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Preservation conditions are key to enriching shallow shale gas. Therefore, the veins of two typical wells in the Shixi syncline in northern Guizhou as research objects. Based on core observation, vein thin-section observation, cathodoluminescence, calcite in situ U-Pb dating, fluid inclusion microthermometry, Raman spectrum shift, single well basin simulation, and C-O isotope geochemical analysis, the researchers clarified the characteristics of the veins and the differences in paleofluid activity, as well as their significance for shale gas preservation. The results showed that: 1) a small number of high-angle fractures had developed mainly in the Shixi syncline in northern Guizhou. The width of viens is small and filled primarily with early calcite-quartz and late calcite. The inclusions were mainly methane and brine. The proportion of brine inclusions in the SD1 well was greater than that in the SX1 well. The SD1 well has experienced more intense second-stage uplift and denudation, and the consequent gas loss is serious. 2) The results of the C-O isotope analysis showed that most of the vein-forming fluids were derived from marine carbonate rocks. The O3b had obvious negative deviations of δ13C and δ18O, which were modified by exogenous or deep hydrothermal fluid. The C-O isotope difference between the vein bodies and the surrounding rock of the SX1 well was small, and the preservation conditions were better. 3) The difference in gas content in the Shixi syncline depends on the degree of damage to gas reservoir preservation conditions caused by burial depth and other factors. Shixi syncline is a wide and gentle syncline with central retention enrichment mode. Therefore, clarifying the development of shale veins, the characteristics of paleofluid activity, and their significance for shale gas preservation can lay a foundation for studying the enrichment mechanism of shallow shale gas and thus guide further exploration and development.

Abstract Semantic segmentation of urban street scenes has attracted much attention in the field of autonomous driving, which not only helps vehicles perceive the environment in real time, but also significantly improves the decision-making ability of autonomous driving systems. However, most of the current methods based on Convolutional Neural Network (CNN) mainly use coding the input image to a low resolution and then try to recover the high resolution, which leads to problems such as loss of spatial information, accumulation of errors, and difficulty in dealing with large-scale changes. To address these problems, in this paper, we propose a new semantic segmentation network (HRDLNet) for urban street scene images with high-resolution representation, which improves the accuracy of segmentation by always maintaining a high-resolution representation of the image. Specifically, we propose a feature extraction module (FHR) with high-resolution representation, which efficiently handles multi-scale targets and high-resolution image information by efficiently fusing high-resolution information and multi-scale features. Secondly, we design a multi-scale feature extraction enhancement (MFE) module, which significantly expands the sensory field of the network, thus enhancing the ability to capture correlations between image details and global contextual information. In addition, we introduce a dual-attention mechanism module (CSD), which dynamically adjusts the network to more accurately capture subtle features and rich semantic information in images. We trained and evaluated HRDLNet on the Cityscapes Dataset and the PASCAL VOC 2012 Augmented Dataset, and verified the model’s excellent performance in the field of urban streetscape image segmentation. The unique advantages of our proposed HRDLNet in the field of semantic segmentation of urban streetscapes are also verified by comparing it with the state-of-the-art methods.

The aggregate gradation of asphalt mixture is one of the most important factors affecting the service life of asphalt pavement. In order to study the gradation of asphalt mixture with the best comprehensive performance, this study puts forward a new method of mineral aggregate gradation optimization based on the fuzzy analytic hierarchy process and comprehensive evaluation method, aiming at the multi-level and multi-index evaluation of the road performance of asphalt mixture. First, the orthogonal test design method is applied to design nine target gradations with coarse aggregate (>4.75 mm) and fine aggregate (

UHP Mg-Ge alloys was recently found to provide excellent corrosion resistance. This paper provides new insights on the mechanism of improved corrosion resistance of UHP Mg-Ge alloys in Hanks' solution. The studied UHP Mg-0.5Ge and UHP Mg-1Ge alloys showed superior corrosion resistance compared to UHP Mg and WE43, with the Mg-1Ge exhibiting the best corrosion performance. The exceptional corrosion resistance of the UHP alloy is attributed to (i) Mg2Ge's ability to suppress cathodic kinetics, (ii) Ge's capability to accelerate the formation of a highly passive layer, and the (iii) low amounts of corrosion-accelerating impurities.

Abstract This study investigated the performance of ultrasonography in diagnosing deep soft-tissue tumors and tumor-like lesions in children with histological results. Demographic information and ultrasound characteristics of benign and malignant masses were statistically analyzed. Three radiologists (Radiologists 1, 2, and 3) independently reviewed the ultrasonography studies while being blinded to the medical history and other imaging findings. The 82 lesions included in the study were histopathologically classified as malignant (n = 25) or benign (n = 57). No statistically significant differences were observed between the benign and malignant subgroups regarding age (p = 0.059), sex (p = 1.0), disease course (p = 0.812), presence or absence of symptoms (p = 0.534), maximum diameter (p = 0.359), margin (p = 1.0), calcification (p = 0.057), or blood Adler type (p = 0.563). However, statistically significant differences were observed between the benign and malignant subgroups in terms of isolated or Multiple occurrences (p

