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Abstract Background Despite the improved survival observed in PD-1/PD-L1 blockade therapy, a substantial proportion of cancer patients, including those with non-small cell lung cancer (NSCLC), still lack a response. Methods Transcriptomic profiling was conducted on a discovery cohort comprising 100 whole blood samples, as collected multiple times from 48 healthy controls (including 43 published data) and 31 NSCLC patients that under treatment with a combination of anti-PD-1 Tislelizumab and chemotherapy. Differentially expressed genes (DEGs), simulated immune cell subsets, and germline DNA mutational markers were identified from patients achieved a pathological complete response during the early treatment cycles. The predictive values of mutational markers were further validated in an independent immunotherapy cohort of 1661 subjects, and then confirmed in genetically matched lung cancer cell lines by a co-culturing model. Results The gene expression of hundreds of DEGs (FDR p 2) distinguished responders from healthy controls, indicating the potential to stratify patients utilizing early on-treatment features from blood. PD-1-mediated cell abundance changes in memory CD4 + and regulatory T cell subset were more significant or exclusively observed in responders. A panel of top-ranked genetic alterations showed significant associations with improved survival (p

Abstract Background Urinary incontinence symptoms severely affect older people with different body mass index (BMI).To compare the efficacy of the pelvic floor muscle training (PFMT) in patients with post-prostatectomy incontinence with different BMI. Methods Thirty-seven patients with post-prostatectomy incontinence were included. They were divided into group A (BMI ≤ 25,12), group B (26 ≤ BMI ≤ 30,14), and group C (BMI ≥ 31,11) based on difference BMI. Three groups of patients underwent the same Pilates combined with kegel training. Participants were assessed with 1-hour pad test, the number of incontinence episodes, International Consultation on Incontinence Questionnaire and Oxford Grading Scale. Results In the 1-hour pad test, the differences before and after training were statistically significant in all three groups of participants. Group A decreased from 81.83 ± 8.79 to 31.08 ± 5.64 g (P

Hepatocellular carcinoma (HCC), one of the most common malignant tumors in China, severely threatens the life and health of patients. In recent years, precision medicine, clinical diagnoses, treatments, and innovative research have led to important breakthroughs in HCC care. The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC. Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment. Multiomics technologies, such as genomics, transcriptomics, and metabolomics, have enabled deeper understanding of the occurrence and development mechanisms, heterogeneity, and genetic mutation characteristics of HCC. The continued promotion and accurate typing of HCC, accurate guidance of treatment, and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC. Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.

Socioeconomic development often leads to environmental pollution and degradation initially while, beyond a certain point, there is the potential for improvements in environmental quality. In this study, we conducted a comprehensive review of published literature and national data to investigate changes in nutrient concentrations and limitations in Poyang Lake from 1978 to 2021. Our objective was to examine the relationships between these changes and the process of socioeconomic development in the watershed. The findings revealed a rapid socioeconomic development of the Poyang Lake Watershed, showing significant changes in various indexes. For example, population, Gross Domestic Product (GDP), urbanization, grain and meat productions, sewage amount and treatment rate, and forest coverage in the watershed showed increasing trends with different fitting curves, each following distinct fitting curves such as exponential, binary, and linear models. Concurrently, the concentrations of total nitrogen (TN) and total phosphorus (TP) in Poyang Lake exhibited a linear increase over the years, surpassing eutrophication thresholds since the early 1980s. However, TN and TP have shown a decreasing trend in recent years. Notably, the lake displayed co-limitation by N and P, with TN primarily driving the N:P ratio. TN and TP showed a significant “∩” shape with the increase in GDP and urbanization, while they increased with the population. TN:TP showed an increasing pattern with GDP and urbanization but a “U” shape with the population. This research contributes significant insights into the long-term changes in nutrient concentrations, shifts in nutrient limitations, and their associations with socioeconomic development. The findings highlight the need for a balanced and strategic approach to appropriately manage both nutrients for effective eutrophication mitigation.

The field of cancer neoantigen investigation has developed swiftly in the past decade. Predicting novel and true neoantigens derived from large multi-omics data became difficult but critical challenges. The rise of Artificial Intelligence (AI) or Machine Learning (ML) in biomedicine application has brought benefits to strengthen the current computational pipeline for neoantigen prediction. ML algorithms offer powerful tools to recognize the multidimensional nature of the omics data and therefore extract the key neoantigen features enabling a successful discovery of new neoantigens. The present review aims to outline the significant technology progress of machine learning approaches, especially the newly deep learning tools and pipelines, that were recently applied in neoantigen prediction. In this review article, we summarize the current state-of-the-art tools developed to predict neoantigens. The standard workflow includes calling genetic variants in paired tumor and blood samples, and rating the binding affinity between mutated peptide, MHC (I and II) and T cell receptor (TCR), followed by characterizing the immunogenicity of tumor epitopes. More specifically, we highlight the outstanding feature extraction tools and multi-layer neural network architectures in typical ML models. It is noted that more integrated neoantigen-predicting pipelines are constructed with hybrid or combined ML algorithms instead of conventional machine learning models. In addition, the trends and challenges in further optimizing and integrating the existing pipelines are discussed.

