Precisely Designed Ultra-Small CoP Nanoparticles-decorated Hollow Carbon Nanospheres as Highly Efficient Host in Lithium-Sulfur Batteries.

Designing porous carbon materials with metal phosphides as host materials holds promise for enhancing the cyclability and durability of lithium-sulfur (Li-S) batteries by mitigating sulfur poisoning and exhibiting high electrocatalytic activity. Nevertheless, it is urgent to precisely control the size of metal phosphides to further optimize the polysulfide conversion reaction kinetics of Li-S batteries. Herein, a subtlety regulation strategy was proposed to obtain ultra-small CoP nanoparticles-decorated hollow carbon nanospheres (CoP@C) by using spherical polyelectrolyte brush (SPB) as the template with stabilizing assistance from polydopamine coating, which also works as carbon source. Leveraging the electrostatic interaction between SPB and Co2+, ultra-small Co particles with sizes measuring 5.5 ± 2.6 nm were endowed after calcination. Subsequently, through a gas-solid phosphating process, these Co particles were converted into CoP nanoparticles with significantly finer sizes (7.1 ± 3.1 nm) compared to state-of-the-art approaches. By uniformly distributing the electrocatalyst nanoparticles on hollow carbon nanospheres, CoP@C facilitated the acceleration of Li ion diffusion and enhanced the conversion reaction kinetics of polysulfides through adsorption-diffusion synergy. As a result, Li-S batteries utilizing the CoP@C/S cathode demonstrated an initial specific discharge capacity of 850.0 mAh g-1 at 1.0 C, with a low-capacity decay rate of 0.03% per cycle.

Entomophagy and entomo-therapeutic practices in a mountainous territory in southeast Guangxi Zhuang Autonomous Region, China.

BACKGROUND: Although China has a long history of using insects as food and medicine and has developed numerous associated knowledge and practices, especially in its rural and mountainous areas, systematic surveys concerning this subject are limited. In-depth ethnobiological research is needed to compile a comprehensive database of edible and medicinal insects and record the associated knowledge of these food and medicinal resources. METHODS: Data on edible and medicinal insects and associated knowledge about them were collected by interviewing 216 local villagers in a mountainous territory in southeast Guangxi Zhuang Autonomous Region, China. RESULTS: Local villagers used at least 16 edible and 9 medicinal insects, of which 4 wasp species were used in both entomophagy and medicinal practices. Parapolybia varia, Polistes olivaceus, and Anomala chamaeleon were newly recorded edible insects in China. The wasps, Euconocephalus sp., Gryllotalpa orientalis, and Cyrtotrachelus longimanus, were preferred and culturally important edible insects. Populations of Euconocephalus sp. and G. orientalis were reported to have substantially decreased in recent years. Wasps and a bamboo bee were used to treat rheumatism, while cockroaches and antlions were used to treat common cold symptoms in infants. Insect-related knowledge was positively correlated with the interviewees' age. CONCLUSIONS: Villagers have accumulated considerable local and traditional knowledge of entomophagy and entomo-therapeutic practices. However, this knowledge is in danger of being lost, which highlights the urgent need to document this information. Edible insects enrich local diets, and a more sustainable supply (such as through insect farming) could maintain local entomophagy practices. Medicinal insects are a part of local folk medicine, and pharmacological and chemical techniques could be applied to identify various biologically active substances in these insects.

Relationships between Bitter Taste Receptor Gene Evolution, Diet, and Gene Repertoire in Primates.

