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The Qinghai-Xizang Plateau， distinguished by its vast array of lakes， exhibits marked seasonal lake ice coverage， which is highly responsive to climatic shifts.This ice coverage plays a crucial role in the dynamic interchange of fluxes between the lake surfaces and the atmosphere.Despite the significance of these ice phenomena， the limited availability of extensive， long-term observational data on plateau lake ice has led to a reliance on reanalyzed ice datasets， particularly ERA5-Land.This study aims to rigorously evaluate the effectiveness and potential enhancements of ERA5-Land's lake ice data in the distinct environment of the Qinghai-Xizang Plateau.Focusing on data collected from 2010 to 2022 for Qinghai Lake and Ngoring Lake， this research meticulously examines the ERA5-Land reanalysis data's ability to accurately capture the intrinsic characteristics of plateau lake ice.The study uncovered that ERA5-Land tends to overestimate the ice thickness by about 0.54~0.62 m and erroneously prolongs the freezing period by roughly 68 days per year for these lakes.This notable discrepancy necessitated an in-depth error analysis， which synthesized ERA5-Land data with direct observational data from Ngoring Lake， revealing that inaccuracies primarily originated from the FLake one-dimensional lake model within the ERA5-Land system.In an effort to address these inaccuracies， the study employed the MCD43A3 surface albedo product for both Qinghai Lake and Ngoring Lake over the same period.This innovative approach significantly refined the FLake model by incorporating both a multi-year average albedo and a dynamic daily average albedo.These methodological improvements led to a substantial reduction in the average bias of ice thickness， by 85% and 90% respectively， and narrowed the deviation in the modeled freezing period by about 6 and 8 days per year.The enhancements were particularly notable in lakes with longer periods of snow cover， where the dynamic albedo adjustment proved to be highly effective.This research has successfully identified the albedo parameter within the FLake model as a key source of error in ERA5-Land's lake ice characterizations and has implemented practical adjustments to rectify this.These enhancements have markedly increased the model's precision in simulating lake ice， thereby significantly improving the accuracy of ERA5-Land reanalyzed lake ice data.This advancement is particularly pertinent for the unique climatic and geographical conditions of Qinghai Lake and Ngoring Lake on the Qinghai-Xizang Plateau and offers invaluable insights for future research and practical applications in this domain.The findings of this study contribute profoundly to our understanding and modeling of lake ice phenomena in high-altitude regions and have broader implications for climatological research and environmental monitoring on the Qinghai-Xizang Plateau.

Abstract Mountain torrents are frequent and severe hazards, causing serious economic losses and personnel casualties, and in particular, they are the most dangerous threat in the complex terrain. Multi‐source precipitation products should be used to drive the hydrological models to improve understanding of the processes of mountain torrents. Fifteen sets of precipitation products are evaluated against the ground observations in situ within a serious mountain torrent caused by a severe rainstorm at June 26, 2020 in Sichuan. The multi‐source merged precipitation products performed better than the others. Satellite‐based precipitation performed better than model‐based products, while IMERG‐Early and FY2G performed better than other satellite‐based precipitation products. The reanalysis datasets are relatively worse than the observed products. The operational NWPs strongly underestimated precipitation in the mountainous areas. Furthermore, the related floods caused by the rainstorm is simulated based on various precipitation products by a raster‐based hydrodynamic two‐dimensional model of FloodArea. Most observation‐based precipitation products represented the flooding area well, while the model‐based precipitation products underestimated the severity of the mountain torrents. Finally, the risk of mountain torrents under variant return‐period rainfall is analyzed. The result shows the potential of real‐time torrent monitoring and forecasting using high‐resolution DEM and precipitation products.

The glaciers in the High Mountain Asia (HMA) region are highly vulnerable to global warming, posing significant threats to downstream populations and infrastructure through glacier lake outburst floods (GLOFs). The monitoring and early warnings of these events are challenging due to sparse observations in these remote regions. To explore reproducing the evolution of GLOFs with sparse observations in situ, this study focuses on the outburst event and corresponding GLOFs in August 2018 caused by the Kyagar Glacier lake, a typical glacier lake of the HMA in the Karakoram, which is known for its frequent outburst events, using a combination of multi-satellite remote sensing data (Sentinel-1 and Sentinel-2) and the HEC-RAS hydrodynamic model. The water depth of the glacier lake and downstream was extracted from satellite data adapted by the Floodwater Depth Elevation Tool (FwDET) as a baseline to compare them with simulations. The elevation-water volume curve was obtained by extrapolation and was applied to calculate the water surface elevation (WSE). The inundation of the downstream of the lake outburst was obtained through flood modeling by incorporating a load elevation-water volume curve and the Digital Elevation Model (DEM) into the hydrodynamic model HEC-RAS. The results showed that the Kyagar glacial lake outburst was rapid and destructive, accompanied by strong currents at the end of each downstream storage ladder. A series of meteorological evaluation indicators showed that HEC-RAS reproduced the medium and low streamflow rates well. This study demonstrated the value of integrating remote sensing and hydrodynamic modeling into GLOF assessments in data-scarce regions, providing insights for disaster risk management and mitigation.

