KinomeMETA: a web platform for kinome-wide polypharmacology profiling with meta-learning.

Kinase-targeted inhibitors hold promise for new therapeutic options, with multi-target inhibitors offering the potential for broader efficacy while minimizing polypharmacology risks. However, comprehensive experimental profiling of kinome-wide activity is expensive, and existing computational approaches often lack scalability or accuracy for understudied kinases. We introduce KinomeMETA, an artificial intelligence (AI)-powered web platform that significantly expands the predictive range with scalability for predicting the polypharmacological effects of small molecules across the kinome. By leveraging a novel meta-learning algorithm, KinomeMETA efficiently utilizes sparse activity data, enabling rapid generalization to new kinase tasks even with limited information. This significantly expands the repertoire of accurately predictable kinases to 661 wild-type and clinically-relevant mutant kinases, far exceeding existing methods. Additionally, KinomeMETA empowers users to customize models with their proprietary data for specific research needs. Case studies demonstrate its ability to discover new active compounds by quickly adapting to small dataset. Overall, KinomeMETA offers enhanced kinome virtual profiling capabilities and is positioned as a powerful tool for developing new kinase inhibitors and advancing kinase research. The KinomeMETA server is freely accessible without registration at https://kinomemeta.alphama.com.cn/.

Assessing patient information needs for new antidiabetic medications to inform shared decision-making: A best-worst scaling experiment in China.

BACKGROUND: Shared decision-making (SDM) is a patient-centred approach to improve the quality of care. An essential requirement for the SDM process is to be fully aware of patient information needs. OBJECTIVES: Our study aimed to assess patient information needs for new antidiabetic medications using the best-worst scaling (BWS) experiment. METHODS: BWS tasks were developed according to a literature review and the focus group discussion. We used a balanced incomplete block design and blocking techniques to generate choice sets. The final BWS contains 11 attributes, with 6-choice scenarios in each block. The one-to-one, face-to-face BWS survey was conducted among type 2 diabetic patients in Jiangsu Province. Results were analyzed using count-based analysis and modelling approaches. We also conducted a subgroup analysis to observe preference heterogeneity. RESULTS: Data from 539 patients were available for analysis. The most desired information domain was the comparative effectiveness of new antidiabetic medications. It consists of the incidence of macrovascular complications, the length of extended life years, changes in health-related quality of life, the incidence of microvascular complications, and the control of glycated haemoglobin. Of all the attributes, the incidence of macrovascular complications was the primary concern. Patients' glycemic control and whether they had diabetes complications exerted a significant influence on their information needs. CONCLUSIONS: Information on health benefits is of critical significance for diabetic patients. Patients have different information needs as their disease progresses. Personalized patient decision aids that integrate patient information needs and provide evidence of new antidiabetic medications are worthy of being established. PATIENT OR PUBLIC CONTRIBUTION: Before data collection, a pilot survey was carried out among diabetic patients to provide feedback on the acceptability and intelligibility of the attributes.

Characteristics and prediction of agricultural ecological efficiency for coordination between economy and environment.

Agricultural ecological efficiency is an important tool with which to measure the coordination of the sustainable development of agricultural economies and ecological environments. In this paper, a super-efficiency slacks-based measures model was used to measure the agricultural ecological efficiency in Hebei Province. The characteristics of spatial and temporal evolution patterns were explored using a spatial Markov transfer matrix. The results showed that (i) based on measurements, the agricultural ecological efficiency in Hebei Province showed regional differences in four regions (eastern, northern, central and southern Hebei) and 141 counties; (ii) from the perspective of evolutionary characteristics of agricultural ecological efficiency, the overall development of in Hebei Province was good, with more concentrated spatial distribution and more obvious direction, while the type of transfer of agricultural ecological efficiency in Hebei Province showed strong stability that was significantly affected by geographical neighborhood conditions and the club convergence phenomenon; (iii) from the perspective of the long-term evolutionary trend of agricultural ecological efficiency, the areas adjacent to counties with low efficiency had limited potential for improvement, and the areas adjacent to counties with high grade had great potential. However, it was difficult to achieve large-scale improvement in agricultural ecological efficiency in Hebei Province, whether the impact of geospatial backgrounds was considered or not.

Assessment of patients' preferences for new anticancer drugs in China: a best-worst discrete choice experiment on three common cancer types.

