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Jiuzhaigou Valley is recognized as both a world natural heritage site and a biosphere reserve. Conducting research on vegetation health within its scope can provide a demonstration role for sustainable development research. In this study, we proposed a technology integration approach that combined remote sensing intelligent identification and quantitative retrieval, and achieved vegetation health monitoring and susceptibility mapping of unhealthy trees. Leveraging WorldView-2 high-resolution satellite images, unhealthy trees were elaborately identified through the object-oriented classification method employing spectral and texture features, with F1 Score exceeding 75%. By applying fuzzy operations on indices related to leaf pigment and canopy architecture, we ultimately generated susceptibility maps of unhealthy trees on Sentinel-2 satellite images, with Area Under the Curve (AUC) exceeding 0.85. Our findings underscore that the vegetation health in Jiuzhaigou Valley is predominantly influenced by human activities and geological hazards. The forests of Jiuzhaigou Valley exhibit a certain degree of resilience to geological disasters, while human activities have been continuously exerting adverse effects on forest health in recent years, necessitating heightened attention. The methodology proposed in this study for mapping unhealthy trees susceptibility presents a cost-effective solution that can be readily applied for vegetation health monitoring and early warning in analogous biosphere reserves.

Abstract Understanding molecular mechanisms of intervertebral disc degeneration (IDD) and providing a novel target for the treatment of IDD have important implications. We sought to explore a new promising gene target for the treatment of IDD. This study integrated 19,678 genes of 38 IDD patients from two gene datasets. Differentially Expressed Genes (DEGs) of annulus fibrosus were analyzed in groups with mild disc degeneration (MDD) and severe disc degeneration (SDD). We screened the hub gene through biological information technology (bioinformatic) methods. Then, we further validated the hub gene using annulus fibrosus and nucleus pulposus tissues from 12 patients with qRT-PCR. In addition, we explored its underlying molecular mechanism with GO, KEGG and GSEA. Through multiple screening bioinformatics methods, the hub gene CD63 was identified. The qRT-PCR explored that CD63 decreased significantly in SDD group compared to that in MDD group (P

A fundamental issue of maritime applications of synthetic aperture radar (SAR) data is the development of precise statistical models for clutter pixels. Several statistical models including the GK, K+R, and ${\mathcal{G}}_{\text{AO}}$ have been demonstrated to be promising for characterizing sea clutter in SAR images. This article is devoted to investigating the improvements in clutter fitting and ship detection performances by using the recently proposed ${\mathcal{G}}_{\text{AO}}$, compared to that using the GK and K+R. First, the solution uniqueness of parameter estimators by applying the “method of log cumulants” for the ${\mathcal{G}}_{\text{AO}}$ is mathematically proven in the first time. Then, we assess the fitting performance of different models for sea surfaces with different wind speed conditions. Next, the constant false alarm rate (CFAR) detection performance of ships based on different models is compared by the indicators of CFAR loss and detection efficiency. Experiments performed on L-band ALOS-PALSAR SAR data verify the modeling capability of the ${\mathcal{G}}_{\text{AO}}$ model for sea clutter. Moreover, several ship detection examples indicate the usefulness and potential of the ${\mathcal{G}}_{\text{AO}}$ model for CFAR detection in practical applications.

Tamoxifen is a drug used for treating breast cancer (BC), especially for individuals diagnosed with estrogen receptor-positive (ER+) BC. Its prolonged use could reduce the risk of recurrence and significantly lengthen the survival rate of BC patients. However, an increasing number of patients developed resistance to tamoxifen treatment, which reduced therapeutic efficiency and caused substandard prognosis. Therefore, the exploration of the molecular processes involved in tamoxifen resistance (TR) is urgently required. This investigation aimed to elucidate the relationship of microRNA-330 (miR-330-3p) with the TR of BC. There is little information on miR-330-3p′s link with drug-resistant BC, although it is well known to regulate cell proliferation and apoptosis. Primarily, miR-330-3p expression in parental BC (MCF7/T47D), TR (MCF7-TR), and T47D/TR cell lines was detected by qRT-PCR. Then, the impact of miR-330-3p on the TR of BC cells was assessed by a cell proliferation assay. Lastly, dual-luciferase reporter, qRT-PCR, and western blot assessments were carried out to identify histone deacetylase 4 (HDAC4) as the potential miR-330-3p target gene. The data indicated that miRNA-330 was overexpressed in TR ER+ BC cells and its overexpression could induce TR. Furthermore, miRNA-330 could also reduce the expression of HDAC4, which is closely linked to TR, and overexpression of HDAC4 could reverse miRNA-330-induced drug resistance. In summary, miR-330-3p could induce TR of ER+ BC cells by downregulating HDAC4 expression, which might be a novel marker of TR and a possible treatment target against BC patients who are tamoxifen-resistant.

Abstract Background Certain risk alleles associated with autoantibody-positive rheumatoid arthritis (RA) have been linked to poorer prognoses. In patients with autoantibody-positive RA, abatacept shows differential efficacy to tumor necrosis factor inhibitors. Our aim was to investigate the relationship between clinical response to abatacept and to adalimumab and presence of risk alleles encoding human leukocyte antigen (HLA)-DRB1 shared epitope (SE) in RA. Methods In this head-to-head study, biologic-naïve adults with early (≤ 12 months), moderate-to-severe RA and inadequate response to methotrexate (MTX-IR), autoantibody-positive for both anti-cyclic citrullinated peptide 2 and rheumatoid factor, were randomized 1:1 to receive subcutaneous abatacept 125 mg weekly or subcutaneous adalimumab 40 mg every 2 weeks for 24 weeks with stable, weekly oral MTX. An open-label period to 48 weeks followed, during which adalimumab-treated patients were switched to abatacept. Patients were genotyped for HLA-DRB1 alleles and classified as SE-positive (≥ 1 SE allele) or SE-negative (no SE alleles). Efficacy was assessed at weeks 24 and 48. Results Forty patients each received abatacept (9 SE-negative, 30 SE-positive, one unknown) or adalimumab (9 SE-negative, 31 SE-positive). Mean age and disease duration were 46.0 years and 5.5 months, respectively. At week 24, a greater percentage of abatacept patients achieved 50% improvement in ACR criteria (ACR50) compared with adalimumab patients (73% vs 45%, respectively) and estimate of difference (95% confidence interval [CI]), 28 (5, 48). In SE-positive patients, ACR50 estimate of difference (95% CI) was 32 (7, 55). During the open-label period, responses were sustained in the abatacept non-switch group and showed trends toward further improvement in the adalimumab-to-abatacept switch group at week 48, in both the overall and the SE-positive subpopulation. No new safety signals were identified. Conclusions In MTX-IR patients with early, autoantibody-positive RA, abatacept resulted in numerically higher efficacy responses versus adalimumab after 24 weeks, with more pronounced treatment differences in SE-positive patients. After 48 weeks, responses were sustained in patients who continued abatacept while those who switched to abatacept showed further clinical improvement, overall, and in SE-positive patients. This supports co-stimulation blockade as an effective treatment strategy for patients with early, autoantibody-positive RA, particularly among SE-positive patients. Trial registration NIH US National Library of Medicine, NCT02557100 . Registered on September 23, 2015.

