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Abstract Patulin (PAT) is a common mycotoxin in moldy fruits that causes gastrointestinal injury if accidentally ingested. Some studies have reported the symptoms of intestinal injury caused by PAT. However, the effects of PAT on the gut microbiota and gut metabolism remain to be investigated, which is important for clarifying the toxicological mechanisms. Thus, C57/BL6J mice were gavaged once with 0, 1, 4, and 16 mg/kg body weight PAT, and the small intestinal and colonic contents were collected. The 16S rRNA sequencing and targeted and untargeted metabolomics were applied to assess the alterations in microbiota and metabolism, respectively. The results showed that Mycoplasma, Dubosiella, and Enterorhabdus were jointly affected by acute PAT exposure in the small intestinal and colonic contents. Some inflammation‐related bacteria, such as Mycoplasma in the small intestine and Mycoplasma, Alistipes, Eubacterium_coprostanoligenes_group, and Candidatus_saccharimona in the colon, increased with increasing doses of PAT. In metabolic results, amino acids decreased and bile acids elevated in both intestinal contents; lipids increased in the small intestinal contents but decreased in the colonic contents. PAT mainly affected host amino acid and lipid metabolism; it also downregulated microbial tryptophan metabolism and short‐chain fatty acid levels (mainly in the colon), which could be explained by the decrease of Bacteroides and Lactobacillus. These influences in microbial abundances and metabolic levels persisted after PAT and its products were cleared. These results fill a gap in the effects of PAT on the gut microbiota and provide a theoretical basis for elucidating the toxic mechanism of mycotoxins.

Peach gummosis, a devastating disease caused by Neofusicoccum parvum, significantly shortens peach tree lifespan and reduces the yield of peach trees. Despite its impact, the molecular mechanism underlying this disease remains largely unexplored. In this study, we used RNA-seq, sugar metabolism measurements, and an integrated transcriptional and metabolomic analysis to uncover the molecular events driving peach gummosis. Our results revealed that N. parvum infection drastically altered the transcripts of cell wall degradation-related genes, the log2Fold change in the transcript level of Prupe.1G088900 encoding xyloglucan endotransglycosylase decreased 2.6-fold, while Prupe.6G075100 encoding expansin increased by 2.58-fold at 12 hpi under N. parvum stress. Additionally, sugar content analysis revealed an increase in maltose, sucrose, L-rhamnose, and inositol levels in the early stages of infection, while D-galactose, D-glucose, D-fructose consistently declined as gummosis progressed. Key genes related to cell wall degradation and starch degradation, as well as UDP-sugar biosynthesis, were significantly upregulated in response to N. parvum. These findings suggest that N. parvum manipulates cell wall degradation and UDP-sugar-related genes to invade peach shoot cells, ultimately triggering gum secretion. Furthermore, weighted gene co-expression network analysis (WGCNA) identified two transcription factors, ERF027 and bZIP9, as central regulators in the downregulated and upregulated modules, respectively. Overall, this study enhances our understanding of the physiological and molecular responses of peach trees to N. parvum infection and provide valuable insights into the mechanisms of peach defense against biotic stresses.

In recent years, the incidence of neurodegenerative diseases (NDs) has gradually increased over the past decades due to the rapid aging of the global population. Traditional research has had difficulty explaining the relationship between its etiology and unhealthy lifestyle and diets. Emerging evidence had proved that the pathogenesis of neurodegenerative diseases may be related to changes of the gut microbiota’s composition. Metabolism of gut microbiota has insidious and far-reaching effects on neurodegenerative diseases and provides new directions for disease intervention. Here, we delineated the basic relationship between gut microbiota and neurodegenerative diseases, highlighting the metabolism of gut microbiota in neurodegenerative diseases and also focusing on treatments for NDs based on gut microbiota. Our review may provide novel insights for neurodegeneration and approach a broadly applicable basis for the clinical therapies for neurodegenerative diseases.

Piezoelectric materials, as a class of materials capable of generating electrical charges under mechanical vibration, have special piezoelectric effects and have been widely applied in various disease treatment fields. People generate vibrations in the oral cavity during daily activities such as brushing teeth, using electric toothbrushes, chewing, and speaking. These natural vibrations (or external ultrasound) provide ideal conditions for activating piezoelectric materials, leading to their high potential applications in protecting oral health and treating oral diseases. Based on this, this review reports on the research progress and trends of piezoelectric materials in the protection of oral health and the treatment of oral diseases in the past 5 years, and discusses its treatment mechanism, challenges and shortcomings, aiming to provide theoretical basis and new ideas for the future application of piezoelectric materials in the field of oral cavity. Finally, a brief outlook is provided, suggesting that the potential of piezoelectric materials may enable them to quickly move towards real clinical applications.

The ETV6-MECOM fusion gene, produced by the rare and recurrent chromosomal translocation t(3; 12) (q26; p13), is associated with high mortality and short survival in myeloid leukemia. However, its function and underlying mechanisms in leukemia progression remain unknown. In this study, leukemia-stable K562 cells expressing the ETV6-MECOM fusion protein were used to investigate the effects of the ETV6-MECOM oncoprotein. K562-ETV6-MECOM cells were undifferentiated and had reduced colony formation, increased cell migration and invasion, and increased sphere number and diameter in a spheroid formation assay, presenting epithelial-to-mesenchymal transition (EMT) traits. The expression of E-cadherin, a hallmark of EMT, was significantly downregulated at the transcriptional and translational level in K562-ETV6-MECOM cells to explore the mechanistic basis of EMT. Stepwise truncation, DNA sequence deletion, mutation analysis for E-cadherin promoter transactivation, and a dual luciferase assay indicated that the regulatory region of ETV6-MECOM is located in the DNA motif −1116 TTAAAA−1111 of E-cadherin promoter. Moreover, a chromatin immunoprecipitation assay showed that this oncoprotein binds to the DNA motif −1116 TTAAAA−1111 with the anti-EVI1 antibody. Although ETV6-MECOM upregulated the expressions of EMT master regulators, including SNAIL, SLUG, ZEB2, and TWIST2, their knockdown had no effect on EMT-related properties. However, overexpression of E-cadherin eliminated EMT traits in the presence of the ETV6-MECOM oncoprotein. These data confirmed that the ETV6-MECOM oncoprotein, not SNAIL, SLUG, ZEB2, or TWIST2, plays a critical role in inducing EMT traits in leukemia K562 cells. ETV6-MECOM induces EMT-related properties by downregulating the transcriptional expression of E-cadherin and repressing its transactivation activity by binding to its core motif −1116TTAAAA−1111 in leukemia K562 cells. These findings could contribute to the development of a therapeutic target for patients with myeloid leukemia characterized by ETV6-MECOM.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor–bed ratio and nurse–bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

Carotid plaque classification from ultrasound images is crucial for predicting ischemic stroke risk. While deep learning has shown effectiveness, it heavily relies on substantial labeled datasets. Achieving high performance with limited labeled images is essential for clinical use. Self-supervised learning (SSL) offers a potential solution; however, the existing works mainly focus on constructing the SSL tasks, neglecting the use of multiple tasks for pretraining. To overcome these limitations, this study proposed a self-supervised fusion network (Fusion-SSL) for carotid plaque ultrasound image classification with limited labeled data. Fusion-SSL consists of two SSL tasks: classifying image block order (Ordering) and predicting image rotation angle (Rotating). A dual-branch residual neural network was developed to fuse feature presentations learned by the two tasks, which can extract richer visual boundary shape and contour information than a single task. In this experiment, 1270 carotid plaque ultrasound images were collected from 844 patients at Zhongnan Hospital (Wuhan, China). The results showed that Fusion-SSL outperforms single SSL methods across different percentages of labeled training data, ranging from 10 to 100%. Moreover, with only 40% labeled training data, Fusion-SSL achieved comparable results to a single SSL method (predicting image rotation angle) with 100% labeled data. These results indicate that Fusion-SSL could be beneficial for the classification of carotid plaques and the early warning of a stroke in clinical practice.

