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Abstract The complexity of hydraulic fracture network generation during the fracturing of shale reservoirs is a key indicator of the effectiveness of fracture stimulation. To obtain as large a reservoir stimulation volume as possible, this paper reviews articles on the study of hydraulic fracture propagation mechanism during hydraulic fracturing, analyses the factors affecting hydraulic fracture propagation, and classifies them into two categories: geological factors and engineering factors. In particular, the geological factors affecting hydraulic fracture propagation are classified into five categories: mineral composition of the shale, connections between mineral grains, defects in the shale, geostress, and temperature. Various influencing factors act together, resulting in the hydraulic fracture propagation path is difficult to predict. Therefore, this paper firstly explores the hydraulic fracture propagation pattern under the action of single geological factors and specifies its action mechanism; secondly, it also analyses the hydraulic fracture propagation pattern under the combined action of multiple geological factors and analyses its action mechanism. It is clear that relatively high brittle mineral content and temperature, low stress anisotropy and cementation strength, and a more developed natural fracture network are conducive to the generation of a complex fracture network. By analyzing the influence mechanism of single factors and multiple factors, the influence mechanism of geological factors on hydraulic fracture propagation is identified, guiding the optimal design of hydraulic fracturing.

Abstract Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354–406 amino acids) to suppress the latter’s ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8+ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25+ Foxp3+) and exhausted T cells (PD1+ CD8+), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.

Research on the enhanced gas recovery (EGR) technology is urgently needed in most of China's major gas fields due to low recovery in their late development stages. To promote progress in ERG theory and technology, this paper establishes a unified and universal model for gas recovery evaluation, analyzes the key factors affecting the gas recovery, and expects the prospect of EGR. The results are obtained as follows. First, the production degree of reserves, pressure drawdown sweep efficiency and pressure depletion efficiency are key factors affecting the gas recovery, which is the product of the coefficients corresponding to these factors. Second, according to the development practice of Anyue Longwangmiao gas reservoir, Kela 2 gas field, Sulige gas field and Southern Sichuan shale gas, it is estimated that the recovery of conventional water-driven gas reservoirs and unconventional gas reservoirs (incl. tight gas and shale gas) can be improved by 6–15 percentage points by increasing the production degree of reserves, the pressure drawdown sweep efficiency and pressure depletion efficiency. Third, it is proposed that clarifying the EGR mechanism, developing new EGR methods, and promoting the field test of EGR technologies are directions for theoretical and technical researches. The study results provide a theoretical foundation for EGR. The EGR methodologies for different types of gas reservoirs provide technical support for improving gas recovery and stable production of existing gas fields, promote healthy and rapid development of natural gas industry in China and provide guidance for guaranteeing national energy security.

Background: Chukrasia tabularisis, a well-known tropical tree native to southeastern China, has anti-inflammatory and antioxidant activities, and contains large amounts of limonoids and triterpenoids. Objective: The aim of this study was to investigate the potential anti-inflammatory activity of limonoids from C. tabularis on lipopolysaccharide (LPS)-mediated RAW264.7 cells. Methods and results: Using a bioassay-guided approach, the chemical fraction with high anti-inflammatory activity was found and its chemical constituents were investigated. Phytochemical studies on active extracts resulted in the separation of three novel phragmalin limonoids (1–3), together with two known limonoids (4–5) and 11 tirucallane triterpenes (6–16). The activity of these isolated compounds in the production of nitric oxide (NO) on LPS-reated macrophages was evaluated. Limonoid 2 indicated significant anti-inflammatory activities with IC50 value of 4.58 μM. Limonoid 2 notably inhibited the production of NO, interleukin- 6 and tumor necrosis factor-α on macrophage. Signal transduction and activation of STAT and NF-κB activators were effectively blocked by limonoid 2. Conclusions: These results indicate that limonoid 2 has an anti-inflammatory effect by the inhibiting JAK2/STAT3, iNOS/eNOS, and NF-κB signaling pathways and regulating inflammatory mediators.

Two new phenylspirodrimanes, stachybotrins K and L (1 and 2), together with eight known analogues (3–10), were isolated from deep-sea-derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Absolute configurations of new compounds were determined through a comparison of their circular dichroism (CD) spectra with other reported compounds. The possible reversal effects of all compounds were assayed in the resistant cancer cell lines. Stachybotrysin B (8) can reverse multidrug resistance (MDR) in ABCB1-overexpression cells (KBv200, Hela/VCR) at the non-cytotoxic concentration. Doxorubicin accumulation assay and molecular-docking analysis reveal that the mechanism of its reversal MDR effect may be related to the increase in the intracellular concentration of substrate anticancer drugs.

Based on more than 20-year operation of gas storages with complex geological conditions and a series of research findings, the pressure-bearing dynamics mechanism of geological body is revealed. With the discovery of gas-water flowing law of multi-cycle relative permeability hysteresis and differential utilization in zones, the extreme utilization theory targeting at the maximum amount of stored gas, maximum injection-production capacity and maximum efficiency in space utilization is proposed to support the three-in-one evaluation method of the maximum pressure-bearing capacity of geological body, maximum well production capacity and maximum peak shaving capacity of storage space. This study realizes the full potential of gas storage (storage capacity) at maximum pressure, maximum formation-wellbore coordinate production, optimum well spacing density match with finite-time unsteady flow, and peaking shaving capacity at minimum pressure, achieving perfect balance between security and capacity. Operation in gas storages, such as Hutubi in Xinjiang, Xiangguosi in Xinan, and Shuang6 in Liaohe, proves that extreme utilization theory has promoted high quality development of gas storages in China.

To efficiently develop deep shale gas in southern Sichuan Basin, under the guidance of “extreme utilization” theory, a basic idea and solutions for deep shale gas development are put forward and applied in practice. In view of multiple influencing factors of shale gas development, low single-well production and marginal profit of wells in this region, the basic idea is to establish “transparent geological body” of the block in concern, evaluate the factors affecting shale gas development through integrated geological-engineering research and optimize the shale gas development of wells in their whole life cycle to balance the relationship between production objectives and development costs. The solutions are as follows: (1) calculate the gold target index and pinpoint the location of horizontal well drilling target, and shale reservoirs are depicted accurately by geophysical and other means to build underground transparent geological body; (2) optimize the drilling and completion process, improve the adaptability of key tools by cooling, reducing density and optimizing the performance of drilling fluid, the “man-made gas reservoir” is built by comprehensively considering the characteristics of in-situ stress and fractures after the development well is drilled; (3) through efficient management, establishment of learning curve and optimization of drainage and production regime, the development quality and efficiency of the well are improved across its whole life cycle, to fulfil “extreme utilization” development of shale gas. The practice shows that the estimated ultimate recovery of single wells in southern Sichuan Basin increase by 10%-20% than last year.

