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Background: Coronary physiology measured by fractional flow reserve (FFR) is superior to angiography for assessing the efficacy of percutaneous coronary intervention (PCI). Yet, the clinical adoption of post-PCI FFR is limited. Murray law-based quantitative flow ratio (μQFR) may represent a promising alternative, as it can quickly compute FFR from a single angiographic view. Objectives: The authors aimed to investigate the potential role of post-PCI μQFR in predicting clinical outcomes. Methods: This was a post hoc blinded analysis of the FLAVOUR trial. Patients with angiographically intermediate lesions randomized 1:1 to receive FFR or intravascular ultrasound-guided PCI were included. Post-PCI μQFR was assessed in successfully stented vessels, blinded to clinical outcomes. Suboptimal physiological outcome post-PCI was defined a priori as post-PCI μQFR

Previous studies have revealed that typhoons can affect the ionosphere. This paper uses GNSS observations provided by GNSS tracking stations of Taiwan region, ERA5 gravity wave dissipation products, and Himawari-8 band 07 brightness temperature observation data to analyze the impact of Typhoon Meranti on Taiwan region's ionosphere from September 13 to 15, 2016. In addition to the daily effects of traveling ionospheric disturbances (TIDs), TIDs of various intensities caused by Meranti-induced gravity waves were observed during this period, which is inseparable from the state of the typhoon and the topographic features during its progress. The ionospheric disturbance caused by the edge of a typhoon is usually larger than that at the typhoon eye. When the typhoon approached Taiwan region with high intensity on September 14, it was observed that the gravity waves caused by the typhoon had a wavelength of about 174–293 km, a period of 13.5–23.5 min, and a propagation speed of 142–302 m/s. When the vortex structure of a typhoon interacts with complex surfaces such as mountains, it is easier to excite more medium-scale gravity waves. The origin that excites gravity waves and causes ionospheric anomalies is different from the location of the typhoon eye and changes over time. The gravity waves caused by the typhoon lasted for three days in the central mountains of Taiwan region. Still, background wind conditions restricted the propagation of gravity waves from the mesosphere to the thermosphere and led to TID predominantly concentrated between 06:00 and 13:00 UT each day.

The paper addresses the challenges of task migration and resource allocation in heterogeneous cloud–edge environments, where dynamic and stochastic conditions complicate efficient scheduling. To tackle this, the authors propose a novel scheduling algorithm combining soft actor–critic (SAC) agent with masked layer and graph convolutional network (GCN), namely MGSAC algorithm. MGSAC utilizes GCN to extract hidden structural features from the environment, enabling better adaptation to dynamic changes. Additionally, a learnable mask layer filters out ineffective actions, refining the selection of scheduling strategies and improving overall performance. By evaluating MGSAC on the real-world Bit-Brain dataset and simulating it using Cloud-Sim, experimental results demonstrate its superiority over existing algorithms in energy consumption, task response time, task migration time, and task Service-Level-Agreement violations rate, showcasing its effectiveness in real-world scenarios.

Abstract Growth Differentiation Factor-15 (GDF-15) is a pleiotropic cytokine that plays a significant role in metabolism and inflammation. Elevated serum levels of GDF-15 have been associated with mood disorders. We propose that GDF-15 may potentially influence cognitive impairment and metabolism in male patients with chronic schizophrenia (CS), although there is limited research on this topic. This study compared serum GDF-15 levels in 72 male patients with CS and 85 healthy controls (HC). The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), while cognitive performance was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The male CS patients performed worse than the healthy controls in both the total score and all subscales of the RBANS. Serum GDF-15 concentrations were significantly higher in the male CS patients compared to the healthy controls. Furthermore, the log-transformed serum GDF-15 concentrations in male CS patients were positively correlated with BMI and negatively correlated with Delayed Memory scores, Immediate Memory, and the total RBANS score. This preliminary study suggests that elevated serum GDF-15 levels in male patients with chronic schizophrenia may play a role in cognitive function and BMI regulation.

Abstract Background Disulfidptosis has recently emerged as a novel form of regulated cell death (RCD). Evasion of cell death is a hallmark of cancer, and the resistance of many tumors to apoptosis-inducing therapies has heightened interest in exploring alternative RCD mechanisms. Methods Transcriptomic and clinical data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA). Glioma samples were classified using non-negative matrix factorization (NMF). A predictive model was constructed using Lasso regression analysis, and its performance was evaluated through receiver operating characteristic (ROC) and Kaplan–Meier survival analyses. The relationship between the model and the tumor immune microenvironment (TIME) as well as treatment sensitivity was also assessed. Finally, we validated the expression of key signature genes in glioma. Results Glioma samples were categorized into two distinct subtypes based on disulfidptosis-related genes, showing significant differences in overall survival (OS) and progression-free survival (PFS) between the subtypes. A genetic risk score model was then developed using these genes. A nomogram predicting OS was constructed using the risk score and clinical variables. Patients were stratified into low- and high-risk groups based on the median risk score from the TCGA cohort. Low-risk patients had significantly better outcomes compared to high-risk patients (TCGA cohort, OS: p

Abstract Background Metastatic castration-resistant prostate cancer is the most dangerous stage of prostate cancer, with a high mortality rate. Docetaxel chemotherapy is one of the most effective treatment methods currently, but some patients do not respond to chemotherapy. To avoid unnecessary toxicity in non-responders, this study explores the potential of circulating microRNAs as early biomarkers of docetaxel response in patients with metastatic castration-resistant prostate cancer. Methods PC3 cells and DU145 cells were divided into the control, NC mimics, and miRNA-136-5p-mimics groups. Cell viability was measured using the CCK-8 assay. Cell apoptosis was determined by flow cytometry. Cell migration and invasion abilities were evaluated using the Transwell assay. Real-time quantitative PCR was used to measure the miRNA levels in cells and peripheral blood of patients. The miRNA-136-5p target genes were predicted by using the PITA, TargetScan, and miRanda databases. The target genes were analyzed with KEGG pathway analysis. Results In both PC3 and DU145 cells, the miRNA-136-5p-mimics group exhibited significantly increased cell survival rates, migration and invasion numbers, and significantly decreased apoptosis rates than the control group (p

Abstract Background Breastfeeding is the optimal source of nutrition for infants and young children, essential for their healthy growth and development. However, a gap in cohort studies tracking breastfeeding up to six months postpartum may lead caregivers to miss critical intervention opportunities. Methods This study conducted a three-wave prospective cohort analysis to examine maternal breastfeeding trajectories within the first six months postpartum and to develop risk prediction models for each period using advanced machine learning algorithms. Conducted at a leading Maternal and Children's hospital in China from October 2021 to June 2022, data were gathered via self-administered surveys and electronic health records. Results Of the 3307 women recruited, 3175 completed the surveys, yielding a 96% effective response rate. Breastfeeding(BF) rates were observed at 100%, 96%,93% and 83% at discharge, 42 day, 3 month and 6 month postpartum, respectively. Exclusively breastfeeding(EBF) rates were recorded at 91%, 64%,72% and 58% for the same intervals. Among the five machine learning methods employed, Random Forest (RF) demonstrated superior accuracy in predicting breastfeeding patterns, with classification accuracies of 0.629 and an area under the receiver operating characteristic curve (AUC) of 0.8122 at 42 days, 0.925 and an AUC of 0.9800 at 3 months, and 0.836 and an AUC of 0.9463 at 6 months postpartum, respectively. Key predictive factors for breastfeeding at 42 days postpartum included the newborn’s birth weight and the mother’s pre-delivery and prenatal weights. Predictors for feeding type at 3 months and 6 months postpartum included early feeding types and the scores from the Breastfeeding Self-Efficacy Scale-short Form (BSES-SF) at 6 months. The predictive model based on follow-up data showed strong performance. Conclusion Breastfeeding rates slightly declined from discharge to 6 months postpartum. The breastfeeding context in this region is comparatively optimistic both within China and internationally. Factors such as newborn’s birth weight, gestational age, maternal weight management before and during pregnancy, early support and breastfeeding success, breastfeeding knowledge and self-efficacy are intricately linked to long-term breastfeeding outcomes. This study highlights critical, modifiable risk factors for early breastfeeding stages, providing valuable insights for enhancing breastfeeding intervention programs and informed decision-making.

