Arf6 GTPase deficiency leads to porcine oocyte quality decline during aging.

Arf6 is a member of ADP-ribosylation factor (Arf) family, which is widely implicated in the regulation of multiple physiological processes including endocytic recycling, cytoskeletal organization, and membrane trafficking during mitosis. In this study, we investigated the potential relationship between Arf6 and aging-related oocyte quality, and its roles on organelle rearrangement and cytoskeleton dynamics in porcine oocytes. Arf6 expressed in porcine oocytes throughout meiotic maturation, and it decreased in aged oocytes. Disruption of Arf6 led to the failure of cumulus expansion and polar body extrusion. Further analysis indicated that Arf6 modulated ac-tubulin for meiotic spindle organization and microtubule stability. Besides, Arf6 regulated cofilin phosphorylation and fascin for actin assembly, which further affected spindle migration, indicating the roles of Arf6 on cytoskeleton dynamics. Moreover, the lack of Arf6 activity caused the dysfunction of Golgi and ER for protein synthesis and signal transduction. Mitochondrial dysfunction was also observed in Arf6-deficient porcine oocytes, which was supported by the increased ROS level and abnormal membrane potential. In conclusion, our results reported that insufficient Arf6 was related to aging-induced oocyte quality decline through spindle organization, actin assembly, and organelle rearrangement in porcine oocytes.

NAMPT regulates mitochondria function and lipid metabolism during porcine oocyte maturation.

Oocyte maturation defect can lead to maternal reproduction disorder. NAMPT is a rate-limiting enzyme in mammalian NAD+ biosynthesis pathway, which can regulate a variety of cellular metabolic processes including glucose metabolism and DNA damage repair. However, the function of NAMPT in porcine oocytes remains unknown. In this study, we showed that NAMPT involved into multiple cellular events during oocyte maturation. NAMPT expressed during all stages of porcine oocyte meiosis, and inhibition of NAMPT activity caused the cumulus expansion and polar body extrusion defects. Mitochondrial dysfunction was observed in NAMPT-deficient porcine oocytes, which showed decreased membrane potential, ATP and mitochondrial DNA content, increased oxidative stress level and apoptosis. We also found that NAMPT was essential for spindle organization and chromosome arrangement based on Ac-tubulin. Moreover, lack of NAMPT activity caused the increase of lipid droplet and affected the imbalance of lipogenesis and lipolysis. In conclusion, our study indicated that lack of NAMPT activity affected porcine oocyte maturation through its effects on mitochondria function, spindle assembly and lipid metabolism.

Benzo[a]pyrene exposure disrupts the organelle distribution and function of mouse oocytes.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.

Dietary Effects on Chronic Venous Disease.

BACKGROUND: Diet is fundamental to maintaining and improving human health. There is ample evidence identifying the beneficial and/or harmful effects of diet on noncommunicable diseases such as obesity, diabetes mellitus, and cardiovascular disease. However, the associations of the diet to chronic venous disease has not been fully described. METHODS: Data were collected through a cross-sectional survey conducted on 1,571 community-dwelling adults in 2018. Diet intake frequency was assessed using valid food group consumption frequency questionnaires. Multivariable logistic regression models were used to evaluate the association of diet with chronic venous disease. RESULTS: In total, 857 participants were diagnosed with chronic venous disease. Those who ate soybean products daily and 4-6 days/week had a 51-31% lower risk of chronic venous disease compared with those who only occasionally consumed soybean food, respectively. Participants who consumed eggs and egg products 1-3 days/week versus those who only occasionally ate eggs showed a lower risk of chronic venous disease [odds ratio (OR) 0.542, 95% confidence interval (CI) 0.375-0.782]. Eating fried food 4-6 days each week was associated with an increased risk of chronic venous disease (OR 3.872, 95% CI 1.263-11.599) compared with those who only occasionally ate fried foods. There is a decreasing tendency of the adjusted OR for eating soybean products daily with the severity of disease [chronic venous disease (C0-C2): OR 0.575, 95% CI 0.408-0.812; chronic venous insufficiency (C3-C6): OR 0.222, 95% CI 0.114-0.435]. CONCLUSIONS: A higher frequency in the consumption of soybean products and eggs were associated with a lower risk of chronic venous disease. High level of fried food consumption was positively associated with risk of chronic venous disease. There are certain specific trends in relation to dietary consumption and severity of disease, although these trends were less strong. These associations are largely independent of other dietary and nondietary factors.

