Development of a piezo stack - laser Doppler vibrometer sensing approach for characterizing shear wave dispersion and local viscoelastic property distributions.

Laser Doppler vibrometry and wavefield analysis have recently shown great potential for nondestructive evaluation, structural health monitoring, and studying wave physics. However, there are limited studies on these approaches for viscoelastic soft materials, especially, very few studies on the laser Doppler vibrometer (LDV)-based acquisition of time-space wavefields of dispersive shear waves in viscoelastic materials and the analysis of these wavefields for characterizing shear wave dispersion and evaluating local viscoelastic property distributions. Therefore, this research focuses on developing a piezo stack-LDV system and shear wave time-space wavefield analysis methods for enabling the functions of characterizing the shear wave dispersion and the distributions of local viscoelastic material properties. Our system leverages a piezo stack to generate shear waves in viscoelastic materials and an LDV to acquire time-space wavefields. We introduced space-frequency-wavenumber analysis and least square regression-based dispersion comparison to analyze shear wave time-space wavefields and offer functions including extracting shear wave dispersion relations from wavefields and characterizing the spatial distributions of local wavenumbers and viscoelastic properties (e.g., shear elasticity and viscosity). Proof-of-concept experiments were performed using a synthetic gelatin phantom. The results show that our system can successfully generate shear waves and acquire time-space wavefields. They also prove that our wavefield analysis methods can reveal the shear wave dispersion relation and show the spatial distributions of local wavenumbers and viscoelastic properties. We expect this research to benefit engineering and biomedical research communities and inspire researchers interested in developing shear wave-based technologies for characterizing viscoelastic materials.

Therapeutic targeting of TNIK in papillary thyroid carcinoma: a novel approach for tumor growth suppression.

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. The pathology of PTC is far from clear. As a kinase that can be targeted, the role of TNIK in PTC has not been investigated. This study was focused on the effects and molecular mechanisms of TNIK in PTC. Both public datasets and clinical specimens were used to verify TNIK expression. The effects of TNIK were investigated in both cell lines and mice models. Transcriptome analysis was used to explore the underlying mechanism of TNIK. Immunofluorescence, wound healing, and qRT-PCR assays were used to validate the mechanism of TNIK in PTC. The therapeutic effects of TNIK inhibitor NCB-0846 were evaluated by flow cytometry, western blot, and subcutaneous xenografts mice. TNIK expression was upregulated in PTC tissues. TNIK knockdown could suppress cell proliferation and tumor growth in no matter cell models or nude mice. The transcriptome analysis, GO enrichment analysis, and GSEA analysis results indicated TNIK was highly correlated with cytoskeleton, cell motility, and Wnt pathways. The mechanistic studies demonstrated that TNIK regulated cytoskeleton remodeling and promoted cell migration. NCB-0846 significantly inhibited TNIK kinase activity, induced cell apoptosis, and activated apoptosis-related proteins in a dose-dependent manner. In addition, NCB-0846 inhibited tumor growth in tumor-bearing mice. In summary, we proposed a novel regulatory mechanism in which TNIK-mediated cytoskeleton remodeling and cell migration to regulate tumor progression in PTC. TNIK is a therapeutic target in PTC and NCB-0846 would act as a novel targeted drug for PTC therapy.

Single nucleotide polymorphisms in the KRT82 promoter region modulate irregular thickening and patchiness in the dorsal skin of New Zealand rabbits.

BACKGROUND: While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype. RESULTS: The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy - Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the - 600 to - 1200 segment, in which the four SNPs were located. CONCLUSIONS: The morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.

Assessing the Diagnostic Efficacy of Handgrip Dynamometry and Diaphragmatic Ultrasound in Intensive Care Unit-Acquired Weakness.

