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Abstract Despite advancements in chemotherapy and the availability of novel therapies, the outcome of adult patients with B-cell acute lymphoblastic leukemia (B-ALL) remains unsatisfactory. Therefore, it is necessary to understand the molecular mechanisms underlying the progression of B-ALL. Brahma-related gene 1 (BRG1) is a poor prognostic factor for multiple cancers. Here, the expression of BRG1 was found to be higher in patients with B-ALL, irrespective of the molecular subtype, than in healthy individuals, and its overexpression was associated with a poor prognosis. Upregulation of BRG1 accelerated cell cycle progression into the S phase, resulting in increased cell proliferation, whereas its downregulation facilitated the apoptosis of B-ALL cells. Mechanistically, BRG1 occupies the transcriptional activation site of PPP2R1A, thereby inhibiting its expression and activating the PI3K/AKT signaling pathway to regulate the proto-oncogenes c-Myc and BCL-2. Consistently, silencing of BRG1 and administration of PFI-3 (a specific inhibitor targeting BRG1) significantly inhibited the progression of leukemia and effectively prolonged survival in cell-derived xenograft mouse models of B-ALL. Altogether, this study demonstrates that BRG1-induced overactivation of the PPP2R1A/PI3K/AKT signaling pathway plays an important role in promoting the progression of B-ALL. Therefore, targeting BRG1 represents a promising strategy for the treatment of B-ALL in adults.

Abstract Background Bread wheat (Triticum aestivum L.) endosperm contains starch and proteins, which determine the final yield, quality, and nutritional value of wheat grain. The preferentially expressed endosperm genes can precisely provide targets in the endosperm for improving wheat grain quality and nutrition using modern bioengineering technologies. However, the genes specifically expressed in developing endosperms remain largely unknown. Results In this study, 315 preferentially expressed endosperm genes (PEEGs) in the spring wheat landrace, Chinese Spring, were screened using data obtained from an open bioinformatics database, which reveals a unique grain reserve deposition process and special signal transduction in a developing wheat endosperm. Furthermore, transcription and accumulation of storage proteins in the wheat cultivar, XC26 were evaluated. The results revealed that 315 PEEG plays a critical role in storage protein fragment deposition and is a potential candidate for modifying grain quality and nutrition. Conclusion These results provide new insights into endosperm development and candidate genes and promoters for improving wheat grain quality through genetic engineering and plant breeding techniques.

Abstract Background Reticuloendotheliosis virus (REV), a member of the family Retroviridae, is a hot area of research, and a previous study showed that exosomes purified from REV-positive semen were not blocked by REV-specific neutralizing antibodies and established productive infections. Methods To further verify the infectivity of exosomes from REV-infected cells, we isolated and purified exosomes from REV-infected DF-1 cells and identified them using Western blot and a transmission electron microscope. We then inoculated 7-day-old embryonated eggs, 1-day-old chicks and 23-week-old hens with and without antibody treatment. REV was administered simultaneously as a control. Results In the absence of antibodies, the results indicated that REV-exosomes and REV could infect chicks, resulting in viremia and viral shedding, compared with the infection caused by REV, REV-exosomes reduced the hatching rate and increased mortality after hatching, causing severe growth inhibition and immune organ damage in 1-day-old chicks; both REV and REV-exosomes also could infect hens, however, lead to transient infection. In the presence of antibodies, REV-exosomes were not blocked by REV-specific neutralizing antibodies and infected 7-day-old embryonated eggs. However, REV could not infect 1-day-old chicks and 23-week-old hens. Conclusion In this study, we compared the infectious ability of REV-exosomes and REV, REV-exosomes could escape from REV-specific neutralizing antibodies in embryonated eggs, providing new insights into the immune escape mechanism of REV.

Abstract Multi-vessel coronary disease (MVCD) is a severe form of coronary artery disease (CAD) that significantly increases the risk of acute coronary syndrome (ACS) and heart attacks. The triglyceride glucose (TyG) index is a reliable and convenient marker for insulin resistance (IR). Recent studies have demonstrated its predictive value for CAD in patients with MVCD. This review aims to explore the application of the TyG index in managing MVCD and its underlying pathogenesis to enhance risk stratification and improve therapeutic decision-making.

The grain protein content (GPC) is the key parameter for wheat grain nutritional quality. This study conducted a resampling GWAS analysis using 406 wheat accessions across eight environments, and identified four previously reported GPC QTLs. An analysis of 87 landraces and 259 modern cultivars revealed the loss of superior GPC haplotypes, especially in Chinese cultivars. These haplotypes were preferentially adopted in different agroecological zones and had broad effects on wheat yield and agronomic traits. Most GPC QTLs did not significantly reduce yield, suggesting that high GPC can be achieved without a yield penalty. The results of this study provide a reference for future GPC breeding in wheat using the four identified QTLs.

Abstract Background Nasopharyngeal carcinoma (NPC) is 22nd most common cancer that occurs all over the world, but the prevalence rate can exhibit significant geographical differences. The Global Burden of Disease (GBD) database provides data related to the incidence, mortality, and disease burden of NPC worldwide from 1990 to 2019. We have designed this study in order to evaluate the potential effectiveness of health care policies and strategies for NPC prevention, diagnosis and treatment in different countries or regions around the world. Methods We used for the first time two distinct indicators, EAPC-ASIR and EACP-ASDR, to perform cluster analysis on 200 countries or regions around the world. Results 200 countries or regions could be divided into five diverse groups. Group 1: The incidence rate showed an increasing trend whereas the mortality rate depicted a decreasing trend. Group 2: Morbidity as well as mortality showed a slight increase; Group 3: Morbidity as well as mortality increased significantly; Group 4: Morbidity and mortality decreased significantly; Group 5: Both morbidity as well as mortality decreased slightly. Moreover, in the context of a global decline in NPC incidence, mortality and disease burden, Group 3 countries, including: “Turkmenistan”, “Bosnia and Herzegovina”, “Dominican Republic”, “Bulgaria”, “Lesotho”, “Cabo Verde”, “Romania”, “Cuba”, “Jamaica”, “Azerbaijan”, “Uzbekistan”, “Chad”, “Belize” and “Ukraine” displayed a significant increase in morbidity, mortality, and disease burden, thus indicating a dangerous trend. Conclusion It is suggested that the medical and health policies formulated by the countries in Group 3 for NPC, as well as their capacity for conducting censuses, preventing, diagnosing, and treating diseases, need to be substantially strengthened.

