bluuebunny/crossref_metadata_2025 huggingface dataset:
Content and distribution of mercury in coal and its relation to depositional environment—A case study on coals from the Shanxi Formation in Huainan Coalfield
Authors: Zheng Liugen , Zhang Liqun , Wang Yunlong , Chen Yeyu , Chen Yongchun , An Shikai , Xu Yanfei
Published: January 2023

Mercury in coals might emit into the environment from coal combination, and finally cause environmental pollution. In this paper, 26 coal samples were selected from No. 1 which is coal in the Shanxi Formation of Zhangji and Xinjier mines in the Huainan coalfield. The mineralogical and geochemical components of coal samples were determined by DMA-80 mercury-measuring instrument, XRF, XRD, ICP-MS, and the relationship between the depositional environment of the coal seam and mercury enrichment was analyzed. The results show that the mercury content of coal in the study area ranged from 0.03 to 0.93 μg/g, with an arithmetic means of 0.21 μg/g, higher than the background values of coal in China and the world. The mercury content of Shanxi Formation coal varied among different mines, the arithmetic mean value of mercury in Zhangji coal mine and Xinjier mine coal is 0.35 μg/g and 0.12 μg/g respectively. Due to the complex depositional environment and depositional facies, the distribution of mercury content in the coal seam is quite different. XRD, Microscopic observation and the ratio of (CaO + MgO + Fe2O3)/(SiO2+ Al2O3) and Al2O3/TiO2 show that the main mineral in the depositional environment of this study area is kaolinite, quartz and pyrite, and the depositional facies are intercontinental and sea-land, so the parent rock type belongs to acid bedrock. The Ni/Co, Sr/Ba, and Sr/Cu ratios were used to indicate a weak oxidation-reduction, Marine salt water, and an arid and hot environment. The vertical distribution of mercury in coal and the characteristics of the depositional environment are combined to show that mercury in coal is easily affected by redox conditions, paleosalinity and paleoclimate in the depositional environment. At the same time, mercury accumulation is more easily in the depositional environment dominated by seawater intrusion than in the terrigenous input.
Petrogenesis and relationship with REE mineralization of the quartz syenite from Chishan and Longbaoshan alkaline complex, southeastern North China Craton: Insights from zircon U–Pb geochronology, element, and Sr–Nd–Pb–Hf isotope geochemistry
Authors: Wei Pengfei , Li Dapeng , Song Zhigang , Liu Qiang , Geng Ke , Zhang Yan , Ding Chengwu , Cai Na , Li Zengsheng , Zhang Chao , Xie Wei
Published: January 2023

Mesozoic alkaline complexes associated with the rare earth element (REE) mineralization are developed in southeastern North China Craton (NCC), and they recorded some important information about the lithospheric thinning and destruction of the NCC. Zircon U–Pb dating results reveal that syenitic rocks from the Chishan and Longbaoshan alkaline complexes were emplaced at ca. 126.2–123.7 Ma. These syenitic rocks have an arc-like affinity with enriched LREEs and LILEs (e.g., Ba and Th) and depleted HFSE (e.g., Nb and Ta). However, they plot within the extensional alkaline–calc-alkaline field in the lg (CaO/(K2O + Na2O)) versus SiO2 discrimination diagram and plot within the fields of the divergent plate and within-plate settings in the NbN versus ThN discrimination diagram, implying an extensional tectonic setting. Thus, we suggest that the syenitic rocks should form in an extensional tectonic settings related to rollback and retreat of the subducting Paleo-Pacific plate. These syenitic rocks have similar Sr–Nd–Pb–Hf isotope compositions ((87Sr/86Sr)i = 0.7062 to 0.7101, εNd(t) = −8.2 to −15.0, εHf(t) = −13.5 to −9.6), which are the same as the enriched subcontinental lithospheric mantle (SCLM) of the NCC. Taking into account not only our new data but also previously published data regarding the evolution of NCC in the Mesozoic, we conclude that the syenitic rocks from the Chishan and Longbaoshan complexes are derived from partial melting of the lithospheric mantle triggered by the Paleo-Pacific plate subduction. Moreover, the geochemical and Sr–Nd–Pb isotopic similarity between the Chishan REE ores, Longbaoshan altered rocks, and the syenitic rocks implied that they are homologous products of Early Cretaceous and that the mineralization shows inheritance to the magmatic hydrothermal evolution.
Study on the influence of the tectonic evolution of Shuangyashan Basin on gas occurrence and extraction in mines
Authors: Lan Tianwei , Zhang Zhijia , LE QUY BAO , Liu Yonghao , Wang Shunxiang
Published: January 2023

