Search

Abstract Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFβ inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.

Abstract Musk is an important animal product, but the musk secretion mechanism of forest musk deer (Moschus berezovskii) is still unclear. The musk synthesis process in forest musk deer is extremely complex, and many raw materials are directly or indirectly derived from forest musk deer blood. In this study, metabolomics was used to analyze the blood of forest musk deer in secretory and non-secretory phases for the first time, aim at explaining the secretion mechanism from the perspective of blood metabolism. We found that P450-related, choline-related, axonal regeneration and other pathways and related metabolites were significantly enriched during the musk secretion of forest musk deer. These pathways and metabolites related to P450 and choline in blood may have important implications for the mechanism of musk secretion in forest musk deer, because blood components were closely related to musk components and could provide raw materials for musk synthesis in musk gland cells.

The purpose of this study was to obtain polysaccharides from Panax ginseng C. A. Meyer stems (PGSPs), agro-byproducts with development potential, and fully explore the potential value in P. ginseng stems. Two novel polysaccharides firstly from P. ginseng stems (PGSP-1 and PGSP-2) were obtained by water extraction and alcohol precipitation method and column chromatography, and then characterized by FT-IR, HPGPC, HPLC, SEM, TGA, GC–MS and NMR. The results demonstrated that PGSP-1 (Mw = 723.83 kDa) and PGSP-2 (Mw = 620.48 kDa) were characterized →4)-β-D-Galp-(1→, →6)-α-D-Glcp-(1 → and →2)-α-L-Rhap-(1 → as the skeleton, →4,6)-β-D-Galp-(1 → and →2,6)-α-D-Manp-(1 → as the cross junction, α-L-Araf-(1 → as the terminal unit, and PGSP-1 still contained →4)-β-D-Galp, while PGSP-2 contained →4)-β-D-Xylp-(1→, →3)-β-D-GlcpA-(1→, →4)-β-D-GalpA-(1 →) and α-D-Glcp-(1→, with different microstructures and thermal stability. And the results of hypoglycemic activity revealed that both PGSP-1 and PGSP-2 showed excellent inhibitory activity against α-glucosidase and α-amylase, in which PGSP-2 had the better performance. The inhibition kinetics result showed that PGSPs on α-glucosidase and α-amylase were non-competitive type and mixed type inhibition. This study provided a theoretical basis for making full use of and exploiting the economic value of agro-byproducts such as P. ginseng stems and offered a theoretical reference for the effective utilization of PGSP as a functional component to prevent and reduce T2DM.

Abstract Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5′ UTR, were specifically recognized by the m6A “reader” protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.

In demanding application scenarios such as clinical psychotherapy and criminal interrogation, the accurate recognition of micro-expressions is of utmost importance but poses significant challenges. One of the main difficulties lies in effectively capturing weak and fleeting facial features and improving recognition performance. To address this fundamental issue, this paper proposed a novel architecture based on a multi-scale 3D residual convolutional neural network. The algorithm leveraged a deep 3D-ResNet50 as the skeleton model and utilized the micro-expression optical flow feature map as the input for the network model. Drawing upon the complex spatial and temporal features inherent in micro-expressions, the network incorporated multi-scale convolutional modules of varying sizes to integrate both global and local information. Furthermore, an attention mechanism feature fusion module was introduced to enhance the model's contextual awareness. Finally, to optimize the model's prediction of the optimal solution, a discriminative network structure with multiple output channels was constructed. The algorithm's performance was evaluated using the public datasets SMIC, SAMM, and CASME Ⅱ. The experimental results demonstrated that the proposed algorithm achieves recognition accuracies of 74.6, 84.77 and 91.35% on these datasets, respectively. This substantial improvement in efficiency compared to existing mainstream methods for extracting micro-expression subtle features effectively enhanced micro-expression recognition performance and increased the accuracy of high-precision micro-expression recognition. Consequently, this paper served as an important reference for researchers working on high-precision micro-expression recognition.

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the “healthy” population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia–Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

Abstract To enhance the ribonucleic acid (RNA) productivity for industrial applications, this study employed strain screening and medium optimization to improve the content of RNA in Cyberlindnera jadinii. A rapid screening method, combining atmospheric and room temperature plasma mutagenesis, 48-deep-well plates fermentation, and microplate reader detection, was developed. A mutant strain named WB15 with high RNA content was successfully obtained, exhibiting the RNA content of 156 ± 4.5 mg/g DCW, 1.4 times of the starting strain CCTCC AY 92020. Furthermore, Plackett–Burman design and response surface methodology were employed to identify three significant factors (yeast extract, soybean peptone, and KH2PO4) affecting the RNA content. By utilizing the optimal medium composed of 13.43 g/L yeast extract, 12.12 g/L soybean peptone and 2.78 g/L KH2PO4, the RNA content of WB15 further increased to 184 ± 4.9 mg/g DCW. Additionally, the mutant strain WB15 exhibited a greater cellular width compared to AY 92020, along with increased growth rate and single-cell RNA content by 22% and 48.9%, respectively. Perturbations in ribosome assembly, specifically a reduction in the ratio of ribosomal proteins to ribosomal RNA of the large subunit, might indirectly contribute to the higher RNA content in the WB15 strain. Overall, the combination of rapid screening with fermentation medium optimization proved to be an effective approach for improving the RNA content of C. jadinii, thus facilitating the industrial production of RNA.

With the increase in master’s degree enrollment in China, ensuring the realization of value-added research skills of master’s degree students with limited educational resources has become an urgent problem. We developed hypotheses and tested the mediating effect of academic passion (AP) in the role of training environment satisfaction (TES) on research skill increment (RSI) and the moderating role of academic self-efficacy (ASE) using the perspective of Research Training Environment Theory (RTE). We used a structured questionnaire to collect responses from 911 master’s students from universities in central China, including 458 males (50.27%) and 453 females (49.73%), and 66.41% of the subjects were between the ages of 23 and 26. Our findings indicate that TES significantly impacts RSI and can influence RSI via a partially mediated effect of AP. In addition, we determined the moderating effect of ASE between the effects of the three variables. Based on RTE theory, we introduced the concept of value-add assessment and combined the two to realize the expansion of RTE theory. This study has implications for administrators and individuals in graduate education. It can help administrators make changes to the management model or methods of graduate education, as well as provide some inspiration for developing and improving master’s students’ research skills.

