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IntroductionWith the growing population of immunocompromised individuals, opportunistic fungal pathogens pose a global health threat. Candida species, particularly C. albicans and non-albicans Candida species such as C. glabrata, are the most prevalent pathogenic fungi. Azoles, especially fluconazole, are widely used therapeutic options.ObjectiveThis study investigates how C. glabrata adapts to fluconazole, with a focus on understanding the factors regulating fluconazole tolerance and its relationship to resistance.MethodsThis study compared the factors regulating fluconazole tolerance between C. albicans and C. glabrata. We analyzed the impact of temperature on fluconazole tolerance, and requirement of calcineurin and Hsp90 for maintenance of fluconazole tolerance. We isolated colonies from edge, inside and outside of inhibition zone in disk diffusion assays. And we exposed C. glabrata strain to high concentrations of fluconazole and investigated the mutants for development of fluconazole resistance and tolerance.ResultsWe found temperature modulated tolerance in the opposite way in C. albicans strain YJB-T1891 and C. glabrata strain CG4. Calcineurin and Hsp90 were required for maintenance of fluconazole tolerance in both species. Colonies from inside and outside of inhibition zones did not exhibited mutated phenotype, but colonies isolated from edge of inhibition zone exhibited diverse phenotype changes. Moreover, we discovered that high concentrations (16-128 μg/mL) of fluconazole induce the simultaneous but parallel development of tolerance and resistance in C. glabrata, unlike the sole development of tolerance in C. albicans.ConclusionThis study highlights that while tolerance to fluconazole is a common response in Candida species, the specific molecular mechanisms and evolutionary pathways that lead to this response vary between species. Our findings emphasize the importance of understanding the regulation of fluconazole tolerance in different Candida species to develop effective therapeutic strategies.

Abstract Background Accumulating clinical evidence suggests that lung microbiome is closely linked to the progression of pulmonary diseases; however, it is still controversial which specimen type is preferred for the evaluation of lung microbiome. Methods and results To address this issue, we established a classical acute lung injury (ALI) mice model by intratracheal instillation of lipopolysaccharides (LPS). We found that the bacterial DNA obtained from the bronchoalveolar lavage fluid (BALF), intact lung tissue [Lung(i)], lung tissue after perfused [Lung(p)], and feces of one mouse were enough for 16S rRNA sequencing, except the BALF of mice treated with phosphate buffer saline (PBS), which might be due to the biomass of lung microbiome in the BALF were upregulated in the mice treated with LPS. Although the alpha diversity among the three specimens from lungs had minimal differences, Lung(p) had higher sample-to-sample variation compared with BALF and Lung(i). Consistently, PCoA analysis at phylum level indicated that BALF was similar to Lung(i), but not Lung(p), in the lungs of mice treated with LPS, suggesting that BALF and Lung(i) were suitable for the evaluation of lung microbiome in ALI. Importantly, Actinobacteria and Firmicutes were identified as the mostly changed phyla in the lungs and might be important factors involved in the gut-lung axis in ALI mice. Moreover, Actinobacteria and Proteobacteria might play indicative roles in the severity of lung injury. Conclusion This study shows both Lung(i) and BALF are suitable for the evaluation of murine lung microbiome in ALI, and several bacterial phyla, such as Actinobacteria, may serve as potential biomarkers for the severity of ALI. Video Abstract

BackgroundThe emergence of tolerance to antifungal agents in Candida albicans complicates the treatment of fungal infections. Understanding the mechanisms underlying this tolerance is crucial for developing effective therapeutic strategies.ObjectiveThis study aims to elucidate the genetic and molecular basis of ketoconazole tolerance in C. albicans, focusing on the roles of chromosomal aneuploidy, Hsp90, and calcineurin.MethodsThe wild-type C. albicans strain SC5314 was exposed to increasing concentrations of ketoconazole (0.015–32 μg/mL) to select for tolerant adaptors. Disk diffusion and spot assays were used to assess tolerance. Whole-genome sequencing identified chromosomal changes in the adaptors. The roles of Hsp90 and calcineurin in maintaining and developing ketoconazole tolerance were investigated using specific inhibitors and knockout strains.ResultsAdaptors exhibited tolerance to ketoconazole concentrations up to 16 μg/mL, a significant increase from the parent strain’s inhibition at 0.015 μg/mL. All tolerant adaptors showed amplification of chromosome R, with 29 adaptors having trisomy and one having tetrasomy. This aneuploidy was unstable, reverting to euploidy and losing tolerance in drug-free conditions. Both Hsp90 and calcineurin were essential for maintaining and developing ketoconazole tolerance. Inhibition of these proteins resulted in loss of tolerance. The efflux gene CDR1 was not required for the development of tolerance. Chromosome R trisomy and tetrasomy induce cross-tolerance to other azole antifungal agents, including clotrimazole and miconazole, but not to other antifungal classes, such as echinocandins and pyrimidines, exemplified by caspofungin and 5-flucytosine.ConclusionKetoconazole tolerance in C. albicans is mediated by chromosomal aneuploidy, specifically chromosome R amplification, and requires Hsp90 and calcineurin. These findings highlight potential targets for therapeutic intervention to combat antifungal tolerance and improve treatment outcomes.

ABSTRACT Some lactic acid bacteria (LAB) can provide significant health benefits, which are critically important for the conservation of endangered animals, such as giant pandas. However, little is known about the diversity and culturability of LAB in the giant panda gut microbiota. To understand the roles of LAB in giant panda conservation, it is critical to culture bacterial strains of interest. In this study, we established a pipeline to culture bacterial strains using enrichment of target bacteria with different liquid media and growth conditions. Then, the strains were isolated in solid media to study their functions. Using 210 samples from the culture enrichment method and 138 culture-independent samples, we obtained 1120 amplicon sequencing variants (ASVs) belonging to Lactobacillales. Out of the 1120 ASVs, 812 ASVs from the culture enrichment approach were twofold more diverse than 336 ASVs from the culture-independent approach. Many ASVs of interest were not detected in the culture-independent approach. Using this pipeline, we isolated many relevant bacterial strains and established a giant panda gut bacteria strain collection that included strains with low-abundance in culture-independent samples and included most of the giant panda LAB described by other researchers. The strain collection consisted of 60 strains representing 35 species of 12 genera. Thus, our pipeline is powerful and provides guidance in culturing gut microbiota of interest in hosts such as the giant panda.IMPORTANCECultivation is necessary to screen strains to experimentally investigate microbial traits, and to confirm the activities of novel genes through functional characterization studies. In the long-term, such work can aid in the identification of potential health benefits conferred by bacteria and this could aid in the identification of bacterial candidate strains that can be applied as probiotics. In this study, we developed a pipeline with low-cost and user-friendly culture enrichment to reveal the diversity of LAB in giant pandas. We compared the difference between culture-independent and culture enrichment methods, screened strains of interest that produced high concentrations of short-chain fatty acids (SCFAs), and we investigated the catalog of virulence factors, antibiotic resistance, butyrate and lactate synthesis genes of the strains at a genomic level. This study will provide guidance for microbiota cultivation and a foundation for future research aiming to understand the functions of specific strains.

Antifungal resistance and antifungal tolerance are two distinct terms that describe different cellular responses to drugs. Antifungal resistance describes the ability of a fungus to grow above the minimal inhibitory concentration (MIC) of a drug. Antifungal tolerance describes the ability of drug susceptible strains to grow slowly at inhibitory drug concentrations. Recent studies indicate antifungal resistance and tolerance have distinct evolutionary trajectories. Superficial candidiasis bothers millions of people yearly. Miconazole has been used for topical treatment of yeast infections for over 40 years. Yet, fungal resistance to miconazole remains relatively low. Here we found different clinical isolates of Candida albicans had different profile of tolerance to miconazole, and the tolerance was modulated by physiological factors including temperature and medium composition. Exposure of non-tolerant strains with different genetic backgrounds to miconazole mainly induced development of tolerance, not resistance, and the tolerance was mainly due to whole chromosomal or segmental amplification of chromosome R. The efflux gene CDR1 was required for maintenance of tolerance in wild type strains but not required for gain of aneuploidy-mediated tolerance. Heat shock protein Hsp90 and calcineurin were essential for maintenance as well as gain of tolerance. Our study indicates development of aneuploidy-mediated tolerance, not resistance, is the predominant mechanism of rapid adaptation to miconazole in C. albicans, and the clinical relevance of tolerance deserves further investigations.