This paper conducted a high-temperature storage test (HTST) on bonded samples made of Pd100 (Pd-coated Cu wire with a Pd layer thickness of 100 nm) and Pd120, and studied the growth law of Cu-Ag intermetallic compounds and the inhibitory mechanism of Pd thickness on Cu-Ag intermetallic compounds. The results show that the Kirkendall effect at the bonding interface of the Pd100-bonded sample is more obvious after the HTST, the sizes of voids and cracks are larger, and the thickness of intermetallic compounds is uneven. But, the bonding interface of the Pd120-bonded sample has almost no microcracks, the Kirkendall voids are small, and the intermetallic compound size is uniform and relatively thin. The formation sequence of intermetallic compounds is as follows: Cu atoms diffuse into the Ag layer to form Ag-rich compounds such as CuAg4 or CuAg2, and then the CuAg forms with the increase in diffused Cu elements. Pd can significantly reduce the Kirkendall effect and slow down the growth of Cu-Ag intermetallic compounds. The growth rate of intermetallic compounds is too fast when the Cu bonding wire has a thin Pd layer, which results in holes and microcracks in the bonding interface and lead to the peeling of the bonding interface. Voids and cracks will hinder the continuous diffusion of Cu and Ag atoms, resulting in the growth of intermetallic compounds being inhibited.

In this paper, three Pd-coated Cu (PCC) wires with different Pd-layer thicknesses were used to make bonding samples, and the influence of Pd-layer thickness on the reliability of bonded points before and after a high-temperature storage test was studied. The results show that smaller bonding pressure and ultrasonic power lead to insufficient plastic deformation of the ball-bonded point, which also leads to small contact area with the pad and low bonding strength. Excessive bonding pressure and ultrasonic power will lead to ‘scratch’ on the surface of the pad and large-scale Ag spatter. The wedge-bonded point has a narrowed width when the bonding pressure and ultrasonic power are too small, and the tail edge will be cocked, resulting in false bonding and low strength. When the bonding pressure or ultrasonic power is too large, it will cause stress concentration, and the pad will appear as an ‘internal injury’, which will improve the failure probability; a high-temperature environment can make Cu-Ag intermetallic compounds (IMCs) grow and improve the bonding strength. With the extension of high-temperature storage time, the shear force of Pd100 gradually reaches the peak and then decreases, due to Kirkendall pores caused by excessive growth of IMCs, while the shear force of Pd120 continued to increase due to the slow growth rate of IMCs. In the high-temperature storage test, the thicker the Pd layer of the bonding wire, the higher the bonding strength; in the cold/hot cycle test, the sample with the largest Pd-layer thickness has the lowest failure rate. The thicker the Pd layer, the stronger its ability to resist changes in the external environment, and the higher its stability and reliability.

Diabetic complications pose a significant threat to life and have a negative impact on quality of life in individuals with diabetes. Among the various factors contributing to the development of these complications, endothelial dysfunction plays a key role. The main mechanism underlying endothelial dysfunction in diabetes is oxidative stress, which adversely affects the production and availability of nitric oxide (NO). Flavonoids, a group of phenolic compounds found in vegetables, fruits, and fungi, exhibit strong antioxidant and anti-inflammatory properties. Several studies have provided evidence to suggest that flavonoids have a protective effect on diabetic complications. This review focuses on the imbalance between reactive oxygen species and the antioxidant system, as well as the changes in endothelial factors in diabetes. Furthermore, we summarize the protective mechanisms of flavonoids and their derivatives on endothelial dysfunction in diabetes by alleviating oxidative stress and modulating other signaling pathways. Although several studies underline the positive influence of flavonoids and their derivatives on endothelial dysfunction induced by oxidative stress in diabetes, numerous aspects still require clarification, such as optimal consumption levels, bioavailability, and side effects. Consequently, further investigations are necessary to enhance our understanding of the therapeutic potential of flavonoids and their derivatives in the treatment of diabetic complications.

Objective: To analyze the risk factors associated with the development of coronavirus disease 2019 (COVID-19) and enhance the understanding of its disease progression, providing a clinical basis for diagnosis, treatment, and prevention of severe diseases. Methods: A retrospective analysis of 399 patients with COVID-19 was conducted at a designated hospital for COVID-19 treatment in Inner Mongolia Autonomous Region, focusing on the characteristics and risk factors associated with the development of COVID-19. Univariate and binary logistic regression analyses were used to explore the risk factors for novel coronavirus infection. Results: There were significant differences in age, underlying disease history, laboratory examination, and clinical symptoms between the two groups. Univariate analysis showed significant differences in age, diabetes, rheumatoid arthritis, albumin concentration, albumin/globulin ratio, and IL-6 and C-reactive protein levels between the two groups. Binary Logistic regression analysis showed that C-reactive protein level, endocrine disease history, and ORF1ab gene CT value may be risk factors for COVID-19, whereas albumin level may be a protective factor. Conclusion: Age, underlying disease history, and elevated C-reactive protein/IL-6 levels are contributing factors to the development of COVID-19. Further targeted preventive interventions should consider the risk factors of the disease.

Objective: To investigate the differences in clinical features of patients with novel coronavirus infection at different ages. Methods: A total of 382 patients with novel coronavirus, hospitalized in a designated hospital for treatment of novel coronavirus in Inner Mongolia Autonomous Region from October 1 to October 31, 2022 were included. The groups were as follows: children group 0~18 years old; youth group 19~44 years old; middle-aged group 45~59 years old; and elderly group ≥60 years old. The demographic and clinical characteristics of cases in different age groups were analyzed retrospectively. Results: Patients were stratified by 10 years of age, and conformed to a normal distribution. The age at onset was orimarily within the young people categrry, the severity of disease was mild in all age groups, and the risk of severe disease was higher in the elderly group (P

Summary: Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95–428.68 h]) than that of Placebo (271.33 h [IQR 219.00–529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07–1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

Mitochondria maintain the normal physiological function of nerve cells by producing sufficient cellular energy and performing crucial roles in maintaining the metabolic balance through intracellular Ca2+ homeostasis, oxidative stress, and axonal development. Depression is a prevalent psychiatric disorder with an unclear pathophysiology. Damage to the hippocampal neurons is a key component of the plasticity regulation of synapses and plays a critical role in the mechanism of depression. There is evidence suggesting that mitochondrial dysfunction is associated with synaptic impairment. The maintenance of mitochondrial homeostasis includes quantitative maintenance and quality control of mitochondria. Mitochondrial biogenesis produces new and healthy mitochondria, and mitochondrial dynamics cooperates with mitophagy to remove damaged mitochondria. These processes maintain mitochondrial population stability and exert neuroprotective effects against early depression. In contrast, mitochondrial dysfunction is observed in various brain regions of patients with major depressive disorders. The accumulation of defective mitochondria accelerates cellular nerve dysfunction. In addition, impaired mitochondria aggravate alterations in the brain microenvironment, promoting neuroinflammation and energy depletion, thereby exacerbating the development of depression. This review summarizes the influence of mitochondrial dysfunction and the underlying molecular pathways on the pathogenesis of depression. Additionally, we discuss the maintenance of mitochondrial homeostasis as a potential therapeutic strategy for depression.

