Overburden failure and water-sand mixture outburst conditions of weakly consolidated overlying strata in Dananhu No.7 coal mine.

This study presents a case of weakly consolidated strata developed in Dananhu No.7 coal mine. Using a combination of numerical simulation, field measurement comparison, and the critical hydraulic gradient criterion, we investigate the overburden failure and the risk possibility of water-sand mixture inrush during excavation. The following are the principal findings: (1) Weakly consolidated rocks have poor physical characteristics, particularly when they are mudded and disintegrated after encountering water, which may become a favorable source of water-sand inrush; (2) The water-conducting zone develops to a height of 160.5 m with a crack-mining ratio of 15.29 times, extending upward to Toutunhe Formation aquifer. The predictions are consistent with measurements in adjacent mines with similar geological conditions; (3) Cracks without larger subsidence are developed at the front edge of the mining direction, and some parallel stepped cracks behind the goaf could be easily observed. Ground subsidence along the goaf center finally displays a symmetrically wide-gentle U shape; (4) The critical hydraulic gradient of Toutunhe Formation aquifer, aquifer above 3# coal seam, and aquifer of 3#-7# coal seam in Xishanyao Formation is 1.314, 1.351, and 1.380, the actual value is 0.692, 2.089, and 7.418 accordingly. It is inferred water-sand mixture outburst will not occur in Toutunhe Formation aquifer, while the potential risk exists in the aquifers of Xishanyao Formation. Through drainage and depressurization projects, a water-sand mixture outburst accident does not occur during excavation. This study reveals the overburden failure characteristics and the initiation mechanism of water-sand inrush in weakly cemented strata, as well as the internal relationship between them, which provides new research ideas for safe operation in other mining areas with similar geological conditions. The research work has certain practical guiding significance.

Follicular fluid aids cell adhesion, spreading in an age independent manner and shows an age-dependent effect on DNA damage in fallopian tube epithelial cells.

Ovarian cancer (OC) is deadly, and likely arises from the fallopian tube epithelium (FTE). Despite the association of OC with ovulation, OC typically presents in post-menopausal women who are no longer ovulating. The goal of this study was to understand how ovulation and aging interact to impact OC progression from the FTE. Follicular fluid released during ovulation induces DNA damage in the FTE, however, the role of aging on FTE exposure to follicular fluid is unexplored. Follicular fluid samples were collected from 14 women and its effects on FTE cells was assessed. Follicular fluid caused DNA damage and lipid oxidation in an age-dependent manner, but instead induced cell proliferation in a dose-dependent manner, independent of age in FTE cells. Follicular fluid regardless of age disrupted FTE spheroid formation and stimulated attachment and growth on ultra-low attachment plates. Proteomics analysis of the adhesion proteins in the follicular fluid samples identified vitronectin, a glycoprotein responsible for FTE cell attachment and spreading.

Study of myopia progression and risk factors in Hubei children aged 7-10 years using machine learning: a longitudinal cohort.

