Alterations of the microbiome across body sites in systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with unclear etiology. Growing evidence suggests the microbiome plays a role in SLE pathogenesis. However, findings are inconsistent across studies due to factors like small sample sizes and geographical variations. A comprehensive meta-analysis is needed to elucidate microbiome alterations in SLE. OBJECTIVE: This study aimed to provide a systematic overview of microbiota dysbiosis across body sites in SLE through a meta-analysis of alpha diversity indices, beta diversity indices, and abundance taxa of microbiome. METHODS: A literature search was conducted across four databases to identify relevant studies comparing SLE patients and healthy controls. Extracted data encompassed alpha and beta diversity metrics, as well as bacterial, fungal, and viral abundance across gut, oral, skin, and other microbiota. Study quality was assessed using the Newcastle-Ottawa Scale. Standardized mean differences and pooled effect sizes were calculated through meta-analytical methods. RESULTS: The analysis showed reduced alpha diversity and distinct beta diversity in SLE, particularly in the gut microbiota. Taxonomic analysis revealed compositional variations in bacteria from the gut and oral cavity. However, results for fungi, viruses, and bacteria from other sites were inconsistent due to limited studies. CONCLUSIONS: This meta-analysis offers a comprehensive perspective on microbiome dysbiosis in SLE patients across diverse body sites and taxa. The observed variations underscore the microbiome's potential role in SLE pathogenesis. Future research should address geographical variations, employ longitudinal designs, and integrate multi-omics approaches.

The correlation between single and mixed trace elements exposure in systemic lupus erythematosus: A case-control study.

BACKGROUND: Recent studies have shown an association between trace elements and systemic lupus erythematosus (SLE), but the relationship between trace elements and SLE is still unclear. This study aims to determine the distribution of plasma trace elements in newly diagnosed SLE patients and the association between these essential and toxic element mixtures and SLE. METHODS: In total, 110 SLE patients and 110 healthy controls were included. Blood samples were collected. 15 plasma trace elements were quantified using an inductively coupled plasma mass spectrometer (ICP-MS). Multivariate logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) are used to analyze the association between single and mixed exposure of elements and SLE. RESULTS: The logistic regression model shows that, plasma lithium (Li) [OR (95 % CI): 1.963 (1.49-2.586)], vanadium (V) [OR (95 % CI): 2.617(1.645-4.166)] and lead (Pb) [OR (95 % CI): 1.603(1.197-2.145)] were positively correlated with SLE, while selenium (Se) [OR (95 % CI): 0.055(0.019-0.157)] and barium (Ba) [OR (95 % CI): 0.792(0.656-0.957)] had been identified as protective factors for SLE. RCS results showed a non-linear correlation between the elements Li, V, Ni, copper, Se, rubidium and SLE. In addition, WQS regression, qgcomp, and BKMR models consistently revealed significant positive effects of plasma Li and Pb on SLE, as well as significant negative effects of plasma Se. CONCLUSIONS: Exposure to heavy metals such as Li and Pb is significantly positively correlated with SLE, but Se may be protective factors for SLE. In addition, there is a nonlinear correlation between the elements Li and Se and SLE, and there are complex interactions between the elements. In the future, larger populations and prospective studies are needed to confirm these associations.

Delivery of SiRNA-PD-L1 by attenuated Salmonella in combination with oxaliplatin in a hepatocellular carcinoma mouse model.

Oxaliplatin is currently used for chemotherapy in patients with hepatocellular carcinoma, but its increasing tolerance to tumours over time limits its clinical application. Studies have shown that high PD-L1 expression promotes the polarization of M2 macrophages. The increased infiltration of M2 macrophages, including those in HCC, is positively correlated with poor prognosis in various solid tumours. We found that oxaliplatin promoted the expression of PD-L1 in liver cancer cells, which might be attributed partly to the tolerance of tumours to oxaliplatin. Therefore, in this study, we explored the antitumour effect of attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin via Western blotting, immunohistochemistry, immunofluorescence, and flow cytometry. The results revealed that attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin more significantly inhibited tumour growth in tumour-bearing mice, suppressed the expression of PD-L1 in tumour tissue, increased the apoptosis of tumour cells and the expression of the tumour-related protein cleaved-caspase3, and increased the infiltration of M1 macrophages and T lymphocytes in tumour tissues. Moreover, the combination therapy increased the activation of T cells and the number of T lymphocytes and NK cells in the spleens of the mice and improved the overall antitumour immune response in the mice. Our results confirmed that attenuated Salmonella harbouring siRNA-PD-L1 combined with oxaliplatin had a significant antitumour effect and did not increase the incidence of toxic side effects, providing a theoretical reference for addressing oxaliplatin tolerance in the treatment of hepatocellular carcinoma.

