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In this article, we construct a new order 2.0 simplified weak Itô–Taylor symmetrical scheme for stochastic delay differential equations. By the new local weak convergence lemma and the connection inequality, we theoretically prove the global weak convergence theorem in two parts on the basis of Malliavin stochastic analysis. Meanwhile, numerical examples are presented to illustrate the error and convergence results. Furthermore, the obtained results display the influence of the delay coefficient on global errors.

Stirling-type pulse tube cryocoolers are used in many applications such as military facilities, aerospace devices and superconductive systems. A major problem in improving its energy conversion efficiency is how to achieve a better impedance matching. In this study, a pulse tube cryocooler is investigated based on the impedance analyses. A group of impedance maps is proposed to analyze the energy conversion performance of the compressor. The velocity map, the efficiency map, the acoustic power map and the phase angle map are provided under the total equivalent impedance. These maps offer a visualized guidance of the maximum performance a compressor could reach and in which direction to optimize. Experiments on a high capacity pulse tube cryocooler are conducted to verify the theoretical analyses. The results show that it is of great help in using the proposed maps to analyze and improve the energy conversion performance of the cryocooler. A cooling capacity of 300W@80K is finally achieved. The study clearly reveals the influence of the impedance on the energy conversion efficiency and it is quite useful in improving the performance of the pulse tube cryocooler.

In this paper, we propose a new weak order 2.0 numerical scheme for solving stochastic differential equations with Markovian switching (SDEwMS). Using the Malliavin stochastic analysis, we theoretically prove that the new scheme has local weak order 3.0 convergence rate. Combining the special property of Markov chain, we study the effects from the changes of state space on the convergence rate of the new scheme. Two numerical experiments are given to verify the theoretical results.

In this paper, we propose a new weak second-order numerical scheme for solving stochastic differential equations with jumps. By using trapezoidal rule and the integration-by-parts formula of Malliavin calculus, we theoretically prove that the numerical scheme has second-order convergence rate. To demonstrate the effectiveness and the second-order convergence rate, three numerical experiments are given.

Abstract Copper ions play a crucial role as cofactors for essential enzymes in cellular processes. However, when the intracellular concentration of copper ions exceeds the homeostatic threshold, they become toxic to cells. In our study, we demonstrated that elesclomol, as a carrier of copper ions, caused an upregulation of protein phosphatase 1 regulatory subunit 15 A (PPP1R15A), which plays a role in regulating substrate selectivity of protein phosphatase 1 during cuproptosis. Mechanistically, we investigated that PPP1R15A activated translation initiation by dephosphorylating eukaryotic translation initiation factor 2 subunit alpha at the S51 residue through protein phosphatase 1 and phosphorylating eukaryotic translation initiation factor 4E binding protein 1 at the T70 residue. In addition, PPP1R15A reduced H3K4 methylation by altering the phosphorylation of histone methyltransferases, which led to the silencing of MYC and G2M phase arrest.

Muscle-invasive and metastatic bladder cancer indicates extra worse prognosis. Accumulating evidence roots for the prominent role of circular RNAs(circRNAs) in bladder cancer, while the mechanisms linking circRNAs and bladder cancer metastasis remain limitedly investigated. Here, we identified a significantly upregulated circRNA candidate, hsa_circ_0001583, from online datasets. Validated by qRT-PCR, PCR, sanger sequencing, actinomycin D and RNase R digestion experiments, hsa_circ_0001583 was proved to be a genuine circular RNA with higher expression levels in bladder cancer tissue. Through gain and loss of function experiments, hsa_circ_0001583 exhibited potent migration and invasion powers both in vitro and in vivo. The staphylococcal nuclease and Tudor domain containing 1 (SND1) was identified as an authentic binding partner for hsa_circ_0001583 through RNA pulldown and RIP experiments. Elevated levels of hsa_circ_0001583 could bind more to SND1 and protect the latter from degradation. Rescue experiments demonstrated that such interaction-induced increased in SND1 levels in bladder cancer cells enabled the protein to pump its endonuclease activity, leading to the degradation of tumor-suppressing MicroRNAs (miRNAs) including miR-126-3p, the suppressor of Disintegrin And Metalloproteinase Domain-Containing Protein 9 (ADAM9), ultimately driving cells into a highly migrative and invasive state. In summary, our study is the first to highlight the upregulation of hsa_circ_0001583 in bladder cancer and its role in downregulating miR-126-3p by binding to and stabilizing the SND1 protein, thereby promoting bladder cancer cell migration and invasion. This study adds hsa_circ_0001583 to the pool of bladder cancer metastasis biomarkers and therapeutic targets.

