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Abstract Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) have dismal prognosis and there are no standard perioperative therapies. This phase 2 trial (ChiCTR2000036385) aimed to investigate the activity and safety of perioperative tislelizumab plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Thirty treatment-naïve patients with MVI received 3 cycles of tislelizumab intravenously (200 mg, every three weeks) and concurrent IMRT (45 Gray in 15 fractions). Primary endpoints were the overall response rate (ORR) and overall survival (OS). Secondary endpoints were the proportion of patients with a complete or major pathological response (pCR or MPR), recurrence-free survival (RFS) and safety. Of patients enrolled, 15 (50%) underwent curative surgery followed by adjuvant tislelizumab. The ORR was 30.0% (90% CI 16.6%-46.5%) and the median OS was 18.7 months. Of the 15 patients underwent surgical resection, 10 (66.7%) achieved pCR or MPR and 8 (53.3%) remained recurrence-free. The median RFS were not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. 4 (13.3%) patients experienced grade 3 treatment-related adverse events. The most common events were thrombocytopenia, leukopenia, and anemia. The trial has met the pre-specified endpoints, and these results support further studies of perioperative immunotherapy plus radiotherapy in HCC.

The stress change of coal body around the gas drainage borehole is one of the important factors affecting its permeability. In order to study the permeability with different degrees of fragmentation around the gas drainage boreholes, some coal particle composite samples with different range of particle diameter were prepared by the method of continuous grading, and the triaxial permeability tests with different Talbol power exponent n were carried out to analyze the influence of the effective stress on the internal structure and permeability characteristics of the fragmented coal samples. The results show that during the loading process, the axial pressure affects the permeability by changing the porosity of the broken coal, which decreases exponentially with the increase of the axial pressure. At the early stage of loading, the increase of axial pressure makes the volume of coal sample compressed, and the internal voids are closed, which causes the decrease of porosity and the weakening of permeability, resulting in the decrease of permeability. When the axial pressure is loaded with the porosity tends to 0.1, the internal compact structure of the coal sample makes a stable permeability. In the process of increasing the Talbol power exponent n of broken coal from 0.1 to 1.0, the permeability k shows three growth periods that are slow, linear and exponential stages, which are affected by the low-grade size particle, ratio of particle size and high-grade size particle respectively. The velocity of permeate is affected by the Talbol power exponent, pressure gradient, confining and axial pressure, however, the effect of pressure gradient is more significant. The larger the Talbol power exponent and pressure gradient with the smaller the confining pressure and axial pressure are, the larger the velocity of permeate is. There are the Talbol power exponent promotion effect of permeate velocity and the axial pressure and confining pressure inhibition effect of permeate velocity. The effective stress can characterize the inhibition effect of permeate velocity caused by the axial and confining pressure very well. The permeability of broken coal with different Talbol power exponents generally decays exponentially with the increase of effective stress, but the promotion effect of the Talbol power exponent on permeability gradually weakens, while the inhibition and amplitude effect of the effective stress on permeability gradually strengthen. The parameter change of the equation between the effective stress and permeability has three stages corresponding to the permeability curve. With the increase of the Talbol power exponent n, the parameter a of the equation decreases gradually, and the inhibition effect of the effective stress increases, while the increase of b, and the amplitude effect is gradually strengthened.

The coordinated arrangement of gas pre-drainage boreholes and anti-impact and pressure relief boreholes can integrate the prevention and control of mine rock burst and gas compound disasters. However, the dense arrangement of these boreholes may lead to the occurrence of phenomena such as string holes and collapse holes, which could potentially impact the efficiency of mine gas extraction. To investigate the deformation around borehole surface and the evolution of fractures during the compression failure process in the coal and rock masses with dual borehole structure, the 3D-DIC observation experiment was conducted on the coal samples containing double circular holes under uniaxial compression conditions using a digital image observation system for coal rock deformation and failure. This experiment yielded some time-series images of sample surface deformation under various stress states. The three-dimensional full-field deformation of the sample surface was calculated using the three-dimensional surface reconstruction technology and VIC3D analysis processing software. Based on the results of strain field analysis, the stress-strain curve was divided into five deformation stages using statistical index analysis methods, providing a detailed description of the deformation and fracture evolution characteristics around the borehole surface. The results show that under uniaxial compression, the grayscale of strain field in the coal samples with double circular holes shifts toward higher gray levels. The proportion of peaks in the strain field gray histogram changes slowly at first and then rapidly, with the peak stress serving as the boundary. The radial displacement curve around the sample holes presents a “从” shape, while the circumferential displacement curve presents a “人” shape. The left hole H1 always accelerates counterclockwise, while the right hole H2 always accelerates clockwise. The fractures around the holes are primarily characterized by counterclockwise dislocation, accompanied by a few instances of clockwise dislocation. The outer zone of strain localization primarily exhibits energy accumulation before the loading peak and energy release after the loading peak. This is accompanied by energy accumulation resulting from partial energy adjustment and transfer. During the loading process of the specimen, the factors such as the stress field environment, the geometry of fracture end, and the length of fracture undergo constant changes. This results in a reduction in the stress intensity factor KⅠ at the tip of the fracture, thereby impeding the expansion of the fracture.

Objective Currently, there is no established guideline on whether to opt for percutaneous endoscopic lumbar discectomy (PELD) or traditional transforaminal lumbar interbody fusion (TLIF) surgery based on specific types of lumbar disc herniation (LDH). Based on the Michigan State University (MSU) classification system, this study conducted a medium‐ to long‐term follow‐up analysis of two surgical methods over 5 years for the first time, aiming to provide empirical evidence to assist in making more informed decisions before surgery for LDH treatment. Methods This was a retrospective study that included 273 patients with single‐level LDH who underwent PELD or TLIF treatment at our hospital between January 1, 2016, and December 31, 2018. Detailed metrics included preoperative and postoperative visual analogue scale (VAS) scores and Oswestry disability index (ODI) at 1‐day, 1‐week, 1‐year, and 5‐year follow‐ups. Complications, recurrences, and 5‐year postoperative modified MacNab criteria scores were also recorded. Statistical methods included independent sample t‐tests, repeated measures analysis of variance (ANOVA), and χ2 tests. Results Classified into seven groups according to the MSU classification, it was found that there was an improvement in the VAS and ODI scores at four postoperative follow‐ups (p

Abstract Objective To investigate the biomechanical effects of percutaneous vertebroplasty combined with cement pedicle plasty (PVCPP) on the unstable osteoporotic vertebral fractures (OVFs) through finite element (FE) analysis. The study compares the biomechanical stability of finite element models between percutaneous vertebroplasty (PVP) and percutaneous vertebroplasty combined with cement pedicle plasty. Methods Two patients with unstable OVFs underwent computed tomography (CT) examination at the thoracolumbar vertebral body levels, respectively. The CT images were reconstructed into three-dimensional finite element models to simulate stress conditions across six dimensions and to evaluate the vertebral von Mises stress before and after bone cement reinforcement. Results The study found that stress distribution differed between groups mainly at the pedicle base. In the surgical vertebral bodies, the maximum stress in the PVP group decreased during flexion and left bending, while it increased in other states. In the PVCPP group, all maximum stresses decreased. In the inferior vertebral bodies, the maximum stress in the PVP group generally increased, while it decreased in the PVCPP group. In the superior vertebral bodies, postoperatively, the maximum stress in the PVP group generally increased, while it almost remained unchanged in the PVCPP group. PVP group had higher cement stress and displacement. Conclusion PVCPP is an effective treatment method for patients with unstable OVFs. It can quickly relieve pain and enhance the stability of the three columns, thereby reducing the risk of some complications.