SIRT3 Regulates Levels of Deacetylated SOD2 to Prevent Oxidative Stress and Mitochondrial Dysfunction During Oocyte Maturation in Pigs.

Mammalian oocyte maturation relies on mitochondrial ATP production, but this can lead to damaging reactive oxygen species (ROS). SIRT3, a mitochondrial sirtuin, plays a critical role in regulating mitochondrial redox balance in mouse oocytes under stress; however, its specific roles in porcine oocytes remain unclear. In this study, we utilized the SIRT3 inhibitor 3-TYP to investigate SIRT3's importance in porcine oocyte maturation. Our findings revealed that SIRT3 is expressed in porcine oocytes and its inhibition leads to maturation failure. This was evident through reduced polar body extrusion, arrested cell cycle, as well as disrupted spindle organization and actin distribution. Furthermore, SIRT3 inhibition resulted in a decrease in mitochondrial DNA copy numbers, disruption of mitochondrial membrane potential, and reduced ATP levels, all indicating impaired mitochondrial function in porcine oocytes. Additionally, the primary source of damaged mitochondria was associated with decreased levels of deacetylated superoxide dismutase 2 (SOD2) after SIRT3 inhibition, which led to ROS accumulation and oxidative stress-induced apoptosis. Taken together, our results suggest that SIRT3 regulates the levels of deacetylated SOD2 to maintain redox balance and preserve mitochondrial function during porcine oocyte maturation, with potential implications for improving pig reproduction.

A novel strategy of gene screen based on multi-omics in Streptomyces roseosporus.

Daptomycin is a new lipopeptide antibiotic for treatment of severe infection caused by multi-drug-resistant bacteria, but its production cost remains high currently. Thus, it is very important to improve the fermentation ability of the daptomycin producer Streptomyces roseosporus. Here, we found that the deletion of proteasome in S. roseosporus would result in the loss of ability to produce daptomycin. Therefore, transcriptome and 4D label-free proteome analyses of the proteasome mutant (Δprc) and wild type were carried out, showing 457 differential genes. Further, five genes were screened by integrated crotonylation omics analysis. Among them, two genes (orf04750/orf05959) could significantly promote the daptomycin synthesis by overexpression, and the fermentation yield in shake flask increased by 54% and 76.7%, respectively. By enhancing the crotonylation modification via lysine site mutation (K-Q), the daptomycin production in shake flask was finally increased by 98.8% and 206.3%, respectively. This result proved that the crotonylation modification of appropriate proteins could effectively modulate daptomycin biosynthesis. In summary, we established a novel strategy of gene screen for antibiotic biosynthesis process, which is more convenient than the previous screening method based on pathway-specific regulators. KEY POINTS: • Δprc strain has lost the ability of daptomycin production • Five genes were screened by multi-omics analysis • Two genes (orf04750/orf05959) could promote the daptomycin synthesis by overexpression.

Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic loci in orthotopic neuroblastoma model.

BACKGROUND: Majority of neuroblastoma patients develop metastatic disease at diagnosis and their prognosis is poor with current therapeutic approach. Major challenges are how to tackle the mechanisms responsible for tumorigenesis and metastasis. Human mesenchymal stem cells (hMSCs) may be actively involved in the constitution of cancer microenvironment. METHODS: An orthotopic neuroblastoma murine model was utilized to mimic the clinical scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without hMSCs into the adrenal area of SCID-beige mice. The growth and metastasis of neuroblastoma was observed by using Xenogen IVIS 100 in vivo imaging and evaluating gross tumors ex vivo. The homing of hMSCs towards tumor was analyzed by tracing fluorescence signal tagged on hMSCs using CRI Maestro™ imaging system. RESULTS: hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and apparently enhanced metastasis of neuroblastoma in vivo. hMSCs could be recruited by primary tumor and also become part of the tumor microenvironment in the metastatic lesion. The metastatic potential was consistently reduced in lung and tumor when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was one of the prime movers in the metastatic process. CONCLUSIONS: hMSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of hMSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered hMSCs as vehicles for targeted anti-cancer therapy.

