Association between Ward's triangle bone mineral density levels and abdominal aortic calcification: Data from the national health and nutrition examination survey 2013-2014.

BACKGROUND & AIMS: Despite extensive research into the cardiovascular implications of abdominal aortic calcification (AAC), there is a scarcity of robust studies exploring its association with Ward's triangle bone mineral density (BMD). This study aimed to evaluate this relationship in a nationally representative sample and compare the predictive value with femoral neck BMD and total femur BMD. METHODS: We conducted a cross-sectional analysis of 2013-2014 National Health and Nutrition Examination Survey (NHANES) data, utilizing a complex, stratified, multistage, cluster sampling design. BMD measurements at Ward's triangle, femoral neck, and total femur were assessed using DXA scans. AAC severity was defined by a Kauppila score of ≥5. Predictors of AAC-24 scores were identified through correlation and linear regression models. Stratified regression and restricted cubic splines were applied to explore subgroup and dose-response relationships. RESULTS: Of the 2965 participants representing 116, 562, 500 individuals in the U.S., 11 % had severe AAC. Ward's triangle BMD showed a significant negative association with AAC-24 scores (ß = -1.90, 95 % CI: -2.80 to -1.00, P < 0.002) and a reduced risk of severe AAC (OR = 0.85, 95 % CI: 0.76 to 0.95, P = 0.010). Non-linear associations were observed between Ward's triangle BMD and AAC outcomes. Ward's triangle BMD outperformed femoral neck and total femur BMD in predicting AAC. CONCLUSIONS: Higher Ward's triangle BMD is linked to lower odds of severe AAC, highlighting its potential for improved early detection of AAC over femoral neck and total femur BMD. Healthcare providers should consider the implications of reduced Ward's triangle BMD for systemic atherosclerosis and recommend early AAC screening for enhanced cardiovascular risk management.

The dynamic immune response of the liver and spleen in leopard coral grouper (Plectropomus leopardus) to Vibrio harveyi infection based on transcriptome analysis.

Leopard coral grouper (Plectropomus leopardus) is one of the most important cultured fish in the Pacific and Indian oceans. Vibrio harveyi is a serious pathogen causing serious skin ulceration and high mortality in P. leopardus. To gain more insight into the tissue-specific and dynamic immune regulation process of P. leopardus in response to V. harveyi infection, RNA sequencing (RNA-seq) was used to examine the transcriptome profiles in the spleen and liver at 0, 6, 12, 24, 48, and 72 h post-infection. The upregulated differentially expressed genes (DEGs) were predominantly involved in the immune response in the spleen and liver at the early infection stage (6-12 h), and downregulated DEGs were mainly involved in metabolic processes in the liver at the early and middle infection stage (6-48 h). Moreover, an overview of the immune response of P. leopardus against V. harveyi was exhibited including innate and adaptive immune-related pathways. Afterwards, the results of WGCNA analysis in the spleen indicated that TAP2, IRF1, SOCS1, and CFLAR were the hub genes closely involved in immune regulation in the gene co-expression network. This study provides a global picture of V. harveyi-induced gene expression profiles of P. leopardus at the transcriptome level and uncovers a set of key immune pathways and genes closely linked to V. harveyi infection, which will lay a foundation for further study the immune regulation of bacterial diseases in P. leopardus.

Lightweight CNN combined with knowledge distillation for the accurate determination of black tea fermentation degree.

Black tea is the second most common type of tea in China. Fermentation is one of the most critical processes in its production, and it affects the quality of the finished product, whether it is insufficient or excessive. At present, the determination of black tea fermentation degree completely relies on artificial experience. It leads to inconsistent quality of black tea. To solve this problem, we use machine vision technology to distinguish the degree of fermentation of black tea based on images, this paper proposes a lightweight convolutional neural network (CNN) combined with knowledge distillation to discriminate the degree of fermentation of black tea. After comparing 12 kinds of CNN models, taking into account the size of the model and the performance of discrimination, as well as the selection principle of teacher models, Shufflenet_v2_x1.0 is selected as the student model, and Efficientnet_v2 is selected as the teacher model. Then, CrossEntropy Loss is replaced by Focal Loss. Finally, for Distillation Loss ratios of 0.6, 0.7, 0.8, 0.9, Soft Target Knowledge Distillation (ST), Masked Generative Distillation (MGD), Similarity-Preserving Knowledge Distillation (SPKD), and Attention Transfer (AT) four knowledge distillation methods are tested for their performance in distilling knowledge from the Shufflenet_v2_x1.0 model. The results show that the model discrimination performance after distillation is the best when the Distillation Loss ratio is 0.8 and the MGD method is used. This setup effectively improves the discrimination performance without increasing the number of parameters and computation volume. The model's P, R and F1 values reach 0.9208, 0.9190 and 0.9192, respectively. It achieves precise discrimination of the fermentation degree of black tea. This meets the requirements of objective black tea fermentation judgment and provides technical support for the intelligent processing of black tea.