Abstract Background Osteoporosis vertebral compression fracture (OVCF) secondary to osteoporosis is a common health problem in the elderly population. Vertebral augmentation (VA) has been widely used as a minimally invasive surgical method. The transpedicle approach is commonly used for VA puncture, but sometimes, it is limited by the anatomy of the vertebral body and can not achieve good surgical results. Therefore, we propose the treatment of OVCF with precise puncture vertebral augmentation (PPVA). This study used finite element analysis to explore the biomechanical properties of PPVA in the treatment of osteoporotic vertebral compression fractures (OVCFs) with wedge, biconcave, and collapse deformities. Method Three-dimensional finite element models of the fractured vertebral body and adjacent superior and inferior vertebral bodies were established using Computed Tomography (CT) data from patients with OVCF, both before and after surgery. Evaluate the stress changes of the wedged deformed vertebral body, biconcave deformed vertebral body, collapsed deformed vertebral body, and adjacent vertebral bodies before and after PPVA. Result In vertebral bodies with wedge deformity and collapsed deformity, PPVA can effectively reduce the stress on the vertebral body but increases the stress on the vertebral body with biconcave deformity. PPVA significantly decreases the stress on the adjacent vertebral bodies of the wedge deformed vertebral body, and decreases the stress on the adjacent superior vertebral body of biconcave deformity and collapsed deformed vertebral bodies, but increases the stress on the adjacent inferior vertebral bodies. PPVA improves the stress distribution of the vertebral body and prevents high-stress areas from being concentrated on one side of the vertebral body. Conclusion PPVA has shown positive surgical outcomes in treating wedge deformed and collapsed deformed vertebral bodies. However, its effectiveness in treating biconcave vertebral body is limited. Furthermore, PPVA has demonstrated favorable results in addressing adjacent superior vertebral body in three types of fractures.

The radial gas seepage flow regime of the coal body around borehole is one of important factors reflecting the seepage movement of extracted gas. In order to investigate the effects of different pore structures and gas pressure on the radial seepage motion of gas in the perimeter of borehole, five kinds of pore-bearing coal samples with different gradations were made, and the radial seepage test was carried out on the pore-bearing coal samples by using the self-designed gas radial seepage test system and the steady-state seepage method to analyze the changes of the Forchheimer number and non-Darcy error with the seepage velocity and gradation, and the flow velocity intervals and the Reynolds number ranges of different flow regimes were obtained by using the Hazen-Dupuit-Darcy equation and the Reynolds number theory. The results show that: ① Through the analysis of the Forchheimer number and non-Darcy error with the change curve of seepage velocity, the Forchheimer number increases with seepage velocity in a quadratic polynomial curve, while non-Darcy error increases linearly, the Forchheimer number and non-Darcy error are closely related to pore structure, and both become larger with the increase of gradation, indicating that seepage velocity and pore structure of the coal body around the pore are important factors for gas seepage deviating from linear seepage; ② The Hazen-Dupuit-Darcy equation was used to characterize and delineate the gas radial permeability flow regime. With the increase of seepage velocity, the gas radial seepage motion appears in order of pre-Darcy, Darcy and Forchheimer flow regimes. The small-graded porous specimens with n=0.2 and n=0.4 are more prone to the Darcy laminar flow, while the porous samples with n=0.6, n=0.8 and n=1.0 are more prone to the Forchheimer flow regime; ③ Through the analysis of the relative error curve of pressure gradient when Darcy’s law was applied, the relative error with the increase of seepage velocity shows the change law of decreasing, keeping stable, and then increasing, which is consistent with the change law of gas seepage flow pattern with seepage velocity; ④ In double logarithmic coordinates, the relationship between different flow regimes of gas seepage and Reynolds number was analyzed, and the Reynolds number intervals of different flow regimes were derived, and it was found that the radial seepage motion of gas conforms to the Reynolds number range of 0.0012～0.0025 for Darcy laminar flow. The results of the study can provide an important theoretical basis for the design of drilling parameters by determining the influence range of drilling extraction based on the flow regime of coal seepage movement around the borehole in coal seam gas pre-drainage work.

Remote sensing, particularly satellite-based, can play a valuable role in monitoring areas prone to geohazards. The high spatial and temporal coverage provided by satellite data can be used to reconstruct past events and continuously monitor sensitive areas for potential hazards. This paper presents a range of techniques and methods that were applied for in-depth analysis and utilization of Earth observation data, with a particular emphasis on: (1) detecting mining subsidence, where a novel approach is proposed by combining an improved U-Net model and Interferometry Synthetic Aperture Radar (InSAR) technology. The results showed that the Efficient Channel Attention (ECA) U-Net model performed better than the U-Net (baseline) model in terms of Mean Intersection over Union (MIoU) and Intersection over Union (IoU) indicators; (2) monitoring water conservancy and hydropower engineering. The Xiaolangdi multipurpose dam complex was monitored using Small BAsline Subsets (SBAS) InSAR method on Sentinel-1 time series data and four small regions with high deformation rates were identified on the slope of the reservoir bank on the north side. The dam body also showed obvious deformation with a velocity exceeding 60 mm/a; (3) the evaluation of the potential of InSAR results to integrate monitoring and warning systems for valuable heritage and architectural preservation. The overall outcome of these methods showed that the use of Artificial Intelligence (AI) techniques in combination with InSAR data leads to more efficient analysis and interpretation, resulting in improved accuracy and prompt identification of potential hazards; and (4) finally, this study also presents a method for detecting landslides in mountainous regions, using optical imagery. The new temporal landslide detection method is evaluated over a 7-year analysis period and unlike conventional bi-temporal change detection methods, this approach does not depend on any prior-knowledge and can potentially detect landslides over extended periods of time such as decades.

Background: The global incidence of neurological diseases has been on the rise, creating an urgent need for a validated marker. Neurofilament Light Chain (NfL) holds promise as such a marker and has garnered significant attention in the field of neurological diseases over the past decades. Methods: Corresponding articles from 2013 to 2023 were collected from the Web of Science database, and data were analyzed by CiteSpace and VOSviewer software. Results: A total of 1350 articles were collected from 296 countries/regions, involving 7246 research organizations. Since 2013, among the top ten institutions and authors with the highest number of published papers, the most are from the US and the UK. The United States leads in the number of published papers, but England holds a more momentous position, because it has higher IF. Henrik Zetterberg is the most influential scholar in the field. Conclusions: The output of papers mainly relies on researchers from developed countries, and scholars from the United States and England have contributed the largest number of papers. Until now, the importance of NfL in neurological diseases has attracted global attention. In addition, NfL contributes to the potential diagnosis of various neurological disorders and can be used to improve the accuracy of differential diagnosis and prognostic assessment as well as predict the response to treatments. More and more in-depth studies are highly needed in the future.

In the acquisition of weld seam images, the presence of light and impurity interference often leads to weak edge problems in weld seam images, making the identification of weld seam defects challenging. In such scenarios, segmentation processing must be performed specifically at the fusion pool of the weld seam. In recent years, Transformers, which leverage self-attention mechanisms, have demonstrated superior sequence modeling capabilities compared to convolutional neural networks (CNNs). The Transformer excels at weighting different positions within a sequence, enabling effective handling of long-range dependencies. However, Transformers lack the ability of CNNs to extract local information. To address this limitation, this paper introduces a novel CvT-UNet semantic segmentation model that combines the strengths of both the convolutional neural network and the transformer. The model combines the global context information capabilities of the Transformer with the spatial information advantages provided by the convolutional neural network. The proposed model employs an encoder-decoder architecture by building a U-shaped network with designed CvT blocks. Depthwise separable convolutions are utilized to balance parameter quantities, and the skip-connection module is redesigned to enable the model to achieve more precise segmentation of weld seam fusion pools with fewer parameters. Experimental evaluations on diverse weld seam datasets under different environmental conditions demonstrate promising results. The model achieves average intersection over union (IoU) values of 93.75 %, 88.31 %, and 90.86 %, respectively. Specifically, on an automotive weld seam dataset, CvT-UNet outperforms the purely convolutional neural network structure UNet3+, with a 1.63 % increase in the mean IoU (MIOU) and a 1.39 % increase in the mean pixel accuracy (MPA). Compared to the TransUNet fusion model, CvT-UNet results in a 0.33 % increase in the MIOU and a 0.6 % increase in the MPA. Furthermore, compared to the state-of-the-art curve segmentation model LIOT, CvT-UNet achieves a 1.94 % increase in the MIOU and a 0.61 % increase in the MPA, demonstrating favorable segmentation performance.