Abstract The advancements in tactile sensor technology have found wide-ranging applications in robotic fields, resulting in remarkable achievements in object manipulation and overall human-machine interactions. However, the widespread availability of high-resolution tactile skins remains limited, due to the challenges of incorporating large-sized, robust sensing units and increased wiring complexity. One approach to achieve high-resolution and robust tactile skins is to integrate a limited number of sensor units (taxels) into a flexible surface material and leverage signal processing techniques to achieve super-resolution sensing. Here, we present a magnetic skin consisting of multi-direction magnetized flexible films and a contactless Hall sensor array. The key features of the proposed sensor include the specific magnetization arrangement, K-Nearest Neighbors (KNN) clustering algorithm and convolutional neural network (CNN) model for signal processing. Using only an array of 4*4 taxels, our magnetic skin is capable of achieving super-resolution perception over an area of 48400 mm2, with an average localization error of 1.2 mm. By employing neural network algorithms to decouple the multi-dimensional signals, the skin can achieve multi-point and multi-scale perception. We also demonstrate the promising potentials of the proposed sensor in intelligent control, by simultaneously controlling two vehicles with trajectory mapping on the magnetic skin.

Abstract Objective To determine the performance of intravoxel incoherent motion (IVIM) parameters and the extracellular volume fraction (ECV) in distinguishing between different subtypes of lung cancer and predicting lymph node metastasis (LNM) status in patients with non-small-cell lung cancer (NSCLC). Methods One hundred sixteen patients with lung cancer were prospectively recruited. IVIM, native, and postcontrast T1 mapping examinations were performed, and the T1 values were measured to calculate the ECV. The differences in IVIM parameters and ECV were compared between NSCLC and small-cell lung cancer (SCLC), adenocarcinoma (Adeno-Ca) and squamous cell carcinoma (SCC), and NSCLC without and with LNM. The assessment of each parameter’s diagnostic performance was based on the area under the receiver operating characteristic curve (AUC). Results The apparent diffusion coefficient (ADC), true diffusion coefficient (D), and ECV values in SCLC were considerably lower compared with NSCLC (all p 0.887). The D value in SCC was substantially lower compared with Adeno-Ca (p 0.708). Conclusion IVIM parameters and ECV can serve as non-invasive biomarkers for assisting in the pathological classification and LNM status assessment of lung cancer patients. Critical relevance statement IVIM parameters and ECV demonstrated remarkable potential in distinguishing pulmonary carcinoma subtypes and predicting LNM status in NSCLC. Key Points Lung cancer is prevalent and differentiating subtype and invasiveness determine the treatment course. True diffusion coefficient and ECV showed promise for subtyping and determining lymph node status. These parameters could serve as non-invasive biomarkers to help determine personalized treatment strategies. Graphical Abstract

The structure of vascular bundles and the mechanical properties of fibers are crucial factors determining the utilization of bamboo. This study investigated the structure of vascular bundles and evaluated the morphological and micromechanical properties of the fibers in Oligostachyum sulcatum. The results showed that the fiber length and width of O. sulcatum meet the requirements of raw materials for the papermaking process. However, the fiber content in O. sulcatum is relatively low, which may increase the cost of papermaking. The vascular bundle growth exhibited non-uniformity, especially at the top part, with no discernible pattern in bundle area changes. The nanoindentation testing demonstrated that the bamboo's indentation modulus of elasticity (IMOE) and hardness values were comparable to those of moso bamboo (Phyllostachys edulis), suggesting its potential as a substitute in engineering applications.

Abstract Acute myeloid leukemia (AML) is a heterogeneous hematological tumor with poor immunotherapy effect. This study was to develop a monocyte/macrophage-related prognostic risk score (MMrisk) and identify new therapeutic biomarkers for AML. We utilized differentially expressed genes (DEGs) in combination with single-cell RNA sequencing to identify monocyte/macrophage-related genes (MMGs). Eight genes were selected for the construction of a MMrisk model using univariate Cox regression analysis and LASSO regression analysis. We then validated the MMrisk on two GEO datasets. Lastly, we investigated the immunologic characteristics and advantages of immunotherapy and potential targeted drugs for MMrisk groups. Our study identified that the MMrisk is composed of eight MMGs, including HOPX, CSTB, MAP3K1, LGALS1, CFD, MXD1, CASP1 and BCL2A1. The low MMrisk group survived longer than high MMrisk group (P

Based on the independently developed true triaxial multi-physical field large-scale physical simulation system of in-situ injection and production, we conducted physical simulation of long-term multi-well injection and production in the hot dry rocks of the Gonghe Basin, Qinghai Province, NW China. Through multi-well connectivity experiments, the spatial distribution characteristics of the natural fracture system in the rock samples and the connectivity between fracture and wellbore were clarified. The injection and production wells were selected to conduct the experiments, namely one injection well and two production wells, one injection well and one production well. The variation of several physical parameters in the production well was analyzed, such as flow rate, temperature, heat recovery rate and fluid recovery. The results show that under the combination of thermal shock and injection pressure, the fracture conductivity was enhanced, and the production temperature showed a downward trend. The larger the flow rate, the faster the decrease. When the local closed area of the fracture was gradually activated, new heat transfer areas were generated, resulting in a lower rate of increase or decrease in the mining temperature. The heat recovery rate was mainly controlled by the extraction flow rate and the temperature difference between injection and production fluid. As the conductivity of the leak-off channel increased, the fluid recovery of the production well rapidly decreased. The influence mechanisms of dominant channels and fluid leak-off on thermal recovery performance are different. The former limits the heat exchange area, while the latter affects the flow rate of the produced fluid. Both of them are important factors affecting the long-term and efficient development of hot dry rock.

The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H2S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, in vivo results demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment.

Nature makes the most beautiful solution to involuted problems. Among them, the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems, which demonstrate an ingenious evolutionary design. This study develops a mini-thermoelectric semiconductor P–N module to create gradient and parallel channeled hydrogels. The modules decrease quickly the temperature of polymer solution from 20 °C to −20 °C within 5 min. In addition to the exceptional liquid absorption rate, the foams exhibited shape memory mechanics. Our mini device universally makes the inspired structure in such as chitosan, gelatin, alginate and polyvinyl alcohol. Non-compressible hemorrhages are the primary cause of death in emergency. The rapid liquid absorption leads to fast activation of coagulation, which provides an efficient strategy for hemostasis management. We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity (96.43%) and rapid expansion rate (2934%). They absorb liquid with 37.25 times of the own weight, show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams. These superior properties lead to strong hemostatic performance in vitro and in vivo.