Prevalence and influencing factors of sleep disorders in medical students after the COVID-19 pandemic.

BACKGROUND: The prevalence of sleep disorders among medical students was high during the COVID-19 pandemic. However, fewer studies have been conducted on sleep disorders among medical students after the COVID-19 pandemic. This study investigated the prevalence and factors influencing sleep disorders among Chinese medical students after COVID-19. METHODS: A total of 1,194 Chinese medical students were included in this study from 9th to 12th July 2023. We used the Self-administered Chinese scale to collect the demographic characteristics. In addition, we used the Chinese versions of the Self-rating Depression Scale (SDS), the Self-rating Anxiety Scale (SAS), and the Pittsburgh Sleep Quality Index (PSQI) to assess subjects' depression, anxiety, and sleep disorders, respectively. The chi-square test and binary logistic regression were used to identify factors influencing sleep disorders. The receiver operating characteristic (ROC) curve was utilized to assess the predictive value of relevant variables for sleep disorders. RESULTS: We found the prevalence of sleep disorders among medical students after COVID-19 was 82.3%. According to logistic regression results, medical students with depression were 1.151 times more likely to have sleep disorders than those without depression (OR = 1.151, 95% CI 1.114 to 1.188). Doctoral students were 1.908 times more likely to have sleep disorders than graduate and undergraduate students (OR = 1.908, 95% CI 1.264 to 2.880). CONCLUSION: The prevalence of sleep disorders among medical students is high after COVID-19. In addition, high academic levels and depression are risk factors for sleep disorders. Therefore, medical colleges and administrators should pay more attention to sleep disorders in medical students after the COVID-19 pandemic. Regular assessment of sleep disorders and depression is essential.

Tubulin participates in establishing protoxylem vessel reinforcement patterns and hydraulic conductivity in maize.

Water transportation to developing tissues relies on the structure and function of plant xylem cells. Plant microtubules govern the direction of cellulose microfibrils and guide secondary cell wall formation and morphogenesis. However, the relevance of microtubule-determined xylem wall thickening patterns in plant hydraulic conductivity remains unclear. In the present study, we identified a maize (Zea mays) semi-dominant mutant, designated drought-overly-sensitive1 (ZmDos1), the upper leaves of which wilted even when exposed to well-watered conditions during growth; the wilting phenotype was aggravated by increased temperatures and decreased humidity. Protoxylem vessels in the stem and leaves of the mutant showed altered thickening patterns of the secondary cell wall (from annular to spiral), decreased inner diameters, and limited water transport efficiency. The causal mutation for this phenotype was found to be a G-to-A mutation in the maize gene α-tubulin4, resulting in a single amino acid substitution at position 196 (E196K). Ectopic expression of the mutant α-tubulin4 in Arabidopsis (Arabidopsis thaliana) changed the orientation of microtubule arrays, suggesting a determinant role of this gene in microtubule assembly and secondary cell wall thickening. Our findings suggest that the spiral wall thickenings triggered by the α-tubulin mutation are stretched during organ elongation, causing a smaller inner diameter of the protoxylem vessels and affecting water transport in maize. This study underscores the importance of tubulin-mediated protoxylem wall thickening in regulating plant hydraulics, improves our understanding of the relationships between protoxylem structural features and functions, and offers candidate genes for the genetic enhancement of maize.

Environmental triggers of autoimmunity: The association between bisphenol analogues and systemic lupus erythematosus.

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development.

Function analysis of transcription factor OSR1 regulating osmotic stress resistance in maize.

