CHAC1 blockade suppresses progression of lung adenocarcinoma by interfering with glucose metabolism via hijacking PKM2 nuclear translocation.

Patients with lung adenocarcinoma (LUAD) generally have poor prognosis. Abnormal cellular energy metabolism is a hallmark of LUAD. Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) is a member of the γ-glutamylcyclotransferase family and an unfolded protein response pathway regulatory gene. Its biological function and molecular regulatory mechanism, especially regarding energy metabolism underlying LUAD, remain unclear. By utilizing tissue microarray and data from The Cancer Genome Atlas and Gene Expression Omnibus, we found that CHAC1 expression was markedly higher in LUAD tissues than in non-tumor tissues, and was positively correlated with poor prognosis. Phenotypically, CHAC1 overexpression enhanced the proliferation, migration, invasion, tumor sphere formation, and glycolysis ability of LUAD cells, resulting in tumor growth both in vitro and in vivo. Mechanistically, through a shotgun mass spectrometry-based proteomic approach and high-throughput RNA sequencing, we found that CHAC1 acted as a bridge connecting UBA2 and PKM2, enhancing the SUMOylation of PKM2. The SUMOylated PKM2 then transferred from the cytoplasm to the nucleus, activating the expression of glycolysis-related genes and enhancing the Warburg effect. Lastly, E2F Transcription Factor 1 potently activated CHAC1 transcription by directly binding to the CHAC1 promoter in LUAD cells. The results of this study implied that CHAC1 regulates energy metabolism and promotes glycolysis in LUAD progression.

Deciphering MOSPD1's impact on breast cancer progression and therapeutic response.

BACKGROUND: Motile Sperm Domain-Containing Protein 1 (MOSPD1) has been implicated in breast cancer (BC) pathophysiology, but its exact role remains unclear. This study aimed to assess MOSPD1 expression levels in BC versus normal tissues and investigate its diagnostic potential. METHODS: MOSPD1 expression was analyzed in BC and normal tissues, with Receiver Operating Characteristic analysis for diagnostic evaluation. Validation was performed using immunohistochemistry. Functional studies included tumor growth assays, MOSPD1 suppression and overexpression experiments, and testing BC cell responses to anti-PD-L1 therapy. RESULTS: MOSPD1 expression was significantly higher in BC samples than normal tissues, correlating with poor clinical outcomes in BC patients. MOSPD1 suppression inhibited tumor growth, while overexpression accelerated it. Silencing MOSPD1 enhanced BC cell sensitivity to anti-PD-L1 therapy and decreased Th2 cell activity. In vivo experiments supported these findings, showing the impact of MOSPD1 on tumor growth and response to therapy. CONCLUSIONS: Elevated MOSPD1 levels in BC suggest its potential as a biomarker for adverse outcomes. Targeting MOSPD1, particularly with anti-PD-L1 therapy, may effectively inhibit BC tumor growth and modulate immune responses. This study emphasizes the significance of MOSPD1 in BC pathophysiology and highlights its promise as a therapeutic target.

Multi-omics profiling and experimental verification of tertiary lymphoid structure-related genes: molecular subgroups, immune infiltration, and prognostic implications in lung adenocarcinoma.

Lung adenocarcinoma (LUAD), characterized by a low 5-year survival rate, is the most common and aggressive type of lung cancer. Recent studies have shown that tertiary lymphoid structures (TLS), which resemble lymphoid structures, are closely linked to the immune response and tumor prognosis. The functions of the tertiary lymphoid structure-related genes (TLS-RGs) in the tumor microenvironment (TME) are poorly understood. Based on publicly available data, we conducted a comprehensive study of the function of TLS-RGs in LUAD. Initially, we categorized LUAD patients into two TLS and two gene subtypes. Subsequently, risk scores were calculated, and prognostic models were constructed using seven genes (CIITA, FCRL2, GBP1, BIRC3, SCGB1A1, CLDN18, and S100P). To enhance the clinical application of TLS scores, we have developed a precise nomogram. Furthermore, drug sensitivity, tumor mutational burden (TMB), and the cancer stem cell (CSC) index were found to be substantially correlated with the TLS scores. Single-cell sequencing results reflected the distribution of TLS-RGs in cells. Finally, we took the intersection of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) prognosis-related genes and then further validated the expression of these genes by qRT-PCR. Our in-depth investigation of TLS-RGs in LUAD revealed their possible contributions to the clinicopathological features, prognosis, and characteristics of TME. These findings underscore the potential of TLS-RGs as prognostic biomarkers and therapeutic targets for LUAD, thereby paving the way for personalized treatment strategies.

