Later Stages Of Development Research Articles

Notch Signaling Plays a Dual Role in Regulating the Neuron-to-Oligodendrocyte Switch in the Developing Dorsal Forebrain.

Neural progenitor cells in the developing dorsal forebrain generate excitatory neurons followed by oligodendrocytes (OLs) and astrocytes. However, the specific mechanisms that regulate the timing of this neuron-glia switch are not fully understood. In this study, we show that the proper balance of Notch signaling in dorsal forebrain progenitors is required to generate oligodendrocytes during late stages of embryonic development. Using ex vivo and in utero approaches in mouse embryos of both sexes, we found that Notch inhibition reduced the number of oligodendrocyte lineage cells in the dorsal pallium. However, Notch overactivation also prevented oligodendrogenesis and maintained a progenitor state. These results point toward a dual role for Notch signaling in both promoting and inhibiting oligodendrogenesis, which must be fine-tuned to generate oligodendrocyte lineage cells at the right time and in the right numbers. We further identified the canonical Notch downstream factors HES1 and HES5 as negative regulators in this process. CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated knockdown of Hes1 and Hes5 caused increased expression of the pro-oligodendrocyte factor ASCL1 and led to precocious oligodendrogenesis. Conversely, combining Notch overactivation with ASCL1 overexpression robustly promoted oligodendrogenesis, indicating a separate mechanism of Notch that operates synergistically with ASCL1 to specify an oligodendrocyte fate. We propose a model in which Notch signaling works together with ASCL1 to specify progenitors toward the oligodendrocyte lineage but also maintains a progenitor state through Hes-dependent repression of Ascl1 so that oligodendrocytes are not made too early, thus contributing to the precise timing of the neuron-glia switch.SIGNIFICANCE STATEMENT Neural progenitors make oligodendrocytes after neurogenesis starts to wind down, but the mechanisms that control the timing of this switch are poorly understood. In this study, we identify Notch signaling as a critical pathway that regulates the balance between progenitor maintenance and oligodendrogenesis. Notch signaling is required for the oligodendrocyte fate, but elevated Notch signaling prevents oligodendrogenesis and maintains a progenitor state. We provide evidence that these opposing functions are controlled by different mechanisms. Before the switch, Notch signaling through Hes factors represses oligodendrogenesis. Later, Notch signaling through an unknown mechanism promotes oligodendrogenesis synergistically with the transcription factor ASCL1. Our study underscores the complexity of Notch and reveals its importance in regulating the timing and numbers of oligodendrocyte production.

Electrochemical Assay Validation of Cancer Biomarkers for Clinical Studies

The high mortality rate of ovarian cancer is due to the late stage of detection and development of resistance despite high initial response rates to chemotherapy in about 60-70% of patients. Hence, detailed analytical and clinical assays' validation is crucial for successful translation to clinical cancer treatment, control, and prevention. We are a team of multidisciplinary researchers focusing on an electrochemical biosensor method development and evaluation for clinically significant circulating cancer biomarkers in biofluids. Electrochemical approaches offer simplicity (analogous to the personalized glucometer), shorter assay time than traditional biological assays, high analytical sensitivity combined with biological selectivity, high reproducibility (within ±5–10% STDEV among replicates) and ultra-low detection capabilities offered by the appropriate surface designs (e.g., femtomolar and lower), smaller sample (10 µL) and reagent volumes (50 µL per sample), semi-automation (microfluidics or multichannel sample dispenser), label and label-free options, throughput designs, and direct biofluid analysis (with a moderate 2–5 fold sample dilution) for minimally invasive (e.g., serum) and noninvasive analyses (e.g., saliva, urine, sweat, and tears). This presentation will discuss our pyrenyl-nanocarbon-based electrochemical immunosensor measuring cancer protein concentrations in clinical serum solutions.

