Gender differences in postoperative pain, sleep quality, and recovery outcomes in patients undergoing visual thoracoscopic surgery.

Objective: The purpose of our study was to investigate the effect of gender on postoperative pain, sleep quality, and recovery outcomes in patients undergoing VATS surgery under general anesthesia. Method: Perioperative peripheral blood inflammatory markers system inflammation Index (SII) was recorded for perioperative inflammatory response. The visual analog scale (VAS) was used to evaluate pain level. And the Athens Insomnia Scale (AIS) was evaluated on the night before surgery (sleep preop 1), the first night after surgery (sleep POD 1), and the third night after surgery (sleep POD 3) for postoperative sleep. Result: In this prospective cohort study, 79 males and 79 females were consecutively included. Females had significantly higher pain score (both rest and cough pain) compared to the males at 3 h after the surgery (3.85 ± 1.2 vs. 3.16 ± 1.1) (rest) (p < 0.001) and 5.10 ± 1.3 vs. 4.46 ± 1.6 (coughing) (p = 0.006)). Patients in the male group had significantly lower AIS scores than those in the female group at Sleep POD 1 and Sleep POD 3 (p = 0.024 and p = 0.045). And in both groups, postoperative SII was increased and statistically significant compared to preoperative SII (p < 0.001, respectively). Women presented higher levels of SII on the first day after surgery, and the increase of postoperative SII in females groups was significantly higher than that in male group when compared to preoperative SII (1806.33 ± 1314.8 vs 1430.55 ± 958.4) (p = 0.042). Conclusion: These findings highlight the complex multidimensional nature of postoperative pain, nausea and vomiting, sleep quality and the potential contributory role of sex in shaping these outcomes. Women had worse sleep quality, higher postoperative inflammatory response level and pain level than men.

Natural polysaccharide hydrogel with bioadhesion characters to synergistically enhance berberine's antibacterial effect by regulating the PTS system of Staphylococcus aureus.

The global spread of Staphylococcus aureus (S. aureus) not only causes significant economic losses but also poses a serious threat to public health. Consequently, there is an urgent need for multidimensional strategies to develop antimicrobial dressings to combat bacterial infections. In response, we have developed a plant polysaccharide antibacterial hydrogel formed through the self-assembly of edible Kudzu powder (KP) and the natural star molecule berberine (BBR). Rheological tests show that natural polysaccharide KP-BBR hydrogel (BBR@KP) exhibits excellent injectability and adhesion. And the degradation of the hydrogel exceeded 90 % within 3 days. The synergistic effect of these two ingredients enhances the antibacterial activity of BBR and can increase the MIC of BBR to 0.05 mM. Specifically, KP promotes the affinity of the Phosphoenolpyruvate Phosphotransferase System (PTS) of S. aureus, enabling KP, with its bioadhesive properties, to adhere to the bacterial surface and continuously release BBR. Subsequently, BBR effectively exerts its antibacterial effect by inhibiting the synthesis of histidine and isoleucine. Furthermore, the BBR@KP hydrogel exhibits negligible cytotoxicity and hemolytic toxicity, underscoring its favorable biosafety profile. This synergistic natural antibacterial hydrogel, formulated through a green and straightforward methodology, not only holds promise for broad clinical applications but also provides novel perspectives for the utilization and development of plant polysaccharides in the biomedical field.

Discovery of novel and potent sulfonamide derivatives as orally available drug for psoriasis.

The retinoid-related orphan receptor gamma-t (RORγt), a member of the nuclear receptor superfamily, functions as a ligand-dependent transcription factor. As a pivotal modulator in the development and functionality of T-helper 17 (Th17) cells, RORγt plays a crucial role in immune response regulation. Inverse agonists targeting RORγt demonstrate significant potential in modulating Th17 cell activity, offering a promising avenue for the development of therapeutics aimed at treating autoimmune diseases associated with Th17 dysregulation. GSK2981278 is a potent RORγt inverse agonist, but a drawback of GSK2981278 is its low pharmacokinetic profile, leading to a clinical failure. We have explored detailed structure-activity relationship of GSK2981278 trying to improve metabolic stability while maintaining RORγt activity. As a result, a novel series of sulfonamide derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. b14 had greatly improved In Vitro metabolic stability (T1/2 = 36.2 min) compared to GSK2981278 (T1/2 = 0.8 min). Oral dosing of compound b14 resulted in a dose-dependent suppression of IL-17A cytokine levels within a murine model of imiquimod-induced skin inflammation, underscoring its potential as a therapeutic intervention.

