miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Development and application of a nitrogen oxides analyzer based on the cavity attenuated phase shift technique.

Nitrogen oxides (NOx) are crucial in tropospheric photochemical ozone (O3) production and oxidation capacity. Currently, the widely used NOx measurement technique is chemiluminescence (CL) (CL-NOx), which tends to overestimate NO2 due to atmospheric oxidation products of NOx (i.e., NOz). We developed and characterized a NOx measurement system using the cavity attenuated phase shift (CAPS) technique (CAPS-NOx), which is free from interferences with nitrogen-containing species. The NOx measured by the CAPS-NOx and CL-NOx analyzers were compared. Results show that both analyzers showed consistent measurement results for NO, but the NO2 measured by the CAPS-NOx analyzer (NO2_CAPS) was mostly lower than that measured by the CL-NOx analyzer (NO2_CL), which led to the deviations in O3 formation sensitivity regime and Ox (= O3 + NO2) sources (i.e., regional background and photochemically produced Ox) determined by the ozone production efficiencies (OPE) calculated from NO2_CL and NO2_CAPS. Overall, OPE_CL exceeded OPE_CAPS by 18.9%, which shifted 3 out of 13 observation days from the VOCs-limited to the transition regime when judging using OPE_CL, as compared to calculations using OPE_CAPS. During the observation period, days dominated by regional background Ox accounted for 46% and 62% when determined using NO2_CL and NO2_CAPS, respectively. These findings suggest that the use of the CL-NOx analyzer tends to underestimate both the VOCs-limited regime and the regional background Ox dominated days. The newly built CAPS-NOx analyzer here can promote the accurate measurement of NO2, which is meaningful for diagnosing O3 formation regimes and Ox sources.

Targeted immune cell therapy for hepatocellular carcinoma using expanded liver mononuclear cell-derived natural killer cells.

Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells in vitro, and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69+ in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions.

PRP improves the outcomes of autologous skin graft transplantation on the esophagus by promoting angiogenesis and inhibiting fibrosis and inflammation.

Background and Objectives: Autologous skin graft (ASG) transplantation is a challenging approach but a promising option for patients to prevent postoperative esophageal stricture. Nonetheless, the current strategies require improvement. We aimed to investigate the effectiveness of the injection of platelet-rich plasma (PRP) before skin graft transplantation for extensive esophageal defects after endoscopic resection. Methods: Standardized complete circular endoscopic resection (5 cm in length) was performed in 27 pigs allocated into 3 groups. The artificial ulcers were treated with a fully covered esophageal stent (control group), ASG (ASG group), and submucosal injection of PRP with ASG (PRP-ASG group). Macroscopic evaluation and histological analysis of the remolded esophagus were performed 7, 14, and 28 days after surgery. Results: The macroscopic evaluation indicated that submucosal injection of PRP before transplantation effectively promoted the survival rate of skin grafts and decreased the rate of mucosal contraction compared with those treated with ASG or stent alone. Histological analysis of submucosal tissue showed that this modified strategy significantly promoted wound healing of reconstructed tissues by enhancing angiogenesis, facilitating collagen deposition, and decreasing inflammation and fibrogenesis. Conclusions: These findings suggested that PRP might be used as a biological supplement to increase the esophageal skin graft survival rate and improve submucosal tissue remolding in a clinically relevant porcine model. With extremely low mucosal contraction, this novel combination strategy showed the potential to effectively prevent stenosis in extensive esophageal ulcers.

Identification and field verification of the aggregation pheromone components produced by male Holotrichia parallela Motschulsky (Coleoptera: Scarabaeidae).