BackgroundFrailty correlates with adverse outcomes in many cardiovascular diseases and is prevalent in individuals with heart failure (HF). The Hospital Frailty Risk Score (HFRS) offers an integrated, validated solution for frailty assessment in acute care settings, but its application in critically ill patients with congestive HF lacks exploration. This study aimed to identify the association between frailty assessed by the HFRS and in-hospital mortality in critically ill patients with congestive HF.MethodsThis observational study retrospectively enrolled 12,179 critically ill patients with congestive HF. Data from the Medical Information Mart for Intensive Care IV database was used. The HFRS was calculated to assess frailty. Patients were categorized into three groups: non-frailty (HFRS

Abstract Background Decompensated liver cirrhosis (DLC), a terminal-stage complication of liver disease, is a major cause of morbidity and mortality in patients with hepatopathies. Human umbilical cord mesenchymal stem cell (hUCMSC) therapy has emerged as a novel treatment alternative for the treatment of DLC. However, optimized therapy protocols and the associated mechanisms are not entirely understood. Methods We constructed a DLC rat model consistent with the typical clinical characteristics combined use of PB and CCL4. Performing dynamic detection of liver morphology and function in rats for 11 weeks, various disease characteristics of DLC and the therapeutic effect of hUCMSCs on DLC in experimental rats were thoroughly investigated, according to ascites examination, histopathological, and related blood biochemical analyses. Flow cytometry analysis of rat liver, immunofluorescence, and RT-qPCR was performed to examine the changes in the liver immune microenvironment after hucMSCs treatment. We performed RNA-seq analysis of liver and primary macrophages and hUCMSCs co-culture system in vitro to explore possible signaling pathways. PPARγ antagonist, GW9662, and clodronate liposomes were used to inhibit PPAR activation and pre-exhaustion of macrophages in DLC rats’ livers, respectively. Results We found that changing the two key issues, the frequency and initial phase of hUCMSCs infusion, can affect the efficacy of hUCMSCs, and the optimal hUCMSCs treatment schedule is once every week for three weeks at the early stage of DLC progression, providing the best therapeutic effect in reducing mortality and ascites, and improving liver function in DLC rats. hUCMSCs treatment skewed the macrophage phenotype from M1-type to M2-type by activating the PPARγ signaling pathway in the liver, which was approved by primary macrophages and hUCMSCs co-culture system in vitro. Both inhibition of PPARγ activation with GW9662 and pre-exhaustion of macrophages in DLC rats’ liver abolished the regulation of hUCMSCs on macrophage polarization, thus attenuating the beneficial effect of hUCMSCs treatment in DLC rats. Conclusions These data demonstrated that the optimal hUCMSCs treatment effectively inhibits the ascites formation, prolongs survival and significantly improves liver structure and function in DLC rats through the activation of the PPARγ signaling pathway within liver macrophages. Our study compared the efficacy of different hUCMSCs infusion regimens for DLC, providing new insights on cell-based therapies for regenerative medicine.

Abstract Background Inflammatory bowel diseases (IBD) are chronic relapsing–remitting inflammatory diseases of the gastrointestinal tract that are typically categorized into two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although MSCs therapy has achieved encouraging outcomes in IBD therapy, objective responses are limited in colon fibrosis stenosis owing to the complicated microenvironment of CD and MSCs heterogeneity of quality. Here, we chose IFN-γ and kynurenic acid (KYNA) to overcome the low response and heterogeneity of human adipose-derived MSCs (hADSCs) to treat IBD and expand the therapeutic effects based on the excellent ability of IFN-γ and KYNA to promote indoleamine 2,3-dioxygenase-1 (IDO-1) signaling, providing a potential protocol to treat IBD and fibrosis disease. Methods hADSCs were isolated, cultured, and identified from human abdominal adipose tissue. The CD pathology-like acute colitis and chronic colon fibrosis rat model was induced by 2,4,6-trinitrobenzen sulfonic acid (TNBS). hADSCs were pretreated in vitro with IFN-γ and KYNA and then were transplanted intravenously at day 1 and 3 of TNBS administration in colitis along with at day 1, 15, and 29 of TNBS administration in chronic colonic fibrosis. Therapeutic efficacy was evaluated by body weights, disease activity index, pathological staining, real-time PCR, Western blot, and flow cytometry. For knockout of IDO-1, hADSCs were transfected with IDO-1-targeting small gRNA carried on a CRISPR-Cas9-lentivirus vector. Results hADSCs treated with IFN-γ and KYNA significantly upregulated the expression and secretion of IDO-1, which has effectively ameliorated CD pathology-like colitis injury and fibrosis. Notably, the ability of hADSCs with IDO-1 knockout to treat colitis was significantly impaired and diminished the protective effects of the primed hADSCs with IFN-γ and KYNA. Conclusion Inflammatory cytokines IFN-γ- and KYNA-treated hADSCs more effectively alleviate TNBS-induced colitis and colonic fibrosis through an IDO-1-dependent manner. Primed hADSCs are a promising new strategy to improve the therapeutic efficacy of MSCs and worth further research.