The formation and later evolution of coal-bearing basins in eastern Heilongjiang are controlled by multi-phase tectonic movements, and the Shuangyashan Basin is tectonically located at the southern end of the Sanjiang Basin in the northeast. The paper focuses on the regional geological and tectonic evolution of the Shuangyashan Basin and its influence on the gas occurrence law and extraction difficulty of the Jixian Coal Mine. The study determined that the gas occurrence of the mine in the Suibin-Jixian depression basin has regional aggregation and caprock sealing characteristics. The gas pressure and content of the 9# Coal Seam were measured in the underground test, and the results showed that the 9# coal seam is a hard-to-extract coal seam with low permeability. Aiming at the issue of hard-to-extract gas in 904 Working Face of 9# Coal Seam which is affected by depression basin and derived secondary tectonic conditions, numerical calculation and analysis of gas extraction effect of working face with different extraction parameters were carried out by COMSOL software, the results showed that: negative extraction pressure has less influence on gas extraction effect under basin conditions; when 113 mm diameter borehole is used for gas extraction, gas pressure decreases to 0.72 MPa; when the spacing of extraction borehole is 2 m, the gas pressure is reduced by 20%; when the coal seam permeability is increased by 10 times to more than 0.015 mD, the gas pressure is reduced by more than 50%. The optimized gas extraction scheme with 113 m diameter, 2 m borehole spacing, and 15 kPa negative pressure was proposed for the test working face, and combined with supercritical CO2 fracturing and permeability enhancement technology. Under underground measurement, the coal seam gas content was reduced by 39.7% compared to the original gas extraction scheme. It can be seen that the reasonable gas extraction scheme and coal seam pressure relief and permeability enhancement technology can significantly improve the gas extraction rate, and the extraction effect is remarkable.
Hydrochemical and stable isotopes (δ2H and δ18O) changes of groundwater from a spring induced by local earthquakes, Northwest China
Authors: Xiang Yang , Peng Suping
Published: January 2023

It has been well reported that earthquakes can cause changes in groundwater chemistry and isotopes, and much of those changes were occurred in wells or hot springs; however, changes in cold spring caused by local small earthquakes have received less attention. Here, we collected continuous monitoring of the X10 spring (September 2018 to December 2019), investigated the hydrogeochemical characteristics of the spring by using water chemistry analysis and isotope methods. We compared the changes in water chemical ion concentrations and hydrogen-oxygen isotope ratios with the surrounding seismic activity, and the results show that 1) major chemical ion concentrations in X10 springs have an annual dynamic pattern of being high in winter and low in summer, and this change may be related to the seasonal effect of snowmelt; 2) the spring water originates from long-distant meteoric water, snowmelt, and bedrock fissure water and is affected by rock weathering and evaporation; 3) the hydrogen and oxygen stable isotope ratios and HCO3− concentration in groundwater are sensitive to local small seismic activity. We considered that small earthquakes can change the permeability in fault zones or aquifers, leading to mixing of groundwater with different chemical composition and isotopes. Our study demonstrates that the hydrogen and oxygen stable isotopes are more sensitive to seismic activity than the commonly used chemical constitutents, and that the sensitive constitutents vary in different observation wells or springs; therefore, combined monitoring of isotopes and water chemistry should be considered in the future to capture hydrogeochemical precursor signals caused by earthquakes.
Simultaneous reconstruction and denoising for DAS-VSP seismic data by RRU-net
Authors: Tang Huanhuan , Cheng Shijun , Li Wuqun , Mao Weijian
Published: January 2023

Distributed acoustic sensing in vertical seismic profile (DAS-VSP) acquisition plays an important role in reservoir monitoring. But the field data can be noisy and associated with missing traces which affects the seismic imaging and geological interpretation. Therefore, the DAS-VSP seismic data reconstruction with a high signal-to-noise ratio (SNR) is worth studying. There are no exact relationships between signals and noise in the t-x domain DAS-VSP seismic data, which means that reconstructing signals and suppressing noise simultaneously by the deep neural network is difficult. We develop a novel algorithm based on U-net in combination with the Hankel matrix as input/output, rather than t-x domain seismic data. The frequency domain Hankel matrix of the seismic data is proposed to facilitate the reconstruction and denoising of DAS-VSP seismic data as a rank reduction problem of the high-rank matrix. The Hankel matrices of incomplete data with noise are high-rank ones while those of complete data without noise are low-rank ones, which is beneficial to the network learning. In our proposed rank reduction U-net (RRU-net), two-channel input/output layers are designed for the real and the imaginary parts of the Hankel matrix in the frequency domain. Thus, reconstructed data with high precision and high SNR could be obtained using a trained RRU-net. Meanwhile, we tested our RRU-net algorithm on two synthetic data and one field data, and the results show the effectiveness and the feasibility of the method. Our algorithm performs better than both the U-net-based method that uses t−x domain data as input/output and the rank reduction approach.
Pharmacologic management of weight regain following bariatric surgery
Authors: Lucas Eugene , Simmons Okeefe , Tchang Beverly , Aronne Louis
Published: January 2023

While bariatric surgery restults in significant long-term weight loss for most patients with obesity, post-surgical weight gain affects a considerable percentage of patients to varying degrees of severity. Furthermore, a small but significant percentage of patients experience inadequate post-surgical weight loss. Although many studies have examined the role of anti-obesity medications to address post-operative weight regain, an evidence-based consensus has not yet been achieved because of the heterogeneity of populations studied and the studies themselves. Observational studies in the post-bariatric surgery population consistently demonstrate the benefit of medical weight management after bariatric surgery, with most evidence highlighting liraglutide, topiramate, and phentermine/topiramate. New anti-obesity medications are anticipated to be helpful for post-surgical weight optimization given their efficacy in the non-surgical population.
Age-related and individual features of the HPA axis stress responsiveness under constant light in nonhuman primates
Authors: Goncharova Nadezhda , Chigarova Olga , Oganyan Tamara
Published: January 2023