OBJECTIVES: Despite the advancement in anticancer drug therapies, cancer treatment decisions are often complex and preference-sensitive, making them well suited for studying shared decision-making (SDM). Our study aimed to assess preferences for new anticancer drugs among three common types of patients with cancer to inform SDM. DESIGN: We identified five attributes of new anticancer drugs and used a Bayesian-efficient design to generate choice sets for a best-worst discrete choice experiment (BWDCE). The mixed logit regression model was applied to estimate patient-reported preferences for each attribute. The interaction model was used to investigate preference heterogeneity. SETTING: The BWDCE was conducted in Jiangsu province and Hebei province in China. PARTICIPANTS: Patients aged 18 years or older, who had a definite diagnosis of lung cancer, breast cancer or colorectal cancer were recruited. RESULTS: Data from 468 patients were available for analysis. On average, the most valued attribute was the improvement in health-related quality of life (HRQoL) (p<0.001). The low incidence of severe to life-threatening side effects, prolonged progression-free survival and the low incidence of mild to moderate side effects were also positive predictors of patients' preferences (p<0.001). Out-of-pocket cost was a negative predictor of their preferences (p<0.001). According to subgroup analysis by type of cancer, the improvement in HRQoL remained the most valuable attribute. However, the relative importance of other attributes varied by type of cancer. Whether patients were newly diagnosed or previously diagnosed cancer cases played a dominant role in the preference heterogeneity within each subgroup. CONCLUSIONS: Our study can assist in the implementation of SDM by providing evidence on patients' preferences for new anticancer drugs. Patients should be informed of the multiattribute values of new drugs and encouraged to make decisions reflecting their values.

Investigating patients' preferences for new anti-diabetic drugs to inform public health insurance coverage decisions: a discrete choice experiment in China.

BACKGROUND: Diabetes is a major public health concern with a considerable impact on healthcare expenditures. Deciding on health insurance coverage for new drugs that meet patient needs is a challenge facing policymakers. Our study aimed to assess patients' preferences for public health insurance coverage of new anti-diabetic drugs in China. METHODS: We identified six attributes of new anti-diabetic drugs and used the Bayesian-efficient design to generate choice sets for a discrete choice experiment (DCE). The DCE was conducted in consecutive samples of type 2 diabetes patients in Jiangsu Province. The mixed logit regression model was applied to estimate patient-reported preferences for each attribute. The interaction model was used to investigate preference heterogeneity. RESULTS: Data from 639 patients were available for analysis. On average, the most valued attribute was the improvement in health-related quality of life (HRQoL) (ß = 1.383, p < 0.001), followed by positive effects on extending life years (ß = 0.787, p < 0.001), and well-controlled glycated haemoglobin (ß = 0.724, p < 0.001). The out-of-pocket cost was a negative predictor of their preferences (ß = -0.138, p < 0.001). Elderly patients showed stronger preferences for drugs with a lower incidence of serious side effects (p < 0.01) and less out-of-pocket costs (p < 0.01). Patients with diabetes complications favored more in the length of extended life (p < 0.01), improvement in HRQoL (p < 0.05), and less out-of-pocket costs (p < 0.001). CONCLUSION: The new anti-diabetic drugs with significant clinical effectiveness and long-term health benefits should become the priority for public health insurance. The findings also highlight the value of accounting for preference heterogeneity in insurance policy-making.

Effects of Culture on the Balance Between Mathematics Achievement and Subjective Wellbeing.

Previous studies suggested that culture have impact on students' mathematics achievement and subjective wellbeing, but few investigated the effects of culture on the balance between them. Drawing on Hofstede's cultural dimensions theory, this study investigated the effects of culture on balance between students' mathematics achievement and subjective wellbeing. Results showed the significant effects of cultural dimensions of long-term orientation vs. short-term orientation and indulgence vs. restraint. Students from countries of high long-term orientation and low indulgence culture were more likely to get both high mathematics achievement and high SWB. Besides, wealth-related variables (family SES and GDP per capita) and gender were also found to influence the odds ratio of balance. The findings confirmed the effects of national culture on the balance between mathematics achievement and SWB. Based on the findings, this study discussed the effects of long-term orientation and restraint culture and Confucian heritage culture's potential benefit. The results indicate that mathematics educators should consider cultural differences in educational practice and stress the importance and meaning of mathematics learning.

Biosynthesis of a water solubility-enhanced succinyl glucoside derivative of luteolin and its neuroprotective effect.

