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Abstract Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998–2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED’s monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944–0.995), Bias (−0.68-0.53), and Root Mean Square Error (5.50–15.59 mm). Additionally, TPRED’s monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED’s annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.

Abstract With the rapid expansion of China’s high-speed rail network, numerous high-speed rail new towns have been established. While these new towns have brought about significant economic opportunities, they also impose pressure on local resources and environment. Accurately assessing the impacts of high-speed rail new towns on urban sustainable development is therefore a crucial issue to address. Our study employs satellite remote sensing data and spatial econometric methods to evaluate the impacts of 223 high-speed rail new towns in China from 2011 to 2021. The results indicate a gradual narrowing of development disparities among high-speed rail new towns in different cities. The construction of high-speed rail new towns has facilitated the sustainable development of cities. Notably, central high-speed rail new towns demonstrate a more considerably driving effect on the urban sustainable development compared to peripheral ones. The findings of the study provide valuable insights for policymakers and urban planners in China and other countries embarking on high-speed rail development projects. Our research highlights the importance of considering the potential impacts of high-speed rail new towns on the urban sustainable development and the need for careful planning and management to ensure that these newly-established towns contribute to a more sustainable urban future.

Abstract Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.

Abstract Controlling the concentrations of H2O and CO2 at the reaction interface is crucial for achieving efficient electrochemical CO2 reduction. However, precise control of these variables during catalysis remains challenging, and the underlying mechanisms are not fully understood. Herein, guided by a multi-physics model, we demonstrate that tuning the local H2O/CO2 concentrations is achievable by thin polymer coatings on the catalyst surface. Beyond the often-explored hydrophobicity, polymer properties of gas permeability and water-uptake ability are even more critical for this purpose. With these insights, we achieve CO2 reduction on copper with Faradaic efficiency exceeding 87% towards multi-carbon products at a high current density of −2 A cm−2. Encouraging cathodic energy efficiency (>50%) is also observed at this high current density due to the substantially reduced cathodic potential. Additionally, we demonstrate stable CO2 reduction for over 150 h at practically relevant current densities owning to the robust reaction interface. Moreover, this strategy has been extended to membrane electrode assemblies and other catalysts for CO2 reduction. Our findings underscore the significance of fine-tuning the local H2O/CO2 balance for future CO2 reduction applications.

Abstract The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Abstract Background New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. Methods This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson’s correlation analysis between the NODDI indicators and clinical characteristics. Results Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. Conclusions Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

Highlights Metal–organic frameworks-derived CoNiM@C (M = Cu, Zn, Fe, Mn) microspheres were successfully fabricated with custom-built magnetic alloy-carbon heterogeneous interfaces. Flower-like CoNiMn@C microspheres achieve broadband electromagnetic wave absorption with effective absorption bandwidth of 5.8 GHz at only 2.0 mm thickness. Visual interface charge distribution and hierarchical magnetic coupling were observed to elucidate the electromagnetic energy absorption mechanism.

In order to establish the standard preparation methodology for bioactive polysaccharide of fucoidan, this study carried out the research of preparation method of fucoidan from Saccharina japonica. Three extraction methods, high temperature pressure extraction (HPE), acid extraction (AE), and microwave extraction at 400 W (M400 W), 500 W (M500 W), and 600 W (M600 W) were selected. Subsequently, two precipitation methods, calcium chloride precipitation (CP) and ethanol precipitation (GAP) were used to remove alginate followed by finally precipitation of fucoidan with high concentration ethanol. Fucoidan extracts prepared in totally ten different conditions were collected, of which the contents of total sugar, total phenols, protein, uronic acid, and sulfate groups were analyzed. Meanwhile their antioxidant activities including Fe3+ reduction ability, ABTS+ and DPPH free radical scavenging ability were determined. The correlation analysis was conducted based on the above determined results to discover the relationship between preparation methods and fucoidan qualities. Accordingly, the preparation methods for fucoidan of high yield, high purity, and excellent antioxidant activities were selected. Results showed that the yields of fucoidan by acid extraction with calcium precipitation (AE-CP) and microwave extraction with calcium precipitation (M400 W-CP, M500 W-CP, M600 W-CP) were 3.821%, 3.516%, 3.376%, and 2.998%, respectively. Meanwhile, the sulfate content was 17.734%, 23.872%, 23.376%, and 22.149%, respectively. Their protein and total phenol content were below 1%, the uronic acid content was below 10%, and the Trolox equivalent (ABTS+ radical scavenging ability) was 5.637, 5.336, 6.567, and 5.616 μg/mg, respectively. Thus, the above four preparation conditions were ideal for processing of fucoidan, among which the method of microwave extraction followed by calcium precipitation showed advantages of short processing time and low solvent consumption that met the requirement of the environmental-friendly processing. This study systematically investigated the effects of preparation methods on the yield and quality of fucoidan, which provided a practical preparation methodology for fucoidan from Saccharina japonica with high yield, purity and antioxidant activity.

Abstract Background In the tumor microenvironment (TME), a bidirectional relationship exists between hypoxia and lactate metabolism, with each component exerting a reciprocal influence on the other, forming an inextricable link. The aim of the present investigation was to develop a prognostic model by amalgamating genes associated with hypoxia and lactate metabolism. This model is intended to serve as a tool for predicting patient outcomes, including survival rates, the status of the immune microenvironment, and responsiveness to therapy in patients with lung adenocarcinoma (LUAD). Methods Transcriptomic sequencing data and patient clinical information specific to LUAD were obtained from comprehensive repositories of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A compendium of genes implicated in hypoxia and lactate metabolism was assembled from an array of accessible datasets. Univariate and multivariate Cox regression analyses were employed. Additional investigative procedures, including tumor mutational load (TMB), microsatellite instability (MSI), functional enrichment assessments and the ESTIMATE, CIBERSORT, and TIDE algorithms, were used to evaluate drug sensitivity and predict the efficacy of immune-based therapies. Results A novel prognostic signature comprising five lactate and hypoxia-related genes (LHRGs), PKFP, SLC2A1, BCAN, CDKN3, and ANLN, was established. This model demonstrated that LUAD patients with elevated LHRG-related risk scores exhibited significantly reduced survival rates. Both univariate and multivariate Cox analyses confirmed that the risk score was a robust prognostic indicator of overall survival. Immunophenotyping revealed increased infiltration of memory CD4 + T cells, dendritic cells and NK cells in patients classified within the high-risk category compared to their low-risk counterparts. Higher probability of mutations in lung adenocarcinoma driver genes in high-risk groups, and the MSI was associated with the risk-score. Functional enrichment analyses indicated a predominance of cell cycle-related pathways in the high-risk group, whereas metabolic pathways were more prevalent in the low-risk group. Moreover, drug sensitivity analyses revealed increased sensitivity to a variety of drugs in the high-risk group, especially inhibitors of the PI3K-AKT, EGFR, and ELK pathways. Conclusions This prognostic model integrates lactate metabolism and hypoxia parameters, offering predictive insights regarding survival, immune cell infiltration and functionality, as well as therapeutic responsiveness in LUAD patients. This model may facilitate personalized treatment strategies, tailoring interventions to the unique molecular profile of each patient’s disease.