Abstract Background About 10–20% of patients with bladder cancer (BC) progress to muscle-invasive diseases, of which the underlying key molecular events have yet to be addressed. Results Here, we identified poly(A) binding protein nuclear 1 (PABPN1), a general factor of alternative polyadenylation (APA), was downregulated in BC. Overexpression and knockdown of PABPN1 significantly decreased and increased BC aggressiveness, respectively. Mechanistically, we provide evidence that the preference of PABPN1-bound polyadenylation signals (PASs) depends on the relative location between canonical and non-canonical PASs. PABPN1 shapes inputs converging on Wnt signaling, cell cycle, and lipid biosynthesis. Conclusions Together, these findings provide insights into how PABPN1-mediated APA regulation contributes to BC progression, and suggest that pharmacological targeting PABPN1 might have therapeutic potential in patients with BC.

Abstract Recent research has shown that ferroptosis, the iron-dependent accumulation of lipid peroxides that leads to cell death, suppresses cancer metastasis. However, the role of ferroptosis in prostate cancer metastasis has not been completely elucidated. In the current study, we identified the essential role of serum/glucocorticoid regulated kinase 2 (SGK2) in promoting prostate cancer metastasis by inhibiting ferroptosis. We found that the expression of SGK2 was higher in metastatic prostate cancer and predicted poor clinical outcomes. SGK2 knockdown inhibited the metastatic capacity of prostate cancer cells in vivo and in vitro, while SGK2 overexpression inhibited ferroptosis and facilitated prostate cancer metastasis by phosphorylating the Thr-24 and Ser-319 sites of forkhead box O1 (FOXO1). This process induced the translocation of FOXO1 from the nucleus to the cytoplasm, relieving the inhibitory effect of FOXO1 on glutathione peroxidase 4 (GPX4). These findings delineated a novel role of SGK2 in ferroptosis regulation of prostate cancer metastasis, identifying a new key pathway driving prostate cancer metastasis and potentially providing new treatment strategies for metastatic prostate cancer.

This article focuses on a finite-time adaptive dynamic surface control (DSC) approach for a kind of nonstrict fractional-order nonlinear systems (FONSs) with input delay. An auxiliary compensation function is presented by using the integral function of the input signal to handle input delay problem. To overcome the problem of inherent computational complexity, a fractional-order filter is applied to approach the virtual controller and its fractional-order derivative in each step of the backstepping procedure. By using backstepping technology and neural network (NN), the finite-time adaptive DSC approach is developed, and finite-time stability criteria based on fractional-order Lyapunov method are introduced to prove the finite-time convergence of the tracking error into a small region around the origin. The effectiveness of the presented control scheme is demonstrated by two examples.

The central part of the Zhangjiakou area is occupied by the Yanshan orogenic basin. A large number of piedmont faults developed over time, controlling the exposure of geothermal anomalies. The fluid chemistry characteristics and their influence on the heat generation mechanism of the medium- and low-temperature convective geothermal field in the area are not fully understood. In this study, the geothermal fluid was sampled and tested, and the hydrogeological background conditions were analyzed. The results show that the sulfate in geothermal fluid originates from the dissolution of gypsum or H2S oxidation in deep magma. The geothermal fluid in the faulted basin flows upward after deep circulation and interacts with shallow groundwater. The main source of geothermal fluid is atmospheric precipitation. The temperature of the hot reservoir is between 82 °C and 121 °C, and the depth of geothermal water circulation is more than 3200 m. It can be seen that the geothermal resources in this area are formed by the long-term contact of residual magma, geothermal heating and mechanical heating of neotectonic movement after atmospheric precipitation recharge.