BACKGROUND: To investigate the trend of refractive error among elementary school students in grades 1 to 3 in Hubei Province, analyze the relevant factors affecting myopia progression, and develop a model to predict myopia progression and the risk of developing high myopia in children. METHODS: Longitudinal study. Using a cluster-stratified sampling method, elementary school students in grades 1 to 3 (15,512 in total) from 17 cities in Hubei Province were included as study subjects. Visual acuity, cycloplegic autorefraction, and height and weight measurements were performed for three consecutive years from 2019 to 2021. Basic information about the students, parental myopia and education level, and the students' behavioral habits of using the eyes were collected through questionnaires. RESULTS: The baseline refractive errors of children in grades 1 ~ 3 in Hubei Province in 2019 were 0.20 (0.11, 0.27)D, -0.14 (-0.21, 0.06)D, and - 0.29 (-0.37, -0.22)D, respectively, and the annual myopia progression was - 0.65 (-0.74, -0.63)D, -0.61 (-0.73, -0.59)D and - 0.59 (-0.64, -0.51)D, with the prevalence of myopia increasing from 17.56%, 20.9%, and 34.08% in 2019 to 24.16%, 32.24%, and 40.37% in 2021 (Χ2 = 63.29, P < 0.001). With growth, children's refractive error moved toward myopia, and the quantity of myopic progression gradually diminished. (F = 291.04, P = 0.027). The myopia progression in boys was less than that in girls in the same grade (P < 0.001). The change in spherical equivalent refraction in myopic children was smaller than that in hyperopic and emmetropic children (F = 59.28, P < 0.001), in which the refractive change in mild myopia, moderate myopia, and high myopia children gradually increased (F = 73.12, P < 0.001). Large baseline refractive error, large body mass index, and high frequency of eating sweets were risk factors for myopia progression, while parental intervention and strong eye-care awareness were protective factors for delaying myopia progression. The nomogram graph predicted the probability of developing high myopia in children and found that baseline refraction had the greatest predictive value. CONCLUSION: Myopia progression varies by age, sex, and myopia severity. Baseline refraction is the most important factor in predicting high myopia in childhood. we should focus on children with large baseline refraction or young age of onset of myopia in clinical myopia prevention and control.

Hepatic arterial infusion chemotherapy combined with bevacizumab plus a PD-1 inhibitor for gallbladder cancer with hepatic oligometastasis: a real-world study.

Background: Gallbladder cancer (GBC) is different from other biliary tract cancers in terms of molecular phenotype and microenvironment. Specific treatments for GBC need to be urgently explored. This study preliminarily investigated the clinical value of hepatic artery infusion chemotherapy (HAIC) combined with bevacizumab plus a programmed death receptor-1 (PD-1) inhibitor for treatment of GBC with hepatic oligometastasis. Methods: We retrospectively collected data on GBC patients with hepatic oligometastasis, who received this combination therapy. The clinical data, conversion rate, treatment response, adverse events (AEs), and short-term survival were summarized. The responses of primary gallbladder lesions and hepatic metastasis, and their effect on prognosis, were investigated. Results: A total of 27 patients were included in the analysis. No grade 4 AEs were observed. The overall objective response rate (ORR) was 55.6% and the disease control rate (DCR) was 85.2%. Median overall survival (OS) time was 15.0 months and the 1-year survival rate was 64.0%. Median progression-free survival (PFS) time was 7.0 months and the 1-year PFS rate was 16.2%. Six patients (22.2%) were successfully converted to resection. Compared with primary gallbladder lesions, it appeared more difficult for patients with hepatic metastasis to achieve remission (ORR: 40.7% vs. 77.8%; P=0.012), but its response appeared to be closely related to the prognosis [median OS: 16.0 months in the complete response (CR) or partial response (PR) group vs. 11.0 months in the stable disease (SD) or progressive disease (PD) group, P=0.070; median PFS: 12.0 months in the CR or PR group vs. 6.5 months in the SD or PD group, P<0.001]. Preoperative CA19-9 of >1,900 U/mL and >5 cm metastatic lesions were associated with an unsatisfactory response, whereas a significant decrease of 18F-fluorodeoxyglucose (18F-FDG) uptake may be a marker of tumor remission. Conclusions: The combination of HAIC, a PD-1 inhibitor, and bevacizumab shows potential for advanced GBC with hepatic oligometastasis. The therapeutic response of hepatic metastasis had a greater influence on prognosis than that of primary gallbladder lesions.

The Impact of Perceived Discrimination on Mobile Phone Addiction Among Chinese Higher Vocational College Students: A Chain Mediating Role of Negative Emotions and Learning Burnout.