Abstract 2D organic molecular crystals (2DOMCs) are promising materials for the fabrication of high‐performance optoelectronic devices. However, the growth of organic molecules into 2DOMCs remains a challenge because of the difficulties in controlling their self‐assembly with a preferential orientation in solution‐process crystallization. Herein, fullerene is chosen as a model molecule to develop a supramolecular gel crystallization approach to grow large‐area 2DOMCs by controlling the perfect arrangement on the {220} crystal plane with the assistance of a gelated solvent. In this case, the gel networks provide tuneable confined spaces to control the crystallization kinetics toward the growth of dominant crystal faces by their inhibiting motions of solvent or solute molecules to enable the growth of perfect crystals at appropriate nucleation rates. As a result, a large‐area fullerene 2DOMC is produced successfully and its corresponding device on a flexible substrate exhibits excellent bendable properties and ultra‐high weak light detection ability (2.9 × 1011 Jones) at a 10 V bias upon irradiation with 450 nm incident light. Moreover, its photoelectric properties remain unchanged after 200 cycles of bending at angles of 45, 90, and 180°. These results can be extended to the growth of other 2DOMCs for potentially fabricating advanced organic (opto)electronics.

Different varieties of fresh lotus seeds have varying levels of amylose content. It has a direct impact on the following processing and final product quality, so the non-destructive detection of amylose content is meaningful before lotus seed production. This study proposed a non-destructive method to detect the amylose content of fresh lotus seeds. Hyperspectral images of 120 fresh lotus seeds of three different varieties were obtained, and different pretreatments were applied to the average spectra obtained from the region of interest (ROI). The calibration and prediction set were divided by the sample set joint x–y distances algorithm (SPXY). Then, the partial lease square regression (PLSR) method was established for modeling, with Savitzky–Golay pretreatment-based PLSR showing the best results. To further improve the stability of the predictive model, different methods of feature variables selection were compared. The results showed that the best PLSR model was established with the inputs of 15 feature bands selected from 472 bands by the successive projection algorithm (SPA). The correlation coefficient of the prediction set (Rp), root mean square error of the prediction set (RMSEP), and residual predictive deviation (RPD) were 0.890, 15.154 mg g−1, and 2.193, respectively. Meanwhile, this study visualized the amylose content distribution maps from which it could estimate the content level directly. This study could provide a reference for further development of portable detection equipment for the amylose content of fresh lotus seeds.

When multiple paralleled distributed generation (DG) units operate in an islanded microgrid, accurate power sharing of each DG unit cannot be achieved with a conventional droop control strategy due to mismatched feeder impedance. In this paper, a small AC signal (SACS)-injection-based modified droop control method is presented for accurate active and reactive power sharing among DG units. The proposed control method adjusts the voltage amplitude of each DG unit by injecting small AC signals to form a reactive power control loop. This strategy does not need communication links or to specifically obtain the physical parameter of the feeder impedance and only requires the local information. Moreover, the parameter design procedure and stability analysis are given full consideration. Finally, simulation and experimental results verify the effectiveness of the proposed control scheme, and accurate active and reactive power sharing can be achieved.

Powder laying is a necessary procedure during powder bed additive manufacturing (PBAM), and the quality of powder bed has an important effect on the performance of products. Because the powder particle motion state during the powder laying process of biomass composites is difficult to observe, and the influence of the powder laying process parameters on the quality of the powder bed is still unclear, a simulation study of the biomass composite powder laying process during powder bed additive manufacturing was conducted using the discrete element method. A discrete element model of walnut shell/Co-PES composite powder was established using the multi-sphere unit method, and the powder-spreading process was numerically simulated using two different powder spreading methods (rollers/scrapers). The results showed that the quality of powder bed formed by roller laying was better than that formed by scrapers with the same powder laying speed and powder laying thickness. For both of the two different spreading methods, the uniformity and density of the powder bed decreased as spreading speed increased, although the spreading speed had a more important influence on scraper spreading compared to roller spreading. As powder laying thickness increased, the powder bed formed by the two different powder laying methods became more uniform and denser. When the powder laying thickness was less than 110μm, the particles were easily blocked at the powder laying gap and are pushed out of the forming platform, forming many voids, and decreasing the powder bed’s quality. When the powder thickness was greater than 140 μm, the uniformity and density of the powder bed increased gradually, the number of voids decreased, and the quality of the powder bed improved.

Abstract Background Alzheimer’s disease (AD) is an extremely complicated neurodegenerative disorder, which accounts for almost 80 % of all dementia diagnoses. Due to the limited treatment efficacy, it is imperative for AD patients to take reliable prevention and diagnosis measures. This study aimed to explore potential biomarkers for AD. Methods GSE63060 and GSE140829 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEG) between AD and control groups in GSE63060 were analyzed using the limma software package. The mRNA expression data in GSE140829 was analyzed using weighted gene co-expression network analysis (WGCNA) function package. Protein functional connections and interactions were analyzed using STRING and key genes were screened based on the degree and Maximal Clique Centrality (MCC) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the key genes. Results There were 65 DEGs in GSE63060 dataset between AD patients and healthy controls. In GSE140829 dataset, the turquoise module was related to the pathogenesis of AD, among which, 42 genes were also differentially expressed in GSE63060 dataset. Then 8 genes, RPS17, RPL26, RPS3A, RPS25, EEF1B2, COX7C, HINT1 and SNRPG, were finally screened. Additionally, these 42 genes were significantly enriched in 12 KEGG pathways and 119 GO terms. Conclusions In conclusion, RPS17, RPL26, RPS3A, RPS25, EEF1B2, COX7C, HINT1 and SNRPG, were potential biomarkers for pathogenesis of AD, which should be further explored in AD in the future.

Diabetic retinopathy (DR) is one of the primary causes of visual impairment in the working-age population. Retinal cell death is recognized as a prominent feature in the pathological changes of DR. Several types of cell death occurrence have been confirmed in DR, which might be the underlying mechanisms of retinal cell loss. Regulated cell death (RCD) originates from too intense or prolonged perturbations of the intracellular or extracellular microenvironment for adaptative responses to cope with stress and restore cellular homeostasis. Pyroptosis, necroptosis, and ferroptosis represent the novel discovered RCD forms, which contribute to retinal cell death in the pathogenesis of DR. This evidence provides new therapeutic targets for DR. In this review, we summarize the mechanisms of three types of RCD and analyse recent advances on the association between novel RCD and DR, aiming to provide new insights into the underlying pathogenic mechanisms and propose a potential new strategy for DR therapy.

Co-inhibitory receptors (IRs) are molecules that protect host against autoimmune reactions and maintain peripheral self-tolerance, playing an essential role in maintaining immune homeostasis. In view of the substantial clinical progresses of negative immune checkpoint blockade in cancer treatment, the role of IRs in autoimmune diseases is also obvious. Several advances highlighted the substantial impacts of T cell immunoglobulin and ITIM domain (TIGIT), a novel IR, in autoimmunity. Blockade of TIGIT pathway exacerbates multiple autoimmune diseases, whereas enhancement of TIGIT function has been shown to alleviate autoimmune settings in mice. These data suggested that TIGIT pathway can be manipulated to achieve durable tolerance to treat autoimmune disorders. In this review, we provide an overview of characteristics of TIGIT and its role in autoimmunity. We then discuss recent approaches and future directions to leverage our knowledge of TIGIT as therapeutic target in autoimmune diseases.

