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In this study, the following four groups of mice with hyperlipidemia were involved: the model control group (MC), the Chrysanthemum flavonoids group (CF), the luteolin group, and the luteoloside group. The whole gene expression profile was detected in the liver tissues of each group. Differential genes significantly enriched in the biological process of gene ontology (GO) items and Kyoto Encyclopedia of Genes and Genomes (KEGG) were selected, and 4 differential genes related to lipid metabolism were selected for further real-time quantitative PCR verification. Compared with the MC, 41 differential genes such as Sqle, Gck, and Idi1 were screened in the CF intervention group; 68 differential genes such as Acsl3, Cyp7a1, and Lpin1 were screened in the luteolin intervention group (CF); and 51 differential genes such as Acaca, Cyp7a1, and Lpin1 were screened in the luteoloside group. The mechanism of CF to improve hyperlipidemia is very complex, mainly involving biological processes such as cholesterol and fatty acid metabolism and glycolysis, luteolin mainly involves the synthesis and transport of cholesterol, and luteoloside mainly involves fatty acid metabolism. The functional pathways of CF may not be completely the same as luteolin and luteoloside, and further study is needed on the mechanism of action of other components.

Abstract Bile acid metabolites have been increasingly recognized as pleiotropic signaling molecules that regulate cardiovascular functions, but their role in mesenchymal stromal cells (MSC)‐based therapy has never been investigated. It is found that overexpression of farnesoid X receptor (FXR), a main receptor for bile acids, improves the retention and cardioprotection of adipose tissue‐derived MSC (ADSC) administered by intramyocardial injection in mice with myocardial infarction (MI), which shows enhanced antiapoptotic, proangiogenic, and antifibrotic effects. RNA sequencing, LC‐MS/MS, and loss‐of‐function studies reveal that FXR overexpression promotes ADSC paracrine angiogenesis via Angptl4. FXR overexpression improves ADSC survival in vivo but fails in vitro. By performing bile acid‐targeted metabolomics using ischemic heart tissue, 19 bile acids are identified. Among them, cholic acid and deoxycholic acid significantly increase Angptl4 secretion from ADSC overexpressing FXR and further improve their proangiogenic capability. Moreover, ADSC overexpressing FXR shows significantly lower apoptosis by upregulating Nqo‐1 expression only in the presence of FXR ligands. Retinoid X receptor α is identified as a coactivator of FXR. It is first demonstrated that there is a bile acid pool in the myocardial microenvironment. Targeting the bile acid‐FXR axis may be a novel strategy for improving the curative effect of MSC‐based therapy for MI.

Extant literature suggested that executive cognitive ability is a critical perspective to answering why and how enterprises perform business model innovation. However, the effect of executive cognitive ability on business model innovation is still insufficiently explored. Drawing on entrepreneurial bricolage theory, we developed a moderated mediation model which takes entrepreneurial bricolage as the mediating mechanism and environmental dynamics as the moderating mechanism to explain how executive cognitive ability influences business model innovation. We collected the data of 316 executives of Chinese start-ups through questionnaires for the model test. Results showed that new venture executives' cognitive ability significantly positively affects business model innovation by mediating with entrepreneurial bricolage. Environmental dynamism positively moderates the effect of executives' cognitive ability on business model innovation. Moreover, environmental dynamism positively moderates the mediating role of entrepreneurial bricolage in executive cognitive ability and business model innovation. This study broadens the research scope of entrepreneurial bricolage theory from the perspective of cognitive ability and provides ideas for new ventures' business model innovation.

Arabinogalactan (AG) participates in forming the cell wall core of mycobacteria, a structure known as the mAGP complex. Few studies have reported the virulence of inartificial AG or its interaction with the host immune system. Using clustered regularly interspaced short palindromic repeats interference gene editing technology, conditional Mycobacterium marinum mutants were constructed with a low expression of embA or glfT2 (EmbA_KD or GlfT2_KD), which are separately involved in the biosynthesis of AG arabinose and galactose domains. High-performance gel permeation chromatography and high-performance liquid chromatography assays confirmed that the EmbA_KD strain showed a remarkable decrease in AG content with fragmentary arabinose chains, and the GlfT2_KD strain displayed less reduction in content with cut-down galactose chains. Based on transmission and scanning electron microscopy observations, the cell walls of the two mutants were found to be dramatically thickened, and the boundaries of different layers were more distinct. Phenotypes including the over-secretion of extracellular substances and enhanced spreading motility with a concomitant decreased resistance to ethambutol appeared in the EmbA_KD strain. The EmbA_KD and GlfT2_KD strains displayed limited intracellular proliferation after infecting murine J774A.1 macrophages. The disease progression infected with the EmbA_KD or GlfT2_KD strain significantly slowed down in zebrafish/murine tail infection models as well. Through transcriptome profiling, macrophages infected by EmbA_KD/GlfT2_KD strains showed enhanced oxidative metabolism. The cell survival measured using the CCK8 assay of macrophages exposed to the EmbA_KD strain was upregulated and consistent with the pathway enrichment analysis of differentially expressed genes in terms of cell cycle/apoptosis. The overexpression of C/EBPβ and the increasing secretion of proinflammatory cytokines were validated in the macrophages infected by the EmbA_KD mutant. In conclusion, the AG of Mycobacterium appears to restrain the host innate immune responses to enhance intracellular proliferation by interfering with oxidative metabolism and causing macrophage death. The arabinose chains of AG influence the Mycobacterium virulence and pathogenicity to a greater extent.