Early dental caries detection by endoscope can prevent complications, such as pulpitis and apical infection. However, automatically identifying dental caries remains challenging due to the uncertainty in size, contrast, low saliency, and high interclass similarity of dental caries. To address these problems, we propose the Global Feature Detector (GFDet) that integrates the proposed Feature Selection Pyramid Network (FSPN) and Adaptive Assignment-Balanced Mechanism (AABM). Specifically, FSPN performs upsampling with the semantic information of adjacent feature layers to mitigate the semantic information loss due to sharp channel reduction and enhance discriminative features by aggregating fine-grained details and high-level semantics. In addition, a new label assignment mechanism is proposed that enables the model to select more high-quality samples as positive samples, which can address the problem of easily ignored small objects. Meanwhile, we have built an endoscopic dataset for caries detection, consisting of 1318 images labeled by five dentists. For experiments on the collected dataset, the F1-score of our model is 75.6%, which out-performances the state-of-the-art models by 7.1%.

Abstract Iron overload (IO) was considered to be a risk factor for cartilage degradation in knee osteoarthritis (KOA) advancement. However, few drugs were found to improve cartilage degeneration by alleviating multiple cell death induced by the impaired iron level of the knee joints. We aimed to elucidate that Arctiin (ARC) plays a role in managing KOA caused by accumulated iron levels by restoring chondrocyte apoptosis and ferroptosis. Single-cell RNA sequencing analysis was used to discover the disparities in chondrocytes between KOA patients and non-KOA individuals. CCK-8 assay was performed to detect chondrocyte viability. Annexin V-FITC/PI staining determined the cell apoptosis rate. The fluorescence density reflected the iron content, ROS, lipid-ROS, and mitochondrial membrane potential. Q-RTPCR and Western Blotting were used to detect the expression levels of genes and proteins expression. Micro-CT and Safranin O-Fast Green staining were used to detect the phenotype of the knee joints. ARC increased cell viability and inhibited chondrocyte apoptosis. Further, ARC acts as an anti-ferroptosis effect by reducing the intracellular iron, ROS, and lipid-ROS content and restoring mitochondrial damage. Based on the results of scRNA-seq, we found that ARC can play a role by activating AKT/NRF2/HO-1 signaling pathway. In vivo, ARC can significantly improve the severity of KOA caused by IO. ARC alleviates oxidative stress in chondrocytes via the AKT/NRF2/HO-1 signaling pathway, suggesting the potential application of ARC in KOA.

Abstract Background Immune checkpoint inhibitors (ICIs) are a cornerstone therapy for advanced renal cell carcinoma (RCC). However, significant rates of primary resistance hinder their efficacy, and the underlying mechanisms remain poorly understood. This study aims to unravel the tumor-immune interactions and signaling pathways driving primary resistance to ICIs in RCC. Methods We integrated single-cell RNA sequencing, spatial transcriptomics, and clinical sample analysis to investigate the tumor microenvironment and intercellular signaling. Advanced computational methods, including cell–cell communication networks, pseudotime trajectories, and gene set enrichment analysis (GSEA), were employed to uncover the underlying resistance mechanisms. Results Compared to the sensitive group, the primary resistance group exhibited a significant increase in SPP1-CD44 signaling-mediated interactions between tumor cells and immune cells. These interactions disrupted antigen presentation in immune effector cells and suppressed key chemokine and cytokine pathways, thereby impairing effective immune responses. In contrast, the sensitive group showed more active antigen presentation and cytokine signaling, which facilitated stronger immune responses. Furthermore, the interaction between SPP1-secreting tumor cells and CD44-expressing exhausted CD8 + T cells activated the MAPK signaling pathway within CD8 + Tex cells, exacerbating T cell exhaustion and driving the development of ICI resistance in RCC. Conclusion Our findings reveal a potential mechanism by which SPP1-CD44 signaling mediates tumor-immune cell interactions leading to ICI resistance, providing a theoretical basis for targeting and disrupting this signaling to overcome primary resistance in RCC.

Magnesium alloys with high strength in combination of good ductility are especially desirable for applications in transportation, aerospace and bio-implants owing to their high stiffness, abundant raw materials, and environmental friendliness. However, the majority of traditional strengthening approaches including grain refining and precipitate strengthening can usually prohibit dislocation movement at the expense of ductility invariably. Herein, we report an effective strategy for simultaneously enhancing yield strength (205 MPa, 2.41 times) and elongation (23%, 1.54 times) in a Mg-0.2Zn-0.6Y (at.%) alloy at room temperature, based on the formation of a nanosized quasi-long period stacking order unit (QLPSO)-twin structure by ultrahigh-pressure treatment followed by annealing. The formation reason and strong-ductile mechanism of the unique QLPSO-twin structure have been clarified by transmission electron microscopy observations and molecule dynamics simulations. The improved strength is mainly associated with the presence of nanosized QLPSO and the modified ∠86.3o QLPSO-twin boundary (TB) interface, effectively pinning dislocation movement. Comparatively, the enhanced ductility is related to the ∠3.7o QLPSO-TB interface and micro-kinks of nanoscale QLPSO, providing some paths for plastic deformation. This strategy on the QLPSO-twin structure might provide an alternative perspective for designing innovative hexagonal close-packed structural materials with superior mechanical properties.

In this study, the cold-spraying process was utilized to deposit Al particles onto an Al slab, an Mg slab, and both Al and Mg slabs to form an ultra-thin interlayer, and then the clad slabs were rolled at 400 °C, developing three roll-bonding processes: the roll-bonding process with cold-sprayed Al powder on the Al slab (CS-Al), the roll-bonding process with cold-sprayed Al powder on the Mg slab (CS-Mg), and the roll-bonding process with cold-sprayed Al powder on both the Al slab and the Mg slab (CS-Both). The effects of three different cold-sprayed Al particle interlayer processes on the mechanical properties of rolled Mg/Al clad plates were investigated to improve the mechanical properties. The microstructure, texture evolution, intermetallic compound formation, mechanical properties, and mechanisms involved in the Mg/Al clad plate rolling were systematically investigated. The results showed that the pre-bonding between the particles and the substrates through cold-spraying had a significant impact on the bonding strength of the Mg/Al clad plates, and the CS-Both process can increase the average shear strength of the Mg/Al clad plates to 49.24 MPa at a medium reduction rate of 37.5 %, 2.5 times that of the conventional rolling process. The CS-Both process constructed more evident dual microscopic three-dimensional interfaces and promoted more thorough atomic diffusion at the interface through the double-sided cold-spraying process. Meanwhile, the dual cold-sprayed Al coatings on both the Mg slab and Al slab underwent dynamic recrystallization during rolling to form a homogeneous unit with no additional coating interfaces. Fine grain strengthening and dislocation strengthening were judged to be important mechanisms for improving the mechanical performance of the interfacial layer.

