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Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ−/− colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.

【Objective】The study was carried out to explore the spatial distribution characteristics of soil physical and chemical properties in Changli Gold Coast National Nature Reserve, with an aim to provide scientific references for establishing a virtuous cycle of vegetation ecosystem in the reserve.【Method】Fifty-seven sampling sites were determined by 1 000 m×1 000 m grid sampling method, and 0-10 cm and 10-20 cm soil samples were collected for physical and chemical properties determination. The kriging interpolation method was used for spatial mapping, and the main influencing factors were discussed according to correlation analysis and variance analysis.【Result】The soil physical and chemical properties of the reserve showed obvious spatial heterogeneity in the horizontal direction, and the farther away from the sea, the higher value of some physical and chemical property indexes. The soil texture was mainly divided into four categories: sand, loamy sand, sandy loam and silty loam, of which sand accounted for about 70%, with the sand content reaching 85%-100%. The western Qilihai experimental area was salinized with the total salt quantity of 5.22 g/kg. The coastal area was mainly non-salinized and mildly salinized. There were significant correlations among the indexes, soil bulk density was negatively correlated with water content and nutrient indexes. In addition to bulk density, soil water content was significantly positively correlated with the other six indexes. The four nutrient indexes were positively correlated with each other, and the pH value was significantly positively correlated with available phosphorus, available potassium and total salt quantity. In addition, the distribution pattern of soil physical and chemical properties was affected by factors such as the distance from the coastline, land use type and soil type. The distance from the soastline played a significant role. The water and nutrients content of farm land were significantly higher than those of wood land, grassland and unused land. Compared with tidal soil and coastal salt soil, coastal aeolian sand soil had higher soil bulk density, lower water content, organic matter content, total salt quantity and pH value.【Conclusion】In the western Qilihai experimental area, saline-alkali tolerant plants should be selected as the main species, and drought-tolerant and wind-resistant tolerant seedlings should be selected in the land buffer area, the southern land core area and the Jinshawan experimental area.

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.

Abstract Convolutional neural networks (CNNs) have successfully demonstrated their powerful predictive performance in a variety of tasks. However, it remains a challenge to estimate the uncertainty of these predictions simply and accurately. Deep Ensemble is widely considered the state-of-the-art method which can estimate the uncertainty accurately, but it is expensive to train and test. MC-Dropout is another popular method that is less costly but lacks the diversity of predictions resulting in less accurate uncertainty estimates. To combine the benefits of both, we introduce a ReLU-Based Uncertainty Estimation (RBUE) method. Instead of using the randomness of the Dropout module during the test phase (MC-Dropout) or using the randomness of the initial weights of CNNs (Deep Ensemble), RBUE uses the randomness of activation function to obtain diverse outputs in the testing phase to estimate uncertainty. Under the method, we propose strategy MC-DropReLU and develop strategy MC-RReLU. The uniform distribution of the activation function’s position in CNNs allows the randomness to be well transferred to the output results and gives a more diverse output, thus improving the accuracy of the uncertainty estimation. Moreover, our method is simple to implement and does not need to modify the existing model. We experimentally validate the RBUE on three widely used datasets, CIFAR10, CIFAR100, and TinyImageNet. The experiments demonstrate that our method has competitive performance but is more favorable in training time.

Although metabolic reprogramming during the differentiation of regulatory T cells (Treg cells) has been extensively studied, the molecular switch to alter energy metabolism remains undefined. The present study explores the critical role of mitochondrial dynamics in the reprogramming and consequent generation of Treg cells. The results showed that during Treg cell differentiation, mitochondrial fusion but not fission led to elevation of oxygen consumption rate values, facilitation of metabolic reprogramming, and increase of number of Treg cells and expression of Foxp3 in vitro and in vivo. Mechanistically, mitochondrial fusion favored fatty acid oxidation but restricted glycolysis in Treg cells through down-regulating the expression of HIF-1α. Transforming growth factor-β1 (TGF-β1) played a crucial role in the induction of mitochondrial fusion, which activated Smad2/3, promoted the expression of PGC-1α and therefore facilitated the expression of mitochondrial fusion proteins. In conclusion, during Treg cell differentiation, TGF-β1 promotes PGC-1α-mediated mitochondrial fusion, which drives metabolic reprogramming from glycolysis to fatty acid oxidation via suppressing HIF-1α expression, and therefore favors the generation of Treg cells. The signals and proteins involved in mitochondrial fusion are potential therapeutic targets for Treg cell-related diseases.