BackgroundOne of the most common diseases that have a negative impact on women’s health is endometrial carcinoma (EC). Advanced endometrial cancer has a dismal prognosis and lacks solid prognostic indicators. IFN-γ is a key cytokine in the inflammatory response, and it has also been suggested that it has a role in the tumor microenvironment. The significance of IFN-γ-related genes and long non-coding RNAs in endometrial cancer, however, is unknown.MethodsThe Cancer Genome Atlas (TCGA) database was used to download RNA-seq data from endometrial cancer tissues and normal controls. Genes associated with IFN-γ were retrieved from the gene set enrichment analysis (GSEA) website. Co-expression analysis was performed to find lncRNAs linked to IFN-γ gene. The researchers employed weighted co-expression network analysis (WGCNA) to find lncRNAs that were strongly linked to survival. The prognostic signature was created using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. The training cohort, validation cohort, and entire cohort of endometrial cancer patients were then split into high-risk and low-risk categories. To investigate variations across different risk groups, we used survival analysis, enrichment analysis, and immune microenvironment analysis. The platform for analysis is R software (version X64 3.6.1).ResultsBased on the transcript expression of IFN-γ-related lncRNAs, two distinct subgroups of EC from TCGA cohort were formed, each with different outcomes. Ten IFN-γ-related lncRNAs were used to build a predictive signature using Cox regression analysis and the LASSO regression, including CFAP58, LINC02014, UNQ6494, AC006369.1, NRAV, BMPR1B-DT, AC068134.2, AP002840.2, GS1-594A7.3, and OLMALINC. The high-risk group had a considerably worse outcome (p < 0.05). In the immunological microenvironment, there were also substantial disparities across different risk categories.ConclusionOur findings give a reference for endometrial cancer prognostic type and immunological status assessment, as well as prospective molecular markers for the disease.

Extreme drought has negative impacts on the health of vegetation and the stability of ecosystems. In this study, the CASA model was employed to estimate the net primary productivity of vegetation over the Yunnan Plateau. The time-lag effects on vegetation were observed within a 0–6 month period of extreme droughts using the Pearson correlation coefficient. The resistance of vegetation during extreme droughts was quantified, and the recovery capability of vegetation following these events was analyzed using the ARIMA model. Moreover, the study investigated the response of vegetation to extreme droughts across diverse altitudinal gradients. The results showed that: (1) This round of extreme drought led to a decrease in the NPP of vegetation in the Yunnan Plateau. (2) Vegetation exhibits a 1–3-month lag period in response to extreme drought, with forests showing slower responses than grasslands and shrubs and higher resistance to the drought. Except for agricultural vegetation, most other vegetation types are able to recover their productivity within a year. (3) Vegetation above 3000 m is less susceptible to the impacts of extreme drought. With increasing elevation, forests exhibit an earlier lag period in response to extreme drought and an increase in resistance, but lower elevation vegetation demonstrates better recovery from extreme drought events. Shrub vegetation shows the highest resistance at elevations between 3000–4000 m, and shrubs at middle to high elevations have better recovery capacity than those at low elevations. Grassland vegetation exhibits increased resistance to extreme drought with higher elevation and shows better recovery. Agricultural vegetation demonstrates higher resistance at middle to high elevations, with no significant elevation differences in recovery capacity. Extreme drought events not only have a lag effect on the vegetation ecosystem, but also affect its stability and resilience to future drought events. To adapt to climate change, future research should emphasize the role of small-scale climate in vegetation’s response to drought.

Apert syndrome (AS) is characterized by synostosis of coronal sutures, midfacial hypoplasia,abnormity of brain, syndactyly of hands and feet. Majority of AS is caused by gain-of-function mutation of fibro‐blast growth factor receptor 2 (FGFR2). To date, the treatment of AS is surgical correction for the deformed skull.The reconstruction of sutures is often executed several times, because of constant premature of sutures. Some dis‐eased tissues, such as brain, are difficult to treat with surgery. CRISPR/Cas9 gene editing technology exhibits pow‐erful prospect in the treatment of human genetic diseases. In this study, small guiding RNA (gRNA) specificallytargeting the Fgfr2 gene was screened and lentivirus mediated Cas9/gRNA was employed to treat mice (Fg‐fr2+/P253R) that mimicking human Apert syndrome in primary calvarial cells, calvarial explants or calvarial bone. Incultured primary calvarial cells, Cas9/gRNA reduced the phosphorylation of ERK1/2 and P38, and resultantly inhibited osteoblastic differentiation and matrix mineralization. Besides, Cas9/gRNA attenuated the premature closure ofcoronal suture and the decreased calvarial bone volume calvarial explants and AS mice. This study provides exper‐imental basis of gene therapy for Apert syndrome, and is prospective to provide new strategies for the treatment ofskeletal genetic diseases.

