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ABSTRACTManufacturing, an industry set in the physical world, is undergoing its digital transformation, also known as the fourth industrial revolution. Sensors, connectivity, and platforms provide unprecedented access to quantify the quality and diversity of manufacturing data. Progress in data-driven modeling is exponential across all industries. This leads to the question of how physics-based and data-driven modeling can be utilized in a hybrid modeling approach to advance our understanding of processes, materials, and systems in manufacturing. In this review, we focus on discrete manufacturing based on the understanding that hybrid modeling is more mature in process manufacturing. This paper aims to provide an overview of projects where hybrid modeling was used in manufacturing and introduce various ways of composing hybrid models. We provide examples highlighting the implementation of models, structure and expand on metrics to test and validate hybrid models, discuss challenges, and future research directions of hybrid modeling in manufacturing.

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application has introduced new challenges, such as safety concerns, off-target toxicities, and significant costs. Natural killer (NK) cells are crucial components of the innate immune system, capable of eliminating tumor cells without prior exposure to specific antigens or pre-activation. This inherent advantage complements the limitations of T cells, making CAR-NK cell therapy a promising avenue for hematological tumor immunotherapy. In recent years, preclinical and clinical studies have yielded preliminary evidence supporting the safety and efficacy of CAR-NK cell therapy in hematological malignancies, paving the way for future advancements in immunotherapy. This review aims to succinctly discuss the characteristics, significant therapeutic progress, and potential challenges associated with CAR-NK cell therapy.

Abstract Atomically precise metal nanoclusters are increasingly exploited in electrocatalysis such as water electrolysis and CO2 reduction. The catalytic effects are generally evaluated by conventional electrochemical methods or end‐product analysis. Herein, near infrared electrochemiluminescence (ECL) of the nanoclusters is introduced as a new signaling mechanism to complement classical voltammetric analysis for elucidating essential electrocatalytic parameters. Coreactant ECL from an aqueous soluble Au22 nanocluster (NCs) enhanced by a common pH buffer materials 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (HEPES) and by a piperazine drug hydroxyzine (HDZ) is studied under oxidative reduction pathways. Foot of the wave analysis on voltametric features and the kinetics profiles in potential‐step experiments are studied in different nanocluster and coreactant concentrations. Benchmark parameters such as rate constants are determined under EC (Electron‐transfer‐Chemical‐reaction) mechanism as feasibility validations. Because the luminescence properties of AuNCs are sensitive to the surface ligands or adsorbents, ECL is proposed as a new signal readout for operando studies providing insights for governing reaction mechanism and kinetics during catalytic reactions. Retrospectively, mechanistic understanding of the complex multi‐step reactions during ECL generation can provide guidance for the evaluation and optimization of ECL property for better quantitative applications.

Abstract E217 is a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. Here, we describe the structure of the whole E217 virion before and after DNA ejection at 3.1 Å and 4.5 Å resolution, respectively, determined using cryogenic electron microscopy (cryo-EM). We identify and build de novo structures for 19 unique E217 gene products, resolve the tail genome-ejection machine in both extended and contracted states, and decipher the complete architecture of the baseplate formed by 66 polypeptide chains. We also determine that E217 recognizes the host O-antigen as a receptor, and we resolve the N-terminal portion of the O-antigen-binding tail fiber. We propose that E217 design principles presented in this paper are conserved across PB1-like Myoviridae phages of the Pbunavirus genus that encode a ~1.4 MDa baseplate, dramatically smaller than the coliphage T4.