Specialized Metabolites From the Husks of Rice Oryza sativa L. and Their Biological Activities.

Rice (Oryza sativa L.) husk harbors a substantial proportion of biological metabolites, as one of the most plentiful agriculture by-products in rice milling process, rice husk remains poorly utilized. As a continuing search for potential bioactive molecules from the husk of rice, a totally of twelve conponents (1-12), including six sterol ferulates (1-6), one flavonoid (7), one dipeptide (8), and four phenylpropanoid derivatives (9-12) were obtained. All the chemical structures were elucidated based on comprehensive spectroscopic data. Wherein, compounds 1 and 2 were yield as previous undescribed metabolites, and the comprehensive NMR data for compounds 3 and 4 were first presented in its entirety. Motivated by the similarity of the structural motifs of components 1-6 to that of reported sterol ferulates, the antioxidant and anti-inflammatory effects for compounds 1-6 were evaluated in vitro. Among them, compounds 5/6 had a significant antioxidant activity compare to that of vitamin E in both DPPH and reducing power assay up to the concentration 40 µg/ml; while compounds 1 and 2 exhibited weak suppressive effect on the production of nitric oxide, with the IC50 values of 53.27 ± 1.37 µM.

Straw return enhances grain yield and quality of three main crops: evidence from a meta-analysis.

Straw return is regarded as a widely used field management strategy for improving soil health, but its comprehensive effect on crop grain yield and quality remains elusive. Herein, a meta-analysis containing 1822 pairs of observations from 78 studies was conducted to quantify the effect of straw return on grain yield and quality of three main crops (maize, rice, and wheat). On average, compared with no straw return, straw return significantly (p< 0.05) increased grain yield (+4.3%), protein content (+2.5%), total amino acids concentration (+1.2%), and grain phosphorus content (+3.6%), respectively. Meanwhile, straw return significantly (p< 0.05) decreased rice chalky grain rate (-14.4%), overall grain hardness (-1.9%), and water absorption of maize and wheat (-0.5%), respectively. Moreover, straw return effects on grain yield and quality traits were infected by cultivated crop types, straw return amounts, straw return methods, and straw return duration. Our findings illustrated that direct straw return increased three main crop grain yields and improved various quality traits among different agricultural production areas. Although improper straw return may increase plant disease risk and affect seed germination, our results suggest that full straw return with covered or plough mode is a more suitable way to enhance grain yield and quality. Our study also highlights that compared with direct straw return, straw burning or composting before application may also be beneficial to farmland productivity and sustainability, but comparative studies in this area are still lacking.

Development and application of a high-sensitivity immunochromatographic test strip for detecting pseudorabies virus.

Introduction: Pseudorabies (PR) is a multi-animal comorbid disease caused by pseudorabies virus (PRV), which are naturally found in pigs. At the end of 2011, the emergence of PRV variant strains in many provinces in China had caused huge economic losses to pig farms. Rapid detection diagnosis of pigs infected with the PRV variant helps prevent outbreaks of PR. The immunochromatography test strip with colloidal gold nanoparticles is often used in clinical testing due to its low cost and high throughput. Methods: This study was designed to produce monoclonal antibodies targeting PRV through immunization of mice using the eukaryotic system to express the gE glycoprotein. Subsequently, paired monoclonal antibodies were screened based on their sensitivity and specificity for use in the preparation of test strips. Results and discussion: The strip prepared in this study was highly specific, only PRV was detected, and there was no cross-reactivity with glycoprotein gB, glycoprotein gC, glycoprotein gD, and glycoprotein gE of herpes simplex virus and varicellazoster virus, porcine epidemic diarrhea virus, Senecavirus A, classical swine fever virus, porcine reproductive and respiratory syndrome virus, and porcine parvovirus. Moreover, it demonstrated high sensitivity with a detection limit of 1.336 × 103 copies/µL (the number of viral genome copies per microliter); the coincidence rate with the RT-PCR detection method was 96.4%. The strip developed by our laboratory provides an effective method for monitoring PRV infection and controlling of PR vaccine quality.