Abstract Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a refractory and recurrent subtype of B-cell ALL enriched with kinase-activating rearrangements. Incomplete understanding of the heterogeneity within the tumor cells presents a major challenge for the diagnosis and therapy of Ph-like ALL. Here, we exhibited a comprehensive cell atlas of one Ph-like ALL patient with a novel TPR-PDGFRB fusion gene at diagnosis and relapse by using single-cell RNA sequencing (scRNA-seq). Twelve heterogeneous B-cell clusters, four with strong MKI67 expression indicating highly proliferating B cells, were identified. A relapse-enriched B-cell subset associated with poor prognosis was discovered, implicating the transcriptomic evolution during disease progression. Integrative single-cell analysis was performed on Ph-like ALL and Ph+ ALL patients, and revealed Ph-like specific B-cell subpopulations and shared malignant B cells characterized by the ectopic expression of the inhibitory receptor CLEC2D. Collectively, scRNA-seq of Ph-like ALL with a novel TPR-PDGFRB fusion gene provides valuable insights into the underlying heterogeneity associated with disease progression and offers useful information for the development of immunotherapeutic techniques in the future.

Focus on the scheduling problem of distributed computing tasks in Internet of Vehicles. Firstly, based on the computing-aware network theory, a distributed computing resource model of the Internet of Vehicles is established, and the seven-dimensional QoS attributes of the computing resources in the Internet of Vehicles (reliability between computing resources, communication costs, computing speed and computing costs of the computing resources themselves , computing energy consumption, computing stability, and computing success rate) are grouped and transformed into two-dimensional comprehensive attribute priorities: computing performance priority and communication performance priority. Secondly, the weighted directed acyclic graph model of distributed computing tasks in the Internet of Vehicles and the seven-dimensional QoS attribute weighted undirected topology graph model of distributed computing resources in the Internet of Vehicles are respectively established. Moreover, a dynamic greedy algorithm-based task of loading and computing resource scheduling algorithm is proposed. Finally, the example analysis shows that the overall performance of this dynamic greedy algorithm-based task of loading and computing resource scheduling algorithm is better than the classic HEFT scheduling algorithm and round robin scheduling algorithm.

The prerequisite for underwater vehicles to accomplish various underwater tasks is to obtain real-time position information about themselves in the underwater environment using internal or external sensors, which is known as underwater positioning and navigation technology. This paper presents a general review of underwater vehicle positioning and navigation technology and illustrates the importance of underwater terrain-aided navigation technology. It also summarizes its general structure and describes the principles and functions of each component. The paper mainly analyzes various mainstream methods applied to underwater terrain-aided navigation, focuses on terrain suitability analysis and terrain matching algorithms, which play a central role in the analysis. Additionally, the research progress of terrain-aided navigation technology is described, and the research methods of terrain suitability analysis, terrain matching navigation, and the latest technology applications are compared. Some shortcomings of the current underwater terrain-aided navigation technology are presented, and future research directions are foreseen to provide a basis for subsequent research.

Abstract Objective Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. Methods Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. Results In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490–9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014–1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002–1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969–0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037–1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069–1.141; P

IntroductionDiabetic cardiomyopathy (DCM) is one of the most prevalent complications of diabetes with complex pathogenesis. YuNü-Jian (YNJ) is a traditional Chinese medicinal formula widely used for diabetes with hypoglycemic and cardioprotective effects. This study aims to investigate the actions and mechanisms of YNJ against DCM which has never been reported.MethodsNetwork pharmacology approach was used to predict the potential pathways and targets of YNJ on DCM. Molecular docking between hub targets and active components of YNJ was performed and visualized by AutoDock Vina and PyMOL. Then type 2 diabetic model was employed and intervened with YNJ for 10 weeks to further validate these critical targets.ResultsFirst, a total of 32 main ingredients of YNJ were identified and 700 potential targets were screened to construct herb-compound-target network. Then 94 differentially expressed genes of DCM were identified from GEO database. After that, PPI network of DCM and YNJ were generated from which hub genes (SIRT1, Nrf2, NQO1, MYC and APP) were assessed by topology analysis. Next, functional and pathway analysis indicated that the candidate targets were enriched in response to oxidative stress and Nrf2 signaling pathway. Furthermore, molecular docking revealed strong affinity between core targets and active components of YNJ. Finally, in rats with type 2 diabetes, YNJ obviously attenuated cardiac collagen accumulation and degree of fibrosis. Meanwhile, YNJ significantly upregulated protein expression of SIRT1, Nrf2 and NQO1 in diabetic myocardium.DiscussionCollectively, our findings suggested that YNJ could effectively ameliorate cardiomyopathy induced by diabetes possibly through SIRT1/Nrf2/NQO1 signaling.

ObjectiveTo understand the varieties, evaluation, treatment, and prognosis of severe neurological diseases using the third NCU survey in China.DesignA cross-sectional questionnaire study. The study was completed in three main steps: filling in the questionnaire, sorting out the survey data, and analyzing the survey data.ResultsOf 206 NCUs, 165 (80%) provided relatively complete information. It was estimated that 96,201 patients with severe neurological diseases were diagnosed and treated throughout the year, with an average fatality rate of 4.1%. The most prevalent severe neurological disease was cerebrovascular disease (55.2%). The most prevalent comorbidity was hypertension (56.7%). The most prevalent complication was hypoproteinemia (24.2%). The most common nosocomial infection was hospital-acquired pneumonia (10.6%). The GCS, APACHE II, EEG, and TCD were the most commonly used (62.4–95.2%). The implementation rate of the five nursing evaluation techniques reached 55.8–90.9%. Routinely raising the head of the bed by 30°, endotracheal intubation and central venous catheterization were the mostprevalent treatment strategies (97.6, 94.5, and 90.3%, respectively). Traditional tracheotomy, invasive mechanical ventilation and nasogastric tube feeding (75.8, 95.8, and 95.8%, respectively) were more common than percutaneous tracheotomy, non-invasive mechanical ventilation and nasogastric tube insertion (57.6, 57.6, and 66.7%, respectively). Body surface hypothermia brain protection technology was more commonly used than intravascular hypothermia technology (67.3 > 6.1%). The rates of minimally invasive hematoma removal and ventricular puncture were only 40.0 and 45.5%, respectively.ConclusionIn addition to traditional recognized basic life assessment and support technology, it is necessary to the use of promote specialized technology for neurological diseases, according to the characteristics of critical neurological diseases.

Abstract Background Rearrangements involving the fibroblast growth factor receptor 1 (FGFR1) gene result in 8p11 myeloproliferative syndrome (EMS), which is a rare and aggressive hematological malignancy that is often initially diagnosed as myelodysplastic syndrome (MDS). Clinical outcomes are typically poor due to relative resistance to tyrosine kinase inhibitors (TKIs) and rapid transformation to acute leukemia. Deciphering the transcriptomic signature of FGFR1 fusions may open new treatment strategies for FGFR1 rearrangement patients. Methods DNA sequencing (DNA-seq) was performed for 20 MDS patients and whole exome sequencing (WES) was performed for one HOOK3-FGFR1 fusion positive patient. RNA sequencing (RNA-seq) was performed for 20 MDS patients and 8 healthy donors. Fusion genes were detected using the STAR-Fusion tool. Fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), and Sanger sequencing were used to confirm the HOOK3-FGFR1 fusion gene. The phosphorylation antibody array was performed to validate the activation of nuclear factor-kappaB (NF-kappaB) signaling. Results We identified frequently recurrent mutations of ASXL1 and U2AF1 in the MDS cohort, which is consistent with previous reports. We also identified a novel in-frame HOOK3-FGFR1 fusion gene in one MDS case with abnormal monoclonal B-cell lymphocytosis and ring chromosome 8. FISH analysis detected the FGFR1 break-apart signal in myeloid blasts only. qRT-PCR and Sanger sequencing confirmed the HOOK3-FGFR1 fusion transcript with breakpoints located at the 11th exon of HOOK3 and 10th exon of FGFR1, and Western blot detected the chimeric HOOK3-FGFR1 fusion protein that is presumed to retain the entire tyrosine kinase domain of FGFR1. The transcriptional feature of HOOK3-FGFR1 fusion was characterized by the significant enrichment of the NF-kappaB pathway by comparing the expression profiling of FGFR1 fusion positive MDS with 8 healthy donors and FGFR1 fusion negative MDS patients. Further validation by phosphorylation antibody array also showed NF-kappaB activation, as evidenced by increased phosphorylation of p65 (Ser 536) and of IKBalpha (Ser 32). Conclusions The HOOK3-FGFR1 fusion gene may contribute to the pathogenesis of MDS and activate the NF-kappaB pathway. These findings highlight a potential novel approach for combination therapy for FGFR1 rearrangement patients.

