Search

Abstract Background Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. Methods Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. Results Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. Conclusions Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.

Abstract Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

Abstract Background There is a scarcity of studies that quantitatively assess the difficulty and importance of knowledge points (KPs) depending on students’ self-efficacy for learning (SEL). This study aims to validate the practical application of psychological measurement tools in physical therapy education by analyzing student SEL and course conceptual structure. Methods From the “Therapeutic Exercise” course curriculum, we extracted 100 KPs and administered a difficulty rating questionnaire to 218 students post-final exam. The pipeline of the non-parametric Item Response Theory (IRT) and parametric IRT modeling was employed to estimate student SEL and describe the hierarchy of KPs in terms of item difficulty. Additionally, Gaussian Graphical Models with Non-Convex Penalties were deployed to create a Knowledge Graph (KG) and identify the main components. A visual analytics approach was then proposed to understand the correlation and difficulty level of KPs. Results We identified 50 KPs to create the Mokken scale, which exhibited high reliability (Cronbach’s alpha = 0.9675) with no gender bias at the overall or at each item level (p > 0.05). The three-parameter logistic model (3PLM) demonstrated good fitness with questionnaire data, whose Root Mean Square Error Approximation was

Abstract The advancement of automation and Internet of Things technology has bolstered the automation process in the logistics sector. To address the challenge of localizing and generating grasping positions for intelligent robots in logistics sorting, this study developed an algorithm for item localization. The algorithm relies on enhanced YOLOv3 target detection and instance segmentation technologies to design a position generation algorithm for the robotic arm, which was further refined using sampling evaluation. The experimental results showed that the research-improved target detection model performed better on different datasets in terms of F1 value, accuracy and Area under the Curve (AUC) metrics, with the highest values of 95.77%, 94.05%, and 91.30%, respectively, which was effective in localizing document-like parcels. Meanwhile, the instance segmentation algorithm with fused features took significantly lower values than other target detection algorithms in terms of average absolute value error and root mean square error. The accuracy rate and all-class average precision value were higher than other target detection models, and the fluctuation of the value taken was smaller, which was suitable for logistics parcel localization. The position generation model, based on a sampling evaluation, yielded significantly different values compared to other algorithms. The relative position error and absolute trajectory error indexes were all below 0.4. The combined indexes of grasping accuracy and error indicate the superior performance of the research-designed algorithms. They can effectively enhance the sorting effects of real logistics scenarios. This research contributes to the improvement of the automated sorting system through the use of visual robotic arm technology. Additionally, it encourages the development of logistics automation and the establishment of intelligent logistics factories.

In this study, Continuous Discontinuous Element Method (CDEM) was employed to analyze the failure of concrete slab under drop-hammer impact at the mesoscopic level. Initially, simulation models of the impact system were established, and concrete slab models, including three-dimensional random aggregates, were generated. Mesoscopic simulations of concrete failure were then conducted by considering different variables, such as impact energy, slab size and the number of hammerheads. Corresponding drop hammer tests were used to validate the simulation results. Furthermore, an energy conversion formula for the dynamic failure of concrete slabs was derived, and the energy conversion process within the impact system was analyzed. The study also revealed the dynamic failure mechanisms of concrete slabs under various impact conditions. The research demonstrates that the simulation results are generally consistent with the impact tests. CDEM effectively investigates the impact characteristic and the energy conversion process of concrete slab failure. Under varying impact energies, slab sizes and hammerhead numbers, distinct differences in the failure characteristics of concrete-slab structure were observed. Increased impact energy accelerates the failure of concrete slabs, whereas larger concrete slab sizes inhibit crack propagation. The number of impact heads determines the initial crack position and its propagation path within the concrete slab. Moreover, the energy conversion process of the impact system significantly influences the failure behavior of the concrete slab. The effect of slab size on the energy utilization rate is greater than those of hammerhead number and impact speed.

Bench blasting is commonly used in open-pit mining. Some design parameters such as positions of hole packing and caving holes have great influences on the blasting effects. In this work, with a hybrid discrete-finite element method, numerical simulations of bench blasting are conducted, capturing the whole continuous-discontinuous processes. Considering two engineering cases, the influences of hole packing and caving holes are evaluated. The numerical results not only lead to some improved designs by relocating the packing positions and caving holes but also indicate the reliability of the adopted numerical tools.

In-depth analysis of asteroid samples will provide a key scientific basis for understanding its evolution history, resource utilization, and life origin. Obtaining rock samples from asteroids is getting more and more attention. However, successful sampling in asteroid is difficult due to extremely complex environmental conditions. In this paper, the dynamic processes of rock failure by sampling device are investigated by a continuum-discontinuum element method (CDEM) to instruct the rock sampling in asteroid. The deformation and failure of rock samples under different conditions (impact speeds, impact positions, rock cut-slot numbers, cut-slot spacings, cut-slot depths and cut-slot widths, etc.) are analyzed, and the relationships between the rock failure and hammer impact method are obtained. The results show that the cut-slot formed by grinding wheel increases the free surface of rock sample, which is beneficial to impact fracture and asteroid sampling. The relative distance between cut-slot free surface and impact position significantly affects the rock fracture under impact loading. The fracture degree of rock with single cut-slot is obviously smaller than that of rock with double cut-slots, the cut-slot scheme of double grinding wheels is more suitable for asteroid sampling. Under the impact loading, the rock fracture is negatively correlated with the cut-slot spacing formed by double grinding wheel cutting, the effective spacing of double cut-slots is 12 mm. The fracture unit number of rock varies nonlinearly with an increase of the depth from impact position, there is an optimal cut-slot depth corresponding to a certain impact velocity, and the rock crushing efficiency of asteroid sampling can be improved as the cut-slot depth matches the crack propagation depth.

Abstract Titanium drill pipe have promising application prospects in ultra-deep drilling, but the nonlinear dynamic characteristics of composite drill strings are very complex. It is very important to use titanium drill pipe safely, economically, and effectively in the drilling process. In this paper, different schemes of the titanium/steel drill pipe composite drill string was designed, and the statics and dynamics characteristics of these composite drill strings were analyzed. The design scheme of titanium/steel composite drill strings were optimized by using whirling characteristics, dynamic stress and vibration acceleration. The results show that the titanium drill pipe can effectively improve the tensile allowance of the wellhead and reduce the whirling velocity, dynamic stress and vibration acceleration of the drill string. By comparing and analyzing the dynamic characteristics of 3 kinds of composite drill strings, the use of titanium drill pipe for the lower 2000 m of the 4′′ drill pipe have the smaller dynamic stress and lateral vibration, and less collision with the wellbore. Based on the analysis of vibration and dynamic characteristics, an optimal scheme of drilling operation parameters for the titanium/steel composite drill string was formed finally, which can provide guidance for the use of the drill string composed of titanium/steel drill pipe in natural gas drilling of ultra-deep well.