Objective: The aim of this study was to compare the variances in-game loads exhibited by Chinese women’s 3 × 3 basketball team across different stages of the preparation cycle for the Tokyo Olympic Games, and to summarize the fundamental regulations governing Chinese women’s 3 × 3 basketball training and games, in order to establish a theoretical research foundation for the team’s new preparation cycle.Methods: This study measured load-related data during the preparation and main competition periods of the 2019–2021 Tokyo Olympics, from April to August 2019 and from April to June 2021. The aim was to compare the changes and differences in a load of competition during different stages and to explore patterns of load changes during the preparation period. This study used wearable devices authorized by FIFA and NBA, along with the Catapult GPS performance monitoring system from Australia (Catapult&Polar Team) as instruments for collecting sports load data. The OptimEye S5 device was worn around the athlete’s neck to collect data prior to the game, while the Open Field™ system was utilized for data editing and report generation post-game.Results: Compared to the primary competition load during the 2019 preparation period, the 2021 preparation period exhibited significant increases and decreases (p < 0.05) in competition load, high-intensity load, the number of explosive moves, the number of high-intensity acceleration, several changes to the left and right, and the number of explosive jumps. During the 2021 preparation period, the mean heart rate, mean heart rate percentage, and mean speed of the race demonstrated significant decreases in comparison to the race during the 2019 preparation period (p < 0.05). Throughout the training period spanning from 2019 to 2021, no significant differences were observed in running distance and maximum speed (p > 0.05).Conclusion: The findings of this study reveal that the national training team has fostered positive adaptive changes in athletes, resulting in a significant enhancement in both load and sports performance science data during competition from 2019 to 2021.

Objective: The purpose of this study was to employ metabolomics for the analysis of urine metabolites in swimmers, with the aim of establishing models for assessing their athletic status and competitive potential. Furthermore, the study sought to compare the identification efficacy of multi-component (urine and blood) model versus single-component (urine or blood) models, in order to determine the optimal approach for evaluating training and competitive status.Methods: A total of 187 Chinese professional swimmers, comprising 103 elite and 84 sub-elite level athletes, were selected as subjects for this study. Urine samples were obtained from each participant and subjected to nuclear magnetic resonance (NMR) metabolomics analysis. Significant urine metabolites were screened through multivariable logistic regression analysis, and an identification model was established. Based on the previously established model of blood metabolites, this study compared the discriminative and predictive performance of three models: either urine or blood metabolites model and urine + blood metabolites model.Results: Among 39 urine metabolites, 10 were found to be significantly associated with the athletic status of swimmers (p < 0.05). Of these, levels of 2-KC, cis-aconitate, formate, and LAC were higher in elite swimmers compared to sub-elite athletes, while levels of 3-HIV, creatinine, 3-HIB, hippurate, pseudouridine, and trigonelline were lower in elite swimmers. Notably, 2-KC and 3-HIB exhibited the most substantial differences. An identification model was developed to estimate physical performance and athletic level of swimmers while adjusting for different covariates and including 2-KC and 3-HIB. The urine metabolites model showed an area under the curve (AUC) of 0.852 (95% CI: 0.793–0.912) for discrimination. Among the three identification models tested, the combination of urine and blood metabolites showed the highest performance than either urine or blood metabolites, with an AUC of 0.925 (95% CI: 0.888–0.963).Conclusion: The two urine metabolites, 2-KC and 3-HIV, can serve as significant urine metabolic markers to establish a discrimination model for identifying the athletic status and competitive potential of Chinese elite swimmers. Combining two screened urine metabolites with four metabolites reported exhibiting significant differences in blood resulted in improved predictive performance compared to using urine metabolites alone. These findings indicate that combining blood and urine metabolites has a greater potential for identifying and predicting the athletic status and competitive potential of Chinese professional swimmers.

Abstract Background High intensity interval training (HIIT) has been reported to exert better effects on cardiovascular fitness in obesity, but little known about the arterial stiffness (AS) in female university students with normal weight obesity (NWO). Thus, this study aimed to investigate the effects of HIIT on the body composition, heart rate (HR), blood pressure (BP), blood lipids metabolism as well as the novel parameters of propensity for AS (arterial velocity pulse index [AVI], arterial pressure volume index [API]) for female university students with NWO. Methods Forty female university students with NWO were randomly assigned to control group (n = 20) and HIIT group (3 bouts of 9‑min intervals at 90% of the maximal heart rate [HRmax], interspersed by 1 min rest, 5 days a week, n = 20). Tests were performed before and after 4 weeks of training. Repeated measures ANOVA and simple effect test analysis were used to analyze dependent variable changes. Results After 4 weeks HIIT statistically significantly improved the body composition by decreasing the body mass index, body fat percent, total body fat mass (BFM), BFM of left arm, measured circumference of left arm, and obesity degree, and increasing the total body skeletal muscle mass, protein content, total body water, fat free mass, body cell mas, and InBody score. HIIT also statistically significantly decreased the HR and BP. As for the lipid profile, HIIT obviously ameliorated the blood lipids metabolism by decreasing the levels of total cholesterol (TC), triglyceride, low-density lipoprotein, and TC/HDL, and increasing the levels of high-density lipoprotein (HDL). In addition, the AVI and API were markedly decreased via HIIT intervention. Conclusions HIIT produced significant and meaningful benefits for body composition, HR, BP, and blood lipids metabolism, and could decrease AS in female university students with NWO. This suggests that HIIT may effectively reduce the risk of arteriosclerosis and protect the cardiovascular function for female university students with NWO. Trial registration ChiCTR2100050711. Registered 3 September 2021. Retrospectively registered.

