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Abstract Three‐coil inductive power transfer (IPT) charging system can not only achieve inherent constant current (CC) to constant voltage (CV) transition but also tolerate load open‐circuit. However, due to the cross‐coupling between the auxiliary coil and the receiver coil, the output voltage in CV mode may deviate from the CV voltage significantly, which makes the design freedom of the three‐coil coupler low. By replacing the auxiliary coil with a transformer, an improved auxiliary circuit is proposed in this paper to address the cross‐coupling issue and to increase the design freedom of the loosely coupled transformer (LCT). The improved auxiliary circuit can achieve load short‐circuit and open‐circuit protection. Besides, the optimization design of LCT is easy to achieve by load impedance matching. The operating principle and parameters design of the improved auxiliary circuit are discussed. A 1 kW experimental prototype is built to verify the feasibility of the proposed method.

A comprehensive understanding of cracking mechanisms and the prevention of interfacial microcrack formation are imperative for additive manufacturing of high-performance multi-material heterostructures. This study systematically investigated 316L/CuSn10 heterostructures and identified solidification cracking and solid-state cracking as the predominant mechanisms. Solidification cracking is closely linked to the copper content within the mixing zone, particularly evident at 10% copper content, which heightens sensitivity to solidification cracking due to the widening of intergranular spacing and the elongation of the liquid film channel. Solid-state cracks tend to initiate from pre-existing solidification cracks, propagate along high-angle grain boundaries (HAGBs), particularly within a specific misorientation angle range of 20°–50°, terminating eventually at low-angle grain boundaries (LAGBs). This is mainly controlled by the distribution of dislocations at crack tips, which are dispersed within the grains at LAGBs, and the resulting back stress contributes to crack termination. These findings contribute valuable insights into the cracking mechanisms in heterostructures and offer guidance for the fabrication of crack-free steel-copper components.

Abstract High‐performance soft magnetic materials are important for energy conservation and emission reduction. One challenge is achieving a combination of reliable temperature stability, high resistivity, high Curie temperature, and high saturation magnetization in a single material, which often comes at the expense of intrinsic coercivity–a typical trade‐off in the family of soft magnetic materials with homogeneous microstructures. Herein, a nanostructured FeCoNiSiAl complex concentrated alloy is developed through a hierarchical structure strategy. This alloy exhibits superior soft magnetic properties up to 897 K, maintaining an ultra‐low intrinsic coercivity (13.6 A m−1 at 297 K) over a wide temperature range, a high resistivity (138.08 µΩ cm−1 at 297 K) and the saturation magnetization with only a 16.7% attenuation at 897 K. These unusual property combinations are attributed to the dual‐magnetic‐state nature with exchange softening due to continuous crystal ordering fluctuations at the atomic scale. By deliberately controlling the microstructure, the comprehensive performance of the alloy can be tuned and controlled. The research provides valuable guidance for the development of soft magnetic materials for high‐temperature applications and expands the potential applications of related functional materials in the field of sustainable energy.

Background Acute respiratory distress syndrome (ARDS) is a severe complication that can lead to fatalities in multiple trauma patients. Nevertheless, the incidence rate and early prediction of ARDS among multiple trauma patients residing in high-altitude areas remain unknown. Methods This study included a total of 168 multiple trauma patients who received treatment at Shigatse People’s Hospital Intensive Care Unit (ICU) between January 1, 2019 and December 31, 2021. The clinical characteristics of the patients and the incidence rate of ARDS were assessed. Univariable and multivariable logistic regression models were employed to identify potential risk factors for ARDS, and the predictive effects of these risk factors were analyzed. Results In the high-altitude area, the incidence of ARDS among multiple trauma patients was 37.5% (63/168), with a hospital mortality rate of 16.1% (27/168). Injury Severity Score (ISS) and thoracic injuries were identified as significant predictors for ARDS using the logistic regression model, with an area under the curve (AUC) of 0.75 and 0.75, respectively. Furthermore, a novel predictive risk score combining ISS and thoracic injuries demonstrated improved predictive ability, achieving an AUC of 0.82. Conclusions This study presents the incidence of ARDS in multiple trauma patients residing in the Tibetan region, and identifies two critical predictive factors along with a risk score for early prediction of ARDS. These findings have the potential to enhance clinicians’ ability to accurately assess the risk of ARDS and proactively prevent its onset.

Abstract Purpose Opioids are currently the most frequently prescribed analgesics in clinical practice. However, their effect on cancer progression remains a topic of debate. Opioid receptors (ORs) are present in various types of tumor cells and their expression levels vary depending on the type of tumor. This study aims to explore and preliminarily characterize the association between four different ORs (μ, δ, κ, and nociception/orphanin FQ peptide receptor) and the prognosis of different types of tumors for comparison, with a focus on nociception/ orphanin FQ peptide receptor. Methods The expression levels of four ORs in normal tissues and immune cells were obtained from Human Protein Atlas (HPA) RNA-seq dataset, Monaco dataset, and Consensus dataset. Pan-cancer analysis was performed using the The Cancer Genome Atlas (TCGA) dataset, which included the expression of four ORs in different cancer types, significant copy-number alterations (sCNA), gene mutations of the four ORs, survival analysis, co-expression genes analysis, functional enrichment analyses, and correlations between ORs and immune cell infiltration levels. Based on the results of bioinformatic analysis, we selected 10 cancer cell lines for validation in vitro using specific agonists for the four ORs. Results OPRL1 (opioid related nociceptin receptor 1 gene) exhibited the highest abundance across different types of cancers, while OPRM1 (opioid receptor mu 1 gene) and OPRD1 (opioid receptor delta 1 gene) were barely detectable in multiple cancer types. Pan-cancer survival analysis revealed the overall worse/better prognosis of the four ORs in certain cancer types. Elevated levels of OPRM1 appear to be associated with poorer outcomes in breast invasive carcinoma and kidney renal clear cell carcinoma. Elevated OPRD1 levels are connected to worsen outcomes in kidney renal clear cell carcinoma and liver hepatocellular carcinoma, but better prognosis in bladder urothelial carcinoma. Increased OPRK1 (opioid receptor kappa 1 gene) expression is linked to a poorer prognosis in kidney renal papillary cell carcinoma. Furthermore, high OPRL1 expression relates to worse outcomes in bladder urothelial carcinoma and liver hepatocellular carcinoma, but better outcomes in breast invasive carcinoma and pancreatic adenocarcinoma. Functional enrichment analyses found that immune-related pathways were enriched in OPRK1 and OPRL1, with OPRL1 exhibiting the highest correlation with immune cell infiltration. Different effects on cell growth, migration, and invasion were observed in different cancer types upon the administration of agonists for the four ORs. Conclusion OPRL1 may play a vital role in monocytes and regulating the immune response and tumor-infiltrating macrophages. Due to its high abundance in different types of tumors, it may hold greater clinical significance for oncology patients. OPRK1 also participates in immune-related pathways. OPRL1 could potentially serve as therapeutic targets for different types of cancers. Graphical Abstract