Fruits are recognized as healthy foods with abundant nutritional content. However, due to their high content of sugar and water, they are easily contaminated by microorganisms leading to spoilage. Probiotic fermentation is an effective method to prevent fruit spoilage. In addition, during fermentation, the probiotics can react with the nutrients in fruits to produce new derived compounds, giving the fruit specific flavor, enhanced color, active ingredients, and nutritional values. Noteworthy, the choice of fermentation strains and strategies has a significant impact on the quality of fermented fruits. Thus, this review provides comprehensive information on the fermentation strains (especially yeast, lactic acid bacteria, and acetic acid bacteria), fermentation strategies (natural or inoculation fermentation, mono- or mixed-strain inoculation fermentation, and liquid- or solid-state fermentation), and the effect of fermentation on the shelf life, flavor, color, functional components, and physiological activities of fruits. This review will provide a theoretical guidance for the production of fermented fruits.

Abstract Thermochromic smart windows have gained increasing popularity in light modulation and energy management in buildings. However, the fabrication of flexible thermochromic smart windows with high luminous transmittance (Tlum), tailorable critical temperature (τc), strong solar modulation ability (ΔTsol), and long‐term durability remains a huge challenge. In this study, hydrogel‐based thermochromic smart windows are fabricated by sandwiching thermochromic hydrogels of polyallylamine hydrochloride, polyacrylic acid, and carbonized polymer dots (CPDs) complexes between two pieces of transparent substrates. Benefiting from the incorporation of nanosized CPDs, the thermochromic hydrogel has an ultrahigh Tlum of ~98.7%, a desirable τc of ~24.2 °C, a ΔTsol of ~89.3% and a rapid transition time of ~3 s from opaque state to transparent state. Moreover, the thermochromic hydrogel exhibits excellent anti‐freezing ability, tight adhesion toward various substrates, and excellent self‐healing capability. The self‐healing capability enables the fabrication of large‐area smart windows by welding multiple hydrogel pieces. The smart windows retain their original thermochromic properties after being stored under ambient conditions for at least 147 days or undergoing 10,000 uninterrupted heating/cooling cycles. The model houses with smart windows can achieve a temperature reduction of 9.2 °C, demonstrating the excellent indoor temperature modulation performance of the smart windows.

It aims to solve the problem that the evacuation state of pedestrians depicted by the traditional social force model in a crowded multiexit scenario has a relatively large difference with the actual state, especially the 'optimal path' considered by the self-driving force is the problem of shortest path, and the multiexit evacuation mode depicted by the 'herd behavior' is the local optimum problem. Through in-depth analysis of actual evacuation data of pedestrians and causes of problem, a new crowd evacuation optimization model is established in order to effectively improve the simulation accuracy of crowd evacuation in a multi-exit environment. The model obtains the direction of motion of pedestrians using a field model, fully considers the factors such as exit distance, distribution of pedestrians and regional crowding degree, makes a global optimization for the self-driving force in the social force model using a centralized and distributed network model, and makes a local optimization for it using an elephant herding algorithm, so as to establish a new evacuation optimization method for optimal self-adaption in the bottleneck area. The performance status is compared between the improved social force model and the new model by experiments, and the key factors that affect the new model are analyzed in an in-depth manner. The results show that the new model can optimize the optimal path choice at the early stage of evacuation and improve the evacuation efficiency of pedestrians at the late stage, so as to ensure relatively even distribution of pedestrians at each exit, and also make the simulated evacuation process be more real; and the improvement in overall evacuation efficiency is greater when the number of pedestrians to be evacuated is larger. Therefore, the new model provides a method to solve the phenomenon of disorder in overall pedestrian evacuation due to excessive crowd density during the process of multi-exit evacuation.

Spinal infections, notably those induced by Aspergillus flavus (A. flavus), represent a complex and uncommon clinical challenge. In individuals with diabetes mellitus, the risk is exacerbated due to a compromised immune response and a heightened vulnerability to non-standard pathogens. This case report chronicles the intricate diagnostic and treatment journey of a 59-year-old diabetic patient grappling with a spinal infection attributed to A. flavus. The diagnosis was delayed due to non-specific symptoms and unclear radiological signs. The administration of voriconazole, a targeted antifungal treatment, resulted in a significant clinical and radiological improvement, underscoring its effectiveness in treating such unusual fungal spinal infections; meanwhile, we found that terbinafine hydrochloride also has a similar effect in treating fungal spinal infections. This case underscores the importance of considering fungal causes in spinal infections among diabetic patients and highlights prompt diagnosis and individualized targeted antifungal therapy.

CO2 blasting has been identified as a potent method for enhancing the permeability of coal seams and improving gas drainage efficiency. This study is focused on elucidating the deformation and fracture mechanisms of coal and rock during CO2 blasting and on identifying the precursor characteristics of these processes. To this end, a CO2 blasting-induced coal rock fracture pressure model and a gas pressure distribution model were developed. The research utilized a self-developed CO2 blasting test platform along with a non-contact full-strain field measurement analysis system. Briquette samples were subjected to CO2 blasting tests under controlled experimental conditions, which included an axial pressure of 1.0 MPa and variable gas pressures of 0.5, 1.0, and 1.5 MPa. This methodology enabled the capture of the principal strain field on the surface of the samples. The Gray Level Co-occurrence Matrix (GLCM) was employed to extract and analyze the grayscale and texture features of the strain cloud maps, facilitating a quantitative assessment of their evolution. The aim was to pinpoint the precursor characteristics associated with coal rock cracking and crack propagation. The results revealed that: (1) During the cracking and subsequent propagation of samples, the strain field's grayscale histogram underwent a transformation from a "broad and low" to a "narrow and high" configuration, with a consistent increase in peak frequency. Specifically, at 3 ms, a primary crack was observed in the sample, evidenced by a grayscale peak frequency of 0.0846. By 9 ms, as the crack propagated, the grayscale peak frequency escalated to 0.1626. (2) The texture feature parameters experienced their initial abrupt change at 3ms. Correlation with the gas pressure distribution model indicated that this was the crack initiation moment in the sample. (3) A secondary abrupt shift in the texture feature parameters occurred at 9ms, in conjunction with experimental phenomena, was identified as the crack propagation phase. Monitoring the grayscale and texture features of the principal strain field on the coal rock surface proved effective in recognizing the precursor characteristics of crack initiation and propagation. This research has the potential to reduce blasting costs in coal mines, optimize blasting effects, and provided theoretical guidance for enhancing gas extraction efficiency from deep and low permeability coal seams.