Abstract Background Liver fibrosis (LF) is a common pathological process characterized by the activation of hepatic stellate cells (HSCs) and accumulation of extracellular matrix. Severe LF causes cirrhosis and even liver failure, a major cause of morbidity and mortality worldwide. Transplantation of human placental mesenchymal stem cells (hPMSCs) has been considered as an alternative therapy. However, the underlying mechanisms and the appropriate time window for hPMSC transplantation are not well understood. Methods We established mouse models of CCl4-injured LF and administered hPMSCs at different stages of LF once a week for 2 weeks. The therapeutic effect of hPMSCs on LF was investigated, according to histopathological and blood biochemical analyses. In vitro, the effect of hPMSCs and the secretomes of hPMSCs on the inhibition of activated HSCs was assessed. RNA sequencing (RNA-seq) analysis, real-time PCR array, and western blot were performed to explore possible signaling pathways involved in treatment of LF with hPMSCs. Results hPMSC treatment notably alleviates experimental hepatic fibrosis, restores liver function, and inhibits inflammation. Furthermore, the therapeutic effect of hPMSCs against mild-to-moderate LF was significantly greater than against severe LF. In vitro, we observed that the hPMSCs as well as the secretomes of hPMSCs were able to decrease the activation of HSCs. Mechanistic dissection studies showed that hPMSC treatment downregulated the expression of fibrosis-related genes, and this was accompanied by the upregulation of Caveolin-1 (Cav1) (p < 0.001). This suggested that the amelioration of LF occurred partly due to the restoration of Cav1 expression in activated HSCs. Upregulation of Cav1 can inhibit the TGF-β/Smad signaling pathway, mainly by reducing Smad2 phosphorylation, resulting in the inhibition of activated HSCs, whereas this effect could be abated if Cav1 was silenced in advance by siRNAs. Conclusions Our findings suggest that hPMSCs could provide multifaceted therapeutic benefits for the treatment of LF, and the TGF-β/Cav1 pathway might act as a therapeutic target for hPMSCs in the treatment of LF.

Most high-altitude lakes are more sensitive to global warming than the regional atmosphere. However, most existing climate models produce unrealistic surface temperatures on the Tibetan Plateau (TP) lakes, and few studies have focused on the influence of ice surface albedo on high-altitude lakes. Based on field albedo measurements, moderate resolution imaging spectrometer (MODIS) albedo products and numerical simulation, this study evaluates the ice albedo parameterization schemes in existing lake models and investigates the characteristics of the ice surface albedo in six typical TP lakes, as well as the influence of ice albedo error in the FLake model. Compared with observations, several ice albedo schemes all clearly overestimate the lake ice albedo by 0.26 to 0.66, while the average bias of MODIS albedo products is only 0.07. The MODIS-observed albedo of a snow-covered lake varies with the snow proportion, and the lake surface albedo in a snow-free state is approximately 0.15 during the frozen period. The MODIS-observed ice surface (snow-free) albedos are concentrated within the ranges of 0.14–0.16, 0.08–0.10 and 0.10–0.12 in Aksai Chin Lake, Nam Co Lake and Ngoring Lake, respectively. The simulated lake surface temperature is sensitive to variations in lake ice albedo especially in the spring and winter.

Abstract Group 2 innate lymphocytes (ILC2) have an important role in orchestrating sepsis-induced immune response. However, the impact of LC2 on sepsis-induced cardiac injury is still not fully understood. This study investigated the mechanisms governing ILC2 activation within the cardiac tissue after sepsis. In vivo experiments using wild-type and IL-33 deficient mice indicated that the presence of interleukin (IL)-33, which participates in expanding and activating ILC2 cells, was correlated with higher ILC2 levels (246 ± 34 vs. 66 ± 18, p

Abstract UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.

