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AbstractBackground The purpose of this study was to explore the changes in blood cellular and biochemical parameters of rats in a natural environment of low pressure and low oxygen on the plateau.Methods Male Sprague-Dawley rats in two groups were raised in different environments from 4 weeks of age for a period of 24 weeks. They were raised to 28 weeks of age and then transported to the plateau medical laboratory of Qinghai University. Blood cellular and biochemical parameters were measured and the data of the two groups were statistically analyzed.Results 1. RBC in the HA group was higher than that in the Control group, but there was no significant difference between the two groups (p > 0.05), Compared with the Control group, HGB, MCV, MCH, MCHC and RDW in the HA group were significantly higher (p

High-altitude areas are characterized by low pressure and hypoxia, which have a significant impact on various body systems. This study aimed to investigate the alterations in cardiac index and right ventricular hypertrophy index(RVHI) in rats at different altitudes.Twenty-one male Sprague-Dawley (SD) rats aged 4 weeks were randomly divided into three groups based on altitude. The rats were raised for 28 weeks and then transferred to Qinghai University Plateau Medicine Laboratory. Body weight was measured, heart organs were isolated and weighed, and cardiac index and right ventricular hypertrophy index were determined. Statistical analysis was performed on the data from the three groups. Compared with the plain group, the body weight of the middle-altitude group was significantly decreased (P

ABSTRACT Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. IMPORTANCE Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health. Aiming to reduce the harm of alcohol consumption, we designed a recombinant probiotic expressing hADH1B. Our results showed that this recombinant probiotic can reduce alcohol absorption and protect the body from alcohol damage, including hangover, liver, and intestinal damage. Reducing alcohol damage is helpful to the health of people with difficulty in abstinence. The engineered probiotic may provide new strategies for treatment and prevention of the negative effects of alcohol, and it also has the potential for widespread application.

The intermittent fasting regimen (IFR) has been certified as an effective strategy for improving metabolism. But the underlying mechanism is still obscure. Beige induction in white adipose tissue (WAT) by IFR may account for this. It has been demonstrated that the erupting of pregnancy zone protein (PZP) from the liver coincides with membrane translocation of grp78 in brown adipocytes during IFR to activate brown adipose tissue (BAT), which may partly explain the metabolic benefits of IFR. Liver-derived PZP appears to be responsible for all metabolic regulatory functions; the effect of boosting energy expenditure disappeared in liver-deficient mice. To verify whether any liver-specific modification was essential for functional PZP, we used the PZP adipose tissue-specific overexpression mice model (PZP TG). We found that the metabolic disorders induced by high-fat diet were improved in PZP TG mice under IFR. Additionally, in addition to the activation of BAT, UCP1 protein and angiogenesis were increased in WAT, as well as the expression of genes associated with glucose utilization. These results demonstrate that PZP fat-specific TG increased the energy conversion of WAT, indicating that WAT may be another direct target for PZP during IFR.

Abstract Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose‐regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK‐ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.

The Lower Cambrian petroleum system in the Tarim Basin has undergone multiple periods of tectonic movements, leading to successive hydrocarbon expulsion events and adjustments. The complex process of hydrocarbon accumulation occurred under deep burial conditions, persisting at depths of nearly 6,000 m over an extended period. This has resulted in the current occurrence of various phases including light oil, condensate, and gas in the deep-ultradeep strata of the Tarim Basin. The intricacies of formation of hydrocarbon accumulations and phase evolution have posed challenges to understanding the accumulation mechanisms and enrichment patterns of the Cambrian in the Tarim Basin, consequently lowering the success rate of oil and gas exploration. Such characteristics of multi-stage accumulation and adjustment are prevalent in deep hydrocarbon systems. Therefore, based on data from Well ZH1 in the Tazhong Uplift, combined with basin simulation, Compositional kinetics model, and PVT performance simulation, this study investigates the hydrocarbon generation and phase evolution processes in the deep hydrocarbon systems of the Tazhong Uplift. The results indicate that Well ZH1 entered the hydrocarbon generation peak during the Late Ordovician, followed by secondary cracking as the predominant hydrocarbon evolution process. Hydrocarbon fluids within the Lower Cambrian reservoir transitioned into the condensate phase towards the end of the Cambrian, with increasing depth resulting in higher gas-oil ratios and a decreasing trend in viscosity and density.