BACKGROUND: Maize is a major cereal crop world widely, however, the yield of maize is frequently limited by dehydration and even death of plants, which resulted from osmotic stress such as drought and salinity. Dissection of molecular mechanisms controlling stress tolerance will enable plant scientists and breeders to increase crops yield by manipulating key regulatory components. METHODS: The candidate OSR1 gene was identified by map-based cloning. The expression level of OSR1 was verified by qRT-PCR and digital PCR in WT and osr1 mutant. Electrophoretic mobility shift assay, transactivation activity assay, subcellular localization, transcriptome analysis and physiological characters measurements were conducted to analyze the function of OSR1 in osmotic stress resistance in maize. RESULTS: The osr1 mutant was significantly less sensitive to osmotic stress than the WT plants and displayed stronger water-holding capacity, and the OSR1 homologous mutant in Arabidopsis showed a phenotype similar with maize osr1 mutant. Differentially expressed genes (DEGs) were identified between WT and osr1 under osmotic stress by transcriptome analysis, the expression levels of many genes, such as LEA, auxin-related factors, PPR family members, and TPR family members, changed notably, which may primarily involve in osmotic stress or promote root development. CONCLUSIONS: OSR1 may serve as a negative regulatory factor in response to osmotic stress in maize. The present study sheds new light on the molecular mechanisms of osmotic stress in maize.

No causal association between pneumoconiosis and three inflammatory immune diseases: a Mendelian randomization study.

Objectives: To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout. Methods: The random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs). Results: There was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20]. Conclusion: Our study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.

Modified artificial neural network based on developed snake optimization algorithm for short-term price prediction.

Short-term prices prediction is a crucial task for participants in the electricity market, as it enables them to optimize their bidding strategies and mitigate risks. However, the price signal is subject to various factors, including supply, demand, weather conditions, and renewable energy sources, resulting in high volatility and nonlinearity. In this study, a novel approach is introduced that combines Artificial Neural Networks (ANN) with a newly developed Snake Optimization Algorithm (SOA) to forecast short-term price signals in the Nord Pool market. The snake optimization algorithm is utilized to optimize both the structure and weights of the neural network, as well as to select relevant input data based on the similarity of price curves and wind production. To evaluate the effectiveness of the proposed technique, experiments have been conducted using data from two regions of the Nord Pool market, namely DK-1 and SE-1, across different seasons and time horizons. The results demonstrate that the proposed technique surpasses two alternative methods based on Particle Swarm Optimization (PSO) and Genetic Algorithms-based Neural Network (PSOGANN) and Gravitational Search Optimization Algorithm-based Neural Network (GSONN), exhibiting superior accuracy and minimal error rates in short-term price prediction. The results show that the average MAPE index of the proposed technique for the DK-1 region is 3.1292%, which is 32.5% lower than the PSOGA method and 47.1% lower than the GSONN method. For the SE-1 region, the average MAPE index of the proposed technique is 2.7621%, which is 40.4% lower than the PSOGA method and 64.7% lower than the GSONN method. Consequently, the proposed technique holds significant potential as a valuable tool for market participants to enhance their decision-making and planning activities.

Perturbations in gut and respiratory microbiota in COVID-19 and influenza patients: a systematic review and meta-analysis.

Objectives: Coronavirus disease-19 (COVID-19)/influenza poses unprecedented challenges to the global economy and healthcare services. Numerous studies have described alterations in the microbiome of COVID-19/influenza patients, but further investigation is needed to understand the relationship between the microbiome and these diseases. Herein, through systematic comparison between COVID-19 patients, long COVID-19 patients, influenza patients, no COVID-19/influenza controls and no COVID-19/influenza patients, we conducted a comprehensive review to describe the microbial change of respiratory tract/digestive tract in COVID-19/influenza patients. Methods: We systematically reviewed relevant literature by searching the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2023. We conducted a comprehensive review to explore microbial alterations in patients with COVID-19/influenza. In addition, the data on α-diversity were summarized and analyzed by meta-analysis. Results: A total of 134 studies comparing COVID-19 patients with controls and 18 studies comparing influenza patients with controls were included. The Shannon indices of the gut and respiratory tract microbiome were slightly decreased in COVID-19/influenza patients compared to no COVID-19/influenza controls. Meanwhile, COVID-19 patients with more severe symptoms also exhibited a lower Shannon index versus COVID-19 patients with milder symptoms. The intestinal microbiome of COVID-19 patients was characterized by elevated opportunistic pathogens along with reduced short-chain fatty acid (SCFAs)-producing microbiota. Moreover, Enterobacteriaceae (including Escherichia and Enterococcus) and Lactococcus, were enriched in the gut and respiratory tract of COVID-19 patients. Conversely, Haemophilus and Neisseria showed reduced abundance in the respiratory tract of both COVID-19 and influenza patients. Conclusion: In this systematic review, we identified the microbiome in COVID-19/influenza patients in comparison with controls. The microbial changes in influenza and COVID-19 are partly similar.