The motion of near-wall bubble-in-chain, which is a crucial aspect of the study of near-wall bubble flows, involves not only the wall effect but also the interactions between bubbles. However, there have been few studies on this topic. In this study, we investigated the motion of near-wall bubble-in-chain using a dual-camera orthogonal shadow method and tracked bubbles using image processing and feature matching techniques. Considering both the wall effect and bubble generation frequency, we discussed the statistical characteristics, motion modes, dynamic characteristics, and energy evolution of bubbles. The results demonstrate that an increase in bubble generation frequency leads to a greater deviation of bubble trajectories from the wall and an increase in trajectory amplitude while weakening the suppression of bubble speed by the wall. Furthermore, changes in both bubble equivalent diameter and drag coefficient reveal how bubble generation frequency affects their shape stability during motion as well as regulation by the wall effect. The drag coefficient decreases with increasing Reynolds number for bubbles; however, an increase in bubble generation frequency broadens its distribution range. Additionally, it is evident that the wall effect significantly impacts drag characteristics for bubbles: uncollided bubbles experience increased drag coefficients with greater distance from the wall while collided bubbles exhibit decreased drag coefficients. In cases of high generation frequency, the conversion of kinetic energy to surface energy during bubble collisions, especially the enhancement of the peak of surface energy, indicates an increase in the bubble’s energy storage capacity and energy conversion efficiency. The findings not only enhance comprehension of behavior exhibited by near-wall bubbles but also offer a novel perspective for regulating near-wall bubble flows in industrial applications.

Primary sclerosing cholangitis (PSC) is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis, with no curative treatment available, and liver transplantation is inevitable for end-stage patients. Human placental mesenchymal stem cell (hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis, inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease. Here, we prepared hpMSC-derived exosomes (ExoMSC) and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2−/− mice and multicellular organoids established from PSC patients. The results showed that ExoMSC ameliorated liver fibrosis in Mdr2−/− mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis, and the percentage of CD4+IL-17A+T cells was reduced both in ExoMSC-treated Mdr2−/− mice (Mdr2−/−-Exo) in vivo and ExoMSC-treated Th17 differentiation progressed in vitro. Furthermore, ExoMSC improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids. Thus, our data demonstrate the anti-fibrosis effect of ExoMSC in PSC disease by inhibiting Th17 differentiation, and ameliorating the Th17-induced microenvironment, indicating the promising potential therapeutic role of ExoMSC in liver fibrosis of PSC or Th17-related diseases.

Wufeng–Longmaxi Formation and Qiongzhusi Formation are the significant shale gas exploration strata in China. The former has made a major breakthrough, and the exploration of the latter is restricted. At present, it shows good exploration potential in the Qiongzhusi Formation. Based on the field outcrop and core logging data, the production data from drilled shale gas wells and previous research results combined with the determination of organic matter content, laser Raman spectroscopy of organic matter, X-ray diffraction experiments, and field emission scanning electron microscopy observations. This study compares the geological conditions and control factors of shale gas enrichment and high yield in the Wufeng–Longmaxi Formation and Qiongzhusi Formation and clarifies the enrichment mode of two sets of shale gas reservoirs. The results show that the organic geochemical conditions of two sets of shale reservoirs are similar, about 0.5%~4.5%. The quartz content of Wufeng–Longmaxi Formation shale (42.5%) is more than that of Qiongzhusi Formation (34.1%~40.2%), and the feldspar content (6.4%) is less than that of Qiongzhusi Formation (20.5~27.3%). The inorganic pores of the Qiongzhusi Formation are more developed than those of the Wufeng–Longmaxi Formation, and the pore size of inorganic pores can reach 100 nm~1 μm. Both of them have good preservation conditions. The enrichment of shale gas in the Wufeng–Longmaxi Formation is controlled by hydrocarbon generation reservoir-preservation conditions, and the enrichment of shale gas in the Qiongzhusi Formation is mainly controlled by geological structure. It is of great significance to clarify the enrichment control factors of the Qiongzhusi Formation for effectively guiding the continuous exploration and development of the Qiongzhusi Formation. Shale gas exploration in the Qiongzhusi Formation has a very large prospect, which is expected to exceed the Longmaxi Formation.

The efficacy of therapeutics for acute promyelocytic leukemia (APL) has exhibited an increase in recent years. Only a few patients experience relapse, including extramedullary relapse, and in patients with extramedullary relapse, the central nervous system (CNS) is the most common site. To date, there is no expert consensus or clinical guidelines available for CNS relapse, at least to the best of our knowledge. The optimal therapeutic strategy and management options for these patients remain unclear. The present study reports the treatment of a patient with APL with multiple isolated relapses in the CNS. In addition, through a mini-review of the literature, the present study provides a summary of various reports of this disease and discusses possible treatment options for these patients.

This research aimed to investigate the hypolipidemic and antioxidant effects of fermented rice buckwheat. A high-fat model of Caenorhabditis elegans (C. elegans) was established by high sugar (10 mmol/L) induction. After the treatment of fermented rice buckwheat, its effects on the longevity, motility, egg production, reactive oxygen species (ROS) levels, resistance to oxidative stress, and antioxidant enzyme activity of high-fat C. elegans were determined. At the same time, its effect on the triglyceride and free fatty acid content in high-fat C. elegans were examined. The results showed that the maximum life span of high-fat C. elegans intervened by fermented rice buckwheat significantly increased by 30.90% (P0.05). Furthermore, fermented rice buckwheat could significantly increase the antioxidant enzyme activity (P

Let [Formula: see text] be a pseudo-differential operator defined by the symbol [Formula: see text] with [Formula: see text] [Formula: see text]. It is shown that if [Formula: see text], then the operator satisfies the following pointwise estimate: (Tau)♯(x) ≲ M(|u|2)1/2(x) for all [Formula: see text] and all Schwartz function [Formula: see text] Here, [Formula: see text] denotes the John-Nirenberg sharp function of [Formula: see text] and [Formula: see text] stands for the Hardy–Littlewood maximal operator.

