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Herein, we employed a central pattern generator (CPG), a spinal cord neural network that regulates lower-limb gait during intra-spinal micro-stimulation (ISMS). Particularly, ISMS was used to determine the spatial distribution pattern of CPG sites in the spinal cord and the signal regulation pattern that induced the CPG network to produce coordinated actions. Based on the oscillation phenomenon of the single CPG neurons of Van der Pol (VDP) oscillators, a double-cell CPG neural network model was constructed to realise double lower limbs, six-joint modelling, the simulation of 12 neural circuits, the CPG loci characterising stimuli-inducing alternating movements and changes in polarity stimulation signals in rat hindlimbs, and leg-state change movements. The feasibility and effectiveness of the CPG neural network were verified by recording the electromyographic burst-release mode of the flexor and extensor muscles of the knee joints during CPG electrical stimulation. The results revealed that the output pattern of the CPG presented stable rhythm and coordination characteristics. The 12-neuron CPG model based on the improved VDP equation realised single-point control while significantly reducing the number of stimulation electrodes in the gait training of spinal cord injury patients. We believe that this study advances motor function recovery in rehabilitation medicine.

Background: Although the majority of members belonging to the small GTPase Ras superfamily have been studied in several malignancies, the function of RBJ has remained unclear, particularly in non-small cell lung cancer (NSCLC). Objective: The research aims to determine the function of RBJ in NSCLC. Methods: The levels of RBJ protein in tumor tissue and para-carcinoma normal tissue were ascertained via immunohistochemistry (IHC). The growth, migration, and invasion of NSCLC cells were assessed by 5-ethynyl-2-deoxyuridine (EdU) assay, colony formation, cell counting kit-8 (CCK8), transwell and wound healing assays. Furthermore, a nude mouse xenograft model was established to study the function of RBJ in tumorigenesis in vivo. Results: The IHC analysis revealed that the protein levels of RBJ were notably increased in tumor tissue and positively associated with the clinical stage. In addition, the knockdown of RBJ restrained the growth, invasion, and migration of NSCLC cell lines by inhibiting the epithelial-mesenchymal transition (EMT) through the MEK/ERK signaling pathway. Accordingly, opposite results were observed when RBJ was overexpressed. In addition, the overexpression of RBJ accelerated tumor formation by A549 cells in nude mice. Conclusion: RBJ promoted cancer progression in NSCLC by activating EMT via the MEK/ERK signaling. Thus, RBJ could be used as a potential therapeutic against NSCLC.

When a restrictor is coupled with groove microstructures, the analysis on the flow-field status of the restrictor’s lubricating gas film becomes more difficult, especially in theoretical calculation. In this study, a single-orifice planar restrictor with double-ring-grooves was researched. First, the theoretical mathematical analysis and calculation of the pressure and temperature distributions of the lubricating gas film, were conducted based on the proposed analysis method of proportional assignation and resynthesis (PAR) along with the finite difference method. Then, the computational fluid dynamics (CFD) simulations based on the simple model were conducted, the results of which show the agreement with the theoretical analysis. Finally and more importantly, experiments were carried out well by using a self-made micro-flow field parameter measurement device (MFFPMD), which verifies the theoretical calculation and the CFD simulation results. The PAR method can be applied in other structures of restrictors, and the experimental study could facilitate the research of the stability of the lubricating gas film.

BackgroundThe association between brain metabolic change and ischemic stroke has attracted a lot of attention in the research community. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging is widely used to measure the metabolism. In experiments, ischemic stroke is usually induced through middle cerebral artery occlusion (MCAO), and quality assessment of this procedure is of vital importance. However, an assessment method based on FDG PET images is still lacking. Herein, we propose an image feature-based protocol to assess the quality of the procedure.MethodsWe performed permanent MCAO to a total of 161 Sprague-Dawley rats. FDG micro-PET images were acquired both before and after the MCAO procedure. Triphenyl tetrazolium chloride (TTC) staining was also conducted to obtain ground truth of the infarct volume. After preprocessing of the PET images, a combination of 3D scale invariant feature transform (SIFT) and support vector machine (SVM) was applied to extract features and train a classifier that can assess the quality of the MCAO procedure.Results106 rats and 212 images were used as training data to construct the classification model. The SVM classifier achieved over 98% accuracy in cross validation. 10 rats with TTC results showing infarction in the ipsilateral brain region served as validation data. Their images were tested by the classifier and all of them were categorized into the correct group. Finally, the remaining 45 rats from a separate experiment were treated as independent test data. The prediction accuracy for these 90 images reached the level of 91%. An online interface was constructed for users to upload their images and obtain the assessment results.ConclusionThis feature-based protocol provides a convenient, accurate and reliable tool to assess the quality of the MCAO procedure in FDG PET study.

To discuss the impact of chemoradiotherapy (CRT) on the survival of patients with stage III endometrial cancer (EC) compared with chemotherapy (CT) alone.Articles involving adjuvant CRT versus CT on survival in stage III EC were retrieved from PubMed and EMBASE. Hazard ratios (HRs) of overall survival (OS) and relapse-free survival (RFS) were collected and pooled, and publication bias was measured by Begg's and Egger's test. Quality of researches was measured by the Newcastle-Ottawa scale and the modified Jadad scale.Eleven were included in the statistical analysis. A significant advantage of CRT over CT on OS was shown (HR 0.59, 95% CI 0.49-0.70). Further subgroup analysis suggested the advantage was mostly associated with stage IIIC (HR 0.63, 95% CI 0.52, 0.76]). A similar result favoring CRT was also reached on RFS (HR 0.66, 95% CI 0.47-0.93). No significant publication bias was observed.CRT was associated with a better OS and RFS than CT alone in stage III EC patients.