Automatic creation of real-time, emotion-based piano music pieces remains a challenge for deep learning models. While Generative Adversarial Networks (GANs) have shown promise, existing methods can struggle with generating musically coherent pieces and often require complex manual configuration. This paper proposes a novel model called Learning Automata-based Self-Attention Generative Adversarial Network (LA-SAGAN) to address these limitations. The proposed model uses a Generative Adversarial Network (GAN), combined with Self-Attention (SA) mechanism to reach this goal. The benefits of using SA modules in GAN architecture is twofold: First, SA mechanism results in generating music pieces with homogenous structure, which means long-distance dependencies in generated outputs are considered. Second, the SA mechanism utilizes the emotional features of the input to produce output pieces. This results in generating music pieces with desired genre or theme. In order to control the complexity of the proposed model, and optimize its structure, a set of Learning Automata (LA) models have been used to determine the activity state of each SA module. To do this, an iterative algorithm based on cooperation of LAs is introduced which optimizes the model by deactivating unnecessary SA modules. The efficiency of the proposed model in generating piano music has been evaluated. Evaluations demonstrate LA-SAGAN’s effectiveness: at least 14.47% improvement in entropy (diversity) and improvements in precision (at least 2.47%) and recall (at least 2.13%). Moreover, human evaluation confirms superior musical coherence and adherence to emotional cues.

Abstract Frozen shoulder (FS) is a common disorder often treated with Tuina, but the mechanisms involved remain unclear. We employed proteomics and phosphoproteomics to investigate the mechanisms associated with the treatment of capsule fibrosis in FS rats. We used a method composed of three weeks of cast immobilization to establish a model of FS. We then administered Tuina once daily for 14 days, evaluated glenohumeral range of motion (ROM), assessed histological changes, and identified differentially expressed proteins (DEPs) using proteomics and phosphoproteomics. This study demonstrated that Tuina could improve glenohumeral ROM and reserve capsule fibrosis in FS rats. Proteomics revealed proteins regulated by Tuina belonging to the PI3K-AKT and ECM receptor interaction signaling pathways. Phosphoproteomics detected differentially phosphorylated proteins regulated by Tuina to be enriched in the MAPK signaling pathway. The combination of proteomics and phosphoproteomics for Protein–Protein Interaction (PPI) network analysis revealed that the phosphorylation of Myh3 and Srsf1 with a node degree larger than the average degree were considered the central regulatory protein modulated by Tuina to reverse capsule fibrosis. Thbs1, Vtn, and Tenascin-W were significantly enriched in PI3K-AKT and ECM receptor interaction signaling pathways and highly expressed in model rats. Tuina resulted in reduced expression of these proteins. Our findings demonstrated some of mechanisms behind the reversal of FS capsule fibrosis following Tuina, a scientific medical therapy for FS patients.

Abstract Rapid and sensitive detection of pathogens is of utmost importance in interrupting the transmission chain of infectious diseases. In recent years, this has proven to be vital during the coronavirus disease (COVID-19) global pandemic that put countless lives at risk. Numerous molecular diagnostic methods were used, including RT-PCR, NASBA, E-SDA, E-RCA, LAMP, and RPA. However, these technologies potentially require primer optimization and complex instruments. Here, we propose the RHAM (RNase Hybridization-Assisted amplification) system as a rapid, specific, and sensitive molecular diagnosis platform. Combining the LAMP and RNase HII-mediated fluorescent reporter, the RHAM system can amplify and visualize the target in one isothermal system with high sensitivity (5 × 102 copies/mL). There was no cross-reactivity with other common respiratory viruses. Analysis of clinical samples revealed the RHAM system to generate positive signals within 15 min without false positive or negative results. The present study shows that RHAM is not only an ideal platform for detecting pathogens, such as SARS-CoV-2 but can be potentially applied in POCT settings.

Fully mechanized top coal caving technology has become the mainstream way of high yield and high efficiency mining in extra thick coal seams in China. The accurate control of the top-coal drawing mechanical parts is of significance to realize the automation and intellectualization of top-coal caving mining. Mastering the spatial motion law of the coal caving mechanism is the premise of accurate control. The immediate shape of the hydraulic support coal caving mechanism is jointly controlled by the support height, support attitude, extension length of the plug plate, and the relative position of the rear scraper, which has an important impact on the coal caving opening and the coal-passing height of the support. This study establishes a 3–D numerical model of four- legs top-coal caving hydraulic support (No. ZF15000/27.5/42) by using the finite element software ABAQUS. Hinge and translator connectors are used to simulate the rotation behavior and expansion-contraction behavior for hinge point and plug plate, respectively. Taking the support height (H), tail beam swing angle (α), and the plug plate extension length (l) as control variables, the spatial motion law of the hinge point between shield beam and tail beam and the end of the plug plate are modeled. The critical security equation for evaluating collision between top-coal drawing mechanical parts and rear scraper is obtained by using Levenberg-Marquardt fitting iteration method. A database for describe the calibration relationship, which contains the end coordination of plug plate, the dimension of the top-coal drawing opening, and H, α, and l, is established. The sensor type and installation position for sensing and controlling the attitude of the top-coal drawing mechanism are recommended, the approach for calculating the tail beam angle based on travel sensor is derived. Through field verification of top-coal drawing opening width, it is concluded that the relative error between measured value and calculated value meets the requirements for accurate control of top-coal drawing mechanism. The approach for controlling the top-coal drawing opening dimension is proposed, which has been successfully applied in the field.

Abstract Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.

ABSTRACTCandida albicans is a prevalent opportunistic human fungal pathogen. Echinocandins are first-line drugs for the treatment of invasive candidiasis. Molecular mechanisms of resistance to echinocandins have been extensively studied; however, the effect of physiological factors on antifungal efficacy of echinocandins is unexplored. Here, we found temperature-modulated susceptibility to caspofungin in medium-independent and strain background-independent manner in C. albicans. Deletions of protein kinase C (PKC) pathway and calcineurin-Crz1 signaling pathway genes conferred hypersensitivity to caspofungin, but only deletion or pharmacological inhibition of calcineurin subunits inverted the temperature effect on susceptibility to caspofungin. Furthermore, the enhanced growth at lower temperature was not due to altered expression of some established genes such as FKS, CHS, or CHT genes; PKC or calcineurin pathway genes; or HSP90. The expressions of other heat shock protein genes, including HSP12 and HSP70, were higher at lower temperature. We posit that the temperature-modulated susceptibility to caspofungin is a non-canonical mechanism that is dependent on heat shock proteins and calcineurin.IMPORTANCEEchinocandins are the newest antifungal drugs and are first-line treatment option for life-threatening systemic infections. Due to lack of consensus regarding what temperature should be used when evaluating susceptibility of yeasts to echinocandins, typically either 30°C, 35°C, or 37°C is used. However, the impact of temperature on antifungal efficacy of echinocandins is unexplored. In the current study, we demonstrated that Candida albicans laboratory strain SC5314 was more susceptible to caspofungin at 37°C than at 30°C. We also found that calcineurin was required for temperature-modulated caspofungin susceptibility. Surprisingly, the altered caspofungin susceptibility was not due to differential expression of some canonical genes such as FKS, CHS, or CHT genes. The molecular mechanism of temperature-modulated caspofungin susceptibility is undetermined and deserves further investigations.

