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In this study, the effect of recombinant porcine interferon alpha (rPoIFNα) on porcine transmissible gastroenteritis virus inactivated vaccine (TGEV IV) in terms of immunological augmentation was examined. Seven experimental piglet groups, including PBS group, rPoIFNα group, inactivated vaccine (IV) alone group, 4.0x104 U rPoIFNα+IV group, 2.0x105 U rPoIFNα+IV group,1.0x106 U rPoIFNα+IV group, 5.0x106 U rPoIFNα+IV group, were divided. The piglets in each group received a secondary vaccination at 28 days following the initial immunization. By using the ELISA assay, neutralization assay, MTT assay, and flow cytometry, we measured anti- TGEV-specific antibody expressions, neutralization antibodies, as well as lymphocyte proliferation index (Stimulation index, SI), specific IL-4 and IFN-γ production, and T cell subpopulations (CD3+, CD4+, and CD8+). Piglets injected with IV supplemented with rPoIFNα at 1.0x106 U or 5.0x106 U developed significantly higher anti-TGEVspecific and neutralizing antibodies compared to those treated with IV alone. IV therapy with rPoIFNα at 1.0x106 U or 5.0x106 U can boost cellular immunity against TGEV by increasing SI, IL-4, IFN-γ, and the ratio of CD3+, CD4+, and CD8+ cell subgroups. The IV+5.0x106 U rPoIFNα group showed a considerably larger immune increase than the IV+2.0x105 U rPoIFNα group, suggesting that it works in a dose-dependent manner. Therefore, rPoIFNα at 1.0x106 U or 5.0x106 U enhances the immune response against TGEV IV and may function as an immune stimulant.

The oxidation behavior of a medium carbon Cr–Mn–Si alloyed steel was investigated under a mold flux melt environment exposed to different high temperatures of 1175–1425 °C, and holding time of 5–85 min. The results showed that the thicknesses of oxide layers contained Cr–Mn–Si oxide particles significantly increased from 10 to 183 μm with the increasing of oxidation temperature and holding time. The selective oxidation of Cr, Mn and Si elements in the grain boundaries is caused by the diffusion of free oxygen (O2−) migrating from mold flux to steel matrix, which leads to the growth of oxide layer thicknesses. Moreover, the oxidation rate constant (kp) of the Cr–Mn–Si alloyed steel was revealed under the mold flux environment at the temperatures of 1175–1375 °C. In addition, it was found that the growth kinetics of oxide particles in the oxide layer consists of a rapid growth stage and a slow-steady growth stage, and the growth of oxide particles is co-controlled by the diffusion of O2− within the steel matrix and the competing oxidation reactions involving Fe, Cr, Mn, and Si elements.

In order to meet the requirements of concrete filling, vibration, and pumping during the construction of the concrete-filled steel tube (CFST) arch bridge, the C80 expansive self-compacting concrete (SCC) is prepared using the absolute volume method. This research investigates the effects of MgO-based expansive agent (EA) and water-to-binder ratio (w/b) on the fresh properties, mechanical properties, autogenous shrinkage, and creep behaviors of expansive SCC. The microstructure of expansive SCC is analyzed by scanning electronic microscopy (SEM) and nuclear magnetic resonance (NMR). Results show that, as the MgO-based EA content increases from 5 % to 10 %, its effect on fresh properties of SCC is negligible. The addition of EA retards the hydration reaction of cement at early ages, thus delaying the strength development. However, the long-term mechanical strengths of the SCC are enhanced, due to the expansion product refines the microstructure at later ages. Moreover, the 14-day autogenous shrinkage of SCC with 10 % EA content is eliminated and shows the micro expansion (155.3 με). The microstructural analysis shows that the porosity of SCC with 10 % EA content is 1.8 % while the pore throat below 0.1 μm accounting for 55 % and the pore size above 30 μm is negligible. This research reveals the mechanism of the effects of MgO-based EA and w/b on the volume stability of the SCC, facilitating the application of expansive SCC in CFST composite structures.

ABSTRACTEvidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 μg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.

Direct imaging of semi-solid lipids, such as myelin, is of great interest as a noninvasive biomarker of neurodegenerative diseases. Yet, the short T2 relaxation times of semi-solid lipid protons hamper direct detection through conventional magnetic resonance imaging (MRI) pulse sequences. In this study, we examined whether a three-dimensional ultrashort echo time (3D UTE) sequence can directly acquire signals from membrane lipids. Membrane lipids from red blood cells (RBC) were collected from commercially available blood as a general model of the myelin lipid bilayer and subjected to D2O exchange and freeze-drying for complete water removal. Sufficiently high MR signals were detected with the 3D UTE sequence, which showed an ultrashort T2* of ∼77–271 µs and a short T1 of ∼189 ms for semi-solid RBC membrane lipids. These measurements can guide designing UTE-based sequences for direct in vivo imaging of membrane lipids.

Abstract Background We investigated the relationship of two commonly used quantitative ultrasound (QUS) parameters, speed of sound (SoS) and attenuation coefficient (α), with water and macromolecular contents of bovine cortical bone strips as measured with ultrashort echo time (UTE) magnetic resonance imaging (MRI). Methods SoS and α were measured in 36 bovine cortical bone strips utilizing a single-element transducer with nominal 5 MHz center frequency based on the time of flight principles after accommodating for reflection losses. Specimens were then scanned using UTE MRI to measure total, bound, and pore water proton density (TWPD, BWPD, and PWPD) as well as macromolecular proton fraction and macromolecular transverse relaxation time (T2-MM). Specimens were also scanned using microcomputed tomography (μCT) at 9-μm isometric voxel size to measure bone mineral density (BMD), porosity, and pore size. The elastic modulus (E) of each specimen was measured using a 4-point bending test. Results α demonstrated significant positive Spearman correlations with E (R = 0.69) and BMD (R = 0.44) while showing significant negative correlations with porosity (R = -0.41), T2-MM (R = -0.47), TWPD (R = -0.68), BWPD (R = -0.67), and PWPD (R = -0.45). Conclusions The negative correlation between α and T2-MM is likely indicating the relationship between QUS and collagen matrix organization. The higher correlations of α with BWPD than with PWPD may indicate that water organized in finer structure (bound to matrix) provides lower acoustic impedance than water in larger pores, which is yet to be investigated thoroughly. Relevance statement This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone, including the collagenous matrix and water. Investigating the full potential of QUS and its validation facilitates a more affordable and accessible tool for bone health monitoring in clinics. Key points • Ultrasound attenuation demonstrated significant positive correlations with bone mechanics and mineral density. • Ultrasound attenuation demonstrated significant negative correlations with porosity and bone water contents. • This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone. Graphical Abstract

The survivability of out-of-hospital cardiac arrest patients in China is notably low, at less than 1%, primarily due to difficulties in accessing nearby Automated External Defibrillator (AED) devices during emergencies. Therefore, the strategic deployment of AEDs is crucial for improving patient survival. This study adopts a novel hybrid methodology that integrates the Fuzzy Analytic Network Process (FANP) and Grey Relational Analysis (GRA) to assess and prioritize the critical factors for optimizing AED deployment in China. In the FANP model, the rate of cardiopulmonary resuscitation training among individuals in the area, the rate of AED training among individuals in the area, and records of AED device usage within the area are key factors for improving the effectiveness of AED deployment. Furthermore, in the GRA model, the factors with higher gray relational degrees are Visibility, Social Environment, and Accessibility. This analysis sheds light on which secondary indicators can have the most significant impact on improving specific primary indicators. The insights from this study can guide the optimization of AED deployment strategies in China and offer practical solutions for enhancing the deployment of relevant public medical facilities.