The proliferation of beneficial bacteria influences the soil C, N, and P cycling in the soybean-maize intercropping system.

Soybean-maize intercropping system can improve the utilization rate of farmland and the sustainability of crop production systems. However, there is a significant gap in understanding the interaction mechanisms between soil carbon (C), nitrogen (N), and phosphorus (P) cycling functional genes, rhizosphere microorganisms, and nutrient availability. To reveal the key microorganisms associated with soil nutrient utilization and C, N, and P cycling function in the soybean-maize intercropping system, we investigated the changes in soil properties, microbial community structure, and abundance of functional genes for C, N, and P cycling under soybean-maize intercropping and monocropping at different fertility stages in a pot experiment. We found that there was no significant difference in the rhizosphere microbial community between soybean-maize intercropping and monocropping at the seeding stage. As the reproductive period progressed, differences in microbial community structure between intercropping and monocropping gradually became significant, manifesting the advantages of intercropping. During the intercropping process of soybean and maize, the relative abundance of beneficial bacteria in soil rhizosphere significantly increased, particularly Streptomycetaceae and Pseudomonadaceae. Moreover, the abundances of C, N, and P cycling functional genes, such as abfA, mnp, rbcL, pmoA (C cycling), nifH, nirS-3, nosZ-2, amoB (N cycling), phoD, and ppx (P cycling), also increased significantly. Redundancy analysis and correlation analysis showed that Streptomycetaceae and Pseudomonadaceae were significantly correlated with soil properties and C, N, and P cycling functional genes. In brief, soybean and maize intercropping can change the structure of microbial community and promote the proliferation of beneficial bacteria in the soil rhizosphere. The accumulation of these beneficial bacteria increased the abundance of C, N, and P cycling functional genes in soil and enhanced the ability of plants to fully utilize environmental nutrients and promoted growth.

Impact of NDUFAF6 on breast cancer prognosis: linking mitochondrial regulation to immune response and PD-L1 expression.

BACKGROUND: Breast cancer is a major global health concern, and there is a continuous search for novel biomarkers to predict its prognosis. The mitochondrial protein NDUFAF6, previously studied in liver cancer, is now being investigated for its role in breast cancer. This study aims to explore the expression and functional significance of NDUFAF6 in breast cancer using various databases and experimental models. METHODS: We analyzed breast cancer samples from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases, supplemented with immunohistochemistry (IHC) staining to assess NDUFAF6 expression. A breast cancer cell xenograft mouse model was used to evaluate tumor growth, apoptosis, and NDUFAF6 expression. Survival probabilities were estimated through Kaplan-Meier plots and Cox regression analysis. A Protein-Protein Interaction (PPI) network was constructed, and differentially expressed genes related to NDUFAF6 were analyzed using GO, KEGG, and GSEA. The relationship between NDUFAF6 expression, immune checkpoints, and immune infiltration was also evaluated. RESULTS: NDUFAF6 was found to be overexpressed in breast cancer patients and in the xenograft mouse model. Its expression correlated with worse clinical features and prognosis. NDUFAF6 expression was an independent predictor of breast cancer outcomes in both univariate and multivariate analyses. Functionally, NDUFAF6 is implicated in several immune-related pathways. Crucially, NDUFAF6 expression correlated with various immune infiltrating cells and checkpoints, particularly promoting PD-L1 expression by inhibiting the NRF2 signaling pathway. CONCLUSION: The study establishes NDUFAF6 as a potential prognostic biomarker in breast cancer. Its mechanism of action, involving the inhibition of NRF2 to upregulate PD-L1, highlights its significance in the disease's progression and potential as a target for immunotherapy.