Polysaccharides coded as CP were extracted from Athyrium Multidentatum (Doll.) Ching and then fractionated into five fractions (FP-1, FP-2, FP-3, FP-4 and FP-5). A purified polysaccharide designated as FP-3-4 was prepared from FP-3 by Sephadex G-100 column chromatography. Chemical analysis disclosed that CP and these fractions were heteropolysaccharides and mainly composed of glucose, galactose, arabinose, mannose, rhamnose, xylose, fucose, ribose and uronic acid with different molar ratios. They presented different images of SEM. FP-3-4 was highly branched polymers with sixteen types of linkages. The in vitro immunomodulatory results stated that CP and these fractions could promote macrophage proliferation, enhance macrophage phagocytosis and increase the production of NO, TNF-α, IFN-γ, IL-1β, IL-6, IL-10 and IL-2, indicating remarkable immune enhancement activities. RNA sequencing analysis revealed that CP and FP-3 induced macrophage activation mainly through MAPK and alternative NF-κΒ signaling pathways via CD14/TLR4 and Dectin-2 receptors, which were verified by RT-qPCR and western blot.

The potentiostat is critical in the development of electrochemical systems; however, its cumbersome detection and high cost considerably limit its large-scale application. To provide an affordable alternative to developing countries and resource-constrained areas, this study designs an electrochemical detection system based on smartphones, which uses Bluetooth Low Energy to convert open-source potentiostat data based on PSoC-5LP. The WeChat application on the smartphone provides an interface for entering experimental parameters and visualizing the results in real time. The smartphone-based electrochemical detection system has a simple design and reduces the size (10?3?0.3 cm3) and the cost of the hardware ($ 18). The system performs the most commonly used cyclic voltammetry for electrochemical detection, with results that are comparable to those obtained using a commercial potentiostat and an error rate of 1.3 %. In the classical teaching experiment of electrochemical determination of ascorbic acid in orange juice samples, the measured value of the system is 0.367?0.012 mg/mL, compared with the standard reference value of 0.37 mg/mL, which is obviously a convincing value. Therefore, this system is a low-cost, reliable alternative to a potentiostat for research, education or product integration development.

Background Abdominal aortic aneurysm (AAA) is a serious life-threatening cardiovascular disease that occurs in middle-aged and elderly people. Previous experimental studies have suggested that autophagy may be involved in the pathological process of AAA, but the pathogenesis of autophagy in AAA is unclear. We aim to identify and validate key potential autophagy-related genes involved in AAA through bioinformatics analysis to further elucidate the mechanisms of autophagy dysregulation in AAA. Methods The GSE57691 microarray dataset was downloaded from the Gene Expression Omnibus database (GEO), including 49 AAA samples and 10 normal aortic samples. 232 autophagy-related genes were obtained from the Human Autophagy Database (HADb). The GSE57691 dataset was crossed with the autophagy gene set to screen for differentially expressed autophagy-related genes (DE-ARGs) involved in AAA. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DE-ARGs in AAA using R software. Protein-protein interaction (PPI) networks were constructed using the STRING database, significant gene cluster modules were identified using the MCODE Cytoscape plugin, and hub genes in AAA associated DE-ARGs were screened using the CytoHubba Cytospace plugin. Meanwhile, DE-ARGs were calculated using the least absolute shrinkage selection algorithm (LASSO) algorithm. By crossing the LASSO calculation results and hub genes, the final key genes were identified, whose expression levels were further validated in AAA aortic samples by qRT-PCR. Finally, the transcription factor regulatory networks and target drugs of these key genes were predicted by the JASPAR database and DsigDB database, respectively. Results A total of 57 DE-ARGs were identified in aortic samples from normal controls and AAA. GO and KEGG analysis showed that these 57 DE-ARGs involved in AAA were particularly enriched in macroautophagy, PI3K-Akt signaling pathway, AMPK signaling pathway, and apoptosis. PPI results indicated that the 57 DE-ARGs interacted with each other. A total of 6 key genes (ATG5, ATG12, MTOR, BCL2L1, EIF4EBP1, and RPTOR) were identified using CytoHubba and LASSO algorithms. Detection of clinical samples by qRT-PCR indicated that ATG5, ATG12, BCL2L1, EIF4EBP1, and RPTOR expression was consistent with bioinformatic analysis. A regulatory network containing 6 key genes and 30 transcription factors was constructed through the JASPAR database. Finally, four targeted autophagy regulatory drugs, rapamycin, Temsirolimus, Sorafenib, and NVP-BEZ235, were screened by the DsigDB database. Conclusions Bioinformatics analysis identified 57 autophagy-related genes that may be involved in AAA. ATG5, ATG12, BCL2L1, EIF4EBP1and RPTOR may serve as potential drug targets and biomarkers as they regulate autophagy. These results expand the understanding of autophagy dysfunction in AAA and may contribute to the diagnosis and prognosis of AAA.

Droplet controllable operation has wide applications in microfluidics, biomedicine, microreactors, and other fields. Droplets can spontaneously transfer from a high-energy state to a low-energy state, but how to reverse transfer the droplets is a difficult task. In this article, we use a special hydrophilic-hydrophobic interphase structure (HHIS) to achieve this reverse transfer. We specifically study the critical conditions under which droplet transfer can be achieved. The length of the hydrophilic surface in this structure and the hydrophilic/hydrophobic properties of the surface must be in the appropriate range. Based on this, an optimized structure used to transfer droplets was designed. Finally, we carried out research on biological applications and successfully achieved the transfer of droplets from zebrafish eggs and zebrafish larvae. This unique method is low-cost, biofriendly, and highly applicable to various surfaces, illustrating the great potential in chemical and biological analysis.

