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Hybrid-dimensional simulations can balance simulation accuracy and computational costs. However, applying hybrid-dimensional simulations to flight status remains challenging due to weak convergence. In this study, an adaptive integration method for hybrid-dimensional simulations was developed by introducing both adaptive incorporation schemes and polynomial transformations into the existing direct integration method. Experimental validations and T-MATS analysis show that errors in the thrust and specific fuel consumption of throttle characteristics are within 2% and 3%, respectively. Hybrid-dimensional simulations using both adaptive and existing direct integration methods were then applied to predict flight speed and altitude characteristics. Overall, the adaptive integration method demonstrates a broad convergence range for altitude (0-10 km) and speed (0-0.9 Ma) characteristics, requiring 25 iteration steps with co-working errors of less than 10−03. However, the direct integration method covers smaller ranges for altitude (0-1 km) and speed (0-0.4 Ma) characteristics, requiring 50 iteration steps with co-working errors of larger than 10−03. The results indicate that hybrid-dimensional simulations using the adaptive integration method exhibit good stability and convergence in the flight status compared to the direct integration method. Moreover, both the speed and altitude characteristics using the adaptive integration method cost approximately 24 hours on a computer workstation.

The lateral stability and control of carrier-based aircraft towbarless tractor system are analysed. Considering the coupled motion effects of carrier roll, pitch and heave, a four degree of freedom time-varying nonlinear dynamic model of the carrier-based aircraft towbarless tractor system is established. The lateral stability of the traction system is analysed, and the discrimination method of the system instability form is proposed. The yaw rate of the tractor and the lateral speed of the carrier-based aircraft are selected as variables, the lateral stability controller is designed using sliding mode control (SMC) theory and the compensation torque and lateral force required for the lateral stability control of the traction system are obtained, thereby achieving tracking of the ideal values. The simulation results show that the designed control scheme can effectively controls the yaw rate of the target tractor and the lateral speed of the carrier-based aircraft, ensuring the lateral stability of the carrier-based aircraft towbarless tractor system.

ABSTRACTThe gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10-/- mice, but not attenuated in Rag1-/- mice. Adoptive transfer of macrophage into Il10-/- mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45+IL-10+ cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target.

Abstract Background The Asian yellow pond turtle (Mauremys mutica) is an important commercial freshwater aquaculture species in China. This species is a highly sexually dimorphic species, with males growing at a faster rate than females and exhibits temperature-dependent sex determination (TSD), in which the incubation temperature during embryonic development determines the sexual fate. However, the mechanisms of the sex determination or sex differentiation in the Asian yellow pond turtle are remain a mystery. Results Temperature-specific gonadal transcriptomics of the Asian yellow pond turtle were performed during the thermosensitive period (stage 15) using RNA-seq technology to identify candidate genes that initiate gonadal differentiation. We uncovered candidates that were the first to respond to temperature. These candidates were sexually dimorphic in expression, reflecting differences in gonadal (Cirbp, Runx1) and germline differentiation (Vasa, Nanos1, Piwil2), gametogenesis (Hmgb3, Zar1, Ovoinhibitor-like, Kif4), steroid hormone biosynthesis (Hsd17b5, Hsd17b6), heat shock (Dnajb6, Hsp90b1, Hsp90aa1) and transient receptor potential channel genes (Trpm1, Trpm4, Trpm6, Trpv1). Conclusions Our work will provide important genetic information to elucidate the mechanisms of sex control in the Asian yellow pond turtles, and will contribute important genetic resources for further studies of temperature-dependent sex determination in turtles.

Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear. Herein, as an extension to our previous investigation, we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B (PKB))/glycogen synthase kinase 3β (GSK3β)/β-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/mitogen-activated protein (MAP) kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways, after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N-phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes. These data conclude that EB can target TYRs and alter their expression, activity, and stability, thus stimulating their pigmentation function, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

Summary: Background: Exclusive enteral nutrition (EEN) is an important alternative strategy for patients with Crohn’s disease (CD), and during this process, microbiota alterations have been observed. However, the underlying mechanisms by which EEN reduces intestinal inflammation are currently unclear. Methods: The therapeutic potential of enteral nutrition (EN) was assessed using various mouse models. Fecal full-length 16S rDNA sequencing analysis and several CD metagenome datasets were used to identify the candidate therapeutic bacteria Faecalibaculum rodentium (F. rodentium). Whole genome sequencing of F. rodentium and widely-targeted metabolome analysis of the supernatant showed that EN-induced F. rodentium accumulation protected against colitis via histidine biosynthesis. Findings: The therapeutic potential of EN therapy was observed in both dextran sulfate sodium (DSS)-induced colitis and Il10−/− spontaneous colitis mouse models. Accumulation of F. rodentium after EN therapy was determined using full-length 16S rDNA sequencing and verified with several metagenome datasets from patients with CD. Colonization of an isolated F. rodentium could reduce colitis in Il10−/− mice. Significant histidine enrichment was observed in the F. rodentium culture supernatant, and a series of histidine biosynthesis genes were observed in the F. rodentium genome. Engineered Escherichia coli Nissle 1917 (EcN), encoding the heterologous hisG of F. rodentium (EcN-hisG), which was a key driver of histidine biosynthesis in F. rodentium, was found to protect against colitis. Interpretation: This study suggests that EN-induced F. rodentium accumulation protects against colitis in mice via gut bacteria-mediated histidine biosynthesis. Funding: A full list of funding bodies can be found in the Acknowledgements section.

Resistant starch (RS) can help prevent diabetes and decrease calorie intake and that from plants are the main source of mankind consumption. Rice is many people’s staple food and that with higher RS will help health management. A significantly positive correlation exists between apparent amylose content (AAC) of rice and its RS content. In this study, 72 accessions with moderate or high AAC were selected to explore the regulatory mechanisms and physicochemical properties on different proceeding types of rice RS. RS in raw milled rice (RSm), hot cooked rice (RSc), and retrogradation rice (RSr) showed a wide variation and distinct controlling mechanisms. They were co-regulated by Waxy (Wx), soluble starch synthase (SS) IIb and SSI. Besides that, RSm was also regulated by SSIIa and SSIVb, RSc by granule-bound starch synthase (GBSS) II and RSr by GBSSII and Pullulanase (PUL). Moreover, Wx had significant interactions with SSIIa, SSI, SSIIb and SSIVb on RSm, but only the dominant interactions with SSIIb and SSI on RSc and RSr. Wx was the key factor for the formation of RS, especially the RSc and RSr. The genes had the highest expression at 17 days after flowering and were beneficial for RS formation. The longer the chain length of starch, the higher the RS3 content. RSc and RSr were likely to be contained in medium-size starch granules. The findings favor understanding the biosynthesis of different subtypes of RS.

The present study aims to examine the process through which empowering leadership shapes employees’ work engagement and in-role performance by facilitating job-crafting behaviors, specifically seeking resources, seeking challenges, and reducing demands. Based on the extensive data from 733 Chinese employees across various organizations located predominantly in Chongqing and Xi’an, China, we carried out different types of statistical analysis such as confirmatory factor analysis (CFA) and structural equation modeling (SEM) to examine the relationships among empowering leadership, specific job-crafting behaviors, work engagement and in-role performance, test our hypothesis and our conceptual model. The results from structural equation modeling (SEM) suggested that empowering leadership was positively related to employees’ work engagement and in-role performance; empowering leadership was positively related to employees’ job crafting (seeking resources, seeking challenges and reducing demands); seeking resources, seeking challenges and reducing demands were positively related to in-role performance, and seeking challenges and reducing demands were positively related to work engagement. In the relationship between empowering leadership and in-role performance, seeking resources serves as a mediating factor. Similarly, seeking challenges mediates the association between empowering leadership and both work engagement and in-role performance. Furthermore, reducing demands mediates the links between empowering leadership and both work engagement and in-role performance. The implications of these findings are subsequently discussed.

