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The medical field is facing a physician-scientist shortage, threatening future medical research and development. Medical institutions can contribute to developing physician-scientists by stimulating students' involvement in research. In this study, a medical undergraduate teaching module to develop research skills and encourage interest in research was held in Chongqing, China. Undergraduate medical students at Chongqing Medical University completed research skills training. Before and after the training, an online, anonymous, self-reported questionnaire was administered. The self-reported questionnaire investigated students' demographic characteristics, students' perception of attitudes toward conducting research, research skills (e.g., identifying and utilizing information, critical appraisal of literature, paper writing, and understanding of research), and feedback on scientific research training. The module was implemented with 25 students from July 2019 to October 2019, and 96.0% (N = 24) of participants responded to the questionnaire both prior to and after the training. In the evaluation of research skills, results showed that use of appropriate tools for research (Z = -3.340, p < 0.01), students' ability to undertake a focused literature search (Z = -3.40, p < 0.01), identifying and utilizing information (Z = -3.34, p < 0.01), and paper-writing skills (Z = -3.49, p < 0.01) were significantly improved after the undergraduates participated in the scientific research training. A qualitative analysis of the feedback showed that students found that the training helped to enhance their knowledge, improve their study scores, and motivate them to conduct research in the future. Early scientific research ability training strengthened the research skills of medical undergraduates and motivated them to pursue research.

Coal energy has made a significant contribution to the development of human industrialization, but coal energy is faced with the major problem of high carbon emissions. Modern coal-based energy is a new path to crack the contradiction between coal energy and carbon. It can realize independent and controllable energy based on China’s resource endowment, enhance the autonomy of China’s oil and gas, support the clean transformation of electricity and the development of the renewable energy industry, and is an important innovative direction for guaranteeing energy security and realizing the dual-carbon goal. Based on the concept and technical system of modern coal-based energy, this paper systematically introduces the connotation and product lineage of modern coal-based energy. By analyzing and discussing the five core technology modules, 19 technical units and 61 key technologies of modern coal-based energy, including the new technologies such as coal-based gas, coal-based oil, coal-based hydrogen, coal-based electricity production, and dynamic carbon neutrality in mining area, ten revolutionary technologies for the development of low carbonization coal-based energy are proposed: ① Intelligent underground coal gasification technology based on self-moving plasma gasification machine which has the functions of automatic combustion, propulsion, sealing, monitoring and controlling; ② The coupling of underground coal gasification and indirect liquefaction can form a low-cost, low-emission, short-process coal-to-oil route (UCG-ICL); ③ In situ retorting chemical mining technology of oil-rich coal using solar heating or hot dry rock heating;④ In the deep coal underground gasification hydrogen production path (UCG-H2) based on in-situ carbon capture, utilization and storage (CCUS), recycled CO2 is used as a gasification agent to improve the production of effective components of coal gas, and captured CO2 is stored in the underground gasification cavity to form a zero-emission UCG-H2 technical route. ⑤ nanometer hydrogen-rich coal water slurry hydrogen-mixed power generation technology to achieve low-carbon coal-based power production at low temperature and low pressure, and significantly reduce carbon dioxide emissions of coal power; ⑥ The Low carbon power generation system concept of underground coal gasification coupled with IGCC (UCG+IGCC) reduces the coal-to-gas process of IGCC and significantly reduces CO2 emissions. ⑦ Pulverized coal deflagration linear drive power generation technology structure, the theoretical work energy is more than 15 times of coal combustion; ⑧ Based on the CO2 hydrogenation synthesis “green methanol” route of modern coal-based energy recycling, methanol is synthesized from coal-based “blue hydrogen” produced by low-carbon UCG and captured CO2; ⑨ The CO2 in situ storage technology system generated by modern coal-based energy can help achieve zero-carbon coal-based energy production; ⑩ Dynamic carbon neutral coal-based energy system architecture in mining area, coupling intelligent supply protection, green development, clean transformation, low-carbon utilization and clean emission in a closed-loop system in mining area to achieve dynamic carbon neutrality in mining area.

Abstract Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.

Acute myeloid leukemia (AML) is a malignant tumor of the hematological system. Because of its characteristics of recurrence, refractory and chemoresistance, new therapeutic targets need to be identified. Adhesion and proliferation are characteristics of AML cells, and critical steps in inducing chemotherapy resistance. In this study, we reported that UNC5B inhibits AML cell bone marrow adhesion, inhibits AML cell proliferation and increases sensitivity to chemotherapy. Mechanistically, RNA sequencing (RNA-seq) and experimental results revealed that overexpression of UNC5B inhibits adhesion and proliferation signaling pathways and inhibits the expression of MPZL1, CLDN23, IGF2 and WNT7B. In conclusion, our findings suggest that UNC5B serves as a prognostic indicator and a potential therapeutic target for AML.