In order to realize data security sharing and reduce the computing costs of clients in data mining process, a joint delegation learning model and protocol based on BCP homomorphic encryption algorithm was proposed.Firstly, a privacy preserving method based on false records was proposed for the security of decision tree model.Secondly, in view of the vertical and horizontal distribution of data, the corresponding delegation learning protocols based on privacy preserving delegation dot product algorithm and privacy preserving delegation entropy algorithm was proposed.Finally, the security proof and the performance analysis of delegation learning protocols and decision tree model structure were given.The results show that the privacy protection method based on false records does not affect the final model construction, and the final model obtained by each client is the same as that constructed by real data.

Abstract Breast cancer is the most common cancer in women and its incidence rates are rapidly increasing in China. Understanding the molecular mechanisms of breast cancer tumorigenesis enables the development of novel therapeutic strategies. SEC61G is a subunit of the endoplasmic reticulum translocon that plays critical roles in various tumors. We aimed to investigate the expression and function of SEC61G in breast cancer. By analyzing The Cancer Genome Atlas breast cancer cohort, we found that SEC61G was highly expressed in breast cancer and predicted poor prognosis of breast cancer patients. Overexpression of SEC61G and its prognostic role was also confirmed in the Nanjing Medical University (NMU) breast cancer cohort. Functionally, we demonstrated that knockdown of SEC61G suppressed breast cancer cell proliferation, migration, invasion, and promoted breast cancer cell apoptosis in vitro. Xenograft breast tumor model revealed that knockdown of SEC61G inhibited breast tumor development in vivo. Furthermore, we demonstrated that SEC61G positively regulated glycolysis in breast cancer cells. Mechanistically, we showed that transcription factor E2F1 directly bound to the promoter of SEC61G and regulated its expression in breast cancer cells. SEC61G overexpression antagonized the effect of E2F1 knockdown in regulating breast cancer cell proliferation, invasion, and apoptosis. Finally, we demonstrated that the E2F1/SEC61G axis regulated glycolysis and chemo-sensitivity of Herceptin in breast cancer cells. Taken together, these results of in vitro and in vivo studies demonstrate that SEC61G promotes breast cancer development and metastasis via modulating glycolysis and is transcriptionally regulated by E2F1, which might be utilized as a promising therapeutic target of breast cancer treatment.

Abstract Background Atherosclerosis (AS) is a leading cause of vascular disease worldwide. MicroRNAs (miRNAs) play an essential role in the development of AS. However, the miRNAs-based biomarkers for the diagnosis of AS are still limited. Here, we aimed to identify the miRNAs significantly related to AS and construct the predicting model based on these miRNAs for distinguishing the AS patients from healthy cases. Methods The miRNA and mRNA expression microarray data of blood samples from patients with AS and healthy cases were obtained from the GSE59421 and GSE20129 of Gene Expression Omnibus (GEO) database, respectively. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to evaluate the correlation of the miRNAs and mRNAs with AS and identify the miRNAs and mRNAs significantly associated with AS. The potentially critical miRNAs were further optimized by functional enrichment analysis. The logistic regression models were constructed based on these optimized miRNAs and validated by threefold cross-validation method. Results WGCNA revealed 42 miRNAs and 532 genes significantly correlated with AS. Functional enrichment analysis identified 12 crucial miRNAs in patients with AS. Moreover, 6 miRNAs among the identified 12 miRNAs, were selected using a stepwise regression model, in which four miRNAs, including hsa-miR-654-5p, hsa-miR-409-3p, hsa-miR-485-5p and hsa-miR-654-3p, were further identified through multivariate regression analysis. The threefold cross-validation method showed that the AUC of logistic regression model based on the four miRNAs was 0.7308, 0.8258, and 0.7483, respectively, with an average AUC of 0.7683. Conclusion We identified a total of four miRNAs, including hsa-miR-654-5p and hsa-miR-409-3p, are identified as the potentially critical biomarkers for AS. The logistic regression model based on the identified 2 miRNAs could reliably distinguish the patients with AS from normal cases.

In order to explore the effect of printing parameter configurations on the forming performance of Digital Light Processing (DLP) 3D printed samples, printing experiments were carried out on the enhanced adhesion and efficient demolding of DLP 3D printing devices. The molding accuracy and mechanical properties of the printed samples with different thickness configurations were tested. The test results show that when the layer thickness increases from 0.02 mm to 0.22 mm, the dimensional accuracy in the X and Y directions increases first and then decreases, while the dimensional accuracy in the Z direction decreases, and the dimensional accuracy is the highest when the layer thickness is 0.1 mm. The mechanical properties of the samples decline with an increasing layer thickness of the samples. The mechanical properties of the 0.08 mm layer thickness are the best, and the tensile, bending, and impact properties are 22.86 Mpa, 48.4 Mpa, and 35.467 KJ/m2, respectively. Under the condition of ensuring molding accuracy, the optimal layer thickness of the printing device is determined to be 0.1 mm. The analysis of the section morphology of samples with different thicknesses illustrates that the fracture of the sample is a river-like brittle fracture, and there are no defects such as pores in the section of samples.

We report a joint experimental and theoretical work on the steady-state spectroscopy and time-resolved emission of the coumarin C153 dye in methanol. The lowest energy excited state of this molecule is characterized by an intramolecular charge transfer thus leading to remarkable shifts of the time-resolved emission spectra, dictated by the methanol reorganization dynamics. We selected this system as a prototypical test case for the first application of a novel computational protocol aimed at the prediction of transient emission spectral shapes, including both vibronic and solvent effects, without applying any phenomenological broadening. It combines a recently developed quantum–classical approach, the adiabatic molecular dynamics generalized vertical Hessian method (Ad-MD|gVH), with nonequilibrium molecular dynamics simulations. For the steady-state spectra we show that the Ad-MD|gVH approach is able to reproduce quite accurately the spectral shapes and the Stokes shift, while a ∼0.15 eV error is found on the prediction of the solvent shift going from gas phase to methanol. The spectral shape of the time-resolved emission signals is, overall, well reproduced, although the simulated spectra are slightly too broad and asymmetric at low energies with respect to experiments. As far as the spectral shift is concerned, the calculated spectra from 4 ps to 100 ps are in excellent agreement with experiments, correctly predicting the end of the solvent reorganization after about 20 ps. On the other hand, before 4 ps solvent dynamics is predicted to be too fast in the simulations and, in the sub-ps timescale, the uncertainty due to the experimental time resolution (300 fs) makes the comparison less straightforward. Finally, analysis of the reorganization of the first solvation shell surrounding the excited solute, based on atomic radial distribution functions and orientational correlations, indicates a fast solvent response (≈100 fs) characterized by the strengthening of the carbonyl–methanol hydrogen bond interactions, followed by the solvent reorientation, occurring on the ps timescale, to maximize local dipolar interactions.