Effects of Saline-Alkali Stress on Sugar Metabolism of Jujube Fruit: A Metabolomic Analysis

There have been numerous studies on the effects of salt stress on jujube fruit; however, only a few studies have reported the changes in fruit quality, particularly sugar content, under conditions of combined salt and alkali stress. Therefore, the present study aimed to investigate the performance of jujube fruits under Saline-Alkali stress and the changes in sugar content in fruits. To achieve this, jujube fruits were treated with varying concentrations of salt and alkali during five developmental periods. The content of relevant sugar components was determined, and metabolomics data were analyzed in combination with relevant quantitative gene data. The results indicated that 100 days after flowering, the surface color of jujube fruit gradually turned red, and the cell structure of the fruit gradually loosened with increasing salt and alkali concentration. The content of sugar components at each stage showed that glucose and fructose primarily accumulate in the early stage of development, while sucrose is the main component in the later stage of development. Metabolomic correlation network maps showed that six differentially accumulated metabolites were closely related to specific genes. Among these metabolites, sucrose was identified as the core metabolite in the metabolic pathway. Quantitative analysis of the related genes revealed that ZjvINV2 and ZjHK2 exhibited prolonged adaptability to stress. Additionally, the expression levels of ZjSS1 and ZjSPS2 under Saline-Alkali stress were consistent with the trend of sucrose content during the same period. In conclusion, the variations in sugar content in jujube fruits during different growth stages and under Saline-Alkali treatment conditions were recorded as reference data, and the primary metabolic substances and related regulatory genes produced in jujube fruits under Saline-Alkali stress were preliminarily identified.

Mammal Reproductive Homeobox (Rhox) Genes: An Update of Their Involvement in Reproduction and Development.

The reproductive homeobox on the X chromosome (RHOX) genes were first identified in the mouse during the 1990s and have a crucial role in reproduction. In various transcription factors with a key regulatory role, the homeobox sequence encodes a "homeodomain" DNA-binding motif. In the mouse, there are three clusters of Rhox genes (α, β, and γ) on the X chromosome. Each cluster shows temporal and/or quantitative collinearity, which regulates the progression of the embryonic development process. Although the RHOX family is conserved in mammals, the interspecies differences in the number of RHOX genes and pseudogenes testifies to a rich evolutionary history with several relatively recent events. In the mouse, Rhox genes are mainly expressed in reproductive tissues, and several have a role in the differentiation of primordial germ cells (Rhox1, Rhox6, and Rhox10) and in spermatogenesis (Rhox1, Rhox8, and Rhox13). Despite the lack of detailed data on human RHOX, these genes appear to be involved in the formation of germ cells because they are predominantly expressed during the early (RHOXF1) and late (RHOXF2/F2B) stages of germ cell development. Furthermore, the few variants identified to date are thought to induce or predispose to impaired spermatogenesis and severe oligozoospermia or azoospermia. In the future, research on the pathophysiology of the human RHOX genes is likely to confirm the essential role of this family in the reproductive process and might help us to better understand the various causes of infertility and characterize the associated human phenotypes.

Characterization of some physiological traits of some bread wheat (Triticum aestivum) landraces for drought tolerance at late developmental stages

Characterization of some physiological traits of some bread wheat (Triticum aestivum) landraces for drought tolerance at late developmental stages

Study of Chemical Additives for Optimization of Binary Systems Used for Downhole Thermochemical Treatment of Heavy Oil

Currently, most explored oil fields in Russia are at a late stage of development, and in order to maintain high levels of oil production, it is rational to put into operation fields with hard-to-recover reserves. For complicated oil fields, in particular fields with high-viscosity oil, the known traditional methods of development are ineffective. Therefore, the search for new technologies for the development and operation of such fields to significantly increase oil recovery and intensify production is of fundamental importance. One such method of heat treatment of the bottomhole formation zone is the use of heat and gas generating systems on site. In this work, new results were obtained on physical modeling of thermochemical reaction initiation with delayed-action catalyst (2,2-bis(hydroxymethyl)butanoic acid) filtration tests on composite core models of sandstone and carbonate with foam heat generation and initiating additives of binary type. Using hydrodynamic modelling, the results of laboratory studies were reproduced, and the preliminary efficiency of the developed technology for thermochemical treatment of deposits in the Samara region (Russia) was evaluated.