Liquid nitrogen has emerged as a promising fracturing medium for unconventional natural gas extraction, particularly in the context of coalbed methane extraction, generating significant interest in recent times. In this paper, we analyze the acoustic emission (AE) characteristics of coal samples treated with liquid nitrogen under three-point bending load conditions using indoor experiments and field investigations. We investigate the impact of liquid nitrogen on coal samples by analyzing AE data. The mechanical properties of coal samples with varying initial temperatures were tested under three-point bending load conditions after treatment with liquid nitrogen. The load-displacement curve was analyzed to study the mechanical properties of the coal samples after treatment with liquid nitrogen. Through indoor three-point bending experiments, data analysis, and knowledge of mechanics, we systematically investigated the changes in mechanical properties caused by liquid nitrogen treatment under different conditions. The results demonstrate that the application of liquid nitrogen has significant impacts on the mechanical and AE characteristics of coal samples. The load-displacement curve indicated that the mechanical properties of the coal samples changed after treatment with liquid nitrogen. The AE experiment revealed regular changes in vibration and energy parameters of coal samples after liquid nitrogen treatment under different conditions. We further investigated the changes in mechanical properties and deformation characteristics of coal samples after undergoing liquid nitrogen freezing and thawing in differing environments. Graphs such as load-displacement curves, load-time curves, cumulative vibration count-energy count graphs, and RA-AF density distribution diagrams visually demonstrated the changes in mechanical properties and deformation characteristics. Through an integrated approach of indoor experiments, data analysis, and knowledge of mechanics, our study provides a better understanding of the behavior of coal samples under different conditions. This understanding can contribute to the development of safer and more efficient methods for extracting coalbed methane.

Abstract Fuel cell technology is a promising alternative to traditional internal combustion engines in various applications, especially in transportation applications. However, the high cost and limited lifetime of fuel cells have hindered their widespread commercialization. Accurately predicting fuel cell lifetime is crucial for reducing the cost of ownership, ensuring safety, and promoting the adoption of this technology. The objective of the present work is to develop a tool that is able to estimate the lifespan of a proton exchange membrane fuel cell and to predict its behavior to anticipate failures. Therefore, this paper contributes to proposing a multi‐input time‐series prediction network based on an echo state network, which takes the future current into consideration. A degradation trend extraction method is proposed in this paper and the remaining useful life of the fuel cell is predicted. Results have shown that the proposed methods in both short‐term and long‐term prediction have achieved satisfying prediction accuracy.

Rock burst is a major disaster in deep mining, where bursting liability is an important indicator of rock burst risk. This study therefore intends to explore the impact of microwave thermal shock on rocks with strong bursting liability by testing the microwave thermal shock and uniaxial compression of typical hard brittle sandstone and analyzing their physical and mechanical properties and the response of bursting liability indicators after microwave thermal shock. The research results show that: (1) After microwaving, the surface temperature of the sandstone continues to rise with the increase of thermal shock time, until it breaks at 150 s; (2) Microwave thermal shock has a significant effect on the structural damage of sandstone. After 120 s of microwaving, the longitudinal wave velocity and elastic modulus decrease by 15.12 % and 8 % respectively. The AE signal density increases at each stage of uniaxial compression, and the maximum absolute energy at the final destruction of sandstone decreases by 42.3 %; The dynamic failure time of rock increases by 259 %, the impact energy index decreases by 95 %, and the elastic energy index decreases by 92 %. This research offer references for efficient rock breaking in deep earth engineering and prevention and control of rock burst in resource mining.