Abstract Satellite‐based precipitation estimations provide frequent, large‐scale measurements. Deep learning has recently shown significant potential for improving estimation accuracy. Most studies have employed a two‐stage framework, which is a sequential architecture of a rain/no‐rain binary classification task followed by a rain rate regression task. This study proposes a novel precipitation retrieval framework in which these two tasks are simultaneously trained using multi‐task learning approach (MTL). Furthermore, a novel network architecture and loss function were designed to reap the benefits of MTL. The proposed two‐task model successfully achieved a better performance than the conventional single‐task model possibly due to efficient knowledge transfer between tasks. Furthermore, the product intercomparison showed that our product outperformed existing products in rain rate retrieval and also yielded better skills in the rain/no‐rain retrieval task.

Intercrops can lower pest densities by increasing plant diversity, altering chemical communication in the arthropod community, and integrating well with other IPM tactics. We used two years of field observations and Y-tube olfactometer assays to explore the effects of intercropping a pear orchard with okra and castor bean on the cosmopolitan fruit-boring pest Grapholita molesta (Lepidoptera: Tortricidae). Intercropping okra reduced G. molesta trap catches in the pear orchard in both years, and intercropping with castor bean reduced them in the second year. Hydrocarbons, phenols, and ketones predominated in the GC-MS assay of okra volatiles, whereas castor bean volatiles were rich in aldehydes, ketones, and esters. Five of the commercially available volatiles released by these plants exhibited repellency to G. molesta in olfactometer trials, especially cinnamaldehyde, dibutyl phthalate, and thymol; the former compound also exhibited attraction to the egg parasitoid Trichogamma dendrolimi (Hymenoptera: Trichogrammatidae). In addition to their repellent properties, okra and castor bean may enhance integrated control of G. molesta in orchards by hosting prey that support populations of generalist predators that either provide biological pest control services within the orchard ecosystem or generate non-consumptive effects that contribute to pest deterence. Among the plant volatiles evaluated, cinnamaldehyde has the best potential for deployment in orchards to repel G. molesta without disrupting augmentative releases of T. dendrolimi.

Thermally activated delayed fluorescence (TADF) molecules have a theoretical 100% photoluminescence quantum yield in comparison with traditional fluorescent materials, leading to broad application in organic light-emitting diode (OLED). However, the application of TADF molecules with conjugated donor-acceptor structures in blue OLED remains a challenge due to their generally narrow energy gap between frontier molecular orbitals. Recently, a strategy has been approved in the improvement of the performance in TADF, in which void-carbon atoms between donor and acceptor fragments (donor-void-acceptor (D-v-A)) could regulate blue light emission. In this study, we first select three reported isomers followed by two proposed D-v-A TADF isomers to verify the feasibility of the void-carbon strategy through evaluation of the electronic structures in the excited state and photophysical properties. We further proposed a series of TADF molecules by replacing different donor and acceptor fragments to assess the applicability of the void-carbon strategy from the aspect of simulations in electronic structures, different properties of donor and acceptor fragments, photophysical properties, and analysis in the molecular conjugation. The results indicate that void-carbon strategy has conditional feasibility and applicability. Donor-acceptor molecular properties could be tuned through void-carbon strategy on aromatic acceptor fragments during the selection of promising candidates of TADF molecules. However, the void-carbon strategy does not work for the molecules with antiaromatic acceptor fragments, where the steric hindrance of the molecules plays a dominant role. Our work provides insightful guidance for the design of the blue-emission TADF molecules.