Abstract Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

Abstract Background Multivariate synchronization index (MSI) has been successfully applied for frequency detection in steady state visual evoked potential (SSVEP) based brain–computer interface (BCI) systems. However, the standard MSI algorithm and its variants cannot simultaneously take full advantage of the time-local structure and the harmonic components in SSVEP signals, which are both crucial for frequency detection performance. To overcome the limitation, we propose a novel filter bank temporally local MSI (FBTMSI) algorithm to further improve SSVEP frequency detection accuracy. The method explicitly utilizes the temporal information of signal for covariance matrix estimation and employs filter bank decomposition to exploits SSVEP-related harmonic components. Results We employed the cross-validation strategy on the public Benchmark dataset to optimize the parameters and evaluate the performance of the FBTMSI algorithm. Experimental results show that FBTMSI outperforms the standard MSI, temporally local MSI (TMSI) and filter bank driven MSI (FBMSI) algorithms across multiple experimental settings. In the case of data length of one second, the average accuracy of FBTMSI is 9.85% and 3.15% higher than that of the FBMSI and the TMSI, respectively. Conclusions The promising results demonstrate the effectiveness of the FBTMSI algorithm for frequency recognition and show its potential in SSVEP-based BCI applications.

Abstract Background Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. Methods The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. Results We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient’s imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. Conclusions Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

Objectives Currently, anterior‐only (AO), posterior‐only, and combined anterior–posterior spinal fusions are common strategies for treating cervical kyphosis in patients with neurofibromatosis‐1 NF‐1. Nevertheless, the choice of surgical strategy remains a topic of controversy. The aim of our study is to evaluate the safety and effectiveness of anterior decompression and spinal reconstruction for the treatment of cervical kyphosis in patients with NF‐1. Methods Twelve patients with NF‐1‐associated cervical kyphotic deformity were reviewed retrospectively between January 2010 and April 2020. All patients underwent AO correction and reconstruction. The X‐ray was followed up in all these patients to assess the preoperative and postoperative local kyphosis angle (LKA), the global kyphosis angle (GKA), the sagittal vertical axis, and the T1 slope. The visual analog scale score, Japanese Orthopedic Association (JOA) score, and neck disability index (NDI) score were used to evaluate the improvement inclinical symptoms. The results of the difference in improvement from preoperatively to the final follow‐up assessment were assessed using a paired t‐test or Mann–Whitney U‐test. Results The LKA and GKA decreased from the preoperative average of 64.42 (range, 38–86) and 35.50 (range, 10–81) to an average of 16.83 (range, −2 to 46) and 4.25 (range, −22 to 39) postoperatively, respectively. The average correction rates of the LKA and GKA were 76.11% and 111.97%, respectively. All patients had achieved satisfactory relief of neurological symptoms (p

Objective Both two‐level anterior cervical corpectomy and fusion (t‐ACCF) and posterior open‐door laminoplasty (ODLP) are effective surgical procedures for the treatment of ossification of the posterior longitudinal ligament (OPLL). Previous studies have identified different effects of different surgical procedures on the upper and subaxial cervical spine (UCS, SCS), however, there are no studies on the effects of t‐ACCF and ODLP on the occipito‐atlantoaxial complex. Therefore, the purpose of this study is to compare the changes in sagittal parameters and range of motion (ROM) of the occipito‐atlantoaxial complex in OPLL patients treated with t‐ACCF and ODLP. Methods This was a retrospective study that included 74 patients who underwent t‐ACCF or ODLP for the treatment of OPLL from January 2012 to August 2022 at our institution. Preoperative, 3‐month, and 1‐year postoperative cervical neutral, flexion‐extension, and lateral flexion radiographs were taken. Sagittal parameters including Cobb angle of C2‐7, C0‐2, C0‐1, C1‐2, C2 slope, and the ROM were measured. The clinical outcome was assessed using the JOA, VAS, and NDI scores preoperatively and at 3 and 12 months postoperatively. Multiple linear regression was employed to identify factors influencing changes in UCS. Results In the ODLP group, the SCS (C2‐7) Cobb angle was significantly reduced (12.85 ± 10.0 to 7.68 ± 11.27; p

In order to study the mechanical properties and strain field evolution of gas-bearing coal under cyclic loading, the mechanical properties of gas-bearing coal under cyclic loading and unloading conditions were tested with the Rock Mechanics Test (MTS816) system and the independently developed gas-bearing coal gas-solid coupling device. The strength and deformation characteristics of coal samples under cyclic loading and unloading were analyzed, and the strain field evolution of gas-bearing coal was investigated with digital image correlation (DIC) technology. The results indicated that: ① Under the action of cyclic loading and unloading, the loading and unloading curves did not coincide with each other, forming a hysteresis loops. With the increase in the number of cycles, the area of the hysteresis loops gradually increased, and gradually moved towards the direction of increasing strain. Coal samples with varying gas pressures exhibited significant brittle failure under cyclic loading. ② Under the action of cyclic loading and unloading, the peak strength of coal samples decreased, and the loading and unloading deformation modulus increased with the increasing gas pressure. The unloading deformation modulus was always greater than the loading deformation modulus. As the number of cycles increased, the difference in deformation modulus gradually decreased and eventually fell within the range of 0 to 0.1 GPa. ③ Under cyclic loading and unloading conditions, the trend between the irreversible strain of coal samples and the number of cycles was a three-stage pattern of “initial, stable and accelerated expansion”, and the overall curve progressed from an L-shape to a U-shape. The trend between the cumulative irreversible strain and the number of cycles was rapidly increasing, slowly increasing and rapidly increasing, and both irreversible strain and cumulative irreversible strain increased with increasing gas pressure. ④ Under low gas pressure, the strain concentration area of coal samples was mainly a single vertical strain concentration zone. As the gas pressure increased, the local strain concentration zone gradually transitioned from vertical single to disordered and complex. The higher the gas pressure, the more pronounced the strain field fluctuation and the intensity was concentrated in the central region. At high gas pressures, the greater the number of peak points, the greater the strain with increasing gas pressure.