A representative molecular model of kerogen is the prerequisite to the study on molecular interaction of fluid molecules with organic nanopores of shale. The molecular kerogen model in Silurian deep gas shale from southern China remains to be developed. In this work, the chemical structure of the targeted deep shale kerogen is characterized by organic geochemical measurements. The derived structural parameters are utilized to build the molecular structure of the kerogen unit. The kerogen unit shows a good representation of realistic kerogen structure in shale reservoir in terms of carbon skeleton, heteroatomic compositions and groups. The kerogen matrix and a extended kerogen slit model are constructed based on the kerogen unit, which match well with the experimental results in matrix density and kerogen porosity, respectively. The kerogen matrix is overall disordered with gentle stacking of polyaromatic fragments, due to the bendable aliphatic linkages and large-size aromatic units. The kerogen nanopores are not saturated with methane at deep shale reservoir conditions. At high pressure, the absolute adsorption tends to reach a maximum, while the excess adsorption shows a decreasing trend. The effect of pressure on the dissolved gas density is not pronounced. The generated kerogen model can serve as a starting point for further theoretical investigations on fluid storage and transport in organic nanopores of deep shale reservoir at microscopic scale.

Tremendous reserves of shale gas resources exhibit broad development prospects in southern Sichuan, China. ”Horizontal well + hydraulic fracturing” is taken as the principal means of shale gas reservoirs development. The design of hydraulic fracturing parameters is of great importance for the formation and extension of artificial fractures. With Well Area X of the shale gas reservoir from the Ordovician Wufeng Formation to the Silurian Longmaxi Formation in Luzhou, southern Sichuan, China, as an example. This paper identifies the artificial fracture-related characterization parameters, presents a detailed portrayal of the spatial characteristics of the fracture network, and optimizes the 4 key parameters of fracturing construction (i.e., injection rate, cluster spacing, fluid injection intensity, and proppant injection intensity) based on the geology–engineering integration fracturing simulation by building a regional 3D geological model. The result suggests that optimal injection rate, optimal cluster spacing, optimal fluid injection intensity, and optimal proppant injection intensity exist under certain geological characteristic parameters. According to the 3D geological model and simulation results of the study area, the optimal injection rate, optimal cluster spacing, optimal fluid injection intensity, and optimal proppant injection intensity are 14 m3/min, 10 m, 30 m3/m, and 2.5 t/m, respectively. The 3D geological model-based method for optimizing the fracturing parameters of shale gas reservoirs using geology–engineering integration can also applies to identifying the optimal fracturing parameters of other shale gas or tight oil well areas.

BackgroundUnderstanding inflammatory and immune responses to Omicron infection based on age is crucial when addressing this global health threat. However, the lacking of comprehensive elucidation hinders the development of distinct treatments tailored to different age populations.Methods1299 cases of Omicron infection in Shanghai were enrolled between April 10, 2022 and June 3, 2022, dividing into three groups by ages: Adult group (18-59 years), Old group (60-79 years), and Elder group (≥ 80 years). Laboratory data including inflammatory cytokines, cellular, and humoral immunity were collected and analyzed.ResultsThe mean age of Adult, Old, and Elder groups were 44.14, 69.98, and 89.35 years, respectively, with 40.9% being men. The Elder group patients exhibited higher white blood cell (WBC) counts and elevated levels of inflammatory cytokines, but their lymphocyte counts were relatively lower. In comparison to the Old group patients, the Elder group patients demonstrated significantly lower CD3+ T-cell counts, CD3+ T-cell proportion, CD4+ T-cell counts, CD8+ T-cell counts, and CD19+ B-cell counts, while the NK-cell counts were higher. Omicron negative patients displayed a higher proportion of CD19+ B-cells and higher levels of Complement-3 and IL-17 compared to the positive patients in the Old group. Omicron negative patients had lower WBC counts, CD3+CD8+ T-cells proportion, and the levels of serum amyloid A and IgA in the Elder group, but the CD4+/CD8+ ratio was higher.ConclusionsOur study identified the distinct profiles of inflammatory and immune responses to Omicron infection varying with age and highlighted the diverse correlations between the levels of various biomarkers and Omicron infected/convalescent patients.

Background Omicron is the recently emerged highly transmissible severe acute respiratory syndrome coronavirus 2 variant that has caused a dramatic increase in coronavirus disease-2019 infection cases worldwide. This study was to investigate the association between demographic and laboratory findings, and the duration of Omicron viral clearance. Methods Approximately 278 Omicron cases at the Ruijin Hospital Luwan Branch, Shanghai Jiaotong University School of Medicine were retrospectively analyzed between August 11 and August 31, 2022. Demographic and laboratory data were also collected. The association between demographics, laboratory findings, and duration of Omicron viral clearance was analyzed using Pearson correlation analysis and univariate and multivariate logistic regression. Results Univariate logistic regression analyses showed that a prolonged viral clearance time was significantly associated with older age and lower immunoglobulin (Ig) G and platelet (PLT) levels. Using multinomial logistic regression analyses, direct bilirubin, IgG, activated partial thromboplastin time (APTT), and PLT were independent factors for longer viral shedding duration. The model combining direct bilirubin, IgG, APTT, and PLT identifies patients infected with Omicron whose viral clearance time was ≥7 days with 62.7% sensitivity and 83.4% specificity. Conclusion These findings suggest that direct bilirubin, IgG, PLT, and APTT are significant risk factors for a longer viral shedding duration in patients infected with Omicron. Measuring levels of direct bilirubin, IgG, PLT, and APTT is advantageous to identify patients infected with Omicron with longer viral shedding duration.

(1) Background: The imaging energy range of a typical Compton camera is limited due to the fact that scattered gamma photons are seldom fully absorbed when the incident energies are above 3 MeV. Further improving the upper energy limit of gamma-ray imaging has important application significance in the active interrogation of special nuclear materials and chemical warfare agents, as well as range verification of proton therapy. (2) Methods: To realize gamma-ray imaging in a wide energy range of 0.3~7 MeV, a principle prototype, named a portable three-layer Compton camera, is developed using the scintillation detector that consists of an silicon photomultiplier array coupled with a Gd3Al2Ga3O12:Ce pixelated scintillator array. Implemented in a list-mode maximum likelihood expectation maximization algorithm, a far-field energy-domain imaging method based on the two interaction events is applied to estimate the initial energy and spatial distribution of gamma-ray sources. The simulation model of the detectors is established based on the Monte Carlo simulation toolkit Geant4. The reconstructed images of a 133Ba, a 137Cs and a 60Co point-like sources have been successfully obtained with our prototype in laboratory tests and compared with simulation studies. (3) Results: The proportion of effective imaging events accounts for about 2%, which allows our prototype to realize the reconstruction of the distribution of a 0.05 μSv/h 137Cs source in 10 s. The angular resolution for resolving two 137Cs point-like sources is 15°. Additional simulated imaging of the 6.13 MeV gamma-rays from 14.1 MeV neutron scattering with water preliminarily demonstrates the imaging capability for high incident energy. (4) Conclusions: We conclude that the prototype has a good imaging performance in a wide energy range (0.3~7 MeV), which shows potential in several MeV gamma-ray imaging applications.

