Fast dentification of overlapping fluorescence spectra of oil species based on LDA and two-dimensional convolutional neural network.

Although most petroleum oil species can be identified by their fluorescence spectra, overlapping fluorescence spectra make identification difficult. This study aims to address the issue that fluorescence spectroscopy is ineffective in identifying overlapping oil species. In this study, an equivalent model of overlapping oil species with fluorescence spectra was established. The linear discriminant analysis (LDA)-assisted machine learning (ML) algorithms K nearest neighbor (KNN), decision tree (DT), and random forest (RF) improved the identification of fluorescent spectrally overlapping oil species for diesel-lubricant oils. The identification accuracies of two-dimensional convolutional neural network (2DCNN), LDA combined with the ML algorithms effectively all 100 %. Furthermore, Partial Least Squares Regression (PLSR) algorithm, Support Vector Regression (SVR) algorithm, DT regression algorithm, and RF regression algorithm were also used to identify the lubricant concentration in diesel-lubricant oils. The coefficient of determination of the DT was 1, and the root-mean-square error was 0, which identified the concentration of lubricant oils in them accurately and without error.

Cancer-Associated Fibroblasts Expressing Sulfatase 1 Facilitate VEGFA-Dependent Microenvironmental Remodeling to Support Colorectal Cancer.

Tumor stroma plays a critical role in fostering tumor progression and metastasis. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma. Identifying the key molecular determinants for the pro-tumor properties of CAFs could enable the development of more effective treatment strategies. Herein, through analyses of single-cell sequencing data, we identified a population of CAFs expressing high levels of sulfatase 1 (SULF1), which was associated with poor prognosis in colorectal cancer (CRC) patients. CRC models using mice with conditional SULF1 knockout in fibroblasts revealed the tumor-supportive function of SULF1+ CAFs. Mechanistically, SULF1+ CAFs enhanced the release of vascular endothelial growth factor A (VEGFA) from heparan sulfate proteoglycan (HSPG). The increased bioavailability of VEGFA initiated the deposition of extracellular matrix (ECM) and enhanced angiogenesis. In addition, intestinal microbiota-produced butyrate suppressed SULF1 expression in CAFs through its HDAC inhibitory activity. The insufficient butyrate production in CRC patients increased the abundance of SULF1+ CAFs, thereby promoting tumor progression. Importantly, tumor growth inhibition by HDAC inhibition was dependent on SULF1 expression in CAFs, and CRC patients with more SULF1+ CAFs were more responsive to treatment with the HDAC inhibitor chidamide. Collectively, these findings unveil the critical role of SULF1+ CAFs in CRC and provide a strategy to stratify CRC patients for HDAC inhibitor treatment.

Unraveling cereal physical barriers composed of cell walls and protein matrix: Insights from structural changes and starch digestion.

Physical barriers composed of cell walls and protein matrix in cereals, as well as their cooking changes, play important roles in starch digestion. In this study, the physical barriers of native and cooked highland barley (HB), brown rice (BR), and oats (OA) kernels and their contribution to starch digestion were investigated. The resistant starch content was similar in cereal flours, but varied among cooked kernels (HB > BR > OA: 45.05 %, 10.30 %, and 24.71 %). The water adsorption, gelatinization enthalpy, and decrease in hardness of HB kernels were lower than those of OA and BR kernels. Microstructural observations of native kernels showed that HB had the thickest cell walls. After cooking, the lowest cell wall deformation and a dense continuous network developed from the protein matrix were observed in HB kernels. During digestion, undigested starch granules encapsulated by the stable cell walls and strong protein network were observed in HB kernels, but not in BR or OA kernels. Furthermore, the heavily milled HB kernels still had more resistant starch than the intact OA and BR kernels. Therefore, the physical barriers of HB kernels exhibited stronger inhibition of starch gelatinization and digestion. Differences in cereal physical barriers led to various inhibitory effects.

Late Bedtime and Altered Diurnal Axial Length Rhythms of the Eye.