In order to deeply analyze the characteristics of the ship’s static electric field signals, the underwater potential characteristics of static electric field related to ship corrosion were studied based on the ship model test and the measured data of the planar potential measurement array at sea. Firstly, based on the ship model test, the characteristics of the ship’s static electric field signals under the cathodic protection system were analyzed, and it was found that the cathodic protection system had a great influence on the magnitude of static electric field signals. Secondly, the time domain and frequency domain of underwater potential signals of typical ships obtained from the measured data at sea were analyzed. The results show that the static electric field energy is mainly concentrated in the frequency band of 0-0.1 Hz. Finally, according to the distribution rule of underwater potential, it is found that when 12 dB is taken as the detection threshold, and the distance between adjacent sensors is no more than 320 m at a shallow depth of 240 m, the sensor array can accurately detect the ship’s electric field with a surface equivalent source intensity of 10 A·m.

Abstract Background and aims Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown. Methods HSOS model was established by gavage of monocrotaline (MCT) in rats. Fecal microbiota transplantation (FMT) with HSOS-derived or healthy gut flora was also conducted to validate the role of gut microflora in MCT-induced liver injury. The microbial 16 s rRNA analysis and untargeted metabolomics analysis in the faeces were performed to identify HSOS-related flora and metabolites. Finally, by supplementation with specific tryptophan metabolites, such as indole-3-acetaldehyde (IAAld) and indole acetic acid (IAA), we further confirmed the role of tryptophan metabolism in HSOS and the role of the AhR/Nrf2 pathway in MCT-induced liver injury. Results MCT induced HSOS-like liver injury in rats with significantly altered gut microbiota. Particularly, some tryptophan-metabolizing bacteria reduced in MCT-treated rats, such as Bacteroides, Bifidobacterium, Lactobacillus and Clostridium, and accompanied by a decrease in microbial tryptophan metabolic activity and a series of tryptophan derivatives. Restoring the gut microbiota via FMT improved MCT-induced liver damage, while HSOS-derived gut microbiota aggravated the liver injury induced by MCT. Supplementation with microbial tryptophan derivatives (IAAld or IAA), or 6-formylindolo(3,2-b)carbazole (Ficz, an AhR agonist) could activate the AhR/Nrf2 signaling pathway, thereby attenuating the MCT-induced liver oxidative stress and liver sinusoidal endothelial cells injury. Conclusions Gut microbiota plays a critical role in MCT-induced HSOS, with inadequate microbial tryptophan metabolism in the gut and consequently a lower activity of the AhR/Nrf2 signaling pathway in the liver, which should be a potential target for the management of HSOS.

The rapid growth of postgraduate education in China necessitates the imperative to augment the innovative behaviors of postgraduates. The purpose of this study was to explore whether a supportive mentoring style affects the innovative behavior of master’s degree students and the potential role that academic aspiration may play in the relationship between the two. A time-lag questionnaire was given to 911 master’s degree students in central China for Study 1. The results revealed that a supportive mentoring style positively predicted innovative behavior. Furthermore, the connection between a supportive mentoring style and innovative behaviors was mediated by academic aspirations. Study 2 matched five pairs of students with mentors to administer the survey using semi-structured interviews. The results confirmed the mechanisms through which supportive mentoring styles impact innovative behavior and provided more evidence for them. This study examines the development path of master’s degree students’ innovative behavior, reveals how internal (academic aspiration) and external (mentoring) factors impact such behavior, and offers insights into graduate students’ educational practices.

Abstract With the explosive growth of photovoltaic (PV) penetration, there is an increasingly urgent expectation for PV sources to provide a full range of ancillary services to the utility. The most critical issue for a PV source to support the power system is the flexible power regulating capability, whereas the PV sources generally operates in the maximum power point tracking (MPPT) mode to maximize the solar harvest. This paper proposes an active power control strategy for PV sources based on a characteristic curve fitting method. With the proposed control strategy, PV sources can operate in the MPPT mode or adaptively switch to the power dispatch mode to flexibly regulate its output power to track the power reference. The characteristic curve fitting method does not require an irradiation sensor, but it has a more stable performance under rapid and continuous change in irradiation with simple calculation and error control since its extremely high similarity with the P–U characteristics of the PV source. Simulation is performed based on a detailed PV dynamic model to validate the proposed control strategy.

Abstract Recently, distributed cooperative control has been popularly used in the secondary control of microgrids due to its reliability and flexibility. However, traditional distributed control schemes based on fixed‐cycle communication usually result in a waste of communication resources. Thus, this paper proposes an event‐triggered distributed control strategy that can significantly reduce the requirements of communication. In addition, compared with existing schemes, the proposed algorithm can achieve the secondary control goal in a directed graph, which can be applied to more scenarios, especially for weaker communication conditions. The stability of the strategy is investigated with the Lyapunov method. The simulation results verify the validity and effectiveness of the proposed scheme.

The compressive strength of ultra great workability concrete (UGWC) is a function of the kind, characteristics and quantities of its material components. Empirically gaining this relation sometimes needs the usage of intelligent algorithms to receive a simulative model that fits into experimental data records. In this study, the usefulness of developing hybridized regression analysis on UGWC was analyzed with the aim of reducing the consumed time and experimental efforts. To this aim, a dataset including 170 samples collected from published papers different hybridized support vector regression (SVR) analyses were produced, where the optimal values of determinant attributes of SVR were explored by metaheuristic optimization algorithms named particle swarm optimization (PSO), Cuckoo optimization algorithm (COA), and Bat algorithm (BAT). The performance evaluators demonstrate that all three hybridized SVR models have remarkable potential in compressive strength estimation of UGWC. The first rank belonged to the SVR-COA model, where it could gain the highest value of R2 and variance account factor (VAF) in both training (R2=0.9056 and VAF=90.17%) and validating section (R2=0.9208 and VAF=91.81%), and the lowest value of root mean square error, and mean absolute error in both training and validating sections. Therefore, the hybridized SVR-COA model could receive the proper accuracy in comparison with other models as well as literature.

Abstract Background Impaired metabolic functions of gut microbiota have been demonstrated in alcohol-related liver disease (ALD), but little is known about changes in phenylalanine metabolism. Methods Bacterial genomics and fecal metabolomics analysis were used to recognize the changes of phenylalanine metabolism and its relationship with intestinal flora. Intestinal barrier function was detected by intestinal alkaline phosphatase (IAP) activity, levels of tight junction protein expression, colonic inflammation and levels of serum LPS. Lactobacillus acidophilus was chosen to correct phenylalanine metabolism of ALD mice by redundancy analysis and Pearson correlation analysis. Results Using 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods, we identified elevated levels of phenylalanine and its’ metabolites in the gut of alcohol-fed mice compared to control mice and were negatively correlated with the abundance of Lactobacillus, which mainly metabolized phenylalanine. The intestinal phenylalanine level was positively correlated with the colon inflammatory factors TNF-α and IL-6, and negatively correlated with ZO-1 and Occludin. While intestinal alkaline phosphatase (IAP) activity was negatively correlated with the colon inflammatory factors TNF-α, IL-6 and MCP-1, and positively correlated with ZO-1 and Occludin. Increased phenylalanine inhibited IAP activity, blocked LPS dephosphorylation, increased colonic inflammation and bacterial translocation. Phenylalanine supplementation aggravated alcohol-induced liver injury and intestinal barrier dysfunction. Among the 37 Lactobacillus species, the abundance of Lactobacillus acidophilus was most significantly decreased in ALD mice. Supplementation with L. acidophilus recovered phenylalanine metabolism and protected mice from alcohol-induced steatohepatitis. Conclusions Recovery of phenylalanine metabolism through the oral supplementation of L. acidophilus boosted intestinal barrier integrity and ameliorated experimental ALD.