PurposeTo test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model.MethodsNon-aqueous myelin protons have ultrashort T2s and are “invisible” with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T2 water signal so that the remaining signal is from the ultrashort T2 myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (n = 4) or control chow (n = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin.ResultsIR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content.Conclusions3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.

Quantitative MRI techniques could be helpful to noninvasively and longitudinally monitor dynamic changes in spinal cord white matter following injury, but imaging and postprocessing techniques in small animals remain lacking. Unilateral C5 hemisection lesions were created in a rat model, and ultrashort echo time magnetization transfer (UTE-MT) and diffusion-weighted sequences were used for imaging following injury. Magnetization transfer ratio (MTR) measurements and preferential diffusion along the longitudinal axis of the spinal cord were calculated as fractional anisotropy or an apparent diffusion coefficient ratio over transverse directions. The area of myelinated white matter was obtained by thresholding the spinal cord using mean MTR or diffusion ratio values from the contralesional side of the spinal cord. A decrease in white matter areas was observed on the ipsilesional side caudal to the lesions, which is consistent with known myelin and axonal changes following spinal cord injury. The myelinated white matter area obtained through the UTE-MT technique and the white matter area obtained through diffusion imaging techniques showed better performance to distinguish evolution after injury (AUCs > 0.94, p < 0.001) than the mean MTR (AUC = 0.74, p = 0.01) or ADC ratio (AUC = 0.68, p = 0.05) values themselves. Immunostaining for myelin basic protein (MBP) and neurofilament protein NF200 (NF200) showed atrophy and axonal degeneration, confirming the MRI results. These compositional and microstructural MRI techniques may be used to detect demyelination or remyelination in the spinal cord after spinal cord injury.

Safe, green and efficient industrial production has always been the pursuit of the chemical industry. Since thermal energy is the driving force for most of chemical reactions, an ideal reaction tank would have the capacity to automatically regulate heat conduction rate. In detail, this reaction tank should endow an ability that resists the heat loss when the reaction temperature is lower than the target, while accelerating the heat dissipation when the system is overheated. In this case, this smart reactor can not only minimize energy consumption but also reduce safety risks. Hollow structures are known to reduce heat conductivity. Particularly, the hollow structure with multishells can provide more interfaces and thus further inhibit heat transmission, which would be more favorable for heat isolation. Step forward, by coupling HoMSs with temperature-sensitive polymer, a smart heat isolation material has been fabricated in this work. It performs as a good heat isolator at a relatively lower temperature. A heat insulation effect of 6.5 °C can be achieved for the TSPU/3S–TiO2 HoMSs with a thickness of 1 mm under the temperature field of 50 °C. The thermal conductivity of composite material would be raised under overheating conditions. Furthermore, this composite displays an unusual two-stage phase transformation during heating. Benefiting from the unique multishelled structure, energy is found to be gradually guided into the hollow structure and stored inside. This localized heat accumulation enables the composite to be a potential coating material for intelligent thermal-regulator and site-defined micro-reactor.

Our minds wander for half of our waking time, and evidence suggests that a wandering mind is often an unhappy one. However, the specific contents of unpleasant thoughts and feelings during mind wandering remain undiscovered. Here, we aim to investigate if mind wandering may closely relate to feelings of loneliness, such as experiencing a sense of being left out and isolated from others, within a cross-cultural context. Our study involved participants from the general populations of China (N= 1123) and Germany (N= 1018), surveyed between December 2021 and February 2022. Using an online survey tool, we assessed self-reported mind wandering (measured by the Mind Wandering Spontaneous and Deliberate Scale) and loneliness (measured by the UCLA Loneliness Scale), while controlling for self-esteem (measured by the Rosenberg Self-Esteem Scale), self-efficacy (measured by the General Self-efficacy Scale), and mental health status (measured by the General Health Questionnaire). Strikingly, we found that approximately half of the respondents in both China and Germany reported feelings of loneliness (49.8% in China versus 49.5% in Germany, p= 0.936). Regression analysis further revealed that higher levels of self-reported spontaneous (β = 0.04, p= 0.047) and deliberate mind wandering (β = 0.05, p= 0.009) were associated with higher levels of loneliness, even after controlling for sociodemographic variables, self-esteem, self-efficacy, and mental health status. These findings suggest that loneliness is a pervasive experience across cultures and may serve as a driving factor underlying unpleasant thoughts and feelings during episodes of mind wandering.

PurposeThis study aims to comprehensively evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) in patients with advanced, recurrent, or metastatic cervical cancer (ARMCC) and identify the population that may benefit the most.MethodsWe conducted a search of PubMed, EMBASE, and the Cochrane Collaboration Library from their inception to September 2023. We extracted and analyzed the results related to the efficacy and safety of PD-1 in patients with ARMCC. The primary endpoints included the overall objective response rate (ORR) and adverse events (AEs), while the secondary endpoints encompassed the 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, as well as OS and PFS. We used a random effects model to conduct a meta-analysis on single-group rates, and the Mantel-Haenszel method was utilized to compare the ORR and the incidence of AEs.ResultsOur study included a total of 21 trials involving 2,097 patients. The ORR of the combination of PD-1 inhibitors with chemotherapy was 56.36%, the combination of PD-1 inhibitors with anti-angiogenic agents was 38.72%, the combination of PD-1 inhibitors with Cytotoxic T-lymphocyte antigen 4 inhibitors was 25.60%, and PD-1 inhibitor monotherapy was 15.99%. The subgroup analysis showed that the group of patients with squamous cell carcinoma (SCC) exhibited a significantly higher ORR compared to the non-SCC group in patients who received PD-1 inhibitors combined with other anti-tumor drugs (Odds Ratio =2.43, P=0.002). Additionally, the group of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 exhibited a significantly higher ORR compared to the PD-L1 CPS

Background Alcohol use disorder (AUD) is one of the most common substance use disorders. People with AUD are in great need of highly accessible and comprehensive management, involving medicine, exercise, and psychotherapy. However, due to limited resources, providing comprehensive treatment for every patient is challenging. Virtual agent-assisted intelligent rehabilitation treatment can improve the accessibility of comprehensive management. Objectives This randomized controlled trial aims to test whether the virtual agent-assisted intelligent rehabilitation treatment (Echo-app-v2.0) plus treatment as usual (TAU) has greater efficacy than only TAU in AUD. Methods One hundred participants with AUD will be recruited and randomly assigned to either TAU or virtual agent-assisted intelligent rehabilitation treatment plus TAU based on the 1:1 ratio. The virtual agent-assisted intelligent rehabilitation treatment is delivered by the Echo app v2.0 developed by our research team. Participants will be assessed at baseline, week 4 of treatment, one month, and three months after the end of treatment. The primary outcome is the participants’ craving for alcohol, measured by Visual Analogue Scale. Other outcomes include the use of alcohol, motivation for treatment, coping style, depression, anxiety, impulsivity, stress, and sleep quality. Discussion The virtual agent, with vivid human image, high privacy, and the ability to interact with users, has the potential to play an important role in the delivery of digital psychotherapy. The development of Echo app v2.0 has the possibility to raise the availability of comprehensive treatment for people with AUD.