PURPOSE: Affecting one-third of the population worldwide and increasing, the sight-threatening condition myopia is causing a significant socio-economic burden. To better understand its etiology, recent studies investigated the role of ocular and systemic rhythms, yet results are conflicting. Here we profiled 24-h variations of axial length of the eye and salivary melatonin concentration in young adults with and without myopia and explored the potential impacts of bedtime on these rhythms. METHODS: A total of 25 healthy young adults (age 25.0 ± 4.8 years, 13 females) completed this study, including 13 myopes (mean spherical equivalent refractive error -2.93 ± 1.46 diopters) and 12 non-myopes (0.14 ± 0.42 diopters). Saliva sample collection and axial length measurements were repeated for seven times over 24 h starting from 8 am. Information on sleep and chronotype was collected at first visit with the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire. RESULTS: Significant diurnal rhythms of axial length and salivary melatonin concentration were identified in both refractive groups (both p < 0.001), with no myopia-related rhythm difference (interaction of measurement time-point × myopia, p = 0.9). Late bedtime was associated with altered rhythms (p = 0.009) and smaller diurnal change (p = 0.01) in axial length. Elevated melatonin levels were observed in myopes (p = 0.006) and in late sleepers (p = 0.017). CONCLUSIONS: These findings suggest that sleep/wake cycles may be involved in the regulation of axial length rhythms. Further research is needed to determine if there exists a causal relationship between the two.

Palladium-catalyzed hydroarylation of 1,3-diynes with arylboronic acids.

Transition-metal-catalyzed selective hydroarylation of alkynes represents a state-of-the-art approach in organic chemistry. Herein, we report the reaction of symmetrical 1,3-diynes and arylboronic acids, with Pd(OAc)2 as the catalyst and PCy3 as the ligand, affording functionalized enynes in good to excellent yields. Its efficiency is demonstrated by its good functional group tolerance and broad substrate scope. This method offers a general, convenient, and practical strategy for the modular synthesis of multisubstituted enynes. To comprehensively elucidate the mechanism of the Pd-based catalytic system in the hydroarylation of 1,3-diynes, we performed detailed DFT computations for the Pd-catalyzed hydroarylation reaction.

Metabolomics Dysfunction in Replicative Senescence of Periodontal Ligament Stem Cells Regulated by AMPK Signaling Pathway.

Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for stem cell-based regenerative medicine in dentistry, but they inevitably acquire a senescent phenotype after prolonged in vitro expansion. The key regulators of PDLSCs during replicative senescence are remain unclear. Here, we sought to elucidate the role of metabolomic changes in determining cellular senescence of PDLSCs. PDLSCs were cultured to passages 4, 10 and 20. The senescent phenotypes of PDLSCs were detected, and metabolomics analysis was performed. We found that PDLSCs manifested senescence phenotype during passaging. Metabolomics analysis showed that the metabolism of replicative senescence in PDLSCs varied significantly. The AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK, FOXO1 and FOXO3a decreased with senescence. We treated PDLSCs with an activator of the AMPK pathway (AICAR), and observed that the phosphorylated AMPK level at P20 PDLSCs was partially restored. These data delineate that the metabolic process of PDLSCs is active in the early stage of senescence, and attenuated in the later stages of senescence; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism.

Sleep Disturbances in Autoimmune Neurological Diseases: Mechanisms, Clinical Characteristics, Assessment, and Treatment Strategies.

PURPOSE OF REVIEW: Sleep disturbances are a hallmark feature of various autoimmune neurological diseases (AINDs). However, limited awareness of these sleep manifestations exists among clinicians. We provide a comprehensive overview of assessment methods, characteristic sleep disturbances, the impact of specific antibodies on sleep patterns, and treatment strategies for sleep disturbances in AINDs. RECENT FINDINGS: Research advancements in sleep disturbances in autoimmune neurological disease focus primarily on four areas: mechanisms, clinical characteristics, assessment, and treatment. Regarding mechanisms, animal models for AINDs, particularly those involving specific antibodies like anti-NMDAR, anti-LGI1, and anti-IgLON5, have become more comprehensive. Recent advancements in animal models have led to the establishment of numerous models for AINDs; these models include a wide range of antibodies, including anti-NMDAR, anti-LGI1, and anti-IgLON5. Several studies using these models have revealed common mechanisms underlying sleep disturbances in these diseases. In terms of clinical characteristics, the identification of antibodies associated with recently discovered AINDs has expanded the spectrum of sleep disturbance symptoms observed compared to prior findings. A comprehensive evaluation system for the assessment of sleep disturbances has been established, including questionnaires, polysomnography, functional magnetic resonance imaging, and 18F-FDG PET/CT. Additionally, cardiopulmonary coupling shows promise as a novel assessment tool. Currently, no universally effective treatment exists for sleep disturbances in autoimmune neurological diseases, either through symptomatic treatment or immunosuppressive therapy. Further studies are needed to confirm the efficacy of new therapies and validate the benefits of existing treatments. Sleep disturbances are a hallmark feature of AINDs. Recent advancements have significantly expanded our understanding of their assessment and treatment. However, further studies are needed to address the remaining uncertainties in sleep disturbance management.