Hypoxia-inducible factor-2α (HIF-2α) is a transcription factor responsible for regulating genes related to angiogenesis and metabolism. This study aims to explore the effect of a previously unreported mutation c.C2473T (p.R825S) in the C-terminal transactivation domain (CTAD) of HIF-2α that we detected in tissue of patients with liver disease. We sequenced available liver and matched blood samples obtained during partial liver resection or liver transplantation performed for clinical indications including hepatocellular carcinoma and liver failure. In tandem, we constructed cell lines and a transgenic mouse model bearing the corresponding identified mutation in HIF-2α from which we extracted primary hepatocytes. Lipid accumulation was evaluated in these cells and liver tissue from the mouse model using Oil Red O staining and biochemical measurements. We identified a mutation in the CTAD of HIF-2α (c.C2473T; p.R825S) in 5 of 356 liver samples obtained from patients with hepatopathy and dyslipidemia. We found that introduction of this mutation into the mouse model led to an elevated triglyceride level, lipid droplet accumulation in liver of the mutant mice and in their extracted primary hepatocytes, and increased transcription of genes related to hepatic fatty acid transport and synthesis in the mutant compared to the control groups. In mutant mice and cells, the protein levels of nuclear HIF-2α and its target perilipin-2 (PLIN2), a lipid droplet-related gene, were also elevated. Decreased lipophagy was observed in mutant groups. Our study defines a subpopulation of dyslipidemia that is caused by this HIF-2α mutation. This may have implications for personalized treatment.

By effectively converting waste heat into electricity, thermoelectric materials and devices can provide an alternative approach to tackle the energy crisis. Amongst thermoelectric materials, bismuth telluride (Bi2Te3) and its derivatives exhibit high figure of merit ZT values in the near-room-temperature region and show great potential for application in thermoelectric devices. Considering the rapid development of Bi2Te3-based thermoelectric materials and their devices in the last few years, a short and systematic review is much needed. Here, we summarize the novel designs, properties, and applications of Bi2Te3-based thermoelectric devices in different contexts, including wearable, portable, implantable, and cross-disciplinary applications. The challenges and outlook for Bi2Te3-based thermoelectric devices are also considered. This work will guide the future development of Bi2Te3-based thermoelectric devices that target broader and more practical applications.

IntroductionMusic therapy has been employed as an alternative treatment modality for the arousal therapy of patients with disorders of consciousness (DOC) in clinical settings. However, due to the absence of continuous quantitative measurements and the lack of a non-musical sound control group in most studies, the identification of the specific impact of music on DOC patients remains challenging. In this study, 20 patients diagnosed with minimally consciousness state (MCS) were selected, and a total of 15 patients completed the experiment.MethodsAll patients were randomly assigned to three groups: an intervention group (music therapy group, n = 5), a control group (familial auditory stimulation group, n = 5), and a standard care group (no sound stimulation group, n = 5). All three groups received 30 min of therapy five times a week for a total of 4 weeks (20 times per group, 60 times in total). Autonomic nervous system (ANS) measurements, Glasgow Coma Scale (GCS), and functional magnetic resonance—diffusion tensor imaging (fMRI-DTI) were used to measure the peripheral nervous system indicators and brain networks, and to evaluate patients’ behavior levels.ResultsThe results reveal that PNN50 (p = 0.0004**), TP (p = 0.0003**), VLF (p = 0.0428**), and LF/HF (p = 0.0001**) in the music group were significantly improved compared with the other two groups. Such findings suggest that the ANS of patients with MCS exhibits higher activity levels during music exposure compared to those exposed to family conversation or no auditory stimulation. In fMRI-DTI detection, due to the relative activity of ANS in the music group, the ascending reticular activation system (ARAS) in the brain network also exhibited significant nerve fiber bundle reconstruction, superior temporal gyrus (STG), transverse temporal gyrus (TTG), inferior temporal gyrus (ITG), limbic system, corpus callosum, subcorticospinal trace, thalamus and brainstem regions. In the music group, the reconstructed network topology was directed rostrally to the diencephalon’s dorsal nucleus, with the brainstem’s medial region serving as the hub. This network was found to be linked with the caudal corticospinal tract and the ascending lateral branch of the sensory nerve within the medulla.ConclusionMusic therapy, as an emerging treatment for DOC, appears to be integral to the awakening of the peripheral nervous system-central nervous system based on the hypothalamic-brainstem-autonomic nervous system (HBA) axis, and is worthy of clinical promotion. The research was supported by the Beijing Science and Technology Project Foundation of China, No. Z181100001718066, and the National Key R&D Program of China No. 2022YFC3600300, No. 2022YFC3600305.

Abstract Background Adverse childhood experiences (ACEs) are prevalent and associated with negative health and social outcomes. However, our understanding of how patterns of ACEs exposure relate to positive outcomes in adulthood remains limited. This study aims to identify patterns of ACEs and examine associations with flourishing in a sample of Chinese young adults. Methods This cross-sectional study was conducted from August to November 2020. Young adults, ages 18–35, enrolled in undergraduate or graduate programs at universities in Mainland China were recruited through convenience and snowball sampling to participate in a survey. The exposure to ACEs was measured by the twelve-item Chinese version of the ACE-International Questionnaire. Additional measures included six domains of flourishing assessed using the Chinese version of the Flourishing Measure, and demographic covariates (i.e., gender, age, year in university, marital status). Descriptive statistical analysis and latent class analysis (LCA) were performed using SPSS 27 and Mplus 8.5. Results Participants included 9468 young adults (mean age = 20.1 years). Majority of participants were female (75.3%), undergraduate students (96.4%), and single (79.8%). Approximately 56% of participants reported at least one ACE; 7.0% reported four or more ACEs. Emotional neglect (33.2%), household violence (20.6%), and parental separation/divorce (13.9%) were the most frequently reported ACEs. LCA identified three ACEs classes: multiple maltreatment and household violence (4.7%), emotional neglect and household violence (16.2%), and low ACEs (79.1%). Individuals in the low ACEs class had the highest level of flourishing whereas individuals in multiple maltreatment and household violence had the lowest level of flourishing in all six domains. There were no significant differences in flourishing between the multiple maltreatment and household violence and the emotional neglect and household violence classes except in the physical and mental health (means = 6.17 vs 6.51, p = 0.02) and the financial and material stability domains (means = 5.25 vs 5.66, p = 0.04). Conclusions Patterns of multiple ACEs exposures were associated with lower levels of flourishing. Our findings have implications for efforts to prevent ACEs exposure through monitoring and promoting family well-being and routine screening to identify those with ACEs exposure to prevent negative social and health sequelae.

