Search

Highlights Photoresponsive black phosphorus (BP)/Ti3C2Tx composites were synthesized by a self-assembly strategy. Enhanced gas sensitive property was achieved by visible light modulation. Light activated virtual sensor array was fabricated based on BP/Ti3C2Tx composite. Diagnosis of coronary heart disease was achieved with the help of machine learning.

Abstract Mutations in the Cockayne Syndrome group B (CSB) gene cause cancer in mice, but premature aging and severe neurodevelopmental defects in humans. CSB, a member of the SWI/SNF family of chromatin remodelers, plays diverse roles in regulating gene expression and transcription-coupled nucleotide excision repair (TC-NER); however, these functions do not explain the distinct phenotypic differences observed between CSB-deficient mice and humans. During investigating Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism that involves elongating RNA polymerase II (RNAPII) undergoing transient pauses at internal T-runs where CSB is required to propel RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, and when coupled with G-rich sequences upstream, exacerbates genome instability by promoting R-loop formation. These R-loop prone motifs are notably abundant in relatively long genes related to neuronal functions in the human genome, but less prevalent in the mouse genome. These findings provide mechanistic insights into differential impacts of CSB deficiency on mice versus humans and suggest that the manifestation of the Cockayne Syndrome phenotype in humans results from the progressive evolution of mammalian genomes.

The structural heterogeneity and complexity of plant cell wall polysaccharides limit the release of phytonutrients in food processing, ultimately affecting the sensory quality, nutritional value, and shelf stability of products. Efficient enzymatic hydrolysis using plant cell wall polysaccharide-degrading enzymes (PCWPE) is a key step in overcoming the plant cell wall, a chemically complex structure composed mostly of polysaccharides, in food processing. PCWPE include cellulase, hemi-cellulase and pectinase, which specifically and efficiently hydrolyze glycosidic bonds in plant cell wall polysaccharides, significantly improving the sensory flavor and nutritional value of products, enhancing the stability of multiphase systems, and increasing the product yield. In recent years, PCWPE have been widely used in beverage processing, phytonutrient extraction, functional sugar preparation, and the processing of emerging sustainable plant-based food and thereby have become a research hotspot in the field of green food processing. This article summarizes the latest research on the mechanism of action of PCWPE, efficient enzymatic hydrolysis techniques and their application in the food industry, with a view to providing a reference for technological innovation in the field of high-quality plant-based food processing.

Background and purpose: Esophageal carcinoma (ESCA) is one of the malignant tumors with high mortality rate, and the underlying mechanism of its development is largely unknown. CDC20 plays an important role in tumorigenesis, and its dysregulated expression is closely related to tumor occurrence and development. The expression of CDC20 is increased in a variety of tumors, and knocking down CDC20 can inhibit tumor cell proliferation. NLRP3 is the main component of the inflammasome, and inflammasome is also closely related to tumor occurrence and development. Here, our study aimed to investigate whether CDC20 promotes the proliferation of ESCA cells through NLRP3 and its regulatory mechanism. Methods: The expression levels of CDC20 and NLRP3 genes in ESCA patients were analyzed using The Cancer Genome Atlas (TCGA) detabase and GTEx public database. We collected clinical and pathological data and tissues from 80 ESCA patients at the First Affiliated Hospital of Xinxiang Medical College, and detected the protein expression of NLRP3 in ESCA patients through immunohistochemistry staining. This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College (Number: EC-021-137). We studied the effects of knocking down CDC20 and NLRP3 gene on the proliferation ability of esophageal squamous cell carcinoma cells EC9706 and KYSE150 using short hairpin RNA (shRNA) technology. Co-immunoprecipitation (Co-IP), proteasome inhibitors and ubiquitination experiments were used to detect whether CDC20 interacts with NLRP3, and to elucidate whether CDC20 regulates NLRP3 expression through the ubiquitination pathway. This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College (Number: EC-021-137). Results: The TCGA database analysis showed that the expression levels of CDC20 and NLRP3 mRNA were significantly higher in the cancer tissues of ESCA patients than in the adjacent tissues. The immunohistochemistry results further showed that compared with adjacent tissues, the protein expression levels of CDC20 and NLRP3 were increased in ESCA tissues. Knocking down CDC20 and NLRP3 genes inhibited the proliferation of ESCA cells. Co-IP, proteasome inhibitors and ubiquitination experiments confirmed that CDC20 interacted with NLRP3 through its leucine-rich repeat (LRR), and CDC20 stabilized its expression by promoting NLRP3 ubiquitination. Conclusion: CDC20 and NLRP3 are upregulated in ESCA tissues, and CDC20 stabilizes their expression through ubiquitination of NLRP3, promoting ESCA cell proliferation. This suggests that CDC20 and NLRP3 may be potential diagnostic targets for ESCA.