Trade-offs between the accumulation of cuticular wax and jasmonic acid-mediated herbivory resistance in maize.

Plants have evolved complex physical and chemical defense systems that allow them to withstand herbivory infestation. Composed of a complex mixture of very-long-chain fatty acids (VLCFAs) and their derivatives, cuticular wax constitutes the first physical line of defense against herbivores. Here, we report the function of Glossy 8 (ZmGL8), which encodes a 3-ketoacyl reductase belonging to the fatty acid elongase complex, in orchestrating wax production and jasmonic acid (JA)-mediated defenses against herbivores in maize (Zea mays). The mutation of GL8 enhanced chemical defenses by activating the JA-dependent pathway. We observed a trade-off between wax accumulation and JA levels across maize glossy mutants and 24 globally collected maize inbred lines. In addition, we demonstrated that mutants defective in cuticular wax biosynthesis in Arabidopsis thaliana and maize exhibit enhanced chemical defenses. Comprehensive transcriptomic and lipidomic analyses indicated that the gl8 mutant confers chemical resistance to herbivores by remodeling VLCFA-related lipid metabolism and subsequent JA biosynthesis and signaling. These results suggest that VLCFA-related lipid metabolism has a critical role in regulating the trade-offs between cuticular wax and JA-mediated chemical defenses.

Plasmid co-expressing siRNA-PD-1 and Endostatin carried by attenuated Salmonella enhanced the anti-melanoma effect via inhibiting the expression of PD-1 and VEGF on tumor-bearing mice.

Melanoma, the most perilous form of skin cancer, is known for its inherent resistance to chemotherapy. Even with advances in tumor immunotherapy, the survival of patients with advanced or recurrent melanomas remains poor. Over time, melanoma tumor cells may produce excessive angiogenic factors, necessitating the use of combinations of angiogenesis inhibitors, including broad-spectrum options, to combat melanoma. Among these inhibitors, Endostatin is one of the most broad-spectrum and least toxic angiogenesis inhibitors. We found Endostatin significantly increased the infiltration of CD8+ T cells and reduced the infiltration of M2 tumor-associated macrophages (TAMs) in the melanoma tumor microenvironment (TME). Interestingly, we also observed high expression levels of programmed death 1 (PD-1), an essential immune checkpoint molecule associated with tumor immune evasion, within the melanoma tumor microenvironment despite the use of Endostatin. To address this issue, we investigated the effects of a plasmid expressing Endostatin and PD-1 siRNA, wherein Endostatin was overexpressed while RNA interference (RNAi) targeted PD-1. These therapeutic agents were delivered using attenuated Salmonella in melanoma-bearing mice. Our results demonstrate that pEndostatin-siRNA-PD-1 therapy exhibits optimal therapeutic efficacy against melanoma. We found that pEndostatin-siRNA-PD-1 therapy promotes the infiltration of CD8+ T cells and the expression of granzyme B in melanoma tumors. Importantly, combined inhibition of angiogenesis and PD-1 significantly suppresses melanoma tumor progression compared with the inhibition of angiogenesis or PD-1 alone. Based on these findings, our study suggests that combining PD-1 inhibition with angiogenesis inhibitors holds promise as a clinical strategy for the treatment of melanoma.

Effect and prediction of physical exercise and diet on blood pressure control in patients with hypertension.

The study aims to explore the current status of hypertension control and its predictors in patients with hypertension in China and provide evidence for preventing and controlling hypertension. A questionnaire survey was conducted among 300 hypertensive patients who visited the Second Affiliated Hospital of Anhui Medical University from February 20, 2023 to March 11, 2023. The patients were divided into a well-controlled group and an untargeted-control group according to their hypertension control status. A total of 294 subjects, including 83 in the well-controlled group and 211 in the untargeted-control group, were included in the analysis. Multivariate logistic regression analysis showed that hypertensive patients with high BMI and family history of hypertension were risk factors for hypertension control. Married status was a protective factor for hypertension control. SVM optimized the model with γ = 0.001 and a penalty factor of C = 0.001. The prediction accuracy of the final model was 80.9%. The findings indicated that BMI, family history of hypertension, and marital status were independent predictors of blood pressure control. Further studies are warranted to illustrate potential mechanisms for improving hypertensive patients' blood pressure control.

[Study of perioperative safety of laparoscopic pancreaticoduodenectomy in elderly patients].

OBJECTIVE: To investigate the safety of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients and the related risk factors admitted to the intensive care unit (ICU) after LPD. METHODS: The perioperative data of patients who underwent LPD in Tianjin Medical University General Hospital from February 2017 to June 2023 were retrospectively collected, including basic data, preoperative laboratory indicators, intraoperative and postoperative indicators, pathological results (tumor size, lymph node dissection and pathological type), postoperative complications, ICU postoperative management and prognosis. The patients were divided into the elderly group (≥ 65 years) and the non-elderly group (< 65 years) according to age. Perioperative data between two groups were compared. Kaplan-Meier survival curve was drawn to analyze the survival rate of the elderly group and the non-elderly group, and the pancreatic head carcinoma group and other type of tumors group after LPD. Logistic regression was used to analyze the risk factors of ICU stay (length of ICU stay > 1 day) after LPD in elderly patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of this risk factor for ICU stay after LPD in elderly patients. RESULTS: A total of 160 patients were enrolled, including 57 cases in the elderly group (17 cases of vascular reconstruction) and 103 cases in the non-elderly group (40 cases of vascular reconstruction). All patients underwent R0 resection and were transferred to the comprehensive ICU for treatment. The follow-up time of patients with malignant tumors was 43 (6, 72) months. The elderly group had significantly longer surgery time, postoperative hospital stay and oral feeding time than the non-elderly group, and the incidence of delayed gastric emptying (DGE) was significantly higher than that in the non-elderly group. There were no significant differences in intraoperative blood transfusion rate, intraoperative blood loss, pathological results, short-term and severe postoperative complications, reoperation rate and 90-day mortality between the two groups. In patients with vascular resection reconstruction, the intraoperative blood loss in the elderly group was significantly higher than that in the non-elderly group, and the operation time and postoperative hospital stay were significantly longer. During ICU, the acute physiology and chronic health evaluation II [APACHE II: 12 (9, 14) vs. 8 (7, 10)], sequential organ failure assessment [SOFA: 6 (4, 8) vs. 3 (2, 5)] within 24 hours after admission to ICU were significantly increased in the elderly group (both P < 0.05), the time of mechanical ventilation [hours: 12 (10, 15) vs. 9 (5, 13)] and the length of ICU stay [days: 2 (1, 2) vs. 1 (1, 1)] were significantly increased in the elderly group (both P < 0.05), and the proportion of multi-disciplinary team (MDT) was also significantly increased in the elderly group (33.3% vs. 17.4%, P < 0.05), there were no significant differences in the levels of hemoglobin (Hb), albumin, and blood lactic acid between the two groups. Logistic regression analysis showed that the APACHE II score was an independent risk factor for ICU stay after LPD in elderly patients (ß = 1.737, P = 0.028). ROC curve showed that the prediction performance was the best when the APACHE II score was 13, with the sensitivity of 72.41% and the specificity of 96.43%, and the area under the ROC curve (AUC) of 0.884. The Kaplan-Meier survival curve showed that there were no significant difference in median survival time (months: 24.1 vs. 24.7) and 5-year survival rate (19.01% vs. 19.02%) between the elderly group (52 cases) and the non-elderly group (92 cases) among the 144 patients with malignant tumors (both P > 0.05). The median survival time in the pancreatic head carcinoma group was significantly shorter than that in the other tumors group (63 cases; months: 20.2 vs. 40.1, P < 0.05), 5-year survival rate was significantly lower than that in the other tumors group (21.98% vs. 30.91%, P < 0.05). CONCLUSIONS: LPD is a safe and feasible treatment for elderly patients. APACHE II score has a certain predictive value for ICU stay after LPD in elderly patients.

Attenuated Salmonella carrying siRNA-CD24 improved the effect of oxaliplatin on HCC.