ABSTRACTEpidemiological and interventional studies have been rarely conducted among those with positive interferon-γ release assay (IGRA) results and radiologically inactive tuberculosis (TB) lesions on chest radiograph. This study aimed to estimate the effectiveness and safety of a six-week twice-weekly regimen (rifapentine plus isoniazid) among this key population in rural China. First, chest digital radiography was conducted to screen individuals with inactive TB lesions. Then, the identified participants were further evaluated and eligible participants with IGRA-positive results were included in subsequent randomized controlled trial (RCT). Of 44,500 recruited residents, 2,988 presented with radiographically inactive TB among 43,670 with complete results of chest radiography and questionnaire, and 28.61% (855/2,988) tested IGRA positive. Subsequently, 677 eligible participants were included in this RCT (345 in the preventive treatment group and 332 in the untreated control group). The treatment completion rate was 80.00% (276/345), and 11.88% (41/345) participants reported side-effects including two cases of hepatotoxicity (0.58%, 2/345). In the intention-to-treat analysis, the cumulative incidence rate of microbiologically confirmed active TB during a two-year follow-up was 1.16 (95% confidence interval [CI]: 0.03–2.29) in the preventive treatment group and 1.51 (95% CI: 0.20–2.82) in the control group (p = .485). Subgroup analyses showed that the protective rates were 55.42% (95% CI: 10.33–93.07%) and 80.17% (95% CI: 25.36–97.96%) for participants with fibrosis and for those aged ≥60 years, respectively. The expected treatment effect was not observed for the six-week regimen in this study. Future studies with sufficient sample size are needed to verify our findings.

Abstract Background We sought to determine whether statin treatment has a protective effect on the outcome of critically ill patients on mechanical ventilation. Methods Patients who underwent mechanical ventilation were selected from the MIMIC-III database. Patients with statin usage were allocated into the statin cohort. Patients without any statin use were matched to the statin cohort in a 1:1 ratio by propensity score. To ensure the robustness of the findings, we utilized the gradient boosted model, propensity score analysis, doubly robust estimation and an inverse probability‐weighting model in the statistical procedure. Results Before matching, 17,452 patients were enrolled in the non-statin group and 3,999 in the statin group. After matching, 3,363 patients were enrolled in each group. Compared with nonusers, the use of statins was associated with improved 28-day survival in the unmatched cohort (HR 0.85 95% CI 0.80–0.90, p

In bridge reinforcement projects, damaged T-beams are the most common objects for reinforcement, yet the interface bonding and bending performance of UHPC reinforcement on T-beams have hardly been studied. To ensure the reliability and stability of UHPC-strengthened T-beams in practical applications, this study introduced a post-installed rebar bonding technique to efficiently connect T-beams with UHPC layers. Initially, using ABAQUS software [2020 version] for finite element simulation, this study investigated the effects of various post-installed rebar parameters (horizontal spacing, yield strength, diameter, and matrix concrete strength) on the shear performance of the UHPC and RC interface, obtaining the optimal connection parameters. Subsequently, by comparing shear formulas in domestic and international standards, a new UHPC-RC steel bar interface shear strength theoretical formula with 93.6% accuracy was derived. Finally, finite element simulations analyzed the impact of different post-installed reinforcing bar layout forms and longitudinal spacing, as well as UHPC-strengthened location and layer thickness, on the bending performance of damaged T-beams. The results showed a good match between simulation outcomes and experimental results, applicable for further reinforcement analysis of T-beams. When the horizontal spacing of post-installed rebars is 12d, with diameters ranging from 10 mm to 14 mm, their anchoring capability is efficiently utilized. A square form of a post-installed rebar with a longitudinal spacing of 300 mm effectively improves the ultimate bending load capacity of the strengthened beam. The simulation analysis and theoretical results help in the design and application of post-installed steel connections and UHPC-strengthened structures in UHPC-strengthened reinforced concrete T-beam structures.

Objective: To obtain the starter culture suitable for rice sour soup fermentation, and realize the standard produc-tion of traditional rice sour soup. Methods: The excellent strains of lactic acid bacteria were screened by calcium-dissolving circle method combined with total acid yield and the tolerance experiments of acid and bile salt; The experiment of glycosidase activity was used to screen the excellent strains of yeast. The strains were identified by physiological and biochemical experiments, 16S rDNA and ITS sequence; The compounded two excellent fermentation strains were applied to rice sour soup, and their pH, total acid, total sugar, reducing sugar and sensory quality were analyzed. Results: The strain G1-3 with strong acid-producing ability was selected from 128 strains of lactic acid bacteria, which grew well in the environment of pH3.0 and 0.3% bovine bile salt. The strain G2-2 with strong glycosidase activity was screened from 20 yeasts. The strains G1-3 and G2-2 were identified as Lactobacillus paracasei and Torulaspora indica, respectively. Compared with natural fermentation, the total acid content of indica white sour soup fermented by two strains of bacteria increased by 5 times, while the total sugar and reducing sugar content decreased by 61.53% and 81.02%, respectively; The total acid content in glutinous rice sour soup increased by 18 times, while the content of total sugar and reducing sugar decreased by 68.86% and 86.99%, respectively. Also, the sensory quality of white sour soup fermented by two strains of bacteria was better than that of natural fermentation. Conclusion: The white sour soup fermented by compound starter of G1-3 and G2-2 has excellent quality, which is expected to be applied to the fermentation production of white sour soup.

Power converters have become increasingly important in the power industry. To enhance design reliability and efficiency, real-time simulation is a popular method for testing control units of these devices. FPGA-based real-time simulation is considered a genuine alternative to CPU-based applications as control unit frequencies increase. Although automated tools can map simulation methods from floating-point high-level languages to fixed-point FPGA, manually selecting the fixed-point word length to meet precision requirements involves a significant amount of tedious and repetitive work. Word length selection also impacts FPGA hardware resource usage. This paper proposes an adaptive word length selection method under accuracy constraints to minimize hardware resources. The innovation lies in using error noise models to compute analytical expressions relating simulation model accuracy to word length. The adaptive word length selection process is combined with commercial high-level synthesis tools to achieve high resource optimization performance. A three-phase inverter example demonstrates the benefits of our method in calculating model accuracy and optimizing FPGA hardware resources in simulations.