Abstract Background Beneficial root-associated microbiomes play crucial roles in enhancing plant growth and suppressing pathogenic threats, and their application for defending against pathogens has garnered increasing attention. Nonetheless, the dynamics of microbiome assembly and defense mechanisms during pathogen invasion remain largely unknown. In this study, we aimed to investigate the diversity and assembly of microbial communities within four niches (bulk soils, rhizosphere, rhizoplane, and endosphere) under the influence of the bacterial plant pathogen Ralstonia solanacearum. Results Our results revealed that healthy tobacco plants exhibited more diverse community compositions and more robust co-occurrence networks in root-associated niches compared to diseased tobacco plants. Stochastic processes (dispersal limitation and drift), rather than determinism, dominated the assembly processes, with a higher impact of drift observed in diseased plants than in healthy ones. Furthermore, during the invasion of R. solanacearum, the abundance of Fusarium genera, a known potential pathogen of Fusarium wilt, significantly increased in diseased plants. Moreover, the response strategies of the microbiomes to pathogens in diseased and healthy plants diverged. Diseased microbiomes recruited beneficial microbial taxa, such as Streptomyces and Bacilli, to mount defenses against pathogens, with an increased presence of microbial taxa negatively correlated with the pathogen. Conversely, the potential defense strategies varied across niches in healthy plants, with significant enrichments of functional genes related to biofilm formation in the rhizoplane and antibiotic biosynthesis in the endosphere. Conclusion Our study revealed the varied community composition and assembly mechanism of microbial communities between healthy and diseased tobacco plants along the soil-root continuum, providing new insights into niche-specific defense mechanisms against pathogen invasions. These findings may underscore the potential utilization of different functional prebiotics to enhance plants’ ability to fend off pathogens.

Infantile spasms (IS) is a neurological disorder causing mental and/or developmental retardation in many infants. Hypsarrhythmia is a typical symptom in the electroencephalography (EEG) signals with IS. Long-term EEG/video monitoring is most frequently employed in clinical practice for IS diagnosis, from which manual screening of hypsarrhythmia is time consuming and lack of sufficient reliability. This study aims to identify potential biomarkers for automatic IS diagnosis by quantitative analysis of the EEG signals. A large cohort of 101 IS patients and 155 healthy controls (HC) were involved. Typical hypsarrhythmia and non-hypsarrhythmia EEG signals were annotated, and normal EEG were randomly picked from the HC. Root mean square (RMS), teager energy (TE), mean frequency, sample entropy (SamEn), multi-channel SamEn, multi-scale SamEn, and nonlinear correlation coefficient were computed in each sub-band of the three EEG signals, and then compared using either a one-way ANOVA or a Kruskal-Wallis test (based on their distribution) and the receiver operating characteristic (ROC) curves. The effects of infant age on these features were also investigated. For most of the employed features, significant ( ${p} < {0}.{05}$ ) differences were observed between hypsarrhythmia EEG and non-hypsarrhythmia EEG or HC, which seem to increase with increased infant age. RMS and TE produce the best classification in the delta and theta bands, while entropy features yields the best performance in the gamma band. Our study suggests RMS and TE (delta and theta bands) and entropy features (gamma band) to be promising biomarkers for automatic detection of hypsarrhythmia in long-term EEG monitoring. The findings of our study indicate the feasibility of automated IS diagnosis using artificial intelligence.

Abstract To explore the microstructure formation mechanism of 42CrMo steel under the strengthening of ultrasonic surface rolling process (USRP), the combination of theoretical analysis and experiment was used to conduct in-depth research on USRP. Firstly, according to contact mechanics and Hertz contact theory, the calculation model of contact stress distribution and elastoplastic strain between the rolling ball and the part during USRP is obtained. Secondly, the USRP processing test was carried out by single-factor experimental design method, and the microstructure of 42CrMo steel after USRP was analyzed by LEXT OLS5100 3D laser surface topography instrument and VEGA3 tungsten filament scanning electron microscopy, which found that with an increase in static pressure, residual stress and plastic strain gradually increase, the hardness firstly increases and then decreases, while surface roughness exhibits an initial decrease followed by an increase. The results show that USRP produces violent plastic deformation inside the material under the superposition of high-frequency impact and static pressure, at the same time, it refines the grains, so as to improve the surface performance of the part and improve its fatigue resistance.

Abstract Purpose Dexmedetomidine (Dexmed) is a highly selective alpha 2 adrenoceptor (α2-AR) agonist with excellent sedation and analgesic effects and is frequently used in breast cancer surgery. However, the exact impact of Dexmed on breast cancer prognosis is still unclear. The primary objective of this pilot study was to explore study feasibility (recruitment and dropout rates) for future large-scale randomized controlled trial (RCT) to test the hypothesis that intraoperative Dexmed reduced recurrence-free survival (RFS) and overall survival (OS) in patients after breast cancer surgery. Methods Interviews with patients were performed during the anesthetic preoperative visit for informed consent. Adult females scheduled for a mastectomy due to primary breast cancer were 1:1 randomised to saline (Group Control) or Dexmed (Group Dexmed) treatment groups. The primary outcomes were descriptions of study feasibility (recruitment and dropout rates). We also performed a preliminary analysis of RFS (time from surgery to the earliest date of recurrence/metastasis) and OS (time from surgery to the date of all-cause death) and collected data on percentages/numbers of circulating immune cells at pre- and 24 h post-operation. Results A total of 964 patients were screened; 40% (385/964) met the inclusion criteria, among which 39% (150/385) were enrolled and randomly assigned to either Group Control (n = 75) or Group Dexmed (n = 75). The median follow-up duration was 49 months (interquartile range (IQR): 34–58 months) for Group Control and 48 months (IQR: 33–60 months) for Group Dexmed. Five percent (5%, 8/150) patients were lost to follow-up and 1% (2/150) died. There was no significant difference in RFS and OS. The percentage/number of natural killer (NK), B and T-cell subsets and the CD4+/CD8+ ratio were similar between groups at 24 h post-operation. Conclusion The pilot study was feasible to deliver. In a future definitive trial, the lower recruitment rate may be improved by increasing the number of anesthesiologists involved in the study. The study about the effects of Dexmed on long-term prognoses of breast cancer patients that is planned to follow this pilot study is a large-scaled randomized control study with the aim of providing evidence-based guidelines for rational use of Dexmed in patients undergoing breast cancer surgery. Trial registration Registered at ClinicalTrials.gov on October 20, 2016 (ID: NCT03109990). Graphical Abstract

ABSTRACTThe formation of microcracks at the interface of steel–copper heterostructures is prone to premature failure, which severely limits the application of heterostructure components. Herein, a new approach was proposed by doping nano-TiC in interface forming by laser powder bed fusion (L-PBF) to prevent the hot crack nucleation and block the solid-state crack propagation in steel–copper heterostructures . Benefitting from the TiC doping, the tensile strength of laminated steel–copper structures increased from 372 to 526 MPa. The findings of this research present a new approach to inhibit cracking in the fabrication of heterostructure component manufacturing using L-PBF.