The unmanned aerial vehicle (UAV) is inexpensive and offers a fast response speed and robust flexibility; thus, it is a promising tool in the maritime buoyage inspection scenario, which involves monitoring and accessing a lateral mark system far away from the coast. However, two main problems can occur during inspection. The first is extreme weather conditions, resulting in a deviation between the inspection route and the design route. The second is that the buoyage beacons are visited only once. Therefore, this article proposes a buoyage inspection system consisting of a single UAV and random coastal buoys. The UAV automatically takes off from the depot, performs a self-check on the buoy beacons, and then returns to the depot. A cascade active disturbance rejection controller (ADRC) is designed to adjust the real-time trajectory of the UAV system. A feasible trajectory planning method is also designed based on the continuous Hopfield neural network (CHNN) and genetic algorithm (GA) to minimize the inspection distance. Extensive simulations are conducted to demonstrate the effectiveness of the proposed method.

The accurate measurement of the output parameters of photovoltaic (PV) cells is a key step in building a PV system. The output parameters of a PV cell under actual test conditions will appear different degrees of the deviation from those under the standard test conditions. In this work, we are primarily concerned with the deviations of the temperature distributions and output parameters of a testing c-Si solar cell caused by the heat transfer process under actual test conditions. The results show that the temperature distributions of c-Si solar cells under actual test conditions will be uneven and obviously deviate from those under the standard test conditions; the heat transfer coefficients at the interfaces between the front surface and environmental air and between the back surface and mental holder have important consequences for the temperature distributions of c-Si solar cells; under the actual test conditions of PV enterprises, the possible deviation range of short-circuit current density, open-circuit voltage, filling factor, and efficiency may be from −17 to 9 µA/cm2, from −11 to 17 mV, from −0.4% to 0.7%, and from −0.4% to 0.7%, respectively.

Background: : P-glycoprotein mediated efflux leads to multidrug resistance of tumor cells, which is an important reason for chemotherapy failure. Thus inhibiting P-gp is an effective approach to reverse multidrug resistance. Purpose: : Swietephragmin D is a limonoid compound isolated from the fruits and leaves of Swietenia mahagoni (L.) Jacq.. The reversal efficiency of swietephragmin D was examined in this study. Methods: : Rhodamine 123 efflux assays were used to measure inhibition efficiency of swietephragmin D. Cytotoxicity assays were used to measure the reversal effect of swietephragmin D. Real-time PCR and ATPase assays were performed to explore the mechanisms of reversion. Results: : Swietephragmin D inhibited P-glycoprotein-induced efflux in a dose and time dependent manner. This compound inhibited P-glycoprotein more effectively than verapamil. The IC50 values of the multidrug resistant cells were reduces by swietephragmin D significantly. The transcription levels of ABCB1 (encoded P-glycoprotein) were not affected by swietephragmin D. However, the ATPase activity of P-glycoprotein was stimulated by swietephragmin D. Conclusion: : Swietephragmin D was a substrate of P-glycoprotein and inhibited P-gp mediated efflux. It did not interfere with expression of ABCB1. Thus swietephragmin D reversed multidrug resistance as a competitive inhibitor of P-glycoprotein.

Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a great challenge to the world's public health system. Nosocomial infections have occurred frequently in medical institutions worldwide during this pandemic. Thus, there is an urgent need to construct an effective surveillance and early warning system for pathogen exposure and infection to prevent nosocomial infections in negative-pressure wards. In this study, visualization and construction of an infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward were performed to describe the distribution regularity and infection risk of SARS-CoV-2, the critical factors of infection, the air changes per hour (ACHs) and the viral variation that affect infection risk. The SARS-CoV-2 distribution data from this model were verified by field test data from the Wuhan Huoshenshan Hospital ICU ward. ACHs have a great impact on the infection risk from airborne exposure, while they have little effect on the infection risk from surface exposure. The variant strains demonstrated significantly increased viral loads and risks of infection. The level of protection for nurses and surgeons should be increased when treating patients infected with variant strains, and new disinfection methods, electrostatic adsorption and other air purification methods should be used in all human environments. The results of this study may provide a theoretical reference and technical support for reducing the occurrence of nosocomial infections.

Background: The pathological differences between Crohn’s disease (CD) and ulcerative colitis (UC) are substantial and unexplained yet. Here, we aimed to identify potential regulators that drive different pathogenesis of CD and UC by causal inference analysis of transcriptome data.Methods: Kruskal–Wallis and Dunnett’s tests were performed to identify differentially expressed genes (DEGs) among CD patients, UC patients, and controls. Subsequently, differentially expressed pathways (DEPs) between CD and UC were identified and used to construct the interaction network of DEPs. Causal inference was performed to identify IBD subtype-regulators. The expression of the subtype-regulators and their downstream genes was validated by qRT-PCR with an independent cohort.Results: Compared with the control group, we identified 1,352 and 2,081 DEGs in CD and UC groups, respectively. Multiple DEPs between CD and UC were closely related to inflammation-related pathways, such as NOD-like receptor signaling, IL-17 signaling, and chemokine signaling pathways. Based on the priori interaction network of DEPs, causal inference analysis identified IFNG and GBP5 as IBD subtype-regulators. The results with the discovery cohort showed that the expression level of IFNG, GBP5, and NLRP3 was significantly higher in the CD group than that in the UC group. The regulation relationships among IFNG, GBP5, and NLRP3 were confirmed with transcriptome data from an independent cohort and validated by qRT-PCR.Conclusion: Our study suggests that IFNG and GBP5 were IBD subtype-regulators that trigger more intense innate immunity and inflammatory responses in CD than those in UC. Our findings reveal pathomechanical differences between CD and UC that may contribute to personalized treatment for CD and UC.

Abstract Non‐obstructive azoospermia is one of the most common causes of male infertility, but there is still no specific treatment drug. Given that the Oct4 (Octamer‐binding transcription factor 4) has an important regulatory effect on spermatogenesis, activating it can effectively promote spermatogenesis, so it is of great value to develop Oct4‐targeted drug design and elucidating its mechanism of action. Here, we screened out the Oct4‐targeted drug molecule NBMA (N‐benzyl‐4‐methoxy‐2‐(1‐(4‐(trifluoromethyl)phenyl)vinyl)aniline) by computer‐assisted technology, and found that it has a significant promoting effect on spermatogenesis in the established mouse azoospermia model. Subsequently, through transcriptome sequencing and enrichment analysis, real‐time fluorescent quantitative PCR (qPCR) and western blot experiments revealed that NBMA promotes the differentiation of spermatogonial stem cells by activating the Oct4 pathway, thereby promoting spermatogenesis. This study proves that NBMA is a molecule with great potential to be developed as a therapeutic drug for azoospermia. It also shows that computer‐assisted, chemical and biological multidisciplinary methods play a very important role in innovative drug discovery.

High Altitude Platform (HAP) systems comprise airborne base stations deployed above 20 km and below 50 km to provide wireless access to devices in large areas. In this paper, two types of applications using HAP systems: one with HAP Station (HAPS) and the other with HAPS as International Mobile Telecommunication (IMT) Base Station (HIBS) are introduced. The HAP system with HAPS has already received wide recognition from the academia and the industry and is considered as an effective solution to provide internet access between fixed points in suburban and rural areas as well as emergencies. HAP systems with HIBS to serve IMT user terminal have just started to draw attention from researchers. The HIBS application is expected to be an anticipate mobile service application complementing the IMT requirement for cell phone or other mobile user terminals in which the service field of HAPS application cannot reach. After describing and characterizing the two types of systems, coexistence studies and simulation results using both the Power Fluxed Density (PFD) mask and separation distance based methods are presented in this paper. This paper also predicts future trends of the evolution paths for the HAP systems along with challenges and possible solutions from the standpoint of system architectures and spectrum regulation.

