Characterization of Escherichia coli pathogenicity and drug resistance in yolk peritonitis.

Yolk Peritonitis can lead to a rapid decline in egg production, which seriously affects the health of laying hens and the profitability of chicken farms. Escherichia coli (E. coli) is the most common cause of yolk peritonitis in laying hens. In this study, bacterial samples were collected from the ovaries and fallopian tubes of laying hens with suspected yolk peritonitis from a laying farm in Jiangsu Province, and their pathogenicity and drug resistance were investigated. Initially, morphological and biochemical detection methods were employed to isolate and identify the pathogenic bacteria. The results showed that a total of 16 strains of E. coli were isolated from laying hens with yolk peritonitis. Subsequently, the drug resistance and pathogenicity of a randomly selected E. coli strain were analyzed and predicted by genome sequencing technology, and the drug resistance of E. coli was verified by drug sensitivity test and PCR. Finally, the virulence was verified by infection experiment in mice. The study revealed that the egg-yolk peritonitis in laying hens was caused by E. coli infection, and the genome sequencing analysis revealed that the bacteria had multidrug resistance and high virulence. The drug susceptibility testing indicates that E. coli exhibited resistance to aminoglycosides, ß-lactam, macrolides, fluoroquinolones, and sulfonamides. In this study, resistance genes including KdpE, aadA5, APH(3 ")-ID, APH(6)-ID, and TEM-1 were identified, and their expression levels varied across different stages of bacterial growth. The results of virulence analysis indicated a mortality rate of 50% in mice infected with E. coli at a concentration of 2.985 × 107 CFU/mL. E. coli infection resulted in damage to various tissues and organs in mice, with the intestinal tissue structure being the most severely affected. This study provides a reference for the study of drug resistance mechanisms in E. coli and provides valuable insights into the selection of drugs for the treatment of vitelline peritonitis.

Effect of Elevated Blood Glucose on Postoperative Complications Among Diabetic Patients After Surgical Treatment of Torsional Ankle Fracture.

BACKGROUND: This study aims to evaluate the association of elevated blood glucose and postoperative complications among diabetic patients after surgical treatment of torsional ankle fracture. METHODS: This was a retrospective study of consecutive diabetic patients treated surgically for a torsional ankle injury between January 2017 and December 2021 at a large tertiary hospital. All patients who met inclusion and exclusion criteria were divided into a high-HbA1c group or a low-HbA1c group according to the HbA1c cutoff of 7.0% within 3 months of operation, then a propensity score match was performed to control potential confounding factors. The primary outcomes were postoperative complications, and secondary outcomes were unplanned secondary procedures. RESULTS: A matched cohort of 238 patients was finally included, with 119 patients with high HbA1c levels and 119 with low HbA1c levels. Patients with high HbA1c levels experienced more complications (31.1% vs 18.5%, P < .01) and more secondary procedures (22.7% and 8.4%, P < .01) than those with low HbA1c levels. Multivariate logistic regression indicated that patients with high HbA1c levels were significantly associated with higher proportions of any complications (OR 2.25, 95% CI 1.08-4.69; P = .03), superficial infection (OR 4.03, 95% CI 2.13-5.41; P < .01), deep infection (OR 1.42, 95% CI 1.23-2.02; P < .01), and any unplanned secondary operations (OR 3.72, 95% CI 1.62-8.52; P < .01) compared with those with low HbA1c levels after controlling for potential confounders. Multivariate linear regression showed that high HbA1c levels were significantly associated with a higher number of complications (ß = 4.61, 95% CI 2.63-18.18; P < .01) and a higher number of secondary procedures (ß = 4.44, 95% CI 2.79-10.87; P < .01). CONCLUSION: Patients with an HbA1c >7.0% within 3 months of operation are more likely to have a wound issue/infection and more likely to undergo a secondary procedure after surgical treatment of torsional ankle fractures in diabetic patients than patients with an HbA1c ≤7.0% within 3 months of operation. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Roles of myosin 1e and the actin cytoskeleton in kidney functions and familial kidney disease.

