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Given the problem that the existing source code loophole detection methods did not explicitly maintain the semantic information related to the loophole in the source code, which led to the difficulty of feature extraction of loo-phole statements and the high false positive rate of loophole detection, a source code loophole detection method based on feature dependency graph was proposed.First, extracted the candidate loophole statements in the function slice, and gen-erated the feature dependency graph by analyzing the control dependency chain and data dependency chain of the candi-date loophole statements.Secondly, the word vector model was used to generate the initial node representation vector of the feature dependency graph.Finally, a loophole detection neural network oriented to feature dependence graph was constructed, in which the graph learning network learned the heterogeneous neighbor node information of the feature de-pendency graph and the detection network extracted global features and performed loophole detection.The experimental results show that the recall rate and F1 score of the proposed method are improved by 1.50%～22.32% and 1.86%～16.69% respectively, which is superior to the existing method.

Stochastic parallel gradient descent (SPGD) is the most frequently used optimization algorithm for correcting wavefront distortion in the wavefront sensorless adaptive optics(WFS-Less AO)system. However, the convergence speed of the SPGD algorithm becomes slow rapidly as increasing of distortion, and the probability of falling into local optimum is rising owing to the fixed gain coefficient. It cannot meet the requirement of real-time wavefront distortion correction. Therefore, a novel algorithm is proposed in this paper, called as adaptive gain stochastic parallel gradient descent (AGSPGD) based on the AMSGrad optimizer in the deep learning, to improve the convergence speed of the algorithm and to reduce the probability of falling into local optimum. The AGSPGD algorithm adopts the first-order moment and the second-order moment of the performance index, which are combined to dynamically adjust the gain. The numerical simulations are completed in this article. The results of ${\bm{D}}/\ {{\bm{r}}}_0 = \ 2.5$ conditions demonstrate that the AGSPGD can reduce the number of iterations by 25%, and the probability of the algorithm falling into local optimum is reduced from 16% to 4%. In addition, the AGSPGD still outperforms the SPGD as ${\bm{D}}/{{\bm{r}}}_0$ increasing.

Abstract While the terrestrial base stations (TBSs) in the fifth‐generation (5G) network provide high throughput for the conventional terrestrial users (TUs), it is still challenging for the network to support massive TUs and unmanned aerial vehicles (UAVs) simultaneously due to the complicated air–ground channel and severe interference. In this paper, the deployment of a high‐altitude platform (HAP) as a supplement for the terrestrial networks, in which the HAP and TBSs serve TUs and UAVs simultaneously in a joint manner, is studied. The novel network has two challenges. First, the deployment of the HAP, which is a new degree of freedom, should be optimized considering the terrestrial network. Second, the channel of the joint HAP and TBS network that serves multiple TUs and UAVs concurrently is complicated, and the resource allocation of the network should be designed. To tackle the above two challenges, a joint resource allocation and HAP deployment problem are formulated, and a gradient‐and‐matching‐based algorithm is proposed to solve it efficiently. Simulation results show that the HAP and the proposed algorithm enhance the sum‐rate of the network by over 30%, and the average data rate of both the TUs and the UAVs can be effectively improved.

Given the problems that the current APT attack detection methods were difficult to perceive the diversity of stage flow features and generally hard to detect the long duration APT attack sequences and potential APT attacks with different attack stages, a multi-stage detection method for APT attack based on sample feature reinforcement was proposed.Firstly, the malicious flow was divided into different attack stages and the APT attack identification sequences were constructed by analyzing the characteristics of the APT attack.In addition, sequence generative adversarial network was used to simulate the generation of identification sequences in the multi-stage of APT attacks.Sample feature reinforcement was achieved by increasing the number of sequence samples in different stages, which improved the diversity of multi-stage sample features.Finally, a multi-stage detection network was proposed.Based on the multi-stage perceptual attention mechanism, the extracted multi-stage flow features and identification sequences were calculated by attention to obtain the stage feature vectors.The feature vectors were used as auxiliary information to splice with the identification sequences.The detection model’s perception ability in different stages was enhanced and the detection accuracy was improved.The experimental results show that the proposed method has remarkable detection effects on two benchmark datasets and has better effects on multi-class potential APT attacks than other models.

With the rapid advancement of fundamental theories and computing capacity, deep learning techniques have made impressive achievements in many fields.Differential equations, as an important tool for describing the physical world, have long been a focus of interest for researchers in various fields.Combining the two methods has gained popularity as a study issue in recent years.Since deep learning can efficiently extract features from large amounts of data and differential equations can reflect objective physical laws, the combination of the two can effectively improve the generalization ability of deep learning and enhance the interpretability of deep learning.Firstly, the problem of solving differential equations by deep learning was briefly introduced.Then, two types of deep learning methods for solving differential equations were introduced: data-driven and physical-informed methods.Furthermore, the applications of relevant deep learning-based solving methods were discussed.Meanwhile, DeDAO (differential equations DAO), a foundation model for artificial intelligence for science, was proposed to address existing challenges.Finally, conclusions of deep learning methods for solving differential equations were presented.

Abstract Mitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3), a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3 (microtubule-associated protein 1 light chain 3), while PP1/2A (protein phosphatase 1/2A) represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.