As we all know, chopsticks can hold food, so can we use this method to carry Newtonian fluids such as droplets? This paper studies the process of this transfer and uses this method to realize the manipulation of open microfluidics by robots. To realize this transfer operation, we first analyzed the force of droplets in this chopstick-like structure and found that the bidirectional movement of droplets in this structure can be achieved by changing the structural parameters. Afterward, the whole process of the transfer of droplets using the chopstick-like structure was analyzed, and the parameter requirements for realizing this transfer were determined. The research in this paper provides a theoretical basis for the controllable manipulation of droplets which can be widely used in unmanned laboratories.

Cr(VI) pollution is a growing problem that causes the deterioration of the environment and human health. We report the development of an effective adsorbent for the removal of Cr(VI) from wastewater. N-doped cellulose-based hydrothermal carbon (N-CHC) was prepared via a two-step hydrothermal method. The morphology and structural properties of N-CHC were investigated by various techniques. N-CHC has many O and N groups, which are suitable for Cr(VI) adsorption and reduction. Intermittent adsorption experiments showed that N-CHC had an adsorption capacity of 151.05 mg/g for Cr(VI) at pH 2, indicating excellent adsorption performance. Kinetic and thermodynamic analyses indicates that the adsorption of Cr(VI) on N-CHC follows a monolayer uniform adsorption process, which is a spontaneous endothermic process dominated by chemical interaction and limited by diffusion within particles. In a multi-ion system (Pb

Pneumocystis pneumonia (PCP) is an opportunity acquired infection, which is usually easy to occur in patients with AIDS, organ transplantation, and immunosuppressive drugs. The prevention and treatment must be necessary for PCP patients with immunocompromise. And the oxidants are currently a typical regimen, including sulfanilamide, dapsone, primaquine, etc. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked gene-disease that affects about 400 million people worldwide. The lack of G6PD in this population results in a decrease in intracellular glutathione synthesis and a weakening of the detoxification ability of the oxidants. As a result, oxidants can directly damage haemoglobin in red blood cells, inducing methemoglobin and hemolysis. When patients with G6PD deficiency have low immunity, they are prone to PCP infection, so choosing drugs that do not induce hemolysis is essential. There are no clear guidelines to recommend the drug choice of this kind of population at home and abroad. This paper aims to demonstrate the drug choice for PCP patients with G6PD deficiency through theoretical research combined with clinical cases.

Restoring the motor function of paralyzed limbs has always been an important aim in the field of biomedical engineering. In view of the discovery of the repeatable experimental phenomenon that positive and negative stimulation pulses applied to specific points, identified as central pattern generator (CPG) sites, could induce switching of the movement patterns of bilateral hindlimbs, an improved Hodgkin–Huxley (HH) neuron model was established by introducing the electric field effect principle. A CPG neural network model comprising 12 neural units in six joints of the bilateral hindlimbs was modeled. The simulation results showed the alternating movement patterns of the bilateral hindlimbs through the action potential release of extensor and flexor neurons. The explosive electromyogram of the gastrocnemius (GM) and quadriceps femoris (QF) when stimulating the CPG sites with intraspinal micro-stimulation (ISMS) was consistent with the action potential diagram of the flexor and extensor neurons obtained via simulation. Our research considers the neural network model of electric field radiation, which can facilitate a deep understanding of the dynamic characteristics of neurons in the electric field environment, and verifies the correlation between the location of CPG sites, stimulus polarity and movement patterns to induce alternating left–right coordinated movements.

Xiaowang Guo,1 Xiaoyan Shen,2 Zhijun Yong3 1Department Emergency Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of China; 2Department of Neurology Medicine, The Fourth People’s Hospital of Shaanxi, Xi’an City, Shaanxi Province, 710000, People’s Republic of China; 3Department of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaCorrespondence: Zhijun YongDepartment of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaEmail zhijunyongmedicine@163.comBackground: Ischemic stroke is a devastating disease with very limited therapeutics. Although miR-101 has been reported to play crucial roles in various human diseases, its role in ischemic stroke remains unclear.Methods: Ischemia-reperfusion (I/R) injury neuronal cells and rat model with I/R injury were constructed. Viability and apoptosis of I/R model cells with miR-101 overexpression or downregulation were evaluated. Potential targets of miR-101 were predicted using miRNA database microRNA.org and confirmed using luciferase reporter assays. Meanwhile, JAK2 and p-STAT3 protein levels were evaluated by Western blot. In addition, rescue experiments (silencing of JAK2) were applied to determine the role of miR-101 in cerebral I/R injury.Results: MiR-101 was significantly downregulated in OGD/R-induced neuronal cells and brain tissues with I/R injury. MiR-101 overexpression (miR-101 mimics) significantly promoted viability and inhibited apoptosis of OGD/R-induced neuronal cells in vitro and efficiently protected rats from ischemic brain injury in vivo. By contrast, miR-101 inhibitor exacerbated growth defect, apoptosis, and ischemic brain injury. Luciferase reporter assay indicated that JAK2 was a direct target of mIR-101, and JAK2 silencing effectively reversed the miR-101 inhibitor-induced neuronal cell apoptosis in vitro and reduced cerebral infarction volume in vivo.Conclusion: Our study demonstrated that miR-101 efficiently protected neuronal cells from apoptosis and ischemic brain injury through regulating the JAK2/STAT3 signaling pathway, suggesting that miR-101 might be a potential target for treatment of ischemic stroke.Keywords: ischemic stroke, miR-101, JAK2/STAT3 signaling