Vibrio parahaemolyticus infection impaired intestinal barrier function and nutrient absorption in Litopenaeus vannamei.

The intestine is the primary target of pathogenic microbes during invasion. However, the interaction of Vibrio parahaemolyticus (V. parahaemolyticus) with intestinal epithelial cells and its effects on the intestinal function of Litopenaeus vannamei (L. vannamei) are poorly studied. Therefore, the aim of this study was to investigate the influence of V. parahaemolyticus infection on intestinal barrier function and nutrient absorption in L. vannamei. In the present study, a total of 90 shrimp were randomly divided into two groups including the control group and V. parahaemolyticus infection group (final concentration of 1 × 105 CFU/mL), with three replicates per group. The result showed that compared with the control group, V. parahaemolyticus infection increased (P < 0.05) serum diamine oxidase activity and endotoxin quantification, and down-regulated (P < 0.05) the mRNA levels of intestinal peroxinectin, integrin, midline fasciclin at 48 h and 72 h; V. parahaemolyticus infection decreased (P < 0.05) the mRNA expression of intestinal amino acid transporter (CAT1, EAAT3 and ASCT1) and glucose transporter (SGLT-1, GLUT) at 24 h, 48 h and 72 h, and increased (P < 0.05) serum glucose and amino acid (Asp, Thr, Ser, Glu, Gly, Ala, Val, Ile, Leu, Tyr, Phe, Lys, His and Arg) concentration at 24 h. The results indicated that V. parahaemolyticus infection increased intestinal permeability, inhibited absorption of glucose and amino acid in L. vannamei.

Predictive Model for Pulmonary Embolism in Patients with Deep Vein Thrombosis.

BACKGROUND: To develop and verify a risk predictive model/scoring system for pulmonary embolism (PE) among hospitalized patients with deep venous thrombosis of the lower extremities (LDVT). METHODS: 776 patients with LDVT were enrolled in a case-control study between January 2016 and June 2017 from the Vascular Surgery Department of Shanxi Dayi Hospital, China. They were randomly divided into development (543 patients, 70%) and validation (233 patients, 30%) databases. Based on the results of pulmonary computed tomography arteriography, patients were divided into 2 categories; those with PE were designated as the case group, whereas those without comprised the controls. A logistic regression model and scoring system for PE in patients with LDVT was established in the development database and verified in the validation database. Scoring system (Shanxi Dayi Hospital score [SDH score]) was tabulated as follows: right lower extremity or bilateral lower extremities, 1; surgery or immobilization, 1; malignant tumor, 1; history of venous thromboembolism (VTE), 2; D-dimer >1,000 ng/mL, 2; and unprovoked, 2. Calibration and discrimination of the model were assessed by the Hosmer-Lemeshow goodness of fit test and the area under the receiver operating characteristic curve (AUC). Wells score, the Revised Geneva score, and the SDH score for predictive value of PE by AUC in the validation database were compared. RESULTS: 776 patients with LDVT were divided into 2 risk categories based on the scores from the risk model as follows: PE unlikely (score <3) and PE likely (score ≥3). Sensitivity, specificity, and crude agreement of the SDH score in the development database were 76.39%, 55.89%, and 61.33%, respectively. In the validation database, the logistic regression model showed good calibration and discriminative power. The Hosmer-Lemeshow goodness of fit test P value was >0.05, and the AUC was 0.705 (95% CI: 0.634-0.776, P < 0.001). The SDH score also showed good discriminative power, and the AUC was 0.702 (95% CI: 0.631-0.774, P < 0.001). Sensitivity, specificity, and crude agreement of the SDH score in the validation database were 67.61%, 61.73%, and 63.52%, respectively. AUC for the Wells score and the Revised Geneva score was 0.611 (95% CI: 0.533-0.688, P = 0.007) and 0.585 (95% CI: 0.503-0.666, P = 0.040), respectively. Difference of the AUC was not statistically significant between the Wells score and the SDH score (0.611 vs. 0.702, P = 0.059) but was so between the Revised Geneva score and the SDH score (0.585 vs. 0.702, P = 0.016). Sensitivity of the Wells score, Revised Geneva score, and the SDH score (64.79%, 67.61% vs. 67.61%) was not statistically significant. However, the specificity of the Wells score and Revised Geneva score was significantly lower than that of the SDH score (48.77%, 39.51% vs. 61.73%). CONCLUSIONS: Our logistic regression model and the SDH score based on 7 risk factors as right lower extremity, bilateral lower extremities, unprovoked, surgery or immobilization, malignant tumor, history of VTE, and D-dimer>1,000 ng/mL showed good calibration and discriminative power for the assessment of PE risk in patients with LDVT. The SDH score is more specific for PE prediction in the Chinese population, compared with the Wells score and the Revised Geneva score.

Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children.

BACKGROUND: Although leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes. METHODS: This study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19+CD10- pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children's Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed. RESULTS: KMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1 + patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively). CONCLUSIONS: Pediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required.

Epac Activation Regulates Human Mesenchymal Stem Cells Migration and Adhesion.

How to enhance the homing of human mesenchymal stem cells (hMSCs) to the target tissues remains a clinical challenge nowadays. To overcome this barrier, the mechanism responsible for the hMSCs migration and engraftment has to be defined. Currently, the exact mechanism involved in migration and adhesion of hMSCs remains unknown. Exchange protein directly activated by cAMP (Epac), a novel protein discovered in cAMP signaling pathway, may have a potential role in regulating cells adhesion and migration by triggering the downstream Rap family signaling cascades. However, the exact role of Epac in cells homing is elusive. Our study evaluated the role of Epac in the homing of hMSCs. We confirmed that hMSCs expressed functional Epac and its activation enhanced the migration and adhesion of hMSCs significantly. The Epac activation was further found to be contributed directly to the chemotactic responses induced by stromal cell derived factor-1 (SDF-1) which is a known chemokine in regulating hMSCs homing. These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in hMSCs homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications.

Sediment water content drives movement of intertidal crab Helice tientsinensis more strongly than salinity variations.

Intertidal wetlands undergo dynamic water and salinity variations, creating both promising and challenging habitats for diverse organisms. Crabs respond strongly to these variations by means such as altering their movements, thereby restructuring their spatial distribution and influencing coastal ecosystem resilience. However, the movements of crabs under varying environmental conditions require further elucidation. We conducted a systematic mesocosm experiment using the ubiquitous intertidal crab species Helice tientsinensis with four amount levels and six salinity levels of sprayed water applied through a custom apparatus, with a primary focus on crab movement. Crab movement from the experimental side of the apparatus (with altered conditions) to the control side (resembling field conditions of the intertidal wetlands of China's Yellow River Delta) and vice versa was recorded. The results revealed significant differences in moving out of the experimental side and moving in among the different water and salinity conditions, both separately for the two factors and simultaneously. Decreases in water content had a more pronounced effect on crab movement, leading to an increased number of crabs moving out of the experimental side of the apparatus. Conversely, as the experimental side became wetter, crabs tended to move towards it, and this movement was intensified by increases or decreases in water salinity. A structural equation model revealed that the moving-out and moving-in played fundamental roles in determining the number of resident crabs at the end of each experiment. While crabs preferred moist sediment with lower salinity, changes in salinity alone had minimal direct effect compared to sediment water contents. Our results clarify crab movements under varying water and salinity conditions, offering valuable insights to support adaptive interventions for crab populations and inform adaptive conservation and management strategies in intertidal wetlands.

Integration method of compressed sensing with variational mode decomposition based on gray wolf optimization and its denoising effect in mud pulse signal.