In contrast to the marine environment, coastal regions encompass substantial saline soils characterized by complex corrosive chemical compositions. This poses notable challenges to the durability of concrete structures erected in coastal dredger fill silty soil environments. This research undertook concrete chloride corrosion assessments in both a dredger fill silty soil environment and a simulated solution environment. The findings demonstrated a progressive escalation in the free chloride concentration within concrete specimens, as the exposure duration was extended from 60 to 120 d, and discernible convection zones were observed with depths ranging from 6 to 8 mm. The investigation revealed a diminishing trend in the apparent chloride diffusion coefficient, corresponding to the elongation of exposure time and the augmentation of burial depth. Paradoxically, the burial depth and exposure duration exhibited converse effects on the apparent surface chloride concentration. Empirical formulations were derived to express the apparent surface chloride concentrations and apparent chloride diffusion coefficients as dependent on the exposure time and burial depth variables. These models exhibited an excellent goodness of fit, reaching up to 0.96. Notably, concrete specimens interred at a depth of 0.0 m displayed a favorable likeness to the simulated solution environment throughout the 60 d exposure period.

The 7050 alloy is a kind of Al-Zn-Mg-Cu alloy that is widely used for aircraft structures. Although the deformation behavior of the solid solution state 7050 aluminum alloy is critical for engineering and manufacturing design, it has received little attention. In this study, the room and warm compression behavior of the solid solution-state 7050 alloy was researched, and a modified model with variable parameters was built for the flow stress and load prediction. The isothermal compression tests of the solid solution-state 7050 alloy were performed under the conditions of a deformation temperature of 333–523 K, a strain rate of 10−3–10−1 s−1, and a total reduction of 50%. The strain-stress curves at different temperatures were corrected by considering interface friction. The flow stress model of aluminum was established using the modified Voce model. For evaluating the modified Voce model’s prediction accuracy, the flow stresses calculated by the model were compared with the experimental values. Consequently, for assessing its prediction abilities in finite element applications, the whole compression process was simulated in the finite element analysis platform. The results sufficiently illustrated that the modified Voce-type model can precisely predict the complex flow behaviors during warm compression. This study will guide the prediction of the warm compression load and the optimization of the heat treatment process of the alloy.

The deployment of mobile robots to conduct search for radioactive sources plays a crucial role in preventing radiation pollution and safeguarding public health. And it is a significant challenge to accurately locate radioactive sources in unknown environments. Herein, a particle filter based on mobile robot search method is proposed to localize radiation sources. By applying an angle constraint technique, the complexity of this algorithm is reduced, the high accuracy of source estimation is maintained, and the range of search is expanded. Additionally, a particle diffusion technology is applied to address particle loss that occurs during filtering. Furthermore, an adaptive gradient descent strategy is adopted to enhance the search efficiency. Experimental results demonstrate that this method achieves a success rate of over 95 % within a rectangular area (e.g., 40m by 40m), outperforming traditional methods, and it could perform effectively in dual radioactive source search tasks.

