Enhancing efficiency of ultrasound-assisted biodiesel production catalyzed by Eversa® Transform 2.0 at low lipase concentration: Enzyme characterization and process optimization.

This study focused on the ultrasound-assisted transesterification of simulated low-quality feedstocks using a low-cost liquid lipase Eversa® Transform 2.0 (ET2). Enzyme characterization was also performed to investigate the effect of ultrasound parameters on enzyme structure. The optimal ultrasound parameters, 40 % amplitude, and 5 % duty cycle effectively enhanced the reaction rate compared to the conventional stirring method while retaining 95 % of the enzyme activity. Analysis of circular dichroism (CD) spectra revealed the preservation of the secondary structure of ET2 under the optimal ultrasound intensities, while fluorescence spectra indicated a slight change in its tertiary structure. The implementation of a two-stage methanol dosing strategy in the ultrasound-assisted reaction effectively mitigated lipase inhibition, yielding a remarkable fatty acid methyl ester (FAME) content of 92.2 % achieved within a 12-h reaction time. Notable, this high FAME content was achieved with only a 4:1 methanol-to-oil molar ratio and a 0.5 wt% enzyme concentration. Under these optimized conditions, the ultrasound-assisted reaction also demonstrated a 15 % improvement in the final FAME content compared to the conventional stirring method. These promising results hold significant potential for advancing the field of biodiesel production via ultrasound technology, contributing substantively to sustainable energy sources.

A Combined Filtering Method for ZigBee Indoor Distance Measurement.

Indoor distance measurement technology utilizing Zigbee's Received Signal Strength Indication (RSSI) offers cost-effective and energy-efficient advantages, making it widely adopted for indoor distance measurement applications. However, challenges such as multipath effects, signal attenuation, and signal blockage often degrade the accuracy of distance measurements. Addressing these issues, this study proposes a combined filtering approach integrating Kalman filtering, Dixon's Q-test, Gaussian filtering, and mean filtering. Initially, the method evaluates Zigbee's transmission power, channel, and other parameters, analyzing their impact on RSSI values. Subsequently, it fits a signal propagation loss model based on actual measured data to understand the filtering algorithm's effect on distance measurement error. Experimental results demonstrate that the proposed method effectively improves the conversion relationship between RSSI and distance. The average distance measurement error, approximately 0.46 m, substantially outperforms errors derived from raw RSSI data. Consequently, this method offers enhanced distance measurement accuracy, making it particularly suitable for indoor positioning applications.

Investigation of the mechanisms behind ochratoxin A-induced cytotoxicity in human astrocytes and the protective effects of N-acetylcysteine.

Ochratoxin A (OTA) is a type of mycotoxin commonly found in raw and processed foods. It is essential to be aware of this toxin, as it can harm your health if consumed in high quantities. OTA can induce toxic effects in various cell models. However, a more comprehensive understanding of the harmful effects of OTA on human astrocytes is required. This study evaluated OTA's neurotoxic effects on the Gibco® Human Astrocyte (GHA) cell line, its underlying mechanisms, and the antioxidant N-acetylcysteine (NAC) ability to prevent them. OTA exposure within 5-30 µM has induced concentration-dependent cytotoxicity. In the OTA-treated cells, the levels of reactive oxygen species (ROS) were found to be significantly increased, while the glutathione (GSH) contents were found to decrease considerably. The western blotting of OTA-treated cells has revealed increased Bax, cleaved caspase-9/caspase-3 protein levels, and increased Bax/Bcl-2 ratio. In addition, exposure to OTA has resulted in the induction of antioxidant responses associated with the protein expressions of Nrf2, HO-1, and NQO1. On the other hand, the pretreatment with NAC has partially alleviated the significant toxic effects of OTA. In conclusion, our findings suggest that oxidative stress and apoptosis are involved in the OTA-induced cytotoxicity in GHA cells. NAC could act as a protective agent against OTA-induced oxidative damage.

An imbalance data quality monitoring based on SMOTE-XGBOOST supported by edge computing.

