Development and validation of a risk prediction model for mild cognitive impairment in elderly patients with type 2 diabetes mellitus.

BACKGROUND: The prevalence of mild cognitive impairment (MCI) is steadily increasing among elderly people with type 2 diabetes (T2DM). This study aimed to create and validate a predictive model based on a nomogram. METHODS: This cross-sectional study collected sociodemographic characteristics, T2DM-related factors, depression, and levels of social support from 530 older adults with T2DM. We used LASSO regression and multifactorial logistic regression to determine the predictors of the model. The performance of the nomogram was evaluated using calibration curves, receiver operating characteristics (ROC), and decision curve analysis (DCA). RESULTS: The nomogram comprised age, smoking, physical activity, social support, depression, living alone, and glycosylated hemoglobin. The AUC for the training and validation sets were 0.914 and 0.859. The DCA showed good clinical applicability. CONCLUSIONS: This predictive nomogram has satisfactory accuracy and discrimination. Therefore, the nomogram can be intuitively and easily used to detect MCI in elderly adults with T2DM.

Supramolecular prodrug of SN38 based on endogenous albumin and SN38 prodrug modified with semaglutide side chain to improve the tumor distribution.

To improve the biodistribution of the drug in the tumor, a supramolecular prodrug of SN38 was fabricated in situ between endogenous albumin and SN38 prodrug modified with semaglutide side chain. Firstly, SN38 was conjugated with semaglutide side chain and octadecanedioic acid via glycine linkers to obtain SI-Gly-SN38 and OA-Gly-SN38 prodrugs, respectively. Both SI-Gly-SN38 and OA-Gly-SN38 exhibited excellent stability in PBS for over 24 h. Due to the strong binding affinity of the semaglutide side chain with albumin, the plasma half-life of SI-Gly-SN38 was 2.7 times higher than that of OA-Gly-SN38. Furthermore, with addition of HSA, the fluorescence intensity of SI-Gly-SN38 was 4 times higher than that of OA-Gly-SN38, confirming its strong binding capability with HSA. MTT assay showed that the cytotoxicity of SI-Gly-SN38 and OA-Gly-SN38 was higher than that of Irinotecan. Even incubated with HSA, the SI-Gly-SN38 and OA-Gly-SN38 still maintained high cytotoxicity, indicating minimal influence of HSA on their cytotoxicity. In vivo pharmacokinetic studies demonstrated that the circulation half-life of SI-Gly-SN38 was twice that of OA-Gly-SN38. SI-Gly-SN38 exhibited significantly reduced accumulation in the lungs, being only 0.23 times that of OA-Gly-SN38. The release of free SN38 in the lungs from SI-Gly-SN38 was only 0.4 times that from OA-Gly-SN38 and Irinotecan. The SI-Gly-SN38 showed the highest accumulation in tumors. The tumor inhibition rate of SI-Gly-SN38 was 6.42% higher than that of OA-Gly-SN38, and 8.67% higher than that of Irinotecan, respectively. These results indicate that the supramolecular prodrug delivery system can be constructed between SI-Gly-SN38 and endogenous albumin, which improves drug biodistribution in vivo, enhances tumor accumulation, and plays a crucial role in tumor growth inhibition.

Enhancing SN38 prodrug delivery using a self-immolative linker and endogenous albumin transport.

Enhancing the delivery and release efficiency of hydroxyl agents, constrained by high pKa values and issues of release rate or unstable linkage, is a critical challenge. To address this, a self-immolative linker, composed of a modifiable p-hydroxybenzyl ether and a fast cyclization adapter (N-(ortho-hydroxyphenyl)-N-methylcarbamate) was strategically designed, for the synthesis of prodrugs. The innovative linker not only provides a side chain modification but also facilitates the rapid release of the active payloads, thereby enabling precise drug delivery. Particularly, five prodrug model compounds (J1, J2, J3, J5 and J6) were synthesized to evaluate the release rates by using ß-glucuronic acid as trigger and five hydroxyl compounds as model payloads. Significantly, all prodrug model compounds could efficiently release the hydroxyl payloads under the action of ß-glucuronidase, validating the robustness of the linker. And then, to assess the drug delivery and release efficiency using endogenous albumin as a transport vehicle, J1148, a SN38 prodrug modified with maleimide side chain was synthesized. Results demonstrated that J1148 covalently bound to plasma albumin through in situ Michael addition, effectively targeting the tumor microenvironment. Activated by ß-glucuronidase, J1148 underwent a classical 1, 6-elimination, followed by rapid cyclization of the adapter, thereby releasing SN38. Impressively, J1148 showed excellent therapeutic efficacy against human colonic cancer xenograft model, leading to a significant reduction or even disappearance of tumors (3/6 of mice cured). These findings underscore the potential of the designed linker in the delivery system of hydroxyl agents, positioning it at the forefront of advancements in drug delivery technology.