Highlights in baryon decays

The aim of this study was to explore a suitable method for analyzing road transport accidents that involve hazardous materials and to explore the main factors that influence the occurrence of accidents of varying severity.The 2015-2019 reported crash data from the Ministry of Transport of the People's Republic of China were obtained, and road transport crashes involving hazardous materials were extracted as the analysis data. The dataset was classified into three injury severity categories: property damage only (PDO), injured (INJ), and fatal (FAT). A statistical model and three machine learning-based models were developed: a random parameters logit model (RPLM), multilayer perceptron (MLP), decision tree C5.0 (C5.0) and support vector machine (SVM). The four models were trained/estimated using the training/estimation dataset, and the best model was used to model accidents of the three different severity levels. The main factors that influence the occurrence of accidents at each crash severity level were obtained.C5.0 had the best modeling performance. The direct accident form (DAF), indirect accident form (IAF) and road segment (RS) were determined to be the critical determinants of PDO accidents. The DAF, IAF, road type, RS and time had a substantial effect on INJ accidents. The DAF, IAF, hazardous material type (HMT) and road surface condition were important factors in the occurrence of FAT accidents.Different data have unique characteristics, and the best modeling and analysis method should be chosen accordingly. The safety of road transport of hazardous materials in China is poor, and the losses caused by accidents are substantial. Strengthening the monitoring of travel speed and travel time; improving driver safety awareness, driving skills and the ability to mitigate emergencies; improving the configuration of vehicle safety equipment and the linkage with the control center and rescue center; improving the environmental differences between inside a tunnel and outside a tunnel; reducing the design of long downhill and steep slope sections; reducing the transport plan in unsafe environments; and improving the ability of road management to mitigate bad environments can be effective measures to reduce the severity of road transport accidents involving hazardous materials.

Objective This study aimed to describe the implementation of the surgical safety check policy and the surgical safety checklist for invasive procedures outside the operating room (OR) and evaluate its effectiveness. Methods In 2017, to improve the safety of patients who underwent invasive procedures outside of the OR, the hospital quality and safety committee established the surgery safety check committee responsible for developing a new working plan, revise the surgery safety check policy, surgery safety check form, and provide training to the related staff, evaluated their competency, and implemented the updated surgical safety check policy and checklist. The study compared the data of pre-implementation (Apr to Sep 2017) and two post-implementation phases (Apr to Sep 2018, Apr to Sep 2019). It also evaluated the number of completed surgery safety checklist, correct signature, and correct timing of signature. Results The results showed an increase in the completion rate of the safety checklist after the program implementation from 41.7% (521/1,249) to 90.4% (3,572/3,950), the correct rates of signature from 41.9% (218/521) to 99.0% (4,423/4,465), and the correct timing rates of signature from 34.4% (179/521) to 98.5% (4,401/4,465), with statistical significance (P Conclusion Implementing the updated surgery safety check significantly is a necessary and effective measure to ensure patient safety for those who underwent invasive procedures outside the OR. Implementing surgical safety checks roused up the clinical staff’s compliance in performing safety checks, and enhanced team collaboration and communication.

The study intends to investigate the regulation of syndecan-1 in human uterine leiomyoma cells. Human syndecan-1 levels were detected by Western blot in uterus leimyoma's tissue. The efficacy of syndecan-1 silencing on the cell proliferation, metalloproteinases and extracellular matrix were determined through Cell Counting Kit (CCK8) assay and Western blot assay, respectively. We compared the respective and combined effect of mifepristone and syndecan-1 on cell proliferation and the expression of metalloproteinases and extracellular matrix (ECM) in human uterine leiomyoma cells. The inhibitory effects of Syndecan-1 silencing on proliferation, ECM and Matrix Metalloproteinase (MMP) were observed in human uterine leiomyoma cells. Furthermore, syndecan-1 inhibition enhanced the effects of mifepristone against uterine leiomyoma cell proliferation. The expression of MMPs and ECM components in human uterine leiomyoma cells was decreased dramatically after syndecan-1 silencing, which was promoted after mifepristone treatment. Altogether, syndecan-1 silencing enhanced the efficacy of mifepristone on the uterine leiomyoma cell proliferation and ECM formation. Therefore, targeting syndecan-1 represents a novel therapeutic strategy to treat uterine leiomyoma.

To reduce the increasingly severe air pollution caused by rapid industrialization, China has introduced a National Industrial Relocation Demonstration Zones (NIRDZs) policy. This paper takes the NIRDZs as a quasi-natural experiment and employs the difference-in-differences (DID) method to test the effects of industrial relocation on air pollution based on panel data of 285 prefecture-level cities from 2003 to 2018. Results show that the NIRDZs have an inhibitory effect on SO2 emissions, although their local effect is significant in the first 5 years and their spillover effect only occurs within 50–100 km. Mechanism analysis reveals that the NIRDZs reduce air emissions by rationalizing and upgrading the industrial structure. Additionally, further discussions suggest that cities with moderate administrative areas and abundant natural resources should be prioritized as pilot cities, and industries including nonferrous metals, steel, automotive, new energy, new materials, and producer services should be designated as priority industries.

A spinal stimulator that can regulate hindlimb movements using monopolar stimulation has not been developed yet. Nevertheless, in a previous study, we found a specific central pattern generator site on the right side of the rat spinal cord. By stimulating these sites with certain pulse signals, the alternating movement of the hindlimb can be obtained using fewer electrodes. Therefore, in this research, considering the specific central pattern generator site as the target, functional electrical stimulation was performed on rats with spinal cord injury using monopolar stimulation. Angle sensors were used to track and capture the knee joint angle data of the right hindlimb; thus, the mapping relationship between the voltage amplitude and the knee angle parameters was established. Based on this relationship, the rats’ hindlimb were controlled. Compared with the traditional spinal stimulator, the proposed approach increases the gait feedback, requires fewer electrodes, and simplifies the timing of stimulation. The rats with spinal cord injury were subjected to stimulation training for half an hour every day for 28 consecutive days. The Basso, Beattie and Bresnahan score showed that 76% of the health level could be achieved on the 28th day. Finally, somatosensory evoked potential analysis showed that the measurement results were close to the standard value on the 28th day. This study lays a foundation for future rehabilitation research on the hindlimb.

