An improved method for diagnosis of Parkinson's disease using deep learning models enhanced with metaheuristic algorithm.

Parkinson's disease (PD) is challenging for clinicians to accurately diagnose in the early stages. Quantitative measures of brain health can be obtained safely and non-invasively using medical imaging techniques like magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). For accurate diagnosis of PD, powerful machine learning and deep learning models as well as the effectiveness of medical imaging tools for assessing neurological health are required. This study proposes four deep learning models with a hybrid model for the early detection of PD. For the simulation study, two standard datasets are chosen. Further to improve the performance of the models, grey wolf optimization (GWO) is used to automatically fine-tune the hyperparameters of the models. The GWO-VGG16, GWO-DenseNet, GWO-DenseNet + LSTM, GWO-InceptionV3 and GWO-VGG16 + InceptionV3 are applied to the T1,T2-weighted and SPECT DaTscan datasets. All the models performed well and obtained near or above 99% accuracy. The highest accuracy of 99.94% and AUC of 99.99% is achieved by the hybrid model (GWO-VGG16 + InceptionV3) for T1,T2-weighted dataset and 100% accuracy and 99.92% AUC is recorded for GWO-VGG16 + InceptionV3 models using SPECT DaTscan dataset.

Comprehensive evaluation of genes related to basement membrane in hepatocellular carcinoma.

In all mammals, the basement membrane serves as a pivotal extracellular matrix. Hepatocellular carcinoma (HCC) is a challenge among numerous cancer types shaped by basement membrane-related genes (BMGs). Our research established an innovative prognostic model that is highly accurate in its prediction of HCC prognoses and immunotherapy efficacy to summarize the crucial role of BMGs in HCC. We obtained HCC transcriptome analysis data and corresponding clinical data from The Cancer Genome Atlas (TCGA). To augment our dataset, we incorporated 222 differentially expressed BMGs identified from relevant literature. A weighted gene coexpression network analysis (WGCNA) of 10158 genes demonstrated four modules that were connected to HCC. Additionally, 66 genes that are found at the intersection of BMGs and HCC-related genes were designated as hub HCC-related BMGs. MMP1, ITGA2, P3H1, and CTSA comprise the novel model that was engineered using univariate and multivariate Cox regression analysis. Furthermore, the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) datasets encouraged the BMs model's validity. The overall survival (OS) of individuals with HCC may be precisely predicted in the TCGA and ICGC databases utilizing the BMs model. A nomogram based on the model was created in the TCGA database at similar time, and displayed a favorable discriminating ability for HCC. Particularly, when compared to the patients at an elevated risk, the patients with a low-risk profile presented different tumor microenvironment (TME) and hallmark pathways. Moreover, we discovered that a lower risk score of HCC patients would display a greater response to immunotherapy. Finally, quantitative real-time PCR (qRT-PCR) experiments were used to verify the expression patterns of BMs model. In summary, BMs model demonstrated efficacy in prognosticating the survival probability of HCC patients and their immunotherapeutic responsiveness.

Deficiency of SDHC promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer.

BACKGROUND: Several studies have demonstrated a strong correlation between impaired Succinate dehydrogenase (SDH) function and the advancement of tumors. As a subunit of SDH, succinate dehydrogenase complex subunit C (SDHC) has been revealed to play tumor suppressive roles in several cancers, while its specific role in colorectal cancer (CRC) still needs further investigation. METHODS: Online database were utilized to investigate the expression of SDHC in colorectal cancer and to assess its correlation with patient prognosis. Cell metastasis was assessed using transwell and wound healing assays, while tumor metastasis was studied in a nude mice model in vivo. Drug screening and RNA sequencing were carried out to reveal the tumor suppressor mechanism of SDHC. Triglycerides, neutral lipids and fatty acid oxidation were measured using the Triglyceride Assay Kit, BODIPY 493/503 and Colorimetric Fatty Acid Oxidation Rate Assay Kit, respectively. The expression levels of enzymes involved in fatty acid metabolism and the PI3K/AKT signaling pathway were determined by quantitative real-time PCR and western blot. RESULTS: Downregulation of SDHC was found to be closely associated with a poor prognosis in CRC. SDHC knockdown promoted CRC metastasis both in vitro and in vivo. Through drug screening and Gene set enrichment analysis, it was discovered that SDHC downregulation was positively associated with the fatty acid metabolism pathways significantly. The effects of SDHC silencing on metastasis were reversed when fatty acid synthesis was blocked. Subsequent experiments revealed that SDHC silencing activated the PI3K/AKT signaling axis, leading to lipid accumulation by upregulating the expression of aldehyde dehydrogenase 3 family member A2 (ALDH3A2) and reduction of fatty acid oxidation rate by suppressing the expression of acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1A (CPT1A). CONCLUSIONS: SDHC deficiency could potentially enhance CRC metastasis by modulating the PI3K/AKT pathways and reprogramming lipid metabolism.