Thermal cracking of rocks can significantly affect the durability of underground structures in engineering practices such as geothermal energy extraction, storage of nuclear waste and tunnelling in freeze–thaw cycle induced areas. It is a scenario of strong coupled thermomechanical process involving discontinuity behaviours of rocks. In this context, a numerical model was proposed to investigate the thermal cracking of rocks, in a framework of the continuous-discontinuous element method (CDEM) for efficiently capturing the initiation and propagation of multiple cracks. A simplex integration strategy was adopted to account for the influences of temperature-dependent material properties. Several benchmark tests were considered and the obtained results were compared with analytical solutions and numerical results from the literature. The results show that the fracture degree of the cases when considering temperature-dependent material parameters had 10% differences approximately compared with the cases with constant parameters.

Nighttime light (NTL) remote sensing has emerged as a powerful tool in various fields such as urban expansion, socio-economic estimation, light pollution, and energy domains. However, current annual NTL products suffer from several critical limitations, including poor consistency, severe background noise, and limited comparability. These issues have significantly interfered with the research of long-term NTL trends and diminished the accuracy of related findings. Therefore, this study developed a de-difference smoothing algorithm for producing high-quality annual NTL products based on monthly National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) NTL data. It enabled the construction of a continuous global high-quality NTL dataset, named the De-Difference Smoothed Nighttime Light (DDSNL), covering the period from 2012 to 2023. Comparative analyses were conducted to validate the accuracy and availability of the DDSNL product against the benchmark EOG NPP-VIIRS and NPP-VIIRS-like NTL datasets. The results showed that DDSNL products had strong correlation with the NTL distribution of EOG NPP-VIIRS, but little correlation with NPP-VIIRS-like. Notably, DDSNL demonstrated better background noise reduction and higher separability between NTL and non-NTL areas compared to EOG NPP-VIIRS NTL. In contrast to the complete exclusion of background in NPP-VIIRS-Like, the retention of background values in DDSNL leads to more reasonable representation in the urban fringes. In the analysis of NTL changes matching impervious surface changes, the DDSNL product demonstrated the least interference from noise, resulting in the smallest segmentation threshold and the highest matching accuracy. This indirectly demonstrates the spatial and temporal consistency of the annual DDSNL product, ensuring its reliability in change detection-related studies. The annual DDSNL product developed in this research exhibits high fidelity, strong consistency, and improved comparability, and can provide reliable data reference for applications in electrification and urban studies.

Abstract Objective: The aim of this study is to determine the predictive values of MRSA swab screenings in patients with cancer. Methods: This is a retrospective cohort observational study of adult patients admitted to The University of Texas MD Anderson Cancer Center between January 2019 and October 2022. Data collected from patients with documented MRSA nasal swab screenings and clinical cultures taken within 7 days were collected. The first documented MRSA swab screening and culture results from unique patients were included for analysis to calculate sensitivity, specificity, positive predictive value, and NPV. Results: A total of 6475 patients with MRSA nasal swab cultures had 13129 clinical cultures from different anatomical sites. Of the patients included, 57% had a solid tumor and 37% had a hematological malignancy, with 82% of patients receiving an anti-MRSA antibiotic prior to MRSA nasal swab. There were 167 documented positive MRSA cultures, most commonly from a wound (41.3%) or respiratory source (24%). Overall sensitivity and specificity for all culture sites were 50.9% and 98.4%, respectively, with an overall NPV of 99.4%. The NPV was 99.8% for bloodstream infections, 98.5% for respiratory infections, 92.6% for wound infections, and greater than 99% for other culture sites. Conclusion: The specificity and negative predictive value of MRSA swab screenings in patients with cancer was high overall and consistent with the literature in immunocompetent patients. These results may aid in antimicrobial stewardship activities that can help guide the discontinuation of empiric antibiotics in patients with cancer.

Overstory and understory vegetation play a vital role in forest ecosystem functionality. However, it is necessary to enhance the knowledge of their diversity and compositional dynamics following cessation of disturbance, which is required to inform restoration approaches and the mechanisms required for maintaining disturbance cessation. We conducted a chronosequence spanning 0–1, 5–6, 11–12, 20–24, and 28–34 years since disturbance cessation, and old-growth forests to investigate the dynamic changes in overstory and understory vegetation diversity and composition, as well as maintenance mechanisms following the cessation of anthropogenic disturbances in subtropical regions of Eastern China. The current study results indicated a decrease in understory cover and periodic fluctuations in the diversity of overstorey and understory vegetation following disturbance cessation efforts. Specifically, the shrub layer exhibited the highest richness in 28–34 years, while the herb layer showed the lowest evenness. Multivariate analysis using multiple-response permutation procedures indicated that the species composition and interspecific quantity ratio of understory plants in the forest at 28–34 years significantly differ from those in the early closure stage. An indicator species analysis revealed that more support was given to sun-loving plants after 0–1 years of the enclosure, while species with shade tolerance and low nutrient requirements were supported after 28–34 years. The structural equation model results show that 38.8% of the impact on herb evenness was related to light and substrate diversity. The ecological restoration time mainly indirectly affects understory vegetation by influencing the upper vegetation, light availability, and substrate heterogeneity. Overall, this study revealed that cessation of anthropogenic disturbance can maintain and care for understorey plant diversity and contribute to the sustainable management of forests.

Abstract Controllable shock wave (CWS) parameters such as amplitude, operating area and number of operations are easy to control and have received extensive attention as a potential new technology for reservoir permeability enhancement. Based on the continuous-discontinuous element method (CDEM) and considering the coupling mechanism of reservoir deformation, failure, pore seepage and fracture flow, a multiphysical field coupling model of reservoir permeability enhancement under CWS is proposed. Under the fluid–solid coupling condition, the formation and development dynamic process of reservoir fractures are obtained, and the change of reservoir permeability is also obtained. The compression fracture zone, tensile fracture zone and undamaged zone are formed around the wellbore. After repeated impact, the number of fractures is more sensitive to tectonic stress, the fracture aperture is more sensitive to reservoir strength. Different from hydraulic fracturing, a large number of fractures in different directions will appear around the main fracture after repeated impact, forming a complex fracture network similar to spider web, which may be beneficial to improve reservoir permeability. The permeability of reservoirs with different tectonic stresses and strengths increases nonlinearly and monotonicly with repeated impacts. Based on CDEM, the change of reservoir permeability with tectonic stress, strength and impact times is obtained, which is a nonlinear monotonic three-dimensional relationship. Based on that relationship, the parameters of CWS can be controlled to predict the change of reservoir permeability, such as peak pressure, duration, impact times, etc. Therefore, it can optimize the reservoir fracturing scheme and improve the reservoir fracturing efficiency, which has considerable practical significance in engineering.