The hypothalamic-pituitary-adrenal (HPA) axis is a key adaptive neuroendocrine system, dysfunction of which plays an important role in the increasing incidence of stress-dependent age-related pathology. Among the environmental factors effecting increase age-related diseases, great importance is given to disturbances of the light-dark schedule, particularly with increased illumination at night. While disruption of the light-dark schedule has long been recognized as a powerful behavioral stressor, little is known regarding stress reactivity of the HPA under constant light (CL) conditions, especially with aging and depending on the features of stress behavior. The purpose of this investigation was to study the age-related and individual features of the HPA axis response to acute stress exposure (ASE) under chronic CL in nonhuman primates that are known to differ in behavioral responsiveness to stress. Young and old female rhesus monkeys (with control standard behavior or anxiety and depression-like behavior) were exposed to CL (24 h light/day, 330-400 lux for 4 to 8 weeks). Control young and old monkeys were exposed to standard lighting (SL) with natural light during the day and darkness at night. All animals were subjected to ASE (restriction of mobility for 2 hours), functional tests with corticotrophin-releasing hormone and arginine-vasopressin, and study of circadian rhythms of cortisol and pineal melatonin secretion. For the first time an inhibitory effect of CL on the reaction of the adrenal cortex to ASE was revealed in all individuals, regardless of age and preexisting behavior stress reactivity, the mechanisms of which were age-dependent: due to inhibition of the pituitary ACTH secretion in young animals and mainly not affecting the ACTH secretion in old individuals. There were no significant changes in melatonin secretion both in young and old animals. The observed CL inhibition of adrenal cortical reactivity to ASE may be useful to correct increased vulnerability to ASE observed in individuals with preexisting anxiety and depression-like stress behaviors. On the other hand, the CL induced decrease in adrenal stress reactivity of behaviorally normal animals suggests a potential risk of reducing the adaptive capacity of the organism under conditions of continuous light exposure.
Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes: A systematic review and meta-analysis
Authors: Wang Yao , Zhong Yujie , Zhang Zhehao , Yang Shuhao , Zhang Qianying , Chu Bingyang , Hu Xulin
Published: January 2023

Objective

This systematic review and meta-analysis was performed to compare the effect of sodium-glucose cotransporter protein-2 inhibitors (SGLT-2i) and placebo on left ventricular hypertrophy (LVH) in patients with type 2 diabetes.

Method

Randomized controlled trials (RCTs) comparing the LVH parameters of SGLT-2i to placebo in patients with type 2 diabetes were included. Our primary outcomes were the changes in left ventricular mass (LVM) and left ventricular mass index (LVMI) from baseline to the study endpoint. Secondary outcomes were the changes in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early mitral inflow velocity to atrial inflow velocity (E/A). Summary odds ratios were estimated using a fixed-effect or random-effect model.

Results

A total of 11 articles were included. Data were extracted from 11 original studies matching our inclusion criteria. In our meta-analysis, there were significant improvement in LVM (SMD −0.23, 95% CI −0.44 to −0.02, I2 = 22.6%, p = 0.034), LVMI (SMD −0.25, 95% CI −0.38 to −0.12, I2 = 0.0%, p = 0.000), LVEDV (SMD −0.19, 95% CI −0.36 to −0.01, I2 = 62.3%, p = 0.035), and LVESV (SMD −0.21, 95% CI −0.39 to −0.04, I2 = 32.9%, p = 0.017) in the SGLT-2i group compared with the placebo group. Furthermore, no significant differences were found in LVEF (SMD 0.13, 95% CI 0.00 to 0.26, I2 = 0.0%, p = 0.050) and E/A (SMD −0.01, 95% CI −0.22 to 0.20, I2 = 0%, p = 0.908) between the two groups.

Conclusions

This meta-analysis confirmed the beneficial effects of SGLT-2i on reversal of left ventricular remodeling. The LVH regression was more pronounced in studies of type 2 diabetes patients receiving SGLT-2i than placebo.
Exploring novel targets of sitagliptin for type 2 diabetes mellitus: Network pharmacology, molecular docking, molecular dynamics simulation, and SPR approaches
Authors: Qi Jian-hong , Chen Pu-yu , Cai Ding-yuan , Wang Yi , Wei Yue-lei , He Su-ping , Zhou Wei
Published: January 2023

Background

Diabetes has become a serious global public health problem. With the increasing prevalence of type 2 diabetes mellitus (T2DM), the incidence of complications of T2DM is also on the rise. Sitagliptin, as a targeted drug of DPP4, has good therapeutic effect for T2DM. It is well known that sitagliptin can specifically inhibit the activity of DPP4 to promote insulin secretion, inhibit islet β cell apoptosis and reduce blood glucose levels, while other pharmacological mechanisms are still unclear, such as improving insulin resistance, anti-inflammatory, anti-oxidative stress, and anti-fibrosis. The aim of this study was to explore novel targets and potential signaling pathways of sitagliptin for T2DM.

Methods

Firstly, network pharmacology was applied to find the novel target most closely related to DPP4. Semi-flexible molecular docking was performed to confirm the binding ability between sitagliptin and the novel target, and molecular dynamics simulation (MD) was carried to verify the stability of the complex formed by sitagliptin and the novel target. Furthermore, surface-plasmon resonance (SPR) was used to explored the affinity and kinetic characteristics of sitagliptin with the novel target. Finally, the molecular mechanism of sitagliptin for T2DM was predicted by the enrichment analysis of GO function and KEGG pathway.