APSES (Asm1p, Phd1p, Sok2p, Efg1p, and StuAp) family transcription factors play crucial roles in various biological processes of fungi, however, their functional characterization in phytopathogenic fungi is limited. In this study, we explored the role of SsStuA, a typical APSES transcription factor, in the regulation of cell wall integrity (CWI), sclerotia formation and pathogenicity of Sclerotinia sclerotiorum, which is a globally important plant pathogenic fungus. A deficiency of SsStuA led to abnormal phosphorylation level of SsSmk3, the key gene SsAGM1 for UDP-GlcNAc synthesis was unable to respond to cell wall stress, and decreased tolerance to tebuconazole. In addition, ΔSsStuA was unable to form sclerotia but produced more compound appressoria. Nevertheless, the virulence of ΔSsStuA was significantly reduced due to the deficiency of the invasive hyphal growth and increased susceptibility to hydrogen peroxide. We also revealed that SsStuA could bind to the promoter of catalase family genes which regulate the expression of catalase genes. Furthermore, the level of reactive oxygen species (ROS) accumulation was found to be increased in ΔSsStuA. In summary, SsStuA, as a core transcription factor involved in the CWI pathway and ROS response, is required for vegetative growth, sclerotia formation, fungicide tolerance and the full virulence of S. sclerotiorum.

In a world where renewable energy solutions are in high demand, solar photovoltaic (PV) systems are at the forefront, emphasizing the need for efficient and eco-friendly logistics. This coincides with the rise of blockchain technology as a game-changer in PV system management. Additionally, cloud computing is playing a pivotal role in transforming the IT landscape, providing seamless access to shared computing resources via the Internet. This research introduces a novel framework that utilizes cloud computing to enhance blockchain-based PV logistics. It employs a sophisticated mathematical model to optimize logistics components such as transportation, storage, inventory management, and supply chain coordination, with the goal of minimizing costs and improving overall efficiency. At the heart of this transformative paradigm lies a visionary cloud-based system, endowing PV logistic planners with the power of real-time access to mission-critical data. This infusion of data-driven decision-making capabilities fosters a seamless symphony of communication and enriches collaboration among stakeholders, setting the stage for monumental shifts in efficiency and management, ushering in a new era of sustainability and scalability within the photovoltaic industry. This technological synergy is not just about immediate gains. It is a testament to our commitment to improved energy sustainability and a testament to our shared vision of a greener future. In lockstep with the global pursuit of renewable energy solutions, this research lights the way toward a brighter, more sustainable tomorrow.

Lung cancer is one of the most common malignant tumors and has a poor prognosis and a low survival rate. Traditional treatments, such as radiotherapy and chemotherapy, still face some challenges because of high drug resistance and toxicity. Therefore, it is necessary to discover a new kind of targeted drug with low toxicity and high efficiency. CDK12 is a cell cycle-dependent kinase whose main function is to activate RNA polymerase II (RNAPII) and promote the transcriptional extension of RNA. However, the role and molecular mechanism of CDK12 in lung cancer are still unclear.In this study, the mutation and RNA-Seq data of CDK12 in lung adenocarcinoma and squamous cell carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database and analyzed with the custom scripts. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and cell colony formation assays. A subcutaneous tumor experiment in nude mice was used to examine the effects of CDK12 knockdown on the in vivo tumor growth of NSCLC cells. The cell cycle distribution and the apoptosis rate of lung cancer cells were assessed by flow cytometry. Regulation of TANK-binding kinase 1 (TBK1) by CDK12 was evaluated by quantitative PCR, immunoprecipitation and Western blot analysis.In this study we have analyzed the mutation and expression data of The Cancer Genome Atlas (TCGA) database and found that CDK12 is highly expressed in lung cancer tissues. Clinical correlation analysis showed that high expression of CDK12 in NSCLC reduces patient survival, but its high expression is only related to early tumor progression and has no significant correlation with late tumor progression and metastasis. Furthermore, we present evidence that CDK12 depletion in lung cancer cell lines not only leads to the inhibition of cell growth and induces apoptosis but also inhibits tumor growth of NSCLC cells in vivo. CDK12 positively regulates the expression of the oncogene TBK1 in lung cancer cells. These results revealed that CDK12 affects the progression of non-small cell lung cancer through positive regulation of TBK1 expression, suggesting that CDK12 might be a potential molecular target for the treatment of non-small cell lung cancer.

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

Abstract The malignant transformation of hepatic progenitor cells (HPCs) in the inflammatory microenvironment is the root cause of hepatocarcinogenesis. However, the potential molecular mechanisms are still elusive. The HPCs subgroup is identified by single‐cell RNA (scRNA) sequencing and the phenotype of HPCs is investigated in the primary HCC model. Bulk RNA sequencing (RNA‐seq) and proteomic analyses are also performed on HPC‐derived organoids. It is found that tumors are formed from HPCs in peritumor tissue at the 16th week in a HCC model. Furthermore, it is confirmed that the macrophage‐derived TWEAK/Fn14 promoted the expression of inhibitor of differentiation‐1 (ID1) in HPCs via NF‐κB signaling and a high level of ID1 induced aberrant differentiation of HPCs. Mechanistically, ID1 suppressed differentiation and promoted proliferation in HPCs through the inhibition of HNF4α and Rap1GAP transcriptions. Finally, scRNA sequencing of HCC patients and investigation of clinical specimens also verified that the expression of ID1 is correlated with aberrant differentiation of HPCs into cancer stem cells, patients with high levels of ID1 in HPCs showed a poorer prognosis. This study provides important intervention targets and a theoretical basis for the clinical diagnosis and treatment of HCC.

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

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

Abstract Smart windows with light management and indoor solar heating modulation capacities are of paramount importance for building energy conservation. Thermochromic poly(N‐isopropylacrylamide) (PNIPAm) hydrogel smart windows exhibit advantages of the relatively suitable transition temperature of 32 °C, high cost‐effective and automatic passive sunlight regulation, but sustain slow response rate and unsatisfactory solar modulation efficiency. Herein, a strategy of one‐step copolymerization of NIPAm and different olefine acids (OA) using reverse atom transfer radical polymerization method is developed to fabricate various chain/microparticle hybrids (CMH) for liquid energy‐saving windows. Synergetic mechanisms of thermal‐induced dissolution and aggregation of linear polymer chains integrated with water capture and release of microgel particles contribute to tunable light‐scattering behaviors and adaptive solar modulation. Without any post‐treatment, the as‐prepared poly(N‐isopropylacrylamide‐co‐acrylic acid) (P(NIPAm‐co‐AA))‐based CMH suspension is injected into sandwich glass to construct energy‐saving windows, which exhibits appreciated near‐room‐temperature transition (26.7 °C), rapid response (5 s), extraordinary luminous transmittance (91.5%), and solar modulation efficiency (85.8%), resulting in a substantial decline of indoor temperature of 24.5 °C in simulation experiment. Combining the versatile strategy with flexible adjustment on transition temperature, multifarious P(NIPAm‐co‐OA)‐based CMH windows with eminent light management capacity are obtained. This work will powerfully promote the development and renovation of energy‐efficient windows.

Abstract Particle loss is an important cause of water inrush catastrophes in collapsed columns. In order to study the relationship between the lost particles of different graded rock samples and the pore structure of the subsidence column filling, experiments were designed and the changes of the seepage parameters of graded rock samples during the particle migration process under different permeable water pressures P and axial loads F were determined. The results show that: (1) There will be obvious collapse, silting and particle loss behaviors in the sample during different loading processes, and the rock samples with gradation values of n = 0.3 and n = 0.5 are dominant; (2) The relationship between porosity φ and bearing pressure The exponential function can be used to fit the loads F well, and the porosity decreases with the increase of the bearing load. The water surging characteristics before and after 1.2 MPa are mainly in the turbulent water gushing stage, accompanied by instantaneous slurry. Possibility of splashing and indenter sliding; (3) After infiltration, the condition of the remaining skeleton rock samples in the cylinder generally shows a trend of first decreasing rapidly, then increasing slowly, and then decreasing; (4) The gradation value n of the sample and the bottom There is a good correlation between the damaged area and the mean value S of the maximum area of the top water inrush channel. The maximum area increase of the damaged area and the maximum area increase of the water inrush channel show an opposite trend. The permeable pores of the graded samples can be divided into There are three situations of digging and collapse, water inrush gap and scouring hole, and the pore seepage process can be divided into 4 stages of inoculation of water seepage, rapid adjustment, rapid scour and steady flow.