HSG-MGAF Net: Heterogeneous subgraph-guided multiscale graph attention fusion network for interpretable prediction of whole-slide image.

BACKGROUND AND OBJECTIVE: Pathological whole slide image (WSI) prediction and region of interest (ROI) localization are important issues in computer-aided diagnosis and postoperative analysis in clinical applications. Existing computer-aided methods for predicting WSI are mainly based on multiple instance learning (MIL) and its variants. However, most of the methods are based on instance independence and identical distribution assumption and performed at a single scale, which not fully exploit the hierarchical multiscale heterogeneous information contained in WSI. METHODS: Heterogeneous Subgraph-Guided Multiscale Graph Attention Fusion Network (HSG-MGAF Net) is proposed to build the topology of critical image patches at two scales for adaptive WSI prediction and lesion localization. The HSG-MGAF Net simulates the hierarchical heterogeneous information of WSI through graph and hypergraph at two scales, respectively. This framework not only fully exploits the low-order and potential high-order correlations of image patches at each scale, but also leverages the heterogeneous information of the two scales for adaptive WSI prediction. RESULTS: We validate the superiority of the proposed method on the CAMELYON16 and the TCGA- NSCLC, and the results show that HSG-MGAF Net outperforms the state-of-the-art method on both datasets. The average ACC, AUC and F1 score of HSG-MGAF Net can reach 92.7 %/0.951/0.892 and 92.2 %/0.957/0.919, respectively. The obtained heatmaps can also localize the positive regions more accurately, which have great consistency with the pixel-level labels. CONCLUSIONS: The results demonstrate that HSG-MGAF Net outperforms existing weakly supervised learning methods by introducing critical heterogeneous information between the two scales. This approach paves the way for further research on light weighted heterogeneous graph-based WSI prediction and ROI localization.

Mechanic study based on untargeted metabolomics of Pi-pa-run-fei-tang on pepper combined with ammonia induced chronic cough model mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-pa-run-fei-tang (PPRFT), a traditional Chinese medicine formula with long-standing history, demonstrated beneficial effect on chronic cough. However, the mechanism underlying efficacy unclear. In current research, we explored the impact and molecular mechanism of chronic cough mouse stimulating with capsaicin combined with ammonia. AIM OF THE STUDY: To investigate the metabolic modulating effects, and potential mechanisms underlying the therapeutic effect of PPRFT in chronic cough. MATERIALS AND METHODS: Chronic cough mouse models were created by stimulating mice by capsaicin combined with ammonia. Number of coughs and cough latency within 2 min were recorded. With lung tissue and serum samples collected for histopathology, metabolomics, RT-qPCR, immunohistochemistry, and WB analysis. Lymphocytes were isolated and flow cytometric assays were conducted to evaluate the differentiation between Th17 and Treg cell among CD4+ cells. RESULTS: Results indicated that PPRFT obviously reduced the number of coughs, prolonged cough latency, reduced inflammatory cell infiltration and lung tissues damage, and decreased the serum level of IL-6, IL-1ß, TNF-α, and IL-17 while increasing IL-10 levels. Notably, PPRFT suppressed Th17 cell divergence and promoted Treg cell divergence. Furthermore, serum metabolomic assays showed that 46 metabolites differed significantly between group, with 35 pathways involved. Moreover, mRNA levels of IL-6, NF-κB, IL-17, RORγT, JAK2, STAT3, PI3K and AKT in lung tissues remarkably reduced and mRNA levels of IL-10 and FOXP3 were elevated after PPRFT pretreatment. Additionally, PPRFT treatments decreased the protein levels of IL-6, NF-κB, IL-17, RORγT, p-JAK2, p-STAT3, p-PI3K, and p-AKT and increased the protein levels of IL-10 and FOXP3, but no significantly effects to the levels on JAK2, STAT3, PI3K, and AKT in the lungs. CONCLUSION: Conclusively, our result suggested the effect with PPRFT on chronic cough may be mediated through IL-6/JAK2/STAT3 and PI3K/AKT/NF-κB pathway, which regulate the differentiation between Th17 and Treg cell. This beneficial effect of PPRFT in capsaicin and ammonia-stimulated chronic cough mice indicates its potential application in treating chronic cough.

