H3K18 Lactylation Potentiates Immune Escape of Non-Small Cell Lung Cancer.

The recently discovered epigenetic modification lysine lactylation (Kla) contributes to tumor development and progression in several types of cancer. In addition to the tumor-intrinsic effects, histone lactylation may mediate tumor microenvironment remodeling and immune evasion. Here, we observed elevated pan Kla and H3K18la levels in non-small cell lung cancer (NSCLC) tissues, which was positively correlated with poor patient prognosis. Interruption of glycolysis by 2-DG and oxamate treatment and silencing of LDHA and LDHB reduced H3K18la levels and circumvented immune evasion of NSCLC cells by enhancing CD8+ T cell cytotoxicity. Mechanistically, H3K18la directly activated the transcription of POM121, which enhanced MYC nuclear transport and direct binding to the CD274 promoter to induce PD-L1 expression. In a mouse NSCLC xenograft model, combination therapy with a glycolysis inhibitor and an anti-PD-1 antibody induced intratumoral CD8+ T cell function and exhibited strong anti-tumor efficacy. Overall, this work revealed that H3K18la potentiates the immune escape of NSCLC cells by activating the POM121/MYC/PD-L1 pathway, which offers insight into the role of post-translational modifications in carcinogenesis and provides a rationale for developing an epigenetic-targeted strategy for treating NSCLC.

Consistency of CSCO AI with Multidisciplinary Clinical Decision-Making Teams in Breast Cancer: A Retrospective Study.

Background: The Chinese Society of Clinical Oncology Artificial Intelligence System (CSCO AI) serves as a clinical decision support system developed utilizing Chinese breast cancer data. Our study delved into the congruence between breast cancer treatment recommendations provided by CSCO AI and their practical application in clinical settings. Methods: A retrospective analysis encompassed 537 breast cancer patients treated at the Second Affiliated Hospital of Anhui Medical University between January 2017 and December 2022. Proficient senior oncology researchers manually input patient data into the CSCO AI system. "Consistent" and "Inconsistent" treatment categories were defined by aligning our treatment protocols with the classification system in the CSCO AI recommendations. Cases that initially showed inconsistency underwent a second evaluation by the Multi-Disciplinary Treatment (MDT) team at the hospital. Concordance was achieved when MDTs' treatment suggestions were in the 'Consistent' categories. Results: An impressive 80.4% concurrence was observed between actual treatment protocols and CSCO AI recommendations across all breast cancer patients. Notably, the alignment was markedly higher for stage I (85.02%) and stage III (88.46%) patients in contrast to stage II patients (76.06%, P=0.023). Moreover, there was a significant concordance between invasive ductal carcinoma and lobular carcinoma (88.46%). Interestingly, triple-negative breast cancer (TNBC) exhibited a high concordance rate (87.50%) compared to other molecular subtypes. When contrasting MDT-recommended treatments with CSCO AI decisions, an overall 92.4% agreement was established. Furthermore, a logistic multivariate analysis highlighted the statistical significance of age, menstrual status, tumor type, molecular subtype, tumor size, and TNM stage in influencing consistency. Conclusion: In the realm of breast cancer treatment, the alignment between recommendations offered by CSCO AI and those from MDT is predominant. CSCO AI can be a useful tool for breast cancer treatment decisions.

Microsecond-Scale Transient Thermal Sensing Enabled by Flexible Mo1-xWxS2 Alloys.

Real-time thermal sensing through flexible temperature sensors in extreme environments is critically essential for precisely monitoring chemical reactions, propellant combustions, and metallurgy processes. However, despite their low response speed, most existing thermal sensors and related sensing materials will degrade or even lose their sensing performances at either high or low temperatures. Achieving a microsecond response time over an ultrawide temperature range remains challenging. Here, we design a flexible temperature sensor that employs ultrathin and consecutive Mo1-x W x S2 alloy films constructed via inkjet printing and a thermal annealing strategy. The sensing elements exhibit a broad work range (20 to 823 K on polyimide and 1,073 K on flexible mica) and a record-low response time (about 30 µs). These properties enable the sensors to detect instantaneous temperature variations induced by contact with liquid nitrogen, water droplets, and flames. Furthermore, a thermal sensing array offers the spatial mapping of arbitrary shapes, heat conduction, and cold traces even under bending deformation. This approach paves the way for designing unique sensitive materials and flexible sensors for transient sensing under harsh conditions.

Peri- and intra-nodular radiomic features based on 18F-FDG PET/CT to distinguish lung adenocarcinomas from pulmonary granulomas.

Objective: To compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas. Methods: For this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1-5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Good and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model. Conclusion: When intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.