Objective: The aim of this study is to examine the diagnostic significance of using handgrip dynamometry and diaphragmatic ultrasound in intensive care unit-acquired weakness (ICU-AW). Methods: This study included patients who received mechanical ventilation in the ICU at the Fourth Hospital of Hebei Medical University from July to December 2020. We collected comprehensive demographic data and selected conscious patients for muscle strength and ICU-AW assessments. The evaluation comprised grip strength measurement and bedside ultrasound for diaphragmatic excursion (DE) and thickening fraction (DTF). Results were documented for comparative analysis between patient groups, focusing on the diagnostic efficacy of grip strength, DE, DTF, and their combined application in diagnosing ICU-AW. Results: A total of 95 patients were initially considered for inclusion in this study. Following the exclusion of 20 patients, a final cohort of 75 patients were enrolled, comprising of 32 patients (42.6%) diagnosed with ICU-AW and 43 patients (57.4%) classified as non-ICU-AW. Comparative analysis revealed that grip strength, DE, and DTF were significantly lower in the ICU-AW group (P < 0.05). Subgroup analysis specific to male patients demonstrated a noteworthy decrease in grip strength, DE, and DTF within the ICU-AW group (P < 0.05). Receiver operating characteristic curve analysis indicated statistically significant diagnostic value for ICU-AW with grip strength, DE, DTF, and grip strength and diaphragmatic ultrasound (P < 0.01). Furthermore, it was observed that the amalgamation of grip strength and diaphragmatic ultrasound significantly enhanced the diagnostic accuracy of ICU-AW in patients who are critically ill. Conclusion: Grip strength, DE, DTF, and the combined use of grip strength with diaphragm ultrasound demonstrated diagnostic efficacy in ICU-AW. Notably, the integration of grip strength with diaphragm ultrasound exhibited a heightened capacity to enhance the diagnostic value specifically in patients diagnosed who are critically ill with ICU-AW.

The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development.

Animal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, ACE2 with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR-Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3×105 PFU) or low (2.5×102 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by all variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.

Proton pump inhibitors stabilize the expression of PD-L1 on cell membrane depending on the phosphorylation of GSK3ß.

BACKGROUND: Preclinical and clinical evidence indicates that proton pump inhibitors (PPIs) may indirectly diminish the microbiome diversity, thereby reducing the effectiveness of immune checkpoint inhibitors (ICIs). Conversely, recent publications have shown that PPIs could potentially enhance the response to ICIs. The precise mechanism through which PPIs modulate the ICIs remains unclear. In this study, we discovered a novel molecular function of PPIs in regulating immune invasion, specifically through inducing PD-L1 translocation in various tumor cells. METHODS: C57BL/6 mice subcutaneous transplantation model is used to verify the potential efficacy of PPIs and PD-L1 antibody. Western blotting analysis and phosphorylated chip are used to verify the alteration of PD-L1-related pathways after being treated with PPIs. The related gene expression is performed by qRT-PCR and luciferase reporter analysis. We also collected 60 clinical patients diagnosed with esophageal cancer or reflux esophagitis and then detected the expression of PD-L1 in the tissue samples by immunohistochemistry. RESULTS: We observed that the IC50 of tumor cells in response to PPIs was significantly higher than that of normal epithelial cells. PPIs significantly increased the expression of PD-L1 on cell membrane at clinically relevant concentrations. Furthermore, pre-treatment with PPIs appeared to synergize the efficiency of anti-PD-L1 antibodies in mouse models. However, PPI administration did not alter the transcription or total protein level of PD-L1 in multiple tumor cells. Using a phosphorylated protein chip, we identified that PPIs enhanced the phosphorylation of GSK3ß, then leading to PD-L1 protein translocation to the cell membranes. The capacity of PPIs to upregulate PD-L1 was negated following GSK3ß knockout. Furthermore, our clinical data showed that the PPIs use resulted in increased PD-L1 expression in esophageal cancer patients. CONCLUSION: We mainly address a significant and novel mechanism that the usage of PPIs could directly induce the expression of PD-L1 by inducing GSK3ß phosphorylation and facilitate primary tumor progression and metastasis.

Enhancing resource utilization: A novel method for effective separation of residual film and impurities in cotton fields.