Abstract A 3D geometric model is established based on a fluid‒solid coupling model for purpose of identifying the influences of mining disturbances on the distribution of gas pressures in front of a working face during gas extraction. Then, the stress distribution and gas extraction process are simulated using COMSOL software. The spatiotemporal evolutions of gas pressures in front of the working face are analyzed from the dimensions of point, line, surface, and volume. A comparative analysis has been conducted to explore the distribution patterns of gas pressure in fractures and pores. The results show that under mining disturbance, the stresses in front of the working face create a stress-relaxation area, a stress concentration area, and an original stress area. Moreover, a low stress concentration is located near the boreholes. In the early stage of gas extraction, corresponding to the stress distribution, the gas pressures present a depressurization area, pressure concentration area, and almost undisturbed area. As the time increases after mining, the effects of mining disturbances gradually decrease, and the range of the gas pressure concentration area steadily shortens and shifts toward the front of the working face. Under the same temporal conditions, the gas pressure in pores is higher than that in fractures. At the onset of mining, the pore gas pressure is even greater than the initial pressure. Furthermore, during the identical extraction period, the “concentration area” of pore gas pressure is situated farther away from the coal wall of the working face compared to the “concentration area” of fracture gas pressure. These results of the study provide theoretical support for arranging drainage boreholes, enhancing gas extraction efficiency, safeguarding against gas accidents.

Abstract Transition metals like Zn are essential for all organisms including bacteria, but fluctuations of their concentrations in the cell can be lethal. Organisms have thus evolved complex mechanisms for cellular metal homeostasis. One mechanistic paradigm involves pairs of transcription regulators sensing intracellular metal concentrations to regulate metal uptake and efflux. Here we report that Zur and ZntR, a prototypical pair of regulators for Zn uptake and efflux in E. coli, respectively, can coordinate their regulation through DNA, besides sensing cellular Zn2+ concentrations. Using a combination of live-cell single-molecule tracking and in vitro single-molecule FRET measurements, we show that unmetallated ZntR can enhance the unbinding kinetics of Zur from DNA by directly acting on Zur-DNA complexes, possibly through forming heteromeric ternary and quaternary complexes that involve both protein-DNA and protein-protein interactions. This ‘through-DNA’ mechanism may functionally facilitate the switching in Zn-uptake regulation when bacteria encounter changing Zn environments, such as facilitating derepression of Zn-uptake genes upon Zn depletion; it could also be relevant for regulating the uptake-vs.-efflux of various metals across different bacterial species and yeast.

Abstract Objective We aimed to develop an AI-based model that uses a portable electronic oral endoscope to capture intraoral images of patients for the detection of oral cancer. Subjects and methods From September 2019 to October 2023, 205 high-quality annotated images of oral cancer were collected using a portable oral electronic endoscope at the Chinese PLA General Hospital for this study. The U-Net and ResNet-34 deep learning models were employed for oral cancer detection. The performance of these models was evaluated using several metrics: Dice coefficient, Intersection over Union (IoU), Loss, Precision, Recall, and F1 Score. Results During the algorithm model training phase, the Dice values were approximately 0.8, the Loss values were close to 0, and the IoU values were around 0.7. In the validation phase, the highest Dice values ranged between 0.4 and 0.5, while the Loss values increased, and the training loss began to decrease gradually. In the test phase, the model achieved a maximum Precision of 0.96 with a confidence threshold of 0.990. Additionally, with a confidence threshold of 0.010, the highest F1 score reached was 0.58. Conclusion This study provides an initial demonstration of the potential of deep learning models in identifying oral cancer.

Context Cephaeline is a natural product isolated from ipecac (Cephaelis ipecacuanha [Brot.] A. Rich. [Rubiaceae]). It exhibits promising anti-lung cancer activity and ferroptosis induction may be a key mechanism for its anti-lung cancer effect.Objectives This study investigates the anti-lung cancer activity and mechanisms of cephaeline both in vitro and in vivo.Materials and methods H460 and A549 lung cancer cells were used. The cephaeline inhibition rate on lung cancer cells was detected via a Cell Counting Kit-8 assay after treatment with cephaeline for 24 h. Subsequently, the concentrations of 25, 50 and 100 nM were used for in vitro experiments. In addition, the antitumour effects of cephaeline (5, 10 mg/kg) in vivo were evaluated after 12 d of cephaeline treatment.Results Cephaeline showed significant inhibitory effects on lung cancer cells, and the IC50 of cephaeline on H460 and A549 at 24, 48 and 72 h were 88, 58 and 35 nM, respectively, for H460 cells and 89, 65 and 43 nM, respectively, for A549 cells. Meanwhile, we demonstrated that ferroptosis is the key mechanism of cephaeline against lung cancer. Finally, we found that cephaeline induced ferroptosis in lung cancer cells by targeting NRF2.Discussion and conclusion We demonstrated for the first time that cephaeline inhibits NRF2, leading to ferroptosis in lung cancer cells. These findings may contribute to the development of innovative therapeutics for lung cancer.

With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment. There are multiple mechanisms of acquired drug resistance in targeted therapy, and the alteration of mesenchymal-epithelial transition factor (MET) signaling pathway is one of the common mechanisms of drug resistance. At present, some selective tyrosine kinase inhibitors (TKIs) of MET has been approved for non-small cell lung cancer with MET gene 14 exon skipping mutation, such as Glumetinib, Savolitinib, Tepotinib, Capmatinib, etc. Drugs that target secondary MET amplification are still in clinical trials. This paper retrospectively analyzed the clinical data of a female patient with EGFR-TKIs resistant secondary MET amplified squamous cell lung cancer, and reviewed relevant literature to explore how to optimize the treatment of lung squamous cell carcinoma patients with EGFR mutation, so as to provide clinical reference for the diagnosis and treatment of such patients.

Cancer has been a severe public health and social problem, a leading disease that has diminished the quality of life, and a barrier to improving life expectancy. Neocryptolepine is an indole-quinoline alkaloid isolated from Cryptolepis sanguinolenta which grows in some African countries. This review summarizes the structures of 228 neocryptolepine derivatives, including 84 neocryptolepine derivatives synthesized by our laboratory, and analyzed the cytotoxic effects and mechanism of action at the cellular level. Neocryptolepine derivatives 43 , 65 , 93 , and 96 have good cytotoxicity against gastric cancer AGS cells and the IC 50 value reached 43 nM, 148 nM, 2.9 μM, and 4.5 μM, respectively. The IC 50 values of compounds 64 and 69 on colorectal cancer HCT116 cells reached 0.33 and 0.35 μM, respectively. In addition, the structure-activity relationship of these compounds is discussed in this review. Topoisomerase II is discussed as a possible inhibition target of neocryptolepine derivatives in several cancer cell lines by binding DNA. The structures of the reported neocryptolepine derivatives and the possible cytotoxic mechanisms are analyzed. This review provides a fundamental reference for anticancer drug development of neocryptolepine and its derivatives as anti-tumor agents.