The lack of diagnostic markers limits the window of effectiveness for rheumatoid arthritis (RA) therapies. Here, we isolated exosomes of serum samples from four distinct groups RA patients, according to disease activity and with/without medication. Then, total RNA of exosomes was extracted for whole-transcriptome sequencing. Focusing on lncRNA sequencing, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed. We found that the number of upregulated lncRNAs were significantly higher than that of downregulated lncRNAs in each four RA groups. And most importantly, we identified two specific lncRNAs from differentially expressed lncRNAs, TCONS_I2_00013502 (up-regulated) and ENST00000363624 (down-regulated) in RA. Receiver Operating Characteristic (ROC) curve analysis showed that the two lncRNAs were promising biomarkers for RA diagnosis. These findings highlight lncRNAs of the serum exosome are important biomarkers and provide application potential for diagnosis of RA.

Studies focusing on the fault system in the Jurassic strata of the Sichuan Basin have been limited, restricting the understanding of the hydrocarbon accumulation mode of the Shaximiao Formation and the expansion of exploration. Through interpretation and coherent slice analysis of extensive seismic data, we have newly discovered that normal faults are widely developed in the northern central Sichuan Basin in the Jurassic strata. These faults mainly extend from the Lower to Upper Jurassic strata and are characterized by the continuous arrangement of NEE-trending small faults in the plane, with a few NNE-trending and NNW-trending faults also present. The distribution of Jurassic fault combinations varies within the basin, with normal faults mainly distributed in the low uplift areas of central Sichuan and the north of central Sichuan. Geochemical data comparisons indicate that these normal faults serve as conduits between the Jurassic source rocks and the Shaximiao Formation reservoir in these areas. Furthermore, the newly discovered normal faults are superimposed with the middle and lower Jurassic source rocks in the northern central Sichuan Basin, suggesting the formation of a new hydrocarbon accumulation model involving hydrocarbon generation from the middle and lower Jurassic, facilitated by communication through normal faults. Notably, one of the promising directions for exploration lies in the multi-stage channel superimposed development zone near these normal faults.

Through the study of organic matter enrichment, hydrocarbon generation and accumulation process of black shale of the Cretaceous Qingshankou Formation in the Songliao Basin, the enrichment mechanism of Gulong shale oil and the distribution of conventional–unconventional oil are revealed. The Songliao Basin is a huge interior lake basin formed in the Early Cretaceous under the control of the subduction and retreat of the western Pacific plate and the massive horizontal displacement of the Tanlu Fault Zone in Northeast China. During the deposition of the Qingshankou Formation, strong terrestrial hydrological cycle led to the lake level rise of the ancient Songliao Basin and the input of a large amount of nutrients, resulting in planktonic bacteria and algae flourish. Intermittent seawater intrusion events promoted the formation of salinization stratification and anoxic environment in the lake, which were beneficial to the enrichment of organic matters. Biomarkers analysis confirms that the biogenic organic matter of planktonic bacteria and algae modified by microorganisms plays an important role in the formation of high-quality source rocks with high oil generation capability. There are four favorable conditions for the enrichment of light shale oil in the Qingshankou Formation of the Gulong Sag, Songliao Basin: the moderate organic matter abundance and high oil potential provide sufficient material basis for oil enrichment; high degree of thermal evolution makes shale oil have high GOR and good mobility; low hydrocarbon expulsion efficiency leads to a high content of retained hydrocarbons in the source rock; and the confinement effect of intra-layer cement in the high maturity stage induces the efficient accumulation of light shale oil. The restoration of hydrocarbon accumulation process suggests that liquid hydrocarbons generated in the early (low–medium maturity) stage of the Qingshankou Formation source rocks accumulated in placanticline and slope after long-distance secondary migration, forming high-quality conventional and tight oil reservoirs. Light oil generated in the late (medium–high maturity) stage accumulated in situ, forming about 15 billion tons of Gulong shale oil resources, which finally enabled the orderly distribution of conventional–unconventional oils that are contiguous horizontally and superposed vertically within the basin, showing a complete pattern of “whole petroleum system” with conventional oil, tight oil and shale oil in sequence.

