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Previous studies have shown that underground natural gas storage (UGS) in California has served a critical role in meeting energy demands in California, and there is no immediate alternative. Therefore, it is important to ensure the safety of UGS infrastructure, especially considering that many of the UGS sites are using a combination of new and old wells, some of which were installed decades ago and re-purposed for UGS. The purpose of this project is to develop an integrated risk management and decision support system (IRMDSS) to manage risks associated with this heterogeneous subsurface infrastructure. The approach of the IRMDSS is to take advantage of the predictive capability of mechanistic models, with support from data acquired from advanced monitoring technologies, for evaluation and analysis of various incident scenarios or potential threats. In this project, we have demonstrated data collection by four advanced monitoring technologies. These include two downhole monitoring technologies, distributed temperature sensing (DTS), distributed acoustic sensing (DAS), and two surface monitoring technologies, Interferometric Synthetic Aperture Radar (InSAR), and unmanned aerial vehicle (UAV). DTS and DAS data are collected continuously, providing information related to individual wells. InSAR data are collected frequently (~every 24 days), and UAV data can be collected as frequently as is practical depending on need. Together, these subsurface and surface monitoring technologies provide near real-time information useful for risk management of UGS facilities.

Background: Cardiac arrest presents a variety of causes and complexities, making it challenging to develop targeted treatment plans. Often, the original data are either inadequate or lack essential patient information. In this study, we introduce an intelligent system for diagnosing and treating in-hospital cardiac arrest (IHCA), aimed at improving the success rate of cardiopulmonary resuscitation and restoring spontaneous circulation. Methods: To compensate for insufficient or incomplete data, a hybrid mega trend diffusion method was used to generate virtual samples, enhancing system performance. The core of the system is a modified episodic deep reinforcement learning module, which facilitates the diagnosis and treatment process while improving sample efficiency. Uncertainty analysis was performed using Monte Carlo simulations, and dependencies between different parameters were assessed using regular vine copula. The system's effectiveness was evaluated using ten years of data from Utstein-style IHCA registries across seven hospitals in China's Hebei Province. Results: The system demonstrated improved performance compared to other models, particularly in scenarios with inadequate data or missing patient information. The average reward scores in two key stages increased by 2.3–9 and 9.9–23, respectively. Conclusions: The intelligent diagnosis and treatment effectively addresses IHCA, providing reliable diagnosis and treatment plans in IHCA scenarios. Moreover, it can effectively induce cardiopulmonary resuscitation and restoration of spontaneous circulation processes even when original data are insufficient or basic patient information is missing. [ABSTRACT FROM AUTHOR]

With the gradual reduction of easily beneficiated copper sulfide ore resources, the recovery and utilization of refractory copper oxide ore has become an important research direction in the field of mineral processing. The grade of copper and gold in a gold-copper ore is 1.86% and 3.52 g/t, respectively. The particle size of independent gold minerals in the ore is mine, basically below 1 µm, or wrapped in metal mineral or gangue minerals in the form of line particles, and the oxidation rate of copper in the ore is 91.85%, so the ore belongs to refractory ore. In order to recover the valuable components in the ore to the greatest extent, different flotation product schemes are compared according to the ore properties, and the segmented Rotation process is determined to recover gold and copper in the ore, that is, copper sulfide minerals and gold-bearing sulfide minerals are preferentially floated from the ore to obtain qualified gold-copper concentrate. Copper oxide minerals are recovered from the tailings of selective flotation, and a copper concentrate product wkh gold valuation is obtained, thus the valuable components in the ore are recovered and utilized by a segmented flotation process. On the basis of detailed flotation condition tests, a small locked-cycle test was carried out, and finally a gold-copper concentrate with 15.39% Cu and 152.39 g/t Au and copper concentrate wkh 28.02% Cu and 10.39 g/t Au were obtained. Overall, the total concentrate had copper grade of 24.73% and gold grade of 47.41 g/t, wkh the total recovery of copper being 87.41% and the total recovery of gold being 88.32%. [ABSTRACT FROM AUTHOR]

Breast cancer has a very high incidence rate worldwide, and effective screening and early diagnosis are particularly important. In this paper, two improved You Only Look Once version 8 (YOLOv8) models, the YOLOv8-GHOST and YOLOv8-P2 models, are proposed to address the difficulty of distinguishing lesions from normal tissues in mammography images. The YOLOv8-GHOST model incorporates GHOSTConv and C3GHOST modules into the original YOLOv8 model to capture richer feature information while using only 57% of the number of parameters required by the original model. The YOLOv8-P2 algorithm significantly reduces the number of necessary parameters by streamlining the number of channels in the feature map. This paper proposes the YOLOv8-GHOST-P2 model by combining the above two improvements. Experiments conducted on the MIAS and DDSM datasets show that the new models achieved significantly improved computational efficiency while maintaining high detection accuracy. Compared with the traditional YOLOv8 method, the three new models improved and achieved F1 scores of 98.38%, 98.8%, and 98.57%, while the number of parameters reduced by 42.9%, 46.64%, and 2.8%. These improvements provide a more efficient and accurate tool for clinical breast cancer screening and lay the foundation for subsequent studies. Future work will explore the potential applications of the developed models to other medical image analysis tasks. [ABSTRACT FROM AUTHOR]