In order to obtain α-glucan phosphorylase with good heterologous expression level and enzymatic properties and to investigate the impact of structural domains on the enzyme, a novel α-glucan phosphorylase TsGP was screened from the hyperthermophilic archaeon Thermococcus sp. EP1 through database mining and sequence analysis. After confirming that the C-terminal of TsGP was a non-catalytic domain in the three-dimensional structure predicted by AlphaFold2, a C-terminal truncated mutant ΔTsGP was constructed. Heterologous recombinant expression of TsGP and ΔTsGP was performed in E.coli BL21(DE3), and their enzymatic properties were characterized. The results showed that the expression level of ΔTsGP in E.coli was 3.76 times higher than that of TsGP. At the optimal reaction temperature 70 ℃, the specific enzyme activity of ΔTsGP was 23.87 U/mg, which was 1.3 times higher than that of TsGP. Under 50~65 ℃ which was widely applied as industrial catalytic temperature, the thermal stability of ΔTsGP was equivalent to that of TsGP, and the enzyme activity was higher. In addition, ΔTsGP and TsGP had the same substrate specificity, their smallest substrate was maltotriose, and as the substrate chain length increased, their specific enzyme activity gradually increased. Using maltoheptaose as the substrate, the kcat value of ΔTsGP was 37.09 s−1, which was 1.21 times higher than that of TsGP, but its substrate affinity (Km=3.30 mmol/L) was reduced by 2.77 times. Through structural analysis and non-catalytic domain truncation strategies, the study successfully improved the expression level of TsGP in E. coli and the specific enzyme activity under industrial enzyme catalytic conditions. The study would provide guidance for the efficient expression and application of αGPase protein and lays the foundation for further optimizing the performance of this enzyme through engineering modification.

This study focuses on the propagation behavior of traveling wave solution in microcrystalline materials using the polynomial complete discriminant system method. By establishing a complete discriminant system, we systematically analyze the formation and evolution process of traveling wave solution in microcrystalline materials. Specifically, we apply the cubic polynomial extension to the strain wave equation to obtain more accurate analytical solutions. Additionally, two-dimensional, three-dimensional, and contour plots are generated to visually illustrate the characteristics of the obtained solutions, facilitating a more intuitive understanding of their physical significance. These findings not only help reveal the propagation mechanism of traveling wave solution but also provide a theoretical foundation for the application of microcrystalline materials.

Abstract The WCAY (weighted channel attention YOLO) model, which is meticulously crafted to identify fracture features across diverse X-ray image sites, is presented herein. This model integrates novel core operators and an innovative attention mechanism to enhance its efficacy. Initially, leveraging the benefits of dynamic snake convolution (DSConv), which is adept at capturing elongated tubular structural features, we introduce the DSC-C2f module to augment the model’s fracture detection performance by replacing a portion of C2f. Subsequently, we integrate the newly proposed weighted channel attention (WCA) mechanism into the architecture to bolster feature fusion and improve fracture detection across various sites. Comparative experiments were conducted, to evaluate the performances of several attention mechanisms. These enhancement strategies were validated through experimentation on public X-ray image datasets (FracAtlas and GRAZPEDWRI-DX). Multiple experimental comparisons substantiated the model’s efficacy, demonstrating its superior accuracy and real-time detection capabilities. According to the experimental findings, on the FracAtlas dataset, our WCAY model exhibits a notable 8.8% improvement in mean average precision (mAP) over the original model. On the GRAZPEDWRI-DX dataset, the mAP reaches 64.4%, with a detection accuracy of 93.9% for the “fracture” category alone. The proposed model represents a substantial improvement over the original algorithm compared to other state-of-the-art object detection models. The code is publicly available at https://github.com/cccp421/Fracture-Detection-WCAY .

Abstract Background Cuproptosis, a recently identified type of programmed cell death triggered by copper, has mechanisms in Wilms tumor (WT) that are not yet fully understood. This research focuses on examining the link between WT and Cuproptosis-related genes (CRGs), with the goal of developing a predictive model for WT. Methods Four gene expression datasets related to WT were sourced from the GEO database. Subsequently, expression profiles of CRGs were extracted for differential analysis and immune infiltration studies. Utilizing 105 WT samples, clusters related to Cuproptosis were identified. This involved analyzing associated immune cell infiltration and conducting functional enrichment analysis. Disease-characteristic genes were pinpointed using weighted gene co-expression network analysis. Finally, the WT risk prediction model was constructed by four machine learning methods: random forest, support vector machine (SVM), generalized linear and extreme gradient strength model. The best-performing machine learning model was chosen, and a nomogram was created. The effectiveness of this predictive model was validated using methods such as the calibration curve, decision curve analysis, and by appiying it to the TARGET-GTEx dataset. Results Thirteen differentially expressed Cuproptosis-related genes were identified. The infiltration level of CD8 + T cells in WT children was lower than that in Normal tissue (NT) children, and the level of M0 infiltration of macrophages and T follicular helper cells was higher than that in NT children. In addition, two clusters of cuproptosis-related WT were identified. Enrichment analysis results indicated that genes in cluster 2 were primarily involved in cell division, nuclear division regulation, DNA biosynthesis process, ubiquitin-mediated proteolysis. The SVM model was judged to be the optimal model using 5 genes. Its accuracy was confirmed through a calibration curve and decision curve analysis, demonstrating satisfactory performance on the TARGET-GTEx validation dataset. Additional analysis revealed that these five genes exhibited high expression in both the TARGET-GTEx validation dataset and sequencing data. Conclusion This research established a link between WT and Cuproptosis. It developed a predictive model for assessing the risk of WT and pinpointed five key genes associated with the disease.

Abstract Purpose It is controversial for the optimal time of breast cancer surgery after COVID-19 infection. Purpose was to assess the risk of postoperative complication in breast cancer patients with COVID-19 infection, in order to select optimal surgery timing after COVID-19 infection. Methods Breast cancer patients infected with COVID-19 and performed surgery between December 20th, 2022 to March 20th, 2023 were included in this prospective study (n = 577). Patients performed surgery between May 1, 2019 to October 1, 2019 were listed as control group (n = 329). They had not been infected with COVID-19 before surgery. Patients were grouped by time of surgery relative to COVID-19 infection. Database was evaluated using logistic regression. Results Patients infected with COVID-19 had a higher incidence of complications after surgery compared to that not-COVID-19 infection (6.59% vs. 3.04%). Multivariable logistic analysis demonstrated that timing of surgery was associated with complications (OR = 4.253; 95% CI: 0.855–21.153, P = 0.044). Patients performed surgery within 2 weeks after COVID-19 infection had the highest rates of complication (17.65%) when compared with other groups, while the incidence was decreased into 5.51% when surgery 2 weeks or more after COVID-19 infection. With a median follow-up was 10 months, all patients with complications were recovered without serious complications or death, which had no adverse effect on subsequent anti-tumor therapy. Conclusions It needs to be cautious when breast cancer surgery was performed within 2 weeks after COVID-19 infection. Although the incidence of complications in patients undergoing surgery 2 weeks after COVID-19 infection is still slightly high, surgery might be recommended considering urgency of treatment, good prognosis of complications and the lack of influence on subsequent adjuvant therapy.