Abstract Programmed cell death ligand 1 (PD-L1) expression remains the most widely used biomarker for predicting response to immune checkpoint inhibitors (ICI), but its predictiveness varies considerably. Identification of factors accounting for the varying PD-L1 performance is urgently needed. Here, using data from three independent trials comprising 1239 patients, we have identified subsets of cancer with distinct PD-L1 predictiveness based on tumor transcriptome. In the Predictiveness-High (PH) group, PD-L1+ tumors show better overall survival, progression-free survival, and objective response rate with ICI than PD-L1- tumors across three trials. However, the Predictiveness-Low (PL) group demonstrates an opposite trend towards better outcomes for PD-L1- tumors. PD-L1+ tumors from the PH group demonstrate the superiority of ICI over chemotherapy, whereas PD-L1+ tumors from the PL group show comparable efficacy between two treatments or exhibit an opposite trend favoring chemotherapy. This observation of context-dependent predictiveness remains strong regardless of immune subtype (Immune-Enriched or Non-Immune), PD-L1 regulation mechanism (adaptative or constitutive), tumor mutation burden, or neoantigen load. This work illuminates avenues for optimizing the use of PD-L1 expression in clinical decision-making and trial design, although this exploratory concept should be further confirmed in large trials.

PCIF1 can mediate the methylation of N6,2′-O-dimethyladenosine (m6Am) in mRNA. Yet, the detailed interplay between PCIF1 and the potential cofactors and its pathological significance remain elusive. Here, we demonstrated that PCIF1-mediated cap mRNA m6Am modification promoted head and neck squamous cell carcinoma progression both in vitro and in vivo. CTBP2 was identified as a cofactor of PCIF1 to catalyze m6Am deposition on mRNA. CLIP-Seq data demonstrated that CTBP2 bound to similar mRNAs as compared with PCIF1. We then used the m6Am-Seq method to profile the mRNA m6Am site at single-base resolution and found that mRNA of TET2, a well-known tumor suppressor, was a major target substrate of the PCIF1-CTBP2 complex. Mechanistically, knockout of CTBP2 reduced PCIF1 occupancy on TET2 mRNA, and the PCIF1-CTBP2 complex negatively regulated the translation of TET2 mRNA. Collectively, our study demonstrates the oncogenic function of the epitranscriptome regulator PCIF1-CTBP2 complex, highlighting the importance of the m6Am modification in tumor progression.

The IMpower010 and KEYNOTE-091 trials have demonstrated the benefit of adjuvant immunotherapy (IO) after chemotherapy (C+IO) in resected non-small cell lung cancer (NSCLC), including those with epidermal growth factor receptor gene (EGFR) mutation. Meanwhile, several studies have reported that EGFR-tyrosine kinase inhibitor (EGFR-TKI) may prolong disease-free survival (DFS) in these patients. However, there is currently a lack of head-to-head comparison between these two adjuvant therapy strategies. Therefore, we designed a comparative analysis of their efficacy to inform clinical decision-making by assessing DFS as the primary outcome. The results of direct meta-analysis indicated that EGFR-TKI reduced the risk of recurrence and/or death in completely resected NSCLC (HREGFR-TKI/chemo = 0.41, 95% CI: 0.23 to 0.74, p=0.003), while C+IO did not significantly improve DFS compared with chemotherapy alone (HRC+IO/chemo=0.68, 95% CI: 0.31 to 1.50, p=0.338). Indirect comparison suggested that EGFR-TKI has a trend to prolong DFS compared with C+IO (HR EGFR-TKI/C+IO = 0.60, 95% CI: 0.23 to 1.61, p=0.312), while the third-generation TKI (3rd-TKI) osimertinib significantly outperformed C+IO (HR3rd-TKI/C+IO = 0.29, 95% CI: 0.12 to 0.70, p=0.006). In conclusion, osimertinib rather than immunotherapy should be regarded as the preferred adjuvant therapy in completely resected, EGFR-mutant NSCLC.