BackgroundWith the increasing incidence and prevalence of alcoholic liver disease, alcohol-related hepatocellular carcinoma has become a serious public health problem worthy of attention in China. However, there is currently no prognostic prediction model for alcohol-related hepatocellular carcinoma.MethodsThe retrospective analysis research of alcohol related hepatocellular carcinoma patients was conducted from January 2010 to December 2014. Independent prognostic factors of alcohol related hepatocellular carcinoma were identified by Lasso regression and multivariate COX proportional model analysis, and the nomogram model was constructed. The reliability and accuracy of the model were assessed using the concordance index(C-Index), receiver operating characteristic (ROC) curve and calibration curve. Evaluate the clinical benefit and application value of the model through clinical decision curve analysis (DCA). The prognosis was assessed by the Kaplan-Meier (KM) survival curve.ResultsIn sum, 383 patients were included in our study. Patients were stochastically assigned to training cohort (n=271) and validation cohort (n=112) according to 7:3 ratio. The predictors included in the nomogram were splenectomy, platelet count (PLT), creatinine (CRE), Prealbumin (PA), mean erythrocyte hemoglobin concentration (MCHC), red blood cell distribution width (RDW) and TNM. Our nomogram demonstrated excellent discriminatory power (C-index) and good calibration at 1-year, 3-year and 5- year overall survival (OS). Compared to TNM and Child-Pugh model, the nomogram had better discriminative ability and higher accuracy. DCA showed high clinical benefit and application value of the model.ConclusionThe nomogram model we established can precisely forcasting the prognosis of alcohol related hepatocellular carcinoma patients, which would be helpful for the early warning of alcohol related hepatocellular carcinoma and predict prognosis in patients with alcoholic hepatocellular carcinoma.

Microstrip filters are widely used in high-frequency circuit design for signal frequency selection. However, designing these filters often requires extensive trial and error to achieve the desired performance metrics, leading to significant time costs. In this work, we propose an automated design flow for hairpin filters, a specific type of microstrip filter. We employ artificial neural network (ANN) modeling techniques to predict the circuit performance of hairpin filters, and leverage the efficiency of low-cost models to deploy reinforcement learning agents. Specifically, we use the proximal policy optimization (PPO) reinforcement learning algorithm to learn abstract design actions for the filters, allowing us to achieve automated optimization design. Through simulation results, we demonstrate the effectiveness of the proposed approach. By optimizing the geometric dimensions, we significantly improve the performance metrics of hairpin filters, and the trained agent successfully meets our specified design goals within 5 to 15 design steps. This work serves as a conceptual validation attempt to apply reinforcement learning techniques and pre-trained ANN models to automate MMIC filter design. It exhibits clear advantages in terms of time-saving and performance efficiency when compared to other optimization algorithms.

Layout stitching is a repetitive and tedious task of the radio frequency integrated circuit (RFIC) design process. While academic research on layout splicing algorithms mainly focuses on analog and digital circuits, there is still a lack of well-developed algorithms for RFICs. An RFIC system usually has a symmetrical layout, such as transmitter and receiver components, low-noise amplifier (LNA), an SPDT switch, etc. This paper aims to address this gap by proposing an automated procedure for the layout of RFICs by relying on the basic device/PCell structure based on the interconnection among circuit topologies. This approach makes the in-series generation of layouts and automatic splicing based on circuit logic possible, resulting in superior stitching performance compared with related modules in Advanced Design System. To demonstrate the physical application possibilities, we implemented our algorithm on an LNA and a switch circuit.

Abstract The vertebral foramen, lamina, and vertebral body are three critical components of the spine structure, essential for maintaining spinal connectivity and stability. Accurately segmenting lumbar structures such as the vertebral body, vertebral foramen, and lamina in MRI cross-sections helps doctors better understand and diagnose the pathological causes of spine-related diseases. This study presents a multi-structure semantic segmentation method for vertebral transverse section MRI slices using WGAN with a residual U-Net and clustered Transformer. The generator network was replaced with a combination of a residual U-Net and a clustered Transformer-based segmentation network. The enhanced U-Net encoder, utilizing dilated convolutions and residual structures, improved multi-scale feature extraction capabilities. Meanwhile, the clustered Transformer structure, with reduced progressive linear complexity, ensured the extraction of global positional information. The results of multiple experiments show that the Dice coefficient for vertebral body segmentation increased by 3.1%, the Hausdorff distance decreased by 0.6 mm, mIOU improved by 4.1–96.2%, and PPV increased by 2.0–98.8% compared to mainstream segmentation models. These improvements are statistically significant (p

Abstract Spinal cord injury (SCI) often accompanies impairment of motor function, yet there is currently no highly effective treatment method specifically for this condition. Oxidative stress and inflammation are pivotal factors contributing to severe neurological deficits after SCI. In this study, a type of curcumin (Cur) nanoparticle (HA-CurNPs) was developed to address this challenge by alleviating oxidative stress and inflammation. Through non-covalent interactions, curcumin (Cur) and poly (-)-epigallocatechin-3-gallate (pEGCG) are co-encapsulated within hyaluronic acid (HA), resulting in nanoparticles termed HA-CurNPs. These nanoparticles gradually release curcumin and pEGCG at the SCI site. The released pEGCG and curcumin not only scavenge reactive oxygen species (ROS) and prevents apoptosis, thereby improving the neuronal microenvironment, but also regulate CD74 to promote microglial polarization toward an M2 phenotype, and inhibits M1 polarization, thereby suppressing the inflammatory response and fostering neuronal regeneration. Moreover, in vivo experiments on SCI mice demonstrate that HA-CurNPs effectively protect neuronal cells and myelin, reduce glial scar formation, thereby facilitating the repair of damaged spinal cord tissues, restoring electrical signaling at the injury site, and improving motor functions. Overall, this study demonstrates that HA-CurNPs significantly reduce oxidative stress and inflammation following SCI, markedly improving motor function in SCI mice. This provides a promising therapeutic approach for the treatment of SCI.