At present, the incidence and mortality rates of lung cancer rank top among malignant tumors. The early diagnosis, treatment and drug resistance of lung cancer still remain as problems in the management of lung cancer. Researchers are dedicated to identifying reliable biomarkers as predictive indicators or effective therapeutic targets for lung cancer. Insulin resistance (IR), a disorder characterized by reduced biological activity of insulin, leads to increased insulin secretion. In recent years, more and more studies have revealed the association between IR and the occurrence and development of cancer, with the insulin/insulin-like growth factor signaling pathway possibly playing a crucial role. In this article, we will focus on the relationship between IR and lung cancer, explore the impact and mechanism of IR on the development, progression and drug resistance of lung cancer. It may guide the development of new predictive tools and therapeutic strategies, and provide new ideas for research dedicated to reducing the incidence and mortality of lung cancer.

Objectives: Diamond tools are widely used in fields such as oil drilling, geological exploration, and stone processing, among which sintered metal bond diamond tools have become the most representative due to their wide applicability and strong durability. Cobalt (Co) has become the preferred material for preparing diamond tools due to its excellent physical properties, but its price is relatively expensive. As market competition gradually intensifies, the application range of Co is becoming limited. It has been found that Fe-based pre-alloy powder has similar properties to Co and can be used as an important way to reduce costs. However, Fe-based diamond tools face problems such as high sintering temperature, narrow controllable process range, easy erosion of diamond, weak holding force, and the tendency for the matrix to burn during production. Additionally, the Sn element is prone to segregation and loss during long-term sintering in the furnace, resulting in unstable performance of diamond tools. This article describes the preparation of FeCuNi-Cu/Sn/Bi alloy powder using a multi-layer coating process to improve the densification of diamond matrix sintering and reduce component segregation. Methods: Co powder, Cu powder, Fe powder, Sn powder, Ni powder, and FeCuNi alloy powder were selected, and Cu, Sn, and Bi were respectively plated onto the surface of FeCuNi alloy powder by chemical methods, forming a uniform coating on the surface. Metal powder and diamond were mixed using a three-dimensional mixer for 2 hours. After mixing, the required weight of uniform powder was weighed, and sample blocks with dimensions of 4 mm × 8 mm × 40 mm were prepared using a hot press sintering machine. The mold material was graphite, and 4 sample blocks were prepared for each group. The experiment was repeated twice. For the tested materials, Rockwell hardness was measured, as well as the three-point bending strength. The microstructure and energy spectrum were analyzed using an electron microscope, and the changes in composition, structure, and mechanical properties of the tire body with fewer joints under different processes were compared and analyzed. Four formulations of sintered diamond tool bodies were designed, and their physical properties were tested. Eight samples were prepared for each formulation. After removing the maximum and minimum values, the average value of the data was calculated for analysis. Results: The hardness of the coated alloy powder formulation body decreased from 110 HRB to 106 HRB, but the decrease was less than 4%, indicating that the hardness remained similar. After adding the coated alloy powder, the flexural strength of the tire body increased by more than 10%. Specifically, for the formulation containing FeCuNi-Bi powder, the flexural strength increased from 945 MPa to 1,120 MPa, an increase of nearly 20%. The improvement was due to the even distribution of low-melting point elements coated on the surface of the alloy powder, which reduced the porosity of the matrix during the sintering process, thereby improving the bending strength of the matrix. Analysis of the microstructure of the four sintered tire bodies revealed that Sn in the original formula reacted with metal elements such as Cu in the tire body, gradually forming CuSn alloy. The distribution of Sn was uneven, and segregation was severe. As the sintering temperature increased, some CuSn alloys with higher Sn content began to melt. However, the wettability between the liquid CuSn alloy and Co or Fe particles was poor, and the distribution in the tire body was discontinuous. The vast majority of the CuSn liquid phase could not penetrate the Co and Fe skeleton phases to form a network connection. Under the interaction of sintering temperature and pressure, a strong and dense bond could not be formed, resulting in an uneven microstructure of the tire body and negatively affecting the performance and application of diamond tools. After adding FeCuNi-Cu/Sn/Bi alloy powder to the formula, the distribution of the coated alloy powder was relatively uniform. During sintering, Sn and Bi on the surface of FeCuNi alloy powder particles melted first, reacting with Cu to form liquid phases such as Cu-Sn and Cu-Bi. These phases gradually diffused along the FeCuNi alloy powder particles from the outside to the inside, entering the gaps between Fe, Ni, FeCuNi and other particles. Ultimately, Cu-Sn and Cu-Bi alloys formed a continuous network structure, encapsulating and bonding particles such as FeCuNi, Fe, and Ni, making the composition and microstructure distribution of the diamond tool bodies more uniform and dense, thus avoiding component segregation. Conclusions: FeCuNi-Cu/Sn/Bi alloy powder was prepared by chemically plating Cu, Sn, and Bi onto the surface of FeCuNi alloy powder. After adding the metal-coated alloy powder to the formula, the microstructure of the matrix was refined, and both hardness and strength were improved. The FeCuNi-Cu/Sn/Bi alloy powder, using coating technology, was sintered to obtain a denser matrix with higher diamond holding force and better mechanical properties.

Abstract Most advanced lung adenocarcinoma (LUAD) patient deaths are attributed to metastasis. However, the complete understanding of the metastatic mechanism in LUAD remains elusive. Single-cell RNA-seq (scRNA-seq), spatial RNA-seq (stRNA-seq) and bulk RNA-seq of primary LUAD were integrated to investigate metastatic driver genes, cell–cell interactions, and spatial colocalization of cells and ligand-receptor pairs. A lung adenocarcinoma metastasis risk scoring model (LMRS) was established to estimate the risk of metastasis in LUAD. Forty-two metastasis driver genes were identified and tumor epithelial cells were classified into two subtypes. Epithelial cell subclass characterized by susceptibility to metastasis are referred to as Epithelial_LM, and the remaining as Epithelial_LL. Epithelial_LM subtype has intimate ligand-receptor interactions with inflammatory endothelial cells (iendo), inflammatory cancer-associated fibroblasts (iCAF), and NKT cells. Epithelial_LM cells have a spatial colocalization relationship with these three types of cells. The LMRS was established and its efficacy was verified in bulk RNA-seq. We identified a subclass of epithelial cells prone to metastasis and demonstrated the contribution of inflammatory stromal cells and NKT cells in facilitating tumor metastasis. Graphical Abstract

Abstract Branching enzymes (BEs) confer to α-glucans, the primary energy-storage reservoir in nature, a variety of features, like slow digestion. The full catalytic cycle of BEs can be divided in six steps, namely two covalent catalytic steps involving glycosylation and transglycosylation, and four noncatalytic steps involving substrate binding and transfers (SBTs). Despite the ever-growing wealth of biochemical and structural information on BEs, clear mechanistic insights into SBTs from an industrial-performance perspective are still missing. Here, we report a Rhodothermus profundi BE (RpBE) endowed with twice as much enzymatic activity as the Rhodothermus obamensis BE currently used in industry. Furthermore, we focus on the SBTs for RpBE by means of large-scale computations supported by experiment. Engineering of the crucial positions responsible for the initial substrate-binding step improves enzymatic activity significantly, while offering a possibility to customize product types. In addition, we show that the high-efficiency substrate-transfer steps preceding glycosylation and transglycosylation are the main reason for the remarkable enzymatic activity of RpBE, suggestive of engineering directions for the BE family.