Breaking the Saturation of Sensitivity for Ultrawide Range Flexible Pressure Sensors by Soft-Strain Effect.

The flexible pressure sensors with a broad pressure range and unsaturated sensitivity are highly desired in practical applications. However, pressure sensors by piezoresistive effect are always limited by the compressibility of sensing layers, resulting in a theoretically decreasing sensitivity of less than 100%. Here, a unique strategy is proposed that utilizes the strain effect, simultaneously achieving a trade-off between a wider pressure detection range and unsaturated sensitivity. Ascribed to the strain effect of sensing layers induced by interlaced microdomes, the sensors possess an increased sensitivity (5.22-70 MPa-1) over an ultrawide pressure range (45 Pa-4.1 MPa), a high-pressure resolution (5 Pa), fast response/recovery time (30/45 ms), and a robust response under a high-pressure loading of 3.5 MPa for more than 5000 cycles. These superior sensing performances allow the sensor to monitor large pressure. The flexible pressure sensor array can assist doctors in restoring the neutral mechanical axis, tracking knee flexion angles, and extracting gait features. Moreover, the flexible sensing array can be integrated into the joint motion surveillance system to map the balance medial-lateral contact forces on the metal compartments in real time, demonstrating the potential for further development into precise medical human-machine interfaces during total knee replacement surgery.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

An electrochemical H2S sensor based on the screen printing Fe@Pt/C/PTFE sensing electrode.

A novel electrochemical gas sensor for sensitive detection of H2S at room temperature is constructed based on the Fe@Pt/C composite material. The core-shell structured Fe@Pt catalyst was synthesized by a two-step reduction method and physically dispersed in Vulcan XC-72 carbon powders. The core-shell structure increases the effective catalytic surface area of Pt while significantly reducing the usage of the noble metal Pt, leading to improved catalytic performance and decreased production costs. Additionally, the mature screen-printing process is used to coat the catalyst film. A waterproof and breathable PTFE film was used as the substrate and the parameters in the screen printing process were also optimized to achieve the best gas sensing performance of the electrode film. Through the detection of hydrogen sulfide (H2S) with different concentrations, it is found that the sensor strictly shows linear correlation in the range of 1-20 ppm, R2 = 0.99974. Notably, the sensor exhibits high sensitivity (658.45 nA ppm-1) and a low detection limit of 0.33 ppm. Moreover, the consistency and stability of the sensor are satisfactory. The constructed gas sensor is expected to be well applied to industrial H2S detection.

Is duct-to-mucosa pancreaticojejunostomy necessary after pancreaticoduodenectomy: A meta-analysis of randomized controlled trials.

The incidence of postoperative pancreatic fistula is influenced by the effectiveness of the pancreaticojejunostomy, and the most suitable pancreaticojejunostomy for pancreaticoduodenectomy remains uncertain. Since grade A postoperative pancreatic fistula is no longer considered a true fistula, the purpose of this meta-analysis was to compare the effectiveness of duct-to-mucosa anastomosis and invagination anastomosis in reducing the incidence of grade B/C postoperative pancreatic fistula. The meta-analysis was conducted using software Review Manager 5.3, and the fixed-effect model was employed for pooled statistic calculations. The Cochrane Collaboration Risk of Bias Tool was utilized for quality assessment. Ten randomized controlled trials from Embase, Web of Science, MEDLINE, and the Cochrane Library (1990.01-2022.10) including 1471 patients, met the inclusion criteria. This meta-analysis has been registered on PROSPERO with the registration number CRD42023491673. The incidence of grade B/C fistula was significantly lower in the invagination group (7.7 %) compared to the duct-to-mucosa group (12.8 %, mostly Cattell manner)(RR = 1.65, 95%CI: 1.14-2.39, P = 0.008; heterogeneity: P = 0.008, I2 = 68 %),heterogeneity among the results was addressed through sensitivity analysis. In patients with a soft pancreas, the incidence of grade B/C fistula was significantly lower in those who underwent invagination anastomosis (10 %) compared to those who underwent duct-to-mucosa anastomosis (41.9 %)(RR = 4.19, 95%CI: 1.33-13.25, P = 0.01).No significant differences were observed in terms of the occurrence of grade B/C fistula in firm pancreas, postoperative mortality, other major postoperative complications, anastomosis time, and postoperative bile leak. Therefore, we concluded that invagination anastomosis is significantly superior to duct-to-mucosa anastomosis in reducing the incidence of grade B/C fistula, especially in patients with a soft pancreas.

Improvement of the YOLOv8 Model in the Optimization of the Weed Recognition Algorithm in Cotton Field.