The creep process of the coal rock around the extraction boreholes under stress-water coupling is an important factor affecting the stability of the boreholes. To study the influence of the water content of perimeter of the coal rock around the boreholes on its creep damage, a creep intrinsic model considering water damage was established by introducing the plastic element model from the Nishihara model. To study the steady-state strain and damage evolution of coal rocks containing pores, and verify the practicality of the model, a graded loading water-bearing creep test was designed to explore the role of different water-bearing conditions in the creep process. The following conclusions were obtained: 1) water has a physical erosion and softening water wedge effect on the perimeter of the coal rock around the boreholes, which affects the loading axial strain and displacement of the perforated specimens; 2) an increase in water content reduces the time taken for perforated specimens to enter the creep phase, making the accelerated creep phase come earlier; 3) the parameters of the water damage model are considered to be exponentially related with the water content. The experimental data are similar to the results of the model parameters, and the model shows some practicality; 4) the damage variables in the accelerated creep phase increase rapidly throughout the creep process, leading to local instability in the borehole. The findings of the study provide important theoretical implications for the study of instability in gas extraction boreholes.

Soybean sclerotinia stem rot (SSR) is a disease caused by Sclerotinia sclerotiorum that causes incalculable losses in soybean yield each year. Considering the lack of effective resistance resources and the elusive resistance mechanisms, we are urged to develop resistance genes and explore their molecular mechanisms. Here, we found that loss of GmSWEET15 enhanced the resistance to S. sclerotiorum, and we explored the molecular mechanisms by which gmsweet15 mutant exhibit enhanced resistance to S. sclerotiorum by comparing transcriptome. At the early stage of inoculation, the wild type (WT) showed moderate defense response, whereas gmsweet15 mutant exhibited more extensive and intense transcription reprogramming. The gmsweet15 mutant enriched more biological processes, including the secretory pathway and tetrapyrrole metabolism, and it showed stronger changes in defense response, protein ubiquitination, MAPK signaling pathway-plant, plant-pathogen interaction, phenylpropanoid biosynthesis, and photosynthesis. The more intense and abundant transcriptional reprogramming of gmsweet15 mutant may explain how it effectively delayed colonization by S. sclerotiorum. In addition, we identified common and specific differentially expressed genes between WT and gmsweet15 mutant after inoculation with S. sclerotiorum, and gene sets and genes related to gmsweet15_24 h were identified through Gene Set Enrichment Analysis. Moreover, we constructed the protein–protein interaction network and gene co-expression networks and identified several groups of regulatory networks of gmsweet15 mutant in response to S. sclerotiorum, which will be helpful for the discovery of candidate functional genes. Taken together, our results elucidate molecular mechanisms of delayed colonization by S. sclerotiorum after loss of GmSWEET15 in soybean, and we propose novel resources for improving resistance to SSR.

The traditional power generation mix and the geographical distribution of units have faced structural reform with the increasing renewables. The existing scheduling schemes confront the optimization challenges of multi-source collaborative and multi-temporal coordination. This paper reviews the optimization of generation scheduling in power systems with renewables integration in different time scales, which are medium- and long-term, short-term and real-time, respectively. First, the scheduling model and method are summarized. The connections and differences of the multi-source mathematic model with uncertainty, as well as the market mechanism, including thermal power, hydroelectric power, wind power, solar energy, and energy storage, are also indicated. Second, the scheduling algorithm and approach are sorted out from the two dimensions of certainty and uncertainty. The innovation and difference in algorithm between the traditional scheduling and the scheduling problem with renewables are presented. Meanwhile, the interaction and coupling relationship among the different time scales are pointed out in each section. The challenges and shortcomings of current research and references future directions are also provided for dispatchers.

To investigate the permeability characteristics in the in-situ fractured coal body around the perimeter of gas extraction boreholes, the steady-state permeability of fractured coal bodies with different gradations was tested using the fractured rock permeability test system. By controlling the axial displacement and permeability pressure, the permeability parameters were obtained under different porosities. The interactions between the permeability parameters and the process of permeability destabilisation are discussed. The results show that the permeability characteristics of the broken coal body obey the Forchheimer relationship: As the axial displacement increases, the permeability resistance of the fluid increases and the non-Darcy property of the sample becomes more significant. With the decrease in the porosity of the sample and the increase in the power index n, the permeability k decreases and the non-Darcy factor β increases. The final fractal structure of the sample will be changed by particle fragmentation and migration during the loading process of the sample with different levels, and the internal pore structure of the sample will further affect the penetration of the penetration channel. A critical characteristic value for the seepage instability in broken coal bodies is given, and an expression for determining the seepage instability by permeability and non-Darcy factors is proposed. The results indicate that a negative non-Darcy factor is not a necessary condition for permeability instability, and the critical Reynolds number for the permeability instability in broken coal bodies was determined from the perspective of the Reynolds number. The conclusions of this study can provide theoretical support for the theoretical study of permeability and the permeability of pre-smoking coal seams.

Models play a crucial role in explaining internal processes, estimating states, and managing lithium-ion batteries. Electrochemical models can effectively illustrate the battery’s mechanism; however, their complexity renders them unsuitable for onboard use in electric vehicles. On the other hand, equivalent circuit models (ECMs) utilize a simple set of circuit elements to simulate voltage–current characteristics. This approach is less complex and easier to implement. However, most ECMs do not currently account for the nonlinear impact of operating conditions on battery impedance, making it difficult to obtain accurate wideband impedance characteristics of the battery when used in online applications. This article delves into the intrinsic mechanism of batteries and discusses the influence of nonstationary conditions on impedance. An ECM designed for non-steady state conditions is presented. Online adaptive adjustment of model parameters is achieved using the forgetting factor recursive least squares (FFRLS) algorithm and varied parameters approach (VPA) algorithm. Experimental results demonstrate the impressive performance of the model and parameter identification method, enabling the accurate acquisition of online impedance.

The necrotrophic fungus Sclerotinia sclerotiorum is a devastating pathogen. S. sclerotiorum can cause Sclerotinia stem rot in more than 600 species of plants, which results in serious economic losses every year. Chitin is one of the most important polysaccharides in fungal cell walls. Chitin and β-Glucan form a scaffold that wraps around the cell and determines the vegetative growth and pathogenicity of pathogens. UDP-GlcNAc is a direct precursor of chitin synthesis. During the synthesis of UDP-GlcNAc, the conversion of GlcNAc-6P to GlcNAc-1P that is catalyzed by AGM1 (N-acetylglucosamine-phosphate mutase) is a key step. However, the significance and role of AGM1 in phytopathogenic fungus are unclear. We identified a cytoplasm-localized SsAGM1 in S. sclerotiorum, which is homologous to AGM1 of Saccharomyces cerevisiae. We utilized RNA interference (RNAi) and overexpression to characterize the function of SsAGM1 in S. sclerotiorum. After reducing the expression of SsAGM1, the contents of chitin and UDP-GlcNAc decreased significantly. Concomitantly, the gene-silenced transformants of SsAGM1 slowed vegetative growth and, importantly, lost the ability to produce sclerotia and infection cushion; it also lost virulence, even on wounded leaves. In addition, SsAGM1 was also involved in the response to osmotic stress and inhibitors of cell wall synthesis. Our results revealed the function of SsAGM1 in the growth, development, stress response, and pathogenicity in S. sclerotiorum.