Identification of watermelon H3K4 and H3K27 genes and their expression profiles during watermelon fruit development.

The ClaH3K4s and ClaH3K27s gene families are subfamilies of the SET family, each with a highly conserved SET structure domain and a PHD structural domain. Both participate in histone protein methylation, which affects the chromosome structure and gene expression, and is essential for fruit growth and development. In order to demonstrate the structure and expression characteristics of ClaH3K4s and ClaH3K27s in watermelon, members of the watermelon H3K4 and H3K27 gene families were identified, and their chromosomal localization, gene structure, and protein structural domains were analyzed. The phylogeny and covariance of the gene families with other species were subsequently determined, and the expression profiles were obtained by performing RNA-Seq and qRT-PCR. The watermelon genome had five H3K4 genes with 3207-8043bp nucleotide sequence lengths and four H3K27 genes with a 1107-5499bp nucleotide sequence. Synteny analysis revealed the close relationship between watermelon and cucumber, with the majority of members displaying a one-to-one covariance. Approximately half of the 'Hua-Jing 13 watermelon' ClaH3K4s and ClaH3K27s genes were expressed more in the late fruit development stages, while the changes were minimal for the remaining half. H3K4-2 expression was observed to be slightly greater on day 21 compared to other periods. Moreover, ClaH3K27-1 and ClaH3K27-2 were hardly expressed throughout the developing period, and ClaH3K27-4 exhibited the highest expression. These results serve as a basis for further functional characterization of the H3K4 and H3K27 genes in the fruit development of watermelon.

The LEA2 gene sub-family: Characterization, evolution, and potential functions in Camellia oleifera seed development and stress response

Camellia oleifera (C. oleifera) is a woody plant that is important economically due to its oil production. Late embryonic abundant (LEA) proteins are hydrophilic and thermostable proteins that accumulate during the late stages of embryo development, serving vital functions in plant development, seed oil accumulation, and stress responses. However, it remains unclear how LEAs regulate seed size, oil accumulation, and stress responses in C. oleifera. In our study, 47 LEA genes were identified across the C. oleifera genome, which were named based on their chromosomal distribution and separated into LEA2 subgroups. Ancient duplication events resulted in 3 tandem and 8 segmental duplications in the C. oleifera genome. Further analysis of genetic structure, motifs, and cis-elements demonstrated that the evolutionary relationships of the LEA gene family in C. oleifera are highly conserved with many of the LEA genes located in the chloroplast. WGCNA was used to identify modules containing co-expressed genes in different seed developmental stages, and the regulatory network revealed that CoLEA6, CoLEA26, CoLEA17, and CoLEA22 were the hub genes, acting alongside the genes involved in plant growth and abiotic stress. The qPCR analysis of 8 C. oleifera LEA genes under simulated drought stress conditions and gradient shade was conducted, and indicated that CoLEAs responded to drought and shade stresses. Overall, CoLEA22 may be critical for responses to abiotic stress and seed development. This study enable valuable insights into the roles of LEA genes in C. oleifera and establishes a foundation for further research on their function in regulating seed development, oil accumulation and stress response.

Off-target pharmacological activity at various kinases: Potential functional and pathological side effects

In drug discovery, during the lead optimization and candidate characterization stages, novel small molecules are frequently evaluated in a battery of in vitro pharmacology assays to identify potential unintended, off-target interactions with various receptors, transporters, ion channels, and enzymes, including kinases. Furthermore, these screening panels may also provide utility at later stages of development to provide a mechanistic understanding of unexpected safety findings. Here, we present a compendium of the most likely functional and pathological outcomes associated with interaction(s) to a panel of 95 kinases based on an extensive curation of the scientific literature. This panel of kinases was designed by AbbVie based on safety-related data extracted from the literature, as well as from over 20 years of institutional knowledge generated from discovery efforts. For each kinase, the scientific literature was reviewed using online databases and the most often reported functional and pathological effects were summarized. This work should serve as a practical guide for small molecule drug discovery scientists and clinical investigators to predict and/or interpret adverse effects related to pharmacological interactions with these kinases.