Tumor complete response and pyogenic liver abscess secondary to concurrent microwave ablation plus atezolizumab and bevacizumab in liver cancer: a case report.

Background: Pyogenic liver abscess (PLA) could be fatal even after standard treatment with antibiotics and percutaneous drainage. Immune checkpoint inhibitors, bevacizumab or microwave ablation may cause PLA, respectively. This paper presents the first case of PLA secondary to the concomitant use of microwave ablation with atezolizumab and bevacizumab in the treatment of liver cancer. Case Description: A 54-year-old Chinese man with Barcelona Clinic Liver Cancer (BCLC) C-stage liver cancer complained of fever and chills twenty-nine days after concurrent microwave ablation plus atezolizumab and bevacizumab. Post-hospitalization, a computed tomography revealed a rim-enhancing hypodensity within the right lobe of the liver, approximately 8.8 cm in diameter containing foci of gas. Laboratory examination revealed elevated white blood cell count, C-reactive protein and procalcitonin, and blood culture indicated the presence of Escherichia coli bacteremia. The patient was diagnosed with PLA complicated by septic shock, and due to recurrent fever, multiple courses of antibiotics (imipenem/cilastatin sodium, cefoperazone/sulbactam, meropenem, respectively) were administered in combination with five percutaneous drainages over the next 90 days. The patient's fever eventually resolved, and the patient was discharged. The patient was re-treated with two cycles of atezolizumab and bevacizumab initiated in March 2024. An imaging evaluation in May 2023 demonstrated tumor progression. Subsequently, the patient underwent one transarterial chemoembolization procedure and two cycles of atezolizumab and bevacizumab over the subsequent 2 months. Notably, the patient achieved a complete response at the July 2024 imaging evaluation. Conclusions: In patients undergoing atezolizumab and bevacizumab, the potential risk of PLA versus the antitumor benefit of microwave ablation requires to be assessed. The use of multiple courses of antibiotics over a prolonged period did not appear to influence the effectiveness of atezolizumab and bevacizumab. Further studies are, however, needed to substantiate this finding.

Structural covariance network activity in the medial prefrontal cortex is modulated by childhood abuse in adolescents with depression.

Aberrant structural covariance (SC) in the medial prefrontal cortex (mPFC) is believed to play a crucial role in adolescent-onset major depressive disorder (AO-MDD). However, the effect of childhood abuse (CA) on SC in AO-MDD patients is still unknown. Here, we measured anomalous SC in the mPFC of AO-MDD patients and assessed the potential modulation of this feature by CA. We acquired T1-weighted structural images of AO-MDD patients (n = 93) and healthy controls (HCs, n = 81). Using voxel-based morphometry analysis, we calculated gray matter volumes for each subject. Subsequently, we classified abnormal SC in the mPFC into three subtypes according to overall CA. Compared with HCs, AO-MDD patients showed alterations in the structural covariance network of the mPFC, which is a central region in the default mode network (DMN). We also found an anterior-posterior dissociation in the structural covariance connectivity of the DMN. A history of CA modulated bilateral mPFC SC. These changes were primarily focused on the SC between the mPFC and the limbic system, indicating a gap in the rate of neural maturation between these regions. In summary, the DMN and frontal-limbic system, which are involved in emotional processing, appear to play a significant role in the development of AO-MDD. These findings highlight the crucial effects of CA on neurophysiological alterations in individuals with AO-MDD.