Product assembly involves extensive production data that is characterized by high dimensionality, multiple samples, and data imbalance. The article proposes an edge computing-based framework for monitoring product assembly quality in industrial Internet of Things. Edge computing technology relieves the pressure of aggregating enormous amounts of data to cloud center for processing. To address the problem of data imbalance, we compared five sampling methods: Borderline SMOTE, Random Downsampling, Random Upsampling, SMOTE, and ADASYN. Finally, the quality monitoring model SMOTE-XGBoost is proposed, and the hyperparameters of the model are optimized by using the Grid Search method. The proposed framework and quality control methodology were applied to an assembly line of IGBT modules for the traction system, and the validity of the model was experimentally verified.

Effects of SARS-COV-2 infection during the frozen-thawed embryo transfer cycle on embryo implantation and pregnancy outcomes.

STUDY QUESTION: Does severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the frozen-thawed embryo transfer (FET) cycle affect embryo implantation and pregnancy rates? SUMMARY ANSWER: There is no evidence that SARS-CoV-2 infection of women during the FET cycle negatively affects embryo implantation and pregnancy rates. WHAT IS KNOWN ALREADY: Coronavirus disease 2019 (COVID-19), as a multi-systemic disease, poses a threat to reproductive health. However, the effects of SARS-CoV-2 infection on embryo implantation and pregnancy following fertility treatments, particularly FET, remain largely unknown. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, included women who underwent FET cycles between 1 November 2022 and 31 December 2022 at an academic fertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who tested positive for SARS-CoV-2 during their FET cycles were included in the COVID-19 group, while those who tested negative during the same study period were included in the non-COVID-19 group. The primary outcome was ongoing pregnancy rate. Secondary outcomes included rates of implantation, biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy. Multivariate logistic regression models were applied to adjust for potential confounders including age, body mass index, gravidity, vaccination status, and endometrial preparation regimen. Subgroup analyses were conducted by time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) and by level of fever (no fever, fever <39°C, or fever ≥39°C). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 243 and 305 women were included in the COVID-19 and non-COVID-19 group, respectively. The rates of biochemical pregnancy (58.8% vs 62.0%, P = 0.46), clinical pregnancy (53.1% vs 54.4%, P = 0.76), implantation (46.4% vs 46.2%, P = 0.95), early pregnancy loss (24.5% vs 26.5%, P = 0.68), and ongoing pregnancy (44.4% vs 45.6%, P = 0.79) were all comparable between groups with or without infection. Results of logistic regression models, both before and after adjustment, revealed no associations between SARS-CoV-2 infection and rates of biochemical pregnancy, clinical pregnancy, early pregnancy loss, or ongoing pregnancy. Moreover, neither the time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) nor the level of fever (no fever, fever <39°C, or fever ≥39°C) was found to be related to pregnancy rates. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study is subject to possible selection bias. Additionally, although the sample size was relatively large for the COVID-19 group, the sample sizes for certain subgroups were relatively small and lacked adequate power, so these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study findings suggest that SARS-CoV-2 infection during the FET cycle in females does not affect embryo implantation and pregnancy rates including biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy, indicating that cycle cancellation due to SARS-CoV-2 infection may not be necessary. Further studies are warranted to verify these findings. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2019YFA0802604), National Natural Science Foundation of China (82130046, 82101747), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SSMU-ZLCX20180401), Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai Sailing Program (21YF1425000), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161413). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Exploration of beauvericin's toxic effects and mechanisms in human astrocytes and N-acetylcysteine's protective role.