Abstract Introduction Chronic neck pain (CNP) is a global public health problem, with high prevalence and absenteeism rates. Central sensitization (CS) as a basis for chronic pain may play an essential role in its development and progression. It is often comorbid with low conditioned pain modulation (CPM) effects, cognitions, and psychological problems. Objectives The purposes of this study were to (1) explore the relationship between pain-related cognitions and psychological factors, CPM effects, and the central sensitization inventory (CSI) scores; and (2) determine whether cognitions and psychological factors can predict CSI scores and CPM effects in individuals with CNP. Methods Fifty-four individuals with CNP were recruited for this cross-sectional study. The following outcome measures were evaluated: The CSI (screening tool) was compared with the cold pressor test (CPT), which was the psychophysical test used to assess the CPM; neck pain intensity using the visual analogue scale (VAS), as well as pain-related cognitions (including kinesiophobia and pain catastrophization) and psychological states (including anxiety and depression) using self-report questionnaires. Results CSI score was not associated with the CPM effect (r = 0.257, p > 0.05), and no cognitions or psychological factors were associated with CPM (p > 0.05), but CSI score was moderately positively correlated with kinesiophobia (r = 0.554, p

Background With the gradual increase of infertility in the world, among which male sperm problems are the main factor for infertility, more and more couples are using computer-assisted sperm analysis (CASA) to assist in the analysis and treatment of infertility. Meanwhile, the rapid development of deep learning (DL) has led to strong results in image classification tasks. However, the classification of sperm images has not been well studied in current deep learning methods, and the sperm images are often affected by noise in practical CASA applications. The purpose of this article is to investigate the anti-noise robustness of deep learning classification methods applied on sperm images.Methods The SVIA dataset is a publicly available large-scale sperm dataset containing three subsets. In this work, we used subset-C, which provides more than 125,000 independent images of sperms and impurities, including 121,401 sperm images and 4,479 impurity images. To investigate the anti-noise robustness of deep learning classification methods applied on sperm images, we conducted a comprehensive comparative study of sperm images using many convolutional neural network (CNN) and visual transformer (VT) deep learning methods to find the deep learning model with the most stable anti-noise robustness.Results This study proved that VT had strong robustness for the classification of tiny object (sperm and impurity) image datasets under some types of conventional noise and some adversarial attacks. In particular, under the influence of Poisson noise, accuracy changed from 91.45% to 91.08%, impurity precison changed from 92.7% to 91.3%, impurity recall changed from 88.8% to 89.5%, and impurity F1-score changed 90.7% to 90.4%. Meanwhile, sperm precision changed from 90.9% to 90.5%, sperm recall changed from 92.5% to 93.8%, and sperm F1-score changed from 92.1% to 90.4%.Conclusion Sperm image classification may be strongly affected by noise in current deep learning methods; the robustness with regard to noise of VT methods based on global information is greater than that of CNN methods based on local information, indicating that the robustness with regard to noise is reflected mainly in global information.

Abstract Background Selenium (Se) fertilizer and arbuscular mycorrhizal fungi (AMF) are known to modulate cadmium (Cd) toxicity in plants. However, the effects of their co-application on wheat growth and soil microbial communities in Cd-contaminated soil are unclear. Results A pot experiment inoculation with two types of AMF and the application of Se fertilizer under Cd stress in wheat showed that inoculation AMF alone or combined with Se fertilizer significantly increased wheat biomass. Se and AMF alone or in combination significantly reduced available Cd concentration in wheat and soil, especially in the Se combined with Ri treatment. High throughput sequencing of soil samples indicated that Se and AMF application had stronger influence on bacterial community compared to fungal community and the bacterial network seemed to have more complex interconnections than the fungal network, and finally shaped the formation of specific microflora to affect Cd availability. Conclusion These results indicate that the application of Se and AMF, particularly in combination, could successfully decrease soil Cd availability and relieve the harm of Cd in wheat by modifying rhizosphere soil microbial communities.

In this work, low cycle fatigue experiments under both strain and stress control modes with different loading levels were conducted on 304 austenitic stainless steel at ambient temperature to discuss the influence of loading mode and level on the cyclic response and physical mechanism. The results demonstrated that the cyclic response generally exhibited three stages: primary cyclic hardening, subsequent cyclic softening, and the secondary hardening finally. The degree of each hardening and softening stage was depended on not only the loading modes but also the strain/stress level. Accelerated cyclic softening and retarded secondary hardening occurred under the stress mode, which made a higher low-cycle fatigue life during stress cyclic loading than that for the strain control mode, especially at relatively high strain/stress level. The secondary hardening stage, occupying the main portion of the lifetime, was proved to be associated with the development of martensitic phase and the extension and intersecting of stacking faults or micro-twin.

Abstract Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.

The complex network of fractures formed by randomly distributed natural fractures in hot-dry rocks (HDRs) complicates the heat transfer regularity of injected fluid. On the basis of the fracture network, exploring the characteristics of the fluid flow and heat transfer as influenced by different parameters helps enable efficient resource extraction and effectively promotes the construction of diversified energy utilization structures. Accordingly, accounting for the effect of the thermal shock on the evolution of the permeability of the rock matrix, a thermo-hydro-mechanical (THM) coupling model is developed to analyze the influences of fracture network characteristics on the heat extraction performance of HDRs. In addition, a large-scale injection and production physical simulation experiment is performed using a newly developed, in-house, large-scale true triaxial experimental system. The corresponding numerical model is established and validated. The good agreement between the numerical and experimental results verifies the reliability and accuracy of the proposed THM model. Subsequently, a two-dimensional model is established under complex fracture network conditions, taking, as a research object, the natural fracture characteristics of HDR in the Qinghai Gonghe Basin in combination with the regional geological information. The effects of different parameters, including the production well location, rock matrix permeability, injection rate, initial fracture width, and number of fractures, on the production temperature and heat extraction performance are systematically analyzed. The results indicate that an increase in the number of fractures, the distance between the injection well and the production well, or the width of the initial fractures leads to an improved heat extraction performance. The number of fractures increased from 11 horizontal fractures and 22 high-angle fractures to 35 horizontal fractures and 70 high-angle fractures, with a 20% increase in heat extraction rate. While the influence of the rock matrix permeability is not highly significant, it cannot be ignored. It is crucial to select an injection rate that is neither too low nor too high, taking into consideration economic factors.