This study addresses the challenge of incomplete separation of mechanically recovered residual films and impurities in cotton fields, examining their impact on resource utilization and environmental pollution. It introduces an innovative screening method that combines pneumatic force and mechanical vibration for processing crushed film residue mixtures. A double-action screening device integrating pneumatic force and a key-type vibrating screen was developed. The working characteristics of this device were analyzed to explore the dynamic characteristics and kinematic laws of the materials using theoretical analysis methods. This led to the revelation of the screening laws of residual films and impurities. Screening tests were conducted using the Central Composite Design method, considering factors such as fan outlet, fan speed, vibration frequency of the screen, and feeding amount, with the impurity-rate-in-film (Q) and film-content-in-impurity (W) as evaluation indexes. The significant influence of each factor on the indexes was determined, regression models between the test factors and indexes were established, and the effect laws of key parameters and their significant interaction terms on the indexes were interpreted. The optimal combination of working parameters for the screening device was identified through multivariable optimization methods. Validation tests under this optimal parameters combination showed that the impurity-rate-in-film was 3.08% and the film-content-in-impurity was 1.94%, with average errors between the test values and the predicted values of 3.36% and 5.98%, respectively, demonstrating the effectiveness of the proposed method. This research provides a novel method and technical reference for achieving effective separation of residual film and impurities, thereby enhancing resource utilization.

Androcin 18-1, a novel scorpion-venom peptide, shows a potent antitumor activity against human U87 cells via inducing mitochondrial dysfunction.

Scorpion venom is a potent natural source for antitumor drug development due to the multiple action modes of anticancer components. Although the sequence of Androcin 18-1 has been identified from the transcriptome profile of the scorpion venom Androctonus bicolor, its bioactivity remains unclear. In this study, we described the antitumor mechanism whereby Androcin 18-1 inhibits the proliferation and induces apoptosis by inducing cell membrane disruption, ROS accumulation, and mitochondrial dysfunction in human U87 glioblastoma cells. Moreover, Androcin 18-1 could suppress cell migration via the mechanisms associated with cytoskeleton disorganization and MMPs/TIMPs expression regulation. The discovery of this work highlights the potential application of Androcin 18-1 in drug development for glioblastoma treatment.

Translational selenium nanoparticles boost GPx1 activation to reverse HAdV-14 virus-induced oxidative damage.

Human adenovirus (HAdV) can cause severe respiratory infections in immunocompromised patients, but its clinical treatment is seriously limited by side effects of drugs such as poor efficacy, low bioavailability and severe nephrotoxicity. Trace element selenium (Se) has been found will affect the disease progression of pneumonia, but its antivirus efficacy could be improved by speciation optimization. Therefore, herein we performed anti-HAdV effects of different Se speciation and found that lentinan (LNT)-decorated selenium nanoparticles (SeNPs) exhibited low cytotoxicity and excellent anti-HAdV antiviral activity. Furthermore, SeNPs@LNT reduced the HAdV infection-induced mitochondrial damage and excessive production of reactive oxygen species (ROS). It was also involved in the repair of host cell DNA damage and inhibition of viral DNA replication. SeNPs@LNT inhibited HAdV-induced apoptosis mainly by modulating the p53/Bcl-2 apoptosis signaling pathway. In vivo, SeNPs@LNT replenished Se by targeting the infected site through the circulatory system and was involved in the synthesis of Glutathione peroxidase 1 (GPx1). More importantly, GPx1 played an antioxidant and immunomodulatory role in alleviating HAdV-induced inflammatory cytokine storm and alleviating adenovirus pneumonia in Se-deficient mice. Collectively, this study provides a Se speciation of SeNPs@LNT with anti-HAdV activity, and demonstrate that SeNPs@LNT is a promising pharmaceutical candidate for the treatment of HAdV.

Incremental value of automatically segmented perirenal adipose tissue for pathological grading of clear cell renal cell carcinoma: a multicenter cohort study.