Due to the existence of cotton weeds in a complex cotton field environment with many different species, dense distribution, partial occlusion, and small target phenomena, the use of the YOLO algorithm is prone to problems such as low detection accuracy, serious misdetection, etc. In this study, we propose a YOLOv8-DMAS model for the detection of cotton weeds in complex environments based on the YOLOv8 detection algorithm. To enhance the ability of the model to capture multi-scale features of different weeds, all the BottleNeck are replaced by the Dilation-wise Residual Module (DWR) in the C2f network, and the Multi-Scale module (MSBlock) is added in the last layer of the backbone. Additionally, a small-target detection layer is added to the head structure to avoid the omission of small-target weed detection, and the Adaptively Spatial Feature Fusion mechanism (ASFF) is used to improve the detection head to solve the spatial inconsistency problem of feature fusion. Finally, the original Non-maximum suppression (NMS) method is replaced with SoftNMS to improve the accuracy under dense weed detection. In comparison to YOLO v8s, the experimental results show that the improved YOLOv8-DMAS improves accuracy, recall, mAP0.5, and mAP0.5:0.95 by 1.7%, 3.8%, 2.1%, and 3.7%, respectively. Furthermore, compared to the mature target detection algorithms YOLOv5s, YOLOv7, and SSD, it improves 4.8%, 4.5%, and 5.9% on mAP0.5:0.95, respectively. The results show that the improved model could accurately detect cotton weeds in complex field environments in real time and provide technical support for intelligent weeding research.

Tripterygium drug-loaded liposome alleviates renal function by promoting vascularization and inhibiting fibrosis.

Introduction: Tripterygium species have been traditionally used in Chinese medicine for treating various conditions. The aim of the study was to construct a drug-modified renal infarction targeting liposome (rTor-LIP) containing Tripterygium in order to improve the therapeutic effect on renal injury. Methods: rTor-LIP was prepared using the extruder method containing Tripterygium solution. The preparation was characterized by transmission electron microscopy, Marvin laser particle size analyzer, and Western blotting. In vitro experiments were conducted to verify the biocompatibility of rTor-LIP, and in vivo experiments were conducted to verify the therapeutic effect of rTor- LIP on renal injury. Results and discussion: The surface of rTor-LIP was regular and oval. In vitro results showed that after co-incubation with rTor-LIP, endothelial cells did not show significant apoptosis, and there were no significant abnormalities in the mitochondrial metabolism. The in vivo results showed that the morphology of endothelial cells in the rTor-LIP group was uniform and the cytoplasmic striations were clear, but the local striations had disappeared. Thus, rTor-LIP nano-targeted liposomes can effectively target hypoxic kidney tissue, providing a new idea for the treatment of renal infarction.

Assessing the influence of the digital economy on carbon emissions: Evidence at the global level.

This paper discusses the influence of the digital economy (DE) on carbon emissions based on evidence at the global level. Specifically, based on the panel data from 80 countries from 2010 to 2020, this paper creates a DE measurement index and uses the System-GMM model to assess the influence of DE on carbon emissions. The results show that: (1) The development of DE significantly promotes carbon emissions reduction. (2) The development of DE significantly promotes carbon emissions reduction through technological advancement, structural optimization, and educational enhancement; (3) Regulatory quality and financial development play a positively moderating role in DE's promoting effect on carbon emissions reduction; (4) DE of European and North American nations have stronger promoting effect on carbon emissions reduction than DE of other countries. Compared to DE of developing countries, DE of developed countries has a stronger promoting effect on carbon emissions reduction. Additionally, this paper also finds that institutional differences can impact the carbon emission reduction effects of DE. Based on the results, this paper suggests that governments globally should promote the development of DE and foster international cooperation to enhance DE's driving role in promoting carbon emissions reduction.

Estimated Human Papillomavirus Vaccine Coverage Among Females 9-45 Years of Age - China, 2017-2022.

What is already known on this topic?: There is a lack of comprehensive data on the coverage of the human papillomavirus (HPV) vaccine in China. The limited published literature hampers our ability to accurately assess the current situation. What is added by this report?: This study aimed to determine the rates of HPV vaccine coverage based on data from the electronic vaccination registry reported to the China Immunization Information System between 2017 and 2022. While there was an increase in HPV vaccine coverage each year, the overall coverage remained below the optimal level. What are the implications for public health practice?: This study presents evidence of low HPV vaccine coverage when administered outside of a national immunization program. Therefore, it is recommended that the HPV vaccine be included in the National Immunization Program in order to meet the 2030 WHO target of achieving 90% vaccination coverage for girls by the age of 15.

Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy.

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor.