Molecular simulation study of liquid sulfur adsorption and diffusion in calcite nanoscale slits under varying temperature and pressure conditions

In the late stages of extensive development of high-sulfur carbonate gas reservoirs, pressure decline leads to sulfur enrichment, and when the temperature exceeds sulfur's melting point, sulfur precipitates in a liquid form, severely restricting the exploitation of high-sulfur carbonate gas reservoirs. However, the adsorption mechanism of sulfur deposition remains poorly understood. In this study, we investigated the microscopic adsorption mechanism of liquid sulfur in calcite nanopores using molecular simulation methods. Our research revealed that liquid sulfur adsorption in calcite nanopores is primarily influenced by pore size. When the pore size is less than 160 Å, multilayer adsorption dominates, with a single-layer sulfur film thickness of approximately 5 Å. At the nanoscale, 1 g of calcite with a 40 Å nanopore structure exhibits excess adsorption of liquid sulfur ranging from 0.00734 to 0.0279 g. As pressure increases, the adsorption of two or more layers intensifies, while the diffusion coefficient decreases. Conversely, as temperature rises, the density of each layer decreases, and the diffusion coefficient increases. Simultaneously, the diffusion coefficient of liquid sulfur in calcite slits exhibits a power function increase as the pore size enlarges. Under a pressure of 15 MPa, when the temperature increases from 420 K to 480 K, the diffusion coefficient increases from 6.96 × 10−11 m²/s to 3.51 × 10−10 m²/s. This study provides valuable insights into the adsorption and diffusion behavior of liquid sulfur in calcite nanopores, which can inform the development of high-sulfur carbonate reservoirs.

Expression analysis of alpha keratins and corneous beta-protein genes during embryonic development of Gekko japonicus

Epidermal appendages of birds and reptiles, including claws, feathers, scales, and setae, are primarily composed of alpha keratins (KRTs) and corneous beta-proteins (CBPs). A comprehensive and systematic knowledge of KRTs and CBPs in Schlegel's Japanese gecko (Gekko japonicus) is still lacking. In this study, 22 candidate Gecko japonicus keratin (GjKRT) family genes (12 type I genes, 10 type II genes) were identified in the G. japonicus genome. The majority of GjKRT genes across various subgroups had undergone a prolonged and highly conservative evolutionary process. Through a combination of morphological observation, RNA-seq analysis, and qRT-PCR assay, it was possible to discern the dynamic alterations in the expression of GjKRTs and Gecko japonicus corneous beta-proteins genes (GjCBPs). These findings strongly indicate that GjKRTs gradually accumulate to constitute an α-layer, which is subsequently succeeded by the formation of the corneous beta layer containing GjCBPs at late stages (40–42) of embryonic development. The epidermal appendages in G. japonicus may result from the joint accumulation of KRTs and CBPs, with stages 40–42 being critical for their development. These findings provide novel insights into KRTs and CBPs of G. japonicus and offer a foundation for investigating the functions of GjKRT and GjCBP gene families. Furthermore, this knowledge contributes to unraveling the molecular mechanisms underlying the formation of epidermal appendages in G. japonicus.