Long daytime napping: A silent danger for hypertensive individuals.

BACKGROUND AND PURPOSE: Hypertension significantly contributes to stroke. Previous research has indicated a connection between daytime napping and stroke. Research on the connection between daytime napping duration and first stroke in hypertensive individuals is lacking nevertheless. METHODS: This research, which ran from 24 August 2013 to 31 December 2022, recruited 11,252 individuals with hypertension and without a history of stroke from the China Stroke Primary Prevention Trial. To determine the relationship between daytime napping duration and stroke onset in hypertensive individuals, we conducted analyses for threshold effects, multivariate-adjusted Cox proportional hazard regression models, and Kaplan-Meier survival curves. RESULTS: The duration of daytime napping (<75 min) was positively correlated with stroke risk; beyond 75 min, the risk did not increase further. When compared to hypertensive individuals who napped for 1-30 min, daytime napping 31-60 min (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 1.06-1.53) and >60 min (HR = 1.37, 95% CI = 1.14-1.65) were substantially related with a greater risk of first stroke. Additionally, this correlation was absent in cases of hemorrhagic stroke, but present in cases of ischemic stroke, specifically for hypertensive individuals who napped for 31-60 min or >60 min (p < 0.05). Kaplan-Meier survival curves displayed that hypertensive individuals who extended daytime napping had an elevated incidence of stroke. CONCLUSIONS: Hypertensive individuals who take longer daytime naps (>30 min) are at an elevated risk of stroke onset, particularly ischemic stroke, irrespective of other factors.

Rapamycin promotes the intestinal barrier repair in ulcerative colitis via the mTOR/PBLD/AMOT signaling pathway.

Intestinal barrier dysfunction characterized by the functional loss of the intestinal epithelium's tight junction (TJ) barrier is a key factor in the pathogenesis of ulcerative colitis (UC). Although rapamycin, an mTOR (mechanistic target of rapamycin) inhibitor, has shown promise in inducing clinical remission and mucosal healing in inflammatory bowel disease, its underlying mechanism remains elusive. Thus, this study investigated the role of the mTOR pathway in regulating the intestinal barrier. To investigate the molecular mechanism regulating the intestinal barrier, specific intestinal epithelial phenazine biosynthesis-like domain-containing protein (PBLD)-deficient (PBLDIEC-/-) mice and control wild-type (WT) mice were intraperitoneally injected with rapamycin or MHY1485. To determine the relevance of the findings for UC, we analyzed transcriptome data and single-cell expression profiles from public databases and intestinal mucosal tissues obtained from patients with active UC or colon cancer. We observed that mTOR activation in the intestinal epithelium of patients with active UC. Moreover, in vivo, rapamycin markedly increased the expressions of PBLD and TJ proteins and reduced intestinal inflammation in mice with dextran sulfate sodium-induced enteritis. However, the therapeutic efficacy of rapamycin was notably reduced in PBLDIEC-/- mice. In vitro, rapamycin influenced PBLD expression by modulating the nuclear transcription of transcription factor EB (TFEB). Angiomotin (AMOT) could directly bind to PBLD, and rapamycin could not effectively increase the expression of TJ proteins after the knockdown of PBLD or AMOT. In summary, the administration of rapamycin is a potential treatment for UC, and targeting the mTOR/PBLD/AMOT axis is a potential novel approach for UC treatment.