Abstract Background To evaluate the etiology, demographic profile, clinical features, and outcomes in patients with peripapillary subretinal hemorrhage (PSH). Methods Thirty-eight eyes of 37 consecutive patients with PSH were enrolled in this prospective observational study over 4 years; all were followed for 2 years. The main outcome measures were demographic profile, possible etiology, clinical features, outcome, and prognosis. Results Sixty-eight percent (26/38) of eyes were in female patients; the mean patient age was 20 years. Only 1 patient (1/37) showed bilateral involvement. All patients experienced acute onset of PSH. All eyes were myopic and their best-corrected visual acuities ranged from 20/1000 to 20/12.5. The fundus features of affected eyes were classified into 3 groups: (1) PSH alone (4/38 eyes, 10.5%); (2) PSH with intrapapillary hemorrhage (17/38 eyes, 44.7%); (3) PSH with intrapapillary and vitreous hemorrhage (17/38 eyes, 44.7%). PSH occurred in nasal edges of optic discs with a crescent shape and dull-red color. All affected optic discs were small and crowded, exhibiting variable degrees of tilting. The cup of affected optic discs was narrower and deeper than that of normal control discs. Other ancillary tests provided no additional value. After a mean follow-up of 2.85 months, the hemorrhages resolved spontaneously without sequelae. Recurrence of disease was not observed in any patients. Conclusions PSH is common in myopic eyes with tilted optic discs. We suspect that these hemorrhages occurred as a result of abrupt movement acting on a morphologically vulnerable optic disc.

Medication recommendation based on Electronic Health Records (EHRs) is an important research direction, which aims to make prescription recommendations according to EHRs of patients. Most existing methods either only make recommendation through EHRs of the current admission while ignoring the patient's historical records, or fail to fully consider the correlations among the clinical events from every single admission. These methods have shown their limitations in dealing with the complex structural correlations and temporal dependencies of clinical events in EHRs, which results in the defect of recommendation quality as well as the lack of temporal prediction ability. For that, a novel graph-attention augmented temporal neural network is proposed to model both the structural and temporal information simultaneously. For each admission record, a co-occurrence graph is constructed to establish the correlations among clinical events, and then a graph-attention augmented mechanism is used to learn the structural correlations on the graphs to obtain better representation of this admission. Then a temporal updating module based on the gated recurrent units is further proposed to learn the temporal dependencies between multiple admissions of each patient. Furthermore, our proposed model is also constrained by the co-occurrence graph, which can capture the internal correlations of clinical events and provide better modeling capability when the training data is sparse. Experiments illustrate that our model is superior to the state-of-the-art methods on a real-world dataset MIMIC-III in all effectiveness measures.

Blockchain-based product traceability systems are receiving increasing attention from both industry and academia. Existing systems make full use of the traceability and non-modification characteristics of blockchain technology and realize the openness and transparency of product traceability information in the entire supply chain. However, existing systems do not consider government regulation, cannot protect enterprise sensitive private data effectively, and have performance bottlenecks. To address these problems, this paper proposes a product traceability scheme based on the permissioned blockchain within a double-layer framework. We introduce the double-layer framework and describe its advantages in detail. We also describe the smart contracts (chain code) in the double-layer framework. Finally, we test the performance of the proposed scheme through simulation experiments. The simulation results demonstrate the performance of nodes in the main layer, which is very important for consumers to obtain product traceability information, is optimized.

Objective: It has recently been shown that the melanoma antigen gene (MAGE) family is expressed in various tumor cell lines but silent in normal tissues, except germ cell lines. Mageb4, a member of the MAGE family, is highly expressed in the testis and homologous in humans and mice. Whole-exome sequencing studies have identified Mageb4 as a possible X-linked cause of inherited male infertility. However, the function of Mageb4 protein remains largely unknown. Methods: Using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 technology, we generated a Mageb4 knockout mouse model (Mageb4−/Y) to explore the role of this gene in spermatogenesis. Results: First, immunostaining of testicular cells showed that Mageb4 is localized in the cytoplasm of spermatogonia. Second, Mageb4−/Y male mice displayed significant increases in apoptosis. However, Mageb4−/Y male mice showed normal fertility, including normal sperm concentration, sperm motility, and testicular and epididymal histology. Conclusions: These findings suggest that, despite testis-exclusive expression, Mageb4 is dispensable for mouse spermatogenesis. Future research should focus on the role of this gene in apoptosis, aiming to provide clinical guidance regarding male infertility.

Purpose: Choroidal neovascularization (CNV) is the main pathogenic process and a leading cause of severe vision loss in neovascular age-related macular degeneration (AMD). We investigated the antiangiogenic efficacy of dihydroartemisinin (DHA) in an experimental laser-induced CNV mouse model.Methods: After fluorescein angiography confirmed that CNV was induced by laser photocoagulation in C57BL/6J mice, DHA or vehicle was given by intragastric administration once a day. On day 6 and day 12, fluorescein angiography, optic coherence tomography, and flat-mounting analysis were performed to grade CNV leakage, measure CNV thickness and evaluate CNV areas, respectively. Immunofluorescence staining and Western blot analysis were performed to evaluate the expression of NF-κB, VEGF, and VEGFR2. To confirm the safety of intragastric DHA application, changes in retinal morphology and neural cell apoptosis were tested by histopathological examination and TUNEL assay, and retinal function was determined by electroretinogram (ERG).Results: Intragastric administration of DHA significantly suppressed CNV leakage and CNV formation in both thickness and area. Immunofluorescence showed that DHA suppressed VEGFR2 and NF-κB p65 expression in laser-induced lesions. Compared to the normal group, the protein expression of VEGF, VGFER2, NF-κB p65, and NF-κB1 p50 increased significantly in the vehicle group after laser photocoagulation, while it was profoundly inhibited by DHA treatment. In addition, histopathological examination, TUNEL analysis, and ERG test showed no obvious evidence of retinal toxicity caused by DHA.Conclusion: Systemic administration of DHA can effectively inhibit laser-induced CNV formation in mice, which might be due to the suppression of the classic NF-κB signaling pathway and downregulation of VEGFR2 and VEGF expression. The current results suggest that DHA could be a natural potential alternative therapeutic strategy for neovascular AMD.

Pyroptosis is a lytic form of programmed cell death mediated by gasdermins (GSDMs) with pore-forming activity in response to certain exogenous and endogenous stimuli. The inflammasomes are intracellular multiprotein complexes consisting of pattern recognition receptors, an adaptor protein ASC (apoptosis speck-like protein), and caspase-1 and cause autocatalytic activation of caspase-1, which cleaves gasdermin D (GSDMD), inducing pyroptosis accompanied by cytokine release. In recent years, the pathogenic roles of inflammasomes and pyroptosis in multiple eye diseases, including keratitis, dry eyes, cataracts, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy, have been continuously confirmed. Inhibiting inflammasome activation and abnormal pyroptosis in eyes generally attenuates inflammation and benefits prognosis. Therefore, insight into the pathogenesis underlying pyroptosis and inflammasome development in various types of eye diseases may provide new therapeutic strategies for ocular disorders. Inhibitors of pyroptosis, such as NLRP3, caspase-1, and GSDMD inhibitors, have been proven to be effective in many eye diseases. The purpose of this article is to illuminate the mechanism underlying inflammasome activation and pyroptosis and emphasize its crucial role in various ocular disorders. In addition, we review the application of pyroptosis modulators in eye diseases.