Abstract P1104: Mantarray 3D Engineered Muscle Tissue Platform Demonstrates Clinically-relevant Disease Stratification Of An In Vitro Human Duchenne Muscular Dystrophy Model

Accurately modeling disease in vitro is vital for the development of new treatment strategies and therapeutics. For cardiac diseases, direct assessment of contractile output is the “ultimate phenotype” and a reliable metric to study overall tissue function, as other ‘proxy’ measurements or biomarkers are not good predictors of muscle strength. Human 3D engineered heart tissues (EHTs) from induced pluripotent stem cells hold great potential for modeling contractile function. However, the bioengineering strategies required to generate these predictive models present limitations for many investigators. Here, we have developed an instrument platform that utilizes 3D EHTs in conjunction with a label-free, magnetic sensing array (Mantarray). The platform enables facile and reproducible fabrication of 3D EHTs using virtually any cell source and is coupled with parallel direct measurement of contractility. This approach enables clinically relevant functional measurements of muscle, stratification of healthy vs. diseased muscle phenotypes, and facilitates therapeutic modality-agnostic compound safety and efficacy screening. We present a 3D model of Duchenne muscular dystrophy (DMD) that utilizes EHTs formed from an isogenic pair of healthy and diseased cells. DMD tissues display functional deficits across numerous metrics of contractility, including force and relaxation kinetics, though beat rate remains unchanged. EHTs remain functional over months in culture and provide a large experimental window to not only study therapeutic effect, but also disease phenotypes that may present at later stages of development and maturity. We show both acute and chronic effects of compounds in EHTs, including a drug (BMS-986094) that failed clinical trials due to unanticipated cardiotoxicity. These data demonstrate a first-and-only commercial platform that integrates individual, well-based control of electrical stimulation across a 24-well plate of tissues to pace muscle constructs, model force-frequency, and enable exercise regimens or damage protocols. Stimulation is coupled with automated assessment of muscle contraction, providing an inclusive, medium-throughput platform for disease modeling and therapeutic discovery.

The impact of industrial structure adjustment on the spatial industrial linkage of carbon emission: From the perspective of climate change mitigation

Industrial structure adjustment is an effective way to reduce carbon emissions. When adjusting the industrial structure, changes in the input and output of industrial sectors in one region may cause changes in industrial sectors of other regions, resulting in inter-regional industrial linkages. What is the impact of industrial structure adjustment on the linkages, and how does it impact climate change? The modified gravity model combines the influence and inductive coefficients to build the carbon emission industrial spatial linkage network (ISL) using social network analysis (SNA) in this work with the data of China's 2008–2019 provincial carbon emissions. The impact of industrial structure adjustment on carbon emission industrial spatial linkage network and its effect on climate change mitigation are explored with the help of the STIRPAT model and quality assurance procedure (QAP). The results of this study are as follows: (1) The provincial carbon emissions under industrial spatial linkages show significant network characteristics, the network density increased from 0.1437 in 2008 to 0.323 in 2019. (2) There is a significant spatial spillover effect in the industrial spatial linkage network (2019) centered on Shandong and Jiangsu. The provinces can be divided into 4 blocks, which play different roles in the network. (3) The industrial structure upgrading can significantly promote the carbon emission industrial linkage network and mitigate climate change. (4) The industrial structure rationalization can promote the development of the network and mitigate climate change in the early and late development stages of carbon emissions industrial linkage. In addition, it is necessary for the government to pay more attention to the development level of the carbon emission spatial industrial linkage network when implementing industrial structure adjustment in response to climate change.

Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a potential CLL precursor state which can be detected in up to 17% in aged individuals. Recently, we described significant B-cell receptor immunoglobulin heavy chain (BCR IGH) gene repertoire skewing and clonotypic evolution up to 22 years before CLL diagnosis. However, pathobiological drivers during the earliest stages of MBL development remain incompletely characterized. In this study, we utilized the EuroClonality-NDC panel to sequence recurrently mutated genes in CLL in 39 peripheral blood samples from 16 CLL patients sampled up to 16 years prior to diagnosis. CLL diagnosis ranged from 5 months to 16 years after first blood sampling. Of 16 CLL patients, 8 (50%) presented with variants of interest in genes recurrently mutated in CLL such as NOTCH1, ATM, and SF3B1 . ATM variants and the IGLV3-21R110 mutation were present from the early stages of (pre)MBL development, while NOTCH1, SF3B1, and XPO1 variants arose closer to diagnosis. We additionally detected variants in FAT1 and PLCG2 as early as 10 years prior to CLL diagnosis. Overall, our data shows specific genetic drivers of CLL are associated with early and late stages of CLL development.