ABSTRACTBackground and Objectives Haemophilia comprises a continuum of blood disorders that often include joint and muscular dysfunction, which may lead to a constellation of activity limitations and participation restrictions. However, there is scant research incorporating functional assessment scales into the common language provided by the International Classification of Functioning, Disability and Health (ICF). This study aims to identify the ICF categories to include in an item bank of functioning aspects relevant for haemophilia.Design and Methods A systematic search was carried out in July 2021 based on the PubMed MEDLINE, CLINICAL, and Cochrane databases for qualified articles, investigating haemophilia-specific scales and the scales recommended by the World Federation of Haemophilia (WFH) linked to ICF categories between 2001 and 2021. Well-trained healthcare professionals in the haemophilia field and ICF evaluation conducted group discussions to determine the ICF items for haemophilia.Results A total of 112 out of 176 items measuring function were collected for the haemophilia ICF item bank, including 32 items for body function (b), 45 items for activity and participation (d), 27 items for environmental factors (e), and 8 items for body structure(s).Interpretation and Conclusions We recommend that future haemophilia research use the haemophilia-specific ICF item bank, which could capture a whole spectrum of functional measurements and facilitate multidisciplinary and worldwide communication. This study also indicates that further development and analysis of the psychometric properties of the 112 haemophilia-related ICF items is warranted.

Ta/MgO/NiFe/MgO/Ta anisotropic magnetoresistive thin film sensors, which can be used for magnetic scales, were prepared. To improve the magnetoresistance ratio of the sensors, these sensors were vacuum-annealed with the magnetic field applied, and then, both the static and dynamic magnetoresistive responses of the sensors were obtained. The experimental results have shown that the instability of magnetic anisotropy occurs in the sensors after vacuum-annealing, leading to the significant hysteresis and abnormal output voltage peaks. To investigate the underlying physics, the distribution of the non-uniform demagnetizing field along the width of an anisotropic magnetoresistive (AMR) strip is considered, and both the static and dynamic responses of the AMR elements have been calculated on the basis of the Stoner–Wohlfarth model. The results have shown that the calculated results are in good agreement with the experimental data. The calculated results have revealed that the angles between the anisotropic field and the external magnetic field are different during the field cyclings of Hmax (maximum magnetic field) to −Hmax and −Hmax to Hmax. The angle difference is up to 6°, leading to different magnetoresistive responses. This paper is helpful for the understanding about the magnetization rotations in magnetic sensors and the manufacturing of sensors.

Fragmentation/disassembly of fiber-like micelles generated by living crystalline-driven self-assembly (CDSA) is usually encountered in aqueous media, which hinders the applications of micelles. Herein, we report the generation of uniform fiber-like micelles consisting of a π-conjugated oligo(p-phenylenevinylene) core and a cross-linking silica shell with grafted poly(ethylene glycol) (PEG) chains by the combination of living CDSA, silica chemistry and surface grafting-onto strategy. Owing to the presence of crosslinking silica shell and the outmost PEG chains, the resulting micelles exhibit excellent dispersity and colloidal stability in PBS buffer, BSA aqueous solution and upon heating at 80 °C for 2 h without micellar fragmentation/disassembly. The micelles also show negligible cytotoxicity toward both HeLa cervical cancer and HEK239T human embryonic kidney cell lines. Interestingly, micelles with Ln of 156 nm show the “stealth” property with no significant uptake by HeLa cells, whereas some certain amounts of micelles with Ln of 535 nm can penetrate into HeLa cells, showing length-dependent cellular uptake behaviors. These results provide a route to prepare uniform, colloidally stable fiber-like nanostructures with tunable length and functions derived for biomedical applications.

Abstract Although striatal delivery of three critical genes for dopamine synthesis by viruses is a potential clinical approach for treating Parkinson’s disease (PD), the approach makes it difficult to finely control dopamine secretion amounts and brings safety concerns. Here, we generate genetically engineered mesenchymal stem cells encoding three critical genes for dopamine synthesis (DOPA-MSCs). DOPA-MSCs retain their MSC identity and stable ability to secrete dopamine during passaging. Following transplantation, DOPA-MSCs reinstate striatal dopamine levels and correct motor function in PD rats. Importantly, after grafting into the caudate and putamen, DOPA-MSCs provide homotopic reconstruction of midbrain dopamine pathways by restoring striatal dopamine levels, and safely and long-term (up to 51 months) correct motor disorders and nonmotor deficits in acute and chronic PD rhesus monkey models of PD even with advanced PD symptoms. The long-term benefits and safety results support the idea that the development of dopamine-synthesized engineered cell transplantation is an important strategy for treating PD.

Abstract Checkpoint suppressor 1 (CHES1), a transcriptional regulator, had been dysregulated in many types of malignancies including breast cancer, and its expression level is strongly associated with progression and prognosis of patients. However, the underlying regulatory mechanisms of CHES1 expression in the breast cancer and the effects of post-translational modifications (PTMs) on its functional performance remain to be fully investigated. Herein, we found that CHES1 had a high abundance in triple-negative breast cancer (TNBC) and its expression was tightly associated with malignant phenotype and poor outcomes of patients. Furthermore, we confirmed that CHES1 was an acetylated protein and its dynamic modification was mediated by p300 and HDAC1, and CHES1 acetylation enhanced its stability via decreasing its ubiquitination and degradation, which resulted in the high abundance of CHES1 in TNBC. RNA-seq and functional study revealed that CHES1 facilitated the activation of oncogenic genes and pathways leading to proliferation and metastasis of TNBC. Taken together, this research established a novel regulatory role of acetylation on the stability and activity of CHES1. The results demonstrate the significance of CHES1 acetylation and underlying mechanisms in the progression of TNBC, offering new potential candidate for molecular-targeted therapy in breast cancer.

Abstract In order to investigate the influence of minor Ru on the electrochemical behaviour and structural characteristics of passive films on the surface of Ti-6Al-4V alloys under various oil and gas exploration conditions, electrochemical techniques, X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and corrosion simulation tests were carried out. The results revealed that the oil and gas exploration conditions had a serious impact on the electrochemical behaviour and corrosion resistance of the tested alloys. The passivation film resistance and corrosion potential of the tested titanium alloys were significantly reduced with increasing acidity and temperature. With the addition of minor ruthenium, the potential of the passive film on the Ti-6Al-4V-0.11Ru alloy surface increased because of the high surface potential of the ruthenium element. The contents of metallic ruthenium and tetravalent titanium oxide TiO2 in the surface film of the Ti-6Al-4V-0.11Ru alloy both increased with increasing temperature, which led to increase the thickness, stability, corrosion resistance and repairability of the passive film on the surface of the Ti-6Al-4V-0.11Ru alloy being better than those qualities of Ti-6Al-4V. These results were also confirmed by corrosion simulation tests.

Keypoints Elevated triglyceride and high-sensitive CRP are associated with a higher risk of acute leukemia in MDS.