Deep shale gas reservoir (3,500 ∼ 4,500 m) of Wufeng–Longmaxi Formation in southern Sichuan Basin in China has great potential for exploration and development, with resource of 16.31 × 1012 m3, counting 84% of the total resources in this area. And the deep shale gas wells in Luzhou and west Chongqing have achieved good development results in the past two years. We systematically summarized the geological characteristics of deep shale gas reservoir of Wufeng–Longmaxi Formation, and discussed the facing challenges and proposed some corresponding strategies. The deep shale gas reservoir in southern Sichuan Basin has six major characteristics. The reservoir is concentrated in depositional center and deep-water shelf environment. The reservoir is rich in silica and organic carbon while low in calcium and clay. Organic pores, inorganic pores, and microfractures are developed and well interconnected to form networks. Surface porosity is generally > 5% and increasing with depth. The gas content is 4.7 ∼ 7.5 m3/t, higher than that in Changning, Weiyuan, and Zhaotong area. The deep shale gas pressure coefficient is greater than 2.0 and is the highest in the southern Sichuan Basin, indicating its best preservation condition. Up to now, deep shale gas exploration is still encountered with many problems and challenges, including great difficulty in accurately obtaining reservoir parameters, unclear of high production mechanism, urgent need for optimal and quick drilling technology, great difficulty in reservoir fracturing, and unclear of hydro-fracture expansion rules. We proposed two strategies corresponding to the challenges, including deepen the delicate reservoir evaluation and clarify the rules of high production and enrichment of shale gas wells, and strengthen field experiments and explore effective and applicable technologies for drilling and fracturing of deep shale gas in China.

Background: The coronavirus disease 2019 (COVID-19) pandemic is currently threatening the health of individuals worldwide. We compared the clinical characteristics between younger patients (aged 14 days) yielded an area under the ROC (AuROC) curve of 0.716. Antiviral and antibiotic treatments were administered to 97.6% and 39.0% of patients, respectively. The antiviral drugs most commonly administered were traditional Chinese medicine (83.7%) and arbidol (75.6%). Conclusions: In this study, older patients and those with primary diseases were at a higher risk of worse clinical manifestations. The physicians who treat the patients should pay close attention to the risk factors that contribute to the length of hospital stay, which could be used for predicting prolonged hospital stay. Traditional Chinese medicine and arbidol were the most frequently used antiviral drugs. Nevertheless, the extent to which these medications can effectively treat COVID-19 warrants further investigation.

Background Ulcerative colitis is a unique inflammatory bowel disease with ulcerative lesions of the colonic mucosa. Melianodiol (MN), a triterpenoid, isolated from the fruits of the Chinese medicinal plant Melia azedarach, possesses significant anti-inflammatory properties. Objective The present study investigated the protective effects of MN on lipopolysaccharide (LPS)-induced macrophages and DSS-mediated ulcerative colitis in mice. Methods In the study, mice were given MN (50, 100, and 200 mg/kg) and 5-ASA (500 mg/kg) daily for 9 days after induction by DSS for 1 week. The progress of the disease was monitored daily by observation of changes in clinical signs and body weight. Results The results showed that MN effectively improved the overproduction of inflammatory factors (IL-6, NO, and TNF-α) and suppressed the activation of the NF-κB signalling cascade in LPS-mediated RAW264.7 cells. For DSS-mediated colitis in mice, MN can reduce weight loss and the disease activity index (DAI) score in UC mice, suppress colon shortening, and alleviate pathological colon injury. Moreover, MN treatment notably up regulated the levels of IL-10 and down regulated those of IL-1β and TNF-α, and inhibited the protein expression of p-JAK2, p-STAT3, iNOS, NF-κB P65, p-P65, p-IKKα/β, and p-IκBα in the colon. After MN treatment, the levels of MDA and NO in colonic tissue were remarkably decreased, whereas the levels of GSH, SOD, Nrf-2, Keap-1, HO-1, IκBα, and eNOS protein expression levels were significantly increased. Conclusion These results indicate that MN can activate the Nrf-2 signalling pathway and inhibit the JAK/STAT, iNOS/eNOS, and NF-κB signalling cascades, enhance intestinal barrier function, and effectively reduce the LPS-mediated inflammatory response in mouse macrophages and DSS-induced intestinal injury in UC.

In the process of unconventional natural gas development practice, the “extreme utilization” concept that focuses on “continuously breaking through the limit of development technology” is gradually formed, and supports the scale benefit exploration of unconventional gas in China. On this basis, the development theory of “extreme utilization” is proposed, its theoretical connotation together with development technologies of unconventional natural gas are clarified. The theoretical connotation is that, aiming at “extreme gas reservoirs”, “extreme techniques” are utilized to build subsurface connected bodies, expand the discharge area, and enlarge the production range, to obtain the maximum single-well production, extreme recovery, and eventually achieve the “extreme effect” of production. The series of development technologies include micro/nano-scale reservoir evaluation, “sweet spot” prediction, unconventional percolation theory and production capacity evaluation, optimization of grid well pattern, optimal-fast drilling and volume fracturing, and working regulation optimization and “integrated” organizing system. The “extreme utilization” development theory has been successfully applied in the development of unconventional gas reservoirs such as Sulige tight gas, South Sichuan shale gas, and Qinshui coalbed methane. Such practices demonstrate that, the “extreme utilization” development theory has effectively promoted the development of unconventional gas industry in China, and can provide theoretical guidance for effective development of other potential unconventional and difficult-to-recovery resources.

MotivationPatients with novel coronavirus disease 2019 (COVID-19) worsen into critical illness suddenly is a matter of great concern. Early identification and effective triaging of patients with a high risk of developing critical illness COVID-19 upon admission can aid in improving patient care, increasing the cure rate, and mitigating the burden on the medical care system. This study proposed and extended classical least absolute shrinkage and selection operator (LASSO) logistic regression to objectively identify clinical determination and risk factors for the early identification of patients at high risk of progression to critical illness at the time of hospital admission.MethodsIn this retrospective multicenter study, data of 1,929 patients with COVID-19 were assessed. The association between laboratory characteristics measured at admission and critical illness was screened with logistic regression. LASSO logistic regression was utilized to construct predictive models for estimating the risk that a patient with COVID-19 will develop a critical illness.ResultsThe development cohort consisted of 1,363 patients with COVID-19 with 133 (9.7%) patients developing the critical illness. Univariate logistic regression analysis revealed 28 variables were prognosis factors for critical illness COVID-19 (p < 0.05). Elevated CK-MB, neutrophils, PCT, α-HBDH, D-dimer, LDH, glucose, PT, APTT, RDW (SD and CV), fibrinogen, and AST were predictors for the early identification of patients at high risk of progression to critical illness. Lymphopenia, a low rate of basophils, eosinophils, thrombopenia, red blood cell, hematocrit, hemoglobin concentration, blood platelet count, and decreased levels of K, Na, albumin, albumin to globulin ratio, and uric acid were clinical determinations associated with the development of critical illness at the time of hospital admission. The risk score accurately predicted critical illness in the development cohort [area under the curve (AUC) = 0.83, 95% CI: 0.78–0.86], also in the external validation cohort (n = 566, AUC = 0.84).ConclusionA risk prediction model based on laboratory findings of patients with COVID-19 was developed for the early identification of patients at high risk of progression to critical illness. This cohort study identified 28 indicators associated with critical illness of patients with COVID-19. The risk model might contribute to the treatment of critical illness disease as early as possible and allow for optimized use of medical resources.