Objective: Metabolites in body fluids, such as lactate, glucose, and creatinine, have been measured by conventional methods to evaluate physical function and performance or athletic status. The objectives of the current study were to explore the novel metabolite biomarkers in professional swimmers with different competition levels using nuclear magnetic resonance (NMR) metabolomics, and try to establish a model to identify the athletic status or predict the competitive potential.Methods: Serum samples were collected from 103 elite and 84 sub-elite level Chinese professional swimmers, and were profiled by NMR analysis.Results: Out of the thirty-six serum metabolites profiled, ten were associated with the athletic status of swimmers (with p < 0.05). When compared with sub-elite swimmers, elite swimmers had higher levels of high-density lipoprotein (HDL), unsaturated fatty acid, lactic acid, and methanol. Elite swimmers had lower levels of isoleucine, 3-hydroxybutyric acid, acetoacetate, glutamine, glycine, and α-glucose. A model with four metabolites, including HDL, glutamine, methanol, and α-glucose, was established to predict athletic status by adjusting with different covariates. The area under the curve (AUC) of the best model was 0.904 (95% CI: 0.862-0.947), with a sensitivity and specificity of 75.5 and 90.2%, respectively.Conclusion: We have identified ten metabolite biomarkers with differentially expressed levels between elite and sub-elite swimmers, the differences could result from genetic or sports level between the two cohorts. A model with four metabolites has successfully differentiated professional swimmers with different competitive levels.

Research to date has provided novel insights into lactate's positive role in multiple brain functions and several brain diseases. Although notable controversies and discrepancies remain, the neurobiological role and the metabolic mechanisms of brain lactate have now been described. A theoretical framework on the relevance between lactate and brain function and brain diseases is presented. This review begins with the source and route of lactate formation in the brain and food; goes on to uncover the regulatory effect of lactate on brain function; and progresses to gathering the application and concentration variation of lactate in several brain diseases (diabetic encephalopathy, Alzheimer's disease, stroke, traumatic brain injury, and epilepsy) treatment. Finally, the dual role of lactate in the brain is discussed. This review highlights the biological effect of lactate, especially L-lactate, in brain function and disease studies and amplifies our understanding of past research.

Abstract Channel fracturing technology has been previously applied in the field; however, there are few studies on the shape and distribution pattern of the proppant pack and its effects on fracture conductivity. In this study, the shape and distribution of proppant packs in the channel fracturing process were studied by plate fracture experiments. Subsequently, proppant distribution geometry models were obtained based on a quantitative analysis of the experimental results. A conductivity calculation model was derived by the lattice Boltzmann method in order to investigate the proppant pack effect on fracture conductivity and optimize the distribution. Experimental results demonstrated that the shape and distribution of proppant packs were mainly controlled by the injection rate and pulse time, and four typical distribution types in the fracture were identified. Simulation results indicated that the flow resistance increased dramatically as the pillar‐fracture ratio (PFR) increased. However, fracture conductivity was also strongly related to the fracture width under closure pressure, in that the average width of the fracture decreased or closed completely as the PFR decreased. Under the same PFR at 50%, fracture conductivity was dominated by the distribution type, and the streamlined proppant packs yielded the highest conductivity. Finally, corresponding laboratory parameters intended for generating the streamlined packs were converted to field application, thereby proposing recommended pumping rates for different fracture heights and fracture widths.