We study the out-of-time-order correlators (OTOC) of Skyrmion as baryon in the D0-D4/D8 model which is expected to be holographically dual to QCD with instantons as D0-branes or with a non-zero theta angle. Baryon states are identified to the excitations of the Skyrmion which are described by a holographic quantum mechanical system in this model. By employing the definition of OTOC in quantum mechanics, we derive the formulas and demonstrate explicitly the numerical calculations of the OTOC. Our calculation illustrates the quantum OTOC with imaginary Lyapunov coefficient indicates the possibly metastable baryonic status in the presence of the instanton while the classical OTOC can not, thus it reveals the instantonic or theta-dependent features of QCD are dominated basically by its quantum properties. Furthermore, the OTOC also implies the baryonic phase becomes really chaotic with real Lyapunov exponent if the instanton charge increases sufficiently which agrees with the unstable baryon spectrum presented in this model. In this sense, we believe the OTOC may be treated as a tool to detect the baryonic phase structure of QCD.

BackgroundOsimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that has become the first-line treatment for non-small cell lung cancer harboring EGFR mutations, with the potential risk of QT prolongation and heart failure. However, few cases have reported malignant ventricular arrhythmias. Here, we report a case of recurrent ventricular fibrillation (VF) and Torsade de Pointes (TdP) secondary to QT prolongation and heart failure induced by osimertinib.Case summaryA 70-year-old woman presented with chest tightness and dyspnea for 1 week and ventricular fibrillation upon admission, with a medical history of lung adenocarcinoma harboring an EGFR exon 21 p.L858R mutation. She was under osimertinib for 3 months. Electrocardiography after defibrillation suggested QTc prolongation (655 ms) and T wave alternans. Ultrasound cardiography displayed left ventricular ejection fraction (LVEF) of 29% and severe mitral regurgitation. Laboratory tests indicated elevated N-terminal pro-B-type natriuretic peptide and hypokalemia. Genetic testing suggested no pathogenic mutations. We considered acquired long QT syndrome and heart failure with reduced ejection fraction induced by osimertinib as the chief causes of ventricular arrhythmia and hypokalemia as an important trigger. Despite intubation, sedation, and the administration intravenous magnesium and potassium and lidocaine, the patient presented with recurrent TdP, which was managed by a low dose of isoproterenol (ISO, 0.17 ug/min). An implantable cardioverter defibrillator was declined. The patient is surviving without any relapse, with QTc of 490 ms and LVEF of 42% after a 6-month follow up.ConclusionRegular monitoring is required during osimertinib administration, considering the risk of life-threatening cardiac events, such as malignant arrhythmias and heart failure. ISO, with an individual dose and target heart rate, may be beneficial for terminating TdP during poor response to other therapies.

Thermal stratification phenomena in SFRs and machine learning applications in nuclear system R&D have captured the community's attention. Existing methods, such as CFD, demand significant time and computational resources, hindering the timely prediction and management of thermal stratification in reactors. In response, this paper introduces a novel approach employing data-driven models for super real-time prediction of thermal stratification. Themodel aims to enhance the efficiency and speed of thermal stratification predictions. Refined flow field data were first obtained via CFD, revealing the transition mechanism between the dominant roles of inertial and buoyancy forces during thermal stratification formation. To select the optimal data-driven model, this paper employs the proper orthogonal decomposition (POD) method to evaluate three algorithms - k-nearest neighbor (KNN), classification and regression tree (CART), and least absolute shrinkage and selection operator (LASSO) - basedon temperature data from a temperature probe. Evaluation reveals that the POD-KNN model offers notable improvements in prediction speed while ensuring consistent accuracy, outperforming traditional numerical simulation methods for super real-time thermal stratification prediction.

Low-density lipoprotein (LDL) is a small lipoprotein that plays a vital role in controlling lipid metabolism. LDL has a delicate nanostructure with unique physicochemical properties: superior payload capacity, long residence time in circulation, excellent biocompatibility, smaller size, and natural targeting. In recent decades, the superiority and feasibility of LDL particles as targeted delivery carriers have attracted much attention. In this review, we introduce the structure, composition, advantages, defects, and reconstruction of LDL delivery systems, summarize their research status and progress in targeted diagnosis and therapy, and finally look forward to the clinical application of LDL as an effective delivery vehicle.