Abstract N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A is pivotal in diverse diseases especially cancer. m6A corelates with the initiation, progression, resistance, invasion, and metastasis of cancer. However, despite these insights, a comprehensive understanding of its specific roles and mechanisms within the complex landscape of cancer is still elusive. This review begins by outlining the key regulatory proteins of m6A modification and their posttranslational modifications (PTMs), as well as the role in chromatin accessibility and transcriptional activity within cancer cells. Additionally, it highlights that m6A modifications impact cancer progression by modulating programmed cell death mechanisms and affecting the tumor microenvironment through various cancer‐associated immune cells. Furthermore, the review discusses how microorganisms can induce enduring epigenetic changes and oncogenic effect in microorganism‐associated cancers by altering m6A modifications. Last, it delves into the role of m6A modification in cancer immunotherapy, encompassing RNA therapy, immune checkpoint blockade, cytokine therapy, adoptive cell transfer therapy, and direct targeting of m6A regulators. Overall, this review clarifies the multifaceted role of m6A modification in cancer and explores targeted therapies aimed at manipulating m6A modification, aiming to advance cancer research and improve patient outcomes.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperative. N6-methyladenosine (m6A) is an important modification of eukaryotic RNAs. It is a critical regulator of gene expression that is involved in different cellular functions and physiological processes. Many studies have indicated that m6A modification regulates the development of many metabolic processes and metabolic diseases. In this review, we summarized recent studies on the role of m6A modification in different metabolic processes and metabolic diseases. Additionally, we highlighted the potential m6A-targeted therapy for metabolic diseases, expecting to facilitate m6A-targeted strategies in the treatment of metabolic diseases.

To address the scheduling challenges associated with the increasing deployment of battery-swapping trucks in open-pit mines, this study proposes a multi-objective scheduling optimization model. This model accounts for the unique characteristics of battery-swapping trucks by incorporating constraints related to battery swapping alerts, the selection of battery-swapping stations, and the impact of ambient temperature on battery capacity. The primary objective is to minimize the total haulage cost and total waiting time. Both a genetic algorithm and an adaptive genetic algorithm are applied to solve the proposed multi-objective scheduling optimization model. The aim is to identify an optimal scheduling solution without violating any model constraints. Results demonstrate that both the basic genetic algorithm and the adaptive genetic algorithm effectively achieve truck transportation scheduling. However, the adaptive genetic algorithm surpasses the basic genetic algorithm, reducing the total transportation costs by 5.6% and total waiting time by 17.4%. It also reduces the number of battery swaps and transportation distance by 15.8% and 1.2%, respectively. The proposed multi-objective scheduling optimization model successfully minimizes the waiting time and transportation costs of battery-swapping trucks while ensuring the completion of production tasks. This approach provides valuable technical support for improving the production and transportation efficiency of open-pit mining operations.

Study designRetrospective Cohort Study.ObjectivesTo explore the feasibility and assess the efficacy of pedicle fixation with the Wiltse approach in the thoracic spine.Summary of background dataThe current application of Wiltse approach is mainly practiced in the lumbar and thoracolumbar spines. Its application in the thoracic spine, however, has received little attention, especially in cases that requires only pedicel screw fixation without spinal decompression.MethodsThe study analyzed the clinical records of consecutive patients with thoracic diseases who underwent pedicle fixation with either Wiltse or the conventional transmuscular approach (Wiltse group: 60 cases; Transmuscular group: 48 cases). Perioperative parameters, Visual Analogue Scale (VAS) scores, accuracy of pedicle screw placement, dead space between the muscles, Magnetic Resonance Imaging (MRI) appearance, electrophysiological changes in the multifidus muscle were compared between the two groups.ResultsCompared with the transmuscular group, the Wiltse group was significantly better in blood loss and postoperative VAS scores. No difference was observed in incision length, operation time, and hospital stay. The dead space between the muscle cross-sectional region in the transmuscular group was 315 ± 53 mm2, and no dead space was found in the Wiltse group. On MRI images, the multifidus cross-sectional area (CSA) in the Wiltse group between the preoperative period and the last follow-up reduced by only 10.1%, while transmuscular group showed 46.1% CSA reduction. Electrophysiologically, the median frequency slope of the transmuscular group grew by 47.8% with average amplitude reduced by 16.4% between the preoperative period and 12-month postoperative.ConclusionThe Wiltse approach for pedicle fixation in the thoracic spine is a feasible and effective treatment, with fewer traumas and reliable clinical results. In particular, the Wiltse approach reduces postoperative dead space between the muscles and causes less atrophy in the multifidus muscle.