Abstract Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. Results We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. Conclusion INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

Abstract The quantum Cramér–Rao bound sets a fundamental limit on the accuracy of unbiased parameter estimation in quantum systems, relating the uncertainty in determining a parameter to the inverse of the quantum Fisher information. We experimentally demonstrate near saturation of the quantum Cramér–Rao bound in the phase estimation of a solid-state spin system, provided by a nitrogen-vacancy center in diamond. This is achieved by comparing the experimental uncertainty in phase estimation with an independent measurement of the related quantum Fisher information. The latter is independently extracted from coherent dynamical responses of the system under weak parametric modulations, without performing any quantum-state tomography. While optimal parameter estimation has already been observed for quantum devices involving a limited number of degrees of freedom, our method offers a versatile and powerful experimental tool to explore the Cramér–Rao bound and the quantum Fisher information in systems of higher complexity, as relevant for quantum technologies.

As countries attach great importance to the ocean-going navigation capability of ships, the energy consumption of shipborne equipment has attracted much attention. Although energy consumption analysis is a guiding method to improve energy efficiency, it often ignores the dynamic characteristics of the system. However, the traditional dynamic analysis method hardly considers the energy consumption characteristics of the system. In this paper, a new type of electric-driven helicopter traction system is designed based on the ASIST system. Combined with power bond graph theory, a system dynamic modeling method that considers both dynamic and energy consumption characteristics is proposed, and simulation analysis is carried out. The results indicate that the designed traction system in this study displays high responsiveness, robust, steady-state characteristics, and superior energy efficiency. When it engages with helicopter-borne aircraft, it swiftly transitions to a stable state within 0.2 s while preserving an efficient speed tracking effect under substantial load force, and no significant fluctuations are detected in the motor rotation rate or the helicopter movement velocity. Moreover, it presents a high energy utilization rate, achieving an impressive energy utilization rate of 84% per single working cycle. Simultaneously, the proposed modeling methodology is validated as sound and effective, particularly apt for the dynamic and power consumption analysis of marine complex machinery systems, guiding the high-efficiency design of the transmission system.

ObjectiveExplore the influence of fear of COVID-19 on depression, with anxiety as a mediator and perceived social support and stress perception as moderates.MethodsFrom February to March 2020, 1,196 valid data were collected online through questionnaire by cluster sampling method. Fear of COVID-19 Questionnaire, the Patient Health Questionnaire 9-Item Scale (PHQ-9), the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Perceived Social Support Scale (PSSS) and the10-item Perceived Stress Scale (PSS-10) were used as the survey instrument, and the participants were female undergraduates from a liberal arts college of a Chinese university. Common method bias was assessed using Harman’s single-factor test in SPSS and confirmatory factor analysis in AMOS. The levels of participants’ anxiety, depression and perceived social support were described using frequency and percentage, Pearson Correlation test was used to measure the correlation between the variables. The PROCESS macro for SPSS (Model 1, Model 4, and Model 21) were applied to examine the mediating effect and moderating effect of the model.ResultsFear of COVID-19 can positively influence depression, anxiety plays a mediating role between fear of COVID-19 and depression, perceived social support negatively moderates the relationship between fear of COVID-19 and anxiety, and stress perception positively moderates the relationship between anxiety and depression. These five variables can form a moderated mediating effect model.ConclusionFear of COVID-19, anxiety and stress perception are risk factors for depression, perceived social support is a protective factor for depression. Reducing the fear of COVID-19, anxiety and stress perception and enhancing perceived social support are beneficial to reduce the level of depression.

Due to the advantages of effectively integrating diversified loads and renewable sources, hybrid DC/AC microgrids have attracted the common attention of industry and academia. Meanwhile, with the increasing number of power electronic devices connected to the system, the complexity of the system increases, which puts forward higher requirements for galvanic isolation and intelligent control methods. This study proposes a unified decentralized framework for isolated interlinking converters (IICs) in hybrid DC/AC microgrids, which include topology and a control strategy to solve the aforementioned problems. Firstly, in terms of topology, a dual active bridge (DAB) converter is adopted to realize galvanic isolation and DC voltage conversion, which can facilitate the interconnection of DC microgrids or be combined with VSC for the interconnection of DC and AC microgrids. Secondly, in terms of the control strategy, a bidirectional voltage–supporting control strategy is proposed for IICs, in which the frequency and voltage are adopted as the indications to balance the power and strengthen the inertia interaction of microgrids. Furthermore, with the proposed control strategy, the voltage sources of different microgrids can share the power fluctuation, cooperatively. The stability of the proposed strategy is analyzed, and the effectiveness is verified by several HIL experiments.

Abstract Most cancer patients die of non-cancer causes, and peptic ulcer is one cause that deserves attention. To characterize the incidence and risk factors of death from peptic ulcer among cancer patients, we extracted the data of cancer patients registered in the Surveillance Epidemiology and End Results (SEER) program from 1975 to 2016. Out of the 8,471,051 patients extracted from SEER, 4,698 died from peptic ulcer, with a mortality rate of 9.08/100,000 person-years. Meanwhile, the mortality rate in the general population was 5.09/100,000 person-years, giving a standardized mortality ratio (SMR) of 1.78 (95% confidence interval, 1.73–1.84). Patients who are female, of other race, unmarried, and with distant tumor stage have greater SMRs. A higher SMR was associated with a younger age at diagnosis. Among those aged 40 years, the majority occurred in those with prostate, breast, colorectum, and lung cancer. Patients with upper digestive system malignancies had the highest SMRs and hazard ratios (HRs), which could be ascribed to radiotherapy-induced damage to the gastroduodenum. The risk declined rapidly one year after diagnosis. However, the SMRs in the upper digestive system cancer survivors increased significantly over ten years after diagnosis. Upper digestive system cancers adjacent to the gastroduodenum were associated with higher SMRs and HRs compared with other types of cancer, possibly contributing partially to the damage caused by radiotherapy on the radiosensitive gastroduodenum.