This study aimed to construct a potential prognostic model for the clinical prediction of esophageal squamous cell adenocarcinoma (ESCA), based on intestinal microbiota-related genes. Microbiome, transcriptome, and clinical phenotype data were downloaded from the TCMA, UCSC, and GEO databases. Intestinal microbiota-related prognostic genes were screened using differential- and univariate Cox regression analyses. The ESCA subtypes were explored based on prognostic genes, followed by infiltration analysis of immune cells in the different subtypes. Feature genes were identified using LASSO and multivariate regression analyses, and a prognostic model was established and validated. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. The amount of Bacteroidetes and Proteobacteria differed significantly between the tumor and paracancerous samples. A total of 17 intestinal microbiota-related prognostic genes were also screened. We then identified three ESCA subtypes that exhibited significant differences in microbiota distribution and immune cell infiltration. Finally, we identified 10 gene signatures that were significantly associated with the survival status of ESCA patients. Furthermore, patients with no immunotherapy response presented a significantly higher risk score and prognostic risk. We constructed a prognostic model based on 10 characteristic genes related to intestinal microbiota, which could potentially predict the prognosis of ESCA patients.

Abstract Background Sepsis-associated encephalopathy (SAE) is one of the most common types of sepsis-related organ dysfunction without overt central nervous system (CNS) infection. It is associated with higher mortality, low quality of life, and long-term neurological sequelae in suspected patients. At present there is no specific treatment for SAE rather than supportive therapy and judicious use of antibiotics, which are sometimes associated with adverse effects. Molecular hydrogen (H2) has been reported to play crucial role in regulating inflammatory responses, neuronal injury, apoptosis and mitochondrial dysfunction in adult models of SAE. Here we report the protective effect of hydrogen-rich saline in juvenile SAE rat model and its possible underling mechanism(s). Materials and methods Rats were challenged with lipopolysaccharide (LPS) at a dose of 8 mg/kg injected intraperitoneally to induce sepsis and hydrogen-rich saline (HRS) administered 1 h following LPS induction at a dose of 5 ml/kg. Rats were divided into: sham, sham + HRS, LPS and LPS + HRS. At 48 h, rats were sacrificed and Nissl staining for neuronal injury, TUNEL assay for apoptotic cells detection, immunohistochemistry, and ELISA protocol for inflammatory cytokines determination, mitochondrial dysfunction parameters, electron microscopy and western blot analysis were studied to examine the effect of HRS in LPS-induced septic rats. Results Rats treated with HRS improved neuronal injury, improvement in rats’ survival rate. ELISA analysis showed decreased TNF-α and IL-1β and increased IL-10 expression levels in the HRS-treated group. Apoptotic cells were decreased after HRS administration in septic rats. The numbers of GFAP and IBA-1positive cells were attenuated in the HRS-treated group when compared to the LPS group. Subsequently, GFAP and IBA-1 immunoreactivity were decreased after HRS treatment. Mitochondrial membrane potential detected by JC-1 dye and ATP content were decreased in septic rats, which were improved after HRS treatment, while release of ROS was increased in the LPS group reverted by HRS treatment, ameliorating mitochondrial dysfunction. Further analysis by transmission electron microscopy showed decreased number of mitochondria and synapses, and disrupted mitochondrial membrane ultrastructure in the LPS group, while HRS administration increased mitochondria and synapses number. Conclusion These data demonstrated that HRS can improve survival rate, attenuate neuroinflammation, astrocyte and microglial activation, neuronal injury and mitochondrial dysfunction in juvenile SAE rat model, making it a potential therapeutic candidate in treating paediatric SAE.

Overuse of fossil energy has accelerated the development of industrialization and improved the quality of human life. However, it also leads to the excessive emission of CO2, and the greenhouse effect is threatening global climate stability and human health. Various countries have implemented measures and initiatives to promote carbon emission reduction and the carbon cycle. Chemical capture and utilizing CO2 generated by fossil energy combustion has proved an efficient and valuable method. This review describes the recent progress in synthesizing high-value-added oxazolidinones from CO2 as a C1 source. Firstly, the development and value of oxazolidinones are discussed, and the necessity of finding efficient and green chemical synthesis methods for oxazolidinones is proved. Furthermore, the significance of the CO2 cycloaddition reaction in the green and efficient synthesis of oxazolidinones is introduced, and we summarize and compare various transition metal-based and organic-based reaction systems that catalyze the cycloaddition reaction of CO2 to oxazolidinones. In order to achieve potential industrial applications, the significance of novel heterogeneous catalysts, such as atomically dispersed catalysis for the CO2 reduction reaction, is expounded by comparing the characteristics of homogeneous and heterogeneous catalysis. Finally, the interaction mechanism of cycloaddition reaction between CO2 and N-propargylamine is discussed in the metallic and metal-free catalytic system, which provides insights for the precise design and control of the reaction and promotes the further development of catalytic systems.

IntroductionPapillomaviruses (PVs) can cause hyperplasia in the skin and mucous membranes of humans, mammals, and non-mammalian animals, and are a significant risk factor for cervical and genital cancers.MethodsUsing next-generation sequencing (NGS), we identified two novel strains of papillomavirus, PV-HMU-1 and PV-HMU-2, in swabs taken from belugas (Delphinapterus leucas) at Polar Ocean Parks in Qingdao and Dalian.ResultsWe amplified the complete genomes of both strains and screened ten belugas and one false killer whale (Pseudorca crassidens) for the late gene (L1) to determine the infection rate. In Qingdao, 50% of the two sampled belugas were infected with PV-HMU-1, while the false killer whale was negative. In Dalian, 71% of the eight sampled belugas were infected with PV-HMU-2. In their L1 genes, PV-HMU-1 and PV-HMU-2 showed 64.99 and 68.12% amino acid identity, respectively, with other members of Papillomaviridae. Phylogenetic analysis of combinatorial amino acid sequences revealed that PV-HMU-1 and PV-HMU-2 clustered with other known dolphin PVs but formed distinct branches. PVs carried by belugas were proposed as novel species under Firstpapillomavirinae.ConclusionThe discovery of these two novel PVs enhances our understanding of the genetic diversity of papillomaviruses and their impact on the beluga population.

BackgroundGambling behaviors can be exhibited by individuals raised in families with impaired parent-child communication and individuals with more impulsive traits. However, it remains unclear how gambling-related beliefs are modulated by impulsivity traits and parent-child communication styles.MethodsA total of 95 adult patients (age ≥ 18 years) diagnosed via DSM-5 criteria with gambling disorder (GD) completed our questionnaire. Participants filled out pen-and-paper questionnaires that included basic demographic information, the Family Assessment Device (FAD), Parent-Adolescent Communication Scale (PACS), Gambling Attitude and Belief Survey (GABS), and Barratt Impulsiveness Scale (BIS). We used a moderation mediation model to explore the relationship between variables. The study results were considered statistically significant if p < 0.05, or the 95% confidence interval did not contain zero.ResultsThe scores of the problems in communication with mother subscale (PCMS) of PACS were significantly positively correlated with the scores of GABS and the general functioning 12-item subscale (GF12) of FAD. The relationship between the scores of GF12 and GABS was completely mediated [β = 4.83, (1.12, 10.02)] by PCMS scores, and the BIS scores moderated this relationship: the predictive path between GF12 and PCMS scores [index of moderated was β = −0.25, (−0.60, −0.04)], and the indirect predictive front path between the scores of GF12 and GABS were significant only in subjects with low BIS scores.ConclusionThese findings suggest that poor general functioning of the family may increase gambling-related beliefs as a result of communication problems with mothers, and this result is only significant for individuals with low impulsivity. When treating patients with GD, more treatment of mother-child communication issues and individual impulsivity may be more conducive to their recovery.