Summary: The efficacy of COVID-19 vaccination relies on the induction of neutralizing antibodies, which can vary among vaccine recipients. In this study, we investigated the potential factors affecting the neutralizing antibody response by combining plasma and urine proteomics and gut microbiota analysis. We found that activation of the LXR/FXR pathway in plasma was associated with the production of ACE2-RBD-inhibiting antibodies, while urine proteins related to complement system, acute phase response signaling, LXR/FXR, and STAT3 pathways were correlated with neutralizing antibody production. Moreover, we observed a correlation between the gut microbiota and plasma and urine proteins, as well as the vaccination response. Based on the above data, we built a predictive model for vaccination response (AUC = 0.85). Our study provides insights into characteristic plasma and urine proteins and gut microbiota associated with the ACE2-RBD-inhibiting antibodies, which could benefit our understanding of the host response to COVID-19 vaccination.

M6A is essential for tumor occurrence and progression. The expression patterns of m6A regulators differ in various kinds of tumors. Transcriptomic expression statistics together with clinical data from a database were analyzed to distinguish patients with digestive tract tumors. Based on the expression patterns of diverse m6A regulators, patients were divided into several clusters. Survival analysis suggested significant differences in patient prognosis among the m6A clusters. The results showed overlapping of m6A expression patterns with energy metabolism and nucleotide metabolism. Functional analyses imply that m6A modifications in tumor cells probably drive metabolic reprogramming to sustain rapid proliferation of cancer cells. Our analysis highlights the m6A risk characterizes various kinds of metabolic features and predicts chemotherapy sensitivity in digestive tract tumors, providing evidence for m6A regulators as markers to predict patient outcomes.

Objective: Discogenic low back pain (LBP) is associated with nociceptive nerve fibers that grow into degenerated intervertebral discs (IVD) but the etiopathogenesis of disease is not fully understood. The purpose of this study was to clarify the role of Netrin-1 in causing discogenic LBP. Methods: The level of nociceptive nerve innervation was examined in disc degenerative patients and rat needle-punctured models by immunohistochemistry. Nucleus pulposus (NP) cells were isolated from IVD tissues of rats and induced degeneration by interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα). The candidate genes related to neuron outgrowth and migration were selected by Next-generation sequencing (NGS). CRISPR/Cas9 was used to knockdown Netrin-1 in NP cells. The impact of Netrin-1 on nerve innervation were evaluated with P2X2、NF200 staining and microfluidics assay. Meanwhile the CD31 staining and transwell assay were used to evaluate the impact of Netrin-1 in angiogenesis. The proteins and RNA extracted from NP cells related to catabolism and anabolism were examined by western blot assay and RT-qPCR experiment. ChIP and luciferase experiments were used to assess the intracellular transcriptional regulation of Netrin-1. Further, a needle-punctured rat model followed by histomorphometry and immunofluorescence histochemistry was used to explore the potential effect of Netrin-1 on LBP in vivo. Results: The level of nerve innervation was increased in severe disc degenerative patients while the expression of Netrin-1 was upregulated. The supernatants of NP cells stimulated with IL-1β or TNFα containing more Netrin-1 could promote axon growth and vascular endothelial cells migration. Knocking down Netrin-1 or overexpressing transcription factor TCF3 as a negative regulator of Netrin-1 attenuated this effect. The needle-punctured rat model brought significant spinal hypersensitivity, nerve innervation and angiogenesis, nevertheless knocking down Netrin-1 effectively prevented disc degeneration-induced adverse impacts. Conclusion: Discogenic LBP was induced by Netrin-1, which mediated nerve innervation and angiogenesis in disc degeneration. Knocking down Netrin-1 by CRISPR/Cas9 or negatively regulating Netrin1 by transcription factor TCF3 could alleviate spinal hypersensitivity. The translational potential of this article: This study on Netrin-1 could provide a new target and theoretical basis for the prevention and treatment for discogenic back pain.

We propose a novel method for estimating the permeability of heterogeneous sandstones based on the nuclear magnetic resonance (NMR) data with multiple echo spacings. The decaying curves and their corresponding spectra are obtained for different echo spacings to investigate the relaxation property, the diffusion term, and the signal loss contributed by higher echo spacing. Moreover, an empirical model is developed to correlate permeability with the differential decay rate. The result shows that the geometric transversal relaxation time is positively related to echo spacing, which disobeys the traditional cognition. Moreover, the absolute value of the differential decay rate is positively correlated with the echo spacing and exhibits a power law behavior. More interestingly, it is observed that the permeability diminishes in a power law behavior with respect to fitting parameters. This marks the first attempt to establish a relationship between the permeability and NMR data with different echo spacings, which is hopeful to be extended to other complex reservoirs with the availability of multiple echo spacing data.