Cancer cases attributable to modifiable lifestyle risk factors in Switzerland between 2015 and 2019.

Several modifiable lifestyle risk factors have been linked to higher cancer risk in the literature. Determining the proportion and number of cancer cases attributable to these risk factors is pivotal in informing effective cancer prevention and control plans that have the greatest effect on reducing cancer incidence. We aimed to estimate the proportion and number of incident cancer cases that were attributable to modifiable lifestyle risk factors (ie, tobacco smoking, high alcohol consumption, excess body weight, physical inactivity and unhealthy diet) in Switzerland between 2015 and 2019. The exposure prevalence of selected risk factors was estimated based on the representative national nutrition survey menuCH, the associated relative risks were obtained from systematic literature reviews and the numbers of incident cancer cases were provided by the National Institute for Cancer Epidemiology and Registration. The fractions and numbers of attributable cases were calculated overall, by sex and by the three major language regions of Switzerland. The investigated modifiable risk factors combined were linked to 25.2% of potentially preventable incident cancer cases in Switzerland between 2015 and 2019. The proportion and numbers were slightly larger in males (28.4%, 6945 cases per year) than in females (21.9%, 4493 cases per year), and variations were observed between language regions. Tobacco smoking, excess body weight and high alcohol consumption were the leading contributors to lifestyle-attributable cancer cases. The observed differences in the leading risk factors both within Switzerland and compared to other countries underline the need for regionally and nationally tailored cancer prevention and education strategies.

Analysis of Prognostic Risk Factors of Sepsis Patients With Myocardial Injury: Six-month Survival Outcome.

Context: Sepsis is a systemic, comprehensive inflammatory response that can induce serious complications for patients. No uniform definition and diagnostic criteria exist internationally for sepsis related to myocardial injury. Studying factors affecting prognosis for sepsis patients with myocardial injury can be helpful in providing a theoretical basis for clinical diagnosis and treatment. Objective: The study intended to explore the predictors of the short-term prognosis for septic patients with myocardial injury and to provide a theoretical basis for improving that prognosis. Design: The research team performed a retrospective study. Setting: The study took place at the Renmin Hospital at Hubei University of Medicine in Shiyan, Hubei, China. Participants: Participants were 138 patients with sepsis and myocardial injury at the hospital between January 2018 and February 2021. Groups: The research team divided participants into a survival group with 114 patients and a mortality group with 24 patients, based on their survival status at six months after being in the hospital. Outcome Measures: The research team collected and analyzed the following data: (1) demographic and clinical characteristics, such as age, gender, underlying disease, and disease severity; (2) echocardiographic indicators, including left ventricular ejection fraction (LVEF), stroke volume (SV), left ventricular end systolic dimension (LVESD), and left ventricular end diastolic dimension (LVEDD); and (3) myocardial injury markers and inflammatory factors, including white blood cell (WBC) count and levels of cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase (CK), C-reactive protein (CRP), and procalcitonin (PCT). Results: The six-month mortality rate for patients with sepsis with myocardial injury was 17.39%. Compared to the survival group at participants' initial visits to the hospital, the mortality group had a significantly greater age (P = .046), sepsis severity (P < .001), heart rate (P < .001), APACHE II score (P < .001), SOFA score (P < .001), and use of vasoactive drugs (P = .002), and its length of hospital stay was significantly shorter (P < .001). The mortality group's LVEF was significantly lower than that of the survival group (P < .001). The mortality group's levels of WBC, cTnI, NT-proBNP, CK, CRP, and PCT were significantly higher than those in survival group (all P < .001). The univariate analysis found that an age>64 years (P < .001), a high APACHE II score (P < .001), an elevated cTnI (P = .017), an elevated NT-proBNP (P = .029), an elevated CK (P < .001), an elevated CRP (P = .031), and an elevated PCT (P < .001) were risk factors for a poor prognosis for patients. Multifactor logistic regression analysis showed that the risk factors for death were an age > 64 years (P < .001), a high APACHE II score (P < .001), and elevated levels of cTnI (P = .013), NT-proBNP (P < .001), CK (P < .001), CRP (P < .001), and PCT (P = .009). Conclusion: In summary, risk factors for poor prognosis in septic patients with myocardial injury included age>64 years, high APACHE II, elevated cTnI, elevated NT-proBNP, elevated CK, elevated CRP, and elevated PCT.

Facile Synthesis of Polymer-Reinforced Silica Aerogel Microspheres as Robust, Hydrophobic and Recyclable Sorbents for Oil Removal from Water.

With the rapid development of industry and the acceleration of urbanization, oil pollution has caused serious damage to water, and its treatment has always been a research hotspot. Compared with traditional adsorption materials, aerogel has the advantages of light weight, large adsorption capacity and high selective adsorption, features that render it ideal as a high-performance sorbent for water treatment. The objective of this research was to develop novel hydrophobic polymer-reinforced silica aerogel microspheres (RSAMs) with water glass as the precursor, aminopropyltriethoxysilane as the modifier, and styrene as the crosslinker for oil removal from water. The effects of drying method and polymerization time on the structure and oil adsorption capacity were investigated. The drying method influenced the microstructure and pore structure in a noteworthy manner, and it also significantly depended on the polymerization time. More crosslinking time led to more volume shrinkage, thus resulting in a larger apparent density, lower pore volume, narrower pore size distribution and more compact network. Notably, the hydrophobicity increased with the increase in crosslinking time. After polymerization for 24 h, the RSAMs possessed the highest water contact angle of 126°. Owing to their excellent hydrophobicity, the RSAMs via supercritical CO2 drying exhibited significant oil and organic liquid adsorption capabilities ranging from 6.3 to 18.6 g/g, higher than their state-of-the-art counterparts. Moreover, their robust mechanical properties ensured excellent reusability and recyclability, allowing for multiple adsorption-desorption cycles without significant degradation in performance. The novel sorbent preparation method is facile and inspiring, and the resulting RSAMs are exceptional in capacity, efficiency, stability and regenerability.

Molecular subtypes and tumor microenvironment infiltration signatures based on cuproptosis-related genes in colon cancer.

Background: Colon cancer is one of the common cancers, and its prognosis remains to be improved. The role of cuproptosis as a newly discovered form of cell death in the development of colon cancer has not been determined. Methods: Based on 983 colon cancer samples in the TCGA database and the GEO database, we performed a comprehensive genomic analysis to explore the molecular subtypes mediated by cuproptosis-related genes. Single-sample gene set enrichment analysis (ssGSEA) was utilized to quantify the relative abundance of each cell infiltrate in the TME. A risk score was established using least absolute shrinkage and selection operator regression (LASSO), and its predictive ability for colon cancer patients was verified to explore its guiding value for treatment. Results: We identified two distinct cuproptosis-related molecular subtypes in colon cancer. These two distinct molecular subtypes can predict clinicopathological features, prognosis, TME activity, and immune-infiltrating cells. A risk model was developed and its predictive ability was verified. Compared with patients in the high-risk score group, patients in the low-risk score group were characterized by lower tumor microenvironment score, higher stem cell activity, lower tumor mutational burden, lower microsatellite instability, higher sensitivity to chemotherapeutics, and better immunotherapy efficacy. Conclusion: This study contributes to understanding the molecular characteristics of cuproptosis-related subtypes. We demonstrate a critical role for cuproptosis genes in colon cancer s in the TME. Our study contributes to the development of individualized treatment regimens for colon cancer.

Identification and verification of pivotal genes promoting the progression of atherosclerosis based on WGCNA.

As the main pathological basis for the development of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) seriously affects human health. The key targets of biological information analysis of AS can help exploit therapeutic targets. The expression data of early and progressive atherosclerotic tissues were downloaded from the Gene Expression Omnibus (GEO) database. Based on GSE28829 and GSE120521, 74 key genes were obtained through differential expression analysis and weighted correlation network analysis (WGCNA) analysis, which were mainly enriched in the regulating of inflammatory response, chemokine signalling pathway, apoptosis, lipid and AS, Toll-like receptor signalling pathway and so on according to the results of the enrichment analysis. Cytoscape software was applied to screen four pivotal genes (TYROBP, ITGB2, ITGAM and TLR2) based on PPI. The results of the correlation analysis showed that the expression level of pivotal genes was positively related to macrophages M0, and was negatively related to T cells follicular helper. In addition, the expression of ITGB2 was positively related to Tregs. In this study, bioinformatics was applied to screen pivotal genes affecting the progress of AS, which were significantly related to immune-related biological functions and signal pathways of atherosclerotic tissues and the infiltration level of immune cells. Therefore, pivotal genes were expected to become therapeutic targets for AS.

Trifolirhizin inhibits proliferation, migration and invasion in nasopharyngeal carcinoma cells via PI3K/Akt signaling pathway suppression.

Nasopharyngeal carcinoma (NPC) is a highly recurrent and metastatic malignant tumor affecting a large number of individuals in southern China. Traditional Chinese herbal medicine has been found to be a rich source of natural compounds with mild therapeutic effects and minimal side effects, making them increasingly popular for treating various diseases. Trifolirhizin, a natural flavonoid derived from leguminous plants, has gained significant attention for its therapeutic potential. In this study, we confirmed that trifolirhizin could effectively inhibit the proliferation, migration and invasion of nasopharyngeal carcinoma 6-10B and HK1 cells. Furthermore, our findings demonstrated that trifolirhizin achieves this by suppressing the PI3K/Akt signaling pathway. The findings of the present study provides a valuable perspective on the potential therapeutic applications of trifolirhizin for the treatment of nasopharyngeal carcinoma.

Maackiain inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by inhibiting the MAPK/Ras signaling pathway.

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.

SOX2 downregulation of PML increases HCMV gene expression and growth of glioma cells.

The presence of human cytomegalovirus (HCMV) in glioblastoma (GBM) and improved outcomes of GBM patients receiving therapies targeting the virus have implicated HCMV in GBM progression. However, a unifying mechanism that accounts for the contribution of HCMV to the malignant phenotype of GBM remains incompletely defined. Here we have identified SOX2, a marker of glioma stem cells (GSCs), as a key determinant of HCMV gene expression in gliomas. Our studies demonstrated that SOX2 downregulated promyelocytic leukemia (PML) and Sp100 and consequently facilitated viral gene expression by decreasing the amount of PML nuclear bodies in HCMV-infected glioma cells. Conversely, the expression of PML antagonized the effects of SOX2 on HCMV gene expression. Furthermore, this regulation of SOX2 on HCMV infection was demonstrated in a neurosphere assay of GSCs and in a murine xenograft model utilizing xenografts from patient-derived glioma tissue. In both cases, SOX2 overexpression facilitated the growth of neurospheres and xenografts implanted in immunodeficient mice. Lastly, the expression of SOX2 and HCMV immediate early 1 (IE1) protein could be correlated in tissues from glioma patients, and interestingly, elevated levels of SOX2 and IE1 were predictive of a worse clinical outcome. These studies argue that HCMV gene expression in gliomas is regulated by SOX2 through its regulation of PML expression and that targeting molecules in this SOX2-PML pathway could identify therapies for glioma treatment.

A cysteine-rich secretory protein involves in phytohormone melatonin mediated plant resistance to CGMMV.

BACKGROUND: Melatonin is considered to be a polyfunctional master regulator in animals and higher plants. Exogenous melatonin inhibits plant infection by multiple diseases; however, the role of melatonin in Cucumber green mottle mosaic virus (CGMMV) infection remains unknown. RESULTS: In this study, we demonstrated that exogenous melatonin treatment can effectively control CGMMV infection. The greatest control effect was achieved by 3 days of root irrigation at a melatonin concentration of 50 µM. Exogenous melatonin showed preventive and therapeutic effects against CGMMV infection at early stage in tobacco and cucumber. We utilized RNA sequencing technology to compare the expression profiles of mock-inoculated, CGMMV-infected, and melatonin+CGMMV-infected tobacco leaves. Defense-related gene CRISP1 was specifically upregulated in response to melatonin, but not to salicylic acid (SA). Silencing CRISP1 enhanced the preventive effects of melatonin on CGMMV infection, but had no effect on CGMMV infection. We also found exogenous melatonin has preventive effects against another Tobamovirus, Pepper mild mottle virus (PMMoV) infection. CONCLUSIONS: Together, these results indicate that exogenous melatonin controls two Tobamovirus infections and inhibition of CRISP1 enhanced melatonin control effects against CGMMV infection, which may lead to the development of a novel melatonin treatment for Tobamovirus control.

METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

[Application of WRF Optimal Parameterization Scheme for Different Air Quality Models].

Accurate meteorological fields and applicable air quality models are important ways to optimize air pollution simulations. To improve the accuracy of winter air pollution models in the Sichuan basin, we conducted a meteorological field simulation using 25 sets of parameterized scheme combinations in the Weather Research and Forecasting (WRF) Model. Based on the optimal parameters, the air pollution levels were simulated using AERMOD and CALPUFF models in a local large steel plant, and the data were verified by comparing the data from four National Ambient Air Monitoring Stations (NAAMS). The results indicated that the WRF model parameters had substantial effects on the simulation of the ground wind field, high-altitude wind field, and ground humidity field. In contrast, the parameters had no significant effect on the simulation of the ground temperature field, high-altitude temperature field, and high-altitude humidity field. The combination of the SLAB land surface process scheme and Dudhia shortwave radiation scheme with four boundary layer schemes, namely YSU, ACM2, BouLac, and MRF, could well-simulate the trends of winter surface wind, temperature, and humidity fields in Sichuan basin. The simulation results were analyzed by combining the statistical parameters of high-altitude wind, temperature, and humidity. The group 1 parameter scheme was applicable to simulate the meteorological field of Dazhou. Group 13 and Group 17 parameters were applicable to simulate the meteorological fields in Chengdu during the day and night, respectively. The correlation between CALPUFF simulation and monitoring value was better than that for AERMOD. CALPUFF was more accurate than AERMOD when referring to the monitoring data from NAAMS No.3. In addition, the simulation quality of CALPUFF was slightly better than that of AERMOD with reference to data from NAAMS No.2. Using air pollutant monitoring data from NAAMS as a reference, the simulated results of CALPUFF on NOx and PM10 were improved compared to AERMOD at all four stations. Data from the Q-Q diagram indicated that the simulated results of CALPUFF on SO2, NOx, and PM10 were closer to the monitored values compared to those of AERMOD.

Chemical analysis of selected harmful and potentially harmful constituents and in vitro toxicological evaluation of leading flavoured e-cigarette aerosols in the Chinese market.

Use of electronic cigarettes (e-cigarettes) has increased significantly over the past decade due to consumer perception that these products represent a less risky alternative to combustible cigarettes. E-liquids generally contain a simple mix of vegetable glycerin, propylene glycerol, nicotine, organic acids, and flavourings. Regulators require that harmful and potentially harmful constituents (HPHCs) that might cause harm to the consumer must be monitored in the aerosol generated by e-cigarettes and in cigarette smoke (CS). To quantify HPHCs in aerosols from commercial flavoured e-cigarettes in Chinese market, this study has systematically compared levels of HPHCs, including eight carbonyls, five volatile organic compounds, four tobacco-specific nitrosamines, 16 polycyclic aromatic hydrocarbons, and seven heavy metals, in the aerosols of four market-leading flavoured e-cigarettes and mainstream CS, alongside in vitro cytotoxicity and mutagenicity assays. The vast majority of HPHCs were either undetected or significantly lower in the e-cigarette aerosols than in commercial CS or reference CS (3R4F). Where HPHCs were detected, there were small variations among the different flavoured e-cigarettes. In the neutral red uptake and Ames assays, aqueous extracts of the e-cigarette aerosols did not induce obvious cytotoxicity or mutagenicity, whereas CS aqueous extract showed dose-related cytotoxicity and mutagenicity. Collectively, these results indicate that use of e-cigarettes might potentially lead to a significant reduction in exposure to harmful substances, with fewer cytotoxic and mutagenic effects, as compared with conventional smoking. Further studies based on human puffing conditions and longer evaluation periods will be needed to substantiate this potential.

Interpretable classification of pathology whole-slide images using attention based context-aware graph convolutional neural network.