Tumor necrosis factor α (TNF-α) has been demonstrated to be a therapeutic target for autoimmune diseases. However, this biological therapy exhibits some inevitable disadvantages, such as risk of infection. Thus, small-molecule alternatives by targeting TNF-α production signaling pathway are still in demand. Herein, we describe the design, synthesis, and structure-activity relationships of 3-aryindanone compounds regarding their modulation of TNF-α production. Among them

Intraspinal microstimulation (ISMS) is considered as a special functional electrical stimulation (FES) method. This method can restore the movement of paralyzed limbs in patients with spinal cord injury (SCI) using electrical stimulation of spinal cord. There is a special site for central pattern generator (CPG) in the spinal cord. The ISMS acts on the CPG site, and single electrode stimulation produces alternating motion in the hindlimbs of SCI rats. Based on the long short-term memory network (LSTM), a mapping model was established between the stimulation intensity of specific CPG sites and the angle of the knee joint to reflect the motor characteristics of the rat hindlimb. We proposed an LSTM-iterative learning control (ILC) strategy to form a closed-loop control to accurately control hindlimb movement. The proposed LSTM model fits the actual joint angle curve well, and the LSTM-ILC strategy can accurately regulate the hindlimb movement, allowing rats to perform rehabilitation training based on pre-set knee trajectories.

Objective. Arsenic trioxide (ATO) has been effectively used for the treatment of hematological malignancies and some solid tumors, while ATO effects were not tested clinically in epithelial ovarian cancer (EOC). Methods. Patients with primary or secondary platinum-resistant EOC were enrolled from October 2015 to December 2019. Patients were mainly treated with ATO-based combined sequential chemotherapy as follows: Regimen 1 (ATO combined taxanes weekly therapy); Regimen 2 (ATO + taxanes + 5-fluorouracil + adriamycin ± bevacizumab sequential chemotherapy), for 5 patients platinum-free interval >12 months, added oxaliplatin). Prespecified end points in this cohort included confirmed best overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results. A total of 33 patients were enrolled in this study. After a median follow-up time of 22.1 months (range 5.5–42.9 months), ORR was 42% and DCR was 85%. The overall PFS was 9.5 months (range 1–38.4 months). The main side effect was myelosuppression. Conclusions. ATO-based sequential combined chemotherapy is effective for primary and recurrent drug-resistant EOC patients in clinical phase II trials. The associated side effects could be controlled, while further study is needed.

Diabetic cardiovascular complications contribute more than half of diabetes mortality. Endothelial damage and subsequent pathological changes play a key role in this process. Phloretin, a plant-derived dihydrochalcone compound, was reported to have the activities in regulating metabolism homeostasis and anti-inflammation. However, its effects and the mechanism on early stage endothelial injury caused by diabetes are not clear yet. In our present study, human umbilical vein endothelial cells (HUVECs) were stimulated by high glucose or advanced glycation end products (AGEs) to induce endothelial damage, and streptozotocin (STZ) -induced diabetes mouse model was used for in vivo study. Our results showed that phloretin effectively reduced endothelial damage marker monocyte chemotactic protein-1 (MCP1) as well as pro-calcification factors bone morphogenetic protein-2 (BMP2) and receptor activator of NF-κB ligand (RANKL) expression, reversed the increased vimentin and decreased CD31 dose-dependently in vitro and in vivo. Phloretin had no effect on blood glucose level. However, it ameliorated endothelial injury and vascular fibrosis in diabetic mice. Further experiments revealed that phloretin could enhance AMP activated protein kinase (AMPK) activation and upregulate peroxidase proliferator activated receptor-gamma coactivator-lα (PGC1α) level, and inhibit the activation of TGFβ-Smad2-Snail signalling pathway which was abrogated by AMPK inhibitor, providing a rational mechanism that AMPK activation was required for the effects of phloretin on endothelial injury and endothelial-mesenchymal transformation (EndMT). Our data reveal a new role of phloretin in protection of diabetic endothelial damage via AMPK-dependent anti-EndMT activation, and also provide a potential therapeutic way for diabetic endothelial damage and its subsequent cardiovascular complications.

This paper examines the impact of economic policy uncertainty (EPU) on market‐driven common stock returns and individual‐driven idiosyncratic stock returns as well as explores the role of corporate environmental responsibility (CER) engagement on this impact based on a sample of 175 firms listed on Shanghai and Shenzhen 300 index from 2008 to 2016. The results show that an increase in EPU significantly reduces the market‐driven common stock returns but increases individual‐driven idiosyncratic stock returns. Further, EPU has a lower negative impact on the common stock returns of high‐CER firms comparing with low‐CER firms. EPU has a higher positive impact on idiosyncratic stock returns of high‐CER firms comparing with low‐CER firms. Overall, the findings of this paper extremely relevant for the government, investors and firm's managers and can be utilised for policy and investment decision‐making.