Optimization of sulfate reduction and methanogenesis via phase separation in a two-phase internal circulation reactor for the treatment of high-sulfate organic wastewater.

To enhance the performance of the internal circulation (IC) reactor when treating high-sulfate organic wastewater, a laboratory-scale two-phase IC reactor with distinct phase separation capabilities was designed, and the sulfate reduction and methanogenesis processes were optimized by segregating the reactor into two specialized reaction zones. The results demonstrated that the first and second reaction areas of the two-phase IC reactor could be maintained at 4.5-6.0 and 7.5-8.5, respectively, turning them into the specialized phase for sulfate reduction and methanogenesis. Through phase separation, the two-phase IC reactor achieved a COD degradation and sulfate reduction efficiency of more than 80% when the influent sulfate concentration exceeded 5,000 mg/L, which were 32.32% and 16.04% higher than that before phase separation. Functional analyses indicated a greater activity of both the dissimilatory and assimilatory sulfate reduction pathways in the acidogenic phase, largely due to a rise in the relative abundance of the genera Desulfovibrio, Bacteroides, and Lacticaseibacillus, the primary carriers of sulfate reduction functional genes. In contrast, all the acetoclastic, hydrogenotrophic, and methylotrophic methanogenesis pathways were inhibited in the acidogenic phase but thrived in the methanogenic phase, coinciding with shifts in the genus Methanothrix, which harbors the mcrA, mcrB, and mcrG genes essential for the final transformation step of all three methanogenesis pathways.

Comparison of chlorine and chlorine dioxide disinfection in drinking water: Evaluation of disinfection byproduct formation under equal disinfection efficiency.

Disinfection efficiency and disinfection byproduct (DBP) formation are two important aspects deserving careful consideration when evaluating different disinfection protocols. However, most of the previous studies on the selection of disinfection methods by comparing DBP formation were carried out under the same initial/residual dose and contact time of different disinfectants, and such a practice may cause overdose or underdose of a certain disinfectant, leading to the inaccurate evaluation of disinfection. In this study, a comprehensive and quantitative comparison of chlorine (Cl2) and chlorine dioxide (ClO2) disinfection was conducted with regard to their DBP formation under equal disinfection efficiency. The microbial inactivation models as well as the Cl2 and ClO2 demand models were developed. On such basis, the integral CT (ICT) values were determined and used as a bridge to connect disinfection efficiency and DBP formation. For 3-log10 and 4-log10 reductions of Pseudomonas aeruginosa, ClO2 had 1.5 and 5.8 times higher inactivation ability than Cl2, respectively. In the premise of equal disinfection efficiency (i.e., the ICT ratios of Cl2 to ClO2 = 1.5 and 5.8), the levels of total organic chlorine, total organic bromine, and total organic halogen formed in the Cl2 disinfection were significantly higher than those formed in the ClO2 disinfection. Among the 35 target aliphatic DBPs, trihalomethanes (THMs) and haloacetic acids (HAAs) were the dominant species formed in both Cl2 and ClO2 disinfection. The total THM levels formed in Cl2 disinfection were 14.6 and 30.3 times higher than those in ClO2 disinfection, respectively. The total HAA levels formed in Cl2 disinfection were 3.5 and 5.4 times higher than those in ClO2 disinfection, respectively. Formation of the target 48 aromatic DBPs was much favored in Cl2 disinfection than that in ClO2 disinfection, and the formation levels was dominated by contact time. This study demonstrated that ClO2 had significant advantages over Cl2, especially at higher microorganism inactivation and lower DBP formation requirements.

Risk factors of acute ischemic stroke and the role of angiotensin I in predicting prognosis of patients undergoing endovascular thrombectomy.