Multiplex Aptamer-Based Fluorescence Assay Using Magnetism-Encoded Nanoparticles for Simultaneous Detection of Multiple Pathogenic Bacteria.

Multiplex assay has emerged as a robust and versatile method for the simultaneous detection of multiple analytes in a single test. However, challenges in terms of poor accuracy and complexity remained. In this work, we developed a multiplex aptamer-based fluorescence assay using magnetism-encoded nanoparticles for the simultaneous detection of multiple pathogenic bacteria. The encapsulation of different amounts of Fe3O4 nanoparticles in zeolitic imidazolate framework-90 (ZIF-90) leads to the formation of Fe3O4@ZIF-90 (FZ) composites with distinct magnetism strengths. By functionalizing a specific aptamer on the surface of the FZ composites, target bacteria can be specifically and precisely separated from a mixed sample in a sequential manner. This property allows for the simultaneous quantitative analysis of multiple target bacteria by using a single-color fluorescence label, thereby resulting in minimal spectral crosstalk interference and improved accuracy. The successful determination of multiple bacteria in contaminated milk samples demonstrates the applicability of this multiplex assay in complex biological matrices. Compared to conventional multiplex fluorescence assays, this approach offers distinct advantages of simplicity, efficiency, and implementation. We believe that this study can provide valuable insights into the development of the multiplex assay while introducing a new method for the simultaneous detection of multiple bacteria.

Liposomal Antibiotic Booster Potentiates Carbapenems for Combating NDMs-Producing Escherichia coli.

Infections caused by Enterobacterales producing New Delhi Metallo-ß-lactamases (NDMs), Zn(II)-dependent enzymes hydrolyzing carbapenems, are difficult to treat. Depriving Zn(II) to inactivate NDMs is an effective solution to reverse carbapenems resistance in NDMs-producing bacteria. However, specific Zn(II) deprivation and better bacterial outer membrane penetrability in vivo are challenges. Herein, authors present a pathogen-primed liposomal antibiotic booster (M-MFL@MB), facilitating drugs transportation into bacteria and removing Zn(II) from NDMs. M-MFL@MB introduces bismuth nanoclusters (BiNCs) as a storage tank of Bi(III) for achieving ROS-initiated Zn(II) removal. Inspired by bacteria-specific maltodextrin transport pathway, meropenem-loaded BiNCs are camouflaged by maltodextrin-cloaked membrane fusion liposome to cross the bacterial envelope barrier via selectively targeting bacteria and directly outer membrane fusion. This fusion disturbs bacterial membrane homeostasis, then triggers intracellular ROS amplification, which activates Bi(III)-mediated Zn(II) replacement and meropenem release, realizing more precise and efficient NDMs producer treatment. Benefiting from specific bacteria-targeting, adequate drugs intracellular accumulation and self-activation Zn(II) replacement, M-MFL@MB rescues all mice infected by NDM producer without systemic side effects. Additionally, M-MFL@MB decreases the bacterial outer membrane vesicles secretion, slowing down NDMs producer's transmission by over 35 times. Taken together, liposomal antibiotic booster as an efficient and safe tool provides new strategy for tackling NDMs producer-induced infections.

A Multi-Layer Classifier Model XR-KS of Human Activity Recognition for the Problem of Similar Human Activity.

Sensor-based human activity recognition is now well developed, but there are still many challenges, such as insufficient accuracy in the identification of similar activities. To overcome this issue, we collect data during similar human activities using three-axis acceleration and gyroscope sensors. We developed a model capable of classifying similar activities of human behavior, and the effectiveness and generalization capabilities of this model are evaluated. Based on the standardization and normalization of data, we consider the inherent similarities of human activity behaviors by introducing the multi-layer classifier model. The first layer of the proposed model is a random forest model based on the XGBoost feature selection algorithm. In the second layer of this model, similar human activities are extracted by applying the kernel Fisher discriminant analysis (KFDA) with feature mapping. Then, the support vector machine (SVM) model is applied to classify similar human activities. Our model is experimentally evaluated, and it is also applied to four benchmark datasets: UCI DSA, UCI HAR, WISDM, and IM-WSHA. The experimental results demonstrate that the proposed approach achieves recognition accuracies of 97.69%, 97.92%, 98.12%, and 90.6%, indicating excellent recognition performance. Additionally, we performed K-fold cross-validation on the random forest model and utilized ROC curves for the SVM classifier to assess the model's generalization ability. The results indicate that our multi-layer classifier model exhibits robust generalization capabilities.