Introduction: Polygala fallax Hemsl (PFH) is a widely used herbal medicine in Guangxi, China. At present, research on PFH mainly focuses on extraction technology and cultivation, lacking quality control standards for systematic evaluation. Objectives: The study aimed to assess the quality of PFH from different sources and to predict markers that would help assess quality. Methods: Fingerprinting of 15 batches of PFH samples was performed by ultra‐high performance liquid chromatography (UPLC) and similarity was assessed using hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares discrimination (OPLS‐DA). Differential components were screened by mathematical analysis, and a "component‐target‐pathway" network map was constructed in combination with network pharmacology, quality markers (Q‐markers) of PFH were predicted, and quantitative analysis was performed. Results: Fifteen batches were fingerprinted for PFH, with 11 common peaks, and peak 5 was identified as 4‐hydroxybenzoic acid, which was generally consistent with the results of HCA, PCA, and OPLS‐DA. Network pharmacology screened 18 potential compounds, 45 core targets, and 20 key pathways, integrating fingerprinting, pattern recognition, and network pharmacology methods. One of the potential Q‐markers that can identify the principle of testability, efficacy, and specificity is 4‐hydroxybenzoic acid, whose content ranges from 0.0188 to 1.4517 mg/g. Conclusion: The potential Q‐markers of PFH were predicted by integrating fingerprinting, pattern recognition, and network pharmacological analysis, which provided a scientific basis for the overall control and evaluation of the quality of PFH and a theoretical reference for the study of the quality standard of multi‐base traditional Chinese medicine. In this work, ultra‐performance liquid chromatography (UPLC) was used to fingerprint 15 batches of Polygala fallax Hemsl (PFH) samples, combined with network pharmacology and chemometrics to screen and analyze quality markers of PFH and to quantify one of the predicted components, 4‐hydroxybenzoic acid. The above analytical model was used for the first time in the study of PFH quality biomarkers. This provides a theoretical reference for the comprehensive control and evaluation of PFH quality. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR‐Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC. [ABSTRACT FROM AUTHOR]

Background: The management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures. Methods: This retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions. Results: A total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17–2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels. Conclusions: There exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD. Clinical trial number: NCT06473324. [ABSTRACT FROM AUTHOR]

Nitrogen (N) loss is a significant source of water quality pollution in alluvial watersheds. However, the mechanisms linking N loss and elevated CO2 concentration (eCO2) are not well recognized. In this study, we comprehensively calibrated the SWAT model equipped with a dynamic CO2 input and response module to investigate the response mechanisms between multiform N losses and eCO2 in a representative large‐scale watershed. Results revealed nitrate loss under eCO2 exceeding 100% in some upstream zones under the SSP5‐8.5 scenario (P < 0.05) compared to the constant CO2 concentration. This was directly related to the great increase in hydrological variables, which were the carriers of N losses, and the intensive inputs of N fertilizer. Results also found that nitrate leaching was greater than the other two processes for future periods, peaking at 309.3%, as compared to the baseline period. The findings suggested reducing fertilizer inputs by 10%–20% was promising, especially for reducing nitrate loss through runoff and leaching by up to 17.7% and 12.2%. This study explored the mechanisms of increased N loss in response to eCO2 and provided scientific evidence for early warning and making decisions to improve water quality at a large watershed scale. [ABSTRACT FROM AUTHOR]

Direct use of geothermal energy is the oldest and most versatile form of utilizing geothermal energy. In the last decade, this utilization has significantly increased, especially with the installation of geothermal (ground-source) heat pumps. Many current and inactive mine land sites across the U.S. could be redeveloped with clean energy technologies such as direct use geothermal, which would revitalize former mining communities, help with reducing greenhouse gas emissions, and accelerate the transition to a clean energy economy. We present a multicriteria screening framework to evaluate various aspects of direct-use geothermal projects on mine lands. The criteria are divided into three categories: (1) technical potential, (2) demand and benefits, and (3) regulatory and permitting. We demonstrate the framework using publicly available data on a national scale (continental U.S.). Then, using an example of abandoned coal mines in Illinois and focusing on resource potential, we illustrate how this evaluation can be applied at the state or more local scales when a region's characteristics drive spatial variability estimates. The strength of this approach is the ability to combine seemingly disparate parameters and inputs from numerous sources. The framework is very flexible—additional criteria can be easily incorporated and weights modified if input data support them. Vice versa, the framework can also help identify additional data needed for evaluating those criteria. The multicriteria screening evaluation methodology provides a framework for identifying potential candidates for detailed site evaluation and characterization. [ABSTRACT FROM AUTHOR]