Abstract Erectile dysfunction (ED) is mostly due to the lack of blood flow into the penis. In the past 20 years, near-infrared spectroscopy (NIRS) was used in measuring the concentrations and temporal dynamics of different hemoglobin types. However, the dynamics of the light absorption (photoplethysmography; PPG) have not been applied to survey penile hemodynamics and erection quality. This paper compared the use of photoplethysmography (PPG) to study vascular ED with standard penile Doppler ultrasonography. Men diagnosed with vascular ED for at least 6 months and nominated for penile ultrasonography were included. PPG signals were collected during the ultrasound examination. All beat-to-beat PPG waveforms were aligned with the peak and averaged to one representative template waveform for feature analysis, including amplitude differences (APD) index, reflection time index (RTI), augmentation index (AI), and perfusion index (PI). An inverse correlation was found between end-erection amplitude and both erection hardness score (EHS) and resistive index (RI). APD index and EHS as well as the international index of erectile function-5 (IIEF) and RI were positively correlated. RTI and AI were inversely correlated to IIEF and RI. PI was positively correlated to RI. PPG may therefore be useful as a noninvasive, convenient, technique for sexual function evaluation.

AIM: To evaluate the diagnostic performance of the isolated-checked visual evoked potential(IC-VEP)in the detection of open angle glaucoma and compared it to the blue-yellow perimetry(B/YP)and optical coherent tomography(OCT).METHODS: In a retrospective analysis, IC-VEP, perimetry and OCT were performed on 101 subjects(n=35, normal; n=30, early glaucoma; n=36, moderate and advanced glaucoma)from China. The sensitivity of IC-VEP, perimetry and OCT for detection of glaucoma, as well as the agreement within these 3 methods, were calculated to evaluate their clinic performance.RESULTS: In the early primary open angle glaucoma(POAG)group the sensitivity of IC-VEP, blue-yellow perimetry and OCT were 70.00%, 70.00% and 63.33%, respectively. In the moderate advanced POAG group, the sensitivity of IC-VEP, OCT and blue-yellow perimetry were 86.11%, 88.89% and 91.67%, respectively. The specificity of IC-VEP was 91.43%. The results of IC-VEP were highly consistent with OCT and blue-yellow visual field tests(kappa: 0.721-1.000, P

Abstract Objective No relapse risk prediction tool is currently available to guide treatment selection for multiple sclerosis (MS). Leveraging electronic health record (EHR) data readily available at the point of care, we developed a clinical tool for predicting MS relapse risk. Methods Using data from a clinic‐based research registry and linked EHR system between 2006 and 2016, we developed models predicting relapse events from the registry in a training set (n = 1435) and tested the model performance in an independent validation set of MS patients (n = 186). This iterative process identified prior 1‐year relapse history as a key predictor of future relapse but ascertaining relapse history through the labor‐intensive chart review is impractical. We pursued two‐stage algorithm development: (1) L1‐regularized logistic regression (LASSO) to phenotype past 1‐year relapse status from contemporaneous EHR data, (2) LASSO to predict future 1‐year relapse risk using imputed prior 1‐year relapse status and other algorithm‐selected features. Results The final model, comprising age, disease duration, and imputed prior 1‐year relapse history, achieved a predictive AUC and F score of 0.707 and 0.307, respectively. The performance was significantly better than the baseline model (age, sex, race/ethnicity, and disease duration) and noninferior to a model containing actual prior 1‐year relapse history. The predicted risk probability declined with disease duration and age. Conclusion Our novel machine‐learning algorithm predicts 1‐year MS relapse with accuracy comparable to other clinical prediction tools and has applicability at the point of care. This EHR‐based two‐stage approach of outcome prediction may have application to neurological disease beyond MS.