Schematic diagram of the protective effect of MSC-derived exosomes on maintaining SLC7A11 function during ferroptosis involved in CCl4-induced ALI.

Abstract Text detection methods based on grouping characters have emerged and have achieved promising performance. Nevertheless, previous methods that grouped characters by learning the relation of adjacent characters or used the heuristic clustering method with a handcrafted feature are unsuitable for dense, curved, or long texts. An effective manner of grouping characters is proposed by introducing K‐Means that is modified by the law of universal gravitation, an outlier detection mechanism and sufficient context information. Based on that, corresponding text detector is presented, named the Text Detector, based on modified K‐Means (KText), which can generate the bounding boundary of word‐level texts with an arbitrary shape. In the experimental stage, two novel stratagems are presented to replenish character‐level annotations to several datasets that provide only word‐level annotations. To evaluate the effectiveness of the method, experiments are carried out on three benchmarks, ICDAR2013, ICDAR2015 and Total‐Text, which contain horizontal, oriented and curved text. The results show that KText performs more competently than most state‐of‐the‐art text detectors when handling dense texts with an arbitrary shape.

Aiming at the problem that the existing stopping sight distance model is out of sync with the development of the times, this paper puts forward a new stopping sight distance model considering the fuzziness and randomness of design parameters, and deduces the calculation method of fuzzy reliability of stopping sight distance. Firstly, the actual braking process of vehicle is divided into three stages: driver’s reaction stage, braking force rising stage and continuous braking stage. Based on MATLAB/Simulink software, the calculation model of complete braking stage is simulated and analyzed, and then the calculation model of stopping sight distance of ESC system is proposed. Secondly, considering the fuzziness of operating speed, the fuzzy reliability theory is introduced to establish the function of the fuzzy reliability of the stopping sight distance. Using the Gaussian fuzzy number and the center point method, the reliability index and failure probability of stopping sight distance are obtained, and the safety and reliability of stopping sight distance are described. Finally, according to the “Unified Standard for Reliability Design of Highway Engineering Structures”, the traditional reliability calculation method and fuzzy reliability calculation method are respectively used to calculate the stopping sight distance value corresponding to the highway safety level. Taking the calculated value of ESC system stopping sight distance model at the design speed of 120 km/h as a reference, the reliability index and failure probability of the two reliability calculation methods are calculated. The results show that the new stopping sight distance model is closer to reality than the existing stopping sight distance model in the continuous braking stage. Compared with the traditional reliability calculation method, the fuzzy reliability calculation method has high reliability index, low failure probability and high calculation accuracy. Implementing road design based on the stopping sight distance value calculated by the new stopping sight distance model and fuzzy reliability theory can improve road safety.

Patchouli (Pogostemon cablin) is an aromatic plant, and its oil has diverse applications in medicine, food, and cosmetics. Patchouli alcohol is the principal bioactive constituent of its volatile oil. In China, patchouli is typically categorized into two types: patchoulol-type (PA-type) and pogostone-type (PO-type). The study evaluated physiological and biochemical indicators, phytohormone metabolites and conducted transcriptome and proteome analyses on both two chemotypes. The PA-type exhibited higher levels of chlorophyll a, b, and carotenoids than the PO-type. In total, 35 phytohormone metabolites representing cytokinin, abscisic acid, gibberellin, jasmonic acid, and their derivatives were identified using UPLC-MS/MS, 10 of which displayed significant differences, mainly belong to cytokinins and jasmonates. Transcriptome analysis identified 4,799 differentially expressed genes (DEGs), while proteome analysis identified 150 differentially expressed proteins (DEPs). Regarding the transcriptome results, the DEGs of the PO-type showed significant downregulation in the pathways of photosynthesis, photosynthesis-antenna protein, porphyrin and chlorophyll metabolism, carotenoid biosynthesis, sesquiterpene and triterpenoid biosynthesis, and starch and sucrose metabolism, but upregulation in the pathway of zeatin synthesis. A combination of transcriptome and proteome analyses revealed that the DEGs and DEPs of lipoxygenase (LOX2), β-glucosidase, and patchouli synthase (PTS) were collectively downregulated, while the DEGs and DEPs of Zeatin O-xylosyltransferase (ZOX1) and α-amylase (AMY) were jointly upregulated in the PO-type compared to the PA-type. Differential levels of phytohormones, variations in photosynthetic efficiency, and differential expression of genes in the sesquiterpene synthesis pathway may account for the morphological and major active component differences between the two chemotypes of patchouli. The findings of this study offer novel perspectives on the underlying mechanisms contributing to the formation of the two patchouli chemotypes.