BACKGROUND AND OBJECTIVE: Whole slide image (WSI) classification and lesion localization within giga-pixel slide are challenging tasks in computational pathology that requires context-aware representations of histological features to adequately infer nidus. The existing weakly supervised learning methods mainly treat different locations in the slide as independent regions and cannot learn potential nonlinear interactions between instances based on i.i.d assumption, resulting in the model unable to effectively utilize context-ware information to predict the labels of WSIs and locate the region of interest (ROI). METHODS: Here, we propose an interpretable classification model named bidirectional Attention-based Multiple Instance Learning Graph Convolutional Network (ABMIL-GCN), which hierarchically aggregates context-aware features of instances into a global representation in a topology fashion to predict the slide labels and localize the region of lymph node metastasis in WSIs. RESULTS: We verified the superiority of this method on the Camelyon16 dataset, and the results show that the average predicted ACC and AUC of the proposed model after flooding optimization can reach 90.89% and 0.9149, respectively. The average accuracy and ACC score are improved by more than 7% and 4% compared with the existing state-of-the-art algorithms. CONCLUSIONS: The results demonstrate that context-aware GCN outperforms existing weakly supervised learning methods by introducing spatial correlations between the neighbor image patches, which also addresses the 'accuracy-interpretability trade-off' problem. The framework provides a novel paradigm for the clinical application of computer-aided diagnosis and intelligent systems.

Development of Regular Hydrophobic Silica Aerogel Microspheres for Efficient Oil Adsorption.

The objective of this research was to develop new hydrophobic silica aerogel microspheres (HSAMs) with water glass and hexmethyldisilazane for oil adsorption. The effects of the hexmethyldisilazane concentration and drying method on the structure and organic liquid adsorption capacity were investigated. The hexmethyldisilazane concentration of the modification solution did not influence the microstructure and pore structure in a noteworthy manner, which depended more on the drying method. Vacuum drying led to more volume shrinkage of the silica gel microsphere (SGM) than supercritical CO2 drying, thus resulting in a larger apparent density, lower pore volume, narrower pore size distribution, and more compact network. Owing to the large pore volume and pore size, the HSAMs synthesized via supercritical CO2 drying had a larger organic liquid adsorption capacity. The adsorption capacities of the HSAMs with pore volumes of 4.04-6.44 cm3/g for colza oil, vacuum pump oil, and hexane are up to 18.3, 18.9, and 11.8 g/g, respectively, higher than for their state-of-the-art counterparts. The new sorbent preparation method is facile, cost-effective, safe, and ecofriendly, and the resulting HSAMs are exceptional in capacity, stability, and regenerability.

Acceptance and commitment therapy reduces psychological distress in patients with cancer: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study aimed to systematically review and meta-analyze the clinical efficacy of acceptance and commitment therapy (ACT) in patients with cancer and psychological distress. Methods: Randomized controlled trials (RCTs) from seven English electronic databases were systematically investigated from inception to 3 October 2023. A total of 16 RCTs from 6 countries with 711 participants were included in this study. Estimated pooled effect sizes (ESs) were calculated via inverse-variance random-effects or fixed-effects (I2 ≤ 50%) model and presented by standardized mean difference (SMD). Subgroup analyses were performed to reduce confounding factors and heterogeneity, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to evaluate the quality of the pooled ESs. Results: The pooled ESs revealed that statistically significant improvements in anxiety [postintervention SMD = -0.41 (95% confidence interval (CI), -0.71, -0.11); p = 0.008; I2 = 65%; follow-up SMD = -0.37 (95% CI, -0.66, -0.08); p = 0.01; I2 = 29%], depression [postintervention SMD = -0.45 (95% CI, -0.63, -0.27); p < 0.001; I2 = 49%; follow-up SMD = -0.52 (95% CI, -0.77, -0.28); p < 0.001; I2 = 0%], and psychological flexibility [postintervention SMD = -0.81 (95% CI, -1.50, -0.11); p = 0.02; I2 = 84%; follow-up SMD = -0.71 (95% CI, -1.12, -0.31); p = 0.0006; I2 = 38%] in ACT-treated participants were observed compared to patients treated with control conditions. However, other outcomes, such as physical symptom alleviation, were not significantly associated. Conclusion: The findings of this systematic review and meta-analysis suggest that ACT is associated with improvements in anxiety, depression, and psychological flexibility in patients with cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022320515.