As a mainstream equipment in the field of "more crushing and less grinding" and selective crushing application in the mining industry, high-pressure grinding mill has been widely used in both metal and non-metal industries due to is advantages of large ore processing capacity, high crushing efficiency, and line particle size of the crushed products. This paper briefly introduces the working principle and crushing process of high pressure grinding rolls, and analyzes the application, advantages and disadvantages of three crushing processes of high pressure grinding rolls in mines combined with practical cases. The typical application of high pressure grinding rolls in mineral processing industry Is introduced, the application of new technology of high pressure grinding rolls at home and abroad Is emphatically expounded, and the application of new technology in mineral processing industry !s prospected. The process of high pressure grinding rolls combined with agitating mill/tower mill, the process of high pressure grinding rolls combined with air classifier, the process of two high pressure grinding rolls in series, the technology of two high pressure grinders in parallel and the technology of double layer vibrating screen with high pressure rolls have obvious advantages in energy saving and consumption reduction, which is expected to provide a new scheme for efficient crushing of materials. [ABSTRACT FROM AUTHOR]

Objective By observing the effects of "three methods and three points" tuina technique on the expression of interleukin-17F(IL-17F), interleukin-17 receptor C(IL-17RC), activator 1 of nuclear transcription factor-?B(Act1), tumour necrosis factor receptor-associated factor 6(TRAF6) and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI) model, we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP). Methods Thirty-six SD rats were divided into the sham group, the model group and the tuina group according to the random number method, twelve rats in each group, and the minor CCI model was replicated by ligating the right sciatic nerve. The rats in the tuina group were subjected to pointing, plucking and kneading at the BL37, BL57 and GB34 points on the affected side using a tuina simulator, while the sham group and the model group were only grasped and restrained, and were intervened for one time. The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention. The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting. The mRNA expression of IL-17F, IL-17RC, Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR. The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence. Results Behavioral results showed that before intervention, compared with the sham group, paw mechanical withdraw threshold(PMWT) decreased and cold sensitivity threshold(CST) increased in the model group and the tuina group; after tuina intervention, PMWT in the tuina group was increased, and CST was decreased compared with the model group; after intervention, PMWT in the tuina group was increased, while CST was decreased(P<0.05). RT-PCR results showed that compared with the sham group, mRNA expression levels of IL-17F, IL-17RC, TRAF6 and Act1 in the spinal dorsal horn of the model group were increased; compared with model group, the mRNA expression levels of above indexes in the tuina group were decreased(P<0.05). Western boltting results showed that compared with the sham group, the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased; compared with the model group, the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P<0.05). Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group; compared with the model group, the mean fluorescence intensity of CD40 in the tuina group was decreased(P<0.05). Conclusion The "three methods and three points" tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F, IL-17RC, Act1, TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention. [ABSTRACT FROM AUTHOR]

Roux-en-Y gastric bypass (RYGB) has been shown to inhibit β-cell apoptosis, but the underlying mechanisms are not yet fully understood. Cytochrome c oxidase subunit 6A2 (COX6A2) is expressed in β-cells. Here, we sought to investigate the role of COX6A2 in β-cell apoptosis, especially following RYGB. We found that RYGB significantly reduced β-cell apoptosis, accompanied by decreased COX6A2 expression in islets from diabetic Goto-Kakizaki (GK) rats. It is noteworthy that overexpression of COX6A2 promoted β-cell apoptosis, whereas COX6A2 deficiency suppressed it, suggesting the pro-apoptotic role of COX6A2 in β-cells. Mechanistically, increased COX6A2 interacted with and upregulated the expression of cyclophilin D (CypD), facilitating the release of cytochrome c from mitochondria to the cytoplasm, thereby promoting β-cell apoptosis. Furthermore, high-glucose-activated ChREBP epigenetically regulated COX6A2 expression by recruiting histone acetyltransferase p300 to augment histone H3 acetylation at the Cox6a2 promoter, a process inhibited by GLP-1 signaling. Given that RYGB enhances GLP-1 signaling, RYGB is likely to deactivate ChREBP by boosting GLP-1/PKA signaling, thereby reducing COX6A2 expression in islets from GK rats. These findings highlight the crucial role of the GLP-1/PKA/ChREBP axis-controlled COX6A2 in β-cell apoptosis, revealing a previously unrecognized mechanism underlying the reduction in β-cell apoptosis induced by RYGB., (© 2024 by the American Diabetes Association.)