Macrophage-mediated heart repair and remodeling: A promising therapeutic target for post-myocardial infarction heart failure.

Heart failure (HF) remains prevalent in patients who survived myocardial infarction (MI). Despite the accessibility of the primary percutaneous coronary intervention and medications that alleviate ventricular remodeling with functional improvement, there is an urgent need for clinicians and basic scientists to further reveal the mechanisms behind post-MI HF as well as investigate earlier and more efficient treatment after MI. Growing numbers of studies have highlighted the crucial role of macrophages in cardiac repair and remodeling following MI, and timely intervention targeting the immune response via macrophages may represent a promising therapeutic avenue. Recently, technology such as single-cell sequencing has provided us with an updated and in-depth understanding of the role of macrophages in MI. Meanwhile, the development of biomaterials has made it possible for macrophage-targeted therapy. Thus, an overall and thorough understanding of the role of macrophages in post-MI HF and the current development status of macrophage-based therapy will assist in the further study and development of macrophage-targeted treatment for post-infarction cardiac remodeling. This review synthesizes the spatiotemporal dynamics, function, mechanism and signaling of macrophages in the process of HF after MI, as well as discusses the emerging bio-materials and possible therapeutic agents targeting macrophages for post-MI HF.

Quality Detection and Grading of Rose Tea Based on a Lightweight Model.

Rose tea is a type of flower tea in China's reprocessed tea category, which is divided into seven grades, including super flower, primary flower, flower bud, flower heart, yellow flower, scattered flower, and waste flower. Grading rose tea into distinct quality levels is a practice that is essential to boosting their competitive advantage. Manual grading is inefficient. We provide a lightweight model to advance rose tea grading automation. Firstly, four kinds of attention mechanisms were introduced into the backbone and compared. According to the experimental results, the Convolutional Block Attention Module (CBAM) was chosen in the end due to its ultimate capacity to enhance the overall detection performance of the model. Second, the lightweight module C2fGhost was utilized to change the original C2f module in the neck to lighten the network while maintaining detection performance. Finally, we used the SIoU loss in place of the CIoU loss to improve the boundary regression performance of the model. The results showed that the mAP, precision (P), recall (R), FPS, GFLOPs, and Params values of the proposed model were 86.16%, 89.77%, 83.01%, 166.58, 7.978, and 2.746 M, respectively. Compared with the original model, the mAP, P, and R values increased by 0.67%, 0.73%, and 0.64%, the GFLOPs and Params decreased by 0.88 and 0.411 M, respectively, and the speed was comparable. The model proposed in this study also performed better than other advanced detection models. It provides theoretical research and technical support for the intelligent grading of roses.

Predictive models for sensory score and physicochemical composition of Yuezhou Longjing tea using near-infrared spectroscopy and data fusion.

In this study, NIR quantitative prediction model was established for sensory score and physicochemical components of different varieties and quality grades of Yuezhou Longjing tea. Firstly, L, a, b color factors and diffuse reflection spectral data are collected for each sample. Subsequently, the original spectrum is preprocessed. Three techniques for selecting variables, CARS, BOSS, and SPA, were utilized to extract optimal feature bands. Finally, the spectral data extracted from feature bands were fused with L, a and b color factors to build SVR and PLSR prediction models. enabling the rapid non-destructive discrimination of different varieties and grades of Yuezhou Longjing tea. The outcomes demonstrated that BOSS was the best variable selection technique for sensory score and the distinctive caffeine wavelengths, CARS, however, was the best variable selection technique for catechins distinctive wavelengths. Additionally, the middle-level data fusion-based non-linear prediction models greatly outperformed the linear prediction models. For the prediction models of sensory score, catechins, and caffeine, the relative percent deviation (RPD) values were 2.8, 1.6, and 2.6, respectively, suggesting the good predictive ability of the models. In conclusion, evaluating the quality of the five Yuezhou Longjing tea varieties using near-infrared spectroscopy and data fusion have proved as feasible.