Objective: The manuscript aims to explore the relationship between power performance and SNPs of Chinese elite athletes and to create polygenic models.Methods: One hundred three Chinese elite athletes were divided into the power group (n = 60) and endurance group (n = 43) by their sports event. Best standing long jump (SLJ) and standing vertical jump (SVJ) were collected. Twenty SNPs were genotyped by SNaPshot. Genotype distribution and allele frequency were compared between groups. Additional genotype data of 125 Chinese elite athletes were used to verify the screened SNPs. Predictive and identifying models were established by multivariate logistic regression analysis.Results: ACTN3 (rs1815739), ADRB3 (rs4994), CNTFR (rs2070802), and PPARGC1A (rs8192678) were significantly different in genotype distribution or allele frequency between groups (p < 0.05). The predictive model consisted of ACTN3 (rs1815739), ADRB3 (rs4994), and PPARGC1A (rs8192678), the area under curve (AUC) of which was 0.736. The identifying model consisted of body mass index (BMI), standing vertical jump (SVJ), ACTN3, ADRB3, and PPARGC1A, the area under curve (AUC) of which was 0.854. Based on the two models, nomograms were created to visualize the results.Conclusion: Two models can be used for talent identification in Chinese athletes, among which the predictive model can be used in adolescent athletes to predict development potential of power performance and the identifying one can be used in elite athletes to evaluate power athletic status. These can be applied quickly and visually by using nomograms. When the score is more than the 130 or 148 cutoff, it suggests that the athlete has a good development potential or a high level for power performance.

The genome packaging motor of bacteriophages and herpesviruses is built by two terminase subunits, known as large (TerL) and small (TerS), both essential for viral genome packaging. TerL structure, composition, and assembly to an empty capsid, as well as the mechanisms of ATP-dependent DNA packaging, have been studied in depth, shedding light on the chemo-mechanical coupling between ATP hydrolysis and DNA translocation. Instead, significantly less is known about the small terminase subunit, TerS, which is dispensable or even inhibitory in vitro, but essential in vivo. By taking advantage of the recent revolution in cryo-electron microscopy (cryo-EM) and building upon a wealth of crystallographic structures of phage TerSs, in this review, we take an inventory of known TerSs studied to date. Our analysis suggests that TerS evolved and diversified into a flexible molecular framework that can conserve biological function with minimal sequence and quaternary structure conservation to fit different packaging strategies and environmental conditions.

Objective: To develop a nomogram for predicting bone development state (BDS) of female children and adolescents in a large scale.Methods: Four hundred forty-seven female students were designated as the training cohort to develop the predictive model, whereas 196 female students were used as the validation cohort to verify the established model. Bone age, height, body mass, body fat percentage, and secondary sexual characteristics were recorded, and BDS was determined with the chronological age and bone age. Multivariate logistic regression was conducted to determine the factors, and nomogram was developed and validated with the training and validation cohorts, respectively.Results: One hundred forty-seven female students were identified as BDS abnormal in the training cohort (32.9%), and 104 were determined in the validation cohort (53.1%). Age, height, weight, and pubes stage were selected for the predictive model. A nomogram was developed and showed a good estimation, with a C-index of 0.78 and a good calibration in the training cohort. Application of the nomogram to the validation cohort showed a similar C-index of 0.75 and a good calibration.Conclusion: A nomogram for predicting bone development was developed, which can provide a relatively good estimation of BDS for female children and adolescents in Chinese metropolis.