Abstract Objectives This study is aimed to evaluate if automated urine sediment analysis UN2000 can be used to screen lupus nephritis. Methods UN2000 was used to examine 160 urine samples from patients with systemic lupus erythematosus and 124 urine samples from Lupus nephritis. The result of protein/creatinine ratio(P/C) and renal tubular epithelial cells (RTEC) were evaluated. With biochemical analysis and microscopic examination as the gold standard, the Kappa consistency test was used to analyze the accuracy of P/C and RTEC. Analysis was to evaluate the accuracy of P/C single item or RTEC single item and both screening lupusnephritis. Results The consistency of P/C and the gold standard, and that of RTEC and the gold standard are respectively strong and good (0.858 vs. 0.673). The specificity, positive predictive value, and coincidence were the highest when P/C ≥ 2 + was set as the only screening standard for lupus nephritis. When the standard was selected between P/C ≥ 2 + or RTEC > 2.8 cells/µl, the sensitivity and negative predictive value were the highest. Conclusion UN 2000 can be used to screen lupus nephritis by detecting P/C and RTEC.

Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (10B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil 7Li nuclei (10B [n, α] 7Li). Therefore, the most important part in BNCT is to selectively deliver a large number of 10B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges.

Summary: Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.

Background: Colon adenocarcinoma (COAD) is a common malignancy with high morbidity and mortality rates. The immune system plays a crucial role in CRC development and progression, making it a potential therapeutic target. In this study, we analyzed transcriptomic data from CRC patients to investigate immune infiltration and identify potential therapeutic targets.Method and results: we used CIBERSORT to analyze the immune infiltration in COAD samples and found that the high infiltration of M2 macrophages and neutrophils was associated with poor prognosis. Next, we identified NR4A1 as a potential therapeutic target based on its protective effect in two predict models. Using cancer therapeutics response analysis, we found that high expression levels of NR4A1 were sensitive to OSI-930, a tyrosine kinase inhibitor with anti-tumor effects.Conclusion: Our findings suggest that targeting NR4A1 with OSI-930 may be a promising therapeutic strategy for COAD patients with high levels of immune infiltration. However, further studies are needed to investigate the clinical efficacy of this approach.

WUSCHEL-related homeobox (WOX) transcription factors (TFs) play a crucial role in regulating plant development and responding to various abiotic stresses. However, the members and functions of WOX proteins in Pinus massoniana remain unclear. In this study, a total of 11 WOX genes were identified, and bioinformatics methods were used for preliminary identification and analysis. The phylogenetic tree revealed that most PmWOXs were distributed in ancient and WUS clades, with only one member found in the intermediate clade. We selected four highly conserved WOX genes within plants for further expression analysis. These genes exhibited expressions across almost all tissues, while PmWOX2, PmWOX3, and PmWOX4 showed high expression levels in the callus, suggesting their potential involvement in specific functions during callus development. Expression patterns under different abiotic stresses indicated that PmWOXs could participate in resisting multiple stresses in P. massoniana. The identification and preliminary analysis of PmWOXs lay the foundation for further research on analyzing the resistance molecular mechanism of P. massoniana to abiotic stresses.

In order to reduce the effect of nonlinear friction and time-varying factors on the servo system of a computer numerical control (CNC) machine tool and improve its motion control accuracy, this paper uses an adaptive sliding mode control (ASMC) method based on model reference adaptive control (MRAC). The method adopts ASMC in the control outer loop and obtains the optimal control parameters by making the sliding mode control (SMC) law continuous and adaptively estimating the control parameters. At the same time, MRAC is used in the control inner loop to enhance the “invariance” of the controlled object so that the switching gain of SMC can satisfy the disturbance matching condition even under lesser conditions. Simulation and experimental results show that compared with the traditional SMC, the ASMC based on MRAC proposed in this paper effectively reduces the influence of nonlinear friction on the system performance, and the reduction in following error reaches 71.2%, which significantly improves the motion control accuracy of the control system. The spectral analysis of the following errors shows that the maximum magnitude reduction rate of the high-frequency chattering is 89.02%, which significantly reduces the effect of the high-frequency chattering and effectively improves the stability performance of the control system.

The Internet of vehicles, the most important component of intelligent transportation system (ITS) in the future, is one of the most important technologies to achieve smart traffic and convenient travel for the people.With the vigorous development and continuous utilization of sensing and communication functions, the combination of these two functions, that is, integrated sensing and communications (ISAC) technology of vehicular communication networks, has become the current research hotspot and is of great significance to the development of ITS.Firstly, two different models of ISAC system, i.e., functional ISAC and signaling ISAC were defined and differentiated.Then, for the two different ISAC models, the existing works were reviewed and analyzed comprehensively.Finally, the future development directions and technical challenges of ISAC design in vehicular communication networks were proposed.

Strain engineering is effective to improve the carrier mobility of semiconductor materials. Here, the authors demonstrate lattice strain-induced mobility enhancement of an azobenzene compound under photoisomerization and its application in large-scale flexible organic field-effect transistors.

To help investors understand the profound impact of Taoism in society, this study systematically evaluates its impact on digital inclusive finance and its mechanisms. Based on theoretical analysis, this study makes an empirical analysis based on Chinese city-level data from 2011 to 2019, in which the core explanatory variable “Taoism” encompasses the Taoist places of religious activity in each city, and the explained variable “digital inclusive finance” is measured using the Peking University digital inclusive finance index. The results of this study show that (1) the Taoist concept of inaction requires people to put aside selfishness and prejudice, and treat others fairly, rationally, and leniently, which is conducive to the development of digital inclusive finance; (2) the dialectical wisdom of Taoism inspires positive psychological capital, which is conducive to digital and traditional technological innovations and the development of digital inclusive finance; and (3) further research indicates that Taoism encourages Chinese-listed enterprises to actively fulfill their social responsibilities by promoting the development of digital inclusive finance. This study can help global investors understand China’s traditional culture and capital markets and serve as the first step in exploring Taoist economics.