Primary sclerosing cholangitis (PSC) is a biliary disease accompanied by chronic inflammation of the liver and biliary stricture. Mesenchymal stem cells (MSCs) are used to treat liver diseases because of their immune regulation and regeneration-promoting functions. This study was performed to explore the therapeutic potential of human placental MSCs (hP-MSCs) in PSC through the Takeda G protein-coupled receptor 5 (TGR5) receptor pathway. Liver tissues were collected from patients with PSC and healthy donors (n = 4) for RNA sequencing and intrahepatic cholangiocyte organoid construction. hP-MSCs were injected via the tail vein into Mdr2−/−, bile duct ligation (BDL), and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary cholangitis. Changes in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Compared with healthy controls, liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis, and marked downregulation of bile acid receptor TGR5 expression. hP-MSC treatment apparently reduced the inflammation, cholestasis, and fibrosis in Mdr2−/−, BDL, and DDC model mice. By activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway, hP-MSC treatment promoted the proliferation of cholangiocytes, and affected the transcription of downstream nuclear factor κB through regulation of the binding of TGR5 and Pellino3, thereby affecting the cholangiocyte inflammatory phenotype.

Background: Perioperative management involving anesthesiologists plays an important role in prognosis of recipients after lung transplantation. Since the development of lung transplantation, the demand for specialized anesthesiologists continues to increase. As the largest lung transplant center in China, the Wuxi People's Hospital was tasked with trainee anesthesiologists throughout the country in lung transplantation anesthesia. This study aimed to evaluate the current status and training needs of anesthesiologists for the anesthetic management of lung transplantation in Wuxi People's Hospital between 2015 to 2020. Methods: Overall, 53 trainee anesthesiologists for lung transplantation from 35 hospitals were investigated anonymously in our survey. The questionnaire included the anesthesiologists' demographic information, level of satisfaction, training needs and current status in their hospitals. We divided the doctors into two groups depending on the trainee anesthesiologists’ seniority and professional title: intermediate and senior. Survey data were compared between the groups. Results: Significantly more doctors in senior-level positions had clinical research experience than did doctors in intermediate-level positions (P = 0.041). All doctors were highly or very highly satisfied with the training received. Doctors in intermediate-level positions preferred training periods of 4–6 months, while those in senior-level positions preferred 1–3 months of training (P = 0.044). Most doctors considered theoretical courses to be lacking (69.0%), followed by a lack of scenario simulation teaching (54.8%). The most desirable programs were transesophageal echocardiography (TEE, 71.4%) and extracorporeal membrane oxygenation (ECMO, 64.3%). ECMO technology was available in the hospitals of 95.2% of respondents; however, only 2.4% of doctors said the anesthesiology department took charge of perioperative ECMO. Significantly more senior-level doctors chose calibrated pulse contour analysis (P = 0.018) and significantly more intermediate-level ones chose TEE (P = 0.049). Disappointingly, 21.4% doctors reported a lack of certification evaluation for trainee anesthesiologists at their hospitals. Conclusions: Different training programs should be set up according to the trainee anesthesiologists’ level of seniority and training needs. Theoretical courses and scenario simulation training must be added to improve the training program. Moreover, the training of TEE and ECMO requires greater attention. Finally, a standardized completion assessment is required for trainee anesthesiologists.

Abstract Background Charcot‐Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation. Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear. Methods A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow‐up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis. Results Thirty three (30.00%) patients developed recurrence during a 24‐month postoperative follow‐up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity. Conclusions The crystalline CLC structures in nasal tissues may serve as an easy‐counting and promising biomarker to predict CRSwNP recurrence.

Plastome sequence data is most often extracted from plant whole genome sequencing data and need to be assembled and annotated separately from the nuclear genome sequence. In projects comprising multiple genomes, it is labour intense to individually process the plastomes as it requires many steps and software. This study developed Plastaumatic - an automated pipeline for both assembly and annotation of plastomes, with the scope of the researcher being able to load whole genome sequence data with minimal manual input, and therefore a faster runtime. The main structure of the current automated pipeline includes trimming of adaptor and low-quality sequences using fastp, de novo plastome assembly using NOVOPlasty, standardization and quality checking of the assembled genomes through a custom script utilizing BLAST+ and SAMtools, annotation of the assembled genomes using AnnoPlast, and finally generating the required files for NCBI GenBank submissions. The pipeline is demonstrated with 12 potato accessions and three soybean accessions.

Low-resistivity shales are widely developed in the Sichuan Basin. The production of low-resistivity shale gas reservoirs ranges from high to low to none. The existing methods for gas-content prediction cannot accurately predict the gas content of low-resistivity shale. This increases the risk of shale-gas exploration. To prove that the random forest algorithm has apparent advantages in predicting the gas content of low-resistivity shale and reducing the risks associated with shale-gas exploration and development, three prediction methods were selected in this paper to compare their effects. The first method is known as the grey-correlation multiple linear regression method. Low-resistivity shale-gas content logging series were optimized using the grey-correlation approach, and then the low-resistivity shale-gas-content prediction model was established using the multiple linear regression method. The second method we selected was the resistivity method. The improved water-saturation model was used to predict the water saturation of low-resistivity shale, and then the gas content of low-resistivity shale was predicted based on the free-gas content and the adsorbed-gas-content model. The random forest algorithm was the third method we selected. Fourteen logging series were used as input data and the measured gas content was used as supervised data to train the model and to apply the trained model to the gas-content prediction. The findings demonstrated that the grey-correlation multiple regression method had poor accuracy in predicting gas content in low-resistivity shale; The resistivity method accurately predicted water saturation, and the predicted gas content was higher than the actual gas content. Because the random forest algorithm accurately predicted low-resistivity shale-gas content, its use in the Sichuan Basin was advantageous. The selection of a low-resistivity shale-gas-content prediction model was guided by the research findings.