BACKGROUND: The chafer beetle, Holotrichia parallela, causes damage to numerous economically significant crops worldwide. Adult beetles exhibit aggregation behavior likely mediated by a male-produced pheromone. Advancements in biological research technology have facilitated the identification of insect aggregation pheromones and promoted their applications as bait for trapping and monitoring pests. Currently, only a few active components of aggregation pheromones from Holotrichia species have been identified. However, the specific components of aggregation pheromones produced by H. parallela remain unknown. RESULT: In this study, we initially observed from Y-tube olfactometer assays that both male and female H. parallela were significantly attracted to volatiles emitted by males, but not to those from females. We then collected hindgut crude extracts of male adults and carried out gas chromatography-mass spectrometry analysis to identify potential aggregation pheromone components. Pentadecyl acetate, cis-13-docosenol, and behenic acid were identified as male-specific compounds in comparison to female extracts, serving as components of the aggregation pheromone in H. parallela. We further evaluated their attractiveness to H. parallea in both laboratory and field experiments. In laboratory settings, pentadecyl acetate, cis-13-docosenol, and behenic acid evoked significant responses to both males and females at specific concentrations, as evidenced by both electroantennography tests and behavioral bioassays. Under field conditions, traps baited with these three compounds captured significantly more H. parallela adults compared to control traps. CONCLUSION: In this study, we found that pentadecyl acetate, cis-13-docosenol, and behenic acid are specifically present in male H. parallela, serving as aggregation pheromones. Both laboratory and field-trapping experiments suggest their potential as monitoring and controlling tools against H. parallela adults. © 2024 Society of Chemical Industry.

In silico prediction of drug-induced nephrotoxicity: current progress and pitfalls.

INTRODUCTION: Due to its role in absorption and metabolism, the kidney is an important target for drug toxicity. Drug-induced nephrotoxicity (DIN) presents a significant challenge in clinical practice and drug development. Conventional methods for assessing nephrotoxicity have limitations, highlighting the need for innovative approaches. In recent years, in silico methods have emerged as promising tools for predicting DIN. AREAS COVERED: A literature search was performed using PubMed and Web of Science, from 2013 to February 2023 for this review. This review provides an overview of the current progress and pitfalls in the in silico prediction of DIN, which discusses the principles and methodologies of computational models. EXPERT OPINION: Despite significant advancements, this review identified issues accentuates the pivotal imperatives of data fidelity, model optimization, interdisciplinary collaboration, and mechanistic comprehension in sculpting the vista of DIN prediction. Integration of multiple data sources and collaboration between disciplines are essential for improving predictive models. Ultimately, a holistic approach combining computational, experimental, and clinical methods will enhance our understanding and management of DIN.

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). The use of corticosteroids as pretreatment might reduce immunotherapy efficacy. AIM: To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy (nIC) outcomes in locally advanced ESCC patients. METHODS: Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included. Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment. Antiallergic efficacy and safety were evaluated, as well as its impact on short-term efficacy [complete pathological response (pCR), major pathological response (MPR)] and long-term efficacy [overall survival (OS), progression-free survival (PFS)] of nIC. RESULTS: From September 2019 to September 2023, 142 patients were analyzed. No severe treatment-related adverse events or deaths were observed. Allergy occurrence was greater in the antihistamine group (P = 0.014). Short-term efficacy was not significantly different: The pCR rates were 29.9% and 40.0%, and the MPR rates were 57.9% and 65.7% in the dexamethasone and antihistamine groups, respectively. The long-term efficacy was not significantly different: The 2 years OS rates were 95.2% and 93.5%, and the 2 years PFS rates were 90.3% and 87.8%. Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the < 20 mg dexamethasone group, but PFS was significantly greater in the 20 mg dexamethasone group (93.9% vs 56.4%, P = 0.001). CONCLUSION: Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short- or long-term efficacy. Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

Preventive health behaviour differences across racial groups during the early stages of COVID-19.

Background: Throughout the COVID-19 pandemic, the practice of preventative health behaviours had been used disparately across different racial groups. This study seeks to identify any differences in preventative health behaviours across racial groups, controlling for other socio-demographic factors. Methods: A US national survey study was electronically conducted from July through November 2020, to measure racial/ethnic differences in health preventive behaviours about COVID-19. We performed 2-part regression models to assess whether preventive health behaviours differed by race and ethnicity. Specifically, we employed generalized logistic regressions for investigating the predictors of the use of complementary or alternative medicine (CAM), or stay-at-home strategy, then performed ordinal logistic regression to examine the predictors of social distancing, face mask wearing, and hand hygiene strategy practice. Results: The results show that non-White respondents were more likely to practice social distancing, mask wearing, and hand hygiene strategy to prevent COVID-19, compared to their White counterparts. Additionally, the findings indicate that individuals who experienced COVID-19-related racial abuse or depression had a higher likelihood of practicing preventive health behaviours. Discussion: We found ethnicity can be a predictor of health preventive behaviours, in accordance with previous research. The causes of these disparities will require further investigation in order to be addressed.

Construction and validation of a pancreatic cancer prognostic model based on genes related to the hypoxic tumor microenvironment.