BackgroundEpicardial adipose tissue (EAT) acts as an active immune organ and plays a critical role in the pathogenesis of heart failure (HF). However, the characteristics of immune cells in EAT of HF patients have rarely been elucidated.MethodsTo identify key immune cells in EAT, an integrated bioinformatics analysis was performed on public datasets. EAT samples with paired subcutaneous adipose tissue (SAT), heart, and peripheral blood samples from HF patients were collected in validation experiments. T cell receptor (TCR) repertoire was assessed by high-throughput sequencing. The phenotypic characteristics and key effector molecules of T lymphocytes in EAT were assessed by flow cytometry and histological staining.ResultsCompared with SAT, EAT was enriched for immune activation-related genes and T lymphocytes. Compared with EAT from the controls, activation of T lymphocytes was more pronounced in EAT from HF patients. T lymphocytes in EAT of HF patients were enriched by highly expanded clonotypes and had greater TCR clonotype sharing with cardiac tissue relative to SAT. Experiments confirmed the abundance of IFN-γ+ effector memory T lymphocytes (TEM) in EAT of HF patients. CCL5 and GZMK were confirmed to be associated with T lymphocytes in EAT of HF patients.ConclusionEAT of HF patients was characterized by pronounced immune activation of clonally expanded IFN-γ+ TEM and a generally higher degree of TCR clonotypes sharing with paired cardiac tissue.

A comprehensive dynamic model is introduced try to further reduce dimensional errors of micromilled micro straight thin walls based on an in-process cutting parameter compensation device. First, a mathematical model is established to predict the dynamic elastic deformation of the thin walls in the micromilling process. Next, the radial deformation and the runout of the cutter are modeled. Then, the comprehensive in-process parametric compensation model and strategy are established. Finally, a real-time in-process cutting force measurement and cutting parameter compensation device is applied to the micromilling system and thin wall fabrication experiments have been conducted. It shows that the comprehensive dimensional error model and iterative compensation method are effective, and the dimension and shape precision of the micro straight thin wall has been obviously improved after the compensation of the radial cutting depth. The average relative errors have been reduced from 6.86% to 1.10%∼1.70%. The in-process compensation method introduced in this study is efficient and convenient as long as compensation strategies are integrated in the controlling unit for a specific micromilling process.

Abstract Background In research on new drug discovery, the traditional wet experiment has a long period. Predicting drug–target interaction (DTI) in silico can greatly narrow the scope of search of candidate medications. Excellent algorithm model may be more effective in revealing the potential connection between drug and target in the bioinformatics network composed of drugs, proteins and other related data. Results In this work, we have developed a heterogeneous graph neural network model, named as HGDTI, which includes a learning phase of network node embedding and a training phase of DTI classification. This method first obtains the molecular fingerprint information of drugs and the pseudo amino acid composition information of proteins, then extracts the initial features of nodes through Bi-LSTM, and uses the attention mechanism to aggregate heterogeneous neighbors. In several comparative experiments, the overall performance of HGDTI significantly outperforms other state-of-the-art DTI prediction models, and the negative sampling technology is employed to further optimize the prediction power of model. In addition, we have proved the robustness of HGDTI through heterogeneous network content reduction tests, and proved the rationality of HGDTI through other comparative experiments. These results indicate that HGDTI can utilize heterogeneous information to capture the embedding of drugs and targets, and provide assistance for drug development. Conclusions The HGDTI based on heterogeneous graph neural network model, can utilize heterogeneous information to capture the embedding of drugs and targets, and provide assistance for drug development. For the convenience of related researchers, a user-friendly web-server has been established at http://bioinfo.jcu.edu.cn/hgdti .

Poly[ADP‐ribose] polymerase (PARP) inhibitors can block DNA single‐strand damage repair and subsequently increase double‐stranded breaks (DSBs) by reducing the activity of the PARP1 protease and by preventing the PARP1 protein from dissociating from chromatin. Tumors with the BRCA mutation are particularly sensitive to PARP inhibitors. So far, PARP inhibitors (Olaparib) have been used to treat pancreatic cancer patients with BRCA mutation. However, these patients are prone to PARP inhibitor resistance. Our previous studies suggest that fructose‐1,6‐bisphosphatase 1 (FBP1) is responsible for the sensitivity to various anticancer agents, such as gemcitabine or mitogen‐activated protein kinase kinase (MEK) inhibitors. In this study, we demonstrate that FBP1 regulates the sensitivity to PARP inhibitors in pancreatic cancer. Then, we showed that nuclear FBP1 is responsible for this process by interacting with DNA (cytosine‐5)‐methyltransferase 1 (DNMT1) and trapping PARP1 in chromatin. Moreover, we revealed that ubiquitin carboxyl‐terminal hydrolase 7 (USP7) binds to and induces the deubiquitination of FBP1, which prevented FBP1 from translocating to the nucleus. Finally, we demonstrated that USP7 inhibitors enhanced the antitumor effect of PARP inhibitors in an FBP1‐dependent manner. Collectively, our results identify a novel USP7–FBP1–DNMT1 signaling axis in pancreatic cancer, which might indicate that USP7 inhibitors and PARP inhibitors might have more powerful antitumor effects than PARP inhibitors alone in pancreatic cancer patients.