Based on analyses of characteristics, hydrocarbon charging history and geological conditions for the formation of Sinian–Cambrian reservoirs in the north slope area of central Sichuan paleo-uplift, the natural gas origin, accumulation evolution, accumulation pattern and formation conditions of large lithologic gas reservoirs have been investigated. Through comprehensive analyses of natural gas composition, carbon and hydrogen isotopic compositions, fluid inclusions, reservoir bitumen, and geological conditions such as lithofacies paleogeography and beach body characterization, it is concluded that: (1) The natural gas in the Sinian–Cambrian of the north slope area is mainly oil cracking gas, and different contribution ratios of multiple sets of source rocks lead to different geochemical characteristics of natural gas in different reservoirs. (2) Although the both Sinian and Cambrian gas reservoirs in this area are lithologic gas reservoirs under monocline background, the former has normal-pressure and the latter has high-pressure. There are three types of source-reservoir-caprock combinations: single source with lower generation and upper reservoir, double sources with lower generation and upper reservoir or with side source and lateral reservoir, double sources with lower generation and upper reservoir or with upper generation and lower reservoir. The Permian–Triassic is the main generation period of oil, Early–Middle Jurassic is the main generation period of oil cracking gas and wet gas, and Late Jurassic–Cretaceous is the main generation period of dry gas. (3) The Sinian–Cambrian system of the north slope area has two favorable conditions for formation of large lithologic gas reservoirs, one is that the large scale beach facies reservoirs are located in the range of ancient oil reservoirs or near the source rocks, which is conducive to the “in-situ” large-scale accumulation of cracked gas in the paleo-oil reservoirs, the other is that the large scale mound-beach complex reservoirs and sealing layers of inter beach tight zones match effectively to form large lithologic traps under the slope background. The research results confirm that the north slope area has large multi-layer lithologic gas reservoirs with more than one trillion cubic meters of natural gas resources and great exploration potential.

ABSTRACT Soil is an essential part of the animal habitat and has a large diversity of microbiota, while the animal body was colonized by a complex bacterial community; so far, the relationship between the animal host microbial community and the soil microbial ecosystem remains largely unknown. In this study, 15 white rhinoceros from three different captive grounds were selected and the bacterial community of the gut, skin, and environment of these rhinoceros were analyzed by 16S rRNA sequencing technology. Our results showed that Firmicutes and Bacteroidota were the predominant phyla in the gut microbiome, whereas skin and environment samples share similar microbiome profiles and are dominated by the phyla of Actinobacteriota, Chloroflexi, and Proteobacteria. Although the bacterial composition of the gut differs from that of the skin and environment, the Venn diagrams showed that there were 22 phyla and 186 genera shared by all the gut, skin, and environmental microbes in white rhinoceroses. Further cooccurrence network analysis indicated a bacterial linkage based on a complex interaction was established by the bacterial communities from the three different niches. In addition, beta diversity and bacterial composition analysis showed that both the captive ground and host ages induced shifts in the microbial composition of white rhinoceroses, which suggested that the bacterial linkage between the captive white rhinoceros and its environment is dynamic. Overall, our data contribute to a better understanding of the bacterial community of the captive white rhinoceros, especially for the relationship between the environment and animal bacterial communities. IMPORTANCE The white rhinoceros is one of the world’s most endangered mammals. The microbial population plays a key role in animal health and welfare; however, studies regarding the microbial communities of the white rhinoceros are relatively limited. As the white rhinoceros has a common behavior of mud baths and thus is in direct contact with the environment, a relationship between the animal microbial community and the soil microbial ecosystem appears possible, but it remains unclear. Here, we described the characteristics and interaction of bacterial communities of the white rhinoceros in three different niches, including gut, skin, and environment. We also analyzed the effects of captive ground and age on the composition of the bacterial community. Our findings highlighted the relationship among the three niches and may have important implications for the conservation and management of this threatened species.

Summary: Aberrant RNA modifications are frequently associated with cancers, while the underlying mechanisms and clinical significance remain poorly understood. Here, we find that the ac4C RNA acetyltransferase NAT10 is significantly upregulated in esophageal cancers (ESCAs) and associated with poor ESCA prognosis. In addition, using ESCA cell lines and mouse models, we confirm the critical functions of NAT10 in promoting ESCA tumorigenesis and progression in vitro and in vivo. Mechanistically, NAT10 depletion reduces the abundance of ac4C-modified tRNAs and decreases the translation efficiencies of mRNAs enriched for ac4C-modified tRNA-decoded codons. We further identify EGFR as a key downstream target that facilitates NAT10’s oncogenic functions. In terms of clinical significance, we demonstrate that NAT10 depletion and gefitinib treatment synergistically inhibit ESCA progression in vitro and in vivo. Our data indicate the mechanisms underlying ESCA progression at the layer of mRNA translation control and provide molecular insights for the development of effective cancer therapeutic strategies.

Deregulation of METTL1-mediated N7- methylguanosine tRNA modification can promote oncogenesis. Here, the authors report that this modification regulates the translation of proteins in both the mTOR and negative regulators of autophagy pathways, resulting in the progression of esophageal squamous cell carcinoma.