Research progress in biological control of tomato bacterial wilt.

Bacterial wilt caused by the infection of Ralstonia solanacearum, is one of the most harmful diseases to tomatoes, one of the most important greenhouse vegetables in China. R. solanacearum can survive and remain active in the deep soil for a long time, and the chemical control of tomato bacterial wilt is consequently limited. In this study, we introduced the characteristics of tomato bacterial wilt disease and the types of R. solanacearum, and systematically reviewed the research progresses of biological control methods from the aspects of botanical insecticides, agricultural antibiotics, biocontrol bacteria. We emphatically introduced the principle and current status of these methods, discussed the limitations and the improvement strategies, and prospected a new environmental protection and efficient biological control system based on micro-ecological regulation would be the development direction of biological control of tomato bacterial wilt.

Biomimetic Mineralized CRISPR/Cas RNA Nanoparticles for Efficient Tumor-Specific Multiplex Gene Editing.

CRISPR/Cas9 systems have great potential to achieve sophisticated gene therapy and cell engineering by editing multiple genomic loci. However, to achieve efficient multiplex gene editing, the delivery system needs adequate capacity to transfect all CRISPR/Cas9 RNA species at the required stoichiometry into the cytosol of each individual cell. Herein, inspired by biomineralization in nature, we develop an all-in-one biomimetic mineralized CRISPR/Cas9 RNA delivery system. This system allows for precise control over the coencapsulation ratio between Cas9 mRNA and multiple sgRNAs, while also exhibiting a high RNA loading capacity. In addition, it enhances the storage stability of RNA at 4 °C for up to one month, and the surface of the nanoparticles can be easily functionalized for precise targeting of RNA nanoparticles in vivo at nonliver sites. Based on the above characteristics, as a proof-of-concept, our system was able to achieve significant gene-editing at each target gene (Survivin: 31.9%, PLK1: 24.41%, HPV: 23.2%) and promote apoptosis of HeLa cells in the mouse model, inhibiting tumor growth without obvious off-target effects in liver tissue. This system addresses various challenges associated with multicomponent RNA delivery in vivo, providing an innovative strategy for the RNA-based CRISPR/Cas9 gene editing.

Pathogen-Targeting Bimetallic Nanozymes as Ultrasonic-Augmented ROS Generator against Multidrug Resistant Bacterial Infection.

Clinical treatment of multidrug resistant (MDR) pathogens-induced infection is emerging as a growing challenge in global public health due to the limited selection of clinically available antibiotics. Nanozymes as artificial enzymes that mimicked natural enzyme-like activities, are received great attention for combating MDR pathogens. However, the relatively deficient catalytic activity in the infectious microenvironment and inability to precisely targeting pathogen restrains their clinical anti-MDR applications. Here, pathogen-targeting bimetallic BiPt nanozymes for nanocatalytic therapy against MDR pathogen are reported. Benefiting from electronic coordination effect, BiPt nanozymes exhibit dual-enzymatic activities, including peroxidase-mimic and oxidase-mimic activities. Moreover, the catalytic efficiency can be efficiently increased 300-fold by ultrasound under inflammatory microenvironment. Notably, BiPt nanozyme is further cloaked with a platelet-bacteria hybrid membrane (BiPt@HMVs), thus presenting excellent homing effect to infectious sites and precise homologous targeting to pathogen. By integrating accurate targeting with highly efficient catalytic, BiPt@HMVs can eliminate carbapenem-resistant Enterobacterales and methicillin-resistant Staphylococcus aureus in osteomyelitis rats model, muscle-infected mice model, and pneumonia mice model. The work provides an alternative strategy based on nanozymes for clinically addressing MDR bacteria-induced infections.