Abstract Background Adaptive resistance and side effects of sorafenib treatment result in unsatisfied survival of patients with hepatocellular carcinoma (HCC). Palmitoyl-protein thioesterase 1 (PPT1) plays a critical role in progression of various cancers. However, its role on prognosis and immune infiltrates in HCC remains unclarified. Methods By data mining in the Cancer Genome Atlas databases, the role of PPT1 in HCC were initially investigated. Furthermore, HCC cell lines Hep 3B and Hep 1-6 were treated with DC661 or siRNA against PPT1. The biological function of PPT1 was determined by CCK-8 test, colony formation assay, TUNEL staining, immunofluorescence staining, Western blot test, and PI-Annexin V apoptosis assays in vitro. Animal models of subcutaneous injection were applied to investigate the therapeutic role of targeting PPT1. Results We found that PPT1 levels were significantly upregulated in HCC tissues compared with normal tissues and were significantly associated with a poor prognosis. Multivariate analysis further confirmed that high expression of PPT1 was an independent risk factor for poor overall survival of HCC patients. We initially found that PPT1 was significantly upregulated in sorafenib-resistant cell lines established in this study. Upon sorafenib treatment, HCC cells acquired adaptive resistance by inducing autophagy. We found that DC661, a selective and potent small-molecule PPT1-inhibitor, induced lysosomal membrane permeability, caused lysosomal deacidification, inhibited autophagy and enhanced sorafenib sensitivity in HCC cells. Interestingly, this sensitization effect was also mediated by the induction mitochondrial pathway apoptosis. In addition, the expression level of PPT1 was associated with the immune infiltration in the HCC tumor microenvironment, and PPT1 inhibitor DC661 significantly enhanced the anti-tumor immune response by promoting dendritic cell maturation and further promoting CD8+ T cell activation. Moreover, DC661 combined with sorafenib was also very effective at treating tumor models in immunized mice. Conclusions Our findings suggest that targeting PPT1 with DC661 in combination with sorafenib might be a novel and effective alternative therapeutic strategy for HCC.

The dynamic process behind the low-speed drop-impact erosion remains challenging to understand. Cheng et al. develop a method of high-speed microscopy, revealing the fast propagation of self-similar stress maxima underneath impacting drops and the formation of surface waves on impacted substrates.

Abstract Objectives Kashgar prefecture is an important transportation and trade hub with a high incidence of tuberculosis. The following study analyzed the composition and differences in Mycobacterium tuberculosis (M.tb) lineage and specific tags to distinguish the lineage of the M.tb in Kashgar prefecture, thus providing a basis for the classification and diagnosis of tuberculosis in this area. Methods Whole-genome sequencing (WGS) of 161 M.tb clinical strains was performed. The phylogenetic tree was constructed using Maximum Likelihood (ML) based on single nucleotide polymorphisms (SNPs) and verified through principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. Results M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%). Moreover, the 3 lineages were subdivided into 11 sublineages, among which lineage 2 included lineage 2.2.2/Asia Ancestral 1 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 2 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 3 (18/73, 24.66%), and lineage 2.2.1-Modern Beijing (39/73, 53.42%). Lineage 3 included lineage 3.2 (14/52, 26.92%) and lineage 3.3 (38/52, 73.08%), while lineage 4 included lineage 4.1 (3/36, 8.33%), lineage 4.2 (2/36, 5.66%), lineage 4.4.2 (1/36, 2.78%), lineage 4.5 (28/36, 77.78%) and lineage 4.8 (2/36, 5.66%), all of which were consistent with the PCA results. One hundred thirty-six markers were proposed for discriminating known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) was lower compared to other regions in China (54.35%-90.27%), while the composition of Lineage 3 (32.30%) was much higher than in other regions of China (0.92%-2.01%), but lower compared to the bordering Pakistan (70.40%). Conclusion Three lineages were identified in M.tb clinical strains from Kashgar prefecture, with 136 branch-specific SNP. Kashgar borders with countries that have a high incidence of tuberculosis, such as Pakistan and India, which results in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces of China.

N6-methyladenosine (m6A) is becoming one of the most important RNA modifications in plant growth and development, including defense, cell differentiation, and secondary metabolism. YT521-B homology (YTH) domain-containing RNA-binding proteins, identified as m6A readers in epitranscriptomics, could affect the fate of m6A-containing RNA by recognizing and binding the m6A site. Therefore, the identification and study of the YTH gene family in Liriodendron chinense (L. chinense) can provide a molecular basis for the study of the role of m6A in L. chinense, but studies on the YTH gene in L. chinense have not been reported. We identified nine putative YTH gene models in the L. chinense genome, which can be divided into DF subgroups and DC subgroups. Domain sequence analysis showed that the LcYTH protein had high sequence conservation. A LcYTH aromatic cage bag is composed of tryptophan and tryptophan (WWW). PrLDs were found in the protein results of YTH, suggesting that these genes may be involved in the process of liquid–liquid phase separation. LcYTH genes have different tissue expression patterns, but the expression of LcYTHDF2 is absolutely dominant in all tissues. In addition, the expression of the LcYTH genes is changed in response to ABA and MeJA. In this study, We identified and analyzed the expression pattern of LcYTH genes. Our results laid a foundation for further study of the function of the LcYTH gene and further genetic and functional analyses of m6A RNA modification in forest trees.

The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.

In recent years, the role of video games in enhancing brain plasticity and learning ability has been verified, and this learning transfer is known as the “learning to learn” effect of video game training. At the same time, against the background of healthy lighting, the influence of non-visual effects of light environment on the human rhythmic system has been gradually confirmed. As a special operation form of Visual Display Terminal (VDT) operation, video game training has a high dependence on VDT equipment and the VDT screen, and the background usually has a huge difference in brightness. Compared with the light environment of ordinary operation space, the light environment of VDT operation space is more complex. This complex light environment's non-visual effects cause human emotions, alertness, fatigue, cognitive ability, and other changes, which may affect the efficiency of the “learning to learn” effect of video game training. This article focuses on the impact of the light environment in the VDT workspace on the “learning to learn” effect of video game training. It first traces the factors that trigger the “learning to learn” effect of video game training, that is, the improvement of people's attention, perception, and cognitive ability. Then, the influencing mechanism and the evaluation method of the VDT workspace space light environment on the human rhythm system are discussed based on the basic theory of photobiological effect. In addition, the VDT display lighting light time pattern, photophysical properties, regulation, and protection mechanism on the human rhythm system are studied to demonstrate the VDT workspace light environment's special characteristics. Finally, combined with the progress of artificial lighting technology and the research results of health lighting, given the “learning to learn” effect of video game training, some thoughts on the design of the light environment of the workplace and future research directions are presented.