Pancreatic ductal adenocarcinoma (PDAC) is the leading cause of cancer-related mortality, primarily due to the abundance of cancer-associated fibroblasts (CAFs), depleted effector T cells, and increased tumor cell stemness; hence, there is an urgent need for efficient biomarkers with prognostic and therapeutic potential. Here, we identified BHLHE40 as a promising target for PDAC through comprehensive analysis and weighted gene coexpression network analysis of RNA sequencing data and public databases, taking into account the unique characteristics of PDAC such as cancer-associated fibroblasts, infiltration of effector T cells, and tumor cell stemness. Additionally, we developed a prognostic risk model based on BHLHE40 and three other candidate genes (ITGA2, ITGA3, and ADAM9) to predict outcomes in PDAC patients. Furthermore, we found that the overexpression of BHLHE40 was significantly associated with T stage, lymph node metastasis, and American Joint Committee on Cancer (AJCC) stage in a cohort of 61 PDAC patients. Moreover, elevated expression levels of BHLHE40 were validated to promote epithelial–mesenchymal transition (EMT) and stemness-related proteins in BXPC3 cell lines. Compared to the parent cells, BXPC3 cells with BHLHE40 overexpression showed resistance to anti-tumor immunity when co-cultured with CD8+ T cells. In summary, these findings suggest that BHLHE40 is a highly effective biomarker for predicting prognosis in PDAC and holds great promise as a target for cancer therapy.

Introduction: The objective of this study was to assess the bi-exponential relaxation times and fractions of the short and long components of the human patellar tendon ex vivo using three-dimensional ultrashort echo time T1ρ (3D UTE-T1ρ) imaging. Materials and Methods: Five cadaveric human knee specimens were scanned using a 3D UTE-T1ρ imaging sequence on a 3T MR scanner. A series of 3D UTE-T1ρ images were acquired and fitted using single-component and bi-component models. Single-component exponential fitting was performed to measure the UTE-T1ρ value of the patellar tendon. Bi-component analysis was performed to measure the short and long UTE-T1ρ values and fractions. Results: The single-component analysis showed a mean single-component UTE-T1ρ value of 8.4 ± 1.7 ms for the five knee patellar tendon samples. Improved fitting was achieved with bi-component analysis, which showed a mean short UTE-T1ρ value of 5.5 ± 0.8 ms with a fraction of 77.6 ± 4.8%, and a mean long UTE-T1ρ value of 27.4 ± 3.8 ms with a fraction of 22.4 ± 4.8%. Conclusion: The 3D UTE-T1ρ sequence can detect the single- and bi-exponential decay in the patellar tendon. Bi-component fitting was superior to single-component fitting.

Abstract Background Orientia tsutsugamushi (O. tsutsugamushi), an obligate intracellular bacterium, is transmitted to humans through infected larval trombiculid mite bites, causing scrub typhus. Mixed genotypes of O. tsutsugamushi in canonical conserved genes were reported in 8–25% of blood samples from patients. Yet, there are few clinical descriptions of these mixed O. tsutsugamushi-infected patients. Case presentation We report a patient with scrub typhus complicated with pulmonary involvement and hepatic dysfunction, who carried mixed genotypes of the conserved genes but had a single immune-dominant 56-kDa type-specific antigen (tsa56) genotype. The patient was successfully recovered by doxycycline treatment. Conclusions In this reported case, both patient’s eschar and blood samples have repeatedly shown the same results, i.e., no variants were discovered in tsa56 gene that bears multiple hypervariable regions. Whereas the selected highly conserved genes were identified with up to 32 variants in a 2700 base-pair concatenated sequence. The prevalence, disease severity and mechanism of these single-tsa56-genotype mixed infections remain to be investigated on a large scale with more cases.

Scrub typhus, caused by mite-borne Orientia tsutsugamushi (O. tsutsugamushi), is a major febrile disease in the Asia-Pacific region. The DNA load of O. tsutsugamushi in the blood was previously found to be significantly higher in patients with fatal disease than those with non-fatal disease and correlated with the duration of illness, presence of eschar, and hepatic enzyme levels. In this prospective observation study, we analyzed the association of bacterial DNA load with clinical features, disease severity, and genotype using real-time PCR targeting the 56 kDa TSA gene of O. tsutsugamushi in the blood samples of 117 surviving patients with scrub typhus who had not received appropriate antibiotic treatment. The median O. tsutsugamushi DNA load was 3.11×103 copies/mL (range, 44 to 3.3×106 copies/mL). The severity of patients was categorized as mild, moderate, and severe based on the number of dysfunctional organs, and no significant difference in O. tsutsugamushi DNA load was found among these groups. Patients infected with the Karp group showed a significantly higher O. tsutsugamushi DNA load than those in the Gilliam (P

Background: Core training can enhance athletic performance by enhancing core strength and stability. To achieve this outcome, however, a tailored training program is required; the normal military training curriculum is inadequate. The connection between cumulative weekly extracurricular training time, cumulative weekly extracurricular core training time and cadet performance is unknown. Methods: The association between cumulative weekly extracurricular training time, cumulative weekly extracurricular core training time and performance has been discovered using a descriptive epidemiological study methodology. Questionnaires were used to collect information on personal characteristics and weekly cumulative extracurricular (core) training time, as well as the results of the Chinese Army Physical Fitness Test (C-APFT), which included 100-m dash, 5000-m run, 3000-m armed training run, 400-m steeplechase, 800 m breaststroke, horizontal bar pull-ups, 2-min sit-ups, 2-min push-ups, and hand grenade throwing. This study recruited two hundred and twenty male cadets (aged 18 to 23 years, 19.68 ± 0.91) from a military medical university. Results: (a) The correlation between cumulative weekly extracurricular training time and C-APFT score is significant. The 100-m dash, 5000-m run, 3000-m armed training run, 400-m steeplechase, and 2-min push-ups performed the best when participants exercised for 5 to 10 h per week. (b) The number of cadets scoring good or excellent on the C-APFT improves with cumulative weekly extracurricular core training time. The recommended amount of core training for cadets per week is 120 min. (c) The average cumulative weekly extracurricular core training time was a effective predictor of performance on the 400-m steeplechase (R2 = 0.470, F = 10.641, P＜0.01), horizontal bar pull-ups (R2 = 0.238, F = 68.191, P＜0.01), 2-min sit-ups (R2 = 0.280, F = 84.710, P＜0.01), 100-m run (R2 = 0.031, F = 6.920, P＜0.01), 3000-m armed training run (R2 = 0.025, F = 5.603, P＜0.05), 2-min push-ups (R2 = 0.019, F = 4.295, P＜0.05), and hand grenade tossing (R2 = 0.025, F = 5.603, P＜0.05). Conclusions: Active participation in extracurricular core training can improve cadets' C-APFT scores. An average cumulative weekly extracurricular training duration of 5–10 h showed the most progress, and more than 120 min per week was ideal for extracurricular core training. The amount of extracurricular time spent on core training exercises each week can be used as a predictor of the C-APFT.