Purpose: Perceived discrimination among higher vocational college students is a prevalent issue in China and is linked to various mental and behavioral problems, including mobile phone addiction. Yet, the mechanisms underlying the relationship between perceived discrimination and mobile phone addiction remain ambiguous. Methods: To address this issue, we recruited 1253 higher vocational college students to elucidate the relationship between perceived discrimination and mobile phone addiction. Participants completed a series of self-report questionnaires assessing perceived discrimination, mobile phone addiction, negative emotions, and learning burnout. Results: Our findings suggest that perceived discrimination positively influences mobile phone addiction. The negative emotions and learning burnout play mediating effects between perceived discrimination and mobile phone addiction, respectively. Notably, we observe a chain mediating role of negative emotions and learning burnout play between perceived discrimination and mobile phone addiction. Conclusion: The results of our study demonstrate that higher vocational college students who perceived stronger discrimination are inclined to exhibit heightened emotional, cognitive, and learning challenges, such as increased negative emotions and learning burnout, which contribute to more serious excessive mobile phone use. These findings elucidate the mechanisms underlying the relationship between perceived discrimination and mobile phone addiction, enriching our understanding of the underlying emotional, cognitive, and learning dynamics in higher vocational college students.

Temporal Alterations in White Matter in An App Knock-In Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia and results in neurodegeneration and cognitive impairment. White matter (WM) is affected in AD and has implications for neural circuitry and cognitive function. The trajectory of these changes across age, however, is still not well understood, especially at earlier stages in life. To address this, we used the AppNL-G-F/NL-G-F knock-in (APPKI) mouse model that harbors a single copy knock-in of the human amyloid precursor protein (APP) gene with three familial AD mutations. We performed in vivo diffusion tensor imaging (DTI) to study how the structural properties of the brain change across age in the context of AD. In late age APPKI mice, we observed reduced fractional anisotropy (FA), a proxy of WM integrity, in multiple brain regions, including the hippocampus, anterior commissure (AC), neocortex, and hypothalamus. At the cellular level, we observed greater numbers of oligodendrocytes in middle age (prior to observations in DTI) in both the AC, a major interhemispheric WM tract, and the hippocampus, which is involved in memory and heavily affected in AD, prior to observations in DTI. Proteomics analysis of the hippocampus also revealed altered expression of oligodendrocyte-related proteins with age and in APPKI mice. Together, these results help to improve our understanding of the development of AD pathology with age, and imply that middle age may be an important temporal window for potential therapeutic intervention.

Analysis of the safety and effectiveness of endoscopic nasal dacryocystorhinostomy in the remedy of chronic dacryocystitis.

To estimate the safety and effectiveness of endoscopic nasal dacryocystorhinostomy in the remedy of chronic dacryocystitis. The clinical data of 105 subjects with chronic dacryocystitis enrolled into our hospital were analyzed retrospectively. The subjects were distinguished into nasal endoscopic group (endoscopic dacryocystorhinostomy; i.e., 51 cases) according to their surgical methods and external-route group (external-route dacryocystorhinostomy; i.e., 54 cases). The therapeutic effect, lacrimal gland secretion function, tear film stability, degree of epiphora, lacrimal passage patency, complications, and recurrence rate were contrasted between the 2 groups. The nasal endoscopic group exhibited a higher effective remedy rate (98.04%) compared with the external-route group (83.33%). Three months postoperation, both groups showed improvements in lacrimal gland secretion function and tear film stability, with the nasal endoscopic group demonstrating more significant enhancement in lacrimal gland secretion function than the external-route group. Six months postoperation, a reduction in the degree of epiphora was observed in both groups, with the nasal endoscopic group displaying a more pronounced decrease in epiphora severity and a higher lacrimal passage patency rate than the external-route group. Furthermore, the nasal endoscopic group experienced lower incidences of postoperative complications and recurrence rates. Endoscopic dacryocystorhinostomy is safe and effective in the remedy of chronic dacryocystitis.

Orexin-A attenuated motion sickness through modulating neural activity in hypothalamus nuclei.