Esophageal cancer is a lethal malignancy with a high mortality rate, while the molecular mechanisms underlying esophageal cancer pathogenesis are still poorly understood. Here, we found that the N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and associated with poor patient prognosis. Depletion of METTL3 results in decreased ESCC growth and progression in vitro and in vivo. We further established ESCC initiation and progression models using Mettl3 conditional knockout mouse and revealed that METTL3-mediated m6A modification promotes ESCC initiation and progression in vivo. Moreover, using METTL3 overexpression ESCC cell model and Mettl3 conditional knockin mouse model, we demonstrated the critical function of METTL3 in promoting ESCC tumorigenesis in vitro and in vivo. Mechanistically, METTL3-catalyzed m6A modification promotes NOTCH1 expression and the activation of the Notch signaling pathway. Forced activation of Notch signaling pathway successfully rescues the growth, migration, and invasion capacities of METTL3-depleted ESCC cells. Our data uncovered important mechanistical insights underlying ESCC tumorigenesis and provided molecular basis for the development of novel strategies for ESCC diagnosis and treatment.

Shale gas is a green, low-carbon and clean unconventional natural gas energy. China is rich in shale gas resources. Accelerating shale gas exploration and development is of great practical significance to improve China's energy structure and achieve the goal of “2030 carbon peak and 2060 carbon neutralization”. The Ordovician Wufeng Formation to Silurian Longmaxi Formation in Sichuan Basin is the key strata for shale gas exploration and development in China. Based on the experimental analysis of shale gas in Wufeng Formation to Longmaxi Formation in Weiyuan, Changning, Zhaotong, Fuling and Weirong areas of Sichuan Basin, this paper systematically analyzes the geochemical characteristics of shale gas in Wufeng Formation to Longmaxi Formation, discusses the genesis of shale gas, the causes of hydrocarbon isotope inversion and the source of shale gas, and looks forward to the exploration prospects of shale gas resources in the basin. It has important guiding significances for shale gas exploration and development in Sichuan Basin and even in China. The results show that: (1) The shale gas of Wufeng-Longmaxi Formations is a typical dry gas, and the hydrocarbon isotopes are distributed in negative sequence. The carbon isotopes of alkane gas in Changning, Zhaotong and Fuling areas are heavier and have a higher degree of thermal evolution than those in Weiyuan and Weirong areas, and the rare gas is of crustal origin. (2) Shale gas of Wufeng-Longmaxi Formations is a thermogenic oil-typed gas at high-over mature stage, which is mainly the mixture of crude oil cracking gas and kerogen cracking gas. The hydrocarbon isotope inversion of alkane gas is mainly caused by the mixing of crude oil cracking gas and kerogen cracking gas at high-over mature stage, the exchange between formation water and methane at high evolution stage and so on. (3) The carbon isotopic values of methane in shale gas of Wufeng-Longmaxi Formations match the carbon isotopic values of kerogen in mudstones of Longmaxi Formation of Lower Silurian, which conforms to the law of carbon isotopic fractionation δ13Ckerogen>δ13Coil>δ13Calkane gas. (4) The total amount of marine, marine continental transitional and continental facies shale gas resources in Sichuan Basin is about 41.5 × 1012 m3, with broad exploration prospects in resource potential.

Tight sandstone gas reservoirs of Xujiahe Formation in central Sichuan Basin have generally high water saturation. The characteristics of natural gas migration and accumulation, as well as gas reservoirs with high water saturation formation mechanism, were investigated using test data from natural gas geochemistry analysis and nuclear magnetic resonance (NMR) high pressure filling simulation experiment. The findings reveal that: (1)The Xujiahe Formation established the foundation for oil and gas near-source accumulation by interacting superimposed large areas of source rock and reservoir. As the maturity of source rocks increases, the wetness becomes smaller and the δ13C1 value becomes heavier of natural gas, indicating a near-source accumulation. (2)The gas saturation of Xujiahe Formation gas reservoirs ranges from 50% to 65%, with a pore radius of the reservoir space 0.1–10 μm. The larger the proportion of relatively large pore size, the higher the gas saturation will be. (3)As charging pressure is increased, natural gas accumulates in tight sandstone by progressively aggregating from large pore diameter to small pore diameter space, culminating “three-stage” charging characteristics of rapid increase, moderate increase and basically stable charge. The coupling between low-pressure drive and relatively large pore reservoir is the fundamental reason why the Xujiahe Formation of natural gas can form large-medium gas reservoirs but high water saturation in central Sichuan Basin. The findings will provide theoretical and technical support for the exploration of tight sandstone.