Background The Rhizophoraceae family comprises crucial mangrove plants that inhabit intertidal environments. In China, eight Rhizophoraceae mangrove species exist. Although complete chloroplast (Cp) genomes of four Rhizophoraceae mangrove plants have been reported, the Cp genomes of the remaining four species remain unclear, impeding a comprehensive understanding of the evolutionary history of this family. Methods Illumina high-throughput sequencing was employed to obtain the DNA sequences of Rhizophoraceae species. Cp genomes were assembled by NOVOPlasty and annotated using CpGAVAS software. Phylogenetic and divergence time analyses were conducted using MEGA and BEAST 2 software. Results Four novel Cp genomes of Rhizophoraceae mangrove species (Bruguiera sexangula, Bruguiera gymnorrhiza, Bruguiera × rhynchopetala and Rhizophora apiculata) were successfully assembled. The four Cp genomes ranged in length from 163,310 to 164,560 bp, with gene numbers varying from 124 to 128. The average nucleotide diversity (Pi) value of the eight Rhizophoraceae Cp genomes was 0.00596. Phylogenetic trees constructed based on the complete Cp genomes supported the monophyletic origin of Rhizophoraceae. Divergence time estimation based on the Cp genomes of representative species from Malpighiales showed that the origin of Rhizophoraceae occurred at approximately 58.54–50.02 million years ago (Mya). The divergence time within the genus Rhizophora (∼4.51 Mya) was much earlier than the divergence time within the genus Bruguiera (∼1.41 Mya), suggesting recent speciation processes in these genera. Our data provides new insights into phylogenetic relationship and evolutionary history of Rhizophoraceae mangrove plants.

To efficiently develop deep shale gas in southern Sichuan Basin, under the guidance of “extreme utilization” theory, a basic idea and solutions for deep shale gas development are put forward and applied in practice. In view of multiple influencing factors of shale gas development, low single-well production and marginal profit of wells in this region, the basic idea is to establish “transparent geological body” of the block in concern, evaluate the factors affecting shale gas development through integrated geological-engineering research and optimize the shale gas development of wells in their whole life cycle to balance the relationship between production objectives and development costs. The solutions are as follows: (1) calculate the gold target index and pinpoint the location of horizontal well drilling target, and shale reservoirs are depicted accurately by geophysical and other means to build underground transparent geological body; (2) optimize the drilling and completion process, improve the adaptability of key tools by cooling, reducing density and optimizing the performance of drilling fluid, the “man-made gas reservoir” is built by comprehensively considering the characteristics of in-situ stress and fractures after the development well is drilled; (3) through efficient management, establishment of learning curve and optimization of drainage and production regime, the development quality and efficiency of the well are improved across its whole life cycle, to fulfil “extreme utilization” development of shale gas. The practice shows that the estimated ultimate recovery of single wells in southern Sichuan Basin increase by 10%-20% than last year.

The nuclear magnetic resonance (NMR) response is known to deviate from the true value for the volcanic reservoirs, particularly when the pore throat size is ultralow. Consequently, the related petrophysical parameters such as porosity, permeability, and pore size distribution from NMR measurements are greatly influenced. An empirical method to correct the NMR calibrated porosity for the tight volcanic rocks is proposed after comprehensive investigations of influential factors combined with mineralogical and petrophysical analyses. The laboratory result indicates that the relative porosity deviation is negatively correlated with the geometric mean of the transversal relaxation time (T2) but positively correlated with the clay content. Moreover, both the paramagnetic materials, such as the manganese (Mn) content, and the diamagnetic materials, such as the magnesium (Mg) content, contribute to the NMR relaxation intensity reduction but with different mechanisms. The NMR calibrated porosity can be compensated through multiple regressions with these controlling factors, which can be generalized to other tight volcanic reservoirs.