BACKGROUND AND PURPOSE: We evaluated the hypothesis that central orexin application could counteract motion sickness responses through regulating neural activity in target brain areas. EXPERIMENTAL APPROACH: Thec effects of intracerebroventricular (i.c.v.) injection of orexin-A and SB-334867 (OX1 antagonist) on motion sickness-induced anorexia, nausea-like behaviour (conditioned gaping), hypoactivity and hypothermia were investigated in rats subjected to Ferris wheel-like rotation. Orexin-A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin-A, SB-334867 and TCS-OX2-29 (OX2 antagonist). The efficacy of intranasal application of orexin-A versus scopolamine on motion sickness symptoms in cats was also investigated. KEY RESULTS: Orexin-A (i.c.v.) dose-dependently attenuated motion sickness-related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin-A (20 µg) in rotated animals. Motion sickness responses were differentially inhibited by orexin-A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB-334867 and TCS-OX2-29 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin-A. Orexin-A (60 µg·kg-1) and scopolamine inhibited rotation-induced emesis and non-retching/vomiting symptoms, while orexin-A also attenuated anorexia with mild salivation in motion sickness cats. CONCLUSION AND IMPLICATIONS: Orexin-A might relieve motion sickness through acting on OX1 and OX2 receptors in various hypothalamus nuclei. Intranasal orexin-A could be a potential strategy against motion sickness.

Caveolin-1 Autonomously Regulates Hippocampal Neurogenesis Via Mitochondrial Dynamics.

The mechanisms underlying adult hippocampal neurogenesis (AHN) are not fully understood. AHN plays instrumental roles in learning and memory. Understanding the signals that regulate AHN has implications for brain function and therapy. Here we show that Caveolin-1 (Cav-1), a protein that is highly enriched in endothelial cells and the principal component of caveolae, autonomously regulates AHN. Conditional deletion of Cav-1 in adult neural progenitor cells (nestin +) led to increased neurogenesis and enhanced performance of mice in contextual discrimination. Proteomic analysis revealed that Cav-1 plays a role in mitochondrial pathways in neural progenitor cells. Importantly, Cav-1 was localized to the mitochondria in neural progenitor cells and modulated mitochondrial fission-fusion, a critical process in neurogenesis. These results suggest that Cav-1 is a novel regulator of AHN and underscore the impact of AHN on cognition.

NADH Photosynthesis System with Affordable Electron Supply and Inhibited NADH Oxidation.

Photosynthesis offers a green approach for the recycling of nicotinamide cofactors primarily NADH in bio-redox reactions. Herein, we report an NADH photosynthesis system where the oxidation of biomass derivatives is designed as an electron supply module (ESM) to afford electrons and superoxide dismutase/catalase (SOD/CAT) cascade catalysis is designed as a reactive oxygen species (ROS) elimination module (REM) to inhibit NADH degradation. Glucose as the electron donor guarantees the reaction sustainability accompanied with oxidative products of gluconic acid and formic acid. Meanwhile, enzyme cascades of SOD/CAT greatly eliminate ROS, leading to a ≈2.00-fold elevation of NADH yield (61.1 % vs. 30.7 %). The initial reaction rate and turnover frequency (TOF) increased by 2.50 times and 2.54 times, respectively, compared with those systems without REM. Our study establishes a novel and efficient platform for NADH photosynthesis coupled to biomass-to-chemical conversion.

Relative quantification of progressive changes in healthy and dysferlin-deficient mouse skeletal muscle proteomes.