Monitoring the physiological changes of organelles is essential for understanding the local biological information of cells and for improving the diagnosis and therapy of diseases. Currently, fluorescent probes are considered as the most powerful tools for imaging and have been widely applied in biomedical fields. However, the expected targeting effects of these probes are often inconsistent with the real experiments. The design of fluorescent probes mainly depends on the empirical knowledge of researchers, which was inhibited by limited chemical space and low efficiency. Herein, we proposed a novel multilevel framework for the prediction of organelle-targeted fluorescent probes by employing advanced artificial intelligence algorithms. In this way, not only the targeting mechanism could be interpreted beyond intuitions but also a quick evaluation method could be established for the rational design. Furthermore, the targeting and imaging powers of the optimized and synthesized probes based on this methodology were verified by quantitative calculation and experiments.

When ascending to high altitude, it is a rigorous challenge to people who living in the low altitude area to acclimatize to hypoxic environment. Hypoxia exposure can cause dramatic disturbances of metabolism. This longitudinal cohort study was conducted to delineate the plasma metabolomics profile following exposure to altitude environments and explore potential metabolic changes after return to low altitude area. 25 healthy volunteers living in the low altitude area (Nor; 40m) were transported to high altitude (HA; 3,650m) for a 7-day sojourn before transported back to the low altitude area (HAP; 40m). Plasma samples were collected on the day before ascending to HA, the third day on HA(day 3) and the fourteenth day after returning to low altitude(14 day) and analyzed using UHPLC-MS/MS tools and then the data were subjected to multivariate statistical analyses. There were 737 metabolites were obtained in plasma samples with 133 significantly changed metabolites. We screened 13 differential metabolites that were significantly changed under hypoxia exposure; enriched metabolic pathways under hypoxia exposure including tryptophan metabolism, purine metabolism, regulation of lipolysis in adipocytes; We verified and relatively quantified eight targeted candidate metabolites including adenosine, guanosine, inosine, xanthurenic acid, 5-oxo-ETE, raffinose, indole-3-acetic acid and biotin for the Nor and HA group. Most of the metabolites recovered when returning to the low altitude area, however, there were still 6 metabolites that were affected by hypoxia exposure. It is apparent that high-altitude exposure alters the metabolic characteristics and two weeks after returning to the low altitude area a small portion of metabolites was still affected by high-altitude exposure, which indicated that high-altitude exposure had a long-term impact on metabolism. This present longitudinal cohort study demonstrated that metabolomics can be a useful tool to monitor metabolic changes exposed to high altitude, providing new insight in the attendant health problem that occur in response to high altitude.

The transcription factor Brn4 exhibits vital roles in the embryonic development of the neural tube, inner ear, pancreas islet, and neural stem cell differentiation. Our previous studies have shown that Brn4 promotes neuronal differentiation of hippocampal neural stem cells (NSCs). However, its mechanism is still unclear. Here, starting from the overlapping genes between RNA-seq and ChIP-seq results, we explored the downstream target genes that mediate Brn4-induced hippocampal neurogenesis. There were 16 genes at the intersection of RNA-seq and ChIP-seq, among which the Lama2 and Samsn1 levels can be upregulated by Brn4, and the combination between their promoters and Brn4 was further determined using ChIP and dual luciferase reporter gene assays. EdU incorporation, cell cycle analysis, and CCK-8 assay indicated that Lama2 and Samsn1 mediated the inhibitory effect of Brn4 on the proliferation of hippocampal NSCs. Immunofluorescence staining, RT-qPCR, and Western blot suggested that Lama2 and Samsn1 mediated the promoting effect of Brn4 on the differentiation of hippocampal NSCs into neurons. In conclusion, our study demonstrates that Brn4 binds to the promoters of Lama2 and Samsn1, and they partially mediate the regulation of Brn4 on the proliferation inhibition and neuronal differentiation promotion of hippocampal NSCs.

Weakly cemented medium-grained sandstone in Ordos mining area of China is widely distributed under phreatic water. The creep behavior of saturated rock is important for the stability of water-resisting strata. In this paper, creep mechanical properties of saturated medium-grained sandstone were studied by triaxial rheological test. The results showed that medium-grained sandstone only shows attenuation creep and stable creep under low stress level, and accelerated creep occurs when axial load reaches about 75% of instantaneous compressive strength. The rock samples exhibit volume dilatancy under most loading levels and finally shear fracture. The failure mechanism is the dislocation separation of mineral particles. Based on the energy dissipation theory, the damage evolution equation was modified and introduced into the Burgers model, which can accurately describe the rheological behavior of saturated medium-grained sandstone. The modified model was used to predict the crack initiation time under different deviatoric stresses, which can provide guidance for early warning of water-resisting rock stability.