Abstract Background Alternative splicing is the process of selecting different combinations of splice sites to produce variably spliced mRNAs. However, the relationships between alternative splicing prevalence and level (ASP/L) and variations of intron size and organism complexity (OC) remain vague. Here, we developed a robust protocol to analyze the relationships between ASP/L and variations of intron size and OC. Approximately 8 Tb raw RNA-Seq data from 37 eumetazoan species were divided into three sets of species based on variations in intron size and OC. Results We found a strong positive correlation between ASP/L and OC, but no correlation between ASP/L and intron size across species. Surprisingly, ASP/L displayed a positive correlation with mean intron size of genes within individual genomes. Moreover, our results revealed that four ASP/L-related pathways contributed to the differences in ASP/L that were associated with OC. In particular, the spliceosome pathway displayed distinct genomic features, such as the highest gene expression level, conservation level, and fraction of disordered regions. Interestingly, lower or no obvious correlations were observed among these genomic features. Conclusions The positive correlation between ASP/L and OC ubiquitously exists in eukaryotes, and this correlation is not affected by the mean intron size of these species. ASP/L-related splicing factors may play an important role in the evolution of OC.

Abstract Background As the survival rates of cancer patients continue to increase, most cancer patients now die of non-cancer causes. Several studies have been showing elevated suicide rates among patients with cancer. However, no large-scale study has thoroughly assessed the risk of suicide among adolescent and young adult (AYA) patients with cancer. This study was conducted to characterize suicide mortality among AYA patients in the US and identify risk factors associated with a higher risk of suicide. Methods Patients aged 15–39 years were residents of the US served by the Surveillance, Epidemiology, and End Results (SEER) program, who were diagnosed with cancers from 1973 to 2015. Results We report that 981 of the 572,500 AYA patients with cancer committed suicide, for an age-, sex-, and race-adjusted suicide rate of 17.68/100,000 person-years. The rate of suicide was 14.33/100,000 person-years in the corresponding general population, giving a standardized mortality ratio (SMR) of 1.234 [95% confidence interval (CI) 1.159–1.313]. Higher suicide rates were associated with male sex, white race, unmarried state, distant tumor stage, and single primary tumor. AYA patients with otorhinolaryngologic, gonad, stomach, soft tissue, and nasopharyngeal cancer were at the greatest risk of suicide compared with those with other types of cancer. In older patients (≥ 40 years), the risk was highest in those with lung, stomach, oral cavity and pharynx, larynx, and bone malignancies. SMRs were highest in the first 5 years after diagnosis for most types of cancer. Conclusion AYA patients with cancer in the US have over 20% higher the incidence of suicide of the general population, and most suicides occurred in the first 5 years following diagnosis. Suicide rates vary among patients with cancers of different anatomic sites. Further examination of the psychological experience of these young patients with cancer, particularly that of those with certain types of cancer, is warranted.

Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in “Synopsis of Golden Chamber” (Han Dynasty in the 3rd century) and the Zhizhu pill in “Differentiation on Endogenous” in Jin Dynasty (1,115–1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD).Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD.Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored.Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats.Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.

Abstract Coronavirus disease 2019 continues to spread worldwide. Given the urgent need for effective treatments, many clinical trials are ongoing through repurposing approved drugs. However, clinical data regarding the cardiotoxicity of these drugs are limited. Human pluripotent stem cell‐derived cardiomyocytes (hCMs) represent a powerful tool for assessing drug‐induced cardiotoxicity. Here, by using hCMs, it is demonstrated that four antiviral drugs, namely, apilimod, remdesivir, ritonavir, and lopinavir, exhibit cardiotoxicity in terms of inducing cell death, sarcomere disarray, and dysregulation of calcium handling and contraction, at clinically relevant concentrations. Human engineered heart tissue (hEHT) model is used to further evaluate the cardiotoxic effects of these drugs and it is found that they weaken hEHT contractile function. RNA‐seq analysis reveals that the expression of genes that regulate cardiomyocyte function, such as sarcomere organization (TNNT2, MYH6) and ion homeostasis (ATP2A2, HCN4), is significantly altered after drug treatments. Using high‐throughput screening of approved drugs, it is found that ceftiofur hydrochloride, astaxanthin, and quetiapine fumarate can ameliorate the cardiotoxicity of remdesivir, with astaxanthin being the most prominent one. These results warrant caution and careful monitoring when prescribing these therapies in patients and provide drug candidates to limit remdesivir‐induced cardiotoxicity.

Autophagy has dual roles in cancer, resulting in cellular adaptation to promote either cell survival or cell death. Modulating autophagy can enhance the cytotoxicity of many chemotherapeutic and targeted drugs and is increasingly considered to be a promising cancer treatment approach. Cynaropicrin (CYN) is a natural compound that was isolated from an edible plant (artichoke). Previous studies have shown that CYN exhibits antitumor effects in several cancer cell lines. However, it anticancer effects against neuroblastoma (NB) and the underlying mechanisms have not yet been investigated. More specifically, the regulation of autophagy in NB cells by CYN has never been reported before. In this study, we demonstrated that CYN induced apoptosis and protective autophagy. Further mechanistic studies suggested that ER stress-induced autophagy inhibited apoptosis by activating the p62/Keap1/Nrf2 pathways. Finally, in vivo data showed that CYN inhibited tumour growth in xenografted nude mice. Overall, our findings suggested that CYN may be a promising candidate for the treatment of NB, and the combination of pharmacological inhibitors of autophagy may hold novel therapeutic potential for the treatment of NB. Our paper will contribute to the rational utility and pharmacological studies of CYN in future anticancer research.

This study proposes a unified voltage regulation and maximum power point tracking (MPPT) method for photovoltaic (PV) sources in islanded direct current (DC) microgrids based on modified model predictive control (MPC). The method enables the PV sources to track the maximum power and serve as voltage sources for DC-bus voltage regulation when their available power is sufficient. Based on the proposed modified predictive model, the desired duty cycles can be calculated and directly applied to the PV sources in a constant switching frequency without a modulator. Real-time laboratory tests show that the PV sources can support the DC-bus voltage without energy storage (ES) and can proportionally share the load. Moreover, power oscillations and voltage ripples of the modified MPC get greatly attenuated compared with the traditional MPC under the same sampling frequency.