Beauvericin (BEA) is a newly identified mycotoxin produced by various Fusarium species, and its contamination in food and animal feed is widespread globally. This mycotoxin demonstrates cytotoxic effects by inducing oxidative stress in multiple models. Furthermore, evidence indicates that BEA possesses diverse toxic activities, making it a promising candidate for toxicological research. Recent studies have highlighted the ability of BEA to traverse the blood-brain barrier, suggesting its potential neurotoxicity. However, limited information is available regarding the neurotoxic effects of BEA on human astrocytes. Therefore, this study aimed to assess the neurotoxic effects of BEA on the Gibco® Human Astrocyte (GHA) cell line and elucidate the underlying mechanisms. Additionally, the study aimed to investigate the protective effects of the antioxidant N-acetylcysteine (NAC) against BEA-induced toxicity. The data show that exposure to BEA within the 2.5-15 µM concentration range resulted in concentration-dependent cytotoxicity. BEA-treated cells exhibited significantly increased levels of reactive oxygen species (ROS), while intracellular glutathione (GSH) content was significantly reduced. Western blot analysis of cells treated with BEA revealed altered protein levels of Bax, cleaved caspase-9, and caspase-3, along with an increased Bax/Bcl-2 ratio, indicating the induction of apoptosis. Additionally, BEA exposure triggered antioxidant responses, as evidenced by increased protein expression of Nrf2, HO-1, and NQO1. Significantly, pretreatment with NAC partially attenuated the significant toxic effects of BEA. In conclusion, our findings suggest that BEA-induced cytotoxicity in GHA cells involves oxidative stress-associated apoptosis. Furthermore, NAC demonstrates potential as a protective agent against BEA-induced oxidative damage.

Time domain turbo equalization based on vector approximate message passing for multiple-input multiple-output underwater acoustic communications.

This paper proposes a high-performance receiver for underwater acoustic communications based on time reversal processing for multiple-input multiple-output (MIMO) systems. The receiver employs the vector approximate message passing (VAMP) algorithm as a soft equalizer in turbo equalization. By performing self-iteration between the inner soft slicer and the inner soft equalizer, the VAMP algorithm achieves near-optimal performance. Furthermore, an iterative channel-estimation-based soft successive interference cancellation method is incorporated to suppress co-channel interference in the MIMO system. Additionally, the introduction of passive time reversal technology can combine multiple channels into a single channel, which greatly reduces the computational complexity of the MIMO system, especially for large MIMO systems. The effectiveness of the proposed receiver is verified using experimental data collected in Songhua Lake, China in 2019. The results demonstrate that the proposed receiver significantly reduces the complexity of the traditional parallel-VAMP receiver without sacrificing performance and outperforms other receivers of the same type. Moreover, our experimental results also verify that the VAMP-turbo outperforms the generalized approximate message passing (GAMP)-turbo in terms of bit error rate and convergence performance.

Trajectory Deformation-Based Multi-Modal Adaptive Compliance Control for a Wearable Lower Limb Rehabilitation Robot.

Adaptive compliance control is critical for rehabilitation robots to cope with the varying rehabilitation needs and enhance training safety. This article presents a trajectory deformation-based multi-modal adaptive compliance control strategy (TD-MACCS) for a wearable lower limb rehabilitation robot (WLLRR), which includes a high-level trajectory planner and a low-level position controller. Dynamic motion primitives (DMPs) and a trajectory deformation algorithm (TDA) are integrated into the high-level trajectory planner, generating multi-joint synchronized desired trajectories through physical human-robot interaction (pHRI). In particular, the amplitude modulation factor of DMPs and the deformation factor of TDA are adapted by a multi-modal adaptive regulator, achieving smooth switching of human-dominant mode, robot-dominant mode, and soft-stop mode. Besides, a linear active disturbance rejection controller is designed as the low-level position controller. Four healthy participants and two stroke survivors are recruited to conduct robot-assisted walking experiments using the TD-MACCS. The results show that the TD-MACCS can smoothly switch three control modes while guaranteeing trajectory tracking accuracy. Moreover, we find that appropriately increasing the upper bound of the deformation factor can enhance the average walking speed (AWS) and root mean square of trajectory deviation (RMSTD).

Edge computing-based proactive control method for industrial product manufacturing quality prediction.

With the emergence of intelligent manufacturing, new-generation information technologies such as big data and artificial intelligence are rapidly integrating with the manufacturing industry. One of the primary applications is to assist manufacturing plants in predicting product quality. Traditional predictive models primarily focus on establishing high-precision classification or regression models, with less emphasis on imbalanced data. This is a specific but common scenario in practical industrial environments concerning quality prediction. A SMOTE-XGboost quality prediction active control method based on joint optimization hyperparameters is proposed to address the problem of imbalanced data classification in product quality prediction. In addition, edge computing technology is introduced to address issues in industrial manufacturing, such as the large bandwidth load and resource limitations associated with traditional cloud computing models. Finally, the practicality and effectiveness of the proposed method are validated through a case study of the brake disc production line. Experimental results indicate that the proposed method outperforms other classification methods in brake disc quality prediction.