Results

In this study, we found the cell surface receptor―angiotensin-converting enzyme 2 (ACE2) most closely related to DPP4. Then, we confirmed that sitagliptin had strong binding ability with ACE2 from a static perspective, and the stability of sitagliptin―ACE2 complex had better stability and longer binding time than BAR708―ACE2 in simulated aqueous solution within 50 ns. Significantly, we have demonstrated a strong affinity between sitagliptin and ACE2 on SPR biosensor, and their kinetic characteristics were “fast binding/fast dissociation”. The guiding significance of clinical administration: low dose can reach saturation, but repeated administration was needed. Finally, there was certain relationship between COVID-19 and T2DM, and ACE2/Ang-(1-7)/Mas receptor (MasR) axis may be the important pathway of sitagliptin targeting ACE2 for T2DM.

Conclusion

This study used different methods to prove that ACE2 may be another novel target of sitagliptin for T2DM, which extended the application of ACE2 in improving diabetes mellitus.
Hypoxia signaling pathway: A central mediator in endocrine tumors
Authors: Watts Deepika , Jaykar Mangesh T. , Bechmann Nicole , Wielockx Ben
Published: January 2023

Adequate oxygen levels are essential for the functioning and maintenance of biological processes in virtually every cell, albeit based on specific need. Thus, any change in oxygen pressure leads to modulated activation of the hypoxia pathway, which affects numerous physiological and pathological processes, including hematopoiesis, inflammation, and tumor development. The Hypoxia Inducible Factors (HIFs) are essential transcription factors and the driving force of the hypoxia pathway; whereas, their inhibitors, HIF prolyl hydroxylase domain (PHDs) proteins are the true oxygen sensors that critically regulate this response. Recently, we and others have described the central role of the PHD/HIF axis in various compartments of the adrenal gland and its potential influence in associated tumors, including pheochromocytomas and paragangliomas. Here, we provide an overview of the most recent findings on the hypoxia signaling pathway in vivo, including its role in the endocrine system, especially in adrenal tumors.
Adaptive robust economic dispatch and real-time control of distribution system considering controllable inverter air-conditioner clusters
Authors: Chen Guanhong , Liu Dong
Published: January 2023

With a tremendous number of renewable energy sources (RES) integrated into the distribution system, the inherent uncertainty of RES power generation brings about significant challenges in distribution and power balance within the distribution system. This article proposes an adaptive robust economic dispatch (ARED) model and a real-time control strategy for distribution systems as countermeasures, which make full use of the adjustable capabilities of controllable inverter air-conditioner (IAC) clusters. Firstly, the concept of the adjustable capacity curve (ACC) is developed to accurately quantify the adjustable capacity of an IAC cluster. Afterward, a two-stage adaptive robust optimization is formulated for ARED, which comprehensively takes the adjustable capacity of the IAC cluster and the uncertainty of RES into consideration. Meanwhile, the solution methodology of ARED is also designed based on the column and constraint generation (C&CG) algorithm, where the master problem is quadratic programming with quadratic constraints (QCQP), and the max-min sub-problem is reformulated to a mixed integer linear programming (MILP) form by taking advantage of linear duality theory and big-M method. Finally, a novel real-time decentralized control strategy for IAC clusters is also proposed for purpose of hedging against stochastic RES power fluctuation after every round of ARED decisions. The results of the case study validate the effectiveness of ARED model and real-time control strategy under different uncertainty scenarios of RES power generation.
Wind speed prediction model using ensemble empirical mode decomposition, least squares support vector machine and long short-term memory
Authors: Ai Xueyi , Li Shijia , Xu Haoxuan
Published: January 2023

Due to the randomness and intermittency of wind, accurate and reliable wind speed prediction is of great importance to the safe and stable operation of power grid. In this paper, a novel hybrid wind speed forecasting model based on EEMD (Ensemble Empirical Mode Decomposition), LSSVM (Least Squares Support Vector Machine), and LSTM (Long Short-Term Memory) is proposed, aiming at enhancing the forecasting accuracy of wind speed. The original data series is firstly processed by EEMD and SE into a series of components with different frequencies. Subsequently, a combined mechanism composed of LSSVM and LSTM is presented to train and predict the high-frequency and low-frequency sequences, respectively. Finally, the predicted values of all the data sequences are superimposed to obtain the ultimate wind speed forecasting results. In order to respectively illustrate the superiority of data feature processing and combined prediction mechanism in the proposed model, two experiments are performed on the two wind speed datasets. In accordance with the four performance metrics of the forecasting results, the EEMD-LSTM-LSSVM model obtains a higher accuracy in wind speed prediction task.
Multi-objective capacity optimization configuration of independent wind-photovoltaic- hydrogen-battery system based on improved MOSSA algorithm
Authors: Gaojun Meng , Yanwen Ding , Pau Giovanni , Linlin Yu , Wenyi Tan
Published: January 2023