Abstract A strong driving force for charge separation and transfer in semiconductors is essential for designing effective photoelectrodes for solar energy conversion. While defect engineering and polarization alignment can enhance this process, their potential interference within a photoelectrode remains unclear. Here we show that oxygen vacancies in bismuth vanadate (BiVO4) can create defect dipoles due to a disruption of symmetry. The modified photoelectrodes exhibit a strong correlation between charge separation and transfer capability and external electrical poling, which is not seen in unmodified samples. Applying poling at −150 Volt boosts charge separation and transfer efficiency to over 90%. A photocurrent density of 6.3 mA cm−2 is achieved on the photoelectrode after loading with a nickel-iron oxide-based cocatalyst. Furthermore, using generated holes for methane partial oxidation can produce methanol with a Faradaic efficiency of approximately 6%. These findings provide valuable insights into the photoelectrocatalytic conversion of greenhouse gases into valuable chemical products.

Abstract Information industry is one of the major drivers of the world economy. Its rapid growth, however, leads to severe heat problem which strongly hinders further development. This calls for a non-charge-based technology. Magnon, capable of transmitting spin information without electron movement, holds tremendous potential in post-Moore era. Given the cornerstone role of the field effect transistor in modern electronics, creating its magnonic equivalent is highly desired but remains a challenge. Here, we demonstrate a nonvolatile three-terminal lateral magnon field effect transistor operating at room temperature. The device consists of a ferrimagnetic insulator (Y3Fe5O12) deposited on a ferroelectric material [Pb(Mg1/3Nb2/3)0.7Ti0.3O3 or Pb(Zr0.52Ti0.48)O3], with three Pt stripes patterned on Y3Fe5O12 as the injector, gate, and detector, respectively. The magnon transport in Y3Fe5O12 can be regulated by the gate voltage pulses in a nonvolatile manner with a high on/off ratio. Our findings provide a solid foundation for designing energy-efficient magnon-based devices.

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl3 for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8+ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.

Osteoporosis (OP)-associated fractures can result in severe morbidity and disability, reduced quality of life, and death. Previous studies have suggested that small noncoding RNAs, for example, small regulatory microRNAs (miRNAs), play a key role in OP by inhibiting target gene expression. Cuproptosis, a recently proposed copper-induced cell death pathway, is linked with OP. Here, we describe the contribution of exosomal miRNAs and cuproptosis to OP. First, we highlight the characteristics of exosomes and roles of exosome-related miRNAs. Next, we discuss the relationship between cuproptosis and OP. Subsequently, we analyze the crosstalk of exosomal miRNAs with cuproptosis in the development of OP. This review aims to investigate a new clinical treatment method for OP.

Abstract Ceracris kiangsu (Orthoptera: Arcypteridae), is greatly affected by climatic factors and exhibits strong adaptability, posing a serious threat to the ecological environment. Therefore, predicting its potential suitable habitat distribution provides a proactive theoretical basis for pest control. This study using the Biomod2 package of R simulated and predicted the current and future potential distribution, area changes, changes in the center points of suitable habitats, and niche shifts of C. kiangsu under two different greenhouse gas emission scenarios, SSP1-26 and SSP5-85. The results show that: (1) Currently, the high suitability areas for C. kiangsu are mainly distributed in Yunnan, Jiangxi, Hunan provinces in southern China and phongsaly province in northern Laos. In the future, the center of the suitable habitat distribution pattern of C. kiangsu will remain unchanged, primarily expanding outward from medium and high suitability areas. Additionally, significant suitable habitats for C. kiangsu were discovered in Southeast Asian countries without previous pest records. (2) Compared to the present, the overall suitable habitat area for C. kiangsu is expected to expand, particularly under the SSP5-85 climate change scenario. (3) In the SSP1-26 and SSP5-85 climate scenarios, the geometric center of the suitable habitat generally shows a trend of gradually shifting northeast. (4) Under different climate scenarios, the suitable habitat of C. kiangsu has highly overlapping, indicating that the suitable habitat of C. kiangsu in the invaded areas is broader than in its native regions. In conclusion, the research findings represent a breakthrough in identifying the potential distribution areas of C. kiangsu, which is of great practical significance for the monitoring and control of C. kiangsu pest infestation in China and Southeast Asian countries.

Abstract For breast cancer patients with physical exam node negative but radiological finding node abnormal (cN0/rNa), the NCCN and ASCO guidelines recommend sentinel lymph node biopsy (SLNB) as the first-line axillary staging. However, patients who undergo surgery firstly may be upstaged to pathological II–III status, and these patients happen to be the adaptive population of neoadjuvant therapy (NAT). There is no consensus on the optimal management of cN0/rNa patients. The aim is to explore the optimal management strategy of these patients. We performed a retrospective real-world study of 1414 cN0/rNa patients from June 2014 to October 2022. There were 1003 patients underwent surgery first and 411 patients underwent surgery after NAT. We analyzed the real-world conditions of these patients, compared axilla tumor burden between these two groups. In addition, we compared benefit ratio of axillary surgery and regional nodal irradiation (RNI) de-escalation under the two strategies. Among 1003 patients underwent surgery first, the positive and negative rates of fine needle aspiration (FNA) were 18.5% and 81.5%, respectively. There were 66.1% had ≤ 2 lymph nodes+. There were 40.8% of FNA+ patients could be exempted from ALND underwent surgery first. In 411 patients underwent surgery after NAT, the FNA positive and negative rates were 60.8% and 49.2%, respectively. There were 54.4% of FNA+ patients achieved axilla pathologic complete response (apCR) and could omit ALND after NAT. The apCR was 67.3% in HER2+/TNBC subtypes. According to the NSABP-B51 trial, there were 0 and 54.4% of FNA+ patients could omit RNI among surgery first and after NAT, respectively. Among 1–2 sentinel lymph node (SLN)-positive patients underwent surgery first, with a median follow-up 49 months, there was no difference of survival benefit between SLNB-only and SLNB-ALND. Compared with 1–2 SLN+ patients without RNI, RNI could bring better invasive disease-free survival (97.38% vs. 89.36%, P = 0.046) and breast cancer special survival (100% vs. 94.68%, P = 0.020). It is safe to perform SLNB omitting ALND when detected 1–2 positive SLNs in cN0/rNa patients. Patients with HER2+/TNBC subtypes underwent surgery after NAT had more chance to benefit from dual de-escalation, including axillary surgery and RNI de-escalation.

Abstract RGS (Regulator of G protein signaling) proteins have long captured the fascination of researchers due to their intricate involvement across a wide array of signaling pathways within cellular systems. Their diverse and nuanced functions have positioned them as continual subjects of scientific inquiry, especially given the implications of certain family members in various cancer types. Of particular note in this context is RGS20, whose clinical relevance and molecular significance in hepatocellular carcinoma we have recently investigated. These investigations have prompted questions into the prevalence of pathogenic mutations within the RGS20 gene and the intricate network of interacting proteins that could contribute to the complex landscape of cancer biology. In our study, we aim to unravel the mutations within the RGS20 gene and the multifaceted interplay between RGS20 and other proteins within the context of cancer. Expanding on this line of inquiry, our research is dedicated to uncovering the intricate mechanisms of RGS20 in various cancers. In particular, we have redirected our attention to examining the role of RGS20 within hematological malignancies, with a specific focus on multiple myeloma and follicular lymphoma. These hematological cancers hold significant promise for further investigation, as understanding the involvement of RGS20 in their pathogenesis could unveil novel therapeutic strategies and treatment avenues. Furthermore, our exploration has extended to encompass the latest discoveries concerning the potential involvement of RGS20 in diseases affecting the central nervous system, thereby broadening the scope of its implications beyond oncology to encompass neurobiology and related fields.