Pulverized fuel ash (PFA) is a by-product from coal-fired power plants. The generation of PFA is huge and increases yearly. A large amount of untreated PFA is harmful to the environment, and it is also a waste of resources. Recycling PFA as construction materials would improve resource utilization efficiency, reduce environmental risks, conform to the demand for high-efficient and low-carbon utilization of solid waste and help to achieve the national strategy goals of carbon peak and carbon neutrality. The utilization efficiency of PFA as construction materials could be improved by optimizing production processes and developing new technologies, which would promote its large-scale and high-value utilization. In this paper, the general situation and physical and chemical properties of PFA are summarized. Various value-added utilization technologies of PFA as construction materials, including raw materials for cement production, supplementary cementitious materials, bricks and blocks, artificial aggregates, glass-ceramic materials, fire-resistant insulation materials, and new intelligent construction materials are comprehensively reviewed. This paper also introduces the research status of the utilization of PFA in construction materials, analyzes the applicability of different technologies, summarizes the latest technologies for preparing the PFA-based green construction materials and challenges faced in future research, provides detailed introductions to the mechanism of PFA application, and proposes thoughts on the problems existing in the utilization of PFA as construction materials. Finally, the further perspectives of the development of the PFA-derived low-carbon construction materials are highlighted. The study suggests that the “traditional large-scale consumption of PFA” and “high-value utilization of PFA” should be researched in parallel, and theoretical research and engineering practice should support each other, which would provide some scientific references for the sustainable management of PFA.

CO2 adsorption causes damage degradation to the coal body and thus reduces its stability, challenging the long-term safety of CO2 sequestration, and it is important to clarify the role of CO2 degradation and establish an ontological model. The damage mechanics theory and statistical theory were used to derive the calculation formula that can comprehensively reflect the total damage variables of the coal body under CO2 adsorption and load coupling, and focusing on the influence of the pressure-tight section, the fine statistical damage ontological equation of the coal body under the action of CO2 was established by segmentation, and the method of determining each parameter of the model was clarified. Finally, the parameters of the constitutive model were determined by CT scanning experiment system and MTS 816 experiment system, and the uniaxial compression experiments of coal body under different CO2 pressures were carried out by the self-developed gas-solid coupling experiment system to verify the rationality of the model. The results show that: ① The damage variables under adsorption and loading were defined based on the fracture rate obtained from CT scanning and by applying the Weibull distribution theory, respectively, and the total damage variable under the coupling of the two was further obtained by combining the damage theory, and a fine-scale statistical damage constitutive model was established; ② Three-dimensional reconstruction of the fracture based on CT scanning technology realistically reflects the fracture extension characteristics before and after CO2 interaction， the higher the CO2 pressure, the fuller the fracture expansion, the greater the three-dimensional fracture parameters and damage variables of the coal samples, and the more complex the spatial fracture network formed; ③ CO2 had a significant deterioration effect on the physical properties of the coal body, and the compressive strength and modulus of elasticity of the coal body were both reduced by 49.78% and 22.63%, respectively, with the increase of CO2 pressure, and the combined effect of dissolution, plasticization and air wedge effect of CO2 on the coal body led to the reduction of the mechanical parameters; ④ The theoretical curves of the fine statistical damage model of the coal body under the action of CO2 have a high degree of agreement with the uniaxial experimental curves, which indicates that the present structural model can better reflect the damage degradation effect of CO2 on the physical properties of the coal body, and embodies the reasonableness and applicability of the constitutive model and the method for determining the model parameters.

Abstract Traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. We unveiled the diagnostic value of serum NLRP3, metalloproteinase‐9 (MMP‐9) and interferon‐γ (IFN‐γ) levels in post‐craniotomy intracranial infections and hydrocephalus in patients with severe craniocerebral trauma to investigate the high risk factors for these in patients with TBI, and the serological factors predicting prognosis, which had a certain clinical predictive value. Study subjects underwent bone flap resection surgery and were categorized into the intracranial infection/hydrocephalus/control (without postoperative hydrocephalus or intracranial infection) groups, with their clinical data documented. Serum levels of NLRP3, MMP‐9 and IFN‐γ were determined using ELISA kits, with their diagnostic efficacy on intracranial infections and hydrocephalus evaluated by receiver operating characteristic curve analysis. The independent risk factors affecting postoperative intracranial infections and hydrocephalus were analysed by logistic multifactorial regression. The remission after postoperative symptomatic treatment was counted. The intracranial infection/control groups had significant differences in Glasgow Coma Scale (GCS) scores, opened injury, surgical time and cerebrospinal fluid leakage, whereas the hydrocephalus and control groups had marked differences in GCS scores, cerebrospinal fluid leakage and subdural effusion. Serum NLRP3, MMP‐9 and IFN‐γ levels were elevated in patients with post‐craniotomy intracranial infections/hydrocephalus. The area under the curve values of independent serum NLRP3, MMP‐9, IFN‐γ and their combination for diagnosing postoperative intracranial infection were 0.822, 0.722, 0.734 and 0.925, respectively, and for diagnosing hydrocephalus were 0.865, 0.828, 0.782 and 0.957, respectively. Serum NLRP3, MMP‐9 and IFN‐γ levels and serum NLRP3 and MMP‐9 levels were independent risk factors influencing postoperative intracranial infection and postoperative hydrocephalus, respectively. Patients with hydrocephalus had a high remission rate after postoperative symptomatic treatment. Serum NLRP3, MMP‐9 and IFN‐γ levels had high diagnostic efficacy in patients with postoperative intracranial infection and hydrocephalus, among which serum NLRP3 level played a major role.