A Potent SOS1 PROTAC Degrader with Synergistic Efficacy in Combination with KRASG12C Inhibitor.

AMG510, as the first approved inhibitor for KRASG12C mutation, has shown promising efficacy in nonsmall-cell lung cancer and colorectal cancer harboring KRASG12C mutation. However, the moderate response rate and the rapid emergence of acquired resistance limit the therapeutic potential of AMG510, highlighting the need for the development of combination strategies. Here, we observed the suppression of RAS-MAPK signaling induced by AMG510 was prolonged and enhanced by SOS1 knockdown. Thus, we design, synthesize, and characterize a potent and specific SOS1 degrader 23. Compound 23 showed efficient SOS1 degradation in KRAS-driven cancer cells and achieved significant antiproliferative potency. Importantly, the combination of 23 with AMG510 suppressed RAS signaling feedback activation, showing synergistic effects against KRASG12C mutant cells in vitro and in vivo. Our findings demonstrated that KRASG12C inhibition plus SOS1 degradation as a potential therapeutic strategy to improve antitumor response and overcome acquired resistance to KRASG12C inhibitor.

A novel subpopulation of monocytes with a strong interferon signature indicated by SIGLEC-1 is present in patients with in recent-onset type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease characterised by pancreatic beta cell destruction. In this study, we explored the pathogenic immune responses in initiation of type 1 diabetes and new immunological targets for type 1 diabetes prevention and treatment. METHODS: We obtained peripheral blood samples from four individuals with newly diagnosed latent autoimmune diabetes in adults (LADA) and from four healthy control participants. Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells to uncover transcriptomic profiles of early LADA. Validation was performed through flow cytometry in a cohort comprising 54 LADA, 17 adult-onset type 2 diabetes, and 26 healthy adults, matched using propensity score matching (PSM) based on age and sex. A similar PSM method matched 15 paediatric type 1 diabetes patients with 15 healthy children. Further flow cytometry analysis was performed in both peripheral blood and pancreatic tissues of non-obese diabetic (NOD) mice. Additionally, cell adoptive transfer and clearance assays were performed in NOD mice to explore the role of this monocyte subset in islet inflammation and onset of type 1 diabetes. RESULTS: The scRNA-seq data showed that upregulated genes in peripheral T cells and monocytes from early-onset LADA patients were primarily enriched in the IFN signalling pathway. A new cluster of classical monocytes (cluster 4) was identified, and the proportion of this cluster was significantly increased in individuals with LADA compared with healthy control individuals (11.93% vs 5.93%, p=0.017) and that exhibited a strong IFN signature marked by SIGLEC-1 (encoding sialoadhesin). These SIGLEC-1+ monocytes expressed high levels of genes encoding C-C chemokine receptors 1 or 2, as well as genes for chemoattractants for T cells and natural killer cells. They also showed relatively low levels of genes for co-stimulatory and HLA molecules. Flow cytometry analysis verified the elevated levels of SIGLEC-1+ monocytes in the peripheral blood of participants with LADA and paediatric type 1 diabetes compared with healthy control participants and those with type 2 diabetes. Interestingly, the proportion of SIGLEC-1+ monocytes positively correlated with disease activity and negatively with disease duration in the LADA patients. In NOD mice, the proportion of SIGLEC-1+ monocytes in the peripheral blood was highest at the age of 6 weeks (16.88%), while the peak occurred at 12 weeks in pancreatic tissues (23.65%). Adoptive transfer experiments revealed a significant acceleration in diabetes onset in the SIGLEC-1+ group compared with the SIGLEC-1- or saline control group. CONCLUSIONS/INTERPRETATION: Our study identified a novel group of SIGLEC-1+ monocytes that may serve as an important indicator for early diagnosis, activity assessment and monitoring of therapeutic efficacy in type 1 diabetes, and may also be a novel target for preventing and treating type 1 diabetes. DATA AVAILABILITY: RNA-seq data have been deposited in the GSA human database ( https://ngdc.cncb.ac.cn/gsa-human/ ) under accession number HRA003649.

The anatomical variations of paranasal sinuses may be related to the formation of antrochoanal polyp by computed tomography imaging study.