The field of person re-identification (re-ID) encounters challenges such as inter-person similarity and occlusion. In this paper, we introduce an occluded pedestrian re-ID method based on Multiple Fusion and Semantic feature Mining (MFSM) to mitigate the adverse effects of occlusion on feature representation. Specifically, we devise a Multi-branch Strategic Enhancement Module (SEM) to bolster the robustness of data augmentation in addressing the issues posed by data memorization more consistently. This module emulates various real-world disturbances by implementing distinct and independent augmentation strategies. Furthermore, we propose the Triplet Cross Unit (TCU) to comprehensively exploit and consolidate both regional and relational visual cues, as well as multi-level features. The TCU facilitates transformers in acquiring an early understanding of translation invariance in images by transferring local patterns such as edges, textures, and colors from the lower CNN layers to the shallower transformer layers. Simultaneously, deeper transformer features offer more abstracted semantic visual representations that complement CNN's high-level semantic features. Lastly, we introduce the Global Squeeze-Excitation Fusion (GSEF) module to address the challenge of global feature segregation across different models in final outputs. The GSEF selectively merges features based on attention mechanisms, prioritizing the comprehensive utilization of valid global features. Extensive experiments demonstrate the state-of-the-art performance of our model in handling pedestrian occlusion, thus validating the efficacy of our method.

African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host’s innate immune responses. However, whether ASFV MGF360-4L could inhibit type I interferon (IFN-I) signaling pathway and the underlying molecular mechanisms remain unknown. Our study, indicated that ASFV MGF360-4L could negatively regulates the cGAS-STING mediated IFN-I signaling pathway. Overexpressing ASFV MGF360-4L could inhibit the cGAS/STING signaling pathway by inhibiting the interferon-β promoter activity, which was induced by cGAS/STING, TBK1, and IRF3-5D, and further reduced the transcriptional levels of ISG15, ISG54, ISG56, STAT1, STAT2, and TYK2. Confocal microscopy and immunoprecipitation revealed that MGF360-4L co-localized and interacted with IRF3, and WB revealed that ASFV MGF360-4L suppressed the phosphorylation of IRF3. 4L-F2 (75-162 aa) and 4L-F3 (146-387 aa) were the crucial immunosuppressive domains and sites. Altogether, our study reveals ASFV MGF360-4L inhibited cGAS‐STING mediated IFN-I signaling pathways, which provides insights into an evasion strategy of ASFV involving in host’s innate immune responses.

Net primary productivity (NPP) is a crucial component of the terrestrial carbon cycle and plays a crucial role in assessing ecological security. Although machine learning models have been widely used in research on ecosystem modelling, however, the performance of deep learning models with interpretability in predicting NPP are still very limited. In this study, we developed an interpretable deep learning predictive model to uncover the historical drivers and future changes of NPP in China using remote sensing data, climate data and topography. The results show that more than three quarters (88 %) of China’s regional NPP have shown an increasing trend over the past 20 years, with an overall trend of 2.46 gC/m2/yr. This extensive range of dynamic processes is a nonlinear response to climatic conditions and topographic factors. The constructed convolutional neural network (CNN) model showed good predictive skill for historical NPP, and revealed that temperature is the main controlling factor, highlighting its importance in vegetation growth in China. Compared to the historical period (2001–2020), in the context of future climate change, the risk of carbon sinks decreasing in China is highly likely in the imminent near term (2021–2039), especially under high emission scenarios. These results suggest that interpretable deep learning method is a useful tool for revealing vegetation productivity drivers and estimating vegetation productivity under a nonstationary climate background.

The zeroth law of black hole mechanics asserts that the stationary black hole has a constant surface gravity on the event horizon. This study investigates the zeroth law within the Einstein-Scalar-Gauss-Bonnet gravity, particularly involving a complex scalar field (ECSGB). Assuming that the Lie derivative of the complex scalar field is proportional to itself other than stationary, and that ECSGB gravity converges to the Einstein's gravity analyticaly as the coupling constant approaches zero, as well as the minimally coupled matter fields satisfy the dominant energy condition, we demonstrate that the surface gravity remains constant over the entire event horizon without reliance on additional symmetries.

Aiming at the problem that it takes a long time and high cost to obtain complete labeled data under intelligent fault diagnosis and unlabeled data is not used. This paper proposes an improved semi-supervised mean teacher deep learning (MTDL) and Gramian angle field (GAF) fusion diagnostic method. This method fully utilizes a small number of labeled samples and a large number of unlabeled samples to deeply mine invisible fault features and potential physical correlations. At the same time, it solves the problem of losing the inter-data correlation structure when one-dimensional time series signals are used as inputs for neural networks. The GAF-MTDL method uses consistency regularization and modifies the network structure in the mean teacher algorithm into a semi-supervised deep learning model enhanced by WideResNet. The experimental results show that the proposed GAF-MTDL method saves a lot of manual labeling costs, improves the recognition accuracy and generalization ability, and can achieve excellent prediction accuracy with very little labeled data. In the end, the accuracy of planetary gear fault identification reached 98.22% under the labeling rate of 20%, and the accuracy of fault identification reached 99.98% through the verification of the bearing data set of Case Western Reserve University. The value of this research is to bring an efficient and low-cost technology to the field of industrial intelligent fault diagnosis, which can significantly improve the accuracy of fault identification.

Abstract Early‐stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non‐invasive and cost‐effective detection method for early‐stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on‐skin sensor with low electrode‐skin contact impedance for early‐stage NAFLD detection is fabricated. A method is developed to synthesize platinum nanoparticles and reduced graphene quantum dots onto the on‐skin sensor to reduce electrode‐skin contact impedance by increasing double‐layer capacitance, thereby enhancing detection accuracy. Furthermore, an attention‐based deep learning algorithm is introduced to differentiate impedance signals associated with early‐stage NAFLD in high‐fat‐diet‐fed low‐density lipoprotein receptor knockout (Ldlr−/−) mice compared to healthy controls. The integration of an adhesive, soft on‐skin sensor with low electrode‐skin contact impedance and the attention‐based deep learning algorithm significantly enhances the detection accuracy for early‐stage NAFLD, achieving a rate above 97.5% with an area under the receiver operating characteristic curve (AUC) of 1.0. The findings present a non‐invasive approach for early‐stage NAFLD detection and display a strategy for improved early detection through on‐skin electronics and deep learning.