Marine shale gas resources have great potential in the south of the Sichuan Basin in China. At present, the high-quality shale gas resources at depth of 2000–3500 m are under effective development, and strategic breakthroughs have been made in deeper shale gas resources at depth of 3500–4500 m. To promote the effective production of shale gas in this area, this study examines key factors controlling high shale gas production and presents the next exploration direction in the southern Sichuan Basin based on summarizing the geological understandings from the Lower Silurian Longmaxi Formation shale gas exploration combined with the latest results of geological evaluation. The results show that: (1) The relative sea depth in marine shelf sedimentary environment controls the development and distribution of reservoirs. In the relatively deep water area in deep-water shelf, grade-I reservoirs with a larger continuous thickness develop. The relative depth of sea in marine shelf sedimentary environment can be determined by redox conditions. The research shows that the uranium to thorium mass ratio greater than 1.25 indicates relatively deep water in anoxic reduction environment, and the uranium to thorium mass ratio of 0.75–1.25 indicates semi-deep water in weak reduction and weak oxidation environment, and the uranium to thorium mass ratio less than 0.75 indicates relatively shallow water in strong oxidation environment. (2) The propped fractures in shale reservoirs subject to fracturing treatment are generally 10–12 m high, if grade-I reservoirs are more than 10 m in continuous thickness, then all the propped section would be high-quality reserves; in this case, the longer the continuous thickness of penetrated grade-I reservoirs, the higher the production will be. (3) The shale gas reservoirs at 3500–4500 m depth in southern Sichuan are characterized by high formation pressure, high pressure coefficient, well preserved pores, good pore structure and high proportion of free gas, making them the most favorable new field for shale gas exploration; and the pressure coefficient greater than 1.2 is a necessary condition for shale gas wells to obtain high production. (4) High production wells in the deep shale gas reservoirs are those in areas where Long11– Long13 sub-beds are more than 10 m thick, with 1500 m long horizontal section, grade-I reservoirs penetration rate of over 90%, and fractured by dense cutting + high intensity sand injection + large displacement + large liquid volume. (5) The relatively deep-water area in the deep-water shelf and the area at depth of 3500–4500 m well overlap in the southern Sichuan, and the overlapping area is the most favorable shale gas exploration and development zones in the southern Sichuan in the future. With advancement in theory and technology, annual shale gas production in the southern Sichuan is expected to reach 450×108 m3.

Abstract: Weiyuan shale gas play is characterized by thin high-quality reservoir thickness, big horizontal stress difference, and big productivity differences between wells. Based on integrated evaluation of shale gas reservoir geology and well logging interpretation of more than 20 appraisal wells, a correlation was built between the single well test production rate and the high-quality reservoir length drilled in the horizontal wells, high-quality reservoir thickness and the stimulation treatment parameters in over 100 horizontal wells, the dominating factors on horizontal well productivity were found out, and optimized development strategies were proposed. The results show that the deployed reserves of high-quality reservoir are the dominating factors on horizontal well productivity. In other words, the shale gas well productivity is controlled by the thickness of the high-quality reservoir, the high-quality reservoir drilling length and the effectiveness of stimulation. Based on the above understanding, the development strategies in Weiyuan shale gas play are optimized as follows: (1) The target of horizontal wells is located in the middle and lower parts of Longyi 11 (Wei202 area) and Longyi 11 (Wei204 area). (2) Producing wells are drilled in priority in the surrounding areas of Weiyuan county with thick high-quality reservoir. (3) A medium to high intensity stimulation is adopted. After the implementation of these strategies, both the production rate and the estimated ultimate recovery (EUR) of individual shale gas wells have increased substantially.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear.Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support.Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5–74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0–76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0–65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0–68.0 mmHg), all P < 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003).Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment.

The characterization of artificial fracture propagation law in the fracturing process of shale reservoirs is the basis for evaluating the fracture conductivity and a key indicator of the reservoir stimulated effect. In order to improve the fracture stimulated volume of shale reservoirs, this paper systematically discusses the current status of research on artificial fracture propagation law from the research methods and main control factors and provides an outlook on its future development direction. The analysis finds that the study of fracture propagation law by using indoor physical simulation experiments has the advantages of simple operation and intuitive image, and the introduction of auxiliary technologies such as acoustic emission monitoring and CT scanning into indoor physical model experiments can correct the experimental results so as to better reveal the propagation mechanism of artificial fractures. At present, the numerical simulation methods commonly used to study the propagation law of artificial fractures include the finite element method, extended finite element method, discrete element method, boundary element method and phase field method, etc. The models established based on these numerical simulation methods have their own advantages and applicability, so the numerical algorithms can be integrated and the numerical methods selected to model and solve the different characteristics of the propagation law of artificial fractures in different regions at different times can greatly improve the accuracy of the model solution and better characterize the propagation law of artificial fractures. The propagation law of artificial fracture in the fracturing process is mainly influenced by geological factors and engineering factors, so when conducting research, geological factors should be taken as the basis, and through detailed study of geological factors, the selection of the fracturing process can be guided and engineering influencing factors can be optimized.

At the Changning block and at the Luzhou block, the genetic mechanism of low-resistivity shale and its impact on reservoir quality are currently a hot topic on a world-wide scale. Shale with resistivity lower than 20 Ω·m is widely developed at the Wufeng-Longmaxi Formation in the Southern Sichuan Basin, bringing a considerable challenge for reservoir prediction using the electromagnetic method. This paper discusses the genetic mechanisms and reservoir qualities of three low-resistivity shale reservoir types in the Southern Sichuan Basin (the Changning block and Luzhou block). Three primary elements controlling low-resistivity shale distribution in the Southern Sichuan Basin have been deduced: widely distributed gravity flow deposits, poor structural preservation conditions and shale graphitization caused by Emeishan basalt. Specifically, (1) the shale reservoir with a resistivity

Granulomatosis with polyangiitis (GPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis with a wide range of clinical symptoms related to the systemic involvement of small blood vessels. The respiratory system is one of the most frequently involved, and life-threatening acute respiratory failure could occur due to diffusive alveolar hemorrhage and tracheal stenosis. When maximum mechanical ventilation is unable to maintain oxygenation, extracorporeal membrane oxygenation (ECMO) should be considered as the final respiratory supportive method, if available. Here we present a 32-year-old male patient with acute respiratory failure (ARF) related to GPA, who was rescued by winning time for accurate diagnosis and appropriate treatment. Additionally, we reviewed more than 60 GPA-related ARF cases on multiple online databases, summarized the clinical manifestations of these patients, and concluded that ECMO plays an important role in further respiratory support for ARF patients with GPA and assists in accurate and timely diagnosis and appropriate treatment, thus helping them recuperate.