The Geriatric Nutritional Risk Index as a prognostic factor in patients treated with immune checkpoint inhibitors with non-small-cell lung cancer.

Background: Globally, non-small cell lung cancer (NSCLC) is a leading factor in cancer-related mortality. Additionally, the Geriatric Nutritional Risk Index (GNRI) has been assessed as a predictive and prognostic indicator in various types of carcinomas. Our study aims to assess the prognostic importance of GNRI computed at diagnosis in NSCLC patients receiving immune checkpoint inhibitors (ICIs). Methods: The study evaluated 148 patients who underwent immunotherapy for NSCLC from January 1, 2018, through December 31, 2021, retrospectively. Patients combined with other malignant tumors or severe comorbidities were excluded from the study. The receiver operating characteristic (ROC) curve was employed in regulating the ideal cutoff worth of GNRI. Survival outcomes were evaluated through Kaplan-Meier analysis. Following this, both univariate and multivariate analyses were conducted utilizing Cox regression analysis to identify any potential factors that may influence the survival outcomes. Results: The cutoff point for GNRI was 108.15 [area under the curve (AUC) =0.575, P=0.048]. Further analysis using the Kaplan-Meier method demonstrated that individuals in the high GNRI group had significantly longer progression-free survival (PFS) and overall survival (OS) compared to those in the low GNRI group (P=0.02, P=0.01). The further stratified study showed that GNRI had greater predictive value in tumor node metastasis (TNM) stage II-III and elderly (age ≥65 years) NSCLC patients undergoing ICI therapy. The multivariate Cox regression analysis indicated that GNRI [hazard ratio (HR): 0.536, P=0.03], obesity (HR: 16.283, P<0.001), and surgical history (HR: 0.305, P<0.001) were associated with poorer survival rates. Conclusions: Among patients undergoing ICI therapy for NSCLC, GNRI is an effective independent prognostic indicator, and a high GNRI at diagnosis is substantially related with longer PFS and OS. The incorporation of GNRI in pre-treatment evaluations within clinical settings is beneficial.

In2O3/Bi2O3 interface induces ultra-stable carbon dioxide electroreduction on heterogeneous InBiOx catalyst.

The electrochemical reduction of CO2 (ERCO2) has emerged as one of the most promising methods for achieving both renewable energy storage and CO2 recovery. However, achieving both high selectivity and stability of catalysts remains a significant challenge. To address this challenge, this study investigated the selective synthesis of formate via ERCO2 at the interface of In2O3 and Bi2O3 in the InBiO6 composite material. Moreover, InBiO6 was synthesized using indium-based metal-organic frameworks as precursor, which underwent continuous processing through ion exchange and thermal reduction. The results revealed that the formate Faradaic efficiency (FEformate) of InBiO6 reached nearly 100 % at -0.86 V vs. reversible hydrogen electrode (RHE) and remained above 90 % after continuous 317-h electrolysis, which exceeded those of previously reported indium-based catalysts. Additionally, the InBiO6 composite material exhibited an FEformate exceeding 80 % across a wide potential range of 500 mV from -0.76 to -1.26 V vs. RHE. Density-functional theory analysis confirmed that the heterogeneous interface of InBiO6 played a role in achieving optimal free energies for *OCHO on its surface. Furthermore, the addition of Bi to the InBiO6 matrix facilitated electron transfer and altered the electronic structure of In2O3, thereby enhancing the adsorption, decomposition, and formate production of *OCHO.

Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression.

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

Sport anxiety and subjective happiness of college athletes: a self-determination theory perspective.