China holds the top position globally in apple production and consumption. Detecting diseases during the planting process is crucial for increasing yields and promoting the rapid development of the apple industry. This study proposes a lightweight algorithm for apple leaf disease detection in natural environments, which is conducive to application on mobile and embedded devices. Our approach modifies the YOLOv8n framework to improve accuracy and efficiency. Key improvements include replacing conventional Conv layers with GhostConv and parts of the C2f structure with C3Ghost, reducing the model’s parameter count, and enhancing performance. Additionally, we integrate a Global attention mechanism (GAM) to improve lesion detection by more accurately identifying affected areas. An improved Bi-Directional Feature Pyramid Network (BiFPN) is also incorporated for better feature fusion, enabling more effective detection of small lesions in complex environments. Experimental results show a 32.9% reduction in computational complexity and a 39.7% reduction in model size to 3.8 M, with performance metrics improving by 3.4% to a mAP@0.5 of 86.9%. Comparisons with popular models like YOLOv7-Tiny, YOLOv6, YOLOv5s, and YOLOv3-Tiny demonstrate that our YOLOv8n–GGi model offers superior detection accuracy, the smallest size, and the best overall performance for identifying critical apple diseases. It can serve as a guide for implementing real-time crop disease detection on mobile and embedded devices.

Pulsed water jet technology has broad application prospects in the field of rock breaking. The pressurized pulsed water jet (PPWJ) is a new type of pulsed jet that offers high-amplitude pressurization, variable pulse pressure and frequency, and a high energy usage rate. To achieve a more destructive and powerful pulsed water jet, a dynamic simulation model of the device was established by using the AMESim software (v1400) based on the operational principle of PPWJs, and the simulation model was validated against the experimental results. The relationships between the key structural parameters of the PPWJ device and the pulse parameters were quantitatively investigated. The pulse pressure and frequency can be increased by appropriately increasing the nozzle diameter or boost ratio, and the pulse pressure will drop if the nozzle diameter or boost ratio exceeds a threshold value. Increasing the maximum displacement or action area of the piston will increase pulse length while decreasing pulse frequency; a proper match of the maximum displacement or action area of the piston will assure pulse peak pressure. The maximum outer diameter of the piston only affects the pulse frequency. The key structural parameters of the device were optimized on that foundation. Compared to the original device, the optimized device resulted in an increase in pulse frequency and jet output energy, leading to larger diameter and volume of erosion pits at the same stand-off distance and erosion time. The findings of this study offer valuable scientific insights for achieving efficient rock breaking with PPWJ.

Abstract Pathogenic and corrosive bacteria pose a significant risk to human health or economic well‐being. The specific, sensitive, and on‐site detection of these bacteria is thus of paramount significance but remains challenging. Taking inspiration from immunoassays with primary and secondary antibodies, we describe here a rational design of microbial sensor (MS) under a dual‐specificity recognition strategy using Pseudomonas aeruginosa (P. aeruginosa) as the detection model. In the MS, engineered aptamers are served as the primary recognition element, while polydopamine‐N‐acetyl‐D‐galactosamine (PDA‐Gal NAc) nanoparticles are employed as the secondary recognition element, which will also generate and amplify changes in the output voltage signal. To achieve self‐powering capability, the MS is constructed based on a triboelectric nanogenerator (TENG) with the specific aptamers immobilized on the TENG electrode surface. The as‐prepared MS‐TENG system exhibits good stability in output performance under external forces, and high specificity toward P. aeruginosa, with no cross‐reactivity observed. A linear relationship (R2 = 0.995) between the output voltage and P. aeruginosa concentration is established, with a limit of detection estimated at around 8.7 × 103 CFU mL−1. The utilization of PDA‐Gal NAc nanoparticles is found to play an important role in enhancing the specific and reliability of detection, and the underlying mechanisms are further clarified by computational simulations. In addition, the MS‐TENG integrates a wireless communication module, enabling real‐time monitoring of bacterial concentration on mobile devices. This work introduces a pioneering approach to designing self‐powered smart microbial sensors with high specificity, using a double recognition strategy applicable to various bacteria beyond P. aeruginosa.

Abstract Radar-based human activity recognition (HAR) offers a non-contact technique with privacy protection and lighting robustness for many advanced applications. Complex deep neural networks demonstrate significant performance advantages when classifying the radar micro-Doppler signals that have unique correspondences with human behavior. However, in embedded applications, the demand for lightweight and low latency poses challenges to the radar-based HAR network construction. In this paper, an efficient network based on a lightweight hybrid Vision Transformer (LH-ViT) is proposed to address the HAR accuracy and network lightweight simultaneously. This network combines the efficient convolution operations with the strength of the self-attention mechanism in ViT. Feature Pyramid architecture is applied for the multi-scale feature extraction for the micro-Doppler map. Feature enhancement is executed by the stacked Radar-ViT subsequently, in which the fold and unfold operations are added to lower the computational load of the attention mechanism. The convolution operator in the LH-ViT is replaced by the RES-SE block, an efficient structure that combines the residual learning framework with the Squeeze-and-Excitation network. Experiments based on two human activity datasets indicate our method’s advantages in terms of expressiveness and computing efficiency over traditional methods.

Abstract Background Intratumour heterogeneity is a hallmark of most solid tumours, including breast cancers. We applied spatial transcriptomics and single‐cell RNA‐sequencing on patient‐derived xenografts (PDXs) to profile spatially resolved cell populations within oestrogen receptor‐positive (ER+) breast cancer and to elucidate their importance in oestrogen‐dependent tumour growth. Methods Two PDXs of ‘ER‐high’ breast cancers with opposite oestrogen‐mediated growth responses were investigated: oestrogen‐suppressed GS3 (80–100% ER) and oestrogen‐dependent SC31 (40–90% ER) models. The observation was validated via single‐cell analyses on an ‘ER‐low’ PDX, GS1 (5% ER). The results from our spatial and single‐cell analyses were further supported by a public ER+ breast cancer single‐cell dataset and protein‐based dual immunohistochemistry (IHC) of SC31 examining important luminal cancer markers (i.e., ER, progesterone receptor and Ki67). The translational implication of our findings was assessed by clinical outcome analyses on publicly available cohorts. Results Our space‐gene‐function study revealed four spatially distinct compartments within ER+ breast cancers. These compartments showed functional diversity (oestrogen‐responsive, proliferative, hypoxia‐induced and inflammation‐related). The ‘proliferative’ population, rather than the ‘oestrogen‐responsive’ compartment, was crucial for oestrogen‐dependent tumour growth, leading to the acquisition of luminal B‐like features. The cells expressing typical oestrogen‐responsive genes like PGR were not directly linked to oestrogen‐dependent proliferation. Dual IHC analyses demonstrated the distinct contribution of the Ki67+ proliferative cells toward oestrogen‐mediated growth and their response to a CDK4/6 inhibitor. The gene signatures derived from the proliferative, hypoxia‐induced and inflammation‐related compartments were significantly correlated with worse clinical outcomes, while patients with the oestrogen‐responsive signature showed better prognoses, suggesting that this compartment would not be directly associated with oestrogen‐dependent tumour progression. Conclusions Our study identified the gene signature in our ‘proliferative’ compartment as an important determinant of luminal cancer subtypes. This ‘proliferative’ cell population is a causative feature of luminal B breast cancer, contributing toward its aggressive behaviours.