Background: Persistent pathological cardiac hypertrophy has been associated with increased risk of heart failure and even sudden death. Multiple Chinese patent medicines (CPMs) have gained attention as alternative and complementary remedies due to their high efficiency and few side effects. However, the effects of CPM-related treatment regimens for cardiac hypertrophy had not been systematically evaluated.Aim: The objective of this study was to estimate and compare the effectiveness of different mechanisms of CPMs to improve clinical outcomes, including clinical efficacy and echocardiographic indices, in the treatment of cardiac hypertrophy patents.Methods: A network meta-analysis was conducted on CPM-related randomized controlled trials (RCTs) published between 2012 and 2022 involving cardiac hypertrophy patients from four foreign and four Chinese databases. The outcomes concerned efficacy and related indicators, including echocardiographic indices, cardiac biomarkers, and functional exercise capacity, which were evaluated as odds ratios, mean differences, and 95% credible intervals. Network plots, league tables, surface-under-the-cumulative ranking (SUCRA), and funnel plots were created for each outcome, and all analyses were conducted using Stata 16.0 software.Results: A total of 25 RCTs were evaluated; these involved 2395 patients in a network meta-analysis (NMA). The results from existing evidence indicate that blood-activating and stasis-removing Chinese patent medicine (BASR-CPM) + Western medicine (WM) showed a good improvement in clinical efficacy (OR = 8.27; 95%CI = 0.97, 70.73). A combined treatment regimen of CPM with a function of qi-replenishing, blood-activating and stasis-removing, and Western medicine was an effective treatment regimen for echocardiographic indices such as decreasing left ventricular end-systolic dimension (LVESD) (SMD = −2.35; 95%CI = −3.09, −1.62) and left ventricular mass index (LVMI) (SMD = −1.73; 95%CI = −2.92, −0.54). Furthermore, KWYR-CPM + WM and BASR-CPM also showed good improvement for echocardiographic indices of LVEDD (SMD = −1.84; 95%CI = −3.46, −0.22) and left ventricular ejection fraction (SMD = 1.90; 95%CI = −0.46, −3.35), respectively.Conclusion: The study showed that BASR-CPM + WM may be the potentially superior treatment regimen for improving clinical efficacy among cardiac hypertrophy patients. QR&BASR-CPM + WM might be the optimal treatment for decreasing LVESD and LVMI. However, due to potential risks from bias and limited RCTs, further studies with larger samples and high-quality RCTs are needed to support these findings.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329589],identifier [CRD42022329589].

Hibernation in turtle species is an adaptive survival strategy to colder winter conditions or food restrictions. However, the mechanisms underlying seasonal adaptions remain unclear. In the present study, we collected hemocytes from Pelochelys cantorii and compared the molecular signature of these cells between the active state and hibernation period based on single-cell RNA sequencing (scRNA-seq) analysis. We found six cell types and identified a list of new marker genes for each cell subpopulation. Moreover, several heat shock genes, including the Hsp40 family chaperone gene (DNAJ) and HSP temperature-responsive genes (HSPs), were upregulated during the hibernation period, which predicted these genes may play crucial roles in the stress response during hibernation. Additionally, compared to hemocytes in the active state, several upregulated differentially expressed immune-related genes, such as stat1, traf3, and socs6, were identified in hemocytes during the hibernation period, thus indicating the important immune function of hemocytes. Therefore, our findings provide a unified classification of P. cantorii hemocytes and identify the genes related to the stress response, thereby providing a better understanding of the adaptive mechanisms of hibernation.

Since 2019, coronavirus disease 2019 (COVID-19) has swept the world and become a new virus threatening the health of all mankind. The survey found that prostate cancer accounts for one in three male cancer patients infected with COVID-19. This undoubtedly makes prostate cancer patients face a more difficult situation. Prostate cancer is the second most harmful malignant tumor in men because of its insidious onset, easy metastasis, and easy development into castration-resistant prostate cancer even after treatment. Due to its high immunogenicity and a small number of specific infiltrating T cells with tumor-associated antigens in the tissue, it is difficult to obtain a good therapeutic effect with immune checkpoint blocking therapy alone. Therefore, in the current study, we developed a platform carrying Doxorubicin (DOX)-loaded black phosphate nanometer combined with photothermal therapy (PTT) and found this drug combination stimulated the immungentic cell death (ICD) process in PC-3 cells and DC maturation. More importantly, zinc ions have a good immunomodulatory function against infectious diseases, and can improve the killing ability of the nanosystem against prostate cancer cells. The introduction of Aptamer (Apt) enhances the targeting of the entire nanomedicine. We hope that this excellent combination will lead to effective treatment strategies for prostate cancer patients infected with COVID-19.