Coal has made important contributions to the industrialization process of human society, and has played a key supporting role in ensuring China’s energy security and stable economic development. Since the mid-19th century, the coal-based fuel of coal, kerosene, gas and coal electricity has gradually entered the era of large-scale use. However, the traditional use of coal produces high carbon emissions, which has become a major problem in energy transition. Facing the development of ecological civilization society, the clean and efficient use of coal is imminent, and the innovation of modern coal-based energy technology is imperative. This paper proposes the definition and connotation of modern coal-based energy technology system, which is defined as the production of low-carbon energy products such as coal-based gas, coal-based oil, coal-based hydrogen and coal-based electricity, and the in-situ absorption of carbon dioxide in mining areas to form a clean and low-carbon energy production system with carbon neutrality. Its technical connotation includes coal-based gas, coal-based oil, coal-based hydrogen, coal-based electricity and dynamic carbon neutrality in mining areas, with a total of 5 technical modules, 19 technical units and 61 key technologies. The modern coal-based energy technology system will play an important role of “one main body, three supports and one breakthrough” in the future new energy system. Coal-based electricity provides the main body of electricity system stability. Coal-based oil supports the China’s oil safety. Coal-based gas supports the China’s gas safety. Coal-based hydrogen plays a supporting role in the development of hydrogen energy in China. The major breakthrough is the dynamic carbon neutral technology of coal-based energy. The paper supposes that when the ratio of non-fossil energy and low-carbon coal-based energy is maintained in the range of 2.5−3.0, coal-based energy, oil and gas and wind, water, nuclear energy can be reasonably integrated to form a new quality energy system with strong complementarity, high reliability and low carbon emissions. Based on the major breakthrough and practical application of modern coal-based energy technology, it is predicted that China’s low-carbon coal-based energy production will reach 1.02 billion −1.46 billion tons of standard coal equivalent (tce) in 2060, equivalent to 18%−24% of the national energy demand, and carbon dioxide emissions will be controlled below 500 million tons. Compared with the current energy transformation planning path based on “de coal” planning, the share of coal in our energy system can increase from 10% to more than 20%, and carbon dioxide emissions will reduce by 50%. At that time, the modern coal-based energy system has great technological innovation significance for China’s energy security and carbon dioxide emission reduction, and helps China to become a country with independent energy supply.

Abstract Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.

BackgroundVariation in facial shape may arise from the combinatorial or overlapping actions of paralogous genes. Given its many members, and overlapping expression and functions, the EPH receptor family is a compelling candidate source of craniofacial morphological variation. We performed a detailed morphometric analysis of an allelic series of E14.5 Ephb1-3 receptor mutants to determine the effect of each paralogous receptor gene on craniofacial morphology.ResultsWe found that Ephb1, Ephb2, and Ephb3 genotypes significantly influenced facial shape, but Ephb1 effects were weaker than Ephb2 and Ephb3 effects. Ephb2-/- and Ephb3-/- mutations affected similar aspects of facial morphology, but Ephb3-/- mutants had additional facial shape effects. Craniofacial differences across the allelic series were largely consistent with predicted additive genetic effects. However, we identified a potentially important nonadditive effect where Ephb1 mutants displayed different morphologies depending on the combination of other Ephb paralogs present, where Ephb1+/- , Ephb1-/- , and Ephb1-/- ; Ephb3-/- mutants exhibited a consistent deviation from their predicted facial shapes.ConclusionsThis study provides a detailed assessment of the effects of Ephb receptor gene paralogs on E14.5 mouse facial morphology and demonstrates how the loss of specific receptors contributes to facial dysmorphology.

Medical research is important to scientific progress and medical education. Institutions worldwide have sought to increase student involvement in research such as clinician-scientists training programs, while little is known about how medical undergraduates perceive research. A cross-sectional study was conducted in Chongqing Medical University, Chongqing, China, with first--fourth year undergraduates. An online, anonymous, and self-rating 5-point Likert questionnaire was conducted to investigate medical undergraduates' demographic characteristics and assess motivation, self-efficacy, perception, curiosity, and barriers regarding medical research. Content validity was checked with experts and face validity was checked for clarity and understanding of the questionnaire. The Cronbach's alpha coefficient of the questions ranged from 0.813 to 0.879. A total of 3273 medical undergraduates were surveyed, and 86.62% (2835) participants (male 962, female 1873) were identified as effective. Males scored higher than females on self-efficacy (p < 0.001), perception (p = 0.017), and curiosity (p < 0.001), and lower on barriers (p < 0.001). The second year students are at the peak of their perception (p = 0.006) and lowest barrier scores (p = 0.003). Students with scientific research experience scored higher in motivation (p = 0.002), self-efficacy (p < 0.001), perception (p < 0.001), and curiosity (p < 0.001). Lack of proper mentoring opportunity (86.2%) and knowledge (84.5%) were the main barriers in conducting research. Even though they have a positive perspective, only a few undergraduates enrolled in research. Medical universities should encourage faculties to supervise and guide undergraduates' projects, and provide feasible solutions for students to learn scientific knowledge and skills. It is vital to build a research-oriented environment and academic atmosphere.