In addition to traditional gypsum salt rocks and shale rocks, many studies have confirmed that carbonate rocks also work as oil and gas seals. Breakthrough pressure is a characteristic parameter for the evaluation of the sealing ability of cap rocks. Different lithology types and lengths of carbonate rocks were subjected to breakthrough pressure measurement experiments at different temperatures, results showed that lithology, permeability and fracture development have obvious effects to rock characteristics. At the same temperature, sample length does not have a good correlation with breakthrough pressure, however, at different temperatures, the breakthrough pressure of most samples gradually decreases with the increase of temperature. Therefore, formation temperature has a non-negligible effect on the sealing ability of cap rocks. It is a key factor that needs to be considered for the evaluation of the sealing capacity of cap rocks. The carbonate rock with a high argillaceous content has better sealing capacity under high geothermal conditions.

Breakthroughs have been made for the natural gas exploration of the Middle Devonian and the Middle Permian formations in the Sichuan Basin in recent years. Nevertheless, its natural gas source is still not clear, which then affects the next exploration deployment decision. A comprehensive study is conducted on the geochemical characteristics of the Middle Devonian and the Middle Permian natural gas, the biomarkers of reservoir bitumen, and the source rocks. The results show that these natural gases are secondary cracking dry gas that includes more than 86% of methane content, a small amount of ethane, propane, and a non-hydrocarbon gas (e.g., nitrogen, carbon dioxide, and hydrogen sulfide). The natural gas maturity varies slightly in different regions. The carbon and hydrogen isotope values of natural gas are as follows: δ13C1 ranges from −35.7‰ to −27.3‰, δ13C2 ranges from −38.7‰ to −26.6‰, δ13C3 ranges from −37‰ to −26.5‰, δ2HCH4 ranges from −141‰ to −138‰, and δ2HC2H6 ranges from −164‰ to −112‰. The isotope values indicate that the genetic type of natural gas is the sapropelic type and the mixture type is dominated by sapropelic type. The difference between natural gas values of δ13C1, δ13C2, and δ2HCH4 in different regions is related to the contribution ratio of source rocks from different ages. The gases of the Middle Devonian and the Middle Permian of the Shuangyushi structure in Northwestern Sichuan, the Middle Permian of Southwestern Sichuan, and the Middle Permian of Paleo-uplift in Central Sichuan are mainly derived from the Cambrian Qiongzhusi Formation and the Middle-Lower Permian source rocks. The Middle-Upper Permian natural gases of the volcanic reservoir in Southwestern Sichuan is mainly from the Qiongzhusi source rock. The Middle Permian natural gases of the Hewanchang structure in Northwestern Sichuan, Eastern Sichuan, and Southern Sichuan are mainly derived from the Silurian Longmaxi source rock. The research results have important guiding significance for developing exploration and deployment solutions for natural gas of the Middle Devonian and the Middle Permian formation in the Sichuan Basin.

A series of quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety were designed, synthesized and evaluated for their biological activities against phytopathogenic microorganisms. Antimicrobial bioassays in vitro indicated that most of the target compounds exhibited more significant antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) than the agricultural bactericide thiadiazole-copper. A comparative molecular similarity index analysis (CoMSIA) model with cross-validated q2 and non-cross-validated r2 values of 0.561 and 0.882 was generated to investigate the structure-activity relationships of title compounds against Xoo. Title compound 6w, which was rationally designed under the guidance of obtained CoMSIA model, exhibited the excellent anti-Xoo effect in vitro with an EC50 value of 29.10 μg/mL, which is approximately 3-folds more effective than thiadiazole-copper (113.93 μg/mL). In addition, compound 6i demonstrated the impressive antifungal effects against Rhizoctonia solani (Rs) and Fusarium graminearum (Fg) in vitro, with the corresponding EC50 values of 11.01 μg/mL and 36.00 μg/mL, which is obviously better than the agricultural fungicide hymexazol (76.74 μg/mL and 56.19 μg/mL, respectively). The above researches indicate that quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety could be further studied as template molecules of novel agricultural microbicides. Keywords: Quinazolin-4(3H)-one, 1,3,4-oxadiazole thioether, Antibacterial activity, Antifungal activity, 3D-QSAR