Ex situ conservation is an important technique for protecting rare and endangered wildlife, and maintaining stable individual health is crucial to its success. Gut microbiota composition is a critical indicator of animal health and should therefore be closely monitored during ex situ conservation to track impacts on animal health. Forest musk deer (Moschus berezovskii) were historically distributed in Hebei Province, China, however, they are now extinct in the region. Thus, ex situ conservation efforts were conducted in 2016 whereby approximately 50 individuals were artificially migrated from Weinan, Shaanxi to Huailai, Hebei. To monitor gut health of these migrated individuals, we used 16S rRNA high-throughput sequencing technology to examine the microbiota differences between Huailai juvenile and Weinan juvenile groups, and between Huailai adult and Weinan adult groups. Alpha diversity analysis indicated that the richness of microbiota significantly decreased after migration to the Huailai area, and the beta diversity results also showed significant dissimilarity in gut microbial communities, demonstrating the distinct microbial structure differences in the forest musk deer population from the two areas, for both juvenile and adult groups, respectively. In addition, PICRUSt functional profile prediction indicated that the functions of gut digestion and absorption, and degradation of toxic substances were significantly weakened after ex situ conservation. Differences in diet composition between the individuals of the two sites were also observed and the impact of food on gut microbiota compositions within forest musk deer during ex situ conservation was investigated. This study provides a theoretical basis for developing ex situ conservation measures, especially for the protection of forest musk deer.

Abstract Background Receiving a cancer diagnosis may trigger immediate fatal non-cancer health outcomes in addition to dying of cancer itself. We aim to investigate the full pattern of non-cancer deaths in patients within a year of a cancer diagnosis. Methods Patients diagnosed with cancer between 1990 and 2016 were identified from the SEER program. Standardized mortality ratios (SMRs) were calculated to characterize the relative risks of non-cancer deaths compared with the general population. Results Among 7,366,229 patients, 241,575 non-cancer deaths (15.9%) were recorded in the first year following a cancer diagnosis. The relative risk of non-cancer deaths was 2.34-fold (95% confidence interval (CI): 2.33–2.35) that of the general population. The majority of non-cancer deaths were caused by cardiovascular diseases (21.8%), followed by infectious diseases (7.2%). Significant elevations in mortality risks were observed for nearly all non-cancer causes, particularly in infectious diseases (SMR: 5.08; 95% CI: 5.03–5.13). Patients with liver cancer (SMR: 12.29; 95% CI: 12.06–12.53) were at the highest risk of early non-cancer deaths. The risks of non-cancer deaths were highest within the first month after diagnosis, and decreased rapidly thereafter. Conclusions Risks of non-cancer deaths vary by the types of causes and anatomic sites of cancer. Our data underscore the importance of close observation and early multidisciplinary care for noncancer conditions in patients who have recently received a cancer diagnosis.

Abstract Frontline healthcare nurses devoted themselves to deal with the outbreak of COVID-19, saving many lives. However, they are under incredible unknown psychological pressures with a considerable risk of infection. In this study, a self-administered questionnaire was used to survey 593 frontline nurses in Wuhan City and non-Hubei provinces for psychological responses from March 1 to March 10, 2020. Compared with nurses outside Hubei Province, those working in Wuhan were more likely to feel physically and mentally exhausted. Their probable depression and anxiety were significantly higher than those of nurses outside Hubei province (31.2%, 18.3% vs. 13.8%, 5.9%). Correspondingly, the depressive symptoms were more often reported in the Wuhan group (70.8% vs. 41.4%). Although Wuhan received wishes, concerns, and abundant psychological and material resources from all of the world, the survey-based study found that frontline nurses in Wuhan still had higher depression and anxiety with less social support compared with nurses from non-Hubei provinces. Unexpectedly, only 4.0% of nurses have sought psychological assistance. These findings suggested that the short-term psychological impact of frontline nurses in Wuhan during the COVID-19 outbreak was extremely high compared with nurses outside Hubei Province. This research enlightened the efficient integration of psychological resources, the optimization of the nurse emergency psychological assistance system, and the mental health care of medical staff during the outbreak of epidemics.

Abstract Background Non-Drosophila insects provide diverse aging types and important complementary systems for studies of aging biology. However, little attention has been paid to the special roles of non-Drosophila insects in aging research. Here, the aging-related features of the migratory locust, Locusta migratoria, were determined at the physiological, cellular, and transcriptional levels. Results In physiological assessments, the flight performance and sperm state of locusts displayed clear aging-related decline in male adults. Transcriptional analyses demonstrated locusts have similar aging-related genes with model species. However, different from those of Drosophila and mammals, the organ-specific aging transcriptional features of locusts were characterized by intensive expression changes in flight muscle and fat body and little transcriptional changes in brain. The predominant transcriptional characteristics of flight muscle and fat body aging were changes in expression of mitochondrion-related genes and detoxification and phagocytosis genes, respectively. Cellular assessments revealed the incidence of mitochondrial abnormalities significantly increased in aged flight muscle, and apoptotic signals and nuclear abnormalities were enhanced in aged fat body but not in brain. In addition, some well-known aging genes and locust aging-related genes (i.e., IAP1, PGRP-SA, and LIPT1), whose roles in aging regulation were rarely reported, were demonstrated to affect lifespan, metabolism, and flight ability of locusts after RNAi. Conclusion This study revealed multi-level aging signatures of locust, thus laying a foundation for further investigation of aging mechanisms in this famous insect in the future.

As dominant power sources, the safe and reliable operation of photovoltaic (PV) generators is crucial for the DC distribution network. This study analyzes the transient stability of PV generators under large disturbances and proposes a variable parameter control strategy to suppress the transient instability. First, the transient stability of the PV generators is analyzed using the proposed power–voltage evolution curve. It is found that the PV side easily suffers undervoltage faults during the transient process, which will cause instability of the system. Based on the revealed unstable mechanism, the variable parameter control is proposed to enhance the transient stability of PV generators. Finally, all the findings have been validated by hardware-in-loop tests.

The boundary layer development on a low-pressure turbine blade surface modified by recessed dimples, U-grooves, and rectangular grooves has been investigated through the large-eddy simulations. The simulations are performed at a Reynolds number of 50,000 (based on the inlet velocity and axial chord length) and extremely low freestream turbulence conditions. The characteristic parameters of the boundary layer are used to estimate the development of the boundary layer, and spectral analysis has also been performed to identify the dominant frequency of shedding vortices. The results of simulations indicate that three surface modifications all reduce the profile losses by restraining the separation bubble size. However, the grooves and dimples show different mechanisms in inhibiting laminar separation. Grooves tend to promote the formation of spanwise vortices, which is more difficult to break into turbulence. A high-speed shedding vortex is induced by the particular 3D structure of dimple, and its shedding frequency is nearly twice the Kelvin–Helmholtz (K-H) instability frequency. The interaction between the shedding vortices and the K-H vortices promotes the breakdown process of the spanwise vortices, which leads to an earlier transition of the boundary layer at a low disturbance level. The current study reveals the different mechanisms of dimples and grooves and shows the great potential of dimples for flow control in low-pressure turbines. Besides, the flow structures inside the dimples with adverse pressure gradients are also explored.