COVID-19 is a highly infectious respiratory virus, which can proliferate by invading the ACE2 receptor of host cells. Clinical studies have found that the virus can cause dyspnea, pneumonia and other cardiopulmonary system damage. In severe cases, it can lead to respiratory failure and even death. Although there are currently no effective drugs or vaccines for the prevention and treatment of COVID-19, the patient’s prognosis recovery can be effectively improved by ameliorating the dysfunction of the respiratory system, cardiovascular systems, and immune function. Intermittent hypoxic preconditioning (IHP) as a new non-drug treatment has been applied in the clinical and rehabilitative practice for treating chronic obstructive pulmonary disease (COPD), diabetes, coronary heart disease, heart failure, hypertension, and other diseases. Many clinical studies have confirmed that IHP can improve the cardiopulmonary function of patients and increase the cardiorespiratory fitness and the tolerance of tissues and organs to ischemia. This article introduces the physiological and biochemical functions of IHP and proposes the potential application plan of IHP for the rehabilitation of patients with COVID-19, so as to provide a better prognosis for patients and speed up the recovery of the disease. The aim of this narrative review is to propose possible causes and pathophysiology of COVID-19 based on the mechanisms of the oxidative stress, inflammation, and immune response, and to provide a new, safe and efficacious strategy for the better rehabilitation from COVID-19.

Depending on the strategy of "Healthy China", more and more people pay attention to health issues. The integration and development of sports industry and health service industry is an inevitable outcome of industrial transformation and upgrading and healthy life in the new era. Through constructing the evaluation index system of the coupling and coordination development degree between sports industry and health service industry, using entropy evaluation method and coupling and coordination degree model, this paper explore the comprehensive level and coupling and coordination development status of sports industry and health service industry in thirty-one provinces, municipality cities and autonomous regions of China from 2013 to 2017. The results of this paper show that the comprehensive China's sports industry and health service industry both present an incremental development trend year by year, and are characterized by the distribution of "high in the east and low in the west" in space. The government's policy support provides superior industrial supporting conditions for the development of sports industry. However, it is not conducive to the promotion of industrial economic benefits. In the health service industry, the rapid development of health insurance is beneficial to the integration of industrial resources and the perfection of industrial chain. Whereas as the core content of health service industry, health service has greater space for development; the coupling and coordination degree between the two industries rises from mild maladjustment to basic coordination, which is characterized by the distribution of "high in the east and low in the west" in space; among provinces, with Beijing, the Yangtze River Delta and Guangdong as the three development center points, it shows the spatial evolutionary process from "dispersion-type plaques" to "gathering type scattered surfaces".

Earthworms enrich the soil and protect the health of their ecological environment. Previous studies on these invertebrates determined their protein content, hormone secretions, medicinal value, and ecological habits, but their whole genomic sequence remains incomplete. We performed whole genome sequencing of Metaphire vulgaris (Chen, 1930), which belongs to the genus Metaphire of the family Megascolecidae. The genome assembly was 729 Mb, with a N50 contig size of 4.2 Mb. In total, 559 contigs were anchored to 41 chromosomes according to the results of Hi-C (High-throughput Chromosome Conformation Capture) technology, which was confirmed by karyological analysis. A comparison of the genomic sequences and genes indicated that there was a whole-genome duplication in M. vulgaris followed by several chromosome fusion events. Hox genes and lumbrokinase genes were identified as partial clusters surrounding the genome. Our high-quality genome assembly of M. vulgaris will provide valuable information for gene function and evolutionary studies in earthworms.

Objectives: The study aims to analyze the status quo of public health emergency measures taken in China in dealing with the spread of new coronavirus pneumonia (COVID-19), and to put forward policy suggestions for system construction and improvement. Methods: According to the official data released by the National Health Commission, the epidemic data of infected people from 0:00 on January 24, 2020 to 24:00 on February 23, 2020 were quantitatively analyzed through statistical analysis. We used EXCEL software to draw the overall epidemic trend chart and Statistical Product and Service Solutions (SPSS) to carry out descriptive statistical analysis of mortality and cure rate. We made qualitative analysis on the emergency measures implemented by national administrative departments and provincial governments to work on controlling and monitoring COVID-19 nationwide spread. Results: The number of patients diagnosed showed a linear increasing trend, with the slope increasing first and decreasing later. Suspected and new cases showed an inverted V pattern, with the peak occurring on February 8 and 12, respectively. There was a linear increase in the number of deaths and an exponential increase in the number of cures. Over the 31-day study period, the mortality rate fluctuated between 2.0% and 3.4%. The mean cure rate was 10.03%, the minimum value was 1.33%, and the maximum value was 32.05%. The quantitative and qualitative analysis shows that the public health emergency response system constructed in China plays a significant role in controlling the epidemic in a certain period of time. Discussion: The four-tier emergency management system and the joint prevention mechanism established in China have provided various resources to control the epidemic, but there are still weakness in dealing with the spread of COVID-19. It is suggested to improve and strengthen the emergency management system, public health service system, health legal system, citizen health education, and international exchange and cooperation.