Background Systemic chemotherapy is often the last resort of advanced cutaneous T-cell lymphoma (CTCL). Tumor recurrence and adverse effects of systemic chemotherapy are the main limitations. Objective We aim to investigate the metabolic alterations in tumor cells after CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy. Methods and results In advanced CTCL, CHOP chemotherapy has no survival benefit and the duration of response is significantly inferior to other canonical treatments. HIF-1α is significantly elevated in lesions of advanced MF patients as well as tumor cell line Hut78 and tumor xenograft mice model. CHOP therapy also increased glycolytic activities in a HIF-1α-dependent manner. In CTCL xenograft tumor mice model, lesional cells showed a significant increase in IL-17F after chemotherapy, shifting toward a Th17 phenotype, which process is also regulated by HIF-1α. Echinomycin, HIF-1α inhibitor, was co-administered in xenograft tumor mouse models with CHOP and showed a significant reduction in tumor growth. Conclusion CHOP chemotherapy promotes glycolysis and IL-17 pathways in a HIF-1α-dependent fashion. Furthermore, HIF-1α blockade is promising as an accompanying agent in systemic chemotherapy for patients with advanced CTCL.

Myocardial infarction (MI) triggers an inflammatory reaction, in which macrophages are of key importance for tissue repairing. Infiltration and/or migration of macrophages into the infarct area early after MI is critical for infarct healing, vascularization, and cardiac function. Hydrogen sulfide (H2S) has been demonstrated to possess cardioprotective effects post MI and during the progress of cardiac remodeling. However, the specific molecular and cellular mechanisms involved in macrophage recruitment by H2S remain to be identified. In this study, the NaHS (exogenous sources of H2S) treatment exerted an increased infiltration of macrophages into the infarcted myocardium at early stage of MI cardiac tissues in both wild type (WT) and cystathionine-γ-lyase-knockout (CSE-KO) mice. And NaHS accelerated the migration of macrophage cells in vitro. While, the inhibitors not only significantly diminished the migratory ability in response to NaHS, but also blocked the activation of phospho-Src, -Pyk2, -FAK(397), and -FAK(925). Furthermore, NaHS induced the internalization of integrin β1 on macrophage surface, but, integrin β1 silencing inhibited macrophage migration and Src signaling activation. These results indicate that H2S may have the potential as an anti-infarct of MI by governing macrophage migration, which was achieved by accelerating internalization of integrin β1 and activating downstream Src-FAK/Pyk2-Rac pathway.

The segmentation of breast ultrasound (US) images has been a challenging task, mainly due to limited data and the inherent image characteristics involved, such as low contrast and speckle noise. Although convolutional neural network-based (CNN-based) methods have made significant progress over the past decade, they lack the ability to model long-range interactions. Recently, the transformer method has been successfully applied to the tasks of computer vision. It has a strong ability to capture distant interactions. However, most transformer-based methods with excellent performance rely on pre-training on large datasets, making it infeasible to directly apply them to medical images analysis, especially that of breast US images with limited high-quality labels. Therefore, it is of great significance to find a robust and efficient transformer-based method for use on small breast US image datasets.We developed a dilated transformer (DT) method which mainly uses the proposed residual axial attention layers to build encoder blocks and the introduced dilation module (DM) to further increase the receptive field. We evaluated the proposed method on 2 breast US image datasets using the 5-fold cross-validation method. Dataset A was a public dataset with 562 images, while dataset B was a private dataset with 878 images. Ground truth (GT) was delineated by 2 radiologists with more than 5 years of experience. The evaluation was followed by related ablation experiments.The DT was found to be comparable with the state-of-the-art (SOTA) CNN-based method and outperformed the related transformer-based method, medical transformer (MT), on both datasets. Especially on dataset B, the DT outperformed the MT on metrics of Jaccard index (JI) and Dice similarity coefficient (DSC) by 2.67% and 4.68%, respectively. Meanwhile, when compared with Unet, the DT improved JI and DSC by 4.89% and 4.66%, respectively. Moreover, the results of the ablation experiments showed that each add-on part of the DT is important and contributes to the segmentation accuracy.The proposed transformer-based method could achieve advanced segmentation performance on different small breast US image datasets without pretraining.

COVID-19 is a highly contagious respiratory disease, which mainly affects the lungs. Critically ill patients are easily complicated by cytokine storms, acute respiratory distress syndrome (ARDS), and respiratory failure, which seriously threaten their lives. Pulmonary fibrosis (PF) is a common interstitial lung disease, and its pathogenesis may involve the participation of a variety of immune cells and inflammatory factors. Current studies have shown that patients with COVID-19 may be complicated by pulmonary fibrosis, and patients with pulmonary fibrosis may also be at higher risk of contracting COVID-19 than healthy people. Pulmonary fibrosis is an important risk factor leading to the aggravation of COVID-19 disease. COVID-19 complicated by cytokine storm and ARDS mechanism pathways are similar to the pathogenesis of pulmonary fibrosis. The potential interaction between pulmonary fibrosis and COVID-19 can cause acute exacerbation of the patient’s condition, but the potential mechanism between the two has not been fully elucidated. Most of the drug treatment programs for COVID-19-related pulmonary fibrosis are currently formulated about the relevant guidelines for idiopathic pulmonary fibrosis (IPF), and there is no clear drug treatment program recommendation. This article aims to summarize the relevant mechanism pathways of COVID-19 and pulmonary fibrosis, explore the interrelationships and possible mechanisms, and discuss the value and risks of existing and potential COVID-19-related pulmonary fibrosis treatment drugs, to provide reference for anti-fibrosis treatment for patients.