BackgroundSufficient attention to trunk rehabilitation after stroke is still lacking. Loss of trunk selective activity is considered to be the leading cause of trunk postural control disorder after stroke. “Taking the Waist as the Axis” Therapy (WAT) was developed as a combination of the concept of “Taking the Waist as the Axis” from Tai Chi and the rehabilitation of trunk dysfunction after stroke. The present clinical trial examined and assessed the effects of WAT on stroke patients.MethodsA total of 43 stroke hemiplegic patients with trunk postural control disorder, whose Trunk Impairment Scale (TIS) scoring between 8 and 18, participated in the present study and were allocated randomly to the experimental (n = 23) or control groups (n = 20). The experimental group received WAT plus conventional therapy, and the control group received “Trunk Selective Activity” Therapy (TSAT) plus conventional therapy. Both groups received treatment once daily and 5 times per week for 3 weeks. The Trunk Impairment Scale (TIS), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), change of Intra-abdominal Pressure (IAP), static balance ability assessment, rapid ventilation lung function test and the Modified Barthel Index (MBI) were evaluated before and after intervention for both groups.ResultsThe experimental group was superior to the control group in TIS [4 (2, 5) vs. 3 (1.25, 4), p = 0.030], change of IAP [−3 (−8, −1.33) vs. −0.02 (−3.08, 6), p = 0.011], FMA-upper extremity [10 (6, 18) vs. 1 (0, 3), p = 0.002], FMA-lower extremity [2 (1, 4) vs. 1 (0, 2), p = 0.009] and FMA [14 (7, 21) vs. 2 (0.25, 3.75), p = 0.001]. Within experimental group, forced vital capacity (FVC) [81.35 (63.30, 94.88) vs. 91.75 (79.40, 97.90), p = 0.02] was significantly improved.ConclusionWAT was an effective trunk treatment after stroke, which significantly improved the patients’ trunk posture control ability, motor function and forced vital capacity. However, the results still need to be interpreted with caution for the intervention only lasted for 3 weeks.

Background and objectiveRetreatment pulmonary tuberculosis (PTB) still accounts for a large proportion of tuberculosis, and the treatment outcome is unfavorable. The recurrence of retreatment PTB based on long-term follow-up has not been well demonstrated. This study aimed to evaluate effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis.MethodsThis multicenter cohort study was conducted in 29 hospitals from 23 regions of China from July 1, 2009, to December 31, 2020. Patients were divided into two treatment regimen groups including experimental group [modified regimen (4H-Rt2-E-Z-S(Lfx)/4H-Rt2-E)]and control group [standard regimen (2H-R-E-Z-S/6H-R-E or 3H-R-E-Z/6H-R-E)]. The patients enrolled were followed up of 56 months after successful treatment. We compared the treatment success rate, treatment failure rate, adverse reaction rate, and recurrence rate between two regimens. Multivariate Cox regression model was used to identify the potential risk factors for recurrence after successful treatment with proportional hazards assumptions tested for all variables.ResultsA total of 381 patients with retreatment PTB were enrolled, including 244 (64.0%) in the experimental group and 137 (36.0%) in the control group. Overall, the treatment success rate was significant higher in the experimental group than control group (84.0 vs. 74.5%, P = 0.024); no difference was observed in adverse reactions between the two groups (25.8 vs. 21.2%, P > 0.05). A total of 307 patients completed the 56 months of follow-up, including 205 with the modified regimen and 102 with the standard regimen. Among these, 10 cases (3.3%) relapsed, including 3 in the experimental group and 7 in the control group (1.5% vs 6.9%, P = 0.035). Reduced risks of recurrence were observed in patients treated with the modified regimen compared with the standard regimen, and the adjusted hazard ratio was 0.19 (0.04–0.77).ConclusionThe modified retreatment regimen had more favorable treatment effects, including higher treatment success rate and lower recurrence rate in patients with retreated drug-sensitive PTB.

The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes and diseases, such as depression. Oxidative stress can result in or aggravate a battery of pathological processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder and ferroptosis, which have been found to be involved in the development of depression. Inhibition of oxidative stress and related pathological processes can help improve depression. In this regard, the nuclear factor erythroid 2-related factor 2 (Nrf2) in the antioxidant defense system may play a pivotal role. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damages, but also directly regulate the genes related to the above pathological processes to combat the corresponding alterations. Therefore, targeting Nrf2 has great potential for the treatment of depression. Activation of Nrf2 has antidepressant effect, but the specific mechanism remains to be elucidated. This article reviews the key role of Nrf2 in depression, focusing on the possible mechanisms of Nrf2 regulating oxidative stress and related pathological processes in depression treatment. Meanwhile, we summarize some natural and synthetic compounds targeting Nrf2 in depression therapy. All the above may provide new insights into targeting Nrf2 for the treatment of depression and provide a broad basis for clinical transformation.

Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the most prevalent neurodegenerative disease worldwide. The primary pathological hallmarks of AD are the deposition of β-amyloid plaques and neurofibrillary tangles. Autophagy, a pathway of clearing damaged organelles, macromolecular aggregates, and long-lived proteins via lysosomal degradation, has emerged as critical for proteostasis in the central nervous system (CNS). Studies have demonstrated that defective autophagy is strongly implicated in AD pathogenesis. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy, enhances the expression of related genes that control autophagosome formation, lysosome function, and autophagic flux. The study of TFEB has greatly increased over the last decade, and the dysfunction of TFEB has been reported to be strongly associated with the pathogenesis of many neurodegenerative disorders, including AD. Here, we delineate the basic understanding of TFEB dysregulation involved in AD pathogenesis, highlighting the existing work that has been conducted on TFEB-mediated autophagy in neurons and other nonneuronal cells in the CNS. Additionally, we summarize the small molecule compounds that target TFEB-regulated autophagy involved in AD therapy. Our review may yield new insights into therapeutic approaches by targeting TFEB and provide a broadly applicable basis for the clinical treatment of AD.