Abstract Due to unique photovoltaic properties, the nanostructured morphologies of TiO2 on flexible substrate have been studied extensively in the recent years for applications in dye sensitized solar cells (DSSCs). Microstructured electrode materials with high surface area can facilitate rapid charge transport and thus improve the light-to-current conversion efficiency. Herein we present an improved photoanode with forest like photoactive TiO2 hierarchical microstructure using a simple and facile hydrothermal route. To utilize the surface plasmon resonance (SPR) and hence increase the photon conversion efficiency, a plasmonic nanoparticle Ag has also been deposited using a very feasible photoreduction method. The branched structure of the photoanode increases the dye loading by filling the space between the nanowires, whereas Ag nanoparticles play the multiple roles of dye absorption and light scattering to increase the light-to-current conversion efficiency of the device. The branched structure provides a suitable matrix for the subsequent Ag deposition. They improve the charge collection efficiency by providing the preferential electron pathways. The high-density Ag nanoparticles deposited on the forest like structure also decrease the charge recombination and therefore improve the photovoltaic efficiency of the cells. As a result, the DSSC based on this novel photoanode shows remarkably higher photon conversion efficiency (ηmax = 4.0% and ηopt = 3.15%) compared to the device based on pristine nanowire or forest-like TiO2 structure. The flexibility of the device showed sustainable and efficient performance of the microcells.

Deep brain stimulation (DBS) is an increasingly utilized treatment for multiple neurological disorders. Continued improvements in DBS outcome are, in part, related to increasing ability to directly visualize stimulation targets by MRI. However, it is challenging to image DBS targets with conventional MRI techniques due to limited contrast. Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) is a commonly used MRI sequence that improves visualization of several key DBS targets by suppressing white matter (WM) signal to better reveal deep-brain gray matter (GM) structures. Due to increased signal level at high field strength, application of FGATIR on 7T MRI may allow higher spatial resolution and better DBS targeting accuracy. However, successful utilization of FGATIR requires meticulous sequence optimization involving multiple parameters to maximize GM signal while suppressing WM. This is further complicated by the transmit RF field (B1+) inhomogeneity on 7T, which can cause severe contrast degradation. In this work, we introduce a systematic approach to optimize FGATIR and to improve visualization of thalamic DBS targets on 7T. FGATIR optimization is cast into a constrained optimization problem whose objective function and constraints are designed to maximize the GM-WM contrast-to-noise ratio (CNR) while accounting for B1+ inhomogeneity. This approach allows a systematic search for optimal parameters across the multi-dimensional parametric space while limiting the negative effect of B1+ variation. Bloch equation simulations were performed to solve the proposed optimization problem and to compare the sequence derived from this method against the sequence optimized without considering B1+ inhomogeneity. The results showed that this approach can improve GM-WM CNR in the presence of B1+ inhomogeneity, especially in some high relative B1+ areas where several key thalamic DBS targets are located. Additionally, in vivo images were acquired on a clinical 7T MRI to further validate this approach. Severe contrast degradation in the thalamus was observed when B1+ effect was not considered in sequence optimization, while the proposed approach yielded improved image contrast in the thalamus with key DBS targets well-defined. These results demonstrated that the proposed method allowed optimization of FGATIR on 7T to better visualize thalamic DBS targets, which may lead to improved DBS targeting accuracy as well as treatment outcome.

Quantitative EEG (qEEG) delineates complex brain activities. Global field synchronization (GFS) is one multichannel EEG analysis that measures global functional connectivity through quantification of synchronization between signals. We hypothesized that preservation of global functional connectivity of brain activity might be a surrogate marker for good outcome in sudden cardiac arrest (SCA) survivors. In addition, we examined the relation of phase coherence and GFS in a mathematical approach. We retrospectively collected EEG data of SCA survivors in one academic medical center. We included 75 comatose patients who were resuscitated following in-hospital or out-of-hospital nontraumatic cardiac arrest between 2013 and 2017 in the intensive care unit (ICU) of National Taiwan University Hospital (NTUH). Twelve patients (16%) were defined as good outcome (GO) (CPC 1–2). The mean age in the GO group was low (51.6 ± 15.7 vs. 68.1 ± 12.9, p < 0.001). We analyzed standard EEG power, computed EEG GFS, and assessed the cerebral performance category (CPC) score 3 months after discharge. The alpha band showed the highest discrimination ability (area under curve [AUC] = 0.78) to predict GO using power. The alpha band of GFS showed the highest AUC value (0.8) to predict GO in GFS. Furthermore, by combining EEG power + GFS, the alpha band showed the best prediction value (AUC 0.86) in predicting GO. The sensitivity of EEG power + GFS was 73%, specificity was 93%, PPV was 0.67%, and NPV was 0.94%. In conclusion, by combining GFS and EEG power analysis, the neurological outcome of the nontraumatic cardiac arrest survivor can be well-predicted. Furthermore, we proved from a mathematical point of view that although both amplitude and phase contribute to obtaining GFS, the interference in phase variation drastically changes the possibility of generating a good GFS score.