Abstract Background Progressive oxidative stress easily occurs as a result of a gradual increase in the intensity of maternal metabolism due to rapid foetal development and increased intensity of lactation. However, studies on the effects of processive oxidative stress on nutrient transport in the placenta have received little attention. The present study was conducted on sows at 85 days of gestation to study the effects of pterostilbene (PTE) on maternal oxidative stress status and placental nutrient transport. Results PTE increased the antioxidant capacity and immunoglobulin content in mothers’ blood and milk, reduced the level of inflammatory factors, and improved the nutrient content of milk. PTE also reduced sow backfat loss and the number of weak sons, and increased piglet weaning weight and total weaning litter weight. We subsequently found that PTE enhanced placental glucose and fatty acid transport and further affected glycolipid metabolism by increasing the expression of LAL, PYGM, and Gbe-1, which activated the PI3K phosphorylation pathway. Moreover, PTE addition altered the relative abundance of the Firmicutes, Proteobacteria, Parabacillus, and Bacteroidetes-like RF16 groups in sow faeces. PTE increased the levels of acetate, propionate, butyrate and isovalerate in the faeces. Conclusions These findings reveal that the addition of PTE during pregnancy and lactation mitigates the effects of processive oxidative stress on offspring development by altering maternal microbial and placental nutrient transport capacity. Graphical Abstract

Abstract Intermetallic nanoparticles (NPs) possess significant potentials for catalytic applications, yet their production presents challenges as achieving the disorder-to-order transition during the atom ordering process involves overcoming a kinetic energy barrier. Here, we demonstrate a robust approach utilizing atomic gas-migration for the in-situ synthesis of stable and homogeneous intermetallic alloys for propane dehydrogenation (PDH). This approach relies on the physical mixture of two separately supported metal species in one reactor. The synthesized platinum-zinc intermetallic catalysts demonstrate exceptional stability for 1300 h in continuous propane dehydrogenation under industrially relevant industrial conditions, with extending 95% propylene selectivity and propane conversions approaching thermodynamic equilibrium values at 550–600 oC. In situ characterizations and density functional theory/molecular dynamics simulation reveal Zn atoms adsorb on the particle surface and then diffuse inward, aiding in the formation of ultrasmall and highly ordered intermetallic alloys. This in-situ gas-migration strategy is applicable to a wide range of intermetallic systems.

ObjectivesPolycrystalline diamond (PCD), as a superhard material with high hardness, high wear resistance, and good impact toughness, has a wide range of applications in fields such as cutting tools for superhard materials. However, due to its high hardness, the precision surface processing of PCD has always been a technical challenge. This paper aims to study the influence of lapping pressure on the surface quality of PCD, particularly focusing on the material removal rate, surface roughness, and changes in surface morphology under high-speed grinding conditions.MethodsThe experiment adopts a single-factor test method, keeping the abrasive particle size W5 of the diamond flat grinding disc and the lapping speed of 43.3 m/s constant, while varying the lapping pressure (from 0.10 MPa to 0.18 MPa) to study its impact on the material removal rate, the surface roughness, and the surface morphology of polycrystalline diamond material. The experimental material is a ϕ13 mm × 2 mm polycrystalline diamond composite sheet with a diamond layer thickness of approximately 1 mm. The experimental apparatus is a high-speed grinding testing machine, which uses an electric spindle to drive the diamond flat grinding disc, with a lapping time of 20 minutes. The lapping process is conducted without the use of coolant to avoid its influence on the experimental results.ResultsThe experimental results indicate that the lapping pressure has a significant impact on the material removal rate of PCD. As the lapping pressure increases from 0.10 MPa to 0.18 MPa, the lapping removal rate increases from 0.005 mg/min to 0.030 mg/min, indicating that an increase in lapping pressure significantly improves material removal efficiency. The influence of lapping pressure on the surface roughness of PCD is also significant. With an increase in lapping pressure, the surface roughness gradually decreases, reducing from a higher value at 0.10 MPa to a lower value at 0.18 MPa, with a roughness Ra reduction of approximately 0.020 μm. The impact of lapping pressure on the surface morphology of PCD is manifested by a reduction in surface defects and an expansion of smooth areas. At lower lapping pressures, the surface exhibits numerous pits, interstitial cracks, and mechanical scratches. As the lapping pressure increases, the number of these defects gradually decrease, and smooth areas gradually expand. Scanning electron microscope observations reveal that an increase in grinding pressure helps reduce defects such as intergranular fractures, minute pits, and mechanical scratches, resulting in a smoother surface.ConclusionsThis paper experimentally studies the influence of lapping pressure on the material removal rate, surface roughness, and surface morphology of PCD, and draws the following conclusions. The lapping removal rate of PCD material significantly increases with an increase in lapping pressure, primarily attributed to the high-frequency collisions and frictional heat between diamond abrasive particles and PCD during the lapping process. An increase in lapping pressure significantly reduces the surface roughness of PCD, primarily benefiting from the decreased cutting depth of abrasive particles and increased actual contact area caused by the increased lapping pressure, and the promotion of surface thermochemical reactions and mechanical thermal removal effects by frictional heat. An increase in lapping pressure leads to a reduction in surface defects, an expansion of smooth areas, smaller mechanical scratches, and a significant improvement in the surface quality of PCD.