Abstract Background We explored whether stem cell therapy was effective for animal models and patients with Crohn’s disease (CD). Methods We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality. Results We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD − 4.58, p = 0.000; rats: SMD − 1.41, P = 0.000) and lower myeloperoxidase levels (SMD − 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD − 2.10, P = 0.000), the CD endoscopic index of severity (SMD − 3.40, P = 0.000) and simplified endoscopy score for CD (SMD − 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3–24 months after transplantation. Conclusions Stem cell transplantation is a valuable supplementary therapy for CD.

Abstract Background Cholangiocyte senescence is an important pathological process in diseases such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Stem cell/induced pluripotent stem cell-derived exosomes have shown anti-senescence effects in various diseases. We applied novel organoid culture technology to establish and characterize cholangiocyte organoids (cholangioids) with oxidative stress-induced senescence and then investigated whether human placenta mesenchymal stem cell (hPMSC)-derived exosomes exerted a protective effect in senescent cholangioids. Methods We identified the growth characteristics of cholangioids by light microscopy and confocal microscopy. Exosomes were introduced concurrently with H2O2 into the cholangioids. Using immunohistochemistry and immunofluorescence staining analyses, we assessed the expression patterns of the senescence markers p16INK4a, p21WAF1/Cip1, and senescence-associated β-galactosidase (SA-β-gal) and then characterized the mRNA and protein expression levels of chemokines and senescence-associated secretory phenotype (SASP) components. Results Well-established cholangioids expressed cholangiocyte-specific markers. Oxidative stress-induced senescence enhanced the expression of the senescence-associated proteins p16INK4a, p21WAF1/Cip1, and SA-β-gal in senescent cholangioids compared with the control group. Treatment with hPMSC-derived exosomes delayed the cholangioid aging progress and reduced the levels of SASP components (i.e., interleukin-6 and chemokine CC ligand 2). Conclusions Senescent organoids are a potential novel model for better understanding senescence progression in cholangiocytes. hPMSC-derived exosomes exert protective effects against senescent cholangioids under oxidative stress-induced injury by delaying aging and reducing SASP components, which might have therapeutic potential for PSC or PBC.

This paper studies the grain refinement mechanisms of 5A06 aluminum alloy sheets in cold rotary forging (CRF). The results show that the grains are clearly refined from 25.1 µm to 11.8 µm during the CRF process. The grain refinement mechanism can be divided into two modes: (1) The grains with a small Schmid factor (SF) are activated by multi-slip systems, and dense dislocations are segregated along the boundaries of interior regions with different slip systems, which results in a rapidly increasing strain localization along these boundaries. Since the strain localization restrains the coordinate slip deformation between different interior regions, the grains are directly separated into several finer grains. (2) The grains with a large SF are primarily activated by a single slip system, and the dislocation migrates smoothly along most microband boundaries. Then, a more severe lattice rotation causes a transformation to a hard orientation and multi-slip system activation, which contributes to an increase in the rapid misorientation across microband boundaries and thus promotes significant SF grain refinement.

The noninvasive diagnosis of cholangiocarcinoma (CCA) is insufficiently accurate. Therefore, the discovery of new prognostic markers is vital for the understanding of the CCA mechanism and related treatment. The information on CCA patients in The Cancer Genome Atlas database was used for weighted gene co-expression network analysis. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to analyze the modules of interest. By using receiver operating characteristic (ROC) analysis to analyze the Human Protein Atlas (HPA), the featured genes were subsequently verified. In addition, clinical samples and GSE119336 cohort data were also collected for the validation of these hub genes. Using WGCNA, we identified 61 hub genes that regulated the progression and prognosis of CCA. Eight hub genes (VSNL1, TH, PCP4, IGDCC3, RAD51AP2, MUC2, BUB1, and BUB1B) were identified which exhibited significant interactions with the tumorigenic mechanism and prognosis of CCA. In addition, GO and KEGG clarified that the blue and magenta modules were involved with chromosome segregation, mitotic and oocyte meiosis, the cell cycle, and sister chromatid segregation. Four hub genes (VSNL1, PCP4, BUB1, and BUB1B) were also verified as featured genes of progression and prognosis by the GSE119336 cohort data and five human tissue samples.

BackgroundOrganoids, which enable disease modeling and drug screening closer to an in vivo environment, can be isolated and grown from organs such as the brain, small intestine, kidney, lungs, and liver. To facilitate the establishment of liver and small intestinal organoids, we developed efficient protocols for cholangiocytes and intestine crypts collecting and organoid culturing.MethodsCholangiocytes were collected from intrahepatic bile ducts, the gallbladder, and small intestine crypts by gravity settling and multistep centrifugation methods. The cells isolated were embedded with Matrigel and grew in three-dimensional spheroids in a suitable culture medium. The stability of organoid cells was assessed by subculture, cryopreservation, and thawing. RNA and DNA extraction of organoids, as well as immunostaining procedure, were also optimized. Hand-picking procedures were developed and performed to ensure similar growth characteristics of organoids.ResultsA large number of cholangiocytes and small intestine crypts were collected under these protocols. Cholangiocytes developed into cyst-like structures after 3–4 days in Matrigel. After 1–2 weeks of cultivation, small intestinal organoids (in-orgs) developed buds and formed a mature structure. Compared to organoids derived from the gallbladder, cholangiocyte organoids (Cho-orgs) from intrahepatic the bile ducts grew more slowly but had a longer culture term, expressed the cholangiocytes markers Krt19 and Krt7, and recapitulated in vivo tissue organization.ConclusionsOur protocols simplified the cell collection procedure and avoided the possibility of exposing tissue-derived stem cells to mechanical damage or chemical injury by gravity settling and multistep centrifugation. In addition, our approach allowed similar growth characteristics of organoids from different mammalian tissue sources. The protocol requires 2–4 weeks to establish a stable organoid growth system. Organoids could be stably passaged, cryopreserved, and recovered under protocol guidance. Besides, the organoids of cholangiocytes and small intestines retained their original tissue characteristics, such as tissue-specific marker expression, which prepares them for further experiments such as preclinical in vitro trials and mechanism research studies.