Objective To investigate the effect of focused ultrasonography on clinical outcomes of septic shock. Methods Patients with septic shock were randomized into an integrated cardiopulmonary ultrasonography (ICUS) group and conventional (CON) group. Within 1 hour of admission, the ICUS group underwent ICUS examination for hemodynamic decision-making, while the CON group received standard treatment. The primary endpoint was 28-day mortality after admission. The secondary endpoints were cumulative fluid administration in the first 6, 24, and 72 hours; use of vasoactive drugs; lactate clearance; duration of ventilation; and ICU stay. Results Ninety-four qualified patients were enrolled (ICUS group, 49; CON group, 45). ICUS showed no significant effect on 28-day mortality. Within the initial 6 hours, the ICUS group tended to have a higher fluid balance and fluid intake than the CON group. The duration of vasopressor support was shorter in the ICUS group. There were no differences in the cumulative fluid infusion within 24 or 72 hours, lactate clearance, ICU stay, or duration of ventilation. Conclusions The initially focused ICUS did not affect the clinical outcomes of septic shock, but it tended to be associated with a higher fluid balance within the initial 6 hours and shorter duration of vasopressor support.

Recently, a high-yield gas flow of 22.5 × 104 m3/d was achieved in the wildcat well Yongtan 1, deployed by PetroChina Southwest Oil and Gasfield Company, and an extrusive facies volcaniclastic gas reservoir was first discovered in the Sichuan Basin, which is a major breakthrough in the exploration of volcanic rock gas reservoirs. In order to further evaluate the exploration potential in Permian volcanic rock gas reservoirs in this basin, we systematically reviewed and summarized the exploration process of volcanic rocks in this study area, as well as the characteristics of gas reservoirs of well Yongtan 1, the controlling factors and modes of hydrocarbon accumulation. The following findings were obtained. (1) Over the past five decades of gas exploration of volcanic rocks, the change of exploration thought and progress in seismic prediction contribute to a major discovery in this study area, i.e., the well location deployment of Yongtan 1 was determined in the Jianyan area, where the volcanic anomalies of the Permian developed outbursts are well developed and the gas reservoir conditions are favorable. This also proves that another new gas exploration area in this basin was found. (2) From the data of Yongtan 1, we found high-quality volcanic porous reservoirs with a thickness of over 100 m developed in the Permian strata, the effusive volcanic rock types dominated by breccia and tuffaceous breccia, reservoir space composed of dissolution pores, interbreccia dissolution pores, and other pores, the porosity of which is 6.68%–13.22% and 10.26% on average, the permeability 0.01–4.43 mD and 2.35 mD on average. (3) This abnormally high pressure gas reservoir was buried 4500–6000 m deep underground with the middle formation pressure being 125.625 MPa and the pressure coefficient being up to 2.22. Methane content in the minor H2S-bearing produced gas flow reached up to 99.03%. (4) Volcanic rocks in the Jianyang–Zhongjiang–Santai area are developed, and they are adjacent to the Cambrian high-quality source rocks in the Deyang–Anyue rifting. The early extensional deep faults play a role in connecting source and storage. There are many sets of caprocks, such as the Upper Permian Longtan Formation and Lower Triassic layered thick paste rocks, providing conditions for forming large-scale tectonic–lithologic composite trap gas reservoirs, and the favorable exploration area reaches up to 6000 km2. In conclusion, this major discovery not only proves that Permian volcanic rocks in the Sichuan Basin has large potential for oil and gas exploration, but reaffirms the confidence in changing our exploration thought, speeding up new exploration zones and areas, and discovering more and bigger gas fields. Keywords: Sichuan basin, Permian, Effusive facies, Volcaniclastic rock, Well Yongtan 1, Volcanic rock gas reservoir, Major breakthrough, Natural gas exploration potential

Based on the newest understandings of geological assessment and new progresses in engineering technologies in the development of shale gas rich in the southern Sichuan Basin, this paper analyzed the shale gas enrichment laws and the key factors of its commercial production, discussed the scale and efficient development modes, and clarified the further developing orientation. The following findings were concluded. (1) The Lower Silurian Longmaxi shale is the sweetest spot in this study area with a low density and a high uranium/thorium (U/Th) ratio, TOC content, quartz content, and free gas content. Besides, its distribution laws are mainly controlled by the sedimentary facies of deep water shelf. (2) The overpressured zones away from the ancient (present) erosion zones and large faults, mainly controlled by multi-stage tectonic evolution, belong to the most favorable sweet spots not only because there are well-developed organic matters and pores but the produced gas there is mainly of secondary cracking retention oil. (3) Layout, drilling, completion (fracturing) and management of wells will be essential to achieve high productions in the shale gas production. (4) The existing main technologies have helped achieve efficient development of quality shale gas resources underground less than 3500 m in such national shale gas demonstration zones as Changning–Weiyuan, Zhaotong, etc. Also, there shows a good potential of shale gas resources in those shallower strata and the strata with the burial depth of 3500–4000 m. In conclusion, with the help of continuous progress in technologies, an annual shale gas production rate of 40 billion cubic meters will be possibly achieved in this study area. Keywords: Southern sichuan basin, Early silurian, Longmaxi Fm, Shale gas, Enrichment laws, Scale effective development, Sweet spots, Resource potential, High productivity

Based on the analysis of outcrop, seismic, logging and drilling data, combined with exploration practice, the characteristics, distribution, reservoir performance and gas-bearing properties of Permian igneous rocks in Sichuan Basin are studied. The study shows that central volcanic eruptive facies are developed in Sichuan Basin, and their lithological assemblages and distribution characteristics show obvious differences. The igneous rocks are mainly distributed in three regions: the southwestern part of the basin has dominantly large- scale overflow facies basalts; the central and western part of the basin, Jianyang-Santai area, develop intrusive rocks, volcanic lavas (basalts) and pyroclastic rocks; and the eastern part of Sichuan, Dazhou-Liangping area, only develop diabase and basalts. Five aspects of understandings are achieved: (1) The Upper Permian igneous rocks can be divided into intrusive rocks and extrusive rocks, with the extrusive rocks as the main body. The chemical compositions of the extrusive rocks are characterized by both alkaline basalt and tholeiitic basalt, and belong to the subalkaline type of transitional basalt magma eruption. (2) There are obvious rhythmic structures vertically among overflow facies basalt, and the single rhythmic layer consists of, from bottom up, pyroclastic rocks (undeveloped), gray and dark gray porphyritic basalts (unstable), dark gray and purple microcrystalline-cryptocrystalline basalts, dark greyish green porous and amygdaloid basalts; the central volcanic eruption shows the rhythm and the vertical sequence of volcanic clastic rocks (agglomerates and breccias), volcanic lava, tuffaceous lava from bottom to top. (3) The pore types of basalt and pyroclastic rocks are diverse, mainly dissolution pore and de-vitrification micropore, but their physical properties are different. Basalt is characterized by ultra-low pore permeability, small reservoir thickness, and reservoirs are distributed in the upper and middle parts of the cycle, with poor lateral comparability. Volcanic clastic rocks are medium to high porous reservoirs (Well YT1: porosity: 8.66%−16.48%, average 13.76%) with large thickness and good reservoir quality. (4) Natural gas in basalts in southwestern basin mainly comes from Middle Permian, and natural gas in volcanic clastic rocks in central and western basin comes from Cambrian Qiongzhusi Formation. (5) Analysis of igneous reservoir-forming conditions in different areas shows that there are relatively insufficient gas sources and great differences in preservation conditions in southwestern basin. Reservoirs are poorly developed and gas-bearing is complex. The Jianyang-Santai area in the central and western part of Sichuan Basin has abundant hydrocarbon sources, developed reservoir, favorable preservation conditions and favorable gas geological conditions, and it is a favorable area for gas exploration. Key Words: Sichuan Basin, Upper Permian, Maokou Formation, igneous rock, volcanic lava, pyroclastic rock, reservoir property, gas bearing, natural gas reservoir