Abstract Forest soils store substantial amounts of carbon in various soil organic matter (SOM) components due to high plant litter inputs and active microbial turnover. However, the variations in plant- and microbial-derived SOM components in surface and subsurface forest soils across a wide geographic scale remain poorly understood. This study investigated the SOM components from aboveground and belowground plant inputs and fungal and bacterial necromass in surface (soil0–5 cm) and subsurface (soil5–10 cm) soils across 32 forest sites in China and analyzed their relationships with climate and edaphic factors. Compared to soil0–5 cm, soil5–10 cm exhibited lower soil organic carbon content and cutin biomarker concentration but higher concentrations of fungal necromass carbon and lignin phenols. Higher mean annual precipitation led to higher concentrations of cutin and suberin biomarkers in soil0–5 cm and soil5–10 cm, respectively. Higher soil organic carbon content was associated with lower plant-derived lignin biomarkers, higher lignin oxidation degrees, and increased microbial necromass-derived amino sugars across sites, highlighting the pivotal role of microbial necromass in SOM stabilization. Additionally, both fungal and bacterial necromass decreased with increasing mineral weathering across sites. These insights improve the understanding of environmental drivers of source-specific carbon storage in forest soils. Graphical Abstract

Abstract The paper combines experimental and numerical simulation methods to investigate the tip leakage vortex (TLV) in an oil–gas multiphase pump. The study aims to understand the evolution and dynamic characteristics of the TLV. The vorticity decomposition theory is used to analyze the spatial–temporal evolution, transient behavior, and rigid vorticity of the TLV. The findings reveal that the TLV is formed near the pressure surface when the tip clearance jet passes through the shear layer. In one impeller rotation period, transient fluctuations of the TLV are attributed to pressure differences and velocity changes across the tip clearance, and the TLV undergoes two split–dissipation–recurrence processes within one impeller rotation cycle. The presence of the gas phase enhances the scale and strength of the TLV while prolonging its existence in the flow channel. Analysis based on the rigid vorticity transport equation shows that the growth of the TLV and collapse are primarily governed by the rigid vortex generation term. The Coriolis force term contributes to stabilizing the TLV, while the rigid vorticity stretching term affects its shape. Furthermore, the gas phase significantly increases the value of the Rigid vorticity Curl of pseudo‐Lamb vector Term (RCT), which plays a crucial role in the prolonged existence of the TLV under gas–liquid two‐phase conditions. From an inlet gas void fraction of 0%–20%, the RCT value increases by 4.8 × 106/s2, the entropy production value increases by 75.55%, and the hydraulic efficiency decreases by 16.29%.

Abstract IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

Abstract Natural killer (NK) cells play a crucial role in immune response against viral infections and tumors. However, further investigation is needed to better understand the key molecules responsible for determining the fate and function of NK cells. In this study, we made an important discovery regarding the involvement of the Hippo kinases Mst1 and Mst2 as novel regulators in maintaining mouse NK cell homeostasis. The presence of high Mst1 and Mst2 (Mst1/2) activity in NK cells is essential for their proper development, survival and function in a canonical Hippo signaling independent mode. Mechanistically, Mst1/2 induce cellular quiescence by regulating the processes of proliferation and mitochondrial metabolism, thereby ensuring the development and survival of NK cells. Furthermore, Mst1/2 effectively sense IL-15 signaling and facilitate the activation of pSTAT3-TCF1, which contributes to NK cell homeostasis. Overall, our investigation highlights the crucial role of Mst1/2 as key regulators in metabolic reprogramming and transcriptional regulation for mouse NK cell survival and function, emphasizing the significance of cellular quiescence during NK cell development and functional maturation.

Abstract Black carbon (BC) is a highly persistent yet poorly understood component of forest soil carbon reservoirs, while its inventory, distribution, and determining factors in forest soils on a large geographic scale remain unclear. Here, we characterized soil BC across 68 Chinese forest sites using benzene polycarboxylic acid method and developed machine learning (ML) models to predict and interpret potential impacts of soil organic matter (SOM) properties, soil physiochemical properties, meteorological conditions, wildfire history, and microbial diversity on BC. Results revealed that SOM properties were the most critical in predicting BC, complemented by the negative impact of mean annual temperature and alkaline mineral composition. The superior prediction accuracy for BC with higher condensed aromaticity (more benzene hexa‐ and penta‐carboxylic acid monomers) likely results from its simpler sources and greater resistance to transformation. This study introduces an effective ML model for predicting and interpreting soil BC inventory to better understand BC cycling.