Reproductive synchrony generally occurs in various group-living animals. However, the underlying mechanisms remain largely unexplored. The migratory locust, Locusta migratoria, a worldwide agricultural pest species, displays synchronous maturation and oviposition when forms huge swarm. The reproductive synchrony among group members is critical for the maintenance of locust swarms and population density of next generation. Here, we showed that gregarious female locusts displayed more synchronous sexual maturation and oviposition than solitarious females and olfactory deficiency mutants. Only the presence of gregarious male adults can stimulate sexual maturation synchrony of female adults. Of the volatiles emitted abundantly by gregarious male adults, the aggregation pheromone, 4-vinylanisole, was identified to play key role in inducing female sexual maturation synchrony. This maturation-accelerating effect of 4-vinylanisole disappeared in the females of Or35-/- lines, the mutants of 4-vinylanisole receptor. Interestingly, 4-vinylanisole displayed a time window action by which mainly accelerates oocyte maturation of young females aged at middle developmental stages (3–4 days post adult eclosion). We further revealed that juvenile hormone/vitellogenin pathway mediated female sexual maturation triggered by 4-vinylanisole. Our results highlight a ‘catch-up’ strategy by which gregarious females synchronize their oocyte maturation and oviposition by time-dependent endocrinal response to 4-vinylanisole, and provide insight into reproductive synchrony induced by olfactory signal released by heterosexual conspecifics in a given group.

Host adaptation has the potential to cause rapid genetic variation in symbiotic microorganisms in insects. How mutations in symbiotic viruses favor viral fitness in hosts and even influence host adaptability to new environments remains elusive. Here, we explored the role of genetic divergence at one site of a symbiotic virus, Acyrthosiphon pisum virus (APV), in the host aphid’s adaptation to unfavorable plants. Based on the transcriptomes of the pea aphid Vicia faba colony and Vicia villosa colony, 46 single nucleotide polymorphism (SNP) sites were found in the APV genomes from the two aphid colonies. One SNP at site 5,990, G5990A, located at the RNA-dependent RNA polymerase (RdRp) domain, demonstrated a predominance from G to A when the host aphids were shifted from V. faba to the low-fitness plants V. villosa or Medicago sativa. This SNP resulted in a substitution from serine (S) to asparagine (N) at site 196 in RdRp. Although S196N was predicted to be located at a random coil far away from conserved functional motifs, the polymerase activity of the N196 type of RdRp was increased by 44.5% compared to that of the S196 type. The promoted enzymatic activity of RdRp was associated with a higher replication level of APV, which was beneficial for aphids as APV suppressed plant’s resistance reactions toward aphids. The findings showed a novel case in which mutations selected in a symbiotic virus may confer a favor on the host as the host adapts to new environmental conditions.

A low exploration success ratio on the Baochu Slope of Xihu Sag of East China Sea has been inferred, and the ratio in the Central Anticline Belt varies significantly in different sub structures. To solve this issue, the petroleum geologic conditions of the sag were systematically reviewed in light of new basin analysis methodologies, and new understanding have been achieved. Due to the differences in tectonic features and evolution histories, the Baochu Slope and Central Anticline Belt developed different petroleum systems and play types. Only those areas with overlapping favorable fairways of all petroleum system elements promise the formation of large oil and gas fields. The Baochu Slope is featured by tectonic rifting, with weak later compression and early structure formation. Its favorable conditions for hydrocarbon accumulation include: short distance to the main source kitchen; multiple, overlapping, large-scale reservoirs; multiple structural-stratigraphic trap types; good vertical sealing zones; and effective lattice pattern migration pathways. The large to medium structural-stratigraphic fields are concentrated in fairways with a large scale source kitchen and updip pinchout of tide-dominated delta sands controlled by paleo slope break which in turn were induced by either faulting or paleo morphology. The Central Anticline Belt has experienced strong inversion and compression during the late depression stage, and developed inverted compressional slip faults and large scale anticlines. Hydrocarbon accumulation is controlled by four major factors: preexisting structural highs before the compressional event, large scale structural-lithological traps, excellent timing of hydrocarbon charging during deformation, and highly effective reservoir-seal combinations. The areas with good congruence of these contro-lling factors promise the occurrence of large-scale deposits such Longjing, Guzhenzhu, Huxinting fields.

The simplification of simulation inevitably leads to model mismatch. In this paper, a once-through steam generator (OTSG) for a small lead bismuth fast reactor (SLBFR) is established and verified, and the OTSG model is simplified by three different methods. Based on the simplified OTSG model, IMC and IMC-PID controllers are designed to verify the sensitivity of the controller to model mismatch. The results show that the sensitivity of the controller to model mismatch is related to the filter parameters. With the increase in λ, the IMC-PID controller becomes insensitive to model mismatch caused by model linearization, non-minimum phase characteristics, noise and time delay. However, the adaptability to model mismatch sacrifices the sensitivity of the system. When λ is too large, the inertia of the controller is too large, resulting in the deterioration of the fast power regulation. Through the research of this paper, the time domain response approximation method is recommended for OTSG model simplification, and λ is recommended to be between 5 and 10 for feedwater IMC-PID controller.

Background: A low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet has been reported to be associated with improving the symptoms of irritable bowel syndrome (IBS); however, its efficacy as evaluated by different studies remains controversial.Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to explore the efficacy of a low-FODMAP diet (LFD) in alleviating the symptoms of IBS.Methods: A search of the literature for RCTs that assessed the efficacy of an LFD in treating IBS patients was conducted using the electronic databases PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. The searches in each database were conducted from the inception of the database to February 2021. Two independent reviewers screened citations and a third reviewer resolved disagreements. Two independent reviewers also performed eligibility assessments and data extraction. The RCTs that evaluated LFDs vs. a normal IBS or usual diet and assessed changes of IBS symptoms were included in the search. Data were synthesized as the relative risk of global symptoms improvement, mean difference of IBS Severity Scoring System (IBS-SSS) score, sub-items of IBS-SSS irritable bowel syndrome-related quality of life (IBS-QOL), hospital anxiety and depression scale (HADS), stool consistency/frequency, and body mass index (BMI) using a random effects model. The risk of bias was assessed using Risk of Bias Tool 2 (RoB 2). The bias of publication was assessed based on Egger's regression analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.Results: A total of 2,768 citations were identified. After full-text screening, a total of 10 studies were eligible for the systematic review and were subsequently used to compare an LFD with various control interventions in 511 participants. An LFD was associated with the improvement of global symptoms [n = 420; Risk Ratio (RR) = 1.54; 95% Confidence Interval (CI) 1.18 to 2; I2 = 38%], improvement of stool consistency [n = 434; Mean difference (MD) = −0.25; 95% CI −0.44 to −0.06; I2= 19%), and a reduction trend of stool frequency (n = 434; MD = −0.28; 95% CI −0.57 to 0.01; I2 = 68%) compared with control interventions. There was no statistically significant change in IBS-QOL (n = 484; MD = 2.77; 95% CI −2 to 7.55; I2 = 62%), anxiety score (n = 150; MD = −0.45; 95% CI −3.38 to 2.49; I2 = 86%), depression score (n = 150; MD = −0.05; 95% CI −2.5 to 2.4; I2 = 88%), and BMI (n = 110; MD = −0.22; 95% CI −1.89 to 1.45; I2 = 14%). The overall quality of the data was “moderate” for “global improvement of IBS symptom,” “stool consistency,” “stool consistency for IBS with diarrhea (IBS-D),” and “stool frequency for IBS-D,” and “low” or “very low” for other outcomes according to GRADE criteria.Conclusion: An LFD is effective in reducing the global symptoms and improving the bowel habits of adult IBS patients. The efficacy for IBS-D patients can also be more pronounced.Systematic Review Registration: CRD42021235843.