Abstract Bladder urothelial carcinoma (BLCA) presents a persistent challenge in clinical management. Despite recent advancements demonstrating the BLCA efficacy of immune checkpoint inhibitors (ICI) in BLCA patients, there remains a critical need to identify and expand the subset of individuals who benefit from this treatment. Mitochondria, as pivotal regulators of various cell death pathways in eukaryotic cells, exert significant influence over tumor cell fate and survival. In this study, our objective was to investigate biomarkers centered around mitochondrial function and cell death mechanisms to facilitate prognostic prediction and guide therapeutic decision-making in BLCA. Utilizing ssGSEA and LASSO regression, we developed a prognostic signature termed mitochondrial function and cell death (mtPCD). Subsequently, we evaluated the associations between mtPCD score and diverse clinical outcomes, including prognosis, functional pathway enrichment, immune cell infiltration, immunotherapy response analysis and drug sensitivity, within high- and low-risk subgroups. Additionally, we employed single-cell level functional assays, RT-qPCR, and immunohistochemistry to validate the differential expression of genes comprising the mtPCD signature. The mtPCD signature comprises a panel of 10 highly influential genes, strongly correlated with survival outcomes in BLCA patients and exhibiting robust predictive capabilities. Importantly, individuals classified as high-risk according to mtPCD score displayed a subdued overall immune response, characterized by diminished immunotherapeutic efficacy. In summary, our findings highlight the development of a novel prognostic signature, which not only holds promise as a biomarker for BLCA prognosis but also offers insights into the immune landscape of BLCA. This paradigm may pave the way for personalized treatment strategies in BLCA management.

Abstract Background Achilles tendon is vital in maintaining the stability and function of ankle joint. It is quite difficult to achieve the structural and functional repair of Achilles tendon in tissue engineering. Methods A tissue-engineered tendon micro-tissue was prepared using rat tail tendon extracellular matrix (TECM) combined with rat adipose stem cells (ADSCs) to repair Achilles tendon injuries. The TECM was prepared by repeated freezing and thawing. The in vitro characteristics of TECM and its effect on ADSCs proliferation were detected. This tissue-engineered tendon micro-tissue for Achilles tendon repair in vivo was evaluated based on general characteristics, gait analysis, ultrasound findings, histological analysis, and biomechanical testing. Results The results showed that the TECM scaffold had good biocompatibility for ADSCs. At 2 weeks post-surgery, collagen types I and III and tenomodulin expression were higher, and vascular endothelial growth factor expression was lower in the micro-tissue group than other groups. At 4 and 8 weeks post-surgery, the results of histological analysis and ultrasound findings showed that the repaired tendon tissue was smooth and lustrous, and was arranged regularly and evenly in the micro-tissue group. Gait analysis confirmed that better motor function recovery was noted in micro-tissue group than other groups. In addition, the mechanical properties of the repaired tendon tissue in micro-tissue group were better than other groups. Conclusion Tissue-engineered tendon micro-tissue fabricated by TECM and ADSCs has good biocompatibility and can promote structural and functional repair of tendon in vivo. This composite biomaterial has broad application prospects in tissue engineering.

Abstract Purpose To analyze the characteristics of PEEK rods retrieved in vivo, specifically their wear and deformation, biodegradability, histocompatibility, and mechanical properties. Method Six PEEK rods were retrieved from revision surgeries along with periprosthetic tissue. The retrieved PEEK rods were evaluated for surface damage and internal changes using Micro-CT, while light and electron microscopy were utilized to determine any histological changes in periprosthetic tissues. Patient history was gathered from medical records. Two intact and retrieved PEEK rods were used for fatigue testing analysis by sinusoidal load to the spinal construct. Results All implants showed evidence of plastic deformation around the screw-rod interface, while the inner structure of PEEK rods appeared unchanged with no visible voids or cracks. Examining images captured through light and electron microscopy indicated that phagocytosis of macrophages around PEEK rods was less severe in comparison to the screw-rod interface. The results of an energy spectrum analysis suggested that the distribution of tissue elements around PEEK rods did not differ significantly from normal tissue. During fatigue testing, it was found that the retrieved PEEK rods cracked after 1.36 million tests, whereas the intact PEEK rods completed 5 million fatigue tests without any failure. Conclusion PEEK rods demonstrate satisfactory biocompatibility, corrosion resistance, chemical stability, and mechanical properties. Nevertheless, it is observed that the indentation at the junction between the nut and the rod exhibits relatively weak strength, making it susceptible to breakage. As a precautionary measure, it is recommended to secure the nut with a counter wrench, applying the preset torque to prevent overtightening.

Abstract This study aimed to perform the first external validation of the modified Child-Turcotte-Pugh score based on plasma ammonia (aCTP) and compare it with other risk scoring systems to predict survival in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. We retrospectively reviewed 473 patients from three cohorts between January 2016 and June 2022 and compared the aCTP score with the Child-Turcotte-Pugh (CTP) score, albumin-bilirubin (ALBI), model for end-stage liver disease (MELD) and sodium MELD (MELD-Na) in predicting transplant-free survival by the concordance index (C-index), area under the receiver operating characteristic curve, calibration plot, and decision curve analysis (DCA) curve. The median follow-up time was 29 months, during which a total of 62 (20.74%) patients died or underwent liver transplantation. The survival curves for the three aCTP grades differed significantly. Patients with aCTP grade C had a shorter expected lifespan than patients with aCTP grades A and B (P

Abstract Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the ‘floristic geo-lithology hypothesis’, which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.