The permeability of crushed coal bodies plays a bottom neck role in seepage processes, which significantly limits the coal resource utilisation. To study the permeability of crushed coal bodies under pressure, the particle size distribution of crushed coal body grains is quantitatively considered by fractal theory. In addition, the parameters of the percolation characteristics of crushed coal body grains are calculated. Moreover, the permeability of the crushed coal body during recrushing is determined by the fractal dimension and porosity. A lateral limit compression test with the crushed coal bodies was carried out to illustrate the effect of the porosity on the permeability, In addition, a compressive crushed coal body size fractal–permeability model was proposed by combination of the fractal dimension and the non-Darcy equivalent permeability. The results show (1) the migration and loss of fine particles lead to a rapid increase in the porosity of the crushed coal body. (2) Increases in the effective stress cause the porosity and permeability to decrease. When the porosity decreases to approximately 0.375, its effect is undermined. (3) The migration and loss of fine particles change the pore structure and enhance the permeability properties of the skeleton, causing sudden seepage changes. (4) At low porosity, the permeability k is slightly larger than the non-Darcy equivalent permeability ke. Thus, the experimental data show an acceptable agreement with the present model. A particle size fractal–percolation model for crushed coal bodies under pressure provides a solution for effectively determining the grain permeability of the crushed coal bodies. The research results can contribute to the formation of more fractal-seepage theoretical models in fractured lithosphere, karst column pillars and coal goaf, and provide theoretical guidance for mine water disaster prevention.

Bacillus mojavensis D50, a biocontrol strain, is used to prevent and treat the fungal plant pathogen Botrytis cinerea. Bacillus mojavensis D50’s biofilms can affect its colonization; thus, the effects of different metal ions and culture conditions on biofilm formation were determined in this study. The results of medium optimization showed that Ca2+ had the best ability to promote biofilm formation. The optimal medium composition for the formation of biofilms contained tryptone (10 g/L), CaCl2 (5.14 g/L), and yeast extract (5.0 g/L), and the optimal fermentation conditions included pH 7, a temperature of 31.4 °C, and a culture time of 51.8 h. We found that the antifungal activity and abilities to form biofilms and colonize roots were improved after optimization. In addition, the levels of expression of the genes luxS, SinR, FlhA, and tasA were up-regulated by 37.56-, 2.87-, 12.46-, and 6.22-fold, respectively. The soil enzymatic activities which related biocontrol-related enzymes were the highest when the soil was treated by strain D50 after optimization. In vivo biocontrol assays indicated that the biocontrol effect of strain D50 after optimization was improved.

PurposeTo compare the efficacy and safety of the combination of transcatheter arterial chemoembolization (TACE), Lenvatinib, and programmed cell death protein-1 (PD-1) inhibitors (combination group) with TACE (TACE group) in the treatment of patients with unresectable hepatocellular carcinoma (uHCC).MethodsWe consecutively enrolled 110 patients with uHCC in this prospective cohort study, with 56 patients receiving combination treatment and 54 patients receiving TACE from November 2017 to September 2020. The differences in tumor response, survival benefit, and adverse events (AEs) were compared between the two groups. Factors affecting survival were identified via Cox regression analysis.ResultsCompared with the TACE group, the combination group had a higher objective response rate (ORR) (67.9% vs. 29.6%, p < 0.001), longer median progression-free survival (mPFS) (11.9 vs. 6.9 months, P = 0.003) and overall survival (mOS) (23.9 vs. 15.3 months, p < 0.001). Multivariate analysis showed that the neutrophil-to-lymphocyte ratio (NLR) and the treatment option were independent factors associated with the PFS and OS. Further subgroup analysis showed that patients with low NLR (≤median 3.11) receiving combination therapy had better mPFS (20.1 vs. 6.2 months, P < 0.001) and mOS (28.9 vs. 15.2 months, P < 0.001) than those receiving TACE, while no obvious difference in PFS or OS was observed between the two groups in patients with high NLR (> 3.11). There were no unexpected toxicities in the combination group.ConclusionCompared with TACE, the combination treatment demonstrated an improved clinical efficacy and manageable safety profile in patients with uHCC. Combination treatment showed better therapeutic efficacy in patients with low NLR; therefore, this ratio could be used to identify patients who will benefit from this treatment.

The plant pathogenic fungus Sclerotinia sclerotiorum can survive on a wide range of hosts and cause significant losses on crop yields. FKH, a forkhead box (FOX)-containing protein, functions to regulate transcription and signal transduction. As a transcription factor (TF) with multiple biological functions in eukaryotic organisms, little research has been done on the role of FKH protein in pathogenic fungi. SsFkh1 encodes a protein which has been predicted to contain FOX domain in S. sclerotiorum. In this study, the deletion mutant of SsFkh1 resulted in severe defects in hyphal development, virulence, and sclerotia formation. Moreover, knockout of SsFkh1 lead to gene functional enrichment in mitogen-activated protein kinase (MAPK) signaling pathway in transcriptome analysis and SsFkh1 was found to be involved in the maintenance of the cell wall integrity (CWI) and the MAPK signaling pathway. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that SsFkh1 interacts with SsMkk1. In addition, we explored the conserved MAPK signaling pathway components, including Bck1, Mkk1, Pkc1, and Smk3 in S. sclerotiorum. ΔSsmkk1, ΔSspkc1, ΔSsbck1, and ΔSssmk3knockout mutant strains together with ΔSsmkk1com, ΔSspkc1com, ΔSsbck1com, and ΔSssmk3com complementation mutant strains were obtained. The results indicated that ΔSsmkk1, ΔSspkc1, ΔSsbck1, and ΔSssmk3 displayed similar phenotypes to ΔSsfkh1 in sclerotia formation, compound appressorium development, and pathogenicity. Taken together, SsFkh1 may be the downstream substrate of SsMkk1 and involved in sclerotia formation, compound appressorium development, and pathogenicity in S. sclerotiorum.

Abstract CO2 presplitting blasting is an effective method to increase coal seams permeability and improve gas drainage efficiency. During the blasting process, the empty holes in the coal and rock mass have a significant effect on crack growth. In the experiment, a sample containing empty holes was used for CO2 presplitting blasting. The VIC‐3D was used to observe the change in the surface displacement of the sample; and the amplitude of the wave during the blasting process was collected using ultrasonic waves. Here, we calculated the attenuation coefficient α, analyzed the internal crack damage of the coal and rock mass, and compared the LS‐DYNA simulation results to analyze the empty hole effect on the crack growth of the coal and rock mass. The results show that: (a) radial tensile stress is generated due to the superposition of compression waves and reflected waves during blasting, resulting in an approximately straight main crack channel between the blast hole and the empty hole; (b) When both the stress and the attenuation coefficient reach their peaks, a main crack is formed and the most severe damage occurs inside the coal and rock mass; (c) the main crack channel was formed at 0.13 seconds, and the energy consumption reached the peak at 0.18 seconds, the negative linear correlation between energy and stress was obtained. Therefore, the empty hole effect provides a good guide for the crack propagation of the coal and rock mass and provides a new experimental scheme for increasing the permeability of coal seams.