Diabetes mellitus during pregnancy, which can be classified into pregestational diabetes and gestational diabetes, has become much more prevalent worldwide. Maternal diabetes fosters an intrauterine abnormal environment for fetus, which not only influences pregnancy outcomes, but also leads to fetal anomaly and development of diseases in later life, such as metabolic and cardiovascular diseases, neuropsychiatric outcomes, reproduction malformation, and immune dysfunction. The underlying mechanisms are comprehensive and ambiguous, which mainly focus on microbiota, inflammation, reactive oxygen species, cell viability, and epigenetics. This review concluded with the influence of intrauterine hyperglycemia on fetal structure development and organ function on later life and outlined potential mechanisms that underpin the development of diseases in adulthood. Maternal diabetes leaves an effect that continues generations after generations through gametes, thus more attention should be paid to the prevention and treatment of diabetes to rescue the pathological attacks of maternal diabetes from the offspring.

We studied a supply chain consisting of multiple suppliers and multiple retailers. We use the Cournot–Stackelberg game, the Market–Stackelberg game, and the Market–Nash game to simulate the situation where the upstream seller’s market dominance power gradually decreases while the downstream buyer’s market power increases. The equilibrium decision and supply chain performance under the three models are compared and analyzed, as well as their responses to external market changes such as demand fluctuation and market competition intensity. The research shows that (1) in a seller-dominated supply chain, the increase in buyer power reduces market equilibrium production and wholesale price; (2) in the face of strong demand fluctuations, equivalent power between upstream and downstream can contribute to the stabilization of production and wholesale prices; (3) when market demand fluctuation is small, market power brings a higher profit level, and supply chain participants would like to actively compete for market power. However, when the demand fluctuates greatly, the profit advantage brought by market dominance is no longer significant, and there is no need to spend much to fight for market dominance; (4) the fierce competition of upstream suppliers will induce upstream to give up the competition for market dominance, and make the market power less attractive to downstream retailers. While the fierce horizontal competition downstream will stimulate both suppliers and retailers to actively compete for market power, (5) sufficient market competition will improve total supply chain profit, so encouraging competition is conducive to the overall economic development of society.

This study focused on 6-year-old ‘Pawnee’ pecan trees to elucidate the differential responses of physicochemical properties of orchard soil and pecan fruit quality when combining chemical and organic fertilizers. The aim was to unveil the mechanisms that underlie the effects of different fertilization treatments on soil fertility, soil enzyme activities, and pecan fruit quality. Four treatments were established: sole chemical fertilizer (CF; N:P2O5:K2O is 15:15:15), chemical fertilizer combined with cake fertilizer (CF+CC), chemical fertilizer combined with manure fertilizer (CF+M), and chemical fertilizer combined with cake and manure fertilizer (CF+CC+M). Measurements were taken to assess the soil nutrient content, soil enzyme activities, and fruit growth quality in some orchards under different fertilization treatments. The results revealed that the combined application could increase yield and enhance pecan quality. Among these, the CF+M+CC treatment demonstrated the most favorable outcomes, with the pecan kernel oil and unsaturated fatty acid contents reaching 72.33% and 97.54%, respectively. The combined fertilization treatments had no significant impacts on soil trace elements such as Mg, Cu, and Mn; however, it significantly increased the Available Phosphorus (AP), Total Nitrogen (TN), Soil Organic Matter (SOM) and S-ACP (soil acid phosphatase) activities. In summary, the combined application of chemical and organic fertilizers can significantly increase the soil nutrient content and enzyme activities in pecan orchards, to promote the enhancement of fruit quality and economic aspects.

The research and application of CO2 storage and enhanced oil recovery (EOR) have gradually emerged in China. However, the vast unconventional oil and gas resources are stored in reservoir pores ranging from several nanometers to several hundred micrometers in size. Additionally, CO2 geological sequestration involves the migration of fluids in tight caprock and target layers, which directly alters the transport and phase behavior of reservoir fluids at different scales. Micro- and nanoscale fluidics technology, with their advantages of in situ visualization, high temperature and pressure resistance, and rapid response, have become a new technical approach to investigate gas–liquid interactions in confined domains and an effective supplement to traditional core displacement experiments. The research progress of micro–nano fluidics visualization technology in various aspects, such as CO2 capture, utilization, and storage, is summarized in this paper, and the future development trends and research directions of micro–nano fluidics technology in the field of carbon capture, utilization, and storage (CCUS) are predicted.

Unbalanced power structures can lead to an inequitable distribution of the supply chain’s profits, creating unstable supply chain relationships and serious social problems. This paper builds a two-tier newsvendor model composed of a single supplier and a single retailer and introduces Nash bargaining as a reference for fairness. We investigate (1) the impact of fairness concerns on the performance of a retailer-dominated supply chain and a manufacturer-dominated supply chain; (2) how demand uncertainty affects the inequitable state; and (3) how overestimated and underestimated values of fairness concerns affect supply chain performance when fairness concerns are private information. After solving the equilibrium solution of the Stackelberg game and Nash-bargaining games and numerical analyses, it is shown that unilateral fairness concerns by the Stackelberg leader or follower can motivate the leader to sacrifice its profit to reduce their income inequality by offering a coordinating wholesale price. Of course, it is also effective for both participants to be fair-minded as soon as their fairness sensitivity is moderate enough. However, followers’ fairness concerns are more effective at decreasing inequity, while leaders can improve social welfare, i.e., increase the entire supply chain’s efficiency as well as market scale. We also find that in a more uncertain market, fewer fairness-concerned participants are supposed to reach a relatively fair condition. In addition, we conclude that sometimes asymmetric information about fairness concerns can improve the profit share of the disadvantaged and even channel efficiency. This paper extends the study of Nash-bargaining fairness concerns to retailer-dominated newsvendor models and enriches the field, when fairness concerns are asymmetric information.

Wettability, as a vital tool for analyzing and describing oil flow, plays a significant role in determining oil/water relative permeability, residual oil distribution, and on–site recovery efficiency. Although the contact angle method is widely used for measuring wetting behavior, it is susceptible to the effects of surface roughness, oil–water saturation, and the distribution of mixed wetting within the range of droplet sizes. Additionally, millimeter–scale droplets fail to accurately represent the wetting distribution and the influencing factors at the micro/nano–scale. Therefore, this study presents a comprehensive investigation of the microstructure and wettability of shale samples. The characterization of the samples was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques to gain insights into their microscopic features, surface properties, and wettability. Results demonstrate the following: (1) Quartz and clay minerals tended to exhibit rough surface topography, appearing as darker areas (DA) under scanning electron microscopy (SEM). It is worth noting that plagioclase minerals exhibited brighter areas (BA) under SEM. (2) An increase in the content of minerals such as quartz and clay minerals was observed to decrease the surface oil wetting behavior. In contrast, plagioclase feldspar exhibited an opposite trend. (3) Based on the adhesive forces of the samples towards oil or water, a wetting index, I, was established to evaluate the wettability of shale at a microscale. The dimensionless contact angle W, obtained by normalizing the contact angle measurement, also consistently indicated oil wetting behavior. (4) By comparing the differences between I and W, it was observed that surface roughness significantly affected the behavior of water droplets. The presence of roughness impeded the contact between the solid and liquid phases, thus influencing the accuracy of the wetting results. Organic matter also plays a significant role in influencing surface wettability, and its distribution within the shale samples can lead to localized variations in wettability.