Abstract Background Though tamoxifen achieves success in treating estrogen receptor α (ERα)-positive breast cancer, the followed development of tamoxifen resistance is a common challenge in clinic. Signals downstream of prolactin receptor (PRLR) could synergize with ERα in breast cancer progression. However, the potential effect of targeting PRL-PRLR axis combined with tamoxifen has not been thoroughly investigated. Methods High-throughput RNA-seq data obtained from TCGA, Metabric and GEO datasets were analyzed to explore PRLR expression in breast cancer cell and the association of PRLR expression with tamoxifen treatment. Exogenous or PRL overexpression cell models were employed to investigate the role of activated PRLR pathway in mediating tamoxifen insensitivity. Immunotoxin targeting PRLR (N8-PE24) was constructed with splicing-intein technique, and the efficacy of N8-PE24 against breast cancer was evaluated using in vitro and in vivo methods, including analysis of cells growth or apoptosis, 3D spheroids culture, and animal xenografts. Results PRLR pathway activated by PRL could significantly decrease sensitivity of ERα-positive breast cancer cells to tamoxifen. Tamoxifen treatment upregulated transcription of PRLR and could induce significant accumulation of PRLR protein in breast cancer cells by alkalizing lysosomes. Meanwhile, tamoxifen-resistant MCF7 achieved by long-term tamoxifen pressure exhibited both upregulated transcription and protein level of PRLR. Immunotoxin N8-PE24 enhanced sensitivity of breast cancer cells to tamoxifen both in vitro and in vivo. In xenograft models, N8-PE24 significantly enhanced the efficacy of tamoxifen and paclitaxel when treating PRLR-positive triple-negative breast cancer. Conclusions PRL-PRLR axis potentially associates with tamoxifen insensitivity in ERα-positive breast cancer cells. N8-PE24 could inhibit cell growth of the breast cancers and promote drug sensitivity of PRLR-positive breast cancer cells to tamoxifen and paclitaxel. Our study provides a new perspective for targeting PRLR to treat breast cancer.

Abstract. Background:. Intrauterine valvuloplasty is an innovative therapy, which promotes ventricular growth and function in some congenital heart diseases (CHDs). The technique remains challenging and can only be performed in a few centers. This study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention (FCI) in fetuses with critical CHD in an experienced tertiary center. Methods:. Five fetal aortic valvuloplasty (FAV) or fetal pulmonary valvuloplasty (FPV) procedures were performed in our fetal heart center between August 2018 and May 2022. Technical success was defined as crossing the aortic or pulmonary valve and balloon inflation, followed by evidence of increased blood flow across the valve and/or new regurgitation. Follow-up clinical records and echocardiography were obtained during the prenatal and postnatal periods. Results:. Five fetuses received FAV or FPV, including critical aortic stenosis ( n = 2) and pulmonary atresia with intact ventricular septum ( n = 3). The mean maternal age was 33.0 ± 2.6 years. The median gestational age (GA) at diagnosis was 24 weeks (range, 22–26 weeks). The median GA at intervention was 29 weeks (range, 28–32 weeks). All five cases underwent successful or partially successful procedures. One patient had pulmonary valve perforation without balloon dilation. No procedure-related deaths or significant complications occurred. However, one neonatal death occurred due to heart and renal failure. The median follow-up period was 29.5 months (range, 8.0–48.0 months). The four surviving patients had achieved biventricular circulation, exhibited improved valve, and ventricular development at the last follow-up visit. Conclusion:. Intrauterine FCI could be performed safely with good prognosis in critical CHD.

Abstract Excitons, pairs of electrons and holes, undergo a Bose-Einstein condensation at low temperatures. An important platform to study excitons is double-layer two-dimensional electron gases, with two parallel planes of electrons and holes separated by a thin insulating layer. Lowering this separation (d) strengthens the exciton binding energy, however, leads to the undesired interlayer tunneling, resulting in annihilation of excitons. Here, we report the observation of a sequences of robust exciton condensates (ECs) in double bilayer graphene twisted to ~ 10° with no insulating mid-layer. The large momentum mismatch between two graphene layers suppresses interlayer tunneling, reaching a d ~ 0.334 nm. Measuring the bulk and edge transport, we find incompressible states corresponding to ECs when both layers are in half-filled N = 0, 1 Landau levels (LLs). Theoretical calculations suggest that the low-energy charged excitation of ECs can be meron-antimeron or particle-hole pair, which relies on both LL index and carrier type. Our results establish a novel platform with extreme coupling strength for studying quantum bosonic phase.

Abstract The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., −0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with insidious onset, commonly seen in the elderly and with increasing incidence, for which there is still no effective treatment. Medicinal and edible homologous substances refer to substances that are both food and traditional Chinese medicine, and have received widespread attention due to their safety and good therapeutic and health effects. This paper describes the pathogenesis of AD, and summarizes the anti-AD mechanism of medicinal and edible homologous substances from the aspects of slowing down the deposition of β-amyloid, inhibiting the over-phosphorylation of Tau protein, improving the cholinergic system, antioxidant, anti-inflammatory, and protection of neurons and synapses, so as to provide references for the development and application of medicinal and edible homologous substances products.

Abstract Background Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. Methods RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. Results Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. Conclusions Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.

Abstract Vegetation changes are expected to alter soil thermal regimes, consequently modifying climate feedbacks related to frozen ground thawing and carbon cycling in cold regions. The Tibetan Plateau (TP) contains diverse alpine ecosystems and the largest area of frozen ground in low–mid latitude regions. Evidence suggests ongoing vegetation greening and permafrost degradation during the past several decades on the TP. However, the effect of vegetation changes on soil thermal regimes on the TP is not well understood. Here, we quantify the response of shallow soil temperature change to vegetation greening on the TP using remote–sensing data, in–situ observations, and physics–based modelling. Our results show that over the past 20 years, vegetation greening on the TP was accompanied a notable decrease in the area of bare land by approximately 0.7% (5000 km2). Annual mean soil temperature showed a significant warming trend of 0.57 °C decade–1 (p

Abstract This study presents a comprehensive investigation into the optimization of PID control parameters for marine dual-fuel engines using an improved particle swarm algorithm. Through the development of a Matlab/Simulink simulation model, the thermodynamic behavior of the engine and the functionality of its control system are analyzed. The PID control parameters for air–fuel ratio control and mode switching control systems are fine-tuned utilizing the improved particle swarm algorithm (PSO). Simulation results demonstrate that the proposed improved PID-PSO approach outperforms traditional PID and traditional PSO-PID control methods in terms of reduced overshoot, minimized steady-state error, faster response times, and improved stability across various operating conditions and response modes. In comparison to traditional PID and PSO-PID controllers, the improved PSO-PID controller reduces the response time by 0.47 s and 0.21 s, the maximum overshoot by 98.43% and 96.05%, and decreases the absolute errors by 87.42% and 90.55%, respectively, in air–fuel ratio control using the step response method. The study's findings offer valuable insights into enhancing the performance and efficiency of marine dual-fuel engines through advanced control strategies.