Our previous animal studies found that the preventive effects of lactoferrin (Lf) on alcoholic liver injury (ALI) are associated with nuclear factor E2-related factor 2 (Nrf2). To further explore the causality, experiments were performed using rat normal liver BRL-3A cells. Lf treatment reduced ethanol-induced death and apoptosis; meanwhile, Lf treatment alleviated excessive LDH release. These findings confirmed the protection of Lf against ethanol-induced injury in BRL-3A cells. Mechanistically, Lf treatment reversed the reduction in nuclear Nrf2 induced by ethanol without affecting the cytoplasmic Nrf2 level, which led to antioxidant enzyme activity restoration. However, the blocking of Nrf2 nuclear translocation by ML385 eliminated the protective effects of Lf. In a conclusion, Lf protects BRL-3A cells from ethanol-induced injury via promoting Nrf2 nuclear translocation.

Abstract Background Acquisition of the chemoresistance to docetaxel (DTX), a microtubule-targeting agent, has been a huge obstacle in treatment for metastatic castration-resistant prostate cancer (mCRPC). Recently, strategies targeting the mitosis error correction mechanism including chromosomal passenger complex (CPC) were reported to reverse the resistance to microtubule-targeting anticancer agents. Meanwhile, accumulating evidence indicated the important roles of circRNAs in DTX resistance of prostate cancer (PCa). However, whether circRNAs could regulate DTX chemosensitivity by affecting the mitosis error correction mechanism remains unclear. Methods Expression patterns of circ_0004087 and BUB1 were determined through mining the public circRNA datasets and performing western blot and qRT-PCR assays. Agarose gel electrophoresis, Sanger sequencing, and RNase R treatment were conducted to examine the circular characteristics of circ_0004087. CircRNA pull-down, mass spectrometry analysis, Co-IP, and dual-luciferase reporter assays were performed to uncover the interaction among circ_0004087, SND1, and MYB. The effects of circ_0004087 and BUB1 on docetaxel-based chemotherapy were explored by flow cytometry and in vivo drug studies upon xenografted tumor model. Results In the present study, we revealed the profound interaction between a novel circRNA, circ_0004087, and the mitosis error correction mechanism. Mechanistically, circ_0004087 binding with transcriptional coactivator SND1 could stimulate the transactivation of MYB and enhance the expression of downstream target BUB1. In turn, elevated BUB1 expression further recruited CPC to centromeres and guaranteed the error-free mitosis of PCa cells. Biologically, the overexpression of circ_0004087 conferred while the knockdown impaired DTX resistance in PCa cells. Conclusions Our study uncovered the crucial role of circ_0004087/SND1/MYB/BUB1 axis in modulating the error mitosis correction mechanism and DTX chemoresistance, suggesting that circ_0004087 may serve as a valuable prognostic biomarker and a potential therapeutic target in DTX-resistant PCa patients.

Abstract Background Circular RNAs (circRNAs) are essential participants in the development and progression of various malignant tumors. Previous studies have shown that cell migration-inducing protein (CEMIP) accelerates prostate cancer (PCa) anoikis resistance (AR) by activating autophagy. This study focused on the effect of circCEMIP on PCa metastasis. Methods This study gradually revealed the role of circ_0004585 in PCa anoikis resistance via quantitative real-time PCR (qRT-PCR) analysis, western blotting, pull-down assays, and dual fluorescence reporter assays. Results Functionally, circ_0004585 promoted PCa cells invasion and metastasis both in vitro and in vivo. Mechanistically, circ_0004585 directly interacted with miR-1248 to upregulate target gene expression. Furthermore, target prediction and dual-luciferase reporter assays identified transmembrane 9 superfamily member 4 (TM9SF4) as a potential miR-1248 target. Pathway analysis revealed that TM9SF4 activated autophagy to promote PCa cells anoikis resistance via mTOR phosphorylation. Conclusions These results demonstrated that circ_0004585 played an oncogenic role during PCa invasion and metastasis by targeting the miR-1248/TM9SF4 axis while providing new insight into therapeutic strategy development for metastatic PCa.