Polyacrylamide, silica, and other nanoparticles have all been realized in the field of enhanced oil recovery. Researchers often explore the mechanisms of spreading behavior and simulated displacement to develop more efficient types of nanoparticles. In this study, copper quantum dots were introduced into a acrylamide copolymerization system to obtain composite nanospheres and its structure, topographic, and application performance were characterized. The results show that the composite nanospheres have a particle size of around 25 nm, are uniformly loaded with copper particles, and have good temperature resistance. The spreading ability on the quartz flake surfaces and displacement effect in microchannels of composite nanospheres, acrylamide copolymer nanospheres, and copper quantum dots were compared by nanofluid spreading experiments and microchannel chip oil displacement experiments. The results indicate that the composite nanospheres can effectively reduce the water contact angle, promote the spreading of aqueous phase, and accelerate the oil droplet removal process; the accelerating effect is stronger than other samples. Its oil displacement effect is also the strongest, and it is minimized by the influence of channel size, temperature, and dispersing medium, with better stratigraphic adaptability. This work supports the practical application of copper quantum dot/polyacrylamide composite nanospheres in the oilfield.

The sand body structure and geochemical characteristics of braided river reservoirs are the key geological factors affecting gas production and development effects. The Sulige gas field in the Ordos Basin is an important large-scale gas-producing layer. Owing to the control of sedimentary facies, the geological structure of the sand body changes greatly and its connectivity is poor. The geological characteristics have not yet been elucidated, and this is an important problem restricting the development of the Sulige Gas Field. To solve this problem, this study focuses on the braided river reservoir of the Shihezi Formation in Block 19 of the Sulige Gas Field, conducts geological surveys in the study area, analyzes the geological and geochemical characteristics of the reservoir, and obtains samples through drilling. Through a thin-section test, gas-water two-phase experiment, and simulation test, the braided river reservoir configuration and pore and gas-water characteristics are obtained. The results show that the reservoir lithology in the study area is mainly composed of quartz sandstone, lithic sandstone, and quartzy lithic sandstone, with a porosity of 3%–13% and a permeability of (0.05–0.7) × 10−3 m2. The reservoir has low porosity and low permeability. After drilling samples were obtained, 32 thin-section rock samples were selected. The pore types of the block reservoir mainly (82.9%) consisted of intragranular and intergranular dissolved pores. The difference in pore structure was mainly reflected by the size and distribution of the throat. The distribution of physical properties was 6%–10%, the gas saturation was 61%, the NMR effective porosity was 7.49%, the permeability was 4.08 × 102 μm2, and the physical properties were relatively good. In terms of the study area, the average thickness of the single braided channel in the lower section of He 8 was 4.7 m, the average width of the channel was 963 m, and the composite channel was distributed in a potato shape, parallel to the direction of the main flow. The average length of the channel was 2,147 m and the average width was 844 m. As the porosity increased, the efficiency of gas-driven water also increased, and there was a linear positive correlation between porosity and gas-driven water efficiency. With the increase in movable water saturation, the water-air ratio became larger and water production was greater. In low-amplitude structures and under low-permeability background conditions, for reservoirs with good local pore structure and physical properties, the water remaining at the bottom of the reservoir or sand body was controlled by the accumulation conditions or the weak structural differentiation after accumulation. In terms of the gas and water produced simultaneously in the study area, gas production was less than 2 × 104 m3/d and water production was relatively large at more than 10 m3/d; gas and water were mainly distributed in the downdip part of the main channel structure or in the island lens-shaped permeable sand bodies trapped by the surrounding tight layers. The study results provide theoretical data support for the exploration and production of the Sulige Gas Field.

Thermal energy storage in long-distance heating supply pipelines can improve the peak shaving and frequency regulation capabilities of combined heat and power (CHP) units participating in the power grid. In this study, a one-dimensional numerical model was established to predict the thermal lag in long-distance pipelines at different scale levels. The dynamic response of the temperature at the end of the heating pipeline was considered. For the one-way pipe lengths of 10 km, 15 km and 20 km, the response times of the temperature at the distal end were 2.33 h, 2.94 h and 3.54 h, respectively. The longer the flow period, the further the warming-up time is delayed. An optimization scheduling approach was also created to illustrate the peak shaving capabilities of a CHP unit combined with a long-distance pipeline thermal energy storage component. It was demonstrated that the maximum heating load of the unit increased up to 503.08 MW, and the heating load could be expanded in the range of 17.88 MW to 203.76 MW at the minimum electric load of the unit of 104.08 MW. Finally, the particle swarm optimization method was adopted to guide the operating strategy through a whole day to meet both the electric power and heating power requirements. For the optimized case, the comprehensive energy utilization efficiency and the exergy efficiency increase to 64.4% and 56.73%. The thermal energy storage applications based on long-distance pipelines were simulated quantitively and proved to be effective in promoting the operational flexibility of the CHP unit.

The application of thermal energy storage (TES) has been proved effective to improve the energy utilization efficiency of renewable energy and industrial waste heat energy. In this paper, a modified one-dimensional dimensionless model for the thermocline thermal energy storage tank is derived to simulate the system more accurately. An adaptive strategy for solving region compartmentalization is proposed for reducing computing time. Based on the proposed model, the effects of three different parameters on the performance of the thermocline tank are studied. The results show that increasing the inlet velocity can reduce the thickness of the thermocline and improve the system efficiency. Increasing the temperature difference between hot and cold water leads to a thicker thermocline, but the thermal energy stored in the tank increases. Increasing the tank height has no effect on the motion characteristic of thermocline, but the system efficiency can be increased.

Abstract Background Recurrence continues to place significant burden on patients and tuberculosis programmes worldwide, and previous studies have rarely provided analysis in negative recurrence cases. We characterized the epidemiological features of recurrent pulmonary tuberculosis (PTB) patients, estimated its probability associated with different bacteriology results and risk factors. Methods Using 2005–2018 provincial surveillance data from Henan, China, where the permanent population approximately were 100 million, we described the epidemiological and bacteriological features of recurrent PTB. The Kaplan–Meier method and Cox proportional hazard models, respectively, were used to estimate probability of recurrent PTB and risk factors. Results A total of 7143 (1.5%) PTB patients had recurrence, and of 21.1% were bacteriological positive on both laboratory tests (positive–positive), and of 34.9% were negative–negative. Compared with bacteriological negative recurrent PTB at first episodes, the bacteriological positive cases were more male (81.70% vs 72.79%; P

Highlights 1. CuONPs exposure activates NRF2 signaling in vascular endothelial cells and mouse thoracic aorta. 2. KEAP1 is dispensable for NRF2 activation in CuONPs-treated vascular endothelial cells. 3. CuONPs-induced autophagy facilitates NRF2 activation in vascular endothelial cells and mouse thoracic aorta. 4. Autophagy and ubiquitin–proteasome reciprocally regulate NRF2 activation in CuONPs-treated vascular endothelial cells and mouse thoracic aorta.

Temporal gravity field comprehensively reflects the migration characteristics of the earth's inner and shallow mass variations, which has been widely used in various geoscience applications. Since the 21st century, several gravimetric satellites have been successfully launched, supporting to continuously detecting global temporal gravity field. The way to determine temporal gravity field model in terms of spherical harmonic coefficients via satellite gravimetric data is the key issue, and it is the prerequisite to further promote numerous geoscience applications. Since the proposal of satellite gravimetry, scholars at home and abroad have been dedicated to studying the theories and methods of retrieving temporal gravity field model for several decades. Due to the refinement of observations and the improvement of retrieval methods, there are significant improvements of the accuracy of temporal gravity field models. This paper summarizes the research progress of determining temporal gravity field models via satellite tracking satellite data in recent decades. In terms of low-low satellite-to-satellite tracking scenario, we summarize the basic principle of retrieval method, the optimization process of observation datasets, the refinement of background force models and the improvement of retrieval methods. Meanwhile, the progress in terms of high-low satellite-to-satellite tracking scenarios is also presented, especially for temporal gravity field models determination. Finally, the future opportunities of the next generation gravimetric mission are discussed. Our findings could benefit the construction and development of autonomous gravity satellites in China.