Remodeling Collagen Microenvironment in Liver Using a Biomimetic Nano-Regulator for Reversal of Liver Fibrosis.

Liver fibrosis is a progressive histological manifestation that happens in almost all chronic liver diseases. An unabated liver fibrosis may eventually develop into liver cirrhosis or hepatocellular carcinoma. Yet, the strategy for reversal of liver fibrosis is still limited. Herein, a biomimetic nano-regulator (P-ZIF8-cirDNAzyme) is developed to affect both collagen synthesis and degradation in liver to remodel collagen microenvironment. It is found that Zn (II) interference can efficiently inhibit collagen synthesis in activated hepatic stellate cells (aHSC) by inactivating proline 4 hydroxylase and affecting many fibrosis-related signaling pathways. Meanwhile, Zn (II)-dependent circular DNAzymes (cirDNAzymes) are used to efficiently silence tissue inhibitors of metalloproteinase-1, accelerating the degradation of collagen. They act in concert to recover the balance between collagen deposition and degradation. Additionally, ZIF-8-cirDNAzyme is coated by platelet membrane (PM) for precisely targeting aHSC via PM's inflammatory tropism and CD62p-CD44 interaction. In carbon tetrachloride-induced fibrotic mice, P-ZIF-8-cirDNAzyme shows a potent anti-fibrotic effect, greatly reducing the expression of collagen by 73.12% and restoring liver function nearly to normal. This work proposes a prospective platform enabling ion interference and gene silencing, collectively acting in aHSC for reversal of liver fibrosis.

Radiotherapy with continued EGFR-TKIs for oligoprogressive disease in EGFR-mutated non-small cell lung cancer: A real-world study.

BACKGROUND: Epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) develops resistance to tyrosine kinase inhibitors (TKIs). Here, we evaluated the efficacy of radiotherapy and continuation of TKIs in patients with advanced NSCLC with oligoprogression after EGFR-TKIs. METHODS: From January 2011 to January 2019, 33 patients with EGFR-mutated NSCLC on TKIs were treated by radiotherapy and continuation of TKIs for oligoprogressive disease. The primary endpoints were median progression-free survival 1 (mPFS1), mPFS2, and median overall survival (mOS). PFS1 was measured from the start of EGFR-TKIs therapy to the oligoprogression of the disease. PFS2 was measured from the date of oligoprogression to the further progression of the disease, while OS was calculated from oligoprogression to death from any cause or was censored at the last follow-up date. RESULT: The mPFS1, mPFS2, and mOS were 11.0 (95% CI, 4.4-17.6), 6.5 (95% CI, 1.4-11.6) and 21.8 (95% CI, 14.8-28.8) months, respectively. Univariate analysis showed that EGFR mutation type (p = 0.024), radiotherapy method (p = 0.001), and performance status (p = 0.017) were significantly correlated with PFS2. Univariate analysis showed that sex (p = 0.038), smoking history (p = 0.031), EGFR mutation type (p = 0.012), and radiotherapy method (p = 0.009) were significantly correlated with OS. Multivariate analysis suggested that radiotherapy method (p = 0.001) and performance status (p = 0.048) were prognostic factors for PFS2, and radiotherapy method (p = 0.040) was a prognostic factor for OS. CONCLUSION: Radiotherapy with continued TKIs is effective for EGFR-mutated NSCLC with oligoprogression, and it should be conducted as soon as possible. T790M+ patients have higher sensitivity to radiotherapy, and patients with good performance status and stereotactic body radiation therapy have better PFS2 and OS.

Study on B16 Cell Cytotoxicity by High Frequency Reversible Electroporation With Bleomycin That Induces Hallmarks of Immunogenic Death.