Purpose: This network meta-analysis was conducted to obtain the relative effectiveness of different pharmacotherapy of macular edema secondary to retinal vein occlusion (RVO) by summarizing all available evidences.Methods: PubMed, Embase, and Cochrane Library databases were searched for all relevant randomized controlled trials. The outcomes were estimated through a network meta-analysis, including the mean change in best-corrected visual acuity (BCVA) from baseline, the proportion of patients who gained ≥15 letters in BCVA from baseline, the mean change in central retinal thickness (CRT).Results: We identified 15 randomized controlled trials (RCTs) involving 3,431 patients with RVO in our study. Different therapeutic regimens were compared including three anti-vascular endothelial growth factor (VEGF) agents (ranibizumab, bevacizumab, and aflibercept), ranibizumab with laser, dexamethasone intravitreal implant, and laser. For branch RVO, ranibizumab 0.5 mg monthly [weighted mean difference (WMD) = 11, 95% confidence intervals (CrI) 3.6 to 19], ranibizumab 0.5 mg 3 + pro re nata (WMD = 9.4, 95% CrI 0.43–18) is most effective in terms of changes of BCVA and 15 letters or more of BCVA improvement. For central RVO, three anti-VEGF regimens can improve visual acuity and there is no significant difference of efficacy among ranibizumab, bevacizumab and aflibercept (p > 0.05). Ranibizumab 0.5 mg monthly could achieve additional efficacy in CRT reduction in eyes with branch RVO or central RVO (WMD = -130, 95% CrI -400 to 140 or WMD = -280, 95% CrI -590 to 16)). Dexamethasone intravitreal implant (WMD = 1.7, 95% CrI -4.2 to 7.1 or WMD = 0.38, 95% CrI -9.8 to 8.8)) did not show a significant improvement in visual acuity at the end of 6 months follow-up in eyes with branch RVO or central RVO.Conclusion: In summary, this network meta-analysis demonstrated several anti-VEGF agents had equivalent effects on mean visual acuity changes and anatomical recovery in 6 months in eyes with branch or central RVO. Only one injection of dexamethasone intravitreal implant in 6 months could not maintain the visual benefit. Patients and clinicians could choose pharmacotherapies with further consideration toward personal factors.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the loss of immune tolerance. Lupus nephritis (LN) is still a major cause of the morbidity and mortality of SLE. In clinical practice, diagnosis, and therapy of SLE is complicated and challenging due to lack of ideal biomarkers. Exosomes could be detected from numerous kinds of biological fluids and their specific contents are considered as hallmarks of autoimmune diseases. The exosomal miRNA profiles of SLE/LN patients significantly differ from those of the healthy controls making them as attractive biomarkers for renal injury. Exosomes are considered as optimal delivery vehicles owing to their higher stable, minimal toxicity, lower immunogenicity features and specific target effects. Endogenous miRNAs can be functionally transferred by exosomes from donor cells to recipient cells, displaying their immunomodulatory effects. In addition, it has been confirmed that exosomal miRNAs could directly interact with Toll-like receptors (TLRs) signaling pathways to regulate NF-κB activation and the secretion of inflammatory cytokines. The present Review mainly focuses on the immunomodulatory effects of exosomal-miRNAs, the complex interplay between exosomes, miRNAs and TLR signaling pathways, and how the exosomal-miRNAs can become non-invasive diagnostic molecules and potential therapeutic strategies for the management of SLE.

Background: We aimed to evaluate the comparative efficacy and safety of anti–vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD).Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost

There is emerging evidence that environmental toxicants, in particular endocrine disrupting chemicals (EDCs) such as cadmium and perfluorooctanesulfonate (PFOS), induce Sertoli cell and testis injury, thereby perturbing spermatogenesis in humans, rodents and also widelife. Recent studies have shown that cadmium (e.g., cadmium chloride, CdCl2) and PFOS exert their disruptive effects through putative signaling proteins and signaling cascade similar to other pharmaceuticals, such as the non-hormonal male contraceptive drug adjudin. More important, these signaling proteins were also shown to be involved in modulating testis function based on studies in rodents. Collectively, these findings suggest that toxicants are using similar mechanisms that used to support spermatogenesis under physiological conditions to perturb Sertoli and testis function. These observations are physiologically significant, since a manipulation on the expression of these signaling proteins can possibly be used to manage the toxicant-induced male reproductive dysfunction. In this review, we highlight some of these findings and critically evaluate the possibility of using this approach to manage toxicant-induced defects in spermatrogenesis based on recent studies in animal models.

Microglia play a vital role in neurodegenerative diseases. However, the effects of microglia-derived exosomes on neuronal cells are poorly understood. This study aimed to explore the role of M1-polarized microglia exosomes in neuronal cells by transcriptome analysis. Exosomes isolated from resting M0-phenotype BV2 (M0-BV2) microglia and M1-polarized BV2 (M1-BV2) microglia were analyzed using high-throughput sequencing of the transcriptome. Differentially expressed genes (DEGs) between the two types of exosomes were identified by analyzing the sequencing data. The biological functions and pathways regulated by the identified DEGs were then identified using bioinformatics analyses. Finally, we evaluated the effects of exosomes on neuronal cells by coculturing M0-BV2 and M1-BV2 exosomes with primary neuronal cells. Enrichment analyses revealed that DEGs were significantly enriched in the ferroptosis pathway (p = 0.0137). M0-BV2 exosomes had no distinct effects on ferroptosis in neuronal cells, whereas M1-BV2 exosomes significantly reduced ferroptosis suppressor proteins (GPX4, SLC7A11, and FTH1) and elevated the levels of intracellular and mitochondrial ferrous iron and lipid peroxidation in neuronal cells. Polarized M1-BV2 microglia exosomes can induce ferroptosis in neuronal cells, thereby aggravating neuronal damage. Taken together, these findings enhance knowledge of the pathogenesis of neurological disorders and suggest potential therapeutic targets against neurodegenerative diseases.