Objective: Glutamate mediated excitotoxicity, such as oxidative stress, neuroinflammation, synaptic loss and neuronal death, is ubiquitous in Alzheimer's disease (AD). Our previous study found that 15 Hz repetitive transcranial magnetic stimulation (rTMS) could reduce cortical excitability. The purpose of this study was to explore the therapeutic effect of higher frequency rTMS on 3xTg-AD model mice and further explore the mechanisms of rTMS. Methods: First, WT and 3xTg-AD model mice received 25 Hz rTMS treatment for 21 days. The Morris water maze test was used to evaluate the cognitive function. The levels of Aβ and neuroinflammation were assessed by ELISA and immunofluorescence. Oxidative stress was quantified by biochemical assay kits. Brain glucose metabolism was assessed by 18F-FDG PET. Apoptosis was assessed by western blot and TUNEL staining. Synaptic plasticity and PI3K/Akt/GLT-1 pathway related protein expression were assessed by western blot. Next, to explore the activity of PI3K/Akt in the therapeutic effect of rTMS, 3xTg-AD model mice were given LY294002 intervention and rTMS treatment for 21 days, the experimental method was the same as before. Results: We found that 25 Hz rTMS could improve cognitive function of 3xTg-AD model mice, reduce hippocampal Aβ1-42 levels, ameliorate oxidative stress and improve glucose metabolism. rTMS alleviated neuroinflammatory response, enhanced synaptic plasticity and reduced neuronal loss and cell apoptosis, accompanied by activation of PI3K/Akt/GLT-1 pathway. After administration of PI3K/Akt inhibitor LY294002, 25 Hz rTMS could not improve the cognitive function and reduce neuron damage of 3xTg-AD model mice, nor could it upregulate the expression of GLT-1, indicating that its therapeutic and protective effects required the involvement of PI3K/Akt/GLT-1 pathway. Conclusion: rTMS exerts protective role for AD through regulating multiple pathological processes. Meanwhile, this study revealed the key role of PI3K/Akt/GLT-1 pathway in the treatment of AD by rTMS, which might be a new target.

AimsLeaf chlorophyll (Chl) is a fundamental component and good proxy for plant photosynthesis. However, we know little about the large-scale patterns of leaf Chl and the relative roles of current environment changes vs. plant evolution in driving leaf Chl variations.LocationsThe east to west grassland transect of the Tibetan Plateau.MethodsWe performed a grassland transect over 1,600 km across the Tibetan Plateau, measuring leaf Chl among 677 site-species.ResultsLeaf Chl showed a significantly spatial pattern across the grasslands in the Tibetan Plateau, decreasing with latitude but increasing with longitude. Along with environmental gradient, leaf Chl decreased with photosynthetically active radiation (PAR), but increased with water availability and soil nitrogen availability. Furthermore, leaf Chl also showed significant differences among functional groups (C4 > C3 species; legumes < non-legume species), but no difference between annual and perennial species. However, we surprisingly found that plant evolution played a dominant role in shaping leaf Chl variations when comparing the sum and individual effects of all the environmental factors above. Moreover, we revealed that leaf Chl non-linearly decreased with plant evolutionary divergence time. This well-matches the non-linearly increasing trend in PAR or decreasing trend in temperature during the geological time-scale uplift of the Tibetan Plateau.Main ConclusionThis study highlights the dominant role of plant evolution in determining leaf Chl variations across the Tibetan Plateau. Given the fundamental role of Chl for photosynthesis, these results provide new insights into reconsidering photosynthesis capacity in alpine plants and the carbon cycle in an evolutionary view.

Polygonatum sibiricum Red. has been used as a medicinal herb and nutritional food in traditional Chinese medicine for a long time. It must be processed prior to clinical use for safe and effective applications. However, the present studies mainly focused on crude Polygonatum sibiricum (PS). This study aimed to investigate the chemical properties, blood-enriching effects and mechanism of polysaccharide from the steam-processed Polygonatum sibiricum (SPS), which is a common form of PS in clinical applications. Instrumentation analyses and chemistry analyses revealed the structure of SPS polysaccharide (SPSP). A mice model of blood deficiency syndrome (BDS) was induced by acetylphenylhydrazine (APH) and cyclophosphamide (CTX). Blood routine test, spleen histopathological changes, serum cytokines, etc. were measured. The spleen transcriptome changes of BDS mice were detected by RNA sequencing (RNA-seq). The results showed that SPSP consists predominantly of Gal and GalA together with fewer amounts of Man, Glc, Ara, Rha and GlcN. It could significantly increase peripheral blood cells, restore the splenic trabecular structure, and reverse hematopoietic cytokines to normal levels. RNA-seq analysis showed that 122 differentially expressed genes (DEGs) were obtained after SPSP treatment. GO and KEGG analysis revealed that SPSP-regulated DEGs were mainly involved in hematopoiesis, immune regulation signaling pathways. The reliability of transcriptome profiling was validated by quantitative real-time PCR and Western blot, and the results indicated that the potential molecular mechanisms of the blood-enriching effects of SPSP might be associated with the regulating of JAK1-STAT1 pathway, and elevated the hematopoietic cytokines (EPO, G-CSF, TNF-α and IL-6). This work provides important information on the potential mechanisms of SPSP against BDS.

The thinned young apple is a by-product and is generally discarded in the orchard during fruit thinning. The polyphenol content of thinned young apples is about 10 times more than that of ripe apples. In our study, the antibacterial effect of thinned young apple polyphenols (YAP) on the halitosis-related bacteria including Porphyromonas gingivalis, Prevotella intermedius, and Fusobacterium nucleatum was investigated. The minimum inhibitory concentrations of YAP against P. gingivalis, P. intermedia, and F. nucleatum were 8.0, 8.0, and 12.0 mg/ml, while the minimum bactericidal concentrations were 10.0, 10.0, and 14.0 mg/ml, respectively. The scanning electron microscopy and transmission electron microscopy analyses showed that after YAP treatment, the membrane surface of halitosis-related bacterial cells was coarse and the cell wall and membrane were separated and eventually ruptured. The integrity of the cell membrane was determined by flow cytometry, indicating that the cells with the integrity membrane significantly reduced as the YAP concentration treatment increased. The release of proteins and nucleic acids into the cell suspension significantly increased, and the membrane potential reduced after the YAP treatment. This research illustrated the antibacterial mechanism of YAP against halitosis-related bacteria and provided a scientific basis of utilizing the polyphenols from the discarded thinned young apples.

The leaves of Lindera aggregate (Sims) Kosterm. are traditionally used as healthy tea for the prevention and treatment of hyperlipidemia in Chinese. The aim of this study was to evaluate the antihyperlipidemic effects and potential mechanisms of the aqueous extracts from L. aggregate leaves (AqLA-L) on normal and hypercholesterolemic (HCL) mice. HCL mice were induced by high fat diet (HFD) and orally administrated with or without AqLA-L for ten days. The results showed that AqLA-L (0.3, 0.6, 1.2 g/kg) significantly reduced serum TG, ALT, but elevated fecal TG in normal mice. AqLA-L (0.3, 0.6, 1.2 g/kg) also remarkably lowered serum TC, TG, LDL, N-HDL, ALT, GLU, APOB, hepatic GLU and increased serum HDL, APOA-I, fecal TG levels in HCL mice. These results revealed that AqLA-L treatment regulated the disorders of the serum lipid and liver function, reduced hepatic GLU contents both in normal and HCL mice. The potential mechanisms for cholesterol-lowering effects of AqLA-L might be up-regulation of cholesterol 7-alpha-hydroxylase (CYP7A1) and ATP-binding cassette transporter A1 (ABCA1), as well as down-regulation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). The data indicated that AqLA-L has potential therapeutic value in treatment of hyperlipidemia with great application security. Keywords: Lindera aggregate leaves, Hypercholesterolemic mice, Lipids, Cholesterol metabolism

Cotton fibers are the main raw materials of the textile industry. Exogenous superior fiber genes have been introduced into upland cotton to develop high-yield cultivars with excellent fiber quality. We used a single chromosomal segment on the chromosome A07 substitution line SL7, with high fiber strength, to investigate the molecular mechanism underlying its fiber quality. RNA-seq and KEGG analysis showed that 70 differentially expressed genes were enriched in plant hormone transduction pathways, including auxin, ethylene and abscisic acid, in fibers at 10 days post-anthesis (DPA). Among these, fiber-development related transcription factors MYB and NAC, including Gh_A11G0981 (MYB108), Gh_A03G0887 (NAC029), and Gh_A08G1691 (NAC021), were significantly upregulated in SL7, as were numerous cellulose synthase-like (CSL) genes involved in non-cellulose polysaccharide and cell wall synthesis. The hemicellulose content of SL7 was significantly higher than that of L22, an upland cotton cultivar. These results suggest that key genes in the introgressed chromosomal segment of SL7 regulate the expression of transcription-factor genes via hormone-transduction pathways, thereby inducing the expression of genes involved in secondary wall synthesis and ultimately improving fiber quality. This study has shed light on the molecular mechanism of fiber development and will contribute to the improvement of fiber quality of upland cotton by molecular breeding. Keywords: Cotton fiber quality, Single-fragment substitution line, RNA-seq, Hormone transduction pathway, Transcription factor