IntroductionThe anti-tumor vindoline and catharanthine alkaloids are naturally existed in Catharanthus roseus (C. roseus), an ornamental plant in many tropical countries. Plant-specific TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors play important roles in various plant developmental processes. However, the roles of C. roseus TCPs (CrTCPs) in terpenoid indole alkaloid (TIA) biosynthesis are largely unknown.MethodsHere, a total of 15 CrTCP genes were identified in the newly updated C. roseus genome and were grouped into three major classes (P-type, C-type and CYC/TB1).ResultsGene structure and protein motif analyses showed that CrTCPs have diverse intron-exon patterns and protein motif distributions. A number of stress responsive cis-elements were identified in promoter regions of CrTCPs. Expression analysis showed that three CrTCP genes (CrTCP2, CrTCP4, and CrTCP7) were expressed specifically in leaves and four CrTCP genes (CrTCP13, CrTCP8, CrTCP6, and CrTCP10) were expressed specifically in flowers. HPLC analysis showed that the contents of three classic TIAs, vindoline, catharanthine and ajmalicine, were significantly increased by ultraviolet-B (UV-B) and methyl jasmonate (MeJA) in leaves. By analyzing the expression patterns under UV-B radiation and MeJA application with qRT-PCR, a number of CrTCP and TIA biosynthesis-related genes were identified to be responsive to UV-B and MeJA treatments. Interestingly, two TCP binding elements (GGNCCCAC and GTGGNCCC) were identified in several TIA biosynthesis-related genes, suggesting that they were potential target genes of CrTCPs. DiscussionThese results suggest that CrTCPs are involved in the regulation of the biosynthesis of TIAs, and provide a basis for further functional identification of CrTCPs.

IntroductionCandida albicans is a prevalent opportunistic human fungal pathogen. However, there are currently very few antifungal treatments available. Inositol phosphoryl ceramide synthase is an essential and fungal-specific protein that also provides a novel and promising antifungal target. Aureobasidin A is a widely used inhibitor of inositol phosphoryl ceramide synthase, however the mechanism of resistance to aureobasidin A is largely unknown in pathogenic fungi.MethodsHere we investigated how C. albicans adapted to low and high concentrations of aureobasidin A.Results and discussionsWe identified trisomy of chromosome 1 as the predominant mechanism of rapid adaptation. Resistance to aureobasidin A was unstable because of the inherent instability of aneuploids. Importantly, chromosome 1 trisomy simultaneously regulated genes which were associated with aureobasidin A resistance that are on this aneuploid chromosome as well as on other chromosomes. Furthermore, the pleiotropic effect of aneuploidy caused altered resistance not only to aureobasidin A but also to other antifungal drugs including caspofungin and 5-flucytosine. We posit aneuploidy provides a rapid and reversible mechanism of development of drug resistance and cross resistance in C. albicans.

Abstract Mechanotransduction sensing of tissue architecture and cellular microenvironment is a fundamental regulator of cell fate, including cancer. Meanwhile, long noncoding RNAs (lncRNAs) play multifunctions during cancer development and treatment. However, the link between lncRNAs and cellular mechanotransduction in the context of cancer progression has not yet been elucidated. In this study, using atomic force microscopy (AFM), we find that ionizing radiation reduces tumor stiffness. Ionizing radiation-induced lncRNA CRYBG3 can blunt YAP/TAZ activity through interference with mechanotransduction, resulting in the inhibition of cell proliferation, invasion, and metastasis of lung cancer cells. In vivo, we found that loss of lncRNA CRYBG3 could power the tumor initiation and metastasis ability, but this was abolished by concomitant deplete TAZ. At the molecular level, lncRNA CRYBG3 that in turn dysregulates F-actin organization, activates the LATS1/2 kinase, all in all resulting in YAP/TAZ nuclear exclusion. Our research proposes that lncRNA CRYBG3 is a mediator of radiotherapy through its control of cancer-tissue mechanotransduction and wiring YAP/TAZ activity to control tumor growth and metastasis.

Highlights 1. CuONPs disturb mitochondrial dynamics and trigger mitophagy in vascular endothelial cells and mouse blood vessel. 2. PINK1/TAX1BP1-mediated mitophagy regulates the removal of excessive ROS and aberrant mitochondria in CuONPs-treated vascular endothelial cells. 3. The mitophagy activator urolithin A attenuates CuONPs-induced vascular endothelial cells death and mice vascular injury.

Background Neutrophilic asthma (NA) is associated with increased airway interleukin (IL)-17 and abnormal bacterial community such as dominance of nontypeable Haemophilus influenzae (NTHi), particularly during asthma exacerbations. Bacteria release various products including DNA, but whether they cooperate with IL-17 in exaggerating neutrophilic inflammation is unclear. We sought to investigate the role of bacteria-derived DNA in airway neutrophilic inflammation related to IL-17-high asthma and underlying mechanisms (e.g. Toll-like receptor 9 (TLR9)/IL-36γ signalling axis). Methods Bacterial DNA, IL-8 and IL-36γ were measured in bronchoalveolar lavage fluid (BALF) of people with asthma and healthy subjects. The role of co-exposure to IL-17 and bacterial DNA or live bacteria in neutrophilic inflammation, and the contribution of the TLR9/IL-36γ signalling axis, were determined in cultured primary human airway epithelial cells and alveolar macrophages, and mouse models. Results Bacterial DNA levels were increased in asthma BALF, which positively correlated with IL-8 and neutrophil levels. Moreover, IL-36γ increased in BALF of NA patients. Bacterial DNA or NTHi infection under an IL-17-high setting amplified IL-8 production and mouse lung neutrophilic inflammation. DNase I treatment in IL-17-exposed and NTHi-infected mouse lungs reduced neutrophilic inflammation. Mechanistically, bacterial DNA-mediated amplification of neutrophilic inflammation is in part dependent on the TLR9/IL-36γ signalling axis. Conclusions Bacterial DNA amplifies airway neutrophilic inflammation in an IL-17-high setting partly through the TLR9 and IL-36γ signalling axis. Our novel findings may offer several potential therapeutic targets including TLR9 antagonists, IL-36γ neutralising antibodies and DNase I to reduce asthma severity associated with exaggerated airway neutrophilic inflammation.

To contribute to the conservation of endangered animals, the utilization of model systems is critical to analyze the function of their gut microbiota. In this study, the results of a fecal microbial transplantation (FMT) experiment with germ-free (GF) mice receiving giant panda or horse fecal microbiota showed a clear clustering by donor microbial communities in GF mice, which was consistent with the results of blood metabolites from these mice. At the genus level, FMT re-established approximately 9% of the giant panda donor microbiota in GF mice compared to about 32% for the horse donor microbiota. In line with this, the difference between the panda donor microbiota and panda-mice microbiota on whole-community level was significantly larger than that between the horse donor microbiota and the horse-mice microbiota. These results were consistent with source tracking analysis that found a significantly higher retention rate of the horse donor microbiota (30.9%) than the giant panda donor microbiota (4.0%) in GF mice where the microbiota remained stable after FMT. Further analyzes indicated that the possible reason for the low retention rate of the panda donor microbiota in GF mice was a low relative abundance of Clostridiaceae in the panda donor microbiota. Our results indicate that the donor microbiota has a large effect on GF mice microbiota after FMT.