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P

Climate change has significantly altered in the distribution of plant and animal species, potentially resulting in either species expansion or extinction. The genus Chimonanthus, an economically significant and endemic group in China, holds substantial medicinal and ornamental value; however, its wild resources are limited. There is a paucity of knowledge regarding the distribution characteristics of the genus Chimonanthus species and the critical ecological factors influencing habitat suitability. Utilizing species distribution data and environmental variables, we performed simulations and analyses to identify suitable habitats, evaluate the primary environmental factors influencing distribution, determine potential distribution areas and centroids, and predict changes in suitable areas under three future climate scenarios (SSP-126, SSP-245, SSP-585) employing MaxEnt and ArcGIS. These findings indicated that the Area Under Curve (AUC) values exceeded 0.97 for all five Chimonanthus species, suggesting that the model predictions are highly accurate. The primary environmental variables influencing the distribution of C. grammatus are temperature, particularly isothermality (BIO3), and the mean temperature of warmest quarter (BIO10). However, precipitation of warmest quarter (BIO18) was an important environmental factor limiting the distributions of C. praecox, C. nitens, C. salicifolius and C. zhejiangensis. In the current period, the area of habitat suitability for C. praecox is the largest, at 2,498,600 km2, while that for C. zhejiangensis is the smallest, at 700,400 km2. The five Chimonanthus species are distributed mainly in southern China under the current climate scenario and will migrate to higher latitudes under future climate scenarios. C. nitens had high niche overlap and range overlap with C. zhejiangensis and C. salicifolius, respectively. A similar situation occurs between C. zhejiangensis and C. salicifolius. These findings suggest that there may be strong interspecific competition among adjacent species. Our results indicate that the establishment of nature reserves at current distribution sites within optimal areas is crucial for the conservation of germplasm resources, particularly for C. grammatus and C. salicifolius. The data generated from this research can serve as a valuable reference for the selection of in situ conservation sites, the determination of appropriate planting locations, the scientific introduction of species, and the development of long-term conservation and management strategies for Chimonanthus.

Neutrophil infiltration has been linked to worse clinical outcomes after ischemic stroke. Microglia, a key type of immune-competent cell, engage in cross-talk with the infiltrating immune cells in the inflamed brain area, yet the molecular mechanisms involved remain largely unexplored. In this study, we investigated the mechanisms of how canonical transient receptor potential 1 (TRPC1) modulated neutrophil infiltration in male mouse cerebral ischemia and reperfusion injury (CIRI) models. Our findings revealed a notable upregulation of TRPC1 in microglia within both middle cerebral artery occlusion reperfusion (MCAO/R) and in vitro oxygen-glucose deprivation/regeneration (OGD/R) model. Conditional Trpc1 knockdown in microglia markedly reduced infarct volumes and alleviated neurological deficits. Microglia conditional Trpc1 knockdown mice displayed less neutrophil infiltration in peri-infarct area. Trpc1 knockdown microglia exhibited a reduced primed proinflammatory phenotype with less secretion of CC-Chemokines ligand (CCL) 5 and CCL2 after MCAO/R. Blocking CCL5/2 significantly mitigated neutrophil infiltration in microglia/neutrophil transwell co-culture system upon OGD/R condition. Trpc1 knockdown markedly reduced store-operated calcium entry and nuclear factor of activated T-cells c1 (NFATc1) level in OGD/R treated microglia. Overexpression of Nfatc1 reversed the CCL5/2 reducing effect of Trpc1 knockdown, which is mediated by small interfering RNA in BV2 cells upon OGD/R. Our data indicate that upregulation of TRPC1 in microglia stimulates the production of CCL5/2 through the Ca2+/NFATc1 pathway. Upregulated CCL5/2 leads to an increase in neutrophil infiltration into the brain, thereby aggravating reperfusion injury. Our results demonstrate the importance of TRPC1 in microglia-mediated neuroinflammation and suggest a potential means for reducing CIRI induced neurological injury.