Abstract Background Prostatic cancer (PCa) is one of the most common malignant tumors in men worldwide. Emerging evidence indicates significance of hypoxia and immunity in PCa invasion and metastasis. This study aimed to develop a hypoxia- and immune-related gene risk signature and explore the molecular mechanisms to formulate a better prognostic tool for PCa patients. Methods The hypoxia and immune scores of all PCa patients in The Cancer Genome Atlas (TCGA) dataset were calculated via the maximally selected rank statistics method and the ESTIMATE algorithm. From common genes identified overlapping hypoxia- and immune-related differentially expressed genes (DE-HRGs and DE-IRGs), a hypoxia- and immune-related gene risk signature was developed utilizing univariate and multivariate Cox regression analyses, and validated in the Memorial Sloan Kettering Cancer Centre (MSKCC) database. The immune cell infiltration level of PCa samples were evaluated with ssGSEA algorithm. Differential expression of prognostic genes was evidenced by immunohistochemistry and western blot (WB) in paired PCa samples. Expression levels of these genes and their variations under regular and hypoxic conditions were examined in cell lines. The functional effects of the prognostic gene on PCa cells were examined by wound healing and transwell assays. Results A hypoxia- and immune-related gene risk signature constructed by ISG15 and ZFP36 displays significant predictive potency, with higher risk score representing worse survival. A nomogram based on independent prognostic factors including the risk score and Gleason score exhibited excellent clinical value in the survival prediction of PCa. Infiltration levels of eosinophils, neutrophils, Tcm, Tem, TFH, Th1 cells, and Th17 cells were significantly lower in the high-risk group. Conversely, aDC, pDC, T helper cells, and Tregs were significantly higher. Additionally, the two prognostic genes were closely correlated with the tumor-infiltrating immune cell subset in PCa progression. RT-qPCR and WB presented higher and lower expression of ISG15 and ZFP36 in PCa cells, respectively. They were correspondingly increased and decreased in PCa cells under hypoxic conditions. Wound healing and transwell assays showed that over-expression of ISG15 promoted the migration and invasion of PCa cells. Conclusion Our study identified a novel hypoxia- and immune-related gene signature, contributing a new perspective to the treatment of PCa

Abstract The survival of cancer cells after detaching from the extracellular matrix (ECM) is essential for the metastatic cascade. The programmed cell death after detachment is known as anoikis, acting as a metastasis barrier. However, the most aggressive cancer cells escape anoikis and other cell death patterns to initiate the metastatic cascade. This study revealed the role of cell migration-inducing protein (CEMIP) in autophagy modulation and anoikis resistance during ECM detachment. CEMIP amplification during ECM detachment resulted in protective autophagy induction via a mechanism dependent on the dissociation of the B-cell lymphoma-2 (Bcl-2)/Beclin1 complex. Additional investigation revealed that acting transcription factor 4 (ATF4) triggered CEMIP transcription and enhanced protein kinase C alpha (PKCα) membrane translocation, which regulated the serine70 phosphorylation of Bcl-2, while the subsequent dissociation of the Bcl-2/Beclin1 complex led to autophagy. Therefore, CEMIP antagonization attenuated metastasis formation in vivo. In conclusion, inhibiting CEMIP-mediated protective autophagy may provide a therapeutic strategy for metastatic prostate cancer (PCa). This study delineates a novel role of CEMIP in anoikis resistance and provides new insight into seeking therapeutic strategies for metastatic PCa.

Bladder cancer (BC) is a common genitourinary malignancy. This study investigated the regulatory effects of an exonic circRNA, circNUDT21, in the progression of BC. The circNUDT21 level was overexpressed in BC tissues and cell lines as compared to normal controls. Overexpression and silencing of circNUDT21 promoted and inhibited, respectively, the proliferative and invasive abilities of BC cells. Mechanistical analysis showed that circNUDT21 acted as a miR-16-1-3p sponge and that MDM2 was a potential downstream target of miR-16-1-3p. We further verified that overexpression of circNUDT21 was associated with elevated MDM2 and reduced p53 expression. CircNUDT21 promoted BC progression by acting as a sponge of miR-16-1-3p to activate the miR-16-1-3p/MDM2/p53 axis. These findings suggest that circNUDT21 functions as an oncogenic circRNA and may be a potential therapy target for BC.