IntroductionGut microbiota plays a crucial role in the development and progression of nonalcoholic steatohepatitis (NASH) and associated hepatocellular carcinoma (HCC). Akkermansia muciniphila was reported to inhibit inflammation-associated cancer in the intestine. The anti-NASH ability of A. muciniphila has recently been found. Thus, we were to investigate whether supplementation of A. muciniphila could prevent NASH-associated HCC.MethodsIn a model we called STAM, male C57BL/6J mice were subcutaneously injected with 200 µg streptozotocin at 4 days after birth, and fed with high-fat diet at 4 weeks of age to induce NASH-associated HCC. Faeces from mice and patients with NASH-related HCC were collected for 16S rRNA sequencing. STAM mice were orally administered either saline or A. muciniphila twice a day starting at 4 or 10 weeks of age. The effects of A. muciniphila on the immune responses were also evaluated.ResultsPatients and mice with NASH-related HCC showed significantly reduced gut A. muciniphila in comparison to healthy controls. Administration of breast milk-isolated A. muciniphila (AM06) but not feces-isolated A. muciniphila (AM02) could improve NASH severity. Interestingly, breast milk-isolated A. muciniphila treatment suppressed the progression of NASH to HCC, accompanied with an increased hepatic CXCR6+ natural killer T (NKT) cell and decreased macrophage infiltration. The antitumor ability of A. muciniphila was not evident in NKT cell-deficient mice (CD1d-/- and CXCR6-/-). In vitro, A. muciniphila promoted the killing of hepG2 cells by NKT cells.DiscussionOur study will provide the rationale for the application of A. muciniphila to treat NASH and for the prevention of its progression to HCC.

Sesamol has moved into biomedical research in recent years. However, its interactions with blood proteins and cancer cells have not been fully explored. Therefore, we aimed to investigate the interaction of sesamol with human serum albumin (HSA), A549 human nonsmall cell lung cancer (NSCLC) cell line, and Raw 264.7 macrophage. The interaction of HSA with sesamol was explored via application of fluorescence and circular dichroism (CD) spectroscopy studies as well as molecular docking analysis. Then, the cytotoxic effects of sesamol on A549 lung cancer cells and Raw 264.7 macrophages were evaluated by qPCR analysis. It was found that sesamol spontaneously (ΔG˚=-45.89 kJ/mol) binds with HSA having a high affinity (log Kb = 8.05, n = 1.70, T = 298 K) and form a static complex trough contribution of hydrogen bonds and van der Waals interactions (ΔH˚=-409.43 kJ/mol, TΔS˚=-363.54 kJ/mol) which was supported by molecular docking study. Furthermore, by using CD and synchronous fluorescence spectroscopy analyses it was found that sesamol induced some minor secondary and tertiary structural changes, respectively in HSA structure. Cellular assays displayed that sesamol triggered selective cytotoxicity against A549 lung cancer cells through regulation of intrinsic apoptosis pathway mediated by mitigation of mitochondrial membrane potential, elevation of ROS generation, downregulation of Bax, and up regulation of caspase-9, −3. In conclusion, it was found that sesamol could show high affinity with HSA and mediate intrinsic apoptosis pathway through ROS generation in the A549 lung cancer cell lines. These data indicate that the biochemical and anticancer mechanisms of sesamol can be further investigated in future studies to integrate it in the biomedical platforms.

Insulator failure is one of the important causes of railway power transmission accidents. In the automatic detection system of railway insulators, the detection and classification of insulator faults is a challenging task due to the complex background, small insulators and unobvious failures. In this article, we propose a railway insulator fault detection network based on convolutional neural network, which can detect faulty insulators from images with high resolution and complex background. The insulator fault detection network realizes the position detection and fault classification of the insulator by cascading the detection network and the fault classification network. The method of cascading two networks can reduce the amount of network calculations and improve the accuracy of fault classification. The insulator detection network uses low-resolution images for position detection, and this method can prevent the detection network from paying too much attention to the details of the image, thereby reducing the amount of network calculations. The fault classification network uses high-resolution insulator images for fault classification. The high-resolution images in this method have rich detailed information, which helps to improve the accuracy of fault classification. The trained insulator detection network and the fault classification network are cascaded to form an insulator fault detection network. The precision, recall and mAP values of the insulator fault detection network are 94.10%, 92.88% and 93.46% respectively. Experiment shows show that this network cascading method can significantly improve the accuracy and robustness of insulator fault detection.

The assessment of local air pollution due to aircraft emissions at/near the airport is an important issue from the standpoint of environment and human health, but has not received due attention in China. In this paper, the pollutant emissions (i.e. HC, CO, NOx, SOx and PM) from aircraft during landing and take-off (LTO) cycles at Nanjing Lukou Airport (NKG) in 2016 were investigated using an improved method, which considered the taxi-in and –out time calculated based on the real data from the Civil Aviation Administration of China (CAAC), instead of using the referenced time recommended by ICAO. First, the pollutant emissions and their characteristics were studied from different perspectives. Second, two various mitigation measures of emissions were proposed, and the performance of emission reduction was analysed. Our analysis shows that: (1) A320 and B738 emitted the largest emissions at NKG; (2) pollutants were mainly emitted during the taxi mode, followed by climb mode; (3) B738 had the lowest emissions per (seat•LTO) among all aircraft, while CRJ had the lowest emissions per unit LTO; (4) shortening the taxiing time and upgrading aircraft engines are both effective measures to mitigate pollutant emissions.

The hydrate-based gas separation for capturing CO2 from flue gas has the characteristics of low energy consumption, simple operation and convenience for the subsequent CO2 storage and utilization. In order to reduce the total cumulative deviation of multi-stage hydration reaction, it is of great importance to establish an accurate thermodynamic model. Based on the vdW–P + CPA model, therefore, we refitted the parameters of the thermodynamic model considering the association between CO2 and H2O. Firstly, the energy parameter α0.5 of H2O and CO2 are developed as the cubic function and the linear function of [1-(T/Tc)0.5], respectively. Then, the calculation parameters of Langmuir absorption coefficient of vdW–P model is refitted based on the temperature dependent binary interaction parameters kij. The following research results are obtained. First, when the novel fitted thermodynamic model is used to predict the density of saturated fluid, the average absolute deviation (AAD) of H2O drops from 1.84% to 0.08% and that of CO2 drops from 4.06% to 2.09%. Second, when it is used to predict the phase equilibrium pressure of the hydrate generated from pure CO2 and pure N2, the AAD is 0.86% and 0.82%, respectively. Third, when it is used to calculate the phase equilibrium condition of hydrate generated from flue gas with different compositions, the AAD is decreased from 15.16% to 5.02%. In conclusion, this novel fitted thermodynamic model is of higher accuracy and it, to some extent, can decrease the total accumulative deviation of multi-stage hydration reaction. The research results provide reference for the actual application of the hydrate-based gas separation for capturing CO2 from flue gas. Keywords: Hydrate-based gas separation, Flue gas, CO2 capture, CO2 thermodynamic model, Multi-stage hydration reaction, Energy parameter, Langmuir absorption coefficient, Prediction

Different renewable energy resources and energy demands between parks lead to waste of resources and frequent interactions between the regional distribution grid and the larger grid. Hence, an optimal dispatching scheme of the regional integrated energy system group (RIESG), which combines the power-to-gas (P2G) and inter-park electric energy mutual aid, is proposed in this paper to solve this problem. Firstly, for the park integrated energy system (PIES) with various structures, the coupling matrix is used to describe the input-output relationship and coupling form of multiple energy sources in the energy-hub (EH), which linearizes the complex multi-energy coupled system and is more conducive to the solution of the model. Secondly, the electrical coupling relationship of the system is improved by adding P2G to enhance the system’s ability to consume renewable energy. Moreover, the installation cost of P2G is introduced to comprehensively consider the impact of the economic efficiency on the system. Finally, to minimize the network loss of energy flow, the optimal dispatching model of RIESG with P2G conversion is constructed through the electric energy mutual aid among the parks. The simulation shows that compared with the independent operation of each park’s integrated energy system (IES), the proposed optimal dispatching strategy of RIESG achieves the mutual benefit of electric energy among park groups, reduces the dependency on the large power grid, and effectively improves the economy of system groups. In this condition, the renewable energy consumption rate reaches 99.59%, the utilization rate of P2G increases to 94.28%, and the total system cost is reduced by 34.83%.