Abstract Retained placenta is a common health issue, and appropriate prevention strategies are effective in postpartum health management. This study aimed to evaluate whether early intervention using GYS can prevent retained placenta and puerperal metritis, as well as enhance reproductive outcomes in cows. Each bovine in the GYS group (n = 591) received a single prophylactic dose of GYS (0.5 g/kg body weight) orally within 2 h after parturition, while those in the control group (n = 598) received no intervention. GYS treatment was associated with a decreased incidence of retained placenta (4.6% vs. 12.0%, P

Abstract Background Actinobacillus pleuropneumoniae is a serious pathogen in pigs. The abundant application of antibiotics has resulted in the gradual emergence of drugresistant bacteria, which has seriously affected treatment of disease. To aid measures to prevent the emergence and spread of drug-resistant bacteria, herein, the kill rate and mutant selection window (MSW) of danofloxacin (DAN) against A. pleuropneumoniae were evaluated. Methods For the kill rate study, the minimum inhibitory concentration (MIC) was tested using the micro dilution broth method and time-killing curves of DAN against A. pleuropneumoniae grown in tryptic soy broth (TSB) at a series drug concentrations (from 0 to 64 MIC) were constructed. The relationships between the kill rate and drug concentrations were analyzed using a Sigmoid Emax model during different time periods. For the MSW study, the MIC99 (the lowest concentration that inhibited the growth of the bacteria by ≥ 99%) and mutant prevention concentration (MPC) of DAN against A. pleuropneumoniae were measured using the agar plate method. Then, a peristaltic pump infection model was established to simulate the dynamic changes of DAN concentrations in pig lungs. The changes in number and sensitivity of A. pleuropneumoniae were measured. The relationships between pharmacokinetic/pharmacodynamic parameters and the antibacterial effect were analyzed using the Sigmoid Emax model. Results In kill rate study, the MIC of DAN against A. pleuropneumoniae was 0.016 µg/mL. According to the kill rate, DAN exhibited concentration-dependent antibacterial activity against A. pleuropneumoniae. A bactericidal effect was observed when the DAN concentration reached 4–8 MIC. The kill rate increased constantly with the increase in DAN concentration, with a maximum value of 3.23 Log10 colony forming units (CFU)/mL/h during the 0–1 h period. When the drug concentration was in the middle part of the MSW, drugresistant bacteria might be induced. Therefore, the dosage should be avoided to produce a mean value of AUC24h/MIC99 (between 31.29 and 62.59 h. The values of AUC24h/MIC99 to achieve bacteriostatic, bactericidal, and eradication effects were 9.46, 25.14, and > 62.59 h, respectively. Conclusion These kill rate and MSW results will provide valuable guidance for the use of DAN to treat A. pleuropneumoniae infections.

Abstract Background The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation. Results The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles. Conclusions This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.

Abstract Background Ruminant gut microbiota are critical in ecological adaptation, evolution, and nutrition utilization because it regulates energy metabolism, promotes nutrient absorption, and improves immune function. To study the functional roles of key gut microbiota in sheep and goats, it is essential to construct reference microbial gene catalogs and high-quality microbial genomes database. Results A total of 320 fecal samples were collected from 21 different sheep and goat breeds, originating from 32 distinct farms. Metagenomic deep sequencing and binning assembly were utilized to construct a comprehensive microbial genome information database for the gut microbiota. We successfully generated the largest reference gene catalogs for gut microbiota in sheep and goats, containing over 162 million and 82 million nonredundant predicted genes, respectively, with 49 million shared nonredundant predicted genes and 1138 shared species. We found that the rearing environment has a greater impact on microbial composition and function than the host’s species effect. Through subsequent assembly, we obtained 5810 medium- and high-quality metagenome-assembled genomes (MAGs), out of which 2661 were yet unidentified species. Among these MAGs, we identified 91 bacterial taxa that specifically colonize the sheep gut, which encode polysaccharide utilization loci for glycan and mucin degradation. Conclusions By shedding light on the co-symbiotic microbial communities in the gut of small ruminants, our study significantly enhances the understanding of their nutrient degradation and disease susceptibility. Our findings emphasize the vast potential of untapped resources in functional bacterial species within ruminants, further expanding our knowledge of how the ruminant gut microbiota recognizes and processes glycan and mucins. Video Abstract

Abstract Efficient charge-carrier injection and transport in organic light-emitting devices (OLEDs) are essential to simultaneously achieving their high efficiency and long-term stability. However, the charge-transporting layers (CTLs) deposited by various vapor or solution processes are usually in amorphous forms, and their low charge-carrier mobilities, defect-induced high trap densities and inhomogeneous thickness with rough surface morphologies have been obstacles towards high-performance devices. Here, organic single-crystalline (SC) films were employed as the hole-transporting layers (HTLs) instead of the conventional amorphous films to fabricate highly efficient and stable OLEDs. The high-mobility and ultrasmooth morphology of the SC-HTLs facilitate superior interfacial characteristics of both HTL/electrode and HTL/emissive layer interfaces, resulting in a high Haacke’s figure of merit (FoM) of the ultrathin top electrode and low series-resistance joule-heat loss ratio of the SC-OLEDs. Moreover, the thick and compact SC-HTL can function as a barrier layer against moisture and oxygen permeation. As a result, the SC-OLEDs show much improved efficiency and stability compared to the OLEDs based on amorphous or polycrystalline HTLs, suggesting a new strategy to developing advanced OLEDs with high efficiency and high stability.