Novel Pyrazole Acyl(thio)urea Derivatives Containing a Biphenyl Scaffold as Potential Succinate Dehydrogenase Inhibitors: Design, Synthesis, Fungicidal Activity, and SAR.

As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, a series of new pyrazole acyl(thio)urea compounds containing a diphenyl motif were designed and synthesized. Their structures were confirmed by 1H NMR, HRMS, and single X-ray crystal diffraction analysis. Most of these compounds possessed excellent activity against 10 fungal plant pathogens at 50 µg mL-1, especially against Rhizoctonia solani, Alternaria solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Cercospora arachidicola. Interestingly, compounds 3-(difluoromethyl)-1-methyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9b, EC50 = 0.97 ± 0.18 µg mL-1), 1,3-dimethyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9a, EC50 = 2.63 ± 0.41 µg mL-1), and N-((4'-chloro-[1,1'-biphenyl]-2-yl)carbamoyl)-1,3-dimethyl-1H-pyrazole-4-carboxamide (9g, EC50 = 1.31 ± 0.15 µg mL-1) exhibited activities against S. sclerotiorum that were better than the commercial fungicide bixafen (EC50 = 9.15 ± 0.05 µg mL-1) and similar to the positive control fluxapyroxad (EC50 = 0.71 ± 0.11 µg mL-1). These compounds were not significantly phytotoxic to monocotyledonous and dicotyledonous plants. Structure-activity relationships (SAR) are discussed by substituent effects/molecular docking, and density functional theory analysis indicated that these compounds are succinate dehydrogenase inhibitors.

CD4+TEM cells drive the progression from acute myocarditis to dilated cardiomyopathy in CVB3-induced BALB/c mice.

Acute viral myocarditis can progress to chronic myocarditis leading to dilated cardiomyopathy (DCM). Persistent CD4+ T-cell-mediated autoimmunity triggered by infection plays a critical role in this progression. Increasing evidence demonstrates that effector memory CD4+T (CD4+TEM) cells, a subset of memory CD4+ T cells, are crucial pathogenic mediators of many autoimmune diseases. However, the role of CD4+TEM cells during the progression from acute viral myocarditis to DCM remains unknown. In this study, we observed an increase in CD4+TEM cells both in the periphery and the heart, and memory CD4+ T cells were the predominant sources of IL-17A and IFN-γ among inflamed heart-infiltrating CD4+ T cells during the progression from acute myocarditis to chronic myocarditis and DCM in CVB3-induced BALB/c mice. Moreover, splenic CD4+TEM cells sorted from DCM mice induced by CVB3 were found to respond to cardiac self-antigens ex vivo. Additionally, adoptive transfer experiments substantiated their pathogenic impact, inducing sustained myocardial inflammation, tissue fibrosis, cardiac injury, and impairment of cardiac systolic function in vivo. Our findings illustrate that long-lived CD4+TEM cells are important contributors to the progression from acute viral myocarditis into DCM.

3'-Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma.

SCOPE: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. METHODS AND RESULTS: In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. CONCLUSION: This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients.

OBJECTIVES: The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. METHODS: A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. RESULTS: In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726-0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739-0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. CONCLUSIONS: The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.

Advances in the study of the effects of gut microflora on microglia in Alzheimer's disease.

Alzheimer's disease (AD) is a central nervous system (CNS) degenerative disorder, is caused by various factors including ß-amyloid toxicity, hyperphosphorylation of tau protein, oxidative stress, and others. The dysfunction of microglia has been associated with the onset and advancement of different neurodevelopmental and neurodegenerative disorders, such as AD. The gut of mammals harbors a vast and complex population of microorganisms, commonly referred to as the microbiota. There's a growing recognition that these gut microbes are intrinsically intertwined with mammalian physiology. Through the circulation of metabolites, they establish metabolic symbiosis, enhance immune function, and establish communication with different remote cells, including those in the brain. The gut microbiome plays a crucial part in influencing the development and performance of microglia, as indicated by recent preclinical studies. Dysbiosis of the intestinal flora leads to alterations in the microglia transcriptome that regulate the interconversion of microglia subtypes. This conversation explores recent research that clarifies how gut bacteria, their byproducts, and harmful elements affect the activation and characteristics of microglia. This understanding opens doors to innovative microbial-based therapeutic strategies for early identification and treatment goals in AD.