Decreased selenium (Se) levels during childhood and infancy are associated with worse respiratory health. Se is biologically active after incorporation into Se-containing antioxidant enzymes (AOE) and proteins. It is unknown how decreased maternal Se during pregnancy and lactation impacts neonatal pulmonary selenoproteins, growth, and lung development. Using a model of neonatal Se deficiency that limits Se intake to the dam during pregnancy and lactation, we evaluated which neonatal pulmonary selenoproteins are decreased in both the saccular (postnatal day 0, P0) and early alveolar (postnatal day 7, P7) stages of lung development. We found that Se deficient (SeD) pups weigh less and exhibit impaired alveolar development compared to Se sufficient (SeS) pups at P7. The activity levels of glutathione peroxidase (GPx) and thioredoxin reductase (Txnrd) were decreased at P0 and P7 in SeD lungs compared to SeS lungs. Protein content of GPx1, GPx3 and Txnrd1 were decreased in SeD lungs at P0 and P7, whereas Txnrd2 content was unaltered compared to SeS controls. The expression of NRF-2 dependent genes and several non-Se containing AOE were similar between SeS and SeD lungs. SeD lungs exhibited a decrease in selenoprotein N, an endoplasmic reticulum protein implicated in alveolar development, at both time points. We conclude that exposure to Se deficiency during pregnancy and lactation impairs weight gain and lung growth in offspring. Our data identify multiple selenoproteins in the neonatal lung that are vulnerable to decreased Se intake, which may impact oxidative stress and cell signaling under physiologic conditions as well as after oxidative stressors.

Intrauterine growth restriction (IUGR) is a relevant predictor for higher rates of neonatal sepsis worldwide and is associated with an impaired neonatal immunity and lower immune cell counts. During the perinatal period, the liver is a key immunological organ responsible for the nuclear factor kappa B (NF-κB)-mediated innate immune response to inflammatory stimuli, but whether this role is affected by IUGR is unknown. Herein, we hypothesized that the newborn liver adapts to calorie-restriction IUGR by inducing changes in the NF-κB signaling transcriptome, leading to an attenuated acute proinflammatory response to intraperitoneal lipopolysaccharide (LPS). We first assessed the hepatic gene expression of key NF-κB factors in the IUGR and normally grown (NG) newborn mice. Real-time quantitative PCR (RT-qPCR) analysis revealed an upregulation of both IκB proteins genes (Nfkbia and Nfkbib) and the NF-κB subunit Nfkb1 in IUGR vs. NG. We next measured the LPS-induced hepatic expression of acute proinflammatory genes (Ccl3, Cxcl1, Il1b, Il6, and Tnf) and observed that the IUGR liver produced an attenuated acute proinflammatory cytokine gene response (Il1b and Tnf) to LPS in IUGR vs. unexposed (CTR). Consistent with these results, LPS-exposed hepatic tumor necrosis factor alpha (TNF-α) protein concentrations were lower in IUGR vs. LPS-exposed NG and did not differ from IUGR CTR. Sex differences at the transcriptome level were observed in the IUGR male vs. female. Our results demonstrate that IUGR induces key modifications in the NF-κB transcriptomic machinery in the newborn that compromised the acute proinflammatory cytokine gene and protein response to LPS. Our results bring novel insights in understanding how the IUGR newborn is immunocompromised due to fundamental changes in NF-κB key factors.

Northern China is vigorously promoting cogeneration and clean heating technologies. The accurate prediction of building energy consumption is the basis for heating regulation. In this paper, the daily, weekly, and annual periods of building energy consumption are determined by Fourier transformation. Accordingly, a period-based neural network (PBNN) is proposed to predict building energy consumption. The main innovation of PBNN is the introduction of a new data structure, which is a time-discontinuous sliding window. The sliding window consists of the past 24 h, 24 h for the same period last week, and 24 h for the same period the previous year. When predicting the building energy consumption for the next 1 h, 12 h, and 24 h, the prediction errors of the PBNN are 2.30%, 3.47%, and 3.66% lower than those of the traditional sliding window PBNN (TSW-PBNN), respectively. The training time of PBNN is approximately half that of TSW-PBNN. The time-discontinuous sliding window reduces the energy consumption prediction error and neural network model training time.

In the core process of fractured marine gas hydrate (hereinafter referred to as hydrate) particles being transported up to the surface platform by airtight pipeline in the solid fluidization exploitation of marine gas hydrate reservoirs, influenced by the rising temperature and the dropping pressure, the solid hydrates will decompose and produce a large amount of gas at a certain critical point, causing the liquid–solid two-phase flow in the wellbore to change into complicated gas–liquid–solid multiphase non-equilibrium flow, which further aggravate well control, solid phase transportation and other safety risks. In view of this, the dynamic hydrate decomposition law in the above process was studied in this paper by establishing multiphase wellbore flow mathematical models of wellbore temperature and pressure field, hydrate phase equilibrium, hydrate dynamic decomposition in multiphase riser pipe flow, wellbore multiphase flow coupled hydrate dynamic decomposition, and a numerical calculation method was proposed and verified. The following results were obtained. First, by numerical model analysis, the effects of liquid phase displacement, solid throughput (daily gas production rate) and wellhead back pressure under different construction parameters on multi-phase non-equilibrium pipe flow were obtained. In addition, the field construction guidance measures were put forward based on multiphase non-equilibrium pipe flow characteristics as follows: to properly increase the solid throughput so as to increase the natural gas production, to appropriately increase the liquid-phase displacement and the wellhead back pressure so as to ensure well control safety. This study provides not only a theoretical basis for the prediction of multiphase non-equilibrium pipe flow in the solid fluidization exploitation, but a technical support for the field construction parameter optimization and well control safety. Keywords: Natural gas hydrate, Solid fluidization exploitation, Non-equilibrium multiphase wellbore flow, Decomposition, Well control risks, Construction parameter, Prediction methods

Naringin is the major polyphenol in bitter orange peel with antioxidant property. However, its pH sensitivity, low solubility, and bitter taste limit its application in food. In this study, naringin–sodium alginate–silk fibroin microspheres were prepared by the ionic gel method. The loading capacity and encapsulation efficiency of naringin in microspheres were 13.2% and 77.6%, respectively. The morphology of microspheres was characterized by scanning electron microscopy. The X-ray diffractometry and differential scanning calorimetry results showed naringin was amorphous after encapsulation. Fourier-transform infrared spectroscopy and molecular docking analysis confirmed the intermolecular hydrogen bonds between naringin and sodium alginate. Naringin could release from the microspheres continuously under different pH conditions. Compared with free naringin, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and the stability of naringin microspheres were significantly improved. The application of naringin microspheres in yogurt indicated the precipitation of whey could be effectively reduced and the decline rate of pH was inhibited. The study suggested that naringin encapsulated microspheres were beneficial for improving the shelf life of this bioactive product as well as providing a new idea for functional yogurt.