Bitter taste perception plays a critical role in deterring animals from consuming harmful and toxic substances. To characterize the evolution of primate Tas2r, test the generality of Tas2r duplication in Cercopithecidae species, and examine whether dietary preferences have shaped the Tas2r repertoire of primate species, we identified Tas2r in the genomes of 35 primate species, including 16 Cercopithecidae, 6 Hominidae, 4 Cebidae, 3 Lemuridae, and 6 other species. The results showed that the total number of primate Tas2r ranged from 27 to 51, concentrating on 2 to 4 scaffolds of each species. Closely related genes were tandemly duplicated in the same scaffold. Phylogenetic construction revealed that Tas2r can be divided into 21 clades, including anthropoid-, Strepsirrhini-, and Cercopithecidae-specific Tas2r duplications. Phylogenetically independent contrast analysis revealed that the number of intact Tas2r significantly correlated with feeding preferences. Altogether, our data support diet as a driver of primate Tas2r evolution, and Cercopithecidae species have developed some specific Tas2r duplication during evolution. These results are probably because most Cercopithecidae species feed on plants containing many toxins, and it is necessary to develop specialized Tas2r to protect them from poisoning.

Rare-earth-based chalcogenides and their derivatives: an encouraging IR nonlinear optical material candidate.

With the continuous development of laser technology and the increasing demand for lasers of different frequencies in the infrared (IR) spectrum, research on infrared nonlinear optical (NLO) crystals has garnered growing attention. Currently, the three main commercially available types of borate materials each have their drawbacks, which limit their applications in various areas. Rare-earth (RE)-based chalcogenide compounds, characterized by the unique f-electron configuration, strong positive charges, and high coordination numbers of RE cations, often exhibit distinctive optical responses. In the field of IR-NLO crystals, they have a research history spanning several decades, with increasing interest. However, there is currently no comprehensive review summarizing and analyzing these promising compounds. In this review, we categorize 85 representative examples out of more than 400 non-centrosymmetric (NCS) compounds into four classes based on the connection of different asymmetric building motifs: (1) RE-based chalcogenides containing tetrahedral motifs; (2) RE-based chalcogenides containing lone-pair-electron motifs; (3) RE-based chalcogenides containing [BS3] and [P2Q6] motifs; and (4) RE-based chalcohalides and oxychalcogenides. We provide detailed discussions on their synthesis methods, structures, optical properties, and structure-performance relationships. Finally, we present several favorable suggestions to further explore RE-based chalcogenide compounds. These suggestions aim to approach these compounds from a new perspective in the field of structural chemistry and potentially uncover hidden treasures within the extensive accumulation of previous research.

Mean platelet volume is associated with periodontitis: a cross-sectional study.

BACKGROUND: It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. METHODS: We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009-2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. RESULTS: Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019-1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052-1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p < 0.05). However, none of the subgroups exhibited significant interactions (p for interaction > 0.05). CONCLUSION: A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States.

High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma.

Protein phosphatase 1 catalytic subunit gamma (PPP1CC) promotes DNA repair and tumor development and progression, however, its underlying mechanisms remain unclear. This study investigated the molecular mechanism of PPP1CC's involvement in DNA repair and the potential clinical implications. High expression of PPP1CC was significantly correlated with radioresistance and poor prognosis in human nasopharyngeal carcinoma (NPC) patients. The mechanistic study revealed that PPP1CC bound to Ku70/Ku80 heterodimers and activated DNA-PKcs by promoting DNA-PK holoenzyme formation, which enhanced nonhomologous end junction (NHEJ) -mediated DNA repair and led to radioresistance. Importantly, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) interacted with PPP1CC to enhance its stability by removing the K48-linked polyubiquitin chain at Lys234 to prevent PPP1CC degradation. Therefore, BRCC3 helped the overexpressed PPP1CC to maintain its high protein level, thereby sustaining the elevation of DNA repair capacity and radioresistance. Our study identified the molecular mechanism by which PPP1CC promotes NHEJ-mediated DNA repair and radioresistance, suggesting that the BRCC3-PPP1CC-Ku70 axis is a potential therapeutic target to improve the efficacy of radiotherapy.

Significance Analysis of the Improvement in Postoperative Recovery of Cardiac Surgery Patients Based on the Graded Management Established Using the Delirium Prediction Model.