The building of cabin hospitals in Wuhan has been proven to be clinically successful in curing mild-symptom COVID-19 patients shortly after the outbreak of COVID-19 in late 2019. At the same time, the psychological effect of patients being treated in cabin hospitals and the features of the psychological status of the whole society remained ambiguous. This study adopted a self-administrated questionnaire to investigate the stress, depression, and anxiety status of patients in cabin hospitals (n = 212) and healthy participants outside of Hubei province (n = 221) in a population level from February 29 to March 01, 2020. The research measured participants’ stress response, depression level, and anxiety level as well as their social support system and their resilience level. Results indicated that in this sudden outbreak of an unknown pandemic, all people (whether or not infected) showed a generally high level of stress, depression, and anxiety, regardless of age, gender, education level, and employment. It also showed that people with a lower level of psychological resilience and social support reported more severe symptoms of depression, anxiety, and stress. Moreover, the research also found a positive effect of cabin hospitals on the psychological recovery of COVID-19 patients. Stress response of patients increased after entering into cabin hospitals, while after 3–4 weeks’ treatment, patients showed a decrease in their depression and anxiety levels. This research advances the understanding of COVID-19 and gives suggestions to optimize the design and the allocation of resources in cabin hospitals and better deal with the unknown pandemics in the future.

Background: The Coronavirus disease 2019 (COVID-19) pandemic has been a major threat to global health. Regional differences in epidemiological and clinical characteristics, treatment and outcomes of patients have not yet been investigated. This study was conducted to investigate these differences amongCOVID-19 patients in Hubei Province, China.Methods: This retrospective cross-sectional study analyzed data on 289 COVID-19 patients from designated hospitals in three regions:Urban (Wuhan Union West Hospital), Suburban areas of Wuhan (Hannan Hospital) and Enshi city, between February 8 and 20, 2020. The final date of follow-up was December 14th, 2020. The outcomes were case fatality rate and epidemiological and clinical data.Results: Urban Wuhan experienced a significantly higher case fatality rate (21.5%) than suburban Wuhan (5.23%) and rural area of Enshi (3.51%). Urban Wuhan had a higher proportion of patients on mechanical ventilation (24.05%) than suburban Wuhan (0%) and rural Enshi (3.57%). Treatment with glucocorticoids was equivalent in urban and suburban Wuhan (46.84 and 45.75%, respectively) and higher than Enshi (25.00%). Urban Wuhan had a higher proportion of patients with abnormal tests including liver function and serum electrolytes and a higher rate of pneumonia (p < 0.01 for all). Urban Wuhan also had a higher incidence of respiratory failure, heart disease, liver disease and shock, compared with the other two regions (all p < 0.05).Conclusions: Our findings revealed that there are regional differences in COVID-19. These findings provide novel insights into the distribution of appropriate resources for the prevention, control and treatment of COVID-19 for the global community.

Long-term flight depends heavily on intensive energy metabolism in animals; however, the neuroendocrine mechanisms underlying efficient substrate utilization remain elusive. Here, we report that the adipokinetic hormone/corazonin-related peptide (ACP) can facilitate muscle lipid utilization in a famous long-term migratory flighting species, Locusta migratoria. By peptidomic analysis and RNAi screening, we identified brain-derived ACP as a key flight-related neuropeptide. ACP gene expression increased notably upon sustained flight. CRISPR/Cas9-mediated knockout of ACP gene and ACP receptor gene (ACPR) significantly abated prolonged flight of locusts. Transcriptomic and metabolomic analyses further revealed that genes and metabolites involved in fatty acid transport and oxidation were notably downregulated in the flight muscle of ACP mutants. Finally, we demonstrated that a fatty-acid-binding protein (FABP) mediated the effects of ACP in regulating muscle lipid metabolism during long-term flight in locusts. Our results elucidated a previously undescribed neuroendocrine mechanism underlying efficient energy utilization associated with long-term flight.

ABSTRACT Phenotypic plasticity plays fundamental roles in successful adaptation of animals in response to environmental variations. Here, to reveal the transcriptome reprogramming in locust phase change, a typical phenotypic plasticity, we conducted a comprehensive analysis of multiple phase-related transcriptomic datasets of the migratory locust. We defined PhaseCore genes according to their contribution to phase differentiation by the adjustment for confounding principal components analysis algorithm (AC-PCA). Compared with other genes, PhaseCore genes predicted phase status with over 87.5% accuracy and displayed more unique gene attributes including the faster evolution rate, higher CpG content and higher specific expression level. Then, we identified 20 transcription factors (TFs) named PhaseCoreTF genes that are associated with the regulation of PhaseCore genes. Finally, we experimentally verified the regulatory roles of three representative TFs (Hr4, Hr46, and grh) in phase change by RNAi. Our findings revealed that core transcriptional signatures are involved in the global regulation of locust phase changes, suggesting a potential common mechanism underlying phenotypic plasticity in insects. The expression and network data are accessible in an online resource called LocustMine (http://www.locustmine.org:8080/locustmine).

Prepulse inhibition (PPI) is the reduction in the acoustic startle reflex (ASR) when the startling stimulus (pulse) is preceded by a weaker, non-starting stimulus. This can be enhanced by facilitating selective attention to the prepulse against a noise-masking background. On the other hand, the facilitation of selective attention to a target speech can release the target speech from masking, particularly from speech informational masking. It is not clear whether attentional regulation also affects PPI in this kind of auditory masking. This study used a speech syllable as the prepulse to examine whether the masker type and perceptual spatial attention can affect the PPI or the scalp EEG responses to the prepulse in healthy younger-adult humans, and whether the ERPs evoked by the prepulse can predict the PPI intensity of the ASR. The results showed that the speech masker produced a larger masking effect than the noise masker, and the perceptual spatial separation facilitated selective attention to the prepulse, enhancing both the N1 component of the prepulse syllable and the PPI of the ASR, particularly when the masker was speech. In addition, there was no significant correlation between the PPI and ERPs under any of the conditions, but the perceptual separation-induced PPI enhancement and ERP N1P2 peak-to-peak amplitude enhancement were correlated under the speech-masking condition. Thus, the attention-mediated PPI is useful for differentiating noise energetic masking and speech informational masking, and the perceptual separation-induced release of the prepulse from informational masking is more associated with attention-mediated early cortical unmasking processing than with energetic masking. However, the processes for the PPI of the ASR and the cortical responses to the prepulse are mediated by different neural mechanisms.