The occurrence state of oil, gas, and water plays a crucial role in exploring shale reservoirs. In this study, molecular dynamics simulations were used to investigate the occurrence states of these fluids in shale nanopores. The results showed that when the alkane is light oil, in narrow pores with a width less than 3 nm, oil molecules exist only in an adsorbed state, whereas both adsorbed and free states exist in larger pores. Due to the stronger interaction of water with the rock surface, the adsorption of oil molecules near the rock is severely prohibited. Oil/water/gas occurrence characteristics in the water-containing pore study indicate that CO2 gas can drive free oil molecules out of the pore, break water bridges, and change the occurrence state of water. During displacement, the gas type affects the oil/gas occurrence state. CO2 has strong adsorption capacity, forming a 1.45 g/cm3 adsorption layer on the rock surface, higher than oil’s density peak of 1.29 g/cm3. Octane solubility in injected gases is CO2 (88.1%) > CH4 (76.8%) > N2 (75.4%), with N2 and CH4 having weak competitive adsorption on the rock. The investigation of different shale reservoir conditions suggests that at high temperature or low pressure, oil/gas molecules are more easily displaced, while at low temperature or high pressure, they are tightly adsorbed to the reservoir rock. These findings contribute to the understanding of fundamental mechanisms governing fluid behavior in shale reservoirs, which could help to develop proper hydrocarbon recovery methods from different oil reservoirs.

Given the digitalization trends within the field of engineering, we propose a practical approach to engineering digitization. This method is established based on a physical sandbox model, camera equipment and simulation technology. We propose an image processing modeling method to establish high-precision continuous mathematical models of transmission towers. The calculation of the wind field is realized by using wind speed calculations, a load-wind-direction-time algorithm and the Continuum-Discontinuum Element Method (CDEM). The sensitivity analysis of displacement- and acceleration-controlled transmission tower loads under two different wind direction conditions is conducted. The results show that the digital model exhibits a proportional relationship with the physical dimensions of the transmission tower model. The error between the numerical simulation results and the experimental results falls within a reasonable range. Nodes at higher positions of the transmission tower experience significantly higher forces compared to those at lower positions, and the structural forms with larger windward projected areas yield similar simulation results. The proposed digital twin system can help monitor the performance of structural bodies and assess the disaster degree in extreme conditions. It can guide specific maintenance and repair tasks.

A new composite material made from mica and a metal–organic framework (MOF) has been developed to improve the anticorrosive capabilities of epoxy resin coatings. The layered mica was loaded with denser and more uniform UIO-66 nanoparticles after modifying the composite with polyethyleneimine (PEI). The composites were used as fillers to prepare epoxy coatings that exhibited long-lasting active (labyrinth effect produced by mica) and passive (pH-sensitive release of corrosion inhibitors) corrosion protection. Settling experiments showed that polyethyleneimine improved the composites’ compatibility in epoxy resin. After being immersed in a 3.5 wt.% NaCl solution for 60 days, the adhesion of PMC–UIO@MBT/EP increases to 9.01 MPa, while the water absorption rate only reaches 2.57%. It indicates that the coating has good barrier properties and stability. After being soaked in a 3.5 wt.% NaCl solution for 60 days at pH = 7, PMC–UIO@MBT/EP exhibits high low-frequency impedance (8.30 × 108 Ω), as demonstrated by the electronic impedance spectrum (EIS). In addition, the coating also exhibited the highest low-frequency impedance after 30 days in 3.5 wt.% NaCl solution at pH = 11.

Abstract Objective The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET). Methods Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle–Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis. Results After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P

BackgroundChimeric Antigen Receptor T cell(CAR T-cell) therapy has been a great success in relapsed/refractory acute B lymphoblastic leukemia and B-cell lymphoma. At the same time, there are also related adverse reactions, especially cytokine release syndrome(CRS) and immune effector cell associated neurotoxicity syndrome(ICANS). However, Double CRS caused by CRA T cells are very rare.Case reportHere, we report a 33-year-male with secondary central diffuse large B-cell lymphoma(CNSL) who develpoed double CRS following sequential infusion of Anti-CD22 and Anti-CD19 CAR T cells after autologous hematopoietic stem cell transplantation(ASCT). On d+5, the patient developed high fever, along with chilly sensation, shivering, headache, blood oxygen desaturation, shock, weakness, severe thirst, and heart rate decline. IL-6 and ferritin increased significantly. The patient was diagnosed with the first CRS (grade 3). On d+36, the patient again had a persistent fever(T>39C) and limbs rash. IL-6 and ferritin again increased significantly on d+38. After exclusion of infection, a diagnosis of double CRS was made. The patient’s symptoms were completely relieved after receiving tocilizumab, glucocorticoids, and other supportive treatments on d+45.On d+90, contrast-enhanced MR angiogram shows that the lesion basically disappeared, indicating the patient had achieved CR. At the end of the follow-up at d+150, the patient was functioning normally without any sequelae.ConclusionThis is the first reported case worldwide where the patient with secondary CNSL suffered double CRS after CAR T-cell infusion. Our findings showed that it is important to increase awareness of early detection and diagnosis of double CRS and adopt appropriate treatment strategies.

Abstract Background Thyroid autoimmunity (TAI) has been demonstrated to be associated with adverse pregnancy including recurrent miscarriage, unexplained infertility, and implantation failure. To settle with the fertility problem, prescribing aspirin combined with prednisone (P + A) to women positive for anti-thyroid antibodies is frequent in clinical practice, but the underlying effect remains controversial. Methods A multicenter, retrospective study was conducted in three reproductive centers from 2017 to 2020. A total of 494 euthyroid infertile women were recruited who were positive for anti-thyroperoxidase and/or thyroglobulin antibodies (TPOAb and TgAb, respectively) with thyroid-stimulating hormone (TSH) levels ranging 0.35-4.0mIU/L and underwent their first in vitro fertilization and embryo transfer (IVF-ET) cycle. Ultimately, 346 women were included of which 150 women were treated with prednisone (10 mg/d) and aspirin (100 mg/d). The remaining 196 women were untreated (control group). Treatment started on the day of embryo transfer and continued until clinical pregnancy was determined. Results The clinical pregnancy rate was 57.5% vs. 63.5% in the control and treated groups (P = 0.414) for first fresh embryo transfer cycles and 57.8% vs. 61.8% for frozen-thawed embryo transfer cycles (P = 0.606). In addition, the live birth rate for the fresh embryo transfer was 49.6% vs. 47.3% in the control and treated groups (P = 0.762). Logistic regression revealed that aspirin plus prednisone did not improve the clinical pregnancy rate or miscarriage rate. Furthermore, it was observed that low free triiodothyronine (FT3) was associated with high miscarriage rates. Conclusions Utilizing an adjuvant treatment of P + A after the embryo transfer may not be necessary in euthyroid women with thyroid autoimmunity undergoing their first IVF-ET, regardless of the embryo type (fresh or frozen).