Introduction: Sport anxiety not only impacts the performance of college athletes but also influences their psychological well-being. The psychological well-being of sports students is crucial for both academic performance and competition, as they need to balance their academic performance with professional athletic training. Method: Based on self-determination theory, this study examines the relationship between various factors in sport anxiety (somatic anxiety, worry, and concentration disruption) and subjective happiness, as well as the mediating role of need satisfaction in this relationship. A total of 835 college athletic students participated in the study, completing the Sport Anxiety Scale-2, Basic Psychological Needs Satisfaction Scale-in General, and Subjective Happiness Scale. Results: An analysis of gender differences revealed that female participants scored significantly higher on somatic anxiety (t = -2.21, df = 833, p = 0.028, Cohen's d = -0.155) and worry (t = -3.17, df = 833, p = 0.002, Cohen's d = -0.223) compared to males. In the analysis by sport type, participants engaged in team sports scored significantly higher on somatic anxiety (t = 2.70, df = 833, p = 0.007, Cohen's d = 0.187), Worry (t = 1.97, df = 833, p = 0.049, Cohen's d = 0.136), and concentration disruption (t = 2.73, df = 833, p = 0.007, Cohen's d = 0.189) than those in individual sports. Additionally, in the analysis by grade level, freshman college athletes exhibited significantly lower sport anxiety compared to sophomore athletes [F(4, 830) = 4.06, p = 0.003, η p 2 =0.019]. The mediation analysis revealed that concentration disruption in sport anxiety is significantly and negatively related to subjective happiness. Additionally, need satisfaction (competence, autonomy, and relatedness) mediates the relationship between worry, as well as concentration disruption in sport anxiety and subjective happiness. Discussion: Future research should build on the current study by employing longitudinal designs and integrating multiple objective measures to further explore the relationship between sport anxiety and subjective happiness.

The visual statistical learning overcomes scene dissimilarity through an independent clustering process.

Contextual cueing is a phenomenon of visual statistical learning observed in visual search tasks. Previous research has found that the degree of deviation of items from its centroid, known as variability, determines the extent of generalization for that repeated scene. Introducing variability increases dissimilarity between multiple occurrences of the same repeated layout significantly. However, current theories do not explain the mechanisms that help to overcome this dissimilarity during contextual cue learning. We propose that the cognitive system initially abstracts specific scenes into scene layouts through an automatic clustering unrelated to specific repeated scenes, and subsequently uses these abstracted scene layouts for contextual cue learning. Experiment 1 indicates that introducing greater variability in search scenes leads to a hindering in the contextual cue learning. Experiment 2 further establishes that conducting extensive visual searches involving spatial variability in entirely novel scenes facilitates subsequent contextual cue learning involving corresponding scene variability, confirming that learning clustering knowledge precedes the contextual cue learning and is independent of specific repeated scenes. Overall, this study demonstrates the existence of multiple levels of learning in visual statistical learning, where item-level learning can serve as material for layout-level learning, and the generalization reflects the constraining role of item-level knowledge on layout-level knowledge.

The association between visceral fat obesity and prefrailty in Chinese older adults: a cross-sectional study.

BACKGROUND: The prevalence of obesity is escalating. Previous research has concentrated on the link between frailty and obesity; however, the association between prefrailty and obesity has been less studied. Prefrailty screening and intervention may prevent or postpone frailty in older persons. OBJECTIVE: The study was to investigate into the relationship between prefrailty and several obesity indicators in Chinese community-dwelling older individuals. METHODS: This research employed the Frailty Screening Index to investigate the frailty phenotype of people living in Shanghai. Bioelectrical impedance analysis was used for evaluating body composition. RESULTS: There were 510 participants (39.0%) with high visceral adipose areas. Participants with a high visceral adipose area showed a higher risk of prefrailty (adjusted OR, 1.53; 95% CI, 1.19-1.96), according to multivariate models. When body mass index (BMI) and visceral fat area (VFA) were combined, it was discovered that having an overweight BMI with normal VFA was a protective factor for prefrailty (corrected OR, 0.62; 95% CI, 0.43-0.90), but having a normal weight but excess VFA increased the risk of prefrailty (corrected OR, 1.87; 95% CI, 1.15-3.03). CONCLUSION: Visceral fat obesity is an independent risk factor for prefrailty in Chinese older adults. Implementing targeted interventions, such as dietary modifications, increased physical activity, and other lifestyle changes, could play a crucial role in reducing the risk of prefrailty and improving overall health outcomes in this population.

Estimating global 0.1° scale gridded anthropogenic CO2 emissions using TROPOMI NO2 and a data-driven method.