Based on the analysis of the basic characteristics of medium- and large-sized marine gas fields in Sichuan Basin, combined with the division of major reservoir forming geological units in the marine craton stage and their control on key hydrocarbon accumulation factors, the distribution law of medium- and large-sized marine carbonate gas fields in the basin was examined and the exploration direction was pointed out. Through the analysis of the periodic stretching-uplifting background, it is concluded that five large scale paleo-rifts, three large scale paleo-uplifts, five large scale paleo erosion surfaces were formed in the marine craton stage of Sichuan Basin, and these geological units control the key reservoir forming factors of medium and large sized gas fields: (1) Large-scale paleo-rifts control the distribution of high-quality hydrocarbon generation centers. (2) The margin of large-scale paleo-rifts, high position of paleo-uplifts and paleo erosion surfaces control the distribution of high-quality reservoirs. (3) Large-scale paleo-rifts, paleo-uplifts, paleo erosion surfaces and present tectonic setting jointly control the formation of many types of large and medium-sized traps. (4) Natural gas accumulation is controlled by the inheritance evolution of traps in large geological units. Based on the comparative analysis of the distribution characteristics of medium- and large-sized gas fields and large geological units, it is proposed that the superimposition relationship between single or multiple geological units and the present structure controls the distribution of medium- and large-sized gas fields, and the “three paleo” superimposed area is the most advantageous. According to the above rules, the main exploration fields and directions of medium- and large-sized marine carbonate gas fields in Sichuan Basin include periphery of Deyang-Anyue paleo-rift, eastern margin of Longmenshan paleo-rift, margins of Kaijiang-Liangping oceanic trough and Chengkou-western Hubei oceanic trough, the high part of the subaqueous paleo-uplifts around Central Sichuan, paleo erosion surfaces of the top boundary of Maokou Formation in eastern and southern Sichuan Basin, paleo erosion surfaces of the top boundary of the Leikoupo Formation in central and western Sichuan Basin. Key words: Sichuan Basin, marine carbonates, medium-and large-sized gas fields, geologic unit, reservoir forming factors, paleo-rifts, paleo-uplifts, paleo erosion surfaces

In this study, we analyze the L3 precision muon spectrometer data from November 2000. The results showed that a 4.7σ muon excess appeared at a time coincident with the solar flare of 8 November 2000. This muon excess corresponded to primary protons above 40 GeV, coming from a sky cell of solid angle 0.048 sr. The probability of being a background fluctuation was estimated to be about 0.1%. It is interesting and noteworthy that an M-class solar flare may also accelerate solar protons to such high energies.

Background: Since the coronavirus disease-2019 (COVID-19) outbreak, intensive care unit (ICU) healthcare workers were responsible for the critical infected patients. However, few studies focused on the mental health of ICU healthcare workers. This study aimed to investigate the psychological impact of COVID-19 on ICU healthcare workers in China.Methods: We distributed the nine-item Patient Health Questionnaire (PHQ-9) and seven-item General Anxiety Disorder questionnaire (GAD-7) online to ICU healthcare workers in China. Respondents were divided into frontline and second-line according to whether they have contact with COVID-19 patients. Depressive and anxiety symptoms of all respondents were evaluated based on their questionnaire scores.Results: There were 731 ICU healthcare workers finally enrolled in our study, including 303 (41.5%) male, 383 (52.4%) doctors, and 617 (84.4%) aged 26–45 years. All in all, 482 (65.9%) ICU healthcare workers reported symptoms of depression, while 429 (58.7%) reported anxiety. There was no significant difference between frontline (n = 325) and second-line (n = 406) respondents in depression (P = 0.15) and anxiety severity (P = 0.56). Logistic regression analysis showed that being female, ICU work time >5 years, and night duty number ≥10 were risk factors of developing depressive and anxiety symptoms. Income reduction was separately identified as risk of anxiety. Additionally, ICU work time >5 years was also identified as risk of developing moderate–severe depressive and anxiety symptoms.Conclusions: Frontline ICU work was not associated with higher risk of depressive and anxiety symptoms during COVID-19 pandemic remission period in China. Actions like controlling night duty number, ensuring vacation, and increasing income should be taken to relieve mental health problem. Furthermore, we should pay close attention to those who had worked long years in ICU.

Hepatocellular carcinoma is one of the most prevalent malignancies and a leading cause of cancer-related mortality worldwide. However, the therapies to prevent hepatocellular carcinoma are still limited and the emergence of drug resistance leads to the development of new anti-cancer drugs and combinational chemotherapy regimens. Our study was aimed to explore the anticancer effects of the essential oil extract (EEEO) from Euphorbia esula which has been widely used in traditional Chinese folk medicine and possessed potential cytotoxic effects in several human tumor cells. However, the mechanisms of EEEO-induced anti-proliferation and apoptosis have not been completely elucidated. In this study, EEEO was prepared by hydro-distillation and the main chemical component of EEEO was identified by GC-MS. HepG2 cells were treated with EEEO in vitro and then evaluated with respect to proliferation, apoptosis, and levels of reactive oxygen species (ROS) and apoptotic proteins. Our studies showed that EEEO decreased cell viability, elevated ROS levels, and induced apoptosis of HepG2 cells in a concentration- and time-dependent manner. Furthermore, Bcl-2 was down-regulated, while Bax was up-regulated in HepG2 after EEEO treatment. These results suggest that EEEO induced apoptosis of HepG2 cells and indicate that this apoptosis might be mediated by the mitochondrial pathway.

Abstract: In view of complex geological characteristics and alternating loading conditions associated with cyclic large amount of gas injection and withdrawal in underground gas storage (UGS) of China, a series of key gas storage construction technologies were established, mainly including UGS site selection and evaluation, key index design, well drilling and completion, surface engineering and operational risk warning and assessment, etc. The effect of field application was discussed and summarized. Firstly, trap dynamic sealing capacity evaluation technology for conversion of UGS from the fault depleted or partially depleted gas reservoirs. A key index design method mainly based on the effective gas storage capacity design for water flooded heterogeneous gas reservoirs was proposed. To effectively guide the engineering construction of UGS, the safe well drilling, high quality cementing and high pressure and large flow surface injection and production engineering optimization suitable for long-term alternate loading condition and ultra-deep and ultra-low temperature formation were developed. The core surface equipment like high pressure gas injection compressor can be manufactured by our own. Last, the full-system operational risk warning and assessment technology for UGS was set up. The above 5 key technologies have been utilized in site selection, development scheme design, engineering construction and annual operations of 6 UGS groups, e.g. the Hutubi UGS in Xinjiang. To date, designed main indexes are highly consistent with actural performance, the 6 UGS groups have the load capacity of over 7.5 billion cubic meters of working gas volume and all the storage facilities have been running efficiently and safely. Key words: gas field storage, trap dynamic sealing capacity, key index design, effective storage volume, drilling and completion in ultra-deep and ultra-low pressure formation, alternating load, surface engineering, core equipment, risk assessment and control