Background and aims: One of the primary causes of lumen narrowing is vascular injury induced during medical procedures. Vascular injury disrupts the integrity of the endothelium, triggering platelet deposition, leukocyte recruitment, and the release of inflammatory factors. This, in turn, induces the proliferation of vascular smooth muscle cells (VSMCs), leading to neointima formation. However, the molecular mechanism underlying VSMC proliferation following injury remains unknown. KIF11 is critical in regulating the cell cycle by forming bipolar spindles during mitotic metaphase. This process may contribute to VSMCs proliferation and neointima formation following vascular injury. Yet, the function of KIF11 in VSMCs has not been elucidated. This study aims to investigate the role and mechanisms of KIF11 in regulating VSMCs cycle progression and proliferation.Methods: After conducting biological analysis of the transcriptome sequencing data from the mouse carotid artery injury model and the cell transcriptome data of PDGF-BB-induced VSMCs, we identified a potential target gene, KIF11, which may play a crucial role in vascular injury. Then we established a vascular injury model to investigate how changes in KIF11 expression and activity influence in vivo VSMCs proliferation and neointimal formation. In addition, we employed siRNA and specific inhibitors to suppress KIF11 expression and activity in VSMCs cultured in vitro to study the mechanisms underlying VSMCs cycle progression and proliferation.Results: The results of immunohistochemistry and immunofluorescence indicate a significant upregulation of KIF11 expression in the injured vascular. The intraperitoneal injection of the KIF11 specific inhibitor, K858, partially inhibits intimal hyperplasia in the vascular injury model. In vitro experiments further demonstrate that PDGF-BB upregulates KIF11 expression through the PI3K/AKT pathway, and enhances KIF11 activity. Inhibition of both KIF11 expression and activity partially reverses the pro-cycle progression and pro-proliferation effects of PDGF-BB on VSMCs. Additionally, KIF11 overexpression partially counteracts the proliferation arrest and cell cycle arrest induced by inhibiting the PI3K/AKT pathway in VSMCs.Conclusion: Our study highlights the crucial role of KIF11 in regulating the cycle progression and proliferation of VSMCs after vascular injury. A comprehensive understanding of these mechanisms could pave the way for potential therapeutic interventions in treating vascular stenosis.

We revisit the previously known local inversion symmetry of the five-dimensional Kerr-AdS metric that relates the over-rotating black hole to the under-rotating one and reinterpret it as an interchanging symmetry between time and the longitudinal angular coordinates. We generalize this to all D dimensions, including D=4, thereby enlarging the trivial linear ZN symmetry of the N=⌊(D−1)/2⌋ longitudinal angular coordinates to the nonlinearly realized ZN+1 symmetry that involves time.

Artificial intelligence (AI) is an umbrella term for a wide range of machine intelligence systems that can replicate the behavior of humans. AI and Big Data have emerged as defining characteristics of the fourth industrial revolution (IR). AI has developed tools. Because of the novelty, the investigation of IR, AI, and their environmental effects is still in the early stages of exploration. This study investigates how IR and AI affect human and environmental health and also discusses IR, AI, machine-human ideas, innovation, and AI's environmental benefits, further examines the challenges of these innovations, and recommends additional studies to explain their progress. As a result, the application of AI technology in environmental management, particularly concerning pollution, has become a significant advancement in reshaping our approach to monitoring the environment. Numerous countries are reaping substantial advantages by integrating AI in creating, executing, and assessing measures to address environmental degradation. These innovations can yield societal advantages and contribute to achieving the Sustainable Development Goals (SDGs) 2030; unfortunately, it is important to acknowledge that these benefits may not align well with environmental sustainability objectives, and the increasing number of electronic gadgets presents an additional concern. Conducting future research is crucial to investigate the growing prevalence of electronic devices utilized for AI, its potential ramifications for the future trajectory of climate change, and the approaches being taken to address the issue. Future research should prioritize conducting lifecycle environmental impact analyses, developing sustainable AI hardware, optimizing renewable energy usage, advancing climate modeling techniques, finding effective solutions for managing e-waste, utilizing AI for environmental monitoring and protection, conducting socio-environmental impact studies, developing policies and regulations, creating energy-efficient AI algorithms, and integrating circular economy principles to ensure that AI advancements align with environmental sustainability.

Background: Although the use of anti-PD-1 antibodies has fundamentally changed traditional cancer treatment, most patients are resistant to anti-PD-1 treatment. Glucocorticoids (GCs) play an important role in tumorigenesis and tumor progression, but the role of endogenous GCs in resistance to anti-PD-1 antibody therapy remains unclear. Methods: Single cell-derived cell lines (SCDCLs) were generated from a colorectal cancer cell line (CT26) using limiting dilution. We analyzed tumor tissues from anti-PD-1 antibody-treated and untreated mice inoculated with SCDCLs via transcriptome sequencing and flow cytometry to detect pathway activity and immune cell composition changes in the tumor microenvironment. Results: Five SCDCLs were inoculated into wild-type BALB/c mice (all tumorigenic). Single-cell clone (SCC)-2 exhibited the slowest growth rates both in vivo and in vitro compared to other single-cell clones, and better long-term survival than SCC1 and CT26. Flow cytometry showed that SCC2 tumor-bearing mice exhibited significantly higher infiltration of T cells within the tumor tissue, and higher expression of PD-1 on these T cells than the other groups in vivo. However, the SCC2 group showed no response to anti-PD-1 therapy. Transcriptome analysis revealed that the SCC2 group exhibited increased expression of genes related to GC (Hsd11b1, Sgk3, Tgfbr2, and Il7r) compared to SCC2-anti-PD-1 treated tumors. Conclusions: GC pathway activation is related to resistance to anti-PD-1 therapy.

Abstract Heterogeneous organ‐specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single‐cell profiling using formalin‐fixed paraffin‐embedded (FFPE) materials. In this study, single‐cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ‐specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single‐cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ‐specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4+ T cells at immunogenic sites. Various organ‐specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM‐3. This study originally deciphers the single‐cell landscape of the organ‐specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ‐specific treatment approaches.

IntroductionGranulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions. MethodsG-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in G-MDSCs were analyzed via RNA sequencing to investigate functional transitions.ResultsG-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes. ConclusionOur findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD.

Summary: Bone tissue represents the most frequent site of cancer metastasis. We developed a hemichannel-activating antibody, Cx43-M2. Cx43-M2, directly targeting osteocytes in situ, activates osteocytic hemichannels and elevates extracellular ATP, thereby inhibiting the growth and migration of cultured breast and osteosarcoma cancer cells. Cx43-M2 significantly decreases breast cancer metastasis, osteosarcoma growth, and osteolytic activity, while improving survival rates in mice. The antibody’s inhibition of breast cancer and osteosarcoma is dose dependent in both mouse and human cancer metastatic models. Furthermore, Cx43-M2 enhances anti-tumor immunity by increasing the population and activation of tumor-infiltrating immune-promoting effector T lymphocytes, while reducing immune-suppressive regulatory T cells. Our results suggest that the Cx43-M2 antibody, by activating Cx43 hemichannels and facilitating ATP release and purinergic signaling, transforms the cancer microenvironment from a supportive to a suppressive state. Collectively, our study underscores the potential of Cx43-M2 as a therapeutic for treating breast cancer bone metastasis and osteosarcoma.