ATP-binding cassette transporter G (ABCG) has been shown to be engaged in export of broad-spectrum compounds with structural differences, but little is known concerning its role in cutin formation of cotton (Gossypium spp.). In this study, we conduct a genome-wide survey and detected 69, 71, 124 and 131 ABCG genes within G. arboretum, G. raimondii, G. hirsutum and G. barbadense, separately. The above ABCGs could be divided into four groups (Ia, Ib, Ic, II). Some ABCG genes such as GhABCG15, whose homologous gene transports cuticular lipid in Arabidopsis, was preferentially expressed in the development of fiber. A weighted gene co-expression network analysis (WGCNA) demonstrated that GhABCG expression was significantly associated with the amount of 16-Hydroxypalmitate (a main component of cutin precursor) in cotton fibers. Further, silencing of GhABCG15 by virus-induced gene silencing (VIGS) in cotton generated brightened and crinkled leaves as well as reduced thickness of cuticle and increased permeability. Chemical composition analysis showed the cutin content in GhABCG15-silenced leaves had decreased while the wax content had increased. Our results provide an insight for better understanding of the role of the Gossypium ABCG family and revealed the essential role of GhABCGs in cotton cutin formation.

This study aimed to investigate the hypolipidemic effect and mechanism of aqueous extract of Lindera aggregate leaves and Aloe vera (AqLL-A) in mice. Chemical profile of AqLL-A, serum/hepatic lipid profiles, and fecal TG were measured. The major components of AqLL-A related to hyperlipidemia, quercitrin and aloin were confirmed by HPLC. AqLL-A reduced serum/hepatic lipids, while elevated serum HDL, APOA1, fecal TG levels in hyperlipidemia mice. Furthermore, 20 potential biomarkers were detected by UPLC-QTOF/MS, and all of them were approached to a normal-like level after treatment of AqLL-A. Network pharmacology combined with metabolomics elucidate the related pathways involved in hyperlipidemia. The experimental validation indicated the differential expressions of CYP7A1, ACAT and HMGCR contribute to the hypolipidemic mechanism of AqLL-A. These results suggested that AqLL-A alleviated hyperlipidemia effectively, it might play synergistic therapeutic efficacies through regulating metabolic profiles and related signaling pathway.

Surrounding rock properties and occurrence stability of a coal seam roof are prerequisites for ensuring the safe and efficient operation of mines. In this study, the mechanisms and control of weakened water-rich roadway roof slabs were investigated regarding the engineering background of water-rich roadway roof slab destabilization in a coal mine in the western Qingyang mining area. The spatial and temporal evolution law of rock deformation and damage of such roadways during excavation were determined through field measurements. First, we tested the strength of the roof slab surrounding rock in water-rich roadways with different water contents and concluded that the primary and excavation-disturbing fissures of the coal-sedimentary rock body are the external conditions for the occurrence of water–rock interaction in water-rich coal seam roadways. Moreover, the rock mechanical damage phenomenon exhibited by clay minerals in contact with water is the key factor leading to the destabilization of the water-rich roof slab’s surrounding rock. Second, a technical approach for controlling the stability of the surrounding rock by adjusting the form of the roadway section and optimizing the support parameters was proposed, and the distribution law of the surrounding rock stress field and displacement field of each section was revealed via numerical calculation. It is considered that adjustment of the stress and displacement control of the surrounding rock of the roadway is more favorable for the straight wall circular arch section. Based on the results of the sensitive orthogonal numerical simulation test, the technical parameters and scheme of the roadway support optimization were proposed. Finally, the research results were applied in the field, and the deformations of the top and bottom slab and the two ribs of the roadway after optimizing the section and support parameters were calculated as 61% and 34% lower, respectively, than those before optimization, indicating that the proposed approach can effectively control the deformation of the water-rich roadway’s surrounding rock and achieve more economic and effective stability control of this type of roadway. The research results provide new ideas and methods for controlling the surrounding rock of water-rich soft rock roadways in the western mining areas of China, which has broad application value and prospects.

The thick and hard gangue layer has long been one of the key obstacles affecting the coal recovery rate in the fully mechanized top-coal caving mining of ultra-thick coal seams, and it is also one key factor restricting the development of the technology used for such work. In this study, to improve the poor top coal cavability and low recovery rate in fully mechanized caving mining of ultra-thick coal seams containing thick and hard gangue layers, the fully mechanized caving mining of longwall working face 42,108 of the Qinggangping Coal Mine is the engineering setting. Then, through a combination of theoretical analysis, numerical simulation, and field practice, a mechanical model of the cantilever beam with uniform load for fracture of the gangue layer is developed. Next, the mechanical action mechanism and influence of the gangue layer and thickness on the fracture of the cantilever beam are analyzed, and a method of pre-fracturing and weakening high-level thick and hard gangue layers using hydraulic fracturing technology is proposed. Finally, using RFPA2D-flow numerical simulation, the key technical parameters of hydraulic fracturing in the working face are designed and applied to field practice. The results show the following: After the high-level thick and hard gangue layer is treated by hydraulic fracturing technology, the amount of fractured gangue behind the support increases, while that of big coal blocks decreases significantly, and the overall fragmentation of top coal is at a reasonable level. In addition, after taking hydraulic fracturing technical measures during the mining period of the working face, the average recovery rate of the working face is 86.6%. This is an increase of 6.5% over the previous area without hydraulic fracturing.

A shale condensate gas reservoir with a high clay content and a high formation pressure was found in the Jurassic shale of the Dongyuemiao Member in the Fuxing area of the eastern Sichuan Basin. Reservoir characteristics and formation pressure have a significant influence on optimal development. The present study investigated the continental shale of the Dongyuemiao Member in Well F. The petrological properties, physical properties, and pore structure of the Dongyuemiao Member were studied using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), N2 adsorption, and mercury intrusion porosimetry (MIP). The permeability stress sensitivity characteristics of the shale reservoirs are discussed based on the change in shale porosity and permeability under overburden pressure. The tested shale samples yielded total organic carbon (TOC) and S1 + S2 values ranging mainly from 1.0 wt.% to 1.5 wt.% and from 0.39 to 2.28 mg/g, respectively, which was in the high maturity stage of the thermal evolution of organic matter (OM). The shales of the Dongyuemiao Member were found to contain high average clay mineral contents (more than 50%) of calcite and quartz, as well as albite, pyrite, dolomite, and halite. The main developments were identified as silica-rich argillaceous shale lithofacies, argillaceous shale lithofacies, and mixed argillaceous shale lithofacies. The pores were found to mainly be plate-like and flake-like interlayer pores of clay minerals and OM pores with various shapes. The pore size was mainly concentrated below 110 nm, and the pore volume increment increased in flakes with pore diameter. The average porosity and permeability of shale were found to be 4.827% and 0.243 mD, respectively. Clay minerals and quartz are beneficial for improving the porosity and permeability of reservoirs, while carbonate minerals have the opposite effect. The permeability of the shale showed a negative exponential change with increasing effective stress under overburden pressure. When the effective confining pressure was greater than 20 MPa, the decline rate of the shale permeability decreased with increases in the effective stress. The higher the clay mineral and TOC content, the stronger the stress sensitivity of shale permeability. The higher the carbonate mineral content, the weaker the stress sensitivity of shale permeability. The porosity sensitivity exponent indicates that matrix pores and micro-fractures are both developed in the Dongyuemiao Member, and the development of internal fractures is the main factor in the strong stress sensitivity of the shale permeability in the study area.