Most clinically non-functioning pituitary tumour arise from gonadotroph cells. However, clinically functional pituitary gonadotroph adenoma is rare. Here we report a female case who presented with menstrual disturbances, however further workup demonstrated a pituitary microadenoma with elevated FSH and oestradiol level. Transsphenoidal resection was performed and the surgical histopathology confirmed pituitary gonadotroph adenoma. Postoperatively, improvement in both symptoms and hormonal profile were observed. Interestingly, the initially enlarged and polycystic ovaries became within normal range around eight months after the surgery. We suggest functional gonadotroph adenoma should be considered in the presence of gynaecological disorder with persistently elevated oestradiol and FSH levels.

The soil microbial community plays a critical role in promoting robust plant growth and serves as an effective defence mechanism against root pathogens. Current research has focused on unravelling the compositions and functions of diverse microbial taxa in plant rhizospheres invaded by Ralstonia solanacearum, however, the specific mechanisms by which key microbial groups with distinct functions exert their effects remain unclear. In this study, we employed a combination of amplicon sequencing and metabolomics analysis to investigate the principal metabolic mechanisms of key microbial taxa in plant rhizosphere soil. Compared to the healthy tobacco rhizosphere samples, the bacterial diversity and co-occurrence network of the diseased tobacco rhizosphere soil were significantly reduced. Notably, certain genera, including Gaiella, Rhodoplanes, and MND1 (Nitrosomonadaceae), were found to be significantly more abundant in the rhizosphere of healthy plants than in that of diseased plants. Eight environmental factors, including exchangeable magnesium, available phosphorus, and pH, were found to be crucial factors influencing the composition of the microbial community. Ralstonia displayed negative correlations with pH, exchangeable magnesium, and cation exchange flux, but showed a positive correlation with available iron. Furthermore, metabolomic analysis revealed that the metabolic pathways related to the synthesis of various antibacterial compounds were significantly enriched in the healthy group. The correlation analysis results indicate that the bacterial genera Polycyclovorans, Lysobacter, Pseudomonas, and Nitrosospira may participate in the synthesis of antibacterial compounds. Collectively, our findings contribute to a more in-depth understanding of disease resistance mechanisms within healthy microbial communities and provide a theoretical foundation for the development of targeted strategies using beneficial microorganisms to suppress disease occurrence.

Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-β, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.

Opioids are commonly used in patients with breast cancer (BC), both for perioperative analgesia and for the relief of chronic cancer pain. Studies have suggested a potential association of opioid receptors (ORs) with the prognosis of BC patients. However, the exact roles of different ORs remain poorly understood. In this study, we found that κ opioid receptor (KOR) was the only OR (among the four types of ORs) that was significantly decreased in BC tumor tissues compared with peritumoral normal tissues. In addition, decreased expression of KOR correlated with poor clinical outcomes in patients with estrogen receptor (ER)-positive BC. In vitro studies confirmed the anti-tumor effects of KOR agonists in ER-positive MCF-7 and T47D cells by showing that activation of KOR significantly inhibited cellular proliferation and promoted apoptosis. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network (PPI) analysis, we found that KOR-ER-XBP1 was the potential downstream signaling pathway mediating the anti-tumor effects of KOR agonist. Finally, the role of XBP1 was confirmed as KOR activation-induced increase in the proliferative and monoclonal formation abilities of ER-positive BC cells were both significantly abolished after silencing of XBP1. These findings provide us a better understanding of the roles of different ORs in BC, identifying KOR agonists as better opioids than traditional μ opioid receptor (MOR) agonists for providing analgesia in ER-positive BC patients owing to their association with better prognosis.

Abstract To obtain the distribution law of residual stress of 42CrMo steel processed by ultrasonic rolling extrusion process (UREP), according to the characteristics of the material treated by ultrasonic rolling extrusion process, 42CrMo steel quasi-static experiment and dynamic experiment are carried out, the improved Johnson–Cook model was proposed. Based on the 42CrMo constitutive equation, the ultrasonic rolling extrusion process finite element method and experiment of 42CrMo steel were carried out. The results show that the simulation value and experimental value of the residual stress distribution after ultrasonic rolling extrusion process of 42CrMo steel have good consistency, with the increase of static pressure and amplitude, the residual stress increases, and with the increase of rotational speed and feed speed, the residual stress decreases, a more accurate residual stress distribution law of ultrasonic rolling extrusion of 42CrMo steel is obtained.

ABSTRACTComposite structures are sensitive to impact damage in practical engineering. Electric resistance change method (ERCM) is an ideal technique for damage monitoring of composite structures. Due to the anisotropy of fiber-resin matrix composites, impact location monitoring is difficult, and research on impact location of fiber composite laminates (FRPs) is limited. A preparation method of MXene/CNT/CuNps thin film sensor is proposed. According to the modeling simulation and theoretical calculation, the resistance change characteristics of the thin film sensor are obtained, the relationship between the impact distance and the resistance change is established, and the sensor array is designed. A three-point localization algorithm and a weight function compensation localization algorithm are proposed, which can improve the imaging accuracy of the impact position. The impact point location was observed and analyzed using ultrasonic C-scan technology. The results show that the weight function compensation positioning algorithm can accurately locate the impact of the composite structure, and the error in the X direction is 7.1%, the error in the Y direction is 0.03%, which verifies the effectiveness of the method.

Background: T-helper 17 (Th17) cell response is engaged in the onset of allergic rhinitis (AR). Moreover, interleukin (IL)-38 is thought to be involved in inhibiting cytokine secretion in the Th17 pathway.Objective: To evaluate the regulatory function of IL-38 on abnormal Th17 responses in Chinese patients with AR.Methods: Forty-five participants, divided into an AR group (n=25) and a control group (n=20), were recruited for the study. In addition, the expression of IL-38 and Th17-related cytokines was measured as well as the Th17 cell count in participants. By implementing recombinant IL-38 (rIL-38), the intervention of human peripheral blood mononuclear cells (PBMCs) was performed. Then, flow cytometry, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used to detect theTh17 milieu.Results: The expression of IL-38 in the AR group notably reduced compared with that in the control, whereas Th17 cell frequency and the expression levels of its transcription factor (RORC) and cytokines (IL-17A and IL-23) increased. The differentiation and immune function of Th17 cells in PBMCs were inhibited by rIL-38.Conclusion: Th17 responses are inhibited by IL-38 in patients with AR. Therefore, the obtained findings indicate that IL-38 is a potential therapeutic target for Chinese patients with AR.