ABSTRACT: Avian leukemia virus subgroup J (ALV-J) and chicken infectious anemia virus (CIAV) can be vertically transmitted; however, the pathogenicity of vertically transmitted coinfection with these 2 pathogens has not been studied. In this study, we created a model of chick morbidity in which chicks carried either ALV-J, CIAV, or both viruses via embryo inoculation. Thereafter, we analyzed the effects of vertically transmitted coinfection with CIAV and ALV-J on the pathogenicity of ALV-J and performed a purification assay based on hatching, mortality viremia positivity, and detection of fecal ALV-p27 antigen rates, and body weight. The hatching rate of the ALV-J+CIAV group was 68.57%, lower than those of the single infection and control groups. The survival curve showed that the mortality rates of the CIAV and ALV-J coinfection groups were higher than those of the single infection and control groups. Body weight statistics showed that coinfection aggravated the 7-d growth inhibition effect. The results of ALV-p27 antigen detection in cell culture supernatants showed that the positivity rates of the ALV-J and ALV-J+CIAV groups were 100% at all ages and 0% in the control group. The results of ALV-p27 antigen detection by anal swabs showed that the positivity rates of the ALV-J group were 92.86, 90.90, 88.89, and 93.33% at all ages, and that the ALV-J p27 positivity detection rate of anal swabs was lower than that of plasma virus isolation. The immune organ index of the ALV-J+CIAV group was significantly or very significantly lower than those of the single infection and control groups. The immune organ viral load showed that coinfection with CIAV and ALV-J promoted the proliferation of ALV-J and CIAV in immune organs. Coinfection with ALV-J and CIAV reduced chicken embryo hatchability and increased chick mortality and growth inhibition relative to their respective single infections. Additionally, coinfection with ALV-J + CIAV was even more detrimental in inducing immune organ atrophy (e.g., the thymus, spleen, and bursa), and promoted individual virus replication during coinfection.

ABSTRACT: Marek's disease virus (MDV) is a significant tumorigenic virus that causes severe immunosuppression in chickens. Lentinan (LNT) is an immunomodulator containing β-glucans and is widely used in areas such as antiviral, anticancer, and immune regulation. To investigate the immunomodulatory effects of LNT on specific pathogen-free (SPF) chicks and its potential to inhibit MDV infection, we conducted an MDV challenge experiment and observed the immune-enhancing effect of LNT on SPF chicks. The results showed that LNT promoted the growth and development of SPF chicks and induced the upregulation of cytokines such as Mx protein, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The specific gravity of CD4+ T-lymphocytes and CD8+ T-lymphocytes and their ratios were also significantly upregulated. Prophylactic use of LNT inhibited MDV replication in lymphocytes, liver, and spleen. It also alleviated MDV-induced weight loss and hepatosplenomegaly in SPF chicks. The present study confirms that LNT can enhance the levels of innate and cellular immunity in SPF chicks and contributes to the inhibition of MDV replication in vivo and mitigation of immune organ damage in chicks due to MDV infection. This provides an adjunctive measure for better control of MDV infection.

Maintaining and restoring ecological connectivity (EC) are important measures of mitigating habitat isolation caused by urbanization. Considering the prominent contradiction of land use in highly urbanized areas, the EC protection measures proposed in the previous studies, such as expanding the ecological sources and widening the ecological corridors, are unrealistic. By using the stepping-stone and complex network theories, this paper simulated the ecological network (EN), evaluated the centrality of each ecological source and stepping-stone, and analysed the network robustness under different damage scenarios, then identified the optimal strategy and key patches for EC maintaining. Meanwhile, this paper evaluated whether the key patches are protected by China’s new policies, which are, Ecological Protection Red Line (EPRL) and the Three Lines One Permit (TLOP). The results were as follows: (1) The EN is composed of 53 ecological sources and 291 stepping-stones, with 591 links between them. (2) The network stability can be optimally maintained by prioritizing the protection of stepping-stones with high centrality. (3) The 53 ecological sources and 51 stepping-stones with the highest centrality can ensure the stable operation of the EN, that is, they are key patches for EC maintaining. (4) Compared with EPRL, the protection rate for ecological sources and stepping-stones are significantly improved by TLOP; however, stepping-stones with high centrality require stronger protection. This study enriched the research cases of complex network theory applied in landscape ecology, and provided references for the improvement of policies in the future.

Concentrating electromagnetic (EM) heat losses on the surface for road microwave deicing have been used to increase the efficiency of surface microwave heating. Here, a numerical model to enhance the surface EM losses based on metamaterial absorbers (MMAs) was developed and validated using experiments with cement as the thermal medium. The model included structure optimization, analysis for characterization of the surface loss mechanism, and tested for determination of the surface heating efficiency. Using the optimized structures, the efficiency of surface microwave heating improved by fivefold when compared to conventional road structures. These effects were consistent across tested and simulated results. In summary, the potential of implementing MMAs for road microwave deicing is highlighted to improve surface microwave heating efficiency.

Wood species can be classified by spectral reflectance. It is unclear whether finish coated on the wood surface affects the accuracy of wood species classification. This paper focused on this issue, using the spectral reflectance of 8 different kinds of finish for wood species classification. The spectral reflectance of wood surface coated with finish was modified by the transfer model in order to reduce the effect of finish on classification accuracy. The experimental results show that it is not feasible to use the spectral reflectance of wood samples coated with finish directly to classify wood species; the best classification accuracy using the eight finishes was 30%. After correcting the spectrum of wood samples coated with finishes with the direct standardization (DS) transfer model, the classification accuracy of the near-infrared (NIR) spectrum was close to that of the original spectrum without finish. However, the visible/near-infrared (VIS/NIR) spectrum did not achieve a good classification effect after correction with the DS transfer model.