Abstract Autonomous vehicles navigating urban roads require technology that combines low latency with high computing power. The limited resources of the vehicle itself compel it to offload task requirements to edge server (ES) for processing assistance. However, as the number of vehicles continues to increase, how edge servers reasonably allocate limited resources to autonomous vehicles becomes critical to the success of urban intelligent transportation services. This paper establishes an urban road scenario with multiple autonomous vehicles and an edge computing server and considers two main driving behaviour transition resource requests, namely car‐following behaviour requests and lane‐changing behaviour requests. Simultaneously, acknowledging that vehicles may encounter unforeseen traffic hazards when switching driving behaviours, a safety redundancy setting strategy is employed to allocate additional resources to the vehicle to ensure safety and model the vehicle resource allocation problem in the autonomous driving system. Double‐deep Q‐network (DDQN) is then used to solve this model and maximize the total system utility by comprehensively considering resource costs, system revenue, and autonomous vehicle safety. Finally, results from the simulation experiment indicate that the proposed dynamic resource allocation scheme, based on deep reinforcement learning for autonomous vehicles under edge computing, not only greatly improves the system's benefits and reduces processing delays compared to traditional greedy algorithms and value iteration, but also effectively ensures security.

Abstract Comprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.

The gut has been a focal point in the research of digestive system disorders. The internal microbiota generates metabolites that function as signaling molecules and substrates, interacting with the intestinal wall and influencing host physiology and pathology. Besides, the gut microbiota and metabolites owe highly diverse types and quantities, posing challenges for quantitative analysis, and monitoring frequent interactions between digestive tract metabolites and the intestinal wall remains a challenge. However, research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases. By modulating metabolites such as short-chain fatty acids, bile acids, and lipopolysaccharides, it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease. Currently, research on gut microbiota is advancing, and more work is required to explore the interactions between host, microbes and underlying mechanisms. In this review, we have revisited the generation of gut microbiota-related metabolites, their impact on diseases, and modes of interaction, emphasizing the significant role of metabolites in digestive system disorders. It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites, providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

The Himalayas and their surrounding areas boast vast glaciers rivaling those in polar regions, supplying vital meltwater to the Indus, Ganges, and Brahmaputra rivers, supporting over a billion downstream inhabitants for drinking, power, and agriculture. With changing runoff patterns due to accelerated glacial melt, understanding and projecting glacio-hydrological processes in these basins is imperative. This review assesses the evolution, applications, and key challenges in diverse glacio-hydrology models across the Himalayas, varying in complexities like ablation algorithms, glacier dynamics, ice avalanches, and permafrost. Previous findings indicate higher glacial melt contributions to annual runoff in the Indus compared to the Ganges and Brahmaputra, with anticipated peak melting in the latter basins — having less glacier cover — before the mid-21st century, contrasting with the delayed peak expected in the Indus Basin due to its larger glacier area. Different modeling studies still have large uncertainties in the simulated runoff components in the Himalayan basins; and the projections of future glacier melt peak time vary at different Himalaya sub-basins under different Coupled Model Intercomparison Project (CMIP) scenarios. We also find that the lack of reliable meteorological forcing data (particularly the precipitation errors) is a major source of uncertainty for glacio-hydrological modeling in the Himalayan basins. Furthermore, permafrost degradation compounds these challenges, complicating assessments of future freshwater availability. Urgent measures include establishing comprehensive in situ observations, innovating remote-sensing technologies (especially for permafrost ice monitoring), and advancing glacio-hydrology models to integrate glacier, snow, and permafrost processes. These endeavors are crucial for informed policymaking and sustainable resource management in this pivotal, glacier-dependent ecosystem.

This study aims to examine the impact of accessibility and destination brand identity on Chinese wellness tourist perceptions. It considers Bama Yao autonomous district’s growth towards longevity tourism and contributes to empirical work on the Chinese wellness tourism market. This quantitative research incorporated a post-positivism paradigm with the non-probability convenience sampling method to collect paper-based questionnaires: a total of 346 were coded for data analysis. The results demonstrated that accessibility positively influenced destination brand identity and tourist perceptions. Equally destination brand identity positively influenced tourist perception. Meanwhile, destination brand identity mediated the relationship between accessibility and tourist perception for wellness tourism destinations. However, the cross-sectional study’s results cannot be generalizable, and the sample may be one of its limitations. The present study provides policymakers and practitioners with the theoretical and practical basis to understand and predict tourists’ perceptions of wellness tourism destinations in China.

The evolution of fractures is affected by internal and external environments such as the distribution characteristics of mineral particles and confining pressure conditions. In order to explore the macro-meso evolution characteristics and influencing factors of fractures in fractured coal under different confining pressures, based on the industrial CT scanning system and its equipped triaxial loading system, the triaxial static load test of fractured coal was carried out. The interaction mechanism of internal and external conditions of primary fractures, mineral particles and confining pressure is reasonably explained by multi-angle joint characterization. the results showed：① The confining pressure will shift the significant area of the initial damage of the coal body, so that it transits from the fracture tip to the upper and lower ends of the coal body with the increase of confining pressure, and it is easier to connect between micropores and large-sized fractures than between micropores and micropores, and new macroscopic cracks are generated. ② The increase of confining pressure will lead to the change of three-dimensional dynamic fractal dimension from slow increase, rapid increase and steady increase to the development stage of steady increase, rapid increase and slow increase, which can be used to characterize the time evolution law of fractures. ③ The fractured coal body exhibits longitudinal tensile failure under uniaxial or low confining pressure. The high confining pressure will change its failure mode and tend to shear failure, and enhance the strength of the coal body through two ways. ④ The deviation between the theoretical value and the experimental value of the cracking angle increases with the increase of confining pressure, which is consistent with the discrete numerical relationship caused by the distribution of mineral particles in coal. ⑤ According to the stress composition of the fracture and the distribution characteristics of mineral particles, the fracture propagation behavior is divided into three types: direct drive, bypassing mineral particles and staggering mineral particles. The above propagation behavior depends on the confining pressure to change the force component of the crack. The cracks under the action of relative pure tensile stress, tensile-shear composite stress and relative pure shear stress correspond to the above three propagation behaviors, that is, the influence form of crack propagation is mainly confining pressure, supplemented by the occurrence form of mineral particles.