In order to investigate the compaction and re-crushing characteristics of crushed coal gangue with different gradation, the compaction fractal test was carried out for crushed coal gangue with different Talbol power index n. The compaction deformation parameters such as displacement, stress-strain were analyzed according to the test results. And according to the test results, the compaction deformation relationship of the lateral limit crushed coal rock body considering the gradation is obtained. The test results show that: the crushing of coal rock particles exists in almost the whole compaction process of the crushed coal rock body, and the crushing of coal rock particles has a non-negligible influence on the deformation of the whole crushed rock body; the structural stability of large-size coal rock particles is not as good as that of small-size coal rock particles, and the large-size coal rock is more likely to be crushed under the same stress conditions; the distribution coefficient r of the crushed coal rock body decreases with the increase of axial stress; and before the Before the axial stress reaches 8 MPa, the distribution coefficient r of crushed rock samples tends to increase with n in general, and after reaching 8 MPa and later, the distribution coefficient r of crushed rock samples tends to decrease with n in general; the difference value of particle crushing increases with the increase of axial stress, and the weight value of particle crushing decreases with the increase of axial stress, and the changes of both are non-linear; according to the stress recovery in the compaction process of crushed coal rock body The compaction deformation model of the crushed coal rock body is constructed according to the crushing characteristics of coal rock particles in the stage of compaction, which effectively combines its fine action mechanism with macroscopic physical phenomena in a simple form and has certain practical engineering significance.

Sclerotinia sclerotiorum is a necrotrophic phytopathogenic fungus that produces sclerotia. Sclerotia are essential components of the survival and disease cycle of this devastating pathogen. In this study, we analyzed comparative transcriptomics of hyphae and sclerotia. A total of 1959 differentially expressed genes, 919 down-regulated and 1040 up-regulated, were identified. Transcriptomes data provide the possibility to precisely comprehend the sclerotia development. We further analyzed the differentially expressed genes (DEGs) in sclerotia to explore the molecular mechanism of sclerotia development, which include ribosome biogenesis and translation, melanin biosynthesis, autophagy and reactivate oxygen metabolism. Among these, the autophagy-related gene SsAtg1 was up-regulated in sclerotia. Atg1 homologs play critical roles in autophagy, a ubiquitous and evolutionarily highly conserved cellular mechanism for turnover of intracellular materials in eukaryotes. Therefore, we investigated the function of SsAtg1 to explore the function of the autophagy pathway in S. sclerotiorum. Deficiency of SsAtg1 inhibited autophagosome accumulation in the vacuoles of nitrogen-starved cells. Notably, ΔSsAtg1 was unable to form sclerotia and displayed defects in vegetative growth under conditions of nutrient restriction. Furthermore, the development and penetration of the compound appressoria in ΔSsAtg1 was abnormal. Pathogenicity analysis showed that SsAtg1 was required for full virulence of S. sclerotiorum. Taken together, these results indicate that SsAtg1 is a core autophagy-related gene that has vital functions in nutrient utilization, sclerotia development and pathogenicity in S. sclerotiorum.

The bore hole is sealed from a sealing hole: the surrounding coal fracture permeability and grout cementation form a new consolidated body and coal material. In this paper, the characteristics of the macroscopic compressive strength, microscopic interface bending, porosity, and fractal dimension of the consolidated body were studied, and the structure strength relationship between loading rates, porosity, fractal dimension, and uniaxial compressive strength (UCS) was established. The results show that the loading rates had a great and consistent effect on the macro- and micro-mechanical properties of the consolidated body. Macroscopically, in the range of 0.1~0.4 mm/min, the UCS and elastic modulus of the solidified body increased with the increase in the loading rate, and there was a critical loading rate (η = 0.4 mm/min). At the microscale, with the increase in loading rates, the interface bending phenomenon, porosity, fractal dimension, and UCS of the grout and coal were consistent, showing a trend of increasing first and then decreasing. The fractal dimension was linearly correlated with the UCS and porosity. The loading rates, porosity, fractal dimension, and UCS had a multivariate nonlinear regression distribution.

The compaction and re-crushing characteristics of crushed gangue are important factors which affect the quality and effectiveness of the filling of the quarry. To study the compaction and re-crushing characteristics of the gangue particles, continuous grading and intermittent grading of two different structures were designed to study the bulk gangue particle size distribution. By conducting a side-limited uniaxial compression test on the crushed gangue, the compaction deformation parameters and particle re-crushing parameters of the samples under different axial pressure and grading conditions were calculated, the interaction between compaction and re-crushing was determined, and a compaction-re-crushing model of the crushed gangue was established. The following conclusions were obtained, (1) the axial displacement increment and fractal dimension of the graded crushed gangue are closely related to the graded structure of the skeletal particles; (2) the compaction stage of the graded crushed gangue can be divided into a fast compaction stage, a slow compaction stage, and a stable compaction stage—the fast compaction stage is significantly elastic, the slow compaction stage is more plastic, and the stable stage behavior approaches that of the original rock body; (3) the degree of crushing of the graded crushed gangue increases with an increase in axial stress, and the re-crushing of the specimen mainly occurs in the slow compaction stage; (4) the compaction-crushing-fractal evolution of the graded crushed gangue in the lateral limit compression process is established as the line of questioning. The physical significance of the parameters in the equation is discussed in this paper. The study can provide theoretical support and engineering guidance for the precise filling of a quarry and the prevention of later collapse.

Soil treatment with disinfectants has been used for controlling soilborne phytopathogens. Besides suppressing specific pathogens, how these disinfectants impact soil health, especially soil microbial communities, is yet to be systemically determined. The objectives of this study were to examine the effects of three representative disinfectants, including the dazomet fumigant, fenaminosulf fungicide, and kasugamycin antibiotic on chemical properties, enzymatic activities, and microbial communities in soil for cucumber cultivation. Results showed that 14 days after soil treatment with these chemicals, residual content of dazomet and kasugamycin quickly declined in soil and were undetectable, while fenaminosulf residues were found at 0.48 ± 0.01 mg/kg. Total nitrogen and total carbon increased in soil after dazomet treatment. Urease and sucrase activities were significantly restrained after disinfectant application. The disinfectants did not significantly change the taxon of predominant bacteria and fungi but altered the relative abundance and diversity of soil microbiome, as well as microbial interspecific relationships. Moreover, cucumber cultivation enhanced the overall soil microbial diversity and enzymatic activities, which diminished the difference of soil microbiome among four treatments. The difference in soil microbial diversity among the four treatments became smaller after planting cucumber. Thus, soil microbial communities were affected by soil disinfectants and gradually recovered by cucumber application.

Abstract Background KH-type splicing regulatory protein (KHSRP) plays an important role in cancer invasion, but the relevant mechanism is not well known. In the present study, we investigated the function and potential molecular mechanism of KHSRP in non-small cell lung cancer (NSCLC) metastasis and elucidated its clinical significance. Methods Isobaric tags for relative and absolute quantitation and the SWATH™ approach were combined with nanoliquid chromatography-tandem mass spectrometry analysis to identify metastasis-associated nucleoproteins in NSCLC. Real-time PCR and Western blot were used to screen for metastasis-associated candidate molecules. Gene knockdown and overexpression were used to investigate their functions and molecular mechanisms in lung cancer cells. Coimmunoprecipitation (Co-IP) experiments were performed to identify the interactions between candidate molecules and their interacting proteins. Gene expression and its association with multiple clinicopathologic characteristics were analyzed by immunohistochemistry (IHC) and Western blot in human lung cancer specimens. Results KHSRP was identified as a metastasis-associated candidate molecule. In NSCLC cell lines, knockdown of KHSRP significantly reduced lung cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas overexpression of KHSRP did the opposite. Mechanistically, the protein heterogeneous nuclear ribonucleoprotein C (C1/C2) (HNRNPC) was identified to interact with KHSRP using Co-IP experiments. In NSCLC cell lines, overexpression of HNRNPC significantly promoted lung cancer cell proliferation, migration, and invasion in vitro and in vivo. KHSRP and HNRNPC may induce human lung cancer cell invasion and metastasis by activating the IFN-α-JAK-STAT1 signaling pathway. Drastically higher expression levels of KHSRP and HNRNPC were observed in lung cancer tissues compared to those in adjacent noncancerous tissues. Increased KHSRP and HNRNPC expression was significantly associated with advanced tumor stages and metastasis (both lymph node and distant). Kaplan-Meier survival analysis showed that patients with high KHSRP and HNRNPC expression levels were predicted to have the shortest survival times and to have a poor prognosis. Conclusions KHSRP plays an important role in NSCLC metastasis and may serve as a potential prognostic marker and novel therapeutic target for lung cancer metastasis treatment.