BACKGROUND: Pancreatic cancer is one of the most lethal malignancies, characterized by poor prognosis and low survival rates. Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy, often failing to capture the complexity of the disease. The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment. This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer. AIM: To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules. METHODS: This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2, PLAU, and CCNA2. The results were validated in an independent dataset. This study also examined the correlations between the model risk score and various clinical features, components of the immune microenvironment, chemotherapeutic drug sensitivity, and metabolism-related pathways. Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines. RESULTS: The prognostic model demonstrated significant predictive value, with the risk score showing a strong correlation with clinical features: It was significantly associated with tumor grade (G) (b P < 0.01), moderately associated with tumor stage (T) (a P < 0.05), and significantly correlated with residual tumor (R) status (b P < 0.01). There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs. Furthermore, the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer. CONCLUSION: The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.

Enhancing transjugular intrahepatic portosystemic shunt procedure efficiency with digital subtraction angiography image overlay technology in esophagogastric variceal bleeding.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a pivotal intervention for managing esophagogastric variceal bleeding in patients with chronic hepatic schistosomiasis. AIM: To evaluate the efficacy of digital subtraction angiography image overlay technology (DIT) in guiding the TIPS procedure. METHODS: We conducted a retrospective analysis of patients who underwent TIPS at our hospital, comparing outcomes between an ultrasound-guided group and a DIT-guided group. Our analysis focused on the duration of the portosystemic shunt puncture, the number of punctures needed, the total surgical time, and various clinical indicators related to the surgery. RESULTS: The study included 52 patients with esophagogastric varices due to chronic hepatic schistosomiasis. Results demonstrated that the DIT-guided group experienced significantly shorter puncture times (P < 0.001) and surgical durations (P = 0.022) compared to the ultrasound-guided group. Additionally, postoperative assessments showed significant reductions in aspartate aminotransferase, B-type natriuretic peptide, and portal vein pressure in both groups. Notably, the DIT-guided group also showed significant reductions in total bilirubin (P = 0.001) and alanine aminotransferase (P = 0.023). CONCLUSION: The use of DIT for guiding TIPS procedures highlights its potential to enhance procedural efficiency and reduce surgical times in the treatment of esophagogastric variceal bleeding in patients with chronic hepatic schistosomiasis.

The effect of intraoperative goal-directed fluid therapy in patients under anesthesia for gastrointestinal surgery.

BACKGROUND: Intraoperative fluid management is an important aspect of anesthesia management in gastrointestinal surgery. Intraoperative goal-directed fluid therapy (GDFT) is a method for optimizing a patient's physiological state by monitoring and regulating fluid input in real-time. AIM: To evaluate the efficacy of intraoperative GDFT in patients under anesthesia for gastrointestinal surgery. METHODS: This study utilized a retrospective comparative study design and included 60 patients who underwent gastrointestinal surgery at a hospital. The experimental group (GDFT group) and the control group, each comprising 30 patients, received intraoperative GDFT and traditional fluid management strategies, respectively. The effect of GDFT was evaluated by comparing postoperative recovery, complication rates, hospitalization time, and other indicators between the two patient groups. RESULTS: Intraoperative blood loss in the experimental and control groups was 296.64 ± 46.71 mL and 470.05 ± 73.26 mL (P < 0.001), and urine volume was 415.13 ± 96.72 mL and 239.15 ± 94.69 mL (P < 0.001), respectively. The postoperative recovery time was 5.44 ± 1.1 days for the experimental group compared to 7.59 ± 1.45 days (P < 0.001) for the control group. Hospitalization time for the experimental group was 10.87 ± 2.36 days vs 13.65 ± 3 days for the control group (P < 0.001). The visual analogue scale scores of the experimental and control groups at 24 h and 48 h post-surgery were 3.38 ± 0.79 and 4.51 ± 0.86, and 2.05 ± 0.57 and 3.51 ± 0.97 (P < 0.001), respectively. The cardiac output of the experimental and control groups was 5.99 ± 1.04 L/min and 4.88 ± 1.17 L/min, respectively, while the pulse pressure variability for these two groups was 10.87 ± 2.36% and 17.5 ± 3.21%, respectively. CONCLUSION: The application of GDFT in gastrointestinal surgery can significantly improve postoperative recovery, reduce the incidence of complications, and shorten hospital stays.