INTRODUCTION/AIMS: Individuals with dysferlinopathies, a group of genetic muscle diseases, experience delay in the onset of muscle weakness. The cause of this delay and subsequent muscle wasting are unknown, and there are currently no clinical interventions to limit or prevent muscle weakness. To better understand molecular drivers of dysferlinopathies, age-dependent changes in the proteomic profile of skeletal muscle (SM) in wild-type (WT) and dysferlin-deficient mice were identified. METHODS: Quadriceps were isolated from 6-, 18-, 42-, and 77-wk-old C57BL/6 (WT, Dysf+/+ ) and BLAJ (Dysf-/- ) mice (n = 3, 2 male/1 female or 1 male/2 female, 24 total). Whole-muscle proteomes were characterized using liquid chromatography-mass spectrometry with relative quantification using TMT10plex isobaric labeling. Principle component analysis was utilized to detect age-dependent proteomic differences over the lifespan of, and between, WT and dysferlin-deficient SM. The biological relevance of proteins with significant variation was established using Ingenuity Pathway Analysis. RESULTS: Over 3200 proteins were identified between 6-, 18-, 42-, and 77-wk-old mice. In total, 46 proteins varied in aging WT SM (p < .01), while 365 varied in dysferlin-deficient SM. However, 569 proteins varied between aged-matched WT and dysferlin-deficient SM. Proteins with significant variation in expression across all comparisons followed distinct temporal trends. DISCUSSION: Proteins involved in sarcolemma repair and regeneration underwent significant changes in SM over the lifespan of WT mice, while those associated with immune infiltration and inflammation were overly represented over the lifespan of dysferlin-deficient mice. The proteins identified herein are likely to contribute to our overall understanding of SM aging and dysferlinopathy disease progression.

Synthesis of tetracyclic dibenzo[b,f][1,4]oxazepine-fused ß-lactams via visible-light-induced Staudinger annulation.

An efficient visible-light-induced Staudinger [2 + 2] annulation reaction between α-diazo ketones and dibenzo[b,f][1,4]oxazepine/thiazepine-imines under catalyst-free conditions has been developed. This protocol provides a facile method to synthesize tetracyclic dibenzo[b,f][1,4]oxazepine/thiazepine-fused ß-lactams bearing a quaternary carbon center with a broad substrate scope and high efficiency (37 examples, up to >99% yield).

Mimickers of neuroendocrine tumors on endoscopic ultrasound-guided fine-needle aspirate material: Need for caution.

Cytologic diagnosis of neuroendocrine tumors can be straightforward on cytologic preparations, given the classical neuroendocrine morphology and expression of neuroendocrine markers confirmed by immunohistochemistry. However, overreliance on neuroendocrine markers can lead to misdiagnosis even if individual cell features suggest a neuroendocrine tumor. We present three unusual cases, two of which were initially diagnosed as neuroendocrine tumors and the third one carried preliminary diagnosis of neuroendocrine tumor on endoscopic ultrasound-guided fine-needle aspirates. These cases subsequently turned out to be cholangioblastic cholangiocarcinoma, metastatic melanoma, and gastric glomus tumor, respectively. We suggest approaches that could have pointed us towards the correct diagnosis at the outset and discuss potential pitfalls.

The use of 3D video in medical education: A scoping review.

Objectives: The use of 3D video in medical education has not been fully explored. This article aims to review the evidence on 3D video currently presented in the medical education literature, including its impact on curriculum activities, to reference future research in this field. Methods: According to the guidelines of Arksey and O'Malley, the authors used a systematic search strategy (the last search was in December 2022) to search nine literature databases published in English, and only primary studies were included. Two authors independently screened all articles based on the eligibility criteria and performed a thematic analysis of the included literature. Results: Of 1,302 articles identified, 23 were included for insights into how opportunities for 3D video in medical education are created, how they are experienced, and how they influence and manifest behavior demonstrated partial congruency. Three themes were identified: (a) advantages of using 3D video in medical education; (b) the effect of using 3D video in medical education on students' academic achievement and ability; and (c) students' experience of 3D video in medical education. Conclusions: The application of 3D video in medical education has won the support of most students and educators. However, the effect of using 3D video in medical education is still controversial. Medical educators should combine the curriculum's characteristics, the students' learning situation, and the existing educational resources and choose to use them after careful consideration.

Investigation of organochlorine pesticides in the Wang Lake Wetland, China: Implications for environmental processes and risks.