Oxaliplatin is a chemotherapy drug currently utilized in the treatment of advanced cancer patients. However, its tolerability poses a limitation to its clinical application. Studies have demonstrated that the presence of tumor-associated macrophages is positively correlated with poor prognosis in various solid tumors, including hepatocellular carcinoma (HCC), and is a significant factor contributing to oxaliplatin resistance. Therefore, targeting tumor-associated macrophages may be an effective strategy to improve the efficacy of oxaliplatin in the treatment of HCC patients. CD24 is a novel target for tumor therapy that can interact with the inhibitory receptor Siglec-10 on tumor-associated macrophages, transmitting immune inhibitory signals and inhibiting macrophage phagocytosis function. In this study, we utilized RNAi technology to inhibit the expression of CD24 in tumor cells and combined it with oxaliplatin, resulting in reduced tumor invasion, migration, and proliferation, as well as increased cell apoptosis. Furthermore, immunofluorescence and flow cytometry results indicated that both the single treatment group and combination treatment group enhanced the infiltration of immune cells. This study presents a novel approach to identifying combination therapy and targets for the clinical treatment of HCC with oxaliplatin.

LWSleepNet: A lightweight attention-based deep learning model for sleep staging with singlechannel EEG.

Introduction: Sleep is vital to human health, and sleep staging is an essential process in sleep assessment. However, manual classification is an inefficient task. Along with the increased demand for portable sleep quality detection devices, lightweight automatic sleep staging needs to be developed. Methods: This study proposes a novel attention-based lightweight deep learning model called LWSleepNet. A depthwise separable multi-resolution convolutional neural network is introduced to analyze the input feature map and captures features at multiple frequencies using two different sized convolutional kernels. The temporal feature extraction module divides the input into patches and feeds them into a multi-head attention block to extract time-dependent information from sleep recordings. The model's convolution operations are replaced with depthwise separable convolutions to minimize its number of parameters and computational cost. The model's performance on two public datasets (Sleep-EDF-20 and Sleep-EDF-78) was evaluated and compared with those of previous studies. Then, an ablation study and sensitivity analysis were performed to evaluate further each module. Results: LWSleepNet achieves an accuracy of 86.6% and Macro-F1 score of 79.2% for the Sleep-EDF-20 dataset and an accuracy of 81.5% and Macro-F1 score of 74.3% for the Sleep-EDF-78 dataset with only 55.3 million floating-point operations per second and 180 K parameters. Conclusion: On two public datasets, LWSleepNet maintains excellent prediction performance while substantially reducing the number of parameters, demonstrating that our proposed Light multiresolution convolutional neural network and temporal feature extraction modules can provide excellent portability and accuracy and can be easily integrated into portable sleep monitoring devices.

A maize epimerase modulates cell wall synthesis and glycosylation during stomatal morphogenesis.

The unique dumbbell-shape of grass guard cells (GCs) is controlled by their cell walls which enable their rapid responses to the environment. The molecular mechanisms regulating the synthesis and assembly of GC walls are as yet unknown. Here we have identified BZU3, a maize gene encoding UDP-glucose 4-epimerase that regulates the supply of UDP-glucose during GC wall synthesis. The BZU3 mutation leads to significant decreases in cellular UDP-glucose levels. Immunofluorescence intensities reporting levels of cellulose and mixed-linkage glucans are reduced in the GCs, resulting in impaired local wall thickening. BZU3 also catalyzes the epimerization of UDP-N-acetylgalactosamine to UDP-N-acetylglucosamine, and the BZU3 mutation affects N-glycosylation of proteins that may be involved in cell wall synthesis and signaling. Our results suggest that the spatiotemporal modulation of BZU3 plays a dual role in controlling cell wall synthesis and glycosylation via controlling UDP-glucose/N-acetylglucosamine homeostasis during stomatal morphogenesis. These findings provide insights into the mechanisms controlling formation of the unique morphology of grass stomata.

Endocrine-disrupting chemicals and autoimmune diseases.

Endocrine-disrupting chemicals (EDCs) widely exist in people's production and life which have great potential to damage human and animal health. Over the past few decades, growing attention has been paid to the impact of EDCs on human health, as well as immune system. So far, researchers have proved that EDCs (such as bisphenol A (BPA), phthalate, tetrachlorodibenzodioxin (TCDD), etc.) affect human immune function and promotes the occurrence and development of autoimmune diseases (ADs). Therefore, in order to better understand how EDCs affect ADs, we summarized the current knowledge about the impact of EDCs on ADs, and elaborated the potential mechanism of the impact of EDCs on ADs in this review.

miR-210 promotes hepatocellular carcinoma progression by modulating macrophage autophagy through PI3K/AKT/mTOR signaling.