The prominent human symbiont Bacteroides fragilis protects animals from intestinal diseases, such as ulcerative colitis, and its capsular polysaccharide plays a key role in reducing inflammation. B. fragilis strain ZY-312 was isolated from the feces of a healthy breast-fed infant, and the zwitterionic capsular polysaccharide zwitterionic polysaccharide, TP2, was extracted. In rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced enteritis, TP2 at an optimal dose of 2.5 mg/kg could significantly alleviate enteritis and reduced the degree of intestinal adhesions, the intestinal ulcer area, and the incidence of ulcers in rats. To understand the underlying mechanism, TP2 was labeled with Fluorescein isothiocyanate and orally administered at a dose of 2.5 mg/kg in rats. TP2 was mainly distributed in the cecum and colorectum, but it was not detected in the blood and other organs except that a compound with a molecular weight greater than that of TP2-FITC was found in liver tissue. During the absorption, distribution, metabolism, and excretion, TP2 was indigestible. These results were further confirmed by investigation in the simulated gastric, intestinal fluid, and colonic fluid with fecal microbiota in vitro, where TP2 remained unaltered at different time points. Furthermore, flora composition was analyzed in simulated colonic fluid with TP2 added and it was found that TP2 increased the abundance of Faecalibacterium, Enterococcus romboutsia, and Ruminococcaceae, whereas the abundance of the phylum Proteobacteria represented by Sutterella, Desulfovibrio, and Enterobacteriaceae was decreased. However, the amount of short-chain fatty acids in the simulated colonic fluid was not changed by intestinal flora post-TP2 addition. In conclusion, these findings confirmed that TP2, a capsular polysaccharide of B. fragilis, protects against ulcerative colitis in an undegraded form.

As an important abiotic stress factor, ultraviolet-B (UV-B) light can stimulate the accumulation of antioxidants in plants. In this study, the possibility of enhancing antioxidant capacity in pakchoi (Brassica rapa L.) by UV-B supplementation was assessed. Irradiation with 4 µmol·m−2·s−1 UV-B for 4 h or 2 µmol·m−2·s−1 UV-B for 24 h significantly increased the 1,1–diphenyl–2–picrylhydrazyl (DPPH) scavenging activity and total reductive capacity, as a result of inducing a greater accumulation of total polyphenols and flavonoids without affecting the plant biomass. A high performance liquid chromatography (HPLC) analysis showed that the concentrations of many flavonoids significantly increased in response to UV-B treatment. The activities of three enzymes involved in the early steps of flavonoid biosynthesis, namely phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), and 4-coumarate: coenzyme A (CoA) ligase (4CL), were significantly increased after the corresponding UV-B treatment. Compared with the control, the expression levels of several flavonoid biosynthesis genes (namely BrPAL, BrC4H, Br4CL, BrCHS, BrF3H, BrF3′H, BrFLS, BrDFR, BrANS, and BrLDOX) were also significantly up–regulated in the UV-B treatment group. The results suggest that appropriate preharvest UV-B supplementation could improve the nutritional quality of greenhouse-grown pakchoi by promoting the accumulation of antioxidants.

Compared to adults, neonates are at increased risk of infection. There is a growing recognition that dynamic qualitative and quantitative differences in immunity over development contribute to these observations. The liver plays a key role as an immunologic organ, but whether its contribution to the acute innate immune response changes over lifetime is unknown. We hypothesized that the liver would activate a developmentally-regulated acute innate immune response to intraperitoneal lipopolysaccharide (LPS). We first assessed the hepatic expression and activity of the NF-κB, a key regulator of the innate immune response, at different developmental ages (p0, p3, p7, p35, and adult). Ontogeny of the NF-κB subunits (p65/p50) revealed a reduction in Rela (p65) and Nfkb1 (p105, precursor to p50) gene expression (p0) and p65 subunit protein levels (p0 and p3) vs. older ages. The acute hepatic innate immune response to LPS was associated by the degradation of the NF-κB inhibitory proteins (IκBα and IκBβ), and nuclear translocation of the NF-κB subunit p50 in all ages, whereas nuclear translocation of the NF-κB subunit p65 was only observed in the p35 and adult mouse. Consistent with these findings, we detected NF-κB subunit p65 nuclear staining exclusively in the LPS-exposed adult liver compared with p7 mouse. We next interrogated the LPS-induced hepatic expression of pro-inflammatory genes (Tnf, Icam1, Ccl3, and Traf1), and observed a gradually increase in gene expression starting from p0. Confirming our results, hepatic NF-κB subunit p65 nuclear translocation was associated with up-regulation of the Icam1 gene in the adult, and was not detected in the p7 mouse. Thus, an inflammatory challenge induces an NF-κB-mediated hepatic innate immune response activation across all developmental ages, but nuclear translocation of the NF-κB subunit p65 and associated induction of pro-inflammatory genes occurred only after the first month of life. Our results demonstrate that the LPS-induced hepatic innate immune response is developmentally regulated by the NF-κB subunit p65 in the mouse.

Recent studies have demonstrated that radiation activates in situ antitumor immunity and consequently induced a synergistic effect of radiotherapy and immunotherapy. However, studies related to radiation-induced changes in immune system of tumor-bearing mice are limited, which are of great significance to improve the efficacy of radioimmunotherapy. In this study, we first established a primary lung tumor mouse model using urethane. Then part of the right lung of the mouse was exposed to X-ray irradiation with a computed tomography–guided small animal irradiator and the changes of immune cells in both peripheral blood and spleen were determined by flow cytometry. Besides, the levels of both cytokines and immunoglobulins in mouse serum were detected by a protein chip. We found that B lymphocytes increased while CD8 + T lymphocytes reduced significantly. Interleukin-3 (IL-3), IL-6, regulated upon activation, normally T-expressed, and presumably secreted factor (RANTES), and vascular endothelial growth factor (VEGF) were found to be decreased after tumor formation, and the similar results have also been observed with kappa, IgG3, IgE, IgM, and IgG2a. After irradiation, lower concentrations of IgD, kappa, and IgM were found in the serum. Our findings indicate that localized tumor irradiation caused some obvious changes like inhibiting the ability of innate immunity, and these changes may be useful in predicting prognosis.

Psoriasis is a multifactorial immune-mediated skin disease with a strong genetic background. Previous studies reported that psoriasis with a family history (PFH) and sporadic psoriasis (SP) have a distinct manifestation and genetic predisposition. However, the genetic heterogeneity of PFH and SP in the major histocompatibility complex (MHC) region has not been fully elucidated. To explore genetic variants in the MHC region that drive family aggregation of psoriasis, we included a total of 8,127 psoriasis cases and 9,906 healthy controls from Han Chinese and divided psoriasis into two subtypes, PFH (n=1,538) and SP (n=5,262). Then, we calculated the heritability of PFH and SP and performed a large-scale stratified association analysis. We confirmed that variants in the MHC region collectively explained a higher heritability of PFH (16.8%) than SP (13.3%). Further stratified association analysis illustrated that HLA-C∗06:02 and NOTCH4:G511S contribute to the family aggregation of psoriasis, and BTNL2:R281K specifically confers risk for SP. HLA-C∗06:02 and NOTCH4:G511S could partially explain why patients with PFH have a stronger genetic predisposition, more complex phenotypes, and more frequent other autoimmune diseases. The identification of the SP-specific variant BTNL2:R281K revealed that the genetic architecture of SP is not just a subset of PFH.

When a horizontal well is drilled through the natural gas hydrate (NGH) strata with different abundance, the NGH-bearing solid debris tends to lead to the deposit and adhesion of solid particles in the lateral sections and consequently cuttings carrying is not smooth. In this paper, the critical return rate model of drilling fluid in the case of cuttings rolling (normal drilling) and saltation (pump off for sand settling) under NGH adhesion in the laterals was established according to the force and migration laws of cuttings under the condition of multiphase flow in a horizontal well and the particle migration theory. Then, numerical simulation was conducted and the influential factors and migration laws of cuttings starting in the case of normal drilling and pump off were analyzed. And the following results were obtained. First, the critical starting flow rate decreases with the rise of NGH abundance and it is higher when the NGH adhesion is taken into account. Besides, the higher the NGH abundance, the greater the effect of NGH adhesion. Second, the critical starting flow rate increases with the rise of drilling cuttings particle size when the NGH abundance is less than 85%; and it decreases with the rise of drilling cuttings particle size when the NGH abundance is more than 85%. Third, the critical starting flow rate decreases with the rise of drilling fluid density and viscosity. And fourth, under the same conditions, the critical return rate for saltation is about 1.28 times that for rolling. It is suggested that the rolling model should be adopted for the normal drilling while the saltation model for the recycle after pump-off sand settling. The research results are of great significance to the optimization of NGH drilling parameters and the reduction of drilling safety risks. Keywords: Different abundance, Natural gas hydrate layer, Horizontal well, Solid cuttings, Migration law, Cuttings carrying laws, Critical flow rate, Numerical simulation, Flow field analysis

Both inhibitory and excitatory input development are shaped by activity, but one may be dependent on the other. Here, the authors examine plasticity of inhibitory inputs in vivo, as well as behavioral consequences in tadpoles where excitatory transmission has been impaired.