Abstract Background μ‐opioid receptor agonists (MORAs) are indispensable for analgesia in bladder cancer (BC) patients, both during surgery and for chronic pain treatment. Whether MORAs affect BC progression and metastasis remains largely unknown. This study focused on the effects of MORAs on the formation of circulating tumor cells (CTCs) in BC and aimed to provide potential therapeutic targets, which would retain the pain‐relieving effects of MORAs in BC patients without sacrificing their long‐term prognosis. Methods Different preclinical models were used to identify the effects of MORAs on the progression of BC. A novel immunocapture microfluidic chip was utilized to analyze whether MORAs affected the number of CTCs in mouse models and clinical BC patients. Bioinformatic analyses, total transcriptome sequencing, and molecular biology methods were then used to investigate the underlying mechanisms in these models and in BC cell lines. Results Mouse models of hematogenous metastasis and in situ BC demonstrated that tumor metastasis was significantly increased after MORA treatment. A significant increase in the number of mesenchymal and/or epithelial CTCs was detected after MORA treatment in both the mouse models and clinical trial patients. Mechanistically, MORAs facilitated the formation of CTCs by activating the MOR/PI3K/AKT/Slug signaling pathway, hereby promoting the epithelial‐mesenchymal transition (EMT) of BC cells, as knockdown of MOR, Slug or blockade of PI3K inhibited the EMT process and CTC formation. Conclusion MORAs promoted BC metastasis by facilitating CTC formation. The EMT‐CTC axis could be targeted for preventive measures during MORA treatment to inhibit the associated tumor metastasis or recurrence in BC patients.

UDP-glycosyltransferases (UGTs) form a large enzyme family that is found in a wide range of organisms. These enzymes are known for accepting a wide variety of substrates, and they derivatize xenobiotics and metabolites for detoxification. However, most UGT homologs have not been well characterized, and their potential for biomedical and environmental applications is underexplored. In this work, we have used a fluorescent assay for screening substrates of a plant UGT homolog by monitoring the formation of UDP. We optimized the assay such that it could be used for high-throughput screening of substrates of the Medicago truncatula UGT enzyme, UGT71G1, and our results show that 34 of the 159 screened compound samples are potential substrates. With an LC–MS/MS method, we confirmed that three of these candidates indeed were glycosylated by UGT71G1, which includes bisphenol A (BPA) and 7-Ethyl-10-hydroxycamptothecin (SN-38); derivatization of these toxic compounds can lead to new environmental and medical applications. This work suggests that UGT homologs may recognize a substrate profile that is much broader than previously anticipated. Additionally, it demonstrates that this screening method provides a new means to study UDP-glycosyltransferases, facilitating the use of these enzymes to tackle a wide range of problems.

The uridine diphosphate glycosyltransferase (UGT) superfamily plays a key role in the metabolism of xenobiotics and metabolic wastes, which is essential for detoxifying those species. Over the last several decades, a huge effort has been put into studying human and mammalian UGT homologs, but family members in other organisms have been explored much less. Potentially, other UGT homologs can have desirable substrate specificity and biological activities that can be harnessed for detoxification in various medical settings. In this review article, we take a plant UGT homology, UGT71G1, and compare its structural and biochemical properties with the human homologs. These comparisons suggest that even though mammalian and plant UGTs are functional in different environments, they may support similar biochemical activities based on their protein structure and function. The known biological functions of these homologs are discussed so as to provide insights into the use of UGT homologs from other organisms for addressing human diseases related to UGTs.

Intervertebral disc degeneration (IDD) has been widely recognized as the primary cause of low back pain and is one of the major chronic diseases imposing a severe socioeconomic burden worldwide. IDD is a degenerative process characterized by inflammatory responses, and its underlying pathological mechanisms remain complex. Genetic, developmental, biochemical, and biomechanical factors contribute to the development of IDD. There is a pressing need for an effective non-surgical treatment, mainly due to the lack of comprehensive understanding of the specific mechanisms involved and the effective therapeutic targets for IDD. Recently, interleukin (IL)-1β has been recognized as an essential inflammatory factor and a key mediator of the inflammatory process in IDD. Current studies have found that IL-1β is mainly involved in IDD by affecting the metabolism of the extracellular matrix and regulating cell death (RCD), such as apoptosis, pyroptosis, and ferroptosis (a new form of RCD). Although analysis of clinical samples from different laboratories confirmed how IL-1β is induced in IDD, its specific signal transduction pathway, and the inflammatory role mediated in IDD remains unclear. This review describes the molecules and mechanisms involved in IL-1β-mediated inflammatory responses, and their roles in resolving the inflammatory process in IDD. Understanding the signaling pathways involved in IL-1β may lead to a new class of targets that promote remission for IDD patients. This review aims to provide a framework for the treatment of IDD by analyzing the signaling mechanism and function related to IL-1β, especially in terms of inflammation, matrix metabolism, and cell death regulation.

Abstract Background To investigate the feasibility, safety and efficacy of the right-side approach to enter Retzius space in laparoscopic transabdominal preperitoneal bilateral inguinal hernia repair. Methods Retrospective analysis was performed on 189 patients who were diagnosed with bilateral inguinal hernia preoperatively or intraoperatively and underwent selective TAPP in the General Surgery I Section of Shaanxi Provincial People’s Hospital from January 2015 to September 2020. 94 cases were performed using the right-side approach (research group), and 95 cases with conventional approach (control group). Intraoperative and postoperative conditions of the two groups were observed and compared. Results All operation were completed successfully. The operative time of research group was significantly shorter than that of control group (128.8 ± 35.4 vs 144.1 ± 40.9 min, P = 0.006). There were no significant differences in postoperative hospital stay, VAS score on first postoperative day, incidence of seroma and hematoma, urinary retention and other complications (P > 0.05). None of the patients occured hernia recurrence, mesh infection, intestinal obstruction and other complications. Conclusions The right-side approach to enter Retzius space is safe and feasible in TAPP surgery of bilateral inguinal hernia. Compared with the conventional approach, it can shorten the operative time and has certain advantages.

Abstract Background Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). Methods Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. Results The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. Conclusions Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

Cellulose is a potential alternative to petroleum-derived polymers, and cellulose membranes are used in many applications such as sensors, flexible materials, and functional membranes. Most bottom-up methods are energy-, chemical-, and time-intensive compared to top-down methods for preparing cellulose membranes. Additionally, most methods to improve the hydrophobicity of cellulose membranes to increase their lifetime are complex and require large amounts of organic solvents. To balance sustainability, degradability, and service life from a whole life cycle perspective, which is the biggest challenge for the industrialization of cellulose membranes, a top-down approach was used here to prepare cellulose membranes using camphor pine, walnut, and loofah materials. The effect of low temperature heat treatment on the prepared membranes’ wettability and water stability were investigated. The results showed that the water stability of loofah cellulose membrane was influenced by both surface and internal wettability due to the non-homogeneous structure. The heat treatment temperature of 200 °C for loofah cellulose membrane, 150 °C for camphor pine cellulose membrane, and 225 °C for walnut cellulose membrane was more effective.

Silylation is an effective means of cellulose modification. However, the condensation reaction process between the hydrolysis products of the silane coupling agent and cellulose, as well as the structure of the coating, which both have a strong influence on the wettability, are still controversial. In this paper, the reactions of different methyltriethoxysilane hydrolysis products with cellulose were simulated via the density functional theory method. The reaction activity centers of the different methyltriethoxysilane hydrolysis products in an ethanol solution were analyzed via the front-line orbital theory and the Fukui function. The silylation reaction of different methyltriethoxysilane hydrolysis products in an ethanol solution on the cellulose surface were investigated via the transition state theory. The results show that although the initial hydrolysis product has the lowest grafting energy barrier, considering the whole process of grafting and condensation on the cellulose surface, the hydrolysis product with two hydroxyl groups is more favorable for the growth of organosilicon on the cellulose surface, so it is desirable to control the reaction where this product is dominant. In addition, the silylation process on the cellulose surface is more inclined to a multilayer coating mechanism.