IntroductionUltrashort echo time (UTE) MRI enables quantitative assessment of cortical bone. The signal ratio in dual-echo UTE imaging, known as porosity index (PI), as well as the signal ratio between UTE and inversion recovery UTE (IR-UTE) imaging, known as the suppression ratio (SR), are two rapid UTE-based bone evaluation techniques developed to reduce the time demand and cost in future clinical studies. The goal of this study was to investigate the performance of PI and SR in detecting bone quality differences between subjects with osteoporosis (OPo), osteopenia (OPe), and normal bone (Normal).MethodsTibial midshaft of fourteen OPe (72 ± 6 years old), thirty-one OPo (72 ± 6 years old), and thirty-seven Normal (36 ± 19 years old) subjects were scanned using dual-echo UTE and IR-UTE sequences on a clinical 3T scanner. Measured PI, SR, and bone thickness were compared between OPo, OPe, and normal bone (Normal) subjects using the Kruskal–Wallis test by ranks. Spearman’s rank correlation coefficients were calculated between dual-energy x-ray absorptiometry (DEXA) T-score and UTE-MRI results.ResultsPI was significantly higher in the OPo group compared with the Normal (24.1%) and OPe (16.3%) groups. SR was significantly higher in the OPo group compared with the Normal (41.5%) and OPe (21.8%) groups. SR differences between the OPe and Normal groups were also statistically significant (16.2%). Cortical bone was significantly thinner in the OPo group compared with the Normal (22.0%) and OPe (13.0%) groups. DEXA T-scores in subjects were significantly correlated with PI (R=-0.32), SR (R=-0.50), and bone thickness (R=0.51).DiscussionPI and SR, as rapid UTE-MRI-based techniques, may be useful tools to detect and monitor bone quality changes, in addition to bone morphology, in individuals affected by osteoporosis.

IntroductionAlthough many lesion-based MRI biomarkers in multiple sclerosis (MS) patients were investigated, none of the previous studies dealt with the signal intensity variations (SIVs) of MS lesions. In this study, the SIVs of MS lesions on direct myelin imaging and standard clinical sequences as possible MRI biomarkers for disability in MS patients were assessed.MethodsTwenty seven MS patients were included in this prospective study. IR-UTE, FLAIR, and MPRAGE sequences were employed on a 3T scanner. Regions of interest (ROIs) were manually drawn within the MS lesions, and the cerebrospinal fluid (CSF) and signal intensity ratios (SIR) were calculated from the derived values. Variations coefficients were determined from the standard deviations (Coeff 1) and the absolute differences (Coeff 2) of the SIRs. Disability grade was assessed by the expanded disability status scale (EDSS). Cortical/gray matter, subcortical, infratentorial, and spinal lesions were excluded.ResultsThe mean diameter of the lesions was 7.8 ± 1.97 mm, while the mean EDSS score was 4.5 ± 1.73. We found moderate correlations between the EDSS and Coeff 1 and 2 on IR-UTE and MPRAGE images. Accordingly, Pearson’s correlations on IR-UTE were R = 0.51 (p = 0.007) and R = 0.49 (p = 0.01) for Coeff 1 and 2, respectively. For MPRAGE, Pearson’s correlations were R = 0.5 (p = 0.008) and R = 0.48 (p = 0.012) for Coeff 1 and 2, respectively. For FLAIR, only poor correlations could be found.ConclusionThe SIVs of MS lesions on IR-UTE and MPRAGE images, assessed by Coeff 1 and 2, could be used as novel potential MRI biomarkers for patients’ disability.

Abstract The long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) acts as tumor-promoting factor in colorectal cancer (CRC). We aimed to elucidate the mechanism by which the transcription factor specificity protein 1 (SP1) regulates TUG1 and microRNAs (miRs)/mRNAs in the context of CRC, which has not been fully studied before. Expression patterns of TUG1 and SP1 were determined in clinical CRC samples and cells, followed by identification of their interaction. Next, the functional significance of TUG1 in CRC was investigated. An in vivo CRC model was established to validate the effect of TUG1. The results demonstrated that TUG1 and SP1 were highly-expressed in CRC, wherein SP1 bound to the TUG1 promoter and consequently, positively regulated its expression. Silencing of TUG1 caused suppression of CRC cell growth and promotion of cell apoptosis. TUG1 could bind to miR-421 to increase KDM2A expression, a target gene of miR-421. TUG1 could activate the ERK pathway by impairing miR-421-targeted inhibition of KDM2A. Additionally, SP1 could facilitate the tumorigenesis of CRC cells in vivo by regulating the TUG1/miR-421/KDM2A/ERK axis. Altogether, the current study emphasizes the oncogenic role of TUG1 in CRC, and illustrates its interactions with the upstream transcription factor SP1 and the downstream modulatory axis miR-421/KDM2A/ERK, thus offering novel insights into the cancerogenic mechanism in CRC.

An improved artificial bee colony algorithm (IABC) was proposed to solve the problems of the k-means clustering (KMC) algorithm, such as poor global search ability, sensitive selection of initial cluster center, randomness of initialization, precocity and slow convergence of the original artificial bee colony (ABC) algorithm. To improve the efficiency of iterative optimization process, a fitness function adapted to KMC algorithm and a position updating formula based on global guidance were constructed. By comparing the improved artificial bee colony algorithm with the original artificial bee colony algorithm and particle swarm optimization algorithm, it is confirmed that IABC algorithm converges speed block and overcomes the shortcoming of the original algorithm which is easy to fall into local optimal solution. IABC algorithm is combined with KMC to get better clustering effect, and the algorithm is used to select typical wind power output scenarios, which plays an important role in actual production.

A Susceptible Infective Recovered (SIR) model is usually unable to mimic the actual epidemiological system exactly. The reasons for this inaccuracy include observation errors and model discrepancies due to assumptions and simplifications made by the SIR model. Hence, this work proposes calibration and prediction methods for the SIR model with a one-time reported number of infected cases. Given that the observation errors of the reported data are assumed to be heteroscedastic, we propose two predictors to predict the actual epidemiological system by modeling the model discrepancy through a Gaussian Process model. One is the calibrated SIR model, and the other one is the discrepancy-corrected predictor, which integrates the calibrated SIR model with the Gaussian Process predictor to solve the model discrepancy. A wild bootstrap method quantifies the two predictors' uncertainty, while two numerical studies assess the performance of the proposed method. The numerical results show that, the proposed predictors outperform the existing ones and the prediction accuracy of the discrepancy-corrected predictor is improved by at least 49.95%.