Anaerobic oxidation of methane (AOM) in wetland soils is widely recognized as a key sink for the greenhouse gas methane (CH

Objective. This paper proposes an automatic breast tumor segmentation method for two-dimensional (2D) ultrasound images, which is significantly more accurate, robust, and adaptable than common deep learning models on small datasets. Approach. A generalized joint training and refined segmentation framework (JR) was established, involving a joint training module (J module ) and a refined segmentation module (R module ). In J module , two segmentation networks are trained simultaneously, under the guidance of the proposed Jocor for Segmentation (JFS) algorithm. In R module , the output of J module is refined by the proposed area first (AF) algorithm, and marked watershed (MW) algorithm. The AF mainly reduces false positives, which arise easily from the inherent features of breast ultrasound images, in the light of the area, distance, average radical derivative (ARD) and radical gradient index (RGI) of candidate contours. Meanwhile, the MW avoids over-segmentation, and refines segmentation results. To verify its performance, the JR framework was evaluated on three breast ultrasound image datasets. Image dataset A contains 1036 images from local hospitals. Image datasets B and C are two public datasets, containing 562 images and 163 images, respectively. The evaluation was followed by related ablation experiments. Main results. The JR outperformed the other state-of-the-art (SOTA) methods on the three image datasets, especially on image dataset B. Compared with the SOTA methods, the JR improved true positive ratio (TPR) and Jaccard index (JI) by 1.5% and 3.2%, respectively, and reduces (false positive ratio) FPR by 3.7% on image dataset B. The results of the ablation experiments show that each component of the JR matters, and contributes to the segmentation accuracy, particularly in the reduction of false positives. Significance. This study successfully combines traditional segmentation methods with deep learning models. The proposed method can segment small-scale breast ultrasound image datasets efficiently and effectively, with excellent generalization performance.

Altered intestinal microbial composition promotes intestinal barrier dysfunction and triggers the initiation and recurrence of inflammatory bowel disease (IBD). Current treatments for IBD are focused on control of inflammation rather than on maintaining intestinal epithelial barrier function. Here, we show that the internalization of Gram-negative bacterial outer membrane vesicles (OMVs) in human intestinal epithelial cells promotes recruitment of caspase-5 and PIKfyve to early endosomal membranes via sorting nexin 10 (SNX10), resulting in LPS release from OMVs into the cytosol. Caspase-5 activated by cytosolic LPS leads to Lyn phosphorylation, which in turn promotes nuclear translocalization of Snail/Slug, downregulation of E-cadherin expression, and intestinal barrier dysfunction. SNX10 deletion or treatment with DC-SX029, a novel SNX10 inhibitor, rescues OMV-induced intestinal barrier dysfunction and ameliorates colitis in mice by blocking cytosolic LPS release, caspase-5 activation, and downstream signaling. Our results show that targeting SNX10 may be a new therapeutic approach for restoring intestinal epithelial barrier function and promising strategy for IBD treatment.

A brain-computer interface (BCI) can be used for function replacement through the control of devices, such as prostheses, by identifying the subject's intent from brain activity. We process electroencephalography (EEG) signals related to motor imagery to improve the accuracy of intent classification. The original signals are decomposed into three layers based on db4 wavelet basis. The wavelet soft threshold denoising method is used to improve the signal-to-noise ratio. The sample entropy algorithm is used to extract the features of the signal after noise reduction and reconstruction. Combined with event-related synchronisation/desynchronisation (ERS/ERD) phenomenon, the sample entropy in the motor imagery time periods of C3, C4 and Cz is selected as the feature value. Feature vectors are then used as the input of three classifiers. From the evaluated classifiers, the backpropagation (BP) neural network provides the best EEG signal classification (93% accuracy). BP neural network is thus selected as the final classifier and used to design a prosthetic control system based on motor imagery. The classification results are wirelessly transmitted to control a prosthesis successfully via commands of hand opening, fist clenching, and external wrist rotation. Such functionality may allow amputees to complete simple activities of daily living. Thus, this study is valuable for subsequent developments in rehabilitation.

Based on the water pollution emission volume of 30 provinces in China from 2004 to 2018 and the temporal and spatial correlation of water pollution, this paper uses the spatial panel model and threshold regression method to incorporate environmental regulations, green total factor productivity and water pollution intensity into the one research framework, to have an experience identification of the key factors affecting water pollution. The results show that: there are apparent spatial spillover and high emission regional clusters in Chinese provinces. Government supervision and market regulation can substantially reduce pollution emissions, while how to mitigate environmental problems through green total factor productivity require government and market regulation guidance. Through the threshold regression, it is proved that the government control-and-command mode performs the optimal action range, for the emission reduction effect gradually converges as the enhancement of regulatory intensifies, yet the promotion effect of the two kinds of regulatory measures will be strengthened with the improvement of green total factor productivity. Therefore, solving water pollution depends on unremitting efforts and joint control to prevent the snowball effect and leakage. The key to pollution reduction lies in the joint-effort of green technology progress and high energy efficiency to achieve green development goals.

β-amyloid peptide (Aβ) deposition derived from sequential cleavage of the amyloid precursor protein (APP) through the amyloidogenic pathway is an important characteristic feature of Alzheimer's disease (AD). During this process, cellular trafficking plays a crucial role. A large Sec7-domain containing ADP-ribosylation factor guanine nucleotide exchange factor (ARF-GEF), Golgi brefeldin A resistance factor 1 (GBF1) has been reported to initiate the ADP-ribosylation factor (Arf) activation cascade at trans-Golgi network, which plays a crucial function at the endoplasmic reticulum-Golgi interface. In this study, we investigated the role of GBF1 in APP transmembrane transport and Aβ formation. Using APP/PS1 (presenilin 1) overexpressing transgenic mice, we demonstrate that GBF1 has upregulated the expression of APP, indicating a role for GBF1 in APP physiological process. Knocking down of GBF1 using small interfering has significantly increased the intracellular but not the surface expression of APP. In contrast, overexpression of wild-type (WT) and guanine nucleotide exchange factor (GEF) in the activated form but not the GEF deficient mutation induced continuous activation of GBF1, which subsequently increased the surface level of APP. Interestingly, inhibition of GBF1 by c(BFA) also impaired APP trafficking and induced endoplasmic reticulum (ER) stress in SH-SY5Y cells. Our results thus for identified the role of GBF1 in APP trafficking and cleavage, and provide evidence for GBF1 as a possible therapeutic target in AD.