Lint percentage (LP) is an important yield component in cotton that is usually affected by initial fiber number and cell wall thickness. To explore how fiber cell wall development affects LP, phenotypic identification and dynamic transcriptome analysis were conducted using a single segment substitution line of chromosome 15 (SL15) that harbors a major quantitative trait locus (QTL) for LP. Compared to its recurrent parent LMY22, SL15 did not differ in initial fiber number, but the fiber cell wall thickness and single-fiber weight decreased significantly, altering LP. The comparative transcriptome profiles revealed that the secondary cell wall (SCW) development phase of SL15 was relatively delayed. Meanwhile, the expression of genes related to cell expansion decreased more slightly in SL15 with fiber development, resulting in relatively higher expression at SL15_25D than at LMY22_25D. SCW development-related genes, such as GhNACs and GhMYBs, in the putative NAC-MYB-CESA network differentially expressed at SL15_25D, along with the lower expression of CESA6, CSLC12, and CSLA2. The substituted chromosomal interval was further investigated, and found 6 of 146 candidate genes were differentially expressed in all four cell development periods including 10, 15, 20 and 25 DPA. Genetic variation and co-expression analysis showed that GH_D01G0052, GH_D01G0099, GH_D01G0100, and GH_D01G0140 may be important candidate genes associated with qLP-C15-1. Our results provide novel insights into cell wall development and its relationship with LP, which is beneficial for lint yield and fiber quality improvement.

Rotavirus enteritis (RVE) is a common acute intestinal infectious disease caused by rotavirus infection. It is an important cause of death in children younger than 5 years worldwide. Shenling baizhu powder (SBP), a classic traditional Chinese formulation, is one of the most popularly prescribed medicines for digestive diseases. Clinical studies have revealed the protective effects of SBP on RVE. However, the potential mechanism is still unclear. In this study, we aimed to evaluate the anti-rotavirus effect of SBP and its mechanism, focusing on the TLR4/MyD88/NF-κB signaling pathway. Our results demonstrated that, based on the inhibition of the virus-induced cytopathic effect in Caco-2 cells, the concentration for 50% of maximal effect (EC50) and selectivity index (SI) of SBP for RV-SA11 in the serum were 5.911% and 11.63, respectively. A total of 219 active compounds with oral bioavailability ≥30% and drug-likeness ≥ 0.18 were selected from the 10 ingredients present in the formulation of SBP, which acted on 471 potential targets. A total of 226 target genes of RVE were obtained from the GeneCards database. The protein-protein interaction (PPI) network showed that there was a close interaction between 44 common targets of SBP and RVE. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SBP acted on RVE through various inflammatory pathways and the intestinal immune network. Subsequently, we investigated the effect of SBP on TLR4/MyD88/NF-κB signaling pathway in vitro. After infection with RV- SA11, the expression of TLR4, MyD88, and NF-κB mRNA and protein increased significantly, which could be abolished by SBP treatment. In addition, the IL-1β, TNF-α, IL-6, and IFN-β levels increased markedly in Caco-2 cells infected with RV-SV11. Treatment with SBP partly reversed the changes of IL-1β, TNF-α, and IL-6, while further increased the level of IFN-β. In conclusion, our study revealed that SBP can significantly inhibit rotavirus replication and proliferation in vitro. The antiviral effect may be related to the regulation of the TLR4/MyD88/NF-κB signaling pathway, followed by the down regulation of inflammatory cytokines and up regulation of IFN-β induced by rotavirus.

To understand the molecular mechanisms of salinity tolerance during seed germination and post-germination stages, this study characterized phenotypic and transcriptome responses of two cotton cultivars during salinity stress. The two cultivars were salt-tolerant (ST) LMY37 and salt-sensitive (SS) ZM12, with the former exhibiting higher germination rate, growth, and primary-root fresh weight under salinity stress. Transcriptomic comparison revealed that up-regulation of differentially expressed genes (DEGs) was the main characteristic of transcriptional regulation in ST, while SS DEGs were mainly down-regulated. GO and KEGG analyses uncovered both common and specific responses in ST and SS. Common processes, such as reactive oxygen species (ROS) metabolism and cell wall biosynthesis, may be general responses to salinity in cotton. In contrast, DEGs involved in MAPK-signaling pathway activated by ROS, carotenoid biosynthesis pathway and cysteine and methionine metabolism pathway [producing the precursors of stress hormone abscisic acid (ABA) and ethylene (ET), respectively] as well as stress tolerance related transcription factor genes, showed significant expression differences between ST and SS. These differences might be the molecular basis leading to contrasting salinity tolerance. Silencing of GhERF12, an ethylene response factor gene, caused higher salinity sensitivity and increased ROS accumulation after salinity stress. In addition, peroxidase (POD) and superoxide dismutase (SOD) activity obviously declined after silencing GhERF12. These results suggest that GhERF12 is involved in salinity tolerance during early development. This study provides a novel and comprehensive perspective to understand key mechanisms of salinity tolerance and explores candidate genes that may be useful in developing stress-tolerant crops through biotechnology.

ObjectivesTo investigate the utility of spectral computed tomography (CT) parameters for the prediction of the preoperative Masaoka-Koga stage of thymic epithelial tumors (TETs).Materials and MethodsFifty-four patients with TETs, aged from 37 to 73 years old, an average age of 55.56 ± 9.79 years, were included in the study.According to the Masaoka-Koga staging method, there were 19 cases of stage I, 15 cases of stage II, 8 cases of stage III, and 12 cases of stage IV disease. All patients underwent dual-phase enhanced energy spectral CT scans. Regions of interest (ROIs) were defined in sections of the lesion with homogeneous density, the thoracic aorta at the same level as the lesion, the outer fat layer of the lesion, and the anterior chest wall fat layer. The single-energy CT value at 40-140 keV, iodine concentration, and energy spectrum curve of all lesion and thoracic aorta were obtained. The energy spectrum CT parameters of the lesions, extracapsular fat of the lesions, and anterior chest wall fat in stage I and stage II were obtained. The energy spectrum CT parameters of the lesions, enlarged lymph nodes and intravascular emboli in the 3 groups were obtained. The slope of the energy spectrum curve and the normalized iodine concentration were calculated.ResultsIn stage I lesions, there was a statistically significant difference between the slope of the energy spectrum curve for the lesion and those of the fat outside the lesion and the anterior chest wall in the arteriovenous phase (P0.05). The energy spectrum curve of the tumor parenchyma was consistent with that of the enlarged lymph nodes and intravascular emboli. The two radiologists have strong consistency in evaluating TETs Masaoka-Koga staging, The Kappa coefficient is 0.873,(95%CI:0.768-0.978).ConclusionSpectral CT parameters, especially the energy spectrum curve and slope, are valuable for preoperative TET and can be used in preoperative staging prediction.