The Pax7+ muscle stem cells (MuSCs) are essential for skeletal muscle homeostasis and muscle regeneration upon injury, while the molecular mechanisms underlying muscle stem cell fate determination and muscle regeneration are still not fully understood. N6-methyladenosine (m6A) RNA modification is catalyzed by METTL3 and plays important functions in posttranscriptional gene expression regulation and various biological processes. Here, we generated muscle stem cell-specific METTL3 conditional knockout mouse model and revealed that METTL3 knockout in muscle stem cells significantly inhibits the proliferation of muscle stem cells and blocks the muscle regeneration after injury. Moreover, knockin of METTL3 in muscle stem cells promotes the muscle stem cell proliferation and muscle regeneration in vivo. Mechanistically, METTL3-m6A-YTHDF1 axis regulates the mRNA translation of Notch signaling pathway. Our data demonstrated the important in vivo physiological function of METTL3-mediated m6A modification in muscle stem cells and muscle regeneration, providing molecular basis for the therapy of stem cell-related muscle diseases.

Abstract Background Tetramic acid, thiophene and hydrazone derivatives were found to exhibit favorable antifungal activity. Aiming to discover novel template molecules with potent antifungal activity, a series of novel 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives containing a hydrazone group were designed, synthesized, and evaluated for their antifungal activity. Results The structures of 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives bearing a hydrazone group were confirmed by FT-IR, 1H NMR, 13C NMR, 1H-1H NOESY, EI-MS and elemental analysis. Antifungal assays indicated that some title compounds exhibited antifungal activity against Fusarium graminearum (Fg), Rhizoctorzia solani (Rs), Botrytis cinerea (Bc) and Colletotrichum capsici (Cc) in vitro. Strikingly, the EC50 value of 5e against Rs was 1.26 µg/mL, which is better than that of drazoxolon (1.77 µg/mL). Meanwhile, title compounds 5b, 5d, 5e–5g, 5n–5q and 5t exhibited remarkable anti-Cc activity, with corresponding EC50 values of 7.65, 9.97, 6.04, 6.66, 7.84, 7.59, 9.47, 5.52, 6.41 and 7.53 µg/mL, respectively, which are better than that of drazoxolon (19.46 µg/mL). Conclusions A series of 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives bearing a hydrazone group were designed, synthesized and evaluated for their antifungal activity against Fg, Rs, Bc and Cc. Bioassays indicated that some target compounds exhibited obvious antifungal activity against the above tested fungi. These results provide a significant basis for the further structural optimization of tetramic acid derivatives as potential fungicides.

The Kuche Depression is considered as the most important gas resource potential and gas exploring area with great gas resource potential and prospect in the Tarim Basin. Based on geochemical experimental analyses and comprehensive geological studies, the general geochemical characteristics of molecular and isotope compositions of rare gases as well as hydrocarbon gases and nonhydrocarbon gases are comparatively studied in the Kuche and Southwestern Depressions. Then, their genetic types are separately identified and gas originations are comprehensively discussed. The main results are as follows. (1) Gas fields in the Kuche Depression have a higher methane abundance, accompanied with low N2 and CO2 abundances, but the Akemomu gas field in the Southwestern Depression has a relatively lower average methane abundance, accompanied with high average N2 and CO2 abundances. The helium abundance of natural gases in gas fields from the Kuche Depression general has 1 order of magnitude higher than the air value. Comparatively, it has more than 2 orders of magnitude higher than the atmospheric value in the Akemomu gas field from the Southwestern Depression. The neon, argon, krypton, and xenon abundances in both Kuche and Southwestern Depressions are lower than the corresponding air values. (2) Natural gases from gas fields in the Kuche Depression and the Southwestern Depressions are generally typical coal-formed gases. The rare gases in the Kuche Depression have typical crustal genesis, mainly deriving from the radioactive decay of elements in the crust, while in the Akemomu gas field from the Southwestern Depression, the rare gases have main crustal genesis with a proportion of 92.5%, probably accompanied with a little mantled genetic contribution. (3) Natural gases in the Kuche Depression are generally derived from coal measure source rocks of Jurassic and Triassic, which principally originated from Jurassic in strata period and coals in source rock types. The Jurassic source rocks account for 55%-75% and the Triassic source rocks account for 25%-45% approximately, while coals occupy 68% and mudstones occupy 32% separately. Natural gases from the Akemomu gas field in the Southwestern Depression mainly originated from humic mudstones of marine and continental transitional source rocks of Carboniferous to Permian.