In large-scale emotional events and complex emotional recognition applications, how to improve the recognition accuracy, computing efficiency, and user experience quality becomes the first problem to be solved. Aiming at the above problems, this paper proposes an emotional computing algorithm based on cross-modal fusion and edge network data incentive. In order to improve the efficiency of emotional data collection and the accuracy of emotional recognition, deep cross-modal fusion can capture the semantic deviation between multi-modal and design fusion methods through non-linear cross-layer mapping. In this paper, a deep fusion cross-modal data fusion method is designed. In order to improve the computational efficiency and user experience quality, a data incentive algorithm for edge network is designed in this paper, based on the overlapping delay gaps and incentive weights of large data collection and error detection. Finally, the edge network is mapped to a finite data set space from the set of emotional data elements inspired by heterogeneous emotional events. In this space, all emotional events and emotional data elements are balanced. In this paper, an emotional computing algorithm based on cross-modal data fusion is designed. The results of simulation experiments and theoretical analysis show that the proposed algorithm is superior to the edge network data incentive algorithm and the cross-modal data fusion algorithm in recognition accuracy, complex emotion recognition efficiency, and computation efficiency and delay.

Physical activity or appropriate exercise prevents the development of osteoporosis. However, the exact mechanism remains unclear although it is well accepted that exercise or mechanical loading regulates the hormones, cytokines, signaling pathways, and noncoding RNAs in bone. Accumulating evidence has shown that bone is a highly vascularized tissue, and dysregulation of vasculature is associated with many bone diseases such as osteoporosis or osteoarthritis. In addition, exercise or mechanical loading regulates bone vascularization in bone microenvironment via the modulation of angiogenic mediators, which play a crucial role in maintaining skeletal health. This review discusses the effects of exercise and its underlying mechanisms for osteoporosis prevention, as well as an angiogenic and osteogenic coupling in response to exercise.

Oxidative stress and inflammation are closely related to neuron ageing. NADPH oxidase 2 (NOX2) is a major source of reactive oxygen species (ROS) generation in brain. The nucleotide-binding oligomerisation domain (NOD)-like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of proinflammatory molecules in neurons. We hypothesize that NOX2-derived ROS accumulation mediates activation of NLRP1 inflammasome, which is involved in age-related neuronal damage. In the present study, we investigated the changes of NOX2-NLRP1 signaling pathway in primary hippocampal neurons cultured for different time (6, 9 and 12 days, d). Meanwhile, we further examined the effect of ROS inhibitor and NLRP1-siRNA on neuronal senescence. The results showed that, compared with 6 d group, the neuronal apoptosis and β-Galactosidase (β-Gal) expression were significantly increased, and the microtubule-associated protein 2 (MAP2) expression significantly decreased in primary hippocampal neurons cultured for 12 d. In addition, the results also showed that the production of ROS, the expressions of NOX2 and NLRP1 inflammasome were significantly increased with the prolongation of culture time in hippocampal neurons. Moreover, the NOX inhibitor (apocynin) and ROS scavenger (tempol) significantly decreased ROS production and alleviated neuronal damage. Meanwhile, the tempol and apocynin treatment significantly decreased the expression of NLRP1 inflammasome in hippocampal neurons. Furthermore, the NLRP1-siRNA and caspase-1 inhibitor treatment also alleviated neuronal damage. These results suggest that NOX2-derived ROS generation may induce brain inflammation via NLRP-1 inflammasome activation and lead to age-related neuronal damage. The NADPH oxidase and NLRP1 inflammasome may be important therapeutic targets for age-related neuronal damage.

In the review of the successful solar thermal electrochemical process (STEP) of acrylonitrile oxidation for the effective wastewater treatment, the process was actually driven by solar two fields - thermofield and electrofield, essentially activated and motivated for both thermochemistry and electrochemistry. In this paper, the synergistic system of solar three fields, induced by the primary photofield, and sub-thermofield and sub-electrofield, was designed and employed firstly for promoted the efficiency of the solar utilization and pollutant oxidation plus hydrogen production. With the correlative action, the three sub-chemical processes were induced by the solar three fields. The action actually conducted a three-field synergy of solar energy with a combination of the thermo-activation, photocatalysis and electrochemistry of the pollutant oxidation. Exemplified by acrylonitrile, the solar oxidation plus hydrogen production was theoretically and experimentally investigated by the single-field, coupled two-fields and coupled three-fields patterns. The results indicated that the coupled three-field pattern achieved high efficiencies in the solar utilization and oxidative reaction plus the hydrogen production, which was superior to ones of the single or two fields. The solar thermofield enables that the activated acrylonitrile was apt to be thermally decomposed, greatly in favor of the subsequent photo- and electrooxidation. The photocatalytic efficiency driven by the single photofield was reached at a rate of 31.01%. The electrolysis efficiency powered by single electrofield gained a rate of 24.56%. For the combination of the solar three-field pattern, the oxidation efficiencies run up to a rates of 32.74%, 38.06%, 55.01% and 76.01% during 60 min at the 25 °C, 40 °C, 60 °C, 75 °C, respectively. Especially, a joint of the coupled field realized the 6.38 times of the COD removal rate of acrylonitrile in comparison with the single field pattern. Due to the easy anodic oxidation of acrylonitrile and operation under the high temperature, the cathodic reduction of water was enhanced for the production of hydrogen in the electrolysis of the less potential plus an addition of photocatalysis. The experimental data and mechanistic analysis significantly revealed that the system achieved such a synergetic action. The full mineralization plus the hydrogen production was attributed to a coupling and matching integration of the solar three fields and subchemistries.