The continuous wave mud pulse transmission holds great promise for the future of downhole data communication. However, significant noise interference during the transmission process poses a formidable challenge for decoding. In particular, effectively eliminating random noise with a substantial amplitude that overlaps with the pulse signal spectrum has long been a complex issue. To address this, an enhanced integration algorithm that merges variational mode decomposition (VMD) and compressed sensing (CS) to suppress high-intensity random noise is proposed in this paper. In response to the inadequacy of manually preset parameters in VMD, which often leads to suboptimal decomposition outcomes, the gray wolf optimization algorithm is designed to obtain the optimal penalty factor and decomposition mode number in VMD. Subsequently, the optimized parameter combination decomposes the signal into a series of intrinsic modes. The mode exhibiting a stronger correlation with the original signal is retained to enhance signal sparsity, thereby fulfilling the prerequisite for compressed sensing. The signal is then observed and reconstructed using the compressed sensing method to yield the final signal. The proposed algorithm has been compared with VMD, CS, and CEEMD; the results demonstrate that the method can enhance the signal-noise ratio by up to ∼20.55 dB. Furthermore, it yields higher correlation coefficients and smaller mean square errors. Moreover, the experimental results using real field data show that the useful pulse waveforms can be recognized effectively, assisting surface workers in acquiring precise downhole information, enhancing drilling efficiency, and significantly reducing the risk of engineering accidents.

[Research and Application Progress of Biochar in Amelioration of Saline-Alkali Soil].

Saline-alkali land， as one of the farmland problems that seriously threatens grain yield in the 21st century， is widely distributed and has great potential for development. Biochar is a relatively efficient novel soil amendment， which can play an important role in alleviating the soil acid-base barrier， soil pollution control， carbon sequestration， and fertilizer slow release and has a great prospect in promoting sustainable agricultural development. In recent years， the research and application of biochar to improve saline-alkali soil have attracted much attention. However， due to the complexity and heterogeneity of the structural components of biochar， the improvement effect of biochar on saline-alkali soil is highly uncertain， and there is also a lack of systematic summary and in-depth discussion of the key mechanisms， which limits the further popularization and application of biochar technology in the improvement of saline-alkali soil. This study comprehensively analyzed the effects of biochar on physicochemical properties， nutrient availability， and biological characteristics of saline-alkali soil； summarized the improvement effects of biochar and modified biochar on saline-alkali soil and their effects on quality and efficiency； and elucidated the possible mechanism of biochar in the improvement of saline-alkali soil. The future research prospect of biochar was discussed in order to provide reference for further research and development of green， efficient， and accurate improvement technology of biochar in saline-alkali soil and its popularization and application.

A city-level dataset of heavy metal emissions into the atmosphere across China from 2015-2020.

The absence of nationwide distribution data regarding heavy metal emissions into the atmosphere poses a significant constraint in environmental research and public health assessment. In response to the critical data deficiency, we have established a dataset covering Cr, Cd, As, and Pb emissions into the atmosphere (HMEAs, unit: ton) across 367 municipalities in China. Initially, we collected HMEAs data and covariates such as industrial emissions, vehicle emissions, meteorological variables, among other ten indicators. Following this, nine machine learning models, including Linear Regression (LR), Ridge, Bayesian Ridge (Bayesian), K-Neighbors Regressor (KNN), MLP Regressor (MLP), Random Forest Regressor (RF), LGBM Regressor (LGBM), Lasso, and ElasticNet, were assessed using coefficient of determination (R2), root-mean-square error (RMSE) and Mean Absolute Error (MAE) on the testing dataset. RF and LGBM models were chosen, due to their favorable predictive performance (R2: 0.58-0.84, lower RMSE/MAE), confirming their robustness in modelling. This dataset serves as a valuable resource for informing environmental policies, monitoring air quality, conducting environmental assessments, and facilitating academic research.

Brain-computer interfaces: the innovative key to unlocking neurological conditions.