Background: There is little investigation into the connection between anatomic variations and the development of antrochoanal polyp (ACP), and the etiology of ACP remains unclear. The study aims to explore the relationship among anatomic variations, maxillary sinus volume, nasal meatus-related parameters, and the occurrence of ACP. Methods: There were 127 patients included in this retrospective cross-sectional study with unilateral ACPs hospitalized at Shandong Provincial ENT Hospital between February 2010 and February 2020. Evaluation indicators included anatomic variations, maxillary sinus volume, and nasal meatus-related parameters in 45 children and 82 adults, which were evaluated twice by 3DSlicer software. Parameters were assessed using the Kolmogorov-Smirnov test, followed by paired t-test and Chi-squared test for multiple comparisons. Results: Significant differences were found in the accessory maxillary ostium (AMO) and maxillary sinus retention cyst between two sides (both P<0.001). Maxillary sinus volume and sex had an association of statistical significance on adults' ACP side (P=0.026) and non-antrochoanal polyp (non-ACP) side (P=0.032). The affected side's maxillary sinus volume was significantly larger than the healthy side (P<0.001). The length from the maxillary sinus orifice to the plane of the most lateral margin of the middle turbinate of the ACP side was larger than the non-ACP side in children (P=0.044). Males' length from the maxillary sinus orifice to the plane of the most lateral margin of the middle turbinate of the ACP side was considerably greater than the healthy side (P<0.001). The length from the maxillary sinus orifice to the plane of the most lateral margin of the middle turbinate (P=0.014) and the length from the inferior turbinate to the nasal septum (P=0.013) on the non-ACP side was higher than the affected side in adults. Males' length from the inferior turbinate to the nasal septum was higher on the healthy side than the affected side (P<0.001). Males had a greater maximum length from the maxillary sinus lateral wall to the nasal septum (P=0.024) and the length from the inferior turbinate to the nasal septum (P=0.003) on the non-ACP side than females. Males had a larger maximum length from the maxillary sinus lateral wall to the nasal septum on the ACP side than females (P=0.011). Conclusions: In our study, the occurrence of the AMO, the maxillary sinus's expanded size, and the stenosis of the associated channels around the ostiomeatal complex and common meatus are regarded as probably connected to the formation of ACPs. In addition, the anatomic variations that involve the ostiomeatal complex and may lead to a change in maxillary sinus pressure and nasal ventilation are important factors in the formation of ACPs.

The TFPI2-PPARγ axis induces M2 polarization and inhibits fibroblast activation to promote recovery from post-myocardial infarction in diabetic mice.

BACKGROUND: Diabetes mellitus is one of the causes of poor ventricular remodelling and poor cardiac recovery after myocardial infarction (MI). We previously reported that tissue factor pathway inhibitor-2 (TFPI2) was downregulated in response to hyperglycaemia and that it played a pivotal role in extracellular matrix (ECM) degradation and cell migration. Nonetheless, the function and mechanism of TFPI2 in post-MI remodelling under diabetic conditions remain unclear. Therefore, in the present study, we investigated the role of TFPI2 in post-MI effects in a diabetic mouse model. RESULTS: TFPI2 expression was markedly decreased in the infarcted myocardium of diabetic MI mice compared with that in non-diabetic mice. TFPI2 knockdown in the MI mouse model promoted fibroblast activation and migration as well as matrix metalloproteinase (MMP) expression, leading to disproportionate fibrosis remodelling and poor cardiac recovery. TFPI2 silencing promoted pro-inflammatory M1 macrophage polarization, which is consistent with the results of TFPI2 downregulation and M1 polarization under diabetic conditions. In contrast, TFPI2 overexpression in diabetic MI mice protected against adverse cardiac remodelling and functional deterioration. TFPI2 overexpression also inhibited MMP2 and MMP9 expression and attenuated fibroblast activation and migration, as well as excessive collagen production, in the infarcted myocardium of diabetic mice. TFPI2 promoted an earlier phenotype transition of pro-inflammatory M1 macrophages to reparative M2 macrophages via activation of peroxisome proliferator-activated receptor gamma. CONCLUSIONS: This study highlights TFPI2 as a promising therapeutic target for early resolution of post-MI inflammation and disproportionate ECM remodelling under diabetic conditions.

Classification of nasal polyps and inverted papillomas using CT-based radiomics.