Full-duplex dynamic TDMA scheme and clock synchronization and compensation method for the multi-user UWOC system.

In this Letter, we propose a full-duplex dynamic time division multiple access (FDD-TDMA) scheme for multi-user underwater wireless optical communication (UWOC). It supports full-duplex communication through wavelength division duplex (WDD) and enhances the system throughput using dynamic time resource allocation. Additionally, a clock synchronization and compensation method is proposed for precise clock synchronization without time-keeping. With the proposed FDD-TDMA scheme and the clock synchronization and compensation method, we establish a two-user UWOC system based on on-off keying (OOK) modulation. Experiments are conducted in a 10 m water pool environment. The experimental results show that the designed system can achieve a data rate of 25 Mbps without error codes and 40 Mbps with a bit error rate (BER) below the forward error correction (FEC) limit. The FDD-TDMA scheme notably improves the system throughput when communication demands among users are variable compared to the conventional time division multiple access (TDMA). Moreover, a reduction in phase deviations from microseconds to ten nanoseconds is achieved by the clock synchronization and compensation method.

Preoperative markers for identifying CT ≤2 cm solid nodules of lung adenocarcinoma based on image deep learning.

BACKGROUND: The solid pattern is a highly malignant subtype of lung adenocarcinoma. In the current era of transitioning from lobectomy to sublobar resection for the surgical treatment of small lung cancers, preoperative identification of this subtype is highly important for patient surgical approach selection and long-term prognosis. METHODS: A total of 1489 patients with clinical stage IA1-2 primary lung adenocarcinoma were enrolled. Based on patient clinical characteristics and lung imaging features obtained via deep learning, highly correlated diagnostic factors were identified through LASSO regression and decision tree analysis. Subsequently, a logistic model and nomogram were constructed. A restricted cubic spline (RCS) was used to calculate the optimal inflection point of quantitative data and the differences between the groups. RESULTS: The three-dimensional proportion of solid component (PSC), sex, and smoking status was identified as being highly correlated diagnostic factors for solid predominant adenocarcinoma. The logistic model had good prediction efficiency, and the area under the ROC curve was 0.85. Decision curve analysis demonstrated that the application of diagnostic factors can improve patient outcomes. RCS analysis indicated that the proportion of solid adenocarcinomas increased by 4.6 times when the PSC was ≥72%. A PSC of 72% is a good cutoff point. CONCLUSION: The preoperative diagnosis of solid-pattern adenocarcinoma can be confirmed by typical imaging features and clinical characteristics, assisting the thoracic surgeon in developing a more precise surgical plan.

Dihuangzicao Granules Regulate the AGE/RAGE/NF-κB Signaling Pathway to Inhibit Inflammation in Psoriatic Mice via Network Pharmacology and Experimental Validation.

AIM: Psoriasis is an immune-mediated skin disease that occurs worldwide and is characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological damage to psoriasis patients. The active ingredients in Dihuang Zicao granules (DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients of DHZCG and their potential mechanisms for treating psoriasis. METHODS: The effective components of DHZCG were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed. Important molecular biological processes and signaling pathways were screened via GO and KEGG analyses. Molecular docking of the active ingredients and key targets was performed via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group (M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining was performed to determine the pathological changes in the skin of each group of mice, and the Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒ PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was used to measure IL-1ß and TNF-a expression in skin tissues. RESULTS: Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding IL-6, TNF-a, AKT1, IL-1ß, TP53, NFKB1, BCL2, and MAPK3, were identified. Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL- 23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE signaling pathway. CONCLUSION: DHZCG reduces inflammation and alleviates psoriasis by downregulating the AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis for the development of drugs for psoriasis and for offering personalized treatment strategies for the clinical management of psoriasis.

MOF Nanosheet-Functionalized Poly(lactic acid) Meta-membranes for Long-Term Air Purification and Intelligent Monitoring.