Water hydraulic fracturing involves pumping low viscosity fluid and proppant mixture into the artificial fracture under a high pumping rate. In that high Reynolds number conditions (HRNCs, Re > 2000), the turbulence effect is one of the key factors affecting proppant transportation and placement. In this paper, a Eulerian multiphase model was used to simulate the proppant particle transport in a parallel slot under HRNCs. Turbulence effects in high pumping rates and frictional stress among the proppant particles were taken into consideration, and the Johnson-Jackson wall boundary conditions were used to describe the particle-wall interaction. The numerical simulation result was validated with laboratory-scale slot experiment results. The simulation results demonstrate that the pattern of the proppant bank is significantly affected by the vortex near the wellbore, and the whole proppant transport process can be divided into four stages under HRNCs. Furthermore, the proppant placement structure and the equilibrium height of proppant dune under HRNCs are comprehensively discussed by a parametrical study, including injection position, velocity, proppant density, concentration, and diameter. As the injection position changes from the lower one to the top one, the unpropped area near the entrance decrease by 7.1 times, and the equilibrium height for the primary dune increase by 5.3%. As the velocity of the slurry jet increases from 2 m/s to 5 m/s (Re = 2000–5000), the vortex becomes stronger, so the non-propped area near the inlet increase by 5.3 times, and the equilibrium height decrease by 5.2%. The change of proppant properties does not significantly change the vortex; however, the equilibrium height is affected by the high-speed flush. Thus, the conventional equilibrium height prediction correlation is not suitable for the HRNCs. Therefore, a modified bi-power law prediction correlation was proposed based on the simulation data, which can be used to accurately predict the equilibrium height of the proppant bank under HRNCs (mean deviation = 3.8%).

Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 promotes CTD compaction but does not affect the affinity for importin α1. The binding of 30 importin α1/β1 augments HBV capsid diameter to ~620 angstroms, close to the maximum size trafficable through the NPC. We propose that phosphorylation favors CTD externalization and prompts its compaction at the capsid surface, exposing the NLS to importins. [ABSTRACT FROM AUTHOR]

From the perspective of embedded governance and public participation, public service coproduction has become a common phenomenon, among which the co-production behavior in the field of environmental governance is particularly prominent. In the governance process of "Zero-waste City" and "smart city", the "environmental protection post station" has served as a forward position, opening up the "last kilometer" of grass-roots governance, which is conducive to promoting public participation and co-production in social governance. On this basis, the current situation, influencing factors and governance countermeasures of public participation in the co-production of citizen post stations are discussed with citizen post stations of environmental governance as an example. The results show that: (1) In the field of environmental governance, there is a common phenomenon of "strong willings and weak behaviors" in the co-production of citizens, who do not understand the function of citizen post stations and seldom use the digital governance platform of the government. (2) In the field of environmental governance, citizens' co-production behavior is affected by individual characteristics, co-production capacity and perceived factors. (3) Among the individual characteristics, the age and political outlook of the public will affect their co-production behavior. (4) Under the background of government digital governance, citizens' co-production behavior will also be significantly affected by their environmental cognitive ability and new media use ability. (5) The citizens' co-production behavior in citizen post stations of environmental governance will be affected by self-efficacy, significant perception of public service and satisfaction perception and other factors. Therefore, it is necessary to formulate differential incentive strategies according to individual characteristics in the future citizen post station construction, so that more subjects can participate effectively. Perhaps, we should also enhance public awareness and participation with the help of new media, pay attention to the cultivation of citizens' co-production capacity and the improvement of public perception factors, promote the co-production of citizen post stations in a more diversified way. [ABSTRACT FROM AUTHOR]