The natural flavonoids luteolin and luteoloside have anti-bacterial, anti-inflammatory, anti-oxidant, anti-tumour, hypolipidemic, cholesterol lowering and neuroprotective effects, but their poor water solubility limits their application in industrial production and the pharmaceutical industry. In this study, luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside, a new compound that was prepared by succinyl glycosylation of luteolin by the organic solvent tolerant bacterium Bacillus amyloliquefaciens FJ18 in an 8.0% DMSO (v/v) system, was obtained and identified. Its greater water solubility (2293 times that of luteolin and 12 232 times that of luteoloside) provides the solution to the application problems of luteolin and luteoloside. The conversion rate of luteolin (1.0 g l-1 ) was almost 100% at 24 h, while the yield of luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside reached 76.2%. In experiments involving the oxygen glucose deprivation/reoxygenation injury model of mouse hippocampal neuron cells, the cell viability was significantly improved with luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside dosing, and the expressions of the anti-oxidant enzyme HO-1 in the nucleus increased, providing a neuroprotective effect for ischemic cerebral cells. The availability of biosynthetic luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside, which is expected to replace luteolin and luteoloside, would effectively expand the clinical application value of luteolin derivatives.

Codonopsis pilosula Polysaccharide Improved Spleen Deficiency in Mice by Modulating Gut Microbiota and Energy Related Metabolisms.

Codonopsis Radix (CR) is an important traditional Chinese medicine used for the treatment of spleen deficiency syndrome (SDS). Codonopsis pilosula polysaccharides (CPP) in CR are considered to be responsible for tonifying the spleen function; however, the mechanisms of the polysaccharides have remained unclear. This study aimed to investigate the treatment mechanisms of CPP in SDS mice using a combinational strategy of 16S rRNA gene sequencing and targeted metabolomics. Here, studies demonstrated that CPP had invigorating effect in vivo in Sennae Folium-induced SDS in mice by organ indexes, D-xylose determination, gastrointestinal hormones levels and goblet cells observation. Antibiotic treatment revealed that the intestinal microbiota was required for the invigorating spleen effect of CPP. Furthermore, gut microbiota analysis found that CPP significantly enriched probiotic Lactobacillus and decreased the abundance of some opportunistic pathogens, such as Enterococcus and Shigella. The metabolic profile analysis of the colonic content revealed that 25 chemicals were altered significantly by CPP, including amino acids, organic acids, fatty acids, carbohydrates and carnitine etc., which are mainly related to "energy conversion" related processes such as amino acids metabolism, tricarboxylic acid cycle, and nitrogen metabolism. Spearman's correlation assays displayed there were strong correlations among biochemical indicators-gut microbiota-metabolomics. In summary, these results provided a new perspective for CPP improving SDS by regulating energy metabolism related bacteria and pathways.

Terragines F-G produced by endophytic Bacillus sp. SH-1.2-ROOT-18 from Dendrobium officinale.

Two new terragine analogs (1‒2) with special succinimide and aminopentane moieties were isolated from the fermentation broth of Bacillus sp. SH-1.2-ROOT-18, an endophyte previously discovered from the root of Dendrobium officinale. The structures were elucidated base on comprehensive 1 D/2D NMR and MS data analysis. Complete NMR assignments for the first reported naturally occurring metabolite 3 was also provided.[Formula: see text].

Zanthoxylum bungeanum Seed Oil Attenuates LPS-Induced BEAS-2B Cell Activation and Inflammation by Inhibiting the TLR4/MyD88/NF-κB Signaling Pathway.

BACKGROUND: Zanthoxylum bungeanum seed oil (ZBSO) is a natural essential oil derived from the seeds of the Chinese medicinal plant Zanthoxylum bungeanum, which has been investigated for antitumor and anti-inflammatory effects. However, little is known regarding the effects of ZBSO in chronic obstructive pulmonary disease (COPD). METHODS: In this study, lung epithelial cells (BEAS-2B) were induced by lipopolysaccharide (LPS) to establish an in vitro model of COPD, and cytotoxicity was detected by a cell counting kit 8 (CCK-8) assay. Griess test, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot, immunofluorescence, and molecular docking analyses were used to investigate the effects of ZBSO and its potential mechanisms. RESULTS: The results showed that LPS promoted the expression of nitric oxide (NO), reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), MMP-9, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2), suggesting that LPS can induce inflammation and oxidative stress in BEAS-2B cells. ZBSO inhibits the LPS-induced expression of inflammatory mediators and proinflammatory cytokines in BEAS-2B cells. The molecular docking results indicated that active components in ZBSO could successfully dock with toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and p65. Immunofluorescence and western blot analyses further demonstrated that ZBSO repressed protein expression associated with the TLR4/MyD88/nuclear factor-κB (NF-κB) signaling pathway. CONCLUSIONS: ZBSO reduced the inflammatory response and oxidative stress induced by LPS by inhibiting the TLR4/MyD88/NF-κB signaling pathway, thereby suppressing COPD. ZBSO may represent a promising therapeutic candidate for COPD treatment.