Purpose: The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk factors of AIS and explore the role of serum indicators such as angiotensin I (Ang I) in the prognosis of patients undergoing endovascular thrombectomy (EVT). Patients and methods: Patients with AIS who underwent EVT and healthy controls were retrospectively enrolled in this study, and the patients were divided into a good or a poor prognosis group. We compared Ang I, blood routine indexes, biochemical indexes, electrolyte indexes, and coagulation indexes between patients and controls. We used univariate and multivariate logistic regression analyses to evaluate possible risk factors for AIS and the prognosis of patients undergoing EVT. Independent risk factors for the prognosis of patients undergoing EVT were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves (ROC). Results: Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. In addition, Ang I levels are lower in AIS compared to the controls. The level of Ang I was higher in the good prognosis group. Furthermore, we developed a nomogram to evaluate its ability to predict the prognosis of AIS after EVT. The AUC value of the combined ROC model (Ang I and albumin-globulin ratio (AGR)) was 0.859. Conclusions: In conclusion, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. The combined Ang I and AGR model has a good predictive ability for the prognosis of AIS patients undergoing arterial thrombectomy.

Protective effects of Wenqingyin on sepsis-induced acute lung injury through regulation of the receptor for advanced glycation end products pathway.

BACKGROUND: Wenqingyin (WQY), an ancient Chinese medicinal agent, has been extensively used in treating infectious ailments throughout history. However, the anti-sepsis mechanism remains unknown. PURPOSE: This study investigated the diverse mechanisms of WQY in mitigating sepsis-induced acute lung injury (ALI). Additionally, the effects of WQY were validated using biological experiments. METHODS: This study combined UHPLC-Orbitrap-HRMS analysis and network pharmacology to predict the potential anti-sepsis mechanism of WQY. Sepsis-induced ALI models were established in vivo via intraperitoneal lipopolysaccharide (LPS) administration and in vitro by LPS-stimulated RAW 264.7 macrophages. Various techniques, including hematoxylin-eosin staining, TUNEL, qPCR, and ELISA, were used to assess lung damage and quantify inflammatory cytokines. Inflammatory cell infiltration was visualized through immunohistochemistry. Hub targets and signaling pathways were identified using Western blotting, immunohistochemistry, and immunofluorescence staining. RESULTS: Seventy-five active components and 237 associated targets were acquired, with 145 of these targets overlapping with processes related to sepsis. Based on the comprehensive protein-protein interaction network analysis, JUN, AKT1, TP53, IL-6, HSP90AA1, CASP3, VEGFA, IL-1ß, RELA, and EGFR may be targets of WQY for sepsis. Analysis of the Kyoto Gene and Genome Encyclopedia revealed that WQY is implicated in the advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE) signaling pathway. In vivo, WQY alleviated sepsis-induced ALI, suppressing proinflammatory cytokines and inhibiting macrophage/neutrophil infiltration. In vitro, WQY reduced TNF-α, IL-6, and IL-1ß in LPS-induced RAW 264.7 macrophages. Furthermore, we verified that WQY protected against sepsis-induced ALI by regulating the RAGE pathway for the first time. Baicalin, coptisine, and paeoniflorin may be the effective components of WQY that inhibit RAGE. CONCLUSION: The primary mechanism of WQY in combating sepsis-induced ALI involves controlling RAGE levels and the PI3K/AKT pathway, suppressing inflammation, and mitigating lung damage. This study establishes a scientific foundation for understanding the mechanism of WQY and its clinical use in treating sepsis.

Occurrence, distribution and potential environmental risks of pollutants in aquaculture ponds during pond cleaning in Taihu Lake Basin, China.

During the process of cleaning aquaculture ponds, the drainage contributes significantly to antibiotic pollution in the surrounding water environment. Therefore, we conducted a study on the distribution of 26 antibiotics in 57 ponds within the Taihu Lake basin. The results revealed that the detection frequency of antibiotics ranged from 1.75 % to 80.7 %, with the overall detection concentrations ranging from 3.27 to 708.72 ng/L. Among them, the detection rate of 8 antibiotics exceeded 50 %. Regarding the spatial distribution, the concentration of antibiotics was relatively high in aquaculture ponds located in the Changzhou area, with the highest concentration reaching 708.72 ng/L. This observation is likely due to the large size and intensive breeding practices in Changzhou. Fish ponds exhibited a significantly higher total antibiotic concentration of 3.27 to 445.57 ng/L compared to crab ponds (13.01 to 206.30 ng/L) and shrimp ponds (23.17 to 107.40 ng/L). Quinolones and sulfonamides were the predominant antibiotic classes found in fish ponds, accounting for 51.49 % of the total antibiotic concentration. Notably, sulfamethoxazole (SMX) and enrofloxacin (ENR) exhibited the highest antibiotic concentrations. Risk assessments demonstrated that SMX, ENR, and ofloxacin (OFX) contributed significantly to ecological risks. Furthermore, the study found that the tertiary constructed wetland treatment process achieved a remarkable removal rate of 92.44 % for antibiotics in aquaculture wastewater, while other treatment processes displayed limited effectiveness in removing antibiotics. This study addresses the knowledge gap concerning antibiotic pollution during the cleaning process of aquaculture ponds within the Taihu Lake basin.