Abstract Abiraterone, a novel androgen synthesis inhibitor, has been approved for castration-resistant prostate cancer (CRPC) treatment. However, most patients eventually acquire resistance to this agent, and the underlying mechanisms related to this resistance remain largely unelucidated. Lysine acetyltransferase 2 A (KAT2A) has been reported to enhance transcriptional activity for certain histone or non-histone proteins through the acetylation and post-translational modification of the androgen receptor (AR). Therefore, we hypothesised that KAT2A might play a critical role in the resistance of prostate tumours to hormonal treatment. In this study, we found that KAT2A expression was increased in abiraterone-resistant prostate cancer C4-2 cells (C4-2-AbiR). Consistently, elevated expression of KAT2A was observed in patients with prostate cancer exhibiting high-grade disease or biochemical recurrence following radical prostatectomy, as well as in those with poor clinical survival outcomes. Moreover, KAT2A knockdown partially re-sensitised C4-2-AbiR cells to abiraterone, whereas KAT2A overexpression promoted abiraterone resistance in parental C4-2 cells. Consistent with this finding, KAT2A knockdown rescued abiraterone sensitivity and inhibited the proliferation of C4-2-AbiR cells in a mouse model. Mechanistically, KAT2A directly acetylated the hinge region of the AR, and induced AR translocation from the cytoplasm to the nucleus, resulting in increased transcriptional activity of the AR-targeted gene prostate specific antigen (PSA) leading to resistance to the inhibitory effect of abiraterone on proliferation. Taken together, our findings demonstrate a substantial role for KAT2A in the regulation of post-translational modifications in AR affecting CRPC development, suggesting that targeting KAT2A might be a potential strategy for CRPC treatment.

There are two high-temperature and high-yield geothermal wells, located in the deep ancient buried hill northeast of the Gaoyang geothermal field at the Xiong'an New Area, are constructed by China Geological Survey during the past two years. The successful implementation of the two deep wells reveal that there is a second space for geothermal development in deep Xiong'an New Area. The deep carbonate rock has a high thermal storage temperature, large flow rate, and huge development potential. On the basis of previous studies, this article fully summarizes the latest survey results of geothermal resources in deep buried hills in the northeast of Gaoyang Geothermal Field and these comprehensive analysis show that the heat accumulation mechanism of the study area are as follows: ① Affected by the westward subduction of the Pacific Plate, the eastern North China Craton is significantly damaged, and the thickness of the lithosphere and crust has been greatly reduced, which is conducive to conduct the mantle-derived heat to the shallow depth; ②The regional Marcy fault and other deep strike-slip faults cut through the lithosphere, which contributed to the deep mantle-derived thermal material and deep magma intruding into the crust; ③The heat flow is gathered from the low thermal conductivity depression to the high thermal conductivity. Besides, groundwater is heated by deep cycle and convection along the fault, and the confluence area of regional karst groundwater also has a certain heat accumulation effect. Because of the combined effect of various favorable factors, a high-temperature and high-productivity carbonate type reservoir is formed in the northeast of the Gaoyang geothermal field.

From 2019 to 2021, we constructed two high-productivity geothermal wells with wellhead temperatures of 109.2 and 123.4°C in the Gaoyang geothermal field. Based on the two wells, it was proved that Gaoyang is a medium-temperature carbonate geothermal field with great development potential. The article reported the latest exploration achievements of deep buried hill geothermal resources in the geothermal field. The productivity of D34 and D35 geothermal wells were evaluated by James end-pressure method: the total flow of steam–water mixture was 234.59–331.92 (t/h), the dryness was 1.36–2.03%, and the single-well power generation potential was 2.10–2.55 MW. Combined with those results, the heat control factors and heat accumulation mechanism of the deep carbonatite geothermal field were confirmed. The westward subduction of the Pacific plate caused obvious damage to the eastern North China Craton and greatly reduced the thickness of the lithosphere and crust. This process facilitated the conduction of mantle-derived heat to shallow crust. Deep strike-slip faults (e.g., Maxi fault) cut through the lithosphere, leading the deep mantle-derived heat and magma to migrate into the crust. The heat accumulated from the depression with low thermal conductivity to the uplift with high thermal conductivity. Groundwater was heated up by deep cycle and convection along faults. The catchment of regional karst groundwater also had a certain effect on the heat accumulation. The Gaoyang geothermal field was formed by these factors.