The structure and function of two isoflavone biosynthetic enzymes are reported revealing a novel cytochrome P450 conformation and identification of key residues for dual dehydratase and carboxylesterase activities

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP) and disability in the elderly, imposing significant public health and economic burden worldwide. Meanwhile, the pathological mechanisms of IDD remain complicated, and treatment strategy to reverse IDD is primarily due to the unclear specific mechanisms of IDD and the lack of particular effective targets. Interleukin-1β (IL-1β), one of the most important members of the IL-1 family, can induce solid pro-inflammatory activity by stimulating the secretion of various pro-inflammatory mediators and is considered the key to IDD mediator. However, in recent years, IL-1β is considered to be able to regulate IVD cell death in many ways, such as apoptosis, pyroptosis, ferroptosis, and so on. At the same time, numerous studies on IL-1β inhibitors suggest that inhibition of IL-1β may be a promising biological therapy for IDD. Many IL-1β inhibitors have been investigated through various pathogenic biological mechanisms, including inhibiting inflammatory processes, regulating ECM degradation, and more. Therefore, anti-IL-1β therapy may have the effect of alleviating disc degeneration. This article mainly reviews the mechanisms and functions of IL-1β in IDD and investigates advances in IL-1β inhibition as a promising biotherapeutic approach for disc degeneration.

Because of its significant advantage of fast postoperative recovery, natural orifice specimen extraction surgery (NOSES) has attracted increasing attention worldwide. However, the NOSES in gastric cancer (GC) treatment still needs more clinical practice, especially for the rare anatomical anomaly. Situs inversus totalis (SIT) is a rare autosomal recessive anatomical anomaly with an incidence ranging between 1/8,000 and 1/25,000 births. We present a video of transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy performed in a 59-year-old woman known to have SIT. Preoperative investigations revealed that the patient had early GC at the antrum. A gastroscopy report from the local hospital showed signet-ring cell carcinoma. The preoperative computed tomography scan revealed irregular thickening of the gastric wall at the junction of the greater curvature and antrum without metastasis to the lymph nodes. In total, laparoscopic D2 distal gastrectomy was performed with transvaginal specimen extraction. Billroth II with Braun anastomosis was performed for reconstruction. The length of the operation was 240 min without intraoperative complications and with minimal blood loss of 50 ml. The patient was uneventfully discharged on postoperative Day 7. The final pathology confirmed signet-ring cell carcinoma confined to the mucosal muscle without metastasis in 16 lymph nodes. Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy can be safely performed in patients with SIT and has similar surgical outcomes to usual laparoscopic gastrectomy.

BackgroundCardiac involvement constitutes the primary cause of mortality in patients with Danon disease (DD). This study aimed to explore the cardiac magnetic resonance (CMR) features and progressions of DD cardiomyopathies in a family with long-term follow-up.MethodsSeven patients (five females and two males), belonging to the same family and afflicted with DD, were enrolled in this study between 2017 and 2022. The cardiac structure, function, strain, tissue characteristics on CMR and their evolutions during follow-up were analyzed.ResultsThree young female patients (3/7, 42.86%) exhibited normal cardiac morphology. Four patients (4/7, 57.14%) displayed left ventricle hypertrophy (LVH), and mostly with septal thickening (3/4, 75%). A single male case (1/7, 14.3%) showed decreased LV ejection fraction (LVEF). Nonetheless, the global LV strain of the four adult patients decreased in different degree. The global strain of adolescent male patients was decreased compared to the age-appropriate female patients. Five patients (5/7, 71.43%) exhibited late gadolinium enhancement (LGE), with proportion ranging from 31.6% to 59.7% (median value 42.7%). The most common LGE location was the LV free wall (5/5, 100%), followed by right ventricle insertion points (4/5, 80%) and intraventricular septum (2/5, 40%). Segmental radial strain (rs = −0.586), circumferential strain (r = 0.589), and longitudinal strain (r = 0.514) were all moderately correlated with the LGE proportions of corresponding segments (P

The Johnson–Cook model is widely used because of its ability to meet the simulation material requirements in various situations. However, under different working conditions, the accuracy of the model may have errors. In this work, based on Abaqus (Abaqus R2022 Education Edition, Dassault Systèmes, Paris, France) simulation software, Johnson–Cook (JC) constitutive model parameters and compression parameters were selected to simulate the improvement of surface roughness during the ball milling of a 7075-T651 aluminum alloy. In the numerical simulation of ball polishing, the changes in the residual stress field when the Johnson–Cook parameters change are analyzed. By comparing the numerically simulated residual stress fields under the JC parameters calculated at different strain rates, a set of parameters that agrees with the experimental values is selected. The results show that the residual stresses are in line with the experimental values when the strain rate is 10−4s −1. The changes in roughness corresponding to the selected parameters are analyzed. The results indicate that the simulated trend of roughness variation is consistent with the experimental values, and the optimal surface roughness value under a static pressure of 300 N is obtained.

This paper presents a comprehensive method for optimizing the controlling parameters of a biomass boiler. The historical data are preprocessed and classified into different conditions with the k-means clustering algorithm. The first-order derivative (FOD) method is used to compensate for the lag of controlling parameters, the backpropagation (BP) neural network is used to map the controlling parameters with the boiler efficiency and unit load, and the ant colony optimization (ACO) algorithm is used to search the opening of air dampers. The results of the FOD-BP-ACO model show an improvement in the boiler efficiency compared to the predicted values of FOD-BP and the data compared to the historical true values were observed. The results suggest that this FOD-BP-ACO method can also be used to search and optimize other controlling parameters.

In view of the serious side effects of chlortetracycline (CTC) on the human body, it is particularly important to develop rapid, sensitive, and selective technologies for the detection of CTC in food. In this work, a molecularly imprinted electrochemical sensor with [Fe(CN)6]3−/4− as signal probe was proposed for the highly sensitive and selective detection of CTC. For this purpose, TiO2, which acts as an interlayer scaffold, was uniformly grown on the surface of Ti3C2Tx sheets through a simple two-step calcination process using Ti3C2Tx as the precursor to effectively avoid the stacking of Ti3C2Tx layers due to hydrogen bonding and van der Waals forces. This endowed TiO2@Ti3C2Tx with large specific surface, abundant functional sites, and rapid mass transfer. Then, polypyrrole molecularly imprinted polymers (MIPs) with outstanding electrical conductivity were modified on the surface of TiO2@Ti3C2Tx via simple electro-polymerization, where the pyrrole was employed as a polymeric monomer and the CTC provided a source of template molecules. This will not only provide specific recognition sites for CTC, but also facilitate electron transport on the electrode surface. The synergistic effects between TiO2@Ti3C2Tx and polypyrrole MIPs afforded the TiO2@Ti3C2Tx/MIP-based electrochemical sensor excellent detection properties toward CTC, including ultra-low limits of detection (LOD) (0.027 nM), a wide linear range (0.06–1000 nM), and outstanding stability, reproducibility, selectivity, and feasibility in real samples. The results indicate that this strategy is feasible and will broaden the horizon for highly sensitive and selective detection of CTC.

