Molecule-rich solutions for achieving novel non-opioid analgesics.

Despite their efficacy, opioids have long been associated with risks of addiction, tolerance, and dependence, leaving an unmet clinical need for pain treatment. Efforts have been devoted to developing novel classes of pain-relieving medication that outperform current options in terms of pain relief, side-effect profiles, and potential for abuse, but with limited success. Recent advances in the neurobiology of pain have shed light on the potential of targeting non-opioid receptors involved in pain processing.

Redox state of NAD modulates the activation of Na-bicarbonate cotransporter NBCe1-B via IRBIT and L-IRBIT.

Nicotinamide adenine dinucleotide (NAD) is well known as a coenzyme involved in many redox reactions in cellular energy metabolism, or as a substrate for many NAD-consuming enzymes, including those that generate the second messenger cyclic ADP-ribose or deacetylate proteins (e.g., histones).

Improvement in XIa Selectivity of Snake Venom Peptide Analogue BF9-N17K Using P2' Amino Acid Replacements.

Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2' amino acid classification scanning strategy.

Influence of elevation angle of tundish filter on removal rate of impurity in molten steel.

To investigate the effect of the filter device on the cleanliness of molten steel and the flow field distribution within the tundish. The tundish filters were designed into five groups of pores with 20°, 25°, 30°, 35° and 40° elevation angles, and the flow field distribution and impurity removal rate of molten steel were calculated by Discrete Phase Model (DPM). The results showed that the removal rate of impurity in the molten steel could be significantly improved by using the tundish filter with elevation angle.

Etiolated-green tea attenuates colonic barrier dysfunction and inflammation in high-fat diet-induced mice by modulating gut microbiota.

Colonic barrier dysfunction and inflammation arising from dysbiosis gut microbiota (GM) are strongly associated with a high-fat diet (HFD). Yellow leaf green tea (YLGT), a novel variety of etiolated-green tea, improving the intestinal barrier and inflammation is related to the regulation of GM disorders. To explore the ameliorative mechanism of YLGT, mice were fed an HFD with or without YLGT at doses of 150, 300, and 450 mg kg for 12 weeks.

Differential potassium channel inhibitory activities of a novel thermostable degradation peptide BmKcug1a-P1 from scorpion medicinal material and its N-terminal truncated/restored peptides.

Thermally stable full-length scorpion toxin peptides and partially degraded peptides with complete disulfide bond pairing are valuable natural peptide resources in traditional Chinese scorpion medicinal material. However, their pharmacological activities are largely unknown. This study discovered BmKcug1a-P1, a novel N-terminal degraded peptide, in this medicinal material.

Pre-trained language models in medicine: A survey.

With the rapid progress in Natural Language Processing (NLP), Pre-trained Language Models (PLM) such as BERT, BioBERT, and ChatGPT have shown great potential in various medical NLP tasks. This paper surveys the cutting-edge achievements in applying PLMs to various medical NLP tasks. Specifically, we first brief PLMS and outline the research of PLMs in medicine.

Improving Classification Performance in Dendritic Neuron Models through Practical Initialization Strategies.

A dendritic neuron model (DNM) is a deep neural network model with a unique dendritic tree structure and activation function. Effective initialization of its model parameters is crucial for its learning performance. This work proposes a novel initialization method specifically designed to improve the performance of DNM in classifying high-dimensional data, notable for its simplicity, speed, and straightforward implementation.

Cationicity Enhancement on the Hydrophilic Face of Ctriporin Significantly Reduces Its Hemolytic Activity and Improves the Antimicrobial Activity against Antibiotic-Resistant ESKAPE Pathogens.

The ESKAPE pathogen-associated antimicrobial resistance is a global public health issue, and novel therapeutic strategies are urgently needed. The short cationic antimicrobial peptide (AMP) family represents an important subfamily of scorpion-derived AMPs, but high hemolysis and poor antimicrobial activity hinder their therapeutic application. Here, we recomposed the hydrophilic face of Ctriporin through lysine substitution.

Function and Mechanism of Antiviral Wasp Venom Peptide Protopolybia-MP III and Its Derivatives against HSV-1.

Viruses are one of the leading causes of human disease, and many highly pathogenic viruses still have no specific treatment drugs. Therefore, producing new antiviral drugs is an urgent matter. In our study, we first found that the natural wasp venom peptide Protopolybia-MP III had a significant inhibitory effect on herpes simplex virus type 1 (HSV-1) replication by using quantitative real-time PCR (qPCR), Western blotting, and plaque-forming assays.

Yellow leaf green tea modulates the AMPK/ACC/SREBP1c signaling pathway and gut microbiota in high-fat diet-induced mice to alleviate obesity.

Background: Yellow leaf green tea (YLGT) is a new variety of Camellia sinensis (L.) O. Ktze, which has yellow leaves and the unique qualities of 'three green through three yellow'.