Wang Lake Wetland is an important habitat for many fish and migratory birds. To explore the effect of periodic hydrological changes on the transfer and ecological risk of OCPs in the multimedia system of the wetland, eight sampling sites were selected for collecting soil (SS), sediment (SD) and water, to acquire dissolved phase (DP) and suspended particulate matter (SPM) samples during low- and high-flow periods. The results indicated that OCPs are pervasive in the various media of Wang Lake Wetland, and there was a significant temporal variability in concentration of ∑23OCPs in the SPM samples. Several OCPs exist certain ecological risks to aquatic organisms, but higher level of OCPs do not always equal to higher ecological risk. The residues of OCPs are largely attributed to their historical use, but recent inputs of some of them are still non-ignorable. The relatively higher values of organic carbon normalized partition coefficient (KOC) for SPM-W (KOC(SPM-W)) were obtained, which reflected the more frequent exchange of OCPs in the SPM samples. The sediment of the Wang Lake Wetland is likely to be a sink for several OCPs with high n-octanol/water partition coefficient (KOW) (e.g., DDTs and its metabolites), and high-temperature and rainfall-driven changes may promote the migration of OCPs with low KOW to the DP.

The 3D Controllable Fabrication of Nanomaterials with FIB-SEM Synchronization Technology.

Nanomaterials with unique structures and functions have been widely used in the fields of microelectronics, biology, medicine, and aerospace, etc. With advantages of high resolution and multi functions (e.g., milling, deposition, and implantation), focused ion beam (FIB) technology has been widely developed due to urgent demands for the 3D fabrication of nanomaterials in recent years. In this paper, FIB technology is illustrated in detail, including ion optical systems, operating modes, and combining equipment with other systems. Together with the in situ and real-time monitoring of scanning electron microscopy (SEM) imaging, a FIB-SEM synchronization system achieved 3D controllable fabrication from conductive to semiconductive and insulative nanomaterials. The controllable FIB-SEM processing of conductive nanomaterials with a high precision is studied, especially for the FIB-induced deposition (FIBID) 3D nano-patterning and nano-origami. As for semiconductive nanomaterials, the realization of high resolution and controllability is focused on nano-origami and 3D milling with a high aspect ratio. The parameters of FIB-SEM and its working modes are analyzed and optimized to achieve the high aspect ratio fabrication and 3D reconstruction of insulative nanomaterials. Furthermore, the current challenges and future outlooks are prospected for the 3D controllable processing of flexible insulative materials with high resolution.

Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3.

The prognosis and treatment outcomes of heart failure (HF) patients rely heavily on disease etiology, yet the majority of underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major point of protein regulation with rapid and profound effects on the function and activity of protein networks. Currently, there is a lack of comprehensive proteomic and phosphoproteomic studies examining cardiac tissue from HF patients with either dilated dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM). Here, we used a combined proteomic and phosphoproteomic approach to identify and quantify more than 5,000 total proteins with greater than 13,000 corresponding phosphorylation sites across explanted left ventricle (LV) tissue samples, including HF patients with DCM vs. nonfailing controls (NFC), and left ventricular infarct vs. noninfarct, and periinfarct vs. noninfarct regions of HF patients with ICM. Each pair-wise comparison revealed unique global proteomic and phosphoproteomic profiles with both shared and etiology-specific perturbations. With this approach, we identified a DCM-associated hyperphosphorylation cluster in the cardiomyocyte intercalated disc (ICD) protein, αT-catenin (CTNNA3). We demonstrate using both ex vivo isolated cardiomyocytes and in vivo using an AAV9-mediated overexpression mouse model, that CTNNA3 phosphorylation at these residues plays a key role in maintaining protein localization at the cardiomyocyte ICD to regulate conductance and cell-cell adhesion. Collectively, this integrative proteomic/phosphoproteomic approach identifies region- and etiology-associated signaling pathways in human HF and describes a role for CTNNA3 phosphorylation in the pathophysiology of DCM.