Lewis acid-rich SrFexTi1-xO3/TiO2 to enhance the photocatalytic reduction of nitrate to N2.

The photocatalytic reduction of nitrate has received considerable attention due to its high efficiency and environmentally friendly nature. The excessive addition of hole scavengers is the most commonly used method to increase the nitrate reduction efficiency. However, achieving high selectivity in the photocatalytic reduction of nitrate to N2 with low concentration of hole scavengers remains challenging. In this study, the SrFexTi1-xO3/TiO2 S-scheme heterojunction photocatalysts with many Lewis acidic adsorption sites have been developed. The experimental results demonstrated that the incorporation of 6% Fe into SrFe0.06Ti0.94O3/TiO2 (SFTO6) resulted in the nitrate conversion rate of 97.68% and the N2 selectivity reached 96.35% with 25 mmol/L formic acid. Moreover, it also exhibited excellent stability and recycle ability. After 5 cycles, SFTO6 still exhibited a stable photocatalytic denitration efficiency of 92.94%, highlighting its potential for practical application. Through comprehensive mechanistic investigations, enhancing direct reduction process is considered the key to its high reduction efficiency with low formic acid. And the Lewis acidic adsorption sites enhance N2 selectivity by enriching NOx- on the surface of the material. Overall, this study provides a novel approach for achieving efficient photocatalytic reduction of nitrate to N2 under conditions with low concentration of hole scavengers.

Effect of plateletcrit and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on folic acid efficacy in stroke prevention.

Previous studies have shown that low platelet count combined with high plasma total homocysteine (tHcy) increased stroke risk and can be lowered by 73% with folic acid. However, the combined role of other platelet activation parameters and the methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on stroke risk and folic acid treatment benefit remain to be examined. This study aimed to investigate if platelet activation parameters and MTHFR genotypes jointly impact folic acid treatment efficacy in first stroke prevention. Data were derived from the China Stroke Primary Prevention Trial. This study includes a total of 11,185 adult hypertensive patients with relevant platelet activation parameters and MTHFR genotype data. When simultaneously considering both platelet activation parameters (plateletcrit, platelet count, mean platelet volume, platelet distribution width) and MTHFR genotypes, patients with both low plateletcrit (Q1) and the TT genotype had the highest stroke incidence rate (5.6%) in the enalapril group. This subgroup significantly benefited from folic acid treatment, with a 66% reduction in first stroke (HR: 0.34; 95% CI: 0.14-0.82; p = 0.016). Consistently, the subgroup with low plateletcrit (Q1) and the CC/CT genotype also benefited from folic acid treatment (HR: 0.40; 95% CI: 0.23-0.70; p = 0.001). In Chinese hypertensive adults, low plateletcrit can identify those who may greatly benefit from folic acid treatment, in particular, those with the TT genotype, a subpopulation known to have the highest stroke risk.

Evaluating a river's ecological health: A multidimensional approach.