Under the background of large-scale and rapid development of renewable energy, in order to improve the economic benefit of the system and ensure the reliability of the system, this paper introduces hydrogen production and energy storage into the independent wind/photovoltaic/hydrogen/storage capacity optimization configuration method. In order to minimize the total planning cost and self-sufficiency rate of system power supply, a capacity optimization allocation model was established. On the basis of this model, the Multi-objective Salp Swarm Algorithm (MOSSA) was improved in Algorithm structure, Tent chaotic mapping was introduced to initialize the population, and the positions of leaders and followers were updated based on the adaptive spiral search strategy. The validity of the algorithm is verified by test function. Finally, the specific example is solved by MATLAB programming, and the improved multi-objective Salp Swarm Algorithm (IMOSSA) is used to obtain the capacity configuration scheme, which provides reference for the optimization design of independent photovoltaic hydrogen storage system.
Gabor-YOLONet: A lightweight and efficient detection network for low-voltage power lines from unmanned aerial vehicle images
Authors: Feng Lei , Zhang Lianmei , Gao Zepu , Zhou Ruoyun , Li Lan
Published: January 2023

Maintaining and monitoring low-voltage overhead power lines are of great importance because such lines are the key link between the power system and low-voltage power users. At present, few networks can be detected accurately on intelligent edge identification devices because of the complex backgrounds and limited characteristics in unmanned aerial vehicle images as well as the low computing abilities of hardware. In order to give consideration to accuracy and speed, a novel power line detection method was proposed, denoted by Gabor-YOLONet, used for intelligent edge identification devices available to UAV. Unlike existing methods, the proposed method uses the Gabor algorithm to extract foreground of power lines from cluttered backgrounds automatically and predict power lines and their auxiliary targets such as insulators in the foreground scene. In addition, a new inference method was introduced, which can summarize the average location and orientation of auxiliary targets by clustering to verify the rationality of the predicted results for power lines. The experiment results showed that the proposed method had the higher accuracy and consumed less computing resources; compared with other methods, the mAP of identification for power lines was 86.6% and the running time was only 25 ms, with excellent performance on intelligent edge devices.
Multi-Objective optimization of an IGV for a large axial fan based on NSGA-II
Authors: Zhou Shuiqing , Zhang Tianle , Mao Zijian , Lu Laifa
Published: January 2023

Large axial fans are widely used in industrial refrigeration, building ventilation, and other scenarios because they have inlet guide vanes (IGVs) and outlet guide vanes (OGVs) to make their operation economical and efficient. However, unreasonable guide vane structure is prone to flow separation, forming a tail vortex and interfering with other blades, thereby resulting in the deterioration of working conditions and large noise. Taking a large axial fan with both IGVs and OGVs as the research object, this paper analyzed the structural variables of the fan by global sensitivity analysis method and determine the target of settings optimization as IGV according to the analysis results and the internal flow characteristics of the fan. Furthermore, IGV was parametrically designed, and Kriging model was established and optimized by the second non-dominated sorting genetic algorithm (NSGA-II). Eventually, total pressure and sound pressure level (SPL) were used as targets for multi-objective optimization. The results indicated that the noise produced by the optimized fan was reduced by 6.4 dB and total pressure was increased by 156.4 Pa, with an increase of 0.86% in the total pressure efficiency at the rated working condition, which proved the reliability of the proposed method. This paper also provides a valuable reference for the optimization of similar fluid equipment.
Determining urban‒rural coordinated development in major grain-producing areas based on urbanization and cultivated land use efficiency coordination level: A case study in Hunan Province, China
Authors: Wei Xue , Liu Liming , Yuan Chengcheng , Xia Zheyi
Published: January 2023

Urbanization and cultivated land use coordination is the key to urban‒rural coordinated development, especially in the major grain-producing areas in China, but it is rarely examined. A coordination framework of urbanization and cultivated land use efficiency systematically clarified how to achieve Urbanization and cultivated land use coordination. Taking Hunan Province as an example, this study explored the spatiotemporal evolution of the level of Urbanization and cultivated land use coordination from 2000 to 2018 at the county level, identified current types of Urbanization and cultivated land use coordination and discussed the key optimization measures for different types. The results showed that 1) urban‒rural coordinated development, abstractly represented by the Urbanization and cultivated land use coordination in major grain-producing areas, depends on the intensity of interactions and the level of integration of urbanization and cultivated land use systems. 2) From 2000 to 2018, the level of Urbanization and cultivated land use coordination in Hunan changed from serious maladjustment to great maladjustment to coordination. 3) The current Urbanization and cultivated land use coordination pattern in Hunan Province has a strong spatial differentiation, which can be divided into eight subregions. The key to the coordinated development of each type is to accelerate the flow of elements through deepening reform and innovation mechanisms to complement the shortcomings of development. This study will provide a scientific reference for the effective implementation of regional coordinated development strategies in major food-producing regions.
A stakeholder perspective on social stability risk of public–private partnerships project for water environmental governance in China: A social network analysis
Authors: Wang Wenke , Guo Xinlin , Cao Qilin , Tang Aomei
Published: January 2023

The pluralism of stakeholders in PPP project for water environmental governance and the complex interrelationship among stakeholders are the important factors affecting social stability risk. Previous studies have mainly focused on risk identification and assessment. We aim to investigate the key social risks of PPP project for water environmental governance, to understand which social risks stakeholders are concerned about, and what interactions they follow. First, relevant risks and their interrelationships were investigated through a literature review and interviews. Second, the key social stability risks were identified based on social network analysis. Third, strategies were proposed to mitigate the social stability risks. The results show that government corruption, government intervention risk, approved risk, poor contract design risk price change and policy and regulation risk are the key risks with the highest in/out-degree, centrality and ego network size. Four core stakeholder groups (i.e., government, contractors, project companies, and the public and the media) and four core challenges (i.e., difficulties in financing, lack of mass incidents prevention mechanism, incomplete project schedule control system and improper handling of benefit compensation issues) have intensive relationships. We concluded that controlling the complicated relationships among four core stakeholder groups can reduce the social stability risks. The social network analysis framework combining stakeholder management and risk management provides a reference for the management of PPP projects for water environmental governance.
Hematopoietic stem and progenitors cells gene editing: Beyond blood disorders
Authors: Buffa Valentina , Alvarez Vargas José Roberto , Galy Anne , Spinozzi Simone , Rocca Céline J.
Published: January 2023