ABSTRACT Granulomas are the pathological hallmark of tuberculosis (TB). In individuals with latent TB infection, Mycobacterium tuberculosis cells reside within granulomas in a nonreplicating dormant state, and a portion of them will develop active TB. Little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4::Tn mutant of M. marinum caused persistent infection in adult zebrafish, which is characterized by the lower but stable bacterial loads, constant number of nonnecrotized granulomas in fewer organs, and reduced inflammation compared to those of zebrafish infected with the wild-type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4::Tn mutant was defective in resuscitation from hypoxia-induced dormancy and the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from persistent infection. IMPORTANCE About one-quarter of the world’s population has latent TB infection, and 5 to 10% of those individuals will fall ill with TB. Our finding suggests that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection, thereby reducing the incidences of active TB.

Designing efficient light-emitting diodes with white-light-emission from broadband-emission metal halides remains a challenge. Here, the authors demonstrate bright and efficient lead-free LEDs based on cesium copper halides enabled by introducing Tween organic additive in the precursor.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder resulting in organ damage including ischemic strokes. We sought to characterize the neuroimaging patterns of stroke in a large cohort of patients with immune-mediated TTP (iTTP) and determined their associations with clinical and laboratory parameters and outcomes. Methods: We analyzed the Alabama TTP Registry who had laboratory confirmation of acute iTTP. We reviewed the neuroimaging patterns of those with ischemic stroke on MRI, clinical information, and laboratory results. Small ischemic strokes were ≤20 mm in their maximum diameter in the axial plane. Large ischemic strokes were >20 mm. Student t test, Mann-Whitney U test, and χ2 test were all used for data analysis. Results: Of 108 iTTP patients, 21 had ischemic stroke on neuroimaging. The median platelet count in these patients was 12 × 109/L (interquartile range, IQR, 8.8–21 × 109/L), plasma ADAMTS13 activity 1.8 U/dL (IQR 0–4.5 U/dL), and the mean plasma level of anti-ADAMTS13 IgG was 6,595.8 U/mL (SD 3,448.9 U/mL). Comparison between patients with large ischemic strokes (n = 10) and small ischemic strokes (n = 11) revealed that patients with small stroke were older (p = 0.043) and had higher plasma levels of citrullinated histone 3 (p = 0.006) and histone/DNA complex (p = 0.014) than those with large strokes. There were no significant differences between 2 stroke groups in mortality or exacerbation. Conclusions: iTTP patients can present with large ischemic strokes and are usually younger. Further research should be performed in assessing different etiologies of iTTP-associated stroke based on neutrophil extracellular trap formation biomarkers (e.g., histone markers) seen in small ischemic stroke.

In order to solve the problem of the lack of life characteristic characterization ability in the prediction of the remaining life of the rolling bearing,a method of the residual life prediction of the rolling bearing based on multi-resolution singular value decomposition and ECNN-LSTM is proposed. Firstly,the time-frequency information of vibration signals in onedimensional multi-space scale is extracted by using the multi-resolution singular value decomposition method,and the health stage is divided according to the standard deviation at the initial time. Secondly,a high-efficiency channel attention mechanism module was added to the two-layer one-dimensional convolutional neural network structure,and the convolution kernel was adaptively adjusted for multi-channel interaction without dimension reduction,so as to fully extract bearing degradation characteristics and establish effective life degradation indicators. Finally,MSE loss function is used to achieve the residual life prediction on LSTM.The feasibility and effectiveness of the proposed method are verified by Cincinnati whole life data.

Background: The skin sympathetic nerve activity (SKNA) is a new method to measure sympathetic nerve activity by using conventional ECG electrodes. We developed a novel approach to analyze the complexity of SKNA time series under different time scales and showed its prognostic significance in patients receiving critical care. Methods: This study measured SKNA in patients admitted to an intensive care unit (ICU). Each recording is 10-minute long with 10000Hz sampling rate. Multi-scale fluctuation analysis (MSFA) was developed to quantify the variation within each time scale after removing the linear trend. The prognostic value of SKNA was combined with traditional prognostics scoring system to improve the predictive values. Results: 155 patients were recruited. After 30 and 90 days, 30 and 48 patients expired. MSFA was significantly higher in survival group than mortality group for 30-day (0.487 ± 0.185 vs 0.401 ± 0.045, p = 0.018) and 90-day (0.499 ± 0.196 vs 0.414 ± 0.061, p = 0.001) follow-up. Sequential Organ Failure Assessment (SOFA) score was significantly lower in the survival group compared to the expired group for 30-day and 90-day (4.1 ± 2.9 vs. 5.5 ± 4.1, p = 0.032 and 3.9 ± 3.0 vs. 5.4 ± 3.5, p = 0.012). The Kaplan–Meier survival analysis showed MSFA lower than 0.401 (log-rank test:4.96, p = 0.03) or with SOFA score lower than 5 (log-rank test:5.49, p = 0.019) have a significantly higher mortality rate. A multivariate Cox regression model showed that the MSFA is an independent predictor for 30-day mortality (HR = 2.35, 1.08–5.09, p = 0.031) and 90-day mortality (HR = 1.96, 1.08–3.58, p = 0.027). Conclusion: MSFA was a significant prognostic predictor for critically ill patients. MSFA adding to SOFA score could help improve risk prediction.