Evaluating the health of river surface water is essential, as rivers support significant biological resources and serve as vital drinking water sources. While the Water Quality Index (WQI) is commonly employed to evaluate surface water quality, it fails to consider biodiversity and does not fully capture the ecological health of rivers. Here we show a comprehensive assessment of the ecological health of surface water in the lower Yangtze River (LYR), integrating chemical and biological metrics. According to traditional WQI metrics, the LYR's surface water generally meets China's Class II standards. However, it also contains 43 high-risk emerging contaminants; nitrobenzenes are found at the highest concentrations, representing 25-90% of total detections, while polycyclic aromatic hydrocarbons present the most substantial environmental risks, accounting for 81-93% of the total risk quotient. Notably, the plankton-based index of biological integrity (P-IBI) rates the ecological health of the majority of LYR water samples (59.7%) as 'fair', with significantly better health observed in autumn compared to other seasons (p < 0.01). Our findings suggest that including emerging contaminants and P-IBI as additional metrics can enhance the traditional WQI analysis in evaluating surface water's ecological health. These results highlight the need for a multidimensional assessment approach and call for improvements to LYR's ecological health, focusing on emerging contaminants and biodiversity rather than solely on reducing conventional indicators.

A group of emerging heterocyclic nitrogenous disinfection byproducts: Formation and cytotoxicity of halopyridinols in drinking water.

Recently, a new group of halopyridinol disinfection byproducts (DBPs) was reported in drinking water. The in vivo developmental and acute toxicity assays have shown that they were more toxic than a few commonly known aliphatic DBPs such as bromoform and iodoacetic acid. However, many pyridinol DBPs with the same main structures but different halogen substitutions were still unknown due to complicated water quality conditions and various disinfection methods applied in drinking water treatment plants. Studies on their transformation mechanisms in drinking water disinfection were quite limited. In this study, comprehensive detection and identification of halopyridinols were conducted, and five new halopyridinols were first reported, including 2-chloro-3-pyridinol, 2,6-dichloro-3-pyridinol, 2-bromo-5-chloro-3-pyridinol, 2,4,6-trichloro-3-pyridinol and 2,5,6-trichloro-3-pyridinol. Formation conditions and mechanisms of the halopyridinols were explored, and results showed that chlorination promoted their formation compared with chloramination. Halopyridinols were intermediate DBPs that could undergo further transformation/degradation with increasing contact time, disinfectant dose, bromide concentration, and pH. The in vitro cytotoxicity of the halopyridinols was evaluated using human hepatocellular carcinoma cells. Results showed that the cytotoxicity of 3,5,6-trichloro-2-pyridinol was the highest (EC50 = 474.3 µM), which was 13.0 and 1.6 times higher than that of 2-bromo-3-pyridinol (EC50 = 6214.5 µM) and tribromomethane (EC50 = 753.6 µM), respectively.

Methylation enables the use of fluorine-free ether electrolytes in high-voltage lithium metal batteries.

Lithium metal batteries represent a promising technology for next-generation energy storage, but they still suffer from poor cycle life due to lithium dendrite formation and cathode cracking. Fluorinated solvents can improve battery longevity by improving LiF content in the solid-electrolyte interphase; however, the high cost and environmental concerns of fluorinated solvents limit battery viability. Here we designed a series of fluorine-free solvents through the methylation of 1,2-dimethoxyethane, which promotes inorganic LiF-rich interphase formation through anion reduction and achieves high oxidation stability. The anion-derived LiF interphases suppress lithium dendrite growth on the lithium anode and minimize cathode cracking under high-voltage operation. The Li+-solvent structure is investigated through in situ techniques and simulations to draw correlations between the interphase compositions and electrochemical performances. The methylation strategy provides an alternative pathway for electrolyte engineering towards high-voltage electrolytes while reducing dependence on expensive fluorinated solvents.

Pathogenic Aspergillus Strains Identification and Antifungal Susceptibility Analysis of 452 Cases with Otomycosis in Jingzhou, China.