Aim: To investigate the compliance and the outcome of Traditional Chinese Medicine (TCM) in patients with coronary heart disease (CHD) after treatment of revascularization.Methods: In this prospective cohort study, the non-exposure group (NEG), low-exposure group (LEG), and high-exposure group (HEG) were divided after 2 years follow-up. The primary outcome was a composite of death from cardiovascular causes, non-lethal myocardial infarction, heart transplantation, or stroke. Time-to-event data were evaluated by using the Cox regression analysis with hazard ratios (HRs) and 95% CIs. Then, the two-sided p-values were calculated by using the Cox models. In order to indicate the therapeutic effects of TCM on the CHD after revascularization, the survival analysis and the nested case–control study were conducted separately.Results: There were 1,003 patients with CHD enrolled, 356 patients (35.49%) did not choose the TCM, 379 patients (37.79%) used the TCM seldom, and only 268 patients (26.72%) used TCM regularly. A total of 653 patients with revascularization participated in the prospective cohort study. Over the duration of the trial, the primary endpoints occurred in 12 (4.35%), 11 (4.80%), and 2 (1.35%) patients in the NEG, LEG, and HEG, while the secondary endpoints occurred in 84 (30.43%), 57 (24.89%), and 15 (10.14%) patients in the NEG, LEG, and HEG, respectively. The occurrence time of secondary endpoint events in HEG was significantly postponed (p < 0.001) compared with the other cohorts. The Cox regression analysis indicated that the HRs in the primary endpoints, the secondary endpoint events, the major adverse cardiac and cerebrovascular events (MACCE), and the composite endpoint events for HEG were all around 0.3 (p < 0.05) and HRs for LEG were all around 0.8. The results of the nested case–control study showed that the TCM exposure was significantly different between the cases and controls in the secondary endpoints (p < 0.05), while no significant difference in the primary endpoints (p > 0.05), but the percentage of HEG in the cases was extremely lower than the controls.Conclusion: The HEG-TCM may improve the outcomes of the patients with CHD after treatment of revascularization.Registration:http://www.chictr.org.cn. Unique identifier: ChiCTR-OOC-17012995.

In recent years, marine oil spills have adversely affected the marine economy and ecosystem, and the detection of marine oil slicks has attracted great attention. Combining different polarimetric features for better oil spill detection is a topic that needs to be studied in depth. Previous studies have shown that the compact polarimetric (CP) synthetic aperture radar (SAR) can be effectively applied to the detection of sea surface oil spill due to its own ability, which is conducive to the extraction of sea surface oil slick. In this paper, we apply the power–entropy (PE) decomposition theory, which decomposes the total scattered power according to the entropy contribution of each cell in the response, to CP SAR data for oil spill detection. The purpose of this study is to enhance the oil slick and the separability of the sea. As a result, an oil spill detection method based on the low-entropy radiation amplitude parameter lesa is proposed. We compare lesa with the other five popular polarimetric features and validate by quantitative evaluation that lesa is superior to other types of polarization feature parameters under different band data. Moreover, the random forest classification is performed on the feature map and achieves the visualization results of oil spill detection. The experimental results show that the lesa can combine the information of the two polarimetric characteristic parameters of entropy and total scattering power, and can clearly indicate the oil slick information under different scenarios.

Breast cancer is one of the most common malignant tumors in women and is the second leading cause of cancer deaths among women. The tumorigenesis and progression of breast cancer are not well understood. The existing researches have indicated that non-coding RNAs, which mainly include long non-coding RNA (lncRNA) and microRNA (miRNA), have gradually become important regulators of breast cancer. We aimed to screen the differential expression of miRNA and lncRNA in the different breast cancer stages and identify the key non-coding RNA using TCGA data. Based on series test of cluster (STC) analysis, bioinformatics analysis, and negatively correlated relationships, 122 lncRNAs, 67 miRNAs, and 119 mRNAs were selected to construct the regulatory network of lncRNA and miRNA. It was shown that the miR-93/20b/106a/106b family was at the center of the regulatory network. Furthermore, 6 miRNAs, 10 lncRNAs, and 15 mRNAs were significantly associated with the overall survival (OS, log-rank P < 0.05) of patients with breast cancer. Overexpressed miR-93 in MCF-7 breast cancer cells was associated with suppressed expression of multiple lncRNAs, and these downregulated lncRNAs (MESTIT1, LOC100128164, and DNMBP-AS1) were significantly associated with poor overall survival in breast cancer patients. Therefore, the miR-93/20b/106a/106b family at the core of the regulatory network discovered by our analysis above may be extremely important for the regulation of lncRNA expression and the progression of breast cancer. The identified key miRNA and lncRNA will enhance the understanding of molecular mechanisms of breast cancer progression. Targeting these key non-coding RNA may provide new therapeutic strategies for breast cancer treatment and may prevent the progression of breast cancer from an early stage to an advanced stage.

Relation classification is a crucial ingredient in numerous information-extraction systems and has attracted a great deal of attention in recent years. Traditional approaches largely rely on feature engineering and suffer from the limitations of the domain adaption and the error propagation. To overcome the above-mentioned problems, many deep neural network-based methods have been proposed; however, these methods cannot effectively locate and utilize the relation trigger features. To locate the relation trigger features and make full use of them, we propose a novel multi-gram convolution neural network-based self-attention model with a recurrent neural network framework. The multi-gram conventional neural network attention model can learn the adaptive relational semantics of inputs based on the fact that a relation can be totally defined by the shortest dependency path between its two entities. With the learned relational semantics, we can obtain the corresponding importance distribution over input sentences and locate the relation trigger features. For effective information propagation and integration, we utilize a bidirectional gated recurrent unit to encode the high-level features during recurrent propagation. The experimental results on two benchmark datasets demonstrate that the proposed model outperforms most of the state-of-the-art models.

When people do the reading comprehension, they often try to find the words from the passages which are similar to the question words first. Then people deduce the answer based on the context around these similar words. Therefore, the position information may be helpful in finding the answer rapidly and is useful for reading comprehension. However, previous attention-based machine reading comprehension models typically focus on the interaction between the question and the context representation without considering the position information. In this paper, we introduce the position information to machine reading comprehension and investigate the performance of the position information. The position information is experimented in three different ways: 1) position encoder; 2) attention mechanism; and 3) position mapping embedding. By experimenting on TriviaQA dataset, we have demonstrated the effectiveness of position information.

We demonstrate a method for testing the real off-state breakdown voltage (VBD) of AlGaN/GaN metal-insulator-semiconductor high electron mobility transistor (MIS-HEMTs) in on-wafer tests. The method prevents the arcing over air at high voltage by depositing the protective layer between the pad electrodes of source and drain. The influence of materials and thickness of the protective layer on the high voltage tests of MIS-HEMTs were investigated. We found that it is helpful to obtain the real VBD of the devices by increasing the thickness of the protective layer and selecting a material with a higher critical breakdown field strength. The real VBD of the device with a gate-to-drain spacing of 25 μm is 1164 V when 1.5 μm SiO2 is deposited as the protective layer, which is 141% higher than that of the value tested in air.

Objective: Testosterone plays an essential role in maintaining spermatogenesis and male fertility, and the primary known source of testosterone is testicular Leydig cells, which are regulated by luteinizing hormone (LH). However, whether any other ways of testosterone secretion exist still remains unknown. Methods: Transmission electron microscopy was used to detect testicular extracellular vesicles (EVs), which were isolated by an ultracentrifuge process. Separately, the concentrations of follicle-stimulating hormone (FSH), LH, and testosterone were measured by enzyme-linked immunosorbent assay. Results: Some EVs were found by tail vein injection to be present in mouse testes that elevate the circulating testosterone and LH levels in the blood, but do not affect FSH. Separately, they also promote testosterone production in the TM3 Leydig cell line in vitro. To determine whether the EVs from spermatogonia were involved in the secretion of testosterone, we used spermatogonial stem/progenitor cell line C18-4 cells and revealed that C18-4 cells promote production of testosterone in the TM3 Leydig cell line using the EVs. Conclusions: EVs in mouse testes likely originate from spermatogonia and involved in the regulation of the serum testosterone. Our results provide a new mechanism for the regulation of testosterone production.