Achieving high strength and ductility for Ti alloys and their composites has been a key objective and also a great challenge for their engineering applications. Herein, we designed TiC/(TC18 + TC4) composites with bionic and heterogeneously lamella structures, achieving an exceptional combination of high strength and ductility. This is attributed to the formation of alternative layers of TC18-coarse grains and TC4-fine grains with TiC precipitated at their interfaces. Plastic incompatibility of these three-phases produces significant hetero-deformation-induced hardening, induced by mutual interactions of heterogeneous grains and TiC precipitates, as well as activation of extensive slip groups. An optimal yield strength of ∼ 1168 MPa and a uniform elongation of ∼ 6% have been achieved, which are much higher than those of the TC4 matrix (i.e. ∼919 MPa and ∼2%). This study provides a new strategy for composite designs to overcome the trade-off dilemma for strength-ductility.

Summary: Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.

In this project, a threshold-free recursive analysis approach was investigated to reveal the recursive properties of dynamic systems. Specifically, the occurrence of recurrent patterns in phase trajectory was identified by a threshold-free recursive matrix whose elements would possess continuous values within the interval of [0, 1] and are inversely proportional to the distance between phase points. Subsequently, mapping and feature extraction were carried out to visualize and quantify the threshold-free recursive matrix. Theoretical time-series, along with observed time-series in the fields of engineering, finance, and hydrology, have been utilized to validate the efficacy of this approach. The results demonstrate the applicability of this method in analyzing the dynamic characteristics of scalar time-series. Furthermore, the rebuilt grayscale recurrence plot morphology and extracted measures through grayscale recurrence quantification analysis measures can effectively unveil the dynamical complexity of nonlinear systems by offering more precise analysis outcomes for investigating the evolution of recursive characteristics.

Due to the high incidence of lumbar vertebral lesions causing spondylolisthesis and intervertebral disc protrusion, lumbar spine (vertebrae and intervertebral discs) MRI image segmentation can provide effective clinical information for the initial diagnosis and early treatment of current lumbar spine-related diseases. However, in MRI images, there is a significant overlap and similarity in features between the vertebral bones and intervertebral discs within the lumbar spine. Therefore, the effective identification and segmentation of each vertebra and intervertebral disc in the lumbar spine pose a significant challenge. We propose a lumbar spine MRI segmentation model based on the 3D Residual U-Net, incorporating boundary segmentation structures and a hybrid attention mechanism. The model achieves boundary-constrained segmentation of individual vertebrae and intervertebral discs by integrating the boundary segmentation module. Additionally, it utilizes a hybrid attention module based on convolutional attention and self-attention mechanisms for multiscale feature extraction in the lumbar spine. The proposed model is trained and validated using the publicly available datasets MRSpineSeg2021 and SpineSagT2Wdataset3. Experimental results demonstrate a significant improvement in segmentation performance, as measured by metrics such as the Dice similarity coefficient (DSC) and Hausdorff distance (HD). This validates the superiority and generalization performance of our proposed lumbar spine MRI.

Abstract The state-of-the-art alkaline hydrogen evolution catalyst of united ruthenium single atoms and small ruthenium nanoparticles has sparked considerable research interest. However, it remains a serious problem that hydrogen evolution primarily proceeds on the less active ruthenium single atoms instead of the more efficient small ruthenium nanoparticles in the catalyst, hence largely falling short of its full activity potential. Here, we report that by combining highly oxophilic cerium single atoms and fully-exposed ruthenium nanoclusters on a nitrogen functionalized carbon support, the alkaline hydrogen evolution centers are facilely reversed to the more active ruthenium nanoclusters driven by the strong oxophilicity of cerium, which significantly improves the hydrogen evolution activity of the catalyst with its mass activity up to −10.1 A mg−1 at −0.05 V. This finding is expected to shed new light on developing more efficient alkaline hydrogen evolution catalyst by rational regulation of the active centers for hydrogen evolution.

High-temperature furnaces and coal-fired boilers are widely employed in the petrochemical and metal-smelting sectors. Over time, the deterioration, corrosion, and wear of pipelines can lead to equipment malfunctions and safety incidents. Nevertheless, effective real-time monitoring of equipment conditions remains insufficient, primarily due to the interference caused by flames generated from fuel combustion. To address this issue, in this study, a through-flame infrared imager is developed based on the mid-wave infrared (MWIR) radiation characteristics of the flame. The imager incorporates a narrowband filter that operates within the wavelength range of 3.80 μm to 4.05 μm, which is integrated into conventional thermal imagers to perform flame filtering. This configuration enables the radiation from the background to pass through the flame and reach the detector, thereby allowing the infrared imager to visualize objects obscured by the flame and measure their temperatures directly. Our experimental findings indicate that the imager is capable of through-flame imaging; specifically, when the temperature of the target exceeds 50 °C, the imager can effectively penetrate the outer flame of an alcohol lamp and distinctly capture the target’s outline. Importantly, as the temperature of the target increases, the clarity of the target’s contour in the images improves. The MWIR through-flame imager presents considerable potential for the real-time monitoring and preventive maintenance of high-temperature furnaces and similar equipment, such as detecting the degradation of refractory materials and damage to pipelines.