Lessons learned from decades-long practice in the transplantation of hematopoietic stem and progenitor cells (HSPCs) to treat severe inherited disorders or cancer, have set the stage for the current ex vivo gene therapies using autologous gene-modified hematopoietic stem and progenitor cells that have treated so far, hundreds of patients with monogenic disorders. With increased knowledge of hematopoietic stem and progenitor cell biology, improved modalities for patient conditioning and with the emergence of new gene editing technologies, a new era of hematopoietic stem and progenitor cell-based gene therapies is poised to emerge. Gene editing has the potential to restore physiological expression of a mutated gene, or to insert a functional gene in a precise locus with reduced off-target activity and toxicity. Advances in patient conditioning has reduced treatment toxicities and may improve the engraftment of gene-modified cells and specific progeny. Thanks to these improvements, new potential treatments of various blood- or immune disorders as well as other inherited diseases will continue to emerge. In the present review, the most recent advances in hematopoietic stem and progenitor cell gene editing will be reported, with a focus on how this approach could be a promising solution to treat non-blood-related inherited disorders and the mechanisms behind the therapeutic actions discussed.
A novel frameshift mutation in TRPV6 is associated with hereditary pancreatitis
Authors: Shah Idrees A. , Prasad Hari , Banerjee Sanghita , Kurien Reuben Thomas , Chowdhury Sudipta Dhar , Visweswariah Sandhya S.
Published: January 2023

Introduction: Hereditary pancreatitis (HP) is a rare debilitating disease with incompletely understood etio-pathophysiology. The reduced penetrance of genes such as PRSS1 associated with hereditary pancreatitis indicates a role for novel inherited factors.

Methods: We performed whole-exome sequencing of three affected members of an Indian family (Father, Son, and Daughter) with chronic pancreatitis and compared variants with those seen in the unaffected mother.

Results: We identified a novel frameshift mutation in exon 11 of TRPV6 (c.1474_1475delGT; p.V492Tfs*136), a calcium channel, in the patients. Functional characterization of this mutant TRPV6 following heterologous expression revealed that it was defective in calcium uptake. Induction of pancreatitis in mice induced Trpv6 expression, indicating that higher expression levels of the mutant protein and consequent dysregulation of calcium levels in patients with chronic pancreatitis could aggravate the disease.

Discussion: We report a novel frameshift mutation in TRPV6 in an Indian family with HP that renders the mutant protein inactive. Our results emphasize the need to expand the list of genes used currently for evaluating patients with hereditary pancreatitis.
Low expression of NR1H3 correlates with macrophage infiltration and indicates worse survival in breast cancer
Authors: Zhang Jing , Zhang Jiawen , Zhao Weiwei , Li Qingxian , Cheng Wenwu
Published: January 2023

Background: Nuclear receptor NR1H3 is a key regulator of macrophage function and lipid homeostasis. Here, we aimed to visualize the prognostic value and immunological characterization of NR1H3 in breast cancer.

Methods: The expression pattern and prognostic value of NR1H3 were analyzed via multiple databases, including TIMER2, GEPIA2 and Kaplan-Meier Plotter. TISIDB, TIMER2 and immunohistochemical analysis were used to investigate the correlation between NR1H3 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB and GeneMANIA were used to visualize the functional enrichment of NR1H3 and signaling pathways related to NR1H3.

Results: We demonstrated that the expression of NR1H3 was significantly lower in breast cancer compared with adjacent normal tissues. Kaplan-Meier survival curves showed shorter overall survival in basal breast cancer patients with low NR1H3 expression, and poorer prognosis of relapse-free survival in breast cancer patients with low NR1H3 expression. NR1H3 was mainly expressed in immune cells, and its expression was closely related with infiltrating levels of tumor-infiltrating immune cells in breast cancer. Additionally, univariate and multivariate analysis indicated that the expression of NR1H3 and the level of macrophage infiltration were independent prognostic factors for breast cancer. Gene interaction network analysis showed the function of NR1H3 involved in regulating of innate immune response and macrophage activation. Moreover, NR1H3 may function as a predictor of chemoresponsiveness in breast cancer.

Conclusion: These findings suggest that NR1H3 serves as a prognostic biomarker and contributes to the regulation of macrophage activation in breast cancer.
The impact of decreased expression of SVEP1 on abnormal neovascularization and poor prognosis in patients with intrahepatic cholangiocarcinoma
Authors: Chen Liwei , He Yuchao , Han Zhiqiang , Gong Wenchen , Tian Xiangdong , Guo Lin , Guo Hua , Song Tianqiang , Chen Lu
Published: January 2023

Introduction: Intrahepatic cholangiocarcinoma (ICC) is one of the most highly heterogeneous malignant solid tumors; it is generally insensitive to clinical treatment and has a poor prognosis. Evidence suggests that abnormal neovascularization in the tumor microenvironment is an important cause of treatment resistance as well as recurrence and metastasis, but the key regulatory molecules are still largely unknown and should be identified.