Triple-negative breast cancer (TNBC) is often treated with anthracyclines (e.g., epirubicin or doxorubicin), but very little is known about anthracycline resistance, especially epirubicin resistance in TNBC. To identify novel long noncoding RNAs (lncRNAs) involved in epirubicin resistance in TNBC, we established a new TNBC MDA-MB-231 cell line that was resistant to epirubicin (Epi-R). A total of 12 differentially expressed lncRNAs were identified using RNA sequencing analysis of Epi-R cells. Among these lncRNAs, we found a novel intronic lncRNA, lnc005620, was highly expressed in Epi-R cells and human TNBC tissues. Further gain- and loss-of-function studies demonstrated that lnc005620 played an oncogenic role and partially abrogated the effects of epirubicin on TNBC cells. Using iTRAQ proteomics analysis, we found that three members of the integrin family, integrin β4, integrin β1 and integrin α6, were all upregulated in Epi-R MDA-MB-231 cells. Integrin β1, encoded by the ITGB1 gene, was validated to be a downstream target of lnc005620 in Epi-R MDA-MB-231 cells. Our study demonstrates that novel lnc005620 promotes TNBC progression and chemoresistance to epirubicin via integrin β1 both in vitro and in vivo and provides a promising therapeutic target for TNBC patients in terms of enhancing the benefits of epirubicin treatment.

A retained gob-side entry technique is popular in longwall mining coal mines, because the excavation of an entry is reduced for the next panel. However, it is influenced by multiple excavations and mining, so the stability control of the surrounding rock becomes a problem. In view of the above problems, a typical retained gob-side entry with thick immediate roof was carried out, and a blasting fracturing roof technology was used in it to improve the stress environment, reduce the deformation and damage, and ensure stability and safety. To study the fracturing roof parameters, a global model with thick immediate roof considering strain-soft and double-yield constitution was built. It found that the stress, damage range, and deformation of surrounding rock were closely related to the height and angle of fracturing roof, and an optimal case was given out. The simulation result was applied to the field practice, and a good application effect was achieved. The above technique and research method can be used as a reference for the coal mine with similar conditions.

The sustainable development of the marine economic system to accurately grasp the dynamic evolution characteristics and main driving factors of the vulnerability of the marine economic system so as to effectively identify the problems in the operation of the marine economy is extremely important. Based on the establishment of a three-level assessment index system for the vulnerability of the marine economic system, the vulnerability of the marine economic system of Jiangsu Province in 2008–2016 was evaluated by using the comprehensive index model and the catastrophe progression model, and the results were compared based on the unified evaluation criteria. The main influencing factors were analyzed by principal component analysis and Pearson correlation analysis. It’s found that 2014, 2015, and 2012 are in a general state, 2009 and 2010 are in a poor state, and the vulnerability state from 2008 to 2011 is lower than that in 2012. The overall volatility is small indicating a stable system. Among them, the scale of marine industry and profit and loss of marine resources are the main components of marine economic system vulnerability having the highest correlation with the vulnerability of marine economic system. This study enriches the theoretical method and empirical research on the vulnerability of the marine economic system and has practical significance in allowing for timely targeted control measures to affect the vulnerability of the marine economic system.

During the drilling and repairing of wells, the pipe string transfer equipment has a high work frequency. The movement accuracy, response speed, and controllability of the equipment have significant impacts on the stability. In this paper, we propose an analysis method of mechanical arms to lift pipe strings using a rigid–flexible coupling model. With the mechanical arm as a flexible body and the mechanical hand as a rigid body, a numerical calculation model of the rigid-flexible coupling of the system was established based on the Lagrangian equation. ADAMS and Ansys software were applied to numerical simulations of this system to investigate the lifting characteristics, the influence of the operation parameters and structure parameters, and the contact collision analysis of the mechanical arm. The conditions of rigid–flexible modeling for the multi-body system and the main factors affecting the vibration characteristics of the flexible arm are described. We conclude that the arm should be modeled as a rigid body if the structure parameter [w/l] (elastic deformation/length) is between 1/650 and 1/1000, the system can be modeled as a rigid–flexible coupling if [w/l] is between 1/400 and 1/650, and the arm should be modeled as a flexible body and the influence and compensation of the control method should be considered if [w/l] is between 1/250 and 1/400.

During meiosis, telomeres attach to the nuclear envelope (NE) to promote homologous chromosome moving, pairing, synapsis, and recombination. The telomere-NE attachment is mediated by SUN1, TERB1-TERB2-MAJIN (TTM complex), and TRF1. The interaction of the TTM complex with shelterin is mediated by TERB1 and TRF1, but how SUN1 interacts with the TTM complex is not yet fully understood. In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. The binding sites of MAJIN and SPDYA at SUN1 were mapped, and both MAJIN and SPDYA bound to the N-terminal domain of SUN1 and the two binding sites were close to each other. Furthermore, SPDYA bound to SUN1 via the Ringo domain and recruited CDK2 to SUN1. Then, we found that the interaction of SUN1 with MAJIN was decreased by the CDK2 inhibitors. Taken together, our results provide the possible mechanism of SUN1, MAJIN, and SPDYA-CDK2 in promoting the telomere-NE attachment during meiosis.

Xin Su Ning (XSN), a China patented and certified multi-herbal medicine, has been available in China since 2005 for treating cardiac ventricular arrhythmia including arrhythmia induced by ischemic heart diseases and viral myocarditis, without adverse reactions being reported. It is vitally important to discover pharmacologically how XSN as a multicomponent medicine exerts its clinical efficacy, and whether the therapeutic effect of XSN can be verified by standard clinical trial studies. In this paper we report our discoveries in a cellular electrophysiological study and in a three-armed, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Conventional electrophysiological techniques were used to study the cellular antiarrhythmic mechanism of XSN. Data was then modeled with computational simulation of human action potential (AP) of the cardiac ventricular myocytes. The clinical trial was conducted with a total of 861 eligible participants randomly assigned in a ratio of 2:2:1 to receive XSN, mexiletine, or the placebo for 4 weeks. The primary and secondary endpoint was the change of premature ventricular contraction (PVC) counts and PVC-related symptoms, respectively. This trial was registered in the Chinese Clinical Trial Register Center (ChiCTR-TRC-14004180). We found that XSN prolonged AP duration of the ventricular myocytes in a dose-dependent, reversible manner and blocked potassium channels. Patients in XSN group exhibited significant total effective responses in the reduction of PVCs compared to those in the placebo group (65.85% vs. 27.27%, P < 0.0001). No severe adverse effects attributable to XSN were observed. In conclusion, XSN is an effective multicomponent antiarrhythmic medicine to treat PVC without adverse effect in patients, which is convincingly supported by its class I & III pharmacological antiarrhythmic mechanism of blocking hERG potassium channels and hNaV1.5 sodium channel reported in our earlier publication and prolongs AP duration both in ventricular myocytes and with computational simulation of human AP presented in this report.