Introduction: Lindera aggregata is a main Chinese herb of ancient prescriptions Suoquan pill applied for treating the chronic kidney disease (CKD). A large number of application histories of Lindera aggregata in the treatment of CKD have been recorded in Chinese traditional medical literature. The previous reports revealed that Lindera aggregata can treat CKD. Methods: Rats were randomly divided into control, model, Huangkui,Lindera aggregata ethanol extract (LEE) and Lindera aggregata water extract (LWE) groups. hematoxylin-eosin (HE) staining was used to detect the pathology of kidney. The levels of serum creatinine (Scr), serum Neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), urine protein (UP), kidney index(KI) were evaluated. The UPLC − QTOF/MS were applied to probe the metabolic profile. Furthermore, Indoxyl sulfate-induced human renal tubular epithelial (HK-2) cell model was built to determine the expression levels of pathogenesis-related proteins. Results: The results demonstrated that LEE and LWE significantly inhibited the rebound in Scr, BUN, NGAL, UP and KI in models, except for the effect of LWE at low dose (LWE-L) and LEE at low dose (LEE-L) on KI and the effect of LWE-H at high dose (LWE-H) and LEE-L on BUN and NGAL. Moreover,Lindera aggregata extracts alleviated renal tubular dilatation, interstitial fibrosis and interstitial inflammation. By analysis, twenty-eight metabolites were related to CKD. After intervention of Lindera aggregata extracts, some metabolites approach to a normal-like level, such as Indoxyl sulfate. These metabolites are mainly involved in tryptophan, fatty acid, glycerophospholipid, tyrosine and arachidonic acid metabolic pathways. Furthermore, Lindera aggregata extracts mediate the expression of smad2, smad3, smad7 and TGF-β in Indoxyl sulfate-induced HK-2 cell. Conclusions: Lindera aggregata extracts can mitigate adenine-induced CKD by modulating the metabolic profile and TGF-β/Smad signaling pathway, providing important supports for developing protective agent of Lindera aggregata for CKD.

In this study, we sequenced the complete chloroplast genome of Lindera aggregate (Sims) Kosterm., an important Chinese herbal medicine. The complete chloroplast genome with a size of 152,714 bp in length, contained two inverted repeats (IRa and IRb) regions of 20,090 bp each, which were separated by a large single copy (LSC, 93,743 bp) regions and a small single copy (SSC, 18,791 bp) regions, the overall GC content was 42.84%. The chloroplast genome contained 122 genes, 77 protein-coding, 37 tRNA, and 8 rRNA genes. The phylogenetic tree showed that Lindera aggregate (Sims) Kosterm. has a close relationship with Lindera chuni.

Comorbidity between diabetes mellitus (DM) and depression, two chronic and devastating diseases spreading worldwide, has been confirmed by a large body of epidemiological and clinical studies. Due to the bidirectional relationship between DM and depression, this comorbidity leads to poorer outcomes in both conditions. Given the adverse effects and limited effectiveness of the existing therapies for depression associated with diabetes, the development of novel therapeutic drugs with more potency and fewer side effects is still the most important goal. Hence, many researchers have made great efforts to investigate the potential usefulness of traditional Chinese medicine (TCM) and natural products, including natural extracts and purified compounds, in the treatment of comorbid depression in diabetes. Here, we reviewed the related literature on TCM and natural products that can remedy the comorbidity of diabetes and depression and presented them on the basis of their mechanism of action, focusing on shared risk factors, including insulin resistance, oxidative stress and inflammation, and nervous disturbances. In short, this review suggests that TCM and natural products could expand the therapeutic alternatives to ameliorate the association between DM and depressive disorders.

Combination therapy is a common approach for clinical treatment of type 2 diabetes mellitus, especially for patients with poor monotherapy. Meta-analysis suggested that omarigliptin, a long-acting DPP-4 inhibitor, combined with pioglitazone might improve the side effects of pioglitazone. However, little is known about the pharmacokinetic properties after a coadministration. In this study, a rapid and reliable method for the simultaneous determination of the pioglitazone and omarigliptin in rat plasma by UHPLC-MS/MS was established and validated for the first time. An exsil mono C18 column (2.0 × 50 mm, 3 μm) was used to separate the analytes and the column temperature was kept at 30°C. Sitagliptin was selected as the internal standard. 0.02% formic acid aqueous solution (A) and methanol-acetonitrile (B) were used as mobile phases with gradient elution at a flow rate of 0.3 mL/min. The elution procedure was as follows: 20%B (0–0.1 min), 80%B (0.1–0.3 min), 80%B (0.3–2.0 min), and 20%B (2.1–3.0 min). A multiple reaction monitor (MRM) was used under positive ionization mode with electrospray ion source to detect pioglitazone (357.1 ⟶ 134.1), omarigliptin (399.2 ⟶ 153.0), and sitagliptin (408.2 ⟶ 235.0). The linear ranges of pioglitazone and omarigliptin were 5–2000 ng/mL and 10–4000 ng/mL, respectively. Good linear relationships were exhibited in the corresponding linear ranges (r ≥ 0.9944). The bioanalytical method was validated, and the selectivity, linearity, sensitivity, accuracy, precision, stability, recovery, and matrix effect were acceptable. The validated method was then successfully applied to pharmacokinetic study of pioglitazone combined with omarigliptin in rats. Results suggested that the combination of the two drugs had little effect on the pharmacokinetic parameters of each other in rats.

Background: The outbreak of coronavirus disease 2019 in Wuhan, Hubei Province, China has seriously affected people's mental health. We aimed to assess the psychological impact of the coronavirus disease 2019 on health care workers and non-health care workers in three different epidemic areas in China and to identify independent risk factors.Methods: We surveyed 1,020 non-health care workers and 480 health care workers in Wuhan, other cities in Hubei except Wuhan and other provinces in China except Hubei.Results: Health care workers in Hubei had higher levels of anxiety and depression than non-health care workers (p < 0.05), but there was no such difference in other provinces in China except Hubei (p > 0.05). Compared with other regions, health care workers in Wuhan was more anxious (p < 0.05), and this anxiety may be caused by concerns about occupational exposure and wearing protective clothing for a long time daily; health care workers in Hubei had more obvious depression (p < 0.05), which may be associated with long days participating in epidemic work and wearing protective clothing for a long time daily. Meanwhile, 62.5% of health care workers were proud of their work. The anxiety and depression of non-health care workers in Wuhan were also the most serious.Conclusions: In Wuhan, where the epidemic is most severe, levels of anxiety and depression seem to be higher, especially among health care workers. This information may help to better prepare for future events.

Multistage fluid activities and hydrocarbon accumulation processes have occurred in the Dengying Formation of the Sichuan Basin during its long geological history. Petrography and cathodoluminescence observations; in situ microanalysis of rare earth elements, carbon, oxygen, and strontium isotopes; fluid inclusion microthermometric experiments; laser Raman experiments; burial history; thermal history; and hydrocarbon generation history simulation have been applied to study the characteristics of vein-forming fluid in the Dengying Formation reservoirs in the southeast and southwest of Sichuan Basin and to analyze in-depth the multistage fluid activity and hydrocarbon accumulation process. The results show that two stages of dolomite and one stage of quartz are developed in the 4th member of the Dengying Formation in the southeast of Sichuan Basin, and three stages of dolomite are developed in the 2nd member of the Dengying Formation in the southwest of Sichuan Basin. The source of the dolomite veins is mainly reservoir marine diagenetic fluid. Dolomites developed in the Hercynian period were affected by hydrothermal activity to a certain extent which may have been caused by the activity of the Emei mantle plume. The diagenetic mineral sequence of the 4th member of the Dengying Formation in the southeast of Sichuan Basin is quartz (432 Ma)/dolomite I (421 Ma)/dolomite II (288 Ma), and the 2nd member of the Dengying Formation in the southwest of the Sichuan Basin is dolomite I (425 Ma)/dolomite II (283 Ma)/dolomite III (262 Ma). The main hydrocarbon accumulation period was during the Hercynian–Indosinian stage which was related to the thermal influence of the Emei mantle plume activity on the source rock of the Qiongzhusi Formation. Combined with petrography, inclusion thermometry, burial history, and hydrocarbon generation history simulation, the fluid activity and hydrocarbon accumulation evolution sequence in the southeast and southwest of the Sichuan Basin are determined comprehensively.