Method: We assessed the novel extracellular matrix protein (ECM) Sushi, von Willebrand factor type A, EGF and pentraxin containing 1 (SVEP1) expression pattern in the ICC by using immunohistochemistry. Multiplex immunofluorescence and Kaplan-Meier analysis were applied to explore the correlation between the low expression of SVEP1 and abnormal blood vessels and the clinical prognosis of ICC.

Results: Our study showed that the expression of SVEP1 in most ICC samples was relatively lower than in the adjacent tissues. Statistical analysis suggested that patients with decreased SVEP1 expression always had shorter overall survival (OS) and disease-free survival (DFS). Moreover, the expression of SVEP1 was negatively correlated with the proportion of abnormal neovascularization in the tumor microenvironment of the ICC. Consistently, the key molecule of promoting vascular normalization, Ang-1, is positively correlated with the SVEP1 expression and prognosis in the ICC. In addition, the proportion of high Ki-67 expression was higher in the ICC samples with low SVEP1 expression, suggesting that the SVEP1 low expressed sample is in a malignant phenotype with high proliferation.

Conclusion: This study reveals that SVEP1 is a promising prognostic biomarker for ICC and provides fresh insight into the role and potential new mechanism of abnormal neovascularization in ICC progression.
A retrospective clinical study of dolutegravir- versus efavirenz-based regimen in treatment-naïve patients with advanced HIV infection in Nanjing, China
Authors: Zhong Mingli , Li Mengqing , Qi Mingxue , Su Yifan , Yu Nawei , Lv Ru , Ye Zi , Zhang Xiang , Xu Xinglian , Cheng Cong , Chen Chen , Wei Hongxia
Published: January 2023

Currently, there are limited data related to the efficacy and safety of ART regimens, as well as factors influencing immune recovery in antiretroviral therapy (ART)-naïve patients with advanced HIV infection, especially in China. We designed a single-center, retrospective cohort study from March 1, 2019, to May 31, 2022, at The Second Hospital of Nanjing, China. ART-naïve adults with advanced HIV infection (CD4+ T-cell count < 200 cells/μL) who met the study criteria were included. The plasma viral load (VL), CD4+ T-cell count, CD4/CD8 ratio, treatment discontinuation, and immune reconstitution inflammatory syndrome (IRIS) events were collected to compare the efficacy and safety of the dolutegravir (DTG) and the efavirenz (EFV) regimens. Factors of immune recovery were analyzed using the Cox regression model. Study enrolled 285 ART-naïve adults with advanced HIV-1 infection, of which 95 (33.3%) started regimens including DTG and 190 (66.7%) were treated with EFV. After ART initiation, the proportion of patients with HIV-1 RNA < 50 copies/mL was higher (22.5% versus 6.5%, P < 0.001) in those on DTG-based regimens at month 1, but no significant difference at other follow-up points. Compared to the baseline, the median CD4+ T-cell count and CD4/CD8 ratio increased significantly during follow-up both in the EFV and the DTG groups. However, the CD4+ T-cell count increased greater in patients on DTG-based regimens at months 6, 12, 24, and 36 (P < 0.05). A total of 52 (18.2%) patients discontinued treatment, with no significant difference between ART regimens in treatment discontinuation rates. Only 7 patients reported IRIS, without significant difference between ART regimens (P=0.224). Overall, 34.0% (97/285) achieved a CD4+ T-cell count ≥ 350 cells/μL during follow-up. Age (P < 0.001), baseline CD4+ T-cell count (P < 0.001), baseline VL (P < 0.001) and ART regimens (P = 0.019) were associated with the CD4+ T-cell count ≥ 350 cells/μL after adjusting for potential confounders. Among ART-naïve adults with advanced HIV infection, it appeared that DTG-based regimens were better options for initial therapy compared to regimens including EFV; in addition, ART regimens, age, baseline VL and CD4+ T-cell count were associated with immune recovery.
Beta 2 glycoprotein I and neutrophil extracellular traps: Potential bridge between innate and adaptive immunity in anti-phospholipid syndrome
Authors: Grossi Claudia , Capitani Nagaja , Benagiano Marisa , Baldari Cosima Tatiana , Della Bella Chiara , Macor Paolo , Tedesco Francesco , Borghi Maria Orietta , Maugeri Norma , D’Elios Mario Milco , Meroni Pier Luigi
Published: January 2023

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by recurrent vascular thrombosis and miscarriages in the absence of known causes. Antibodies against phospholipid-binding proteins (aPL) are pathogenic players in both clotting and pregnancy APS manifestations. There is sound evidence that antibodies specific for beta2 glycoprotein I (β2GPI) trigger thrombotic and pregnancy complications by interacting with the molecule on the membranes of different cell types of the coagulation cascade, and in placenta tissues. In addition to the humoral response against β2GPI, both peripheral and tissue CD4+ β2GPI-specific T cells have been reported in primary APS as well as in systemic lupus erythematosus (SLE)-associated APS. While adaptive immunity plays a clear role in APS, it is still debated whether innate immunity is involved as well. Acute systemic inflammation does not seem to be present in the syndrome, however, there is sound evidence that complement activation is crucial in animal models and can be found also in patients. Furthermore, neutrophil extracellular traps (NETs) have been documented in arterial and venous thrombi with different etiology, including clots in APS models. Keeping in mind that β2GPI is a pleiotropic glycoprotein, acting as scavenger molecule for infectious agents and apoptotic/damaged body constituents and that self-molecules externalized through NETs formation may become immunogenic autoantigens, we demonstrated β2GPI on NETs, and its ability to stimulate CD4+β2GPI-specific T cells. The aim of this review is to elucidate the role of β2GPI in the cross-talk between the innate and adaptive immunity in APS.
Metabolic syndrome in antiphospholipid syndrome versus rheumatoid arthritis and diabetes mellitus: Association with arterial thrombosis, cardiovascular risk biomarkers, physical activity, and coronary atherosclerotic plaques
Authors: Bolla Eleana , Tentolouris Nikolaos , Sfikakis Petros P. , Tektonidou Maria G.
Published: January 2023