AbstractThe fracturing behavior of enhanced geothermal system (EGS) reservoirs merits investigation under field-relevant temperature and stress conditions, in order to understand the creation of an extensive fracture network that helps achieve a high heat exchange efficiency. In this work, hydraulic fracturing tests were conducted on two 300 mm sized cubic granite samples at room (32°C) and field-relevant (250°C) temperatures under true triaxial compression conditions. The failure behavior and fracturing plane were studied using acoustic emission (AE) testing, μm-scale computed tomography (μm-CT), and scanning electronic microscopy (SEM), in addition to the monitoring and analyses of pressure-flow curve during fracturing. The results show that (1) at the macroscale, the strength of the granite sample was weakened at high (field-relevant) temperature, as shown by a decrease in the breakdown pressure and increase in closure pressure from the pressure-flow curve; (2) at the microscale, the failure pattern of grains during fracturing did not differ much at high and room temperatures for both intergranular and transgranular fractures; and (3) due to upscaling issues from the laboratory to field, however, the laboratory experiment will not directly provide some critical parameters (e.g., mud window pressure needed for fracture initiation and borehole failure avoidance) needed for an EGS field exploration.

Abstract Background Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment. Methods We investigated the effects of MSCs on lung B cells in a mouse model of lipopolysaccharide (LPS)-induced ALI. MSCs were administered intratracheally 4 h after LPS. As vehicle-treated controls, mice were treated with phosphate-buffered saline (PBS) containing 2% C57BL/6 (PBS group). Histopathological changes, survival rate, inflammatory factor levels, and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. Single-cell RNA sequencing (scRNA-Seq) analysis was performed to evaluate the transcriptional changes in lung B cells between the PBS, LPS, and LPS/MSC groups on days 3 and 7. Results MSC treatment ameliorated LPS-induced ALI, as indicated by the reductions in mortality, the levels of chemokines and cytokines in BALF, and the severity of lung tissue histopathology in ALI mice. Lung B cells in the PBS group remained undifferentiated and had an inhibitory phenotype. Based on our scRNA-Seq results, the differentially expressed genes (DEGs) in lung B cells in both the PBS group and LPS group were involved in chemotaxis processes and some proinflammatory pathways. MSC treatment inhibited the expression of chemokine genes that were upregulated by LPS and were related to the recruitment of neutrophils into lung tissues. Immunoglobulin-related gene expression was decreased in lung B cells of mice treated with LPS/MSC for 7 days. The DEGs regulated by MSCs were enriched in biological processes, including humoral immune response and apoptotic signaling. Conclusions Lung B cells played an important role in the effects of treatment of ALI with MSCs. These observations provide new insights into the mechanisms underlying the effects of MSC treatment for ALI.

Abstract Let T a , φ $T_{a,\varphi }$ be a Fourier integral operator with symbol a and phase φ. In this paper, under the conditions a ( x , ξ ) ∈ L ∞ S ρ n ( ρ − 1 ) / 2 ( ω ) $a(x,\xi )\in L^{\infty }S^{n(\rho -1)/2}_{\rho }(\omega )$ and φ ∈ L ∞ Φ 2 $\varphi \in L^{\infty }\varPhi ^{2}$ , the authors show that T a , φ $T_{a,\varphi }$ is bounded from L 2 ( R n ) $L^{2}(\mathbb{R}^{n})$ to L 2 ( R n ) $L^{2}(\mathbb{R}^{n})$ .

In order to reveal the effect of baffles on flow structure and cyclic variation stirred by Rushton turbines, particle image velocimetry experiments were performed in baffled and unbaffled stirred tanks. In a baffled tank, the peak value of time-averaged velocity obviously increases, the high velocity region enlarges significantly, and the fluctuation of fluid elements near the turbine increases significantly. In the 20° phase plane of the baffled tank, the high swirl strength region slightly enlarges, but the peak of phase-resolved swirl strength is lower. The peak value and high value regions of turbulent kinetic energy are larger in the baffled stirred tank at various phase planes. Using quadruple proper orthogonal decomposition, the flow field is decomposed into a small-scale part, a transition part, a large-scale part, and a mean part with different spatial scales. Adding the baffle, the mean part with largest spatial scale obviously increases (it is favorable for mass transfer at different liquid levels) and the transition part, which mainly includes the random fluctuation of a turbulent cascade, slightly enhances (it is conducive to diffusion). The main influence of cyclic variation for various blade passages is the flow with large-scale, and the standard deviation of time coefficients decreases by 3%–4% for the mean part and the large-scale part by adding the baffle.

Immunogenicity is a major issue associated with the PK, efficacy, and safety evaluation of therapeutic protein products during pre-clinical and clinical studies. A multi-tiered approach consisting of screening, confirmatory, and titration assays has been widely adopted for anti-drug antibody testing. GQ1001, a recombinant humanized anti-human epidermal growth factor receptor 2 monoclonal antibody covalently linked to a cytotoxin of DM1, possesses a novel format of antibody–drug conjugates. In this study, we reported the development, validation, and application of an acid-dissociation bridging enzyme-linked immunosorbent assay for the detection of antibodies against GQ1001 in cynomolgus monkey serum. The sensitivity of the screening assay was 126.141 ng/mL in undiluted serum. The screening assay and confirmatory assay were neither affected by the naïve monkey serum nor by 2% and 5% (v/v) erythrocyte hemolysates. Moreover, the assay was not subject to interference by 2500 ng/mL of human IgG1 in the samples. Drug interference at low positive control (150 ng/mL) and high positive control (8000 ng/mL) of anti-GQ1001 antibodies was not observed when GQ1001 concentrations were below 3.125 μg/mL and 100 μg/mL, respectively. Furthermore, no hook effect was observed for the positive antibodies in the concentration range of 8 to 64 μg/mL. The validated assay was, thereafter, successfully applied to a single-dose toxicity study of GQ1001. Anti-drug antibody positive rates among dosing animals and testing samples were reported, and no significant impact was found on toxicokinetic outcomes.