Neurological disorders such as Parkinson's disease, stroke, and spinal cord injury can pose significant threats to human mortality, morbidity, and functional independence. Brain-Computer Interface (BCI) technology, which facilitates direct communication between the brain and external devices, emerges as an innovative key to unlocking neurological conditions, demonstrating significant promise in this context. This comprehensive review uniquely synthesizes the latest advancements in BCI research across multiple neurological disorders, offering an interdisciplinary perspective on both clinical applications and emerging technologies. We explore the progress in BCI research and its applications in addressing various neurological conditions, with a particular focus on recent clinical studies and prospective developments. Initially, the review provides an up-to-date overview of BCI technology, encompassing its classification, operational principles, and prevalent paradigms. It then critically examines specific BCI applications in movement disorders, disorders of consciousness, cognitive and mental disorders, as well as sensory disorders, highlighting novel approaches and their potential impact on patient care. This review reveals emerging trends in BCI applications, such as the integration of artificial intelligence and the development of closed-loop systems, which represent significant advancements over previous technologies. The review concludes by discussing the prospects and directions of BCI technology, underscoring the need for interdisciplinary collaboration and ethical considerations. It emphasizes the importance of prioritizing bidirectional and high-performance BCIs, areas that have been underexplored in previous reviews. Additionally, we identify crucial gaps in current research, particularly in long-term clinical efficacy and the need for standardized protocols. The role of neurosurgery in spearheading the clinical translation of BCI research is highlighted. Our comprehensive analysis presents BCI technology as an innovative key to unlocking neurological disorders, offering a transformative approach to diagnosing, treating, and rehabilitating neurological conditions, with substantial potential to enhance patients' quality of life and advance the field of neurotechnology.

PKD regulates mitophagy to prevent oxidative stress and mitochondrial dysfunction during mouse oocyte maturation.

Mitochondria play dominant roles in various cellular processes such as energy production, apoptosis, calcium homeostasis, and oxidation-reduction balance. Maintaining mitochondrial quality through mitophagy is essential, especially as its impairment leads to the accumulation of dysfunctional mitochondria in aging oocytes. Our previous research revealed that PKD expression decreases in aging oocytes, and its inhibition negatively impacts oocyte quality. Given PKD's role in autophagy mechanisms, this study investigates whether PKD regulates mitophagy to maintain mitochondrial function and support oocyte maturation. When fully grown oocytes were treated with CID755673, a potent PKD inhibitor, we observed meiosis arrest at the metaphase I stage, along with decreased spindle stability. Our results demonstrate an association with mitochondrial dysfunction, including reduced ATP production and fluctuations in Ca2+ homeostasis, which ultimately lead to increased ROS accumulation, stimulating oxidative stress-induced apoptosis and DNA damage. Further research has revealed that these phenomena result from PKD inhibition, which affects the phosphorylation of ULK, thereby reducing autophagy levels. Additionally, PKD inhibition leads to decreased Parkin expression, which directly and negatively affects mitophagy. These defects result in the accumulation of damaged mitochondria in oocytes, which is the primary cause of mitochondrial dysfunction. Taken together, these findings suggest that PKD regulates mitophagy to support mitochondrial function and mouse oocyte maturation, offering insights into potential targets for improving oocyte quality and addressing mitochondrial-related diseases in aging females.

Development and external validation of a novel prognostic nomogram for overall survival in prostate cancer patients with bone metastatic: a retrospective study of the SEER-based and a single Chinese center.

BACKGROUND: Prostate cancer (PCa) patients with bone metastases (BM) often face a poor prognosis, a leading contributor to mortality within this group. This study aims to develop a novel prognostic nomogram to predict overall survival for them. METHODS: We retrospectively analyzed PCa patients with BM from Surveillance, Epidemiology, and End Results (SEER) database and our hospital. Independent prognostic factors were identified using univariate and multivariate Cox regression analyses for the creation of a nomogram. Calibration curves and receiver operating characteristic (ROC) curves, along with the concordance index (C-index) and decision curve analysis (DCA), were employed to evaluate the performance of the constructed nomogram. RESULTS: A total of 12,344 PCa patients with BM, derived from 2010 to 2019 SEER database, were randomly allocated into a training cohort (n = 8640) and an internal validation cohort (n = 3704). Additionally, an external validation cohort (n = 126) from our hospital. The novel nomogram integrates multiple factors: age, race, histopathology, organ metastasis, chemotherapy, Gleason score, and prostate-specific antigen (PSA). C-index for the training, internal validation, and external validation cohorts were 0.770 (0.766-0.774), 0.756 (0.749-0.763), and 0.751 (0.745-0.757) respectively. Similarly, the area under the curve (AUC) for each cohort exhibited comparable results (training cohort-3-year: 0.682, 6-year: 0.775, 9-year: 0.824; internal validation cohort-3-year: 0.681, 6-year: 0.750, 9-year: 0.806; external validation cohort-2-year: 0.667, 3-year: 0.744, 4-year: 0.800), indicating that the nomogram possesses robust discriminative ability. Calibration curve and DCA curve further proved the reliability and accuracy of the prognostic nomogram. CONCLUSION: This study determined the independent risk factors for prostate cancer (PCa) patients with bone metastasis (BM) and subsequently developed a robust prognostic nomogram to predict overall survival (OS). This tool can serve to guide precise clinical treatment strategies for these patients.