Background: Nasopharyngeal carcinoma (NPC) is a rare malignant tumor developing from epithelial linings of nasopharynx, and 10–50 out of 100,000 NPC cases were recorded globally particularly in the Asian countries. Methodology: The cytotoxicity of geraniin against the NPC C666-1 cells were analyzed using MTT assay. The influences of geraniin on the C666-1 cell viability with the presence of ROS and apoptosis inhibitors were also studied. The expressions of PI3K, Akt, mTOR, and autophagic markers LC3, ATG7, P62/SQSTM1 expressions in the C666-1 cells were studied by western blotting analysis. The ROS production was assayed using DCFH-DA staining. The immunofluorescence assay was performed to detect the NF-κB and β-catenin expressions in the C666-1 cells. Results: The cell viability of C666-1 cells were appreciably prevented by the geraniin. The geraniin treatment also inhibited the C666-1 cell growth with the presence of apoptotic inhibitor Z-VAD-FMK. The geraniin-treatment effectively improved the ROS production and inhibited the NF-κB and β-catenin expressions in the C666-1 cells. Geraniin appreciably modulated the PI3K/Akt/mTOR signaling axis and improved the autophagy-mediated cell death via improving the autophagic markers LC3 and ATG7 expressions in the C666-1 cells. Conclusion: In conclusion, our results proved that geraniin inhibits C666-1 cell growth and initiated autophagy-mediated cell death via modulating PI3K/Akt/mTOR cascade and improving LC3 and ATG7 expressions in the C666-1. Geraniin and it could be a hopeful and efficient candidate to treat the human NPC in the future.

The changes in the working environment have necessitated greater requirements in terms of the long−term anti−corrosion ability of metal anti−corrosion coatings, and the emergence of intelligent coatings has met this demand. A nanocontainer with a hydrophobic inner cavity and hydrophilic outer cavity called β−cyclodextrin (β−CD) was grafted onto the surface of hydroxyapatite (HAp) with a silane coupling agent, encapsulating benzotriazole (BTA) and embedded in epoxy resin to improve the coating anticorrosion performance. The excellent corrosion resistance of the coating in immersion and scratch experiments was derived from the inert protective layer formed by the reaction of the rapidly released corrosion inhibitor with the corrosion products on the metal surface. After 30 days of immersion experiment, the coating could still maintain the low−frequency impedance value of 6.28 × 107 Ω cm2. In this work, the enhancement of the physical barrier function of HAp nanoparticle and the pH−response function conferred by β−cyclodextrin provided the coating with good passive and active acting abilities in corrosive environments, respectively.

The scattering of fragments is a notable characteristic of the explosive detonation of a shelled charge. This study examines the fracture and fragmentation of the shell and the process by which natural fragments form under the strains of implosion. The analysis takes into account both the explosive’s energy output and the casing’s dynamic response. For this purpose, utilizing a thermochemical code as an alternative to the conventionally employed cylinder test, the Jones–Wilkins–Lee equation of state (JWL EOS) was calibrated within a range of relative specific volume up to 13. The detonation of the shelled charge was subsequently analyzed using the continuum–discontinuum element method (CDEM). Following this, the formation mechanisms and scattering characteristics of natural fragments were scrutinized. The analysis found that the shell predominantly experiences shear failure with uniform evolution, displaying a “hysteresis effect” and two mutation stages in the evolution of tensile failure. Within the JWL EOS’s calibrated range, the representation of fragment displacement and velocity improved by 47.97% and 5.30%, respectively. This study provides valuable guidance for designing the power field of warheads and assessing their destructive power.

In the context of the continuous development and maturity of intelligent manufacturing and intelligent logistics, it has been observed that the majority of vehicle maintenance in EMU trains still relies on traditional methods, which are characterized by excessive manual intervention and low efficiency. To address these deficiencies, the present study proposes the integration of Automatic Guided Vehicles (AGVs) to improve the traditional maintenance processes, thereby enhancing the efficiency and quality of vehicle maintenance. Specifically, this research focuses on the scenario of the maintenance workshop in EMU trains and investigates the task allocation problem for multiple AGVs. Taking into consideration factors such as the maximum load capacity of AGVs, remaining battery power, and task execution time, a mathematical model is formulated with the objective of minimizing the total distance and time required to complete all tasks. A multi-population genetic algorithm is designed to solve the model. The effectiveness of the proposed model and algorithm is validated through simulation experiments, considering both small-scale and large-scale scenarios. The results indicate that the multi-population genetic algorithm outperforms the particle swarm algorithm and the genetic algorithm in terms of stability, optimization performance, and convergence. This research provides scientific guidance and practical insights for enterprises adopting task allocation strategies using multiple AGVs.

Creating new fracture networks in coal seams with natural fractures through hydraulic fracturing techniques is an effective method for exploiting coal-bed methane. In this paper, a continuum-discontinuum element method (CDEM) is developed for simulating and assessing hydraulic fracture propagation in coal seams. An elastic-damage-fracture model is proposed for capturing the deformation and cracking processes of fractured coal. A stress-fracture percolation relation is implemented to simulate the hydro-mechanical coupling processes. The influence of X-direction angles, mechanical strengths, distances and lengths of natural fractures are analyzed in detail. The results are potentially useful to optimize the fracturing design.

Abstract Aims We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). Methods We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. Results A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) − 0.07; 95%CI − 0.11, − 0.02) and preeclampsia (RD − 0.03; 95%CI − 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD − 0.17; 95%CI − 0.25, − 0.08) and maternal weight gain (SMD − 0.61; 95%CI − 0.86,− 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. Conclusions The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.