Abstract Various microbes isolated from healthy plants are detrimental under laboratory conditions, indicating the existence of molecular mechanisms preventing disease in nature. Here, we demonstrated that application of sodium chloride (NaCl) in natural and gnotobiotic soil systems is sufficient to induce plant disease caused by an otherwise non-pathogenic root-derived Pseudomonas brassicacearum isolate (R401). Disease caused by combinatorial treatment of NaCl and R401 triggered extensive, root-specific transcriptional reprogramming that did not involve down-regulation of host innate immune genes, nor dampening of ROS-mediated immunity. Instead, we identified and structurally characterized the R401 lipopeptide brassicapeptin A as necessary and sufficient to promote disease on salt-treated plants. Brassicapeptin A production is salt-inducible, promotes root colonization and transitions R401 from being beneficial to being detrimental on salt-treated plants by disturbing host ion homeostasis, thereby bolstering susceptibility to osmolytes. We conclude that the interaction between a global change stressor and a single exometabolite from a member of the root microbiome promotes plant disease in complex soil systems.

Abstract Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients’ quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

ABSTRACTCapsule Robot Endoscope (CRE), as one of the widely used methods of gastrointestinal medical examination, has the characteristics of painless, non-cross infection, and no movement restriction, compared with other traditional endoscopes. To obtain the precise location of the lesion, positioning the capsule robot in the digestive tract has become a hot research topic in related fields. In recent decades, with the rapid advancement of indoor and outdoor positioning technologies, several well-established methods have emerged that enable the acquisition of high-precision real-time spatiotemporal integration data. These methods hold great potential for interdisciplinary applications in location services across various domains. The manuscript aims to draw inspiration from surveying and mapping positioning techniques by reviewing existing microspace positioning technologies to overcome inherent technical challenges. This article has reviewed more than 100 pieces of literature at home and abroad from four major academic search engines and has further studied the state of the art of several capsule robot positioning technologies commonly used. Microspace positioning technology in capsule robots is evaluated across eight factors: positioning accuracy, power consumption, portability, comfort, complexity, robustness, extensibility, and cost. We summarize the technical challenges associated with capsule robot positioning technology from each positioning technology’s limitations, finally proffering prospective avenues for future research. Our investigation reveals that the six identified capsule robot positioning technologies have distinct advantages and disadvantages. Among these, magnetic field-based positioning technology exhibited superior overall performance and is gradually advancing toward commercialization. Vision-based positioning technology, while significantly contributing to medical applications, particularly in enhancing augmented reality and surgical navigation, faces challenges related to the weak-textured and non-rigid characteristics of the gastrointestinal environment. Additionally, the limitation posed by the size and energy consumption of capsule robots make difficulties for single-source positioning techniques. We have proposed several promising future research directions by considering the capsule robot’s current positioning technological challenges and the advancements of cutting-edge indoor and outdoor positioning technologies. These include exploring new positioning sources, integrating multiple sensor fusion, and developing real-time three-dimensional gastrointestinal models. These new approaches are expected to enhance the safety and reliability of capsule robot positioning technology. They can potentially promote the development of capsule robots further and provide support for diagnosing and treating gastrointestinal diseases.

Objective: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. Methods: This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150–200 mg/m2 × 5 d during each 28-d cycle) plus anlotinib (8 mg/d on d 1–14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Results: Thirty-three patients received the planned treatment. The median PFS was 10.9 months (95% CI, 9.9–18.7 months) and the 12-month PFS rate was 48.5%. The median OS was 17.4 months (95% CI, 14.5–21.1 months) and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58% (n = 19)], hypoalbuminemia [46% (n = 15)], and hypercholesterolemia [46% (n = 15)] during concurrent chemoradiotherapy and leukopenia [73% (n = 24)], hypertriglyceridemia [67% (n = 22)], and neutropenia [52% (n = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1 (HR, 5.6; 95% CI, 1.3–23.7; P = 0.021) and RP1L1 alterations (HR, 11.1; 95% CI, 2.2–57.2; P = 0.004) were associated with a significantly shorter PFS. Conclusions: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Abstract Introduction Post-stroke depression (PSD) is a prevalent complication that has been shown to have a negative impact on rehabilitation outcomes and quality of life and poses a significant risk for suicidal intention. However, models for discriminating and predicting PSD in stroke survivors for effective secondary prevention strategies are inadequate as the pathogenesis of PSD remains unknown. Prognostic prediction models that exhibit greater rule-in capacity have the potential to mitigate the issue of underdiagnosis and undertreatment of PSD. Thus, the planned study aims to systematically review and critically evaluate published studies on prognostic prediction models for PSD. Methods and analysis A systematic literature search will be conducted in PubMed and Embase through Ovid. Two reviewers will complete study screening, data extraction, and quality assessment utilizing appropriate tools. Qualitative data on the characteristics of the included studies, methodological quality, and the appraisal of the clinical applicability of models will be summarized in the form of narrative comments and tables or figures. The predictive performance of the same model involving multiple studies will be synthesized with a random effects meta-analysis model or meta-regression, taking into account heterogeneity. Ethics and dissemination Ethical approval is considered not applicable for this systematic review. Findings will be shared through dissemination at academic conferences and/or publication in peer-reviewed academic journals. Systematic review registration PROSPERO CRD42023388548.

Abstract Background The Chinese pig breed Bamei faces numerous challenges, such as antibiotic abuse, feed shortages, weaning stress, low immunity and disease resistance after weaning. Probiotic-fermented feed is an ideal profile that can improve the intestinal microbiota, promote the digestion and absorption of nutrients, and improve immunity. However, the combined effect of long-term intake of probiotic-fermented feeds on the intestinal microbiota, intestinal metabolic profiles, and immunity in pigs is not well understood. Here, we investigated the effects of feeding basal feed, Lactiplantibacillus-fermented feed, Bacillus subtilis-fermented feed, mixed-fermented feed, and antibiotic-added feed for 100 days on the gut microbiota, immunity, and metabolism of Bamei pigs after feeding five different fermented feeds by using 16S rDNA high-throughput sequencing, enzyme-linked immunoassay, and untargeted metabolomics, respectively. Results 16S rDNA sequencing revealed that after the piglets were fed five different feeds for 50 days, the structure of the intestinal microbiota of the Bamei pigs was significantly altered, and feeding the mixed Lactiplantibacillus (L.) plantarum and Bacillus (B.) subtilis-fermented feed not only increased the α-diversity of the intestinal microbiota and the relative abundance of Lactobacillus, but also suppressed the growth of the conditional pathogens, Clostridium and Streptococcus. The Sobs and Shannon indices were significantly lower (p