Potent NTD-Targeting Neutralizing Antibodies against SARS-CoV-2 Selected from a Synthetic Immune System.

The majority of neutralizing antibodies (NAbs) against SARS-CoV-2 recognize the receptor-binding domain (RBD) of the spike (S) protein. As an escaping strategy, the RBD of the virus is highly variable, evolving mutations to thwart a natural immune response or vaccination. Targeting non-RBD regions of the S protein thus provides a viable alternative to generating potential, robust NAbs. Using a pre-pandemic combinatorial antibody library of 1011, through an alternate negative and positive screening strategy, 11 non-RBD-targeting antibodies are identified. Amongst one NAb that binds specifically to the N-terminal domain of the S protein, SA3, shows mutually non-exclusive binding of the angiotensin-converting enzyme 2 receptor with the S protein. SA3 appears to be insensitive to the conformational change and to interact with both the "open" and "closed" configurations of the trimeric S protein. SA3 shows compatible neutralization as S-E6, an RBD-targeting NAb, against the wild type and variant of concern (VOC) B.1.351 (Beta) of the SARS-CoV-2 pseudo virus. More importantly, the combination of SA3 with S-E6 is synergistic and recovers from the 10-fold loss in neutralization efficacy against the VOC B.1.351 pseudo virus.

An improved risk zoning method of bed-separation water inrush in underground coal mines: a case study in Ningxia, China.

Bed-separation water inrush (BSWI) is a new type of coal mine disaster that has caused serious damage. The shortcomings of previous studies on this topic are as follows: 1) most studies focused on the BSWI mechanism, evolution, and control methods, and there is a lack of research on BSWI risk assessment methods and 2) previous risk assessment studies ignored the factors of the water yield property. First, based on the proposed BSWI engineering geological model, three first-order factors are proposed: 1) separation space between layers, 2) water production characteristics, and 3) water resistance effect. Then, eight secondary factors are determined: 1) production thickness (MT), 2) hard rock thickness (HRT), 3) improved lithology index (ILCI), 4) core recovery (CR), 5) aquifer depth (AD), 6) drilling fluid consumption (DFC), 7) protective layer thickness (PLT), and 8) self-healing potential index (SPI). Subsequently, the corresponding weights are calculated, and the multifactor superposition method is used to draw the BSWI risk map. The area is divided into three risk grades: low, medium, and high. The results are validated by observations of BSWI accidents and bed-separation water exploration and discharge boreholes in the study area. The proposed method can be used to effectively prevent BSWI disasters in other coal mines with similar geological conditions.

Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes.

Patients with type 2 diabetes exhibit severe impairments in insulin signalling in the brain and are five times more likely to develop Alzheimer's disease. However, what leads to these impairments is not fully understood. Here, we show reduced expression of endothelial cell caveolin-1 (Cav-1) in the db/db (Leprdb) mouse model of type 2 diabetes. This reduction correlated with alterations in insulin receptor expression and signalling in brain microvessels as well as brain parenchyma. These findings were recapitulated in the brains of endothelial cell-specific Cav-1 knock-out (Tie2Cre; Cav-1fl/fl) mice. Lack of Cav-1 in endothelial cells led to reduced response to insulin as well as reduced insulin uptake. Furthermore, we observed that Cav-1 was necessary for the stabilization of insulin receptors in lipid rafts. Interactome analysis revealed that insulin receptor interacts with Cav-1 and caveolae-associated proteins, insulin-degrading enzyme and the tight junction protein Zonula Occludence-1 in brain endothelial cells. Restoration of Cav-1 in Cav-1 knock-out brain endothelial cells rescued insulin receptor expression and localization. Overall, these results suggest that Cav-1 regulates insulin signalling and uptake by brain endothelial cells by modulating IR-α and IR-ß localization and function in lipid rafts. Furthermore, depletion of endothelial cell-specific Cav-1 and the resulting impairment in insulin transport leads to alteration in insulin signalling in the brain parenchyma of type 2 diabetics.