Plastic pollution and its potential risks have been raising public concerns as a global environmental issue. Global plastic waste may double by 2030, posing a significant challenge to the remediation of environmental plastics. In addition to finding alternative products and managing plastic emission sources, effective removal technologies are crucial to mitigate the negative impact of plastic pollution. However, current remediation strategies, including physical, chemical, and biological measures, are unable to compete with the surging amounts of plastics entering the environment. This perspective lays out recent advances to propel both research and action. In this process, phytoaccumulation, phytostabilization, and phytofiltration can be applied to reduce the concentration of nanoplastics and submicron plastics in terrestrial, aquatic, and atmospheric environments, as well as to prevent the transport of microplastics from sources to sinks. Meanwhile, advocating for a more promising future still requires significant efforts in screening hyperaccumulators, coupling multiple measures, and recycling stabilized plastics from plants. Phytoremediation can be an excellent strategy to alleviate global micro/nanoplastic pollution because of the cost-effectiveness and environmental sustainability of green technologies.

Abstract Hepatic ischemia-reperfusion injury (HIRI) is a significant issue during liver transplantation and surgery, contributing to the liver failure or even mortality. Although extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown substantial potentials in cell replacement therapy of various organ ischemia reperfusion injuries (IRIs), the precise mechanisms remain unclear. In this study, we demonstrate that systemic MSC-EVs administration is predominantly absorbed by macrophages, and verified that it could significantly reduce the liver injury and inflammatory response in mice suffering from HIRI. Furthermore, treatment with MSC-EVs induces macrophage polarization toward an anti-inflammatory phenotype. Mechanistically, proteomic profiling reveals an enrichment of growth arrest-specific 6 (GAS6) in MSC-EVs, significantly promoting the activation of myeloid-epithelial-reproductive tyrosine kinase/extracellular regulated protein kinases/cyclooxygenase 2 (MerTK/ERK/COX2) signaling pathway in macrophages and further enhancing their efferocytosis efficiency. Knockdown of GAS6 via lentiviral transfection or inhibition of MerTK using UNC2025 (a MerTK small molecule inhibitor) partially eliminates the protective effects of MSC-EVs on macrophage efferocytosis and liver injury. Overall, our findings support that MSC-EVs enriched GAS6 execute an anti-inflammation effect, highlighting that treatment based on the modulation of macrophage function by MSC-EVs as a promising approach in IRI. HIRI is a thorny problem after liver surgery such as liver transplantation. In a murine model of HIRI, MSC-EVs enriched GAS6 effectively enhance macrophage efferocytosis both in vivo and in vitro through the GAS6/MerTK/ERK/COX2 signaling pathway and significantly mitigate liver injury. This image was drawn by the authors.

Abstract Previous studies typically assumed a constant total organic carbon (OC) storage in the lake water column, neglecting its significant variability within a changing world. Based on extensive field data and satellite monitoring techniques, we demonstrate considerable spatiotemporal variability in OC concentration and storage for 24,366 Chinese lakes during 1984–2023. Here we show that dissolved OC concentration is high in northwest saline lakes and particulate OC concentration is high in southeast eutrophic lakes. Along with increasing OC concentration and water volume, dissolved and particulate OC storage increase by 44.6% and 33.5%, respectively. Intensified human activities, water input, and wind disturbance are the key drivers for increasing OC storage. Moreover, higher OC storage further leads to an 11.0% increase in nationwide OC burial and a decrease in carbon emissions from 71.1% of northwest lakes. Similar changes are occurring globally, which suggests that lakes are playing an increasingly important role in carbon sequestration.

Abstract Conventional hyperspectral cameras cascade lenses and spectrometers to acquire the spectral datacube, which forms the fundamental framework for hyperspectral imaging. However, this cascading framework involves tradeoffs among spectral and imaging performances when the system is driven toward miniaturization. Here, we propose a spectral singlet lens that unifies optical imaging and computational spectrometry functions, enabling the creation of minimalist, miniaturized and high-performance hyperspectral cameras. As a paradigm, we capitalize on planar liquid crystal optics to implement the proposed framework, with each liquid-crystal unit cell acting as both phase modulator and electrically tunable spectral filter. Experiments with various targets show that the resulting millimeter-scale hyperspectral camera exhibits both high spectral fidelity ( > 95%) and high spatial resolutions ( ~1.7 times the diffraction limit). The proposed “two-in-one” framework can resolve the conflicts between spectral and imaging resolutions, which paves a practical pathway for advancing hyperspectral imaging systems toward miniaturization and portable applications.

For Nd2Fe14B/α-Fe nanocomposite magnets, which exhibit great superiority in theoretical energy products, it is a great challenge to obtain controlled nano-scale microstructural features while eliminating the harmful metastable phases due to the general metastable fabrication methods. Here, we report a strategy to control the nano-scale features and simultaneously eliminate metastable phases for Nd2Fe14B/α-Fe nanocomposites through low-temperature pre-deformation of amorphous alloys combined with subsequent thermal annealing. The resultant bulk Nd2Fe14B/α-Fe nanostructure exhibits desired ultrafine grain sizes, ∼20 nm for soft-magnetic α-Fe phase with a high fraction of Vα-Fe ≈ 30 wt% and ∼33 nm for hard-magnetic Nd2Fe14B phase. The desired microstructure results in a larger coercivity (Hci = 4.1 kOe) and higher saturation magnetization (Ms = 1.51 T) compared to those (Hci = 3.3 kOe and Ms = 1.35 T) of the counterpart without pre-deformation, contributing to a high energy density of 26.3 MGOe. This energy density is 200% larger than that of the counterpart without pre-deformation and far beyond that (around 20 MGOe) of previously reported bulk Nd2Fe14B/α-Fe nanocomposites with Vα-Fe ≥ 20 wt%. The superior property stems from the purposely introduced low-temperature pre-deformation that changed the structure and local chemistry of the amorphous alloy, facilitating the decomposition of harmful metastable phases and the formation of Nd2Fe14B phase during annealing processes, which lowers the temperature, from 750 to 700 °C for producing the Nd2Fe14B/α-Fe nanostructure and thus yields ultrafine nanograins. These results demonstrate an effective means to prepare high-performance bulk Nd2Fe14B/α-Fe nanocomposite magnets.