Objective: Sympathetic hyperinnervation following myocardial infarction (MI) is one of the primary causes of ventricular arrhythmias (VAs) after MI. Nerve growth factor (NGF) is a key molecule that induces sympathetic nerve remodeling. Previous studies have confirmed that microRNA (miR)-let-7a interacts with NGF. However, whether miR-let-7a is involved in sympathetic remodeling after MI remains unknown. We aimed to investigate whether miR-let-7a was associated with the occurrence of VA after MI. Methods and results: A rat model of myocardial infarction was established using left coronary artery ligation. miR-let-7a expression levels were analyzed by reverse transcription-quantitative PCR. Western blotting was also used to examine NGF expression levels in vivo and in M1 macrophages in vitro. The relationship between miR-let-7a and NGF levels was investigated using a luciferase reporter assay. The results revealed that the expression of miR-let-7a decreased significantly after MI, while NGF expression was significantly upregulated. In addition, overexpression of miR-let-7a effectively inhibited NGF expression in rats, which was also verified in M1 macrophages. Tyrosine hydroxylase and growth-associated protein 43 immunofluorescence results revealed that the administration of a miR-let-7a overexpression lentivirus to rats inhibited sympathetic remodeling after MI. Programmed electrical stimulation, renal sympathetic nerve activity recording, and heart rate variability measurements showed that miR-let-7a overexpression decreased sympathetic activity. Conclusions: These findings provide novel insights into the molecular mechanisms by which miR-let-7a and NGF contribute to the progression of sympathetic nerve remodeling after MI. Therefore, miR-let-7a may be a promising therapeutic target to reduce the incidence of arrhythmia following MI.

BaCu, a Two-Dimensional Electride with Cu Anions.

The electron-rich characteristic and low work function endow electrides with excellent performance in (opto)electronics and catalytic applications; these two features are closely related to the structural topology, constituents, and valence electron concentration of electrides. However, the synthesized electrides, especially two-dimensional (2D) electrides, are limited to specific structural prototypes and anionic p-block elements. Here we synthesize and identify a distinct 2D electride of BaCu with delocalized anionic electrons confined to the interlayer spaces of the BaCu framework. The bonding between Cu and Ba atoms exhibits ionic characteristics, and the adjacent Cu anions form a planar honeycomb structure with metallic Cu-Cu bonding. The negatively charged Cu ions are revealed by the theoretical calculations and experimental X-ray absorption near-edge structure. Physical property measurements reveal that BaCu electride has a high electronic conductivity (ρ = 3.20 µΩ cm) and a low work function (2.5 eV), attributed to the metallic Cu-Cu bonding and delocalized anionic electrons. In contrast to typical ionic 2D electrides with p-block anions, density functional theory calculations find that the orbital hybridization between the delocalized anionic electrons and BaCu framework leads to unique isotropic physical properties, such as mechanical properties, and work function. The freestanding BaCu monolayer with half-metal conductivity exhibits low exfoliation energy (0.84 J/m2) and high mechanical/thermal stability, suggesting the potential to achieve low-dimensional BaCu from the bulk. Our results expand the space for the structure and attributes of 2D electrides, facilitating the discovery and potential application of novel 2D electrides with transition metal anions.

Extraction of Proteins from Soil.

Soil metaproteomics could explore the proteins involved in life activities and their abundance in the soils to overcome the difficulty in pure cultures of soil microorganisms and the limitations of proteomics of pure cultures. However, the complexity and heterogeneity of soil composition, the low abundance of soil proteins, and the presence of massive interfering substances (including humic compounds) generally lead to an extremely low extraction efficiency of soil proteins. Therefore, the efficient extraction of soil proteins is a prerequisite and bottleneck problem in soil metaproteomics. In this chapter, a soil protein extraction method suitable for most types of soils with low cost and enabling simple operation (about 150 µg protein can be extracted from 5.0 g soil) is described. The quantity and purity of the extracted soil proteins could meet the requirements for further analysis using routine mass spectrometry-based proteomics.

Fungal Secretomics Through iTRAQ-Based Analysis.

Our understanding of how fungi respond and adapt to external environments can be increased by the comprehensive data sets of fungal-secreted proteins. Fungi produce a variety of secreted proteins, and environmental conditions can easily influence the fungal secretome. However, the low abundance of secreted proteins and their post-translational modifications make protein extraction more challenging. Hence, the enrichment of secreted proteins is a crucial procedure for secretome analysis. This chapter illustrates a protocol for iTRAQ-based quantitative secretome analysis describing the example of fungi exposed to different environmental conditions. The fungal-secreted proteins can be extracted by combining ultrafiltration and TCA-acetone precipitation. Subsequently, the secreted proteins can be identified and quantified by the iTRAQ-based quantitative proteomics approach.