Mammalian kidneys are responsible for removing metabolic waste and maintaining fluid and electrolyte homeostasis via selective filtration. One of the proteins closely linked to selective renal filtration is myosin 1e (Myo1e), an actin-dependent molecular motor found in the specialized kidney epithelial cells involved in the assembly and maintenance of the renal filter. Point mutations in the gene encoding Myo1e, MYO1E, have been linked to familial kidney disease, and Myo1e knockout in mice leads to the disruption of selective filtration. In this review, we discuss the role of the actin cytoskeleton in renal filtration, the known and hypothesized functions of Myo1e, and the possible explanations for the impact of MYO1E mutations on renal function.

Development and validation of a machine-learning model for predicting the risk of death in sepsis patients with acute kidney injury.

The mortality rate of patients with sepsis-induced acute kidney injury (S-AKI) is notably elevated. The initial categorization of prognostic indicators has a beneficial impact on elucidating and enhancing disease outcomes. This study aimed to predict the mortality risk of S-AKI patients by employing machine learning techniques. The sample size determined by a four-step procedure yielded 1508 samples. The research design necessitated the inclusion of individuals with S-AKI from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The patients were initially admitted to the Intensive Care Unit (ICU) for their hospital stay. Additionally, these patients (aged from 18 to 89 years old) had encountered S-AKI on the day of their admittance. Forty-two predictive factors were analyzed, with hospitalization death as the outcome variable. The training set (4001 cases) consisted of 70 % of the participants, and the remaining (1714 cases) participants were allocated to the validation set. Furthermore, an additional validation set (MIMIC-III) consisted of 1757 patients from the MIMIC-III database. Moreover, an external validation set from the Intensive Care Department of Beijing Friendship Hospital (BFH) comprised 72 patients. Six machine learning models were employed in the prediction, namely the logistic, lasso, rpart, random forest, xgboost, and artificial neural network models. The comparative efficacy of the newly developed model in relation to the APACHE II model for predicting mortality risk was also assessed. The XGBoost model exhibited a superior performance with the training set. With the internal validation set and the two external validation sets (MIMIC-III and BFH), the xgboost algorithm demonstrated the highest performance. Meanwhile, APACHE II performed poorly at predicting the mortality risk with the BFH validation set. The mortality risk was influenced by three primary clinical parameters: urine volume, lactate, and Glasgow Coma Scale (GCS) score. Thus, we developed a prediction model for the risk of death among S-AKI patients that has an improved performance compared to previous models and is a potentially valuable tool for S-AKI prediction and treatment in the clinic.

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Regulation of hepatocyte phospholipid peroxidation signaling by a Chinese patent medicine against psychological stress-induced liver injury.

BACKGROUND: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism. PURPOSE: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH). METHODS: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling. RESULTS: The present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation. CONCLUSION: Our findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention.

Propensity score matched analysis of treatment outcomes in pediatric ureteropelvic junction obstruction: a comparison between horseshoe and non-horseshoe kidneys.

BACKGROUND: Pediatric hydronephrosis poses distinct challenges, particularly in cases involving horseshoe kidneys (HSK). This retrospective study compares treatment outcomes between HSK and non-horseshoe kidneys (NHSK) in pediatric ureteropelvic junction obstruction (UPJO) patients. METHODS: A retrospective cohort study included 35 patients with HSK and 790 patients with NHSK undergoing pyeloplasty. Preoperative, intraoperative, and postoperative parameters were evaluated. Propensity score matching (PSM) balanced patient characteristics in the NHSK group. RESULTS: In comparison with NHSK, HSK exhibited a higher crossing vessel incidence (51.6% vs. 5.12%, P < 0.001) and smaller preoperative anteroposterior pelvic diameter (APD). Post 6 and 12 months, NHSK maintained a larger APD, with a higher P/C ratio at 12 months. PSM retained significantly higher crossing vessel incidence in HSK (51.6 vs. 3.61%, P < 0.001). Laparoscopic pyeloplasty (LP) in HSK showed lower postoperative length of stay (LOS). Postoperative ultrasound parameters favored NHSK. In HSK and NHSK with crossing vessels, HSK demonstrated higher complications even post-PSM (38.5% vs. 0%, P = 0.039). CONCLUSIONS: The study emphasizes the importance of recognizing crossing vessels in HSK-related hydronephrosis. Surgical success, although comparable between HSK and NHSK, requires tailored approaches. This investigation contributes valuable insights to pediatric urology, emphasizing personalized management for optimal outcomes.

Feasibility and Preliminary Efficacy of American Elderberry Juice for Improving Cognition and Inflammation in Patients with Mild Cognitive Impairment.

Despite data showing that nutritional interventions high in antioxidant/anti-inflammatory properties (anthocyanin-rich foods, such as blueberries/elderberries) may decrease risk of memory loss and cognitive decline, evidence for such effects in mild cognitive impairment (MCI) is limited. This study examined preliminary effects of American elderberry (Sambucus nigra subsp. canadensis) juice on cognition and inflammatory markers in patients with MCI. In a randomized, double-blind, placebo-controlled trial, patients with MCI (n = 24, Mage = 76.33 ± 6.95) received American elderberry (n = 11) or placebo (n = 13) juice (5 mL orally 3 times a day) for 6 months. At baseline, 3 months, and 6 months, patients completed tasks measuring global cognition, verbal memory, language, visuospatial cognitive flexibility/problem solving, and memory. A subsample (n = 12, 7 elderberry/5 placebo) provided blood samples to measure serum inflammatory markers. Multilevel models examined effects of the condition (elderberry/placebo), time (baseline/3 months/6 months), and condition by time interactions on cognition/inflammation outcomes. Attrition rates for elderberry (18%) and placebo (15%) conditions were fairly low. The dosage compliance (elderberry-97%; placebo-97%) and completion of cognitive (elderberry-88%; placebo-87%) and blood-based (elderberry-100%; placebo-100%) assessments was high. Elderberry (not placebo) trended (p = 0.09) towards faster visuospatial problem solving performance from baseline to 6 months. For the elderberry condition, there were significant or significantly trending decreases over time across several markers of low-grade peripheral inflammation, including vasorin, prenylcysteine oxidase 1, and complement Factor D. Only one inflammatory marker showed an increase over time (alpha-2-macroglobin). In contrast, for the placebo, several inflammatory marker levels increased across time (L-lactate dehydrogenase B chain, complement Factor D), with one showing deceased levels over time (L-lactate dehydrogenase A chain). Daily elderberry juice consumption in patients with MCI is feasible and well tolerated and may provide some benefit to visuospatial cognitive flexibility. Preliminary findings suggest elderberry juice may reduce low-grade inflammation compared to a placebo-control. These promising findings support the need for larger, more definitive prospective studies with longer follow-ups to better understand mechanisms of action and the clinical utility of elderberries for potentially mitigating cognitive decline.

Heterogeneous CNF/MoO3 nanofluidic membranes with tunable surface plasmon resonances for solar-osmotic energy conversion.

Two-dimensional (2D) nanofluidic membranes are competitive candidates for osmotic energy harvesting and have been greatly developed. However, the use of diverse inherent characteristics of 2D nanosheets, such as electronic or optoelectronic properties, to achieve intelligent ion transport, still lacks sufficient exploration. Here, a cellulose nanofiber/molybdenum oxide (CNF/MoO3) heterogeneous nanofluidic membrane with high performance solar-osmotic energy conversion is reported, and how surface plasmon resonances (SPR) regulate selective cation transport is revealed. The SPR of amorphous MoO3 endows the heterogeneous nanofluidic membranes with tunable surface charge and good photothermal conversion. Through DFT calculations and finite element modeling, the regulation of electronic and optoelectronic properties on the surface of materials by SPR and the influence of surface charge density and temperature gradient on ion transport in nanofluidic membranes are demonstrated. By mixing 0.01/0.5 M NaCl solutions using SPR and photothermal effects, the power density can achieve a remarkable value of ≈13.24 W m-2, outperforming state-of-the-art 2D-based nanofluidic membranes. This work first reveals the regulation and mechanism of SPR on ion transport in nanofluidic membranes and systematically studies photon-electron-ion interactions in nanofluidic membranes, which could also provide a new viewpoint for promoting osmotic energy conversion.

Can oral microbiome predict low birth weight infant delivery?

OBJECTIVES: This study aimed to identify the oral microbiota factors contributing to low birth weight (LBW) in Chinese pregnant women and develop a prediction model using machine learning. METHODS: A nested case-control study was conducted in a prospective cohort of 580 Chinese pregnant women, with 23 LBW cases and 23 healthy delivery controls matched for age and smoking habit. Saliva samples were collected at early and late pregnancy, and microbiome profiles were analyzed through 16S rRNA gene sequencing. RESULTS: The relative abundance of Streptococcus was over-represented (median 0.259 vs. 0.116) and Saccharibacteria_TM7 was under-represented (median 0.033 vs. 0.068) in the LBW case group than in controls (p < 0.001, p = 0.015 respectively). Ten species were identified as microbiome biomarkers of LBW by LEfSe analysis, which included 7 species within the genus of Streptococcus or as part of 'nutritionally variant streptococci' (NVS), 2 species of opportunistic pathogen Leptotrichia buccalis and Gemella sanguinis (all LDA score>3.5) as risk biomarkers, and one species of Saccharibacteria TM7 as a beneficial biomarker (LDA= -4.5). The machine-learning model based on these 10 distinguished oral microbiota species could predict LBW, with an accuracy of 82 %, sensitivity of 91 %, and specificity of 73 % (AUC-ROC score 0.89, 95 % CI: 0.75-1.0). Results of α-diversity showed that mothers who delivered LBW infants had less stable salivary microbiota construction throughout pregnancy than the control group (measured by Shannon, p = 0.048; and Pielou's, p = 0.021), however the microbiome diversity did not improve the prediction accuracy of LBW. CONCLUSIONS: A machine-learning oral microbiome model shows promise in predicting low-birth-weight delivery. Even in cases where oral health is not significantly compromised, opportunistic pathogens or rarer taxa associated with adverse pregnancy outcomes can still be identified in the oral cavity. CLINICAL SIGNIFICANCE: This study highlights the potential complexity of the relationship between oral microbiome and pregnancy outcomes, indicating that mechanisms underlying the association between oral microbiota and adverse pregnancy outcomes may involve complex interactions between host factors, microbiota, and systemic conditions. Using machine learning to develop a predictive model based on specific oral microbiota biomarkers provides a potential for personalized medicine approaches. Future prediction models should incorporate clinical metadata to be clinically useful for improving maternal and child health.

Local Tumor Progression Predictive Model Based on MRI for Colorectal Cancer Liver Metastases after Radiofrequency Ablation.

PURPOSE: To investigate the post-radiofrequency ablation (RFA) magnetic resonance imaging (MRI) characteristics in patients with liver metastases from colorectal cancer and to build a predictive model for local tumor progression based on these imaging markers. MATERIALS AND METHODS: A cohort of 73 patients with 110 colorectal cancer liver metastases (CRCLM) who underwent RFA and MRI one month post-ablation was included in image signs analysis and predictive model training. Using a newly developed MRI appearance scoring criteria, MR Image Appearance Scoring at One Month after RFA (MRIAS 1MO), the semi-quantitative analysis of MRI findings within the ablation zone were conducted independently by two radiologists. The intraclass correlation coefficient (ICC) was calculated to evaluate measurement reliability. Differences in MRIAS 1MO scores were compared using Mann-Whitney U test, focusing on local tumor response outcomes. Using local tumor progression (LTP) as the primary end point, MRIAS 1MO scores and other lesion morphological and clinical characteristics were included to establish predictive model. Predication accuracy was subsequently evaluated using calibration curve, time-dependent concordance index (C index) curve, and LTP-free survival (LTPFS) curve. Another cohort comprising 60 patients with 76 CRCLMs provided additional MRIAS 1MO scores and clinical data associated with LTP. We evaluated the performance of the established predictive model using calibration curve, time-dependent C index curve, and LTPFS curve. RESULTS: The MRIAS 1MO criteria exhibited strong measurement reliability. The ICC values of T1S (scores from T1WI), T2S (scores form T2WI) and NCES (scores by adding T1S to T2S) MRIS (the overall scores) were 0.825, 0.779, 0.826 and 0.873, respectively. Lesions with LTP showed significantly higher median values for the overall MRIAS 1MO score (MRIS) compared to lesions without LTP (16 vs. 12, p < 0.001). MRIS and lesion diameter were independent prognostic factors of LTP and were included in predictive model (hazard ratio: MRIS over 13.5:4.275, lesion diameter larger than 30 mm: 2.056). The predictive model demonstrated an overall C index of 0.721 and risk stratification using the predictive model resulted in significantly different LPTFS times. In the validation cohort, the C index were 0.825, 0.794 and 0.764 at six, twelve and twenty-four months, respectively. Patients classified as high-risk in the validation cohort had a median LTPFS time of 10.0 months, while the median LTPFS time was not reached in the low-risk group. CONCLUSIONS: The semi-quantitative MRIAS 1MO criteria, used for post-RFA MRI appearance analysis, exhibited strong measurement reliability. Prediction models established based on overall MRIAS 1MO score (MRIS) and lesion diameter had good predictive performance for LTP in patients undergoing RFA for CRCLM treatment.

[Effect of Emotion Regulation on Anxiety/Depression Symptoms in Children With Attention-Deficit/Hyperactivity Disorder: The Mediating Role of Social Problems and the Moderating Role of Family Functioning]. / æƒ ç»ªè°ƒèŠ‚ä¸Žæ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢æ‚£å„¿ç„¦è™‘/抑郁症状：社交问题的中介效应和家庭功能的调节.

Objective: To investigate the mediating effect of social problems in the effect pathway of emotional dysregulation influencing anxiety/depression emotions in children with attention-deficit/hyperactivity disorder (ADHD) and to explore the potential moderating effect of family functionality. Methods: A total of 235 children diagnosed with ADHD were enrolled in the study. The paticipants' age ranged from 6 to 12. Emotion Regulation Checklist, Achenbach's Child Behavior Checklist (CBCL) Social Problems Subscale, CBCL Anxious/Depressed Subscale, and Family Assessment Device were used to evaluate the emotional regulation, social problems, anxiety/depression emotions, and family functionality of the participants. A moderated mediation model was employed to analyze whether social problems and family functionality mediate and moderate the relationship between emotional regulation and anxiety/depression emotions. Results: Social problems partially mediated the impact of emotional dysregulation on anxiety/depression emotions in ADHD children, with the direct effect being 0.26 (95% confidence interval [CI]: [0.17, 0.36], P<0.001), the indirect effect being 0.13 (95% CI: [0.07, 0.19], P<0.001), and the mediating effect accounting for 33% of the total effect. Family functionality exhibited a positive moderating effect on the relationship between social problems and anxiety/depression emotions. Conclusion: This study contributes to the understanding of complex factors influencing anxiety/depression in children with ADHD, providing reference for the further development of targeted interventions for children with ADHD and the improvement of prognosis.

ProDiv: Prototype-driven consistent pseudo-bag division for whole-slide image classification.

BACKGROUND AND OBJECTIVE: Pathology image classification is one of the most essential auxiliary processes in cancer diagnosis. To overcome the problem of inadequate Whole-Slide Image (WSI) samples with weak labels, pseudo-bag-based multiple instance learning (MIL) methods have attracted wide attention in pathology image classification. In this type of method, the division scheme of pseudo-bags is usually a primary factor affecting classification performance. In order to improve the division of WSI pseudo-bags on existing random/clustering approaches, this paper proposes a new Prototype-driven Division (ProDiv) scheme for the pseudo-bag-based MIL classification framework on pathology images. METHODS: This scheme first designs an attention-based method to generate a bag prototype for each slide. On this basis, it further groups WSI patch instances into a series of instance clusters according to the feature similarities between the prototype and patches. Finally, pseudo-bags are obtained by randomly combining the non-overlapping patch instances of different instance clusters. Moreover, the design scheme of our ProDiv considers practicality, and it could be smoothly assembled with almost all the MIL-based WSI classification methods in recent years. RESULTS: Empirical results show that our ProDiv, when integrated with several existing methods, can deliver classification AUC improvements of up to 7.3% and 10.3%, respectively on two public WSI datasets. CONCLUSIONS: ProDiv could almost always bring obvious performance improvements to compared MIL models on typical metrics, which suggests the effectiveness of our scheme. Experimental visualization also visually interprets the correctness of the proposed ProDiv.

A pollen selection system links self and interspecific incompatibility in the Brassicaceae.

Self-incompatibility and recurrent transitions to self-compatibility have shaped the extant mating systems underlying the nonrandom mating critical for speciation in angiosperms. Linkage between self-incompatibility and speciation is illustrated by the shared pollen rejection pathway between self-incompatibility and interspecific unilateral incompatibility (UI) in the Brassicaceae. However, the pollen discrimination system that activates this shared pathway for heterospecific pollen rejection remains unknown. Here we show that Stigma UI3.1, the genetically identified stigma determinant of UI in Arabidopsis lyrata × Arabidopsis arenosa crosses, encodes the S-locus-related glycoprotein 1 (SLR1). Heterologous expression of A. lyrata or Capsella grandiflora SLR1 confers on some Arabidopsis thaliana accessions the ability to discriminate against heterospecific pollen. Acquisition of this ability also requires a functional S-locus receptor kinase (SRK), whose ligand-induced dimerization activates the self-pollen rejection pathway in the stigma. SLR1 interacts with SRK and interferes with SRK homomer formation. We propose a pollen discrimination system based on competition between basal or ligand-induced SLR1-SRK and SRK-SRK complex formation. The resulting SRK homomer levels would be sensed by the common pollen rejection pathway, allowing discrimination among conspecific self- and cross-pollen as well as heterospecific pollen. Our results establish a mechanistic link at the pollen recognition phase between self-incompatibility and interspecific incompatibility.

Enhanced expression of activity-regulated cytoskeleton-associated protein in the medial prefrontal cortex is involved in working memory performance.

Working memory (WM) is a cognitive function important for guiding the on-going or upcoming behavior. A memory-related protein Arc (activity-regulated cytoskeleton-associated protein) is implicated in long-term memory consolidation. Recent evidence further suggests the involvement of hippocampal Arc in spatial WM. The medial prefrontal cortex (mPFC) is a key brain region mediating WM. However, the role of mPFC Arc in WM is still uncertain. To investigate whether mPFC Arc protein is involved in WM performance, delayed non-match to sample (DNMS) T-maze task was performed in rats with or without blocking new synthesis of mPFC Arc. In DNMS task, a 10-s or 30-s delay between the sample run and the choice run was given to evaluate WM performance. To block new Arc protein synthesis during the DNMS task, Arc antisense oligodeoxynucleotides (ODNs) were injected to the bilateral mPFC. The results show that, in rats without surgery for cannula implantation and subsequent intracerebral injection of ODNs, WM was functioning well during the DNMS task with a delay of 10 s but not 30 s, which was accompanied with a significantly increased level of mPFC Arc protein, indicating a possible link between enhanced Arc protein expression and the performance of WM. After preventing the enhancement of mPFC Arc protein expression with Arc antisense ODNs, rat's WM performance was impaired. These findings support enhanced mPFC Arc protein expression playing a role during WM performance.

Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCß], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCß, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

Cytosolic DNA initiates a vicious circle of aging-related endothelial inflammation and mitochondrial dysfunction via STING: the inhibitory effect of Cilostazol.

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.

The expression profiles of cyp19a1, sf-1, esrs and gths in the brain-pituitary during gonadal sex differentiation in juvenile Japanese eels.

Eels are gonochoristic species whose gonadal differentiation initiates at the yellow eel stage and is influenced by environmental factors. We revealed some sex-related genes were sex dimorphically expressed in gonads during gonadal sex differentiation of Japanese eel (Anguilla japonica); however, the expression of sex-related genes in the brain-pituitary during gonadal sex differentiation in eels is still unclear. This study aimed to investigate the sex-related gene expressions in the brain-pituitary and tried to clarify their roles in the brain and gonads during gonadal sex differentiation. Based on our previous histological study, the control eels developed as males, and estradiol-17ß (E2) was used for feminization. Our results showed that during testicular differentiation, the brain cyp19a1 transcripts and aromatase proteins were increased significantly; moreover, the cyp19a1, sf-1, foxl2s, and esrs (except gperb) transcripts in the midbrain/pituitary also were increased significantly. Forebrain gnrh1 transcripts increased slightly during gonadal differentiation of both sexes, but the gnrhr1b and gnrhr2 transcripts in the midbrain/pituitary were stable during gonadal differentiation. The expression levels of gths and gh in the midbrain/pituitary were significantly increased during testicular differentiation and were much higher in males than in E2-feminized females. These results implied that endogenous estrogens might play essential roles in the brain/pituitary during testicular differentiation, sf-1, foxl2s, and esrs may have roles in cyp19a1 regulation in the midbrain/pituitary of Japanese eels. For the GnRH-GTH axis, gths, especially fshb, may be regulated by esrs and involved in regulating testicular differentiation and development in Japanese eels.

HDS-Net: Achieving fine-grained skin lesion segmentation using hybrid encoding and dynamic sparse attention.

Skin cancer is one of the most common malignant tumors worldwide, and early detection is crucial for improving its cure rate. In the field of medical imaging, accurate segmentation of lesion areas within skin images is essential for precise diagnosis and effective treatment. Due to the capacity of deep learning models to conduct adaptive feature learning through end-to-end training, they have been widely applied in medical image segmentation tasks. However, challenges such as boundary ambiguity between normal skin and lesion areas, significant variations in the size and shape of lesion areas, and different types of lesions in different samples pose significant obstacles to skin lesion segmentation. Therefore, this study introduces a novel network model called HDS-Net (Hybrid Dynamic Sparse Network), aiming to address the challenges of boundary ambiguity and variations in lesion areas in skin image segmentation. Specifically, the proposed hybrid encoder can effectively extract local feature information and integrate it with global features. Additionally, a dynamic sparse attention mechanism is introduced, mitigating the impact of irrelevant redundancies on segmentation performance by precisely controlling the sparsity ratio. Experimental results on multiple public datasets demonstrate a significant improvement in Dice coefficients, reaching 0.914, 0.857, and 0.898, respectively.

Highly elastic, fatigue-resistant, antibacterial, conductive, and nanocellulose-enhanced hydrogels with selenium nanoparticles loading as strain sensors.

The fabrication of highly elastic, fatigue-resistant and conductive hydrogels with antibacterial properties is highly desirable in the field of wearable devices. However, it remains challenging to simultaneously realize the above properties within one hydrogel without compromising excellent sensing ability. Herein, we fabricated a highly elastic, fatigue-resistant, conductive, antibacterial and cellulose nanocrystal (CNC) enhanced hydrogel as a sensitive strain sensor by the synergistic effect of biosynthesized selenium nanoparticles (BioSeNPs), MXene and nanocellulose. The structure and potential mechanism to generate biologically synthesized SeNPs (BioSeNPs) were systematically investigated, and the role of protease A (PrA) in enhancing the adsorption between proteins and SeNPs was demonstrated. Additionally, owing to the incorporation of BioSeNPs, CNC and MXene, the synthesized hydrogels showed high elasticity, excellent fatigue resistance and antibacterial properties. More importantly, the sensitivity of hydrogels determined by the gauge factor was as high as 6.24 when a high strain was applied (400-700 %). This study provides a new horizon to synthesize high-performance antibacterial and conductive hydrogels for soft electronics applications.