BackgroundSubstance use disorder is one of the severe public health problems worldwide. Inequitable resources, discrimination, and physical distances limit patients’ access to medical help. Automated conversational agents have the potential to provide in-home and remote therapy. However, automatic dialogue agents mostly use text and other methods to interact, which affects the interaction experience, treatment immersion, and clinical efficacy. ObjectiveThe aim of this paper is to describe the design and development of Echo-APP, a tablet-based app with the function of a virtual digital psychotherapist, and to conduct a pilot study to explore the feasibility and preliminary efficacy results of Echo-APP for patients with methamphetamine use disorder. MethodsEcho-APP is an assessment and rehabilitation program developed for substance use disorder (SUD) by a team of clinicians, psychotherapists, and computer experts. The program is available for Android tablets. In terms of assessment, the focus is on the core characteristics of SUD, such as mood, impulsivity, treatment motivation, and craving level. In terms of treatment, Echo-APP provides 10 treatment units, involving awareness of addiction, motivation enhancement, emotion regulation, meditation, etc. A total of 47 patients with methamphetamine dependence were eventually enrolled in the pilot study to receive a single session of the Echo-APP–based motivational enhancement treatment. The outcomes were assessed before and after the patients’ treatment, including treatment motivation, craving levels, self-perception on the importance of drug abstinence, and their confidence in stopping the drug use. ResultsIn the pilot study, scores on the Stages of Change Readiness and Treatment Eagerness Scale and the questionnaire on motivation for abstaining from drugs significantly increased after the Echo-APP–based treatment (P

Abstract Autophagy is a highly conserved catabolic process seen in eukaryotes and is essentially a lysosome-dependent protein degradation pathway. The dysregulation of autophagy is often associated with the pathogenesis of numerous types of cancers, and can not only promote the survival of cancer but also trigger the tumor cell death. During cancer development, the microbial community might predispose cells to tumorigenesis by promoting mucosal inflammation, causing systemic disorders, and may also regulate the immune response to cancer. The complex relationship between autophagy and microorganisms can protect the body by activating the immune system. In addition, autophagy and microorganisms can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses involved in cancer progression. Various molecular mechanisms, correlating the microbiota disorders and autophagy activation, control the outcomes of protumor or antitumor responses, which depend on the cancer type, tumor microenvironment and disease stage. In this review, we mainly emphasize the leading role of autophagy during the interaction between pathogenic microorganisms and human cancers and investigate the various molecular mechanisms by which autophagy modulates such complicated biological processes. Moreover, we also highlight the possibility of curing cancers with multiple molecular agents targeting the microbiota/autophagy axis. Finally, we summarize the emerging clinical trials investigating the therapeutic potential of targeting either autophagy or microbiota as anticancer strategies, although the crosstalk between them has not been explored thoroughly.

BackgroundDiabetes mellitus (DM) patients with latent tuberculosis infection (LTBI) have an increased risk of developing active tuberculosis (TB) due to impaired immunity. The performance of currently available immune response-based assays for identification of TB infection had been rarely evaluated in patients with type 2 DM (T2DM) in China.MethodsA prospective study was conducted to investigate the status of LTBI in patients with confirmed T2DM. At the baseline survey, the prevalence of LTBI was tested using interferon-gamma release assay (IGRA), tuberculin skin test (TST) and creation tuberculin skin test (C-TST) in parallel. After a 3-month interval, the participants were retested by the three assays to estimate their performance in the serial testing.ResultsA total of 404 participants with T2DM were included in the study. At baseline, after excluding active TB, the prevalence of LTBI identified by TST (≥ 10 mm), C-TST (≥ 5 mm) and IGRA (≥ 0.35 IU/ml) were 9.65% (39/404), 10.40% (42/404) and 14.85% (60/404), respectively. The concordance of TST and C-TST results with IGRA results was 86.39% (349/404) and 92.08% (372/404) with a Kappa coefficient of 0.37 [95% confidence interval (CI): 0.24– 0.50] and 0.64 (95% CI: 0.53– 0.76), respectively. After a 3-month interval, the continuous results of TST, C-TST and IGRA were observed to be increased with testing conversion for 50, 26 and 27 patients, respectively. For TST and C-TST conversions, the distribution of their quantitative results in serial tests varied significantly when further classified by baseline IGRA dichotomous results.ConclusionIn studied patients with T2DM, C-TST showed higher consistency with IGRA as compared to TST. The present of conversion observed in serial testing suggested that boosting effect of skin testing should be considered for identify of LTBI in patients with T2DM.

Abstract The discovery of new viruses is important for predicting their potential threats to the health of humans and other animals. A novel picornavirus was identified from oral, throat, and anal swab samples collected from belugas (Delphinapterus leucas), from Dalian Sun Asia Tourism Holding Co., China, between January and December 2018, using a metagenomics approach. The genome of this novel PicoV-HMU-1 strain was 8197 nucleotides (nt) in length, with a open reading frame (from 1091 to 8074 nt) that encoded a polyprotein precursor of 2328 amino acids. Moreover, the genomic length and GC content of PicoV-HMU-1 were within the ranges found in other picornaviruses, and the genome organization was also similar. Nevertheless, PicoV-HMU-1 had a lower amino acid identity and distinct host species compared with other members of the Picornaviridae family. Phylogenetic trees were constructed based on the P1 and 3D amino acid sequences of PicoV-HMU-1 along with representative members of the Picornaviridae family, which showed that PicoV-HMU-1 was related to unclassified bat picornaviruses groups. These findings suggest that the PicoV-HMU-1 strain represents a potentially novel genus of picornavirus. These data can enhance our understanding of the picornavirus genetic diversity and evolution.

BackgroundThe outbreak of COVID-19 has affected the mental health of adolescents. To describe the Internet behavior-changing patterns of adolescents and to understand the impact of clinical features on changing patterns during the COVID-19 pandemic.Materials and methodsWe conducted a cross-sectional cohort study using data collected through online investigation in China. A total of 625 adolescents completed the online survey from May 15 to June 7, 2020. The adolescents were asked to retrospect to the Internet behaviors and game behaviors of three time periods as follows: before the COVID-19 outbreak in China, during the COVID-19 outbreak in China, and back to school. The clinical variables of the demographic data, family functionality, and emotional and behavioral symptoms were also collected. According to the Internet behaviors and game behaviors patterns across the three time periods, the subjects will be sub-grouped.ResultsFour Internet behavior-changing patterns during the COVID-19 was identified: (1) Continuous Normal Group (55.52%); (2) Normal to Internet Addiction Group (5.28%); (3) Internet Addiction to Normal Group (14.56%); and (4) Continuous Internet Addiction Group (24.64%). Years of education, academic score ranking, family functionality, and emotional and behavioral symptoms were different across the four groups. Proportions of game behaviors, scores of Strengths and Difficulties Questionnaire (SDQ), and SDQ subscale during the period before the COVID-19 outbreak were significant in predicting changing patterns.ConclusionThe Internet behavior patterns of adolescents during the COVID-19 period were various. Clinical features before the COVID-19 pandemic may predict changing patterns. The heterogeneity in characteristics between different changing patterns should be considered when intervening in adolescents’ problematic Internet behavior.