Abstract DNA origami nanodevices achieve programmable structure and tunable mechanical and dynamic properties by leveraging the sequence‐specific interactions of nucleic acids. Previous advances have also established DNA origami as a useful building block to make well‐defined micron‐scale structures through hierarchical self‐assembly, but these efforts have largely leveraged the structural features of DNA origami. The tunable dynamic and mechanical properties also provide an opportunity to make assemblies with adaptive structures and properties. Here the integration of DNA origami hinge nanodevices and coiled‐coil peptides are reported into hybrid reconfigurable assemblies. With the same dynamic device and peptide interaction, it is made multiple higher‐order assemblies (i.e., polymorphic assembly) by organizing clusters of peptides into patches or arranging single peptides into patterns on the surfaces of DNA origami to control the relative orientation of devices. The coiled‐coil interactions are used to construct circular and linear assemblies whose structure and mechanical properties can be modulated with DNA‐based reconfiguration. Reconfiguration of linear assemblies leads to micron scale motions and ≈2.5‐10‐fold increase in bending stiffness. The results provide a foundation for stimulus‐responsive hybrid assemblies that can adapt their structure and properties in response to nucleic acid, peptide, protein, or other triggers.

Background S100a8/9 (S100 calcium binding protein a8/9) belongs to the S100 family and has gained a lot of interest as a critical regulator of inflammatory response. Our previous study found that S100a8/9 homolog promoted aortic valve sclerosis in mice with chronic kidney disease. However, the role of S100a8/9 in pressure overload‐induced cardiac hypertrophy remains unclear. The present study was to explore the role of S100a8/9 in cardiac hypertrophy. Methods and Results Cardiomyocyte‐specific S100a9 loss or gain of function was achieved using an adeno‐associated virus system, and the model of cardiac hypertrophy was established by aortic banding‐induced pressure overload. The results indicate that S100a8/9 expression was increased in response to pressure overload. S100a9 deficiency alleviated pressure overload‐induced hypertrophic response, whereas S100a9 overexpression accelerated cardiac hypertrophy. S100a9‐overexpressed mice showed increased FGF23 (fibroblast growth factor 23) expression in the hearts after exposure to pressure overload, which activated calcineurin/NFAT (nuclear factor of activated T cells) signaling in cardiac myocytes and thus promoted hypertrophic response. A specific antibody that blocks FGFR4 (FGF receptor 4) largely abolished the prohypertrophic response of S100a9 in mice. Conclusions In conclusion, S100a8/9 promoted the development of cardiac hypertrophy in mice. Targeting S100a8/9 may be a promising therapeutic approach to treat cardiac hypertrophy.

The hybrid power system with dual motors and multiple clutches experiences significant torque fluctuation during mode switching process due to the different torque response characteristics of the motor and engine. To address this issue, this paper focuses on the estimation of clutch friction torque and the development of dynamic coordinated control strategies for the components. Firstly, based on the dynamic model of the novel dual-motor hybrid electric vehicle, a torque observer based on the Kalman filter algorithm is developed to predict the friction torque generated in the clutch sliding friction stage. Secondly, the control strategies are developed for the mode switching process from single-motor to dual-motor and from dual-motor to parallel drive on a co-simulation platform. Thirdly, a power level Hardware-In-the-Loop test platform is built, and the performance of the designed control strategies is verified by the HIL platform. The results show that for the mode switching process from dual-motor to parallel drive, compared with the control strategy using the engine target speed, the control strategy based on engine idle speed proposed in this paper reduces the clutch sliding friction work and the maximum longitudinal jerk of the vehicle by 42.5% and 25.4%, respectively.

Abstract Background Adolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well. Methods We developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children’s Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. Discussion The results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD. Trial registration This protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

Lanthanide (Ln) elements are generally found in the oxidation state +II or +III, and a few examples of +IV and +V compounds have also been reported. In contrast, monovalent Ln(+I) complexes remain scarce. Here we combine photoelectron spectroscopy and theoretical calculations to study Ln-doped octa-boron clusters (LnB8-, Ln = La, Pr, Tb, Tm, Yb) with the rare +I oxidation state. The global minimum of the LnB8- species changes from Cs to C7v symmetry accompanied by an oxidation-state change from +III to +I from the early to late lanthanides. All the C7v-LnB8- clusters can be viewed as a monovalent Ln(I) coordinated by a η8-B82- doubly aromatic ligand. The B73-, B82-, and B9- series of aromatic boron clusters are analogous to the classical aromatic hydrocarbon molecules, C5H5-, C6H6, and C7H7+, respectively, with similar trends of size and charge state and they are named collectively as "borozenes". Lanthanides with variable oxidation states and magnetic properties may be formed with different borozenes.