Phytophthora infestans is a notorious oomycete pathogen that causes potato late blight. It secretes numerous effector proteins to manipulate host immunity. Understanding mechanisms underlying their host cell manipulation is crucial for developing disease resistance strategies. Here, we report that the conserved RXLR effector Pi05910 of P. infestans is a genotype-specific avirulence elicitor on potato variety Longshu 12 and contributes virulence by suppressing and destabilizing host glycolate oxidase StGOX4. By performing co-immunoprecipitation, yeast-two-hybrid assays, luciferase complementation imaging, bimolecular fluorescence complementation and isothermal titration calorimetry assays, we identified and confirmed potato StGOX4 as a target of Pi05910. Further analysis revealed that StGOX4 and its homologue NbGOX4 are positive immune regulators against P. infestans, as indicated by infection assays on potato and Nicotiana benthamiana overexpressing StGOX4 and TRV-NbGOX4 plants. StGOX4-mediated disease resistance involves enhanced reactive oxygen species accumulation and activated the salicylic acid signalling pathway. Pi05910 binding inhibited enzymatic activity and destabilized StGOX4. Furthermore, mutagenesis analyses indicated that the 25th residue (tyrosine, Y25) of StGOX4 mediates Pi05910 binding and is required for its immune function. Our results revealed that the core RXLR effector of P. infestans Pi05910 suppresses plant immunity by targeting StGOX4, which results in decreased enzymatic activity and protein accumulation, leading to enhanced plant susceptibility., (© 2024 The Author(s). Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Background: The tumor microenvironment (TME) plays a crucial role in the limited efficacy of existing treatments for hepatocellular carcinoma (HCC), with tumor-associated endothelial cells (TECs) serving as fundamental TME components that substantially influence tumor progression and treatment efficacy. However, the precise roles and mechanisms of TECs in HCC remain inadequately understood., Methods: We employed a multi-omics profiling strategy to investigate the single-cell and spatiotemporal evolution of TECs within the microenvironment of HCC tumors showcasing varied responses to immunotherapy. Through an analysis of a clinical cohort of HCC patients, we explored the correlation between TEC subpopulations and immunotherapy outcomes. The influence of TEC subsets on the immune microenvironment was confirmed through comprehensive in vitro and in vivo studies. To further explore the mechanisms of distinct TEC subpopulations in microenvironmental modulation and their impact on immunotherapy, we utilized TEC subset-specific knockout mouse models as well as humanized mouse models., Results: In this research, we identified a new subset of CXCL12 + TECs that exert a crucial role in immune suppression within the HCC TME. Functionally, CXCL12 + TECs impede the differentiation of CD8 + naïve T cells into CD8 + cytotoxic T cells by secreting CXCL12. Furthermore, they attract myeloid-derived suppressor cells (MDSCs). A bispecific antibody was developed to target both CXCL12 and PD1 specifically, showing significant promise in bolstering anti-tumor immune responses and advancing HCC therapy., Conclusions: CXCL12 + TECs are pivotal in mediating immunosuppression within HCC microenvironment and targeting CXCL12 + TECs presents a promising approach to augment the efficacy of immunotherapies in HCC patients., Impact and Implication: This investigation reveals a pivotal mechanism in the HCC TME, where CXCL12 + TECs emerge as crucial modulators of immune suppression. The discovery of CXCL12 + TECs as inhibitors of CD8 + naïve T cell activation and recruiters of MDSCs significantly advances our grasp of the dynamic between HCC and immune regulation. Moreover, the development and application of a bispecific antibody precisely targeting CXCL12 and PD1 has proven to enhance immune responses in a humanized mouse HCC model. This finding underscores a promising therapeutic direction for HCC, offering the potential to amplify the impact of current immunotherapies., (Copyright © 2024. Published by Elsevier B.V.)

Tuina, as an external treatment method of traditional Chinese medicine, has been proven to have an analgesic effect on peripheral neuropathic pain (pNP) in clinical and basic research. However, the optimal time point for the analgesic effect of tuina may vary according to different injury sensations, affecting the exploration of the initiation mechanism of tuina analgesia. The research used minor chronic constriction injury (minor CCI) model rats to simulate pNP and used the intelligent tuina manipulation simulator to simulate the three methods (point-pressing, plucking, and kneading) and three acupoints (Yinmen BL37, Chengshan BL57, and Yanglingquan GB34) for performing tuina therapy. The study evaluated the changes in pain within 24 h and the optimal time point for the efficacy of tuina analgesia in rats with minor CCI models by testing cold sensitivity threshold (CST), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). Furthermore, the study evaluated IL-10 and TNF-α expression changes through Elisa detection. The results show that tuina has both immediate and sustained analgesic effects. For the three different injury sensitivity thresholds of CST, MWT, TWL, and two cytokines of IL-10 and TNF-α, the analgesic efficacy of tuina within 24 h after intervention is significantly different at different time points.