Application of deep learning in the diagnosis and evaluation of ulcerative colitis disease severity.

Background: Achieving endoscopic and histological remission is a critical treatment objective in ulcerative colitis (UC). Nevertheless, interobserver variability can significantly impact overall assessment performance.

Objectives: We aimed to develop a deep learning algorithm for the real-time and objective evaluation of endoscopic disease activity and prediction of histological remission in UC.

Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients.

Background: Schizophrenia (SCZ) is a serious chronic mental disorder. Our previous case-control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study.

Genetic contribution of synapse-associated protein 97 to cerebellar functional connectivity changes in first-episode schizophrenia.

Our previous study data suggested that the synapse-associated protein 97 (SAP97) rs3915512 polymorphism is significantly related to clinical performance in schizophrenia. The cerebellum exhibits abundant expression of SAP97, which is involved with negative symptoms, cognition and emotion in schizophrenia. As functional dysconnectivity with the cortical-subcortical-cerebellar circuitry has been widely shown in patients with schizophrenia, cortical-subcortical-cerebellar dysconnectivity can therefore be considered a possible intermediate phenotype that connects risk genes with schizophrenia.

Interpretability Diversity for Decision-Tree-Initialized Dendritic Neuron Model Ensemble.

To construct a strong classifier ensemble, base classifiers should be accurate and diverse. However, there is no uniform standard for the definition and measurement of diversity. This work proposes a learners' interpretability diversity (LID) to measure the diversity of interpretable machine learners.

Semantic matching based legal information retrieval system for COVID-19 pandemic.

Recently, the pandemic caused by COVID-19 is severe in the entire world. The prevention and control of crimes associated with COVID-19 are critical for controlling the pandemic. Therefore, to provide efficient and convenient intelligent legal knowledge services during the pandemic, we develop an intelligent system for legal information retrieval on the WeChat platform in this paper.

Genetic variations in DOCK4 contribute to schizophrenia susceptibility in a Chinese cohort: A genetic neuroimaging study.

Background: Emerging evidence suggests that the DOCK4 gene increases susceptibility to schizophrenia. However, no study has hitherto repeated this association in Chinese, and further investigated the relationship between DOCK4 and clinical symptoms in schizophrenic patients using clinical scales and functional magnetic resonance imaging (fMRI).

Methods: In this study, we genotyped three single nucleotide polymorphisms (SNPs) (rs2074127, rs2217262, and rs2074130) within the DOCK4 gene using a case-control design (including 1289 healthy controls and 1351 patients with schizophrenia).

Electroacupuncture reverses endothelial cell death and promotes angiogenesis through the VEGF/Notch signaling pathway after focal cerebral ischemia-reperfusion injury.

Background: Angiogenesis is an important mechanism of recovery from ischemic stroke. Recent studies have found that there is a close relationship between the VEGF/Notch pathway and angiogenesis. It is unknown whether EA can exert a brain protection effect and promote angiogenesis by acting on the VEGF/Notch signaling pathway after focal cerebral ischemia-reperfusion injury (CIRI).

Giant seminal vesicle cyst with hemorrhage in Zinner syndrome: A case report.

Rationale: Zinner syndrome (ZS) is a rare congenital malformation of the urogenital tract that is associated with seminal vesicle cysts, ejaculatory duct obstruction, and ipsilateral renal agenesis. This unique condition was first reported by Zinner (1914). ZS is caused by malformation of the distal mesonephric duct during embryogenesis.

Multimodal fusion diagnosis of depression and anxiety based on CNN-LSTM model.

Background: In recent years, more and more people suffer from depression and anxiety. These symptoms are hard to be spotted and can be very dangerous. Currently, the Self-Reported Anxiety Scale (SAS) and Self-Reported Depression Scale (SDS) are commonly used for initial screening for depression and anxiety disorders.

Stochastic growth tree networks with an identical fractal dimension: Construction and mean hitting time for random walks.

There is little attention paid to stochastic tree networks in comparison with the corresponding deterministic analogs in the current study of fractal trees. In this paper, we propose a principled framework for producing a family of stochastic growth tree networks possessing fractal characteristic, where t represents the time step and parameter m is the number of vertices newly created for each existing vertex at generation. To this end, we introduce two types of generative ways, i.

Schixator, a new FXa inhibitor from Schistosoma japonicum with antithrombotic effect and low bleeding risk.

Schistosoma japonicum is a parasitic worm that lives in the mesenteric vein of its host and feeds on blood, suggesting that it might be a natural resource of novel anticoagulants. Here, by comprehensive analyses of the genomic sequences of Schistosoma japonicum, a new Kunitz-type gene precursor was identified. The Kunitz-type gene precursor codes for an 18-residue signal peptide and a 60-residue mature peptide.