OBJECTIVE: To study the distribution of pathogenic Aspergillus strains of otomycosis in central China and the identification of their antifungal sensitivity. METHODS: We collected external ear canal secretions clinically diagnosed as otomycosis from April 2020 to January 2023 from the Department of Otolaryngology-Head and Neck Surgery in central China. The pathogenic Aspergillus strains were identified through morphological examination and sequencing. The antifungal sensitivity was performed using the broth microdilution method described in the Clinical Laboratory Standard Institute document M38-A3. RESULTS: In the 452 clinical strains isolated from the external ear canal, 284 were identified as Aspergillus terreus (62.83%), 92 as Aspergillus flavus (20.35%), 55 as Aspergillus niger (12.17%). In antifungal susceptibility tests the MIC of Aspergillus strains to bifonazole and clotrimazole was high,all the MIC90 is > 16 ug/mL. However, most Aspergillus isolates show moderate greatly against terbinafine, itraconazole and voriconazole. CONCLUSION: A. terreus is the most common pathogenic Aspergillus strain in otomycosis in central China. The selected topical antifungal drugs were bifonazole and clotrimazole; the drug resistance rate was approximately 30%. If the infection is persistent and requires systemic treatment, terbinafine and itraconazole can be used. The resistance of Aspergillus in otomycosis to voriconazole should be screened to avoid the systemic spread of infection in immunocompromised people and poor compliance with treatment. However, the pan-azole-resistant strain of Aspergillus should be monitored, particularly in high-risk patients with otomycosis.

CircDiaph3 aggravates H/R-induced cardiomyocyte apoptosis and inflammation through miR-338-3p/SRSF1 axis.

Acute myocardial infarction (AMI) is one of the most prevalent cardiovascular diseases, accounting for a high incidence rate and high mortality worldwide. Hypoxia/reoxygenation (H/R)-induced myocardial cell injury is the main cause of AMI. Several studies have shown that circular RNA contributes significantly to the pathogenesis of AMI. Here, we established an AMI mouse model to investigate the effect of circDiaph3 in cardiac function and explore the functional role of circDiaph3 in H/R-induced cardiomyocyte injury and its molecular mechanism. Bioinformatics tool and RT-qPCR techniques were applied to detect circDiaph3 expression in human patient samples, heart tissues of AMI mice, and H/R-induced H9C2 cells. CCK-8 was used to examine cell viability, while annexin-V/PI staining was used to assess cell apoptosis. Myocardial reactive oxygen species (ROS) levels were detected by immunofluorescence. Western blot was used to detect the protein expression of anti-apoptotic Bcl-2 while pro-apoptotic Bax and cleaved-Caspase-3. Furthermore, ELISA was used to detect inflammatory cytokines production. While bioinformatics tool and RNA pull-down assay were used to verify the interaction between circDiaph3 and miR-338-3p. We found that circDiaph3 expression was high in AMI patients and mice, as well as in H/R-treated H9C2 cells. CircDiaph3 silencing ameliorated apoptosis and inflammatory response of cardiomyocytes in vivo. Moreover, the knockdown of cirDiaph3 mitigated H/R-induced apoptosis and the release of inflammatory mediators like IL-1ß, IL-6, and TNF-α in H9C2 cells. Mechanistically, circDiaph3 induced cell apoptosis and inflammatory responses in H/R-treated H9C2 cells by sponging miR-338-3p. Overexpressing miR-338-3p in H/R-treated cells prominently reversed circDiaph3-induced effects. Notably, miR-338-3p inhibited SRSF1 expression in H/R-treated H9C2 cells. While overexpressing SRSF1 abrogated miR-338-3p-mediated alleviation of apoptosis and inflammation after H/R treatment. To summarize, circDiaph3 aggravates H/R-induced cardiomyocyte apoptosis and inflammation through the miR-338-3p/SRSF1 axis. These findings suggest that the circDiaph3/miR-338-3pp/SRSF1 axis could be a potential therapeutic target for treating H/R-induced myocardial injury.

Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-ß1/SMAD3/ANGPTL4 axis in colorectal cancer.

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-ß1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-ß signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-ß1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-ß signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.

Integrin αvß3 and LHRH Receptor Double Directed Nano-Analogue Effective Against Ovarian Cancer in Mice Model.

Introduction: The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvß3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LP-PTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects. Methods: LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice. Results: The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytotoxicity, and hand a more potent inhibitory effect on tumor spheroids of A2780 cells. It also showed enhanced co-localization with endosomes or lysosome in A2780 cells, improved tumor-targeting capability, and demonstrated an enhanced anti-tumor effect in LHRHR-positive ovarian cancers. Conclusion: The designed LHRHa-RGD-LP-PTX liposomes significantly enhanced the tumor-targeting ability and therapeutic efficacy for LHRH receptor-positive ovarian cancers.