Oil and gas resources are of important strategic importance for China's economic development. After more than 50 years of mining in main oil fields, the water cut of oil fields in China has exceeded 90%. China's external dependence on oil and natural gas has increased from 58.9% and 29.2% in 2013 to 71.2% and 40.2% in 2022 respectively, reaching the oil security warning line and impeding national security. In order to find more replacement reserves, oil and gas exploration has been promoted to the "deeper and more complicated" ultra-deep exploration area of 10 000-meter depth. Recently, domestic oil companies have successively implemented the "Deep Sea No. 1" and "Deep Earth No. 1" oil and gas exploration plans, which have explored and practiced new technologies of intelligent drilling and promoted the implementation of the 10 000-meter exploration plans, and reservoirs have been encountered by wells over 9 000 m deep. Based on recent exploration practice, this paper demonstrates the basis of petroleum geological theory for exploration of 10 000-meter depth from the aspects of ultra-deep hydrocarbon generation, storage and accumulation mechanisms, and it suggests that multi-source hydrocarbon generation can be identified in ultra-deep strata and the hydrocarbon generation threshold has exceeded 120-160 ℃. The "three-element controlling reservoir" theory points out that deep and ultra-deep reservoirs can be developed at depths greater than 4 500 meters and multi-phase hydrocarbon accumulation and preservation constitute a favorable condition for the development of ultra-deep large-scale oil and gas reservoirs. The Sichuan Basin has the total resources of about 15.22×1012 m3 in deep marine strata, wherein the Sinian system on the margin of Mianyang-Changning taphrogenic trough, the Longwangmiao Formation on the margin of central Sichuan palaeo-uplift, the Longwangmiao Formation in Micang Mountain-Daba Mountain areas to the east of Chengkou oceanic trough, and the Upper Paleozoic in western Sichuan have a resource potential of more than hundreds of billions of cubic meters. The Tarim Basin has about 15.262×109 tons of equivalent oil in deep marine strata, wherein the Middle-Lower Ordovician karst area in the Tabei uplift, Tazhong uplift and Maigaiti slope, the Middle-Lower Cambrian platform marginal zone on the western margin of Manjiaer Sag, and the Middle and Lower Cambrian intraplatform shoal of Awat-Shuntuoguole are all oil potential areas of hundreds of millions of tons. There are important oil and gas discovery in the Middle Neoproterozoic in the southwest edge of Ordos Basin. Additionally, the field of clastic rocks such as the deep strata in the central deep depression zone in Junggar Basin and the Kuqa Depression in Tarim Basin are also important areas of exploration of 10 000-meter depth.

In-situ stress is an important basic data for determining the top and bottom limit of operating pressure of underground gas storage, evaluating the stability of geological body and analyzing the fault activity in the storage area. Herein, the layered in-situ stress measurement method, test equipment and construction process of perforated interval were briefly introduced, and the minimum principal stresses of 2 reservoir sections and 3 mudstone caprock sections in the depth range of 4 150.0 m to 4 338.0 m of Well NP36-X in Pugu-2 Block of Jidong Oilfield were measured with this method. As shown by the results, the tests were repeated over 3 times for each section, and the fracture shut-in pressure in multiple tests had good consistency with the relative error less than 5%. Besides, the minimum principal stress in the mudstone caprock of Well NP36-X was determined to be 72.40 MPa to 74.27 MPa with various fracture shut-in pressure analysis methods. Moreover, the minimum principal stress of high permeability formation was comprehensively determined to be 54.89 MPa to 60.25 MPa with the fracture extension pressure and the injection flow. As an exploration based on the in-situ stress measurement method for the perforated interval of old wells, this method, especially the field application test based on the fracture extension pressure and the injection flow, can partly compensate the insufficiency that the classical in-situ stress measurement method of hydraulic fracturing is not applicable to the high permeability formation.

As an important type of hydrocarbon reservoir, microbial carbonate contains great amount of hydrocarbon resources. The recent discovery of industrial gas in the Majiagou Formation in the east-central part of the Ordos Basin indicates that this type of reservoir also has very extensive exploration prospects in the Ordos Basin. Similar reservoirs were also found on the southern margin of the basin, but no systematic research has been achieved. In this paper, petrological and geochemical anatomy of microbial carbonate reservoirs of the Pingliang Formation on the southern margin of the Ordos Basin were carried out. Results show that the study area developed a larger-scale microbial mound and beach complex than that in the basin, and the thickness can be more than 100 m. The microbial rock is mainly agglomerate limestone with dissolution pores. The microbial rock reservoir of the Pingliang Formation has experienced two stages of karsting, quasi-syngenesis and epigenesis, which are the key for the formation of reservoir, and there is oil and gas charging during the burial period. Among them, the quasi-syngenetic stage experienced a brief exposure, forming a large amount of irregular-shaped solution pores, and radial fibrous calcite pores filled in the early pores, with similar oxygen/carbon isotope and trace element contents such as Sr and Mg as the matrix calcite, it is then indicated that they were originated from seawater in the same period. During the epigenetic stage, the early solution pores expanded, forming a large number of fractures and cavities, accompanied by the filling of coarse-crystal calcite and mud, and some of the coarse crystalline calcite shows the characteristics of atmospheric precipitation. There is oil and gas charging during the burial period. There are bituminous residues in the present-day solution holes and fractures, and a large amount of liquid hydrocarbon-bearing inclusions can be observed in the calcite filling during the burial period. In summary, the microbial carbonate of the Pingliang Formation at the southern edge of the Ordos Basin, where both reservoir formation and hydrocarbon filling processes exist, is a potential exploration field.

CircRNAs have been the focus of research in recent years. They are differentially expressed in various human tumors and can regulate oncogenes and tumor suppressor genes expression through various mechanisms. The diversity, stability, evolutionary conservatism and cell- or tissue-specific expression patterns of circRNAs also endow them with important regulatory roles in promoting or inhibiting tumor cells malignant biological behaviors progression. More interestingly, emerging studies also found that circRNAs can regulate not only other genes expression, but also their parental gene expression and thus influence tumors development. Apart from some conventional features, circRNAs have a certain specificity in the regulation of parental gene expression, with a higher proportion affecting parental gene transcription and easier translation into protein to regulate parental gene expression. CircRNAs are generally thought to be unable to produce proteins and therefore the protein-coding ability exhibited by circRNAs in regulating parental gene expression is unique and indicates that the regulatory effects of parental gene expression by circRNAs are not only a competitive binding relationship, but also a more complex molecular relationship between circRNAs and parental gene, which deserves further study. This review summarizes the molecular mechanisms of circRNAs regulating parental gene expression and their biological roles in tumorigenesis and development, aiming to provide new ideas for the clinical application of circRNAs in tumor-targeted therapy.

Gas of hydrogen is combustible and has been regarded as one of the important form of clean energy. With the increasing environmental concerns caused by the continues and high dependence on fossil fuels, more attention is being paid to the research on hydrogen exploration. However, only limited understanding about the geological, genetic as well as distribution characteristics of hydrogen gas has been addressed. In this paper, the formation and enrichment mechanisms of hydrogen gas under different geological conditions were compared, results showed that reservoirs of high-content hydrogen gas may develop in rift system and the front edge of plate subduction zone. By further summarizing the distribution of hydrogen gas in different tectonic members, it is concluded that the plate collision zone and subduction zone and their peripheries controlling the distribution of the development of high-content hydrogen gas and thus the petroliferous basins developed in these tectonic positions have good natural gas preservation conditions, hence are promising for the preservation of high-content hydrogen gas.

PurposeOur previous study observed that long non-coding RNA PKD2-2-3 (lnc-PKD2-2-3) is related to advanced tumor features and worse prognosis in cholangiocarcinoma (CCA). Then, this study aimed to further explore the linkage between lnc-PKD2-2-3, miR-328, and GPAM, as well as their effects on regulating CCA viability, mobility, and chemosensitivity.MethodsLnc-PKD2-2-3, miR-328, and GPAM expression in 30 pairs of CCA tumor and adjacent tissues, as well as in CCA cell lines, were determined. Two CCA cell lines (HuCCT1 and TFK1) were transfected by lnc-PKD2-2-3 overexpression plasmid, lnc-PKD2-2-3 siRNA, miR-328 inhibitor, and GPAM siRNA alone or in combination, followed by cell proliferation, apoptosis, invasion, and 5-FU chemosensitivity detection. Besides, xenograft mice were established for validation.ResultsLnc-PKD2-2-3 and GPAM were higher, whereas miR-328 was lower in CCA tissues versus adjacent tissues and also in CCA cell lines versus control cells; meanwhile, they were correlated with each other (all P

By comparing the quantitative pore results of geological samples from natural evolution profiles and simulated experiment samples, it is believed that the volume changes of pores of different scales are basically similar throughout the evolution of source rocks. Macropores and mesopores have a greater impact on pore changes. They should be the main contributors to the total porosity of rocks, and there is a certain conversion relationship between pores of different sizes. Diagenetic evolution and tectonic changes are the main external factors that cause pore changes while hydrocarbon generation and expulsion processes are the internal factors. In addition, there are some differences in the pore space and size (scale) of hydrocarbon products formed by source rocks during different evolutionary stages. This is useful for determining the storage mechanism of conventional and unconventional oil and gas resources corresponding to different evolutionary stages in the shale formation.

CircRNAs (circular RNAs) are single-stranded RNAs that form covalently closed loops and function as important regulatory elements of the genome through multiple mechanisms. Increasing evidence had indicated that circRNAs, which might serve as either oncogenes or tumor suppressors, played vital roles in the pathophysiology of human diseases, especially in tumorigenesis and progression. CircRNA-ZFR (circular RNA zinc finger RNA binding protein) is a circular RNA that had attracted much attention in recent years. It has been found that circRNA-ZFR was abnormally expressed in a variety of malignant tumors, and its dysregulated expression was closely related to tumor stage, cancer metastasis and patients’ prognosis. Recent studies had shown that aberrantly expressed circRNA-ZFR could regulate the malignant biological behaviors of tumors through various mechanisms; further exploration of circRNA-ZFR expression in tumors and its regulation on malignant biological behaviors such as tumor proliferation, invasion and drug resistance will provide new ideas for clinical tumors diagnosis and treatment.

Background. Obstructive sleep apnea (OSA) is common in patients with hypertension. Nonetheless, OSA is underdiagnosed despite considerable evidence of the association between OSA and adverse health outcomes. This study developed and validated a clinical nomogram to predict OSA in patients with hypertension based on the Epworth Sleepiness Scale (ESS) score and OSA-related parameters. Methods. A total of 347 hypertensive patients with suspected OSA were retrospectively enrolled and randomly assigned to a training set and a validation set at 70 : 30 (N = 242/N = 105) ratio. OSA was diagnosed through sleep monitoring and was defined as an apnea-hypopnea index ≥5 events/h. Using the least absolute shrinkage and selection operator regression model, we identified potential predictors of OSA and constructed a nomogram model in the training set. The predictive performance of the nomogram was assessed and validated by discrimination and calibration. The nomogram was also compared with ESS scores according to decision curve analysis (DCA), integrated discrimination index (IDI), and net reclassification index (NRI). Results. ESS scores, body mass index, neck circumference, snoring, and observed apnea predicted OSA are considered. The nomogram showed similar discrimination between the training set (AUC: 0.799, 95% CI: 0.743–0.847) and validation set (AUC: 0.766, 95% CI: 0.673–0.843) and good calibration in the training (P=0.925>0.05) and validation (P=0.906>0.05) sets. Compared with the predictive value of the ESS, the nomogram was clinically useful and significantly improved reclassification accuracy (NRI: 0.552, 95% CI: 0.282–0.822, P42%. Conclusions. We developed a novel OSA prediction nomogram based on ESS scores and OSA-related parameters. This nomogram may help improve clinical decision-making, especially in communities and primary clinics, where polysomnography is unavailable.

Neddylation is a process in which a ubiquitin-like molecule NEDD8 is conjugated to a lysine residue of the substrate protein via successive enzymatic cascade reactions. Inactivation of neddylation pathway triggers tumor cell apoptosis or senescence to suppress the tumor growth. So far, there has been limited research on the role of the neddylation pathway (NEDD8-UBE2M-RBX1 axis) in the immune response. In this study, we investigated the association between the neddylation pathway and immune function in HCC by comprehensively analyzing transcriptome and clinical data of HCC samples from TCGA database. The analysis showed that the mRNA expression of neddylation pathway components was up-regulated in HCC and increased with disease severity. Moreover, we observed that activated neddylation pathway was associated with enriched infiltration of T helper 2 (Th2) cells in HCC, while transactivation of STAT5A signaling may mediate this association. On the contrary, no significant correlation between the neddylation pathway and Th1 cells infiltration was identified. Taken together, these findings suggest a potential role of the neddylation pathway in promoting a shift in Th1/Th2 balance toward Th2-dominant immunosuppression. Hence, targeting neddylation pathway could serve as an attractive immunotherapy strategy for suppressing the development of Th2 cells.

We present cosmological-scale three-dimensional neutral hydrogen (H i ) tomographic maps at z = 2–3 over a total of 837 deg ^2 in two blank fields that are developed with Ly α forest absorptions of 14,736 background Sloan Digital Sky Survey (SDSS) quasars at z = 2.08–3.67. Using the tomographic maps, we investigate the large-scale (≳10 h ^−1 cMpc) average H i radial profiles and two-direction profiles of the line-of-sight (LOS) and transverse directions around galaxies and active galactic nuclei (AGNs) at z = 2–3 identified by the Hobby–Eberly Telescope Dark Energy eXperiment survey and SDSS, respectively. The peak of the H i radial profile around galaxies is lower than the one around AGNs, suggesting that the dark matter halos of galaxies are less massive on average than those of AGNs. The LOS profile of AGNs is narrower than the transverse profile, indicating the Kaiser effect. There exist weak absorption outskirts at ≳30 h ^−1 cMpc beyond H i structures of galaxies and AGNs found in the LOS profiles that can be explained by the H i gas at ≳30 h ^−1 cMpc falling toward the source position. Our findings indicate that the H i radial profile of AGNs has transitions from proximity zones (≲a few h ^−1 cMpc) to the H i structures (∼1–30 h ^−1 cMpc) and the weak absorption outskirts (≳30 h ^−1 cMpc). Although there is no significant dependence of AGN types (type 1 vs. type 2) on the H i profiles, the peaks of the radial profiles anticorrelate with AGN luminosities, suggesting that AGNs’ ionization effects are stronger than the gas mass differences.

Abstract Background Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer’s disease (AD), while how to initiate early cognitive stimulation is unclear. Given that the immature brain is more sensitive to environmental stimuli and that brain dynamics decrease with ageing, we reasoned that it would be effective to initiate cognitive stimulation against AD as early as the fetal period. Methods After conception, maternal AD transgenic mice (3 × Tg AD) were exposed to gestational environment enrichment (GEE) until the day of delivery. The cognitive capacity of the offspring was assessed by the Morris water maze and contextual fear-conditioning tests when the offspring were raised in a standard environment to 7 months of age. Western blotting, immunohistochemistry, real-time PCR, immunoprecipitation, chromatin immunoprecipitation (ChIP) assay, electrophysiology, Golgi staining, activity assays and sandwich ELISA were employed to gain insight into the mechanisms underlying the beneficial effects of GEE on embryos and 7–10-month-old adult offspring. Results We found that GEE markedly preserved synaptic plasticity and memory capacity with amelioration of hallmark pathologies in 7–10-m-old AD offspring. The beneficial effects of GEE were accompanied by global histone hyperacetylation, including those at bdnf promoter-binding regions, with robust BDNF mRNA and protein expression in both embryo and progeny hippocampus. GEE increased insulin-like growth factor 1 (IGF1) and activated its receptor (IGF1R), which phosphorylates Ca2+/calmodulin-dependent kinase IV (CaMKIV) at tyrosine sites and triggers its nuclear translocation, subsequently upregulating histone acetyltransferase (HAT) and BDNF transcription. The upregulation of IGF1 mimicked the effects of GEE, while IGF1R or HAT inhibition during pregnancy abolished the GEE-induced CaMKIV-dependent histone hyperacetylation and BDNF upregulation. Conclusions These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression.

The theory holds that the anterior pituitary in mammals receives humoral regulation. Previous studies have reported that the pars distalis of the anterior pituitary of several mammalian species contains substance P-, calcitonin gene-related peptide (CGRP)-, and galanin-like immunoreactive nerve fibers, but the origins of these nerve fibers are unclear. Removal of the pituitary gland, also called hypophysectomy, involves methods that access the pituitary gland via the transauricular or parapharyngeal pathways. However, these methods are not applicable for viral tracer injection to investigate the innervation of the anterior pituitary. The transauricular technique leads to inaccuracies in locating the pituitary gland, while the parapharyngeal approach causes high mortality in animals. Here, we introduce a protocol that accesses the pituitary gland in the rat via the transsphenoidal pathway. This method imitates surgical manipulations such as endotracheal intubation and sphenoid bone drilling, which involve the use of custom-made devices. Using the transsphenoidal pathway greatly improves the survival rate of rats because no additional dissection of blood vessels and nerves is required. Moreover, the pituitary gland can be viewed clearly and directly during the operation, making it possible to accurately inject pseudorabies virus (PRV) 152-expressing enhanced green fluorescent protein (EGFP) into the anterior or posterior pituitary, respectively. After injecting PRV 152 into the anterior pituitary, we found no evidence of direct innervation of the anterior pituitary in the rat brain. However, PRV 152 injection into the posterior pituitary revealed retrograde transneuronal cell bodies in many brain areas, including the CA1 field of the hippocampus, the basolateral amygdaloid nucleus, posterior part (BLP), the arcuate hypothalamic nucleus (Arc), the dorsal portion of the dorsomedial hypothalamic nucleus (DMD), the suprachiasmatic nucleus (SCh), and the subfornical organ (SFO). In the present study, we provide a description of a possible model of hypophysectomy or pituitary injection, and identify brain regions involved in regulating the rat pituitary gland using transneuronal retrograde cell body labeling with PRV.

Abstract The in-situ stress state in the Tarim Basin, Northwest China, down to 7 km depth is constrained using the anelastic strain recovery (ASR) method and wellbore failure analysis. Results are consistent between the two methods, and indicate that the maximum principal stresses (σ1) are close to vertical and the intermediate and minimum principal stresses (σ2 and σ3) are approximately horizontal. The states of stress at the studied wellbore is in the normal faulting stress regime within the Tarim Basin rather than in the compressional tectonic stress regime as in the periphery of the Tarim Basin, which explains the presence of the normal faults interpreted in 3-D seismic profiles collected from adjacent areas. Our results demonstrate that the ASR method can be used for rocks recovered from depths as deep as 7 km to recover reliable stress state information. The in-situ stress measurement results revealed in this paper will help future development of the petroleum resources and kinematics study in the Tarim Basin.

Taking the Well JY1 and Well PY1 in the Eastern Sichuan Basin as examples, the formation mechanism of shale gas overpressure was studied by using the cross plot of acoustic versus density logging data. During the processes of hydrocarbon generation and the uplifting, the pressure evolution of fluids in shale gas layers was reconstructed by fluid inclusions and PVTSIM software. The major factors controlling the evolution of shale gas overpressure were established according to the study of fracture, the timing of the uplifting, and episodes of tectonic deformation. Our results showed that the main mechanism of overpressure in the Silurian shale gas reservoirs in the Sichuan Basin was the fluid expansion, which was caused by hydrocarbon generation. Since the Yanshanian, the strata were uplifted and fluid pressure generally showed a decreasing trend. However, due to the low compression rebound ratio of shale gas reservoir rocks, poor connectivity of reservoir rocks, and low content of formation water and so on, such factors made fluid pressure decrease, but these would not be enough to make up the effects of strata erosion resulting in a further increase in fluid pressure in shale gas reservoirs during the whole uplifting processes. Since the Yanshanian, the Well PY1 zone had been reconstructed by at least three episodes of tectonic movement. The initial timing of the uplifting is 130 Ma. Compared to the former, the Well JY1 zone was firstly uplifted at 90 Ma, which was weakly reconstructed. As a result, low-angle fractures and few high resistance fractures developed in the Well JY1, while high-angle fractures and many high resistance fractures developed in the Well PY1. In totality, the factors controlling the overpressure preservation in shale gas reservoirs during the late periods include timing of late uplifting, superposition and reconstruction of stress fields, and development of high-angle fractures.

Weiyuan gas field, located in the Sichuan basin of south China, is a large marine gas field with the oldest reservoir (the Sinian sequences) in south China. The hydrocarbon origin of the gas field has long been debated by petroleum geologists. Recently, it was recognized that a paleo-oil pool maybe the significant contributor to the gas field. Consequently, when the paleo-oil pool had been cracked into gas has become an interesting topic. Actually, the time determination of oil cracking into gas is of significance to marine gas reservoir exploration in south China, because it is a pervasive hydrocarbon resource of marine gas reservoirs in south China. Characteristics of the gas composition, fluid inclusion, and bitumen in Sinian reservoir show that the present-day Weiyuan gas field originates from a paleo-oil pool cracked at high temperature. Data collected from the previous documents show that the temperature window of oil cracking into gas is around 160 to 210 °C on a geological time scale. On the basis of vitrinite reflectance, the heat flow history and erosion thickness in Weiyuan area were reconstructed. With the combination of heat flow history and burial history, the temperature history the paleo-oil pool experienced was reconstructed. The time of the paleo-oil cracking into gas is determined according to the oil cracking temperature window. The results show that the oil in the Weiyuan Sinian paleo-oil pool cracked into gas during the late Triassic to Eocene age.

Based on the analysis of numerous drill cores and drilling data, lacustrine gravity flow depositional systems were analyzed comprehensively in the Chang6 and Chang7 oil members (Triassic Yanchang Formation) in the southern part of the Ordos Basin. The gravity flow depositional systems in these members are made up of slides, slumps, sandy debris flows, liquefied flows, turbidity current etc, forming well developed units in the study area. Successive beds characterized by, from bottom to top, massive bedding (MB), graded bedding (GB) and horizontal bedding (HB) form well developed sequences; parallel bedding (GB) and ripple bedding (RB) are rare. It turns out that the depositional sequences are quite different from turbidites with a Bouma sequence: (1) MB represents a sandy debris flow, (2) GB deposits in a turbidity current, (3) PB and RB are deposits that were reworked by bottom currents (traction flow), and (4) HB represents a deep-water environment rather than gravity flows. Deposits in the proximal part of the subaqueous lacustrine fan consist mainly of slides, slumps and massive sandy debris flows. Deposits at the middle part of the fan are characterized by an MB-GB-HB sequence of massive sandy debris flows, graded turbidites and horizontally bedded lacustrine mudstones. Deposits at the end of the subaqueous lacustrine fan were mainly graded turbidites and horizontally bedded lacustrine mudstones (GB-HB sequence). Sandy gravity flow deposits mainly developed on the delta front and in the basin plain, extending for dozens of kilometers. They directly cover the source rock in the Chang7 oil members, which has the advantage of near-source oil accumulation. The sandstones at the bottom of each sedimentary cycle are worth further exploration because of their good reservoir properties and high oil content. Key words: Ordos Basin, Yanchang Formation, gravity flows, turbidites, sandy debris flows, depositional system