The Tröger's base derivative rac-TBPP was synthesized and separated into two enantiomers R2N-TBPP and S2N-TBPP by chiral column chromatography. These compounds show a strong circularly polarized luminescence with glum values of +0.0021, and −0.0025, respectively. The second way to fabricate the rac-TBPP-based CPL-active material is to co-gel the fluorescent rac-TBPP with a chiral ᴅ-glutamic acid gelator DGG by co-assembly strategy. At the molar ratio of rac-TBPP/DGG = 1:80, the glum value of the co-gel was about three times higher than the glum values of R2N-TBPP and S2N-TBPP enantiomers. Interestingly, the CPL handedness of the rac-TBPP/DGG co-gel could be adjusted effectively by changing their stoichiometric ratios.

Poverty has long plagued humanity. The main factors affecting the gap between the rich and the poor are natural resources, human resources, information resources and science and technology. Using data from various clean energy industries and historical research methods, this paper shows that the clean energy industry is a new way to reduce poverty in developing countries. In the history of agricultural development, land and water resources are the important sources of wealth growth. In the history of industrial development, mineral resources, coal and oil energy have become the material basis for getting rich. In the 21st century with the great development of artificial intelligence, the importance of power resources is becoming more and more prominent, and clean energy such as solar energy and wind energy has become a new natural resource to create social wealth. Chinese successful practice in the development of clean energy industry shows that the clean energy industry is an effective way to get out of poverty. The results of the cooperation between China and African countries in developing clean energy industries show that the energy industry plays an increasingly important role in helping developing countries out of poverty. Although the development of clean energy industry is still restricted by market competition and monopoly organizations, the development road is still tortuous and long, it has a very bright future.

Gas hydrates are considered near-future energy resources with their vast amounts all around the world, especially in permafrost and marine environments. Since the beginning of the 2000s, there have been many gas hydrate exploration, drilling, coring, and production trials in the world. The countries (i.e., Japan, China, India) that need urgent energy resources are in a rush to produce feasible natural gas from gas hydrate reservoirs. However, according to available production trial data, there are many obstacles to reaching the commercial level of gas production. Due to the sensitive nature of gas hydrate reservoirs, the health, safety, and environmental risks of all production trials should be discussed. Moreover, it is crucial to control the risks of these production trials. This study aims to investigate the worldwide regulations and policy trends related to gas hydrate production trials.

Laser plasma acceleration has made remarkable progress in the last few decades, but it also faces many challenges. Although the high gradient is a great potential advantage, the beam quality of the laser accelerator has a certain gap, or it is different from that of traditional accelerators. Therefore, it is important to explore and utilize its own features. In this article, some recent research progress on laser proton acceleration and its irradiation application, which was carried out on the compact laser plasma accelerator (CLAPA) platform at Peking University, have been introduced. By combining a TW laser accelerator and a monoenergetic beamline, proton beams with energies of less than 10 MeV, an energy spread of less than 1%, and with several to tens of pC charge, have been stably produced and transported in CLAPA. The beamline is an object–image point analyzing system, which ensures the transmission efficiency and the energy selection accuracy for proton beams with large initial divergence angle and energy spread. A spread-out Bragg peak (SOBP) is produced with high precision beam control, which preliminarily proved the feasibility of the laser accelerator for radiotherapy. Some application experiments based on laser-accelerated proton beams have also been carried out, such as proton radiograph, preparation of graphene on SiC, ultra-high dose FLASH radiation of cancer cells, and ion-beam trace probes for plasma diagnosis. The above applications take advantage of the unique characteristics of laser-driven protons, such as a micron scale point source, an ultra-short pulse duration, a wide energy spectrum, etc. A new laser-driven proton therapy facility (CLAPA II) is being designed and is under construction at Peking University. The 100 MeV proton beams will be produced via laser–plasma interaction by using a 2-PW laser, which may promote the real-world applications of laser accelerators in malignant tumor treatment soon.

The long-legged fly Lichtwardtia dentalis Zhang, Masunaga et Yang, 2009 belongs to the subfamily Dolichopodinae of Dolichopodidae. The newly sequenced mitogenome of L. dentalis is a new representative of the subfamily. The nearly complete mitogenome is 15,124 bp in length, consisting of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), and 22 transfer RNA genes (tRNAs). All genes have similar locations and encoding directions with that of other published mitogenomes of Dolichopodidae. The nucleotide composition biases toward A and T with the overall A + T % is 73.9%. All protein-coding genes initiate with standard start codon ATN except COI and NAD1, and TAA/TAG are conventionally used as stop codons. All tRNAs, ranging from 62 to 71 bp, have a clover-leaf structure. Based on the result of the phylogenetic analysis, Dolichopodidae and Empididae were monophyletic, and the relationships among subfamilies of Dolichopodidae were Diaphorinae + (Peloropeodinae + (Xanthochlorinae + (Medeterinae + Dolichopodinae))). The monophyly of the subfamily Dolichopodinae and the sister relationship between Dolichopus and Lichtwardtia were also strongly supported.