Identification of an adverse outcome pathway (AOP) for chemical-induced craniofacial anomalies using the transgenic zebrafish model.

Craniofacial anomalies are one of the most frequent birth defects worldwide and are often caused by genetic and environmental factors such as pharmaceuticals and chemical agents. Although identifying adverse outcome pathways (AOPs) is a central issue for evaluating the teratogenicity, the AOP causing craniofacial anomalies has not been identified. Recently, zebrafish has gained interest as an emerging model for predicting teratogenicity because of high throughput, cost-effectiveness and availability of various tools for examining teratogenic mechanisms. Here, we established zebrafish sox10-EGFP reporter lines to visualize cranial neural crest cells (CNCCs) and have identified the AOPs for craniofacial anomalies. When we exposed the transgenic embryos to teratogens that were reported to cause craniofacial anomalies in mammals, CNCC migration and subsequent morphogenesis of the first pharyngeal arch were impaired at 24 hours post-fertilization. We also found that cell proliferation and apoptosis of the migratory CNCCs were disturbed, which would be key events of the AOP. From these results, we propose that our sox10-EGFP reporter lines serve as a valuable model for detecting craniofacial skeletal abnormalities, from early to late developmental stages. Given that the developmental process of CNCCs around this stage is highly conserved between zebrafish and mammals, our findings can be extrapolated to mammalian craniofacial development and thus help in predicting craniofacial anomalies in human.

Content and uptake of macroelements in green fodder of mixtures of narrowleaf lupin with spring triticale

AbstractThis paper presents the results of a study conducted in 2016–2018 in the temperate conditions to evaluate the content and uptake of P, K, Ca and Mg in mixtures of narrowleaf lupin with spring triticale grown for green fodder. Two factors were analysed in the experiment: A – the proportion of components in the mixture: narrowleaf lupine 100%, narrowleaf lupine + spring triticale 75 + 25%, 50 + 50%, 25 + 75%, and spring triticale 100%; B – the harvest stage the flowering stage of narrowleaf lupine, the stage of flat green pod of narrowleaf lupine. Increasing the proportion of spring triticale in the sown mixtures in relation to narrowleaf lupine resulted in a decrease in the content of the analysed macroelements by 8.9%–28.7% on a g/kg DM basis. The greatest uptake on a kg/ha basis of macroelements was found in the mixture with an equal share of both components. Harvesting mixtures at a later stage of development increased the uptake of P, K, Ca and Mg by 98.7%–111.8% because of greater DM yield, but reduced the content of these macroelements by 12.6%–20.8% in the more mature fodder. Mixtures of narrowleaf lupine with spring triticale can provide valuable mineral nutrients for livestock.

Enhanced gas recovery: Theory, technology, and prospects

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.

Evolutionary divergence of subgenomes in common carp provides insights into speciation and allopolyploid success

Hybridization and polyploidization have made great contributions to speciation, heterosis, and agricultural production within plants, but there is still limited understanding and utilization in animals. Subgenome structure and expression reorganization and cooperation post hybridization and polyploidization are essential for speciation and allopolyploid success. However, the mechanisms have not yet been comprehensively assessed in animals. Here, we produced a high-fidelity reference genome sequence for common carp, a typical allotetraploid fish species cultured worldwide. This genome enabled in-depth analysis of the evolution of subgenome architecture and expression responses. Most genes were expressed with subgenome biases, with a trend of transition from the expression of subgenome A during the early stages to that of subgenome B during the late stages of embryonic development. While subgenome A evolved more rapidly, subgenome B contributed to a greater level of expression during development and under stressful conditions. Stable dominant patterns for homoeologous gene pairs (HGs) both during development and under thermal stress suggest a potential fixed heterosis in the allotetraploid genome. Preferentially expressing either copy of a homologous gene at higher levels to confer development and response to stress indicates the dominant effect of heterosis. The plasticity of subgenomes and their shifting of dominant expression during early development, and in response to stressful conditions, provide novel insights into the molecular basis of the successful speciation, evolution, and heterosis of the allotetraploid common carp.