Root microbiota have a significant effect on plant health. However, the role of root microbiota in the resistance of Rhododendron against root rot is not known. In this study, we employed amplicon 16S and ITS sequencing to investigate the bacterial and fungal communities associated with four distinct niches (bulk soil, rhizosphere, rhizoplane, and endosphere) of both healthy and diseased Rhododendron plants in the Baili Rhododendron nature reserve in China. The amplicon data analysis identified 182 bacterial genera and 141 fungal genera that were impacted by root rot across all niches. Specifically, the rhizoplane appeared to exert a selective gating effect, resulting in a reduction in the complexity of bacterial communities, but not fungal communities, in wild Rhododendron delavayi Franch roots. Nevertheless, the stress induced by root rot led to alterations in the root microbiota and compromised the gating function of the rhizoplane, thereby significantly increasing the complexity of the bacterial community within the plant root. In the root tissue following root rot outbreak, the relative abundance of the pathogenic species Pezicula brunnea and Diaporthe helianthi was enriched by as much as 6.13% and 1.71%, respectively. These findings provide novel insights into the contribution of enrichment of root-associated microbiota to wild plant hosts under the disease stress of root rot. The root rot-causing pathogenic fungi may interact with beneficial bacteria and induce plants to send out “cry for help” signals, which may encourage the specific assembly of microbiota. In the Rhododendron delavayi Franch root microbiota, we found 23 potentially beneficial microbes. Notably, certain beneficial bacteria, such as Sporolactobacillus and Stenotrophomonas, were found to accumulate in the rhizoplane and endosphere under root rot disease stress. Overall, our results lend support to our hypothesis that Rhododendron recruits protective microbes as a strategy to suppress root rot outbreaks. Future endeavors in isolating beneficial microbes capable of mitigating root rot have the potential to enhance plant resilience against root diseases.

This paper adopts the tail-event driven network (TENET) framework to explore the connectedness and systemic risk of the banking industry along the Belt and Road (B&R) based on weekly returns of 377 publicly-listed banks from 2014 to 2019. We conduct the connectedness analysis from four levels (i.e., system, region, country and institution) and identify the systemic risk contribution of banks. We find that the dynamic total connectedness reached its peak during the outbreak of the abnormal fluctuations of Chinese stock market in 2015-2016 and its trough during the Brexit vote, and subsequently experienced several periodic fluctuations at a relatively high position. In the B&R banking system, the intra-regional tail risk spillovers are remarkably stronger than the inter-regional tail risk spillovers during the post-crisis period. In addition, the panel regressions estimated by the least squares dummy variable model show that the cross-border merger and acquisitions (M&As) and the merchandise trade export are important drivers for the tail-connectedness across the B&R countries. Our study provides regulators with insightful implications on the systemic risk supervision of the B&R banking industry.

The shales in the 2nd Member of Permian Shanxi Formation (Shan2 Member) at the Daning-Jixian block at the eastern margin of the Ordos Basin were deposited in a marine–continental transitional environment. The Shan23 sub-member, which is the target interval for transitional shale gas exploration and development in China, is characterized by substantial shale thickness, few and thin interlayers. This interval, however, has been rarely investigated for reservoir characteristics, especially the controlling factors of high-quality reservoirs. In this paper, the reservoir characteristics and main controlling factors of high-quality reservoirs in Shan23 in the Daning-Jixian block were systematically discussed by organic geochemical analysis, mineral compositional analysis, and microscopic reservoir characterization. The results indicate that the lagoon facies shale interval in the upper part of the Shan23 sub-member has a high total organic carbon (TOC) content, a high brittle mineral content, and high BET surface area and BJH pore volume values, indicating that this is the sweet spot for shale gas exploration and development. Pore space in the Shan23 sub-member shale is dominated by clay mineral intercrystalline pores (76.9%), which also contains organic matter pores (18.7%). The SEM observations reveal that the mineral components are different in pore size distribution (PSD) and the organic matter pores and calcite dissolved pores are mainly in meso-scale, the pores in clay minerals and quartz are in meso- and macro-scale, while the pores in feldspar and pyrite exhibit a wide and uniform size distribution. The single-factor analysis shows that the clay mineral content is the dominant factor controlling pore development in the Shan23 sub-member transitional shales, the TOC content has a certain effect on pore development, and the kerogen type has no discernible effect on pore development.