The Ordovician Wufeng Formation-Silurian Longmaxi Formation organic-rich shales distributed widely and stably in Southern Sichuan Basin were investigated based on drilling data. Geological evaluation of wells show that the shale reservoirs have good properties in the Yibin, Weiyuan, Zigong, Changning, Luzhou, Dazu areas, with key parameters such as TOC, porosity, gas content similar to the core shale gas production zones. Moreover, these areas are stable in structure, good in preservation conditions and highly certain in resources. The shale reservoirs have a burial depth of 4 500 m or shallow, a total area of over 2×104 km2 and estimated resource of over 10×1012 m3, so they are the most resource-rich and practical areas for shale gas exploitation in China. Through construction of the Changning-Weiyuan national demonstration region, the production and EUR of shale gas wells increased significantly, the cost of shale gas wells decreased remarkable, resulting in economic benefit better than expected. Moreover, the localized exploration and development technologies and methods are effective and repeatable, so it is the right time for accelerating shale gas exploitation. Based on the production decline pattern of horizontal wells at present and wells to be drilled in the near future, at the end of the 13th Five Year Plan, the production of shale gas in southern Sichuan Basin is expected to reach or exceed 10 billion cubic meters per year. The resources are sufficient for a stable production period at 30 billion cubic meters per year, which will make the South Sichuan basin become the largest production base of shale gas in China. Key words: Sichuan Basin, southern Sichuan Basin, shale gas, Ordovician Wufeng Formation, Silurian Longmaxi Formation, resource potential

Our present study investigated the anti-diabetic activity and potential mechanism of β-ecdysterone (β-EC) derived from Cyanotis arachnoidea. In vitro, β-EC exhibited a promising effect on increasing GLUT4 translocation by 1.6 folds and glucose uptake by 1.75 folds in L6 cells. In vivo, KK-Ay mice’s body weight, blood glucose levels and other related blood–lipid indexes can be significantly reduced with β-EC treatment. For the mechanism study, we have found that β-EC exhibited a significant protective effect on insulin resistance (IR) in L6 and HepG2 cells through increasing expressions of IRβ, p-Akt, p-IRS-1 and increasing the expressions of GLUT4 and GLUT2. The phosphorylation of Akt, IRS-1 and the expression of IRβ, GLUT4 and GLUT2 in the liver and skeletal muscle in KK-Ay mice were also significantly ameliorated after 4-weeks treatment with β-EC. According to our present findings, we could conclude that β-EC possessed the potential anti-diabetic effects through activating IRS-1/AKT/GLUT4 and IRS-1/AKT/GLUT2 pathways.

Owing to the technical innovation as well as a better understanding of gas exploration, nine giant gas fields have been successively discovered in the Sichuan Basin with cumulative proven gas reserves of 3.69 trillion cubic meters, where the annual natural gas productivity ranks the second in China. The CNPC latest oil & gas resources evaluation results demonstrate that natural gas resources in the Sichuan Basin takes the first place among those petroliferous basins all over China, but its proved gas reserves is only 10%, so the exploration prospect is bright. Over the past decades, PetroChina Southwest Oil & Gas Field Company has made great efforts to complete its technical systems, improve gas pipeline networks, and streamline gas markets, laying a robust foundation for the natural gas development in the Sichuan Basin. To further enhance the natural gas reserves and productivity in this basin and to achieve the biggest gas province in China, this company presents the following major projects: progressive multi-strata exploration and development in the central Sichuan area, Safe and efficient development of high-sulfur gas fields in the northeastern Sichuan area, Demonstrative exploration and development of deep marine carbonate gas reservoirs in the northwestern Sichuan area, Exploitation and development of large Cambrian pre-salt structural gas reservoirs in the eastern Sichuan area, and Extensive and beneficial development of shale gas in southern Sichuan. As the key to the Southwest growth pole, the above projects cover all the important, hard and hot fields of the whole basin and multiple gas-bearing strata and layers. With all the projects fulfilled, natural gas productivity will be 25–29 billion cubic meters (bcm) in 2020, accounting for most parts of this company's whole planning production (30 bcm in total), and will reach up to 50–70 bcm in 2030. It is predicted that natural gas development in the Sichuan Basin will be in a golden era in the long term.

For a full and accurate understanding of the position and role of natural gas in China's energy revolution and providing a decision-making reference for the scientific establishment of natural gas development strategies and the deepening of the energy revolution, this paper analyzed the role of natural gas in guiding the energy revolution in China and points out the main direction of natural gas utilization in the Sichuan–Chongqing gas province which takes the lead in China's natural gas industry. The study provides the following findings. First, with a huge space for development, natural gas will play an important role in China's third energy revolution. Second, natural gas resources are abundant and have a huge potential for development in China. Third, natural gas can be used for a large range of purposes in the Sichuan–Chongqing gas province. In addition to be used as city gas, natural gas can also be used for industrial fuel mainly as a substitute for coal, transportation, distributed energy, peak-shaving power generation, and high-end natural gas chemical raw materials. Some conclusions are made. First, as the cleanest fossil energy and the best fuel, natural gas will play an irreplaceable role in China's third energy revolution in the 21st century. Second, the Sichuan–Chongqing gas province is rich in natural gas, hydropower and other renewable resources. By 2020, it will become the largest gas production province in China, with natural gas production over 550 × 108 m3. By 2030, driven by the rapid development of shale gas, gas production in the province is expected to exceed 800 × 108 m3. Third, the Sichuan–Chongqing gas province is likely to become the leader in China's third energy revolution.

The title compound, 6,7-dehydroroyleanone, C20H26O3 [systematic name: (4bS)-3-hydroxy-2-isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a-hexahydrophenanthrene-1,4-dione] was isolated from Taxodium distichum (L.) Rich. The compound crystallizes in the space group P21. The crystal structure features two O—H...O hydrogen bonds, forming chains along the [010] direction.

The title compound, C20H28O4 [systematic name: (4bS,8aS,10S)-3,10-dihydroxy-2-isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-1,4-dione], is an abietane-type diterpene, which was isolated from Taxodium ascendens (B.). The compound crystallizes in the chiral space group P21, but it was not possible to determine the absolute structure of the molecule in the crystal by resonant scattering. The molecular structure is stabilized by two intramolecular O—H...O hydrogen bonds, enclosing S(5) and S(6) ring motifs. In the crystal, molecules are linked by O—H...O and C—H...O hydrogen bonds, forming chains along the [010] direction. The crystal structure of the 10R stereoisomer of the title compound, isolated from the roots of Premna obtusifolia (Verbenaceae), has been reported. It crystallized in the chiral space group P212121, and the absolute structure was determined as (4bS,8aS,10R), by resonant scattering using Cu Kα radiation [Razak et al. (2010). Acta Cryst. E66, o1566–o1567].