Curcumin is a natural polyphenol compound with anti-diabetic, anti-oxidative, and anti-inflammatory effects. Although many studies have reported the protective effect of curcumin in diabetes mellitus or diabetic nephropathy, there is a lack of research on curcumin in diabetic retinopathy. The purpose of this study was to investigate the therapeutic effects of curcumin on the diabetic retinal injury. Streptozotocin (STZ)-induced diabetic rats (60, n = 12 each) were respectively given curcumin orally (200 mg/kg/day), insulin subcutaneously (4–6 IU/day), and combined therapy with curcumin and insulin for 4 weeks. Retinal histopathological changes, oxidative stress markers, and transcriptome profiles from each group were observed. Curcumin, insulin, or combination therapy significantly reduced blood glucose, alleviated oxidative stress, and improved pathological damage in diabetic rats. Curcumin not only significantly reduced retinal edema but also had a better anti-photoreceptor apoptosis effect than insulin. In the early stage of diabetes, the enhancement of oxidative stress in the retina induced the adaptive activation of the nuclear factor E2-associated factor 2 (Nrf2) pathway. Treatment of curcumin alleviated the compensatory activation of the Nrf2 pathway induced by oxidative stress, by virtue of its antioxidant ability to transfer hydrogen atoms to free radicals. When curcumin combined with insulin, the effect of maintaining Nrf2 pathway homeostasis in diabetic rats was better than that of insulin alone. Transcriptomic analyses revealed that curcumin either alone, or combined with insulin, inhibited the AGE-RAGE signaling pathway and the extracellular matrix (ECM)-receptor interaction in the diabetic retina. Thus, at the early stage of diabetes, curcumin can be used to alleviate diabetic retinal injury through its anti-oxidative effect. If taking curcumin as a potential complementary therapeutic option in combination with antihyperglycemic agents, which would lead to more effective therapeutic outcomes against diabetic complications.

Background and Aims: Viral hepatitis are one of the main causes of liver cirrhosis. The treatment of portal hypertension caused by liver cirrhosis is difficult and diverse, and the therapeutic effect is unknown. Bayesian network meta-analysis was performed to compare the efficacy and safety of treatments for patients with portal hypertension and cirrhosis, including a transjugular intrahepatic portosystemic shunt (TIPS), endoscopic therapy, surgical therapy and medications.Methods: Eligible articles were searched for in PubMed, Embase, Cochrane Library and Web of Science databases from their inception until June 2020. Using the “gemtc-0.8.4” package in R v.3.6.3 software and the Just Another Gibbs Sampler v.4.2.0 program, network meta-analysis was performed using a random effects model within a Bayesian framework. The odds ratios for all-cause rebleeding, bleeding-related mortality, overall survival (OS), treatment failure and hepatic encephalopathy were determined within the Bayesian framework.Results: Forty randomized controlled trials were identified, including 4,006 adult patients and nine treatment strategies. Our results showed that distal splenorenal shunt and TIPS provided the best control of hemorrhage. Endoscopic variceal ligation with medication resulted in the highest OS rate. Medication alone resulted in poor OS and treatment failure.Conclusions: We performed a systematic comparison of diverse treatments for cirrhotic patients with portal hypertension. Our meta-analysis indicated that a TIPS and distal splenorenal shunt resulted in lower rates of rebleeding than did other therapies. Furthermore, drugs are more suitable for combination therapy than monotherapy.

Abstract Background The efficacy of mesenchymal stem cell (MSC)-based therapy for acute liver injury (ALI) involves coordination with the hepatic immune system, a complex and coordinated network of immune-cell interactions. However, studies of the immunomodulatory effects of MSCs have focused on a limited number of cell subsets rather than a systematic assessment. Methods Carbon tetrachloride (CCl4) was used to induce ALI in mice. To determine the efficacy of MSCs, ALI mice were injected with MSCs via the tail vein, and histopathological changes, survival rate, and the serum levels of liver enzymes were determined. To assess the immune response induced by MSCs, a mass cytometry panel of 43 metal isotope-tagged antibodies was used to characterize the hepatic immune compartment at days 1, 2, 3, and 7 after administration of MSCs or PBS. Results MSC treatment significantly alleviated CCl4-induced ALI and improved the survival rate. MSC treatment also modulated the hepatic immune system in terms of the distribution of immune-cell subsets and the phenotype of single cells. During the injured phase, MSCs inhibited a systemic response by reducing the numbers of Ly6ClowCD8+ TRM cells, conventional NK cells, and IgM+IgD+ B cells; suppressing the activation of Ly6ChiCD8+ TRM cells; downregulating MHC II and IgM expression in IgM+IgD+ B cells; and increasing the number of immunosuppressive monocyte-derived macrophages. During the recovery phase, MSCs promoted the retention of Ly6ClowCD8+ TRM cells and maintained the immunosuppressive activity of monocyte-derived macrophages. The response to MSC treatment differed between the injured and recovery phases, emphasizing the benefit of dynamic assessment of the immunomodulatory effects of MSCs. Conclusions We determined the immunomodulatory effects of MSC treatment on the subtype distribution and phenotypes of hepatic immune cells.