The multiple-action allosteric inhibition of TYK2 by deucravacitinib: Insights from computational simulations.

Participating in the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, TYK2 emerges as a promising therapy target in controlling various autoimmune diseases, including psoriasis and multiple sclerosis. Deucravacitinib (DEU) is a novel oral TYK2-specific inhibitor approved in 2022 that is clinically effective in moderate to severe psoriasis trials. Upon the AlphaFold2 predicted TYK2 pseudokinase domain (JH2) and kinase domain (JH1), we explored the details of the underlined allosteric inhibition mechanism on TYK2 JH2-JH1 with the aid of molecular dynamics simulation. Our results suggest that the allosteric inhibition of DEU on TYK2 is accomplished by affecting the JH2-JH1 interface and hampering the state transition and ATP binding in JH1. Particularly, DEU binding stabilized the autoinhibitory interface between JH2 and JH1 while disrupting the formation of the activation interface. As a result, the negative regulation of JH2 on JH1 was greatly enhanced. These findings offer additional details on the pseudokinase-dependent autoinhibition of the JAK kinase domain and provide theoretical support for the JH2-targeted drug discovery in JAK members.

Evaluating peritumoral and intratumoral radiomics signatures for predicting lymph node metastasis in surgically resectable non-small cell lung cancer.

Background: Whether lymph node metastasis in non-small cell lung cancer is critical to clinical decision-making. This study was to develop a non-invasive predictive model for preoperative assessing lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using radiomic features from chest CT images. Materials & methods: In this retrospective study, 247 patients with resectable non-small cell lung cancer (NSCLC) were enrolled. These individuals underwent preoperative chest CT scans that identified lung nodules, followed by lobectomies and either lymph node sampling or dissection. We extracted both intratumoral and peritumoral radiomic features from the CT images, which were used as covariates to predict the lymph node metastasis status. By using ROC curves, Delong tests, Calibration curve, and DCA curves, intra-tumoral-peri-tumoral model performance were compared with models using only intratumoral features or clinical information. Finally, we constructed a model that combined clinical information and radiomic features to increase clinical applicability. Results: This study enrolled 247 patients (117 male and 130 females). In terms of predicting lymph node metastasis, the intra-tumoral-peri-tumoral model (0.953, 95%CI 0.9272-0.9792) has a higher AUC compared to the intratumoral radiomics model (0.898, 95%CI 0.8553-0.9402) and the clinical model (0.818, 95%CI 0.7653-0.8709). The DeLong test shows that the performance of the Intratumoral and Peritumoral radiomics models is superior to that of the Intratumoral or clinical feature model (p <0.001). In addition, to increase the clinical applicability of the model, we combined the intratumoral-peritumoral model and clinical information to construct a nomogram. Nomograms still have good predictive performance. Conclusion: The radiomics-based model incorporating both peritumoral and intratumoral features from CT images can more accurately predict lymph node metastasis in NSCLC than traditional methods.

Stenting for symptomatic intracranial arterial stenosis with different qualifying arteries: a preplanned pooled individual patient data analysis.