B-cell acute lymphoblastic leukemia (B-ALL) is a malignant blood disorder, particularly detrimental to children and adolescents, with recurrent or unresponsive cases contributing significantly to cancer-associated fatalities. IKBKE, associated with innate immunity, tumor promotion, and drug resistance, remains poorly understood in the context of B-ALL. Thus, this research aimed to explore the impact of the IKBKE inhibitor MCCK1 on B-ALL cells. The study encompassed diverse experiments, including clinical samples, in vitro and in vivo investigations. Quantitative real-time fluorescence PCR and protein blotting revealed heightened IKBKE mRNA and protein expression in B-ALL patients. Subsequent in vitro experiments with B-ALL cell lines demonstrated that MCCK1 treatment resulted in reduced cell viability and survival rates, with flow cytometry indicating cell cycle arrest. In vivo experiments using B-ALL mouse tumor models substantiated MCCK1's efficacy in impeding tumor proliferation. These findings collectively suggest that IKBKE, found to be elevated in B-ALL patients, may serve as a promising drug target, with MCCK1 demonstrating potential for inducing apoptosis in B-ALL cells both in vitro and in vivo.

Abstract The anti-dip bedding rock slopes have threatened global infrastructure construction and urban expansion seriously. Taking the Guang'an Village rockslide as an example, this paper firstly studied the deformation characteristics of the rockslide with anti-dip bedding structure based on in-situ investigation and monitoring, and then the relevant influencing factors were summarized. On this basis, a new evolution model of continuous-pushing-section pressing locked-section and the instability mechanism of the rock slope were proposed. Finally, the applicability of the model and the deformation tendency of the rock slope were further discussed. A catastrophic sliding event has once occurred in the Guang'an Village rockslide in 2017, after which the deformation of the potential source area III (PSA-III) was accelerating. The presence of the sliding-prone geological structure provides the basic conditions for the deformation of the rock slope and the development of the sliding zone. Rainfall is the major external trigger that promotes the deformation. As the sliding zone extends forward, the overlying deformation body will keep on pushing against the preceding rock mass, which will contribute to the forward extension of the sliding zone as well. When the final locked section is crushed, the rock slope will lose balance. According to the observation in the field, the PSA-III is in the late stage of the deformation-increasing phase currently. This study can provide a reference for the analysis of failure mechanism and the design of monitoring and mitigation of other large anti-dip bedding rock slides.

Abstract Autophagy modulates the degradation and recycling of intracellular materials and contributes to male gametophyte development and male fertility in plants. However, whether autophagy participates in seed development remains largely unknown. Here, we demonstrate that autophagy is crucial for timely programmed cell death (PCD) in the integumentary tapetum, the counterpart of anther tapetum, influencing embryo pattern formation and seed viability. Inhibition of autophagy resulted in delayed PCD of the integumentary tapetum and defects in embryo patterning. Cell-type-specific restoration of autophagic activities revealed that the integumentary tapetum plays a non-autonomous role in embryo patterning. Furthermore, high-throughput, comprehensive lipidomic analyzes uncovered an unexpected seed-developmental-stage-dependent role of autophagy in seed lipid metabolism: it contributes to triacylglycerol degradation before fertilization and to triacylglycerol biosynthesis after fertilization. This study highlights the critical role of autophagy in regulating timely integumentary tapetum PCD and reveals its significance in seed lipid metabolism and viability.

Abstract Persian walnut (Juglans regia) and Manchurian walnut (Juglans mandshurica) belong to Juglandaceae, which are vulnerable, temperate deciduous perennial trees with high economical, ecological, and industrial values. 4-Coumarate: CoA ligase (4CL) plays an essential function in plant development, growth, and stress. Walnut production is challenged by diverse stresses, such as salinity, drought, and diseases. However, the characteristics and expression levels of 4CL gene family in Juglans species resistance and under salt stress are unknown. Here, we identified 36 Jr4CL genes and 31 Jm4CL genes, respectively. Based on phylogenetic relationship analysis, all 4CL genes were divided into three branches. WGD was the major duplication mode for 4CLs in two Juglans species. The phylogenic and collinearity analyses showed that the 4CLs were relatively conserved during evolution, but the gene structures varied widely. 4CLs promoter region contained multiply cis-acting elements related to phytohormones and stress responses. We found that Jr4CLs may be participated in the regulation of resistance to anthracnose. The expression level and some physiological of 4CLs were changed significantly after salt treatment. According to qRT-PCR results, positive regulation was found to be the main mode of regulation of 4CL genes after salt stress. Overall, J. mandshurica outperformed J. regia. Therefore, J. mandshurica can be used as a walnut rootstock to improve salt tolerance. Our results provide new understanding the potential functions of 4CL genes in stress tolerance, offer the theoretical genetic basis of walnut varieties adapted to salt stress, and provide an important reference for breeding cultivated walnuts for stress tolerance.

Abstract Background The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical trial, KEYNOTE394. Additionally, we sought to elucidate the underlying molecular mechanisms for resistance to immune checkpoint blockade (ICB) and propose innovative combination immunotherapy strategies for future clinical application. Methods Patient blood samples were collected for single-cell RNA sequencing to evaluate the immune cell signature before receiving ICB therapy. Subsequently, in vitro assays and in vivo murine model experiments were conducted to validate the mechanism that S100A9+CD14+ monocytes play a role in ICB resistance. Results Our study demonstrates a notable enrichment of S100A9+CD14+ monocytes in the peripheral blood of patients exhibiting suboptimal responses to anti-PD-1 therapy. Moreover, we identified the Mono_S100A9 signature as a predictive biomarker, indicative of reduced efficacy in immunotherapy and decreased survival benefits across various tumor types. Mechanistically, S100A9 activates PD-L1 transcription by directly binding to the CD274 (PD-L1) gene promoter, thereby suppressing T-cell proliferation and cytotoxicity via the PD-1/PD-L1 axis, consequently diminishing the therapeutic effectiveness of subsequent anti-PD-1 treatments. Furthermore, our in vivo studies revealed that inhibiting S100A9 can synergistically enhance the efficacy of anti-PD-1 drugs in the eradication of hepatocellular carcinoma. Conclusions Our study underscores the significance of S100A9+CD14+ monocytes in predicting inadequate response to ICB treatment and provides insights into the monocyte cell-intrinsic mechanisms of resistance to ICB therapy. We also propose a combined therapeutic approach to enhance ICB efficacy by targeting S100A9.