Satellite remote sensing is a promising approach for monitoring global CO2 emissions. However, existing satellite-based CO2 observations are too coarse to meet the requirements of fine-scale global mapping. We propose a novel data-driven method to estimate global anthropogenic CO2 emissions at a 0.1° scale, which integrates emissions inventories and satellite data while bypassing the inadequate accuracy of CO2 observations. Due to the co-emitted anthropogenic emissions of nitrogen oxides (NOx = NO + NO2) and CO2, high-resolution NO2 measurements from the TROPOspheric Monitoring Instrument (TROPOMI) are employed to map the global anthropogenic emissions at a global 0.1° scale. We construct the driving features from NO2 data and also incorporate gridded CO2/NOx emission ratios and NOx/NO2 conversion ratios as driving data to describe co-emissions. Both ratios are predicted using a long short-term memory (LSTM) neural network (with an R2 of 0.984 for the CO2/NOx emission ratio and an R2 of 0.980 for the NOx/NO2 conversion ratio). The data-driven model for estimating anthropogenic CO2 emissions is implemented by random forest regression (RFR) and trained using the Emissions Database for Global Atmospheric Research (EDGAR). The satellite-based anthropogenic CO2 emission dataset at a global 0.1° scale agrees well with the national CO2 emission inventories (an R2 of 0.998 with Global Carbon Budget (GCB) and an R2 of 0.996 with EDGAR) and consistent with city-level emission estimates from Carbon Monitor Cities (CMC) with the R2 of 0.824. This data-driven method based on satellite-observed NO2 provides a new perspective for fine-resolution anthropogenic CO2 emissions estimation.

Understanding user engagement in mobile health applications from a privacy management perspective.

Mobile health applications (mHealth apps) have surged in popularity for their role in promoting knowledge exchange and providing emotional support among health consumers. However, this enhanced social connectivity via these apps has led to an escalation in privacy breaches, potentially hindering user engagement. Drawing upon the communication privacy management theory, this study proposes a moderated mediation model to link social privacy concerns to user engagement in mHealth apps. An online survey involving 1149 mHealth app users was conducted in China to empirically validate the proposed model. Results indicated that social privacy concerns were negatively related to user engagement in mHealth apps, and perceived privacy of the app partially mediated this relationship. Moreover, perceived control positively moderated the indirect relationship between social privacy concerns and user engagement via perceived privacy. Specifically, the negative impact of social privacy concerns on perceived privacy was mitigated for users who reported higher levels of perceived control, indicating that when users feel more in control of their personal data, they are less affected by concerns over social privacy. Theoretically, this study has the potential to help scholars understand user engagement in mHealth apps from a privacy management perspective. Practically, the results of this study could assist mobile app providers and health professionals in devising evidence-based strategies to enhance social engagement and promote effective and sustainable use of mHealth apps among health consumers.

Impact of canagliflozin combined with metformin therapy on reducing cardiovascular risk in type 2 diabetes patients.

PURPOSE: To investigate the impact and safety of canagliflozin combined with metformin on reducing cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 258 patients with T2DM admitted to our hospital from March 2021 to March 2022 were selected and divided into a control group and an observation group using a random number table. The control group received metformin combined with a placebo, while the observation group received canagliflozin combined with metformin therapy. All patients received drug treatment for 52 weeks. The primary endpoint of the study was major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and cardiovascular death. Other study parameters included safety after medication, severe adverse reactions, levels of glycated hemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and estimated glomerular filtration rate (eGFR). RESULTS: After treatment, HbA1c, FPG, BMI, SBP, and DBP in both groups were lower than before treatment, and those indicators in the observation group were lower than those in the control group (P < 0.05). The eGFR, HDL-C, and LDL-C levels in both groups were higher than before treatment, with the eGFR in the observation group being higher than that in the control group (P < 0.05). The incidence of MACE (myocardial infarction, ischemic stroke, cardiovascular death) in the observation group (5.17%) was significantly lower than that in the control group (12.93%) (HR: 2.16, 95%CI:2.04-2.59, P < 0.05). There were no significant differences in the rates of hospitalization for heart failure (3.45% vs. 1.72%), renal adverse events (4.31% vs. 3.45%), non-cardiovascular death (1.72% vs. 0.86%), all-cause mortality (2.59% vs. 0.86%), and severe adverse reactions (12.07% vs. 9.48%) between the two groups (P > 0.05). CONCLUSION: In patients with T2DM who received the canagliflozin combined with metformin, the mortality rate of cardiovascular causes was significantly reduced. Compared with metformin monotherapy, there is no significant difference in the incidence of serious adverse reactions, and the safety of medication is better, while the blood sugar, blood pressure, and weight of T2DM patients are more actively improved. For T2DM patients with high risk of cardiovascular disease, the combination of canagliflozin and metformin could have a higher benefit in cardiovascular outcomes.