Lipid peroxidation and redox imbalance are hallmarks of ferroptosis, an iron-dependent form of cell death. Growing evidence suggests that dysregulation in glycolipid metabolism and iron homeostasis substantially contribute to the development of hepatocellular carcinoma (HCC). However, there is still a lack of comprehensive understanding regarding the specific transcription factors that are capable of coordinating glycolipid and redox homeostasis to initiate the onset of ferroptosis. We discovered that overexpression of SOX8 leads to impaired mitochondria integrate, increased oxidative stress, and enhanced lipid peroxidation. These effects can be attributed to the inhibitory impact of SOX8 on de novo lipogenesis, glycolysis, the tricarboxylic acid cycle (TCA), and the pentose phosphate pathway (PPP). Additionally, upregulation of SOX8 results in reduced synthesis of NADPH, disturbance of redox homeostasis, disruption of mitochondrial structure, and impairment of the electron transport chain. Furthermore, the overexpression of SOX8 enhances the process of ferroptosis by upregulating the expression of genes associated with ferroptosis and elevating intracellular levels of ferrous ion. Importantly, the overexpressing of SOX8 has been observed to inhibit the proliferation of HCC in immunodeficient animal models. In conclusion, the findings suggest that SOX8 has the ability to alter glycolipid and iron metabolism of HCC cells, hence triggering the process of ferroptosis. The results of our study present a novel strategy for targeting ferroptosis in the therapy of HCC.

In the era of big data, data centers with high energy consumption, interconnectivity, and load flexibility have developed rapidly. However, due to data privacy issues, the traditional power-system operational reliability assessment (ORA) struggles to precisely consider the load flexibility of data centers, leading to inaccurate evaluation. To this end, this article proposes an ORA method considering the load flexibility of data centers via the energy consumption elastic space. By transforming the inner operation constraints of data centers into an equivalent elastic space, the ORA does not require any private data to complete the evaluation. Specifically, the energy consumption model of data centers is established to accurately describe the load flexibility. Then, based on multi-parametric programming techniques, the energy consumption elastic space of data centers is characterized by data centers’ power demand constraints, which do not involve privacy data, and no privacy concerns exist. Finally, the ORA model and the evaluation method based on the energy consumption elastic space can be constructed. With a lot of data center operation constraints being replaced by power demand constraints, the proposed method can complete an evaluation faster without accuracy loss. Its effectiveness is validated through simulations using the IEEE RTS 24-bus system and a provincial 661-bus system.

Chlorpyrifos is one of the most widely used broad-spectrum insecticides in agriculture. Given its potential toxicity and residue in food (e.g., tea), establishing a rapid and reliable method for the determination of chlorpyrifos residue is crucial. In this study, a strategy combining surface-enhanced Raman spectroscopy (SERS) and intelligent variable selection models for detecting chlorpyrifos residue in tea was established. First, gold nanostars were fabricated as a SERS sensor for measuring the SERS spectra. Second, the raw SERS spectra were preprocessed to facilitate the quantitative analysis. Third, a partial least squares model and four outstanding intelligent variable selection models, Monte Carlo-based uninformative variable elimination, competitive adaptive reweighted sampling, iteratively retaining informative variables, and variable iterative space shrinkage approach, were developed for detecting chlorpyrifos residue in a comparative study. The repeatability and reproducibility tests demonstrated the excellent stability of the proposed strategy. Furthermore, the sensitivity of the proposed strategy was assessed by estimating limit of detection values of the various models. Finally, two-tailed paired t-tests confirmed that the accuracy of the proposed strategy was equivalent to that of gas chromatography–mass spectrometry. Hence, the proposed method provides a promising strategy for detecting chlorpyrifos residue in tea.

Objective: To elucidate the chemical profile of Xanthocerais lignum’s extracts of different polarities and their impact on rheumatoid arthritis (RA), we identified anti-RA markers and predicted their action mechanisms. Methods: A collagen-induced arthritis rat model was established, and UPLC-Q-Exactive Orbitrap MS technology was employed to analyze and identify the chemical constituents within the alcohol extract of Xanthocerais lignum and its various extraction fractions, as well as their translocation into the bloodstream. Serum spectrum–effect correlation analysis was utilized to elucidate the pharmacodynamic material basis of Xanthocerais lignum against RA and to screen for Q-Markers. Finally, the potential anti-RA mechanisms of the Q-Markers were predicted through compound-target interaction data and validated using molecular docking techniques. Results: We identified 71 compounds, with flavan-3-ols and flavanones as key components. Of these, 36 were detected in the bloodstream, including 17 original and 19 metabolized forms. Proanthocyanidin A2, dihydroquercetin, catechin, and epicatechin (plus glucuronides) showed potential anti-RA activity. These compounds, acting as Q-Markers, may modulate ERK, NF-κB, HIF-1α, and VEGF in the HIF-1 pathway. Conclusions: This research clarifies Xanthocerais lignum’s pharmacodynamic material basis against RA, identifies 4 Q-Markers, and offers insights into their mechanisms, aiding quality assessment and lead compound development for RA treatment.