PurposeQuantitative susceptibility mapping (QSM) has surfaced as a promising non-invasive quantitative biomarker that provides information about tissue composition and microenvironment. Recently, ultrashort echo time quantitative susceptibility mapping (UTE-QSM) has been investigated to achieve QSM of short T2 tissues. As the feasibility of UTE-QSM has not been demonstrated in the brain, the goal of this study was to develop a UTE-QSM with an efficient 3D cones trajectory and validate it in the human brain.Materials and methodsAn ultrashort echo time (UTE) cones sequence was implemented in a 3T clinical MRI scanner. Six images were acquired within a single acquisition, including UTE and gradient recalled echo (GRE) images. To achieve QSM, a morphology-enabled dipole inversion (MEDI) algorithm was incorporated, which utilizes both magnitude and phase images. Three fresh cadaveric human brains were scanned using the 3D cones trajectory with eight stretching factors (SFs) ranging from 1.0 to 1.7. In addition, five healthy volunteers were recruited and underwent UTE-QSM to demonstrate the feasibility in vivo. The acquired data were processed with the MEDI-QSM pipeline.ResultsThe susceptibility maps estimated by UTE-QSM showed reliable tissue contrast. In the ex vivo experiment, high correlations were found between the baseline (SF of 1.0) and SFs from 1.1 to 1.7 with Pearson’s correlations of 0.9983, 0.9968, 0.9959, 0.9960, 0.9954, 0.9943, and 0.9879, respectively (all p-values < 0.05). In the in vivo experiment, the measured QSM values in cortical gray matter, juxtacortical white matter, corpus callosum, caudate, and putamen were 25.4 ± 4.0, −21.8 ± 3.2, −22.6 ± 10.0, 77.5 ± 18.8, and 53.8 ± 7.1 ppb, consistent with the values reported in the literature.ConclusionUltrashort echo time quantitative susceptibility mapping enables direct estimation of the magnetic susceptibility in the brain with a dramatically reduced total scan time by use of a stretched 3D cones trajectory. This technique provides a new biomarker for susceptibility mapping in the in vivo brain.

The Ziyun-Luodian area of southern Guizhou province in China is chosen as the research area and the Dawuba formation in Carboniferous system is the target stratum in this paper. Combined with laboratory experiments and mathematical analyses, geological evaluations on organic geochemistry, physical property of the reservoir, and gas bearing feature are all studied, and geological controls on gas occurrence are then analyzed. The following conclusions are achieved. The organic type is mainly II2 or III. TOC is generally in a range of 1%–3%, and Ro,max ranges from 1.7% to 4.4%, with an average value of 2.4%. Mineral compositions are mainly clay and quartz, with a few calcite and dolomite. The Specific surface area ranges from 6.6 to 29.8 m2/g, with an average value of 15.2 m2/g, and the pore volume varies from 0.012 to 0.046 cm3/g, with an average value of about 0.02 cm3/g. There is a strongly and positively linear relationship between specific surface area and pore volume. The porosity is mostly in the range of 1%–3%, with an average value of 1.8%. Most of permeability is below 0.01 mD, with an average value of about 0.004 mD. There is an exponential and positive relationship between porosity and permeability. The gas content is generally below 2.0 m3/t. There are three obvious correlations for gas content versus buried depth ranges of 500–700 m, 700–1,000 m, and 2,700–3,000 m. TOC influences gas content in a linear mode, and Ro,max influences gas content positively. The gas content has a positive relationship with clay mineral and a negative relationship with sapropelic percentage. The porosity and permeability are both positively correlated with gas content. The pore volume has a positive trend with gas content, and the specific surface area has a positively and strongly linear relationship with gas content.

To analyze the geological occurrence and predict the drainage performance of coalbed methane in the central Hunan depression of China, coal samples were collected to conduct physical experiments and numerical simulations. The following conclusions were reached. The vitrinite ranges from 54.37 to 87.80%, the inertinite is between 11.14–25.89%, and exinite is less than 1%. The inorganic components are mainly clay minerals and vary from 0.71 to 5.66%. The major porosity ranges from 7 to 9%, and it is influenced by organic/inorganic components and maturity. Both the vertical and horizontal permeabilities are at a relatively low level, mostly below 0.05 mD, indicating the reservoir is low permeable or non-permeable. The reservoir pressure ranges from 3.74 to 11.58 MPa, which has significant and positive linear correlations with closure pressure and burial depth. Gas content varies from 5 m3/t to 20 m3/t. The theoretical recovery ratio in the Hongshandian mining area is about 61.7%, while the values of the two spots in the Duanpiqiao mining area are 49.1 and 54.5%. Production predictions show that under the permeability of 0.01 mD, 0.05 mD, and 0.10 mD, cumulative gas productions in 10 years for a single well range from 1.7 × 106 m3 to 3.2 × 106 m3, and those for a well group consisting of five wells vary from 10.5 × 106 m3 to 19.2 × 106 m3. Thus, this area will have a high value for coalbed methane exploitation after stimulating the reservoir to increase permeability successfully.

In the original publication, there was a mistake in Figure 1 as published [...]

The reliable folding of proteins is essential for their biological activities, while misfolding may lead to severe diseases, such as Alzheimer’s disease. However, our current knowledge of protein folding arises mainly from studies on small, single-domain proteins rather than multidomain proteins, although the latter make up most of proteins in the cell. Due to complex topological structures and potential interdomain interactions, the refolding of many multidomain proteins often passes through long-lived partially folded intermediates and exhibits complex kinetics. Here, we survey recent progress in understanding the folding and misfolding of multidomain proteins in vitro, with particular reference to theoretical aspects, and briefly summarize the researches on how ribosome regulates folding kinetics of nascent chains during translation in vivo, such as the environmental effects of the ribosome, translation rate effects, and self-interactions effects of polypeptide chain. In addition to these important advances, many questions are still waiting for answer, including: Can a purely structure-based model capture the complex folding kinetics of some multidomain proteins caused by the significant energetic frustration? Is the energy landscape of cotranslational folding still perfectly funnel-like? Are the observed principles that ribosome promotes the proper folding of proteins universal? To what extent does cotranslational folding affect nonnative interactions? Collectively, to address these issues, further innovation and improvement on both experimental techniques and the computational models are in great demand.

To address the problems of serious tool loss and the easy deformation of aero-rotor blade profiles in NC milling technology, electrochemical machining can realize the processing of complex, specially structured products with advanced materials such as nickel alloy Inconel®718 by means of a non-contact electrochemical etching process. In this paper, by analysing the electrochemical reaction state of Inconel®718 alloy in vertical electrolytic processing, the electrolyte side flow of aero-blade electrochemical machining technology is innovatively transplanted to the traditional vertical single-axis feed machining tool, and the corresponding optimized flow channel structure that combines the characteristics of positive flow mode and side flow mode are proposed. Then, the verification test shows that the vertical machining of aero-blade with the characteristics of positive flow and side flow of electrolyte has high machining quality, and its surface error is in the range of 0.02–0.12 mm (the average surface error can reach 0.07 mm), the corresponding surface roughness is 1.16 µm. Therefore, the research foundation and technical potential are laid for the vertical electrochemical machining of the aero-rotor blades.