The geothermal resources in mountainous areas are usually controlled by neotectonic faults. To minimize the risk in site selection for geothermal drilling, the controlling mechanism must be identified. Based on the neotectonic control theory for geothermal resources, the occurrence of the geothermal resources in the mountainous area in southeastern Zhangjiakou city was investigated. The investigation was divided into three stages. Firstly, field investigation for neotectonics was carried out to characterize the kinematics and the stress state of the faults, including fault occurrences, tectonic stages, and paleostress analysis, and in total 19 neotectonic faults were confirmed. Based on Riedel shear model and present stress field, their conductivity for geothermal water was inferred; secondly, geophysical and geochemical surveys were applied to identify the stress state and characterize the occurrence of the potential water conductive faults. The results showed that the combined use of magnetotelluric sounding (MT), controllable source audio magnetotelluric sounding (CSAMT), and 2D seismologic survey is effective in delineating fault occurrence, strata distribution, and water conductivity within 1,000 m depth, while measurement of 222Rn activity in soil gas across the neotectonic faults is effective to investigate the groundwater conductivity of the faults, and all the neotectonic faults in the study area striking clockwise from N5°E to N25°W are considered to be water conductive; thus, the areas at the intersection zones of neotectonic faults in the basin in groundwater runoff and discharge regions are promising targets for geothermal exploration. This conceptual model was verified by the geothermal fields already discovered in the study area and proved to be reasonable, and then a potential drilling site was predicted and proved to be successful. It is suggested that this workflow for geothermal exploration is suitable for Zhangjiakou city and may also be applied to other mountainous areas.

Studying the flow path of geothermal water in geothermal fields is an important basis for the scientific development and management of geothermal resources. However, due to the influence of engineering volume, economic benefits and demand, it is very difficult to fully grasp the flow path of deep geothermal water in large areas. The use of hydrogeochemical tracers to determine the flow path of geothermal water is a scientific and effective research method. In order to accurately describe the flow path of carbonate geothermal water in the Xiong’an New Area and its surrounding areas, this study systematically analyzed the 14C, 18O, and 2H data of carbonate and Cenozoic sandstone geothermal water, Quaternary groundwater, as well as mountain spring water of the study area. Based on these results, we can conclude that 1) The 14C, d, and 18O values are favourable clues for indicating the circulating runoff conditions and runoff paths of geothermal water. 2) The salinity of the Xushui-Wenan and Lilan transfer zone are 3 g/l, the 14C values are higher than 40,000 years, the d value is lower, and the phenomenon of “18O drift” is obvious, all these indicating that the tectonic sites are the convergence areas of regional karst geothermal water, featured by relative high temperature. 4) The hydrochemical indicators combined with previous carbonate groundwater flow field indicate that the recharge of carbonate geothermal water in the Xiong’an New Area may not only drive from the western Taihang Mountains, but also along the Xushui-Wenan transfer zone and the Lilan fault, with the recharge of carbonate groundwater from the Cangxian uplift from east to west. By further identifying and defining the dominant flow path and supply direction of carbonate geothermal water in the Xiong’an New Area and surrounding areas, it provides strong support for the scientific development of regional carbonate geothermal water.

Geothermal resources are clean energy with a great potential for development and utilization. Gaoyang geothermal field, located in the middle of the raised area in Hebei province, China, is one of the three major geothermal fields in the Xiong’an New Area. With the development of the Xiong’an New Area, this geothermal field has become a research hotspot. According to the latest survey, the bottom-hole temperature of the D34 and D35 areas in the north of Gaoyang geothermal field is 149°C and 116°C, respectively, which indicates favorable target areas for geothermal exploitation The circulation mechanism and chemical origins of geothermal fluid are unclear in the Gaoyang geothermal field, which hinders the evaluation of geothermal resources in this region. Therefore, water chemistry and isotopic studies were performed on the Gaoyang geothermal fluid to understand the genesis of the Gaoyang geothermal field. Piper trigram and Na-K-Mg software were also used to explore the genesis of the underground hot water. Combined with stratigraphy and geothermal geology, it can be concluded that the primary hydrochemical type of the Gaoyang geothermal field is Na-HCO3·Cl. In the process of upward migration of geothermal water, leaching and cation alternating adsorption took place, and finally, high TDS geothermal water was formed. Our results are helpful for geothermal resource evaluation and utilization and provide scientific guidance for the sustainable development of geothermal resources.