BACKGROUND: Tumor-associated macrophages (TAMs) play an important role in tumor development. Increasing research suggests that miR-210 may promote the progression of tumor virulence, but whether its pro-carcinogenic effect in primary hepatocellular carcinoma (HCC) is via an action on M2 macrophages has not been examined. METHODS: Differentiation of THP-1 monocytes into M2-polarized macrophages was induced with phorbol myristate acetate (PMA) and IL-4, IL-13. M2 macrophages were transfected with miR-210 mimics or miR-210 inhibitors. Flow cytometry was used to identify macrophage-related markers and apoptosis levels. The autophagy level of M2 macrophages, expression of PI3K/AKT/mTOR signaling pathway-related mRNAs and protein were detected by qRT-PCR and Western blot. HepG2 and MHCC-97H HCC cell lines were cultured with M2 macrophages conditioned medium to explore the effects of M2 macrophage-derived miR-210 on the proliferation, migration, invasion and apoptosis of HCC cells. RESULTS: qRT-PCR showed increased expression of miR-210 in M2 macrophages. Autophagy-related gene and protein expression was enhanced in M2 macrophages transfected with miR-210 mimics, while apoptosis-related proteins were decreased. MDC staining and transmission electron microscopy observed the accumulation of MDC-labeled vesicles and autophagosomes in M2 macrophages in the miR-210 mimic group. The expression of PI3K/AKT/mTOR signaling pathway in M2 macrophages was reduced in miR-210 mimic group. HCC cells co-cultured with M2 macrophages transfected with miR-210 mimics exhibited enhanced proliferation and invasive ability as compared to the control group, while apoptosis levels were reduced. Moreover, promoting or inhibiting autophagy could enhance or abolish the above observed biological effects, respectively. CONCLUSIONS: miR-210 can promote autophagy of M2 macrophages via PI3K/AKT/mTOR signaling pathway. M2 macrophage-derived miR-210 promotes the malignant progression of HCC via autophagy, suggesting that macrophage autophagy may serve as a new therapeutic target for HCC, and targeting miR-210 may reset the effect of M2 macrophages on HCC.

Suicide and suicidality in people exposed to pesticides: A systematic review and meta-analysis.

Exposure to pesticides has been proposed to be a positive association in suicide and suicidality. Many studies have explored this topic, but have reported inconsistent findings. We carried out a systematic review and meta-analysis of the now existing evidence on the association between pesticide exposure and the risk of suicide and suicidality. We searched PubMed, EMBASE and Web of Science databases for studies published up to February 1, 2023. For studies that provided detailed data, we applied quantitative meta-analysis to calculate Odds ratio (OR) with 95% Confidence Intervals (CIs) to evaluate the results. Heterogeneity among the included studies was assessed using Cochran's Q test, I2 statistic and tau-squared (τ2). Publication bias was evaluated by funnel plots, Egger's test, and Begg's test. In addition, subgroup analyses according to pesticides category and geographical area were performed. 2906 studies were initially identified, and 20 studies were eventually included. Fifteen of the studies were on suicide deaths and suicide attempts, and five were on suicidal ideation. Pesticide exposure was positively related to suicide deaths and suicide attempts (pooled OR = 1.31; 95%CI: 1.04-1.64, p < 0.001) and suicidal ideation (pooled OR = 2.43; 95%CI: 1.51-3.91, p = 0.015). In the subgroup analysis, mixed pesticide type (pooled OR = 1.55; 95%CI: 1.39-1.74) increased the risk of suicide deaths and suicide attempts. The results of the analysis by geographic area showed that the risk of suicide deaths and suicide attempts with pesticide exposure was 2.27 (95%CI = 1.36-3.78), and 1.33 (95%CI = 1.14-1.56) in Asia and Europe, respectively. The risk of suicidal ideation caused by pesticide exposure in Asia and America were 2.19 (95%CI = 1.08-4.42) and 2.99 (95%CI = 1.76-5.06). In conclusion, pesticide exposure may increase the risk of suicide and suicidality based on the current evidence.