Background

Cardiovascular disease (CVD) is the foremost cause of morbidity and deaths in antiphospholipid syndrome (APS), driven by thrombo-inflammation and atherothrombosis mechanisms. Metabolic syndrome (MetS) is a proinflammatory and prothrombotic state characterized by increased CVD risk. We aimed to evaluate the prevalence of MetS in APS patients compared to rheumatoid arthritis (RA) and diabetes mellitus (DM) and its associations with clinical and laboratory patient characteristics and vascular ultrasound (US) markers of subclinical atherosclerosis.

Methods

We included 414 patients in our study: 138 patients with APS (median age: 44.9 years, females 70%) and matched 1:1 for age and sex RA and DM subjects. Three sets of criteria were used for MetS diagnosis: Joint Interim Statement (JIS), International Diabetes Federation (IDF) and modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). The demographic, clinical and laboratory characteristics of all participants were recorded and carotid and femoral US was performed in patients with APS. Multivariate regression models were applied.

Results

Prevalence of MetS was 23.9%, 23.2%, 20.3% (based on JIS, IDF, modified NCEP-ATPIII criteria, respectively) in APS versus 17.4%, 17.4%, 13% in RA (p=0.181, p=0.231, p=0.106, respectively), and 44.2%, 44.2%, 40.6% in DM patients. In multivariate analysis, patients with systemic lupus erythematosus- related APS had an approximately 2.5-fold higher risk of MetS versus RA patients. MetS in APS was independently associated with arterial thrombosis (Odds ratio 3.5, p=0.030). Odds ratio for MetS was 1.16 for each one unit increase in C-reactive protein levels according to JIS and IDF criteria, and 1.49 and 1.47 for each one unit increase in uric acid levels using the IDF and modified NCEP-ATPIII models, respectively. APS patients with atherosclerotic carotid plaques had 4 to 6.5-fold increased risk of MetS. Odds for MetS were decreased by 26% with an increase in physical activity by one hour per week.

Conclusions

MetS is present in approximately one-fourth of APS patients at a comparable prevalence to that observed in patients with RA. MetS in APS is associated with arterial thrombosis, cardiovascular risk biomarkers, physical activity, and subclinical atherosclerosis, supporting its role in cardiovascular risk stratification and management in APS.
Pre-clinical models for evaluating glioma targeted immunotherapies
Authors: Frederico Stephen C. , Zhang Xiaoran , Hu Baoli , Kohanbash Gary
Published: January 2023

Gliomas have an extremely poor prognosis in both adult and pediatric patient populations as these tumors are known to grow aggressively and respond poorly to standard of care treatment. Currently, treatment for gliomas involves surgical resection followed by chemoradiation therapy. However, some gliomas, such as diffuse midline glioma, have more limited treatment options such as radiotherapy alone. Even with these interventions, the prognosis for those diagnosed with a glioma remains poor. Immunotherapy is highly effective for some cancers and there is great interest in the development of effective immunotherapies for the treatment of gliomas. Clinical trials evaluating the efficacy of immunotherapies targeted to gliomas have largely failed to date, and we believe this is partially due to the poor choice in pre-clinical mouse models that are used to evaluate these immunotherapies. A key consideration in evaluating new immunotherapies is the selection of pre-clinical models that mimic the glioma-immune response in humans. Multiple pre-clinical options are currently available, each one with their own benefits and limitations. Informed selection of pre-clinical models for testing can facilitate translation of more promising immunotherapies in the clinical setting. In this review we plan to present glioma cell lines and mouse models, as well as alternatives to mouse models, that are available for pre-clinical glioma immunotherapy studies. We plan to discuss considerations of model selection that should be made for future studies as we hope this review can serve as a guide for investigators as they choose which model is best suited for their study.
Crosstalk between fibroblasts and T cells in immune networks
Authors: Lee Byunghyuk , Lee Seung-Hyo , Shin Kihyuk
Published: January 2023

Fibroblasts are primarily considered as cells that support organ structures and are currently receiving attention for their roles in regulating immune responses in health and disease. Fibroblasts are assigned distinct phenotypes and functions in different organs owing to their diverse origins and functions. Their roles in the immune system are multifaceted, ranging from supporting homeostasis to inducing or suppressing inflammatory responses of immune cells. As a major component of immune cells, T cells are responsible for adaptive immune responses and are involved in the exacerbation or alleviation of various inflammatory diseases. In this review, we discuss the mechanisms by which fibroblasts regulate immune responses by interacting with T cells in host health and diseases, as well as their potential as advanced therapeutic targets.