OBJECTIVES: Nasal polyp (NP) and inverted papilloma (IP) are two common types of nasal masses. And their differentiation is essential for determining optimal surgical strategies and predicting outcomes. Thus, we aimed to develop several radiomic models to differentiate them based on computed tomography (CT)-extracted radiomic features. METHODS: A total of 296 patients with nasal polyps or papillomas were enrolled in our study. Radiomics features were extracted from non-contrast CT images. For feature selection, three methods including Boruta, random forest, and correlation coefficient were used. We choose three models, namely SVM, naive Bayes, and XGBoost, to perform binary classification on the selected features. And the data was validated with tenfold cross-validation. Then, the performance was assessed by receiver operator characteristic (ROC) curve and related parameters. RESULTS: In this study, the performance ability of the models was in the following order: XGBoost > SVM > Naive Bayes. And the XGBoost model showed excellent AUC performance at 0.922, 0.9078, 0.9184, and 0.9141 under four conditions (no feature selection, Boruta, random forest, and correlation coefficient). CONCLUSIONS: We demonstrated that CT-based radiomics plays a crucial role in distinguishing IP from NP. It can provide added diagnostic value by distinguishing benign nasal lesions and reducing the need for invasive diagnostic procedures and may play a vital role in guiding personalized treatment strategies and developing optimal therapies. CRITICAL RELEVANCE STATEMENT: Based on the extraction of radiomic features of tumor regions from non-contrast CT, optimized by radiomics to achieve non-invasive classification of IP and NP which provide support for respective therapy of IP and NP. KEY POINTS: • CT images are commonly used to diagnose IP and NP. • Radiomics excels in feature extraction and analysis. • CT-based radiomics can be applied to distinguish IP from NP. • Use multiple feature selection methods and classifier models. • Derived from real clinical cases with abundant data.

Association of age at menarche with valvular heart disease: An analysis based on electronic health record (CREAT2109).

Background: The association between age at menarche and coronary heart disease has been reported, but the association between age at menarche and valvular heart disease (VHD) has not been described. We aimed to examine the association between age at menarche and VHD. Methods: By collecting data from four medical centers of the Affiliated Hospital of Qingdao University (QUAH) from January 1, 2016, to December 31, 2020, we sampled 105,707 inpatients. The main outcome of this study was newly diagnosed VHD, which was diagnosed based on ICD-10 coding, and the exposure factor was age at menarche, which was accessed through the electronic health records. We used logistic regression model to investigate the association between age at menarche and VHD. Results: In this sample (mean age 55.31 ± 13.63 years), the mean age at menarche was 15. Compared with women with age at menarche 14-15 years, the odds ratio of VHD in women with age at menarche ≤13, 16-17, and ≥18 years was 0.68 (95% CI 0.57-0.81), 1.22 (95% CI 1.08-1.38), and 1.31 (95% CI 1.13-1.52), respectively (P for all < 0.001). By restricting cubic splines, we found that later menarche was associated with increased odds of VHD (P < 0.001). Furthermore, in subgroup analysis of different etiologies, the similar trend persisted for non-rheumatic VHD. Conclusions: In this large inpatient sample, later menarche was associated with higher risk of VHD.

Sensor Fusion of GNSS and IMU Data for Robust Localization via Smoothed Error State Kalman Filter.

High-precision and robust localization is critical for intelligent vehicle and transportation systems, while the sensor signal loss or variance could dramatically affect the localization performance. The vehicle localization problem in an environment with Global Navigation Satellite System (GNSS) signal errors is investigated in this study. The error state Kalman filtering (ESKF) and Rauch-Tung-Striebel (RTS) smoother are integrated using the data from Inertial Measurement Unit (IMU) and GNSS sensors. A segmented RTS smoothing algorithm is proposed in order to estimate the error state, which is typically close to zero and mostly linear, which allows more accurate linearization and improved state estimation accuracy. The proposed algorithm is evaluated using simulated GNSS signals with and without signal errors. The simulation results demonstrate its superior accuracy and stability for state estimation. The designed ESKF algorithm yielded an approximate 3% improvement in long straight line and turning scenarios compared to classical EKF algorithm. Additionally, the ESKF-RTS algorithm exhibited a 10% increase in the localization accuracy compared to the ESKF algorithm. In the double turning scenarios, the ESKF algorithm resulted in an improvement of about 50% in comparison to the EKF algorithm, while the ESKF-RTS algorithm improved by about 50% compared to the ESKF algorithm. These results indicated that the proposed ESKF-RTS algorithm is more robust and provides more accurate localization.