Identification and Characterization of a New Regulator, TagR, for Environmental Stress Resistance Based on the DNA Methylome of Streptomyces roseosporus.

DNA methylation is a defense that microorganisms use against extreme environmental stress, and improving resistance against environmental stress is essential for industrial actinomycetes. However, research on strain optimization utilizing DNA methylation for breakthroughs is rare. Based on DNA methylome analysis and KEGG pathway assignment in Streptomyces roseosporus, we discovered an environmental stress resistance regulator, TagR. A series of in vivo and in vitro experiments identified TagR as a negative regulator, and it is the first reported regulator of the wall teichoic acid (WTA) ABC transport system. Further study showed that TagR had a positive self-regulatory loop and m4C methylation in the promoter improved its expression. The ΔtagR mutant exhibited better hyperosmotic resistance and higher decanoic acid tolerance than the wild type, which led to a 100% increase in the yield of daptomycin. Moreover, enhancing the expression of the WTA transporter resulted in better osmotic stress resistance in Streptomyces lividans TK24, indicating the potential for wide application of the TagR-WTA transporter regulatory pathway. This research confirmed the feasibility and effectiveness of mining regulators of environmental stress resistance based on the DNA methylome, characterized the mechanism of TagR, and improved the resistance and daptomycin yield of strains. Furthermore, this research provides a new perspective on the optimization of industrial actinomycetes. IMPORTANCE This study established a novel strategy for screening regulators of environmental stress resistance based on the DNA methylome and discovered a new regulator, TagR. The TagR-WTA transporter regulatory pathway improved the resistance and antibiotic yield of strains and has the potential for wide application. Our research provides a new perspective on the optimization and reconstruction of industrial actinomycetes.

Nivalenol affects Cyclin B1 level and activates SAC for cell cycle progression in mouse oocyte meiosis.

OBJECTIVES: Nivalenol (NIV) is a secondary metabolite of type B trichothecene mycotoxin produced by Fusarium genera, which is widely found in contaminated food and crops such as corn, wheat and peanuts. NIV is reported to have hepatotoxicity, immunotoxicity, genotoxicity, and reproductive toxicity. Previous studies indicate that NIV disturbs mammalian oocyte maturation. Here, we reported that delayed cell cycle progression might be the reason for oocyte maturation defect caused by NIV exposure. METHODS AND RESULTS: We set up a NIV exposure model and showed that NIV did not affect G2/M transition for meiosis resumption, but disrupted the polar body extrusion of oocytes. Further analysis revealed that oocytes were arrested at metaphase I, which might be due to the lower expression of Cyclin B1 after NIV exposure. After cold treatment, the microtubules were disassembled in the NIV-exposed oocytes, indicating that NIV disrupted microtubule stability. Moreover, NIV affected the attachment between kinetochore and microtubules, which further induced the activation of MAD2/BUBR1 at the kinetochores, suggesting that spindle assemble checkpoint (SAC) was continuously activated during oocyte meiotic maturation. CONCLUSIONS: Taken together, our study demonstrated that exposure to NIV affected Cyclin B1 expression and activated microtubule stability-dependent SAC to ultimately disturb cell cycle progression in mouse oocyte meiosis.