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3−CD19−CD14+CD16−HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.

Abstract Anoikis resistance, a notable factor in osteosarcoma, plays a significant role in tumor invasion and metastasis. This study seeks to identify a distinct gene signature that is specifically associated with the anoikis subcluster in osteosarcoma. Clinical, single-cell, and transcriptional data from TARGET and GEO datasets were used to develop a gene signature for osteosarcoma based on the anoikis subcluster. Univariate Cox and LASSO regression analyses were employed. The signature's predictive value was evaluated using time-dependent ROC and Kaplan–Meier analyses. Functional enrichment analyses and drug sensitivity analyses were conducted. Validation of three modular genes was performed using RT-qPCR and Western blotting. Signature (ZNF583, CGNL1, CXCL13) was developed to predict overall survival in osteosarcoma patients, targeting the anoikis subcluster. The signature demonstrated good performance in external validation. Stratification based on the signature revealed significantly different prognoses. The signature was an independent prognostic factor. The low-risk group showed enhanced immune cell infiltration and improved immune function. Drug sensitivity analysis indicated efficacy of chemotherapy agents. Prognostic nomograms incorporating the signature provided greater predictive accuracy and clinical utility. Signatures related to the anoikis subcluster play a significant role in osteosarcoma progression. Incorporating these findings into clinical decision-making can improve osteosarcoma treatment and patient outcomes.

Real-time seed detection on resource-constrained embedded devices is essential for the agriculture industry and crop yield. However, traditional seed variety detection methods either suffer from low accuracy or cannot directly run on embedded devices with desirable real-time performance. In this paper, we focus on the detection of rapeseed varieties and design a dual-dimensional (spatial and channel) pruning method to lighten the YOLOv7 (a popular object detection model based on deep learning). We design experiments to prove the effectiveness of the spatial dimension pruning strategy. And after evaluating three different channel pruning methods, we select the custom ratio layer-by-layer pruning, which offers the best performance for the model. The results show that using custom ratio layer-by-layer pruning can achieve the best model performance. Compared to the YOLOv7 model, this approach results in mAP increasing from 96.68% to 96.89%, the number of parameters reducing from 36.5 M to 9.19 M, and the inference time per image on the Raspberry Pi 4B reducing from 4.48 s to 1.18 s. Overall, our model is suitable for deployment on embedded devices and can perform real-time detection tasks accurately and efficiently in various application scenarios.

Cuttage is the main propagation method of tea plant cultivars in China. However, some tea softwood cuttings just form an expanded and loose callus at the base, without adventitious root (AR) formation during the propagation period. Meanwhile, exogenous auxin could promote the AR formation of tea plant cuttings, but the regulation mechanism has not yet explained clearly. We conducted this study to elucidate the regulatory mechanism of exogenous auxin-induced adventitious root (AR) formation of such cuttings. The transcriptional expression profile of non-rooting tea calluses in response to exogenous IBA and NAA was analyzed using ONT RNA Seq technology. In total, 56,178 differentially expressed genes (DEGs) were detected, and most of genes were significantly differentially expressed after 12 h of exogenous auxin treatment. Among these DEGs, we further identified 80 DEGs involved in the auxin induction pathway and AR formation. Specifically, 14 auxin respective genes (ARFs, GH3s, and AUX/IAAs), 3 auxin transporters (AUX22), 19 auxin synthesis- and homeostasis-related genes (cytochrome P450 (CYP450) and calmodulin-like protein (CML) genes), and 44 transcription factors (LOB domain-containing protein (LBDs), SCARECROW-LIKE (SCL), zinc finger protein, WRKY, MYB, and NAC) were identified from these DEGs. Moreover, we found most of these DEGs were highly up-regulated at some stage before AR formation, suggesting that they may play a potential role in the AR formation of tea plant cuttings. In summary, this study will provide a theoretical foundation to deepen our understanding of the molecular mechanism of AR formation in tea cuttings induced by auxin during propagation time.

Abstract Background Cold regions have long autumn and winter seasons and low ambient temperatures. When pigs are unable to adjust to the cold, oxidative damage and inflammation may develop. However, the differences between cold and non-cold adaptation regarding glucose and lipid metabolism, gut microbiota and colonic mucosal immunological features in pigs are unknown. This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation. Moreover, the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs. Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs. Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models (Yorkshire pigs), decreasing plasma glucose concentrations. In this case, cold exposure enhanced the ATGL and CPT-1α expression to promote liver lipolysis and fatty acid oxidation. Meanwhile, the two probiotics (Collinsella and Bifidobacterium) depletion and the enrichment of two pathogens (Sutterella and Escherichia-Shigella) in colonic microbiota are not conducive to colonic mucosal immunity. However, glucagon-mediated hepatic glycogenolysis in cold-adapted pig models (Min pigs) maintained the stability of glucose homeostasis during cold exposure. It contributed to the gut microbiota (including the enrichment of the Rikenellaceae RC9 gut group, [Eubacterium] coprostanoligenes group and WCHB1-41) that favored cold-adapted metabolism. Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa. During non-cold adaptation, cold-induced glucose overconsumption promotes thermogenesis through lipolysis, but interferes with the gut microbiome and colonic mucosal immunity. Furthermore, glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.