OBJECTIVES: Accurate preoperative prediction of the pathological grade of clear cell renal cell carcinoma (ccRCC) is crucial for optimal treatment planning and patient outcomes. This study aims to develop and validate a deep-learning (DL) algorithm to automatically segment renal tumours, kidneys, and perirenal adipose tissue (PRAT) from computed tomography (CT) images and extract radiomics features to predict the pathological grade of ccRCC. METHODS: In this cross-ethnic retrospective study, a total of 614 patients were divided into a training set (383 patients from the local hospital), an internal validation set (88 patients from the local hospital), and an external validation set (143 patients from the public dataset). A two-dimensional TransUNet-based DL model combined with the train-while-annotation method was trained for automatic volumetric segmentation of renal tumours, kidneys, and visceral adipose tissue (VAT) on images from two groups of datasets. PRAT was extracted using a dilation algorithm by calculating voxels of VAT surrounding the kidneys. Radiomics features were subsequently extracted from three regions of interest of CT images, adopting multiple filtering strategies. The least absolute shrinkage and selection operator (LASSO) regression was used for feature selection, and the support vector machine (SVM) for developing the pathological grading model. Ensemble learning was used for imbalanced data classification. Performance evaluation included the Dice coefficient for segmentation and metrics such as accuracy and area under curve (AUC) for classification. The WHO/International Society of Urological Pathology (ISUP) grading models were finally interpreted and visualized using the SHapley Additive exPlanations (SHAP) method. RESULTS: For automatic segmentation, the mean Dice coefficient achieved 0.836 for renal tumours and 0.967 for VAT on the internal validation dataset. For WHO/ISUP grading, a model built with features of PRAT achieved a moderate AUC of 0.711 (95% CI, 0.604-0.802) in the internal validation set, coupled with a sensitivity of 0.400 and a specificity of 0.781. While model built with combination features of the renal tumour, kidney, and PRAT showed an AUC of 0.814 (95% CI, 0.717-0.889) in the internal validation set, with a sensitivity of 0.800 and a specificity of 0.753, significantly higher than the model built with features solely from tumour lesion (0.760; 95% CI, 0.657-0.845), with a sensitivity of 0.533 and a specificity of 0.767. CONCLUSION: Automated segmentation of kidneys and visceral adipose tissue (VAT) through TransUNet combined with a conventional image morphology processing algorithm offers a standardized approach to extract PRAT with high reproducibility. The radiomics features of PRAT and tumour lesions, along with machine learning, accurately predict the pathological grade of ccRCC and reveal the incremental significance of PRAT in this prediction.

Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome.

Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood-brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress.

Regulation of Hair Follicle Growth and Development by Different Alternative Spliceosomes of FGF5 in Rabbits.

This study investigated the regulatory effect of alternative spliceosomes of the fibroblast growth factor 5 (FGF5) gene on hair follicle (HF) growth and development in rabbits. The FGF5 alternative spliceosomes (called FGF5-X1, FGF5-X2, FGF5-X3) were cloned. The overexpression vector and siRNA of spliceosomes were transfected into dermal papilla cells (DPCs) to analyze the regulatory effect on DPCs. The results revealed that FGF5-X2 and FGF5-X3 overexpression significantly decreased LEF1 mRNA expression (p < 0.01). FGF5-X1 overexpression significantly reduced CCND1 expression (p < 0.01). FGF5-X1 and FGF5-X2 possibly downregulated the expression level of FGF2 mRNA (p < 0.05), and FGF5-X3 significantly downregulated the expression level of FGF2 mRNA (p < 0.01). The FGF5 alternative spliceosomes significantly downregulated the BCL2 mRNA expression level in both cases (p < 0.01). FGF5-X1 and FGF5-X2 significantly increased TGFß mRNA expression (p < 0.01). All three FGF5 alternative spliceosomes inhibited DPC proliferation. In conclusion, the expression profile of HF growth and development-related genes can be regulated by FGF5 alternative spliceosomes, inhibiting the proliferation of DPCs and has an influence on the regulation of HF growth in rabbits. This study provides insights to further investigate the mechanism of HF development in rabbits via FGF5 regulation.

Prevalence and related factors of sleep quality among Chinese undergraduates in Jiangsu Province: multiple models' analysis.

Background and aims: In China, a significant number of undergraduates are experiencing poor sleep quality. This study was designed to investigate the prevalence of poor sleep quality and identify associated factors among undergraduates in Jiangsu Province, China. Methods: A total of 8,457 participants were collected in 2022 using whole-group convenience sampling. The factors studied included basic demographics, family and social support, personal lifestyles, physical and mental health, mobile phone addiction index (MPAI), and the Connor-Davidson resilience scale (CD-RISC). The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Four models, including weighted multiple linear regression, binary logistic regression, weighted linear mixed model, and logistic regression with random effects, were applied to identify associated factors for sleep quality. Results: Of the 8,457 participants analyzed, 26.64% (2,253) were classified into the poor sleep quality group with a PSQI score >7. No significant relationship was found between sleep quality and gender, native place, economic level of family, physical exercise, dormitory light, dormitory hygiene, and amativeness matter. Risk factors for sleep quality identified by the four models included lower CD-RISC, higher MPAI, fourth grade or above, smoking, drinking, greater academic pressure, greater employment pressure, roommate sleeping late, noisy dormitory, poorer physical health status, poorer mental health status, and psychological counseling. Conclusions: These findings provide valuable insights for university administrators, enabling them to better understand the risk factors associated with poor sleep quality in undergraduates. By identifying these factors, administrators can provide targeted intervention measures and counseling programs to improve students' sleep quality.

Fat fraction quantification with MRI estimates tumor proliferation of hepatocellular carcinoma.

Purpose: To assess the utility of fat fraction quantification using quantitative multi-echo Dixon for evaluating tumor proliferation and microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: A total of 66 patients with resection and histopathologic confirmed HCC were enrolled. Preoperative MRI with proton density fat fraction and R2* mapping was analyzed. Intratumoral and peritumoral regions were delineated with manually placed regions of interest at the maximum level of intratumoral fat. Correlation analysis explored the relationship between fat fraction and Ki67. The fat fraction and R2* were compared between high Ki67(>30%) and low Ki67 nodules, and between MVI negative and positive groups. Receiver operating characteristic (ROC) analysis was used for further analysis if statistically different. Results: The median fat fraction of tumor (tFF) was higher than peritumor liver (5.24% vs 3.51%, P=0.012). The tFF was negatively correlated with Ki67 (r=-0.306, P=0.012), and tFF of high Ki67 nodules was lower than that of low Ki67 nodules (2.10% vs 4.90%, P=0.001). The tFF was a good estimator for low proliferation nodules (AUC 0.747, cut-off 3.39%, sensitivity 0.778, specificity 0.692). There was no significant difference in tFF and R2* between MVI positive and negative nodules (3.00% vs 2.90%, P=0.784; 55.80s-1 vs 49.15s-1, P=0.227). Conclusion: We infer that intratumor fat can be identified in HCC and fat fraction quantification using quantitative multi-echo Dixon can distinguish low proliferative HCCs.

CRISPR/Cas9-mediated ebony knockout causes melanin pigmentation and prevents moth Eclosion in Ectropis grisescens.

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive tea pest in China. Mimesis, characterized by changing body color, is an important trait of E. grisescens larvae. Hence, identifying melanin pathway-related genes may contribute to developing new pest control strategies. In the present study, we cloned Egebony, a gene potentially involved in melanin pigmentation in E. grisescens, and subsequently conducted CRISPR/Cas9-mediated targeted mutagenesis of Egebony to analyze its role in pigmentation and development. At the larvae, prepupae, and pupae stages, Egebony-knockout individuals exhibited darker pigmentation than the wild-type. However, Egebony knockout did not impact the colors of sclerotized appendants, including ocelli, setae, and claws. While mutant pupae could successfully develop into moths, they were unable to emerge from the puparium. Notably, embryo hatchability and larval survival of mutants remained normal. Further investigation indicated that mutant pupae exhibited significantly stronger shearing force than the wild-type, with the pigmented layer of mutant pupae appearing darker and thicker. Collectively, these results suggest that the loss of Egebony might increase the rigidity of the puparium and prevent moth eclosion. This study provides new insights into understanding the function and diversification of ebony in insect development and identifies a lethal gene that can be manipulated for developing effective pest control strategies.

Optimized BEAC conditioning regimen improves clinical outcomes of autologous hematopoietic stem cell transplantation in non-Hodgkin lymphomas.

The conditioning regimen is an important part of autologous hematopoietic stem cell transplantation (ASCT). We explored the efficacy and safety of an optimized BEAC (adjusted-dose, intermediate-dose cytarabine and reduced-dose cyclophosphamide, AD-BEAC) conditioning regimen for non-Hodgkin lymphoma (NHL). A total of 141 NHL patients received AD-BEAC or a standard-dose BEAC (SD-BEAC) conditioning regimen from January 2007 to December 2017, and 104 patients were included in the study after 1:1 propensity matching. The 5-year overall survival (OS) and progression free survival (PFS) rates were significantly higher with AD-BEAC than with SD-BEAC (82.7% vs. 67.3%, P = 0.039; 76.9% vs. 57.7%, P = 0.039). Transplant-related mortality (TRM) was 3.8% in both the AD-BEAC and SD-BEAC groups. The AD-BEAC group had lower incidence of oral ulcers and cardiotoxicity than the SD-BEAC group. An optimized BEAC conditioning regimen is an effective conditioning regimen for ASCT in NHL with acceptable toxicity, that is more effective and safer than a standard BEAC conditioning regimen.

N-Acetylcysteine Alleviates D-Galactose-Induced Injury of Ovarian Granulosa Cells in Female Rabbits by Regulating the PI3K/Akt/mTOR Signaling Pathway.

The ovary plays a crucial role in the reproductive system of female animals. Ovarian problems such as ovarian insufficiency, premature aging, polycystic ovary syndrome, and ovarian cysts may lead to ovulation disorders, abnormal hormone secretion, or luteal dysfunction, thereby increasing the risk of infertility and abortion. Only when the ovarian function and other organs in the reproductive system remain healthy and work normally can female animals be ensured to carry out reproductive activities regularly, improve the pregnancy rate and litter size, promote the healthy development of the fetus, and then improve their economic value. The follicle, as the functional unit of the ovary, is composed of theca cells, granulosa cells (GCs), and oocytes. GCs are the largest cell population and main functional unit in follicles and provide the necessary nutrients for the growth and development of follicles. N-acetylcysteine (NAC) is a prevalent and cell-permeable antioxidant molecule that effectively prevents apoptosis and promotes cellular survival. Over the past few years, its function in boosting reproductive performance in animals at the cellular level has been widely acknowledged. However, its specific role and mechanism in influencing GCs is yet to be fully understood. The objective of this study was to examine the effects of NAC on ovarian damage in female rabbits. For this purpose, D-galactose (D-gal) was first used to establish a model of damaged GCs, with exposure to 1.5 mg/mL of D-gal leading to substantial damage. Subsequently, varying concentrations of NAC were introduced to determine the precise mechanism through which it influences cell damage. Based on the results of the Cell Counting Kit-8 assay, flow cytometry, and Western blotting, it was found that 0.5 mg/mL of NAC could significantly suppress cell apoptosis and promote proliferation. In particular, it decreased the expression levels of Bax, p53, and Caspase-9 genes, while concurrently upregulating the expression of the BCL-2 gene. Moreover, NAC was found to alleviate intracellular oxidative stress, suppress the discharge of mitochondrial Cytochrome c, and boost the enzymatic activities of CAT (Catalase), GSH (Glutathione), and SOD (Superoxide dismutase). RNA sequencing analysis subsequently underscored the critical role of the PI3K/Akt/mTOR pathway in governing proliferation and apoptosis within GCs. These findings demonstrated that NAC could significantly influence gene expression within this pathway, thereby clarifying the exact relationship between the PI3K/Akt/mTOR signaling cascade and the underlying cellular processes controlling proliferation and apoptosis. In conclusion, NAC can reduce the expression of Bax, p53, and Caspase-9 genes, inhibit the apoptosis of GCs, improve cell viability, and resist D-gal-induced oxidative stress by increasing the activity of CAT, GSH, and SOD. The molecular mechanism of NAC in alleviating D-gal-induced ovarian GC injury in female rabbits by regulating the PI3K/Akt/mTOR signaling pathway provides experimental evidence for the effect of NAC on animal reproductive function at the cellular level.