Comparative validation of machine learning algorithms for surgical workflow and skill analysis with the HeiChole benchmark.

PURPOSE: Surgical workflow and skill analysis are key technologies for the next generation of cognitive surgical assistance systems. These systems could increase the safety of the operation through context-sensitive warnings and semi-autonomous robotic assistance or improve training of surgeons via data-driven feedback. In surgical workflow analysis up to 91% average precision has been reported for phase recognition on an open data single-center video dataset. In this work we investigated the generalizability of phase recognition algorithms in a multicenter setting including more difficult recognition tasks such as surgical action and surgical skill. METHODS: To achieve this goal, a dataset with 33 laparoscopic cholecystectomy videos from three surgical centers with a total operation time of 22 h was created. Labels included framewise annotation of seven surgical phases with 250 phase transitions, 5514 occurences of four surgical actions, 6980 occurences of 21 surgical instruments from seven instrument categories and 495 skill classifications in five skill dimensions. The dataset was used in the 2019 international Endoscopic Vision challenge, sub-challenge for surgical workflow and skill analysis. Here, 12 research teams trained and submitted their machine learning algorithms for recognition of phase, action, instrument and/or skill assessment. RESULTS: F1-scores were achieved for phase recognition between 23.9% and 67.7% (n = 9 teams), for instrument presence detection between 38.5% and 63.8% (n = 8 teams), but for action recognition only between 21.8% and 23.3% (n = 5 teams). The average absolute error for skill assessment was 0.78 (n = 1 team). CONCLUSION: Surgical workflow and skill analysis are promising technologies to support the surgical team, but there is still room for improvement, as shown by our comparison of machine learning algorithms. This novel HeiChole benchmark can be used for comparable evaluation and validation of future work. In future studies, it is of utmost importance to create more open, high-quality datasets in order to allow the development of artificial intelligence and cognitive robotics in surgery.

SAR study of 1,2-benzisothiazole dioxide compounds that agonize HIF-2 stabilization and EPO production.

Benzisothiazole dioxide compound was reported to agonize HIF-2 stabilization and improve EPO production, thus conceiving a potential strategy to treat disease with chronic hypoxia exemplified by renal anemia. Herein, on the bases of multiple molecular and cellular assays, a series of benzisothiazole derivatives have been synthesized and their structure-activity relationship was evaluated. The SAR and molecular docking studies have revealed the structural insights on the rational design of HIF-2 agonist and discovered a more potential 5-bromine substituted analogue, which showed 2-4 times improvement of HIF-2 downstream gene transcriptions, including EPO production. The present results suggest the therapeutic potential of the compounds for diseases related to EPO insufficiency.

The effect of crisping, misting, and storage temperature on the survival or growth of Listeria monocytogenes and natural psychrotrophic bacteria on romaine lettuce.

L. monocytogenes has been linked to fresh produce and detected in the retail environment. This study simulated the retail practices (crisping, misting, and storage) of unbagged whole heads of romaine lettuce to determine the growth of L. monocytogenes and natural psychrotrophic microflora. Three nalidixic acid-resistant strains of L. monocytogenes strains were inoculated to each head of lettuce (≈5 log10 CFU/g). For crisping, 24 heads of romaine lettuce were immersed in tap water or electrolyzed water (EW; free chlorine: 55 ppm) for 5 min, followed by holding at 5 °C for 2 h. The water-crisped (WC), EW crisped (EWC), or non-crisped (NC) lettuces were placed in a commercial refrigerated cabinet for misting at 5 °C. After 24-h misting, heads of lettuce were placed in perforated drain boxes with cover at 5 °C or 15 °C. The tap water and EW crisping achieved 1.3 and 2.9 log10 CFU/g reduction of L. monocytogenes, respectively. Approximately 1 log additional reduction of L. monocytogenes in the non-crisped lettuce was shown after misting (p < 0.05), but no significant effect of misting on the population of L. monocytogenes was observed on WC or EWC lettuces (p > 0.05). Regardless of the storage temperature or misting, L. monocytogenes populations remained significantly (p < 0.05) lower on EWC lettuce than NC and WC lettuce. On days 4 and 7 of storage, the natural psychrotrophic bacteria on lettuce stored at 5 °C was significantly lower than stored at 15 °C, and its population was not affected by crisping and misting. These provide insight into the influence of retail lettuce handling practices on the risk of L. monocytogenes.