Objective: To investigate the impact of graded management based on delirium prediction modeling on the improvement of recovery of cardiac surgery patients. Methods: Three hundred and twenty patients admitted to the Department of Critical Care Medicine of Nanjing Hospital affiliated with Nanjing Medical University from June 2021 to December 2023 after Type A aortic coarctation were selected as study subjects. They were grouped according to the randomized scale method and divided into 160 cases in each the control group and the observation group. In the control group, conventional nursing measures were adopted, and in the observation group, graded nursing interventions were carried out according to the established delirium risk prediction model. Comparison between the two groups in terms of the intensive care unit (ICU) monitoring time, hospitalization time, duration of delirium, and delirium incidence, and investigated nursing satisfaction, and quality of care scores. Results: Compared with the control group, the observation group's ICU custody time, hospitalization time, and delirium duration, decreased, and the quality of care, and satisfaction increased (P < .05). At the same time, the incidence of delirium in the observation group was also lower than that in the control group (P < .05). Conclusion: The graded management based on the delirium prediction model can effectively reduce the incidence of postoperative delirium in critically ill patients with Type A aortic coarctation, and at the same time improve patient satisfaction and quality of care.

Rutaecarpine Protects Against Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease (COPD) in Rats.

Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease that causes restricted airflow and breathing difficulties. In this work, we attempted to explore the salutary effects of rutaecarpine on COPD-induced rats. Healthy Wistar rats were employed in this study and exposed to cigarette smoke to initiate COPD. The rutaecarpine was given to the rats at 20 and 30 mg/kg dosages, respectively, for 12 weeks. Body weight gain, food uptake, and food efficiency were assessed after treatment completion. The grip strength test was performed to assess muscle strength. The C-reactive protein (CRP), leptin, inflammatory cytokines, and oxidative stress markers were assessed using the corresponding assay kits. The inflammatory cells on the bronchoalveolar lavage fluid (BALF) were counted using Wright-Giemsa staining. The respiratory functions of the experimental rats were measured. The histopathological analysis was done on the lung tissues. The rutaecarpine treatment effectively increased body weight gain, food uptake, and food efficiency in the COPD rats. The levels of leptin were increased, and CRP was reduced by the rutaecarpine. The rutaecarpine regulated the respiratory functions and reduced the inflammatory cell counts and pro-inflammatory markers in the COPD rats. The levels of antioxidants were increased by the rutaecarpine treatment in the COPD rats. The findings of the lung histopathological study also demonstrated the therapeutic effects of rutaecarpine. Overall, the findings of the current study witness the salutary role of rutaecarpine against cigarette smoke-induced COPD in rats. Therefore, it was clear that rutaecarpine could be a promising salutary candidate to treat COPD.

Escherichia coli-Induced cGLIS3-Mediated Stress Granules Activate the NF-κB Pathway to Promote Intrahepatic Cholangiocarcinoma Progression.

Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient-derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF-κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.

Mechanism of miR-7 mediating TLR4/TRAF6/NF-κB inflammatory pathway in colorectal cancer.

This study is aimed at investigating the roles of Toll-like receptor 4 (TLR4) and microRNA-7 (miR-7) in colorectal cancer (CRC) development and progression. We assessed TLR4 and miR-7 expression in CRC cells and tissues using reverse transcription-quantitative polymerase chain reaction. The relationship between miR-7 and TLR4 was analyzed through dual luciferase reporter assays. MTT, wound healing, and cell invasion assays were conducted to examine the effects of TLR4 and miR-7 on CRC cell proliferation, migration, and invasion. Western blotting was used to explore the involvement of the TRAF6/NF-κB signaling pathway. miR-7 was underexpressed in CRC, while TLR4 levels were increased. miR-7 negatively regulated TLR4 expression and its knockdown enhanced CRC cell proliferation, migration, and invasion. TLR4 knockdown had the opposite effects. The TRAF6/NF-κB pathway was linked to TLR4's role in tumor progression. miR-7 might inhibit TRAF6/NF-κB target a signaling pathway of TLR4 and promote CRC occurrence. miR-7 may therefore be used as a sensitive biomarker in CRC patients.

Spatial and temporal variations of ecosystem water use efficiency and its response to soil moisture drought in a water-limited watershed of northern China.