Objective To observe whether serotonin (5-HT)-mediated proliferation of pulmonary artery smooth muscle cells (PASMCs) is related to the increase of intracellular reactive oxygen species (ROS), and identify the role of NADPH oxidase (NOX) in the production of ROS and 5-HT-mediated proliferation. Methods Tissue block culture method was used to establish a cell line of human PASMCs. Then the cells were divided into 6 groups, normal control (no treatment), 5-HT treatment (1 μmol/L 5-HT), and 3 intervention groups. Then NOX activity was analyzed by using spectrophotometer to calculate the amount of NADPH consumed. ROS production was measured by DCF-DA assay. The expression of phosphorylated-ERK1/2 (p-ERK1/2) was detected by Western blotting. The changes of PASMC proliferation were determined 3H-TdR incorporation assay. Results 5-HT stimulation for 30 min obviously enhanced the NOX activity, ROS production, DNA synthesis, and expression of p-ERK1/2 (all P < 0.05). While the pretreatment of DPI, Tempol or PD98059 could significantly reverse the ERK1/2 phosphorylation and DNA synthesis induced by 5-HT stimulation (both P < 0.05). What's more, DPI also notably reduced the generation of ROS (P < 0.05). Conclusion NOX/ROS may be the key proteins in the signaling pathways of 5-HT mediated proliferation of PASMCs.

Abstract Few intravenously administered mesenchymal stromal cells (MSCs) engraft to the injured myocardium, thereby limiting their therapeutic efficacy for the treatment of ischemic heart injury. Here, it is found that irisin pretreatment increases the cardiac homing of adipose tissue‐derived MSCs (ADSCs) administered by single and multiple intravenous injections to mice with MI/R by more than fivefold, which subsequently increases their antiapoptotic, proangiogenic, and antifibrotic effects in rats and mice that underwent MI/R. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and loss‐of‐function studies identified CSF2RB as a cytokine receptor that facilitates the chemotaxis of irisin‐treated ADSCs in the presence of CSF2, a chemokine that is significantly upregulated in the ischemic heart. Cardiac‐specific CSF2 knockdown blocked the cardiac homing and cardioprotection abilities of intravenously injected irisin‐treated ADSCs in mice subjected to MI/R. Moreover, irisin pretreatment reduced the apoptosis of hydrogen peroxide‐induced ADSCs and increased the paracrine proangiogenic effect of ADSCs. ERK1/2‐SOD2, and ERK1/2‐ANGPTL4 are responsible for the antiapoptotic and paracrine angiogenic effects of irisin‐treated ADSCs, respectively. Integrin αV/β5 is identified as the irisin receptor in ADSCs. These results provide compelling evidence that irisin pretreatment can be an effective means to optimize intravenously delivered MSCs as therapy for ischemic heart injury.

To realize the processing demands of the sapphire wafer surface with scratch-free and nano-scale roughness by mechanical polishing, a novel flexible polishing plate was developed by using soft unsaturated resin. The surface characteristics, material removal rate, and residual stress of the sapphire wafer after the flexible polishing process have been compared with those of the sapphire wafer after the rigid polishing process. Both theoretical and simulation analysis results show that the abrasive particles in the flexible polishing exhibit an apparent yielding effect during the polishing course, which contributes to the achievement of plastic flow removal for the wafer surface. The experimental results show that the surface roughness and subsurface damage of the sapphire wafer polished by the flexible polishing process can be decreased by 18.7% and 57.3%, respectively, compared with those of the sapphire wafer polished by the rigid polishing process.

Dendrite formation is a critical issue in uranium recovery from spent nuclear fuel (SNF) through a molten-salt electrorefining process. To understand and modulate uranium dendritic formation, we developed a computation model that involves all the complexities in the mechano-electrochemical process, such as diffusion–reaction kinetics, interfacial anisotropy and the variations of electric and stress fields. In particular, the lattice mismatch between deposit and substrate is considered which addressed the importance of cathode material. The model explains various morphologies of dendrites, which in a two-dimensional scenario can be demarcated based on the perimeter-to-area ratio, χ/S. Dendrites can be needle-like, tooth-like, or tree-like when χ/S

Summary: The type VII secretion system (T7SS) of Mycobacterium tuberculosis secretes three substrate classes: Esx, Esp, and PE/PPE proteins, that play important roles in bacterial physiology and host interaction. Five subtypes of T7SS, namely ESX-1 to ESX-5, are present in M. tb. ESX-4 is the progenitor of T7SS but its function is not understood. We investigated the ESX-4 system in Mycobacterium marinum. We show that ESX-4 of M. marinum does not secrete its cognate substrates, EsxT and EsxU, under the conditions tested. Paradoxically, the deletion of eccC4, an essential component of ESX-4, resulted in elevated secretion of protein substrates of ESX-1 and ESX-5. Consequently, the ΔeccC4 mutant was more efficient in inducing actin cytoskeleton rearrangement, which led to enhanced phagocytosis by macrophages. Our results reveal an intimate crosstalk between the progenitor of T7SS and its more recent duplication and expansion, and provide new insight into the evolution of T7SS in mycobacteria.