Immune checkpoint blockade (ICB) therapy has emerged as a promising approach for the treatment of hepatocellular carcinoma (HCC), especially for advanced and metastatic tumors. However, many HCC patients do not respond due to low tumor antigen exposure and the highly immunosuppressive tumor microenvironment (ITM). Chemotherapy and photodynamic therapy are considered to be effective methods for eliciting anti-tumor immune responses. Here, we developed a light-triggered nanoplatform Ce6@PMTKP for combination chemo-photodynamic therapy and the potentiation of ICB therapy. The Ce6@PMTKP micelles entrapped Ce6 for photodynamic therapy, while PMTKP contains the ROS-sensitive paclitaxel (PTX) polymeric prodrug for chemotherapy. The Ce6@PMTKP micelles showed excellent tumor accumulation and light-triggered drug release. Compared with chemotherapy or photodynamic therapy alone, the combination therapy mediated by Ce6@PMTKP was found to be more effective in the elimination of tumors, induction of immunogenic cell death, and the promotion of dendritic cell maturation and cytotoxic T lymphocytes infiltration, thus mitigating ITM immunosuppression. When combined with anti-PD-L1 immunotherapy, the Ce6@PMTKP micelles induced complete regression of primary tumors and effectively inhibited distant metastatic tumors by enhancing anti-tumor immune responses.

Abstract Autonomous motion and motility are hallmarks of active matter. Active agents, such as biological cells and synthetic colloidal particles, consume internal energy or extract energy from the environment to generate self-propulsion and locomotion. These systems are persistently out of equilibrium due to continuous energy consumption. It is known that pressure is not always a state function for generic active matter. Torque interaction between active constituents and confinement renders the pressure of the system a boundary-dependent property. The mechanical pressure of anisotropic active particles depends on their microscopic interactions with a solid wall. Using self-propelled dumbbells confined by solid walls as a model system, we perform numerical simulations to explore how variations in the wall stiffness influence the mechanical pressure of dry active matter. In contrast to previous findings, we find that mechanical pressure can be independent of the interaction of anisotropic active particles with walls, even in the presence of intrinsic torque interaction. Particularly, the dependency of pressure on the wall stiffness vanishes when the stiffness is above a critical level. In such a limit, the dynamics of dumbbells near the walls are randomized due to the large torque experienced by the dumbbells, leading to the recovery of pressure as a state variable of density.

Abstract Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. Methods Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. Results IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. Conclusions This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.

Despite recent progress in cancer treatment, the prognosis of patients with pancreatic cancer still remains poor. Pancreatic tumors are reported to display high molecular heterogeneity. Elucidating the molecular mechanisms underlying pancreatic cancer progression is essential for improving patient treatment and survival. The overexpression of E3 ubiquitin ligase mind bomb 1 (MIB1) was previously described in pancreatic cancer cells, where it enhanced tumor cell proliferation. However, the role of MIB1 in pancreatic cancer progression remains elusive. In the present study, we confirmed that MIB1 expression is elevated in pancreatic cancer tissues and that high levels of MIB associate with unfavorable prognosis. Overexpression of MIB1 enhanced proliferation and invasion of pancreatic cancer cells both in vitro and in vivo. We further investigated the molecular mechanisms downstream of MIB1 and observed for the first time that MIB1 targets suppressor of tumorigenicity 7 protein (ST7), previously described as suppressor of tumorigenicity, for proteasomal degradation. Furthermore, we found that ST7 suppressed tumor growth by downregulating IQ motif containing GTPase activating protein 1 (IQGAP1) in pancreatic tumor cells. Thus, these data show that MIB1 promotes pancreatic cancer progression by inducing ST7 degradation followed by downregulation of IQGAP1 in pancreatic cancer cells. In conclusion, our research shows that the MIB1/ST7/IQGAP1 axis is essential for pancreatic cancer progression, and MIB1 inhibition may serve as a novel therapeutic strategy in patients with pancreatic cancer.

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. Results The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. Conclusion Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC. Graphical Abstract

Genes containing GTP_EFTU domain mainly express elongation factors (EF), Small GTPases, and GTP-binding proteins, which are closely related to protein synthesis, extension and ATP synthesis. In this study, we identified 39 genes containing GTP_EFTU domains from peppers. The evolutionary trees constructed from capsicum, Arabidopsis, rice, and tomato are mainly divided into 7 subfamilies. Using PacBio (Pacific Biosciences) sequencing and assembly data, we extracted these 39 gene sequences, from which 25 genes had alternative splicing. Particularly, the Capana08g000545 had 16 alternative splicing processes. Accordingly, we performed promoter sequence analysis, subcellular location prediction, the expression analysis of different tissues and periods, and also the GO (Gene ontology) analysis of co-expressed genes. Lastly we did the qRT-PCR analysis in 5 stages of pepper fruit development. These analyses revealed important structural and functional information for the identified 39 genes that contain GTP_EFTU domains, providing important references for further follow-up experiments to verify the genes function on plants or their unique roles in peppers.

The electrohydrodynamic direct-writing (EDW) technology has been widely used in the integration of micro-/nano-systems. However, the complex model is a critical obstacle for the uniformity and controllability of the EDW fiber. It is difficult to gain an appropriate control strategy for position accuracy and the industrial application of EDW technology. Fuzzy control has a significant effect on objects in which the mathematical models are complex and the dynamic characteristics are difficult to capture. In this paper, the integrated fuzzy control method based on the jet mode and the electrospinning current was designed for the EDW system, and four groups of experiments were set up in different control schemes: the open-loop control, the current control, the jet mode control, and the integrated control. With the integrated control, the volatility percentage of the fiber spacing decreased from 23% to 9.7%, and the volatility percentage of the electrospinning current decreased from 35% to 14%. The fuzzy control shows dramatic effects on the uniformity and the deposition precision of the EDW fibers, which will extend the fields of application of EDW.