Drought synchronously affects the water cycle and interferes with the carbon cycle in terrestrial ecosystems. Ecosystem water use efficiency (WUE), serving as a vital metric for assessing the interplay between water and carbon cycles, has found extensively use in exploring how ecosystems responses to drought. However, the effects of soil moisture drought on WUE are still poorly recognized. Taking Ziya River Basin as an example, the spatial-temporal variations of WUE from 2001 to 2020 were estimated by the Penman-Monteith-Leuning Version 2 (PML-V2) data. Based on the Standardized Soil Moisture Index (SSI) calculated from Soil Moisture of China by in situ data, version 1.0 (SMCI1.0) data, the sensitivity and thresholds of different vegetation WUE to drought magnitudes were investigated, and the influences of both lagged and cumulative effects of drought on WUE were further analyzed. Results showed that the annual mean WUE was 2.160 ± 0.975 g C kg-1 H2O-1 in the Ziya River Basin, with a significant increasing trend of 0.037 g C kg-1 H2O-1 yr-1 (p < 0.05). For all the vegetation types, the WUE reached the maximum value at a certain drought threshold (SSI = -1.5 ± 0.1). The dominant factor controlling WUE sensitivity to drought changed from evapotranspiration (ET) to gross primary production (GPP) when severe drought transformed into extreme drought. Significant lagged and cumulative effects were found in the response of WUE to drought in nearly 58.64 % (72.94 %) of the study area, with an average time scale of 6.65 and 2.11 months (p < 0.05) respectively. Drought resistance in descending order was: forest > shrub > grassland > cropland. Our findings enrich the understanding of the coupled carbon and water cycle processes in terrestrial ecosystems and their response to soil moisture drought in the context of global climate change.

BubR1 controls starvation-induced lipolysis via IMD signaling pathway in Drosophila.

Lipolysis, the key process releasing fat acids to generate energy in adipose tissues, correlates with starvation resistance. Nevertheless, its detail mechanisms remain elusive. BubR1, an essential mitotic regulator, ensures proper chromosome alignment and segregation during mitosis, but its physiological functions are largely unknown. Here, we use Drosophila adult fat body, the major lipid storage organ, to study the functions of BubR1 in lipolysis. We show that both whole body- and fat body-specific BubR1 depletions increase lipid degradation and shorten the lifespan under fasting but not feeding. Relish, the conserved regulator of IMD signaling pathway, acts as the downstream target of BubR1 to control the expression level of Bmm and modulate the lipolysis upon fasting. Thus, our study reveals new functions of BubR1 in starvation-induced lipolysis and provides new insights into the molecular mechanisms of lipolysis mediated by IMD signaling pathway.

Tandem Sulfonylative Annulation/Halogenation of 1,7-Enynes with Sodium Sulfinate and TBAX for the Assembly of 4-Methylenechromanes.

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

Molecular dynamics simulation on the displacement behaviour of crude oil by CO2/CH4 mixtures on a silica surface.

Produced gas re-injection is an effective and eco-friendly approach for enhancing oil recovery from shale oil reservoirs. However, the interactions between different gas phase components, and the oil phase and rocks are still unclear during the re-injection process. This study aims to investigate the potential of produced gas re-injection, particularly focusing on the effects of methane (CH4) content in the produced gas on shale oil displacement. Molecular dynamics simulations were employed to analyze the interactions between gas, oil, and matrix phases with different CH4 proportions (0%, 25%, 50%, and 100%), alkanes and under various burial depth. Results show that a 25% CH4 content in the produced gas achieves almost the same displacement effect as pure carbon dioxide (CO2) injection. However, when the CH4 content increases to 50% and 100%, the interaction between gas and quartz becomes insufficient to effectively isolate oil from quartz, causing only expansion and slight dispersion. Interestingly, the presence of CH4 has a synergistic effect on CO2, facilitating the diffusion of CO2 into the oil film. During the gas stripping process, CO2 is the main factor separating oil from quartz, while CH4 mainly contributes to oil expansion. In addition, for crude oil containing a large amount of light alkanes, extracting light components through mixed gas may be more effective than pure CO2. This study offers valuable insights for applications of produced gas re-injection to promote shale oil recovery.

