigating anti-nutritional factors. Substituting soybean meal with ESBM enhances animal performance, though optimal piglet dietary supplementation levels vary. The present study aimed to assess the impact of ESBM on the growth performance, nutrient digestibility, antioxidative capacity and intestinal health of weaned piglets.

The binding affinity-dependent inhibition of cell growth and viability by DNA sulfur-binding domains.

Increasing evidence suggests that DNA phosphorothioate (PT) modification serves several purposes in the bacterial host, and some restriction enzymes specifically target PT-DNA. PT-dependent restriction enzymes (PDREs) bind PT-DNA through their DNA sulfur binding domain (SBD) with dissociation constants (K) of 5 nM~1 μM. Here, we report that SprMcrA, a PDRE, failed to dissociate from PT-DNA after cleavage due to high binding affinity, resulting in low DNA cleavage efficiency.

Translation of nonclinical to clinical safety findings for 27 biotherapeutics.

Human adverse drug reactions (ADRs), and in vivo nonclinical adverse and nonadverse findings, were identified in 27 biotherapeutic programs and placed into organ categories to determine translation. The sensitivity of detecting human ADRs was 30.8% with a positive predictive value (PPV) of 53.

Adaptive class augmented prototype network for few-shot relation extraction.

Relation extraction is one of the most essential tasks of knowledge construction, but it depends on a large amount of annotated data corpus. Few-shot relation extraction is proposed as a new paradigm, which is designed to learn new relationships between entities with merely a small number of annotated instances, effectively mitigating the cost of large-scale annotation and long-tail problems. To generalize to novel classes not included in the training set, existing approaches mainly focus on tuning pre-trained language models with relation instructions and developing class prototypes based on metric learning to extract relations.

Melatonin alleviates Hg toxicity by modulating redox homeostasis and the urea cycle in moss.

Mercury (Hg) is a highly toxic metal and can cause severe damage to many organisms under natural conditions. As an effective free radical scavenger and antioxidant, Melatonin (MT) has played important protective roles in alleviating oxidative damage caused by environmental cues including heavy metal stress in plants. However, the detailed mechanisms of melatonin in alleviating Hg toxicity still remain unclear in plants.

Characterization of a promiscuous DNA sulfur binding domain and application in site-directed RNA base editing.

Phosphorothioate (PT)-modification was discovered in prokaryotes and is involved in many biological functions such as restriction-modification systems. PT-modification can be recognized by the sulfur binding domains (SBDs) of PT-dependent restriction endonucleases, through coordination with the sulfur atom, accompanied by interactions with the DNA backbone and bases. The unique characteristics of PT recognition endow SBDs with the potential to be developed into gene-targeting tools, but previously reported SBDs display sequence-specificity for PT-DNA, which limits their applications.

Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities.

The degradation tag (dTAG) system for target protein degradation can remove proteins from biological systems without the drawbacks of some genetic methods, such as slow kinetics, lack of reversibility, low specificity, and the inability to titrate dosage. These drawbacks can make it difficult to compare toxicity resulting from genetic and pharmacological interventions, especially in vivo. Because the dTAG system has not been studied extensively in vivo, we explored the use of this system to study the physiological sequalae resulting from CDK2 or CDK5 degradation in adult mice.

Development of a Machine-Learning Model for Prediction of Extubation Failure in Patients with Difficult Airways after General Anesthesia of Head, Neck, and Maxillofacial Surgeries.

(1) Background: Extubation failure after general anesthesia is significantly associated with morbidity and mortality. The risk of a difficult airway after the general anesthesia of head, neck, and maxillofacial surgeries is significantly higher than that after general surgery, increasing the incidence of extubation failure. This study aimed to develop a multivariable prediction model based on a supervised machine-learning algorithm to predict extubation failure in adult patients after head, neck, and maxillofacial surgeries.

An ethyl acetate fraction of flavonoids from L. exhibits an anti-inflammatory activity in PCV2-infected porcine alveolar macrophages via PI3K/Akt and NF-κB pathways.

Porcine circovirus type 2 (PCV2) widely exists in swine production systems causing porcine circovirus diseases (PCVD) which is associated with significant economic losses. . was used as a traditional Chinese medicine to treat a variety of diseases.

Gemtuzumab Ozogamicin Treatment Results in Decreased Proliferation and Differentiation of Human Megakaryocytes but Does Not Inhibit Mature Platelet Function.

Mylotarg (Gemtuzumab ozogamicin [GO]), an antibody drug conjugate comprising a CD33-directed antibody linked to calicheamicin, is approved for use in certain acute myeloid leukemia patients. Following reports of prolonged thrombocytopenia and hemorrhagic events in a subset of patients, a detailed series of in vitro and ex vivo studies was performed at the request of regulators, both to look at the effects of GO on platelet production and to determine whether treatment with GO was likely to affect platelet aggregation under a variety of conditions. Treatment with GO resulted in cellular cytotoxicity and/or decreased differentiation during human megakaryocyte development.

Comparative Analyses of Poly(ADP-Ribose) Polymerase Inhibitors.

Poly(ADP-ribose) polymerase inhibitors (PARPi) are approved as monotherapies in -mutated (m) metastatic breast and ovarian cancers, and in advanced pancreatic and metastatic castration-resistant prostate cancers. Differential safety profiles across PARPi necessitate improved mechanistic understanding of inhibitor differences, especially with expansion of PARPi indications and drug combinations. Here, we report in vitro evaluations of PARPi (-/+ PARP trapper temozolomide, TMZ) with reference to total clinical mean concentration average or maximum (tC, tC), to elucidate contributions of primary pharmacology and structural differences to clinical efficacy and safety.

Medication Rules in Herbal Medicine for Mild Cognitive Impairment: A Network Pharmacology and Data Mining Study.

Background: Although traditional Chinese medicine (TCM) has good efficacy in the treatment of mild cognitive impairment (MCI), especially memory improvement and safety, its substance basis and intervention mechanism are particularly complex and unknown. Therefore, based on network pharmacology and data mining, this study aims to explore the rules, active ingredients and mechanism of TCM in the treatment of MCI.

Methods: By searching the GeneCard, OMIM, DisGeNET and DrugBank databases, we obtained the critical targets associated with MCI.

The effect of nasal tube stabilization on pressure between tube and nose: A prospective, randomized controlled trial.

Objective: This clinical trial was performed to evaluate the effect of nasal tube stabilization (NTS) on the pressure between tube and nose (PTN) in both supine and neck extension positions.

Study Design: This prospective randomized controlled trial recruited 24 American Society of Anesthesiologists physical status I or II adult patients who underwent oral and maxillofacial surgeries requiring nasotracheal intubation. Patients were randomly assigned to intubate with either wire-reinforced or RAE (Ring-Adair-Elwyn) tube.

Rational design and fabrication of monophasic bioceramic microspheres with enhanced mechanical and biological performances in reconstruction of segmental bone defect.

Over the past decades, there has been extensive study on the design of porous bioceramic scaffolds with controlled bioactivity and biodegradation in bone tissue repair. A variety of suggestive models and concepts have been proposed with regard to the role of microstructure and composition of biomaterials which affect new bone tissue growth. However, it is a challenge to fabricate functional scaffolds with the desired physiological properties and osteogenic potentials that is comparable to the bone's natural healing time scale.

Regulatory effect of Panax notoginseng saponins on the oxidative stress and histone acetylation induced by porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) exists widely in swine populations worldwide, and healthy PCV2 virus carriers have enhanced the severity of the infection, which is becoming more difficult to control. This study investigated the regulatory effect of Panax notoginseng saponins (PNS) on the oxidative stress and histone acetylation modification induced by PCV2 in vitro and in mice. In vitro, PNS significantly increased the scavenging capacities of superoxide anion radicals (O) and hydroxyl radicals (OH) and reduced the content of hydrogen peroxide (HO) induced by PCV2 in porcine alveolar macrophages (3D4/2).

Separation, Purification, Structure Analysis, In Vitro Antioxidant Activity and circRNA-miRNA-mRNA Regulatory Network on PRV-Infected RAW264.7 Cells of a Polysaccharide Derived from .

To investigate the structure of polysaccharide (PAP) (intracellular polysaccharide) and the antioxidant activity of the first component of PAP (PAP-1) on pseudorabies virus (PRV) -infected RAW264.7 cells. The PAP was separated and purified by the Cellulose DE-52 chromatography column and Sephacryl S-200 high-resolution gel column to obtain PAP-1.

Efficacy of therapies in the treatment of Guillain-Barre syndrome: A network meta-analysis.

Background: Guillain-Barre syndrome (GBS) is a disease with the features of acuteness, paralysis, inflammation, and in peripheral nerves. There are many current treatment options with varying efficacy, and to assess their effectiveness, we performed a network meta-analysis (NMA). The study protocol was registered at PROSPERO (CRD: 42019119178).

Liver Toxicity Observed With Lorlatinib When Combined With Strong CYP3A Inducers: Evaluation of Cynomolgus Monkey as a Nonclinical Model for Assessing the Mechanism of Combinational Toxicity.

Lorlatinib is a potent small-molecule anaplastic lymphoma kinase inhibitor approved for the treatment of patients with nonsmall cell lung cancer. In a drug-drug interaction study in healthy human participants, liver enzyme elevations were observed when a single 100 mg dose of lorlatinib was administered after multiple doses of rifampin, a strong cytochrome P450 (CYP) 3A inducer and a pregnane X receptor (PXR) agonist. A series of in vitro and in vivo studies were conducted to evaluate potential mechanisms for the observed clinical toxicity.