Abstract With the development of blue laser endoscopy (BLE) technique, it's often used to diagnose early gastric cancer (EGC) by the morphological changes of blood vessels through BLE. However, EGC is still not obvious to identify, resulting in a high rate of missed diagnosis. Molecular imaging can show the changes in early tumors at molecular level, which provides a possibility for diagnosing EGC. Therefore, developing a probe that visually monitors blood vessels of EGC under BLE is particularly necessary. Herein, a bis‐pyrene (BP) based nanoprobe (BP‐FFVLK‐(PEG)‐RGD, M1) is designed, which can target angiogenesis and self‐assemble into fibers in situ, resulting in stable and long‐term retention in tumor. Moreover, M1 probe can emit yellow‐green fluorescence for imaging under BLE. M1 probe is confirmed to steadily remain in tumor for up to 96 hours in mice transplanted subcutaneously. In addition, the M1 probe is able to target angiogenesis for molecular imaging of isolated human gastric cancer tissue under BLE. Finally, M1 probe i.v. injected into primary gastric cancer model rabbits successfully highlighted the tumor site under BLE, which is confirmed by pathological analysis. It's the first time to develop a probe for diagnosing EGC by visualizing angiogenesis under BLE, showing great clinical significance.

Detecting pump-and-dump schemes involving cryptoassets with high-frequency data is challenging due to imbalanced datasets and the early occurrence of unusual trading volumes. To address these issues, we propose constructing synthetic balanced datasets using resampling methods and flagging a pump-and-dump from the moment of public announcement up to 60 min beforehand. We validated our proposals using data from Pumpolymp and the CryptoCurrency eXchange Trading Library to identify 351 pump signals relative to the Binance crypto exchange in 2021 and 2022. We found that the most effective approach was using the original imbalanced dataset with pump-and-dumps flagged 60 min in advance, together with a random forest model with data segmented into 30-s chunks and regressors computed with a moving window of 1 h. Our analysis revealed that a better balance between sensitivity and specificity could be achieved by simply selecting an appropriate probability threshold, such as setting the threshold close to the observed prevalence in the original dataset. Resampling methods were useful in some cases, but threshold-independent measures were not affected. Moreover, detecting pump-and-dumps in real-time involves high-dimensional data, and the use of resampling methods to build synthetic datasets can be time-consuming, making them less practical.

Pore and pore network evolution of shale is critical for the evaluation the pore system in shale gas reservoirs. Thermal maturation effect acts as an indispensable role in porosity evolution. In this paper, high-temperature and high-pressure in-situ thermal simulation experiments were conducted to investigate the process and controlling factors of pore evolution in marine-continental transitional shale. Multiple methods, including scanning electron microscopy (SEM), X-ray diffraction, helium porosimetry and low-pressure N2 and CO2 adsorption were used to investigate the evolution of mineral composition and pore structure at different stages of thermal maturity. The results showed that type III organic matter (OM) generated petroleum with the thermal maturity increasing. The total organic carbon (TOC) decreased by 13.3% when temperature reached 607°C. At the same time, it produced numerous organic and mineral pores during hydrocarbon generation. Besides, some changes in mineral composition have occurred, especially in illite (from 11% to 31%) and kaolinite (from 89% to 69%). In general, it can divide into 3 stages (maturity, high maturity and over maturity) for shale pore system evolution with the thermal maturity increasing. In the low maturity period, large amounts of pyrolytic bitumen and oil generated to fill the pores, causing the pore system to diminish; in the high maturity period, a large number of pores were generated when oil is cracked into gas, resulting in a rapid expansion of the pore system; in the over-maturity period, the cracking of pyrolysis and hydrocarbon slowed down, allowing the pore system to stabilize. Shale pore evolution is primarily controlled by the thermal evolution of OM, and the conversion of inorganic minerals contributes less to pore evolution compared to organic matter. The high maturity period (1.2% < Ro < 2.0%) was the period when extensive pyrolysis and hydrocarbon generated in the Shanxi Formation shale, which contributed mostly for the pores generation and accumulation of shale gas.