Low back pain (LBP) is one of the most common health problems in people's lives, which brings a massive burden to clinicians, and the leading cause of LBP is intervertebral disc degeneration (IDD). IDD is mainly caused by factors such as aging, mechanical stress, and lack of nutrition. The pathological mechanism of IDD is very complex, involving inflammatory response, cell metabolism disorder, and so on. Unfortunately, in the current treatment of IDD, only relieving symptoms as the primary means of relieving a patient's pain cannot effectively inhibit or reverse the progression of IDD. Tumor necrosis factor-α (TNF-α) is a multifunctional pro-inflammatory factor involved in many diseases' pathological processes. With the in-depth study of the pathological mechanism of IDD, more and more evidence has shown that TNF-α is an essential activator of IDD, which is related to the metabolic disorder, inflammatory responses, apoptosis, and other pathological processes of extracellular dissociation in the intervertebral disc. Therefore, anti-TNF-α therapy is an effective therapeutic target for alleviating IDD, especially in inhibiting extracellular matrix degradation and reducing inflammatory responses. This article reviews the pathological role of TNF-α in IDD and the latest research progress of TNF-α inhibitors in treating IDD.

BackgroundHepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear.MethodsWe investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram.ResultsA total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients’ characteristics and risk scores.ConclusionCRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.

BackgroundAlthough dexmedetomidine (DEX) is widely used during the perioperative period in patients with hepatocellular carcinoma (HCC), its clinical effects on liver function and postoperative inflammation are unclear. This study aimed to explore effects of DEX on postoperative liver function and inflammation in patients with HCC after hepatectomy.MethodsA retrospective cohort study with propensity score matching was performed. A total of 494 patients who underwent hepatectomy from June 2019 to July 2020 and fulfilled the eligibility criteria were included in this study. Baseline data, liver function indexes and inflammation-related biomarkers were collected and compared between the two groups. Survival analysis was conducted to investigate the effects of DEX on the overall survival (OS) of patients. Propensity score matching (PSM) was used to minimize bias between the two groups.ResultsThe study cohort comprised 189 patients in the DEX-free group and 305 patients in the DEX group. Patients in the DEX group had lower levels of alanine transaminase (ALT, P = 0.018) and lactate dehydrogenase (LDH, P = 0.046) and higher level of serum albumin (ALB, P < 0.001) than patients in the DEX-free group before discharge. A total of 107 pairs of patients were successfully matched by PSM. Results consistently suggested that ALT and LDH levels were significantly lower (P = 0.044 and P = 0.046, respectively) and ALB levels were significantly higher (P = 0.002) in the DEX group than in the DEX-free group in the early postoperative period. No significant differences of inflammation-related biomarkers were observed between two groups after PSM. Neither the Kaplan–Meier survival analysis nor the multiple Cox regression survival analysis identified DEX as a contributing factor that would affect the OS of patients after PSM.ConclusionDEX exerts protective effects on liver function while has little effects on inflammation-related biomarkers in the early postoperative period in patients undergoing hepatectomy due to HCC.

Abstract Inflammatory bowel disease (IBD) is a collective term for inflammatory diseases including Crohn’s disease and ulcerative colitis. Toll-like receptor 4 (TLR4) is thought to play a key role in the pathogenesis of IBD. Inhibition of TLR4 has been recognized as an effective target for the treatment of IBD. Many phytochemicals have been shown to have potential as new drugs for the treatment of IBD. This review surveyed the available literature and reports which focused on the in vivo effects of phytochemicals targeting TLR4 in different models of IBD, and clarified the significance of TLR4 as a current therapeutic target for IBD. Based on our review, we have concluded that phytochemicals targeting TLR4 are potentially effective candidates for developing new therapeutic drugs against IBD.

Summary Bacterial wilt, caused by the Ralstonia solanacearum, can infect several economically important crops. However, the management strategies available to control this disease are limited. Plant growth‐promoting rhizobacteria (PGPR) have been considered promising biocontrol agents. In this study, Bacillus amyloliquefaciens strain Cas02 was isolated from the rhizosphere soil of healthy tobacco plants and evaluated for its effect on plant growth promotion and bacterial wilt suppression. Strain Cas02 exhibited several growth‐promoting–related features including siderophore production, cellulase activity, protease activity, ammonia production and catalase activity. Moreover, strain Cas02 showed a significant inhibitory growth effect on R. solanacearum, and its active substances were separated and identified to be macrolactin A and macrolactin W by HPLC‐DAD‐ESI‐MS/MS. Both greenhouse and field experiments demonstrated a good performance of Cas02 in plant growth promotion and bacterial wilt suppression. To explore the underlying genetic mechanisms, complete genome sequencing was performed and the gene clusters responsible for antibacterial metabolites expression were identified. Overall, these findings suggest that the strain Cas02 could be a potential biocontrol agent in bacterial wilt management and a source of antimicrobial compounds for further exploitation.

Abstract To obtain the optimal processing parameters of ultrasonic roll extrusion, 42CrMo bearing steel was taken as the research object, and the orthogonal test method was used to design an ultrasonic roll extrusion experiment with spindle speed, feed speed, static pressure and amplitude as parameters. Based on the orthogonal test data, the prediction models of surface roughness, surface residual stress and surface hardness were established by a multiple regression method, and the reliability of the model was verified. An algorithm combining SPEA2 and the shift density estimation strategy (SPEA2SDE) was introduced. The performance of the SPEA2SDE algorithm, NSGA II algorithm and SPEA2 algorithm is tested and compared on a three-dimensional test function set to verify its effectiveness. The SPEA2SDE algorithm are used to solve the multi-objective optimization model to obtain the optimal combination of processing parameters, and the ultrasonic roll extrusion experiment is carried out. The research results show that the surface roughness, surface residual stress and surface hardness optimized by the SPEA2SDE algorithm are in good agreement with the experimental values, and the average error is controlled within 10%, which shows that the algorithm can achieve high precision. It can effectively solve the multi-objective optimization problem of ultrasonic roll extrusion process parameters and can be used to guide actual production machining.

In battery management systems, state of charge (SOC) estimation is important for ensuring the safety and reliability of batteries. Currently, there are various methods for estimating SOC, and the neural network method is the most popular. However, when the battery’s SOC is low (below 20%), the uncertainty in neural network parameters can lead to significant bias in SOC estimation. To address these problems, this study proposes a method based on genetic algorithm (GA) optimization of a time-serialization convolutional neural network (TSCNN) model. First, the population is initialized according to the optimized hyperparameters of the TSCNN model, whereby the experimental data are converted into time-series data. Subsequently, neural network models are built based on the population, thereby using the effect of the network as the fitness function for GA optimization. Finally, an optimized network structure is obtained for accurate SOC estimation. During the optimization process, the optimized data exhibited abnormal phenomena, usually manifested as exceeding the data limits or being zero. In the past, abnormal data were discarded and new data were regenerated; however, this reduces the correlation between data. Therefore, this study proposes a check function to enhance the correlation between the data, converting abnormal data into normal data by limiting the data range. To the best of our knowledge, it is the first time that a GA is being proposed to optimize the time-series length of a convolutional neural network (CNN) while the neural network parameters are optimized so that the time-series length and neural network parameters achieve the best match. In the experimental results, the maximum error was 4.55% for the dynamic stress test (DST) dataset and 2.58% for the urban dynamometer driving schedule (UDDS) dataset. When the battery SOC was below 20%, the estimation error did not incur a huge error. Therefore, the optimization method proposed for the TSCNN model in this study can effectively improve the accuracy and reliability of SOC estimation in the low-battery state.