Microscopic gas displacement efficiency of enhanced gas recovery in carbonate gas reservoirs with edge and bottom water

Carbonate gas reservoirs with edge and bottom water contain abundant reserves, making them key production targets in the Tarim Basin, Sichuan Basin, Ordos Basin, and other petroleum provinces. Water invasion may occur in the middle and late development stages of such reservoirs, leading to reduction of gas displacement efficiency and gas recovery. In this paper, a pore-scale water-gas immiscible flow model is established by coupling the fluid flow equation and the gas-water contact (GWC) tracking equation. The process of gas displacement with water is simulated in the heterogeneous porous media generated by the quartet structure generation set (QSGS). Finally, the mechanisms of remaining gas distribution and formation are analyzed, and the variation mechanism of microscopic gas displacement efficiency is discussed. The results are obtained in three aspects. First, the remaining gas is distributed at the blind end, in the pore-throat and as clusters, with their proportions and scales jointly controlled by microscopic pore structures, wettability and capillary number. The remaining gas can be further produced by changing the production pressure differential to disturb the original pressure system and gas expansion, so as to improve the microscopic gas displacement efficiency. Second, the microscopic gas displacement efficiency is closely related to the gas flow process. Formation or expansion of each water flow path may cause rapid increase of water cut and slows down the increase of gas displacement efficiency. Third, the microscopic pore structure and wettability are the inherent features of the gas reservoir, so the capillary number can be optimized to change the mode of GWC advancement, and then to effectively improve the microscopic gas displacement efficiency. It is concluded that for real gas wells, the evolution of mechanical mechanisms of GWC advancement should be revealed depending upon the microscopic pore structure and wettability of the reservoir, and then the optimal capillary number can be determined. Furthermore, clarifying the pore-scale water-gas flow characteristics and physical mechanism of microscopic gas displacement provides guidance for the planning of enhanced gas recovery.

A new method for evaluating the utilization effect of carbonate gas reservoir reserves

After nearly 60 years of development, the carbonate gas reservoirs in Sichuan Basin have entered the middle and late stages of development. Affected by various geological factors such as complex structure, formation water distribution and water invasion intensity, low permeability, fracture development degree, fracture-cavity combination, etc., and the difference of development technical policies, the utilization effect of reserves varies greatly among different gas reservoirs. Moreover, the current indicators for evaluating the utilization effect of reserves are mainly reserve utilization degree, dynamic-static reserve ratio, recovery degree, etc., yet a unified evaluation method has not been formed. In order to effectively evaluate the utilization effect of reserves and improve the development benefit of gas reservoirs, the evaluation of utilization effect of reserves was carried out by comprehensively considering geological characteristics and development technical policies. On this basis, a new method for evaluating the utilization effect of carbonate gas reservoir reserves was formed and applied in specific gas reservoirs. The research results show that: 1) The quality of reserve utilization can accurately evaluate the utilization effect of gas reservoir reserves; 2) By introducing big data analysis technology, comprehensively using ward clustering analysis method and Pearson coefficient to correlate the main influencing factors of reserve utilization effect, a prediction model of reserve utilization effect was established; 3) The WBT Carboniferous gas reservoir was chosen to verify the aforementioned model, and the result shows that the model has high prediction accuracy and strong adaptability, which can accurately evaluate the utilization effect of developed gas reservoir reserves. The model is also applicable to evaluating the utilization effect of undeveloped gas reservoirs. In conclusion, by adopting big data analysis, the established prediction model of reserve utilization effect is suitable for quantitative evaluation and analysis of reserve utilization effect of carbonate gas reservoirs, which can provide a basis for guiding the formulation of reasonable development technical policies and improving the reserve utilization effect for similar types of gas reservoirs.