BACKGROUND: The efficacy of percutaneous transluminal angioplasty and stenting (PTAS) relative to medical management in treating symptomatic intracranial arterial stenosis (ICAS) varies based on the qualifying artery. This study aims to evaluate PTAS compared with medical therapy alone in cases of ICAS involving the internal carotid artery (ICA), middle cerebral artery (MCA), vertebral artery (VA) and basilar artery (BA). METHODS: This study involves a thorough pooled analysis of individual patient data from two randomised controlled trials, evaluating the efficacy of PTAS in comparison to medical management for symptomatic ICAS with different qualifying arteries. The primary outcome was stroke or death within 30 days postenrolment, or stroke in the region of the qualifying artery beyond 30 days through 1 year. A methodology based on intention-to-treat was employed, and HR accompanied by 95% CIs were used to convey risk estimates. RESULTS: The data of 809 individuals were collected from Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial and China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis trial. Four hundred were designated for PTAS, while 409 were assigned to medical therapy alone. For the primary outcome, patients with symptomatic BA stenosis had a significantly higher risk of receiving PTAS compared with medical therapy (17.17% vs 7.77%; 9.40; HR, 2.38 (1.03 to 5.52); p=0.04). However, PTAS had no significant difference in patients with symptomatic ICA (26.67% vs 16.67%; HR, 1.68 (0.78 to 3.62); p=0.19), MCA (8.28% vs 9.79%; HR, 0.85 (0.42 to 1.74); p=0.66) and VA stenosis (9.52% vs 10.71%; HR, 0.91 (0.32 to 2.62); p=0.86) compared with medical therapy. CONCLUSIONS: PTAS significantly increases the risk of both short-term and long-term stroke in patients with symptomatic BA stenosis. Without significant technological advancements to mitigate these risks, PTAS offers limited benefits. For symptomatic ICA, MCA and VA stenosis, PTAS provided no significant advantage.

Chemical and Transcriptomic Analyses Provide New Insights into Key Genes for Ginsenoside Biosynthesis in the Rhizome of Panax japonicus C. A. Meyer.

Panax japonicus C. A. Meyer is renowned for its significant therapeutic effects and is commonly used worldwide. Its active ingredients, triterpenoid saponins, show variation in content among different tissues. The tissue-specific distribution of saponins is potentially related to the expression of vital genes in the biosynthesis pathway. In this study, the contents of five saponins (ginsenoside Ro, chikusetsusaponin IV, chikusetsusaponin IVa, ginsenoside Rg1, and ginsenoside Rb1) in three different tissues were determined by HPLC. Transcriptome sequencing analysis identified differentially expressed genes (DEGs) involved in triterpenoid saponin biosynthesis, highlighting significant correlations between saponin contents and the expression levels of 10 cytochrome p450 monooxygenase (CYP) and 3 UDP-glycosyltransferase (UGT) genes. Cloning, sequencing, and prokaryotic expression of UGT genes confirmed the molecular weights of UGT proteins. Gene sequence alignment and phylogenetic analysis provided preliminary insights into UGT gene functions. Meanwhile, the function of one UGT gene was characterized in the yeast. These findings advance our understanding of the triterpenoid saponin biosynthesis in P. japonicus and support future research in traditional Chinese medicine (TCM) and synthetic biology.

TMT-based quantitative proteomics unveils the protective mechanism of Polygonatum sibiricum polysaccharides on septic acute liver injury.

Polygonatum sibiricum polysaccharides (PSP) has been shown to possess multiple pharmacological functions. Our previous study found that PSP could protect against acute liver injury during sepsis via inhibiting inflammatory response. However, the underlying molecular mechanism by which PSP alleviates septic acute liver injury (SALI) remains unknown. Herein, TMT-based quantitative proteomics was utilized to explore the essential pathways and proteins involved in the protective effects of PSP on SALI. The results revealed that 632 and 176 differentially expressed proteins (DEPs) were identified in Model_vs_Control and PSP_vs_Model, respectively. GO annotation showed similar trends, suggesting that these DEPs were primarily involved in the cellular anatomical entity in Cellular Component, the cellular processe and the biological regulation in Biological Process, the binding and the catalytic activity in Molecular Function. Meanwhile, KEGG enrichment analysis implied that four common pathways, including the NF-κB signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway and the Toll-like receptor signaling pathway, were closely associated with the pathogenesis of sepsis among the top 20 remarkably enriched pathways in Model_vs_Control_up and PSP_vs_Model_down. Moreover, the levels of several common DEPs, including TLR2, IKKi, JunB and CXCL9, were validated by WB, which was in line with the results of proteomics. Therefore, the protective effects of PSP on SALI might exert via blocking the above-mentioned inflammation pathways. Significance: PSP, recognized as a key component of Polygonatum sibiricum, exhibits a range of pharmacological functions. Our previous study found that PSP could protect against SALI, yet failing to clarify the mechanism of action. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP. SIGNIFICANCE: PSP have been identified as the most crucial components of Polygonatum sibiricum with various pharmacological functions. Our previous study found that PSP could protect against SALI, but the mechanism of action remains unknown. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP.