Hundreds of high frequency bipolar pulse bursts with ∼1 µs have been suggested to alleviate muscle contractions and pain during the irreversible electroporation (IRE) tumor treatment. This study is performed to verify whether eight bursts of high frequency reversible electroporation pulses (HFREs) with bleomycin could be used for electrochemotherapy (ECT) tumor treatment. Firstly, in vitro experiments on B16 cells are performed to determine the cytotoxicity of the HFREs with bleomycin. The result indicates that the protocol of HFREs with bleomycin has a significant killing effect compared with only bleomycin, in which the used HFRE pulses are set to induce high membrane permeabilization while maintaining high cell viability. The immunogenic cell death (ICD) that generates danger associated molecular patterns (DAMPs) could trigger an adaptive immune response against tumors. We demonstrated that HFREs with bleomycin could trigger the hallmarks of ICD with obvious up-regulation of DAMPs, including ATP, HMGB1, and CRT. The ICD process may begin at 3 h but perform at 6 h after HFREs with bleomycin stimulation. The in vivo experiment on mice tumor treatment also showed that the protocol of HFREs with bleomycin could inhibit tumor growth with more cytotoxic CD8+ T cells infiltration. The results obtained from in vitro and in vitro experiments preliminary confirmed that the HFREs with bleomycin could be used for ECT tumor treatment associated with the hallmarks of ICD and preliminary trigger the adaptive immune response.

Identification of a novel B-cell epitope of the African swine fever virus p34 protein and development of an indirect ELISA for the detection of serum antibodies.

African swine fever (ASF) is a viral disease caused by the African swine fever virus that can be highly transmitted and lethal in domestic pigs. In the absence of a vaccine, effective diagnosis is critical for minimizing the virus's spread. In recent years, with the decline of African swine fever virus (ASFV) virulence, antibody detection has become an important means of detection. ASFV nucleocapsid protein p34 is a mature hydrolytic product of pp220, which is highly conserved and has a high content in the structural protein of the virus. Prokaryotic cells were chosen to generate highly active and high-yield p34 protein, which was then used as an antigen for producing mouse monoclonal antibodies. The B-cell epitope 202QKELDKLQT210, which was highly conserved and found on the surface of the p34 protein, was first identified by an anti-p34 monoclonal antibody utilizing the peptide scanning technique and visualized in helix. This supported the viability of p34 protein detection even further. In addition, we established an indirect ELISA assay based on p34 to detect ASFV antibodies. The coincidence rate of this method with commercially available kits was shown to be 97.83%. Sensitivity analysis revealed that it could be detected in serum dilution as low as 1:6400, and there was no cross-reaction with other prevalent porcine epidemic diseases classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine circovirus 2 (PCV2). In summary, the established ELISA method and anti-P34 monoclonal antibody have demonstrated that the p34 protein has a promising application prospect for the detection of African swine fever antibodies.

Calibration of an Accelerometer Activity Index among Older Women and Its Association with Cardiometabolic Risk Factors.

Purpose: Traditional summary metrics provided by accelerometer device manufacturers, known as counts, are proprietary and manufacturer specific, making them difficult to compare studies using different devices. Alternative summary metrics based on raw accelerometry data have been introduced in recent years. However, they were often not calibrated on ground truth measures of activity-related energy expenditure for direct translation into continuous activity intensity levels. Our purpose is to calibrate, derive, and validate thresholds among women 60 years and older based on a recently proposed transparent raw data based accelerometer activity index (AAI), and to demonstrate its application in association with cardiometabolic risk factors. Methods: We first built calibration equations for estimating metabolic equivalents (METs) continuously using AAI and personal characteristics using internal calibration data (n=199). We then derived AAI cutpoints to classify epochs into sedentary behavior and intensity categories. The AAI cutpoints were applied to 4,655 data units in the main study. We then utilized linear models to investigate associations of AAI sedentary behavior and physical activity intensity with cardiometabolic risk factors. Results: We found that AAI demonstrated great predictive accuracy for METs (R2=0.74). AAI-based physical activity measures were associated in the expected directions with body mass index (BMI), blood glucose, and high density lipoprotein (HDL) cholesterol. Conclusion: The calibration framework for AAI and the cutpoints derived for women older than 60 years can be applied to ongoing epidemiologic studies to more accurately define sedentary behavior and physical activity intensity exposures which could improve accuracy of estimated associations with health outcomes.