Natural secondary Carya dabieshanensis forests comprise the natural wealth of the Dabie Mountains, which maintain the ecological balance of this region and enhance the incomes of farmers. However, forest ecosystems are being increasingly challenged due to increasing long-term anthropogenic development and management. Elucidating the impacts of management intensity and duration on the diversity and stability of vegetation communities in natural secondary Carya dabieshanensis forests is of great significance toward achieving sustainable forest management. For this study, we compared the effects of three forest management intensities (no management (CK), extensive management (EM), and intensive management (IM)), and five management durations (0, 3, 8, 15, and 20 y) on species diversity and the stability of vegetation communities (trees, shrubs, and herbaceous layers) of a Carya dabieshanensis forest. Our results revealed that the diversity of the vegetation communities continued to decline following the onset of management activities. The diversity, dominance, evenness, and richness indices of the vegetation communities decreased by 53.37%–62.77%, 46.04%–59.17%, 32.58%–53.55%, and 50.18%–51.30%, respectively, after 20 y of forest management. Intensive management translated to species diversity loss more so than extensive management. All vegetation communities of the forest stands under study were generally unstable; however, the stability they did have was not at risk under greater management intensity and duration, and neither did greater species diversity enhance it. This study provides new evidence to support the non-synchronicity of species diversity and community stability in forest resident vegetation communities. Since the species diversity and structural composition of tree layers have a positive effect on community stability, so we suggest that both extensive and intensive forest lands need to retain or replant more tree species other than Carya dabieshanensis.

The precise characterization of a tight glutenite reservoir’s microscopic pore structure is essential for its efficient development. However, it is difficult to accurately evaluate using a single method, and its microscopic heterogeneity is not fully understood. In this study, a combination of X-ray diffraction, casting thin section observations, scanning electron microscopy, high-pressure mercury injection, constant-speed mercury injection, X-ray computed tomography, and the advanced mathematical algorithms in the AVIZO 8.0 visualization software was used to construct the three-dimensional digital core of a glutenite reservoir at the study site, and the parameters of the pore network model were extracted. The overall microscopic pore structure characteristics were quantitatively investigated from multiple scales. Based on this, the mineral quantitative evaluation system (QEMSCAN) examined the microscopic heterogeneity of the glutenite reservoir and its impact on seepage. The results show that the glutenite reservoir in the study block can be classified into three categories based on lithology and capillary pressure curve characteristics. The type I reservoir samples have large and wide pore throats, low threshold pressure, and high reservoir quality; type II reservoir samples are characterized by medium-sized pore throat, medium threshold pressure, and moderate reservoir quality; and the small and narrow pore throat, high threshold pressure, and poor reservoir quality are characteristics of type III reservoir samples. The various pore throat types and mineral distributions are due to the differences in dissolution, compaction, and cementation. The continuous sheet pores have good connectivity, which is related to the interconnection of primary intergranular pores and strip fractures, while the connectivity of isolated pores is significantly poor, which is related to the development of intragranular dissolved pores and intercrystalline pores. This suggests the deterioration of physical properties and pore throat connectivity, reduced average pore radius, and decreased pore sorting as decreasing permeability. The tight glutenite pores range in size from 5 nm to 80 μm and primarily feature Gaussian and bimodal distribution patterns, and submicron–micron pores contribute more to seepage. The effective pores were found to be attributed to the slowing effect of abnormally high pressure on the vertical stress, and the protective effect was positively correlated with the high-pressure strength. Notably, there is strong microscopic heterogeneity in the distribution of the reservoir matrix minerals and the pore throat size. As a result, the injected fluid easily flows along the preferential seepage channel with pore development and connectivity. This study provides new insights into the exploration and development of similar tight reservoirs.

Understanding the vertical distribution and driving mechanisms behind soil carbon (C), nitrogen (N), and phosphorus (P) contents and enzyme activities along elevation gradients is of great significance for the healthy and sustainable management of forest ecosystems. For this study, the 0–20 cm soil-layer samples of different natural Quercus spp. secondary forests from eight altitude gradients (ranging from 250 to 950 m) were investigated to quantify their physicochemical properties, ecological stoichiometry characteristics, and enzyme activities. The results indicated that the soil nutrient content of natural secondary Quercus spp. forests in the Dabie Mountains was low, with average soil organic carbon (SOC) and total phosphorus (TP) contents of 19.86 ± 3.56 g·kg−1 and 0.68 ± 0.10 g·kg−1, respectively, which were 19.14% and 12.82% lower, respectively, than the Chinese average. In terms of vertical spatial distribution, the SOC, total nitrogen (TN), and TP contents of the soil at high altitudes (≥750 m) were greater than those at middle- and low-altitude areas and reached the maximum value at or near the top of the mountain (850–950 m). The stoichiometric attributes of the soil ecosystem fluctuated with the higher altitudes in vertical space; however, the fluctuation range was not significant. The C:N, N:P, and C:P ratios reached their maximum values at altitudes of 250, 750, and 850 m, respectively. However, the overall average value remained generally lower than the national average; thus, in forest management, attention should be paid to the supplementation of the soil with C and P. The activities of soil sucrase, urease, acid phosphatase, and catalase were interconnected across the overall space, and increased with altitude. The SOC, TP, and pH were the main factors that influenced the changes in soil enzyme activities.

Background: We aimed to investigate the clinical effect of low molecular weight heparin (LMWH) combined with magnesium sulfate in patients with severe pre-eclampsia (PE). Methods: A total of 70 patients with severe PE admitted in Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, China from Jun 2020 to May 2021 were enrolled and randomized into observation and control groups. The control group was treated with magnesium sulfate only, and the observation group was treated with small-dose LMWH combined with magnesium sulfate. The clinical effects and artery blood flow index were analyzed. Results: The observation group had higher coagulation function than that in the control group. RI, S/D, and PI in the observation group after treatment were lower than those in the control group, with statistically significant differences (P

PurposeThis study aims to accomplish two tasks for International Classification of Functioning, Disability and Health (ICF) application among persons with stroke: (1) to make an ICF tool for measuring personal abilities with simplified assessment operations; (2) to quantitatively evaluate ICF categories for being functioning rather than being disabled.MethodsA total of 130 inpatients with stroke via convenience sampling were evaluated by the extended comprehensive ICF core set for stroke, modified Rankin scale, and modified Barthel index (MBI). This study investigated the responses to 118 stroke-related ICF items (59 items in b and d domains individually) using Mokken scale analysis followed with Rasch modeling.ResultsA Mokken scale with 47 items was extracted from the binary data (1 as no-impairment or mild-impairment and 0 as moderate to complete impairment). A Rasch model with 45 items was derived from the Mokken scale. The conversion chart was available involving the original ordinal scores to Rasch-transformed scores from 0 to 100 (interval scale). Total scores exhibited a high correlation with the personal abilities estimated by the Rasch model. The personal ability also demonstrated a significantly strong correlation with the score of the MBI. Thus, the 45 ICF items were suggested to rate potential functional ability as a single measurement.ConclusionBased on simple “functioning or disabled” judgment tasks, ICF assessment can be simplified to a questionnaire with answering “yes-or-no” questions for each category. Functioning level for each person and difficulty of being functioning for each category can be estimated by the Rasch model of this questionnaire.