Abstract Background Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. It is essential to identify new CRC-associated therapeutic targets and diagnostic biomarkers. Previous studies have demonstrated that a series of circular RNAs (circRNAs) play a crucial role in CRC pathogenesis. This study assessed the potential of hsa_circ_0064559 in tumor cell growth and progression of CRC. Methods Six pairs of matched CRC and normal colorectal tissue samples were sequenced using the Affymetrix Clariom D array. Using RNA interference, the expression of thirteen circRNAs was knocked down in CRC cells. The proliferation of CRC cell lines (RKO and SW620 cells) was detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were determined by flow-cytometric analysis. An in vivo study uses nude mice to establish a CRC mouse model. The differentially expressed genes were analyzed using Affymetrix primeview human GeneChip array and verified by polymerase chain reaction. Results Affymetrix Clariom D array analysis revealed that thirteen circRNAs were upregulated in CRC. The proliferation of CRC cell lines was decreased, while the proportion of apoptotic and G1 phase cells was higher after hsa_circ_0064559 knockdown. In vivo xenograft nude mice model revealed that the volume and weight of the tumor were reduced by hsa_circ_0064559 knockdown. In Affymetrix primeview human GeneChip array, we found six upregulated genes (STAT1, ATF2, TNFRSF10B, TGFBR2, BAX, and SQSTM1) and two downregulated genes (SLC4A7 and CD274) related to apoptosis and proliferation of colorectal cancer cells after hsa_circ_0064559 knockdown. Conclusions The hsa_circ_0064559 knockdown could inhibit the proliferation, promote apoptosis in CRC cell lines in vitro, and inhibit the development of CRC tumors in vivo. The mechanism may be related to activating a wide range of signaling pathways. The hsa_circ_0064559 may be a potential biomarker for early diagnosis or prognosis of CRC and a novel drug target for CRC therapy.

The design of ceramic matrix composite (CMC) mechanical joints takes into account the pseudoplastic mechanical behavior of CMC fasteners and the effect of the nonuniform microstructure. In this study, based on the linear correlation between the shear performance of two-dimensional (2D) C/SiC rivets and the rivet porosity, special z-pinned joints with four pins in a rectangular array with different porosities were prepared via the chemical vapor infiltration online gas-phase joining method, and a method is proposed to indirectly characterize the pin load distribution by measuring the strain distribution around the holes. The results show that the nonuniform distribution of the 2D C/SiC rivet density leads to an uneven distribution of the pin loads in the z-pinned joints with four pins in a rectangular array. The bearing ratio of the transversal rivets depends on the inverse of the ratio of the compliance coefficient of the two. The longitudinal rivets are capable to transfer the load; that is, the bottom transversal joint of the rivets is loaded first, and after the load limit is reached, the top transversal joint of the rivets starts to be loaded. Matrix cracking, crack deflection, interlayer sliding, fiber shearing, and fiber pull-out control rivet shearing. The dense rivets squeeze around the holes, leading to an uneven distribution of the pin loads. Oxidation at 700 °C leads to the fibers debonding from the matrix and cracking, which promotes crack deflection, interlayer sliding, and fiber pull-out; thus, the uneven pin load distribution tends to be uniform.

Abstract Redox catalysts play a vital role in chemical looping oxidative dehydrogenation processes, which have recently been considered to be a promising prospect for propylene production. This work describes the coupling of surface acid catalysis and selective oxidation from lattice oxygen over MoO3-Fe2O3 redox catalysts for promoted propylene production. Atomically dispersed Mo species over γ-Fe2O3 introduce effective acid sites for the promotion of propane conversion. In addition, Mo could also regulate the lattice oxygen activity, which makes the oxygen species from the reduction of γ-Fe2O3 to Fe3O4 contribute to selectively oxidative dehydrogenation instead of over-oxidation in pristine γ-Fe2O3. The enhanced surface acidity, coupled with proper lattice oxygen activity, leads to a higher surface reaction rate and moderate oxygen diffusion rate. Consequently, this coupling strategy achieves a robust performance with 49% of propane conversion and 90% of propylene selectivity for at least 300 redox cycles and ultimately demonstrates a potential design strategy for more advanced redox catalysts.

Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons. The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models (cold adaptation) and Yorkshire pig models (non-cold adaptation). Furthermore, this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs. Min pigs (Exp. 1) and Yorkshire pigs (Exp. 2) were divided into a control group (17 °C, n = 6) and chronic cold exposure group (7 °C, n = 6), respectively. Twelve Yorkshire pigs (Exp. 3) were divided into a cold control group and cold glucose supplementation group (8 °C). The results showed that chronic cold exposure inhibited peptide transporter protein 1 (PepT1) and excitatory amino acid transporter 3 (EAAT3) expression in ileal mucosa and cationic amino acid transporter-1 (CAT-1) in the jejunal mucosa of Yorkshire pigs (P

In the existing literature, direct torque control (DTC) by synthesizing virtual vectors can effectively suppress low-order harmonic currents under the single open-phase fault (OPF) of the five-phase permanent magnet synchronous motor (PMSM), but the sectors and the look-up tables need to be redesigned, which makes the control process more complicated. In order to solve this problem, an indirect correction method of virtual vectors is proposed, and the amplitudes of the virtual vectors are maximized. The fault-tolerant DTC strategy under the OPF ensures that there is no need to re-divide the sectors under the fault. And the selection rules of the look-up tables are consistent with the healthy operation. The difference is that the amplitudes of ten virtual vectors in the faulty operation are reduced, which simplifies the control process and is easy to implement. Finally, the correctness and effectiveness of the proposed control strategy were verified by experiments.