As part of the United Arab Emirates’ and the world’s aviation goal of reaching net-zero greenhouse gas emissions by 2050, this paper studied the potential of successfully implementing both biofuel “drop-in” alternatives and aerodynamically efficient configurations to decarbonize the aviation industry. By investigating various proposed designs through a PUGH analysis, it was concluded that the optimum design has a Transonic Truss-Braced Wing configuration and runs on 60% biofuel. Although the design stipulates a 1.3% increase in weight, this does not negate the reduction in emissions and fuel consumption. This study also explored the various types of biofuels and found camelina seeds to be the best choice. The effects of biofuels in comparison with Jet-A fuel were further deliberated in a fuel combustion simulation performed on the Ansys-Fluent software. The results of the simulation showed a reduction of 50% in carbon monoxide (CO) and 24% in carbon dioxide (CO2) emissions when burning camelina biofuel rather than Jet-A, making it an ideal alternative to those conventional jet fuels. A primary cost analysis of biofuel applications showed an increase of 453 USD (1653.18 AED) per passenger flying on board 100%-biofuel-powered aircrafts. Yet, considering the trend of the cost increase with the biofuel blend ratio, a solution may exist to the increased cost of biofuel-powered aircrafts.

Gonadal cell lines possess the abilities of self-renewal and differentiation, being used as an efficient tool to analyzing the genes’ functions involved in sex differentiation and gametogenesis. Although some significant achievements have been obtained in the gonadal cells’ culture or manipulation across multiple phyla including teleost and mammals, there is limited study on gonadal cell manipulation in turtles. In this study, we established a new ovarian cell line from the young Asian yellow pond turtle (Mauremys mutica), which exhibited a normal diploid karyotype with high alkaline phosphatase activity. The cell line, designated as YTO2, was then characterized through the analysis of gene expression profiles. The transcriptome analysis and the reverse transcription polymerase chain reaction (RT-PCR) showed that the cells expressed germline genes such as tdrd7, nanos1, klf5, igtb1, hsd17b4 and rad51. Moreover, the immunostaining showed that the germ cell markers, Tdrd7 and Rad51 proteins, were detected predominant in cytoplasm of perinuclear region, while proliferation marker, PCNA, was dominantly observed in the nuclei of cultured cells. Intriguingly, the cells could respond to the retinoic acid induction with significantly increasing the expression level of some meiosis genes, including vasa, dazl, figla, and dmc1. Furthermore, YTO2 cells could be efficiently transfected with the pHBAd-BHG-EGFP adenovirus and properly expressed the exogenous genes. To sum up, an ovarian cell line of the Asian yellow pond turtle had been established and could be stably propagated under in vitro culture condition, as well as being capable of efficiently expressing the exogenous gene tdrd7. This cell line would provide a valuable tool to elaborate the molecular mechanisms behind germ cells development, differentiation and oogenesis in the turtle, even in reptiles.

This study sheds light on the exploration of photoresponsive host-guest systems, highlighting the intricate interplay between confined spaces and photosensitive guest molecules. Conducting nonadiabatic molecular dynamics (NAMD) simulations based on electronic structure calculations for such large systems remains a formidable challenge. By leveraging machine learning (ML) as an accelerator for NAMD simulations, we analytically constructed excited-state potential energy surfaces along relevant collective variables to investigate photoisomerization processes efficiently. Combining the quantum mechanics/molecular mechanics (QM/MM) methodology with ML-based NAMD simulations, we elucidated the reaction pathways and identified the key degrees of freedom as reaction coordinates leading to conical intersections. A machine learning-based nonadiabatic dynamics model has been developed to compare the excited-state dynamics of the guest molecule, benzopyran, in both the gas phase and its behavior within the confined space of cucurbit[5]uril. This comparative analysis was designed to determine the influence of the environment on the photoisomerization rate of the guest molecule. The results underscore the effectiveness of ML models in simulating trajectory evolution in a cost-effective manner. This research offers a practical approach to accelerate NAMD simulations in large-scale systems of photochemical reactions, with potential applications in other host-guest complex systems. [ABSTRACT FROM AUTHOR]