Abstract Background Calcaneal osteomyelitis (CO) poses a formidable challenge in treatment due to the distinct anatomical structure and functional properties of the calcaneus. The present study endeavors to furnish a thorough and comprehensive understanding of the clinical manifestations, therapeutic strategies, and therapeutic outcomes pertaining to pediatric calcaneal osteomyelitis (PCO) by conducting a meticulous synthesis and analysis of cases reported in the literature. Methods A systematic search of the PubMed, Embase, and Cochrane Library databases was conducted to identify English-language studies analyzing PCO between 2000 and 2021. The quality of the included studies was assessed using the National Institutes of Health (NIH) assessment scale. Effective data were extracted and analyzed. Results A total of 42 studies, encompassing 128 patients, fulfilled the established inclusion criteria. The gender distribution revealed a male-to-female ratio of 2:1 (81 boys and 40 girls). The median age at the time of diagnosis was 8 years, while the median duration of symptoms was 0.6 month. Trauma emerged as the primary etiology (41 cases, 54%), and limited activity was the most prevalent symptom (68 cases). The positive rate for pathogen culture was 75.4% (49/65), with Staphylococcus aureus being the most commonly isolated pathogen (28 cases, 57.1%). Surgical intervention was performed in 51% (64/126) of the patients, with debridement serving as the primary surgical strategy. The rate of infection recurrence was 6.8% (8/118), and the risk of below-knee amputation was 0.8% (1/124). Conclusions PCO occurred more frequently in male patients, with trauma being the primary underlying cause and Staphylococcus aureus being the most prevalent bacterial pathogen isolated. Over half of the patients underwent surgical intervention. Nonetheless, it is imperative that treatment strategies undergo further refinement, as approximately 7% of patients experienced infection recurrence.

Abstract Drought and salt stress are two important environmental factors that significantly restrict plant growth and reproduction. Malate dehydrogenase is essential to life as it is engaged in numerous physiological processes in cells, particularly those related to abiotic stress reactions. However, a complete understanding of MDH family members in kenaf is not clear yet. In this study, subcellular localization analysis and a yeast transcriptional activation assay revealed that HcMDH1 was localized in chloroplasts but had no transcriptional activation activity. When exposed to salt or drought stress, yeast cells expressing the HcMDH1 gene exhibit an increased survival rate. Overexpression of HcMDH1 in Arabidopsis increased seed germination rate and root growth when transgenic lines were exposed to varying concentrations of mannitol and NaCl. Subsequent physiological studies revealed that transgenic lines had higher concentrations of soluble carbohydrates, proline, and chlorophyll and lower concentrations of malondialdehyde (MDA) and reactive oxygen species (ROS). Furthermore, inhibiting HcMDH1 in kenaf using virus-induced gene silencing (VIGS) decreased salt and drought tolerance due to elevated ROS and MDA levels. In these silenced lines, the expression of six essential genes engaged in stress-resistance and photosynthesis, namely HcGAPDH, HcGLYK, HcFBA, HcFBPase, HcPGA, and HcLSD, is significantly altered under salt and drought stress. In summary, HcMDH1 is a complex and positive regulatory gene that plays a key role in regulating chlorophyll content, antioxidant enzyme activity and osmotic regulation under salt and drought stress, which may have implications for kenaf transgenic breeding. Graphical Abstract

Abstract Lishu County, which is located in the black soil region of Northeast China, represents a key site for the analysis of soil erosion intensity. This study offers a scientific foundation for the development of targeted soil and water conservation strategies within the region. The Revised Universal Soil Loss Equation (RUSLE) was employed to compute the soil erosion modulus in Lishu County, with the objective of conducting a quantitative analysis of the temporal and spatial distribution patterns of soil erosion. Additionally, the changing characteristics of soil erosion were examined from the perspectives of land use types and slope variations. The Generalized Connectivity Causality Model (GCCM) was utilized to identify the causal relationship between soil erosion and land use types through the reconstruction of state space and cross-mapping predictions. (1) Soil erosion in Lishu County between 2000 and 2020 predominantly exhibited mild to moderate levels, characterized by patchy and sporadic erosion, with relatively severe occurrences in the northern and central regions. (2) Soil erosion was correlated with land use and slope variations, with more than 90% of erosion incidents transpiring in cultivated land areas. The 3°-5° slope range in Lishu County emerged as a focal point for erosion, necessitating targeted prevention and control measures. (3) The GCCM model illustrated a discernible causal relationship between soil erosion and land use, revealing mutual influences between the two factors. Between 2000 and 2020, both the area and intensity of soil erosion in Lishu County exhibited an initial increase, followed by a subsequent decrease. This suggests an overall trend of amelioration in soil erosion conditions. However, notable spatial disparities persist in the erosion distribution across the region.

Abstract Resistance to epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) is a significant cause of treatment failure and cancer recurrence in non-small cell lung cancer (NSCLC). Approximately 30% of patients with EGFR-activating mutations exhibit primary resistance to EGFR–TKIs. However, the potential mechanisms of primary resistance to EGFR–TKIs remain poorly understood. Recent studies have shown that increased expression of programmed death ligand-1 (PD-L1) is associated with EGFR–TKIs resistance. Therefore, the present study aimed to investigate the mechanism of PD-L1 in primary resistance to EGFR–TKIs in EGFR-mutant lung adenocarcinoma (LUAD) cells. We found that PD-L1 was associated with poor prognosis in patients with EGFR-mutant LUAD, while the combination of EGFR–TKIs with chemotherapy could improve its therapeutic efficacy. In vitro and in vivo experiments revealed that PD-L1 promoted the proliferation and autophagy and inhibited the apoptosis of LUAD cells. Mechanistic studies demonstrated that upregulation of PD-L1 was critical in inducing autophagy through the mitogen-activated protein kinase (MAPK) signaling pathway, which was beneficial for tumor progression and the development of gefitinib resistance. Furthermore, we found that gefitinib combined with pemetrexed could synergistically enhance antitumor efficacy in PD-L1-overexpression LUAD cells. Overall, our study demonstrated that PD-L1 contributed to primary resistance to EGFR–TKIs in EGFR-mutant LUAD cells, which may be mediated by inducing autophagy via the MAPK signaling pathway. These findings not only help improve the prognosis of patients with EGFR-mutant LUAD but also provide a reference for the research of other cancer types.

ObjectiveThis study uses the structural load inversion method to conduct a dynamic response state analysis of a floating wind turbine tower under wave action. MethodBased on a semi-submersible wind turbine, the measurement data is simulated in the time domain, and the mass-normalized modes of the tower are calculated using a frequency-domain simulation model of the floating wind turbine. Both are used as inputs to a joint input-state estimation (JIS) algorithm to conduct the structural load inversion and real-time state analysis of the floating wind turbine tower. ResultsThe results show that when using the simulated data of tower nodes as inputs to the JIS algorithm, the estimated tower root loads and node responses agree well with the simulated results, achieving high-precision inversion. ConclusionThe inversion results verify that the JIS algorithm is effective and can be used for the real-time state analysis of floating wind turbines to ensure their long-term safe and stable operation.

ObjectiveThis study aims to explore the structural strength deterioration mechanism of pipelines with corrosion defects in hydrogen-blended environments.MethodsBased on the experimental data, an analysis is made of the load bearing performance of X52 steel under different levels of hydrogen blending , and the structural strength failure mechanism of an X52 hydrogen-blended natural gas pipeline under different corrosion defects is described using the nonlinear finite element method. ResultsWhen the hydrogen blend level increases to 50.0%, under a combined load, the pipeline reaches minimum displacement failure at 2.58 mm, and the structural toughness deteriorates to a greater degree; at a hydrogen blend level of 25.0%, the defect depth is greater and the degree of structural failure more serious; comparing square and circular defects, the maximum stress of the square defects is higher than that of the circular defects. ConclusionsThe material property-based defective pipeline model can realize the assessment of the structural bearing capacity deterioration of natural gas pipelines under different hydrogen-blending conditions, providing engineering suggestions for the design and health monitoring of new energy pipelines.

Abstract Background Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks. Methods This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR). Results Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P