The Xifeng geothermal field is located in the Yangtze Craton, SW China, and is one of the most representative low-temperature geothermal fields in China. Widespread thermal anomalies, hot springs, and geothermal wells have been reported by previous studies. However, the nature and forming mechanisms of the field remain poorly understood. Element geochemical (ions, rare earth elements) and stable isotopic (D, O) composition of hot springs, geothermal fluids, rivers, and cold springs from different locations of the Xifeng geothermal field were analyzed in this study. The ions studies revealed that most samples featured the Ca-Mg-HCO3 type, except Xifeng hot springs, and which were characterized by the Ca-Mg-HCO3-SO4 type. Based on quartz geothermometers, the estimated reservoir temperature was 77°C. The results of stable isotopes (D, O) manifest that the Xifeng geothermal system was recharged by meteoric water at an elevation of 1,583 m from SW to NE. The research of rare earth elements (REE) revealed that their accumulation characteristics and obvious positive Eu anomaly were inherited from host feldspar-bearing reservoir dolomites through water-rock interactions. Combined with these observations, geological setting, and previous studies, it was concluded that the formation of the Xifeng geothermal field resulted from recharge, deep circulation, and secondary rising of the meteoric water along the faults. First, meteoric water infiltrated to depth through faults and crack zones. Second, the deep-infiltrated water was heated by radioactive heat, deep heat, and tectonic frictional heat. Finally, as the warmed-up waters underwent considerable deep circulation in the reservoir, it rose again along the main faults, and mixed with groundwater near the surface. Taken together, we suggest that the Xifeng geothermal system should be assigned as a faults-controlling, and deeply circulating meteoric water of low-temperature category.

IntroductionIt’s widely reported the “writer” enzymes mediated RNA adenosine modifications which is known as a crucial mechanism of epigenetic regulation in development of tumor and the immunologic response in many kinds of cancers. However, the potential roles of these writer genes in the progression of bladder cancer (BLCA) remain unclear.Materials and MethodsWe comprehensively described the alterations of 26 RNA modification writer genes in BLCA from the genetic and transcriptional fields and identified writer-related genes from four independent datasets. Utilizing least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, we constructed a ten writer-related gene signature. After that, we confirmed the predictive and prognostic value of this signature on another six independent datasets and established a nomogram to forecast the overall survival (OS) and mortality odds of BLCA patients clinically.ResultsThe writer-related genes signature showed good performance in predicting the OS for BLCA patients. Moreover, the writer-related gene signature was related to EMT-related pathways and immune characteristics. Furthermore, the immune cell infiltration levels of CD8 T cells, cytotoxic cells, M1/2 macrophage cells and tumor mutation burden might be able to predict which patients will benefit from immunotherapy. This could also be reflected by the writer-related gene signature.ConclusionsThis signature might play an important role in precision individualized immunotherapy. The present work highlights the crucial clinical implications of RNA modifications and may help developing individualized therapeutic strategies for patients with BLCA.

High-frequency measurements can provide much more new insights for drillstring dynamics compared to traditional instruments, leading to a new realm of understanding of drillstring behaviors in great detail than before. In this paper, data acquisition tools with high-frequency sample rates and the data processing are introduced. Based on high-frequency data, progress of drilling dynamics is summarized, including new understandings of low-frequency drillstring dynamics, high-frequency torsional oscillations (HFTOs), and high-frequency axial oscillations (HFAOs) and new findings for the coupling of vibrations and motions, as well as models and simulation methods to deeply comprehend high-frequency dynamics of drillstring. High-frequency measurements have been used for enabling drillers to improve drill performance, especially for field decision making, BHA selection, and bit design, usually through the ways of minimizing vibrations to obtain high-efficient drilling conditions, the high-frequency response near bit can also be used for lithology identification during drilling. Though there still exists a gap between research perspective and drilling practice, the industry of high-frequency measurements has gotten off a good start, which has huge potential to avoid nonproductive time thereupon reducing drilling cost in the future.