Abstract Background Spinal cord injury (SCI) is a debilitating medical condition that can result in the irreversible loss of sensorimotor function. Current therapies fail to provide an effective recovery being crucial to develop more effective approaches. Mesenchymal stem cell (MSC) exosomes have been shown to be able to facilitate axonal growth and act as mediators to regulate neurogenesis and neuroprotection, holding great therapeutic potential in SCI conditions. This study aimed to assess the potential of human placental MSC (hpMSC)-derived exosomes on the functional recovery and reactivation of endogenous neurogenesis in an experimental animal model of SCI and to explore the possible mechanisms involved. Methods The hpMSC-derived exosomes were extracted and transplanted in an experimental animal model of SCI with complete transection of the thoracic segment. Functional recovery, the expression of neural stem/progenitor cell markers and the occurrence of neurogenesis, was assessed 60 days after the treatment. In vitro, neural stem cells (NSCs) were incubated with the isolated exosomes for 24 h, and the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinases (ERK), and cAMP response element binding (CREB) proteins were assessed by western blot. Results Exosomes were successfully isolated and purified from hpMSCs. Intravenous injections of these purified exosomes significantly improved the locomotor activity and bladder dysfunction of SCI animals. Further study of the exosomes’ therapeutic action revealed that hpMSC-derived exosomes promoted the activation of proliferating endogenous neural stem/progenitor cells as denoted by the significant increase of spinal SOX2+GFAP+, PAX6+Nestin+, and SOX1+KI67+ cells. Moreover, animals treated with exosomes exhibited a significative higher neurogenesis, as indicated by the higher percentage of DCX+MAP 2+ neurons. In vitro, hpMSC-derived exosomes promoted the proliferation of NSCs and the increase of the phosphorylated levels of MEK, ERK, and CREB. Conclusions This study provides evidence that the use of hpMSC-derived exosomes may constitute a promising therapeutic strategy for the treatment of SCI.

Background: Cross talk of tumor–immune cells at the gene expression level has been an area of intense research. However, it is largely unknown at the alternative splicing level which has been found to play important roles in the tumor–immune microenvironment. Results: Here, we re-exploited one transcriptomic dataset to gain insight into tumor–immune interactions from the point of AS level. Our results showed that the AS profiles of triple-negative breast cancer cells co-cultured with activated T cells were significantly changed but not Estrogen receptor positive cells. We further suggested that the alteration in AS profiles in triple-negative breast cancer cells was largely caused by activated T cells rather than paracrine factors from activated T cells. Biological pathway analyses showed that translation initiation and tRNA aminoacylation pathways were most disturbed with T cell treatment. We also established an approach largely based on the AS factor–AS events associations and identified LSM7, an alternative splicing factor, may be responsible for the major altered events. Conclusions: Our study reveals the notable differences of response to T cells among breast cancer types which may facilitate the development or improvement of tumor immunotherapy.How to cite: Zhao L, Yang X, Feng C, et al. Triple-negative breast cancer cells respond to T cells severely at the alternative splicing layer. Electron J Biotechnol 2021;50.https://doi.org/10.1016/j.ejbt.2021.01.001

In this paper, using the continuum-discontinuum element method (CDEM), the fragmentation and outburst process of coal specimen are simulated, and the main factors affecting coal breaking and outburst are explored. The results show that after the coal seam is uncovered, coal generates obvious failure and outburst trend. Near coal-free surface, the fracture coal blocks generate significant displacement, resulting in larger opening widths of coal cracks. Coal deep generates the cracks without an obvious opening width. The crack density of coal with pore gas is larger than those of coal without gas, and it is larger than those of coal without pores. However, in the early stage of coal failure, the obvious separation and outburst ranges of coal with gas are smaller than those of coal without gas, and are smaller than those of coal without pores. The numbers of fracture coal blocks show an increase with the growth of in situ stress, pore ratio and gas pressure. The effect of in situ stress on fracture coal block number (517–10,203) is larger than the effect (7589–15,170) of pore ratio and is larger than the effect (5803–6836) of gas pressure. The effect of in situ stress on a maximum size (0.0387–0.138 m) of fracture blocks is larger than the effect (0.0342–0.0733 m) of pore ratio and is larger than the effect (0.0454–0.0578 m) of gas pressure. The coal outburst velocity and range show an increase with the growth of gas pressure and in situ stress (3.77–5.65 m/s); however, the coal outburst shows a slow decrease with a growth of pore ratio. The effect of gas pressure on the coal outburst velocity (11.51–21.9 m/s) is larger than the effect (3.77–5.65 m/s) of in situ stress and is larger than the effect (4.52–5.23 m/s) of pore ratio. This investigation is beneficial to understand the mechanisms of coal–gas outburst in coal mining and roadway excavation.

Abstract Background and aims It has been reported that Helicobacter pylori (HP) infection was more prevalent in infertile populations. HP infection could lead to decreased sperm parameters, and treating the HP infection could improve the quality of sperm. However, studies investigating the relationship between infertility and HP infection are still limited, and more evidence is required. Therefore, we performed the present study to investigate the impact of HP infection on sperm quality in males and on ovarian reserve in females. Methods A total of 16,522 patients who visited the Second Hospital of Zhejiang University from January 2016 to June 2019 due to abdominal discomfort and underwent a 13/14C-urea breath HP test were included in this retrospective cross-sectional study. Among them, 565 had performed sperm analysis or ovarian reserve tests in the past three months and were involved for further analyses. Sperm parameters were examined with a computer-assisted sperm analysis system, and serum anti-Müllerian hormone (AMH) and sex hormones were tested with an electrochemiluminescence method. Results Among 363 patients who underwent the sperm test, 136 (37.47%) had HP infection. Among 202 patients who underwent the AMH test, 55 (27.23%) had HP infection. There was no difference in sperm concentration and motility between the HP+ and HP− groups (P > 0.05). Further subgroup analyses stratified into 5-year age groups confirmed that there was no significant difference in sperm parameters (P > 0.05). When pooled with previously published data, no significant difference in sperm concentration or motility was found (P > 0.05). Meanwhile, this study found that the serum AMH level was similar between the HP+ and HP− groups (P > 0.05). Further subgroup analyses confirmed that there was no significant difference in serum AMH level (P > 0.05). Conclusions There were no differences in sperm parameters and AMH levels based on history of HP infection among Chinese patients.

Abstract Background Baicalin, the main metabolic component of Scutellaria baicalensis Georgi, has various pharmacological properties including anti-inflammatory, anti-oxidant, anti-apoptotic, anti-bactericidal and anti-viral. The purpose of this study was to investigate the anti-Marek’s disease virus (MDV) activities of baicalin in CEF cells. Results Here, we showed that baicalin could inhibit viral mRNA, protein levels and overall plaque formation in a time-dependent manner. We also found that baicalin could consistently inhibit MDV replication and directly affect the virus infectivity. Moreover, baicalin treatment has no effect on expression level of antiviral cytokine and inflammatory cytokines in MDV infected CEFs. Conclusions These results demonstrate that baicalin could be a potential drug against MDV infection.