ELF5 drives angiogenesis suppression though stabilizing WDTC1 in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. Angiogenesis is a main contributing factor for tumorigenesis. E74-like transcription factor 5 (ELF5) has been verified to participate in the progression of different cancers and can regulate angiogenesis. This study was aimed to explore the functions of ELF5 in RCC. METHODS: Bioinformatics tools were used to predict the expression of ELF5 in RCC. RT-qPCR was applied for testing ELF5 expression in RCC cells. Cell behaviors were evaluated by colony formation, CCK-8, and transwell assays. The tube formation assay was used for determining angiogenesis. Methylation-specific PCR (MSP) was utilized for measuring the methylation level of ELF5 in RCC cells. ChIP and luciferase reporter assays were applied for assessing the binding of ELF5 and ubiquitin-specific protease 3 (USP3). Co-IP and GST pull-down were utilized for detecting the interaction of WD40 and tetratricopeptide repeats 1 (WDTC1) and USP3. Ubiquitination level of WDTC1 was determined by ubiquitination assay. RESULTS: ELF5 was lowly expressed in RCC cells and tissues. High expression of ELF5 expression notably suppressed RCC cell proliferative, migratory, and invasive capabilities, and inhibited angiogenesis. The tumor growth in mice was inhibited by ELF5 overexpression. ELF5 was highly methylated in RCC samples, and DNA methyltransferases (DNMTs) can promote hypermethylation level of ELF5 in RCC cells. ELF5 was further proved to transcriptionally activate USP3 in RCC. Moreover, USP3 inhibited WDTC1 ubiquitination. ELF5 can promote USP3-mediated WDTC1 stabilization. Additionally, WDTC1 silencing reversed the functions of ELF5 overexpression on RCC progression. CONCLUSION: Downregulation of ELF5 due to DNA hypermethylation inhibits RCC development though the USP3/WDTC1axis in RCC.

Deoxythymidylate kinase (DTYMK) participates in cell cycle arrest to promote pancreatic adenocarcinoma progression regulated by miR-491-5p through TP53 and is associated with tumor immune infiltration.

Background: This study aimed to understand the mechanism of action of deoxythymidylate kinase (DTYMK) and its effect on the prognosis of patients with pancreatic cancer. So as to provide better reference value for improving the clinical management of pancreatic cancer patients. Methods: First, The Cancer Genome Atlas (TCGA) database was employed to identify DTYMK as a differentially expressed gene and to further confirm its expression and its association with the prognosis of pancreatic adenocarcinoma (PAAD) patients. Furthermore, Cox Law of Return is used for multi factor analysis. By constructing a multi factor regression model, a nomogram is constructed according to the contribution of each influencing factor in the model to the outcome variables, The GeneMania and STRING databases served as the basis for investigating the protein-gene interaction network. Moreover, to understand the correlation between DTYMK and immune cells, the TIMER and TCGA databases were explored. Then, Gene Set Enrichment Analysis (GSEA) was performed to investigate potential mechanisms of action. TargetScan was used to identify the miRNAs binding to the 3'UTR of DTYMK mRNA, and starBase was used to verify a possible link between candidate miRNAs and DTYMK. In parallel, the expression of these potential miRNAs in PAAD and their correlation with prognosis was validated through the TCGA database. Results: PAAD patients were observed to have high overall survival (OS), progression free interval (PFI), and disease-specific survival (DSS) with reduced DTYMK expression. Data from the TIMER database show that DTYMK expression inversely correlated with the infiltration levels of most immune cells. GSEA results suggested that DTYMK has a role in cell senescence, DNA repair, pyrimidine metabolism, MYC activation, TP53 control of cell cycle arrest, apoptosis, and the MAPK6/MAPK4 pathway, all of which might influence the biological processes of PAAD. Conclusions: Reduced DTYMK expression may be considered a novel prognostic biomarker for PAAD patients, associated with improved OS, DSS, and PFI. Immune escape may play an important facilitative role. Moreover, we found that miR-491-5p may negatively regulate DTYMK and participate in cell cycle arrest through TP53 to promote pancreatic cancer progression.