The intuitive and effective haptic feedback interaction is essential for human–machine interfaces. However, most current commercial haptic feedback solutions are rigid, simplex, and insufficient to fully immerse users in virtual and teleoperated environments. Here, we report the design, fabrication and performance of a low-cost and lightweight self-sensing actuator (SenAct) that provides accurate force and vibration feedback to recreate the tactile perception. The SenAct shows good performance such as fast response (10 ms), high robustness (>10,000 cycles), and large output force (up to 1.55 N) with high controllable resolution (up to 0.02 N) based on the real-time closed-loop control. It is capable of providing the corresponding haptic feedback to the wearer through external force or vibration signal input. With this prototype, we presented a haptic feedback glove that supports precise operation by enhancing immersion and comprehensive sensation. Furthermore, we demonstrated it could shape appropriate interaction in different scenarios, including touching or grasping objects in virtual reality and teleoperation, illustrating its potential applications in human-in-loop interaction system and metaverse.

This paper attempts to realize the balance between humans and ecology in designing the nighttime light environment of urban parks by clarifying the influence of nighttime artificial light on the ecosystem of urban parks. Firstly, we reviewed the effects of nighttime artificial light on individual predation and reproduction of animals and personal growth and reproduction of plants. Secondly, we discuss the impact of individual changes caused by artificial lighting on ecosystem function at the ecosystem and analyze its advantages and disadvantages. The results showed that nighttime artificial light had a double-sided impact on the ecosystem, which would hurt the ecosystem function, but had a positive effect on the green space, which lacked natural light and had high plant density. This paper focuses on the areas with increased application of artificial lighting and rich species of animals and plants in night cities, such as urban forest parks and urban green spaces. It discusses how to reduce the intrusion of artificial lighting on ecosystems and how to make better use of the positive effect of artificial light.

Neuroinflammation is a common pathogenetic sign of depression and is closely linked to the development of depression. Many clinical anti-inflammatory drugs act as antidepressants by reducing the neuroinflammatory response. Previous research found that gypenosides and their bioactive compound gypenoside-14 (GP-14) had neuroprotective effects against hypoxia-induced injury and reduced neuroinflammation-related high-altitude cerebral edema. Here we investigated the effects of GP-14 on the lipopolysaccharide (LPS)-induced depression-like behavior model. LPS (0.5 mg/kg) was injected into mice intraperitoneally for 7 consecutive days to induce depression-like behavior, which is considered a model for the exacerbation of depression. GP-14 in the amount of 100 mg/kg was simultaneously administered by gavage for 7 days. In the LPS-induced depression model, GP-14 not only attenuated depression-like behavior but also improved the anxiety-like behavior of the mice. Additionally, GP-14 treatment mitigated learning and cognitive decline in depressed mice. ELISA and immunofluorescence staining results revealed that GP-14 inhibited the upregulation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and suppressed the activation of astrocytes induced with LPS, indicating its potent anti-inflammatory effect. GP-14 pretreatment in C8 cells and primary astrocytes can inhibit the activation of the NF-κB signaling pathway and downregulate the levels of pro-inflammatory factors. In summary, our findings showed that GP-14 had significant anti-inflammation and anti-depression properties; thus, GP-14 could be a promising lead compound for treating depression.

How to balance the artistry and comfort of the light environment in an architecturalized immersive new media public art installation (AINMPAI) to ensure the safety of the audiences’ visual safety has become a new issue. The lack of corresponding lighting design standards makes this issue more challenging. This paper explores the appropriate luminance range of the irregularly curved LED screens of the AINMPAI with high-luminance natural light as the background. The influence of the audience behavior mode on the brightness threshold of the LED screens in the AINMPAI under the background of Internet communication is discussed. Through software simulation and field measurement, the effectiveness of the design measures based on the local characteristics of the work is verified. The overall average luminance, the regional luminance, the partial luminance, and the corresponding luminance contrast of the inner screen surface were measured at every 10° change in the solar altitude angle during daytime. The nighttime light environment parameters and the temperature of the device throughout the day were also measured. A total of 487 visitors were interviewed for subjective evaluation of the comfort of the light and thermal environments. The results show that: (1) the overall average luminance cannot wholly describe the actual luminance of the critical parts of the special-shaped curved screen in the device and that two indicators, the regional luminance and the partial average luminance, need to be added; (2) the maximum brightness limit of LED screens in the daytime can be 1000 cd/m2 but at night it should be controlled within 200 cd/m2; (3) natural light is the main factor that causes the high average brightness and low contrast of the daytime device screen; (4) the recommended indicators for such artistic installations should balance the absolute values of average brightness, artistic effect, and transmission priority. This study can provide foundational data and a methodological reference for establishing AINMPAI light environment design guidelines or recommended standards based on audiences’ visual safety.

ABSTRACT: Purpose: This study was to investigate the work experience of newly recruited male nurses during the COVID-19 pandemic. Methods: With a phenomenological approach, this qualitative study was adopted semistructured interviews by phone or video calls. A total of 9 male nurses newly recruited for the COVID-19 wards in Chinese hospitals were interviewed for this study. And Colaizzi's method was applied for evaluation in the data analysis. Results: Based on our findings, three themes were extracted. First, the newly recruited male nurses showed negative emotions at the beginning of COVID-19 epidemic, which was caused by changes in working conditions and content, but also prompted the nurses to change the way of coping with the crisis. Second, they gradually mastered the working skills and psychological training to cope with COVID-19 and developed a positive attitude toward life and a high sense of professional responsibility. Finally, we learned about their needs to respond to public health emergencies such as the COVID-19 pandemic. Conclusion: COVID-19 is a disaster for all of humanity. The newly recruited male nurses are an important force in emergency rescue. Although they suffered from short-term negative emotions, they quickly adapted to the crisis. In order to better prepare for future emergencies, the disaster response capacity of newly recruited male nurses needs to be further improved. In addition, newly recruited male nurses have a strong demand for timely and personalized career development guidance.