Convolutional Neural Network-Based Pattern Recognition of Partial Discharge in High-Speed Electric-Multiple-Unit Cable Termination.

Partial discharge detection is considered a crucial technique for evaluating insulation performance and identifying defect types in cable terminals of high-speed electric multiple units (EMUs). In this study, terminal samples exhibiting four typical defects were prepared from high-speed EMUs. A cable discharge testing system, utilizing high-frequency current sensing, was developed to collect discharge signals, and datasets corresponding to these defects were established. This study proposes the use of the convolutional neural network (CNN) for the classification of discharge signals associated with specific defects, comparing this method with two existing neural network (NN)-based classification models that employ the back-propagation NN and the radial basis function NN, respectively. The comparative results demonstrate that the CNN-based model excels in accurately identifying signals from various defect types in the cable terminals of high-speed EMUs, surpassing the two existing NN-based classification models.

Purinergic Astrocyte Signaling Driven by TNF-α After Cannabidiol Administration Restores Normal Synaptic Remodeling Following Traumatic Brain Injury.

Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca2+ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.

Evaluation of multiplexed sensitivity encoding diffusion-weighted imaging in detecting uterine lesions: Image quality optimization.

PURPOSE: To compare the image quality of multiplexed sensitivity-encoding diffusion-weighted imaging (MUSE-DWI) and single-shot echo-planar imaging (SS-EPI-DWI) techniques in uterine MRI. METHODS: Eighty-eight eligible patients underwent MUSE-DWI and SS-EPI-DWI examinations simultaneously using a 3.0 T MRI system. Two radiologists independently performed quantitative and qualitative analysis of the two groups of images using a double-blind method. The weighted Kappa test was used to evaluate the interobserver agreement. Wilcoxon's rank sum test was used for qualitative parameters, and paired t-test was used for quantitative parameters. Spearman rank correlation analysis was used to obtained correlation between pathological results and mean apparent diffusion coefficient (ADC) value. RESULTS: The qualitative and quantitative analysis of the images by the two radiologists were in good or excellent agreement, with weighted kappa value ranging from 0.636 to 0.981. The scores of total subjective image quality (15.4 ± 0.99) and signal-to-noise ratio (158.99 ± 60.71) of MUSE-DWI were significantly higher than those of SS-EPI-DWI (12.93 ± 1.62 P < 0.001; 130.23 ± 48.29 P < 0.05). It effectively reduced image distortion and artifact, and had better lesion conspicuity. There was no significant difference in contrast-to-noise ratio score and average ADC values between the two DWI sequences. The average ADC values of the two DWI sequences were highest in the normal uterus group and lowest in the endometrial cancer group, with statistically significant differences among groups (P < 0.01). In addition, the average ADC values of the two DWI sequences were negatively correlated with the type of lesions, decreasing with the malignancy of the lesions (r = -0.805 P < 0.01, r = -0.815 P < 0.01). CONCLUSION: Compared to SS-EPI-DWI, MUSE-DWI can significantly reduce distortion, artifacts, and fuzziness in MRI of uterine lesions, which is more conducive to lesion detection.