Circular RNAs (circRNAs) are non-coding RNAs with a special circular structure produced formed by the reverse splicing mechanism. Increasing evidence shows that circular RNAs can directly bind to RNA-binding proteins (RBP) and play an important role in a variety of biological activities. The interactions between circRNAs and RBPs are key to comprehending the mechanism of posttranscriptional regulation. Accurately identifying binding sites is very useful for analyzing interactions. In past research, some predictors on the basis of machine learning (ML) have been presented, but prediction accuracy still needs to be ameliorated. Therefore, we present a novel calculation model, CRBPDL, which uses an Adaboost integrated deep hierarchical network to identify the binding sites of circular RNA-RBP. CRBPDL combines five different feature encoding schemes to encode the original RNA sequence, uses deep multiscale residual networks (MSRN) and bidirectional gating recurrent units (BiGRUs) to effectively learn high-level feature representations, it is sufficient to extract local and global context information at the same time. Additionally, a self-attention mechanism is employed to train the robustness of the CRBPDL. Ultimately, the Adaboost algorithm is applied to integrate deep learning (DL) model to improve prediction performance and reliability of the model. To verify the usefulness of CRBPDL, we compared the efficiency with state-of-the-art methods on 37 circular RNA data sets and 31 linear RNA data sets. Moreover, results display that CRBPDL is capable of performing universal, reliable, and robust. The code and data sets are obtainable at https://github.com/nmt315320/CRBPDL.git.

Background. Both long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are widely used in the treatment of chronic obstructive pulmonary disease (COPD). A novel LAMA/LABA combination of umeclidinium/vilanterol (UMEC/VI; 62.5 μg/25 μg) is approved for chronic obstructive pulmonary disease (COPD) treatment. Objective. This study aimed to assess the efficacy and cost-effectiveness of UMEC/VI versus tiotropium (TIO) 18 μg in symptomatic patients with COPD from the perspective of the Chinese National Healthcare System. Methods. A simple analysis included three studies in the meta-analysis that compared UMEC/VI with TIO. A Markov model was developed to estimate the cost-effectiveness of UMEC/VI compared with TIO treatment in symptomatic patients with COPD. First, utilities, clinical efficacy, and adverse events obtained from the literature were utilized as model inputs. Costs were from Chinese average data, including local data. Costs were expressed in dollars based on 2020 prices. Then, the model outputs including drug costs, other medical costs, and total costs, and quality-adjusted life years (QALYs) were estimated. Costs and outcomes were discounted at a 5% annual rate. Furthermore, incremental cost-effective ratios (ICERs) were analyzed. Finally, the influences of changing parameters on the uncertainty of the results were assessed by means of one-way and probabilistic sensitivity analyses. Results. This study revealed that UMEC/VI treatment had a higher rate of clinical efficacy in comparison with TIO, and the differences in the rate of adverse events between the two treatments were not significant. The results indicated that UMEC/VI was superior to TIO, which provided an increase in QALYs (0.002) and a total cost savings of $765.67 per patient over 3 years. In the base case, the ICER of UMEC/VI is -$397468.04/QALY compared with TIO, suggesting that UMEC/VI may be considered a dominant option over TIO. According to the Chinese medical system, the probability of UMEC/VI being cost-effective was 61.6% at a willingness-to-pay (WTP) of $31554/QALY. Sensitivity analyses confirmed that the results were robust. Conclusion. UMEC/VI could be considered a cost-effective treatment compared with TIO in symptomatic COPD patients from the Chinese National Healthcare System perspective. These results may help decision-makers in China when making judgements on which treatments to administer.

The complete Eclipophleps carinata mitogenome was sequenced through Illumina HiSeq 2500 platform and the resulting data were analyzed in this paper. The mitochondrial genome of E. carinata is a typical circular DNA molecule of 15,781 bp with 37 genes and 74.5% A + T content, which encoded 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and the control region. The E. carinata mitochondrial genome and 27 mitochondrial genomes (downloaded from NCBI) were employed to construct phylogenetic tree, in which Ruspolia dubia and Teleogryllus occipitails were the outgroups. Phylogenetic reconstruction validated the taxonomic status of E. carinata, which was placed in the monophyletic Gomphocerinae in Acrididae.