In this paper, we investigate the intersection traffic management for connected automated vehicles (CAVs). In particular, a decentralized autonomous intersection management scheme that takes into account both the traffic efficiency and scheduling flexibility is proposed, which adopts a novel intersection–vehicle model to check conflicts among CAVs in the entire intersection area. In addition, a priority-based collision-avoidance rule is set to improve the performance of traffic efficiency and shorten the delays of emergency CAVs. Moreover, a multi-objective function is designed to obtain the optimal trajectories of CAVs, which considers ride comfort, velocities of CAVs, fuel consumption, and the constraints of safety, velocity, and acceleration. Simulation results demonstrate that our proposed scheme can achieve good performance in terms of traffic efficiency and shortening the delays of emergency CAVs.

Developing materials with high biocompatibility is key to improve the artificial medical implant. Bulk metallic glasses (BMGs) based on Zr have been proposed as promising biomaterials. The present work investigated the biocompatibility of Zr46(Cu4.5/5.5Ag1/5.5)46Al8 BMG in depth by using several biomedical methods. Our results indicate that the BMG material treated by micro-arc oxidation technology (MAO) has good biocompatibility comparable to as-cast Ti–6Al–4V alloy. MAO introduced high density of pores and hydroxyapatite in the surface layer. At a moderate MAO voltage, 350 V, a surface with the highest density of uniform size pores and suitable surface roughness was obtained. The BMG material treated at 350 V thus demonstrated the strongest platelet adhesion, the best blood compatibility, the weakest oral mucous membrane irritation, the weakest inflammation, and fastest recovery of injured cells during the subcutaneous implantation tests, in comparison with the samples treated at other voltages. These results may advance the applications of Zr-based BMGs as biomaterials in future.

Carbon fiber composites are widely used in aerospace, military and other fields. Their tensile properties are mainly borne by interwoven carbon fibers, wear of carbon fiber seriously affects the mechanical properties of carbon fiber composite material. In the process of prefab weaving, the end of the weaving needles carrying the movement of the carbon fibers causes serious wear on the fibers. In order to study the effect of weaving needle parameters and process parameters on the wear of carbon fiber bundle, a friction and wear experimental device of carbon fiber bundle was made. According to the research results, the corresponding parameters were optimized to reduce the wear of the carbon fiber bundle during weaving. The wear of carbon fiber bundle modified by imidazoline surfactant was also studied. The effects of fiber tension, weaving angle and needle end angle on the wear of carbon fiber bundle were studied by the control variable method. The wear of carbon fiber bundle was characterized by image binarization, SEM scanning and residual fracture strength detection. The residual fracture strength of the optimized weaving needles was increased by 23.92%, the residual fracture strength of the modified carbon fiber bundle increased by 14.57% after needle end wear.

This research reviewed the mechanics and gas desorption properties of intact coal, and tested the crushing work ratios of different intact coals, and then, studied the stress conditions for the failure or crushing of intact coal and the gas demand for the pulverization of intact coal particles. When a real-life outburst case is examined, the required minimum stress for intact coal outburst is estimated. The study concludes that the crushing work ratios of three intact coal samples vary from 294.3732 to 945.8048 J/m2. For the real-life case, more than 2300 MJ of transport work is needed, and 10062.09, 7046.57 and 5895.47 m3 of gas is required when the gas pressure is 1, 2 and 3 MPa, respectively. The crushing work exceeds the transport work and even reaches 13.96 times of the transport work. How to provide such an enormous crushing work is an energy-limiting factor for the outburst in intact coal. The strain energy is needed for the crushing work, and the required minimum stress is over 54.35 MPa, even reaching 300.44 MPa. These minimum stresses far exceed the in-situ vertical and horizontal stresses that can be provided at the 300–700 m mining depth range.

Intervertebral disc degeneration (IVDD) is a predominant cause of disc herniation and is widespread worldwide. Inflammatory responses, mitochondrial dysfunction, and extracellular matrix degradation are known to be involved in IVDD. Scutellarin, an active ingredient extracted from Erigeron breviscapus (Vaniot) Ha, Hand-Mazz, is reported to exhibit therapeutic potential in several degenerative diseases by suppressing inflammation and regulating metabolism. However, whether scutellarin can improve IVDD remains unknown. Human primary nucleus pulposus cells (HNPCs) were cultured and stimulated with TNF-α in the presence or absence of scutellarin. Furthermore, a rat needle puncture model was established, and scutellarin was injected into the IVD to verify its protective function against IVDD. Scutellarin attenuated the inflammatory reaction and retained the production of major IVD components both in vitro and in vivo. Mechanistically, scutellarin reduced the amount of reactive oxygen species (ROS), alleviated mitochondrial damage, and decreased the expression levels of apoptosis-related biomarkers upon stimulation with TNF-α. In addition, scutellarin antagonized the activation of the nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway and suppressed the activity of the NLRP3 inflammasome mediated by TNF-α. This study reveals that scutellarin protects against degeneration of nucleus pulposus cells, which might shed light on treatment of IVDD in the future.

Abstract Background Clostridioides difficile usually causes intestinal infections. However, a 75-year-old lady had a periprosthetic joint infection due to this microorganism. We report a C. difficile infection of a prosthetic hip joint. Such an infection is rarely reported around the world. Case presentation The elder female patient presented with a 2-year history of right hip pain with movement restriction. Her right leg was shorter than another. The skin around the right hip joint was red and swollen without sinus. Her lab test result showed elevator ESR and CRP. Her X-ray film showed a massive bone defect. The patient had a total hip arthroplasty 16 years ago and had a revision 5 years ago. During this hospitalization, her cultures of the synovial fluid and tissue repeatedly grew C. difficile. She improved following two-stage revision surgery and antibiotic treatment. The patient has no recurrence of infection after a one-year follow-up. Conclusion A rapid and accurate sample collection is significant for culture results, making an outstanding contribution to the successful treatment.