Relationship matters: Using machine learning methods to predict the mental health severity of Chinese college freshmen during the pandemic period.

BACKGROUND: Pandemics act as stressors and may lead to frequent mental health disorders. College student, especially freshmen, are particularly susceptible to experiencing intense mental stress reactions during a pandemic. We aimed to identify stable and intervenable variables including academic, relationship and economic factors, and focused on their impact on mental health severity during the pandemic period. METHODS: We innovatively combined diverse machine learning methods, including XGBoost, SHAP, and K-means clustering, to predict the mental health severity of college freshmen. A total of 3281 college freshmen participated in the research. Discriminant analyses were performed on groups of participants with depression (PHQ-9), anxiety (GAD-7). All characteristic variables were selected based on their importance and interventionability. Further analyses were conducted with selected features to determine the optimal variable combination. RESULTS: XGBoost analysis revealed that relationship factors exhibited the highest predictive capacity for mental health severity among college freshmen (SHAPFamily Relationship = 0.373; SHAPPeer Support = 0.236). The impact of academic factors on college freshmen's mental health severity depended on their intricate interplay with relationship factors, resulting in complex interactive effects. These effects were heterogeneous among different subgroups. CONCLUSIONS: The proposed machine learning approach utilizing XGBoost, SHAP and K-means clustering methods provides a valuable tool to gain insights into the relative contributions of academic, relationship and economic factors to Chinese college freshmen's mental health severity during the COVID-19 pandemic. The result guide the development of targeted intervention measures tailored to meet specific requirements within each subgroup.

Causal Associations between Tea Consumption and Rapid Eye Movement Sleep Behavior Disorder: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely, REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. METHODS: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. RESULTS: In the MR analysis using the inverse-variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR = 0.046, 95% CI: 0.004-0.563, p = 0.016). The consistency of findings across maximum likelihood, MR Pleiotropy RESidual Sum and Outlier, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. CONCLUSIONS: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.

Effect of graphene oxide on carbon and nitrogen metabolism and growth of kidney bean at flowering stage.

Graphene oxide (GO) is a novel nanomaterial being applied in different fields, but was less used as foliar fertilizer in agriculture. We conducted a pot experiment to analyze the effects of foliar spraying GO from 0 (control), 50 (T1), 100 (T2), 150 (T3) and 200 mg·L-1 (T4) on the morphogenesis and carbon and nitrogen metabolism of kidney bean plants during the initiation of flowering to clarify the physiological effects of foliar spraying GO. The results showed that dry matter accumulation, the content of photosynthetic pigments, soluble sugars of T1 to T4 treatments, were significantly increased by 40.7%-43.4%, 10.4%-80.7%, 6.4%-9.1% in kidney bean plants compared with CK treatment, respectively. T3 treatment performed the best. Meanwhile, the activities of sucrose phosphate synthase, acid converting enzyme and neutral converting enzyme of T3 and T4 treatments were increased by 25.7%-45.5%, 17.4%-28.6%, and 14.7%-20.1%, and the activities of nitrate reductase, glutamine synthetase, and glutamate synthetase of T2 and T3 treatments were increased by 8.1%-15.2%, 11.5%-25.0%, and 89.7%-93.1%, respectively. In conclusion, foliar spraying of appropriate GO in early flowering stage of kidney bean could increase the content of photosynthetic pigments, improve the level of photosynthetic carbon and nitrogen metabolism, and increase dry matter accumulation. T3 treatment (150 mg·L-1) was the most effective in this study.

Best Practices for Designing and Testing Behavioral and Health Communication Interventions for Delivery in Private Facebook Groups: Tutorial.

Facebook, the most popular social media platform in the United States, is used by 239 million US adults, which represents 71% of the population. Not only do most US adults use Facebook but they also spend an average of 40 minutes per day on the platform. Due to Facebook's reach and ease of use, it is increasingly being used as a modality for delivering behavioral and health communication interventions. Typically, a Facebook-delivered intervention involves creating a private group to deliver intervention content for participants to engage with asynchronously. In many interventions, a counselor is present to facilitate discussions and provide feedback and support. Studies of Facebook-delivered interventions have been conducted on a variety of topics, and they vary widely in terms of the intervention content used in the group, use of human counselors, group size, engagement, and other characteristics. In addition, results vary widely and may depend on how well the intervention was executed and the degree to which it elicited engagement among participants. Best practices for designing and delivering behavioral intervention content for asynchronous delivery in Facebook groups are lacking, as are best practices for engaging participants via this modality. In this tutorial, we propose best practices for the use of private Facebook groups for delivery and testing the efficacy of behavioral or health communication interventions, including converting traditional intervention content into Facebook posts; creating protocols for onboarding, counseling, engagement, and data management; designing and branding intervention content; and using engagement data to optimize engagement and outcomes.

Precision molecular insights for prostate cancer prognosis: tumor immune microenvironment and cell death analysis of senescence-related genes by machine learning and single-cell analysis.

BACKGROUND: Prostate cancer (PCa) is a prevalent malignancy among men, primarily originating from the prostate epithelium. It ranks first in global cancer incidence and second in mortality rates, with a rising trend in China. PCa's subtle initial symptoms, such as urinary issues, necessitate diagnostic measures like digital rectal examination, prostate-specific antigen (PSA) testing, and tissue biopsy. Advanced PCa management typically involves a multifaceted approach encompassing surgery, radiation, chemotherapy, and hormonal therapy. The involvement of aging genes in PCa development and progression, particularly through the mTOR pathway, has garnered increasing attention. METHODS: This study aimed to explore the association between aging genes and biochemical PCa recurrence and construct predictive models. Utilizing public gene expression datasets (GSE70768, GSE116918, and TCGA), we conducted extensive analyses, including Cox regression, functional enrichment, immune cell infiltration estimation, and drug sensitivity assessments. The constructed risk score model, based on aging-related genes (ARGs), demonstrated superior predictive capability for PCa prognosis compared to conventional clinical features. High-risk genes positively correlated with risk, while low-risk genes displayed a negative correlation. RESULTS: An ARGs-based risk score model was developed and validated for predicting prognosis in prostate adenocarcinoma (PRAD) patients. LASSO regression analysis and cross-validation plots were employed to select ARGs with prognostic significance. The risk score outperformed traditional clinicopathological features in predicting PRAD prognosis, as evidenced by its high AUC (0.787). The model demonstrated good sensitivity and specificity, with AUC values of 0.67, 0.675, 0.696, and 0.696 at 1, 3, 5, and 8 years, respectively, in the GEO cohort. Similar AUC values were observed in the TCGA cohort at 1, 3, and 5 years (0.67, 0.659, 0.667, and 0.743). The model included 12 genes, with high-risk genes positively correlated with risk and low-risk genes negatively correlated. CONCLUSIONS: This study presents a robust ARGs-based risk score model for predicting biochemical recurrence in PCa patients, highlighting the potential significance of aging genes in PCa prognosis and offering enhanced predictive accuracy compared to traditional clinical parameters. These findings open new avenues for research on PCa recurrence prediction and therapeutic strategies.

Adult intensive care unit nurses' knowledge of and compliance barriers to evidence-based guidelines for prevention of ventilator-associated pneumonia: A cross-sectional survey.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICUs) and is a common cause of morbidity and mortality in intensive care patients. Previous studies show that insufficient knowledge and compliance barriers among nurses affect pneumonia. There have been no investigations into intensive care nurses' knowledge and compliance barriers to evidence-based guidelines (EBGs) for VAP prevention in county-level hospitals in China. AIM: To explore adult ICU nurses' knowledge and compliance barriers to EBGs for preventing VAP in county-level hospitals in Hunan Province, China, examine the correlation between knowledge and compliance barriers, and analyse associated factors. STUDY DESIGN: A cross-sectional electronic survey was conducted to focus on nurses' knowledge of and compliance barriers to EBGs for preventing VAP. RESULTS: A total of 386 valid questionnaires were collected, with a response rate of 97.47% (386/396 = 97.47%). The median scores for nurses' knowledge (out of 9) and compliance barriers (out of 8) to EBGs for preventing VAP were 7 (interquartile range: 5-8) and 3 (interquartile range: 2-4), respectively. Knowledge was negatively associated with compliance barriers (r = -0.437, p < .01). The results of the multiple linear regression analysis showed that hospital level, age, nurses' attendance at VAP training and years of experience in ICUs were related to the level of knowledge. Nurses' attendance at VAP training, age and years of experience in ICUs were associated with the level of compliance barriers. CONCLUSIONS: Intensive care nurses have satisfactory knowledge of EBGs for preventing VAP, but compliance barriers can be reduced. Better knowledge helps reduce the barriers to compliance among nurses. RELEVANCE TO CLINICAL PRACTICE: Nurse managers and nurse educators are suggested to examine nurses' knowledge and compliance barriers to EBGs for preventing VAP, develop personalized training plans, promote continuous education based on the latest EBGs and raise the nurse-patient ratio reasonably.

Polystyrene nano-plastics impede skeletal muscle development and induce lipid accumulation via the PPARγ/LXRß pathway in vivo and in vitro in mice.

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.

The INSIGHT platform: Enhancing NAD(P)-dependent specificity prediction for co-factor specificity engineering.

Enzyme specificity towards cofactors like NAD(P)H is crucial for applications in bioremediation and eco-friendly chemical synthesis. Despite their role in converting pollutants and creating sustainable products, predicting enzyme specificity faces challenges due to sparse data and inadequate models. To bridge this gap, we developed the cutting-edge INSIGHT platform to enhance the prediction of coenzyme specificity in NAD(P)-dependent enzymes. INSIGHT integrates extensive data from principal bioinformatics resources, concentrating on both NADH and NADPH specificities, and utilizes advanced protein language models to refine the predictions. This integration not only strengthens computational predictions but also meets the practical demands of high-throughput screening and optimization. Experimental validation confirms INSIGHT's effectiveness, boosting our ability to engineer enzymes for efficient, sustainable industrial and environmental processes. This work advances the practical use of computational tools in enzyme research, addressing industrial needs and offering scalable solutions for environmental challenges.

Randomized non-inferiority trial comparing an asynchronous remotely-delivered versus clinic-delivered lifestyle intervention.

OBJECTIVE: Lifestyle interventions are effective, but those delivered via in-person group meetings have poor scalability and reach. Research is needed to establish if remotely delivered lifestyle interventions are non-inferior to in-person delivered lifestyle interventions. METHODS: We conducted a randomized non-inferiority trial (N = 329) to compare a lifestyle intervention delivered remotely and asynchronously via an online social network (Get Social condition) to one delivered via in-person groups (Traditional condition). We hypothesized that the Get Social condition would result in a mean percent weight loss at 12 months that was not inferior to the Traditional condition. Additional outcomes included intervention delivery costs per pound lost and acceptability (e.g., convenience, support, modality preferences). RESULTS: At 12 months, no significant difference in percent weight change was observed between the Get Social and Traditional conditions (2.7% vs. 3.7%, p = 0.17) however, criteria for non-inferiority were not met. The Get Social condition costs $21.45 per pound lost versus $26.24 for the Traditional condition. A greater percentage of Get Social condition participants rated participation as convenient (65% vs 44%; p = 0.001). CONCLUSIONS: Results revealed a remotely-delivered asynchronous lifestyle intervention resulted in slightly less weight loss than an in-person version but may be more economical and convenient. TRIAL REGISTRATION: ClinicalTrials.gov NCT02646618; https://clinicaltrials.gov/ct2/show/NCT02646618 .

ThermoLink: Bridging disulfide bonds and enzyme thermostability through database construction and machine learning prediction.

Disulfide bonds, covalently formed by sulfur atoms in cysteine residues, play a crucial role in protein folding and structure stability. Considering their significance, artificial disulfide bonds are often introduced to enhance protein thermostability. Although an increasing number of tools can assist with this task, significant amounts of time and resources are often wasted owing to inadequate consideration. To enhance the accuracy and efficiency of designing disulfide bonds for protein thermostability improvement, we initially collected disulfide bond and protein thermostability data from extensive literature sources. Thereafter, we extracted various sequence- and structure-based features and constructed machine-learning models to predict whether disulfide bonds can improve protein thermostability. Among all models, the neighborhood context model based on the Adaboost-DT algorithm performed the best, yielding "area under the receiver operating characteristic curve" and accuracy scores of 0.773 and 0.714, respectively. Furthermore, we also found AlphaFold2 to exhibit high superiority in predicting disulfide bonds, and to some extent, the coevolutionary relationship between residue pairs potentially guided artificial disulfide bond design. Moreover, several mutants of imine reductase 89 (IR89) with artificially designed thermostable disulfide bonds were experimentally proven to be considerably efficient for substrate catalysis. The SS-bond data have been integrated into an online server, namely, ThermoLink, available at guolab.mpu.edu.mo/thermoLink.

Prevalence of intracerebral thrombus detected by optical coherence tomography in patients with posterior circulation stroke or transient ischemic attack.

BACKGROUND: The incidence of thrombosis in patients with intracranial atherosclerotic stenosis (ICAS) remains unclear. Optical coherence tomography (OCT) has the potential to explore the vessel wall structure of posterior-circulation ICAS because of its relatively straight anatomical structure compared with that of the anterior cerebral arteries. This study aimed to determine the prevalence and characteristics of thrombosis in the posterior-circulation ICAS using OCT. METHODS: This prospective study was conducted on 135 patients with posterior-circulation arterial stenosis who underwent OCT. All patients were symptomatic and had a severely stenotic lesion (70-99%) in the vetebrobasilar artery. The enrolled patients were classified according to the presence of in situ thrombus as defined by OCT. Clinical data and OCT characteristics were compared. RESULTS: Eighty-two patients diagnosed with posterior-circulation ICAS were enrolled. In situ thrombi were identified in 34 patients. Clinically, patients with in situ thrombus were more prone to cerebral infarctions than transient ischemic attacks. The percentage area of stenosis in the non-thrombus group was significantly lower than that in the thrombus group. The thrombus burden, mean flow area, mean thrombus area, maximum lipid arc, and mean lumen area were significantly different among white, red, and mixed thrombi. CONCLUSIONS: We achieved in vivo vessel wall structural analysis of posterior-circulation ICAS with the largest sample size. We also revealed the true incidence of in situ thrombosis and potential corresponding clinical events of posterior-circulation ICAS for the first time.

Engineered mouse H1 promoter mutants with superior RNA polymerase III activity.

Vectors incorporating the human H1 (hH1) promoter are being applied for RNA interference (RNAi) experiments and genome editing. Although extensive studies have been conducted on the hH1 promoter, our understanding of the mouse H1 promoter remains limited. In this study, we predicted the 163 bp mouse H1 (mH1) promoter and 84 bp mouse H1 core (mH1 core) promoter through global alignment and detected its RNA polymerase II (Pol II) and III activities through the expression of the EGFP and the abundance of artificial sequence, which were generally slightly weaker than those of the hH1 promoter. Furthermore, to boost its Pol III activity, we engineered various promoter mutants by introducing mutations or systematically swapping elements. Surprisingly, the Pol II activity of mH1 core mut5 with AT stretch was at least 2-fold greater than that of the wild type, making it a potential candidate for target protein expression purposes. Fortunately, the Pol III activities of mH1 mut1 and mH1 core mut5 were at least 1.5 times stronger than those of the parental promoters in human and mouse cell lines on account of AT stretch, as did the mH1 mut4 with AT stretch and proximal sequence element (PSE) and TATA box insertion mutations. We highly recommend these three promoters as valuable supplements to the type 3 Pol III promoter toolbox.