Identification of sanguinarine as a novel antagonist for perfluorooctanoate/perfluorooctane sulfonate-induced senescence of hepatocytes: An integrated computational and experimental analysis.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), two prominent per- and polyfluoroalkyl substances (PFASs), are potentially harmful to many human organs. However, there only exist limited methods to mitigate their health hazards. The aim of this study is to combine a bioinformatics analysis with in vitro experiments to discover small molecules that can alleviate liver damage caused by PFOA/PFOS. We identified 192 and 82 key genes related to hepatocytes exposed to PFOA and PFOS, respectively. The functional enrichment analysis of key genes suggested cellular senescence may be important in PFOA/PFOS-induced hepatotoxicity. The in vitro models revealed that PFOA/PFOS led to hepatocyte senescence by increasing the activity of SA-ß-gal, inducing mitochondrial dysfunction, impacting cell cycle arrest, and elevating the expressions of p21, p53, IL-1ß, and SASP-related cytokines. The drug-target gene set enrichment analysis method was employed to compare the transcriptome data from the Gene Expression Omnibus database (GEO), Comparative Toxicogenomics Database (CTD), and the high-throughput experiment- and reference-guided database (HERB), and 21 traditional Chinese medicines (TCMs) were identified that may alleviate PFOA/PFOS-induced liver aging. The experimental results of co-exposure to PFOA/PFOS and TCMs showed that sanguinarine has particular promise in alleviating cellular senescence caused by PFOA/PFOS. Further investigations revealed that the mTOR-p53 signaling pathway was involved in PFOA/PFOS-mediated hepatic senescence and can be blocked using sanguinarine.

A Novel Microbial Compound Inhibitor and Its Efficacy in Preventing and Controlling Mine Fire Risks: A Case Study on Low-Rank Coal Spontaneous Combustion.

To guarantee the safety and sustainability of coal mining by effectively mitigating the substantial risk associated with coal spontaneous combustion, this study proposes a multifaceted prevention strategy aligned with green environmental principles. A compound flame retardant with a physicochemical control mechanism was prepared using indigenous microorganisms to mineralize residual coal after mining, utilizing Bacillus pasteurelli as a substitute material for inorganic salts. Under laboratory conditions simulating coal self-combustion, biobased flame retardants were employed to investigate the physical and chemical transformations of heat and mass evolution from ambient temperature to combustion in two representative low-rank coals. By quantitatively comparing alterations in microbiome-based groups among raw lignite, bioretarded lignite, and two control samples, the inhibitory mechanism of biobased materials on the oxygen reaction pathway was elucidated. The findings substantiated that biobased modification can consolidate the methyl and methylene groups present in aliphatic hydrocarbon side chains, which are prone to instigating low-temperature oxidation reactions. Additionally, the preventive performance of biobased flame retardants was assessed through temperature-programmed experiments, which involved estimating the critical self-heating temperature, oxygen consumption, and gas production rates of compared coal samples. The results demonstrated significant enhancements in the resistance to spontaneous combustion following bioretarded modification. Notably, the identification grade of long flame coal shifted from easy to moderate susceptibility to spontaneous combustion. Furthermore, biobased flame retardants exhibited remarkable flame retardancy rates of approximately 80% for lignite, thereby validating their efficacy as more environmentally friendly and technologically advanced substitute materials for inhibiting spontaneous combustion in low-rank coals.