The wide use of conventional polymeric air filters is causing a dramatically increasing accumulation of plastic and microplastic pollution. The development of poly(lactic acid) (PLA) fibrous membranes for efficient air purification is of important significance but frequently challenged by the rapid decay of filtration performance due to the intrinsically poor electret properties of PLA. Here, we propose an electroactivity promotion methodology, involving the one-step synthesis and homogeneous incorporation of high-dielectric ZIF-8 nanosheets (ZIFNSs), to facilitate interfacial polarization and fiber refinement during electrospinning of PLA nanofibers. The preparative electrospun PLA/ZIFNS meta-membranes exhibited an unusual combination of significantly reduced nanofiber diameter (∼462 nm), enhanced surface potential (approaching 10 kV), and increased surface activity and facilitated the formation of electroactive phases. With well-controlled morphological features, the highly electroactive PLA/ZIFNS meta-membranes exhibited exceptional filtration efficiencies for PM2.5 and PM0.3 (99.2 and 96.0%, respectively) even at the highest airflow rate of 85 L/min, in clear contrast to that of its pure PLA counterpart (only 79.3 and 74.6%). Arising from the increased electroactivity and active contact sites, remarkable triboelectric performance and self-charging mechanisms were demonstrated for the PLA/ZIFNS meta-membranes, contributing to long-term efficient PM0.3 filtration (97.5% for over 360 min). Moreover, as triggered by physiological activities like respiration and speaking, the electroactive PLA/ZIFNS meta-membranes enabled real-time monitoring with high sensitivity and specificity. The proposed strategy affords significant promotion of electroactivity and triboelectric performance for PLA nanofibers, which may motivate the development of ecofriendly protective membranes for respiratory healthcare and real-time monitoring.

Machine learning models based on CT radiomics features for distinguishing benign and malignant vertebral compression fractures in patients with malignant tumors.

BACKGROUND: Radiomics has become an important tool for distinguishing benign and malignant vertebral compression fractures (VCFs). It is more clinically significant to concentrate on patients who have malignant tumors and differentiate between benign and malignant VCFs. PURPOSE: To explore the value of multiple machine learning (ML) models based on CT radiomics features for differentiating benign and malignant VCFs in patients with malignant tumors. MATERIAL AND METHODS: This study retrospectively analyzed 78 patients with malignant tumors accompanied by VCFs, 45 patients with benign VCFs, and 33 patients with malignant VCFs. A total of 140 lesions (86 benign lesions, 54 malignant lesions) were ultimately included in this study. All patients were divided into training sets (n = 98) and validation sets (n = 42) according to the 7:3 ratio. The radiomics features were screened and dimensioned, and multiple radiomics ML models were constructed. The receiver operating characteristic (ROC) curve was performed to assess the diagnostic performance. RESULTS: Five radiomics features were included in the model. All the ML models built have good diagnostic efficiency, among which the support vector machine (SVM) model performs better. The area under the curve (AUC), sensitivity, specificity, and accuracy in the training set were 0.908, 0.816, 0.883, and 0.857, respectively, while those in the validation set were 0.911, 0.647, 0.92, and 0.81, respectively. CONCLUSION: A variety of ML models built based on CT radiomics features have good value for differentiating benign and malignant VCFs in malignant tumor patients, and the SVM model has a better performance.

Mechanisms of action and applications of Polygonatum sibiricum polysaccharide at the intestinal mucosa barrier: a review.

As a medicinal and edible homologous Chinese herb, Polygonatum sibiricum has been used as a primary ingredient in various functional and medicinal products. Damage to the intestinal mucosal barrier can lead to or worsen conditions such as type 2 diabetes and Alzheimer's disease. Traditional Chinese medicine and its bioactive components can help prevent and manage these conditions by restoring the integrity of the intestinal mucosal barrier. This review delves into the mode of action of P. sibiricum polysaccharide in disease prevention and management through the restoration of the intestinal barrier. Polysaccharide from P. sibiricum effectively treats conditions by repairing the intestinal mucosal barrier, offering insights for treating complex diseases and supporting the application of P. sibiricum in clinical settings.

Causal relationship between key genes and metabolic dysfunction-associated fatty liver disease risk mediated by immune cells: A Mendelian randomization and mediation analysis.