Aiming to address the problem of construction and environmental risks in tunnel construction through the soil–rock mixture backfill area, this paper carried out a seismic dynamic response model test of a pile-supported tunnel based on practical projects. Firstly, the stress–strain curves and failure characteristics of the soil–rock mixture in the study area were obtained through triaxial tests, and based on this, similar materials for the model test were developed. Then, a vibration table model test was devised to investigate the seismic dynamic response of the pile–tunnel structure. The findings revealed the following: when subjected to seismic waves, the soil–rock mixture stratum displayed a “skin effect” in its acceleration response, indicating that closer proximity to the surface led to heightened horizontal acceleration responses; the horizontal peak acceleration of the grouting mixture stratum in the vertical direction exhibited a “Zigzag” pattern; the peak values of strain response and bending moment in the tunnel lining cross-section exhibited an “X” shape and inverted “V” shape, respectively. The bending moment at the pile crown increased alongside the peak value of the input seismic wave acceleration. The maximum surface settlement in the model ranged from 0.5 to 1 cm, with the tunnel–pile structure effectively mitigating surface settlement.

Abstract Understanding eastward‐propagating mechanisms of the Madden–Julian Oscillation (MJO) is of great importance for the subseasonal prediction of extreme weather and climate worldwide. Using global satellite observations and reanalysis data, this study unravels that dual combinations of strong/weak westward‐ (ISOw) and eastward‐propagating intraseasonal oscillation (ISOe) can shape diverse MJO propagations documented previously using clustering analysis. The dry ISOw signals from the Central Pacific strengthen the leading suppressed convection over the Western Pacific (WP) and, on the contrary, weaken the moist ISOe convection over the Maritime Continent. Thus, when ISOe is weak over the WP, the strong (weak) dryness of ISOw likely causes a jump‐like (stand‐like) MJO mode. In contrast, a propagating MJO is supported when ISOe becomes strong over the WP, and a further strengthening of the ISOw dryness will presumably accelerate MJO; moreover, a weakening of ISOw might slow down the MJO speed.

Abstract In a multiphase pump, tip clearance is the required distance between the blade tip and the pump body wall of the impeller, forming tip leakage vortex (TLV), causing unstable flow and energy dissipation. In the present work, the enstrophy dissipation theory is innovatively applied to quantitatively study the energy dissipation of the TLV. The flow rate, tip clearance, and inlet gas void fraction (IGVF) play a crucial role in affecting the enstrophy dissipation of the TLV. The results show that increasing flow rate, tip clearance, and IGVF significantly exacerbate the TLV pattern and raise the TLV scale, which gradually raises volume enstrophy dissipation and decreases wall enstrophy dissipation. As the flow rate increases, the separation angle between the primary TLV trajectory and the blade gradually decreases, and widely dispersing the enstrophy dissipation near the shroud. However, as the tip clearance increases, the tip separated vortex scale increases and extends to the suction surface, raising the velocity gradient. Besides, as the IGVF increases, the secondary TLV develops from a continuous sheet vortex to a scattered strip vortex, increasing the significantly increasing the enstrophy dissipation. Considering the flow rate, tip clearance, and IGVF as independent variables, simple and multiple nonlinear regression models have the ability to predict the enstrophy dissipation of the TLV accurately.

ObjectivesLipoarabinomannan (LAM), an abundant cell wall glycolipid of mycobacteria including Mycobacterium tuberculosis (Mtb), is a promising TB diagnostic marker. The current commercially available urine LAM assays are not sufficiently sensitive, and more novel detection strategies are urgently needed to fill the current diagnostic gap.MethodsA proteinase K-pretreated Concanavalin A (ConA)-based ELISA assay was developed. Diagnostic performance was assessed by several bacterial strains and clinical urine samples.ResultsThe limit of detection (LoD) of the assay against ManLAM was 6 ng/ml. The assay reacted strongly to Mtb H37Rv and M. bovis BCG, intermediately to M. smegmatis mc2155, and weakly to four non-mycobacteria pathogens. This method could distinguish TB patients from healthy controls (HCs) and close contacts (CCs) in 71 urine samples treated with proteinase K, which increases urine LAM antibody reactiveness. In TB+HIV+ and TB+HIV− patients, the sensitivity was 43.8 and 37.5%, respectively, while the specificity was 100.0%. The areas under ROC curves (AUCs) were 0.74 and 0.82, respectively.ConclusionThis study implies that ConA can be paired with antibodies to detect LAM. Proteinase K treatment could effectively enhance the sensitivity by restoring the reactiveness of antibodies to LAM.

Summary: Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1β from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.