Animals often exhibit dramatically behavioral plasticity depending on their internal physiological state, yet little is known about the underlying molecular mechanisms. The migratory locust, Locusta migratoria, provides an excellent model for addressing these questions because of their famous phase polyphenism involving remarkably behavioral plasticity between gregarious and solitarious phases. Here, we report that a major insect hormone, juvenile hormone, is involved in the regulation of this behavioral plasticity related to phase change by influencing the expression levels of olfactory-related genes in the migratory locust. We found that the treatment of juvenile hormone analog, methoprene, can significantly shift the olfactory responses of gregarious nymphs from attraction to repulsion to the volatiles released by gregarious nymphs. In contrast, the repulsion behavior of solitarious nymphs significantly decreased when they were treated with precocene or injected with double-stranded RNA of JHAMT, a juvenile hormone acid O-methyltransferase. Further, JH receptor Met or JH-response gene Kr-h1 knockdown phenocopied the JH-deprivation effects on olfactory behavior. RNA-seq analysis identified 122 differentially expressed genes in antennae after methoprene application on gregarious nymphs. Interestingly, several olfactory-related genes were especially enriched, including takeout (TO) and chemosensory protein (CSP) which have key roles in behavioral phase change of locusts. Furthermore, methoprene application and Met or Kr-h1 knockdown resulted in simultaneous changes of both TO1 and CSP3 expression to reverse pattern, which mediated the transition between repulsion and attraction responses to gregarious volatiles. Our results suggest the regulatory roles of a pleiotropic hormone in locust behavioral plasticity through modulating gene expression in the peripheral olfactory system.

Metarhizium is a group of insect-pathogenic fungi that can produce insecticidal metabolites, such as destruxins. Interestingly, the acridid-specific fungus Metarhizium acridum (MAC) can kill locusts faster than the generalist fungus Metarhizium robertsii (MAA) even without destruxin. However, the underlying mechanisms of different pathogenesis between host-generalist and host-specialist fungi remain unknown. This study compared transcriptomes and metabolite profiles to analyze the difference in responsiveness of locusts to MAA and MAC infections. Results confirmed that the detoxification and tryptamine catabolic pathways were significantly enriched in locusts after MAC infection compared with MAA infection and that high levels of tryptamine could kill locusts. Furthermore, tryptamine was found to be capable of activating the aryl hydrocarbon receptor of locusts (LmAhR) to produce damaging effects by inducing reactive oxygen species production and immune suppression. Therefore, reducing LmAhR expression by RNAi or inhibitor (SR1) attenuates the lethal effects of tryptamine on locusts. In addition, MAA, not MAC, possessed the monoamine oxidase (Mao) genes in tryptamine catabolism. Hence, deleting MrMao-1 could increase the virulence of generalist MAA on locusts and other insects. Therefore, our study provides a rather feasible way to design novel mycoinsecticides by deleting a gene instead of introducing any exogenous gene or domain.

Early diagnosis and prevention play a crucial role in the treatment of patients with ARDS. The definition of ARDS requires an arterial blood gas to define the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio). However, many patients with ARDS do not have a blood gas measured, which may result in under-diagnosis of the condition. Using data from MIMIC-III Database, we propose an algorithm based on patient non-invasive physiological parameters to estimate P/F levels to aid in the diagnosis of ARDS disease. The machine learning algorithm was combined with the filter feature selection method to study the correlation of various noninvasive parameters from patients to identify the ARDS disease. Cross-validation techniques are used to verify the performance of algorithms for different feature subsets. XGBoost using the optimal feature subset had the best performance of ARDS identification with the sensitivity of 84.03%, the specificity of 87.75% and the AUC of 0.9128. For the four machine learning algorithms, reducing a certain number of features, AUC can still above 0.8. Compared to Rice Linear Model, this method has the advantages of high reliability and continually monitoring the development of patients with ARDS.

The research objective of this paper is to propose a new type of ERSD to solve the problem of the uncontrollable velocity of the claw in the current RSD. Firstly, the working characteristics of the RSD in ASIST are analyzed, and the design scheme of the transmission system of the ERSD is provided. The control system is designed by combining the vector control algorithm with the fuzzy adaptive PID control algorithm. On this basis, the trajectory planning of claw capture velocity is completed. Finally, the dynamics model of the transmission system of the ERSD is built by power bond graph theory, and the system simulation is carried out. The results show that the maximum capture time, velocity, and force were reduced by 47%, 53%, and 80%. In addition, when the ERSD is towing the helicopter, the mechanical claw can still provide good velocity tracking performance under a maximum interference load of 34,000 N.

The quantum Fisher information (QFI) represents a fundamental concept in quantum physics. It quantifies the metrological potential of quantum states in quantum parameter estimation measurements, and is intrinsically related to quantum geometry and multipartite entanglement of many-body systems. Using a nitrogen-vacancy center spin in diamond, we experimentally demonstrate a randomized-measurement method to extract the QFI of the qubit, for both pure and mixed states. We then apply this scheme to a 4-qubit state, using a superconducting quantum computer, and show that it provides access to the sub-QFI, which sets a lower bound on the QFI for general mixed states. We numerically study the scaling of statistical error, considering N-qubit states, to illustrate the advantage of our randomized-measurement approach in estimating the QFI and multipartite entanglement. Our results highlight the general applicability of our method to different quantum platforms, including solid-state spin systems, superconducting quantum computers, and trapped ions.

In the last several years, the coordination control of hybrid AC/DC microgrids (HMGs) has been gaining increasingly more attention. However, most of these discussions are focused on single-bus HMGs whose AC or DC bus is not sectionalized by AC or DC breakers. Compared with these single-bus HMGs, the bus-sectionalized HMG has more flexible topologies, more diverse operation modes, and consequently higher service reliability. However, meanwhile, these benefits also bring challenges to the stable operation of bus-sectionalized HMGs, particularly for mode switching. Relying on the national HMG demonstrative project in Shaoxing, China, this paper makes efforts to present the hierarchical control paradigm of a typical bus-sectionalized HMG toward standardization. The test results demonstrate that the proposed system provides seamless switching and uninterrupted power supply without controller reconfiguration among different operation modes. The operational data are also brought forth and analyzed to provide significant and useful experiences for designing and developing similar HMGs in the future.