The difficulty of Multi-Agent Reinforcement Learning (MARL) increases with the growing number of agents in system. The value function decomposition is an effective way to alleviate the curse of dimension. However, the existing methods usually either can only provide the low-order approximate decomposition of no more than the second-order, or need to spend a lot of effort manually designing the high-order interaction among agents according to experience. Therefore, the existing methods either tend to bear large decomposition error or are not convenient to use. In this paper, a high-order approximate value function decomposition method is proposed, which has the following prominent characteristics: the low-rank vector is exploited to represent value function, the low-order and high-order components share the same input (i.e., the embedding vector), the attention mechanism is used to select the agents participating in the high-order interaction, and all agents share the model parameters if the agents are homogeneous. To our knowledge, this is the first MARL method modeling low- and high-order interaction simultaneously among agents that can be trained end-to-end. Extensive experiments on two different multi-agent problems demonstrate the performance gain of our proposed approach in comparison with strong baselines, particularly when there are a large number of agents.

Tendon injury is one of the prevalent disorders of the musculoskeletal system in orthopedics and is characterized by pain and limitation of joint function. Due to the difficulty of spontaneous tendon healing, and the scar tissue and low mechanical properties that usually develops after healing. Therefore, the healing of tendon injury remains a clinical challenge. Although there are a multitude of approaches to treating tendon injury, the therapeutic effects have not been satisfactory to date. Recent studies have shown that stem cell therapy has a facilitative effect on tendon healing. In particular, tendon stem/progenitor cells (TSPCs), a type of stem cell from tendon tissue, play an important role not only in tendon development and tendon homeostasis, but also in tendon healing. Compared to other stem cells, TSPCs have the potential to spontaneously differentiate into tenocytes and express higher levels of tendon-related genes. TSPCs promote tendon healing by three mechanisms: modulating the inflammatory response, promoting tenocyte proliferation, and accelerating collagen production and balancing extracellular matrix remodeling. However, current investigations have shown that TSPCs also have a negative effect on tendon healing. For example, misdifferentiation of TSPCs leads to a “failed healing response,” which in turn leads to the development of chronic tendon injury (tendinopathy). The focus of this paper is to describe the characteristics of TSPCs and tenocytes, to demonstrate the roles of TSPCs in tendon healing, while discussing the approaches used to culture and differentiate TSPCs. In addition, the limitations of TSPCs in clinical application and their potential therapeutic strategies are elucidated.

BackgroundAcute respiratory distress syndrome (ARDS) is a serious organ failure and postoperative complication. However, the incidence rate, early prediction and prevention of postoperative ARDS in patients undergoing hepatectomy remain unidentified.MethodsA total of 1,032 patients undergoing hepatectomy between 2019 and 2020, at the Eastern Hepatobiliary Surgery Hospital were included. Patients in 2019 and 2020 were used as the development and validation cohorts, respectively. The incidence rate of ARDS was assessed. A logistic regression model and a least absolute shrinkage and selection operator (LASSO) regression model were used for constructing ARDS prediction models.ResultsThe incidence of ARDS was 8.8% (43/490) in the development cohort and 5.7% (31/542) in the validation cohort. Operation time, postoperative aspartate aminotransferase (AST), and postoperative hemoglobin (Hb) were all critical predictors identified by the logistic regression model, with an area under the curve (AUC) of 0.804 in the development cohort and 0.752 in the validation cohort. Additionally, nine predictors were identified by the LASSO regression model, with an AUC of 0.848 in the development cohort and 0.786 in the validation cohort.ConclusionWe reported the incidence of ARDS in patients undergoing hepatectomy and developed two simple and practical prediction models for early predicting postoperative ARDS in patients undergoing hepatectomy. These tools may improve clinicians’ ability to early estimate the risk of postoperative ARDS and timely prevent its emergence.

The ability to biosynthesize oxalic acid can provide beneficial functions to plants; however, uncontrolled or prolonged exposure to this strong organic acid results in multiple physiological problems. Such problems include a disruption of membrane integrity, mitochondrial function, metal chelation, and free radical formation. Recent work suggests that a CoA-dependent pathway of oxalate catabolism plays a critical role in regulating tissue oxalate concentrations in plants. Although this CoA-dependent pathway of oxalate catabolism is important, large gaps in our knowledge of the enzymes catalyzing each step remain. Evidence that an oxalyl-CoA decarboxylase (OXC) catalyzes the second step in this pathway, accelerating the conversion of oxalyl-CoA to formyl-CoA, has been reported. Induction studies revealed that OXC gene expression was upregulated in response to an exogenous oxalate supply. Phylogenetic analysis indicates that OXCs are conserved across plant species. Evolutionarily the plant OXCs can be separated into dicot and monocot classes. Multiple sequence alignments and molecular modeling suggest that OXCs have similar functionality with three conserved domains, the N-terminal PYR domain, the middle R domain, and the C-terminal PP domain. Further study of this CoA-dependent pathway of oxalate degradation would benefit efforts to develop new strategies to improve the nutrition quality of crops.

Tobacco black shank caused by Phytophthora nicotianae is a devastating disease that causes huge losses to tobacco production across the world. Investigating the regulatory mechanism of tobacco resistance to P. nicotianae is of great importance for tobacco resistance breeding. The jasmonate (JA) signaling pathway plays a pivotal role in modulating plant pathogen resistance, but the mechanism underlying JA-mediated tobacco resistance to P. nicotianae remains largely unclear. This work explored the P. nicotianae responses of common tobacco cultivar TN90 using plants with RNAi-mediated silencing of NtCOI1 (encoding the perception protein of JA signal), and identified genes involved in this process by comparative transcriptome analyses. Interestingly, the majority of the differentially expressed bHLH transcription factor genes, whose homologs are correlated with JA-signaling, encode AtBPE-like regulators and were up-regulated in NtCOI1-RI plants, implying a negative role in regulating tobacco response to P. nicotianae. A subsequent study on NtbHLH49, a member of this group, showed that it’s negatively regulated by JA treatment or P. nicotianae infection, and its protein was localized to the nucleus. Furthermore, overexpression of NtbHLH49 decreased tobacco resistance to P. nicotianae, while knockdown of its expression increased the resistance. Manipulation of NtbHLH49 expression also altered the expression of a set of pathogen resistance genes. This study identified a set of genes correlated with JA-mediated tobacco response to P. nicotianae, and revealed the function of AtBPE-like regulator NtbHLH49 in regulating tobacco resistance to this pathogen, providing insights into the JA-mediated tobacco responses to P. nicotianae.