[Research Progress of Oral BCL-2 Inhibitor Venetoclax in the Treatment of Non-Hodgkin's Lymphoma --Review].

Abnormal cell apoptosis is closely related to the occurrence of hematologic tumors, B-cell lymphoma-2 (BCL-2), as a key anti-apoptotic protein in intrinsic programmed cell death, has become a hot spot in the treatment of hematologic tumors in recent years. Venetoclax is an oral small-molecule selective BCL-2 inhibitor approved by the Food and Drug Administration (FDA） for the treatment of chronic lymphocytic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) patients and for the treatment of elderly acute myeloid leukemia (AML) patients that is not suitable for aggressive chemotherapy. In addition, it also showed a promising clinical application in treatment of non-Hodgkin's lymphoma (NHL) patients, which is a new expansion of the clinical indications for venetoclax. In this review, the role of BCL-2 protein family played in the regulation of NHL cell apoptosis, the development of BCL-2 inhibitors and the recent research progress of venetoclax in the treatment of NHL are reviewed.

A novel approach for relapsed/refractory FLT3mut+ acute myeloid leukaemia: synergistic effect of the combination of bispecific FLT3scFv/NKG2D-CAR T cells and gilteritinib.

BACKGROUND: Patients with relapsed/refractory acute myeloid leukaemia (AML) with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have limited treatment options and poor prognosis. Therefore, novel treatment modalities are needed. Since high expression of natural killer group 2 member D ligands (NKG2DLs) can be induced by FLT3 inhibitors, we constructed dual-target FLT3 single-chain fragment variable (scFv)/NKG2D-chimeric antigen receptor (CAR) T cells, and explored whether FLT3 inhibitors combined with FLT3scFv/NKG2D-CAR T cells could have synergistic anti-leukaemia effects. METHODS: FLT3scFv and NKG2D expression in CAR T cells, FLT3 and NKG2DL expression in AML cells, and the in vitro cytotoxicity of combining CAR T cells with gilteritinib were assessed by flow cytometry. The therapeutic effect was evaluated in a xenograft mouse model established by injection of MOLM-13 cells. Mechanisms underlying the gilteritinib-induced NKG2DL upregulation were investigated using siRNA, ChIP-QPCR and luciferase assays. RESULTS: The FLT3scFv/NKG2D-CAR T cells specifically lysed AML cells both in vitro and in the xenograft mouse model. The efficacy of FLT3scFv/NKG2D-CAR T cells was improved by gilteritinib-pretreatment. The noncanonical NF-κB2/Rel B signalling pathway was found to mediate gilteritinib-induced NKG2DL upregulation in AML cells. CONCLUSIONS: Bispecific FLT3scFv/NKG2D-CAR T cells can effectively eradicate AML cells. The FLT3 inhibitor gilteritinib can synergistically improve this effect by upregulating NF-κB2-dependent NKG2DL expression in AML cells.

A small-molecule inhibitor of MDMX suppresses cervical cancer cells via the inhibition of E6-E6AP-p53 axis.

Dysfunction of p53 is observed in many malignant tumors, which is related to cancer susceptibility. In cervical cancer, p53 is primarily degradated through the complex of high-risk human papillomaviruses (HPV) oncoprotein E6 and E6-associated protein (E6AP) ubiquitin ligase. What is less clear is the mechanism and role of murine double minute X (MDMX) in cervical carcinogenesis due to the inactive status of murine double minute 2 (MDM2). In the current study, XI-011 (NSC146109), a small-molecule inhibitor of MDMX, showed robust anti-proliferation activity against several cervical cancer cell lines. XI-011 promoted apoptosis of cervical cancer cells via stabilizing p53 and activating its transcription activity. Moreover, XI-011 inhibited the growth of xenograft tumor in HeLa tumor-bearing mice, as well as enhanced the cytotoxic activity of cisplatin both in vitro and in vivo. Interestingly, MDMX co-localized with E6AP and seems to be a novel binding partner of E6AP to promote p53 ubiquitination. In conclusion, this work revealed a novel mechanism of ubiquitin-dependent p53 degredation via MDMX-E6AP axis in cervical carcinogenesis, and offered the first evidence that MDMX could be a viable drug target for the treatment of cervical cancer.