Sorting nexins are a conserved protein family involved in many cellular processes in fungi, and the function of sorting nexin Snx4 (Atg24) and Snx41 (Atg20) in Cochliobolus heterostrophus was not clear. The ΔChsnx4 and ΔChsnx41 mutants were generated by a PCR-based marker method to determine the roles of Snx4 and Snx41 in reproductive development, stress adaption, and virulence in C. heterostrophus. Compared with the wild-type strain, the ΔChsnx4 and ΔChsnx41 mutants exhibited obvious changes in vegetative growth and in morphology of conidia. In addition, the conidiation, appressorium formation, and virulence of snx4 and snx41 mutants were dramatically reduced. Moreover, ΔChsnx4 and ΔChsnx41 mutants were more sensitive to oxidative stress (menadione and H2O2), cell wall integrity stress (Congo red and calcofluor white), fungicides, and isothiocyanates. All the phenotypes mentioned above were restored in complemented strains. In addition, ChSnx4 and ChSnx41 were proven to interact with each other through yeast two-hybrid. Taken together, these findings indicated that ChSNX4 and ChSNX41 were important for fungal growth, asexual development, stress adaption, and virulence in C. heterostrophus.

Higher plants and some algae convert the absorbed light into chemical energy through one of the most important organelles, chloroplast, for photosynthesis and store it in the form of organic compounds to supply their life activities. However, more and more studies have shown that the role of chloroplasts is more than a factory for photosynthesis. In the process of light conversion to chemical energy, any damage to the components of chloroplast may affect the photosynthesis efficiency and promote the production of by-products, reactive oxygen species, that are mainly produced in the chloroplasts. Substantial evidence show that chloroplasts are also involved in the battle of plants and microbes. Chloroplasts are important in integrating a variety of external environmental stimuli and regulate plant immune responses by transmitting signals to the nucleus and other cell compartments through retrograde signaling pathways. Besides, chloroplasts can also regulate the biosynthesis and signal transduction of phytohormones, including salicylic acid and jasmonic acid, to affect the interaction between the plants and microbes. Since chloroplasts play such an important role in plant immunity, correspondingly, chloroplasts have become the target of pathogens. Different microbial pathogens target the chloroplast and affect its functions to promote their colonization in the host plants.

Buckwheat is an important cereal crop with high nutritional and health value. Buckwheat disease greatly affects the quality and yield of buckwheat. The real-time monitoring of disease is an essential part of ensuring the development of the buckwheat industry. In this research work, we proposed an automated way to identify buckwheat diseases. It was achieved by integrating a convolutional neural network (CNN) with the image processing technology. Firstly, the proposed approach would detect the buckwheat disease area accurately. Then, to improve the accuracy of classification, a two-level inception structure was added to the traditional convolutional neural network for accurate feature extraction. It also helps to handle low-quality image problems, which includes complex imaging environment and leaf crossing in sampling buckwheat image, etc. At the same time, instead of the traditional convolution, the convolution based on cosine similarity was adopted to reduce the influence of uneven illumination during the imaging. The experiment proved that the revised convolution enabled better feature extraction within samples with uneven illumination. Finally, the experiment results showed that the accuracy, recall, and F1-measure of the disease detection reached 97.54, 96.38, and 97.82%, respectively. For identifying disease categories, the mean values of precision, recall, and F1-measure were 84.86, 85.78, and 85.4%. Our method has provided important technical support for realizing the automatic recognition of buckwheat diseases.

Magnaporthe oryzae is a fungal pathogen that causes rice blast, a highly destructive disease. In the present study, the bacteria strain GS-1 was isolated from the rhizosphere soil of ginseng and identified as Bacillus velezensis through 16S rRNA gene sequencing, whole genome assembly, and average nucleotide identity analysis. B. velezensis strain GS-1 exhibited significant antagonistic activity to several plant fungal pathogens. Through whole genome sequencing, 92 Carbohydrate-Active Enzymes and 13 gene clusters that encoded for secondary metabolites were identified. In addition, strain GS-1 was able to produce the lipopeptide compounds, surfactin, fengycin, and plantazolicin. The inhibitory effects of lipopeptide compounds on M. oryzae were confirmed, and the antagonistic mechanism was explored using transcriptomics and metabolomics analysis. Differential expressed genes (DEGs) and differential accumulated metabolites (DAMs) revealed that the inhibition of M. oryzae by lipopeptide produced by GS-1 downregulated the expression of genes involved in amino acid metabolism, sugar metabolism, oxidative phosphorylation, and autophagy. These results may explain why GS-1 has antagonistic activity to fungal pathogens and revealed the mechanisms underlying the inhibitory effects of lipopeptides produced by GS-1 on fungal growth, which may provide a theoretical basis for the potential application of B. velezensis GS-1 in future plant protection.

Lithium nickel manganese cobalt oxide (NMC) cathodes are of great importance for the development of lithium ion batteries with high energy density. Currently, most commercially available NMC products are polycrystalline secondary particles, which are aggregated by anisotropic primary particles. Although the polycrystalline NMC particles have demonstrated large gravimetric capacity and good rate capabilities, the volumetric energy density, cycling stability as well as production adaptability are not satisfactory. Well-dispersed single-crystalline NMC is therefore proposed to be an alternative solution for further development of high-energy-density batteries. Various techniques have been explored to synthesize the single-crystalline NMC product, but the fundamental mechanisms behind these techniques are still fragmented and incoherent. In this manuscript, we start a journey from the fundamental crystal growth theory, compare the crystal growth of NMC among different techniques, and disclose the key factors governing the growth of single-crystalline NMC. We expect that the more generalized growth mechanism drawn from invaluable previous works could enhance the rational design and the synthesis of cathode materials with superior energy density.

The karst collapse pillar (KCP) is a common geological structure in the coal mines of northern China. KCPs contain many fractured coal rocks, which can easily migrate under the action of high-pressure water. The destruction or instability of the cementation structure between the rocks can directly induce coalmine water-inrush accidents. To study the seepage stability of cemented and fractured coal rock under triaxial pressures, a self-designed triaxial seepage testing system was used and the permeability k and non-Darcy factor β of the cemented and fractured coal rock were tested. Furthermore, the 1D non-Darcy seepage equations were used to calculate the evolution criteria of the seepage loss stability. The results show the following: (1) The cemented structure in the KCP under the triaxial pressures can be easily destroyed. The damaged coal and rock body mainly exists in bulk form, and the permeability depends mainly on the effective stress of the particles. (2) The seepage process in the KCP structure is a combination of pore flow, fracture flow, and pipe flow, and the transition of the seepage state is closely related to the change in the magnitude of β. (3) Under the long-term effect of confined underground water, the migration of small fractured particles in the KCP will increase the structural porosity. If the parameter βk2 reaches the threshold value, the seepage system will evolve into a pipeline flow state, eventually causing a water-inrush accident.

Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels.