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Abstract Disasters caused by mine water inflows significantly threaten the safety of coal mining operations. Deep mining complicates the acquisition of hydrogeological parameters, the mechanics of water inrush, and the prediction of sudden changes in mine water inflow. Traditional models and singular machine learning approaches often fail to accurately forecast abrupt shifts in mine water inflows. This study introduces a novel coupled decomposition-optimization-deep learning model that integrates Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN), Northern Goshawk Optimization (NGO), and Long Short-Term Memory (LSTM) networks. We evaluate three types of mine water inflow forecasting methods: a singular time series prediction model, a decomposition-prediction coupled model, and a decomposition-optimization-prediction coupled model, assessing their ability to capture sudden changes in data trends and their prediction accuracy. Results show that the singular prediction model is optimal with a sliding input step of 3 and a maximum of 400 epochs. Compared to the CEEMDAN-LSTM model, the CEEMDAN-NGO-LSTM model demonstrates superior performance in predicting local extreme shifts in mine water inflow volumes. Specifically, the CEEMDAN-NGO-LSTM model achieves scores of 96.578 in MAE, 1.471% in MAPE, 122.143 in RMSE, and 0.958 in NSE, representing average performance improvements of 44.950% and 19.400% over the LSTM model and CEEMDAN-LSTM model, respectively. Additionally, this model provides the most accurate predictions of mine water inflow volumes over the next five days. Therefore, the decomposition-optimization-prediction coupled model presents a novel technical solution for the safety monitoring of smart mines, offering significant theoretical and practical value for ensuring safe mining operations.

Background Despite the successful application of immunotherapy, both innate and acquired resistance are typical in melanoma. Ferroptosis induction appears to be a potential strategy to enhance the effectiveness of immunotherapy. However, the relationship between the status of ferroptosis and the effectiveness of immunotherapy, as well as viable strategies to augment ferroptosis, remains unclear.Methods A screening of 200 cardiovascular drugs obtained from the Food and Drug Administration-approved drug library was conducted to identify the potential ferroptosis sensitizer. In vitro and in vivo experiments explored the effects of propafenone on ferroptosis in melanoma. Animal models and transcriptomic analyses evaluated the therapeutic effects and survival benefits of propafenone combined with immune checkpoint blockades (ICBs). The relationship between propafenone targets and the efficacy of ICBs was validated using the Xiangya melanoma data set and publicly available clinical data sets.Results Through large-scale drug screening of cardiovascular drugs, we identified propafenone, an anti-arrhythmia medication, as capable of synergizing with ferroptosis inducers in melanoma. Furthermore, we observed that propafenone, in combination with glutathione peroxidase 4 inhibitor RSL3, collaboratively induces mitochondrial-associated ferroptosis. Mechanistically, propafenone transcriptionally upregulates mitochondrial heme oxygenase 1 through the activation of the Jun N-terminal kinase (JNK)/JUN signaling pathway under RSL3 treatment, leading to overloaded ferrous iron and reactive oxygen species within the mitochondria. In xenograft models, the combination of propafenone and ferroptosis induction led to nearly complete tumor regression and prolonged survival. Consistently, propafenone enhances immunotherapy-induced tumorous ferroptosis and antitumor immunity in tumor-bearing mice. Significantly, patients exhibiting high levels of ferroptosis/JUN/HMOX1 exhibited improved efficacy of immunotherapy and prolonged progression-free survival.Conclusions Taken together, our findings suggest that propafenone holds promise as a candidate drug for enhancing the efficacy of immunotherapy and other ferroptosis-targeted therapies in the treatment of melanoma.

To better understand the growth mechanism of diamond films via low-temperature chemical vapor deposition in a C-H-F atmosphere, this paper employed density functional theory based on first principle. It calculated the adsorption energy, reaction heat, and reaction energy barrier of H and F atoms undergoing extraction reactions on the hydrogen-terminated diamond surface. Additionally, the analysis included the adsorption of CF3, CF2, and CF growth groups on the active site substrate. The results show that compared with H atoms, F atoms are more likely to extract H from the surface of hydrogen terminated diamond and desorb it in the form of HF. This process is advantageous for generating more active sites at low temperatures in a C-H-F atmosphere. Both the structure and the absolute value of the adsorption energy of CF3, CF2, and CF groups are more favorable for the generation of the diamond phase after adsorption. Increasing the concentration of CF3, CF2, and CF growth groups appropriately can facilitate the growth of diamond phase at a higher rate.

Abstract Background According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long‐term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. Methods From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. Results The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13–14 years and 262 cases (95.3%) aged 15–19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p

In order to reveal the impact of fracturing fluid retention and flowback on the development effect after large-scale fracturing in shale oil wells, and to formulate a reasonable flowback policy, this paper employs a combination of core physical simulation experiments and theoretical analysis. We have designed a specially designed device that can evaluate the development effect of quasi-natural energy in oil reservoirs. The impact of fracturing fluid retention on development is simulated by changing the amount of fracturing fluid injected into the formation in a fractured horizontal well model (referred as injection volume), and the impact on development effect is analyzed by changing the properties of fracturing fluid to adjust the difference in the degree of flowback. Based on the experimental results, the mechanism of fracturing fluid retention and flowback after large-scale fracturing in shale reservoirs is further explored. The results of the experiments show that the flowback rate of fracturing fluid exhibits a monotonic decreasing trend with increasing the volume of injected fluid, as increasing the volume of injected fluid helps to enhance its retention in the formation and reduce the flowback rate. The degree of fracturing fluid flowback is critical to the mobility of crude oil in the tight reservoir. The entering of fracturing fluid into the reservoir slows down the rate of discharge in the fracture network, effectively extending the reach of the fracturing fluid in the tight reservoir and allowing more crude oil to be used, which in turn results in higher crude oil production. However, too much injection fluid may affect the fluid production. Simulation experiments reveal that the use of fracturing fluid retention or controlling the rate of flowback by changing the viscosity of fracturing fluid can be a way to enhance the development effect of horizontal shale oil wells. The results of this paper provide a basis for understanding the mechanism of shale oil development, exploring technical ideas to improve the development effect, and making decisions on the flowback parameters.

Since the discovery of hydride superconductors, a significant challenge has been to reduce the pressure required for their stabilization. In this context, we propose that alloying could be an effective strategy to achieve this. We focus on a series of alloyed hydrides with the AMH6 composition, which can be made via alloying A15 AH3 (A = Al or Ga) with M (M = a group ⅢB or IVB metal), and study their behavior under pressure. Seven of them are predicted to maintain the A15-type structure, similar to AH3 under pressure, providing a platform for studying the effects of alloying on the stability and superconductivity of AH3. Among these, the A15-type phases of AlZrH6 and AlHfH6 are found to be thermodynamically stable in the pressure ranges of 40–150 and 30–181 GPa, respectively. Furthermore, they remain dynamically stable at even lower pressures, as low as 13 GPa for AlZrH6 and 6 GPa for AlHfH6. These pressures are significantly lower than that required for stabilizing A15 AlH3. Additionally, the introduction of Zr or Hf increases the electronic density of states at the Fermi level compared with AlH3. This enhancement leads to higher critical temperatures (Tc) of 75 and 76 K for AlZrH6 and AlHfH6 at 20 and 10 GPa, respectively. In the case of GaMH6 alloys, where M represents Sc, Ti, Zr, or Hf, these metals reinforce the stability of the A15-type structure and reduce the lowest thermodynamically stable pressure for GaH3 from 160 GPa to 116, 95, 80, and 85 GPa, respectively. Particularly noteworthy are the A15-type GaMH6 alloys, which remain dynamically stable at low pressures of 97, 28, 5, and 6 GPa, simultaneously exhibiting high Tc of 88, 39, 70, and 49 K at 100, 35, 10, and 10 GPa, respectively. Overall, these findings enrich the family of A15-type superconductors and provide insights for the future exploration of high-temperature hydride superconductors that can be stabilized at lower pressures.

In the cognitive internet of things (CIoT), due to the non-cooperative characteristics between the primary user (PU) and the secondary user (SU), it is unreliable to seek the spectrum access opportunity by merely relying on traditional spectrum sensing technology.As an important type of auxiliary information, the mutual location information between PU and SU can assist in determining the possibility of secondary access to the licensed frequency band (LFB).A low-complexity neighbor-based weighted centroid localization (NB-WCL) algorithm was proposed to solve the localization problem of SUs in CIoT, so as to complete the decision of whether spectrum access can be performed at each geographical location in CIoT.The root mean square root error (RMSE) performance of two-dimensional position estimation was analyzed and the impacts of factors were verified such as communication radius, node density, shadowing influence, path loss exponent, connectivity metric, and the number of data transmitted on the algorithm performance in simulations.The theoretical derivation and experimental results show that the proposed scheme provides more robust and better localization error performance for the SU localization algorithm in CIoT than the traditional localization algorithms, which can effectively enhance the reliability of CIoT for spectrum access.The proposed scheme can serve as a practically effective candidate solution in the CIoT.

Based on the comparison of basic geological conditions and enrichment characteristics of shale oil plays, the heterogeneity of source and reservoir conditions and differential enrichment of medium-high maturity continental shale oil plays in China have been confirmed. (1) Compared with the homogeneous geological settings and wide distribution of marine shale oil strata in North America, the continental medium and high maturity shale oil plays in China are significantly different in geological conditions generally; continental multi-cyclic tectonic evolution forms multiple types of lake basins in multi-stages, providing sites for large-scale development of continental shale oil, and giving rise to large scale high-quality source rocks, multiple types of reservoirs, and diverse source-reservoir combinations with significant heterogeneity. (2) The differences in sedimentary water environments lead to the heterogeneity in lithology, lithofacies, and organic material types of source rocks; the differences in material source supply and sedimentary facies belt result in reservoirs of different lithologies, including argillaceous and transition rocks, and tight siltstone, and complex source-reservoir combination types. (3) The heterogeneity of the source rock controls the differentiation of hydrocarbon generation and expulsion, the diverse reservoir types make reservoir performance different and the source-reservoir configurations complex, and these two factors ultimately make the shale oil enrichment patterns different. Among them, the hydrocarbon generation and expulsion capacity of high-quality source rocks affect the degree of shale oil enrichment. Freshwater hydrocarbon source rocks with TOC larger than 2.5% and saline hydrocarbon source rocks with TOC of 2% to 10% have a high content of retained hydrocarbons and are favorable. (4) High-abundance organic shale is the basis for the enrichment of shale oil inside the source. In addition to being retained in shale, liquid hydrocarbons migrate along laminae, diagenetic fractures, and thin sandy layers, and then accumulate in laminae of argillaceous siltstone, siltstone, and argillaceous dolomite, and dolomitic siltstone suites, etc. with low organic matter abundance in the shale strata, resulting in differences in enrichment pattern.

BackgroundIndoleamine-2,3-dioxygenase 1 (IDO1) is responsible for tumor immune escape by regulating T cell-associated immune responses and promoting the activation of immunosuppressive. Given the vital role of IDO1 in immune response, further investigation on the regulation of IDO1 in tumors is needed.MethodsHerein, we used ELISA kit to detect the interferon-gamma (IFN-γ), Tryptophan (Trp), and kynurenic acid (Kyn) levels; western blot, Flow cytometry, and immunofluorescence assays detected the expression of the proteins; Molecular docking assay, SPR assay and Cellular Thermal Shift Assay (CETSA) were used to detect the interaction between IDO1 and Abrine; nano live label-free system was used to detect the phagocytosis activity; tumor xenografts animal experiments were used to explore the anti-tumor effect of Abrine; flow cytometry detected the immune cells changes.ResultsThe important immune and inflammatory response cytokine interferon-gamma (IFN-γ) up-regulated the IDO1 expression in cancer cells through the methylation of 6-methyladenosine (m6A) m6A modification of RNA, metabolism of Trp into Kyn, and JAK1/STAT1 signaling pathway, which could be inhibited by IDO1 inhibitor Abrine. CD47 is IFN-γ-stimulated genes (ISGs) and prevents the phagocytosis of macrophages, leading to the cancer immune escape, and this effect could be inhibited by Abrine both in vivo and in vitro. The PD-1/PD-L1 axis is an important immune checkpoint in regulating immune response, overexpression of PD-1 or PD-L1 promotes immune suppression, while in this study Abrine could inhibit the expression of PD-L1 in cancer cells or tumor tissue. The combination treatment of Abrine and anti-PD-1 antibody has a synergistic effect on suppressing the tumor growth through up-regulating CD4+ or CD8+ T cells, down-regulating the Foxp3+ Treg cells, and inhibiting the expression of IDO1, CD47, and PD-L1.ConclusionOverall, this study reveals that Abrine as an IDO1 inhibitor has an inhibition effect on immune escape and has a synergistic effect with the anti-PD-1 antibody on the treatment of HCC.

Abstract Background Lung cancer is the leading cause of cancer mortality worldwide, and most of the patients after treatment with EGF-TKIs develop drug resistance, which is closely correlated with EMT. Cucurbitacin B (CuB) is a natural product of the Chinese herb Cucurbitaceae plant, which has a favorable role in anti-inflammation and anti-cancer activities. However, the effect of CuB on EMT is still far from fully explored. In this study, the inhibition effect of CuB on EMT was investigated. Methods In this study, TGF-β1 was used to induce EMT in A549 cells. MTS assay was used to detect the cell viability of CuB co-treated with TGF-β1. Wound healing assay and transwell assay were used to determine the migration and invasion capacity of cells. Flow cytometry and fluorescence microscope were used to detect the ROS level in cells. Western blotting assay and immunofluorescence assay were used to detect the proteins expression. Gefitinib was used to establish EGF-TKI resistant NSCLC cells. B16-F10 intravenous injection mice model was used to evaluate the effect of CuB on lung cancer metastasis in vivo. Caliper IVIS Lumina and HE staining were used to detect the lung cancer metastasis of mice. Results In this study, the results indicated that CuB inhibited TGF-β1-induced EMT in A549 cells through reversing the cell morphology changes of EMT, increasing the protein expression of E-cadherin, decreasing the proteins expression of N-cadherin and Vimentin, suppressing the migration and invasion ability. CuB also decreased the ROS production and p-PI3K, p-Akt and p-mTOR expression in TGF-β1-induced EMT in A549 cells. Furthermore, Gefitinib resistant A549 cells (A549-GR) were well established, which has the EMT characteristics, and CuB could inhibit the EMT in A549-GR cells through ROS and PI3K/Akt/mTOR pathways. In vivo study showed that CuB inhibited the lung cancer metastasis effectively through intratracheal administration. Conclusion CuB inhibits EMT in TGF-β1-induced A549 cells and Gefitinib resistant A549 cells through decreasing ROS production and PI3K/Akt/mTOR signaling pathway. In vivo study validated that CuB inhibits lung cancer metastasis in mice. The study may be supporting CuB as a promising therapeutic agent for NSCLC and Gefitinib resistant NSCLC.

The Chang-7 Member of the Upper-Triassic Yanchang Formation has favorable geological conditions (e.g., extensive distribution of source rock, broad distribution of fine-grained sand bodies, stable structure, etc.) for developing a large shale oil pool. Initial assessments have estimated that the Chang-7 has shale oil resources of 3.0 × 109 t approximately. The discovered Xin'anbian giant shale oil field has an estimated reserve of one billion tons. The shale oil in the Chang-7 Member has been developed by volumetric fracturing in long horizontal wells since 2011. By the end of 2021, more than 500 horizontal wells had been drilled, with average initial production of 9.6 t/d per well. Some large-scale effective development pilot zones (e.g., X233, Z183, A83, etc.) have been constructed. The source rock and reservoir in the Chang-7 Member are heterogeneous. Under an extensive distribution background of shale oil layers, there are some local 'sweet spots'. In order to reveal controlling factors for the productivity of shale oil, research involving the comparison of development effects, formation of geologic conditions, and technologies of the three typical pilot zones, has been conducted. The results showed that organic abundance in the source rock is the primary controlling factor for “sweet spot” distribution of the shale oil. The average TOC value in the black shale source rock in the Chang-7 Member is about 10% higher than that in the dark gray mudstone. The average hydrocarbon generation intensity is about 2.0 × 103 t/km2, the average hydrocarbon expulsion rate is 34.6%, and the production rate of gaseous hydrocarbons is 14.65–39.46 m3/t. In the vicinity of black shale with a high TOC value, the oil filling intensity in the shale oil reservoirs is high, with oil saturation of up to about 70%, and a gas-to-oil ratio >90 m3/t. Secondly, the 'sweet spots' with such petrophysical properties control the enrichment of reservoirs. Owing to conditions of low-porosityand low-permeability, the shale oil reservoirs in the Chang-7 Member of the Ordos Basin still developed 'sweet spots',with porosity larger than 9% and permeability larger than 0.08 × 10−3 μm2 . These reservoir sweet spots have a pyrolysis yield of hydrocarbons >9 mg/g and the development wells have high initial and total production, a slow decline rate, and low water cut. Moreover, the dissolved gas in shale oil in the Chang-7 Member of the Ordos Basin is an oil-type gas that was generated during the primary pyrolysis stage of sapropel kerogen after entering a mature period. The gas-to-oil ratio in crude oil is controlled by several factors, such as organic abundance and maturity in source rock, thickness, petrophysical properties, and fractures in reservoirs. The overlap of black shale with high TOC, source rock thickness >10 m, thermal maturity Ro > 0.8%, and type I and II high-quality reservoir beds are the pre-requisites for the development of sweet spots with high and stable production of shale oil. The produced gas-to-oil ratio in the development wells is stable (generally 19.68 m3/t). Some wells have produced oil continuously and stably at over 14 t/d for 5 years. This paper delineates the distribution patterns of shale oil sweet spots in the Chang-7 Member of the Ordos Basin and confirms that profitable and efficient development of shale oil can be achieved in this basin.

RAS, the most frequently mutated oncogene that drives tumorigenesis by promoting cell proliferation, survival, and motility, has been perceived as undruggable for the past three decades. However, intense research in the past has mainly focused on KRAS mutations, and targeted therapy for NRAS mutations remains an unmet medical need. NRAS mutation is frequently observed in several cancer types, including melanoma (15-20%), leukemia (10%), and occasionally other cancer types. Here, we report using miRNA-708, which targets the distinct 3' untranslated region (3'UTR) of NRAS, to develop miRNA-based precision medicine to treat NRAS mutation-driven cancers. We first confirmed that NRAS is a direct target of miRNA-708. Overexpression of miRNA-708 successfully reduced NRAS protein levels in melanoma, leukemia, and lung cancer cell lines with NRAS mutations, resulting in suppressed cell proliferation, anchorage-independent growth, and promotion of reactive oxygen species-induced apoptosis. Consistent with the functional data, the activities of NRAS-downstream effectors, the PI3K-AKT-mTOR or RAF-MEK-ERK signaling pathway, were impaired in miR-708 overexpressing cells. On the other hand, cell proliferation was not disturbed by miRNA-708 in cell lines carrying wild-type NRAS. Collectively, our data unveil the therapeutic potential of using miRNA-708 in NRAS mutation-driven cancers through direct depletion of constitutively active NRAS and thus inhibition of its downstream effectors to decelerate cancer progression. Harnessing the beneficial effects of miR-708 may therefore offer a potential avenue for small RNA-mediated precision medicine in cancer treatment.

Hydraulic fracturing is widely recognized as a potential stimulation technology for the development of challenging natural gas hydrate. However, the fracturing behavior of non-diagenetic hydrate reservoirs has peculiar characteristics that are different from those of conventional oil and gas reservoirs. Herein, a fully coupled fluid-mechanical model for simulating hydraulic fracturing in hydrate-bearing sediments (HBS) was established based on the discrete element method, and the influence of hydrate saturation, in situ stress, and injection rate on the meso-fracture evolution was investigated. The results indicate that with the increase in hydrate saturation, the fracture morphology transitions from bi-wing to multi-branch, thereby enhancing fracture complexity. Both tensile and shear failure modes exist, and the tensile failure between the weakly cemented sediment particles is dominant. The tensile strength of HBS is an exponential function of hydrate saturation, with the breakdown pressure being governed by hydrate saturation and in situ stress, with the form being consistent with the classical Kirsch equation. Additionally, lower in situ stress and higher injection rates are conducive to the generation of microcracks, whereas an excessive injection rate reduces the fracture length. These findings contribute to understanding the meso-evolution mechanism of hydraulic fractures and guide the design of on-site hydraulic fracturing plans of natural gas hydrate reservoirs.

The Chang 73 sub-member of Triassic Yanchang Formation in the Ordos Basin was taken as an example and the lamina types and combinations, reservoir space features and shale oil enrichment patterns in organic-rich shale strata were investigated using core observation, thin section analysis, XRF element measurement, XRD analysis, SEM, high solution laser Raman spectroscopy analysis, and micro-FTIR spectroscopy analysis, etc. According to the mineral composition and thickness of the laminae, the Chang 73 organic-rich shales have four major types of laminae, tuff-rich lamina, organic-rich lamina, silt-grade feldspar-quartz lamina and clay lamina. They have two kinds of shale oil-bearing layers, “organic-rich lamina + silt-grade feldspar-quartz lamina” and “organic-rich lamina + tuff-rich lamina” layers. In the “organic-rich + silt-grade feldspar-quartz” laminae combination shale strata, oil was characterized by relative high maturation, and always filled in K-feldspar dissolution pores in the silt-grade feldspar-quartz laminae, forming oil generation, migration and accumulation process between laminae inside the organic shales. In the “organic-rich + tuff-rich lamina” binary laminae combination shale strata, however, the reservoir properties were poor in organic-rich shales, the oil maturation was relatively lower, and mainly accumulated in the intergranular pores of interbedded thin-layered sandstones. The oil generation, migration and accumulation mainly occurred between organic-rich shales and interbedded thin-layered sandstones.

Abstract Imbibition is an important recovery mechanism for tight oil reservoirs, which occurs during hydraulic fracturing and development. Due to the massive distribution of micro‐nano scale pore throats and the existence of a boundary layer in tight formation, agreement consensus has not been reached on the imbibition mechanism. Based on the effect of the boundary layer, experiments were conducted to study the imbibition in tight sandstone, and NMR was used to determine the efficiency of imbibition. The results reveal that the imbibition rate is related to the connection area of the matrix‐fracture, throat connection, and radius. Then, the effective capillary pressure was modified by describing the thickness of the boundary layer in the micro‐nano pore throats. The calculation results show that the existence of boundary layer in micro‐nano throats makes the capillary pressure much larger than those of reservoirs without boundary layer. And the boundary layer reduces the effective flow radius, which dramatically decreases the imbibition quantity. The final result of existence of a boundary layer dramatically weakens the imbibition ability of a tight oil reservoir, and thus, the existence of a boundary layer cannot be ignored. Finally, the effective throat radius limit was analyzed during imbibition in a water‐oil‐rock system of a tight oil reservoir. Without a boundary layer, the effective radius of the pore throats in the water‐oil‐rock system during imbibition is greater than 200 nm, which is due to the advantages of the large capillary force and pore throats that are not too small. With a boundary layer, the main radius of the pore throats used for the water‐oil‐rock imbibition is approximately 400 nm. Thus, the imbibition occurs in the pore throats larger than 200 nm in the water‐oil‐rock system, and a surfactant could reduce the limit of the throat radius during imbibition in tight oil reservoirs.

Abstracts Background Qilin pills (QLPs), a classic Traditional Chinese Medicine (TCM) formula for treating male infertility, effectively improve semen quality in clinical trials. This study was designed to evaluate the effects of QLPs on spermatogenesis, reproductive hormones, oxidative stress, and the testis-specific serinekinase-2 (TSSK2) gene in a rat model of oligoasthenospermia. Methods Forty adult male Sprague-Dawley (SD) rats were randomly divided into four groups. The rat model with oligoasthenospermia was generated by intragastric administration of tripterygium glycosides (TGs) once daily for 4 weeks. Then, two treatment groups were given different doses (1.62 g/kg and 3.24 g/kg) of QLPs once daily for 60 days. Sperm parameters, testicular histology and reproductive hormone measurements, oxidative stress tests, and TSSK2 expression tests were carried out. Results QLPs effectively improved semen parameters and testicular histology; restored the levels of FSH, LH, PRL, fT, and SHBG; reduced the levels of oxidative stress products (ROS and MDA); increased testicular SOD activity; and restored the expression of spermatogenesis-related gene TSSK2. Conclusion QLPs have a therapeutic effect on a rat model of oligoasthenospermia, and this effect is manifested as improvement of semen quality and testis histology, gonadal axis stability, decreased oxidative stress, and the regulation of testis-specific spermatogenesis-related gene TSSK2.

Abstract Background Human sperm cryopreservation is a simple and effective approach for male fertility preservation. Methods To identify potential proteomic changes in this process, data-independent acquisition (DIA), a technology with high quantitative accuracy and highly reproducible proteomics, was used to quantitatively characterize the proteomics of human sperm cryopreservation. Results A total of 174 significantly differential proteins were identified between fresh and cryoperservated sperm: 98 proteins decreased and 76 proteins increased in the cryopreservation group. Bioinformatic analysis revealed that metabolic pathways play an important role in cryopreservation, including: propanoate metabolism, glyoxylate and dicarboxylate metabolism, glycolysis/gluconeogenesis, and pyruvate metabolism. Four different proteins involved in glycolysis were identified by Western blotting: GPI, LDHB, ADH5, and PGAM1. Conclusions Our work will provide valuable information for future investigations and pathological studies involving sperm cryopreservation.

Continental tight oil is a promising unconventional resource found in recent years and an important supplement to the growth of domestic petroleum reserves and production in China. Guided by the research objectives set by the China National Science and Technology Major Project “Enrichment Law and Key Technologies of Exploration and Development of Tight Oil,” and based on laboratory experiments and field tests by eight PetroChina petroleum companies, three signs of progress in theoretical technology and practical exploration and development have been made to continental tight oil in China. (1) Forming conditions: It is found that laminated organic-rich shale is primary source rock. Furthermore, many types of favorable reservoirs, such as terrigenous clasts and internal clasts, are developed and accumulate into two kinds of large-scale and continuous distribution of in-source and near-source assemblages. (2) Enrichment Law: Favorable reservoir facies zones, being near the hydrocarbon source center, and having a supportive tectonic background are three common factors controlling oil enrichment and high production. The proven tight oil resources are 10.65 × 109 t, whereas 40 enrichment zones have been identified and a number of drillable “sweet sections” have been found. (3) Key technologies of exploration and development: Key technologies have been developed involving multi-scale tight reservoir characterization, resource classification evaluation, seismic response and engineering evaluation of “sweet sections,” as well as reservoir stimulation and effective development. The research results support the rapid continental tight oil in China. By the end of 2018, proven tight oil geological reserves were 437 × 106t, while proved, controlled and predicted reserves were 3.019 × 109t, and the new production capacity was 3.31 × 106t. It is suggested that follow-up studies should focus on three fields—clastic rocks, peperite-sedimentary tuff, and lacustrine carbonate rocks. The above should be done in five aspects – enrichment law, sweet area evaluation and prediction, key development technology, efficient reservoir stimulation, and practical application in key basins so as to support steady integration of geology and engineering for developing continental tight oil in China. Keywords: Continental strata, Tight oil, Sweet section, Exploring oil inside source kitchen, Enrichment law, Key technology, Unconventional oil

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The roles of long noncoding RNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) in oral squamous cell carcinoma (OSCC) remain largely unknown. Here, the Atlas of Noncoding RNAs in Cancer online database was utilized to analyze the expression and clinical significance of FOXD2-AS1 in OSCC. Then, the cell proliferation of FOXD2-AS1-silenced OSCC cells (CAL-27) was assessed by MTT and clone formation experiments. FOXD2-AS1-coexpressed genes were enriched and analyzed via circlncRNAnet and Metascape tools. Finally, key molecules of the signal pathways of the aforementioned coexpressed genes were verified by western blotting. We found that FOXD2-AS1 was significantly highly expressed in OSCC tissues, and correlated with poor pathological grade and prognosis in patients with OSCC. Cell viability and clone formation ability were significantly inhibited after the knockdown of FOXD2-AS1. A total of 32 coexpressed genes of FOXD2-AS1 were identified, and those genes were enriched in the cell cycle. In conclusion, FOXD2-AS1 may be served as a potential prognostic indicator and therapeutic target for OSCC.

Severe aplastic anemia (SAA) is a rare disease characterized by severe pancytopenia and bone marrow failure. Most patients with AA respond to immunosuppressive therapy (IST), usually as antithymocyte globulin (ATG) and cyclosporine (CsA), but some relapse on CsA withdrawal or require long-term administration of CsA to maintain blood counts. Recent research has found that rapamycin (Rapa) was an effective therapy in mouse models of immune-mediated bone marrow failure. However, it has not achieved a satisfactory effect in clinical application. At present, many studies have confirmed that eltrombopag (ELT) combined with IST can improve the curative effect of AA patients. Then, whether Rapa combined Elt in the treatment of AA will acquire better efficacy than a single drug application remains unclear. In this study, an immune attack-mediated AA mouse model was constructed by total body irradiation (TBI) and allo-lymphocyte infusion. In our study, we tested the efficacy of Rapa combined with Elt as a new treatment in mouse models of immune-mediated bone marrow failure. It showed that treatment with Rapa in combination Elt in the AA mouse model ameliorated pancytopenia and extended animal survival in a manner comparable to the standard dose of CsA and Rapa alone. However, there was no significant improvement effect on the number and function of NK cells and their subsets, mDCs, and CD4+/CD8+ ratio in AA mice after the therapy of Rapa combined with Elt compared with Rapa alone. Furthermore, the secretion of IL-10 of Tregs in AA mice increased significantly after the therapy of Rapa combined with Elt, but there was no significant difference in the number of Treg cells. We did not observe the difference in the curative effect of the Rapa group and CsA group, but for IL-10/Tregs ratio, the Rapa group was superior to the CsA group. And the IFN-r secretion of CD8+T cells in AA mice decreased significantly after the combination therapy of Rapa and Elt than Rapa alone. Compared with the AA group, the level of plasma IFN-γ, IL-2, and TNF-α decreased significantly (P

The Chang7 Member of the Triassic Yanchang Formation in the Ordos Basin is a typical continental tight oil province. The geological conditions and the main controlling factors for the formation of tight oil province in Chang 7 Member were studied based on extensive core analysis data, laboratory simulation tests and practical work of tight oil exploration and development in the basin. The tight oil in the Chang 7 Member is characterized by wide distribution, excellent source rock conditions, tight sandstone reservoirs, complicated pore-throat structure, poor physical properties, high oil saturation, high quality oil, and low pressure coefficient. During the depositional period of Chang7 Member, the bottom shape of the basin was steep at southwest and gentle at northeast, the tectonic movements were active, favorable for the deposition of source rock and reservoir; the widespread high quality source rock can provide sufficient oil supply for the large tight oil province; the large scale sand bodies provide good reservoir condition for the large tight oil province; the abundant structural fractures in the tight reservoir act as pathways for tight oil migration; and the stable deposition and tectonic evolution of the basin provide good preservation conditions for the tight oil province. The main controlling factors of Chang7 Member tight oil enrichment are as follows: (1) good configuration of source rock and reservoir and constant charging are the key to the formation of the tight oil province; (2) abundant micro-scale pores are the premise of tight oil enrichment; (3) strong and sustained charging guarantees the enrichment and high yield of oil in the tight reservoirs. Key words: Triassic, Yanchang Formation, tight oil, oil enrichment controlling factors, source rock and reservoir configuration, hydrocarbon-generating overpressure, sustained charge, Ordos Basin

The geological conditions and exploration potential of shale oil in Chang7 Member, Upper Triassic Yanchang Formation, Ordos Basin, were studied from various aspects, including petrographic characteristics, storage ability, geochemical features, friability and mobility of hydrocarbon in the source rock, etc. A classification criterion of lithofacies for Upper Triassic Chang 7 source rock in Ordos Basin were established based on the correlation between lithology, organic carbon content and logging parameters, from which, the spatial distribution and development scale of two types of shale, black shale and dark massive mudstone, have been predicted. Qualitative and quantitative characterization of the micro-structures of Chang7 source rock using state-of-the-art microscopic facilities including argon ion milling – field emission scanning electron microscopy (FESEM), focused ion beam scanning electron microscopy (FIB-SEM) and Nano-CT reveal that the dominant pore types in Chang7 source rock are intra-granular pores and inter-granular pores; the pores and throats in the two kinds of lithofacies are both nano-scale, and the dark massive mudstone has better physical properties than the black shale. The Chang7 shale oil resources and mineability were evaluated based on the parameters from geochemical experiments on the source rock, including pyrolysis S1, chloroform bitumen ‘A’, TOC and thermal maturity, free hydrocarbon content, as well as geo-mechanical properties such as brittle mineral content and development of fractures. With large scale of favorable lithofacies, good storage ability and abundant hydrocarbon, Chang7 Member has the material basis for shale oil occurrence and accumulation, in addition, the shale oil there has accumulated greatly and has favorable properties for flowing in nano-scale pores and throats. All these show that Chang7 Member has high potential for shale oil exploration, in which, the dark massive mudstone is a more favorable target for shale oil exploration under the present technical conditions. Key words: Ordos Basin, Triassic Chang 7 Member, shale oil, geological condition, exploration potential

We have systematically explored the crystal structures of alkaline-earth metal sulfides under pressure by using a swarm-intelligence structural prediction method. At low pressures we successfully reproduced their known structures and phase transition sequences. Under high pressure, MgS is predicted to transform from B28 to a β -NbP-type structure at 262 GPa. CaS and SrS present the same phase transition sequence, from B2 to a β -NbP-type structure, while BaS is predicted to transform to a Imma structure. The Imma structure is actually similar to the β -NbP-type structure, as it can be seen as a modulated distortion of the latter structure. The absence of any imaginary phonon mode for the predicted structures suggests that they are dynamically stable. The calculated electronic band structures and density of states reveal that all the predicted phases are metallic, except that MgS is a semiconductor. Subsequent electron-phonon coupling calculations suggest that Imma BaS is a superconductor with a low T _c of 1.32 K, while β -NbP MgS, CaS and SrS are not superconductors. The current study provides a comprehensive analysis of phase transitions for alkaline-earth metal sulfides up to 300 GPa and might stimulate experimental studies in the future.

Based on cores and logging data, and gravity flow theory, the sedimentary characteristics and facies model of gravity flow deposits in the Longdong area in southwestern Ordos Basin were analyzed. Five types of gravity flow deposits are recognized: slides, slumps, sandy debris flows, muddy debris flows and turbidity currents. Affected by multiple provenances, paleogeomorphology and triggering mechanisms jointly, the gravity flows resulted in sublacustrine fans and slump olistoliths in the basin center. Containing channels, the sublacustrine fans can be divided into three subfacies, inner fan, middle fan and outer fan and subdivided into six microfacies, main channel, main channel lateral margin, distributary channel, distributary channel lateral margin, inter-channel and sheeted turbidite sand. It is inferred that they are caused by seasonal floods. The slump olistoliths, with no channels, consist four parts: slide rock, slump rock, debris flow lobe and sheeted turbidite sand, and are inferred to be the product of collapse of break belts triggered by events like earthquakes. Combining facies models with types of gravity flow deposits can reveal the sedimentary characteristics and genetic models of gravity flow deposits in deep water more directly and provide theoretical basis for deep water oil and gas exploration. Key words: gravity flow deposit, genetic type, sedimentary system, sedimentary model, Yanchang Formation, Ordos Basin

Petrologic features, diagenetic processes and origins of different pore types of Upper Triassic Chang 7 (7th member of Yanchang Formation) tight sandstones in the Ordos Basin were analyzed based on cast thin sections, scanning electron microscope (SEM), and X-ray diffraction analysis (XRD). The diagenetic processes caused by alkaline pore fluid and associated pores were studied in detail and the relationship between porosity evolution and hydrocarbon accumulation was analyzed. The Chang 7 tight sandstone commonly experienced alkaline environment and associated diagenesis, including quartz dissolution or replaced by mica, clay and carbonate minerals, carbonate cementation, abundant authigenic illite and chlorite with minor kaolinte and smectite, and albitization. Several types of associated pores were formed in the alkaline environment, including quartz dissolution pore, intercrystal pore of clay minerals, interlamination pore of hydrated mica and pores associated with albitization. The alkaline diagenesis mainly occurred in two periods during the burial process: B stage of early diagenesis and A2 stage of mesogenetic diagenesis. The abundant intercrystal micropores of clay minerals, which mainly occurred during the B stage of early diagenesis, seriously reduced the permeability of sandstone. As a result, the acid dissolution in the later stage was not intense enough due to the low permeability, so it is inferred that the sandstone had already been compacted very tight before the major hydrocarbon charging. Key words: Ordos Basin, tight oil reservoir, alkaline diagenetic environment, diagenesis, pore type

Abstract The very low-density lipoprotein receptor (VLDLR) transports egg yolk precursors into oocytes. However, our knowledge of the distribution patterns of VLDLR variants among breeds and their relationship to egg production is still incomplete. In this study, eight single nucleotide polymorphisms (SNPs) that account for 87% of all VLDLR variants were genotyped in Nick Chick (NC, n=91), Lohmann Brown (LohB, n=50) and Lueyang (LY, n=381) chickens, the latter being an Chinese indigenous breed. Egg production by NC and LY chickens was recorded from 17 to 50 weeks. Only four similar haplotypes were found in NC and LohB, of which two accounted for 100% of all NC haplotypes and 92.5% of LohB haplotypes. In contrast, there was considerable haplotypic diversity in LY. Comparison of egg production in LY showed that hens with NC-like haplotypes had a significantly higher production (p < 0.05) than those without the haplotypes. However, VLDLR expression was not significantly different between the haplotypes. These findings indicate a divergence in the distribution of VLDLR haplotypes between selected and non-selected breeds and suggest that the near fixation of VLDLR variants in NC and LohB is compatible with signature of selection. These data also support VLDLR as a candidate gene for modulating egg production.