Abstract Platycarya strobilacea belongs to the walnut family (Juglandaceae), is commonly known as species endemic to East Asia, and is an ecologically important, wind pollinated, woody deciduous tree. To facilitate this ancient tree for the ecological value and conservation of this ancient tree, we report a new high-quality genome assembly of P. strobilacea. The genome size was 677.30 Mb, with a scaffold N50 size of 45,791,698 bp, and 98.43% of the assembly was anchored to 15 chromosomes. We annotated 32,246 protein-coding genes in the genome, of which 96.30% were functionally annotated in six databases. This new high-quality assembly of P. strobilacea provide valuable resource for the phylogenetic and evolutionary analysis of the walnut family and angiosperm.

The spraying method offers the advantages of environmental protection, convenient construction, and cost-effectiveness, making it widely used in pipeline structure repair. Given the complex service environment of pipelines, there is an urgent demand for high-strength and durable spraying materials. To achieve this goal, a PVA fiber reinforced cement mortar material (PFCM) with high early strength, excellent impermeability and stable acid corrosion resistance was developed through orthogonal test design. The optimal material was obtained through factors such as setting time, fluidity, compressive strength and flexural strength. The effects of the contents of fly ash, redispersible polymer powder and PVA fiber on the working and mechanical properties of the material were investigated, and further research was conducted on its tensile strength, impermeability, acid corrosion resistance. In addition, Thermogravimetric-differential Thermal Analysis (TG-DTA) was utilized to analyze the thermal stability of PFCM. X-ray diffraction (XRD) was utilized to analyze the composition of PFCM. Mercury intrusion porosimetry (MIP) was utilized to analyze the pore structure of PFCM, and the feasibility of the PFCM was verified. The results indicate that the contents of fly ash, redispersible polymer powder and PVA fiber have significant effects on the working and mechanical properties. The optimum initial setting time is 60–80 min, and the optimum fluidity is between 170 and 180 mm. The compressive strength and flexural strength of the mortar prepared with the optimum parameters are 102.5 MPa and 20 MPa, respectively. The material has an excellent spraying effect with no sagging, and exhibits high early strength, outstanding corrosion resistance, low porosity, and exceptional impermeability. This study lays the foundation for achieving high-quality spray repairs of underground drainage pipelines.

Fiberglass-reinforced ultraviolet cured-in-place pipe (UV–CIPP) composite material is one of the most trenchless materials for underground pipelines’ rehabilitation. In this paper, the bending resistance and damage evolution mechanism of glass fiber-reinforced UV-CIPP composites were investigated under the influence of glass fiber structure, the number of layers of glass fibers, the angle of fiber layups, and the thickness of the material by high-definition video, SEM and infrared thermal imaging. The results indicate that the damage evolution modes of UV-CIPP materials mainly include: (1) fiber pull-out and overall fiber bundle tensile failure caused by strong interfacial bonding, (2) fiber/matrix debonding and delamination, fiber fracture, and matrix cracking caused by weak interfacial bonding. Furthermore, among the seven different fiberglass structures of UV-CIPP materials, the [0°/90°] warp-knit axial/short-cut felt fiberglass fabric exhibit the best flexural performance, with a bending strength of 412 MPa and a bending modulus of 16.1 GPa for the 4 layers glass fiber fabric. Moreover, in the bending process of UV-CIPP materials, the surface temperature rises primarily due to fiber break, the temperature transition aligning with the stress transition. Finally, the energy release is mainly caused by the failure of the glass fibers, but the resin contributed comparatively little. This study provides a scientific reference for the structural design and optimization of UV-CIPP materials.

Abstract Background The color of endopleura is a vital factor in determining the economic value and aesthetics appeal of nut. Walnuts (Juglans) are a key source of edible nuts, high in proteins, amino acids, lipids, carbohydrates. Walnut had a variety endopleura color as yellow, red, and purple. However, the regulation of walnut endopleura color remains little known. Results To understand the process of coloration in endopleura, we performed the integrative analysis of transcriptomes and metabolomes at two developmental stages of walnut endopleura. We obtained total of 4,950 differentially expressed genes (DEGs) and 794 metabolites from walnut endopleura, which are involved in flavonoid and phenolic biosynthesis pathways. The enrichment analysis revealed that the cinnamic acid, coniferyl alcohol, naringenin, and naringenin-7-O-glucoside were important metabolites in the development process of walnut endopleura. Transcriptome and metabolome analyses revealed that the DEGs and differentially regulated metabolites (DRMs) were significantly enriched in flavonoid biosynthesis and phenolic metabolic pathways. Through co-expression analysis, CHS (chalcone synthase), CHI (chalcone isomerase), CCR (cinnamoyl CoA reductase), CAD (cinnamyl alcohol dehydrogenase), COMT (catechol-Omethyl transferase), and 4CL (4-coumaroyl: CoA-ligase) may be the key genes that potentially regulate walnut endopleura color in flavonoid biosynthesis and phenolic metabolic pathways. Conclusions This study illuminates the metabolic pathways and candidate genes that underlie the endopleura coloration in walnuts, lay the foundation for further study and provides insights into controlling nut’s colour.

Abstract Background The increasing number of sequential treatments complicates the evaluation of overall survival (OS) in clinical trials for hepatocellular carcinoma (HCC), therefore, reliable surrogate endpoints (SEs) are required. This study aimed to evaluate the surrogacy of progression-free survival (PFS) and one-year (1-yr) milestone survival for OS in HCC trials. Methods We systematically searched databases for randomized clinical trials that evaluated systemic treatments for advanced HCC. Individual patient data were reconstructed to calculate the 1-yr survival rate. We adopted a two-stage meta-analytic validation model to evaluate the correlation between SEs and OS, and the correlation between treatment effects on SEs and OS. The hazard ratio (HR) was calculated to assess the treatment effects on PFS and OS, and the 1-yr survival ratio was calculated to evaluate the treatment effects on the 1-yr milestone survival. Results Thirty-two HCC trials involving 13,808 patients were included. A weak correlation was detected between the median PFS and median OS (R2 = 0.32), whereas the correlation improved between PFS HR and OS HR (R2 = 0.58). We identified strong correlations between the 1-yr survival rate and median OS and between the 1-yr survival ratio and OS HR (R2 = 0.74 and 0.65, respectively). In subgroup analyses, PFS HR strongly correlated with OS HR in trials relevant to immune checkpoint inhibitors (ICIs). Although the correlation remained weak between PFS and OS even in trials with PFS HR ≤ 0.6, the 1-yr survival rate and 1-yr survival ratio were strong surrogates for median OS and OS HR, respectively (R2 = 0.77 and 0.75). Conclusions One-year milestone survival outperformed PFS as a SE for OS in HCC, indicating the application of 1-yr survival as a secondary endpoint. In particular, PFS HR was a potential SE for OS HR in the ICI trials.