Abstract MoS2 has attracted attention as a promising hydrogen evolution reaction (HER) catalyst and a supercapacitor electrode material. However, its catalytic activity and capacitive performance are still hindered by its aggregation and poor intrinsic conductivity. Here, hollow rGO sphere-supported ultrathin MoS2 nanosheet arrays (h-rGO@MoS2) are constructed via a dual-template approach and employed as bifunctional HER catalyst and supercapacitor electrode material. Because of the expanded interlayer spacing in MoS2 nanosheets and more exposed electroactive S–Mo–S edges, the constructed h-rGO@MoS2 architectures exhibit enhanced HER performance. Furthermore, benefiting from the synergistic effect of the improved conductivity and boosted specific surface areas (144.9 m2 g−1, ca. 4.6-times that of pristine MoS2), the h-rGO@MoS2 architecture shows a high specific capacitance (238 F g−1 at a current density of 0.5 A g−1), excellent rate capacitance, and remarkable cycle stability. Our synthesis method may be extended to construct other vertically aligned hollow architectures, which may serve both as efficient HER catalysts and supercapacitor electrodes.

Aiming at the problems of difficult attitude stabilization, low landing accuracy, large external disturbance and slow dynamic response during the quadrotor dynamic landing on the wave glider, an improved series active disturbance rejection control method for the quadrotor is proposed. The quadrotor controller with inner-loop attitude angular velocity control and outer-loop position control based on the active disturbance rejection controller (ADRC) is designed by analyzing the dynamic model of the quadrotor. A tracking differentiator (TD) is adopted to track the input signal, and an expansive state observer (ESO) is used to estimate the total disturbance. Moreover, a nonlinear law state error feedback (NLSEF) is used to generate the virtual control volume of the system to realize the control of the quadrotor, and the stability of the cascaded self-turbulent controller is verified by Lyapunov’s theory. The simulation verifies that the proposed controller can accurately control the attitude and the position with better anti-interference capability and faster tracking speed. According to the final sea trial, a combination of an active disturbance rejection controller optimized with improved crow search algorithm (ICADRC) and April Tag visual reference system is used to land the quadrotor efficiently and successfully even under the surface float attitude uncertainty.

This study examined the association between mental rotation ability and facial masculinity preference in gay and bisexual men in China. The participants (436 gay/bisexual men, 132 heterosexual men, and 254 heterosexual women) completed an online Shepard and Metzler-type mental rotation task and a forced-choice preference task of 10 pairs of masculinized/feminized male faces. The results revealed that mental rotation ability was significantly associated with preference for masculinized faces in both gay and bisexual men. There were no significant correlations between mental rotation ability and facial masculinity preference in both heterosexual men and women. The findings imply homogamy in partner preference in gay and bisexual men in terms of masculinity.

The aim of this study was to examine the influences of internalized homophobia on Chinese gay and bisexual men’s quality of life and life satisfaction. Four hundred and eighty-three participants completed the Internalized Homophobia Scale, Chinese SF-12 Health Survey Version 2, and Satisfaction With Life Scale via the Internet. Scores for quality of life in several domains and life satisfaction were significantly lower than the heterosexuals’ norm scores. The present study revealed that internalized homophobia significantly negatively correlated with the mental component summary score and life satisfaction. The mental component summary score mediated the relationship between internalized homophobia and life satisfaction. Sexual orientation moderated the relationship between internalized homophobia and mental component score. Gay and bisexual men in China experience poorer quality of life and less satisfaction with life compared to heterosexuals, and internalized homophobia contributes to both.

Theory and some evidence suggest that masculine characteristics (e.g., lower pitched voice) will predict indices of men’s long-term health. In a related finding, researchers have demonstrated that the attractiveness of individuals predicts variation in their mate preferences. As self-perceived attractiveness may predict sociosexuality (i.e., the willingness of individuals to engage in restricted or unrestricted sexual relationships), we investigated how self-rated attractiveness and sociosexuality influence preferences regarding male voices among 338 gay men across different cities in China. Each participant was randomly presented with six pairs of male voices and gave preferences using a forced-choice method; each pair of male voices consisted of a masculine (lower pitched) and feminine (higher pitched) version of the same original voice. Our findings suggested that gay men who perceived themselves as more attractive showed stronger preference for lower pitched voices compared with self-perceived less attractive individuals. In addition, we found that gay men’s sociosexuality score was positively correlated with their preference for masculine cues in male voices, indicating that gay men who were less sociosexually restricted preferred lower pitched voices over higher pitched versions compared with men who were more restricted. Our study presents evidence contributing to a better understanding of condition-dependent strategies of partner choice in gay men.

Sexual objectification is very common in modern Western societies, especially toward women. Previous research has suggested that in Western cultures, social power could lead to objectification. Specifically, power activates an approaching tendency toward useful targets, in turn leading to instrumental objectification and sexual objectification of targets. However, previous research has mostly focused on Western cultures, and the neural correlates underlying this phenomenon remain unclear. To examine whether the effects of power can be generalized to Chinese cultural contexts and how power promotes the objectification of sexualized bodies, we conducted two studies using Chinese samples. In Study 1, we replicated the behavioral effects of social power on sexual objectification. Specifically, we found that power increased sexual objectification toward sexualized female rather than male bodies. In Study 2, we examined the absence of an N170 amplitude inversion effect as a possible neural correlate of sexual objectification and replicated the effects of power on sexual objectification through event-related potentials (ERPs). For participants in a high-power group, the N170 amplitude inversion effect emerged when processing sexualized male bodies (less sexual objectification) but not female bodies (more sexual objectification); this effect was not seen for those participants in a low-power group. Our findings provide behavioral and neural data that power leads to increased sexual objectification toward sexualized women in Chinese participants.

Maternal selenium (Se) deficiency is associated with decreased neonatal Se levels, which increases the risk for neonatal morbidities. There is a hierarchy to selenoprotein expression after Se deficiency in adult rodents, depending on the particular protein and organ evaluated. However, it is unknown how limited Se supply during pregnancy impacts neonatal selenoprotein expression. We used an Se-deficient diet to induce perinatal Se deficiency (SeD), initiated 2–4 weeks before onset of breeding and continuing through gestation. Neonatal plasma, liver, heart, kidney, and lung were collected on the day of birth and assessed for selenoproteins, factors required for Se processing, and non-Se containing antioxidant enzymes (AOE). Maternal SeD reduced neonatal circulating and hepatic glutathione peroxidase (GPx) activity, as well as hepatic expression of Gpx1 and selenophosphate synthetase 2 (Sps2). In contrast, the impact of maternal SeD on hepatic thioredoxin reductase 1, hepatic non-Se containing AOEs, as well as cardiac, renal, and pulmonary GPx activity, varied based on duration of maternal exposure to SeD diet. We conclude that the neonatal liver and circulation demonstrate earlier depletion in selenoenzyme activity after maternal SeD. Our data indicate that prolonged maternal SeD may escalate risk to the neonate by progressively diminishing Se-containing AOE across multiple organs.