A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

Involvement of oxidative stress-related apoptosis in chlorpyrifos-induced cytotoxicity and the ameliorating potential of the antioxidant vitamin E in human glioblastoma cells.

Organophosphate pesticides (OPs), which are among the most widely used synthetic chemicals for the control of a wide variety of pests, are however associated with various adverse reactions in animals and humans. Chlorpyrifos, an OP, has been shown to cause various health complications due to ingestion, inhalation, or skin absorption. The mechanisms underlying the adverse effect of chlorpyrifos on neurotoxicity have not been elucidated. Therefore, we aimed to determine the mechanism of chlorpyrifos-induced cytotoxicity and to examine whether the antioxidant vitamin E (VE) ameliorated these cytotoxic effects using DBTRG-05MG, a human glioblastoma cell line. The DBTRG-05MG cells were treated with chlorpyrifos, VE, or chlorpyrifos plus VE and compared with the untreated control cells. Chlorpyrifos induced a significant decrease in cell viability and caused morphological changes in treated cultures. Furthermore, chlorpyrifos led to the increased production of reactive oxygen species (ROS) accompanied by a decrease in the level of reduced glutathione. Additionally, chlorpyrifos induced apoptosis by upregulating the protein levels of Bax and cleaved caspase-9/caspase-3 and by downregulating the protein levels of Bcl-2. Moreover, chlorpyrifos modulated the antioxidant response by increasing the protein levels of Nrf2, HO-1, and NQO1. However, VE reversed the cytotoxicity and oxidative stress induced by chlorpyrifos treatment in DBTRG-05MG cells. Overall, these findings suggest that chlorpyrifos causes cytotoxicity through oxidative stress, a process that may play an important role in the development of chlorpyrifos-associated glioblastoma.

Novel mutations in PLCZ1 lead to early embryonic arrest as a male factor.

Early embryonic arrest is one of the causes of assist reproduction technology (ART) failure. We have previously reported that the first sperm-derived genetic factor, ACTL7a mutations, could lead to early embryonic arrest. However, whether there are other male genetic factors associated with early embryonic arrest remains elusive. Here, we reported bi-allelic mutations in PLCZ1, a well-known causal gene of total fertilization failure, in four infertile males. Among these mutations, p.403_404del, p.I489S, and p.W536X were newly reported in this study. Histological and Western blotting analysis of the patients' sperm indicated these variants as loss-of-function mutations. These patients manifested normal conventional semen parameters and ultra-structures in sperm heads. However, among four in vitro fertilization (IVF) cycles, 81.8% (18/22) of the oocytes were polyspermic fertilized, which was rarely reported in PLCZ1-related male patients. In the following six ICSI cycles, artificial oocyte activation (AOA) was applied and successfully rescued the fertilization failure and polyspermy phenotypes, with 31.3% (15/48) of the MII oocytes normally fertilized. However, 60.0% (9/15) of these normally fertilized zygotes were arrested at 2-5-cell stage, with one failing to cleave, indicating that PLCZ1 was not only necessary for fertilization, but also crucial for early embryonic development. However, these rescued zygotes showed a lower potential in developing into blastocysts when cultured in vitro. Thus, fresh cleavage transfer was tried and two live births were successfully achieved thereafter. In conclusion, this study provided novel mutations in PLCZ1 gene to expand the pathogenic mutational spectrum in male infertility and demonstrated that PLCZ1 was a crucial sperm-related genetic factor for early embryonic arrest. We also proposed that cleavage transfer after ICSI and AOA treatment could be a potential treatment method for male patients carrying bi-allelic mutations in PLCZ1.