The E3 ligase NEURL3 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma by promoting vimentin degradation.

BACKGROUND: Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood. METHODS: Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3. RESULTS: The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells. CONCLUSIONS: Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.

Large-scale preparation of CsPbBr3perovskite quantum dot/EVA composite adhesive film by melting for crystal silicon solar cell.

Silicon solar cell is the most mature photovoltaic conversion device, and in order to further improve the performance of the device, application of downshifting films has become a research hotspot. In this paper, CsPbBr3perovskite quantum dot/EVA composite adhesive film was prepared by melting method with CsPbBr3perovskite quantum dot film under solution processing as masterbatch and EVA particles as excipient. The effect of synthesis conditions on the luminescence properties of the composite films were thoroughly studied. The optimized CsPbBr3perovskite quantum dot/EVA composite adhesive film has excellent performance, and its light transmission reaches 85%. The CsPbBr3perovskite quantum dot/EVA composite adhesive film absolutely improves the efficiency of silicon solar cells by 1.08%, which is much higher than that of pure EVA adhesive film (0.63%). In addition, the device efficiencies have almost no change after 30 d in the air, maintaining the working stability of the device and contributing to industrial applications. This study provides a novel, industrial and low-cost synthesis route for the synthesis of CsPbBr3perovskite quantum dot/EVA composite adhesive film, which is expected to have broad application.

Experiences of maintaining awake prone positioning in non-intubated patients with COVID-19: A qualitative study.

BACKGROUND: Patient compliance is crucial to maintaining the awake prone position, which has been found to be intolerable by several patients. Addressing patients' compliance while being treated with awake prone positioning and prolonging its duration may be prerequisites for further research. AIM: This study was conducted to explore the personal experiences of non-intubated patients during the implementation of awake prone positioning. STUDY DESIGN: We conducted a qualitative study recruiting a purposive sample of twelve adult patients diagnosed with COVID-19 who were previously treated with awake prone positioning. They were recruited from an intermediate care unit (that provides pre- and post-intensive care) in a COVID-19-designated hospital in Nanjing, China from July 15, 2021, to September 20, 2021. Data were collected through individual in-depth interviews and then analysed using Colaizzi's phenomenological method. RESULTS: Content analysis of the interviews revealed two main themes, each containing three and four sub-themes, respectively, as follows: (1) barriers to the implementation of awake prone positioning, including (i) generalised discomfort, (ii) a lack of both understanding and trust, and (iii) low satisfaction with the implementation plan; (2) factors promoting the implementation of awake prone positioning, including (i) health education and supervision, (ii) self-motivation and support from healthcare staff and family members, (iii) finding a comfortable position and having access to entertainment, and (iv) symptom improvement. CONCLUSIONS: Healthcare staff should clarify the mechanism underlying the effectiveness of the awake prone position to patients to eliminate any doubts that they may have. Psychological support and appropriate supervision should be emphasised. Pain relief programmes should also be established, including the use of a comfortable prone posture in conjunction with access to entertainment. Finally, individualised awake prone positioning protocols should be formulated according to patients' living habits and attempted in combination with out-of-bed activities. These measures may help to enhance the experience and compliance of patients undergoing the treatment. RELEVANCE TO CLINICAL PRACTICE: For future instances involving the implementation of awake prone positioning, several measures should be established and implemented alongside it, including a health education programme, supervision programme, support system, and pain relief programme. Personalisation should also be considered during its implementation. These measures may help to enhance the compliance of patients and prolong the duration of the awake prone position.

Identification of the first selective bioluminescent probe for real-time monitoring of carboxylesterase 2 in vitro and in vivo.