The Lower Cambrian Longwangmiao Fm gas reservoir in Moxi block of the Anyue Gas field, Sichuan Basin, is the largest single-sandbody integrated carbonate gas reservoir proved so far in China. Notwithstanding this reservoir's advantages like large-scale reserves and high single-well productivity, there are multiple complicated factors restricting its efficient development, such as a median content of hydrogen sulfide, low porosity and strong heterogeneity of fracture–cave formation, various modes of gas–water occurrences, and close relation between overpressure and stress sensitivity. Up till now, since only a few Cambrian large-scale carbonate gas reservoirs have ever been developed in the world, there still exists some blind spots especially about its exploration and production rules. Besides, as for large-scale sulfur gas reservoirs, the exploration and construction is costly, and production test in the early evaluation stage is severely limited, all of which will bring about great challenges in productivity construction and high potential risks. In this regard, combining with Chinese strategic demand of strengthening clean energy supply security, the PetroChina Southwest Oil & Gas Field Company has carried out researches and field tests for the purpose of providing high-production wells, optimizing development design, rapidly constructing high-quality productivity and upgrading HSE security in the Longwangmiao Fm gas reservoir in Moxi block. Through the innovations of technology and management mode within 3 years, this gas reservoir has been built into a modern large-scale gas field with high quality, high efficiency and high benefit, and its annual capacity is now up to over 100 × 108 m3, with a desirable production capacity and development indexes gained as originally anticipated. It has become a new model of large-scale gas reservoirs with efficient development, providing a reference for other types of gas reservoirs in China.

Eupatorium adenophorum Spreng. (EA) is a well-known noxious invasive species. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the essential oil derived from EA (EAEO) is mainly composed of sesquiterpenes. However, the pharmacological value of EAEO in hepatocellular carcinoma (HCC) remains largely unexplored. Herein, we investigated the anti-HCC activities of EAEO, and explored the potential mechanisms of EAEO-induced apoptosis. An MTT assay showed that EAEO inhibited HCC cell proliferation with little toxicity on normal liver cells. Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle, respectively. Moreover, EAEO promoted in vitro HCC cell apoptosis, and EAEO treatment inhibited HepG2 xenografts growth and enhanced apoptotic nucleus of xenografts in HepG2-bearing nude mice. Mechanistically, EAEO significantly decreased the ratio of Bcl-2/Bax and resulted in the activation of caspase-9 and -3. EAEO also reduced the expression of Grp78, which in turn relieved the inhibition of caspase-12 and -7. Meanwhile, EAEO suppressed the phosphorylation of STAT3 and AKT, indicative of its anti-HCC potential. In summary, we determined that EAEO treatment promoted HCC apoptosis via activation of the apoptotic signaling pathway in mitochondria and endoplasmic reticulum, as well as repressed the activity of STAT3 and AKT in HCC cells.

Kurarinone, a flavonoid isolated from Sophora flavescens Aiton, has been reported to have significant antitumor activity. However, the cytotoxic activity of kurarinone against non-small cell lung cancer (NSCLC) cells is still under explored. In our study, we have evaluated the inhibitory effects of kurarinone on the growth of NSCLC both in vivo and in vitro as well as the molecular mechanisms underlying kurarinone-induced A549 cell apoptosis. The results showed that kurarinone effectively inhibited the proliferation of A549 cells with little toxic effects on human bronchial epithelial cell line BEAS-2B. FASC examination and Hoechst 33258 staining assay showed that kurarinone dose-dependently provoked A549 cells apoptosis. Mechanistically, kurarinone significantly decreased the ratio of Bcl-2/Bax, thereby causing the activation of caspase 9 and caspase 3, and reduced the expression of Grp78, which led to relieve the inhibition of caspase-12 and caspase-7, as well as suppressing the activity of AKT. Meanwhile, modeling results from the Surflex-Dock program suggested that residue Ser473 of Akt is a potential binding site for kurarinone. In vivo, kurarinone inhibited the growth of A549 xenograft mouse models without apparent signs of toxicity. Our study indicated that kurarinone has the potential effects of anti-NSCLC, implemented through activating mitochondria apoptosis signaling pathway, as well as repressing the activity of endoplasmic reticulum pathway and AKT in A549 cells.

Tight sand gas is the main type of unconventional natural gas. According to the geologic characteristics of large-scale tight sandstone gas reservoirs discovered in China in recent years, tight sand gas reservoirs can be classified into three main types, multi-layer lens overlaid tight sand gas reservoir, multilayered tight sandstone gas reservoir and massive tight sand gas reservoir. A series of development technologies for the first 2 types of reservoirs have been formed, focusing on improving individual well producing rate and reducing development cost. They drive the scale development of tight gas. As to multi-layer lens overlaid tight sand gas, the specific technologies include well location optimization, multi-stage sand fracturing, down hole choking and low-pressure surface gas gathering system. As to multilayered tight sand gas, the specific technologies include sweet-spot prediction and evaluation, integrated horizontal well development technique, and drainage gas recovery technique. There are still great challenges in tight gas development from several aspects, such as the enhancement of reserve deployment ratio and recovery ratio, the improvement of individual well producing rate, the development of new and difficult-to-produce reserves as well as the rate maintenance, and gas well management in its later stage of life cycle. Key words: tight sand gas, classification and evaluation, development technology series, technology challenges

This study investigated the active principles, hypoglycemic activity and potential mechanisms of the flavonoid rich extract from Sophora tonkinensis Gagnep. (SS-EtOAc) in KK-Ay diabetic mice. An off-line semipreparative LC-NMR and LC-UV-ESIMS protocol was performed to determine 13 flavonoids from SS-EtOAc. SS-EtOAc administrated orally to the KK-Ay mice significantly increased their sensibility to insulin, reduced fasting blood-glucose levels and blood lipid indexes such as triglyceride and cholesterol. Moreover, SS-EtOAc exhibited a strong effect of stimulation on GLUT4 translocation by 2.7 fold in L6 cells. However, the selective AMP-activated protein kinase (AMPK) inhibitor Compound C can completely inhibit the activation of the AMPK pathway and prevent the GLUT4 translocation caused by SS-EtOAc. In vivo, phosphorylation of the AMPK expression in the liver and skeletal muscle was measured. The results showed phosphorylation of the AMPK had been improved and GLUT4 expression had been also enhanced. In this paper we conclude that, SS-EtOAc seems to have potential beneficial effects on the treatment of type 2 diabetes mellitus (T2DM) with the probable mechanism of stimulating GLUT4 translocation modulated by the AMPK pathway.

This paper presents two representative models to analyze the flow dynamic of multi-scale porous medium in hydraulic fractured horizontal shale gas wells. In this work, considering the characteristic mechanisms (multi-scale porous space, desorption and diffusion), flow equations in shale are established. After that, two representative models (discrete fracture model and dual-porosity model) are tailored to our issues. Solved by the control-volume finite element method (CVFEM), influences of fracture network system on productivity in shale reservoirs are analyzed in detail. Based on the analysis, the effects can be summarized as follow: at the beginning of production, high conductivity fracture network means more free gas could be produced; at the later part of production, high conductive fracture network can form a large low pressure region, which can not only stimulate the desorption of adsorbed gas, but also reduce the flow resistance to the well. Finally, the sensitivities of characteristic parameters in shale are discussed.