AIM: Non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease (MAFLD) remain challenging. We aimed to identify novel key genes as non-invasive biomarkers for MAFLD, elucidate causal relationships between biomarkers and MAFLD and determine the role of immune cells as potential mediators. MATERIALS AND METHODS: Utilizing published transcriptome data of patients with biopsy-proven MAFLD, we applied linear models for microarray data, least absolute shrinkage and selector operation (LASSO) regressions and receiver operating characteristic (ROC) curve analyses to identify and validate biomarkers for MAFLD. Using the expression quantitative trait loci database and a cohort of 778 614 Europeans, we used Mendelian randomization to analyse the causal relationships between key biomarkers and MAFLD. Additionally, mediation analysis was performed to examine the involvement of 731 immunophenotypes in these relationships. RESULTS: We identified 31 differentially expressed genes, and LASSO regression showed three hub genes, IGFBP2, PEG10, and P4HA1, with area under the receiver operating characteristic (AUROC) curve of 0.807, 0.772 and 0.791, respectively, for identifying MAFLD. The model of these three genes had an AUROC of 0.959 and 0.800 in the development and validation data sets, respectively. This model was also validated using serum-based enzyme-linked immunosorbent assay data from MAFLD patients and control subjects (AUROC: 0.819, 95% confidence interval: 0.736-0.902). PEG10 was associated with an increased MAFLD risk (odds ratio = 1.106, p = 0.032) via inverse variance-weighted analysis, and about 30% of this risk was mediated by the percentage of CD11c + CD62L- monocytes. CONCLUSIONS: The MAFLD panels have good diagnostic accuracy, and the causal link between PEG10 and MAFLD was mediated by the percentage of CD11c + CD62L- monocytes.

Pathogenicity and transcriptomic resolution in dengue virus serotype 1 infected AGB6 mouse model.

Dengue viruses are the causative agents of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, which are mainly transmitted by Aedes aegypti and Aedes albopictus mosquitoes, and cost billions of dollars annually in patient treatment and mosquito control. Progress in understanding DENV pathogenesis and developing effective treatments has been hampered by the lack of a suitable small pathological animal model. Until now, the candidate vaccine, antibody, and drug for DENV have not been effectively evaluated. Here, we analyzed the pathogenicity of DENV-1 in type Ⅰ and type Ⅱ interferon receptor-deficient mice (AGB6) by intraperitoneal inoculation. Infected mice showed such neurological symptoms as opisthotonus, hunching, ataxia, and paralysis of one or both hind limbs. Viremia can be detected 3 days after infection. It was found that 6.98 × 103 PFU or higher dose induce 100% mortality. To determine the cause of lethality in mice, heart, liver, spleen, lung, kidney, intestinal, and brain tissues were collected from AGB6 mice (at an attack dose of 6.98 × 103 PFU) for RNA quantification, and it was found that the viral load in brain tissues peaked at moribund states (14 dpi) and that the viral loads in the other tissues and organs decreased over time. Significant histopathologic changes were observed in brain tissue (hippocampal region and cerebral cortex). Hematological analysis showed hemorrhage and hemoconcentration in infected mice. DENV-1 can be isolated from the brain tissue of infected mice. Subsequently, brain tissue transcriptome sequencing was performed to assess host response characteristics in infected AGB6 mice. Transcriptional patterns in brain tissue suggest that aberrant expression of pro-inflammatory cytokines induces antiviral responses and tissue damage. Screening of hub genes and their characterization by qPCR and ELISA, it was hypothesized that IL-6 and IFN-γ might be the key factors in dengue virus-induced inflammatory response. Therefore, this study provides an opportunity to decipher certain aspects of dengue pathogenesis further and provides a new platform for drug, antibody, and vaccine testing.

Effect of paternal age on clinical outcomes of in vitro fertilization-embryo transfer cycles.

Purpose: This study aimed to investigate the impact of paternal age > 40 years on clinical pregnancy and perinatal outcomes among patients undergoing in vitro fertilization treatment. Methods: We selected 75 male patients (aged > 40 years) based on predefined inclusion and exclusion criteria. Propensity score matching was performed in a 1:3 ratio, resulting in a control group (aged ≤ 40 years) of 225 individuals. Various statistical tests, including the Mann-Whitney U test, Chi-square test, Fisher's exact test, and binary logistic regression, were used to analyze the association between paternal age and clinical outcomes. Results: We found no statistically significant differences in semen routine parameters, clinical pregnancy outcomes, and perinatal outcomes between paternal aged > 40 and ≤ 40 years. However, in the subgroup analysis, the live birth rate significantly decreased in those aged ≥ 45 compared to those aged 41-42 and 43-44 years (31.25% vs. 69.23% and 65%, respectively; all p < 0.05). Additionally, the clinical pregnancy rate was significantly lower among those aged ≥ 45 than among those aged 41-42 (43.75% vs. 74.36%; p=0.035). Conclusion: Paternal age ≥ 45 years was associated with lower live birth and clinical pregnancy rates.