Carboxylesterase (CES), a main hydrolysis enzyme family in the human body, plays a crucial role in drug metabolism. Among them, CES1 and CES2 are the primary subtypes, and each exhibits distinct distribution and functions. However, convenient and non-invasive methods for distinguishing them and the real-time monitoring of CES2 are relatively rare, hindering the further understanding of physiological functions and underlying mechanisms. In this study, we have designed, synthesized, and evaluated the first selective bioluminescent probe (CBP 1) for CES2 with high sensitivity, high specificity and rapid reactivity. This probe offers a promising approach for the real-time detection of CES2 and its dynamic fluctuations both in vitro and in vivo.

Safety, pharmacokinetics and pharmacodynamics of HWH486 capsules in healthy adults: A randomized, double-blind, placebo-controlled, phase I dose-escalation study.

OBJECTIVES: HWH486 inhibits Bruton's tyrosine kinase and therefore shows promise as a treatment against rheumatoid arthritis and chronic spontaneous urticaria. This phase I trial assessed tolerability, safety, pharmacokinetics and pharmacodynamics of a single oral dose of HWH486 capsules in healthy adults. METHODS: A single-center, randomized, double-blind, placebo-controlled, dose-escalation study from 10 to 800 mg was conducted in 96 healthy Chinese adults, of whom 80 received HWH486 and 16 received placebo. RESULTS: A total of 96 subjects were enrolled, and all completed the study. In the HWH486 group, mean Tmax ranged from 1.03 to 2.00 h, and mean T1/2 ranged from 0.85 to 8.67 h across the dose range from 10 to 800 mg. Mean Cmax increased linearly with dose, while mean AUC0-t increased non-linearly. Occupancy of Bruton's tyrosine kinase peaked within 0.50-4.00 h after administration across the dose groups, and the delay until peak occupancy decreased with increasing dose. Twenty-five subjects (31.25 %) in the HWH486 group experienced 35 treatment-emergent adverse events, while four subjects (25.00 %) in the placebo group experienced eight such events. CONCLUSIONS: HWH486 is well tolerated and safe in healthy adults, in whom it can strongly bind Bruton's tyrosine kinase. These findings justify clinical studies of HWH486 efficacy against autoimmune diseases.

Diagnostic efficacy of the triglyceride-glucose index in the prediction of contrast-induced nephropathy following percutaneous coronary intervention.

Introduction: Contrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). Identifying patients at high CIN risk remains challenging. The triglyceride-glucose (TyG) index may help predict CIN but evidence is limited. We conducted a meta-analysis to evaluate the diagnostic value of TyG index for CIN after PCI. Methods: A systematic literature search was performed in MEDLINE, Cochrane, and EMBASE until August 2023 (PROSPERO registration: CRD42023452257). Observational studies examining TyG index for predicting CIN risk in PCI patients were included. This diagnostic meta-analysis aimed to evaluate the accuracy of the TyG index in predicting the likelihood of CIN. Secondary outcomes aimed to assess the pooled incidence of CIN and the association between an elevated TyG index and the risk of CIN. Results: Five studies (Turkey, n=2; China, n=3) with 3518 patients (age range: 57.6 to 68.22 years) were included. The pooled incidence of CIN was 15.3% [95% confidence interval (CI) 11-20.8%]. A high TyG index associated with increased CIN risk (odds ratio: 2.25, 95% CI 1.82-2.77). Pooled sensitivity and specificity were 0.77 (95% CI 0.59-0.88) and 0.55 (95% CI 0.43-0.68) respectively. Analysis of the summary receiver operating characteristic (sROC) curve revealed an area under the curve of 0.69 (95% CI 0.65-0.73). There was a low risk of publication bias (p = 0.81). Conclusion: The TyG index displayed a noteworthy correlation with the risk of CIN subsequent to PCI. However, its overall diagnostic accuracy was found to be moderate in nature. While promising, the TyG index should not be used in isolation for CIN screening given the heterogeneity between studies. In addition, the findings cannot be considered conclusive given the scarcity of data. Further large-scale studies are warranted to validate TyG cutoffs and determine how to optimally incorporate it into current risk prediction models. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452257, identifier CRD42023452257.