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Tight reservoirs are the focus of unconventional oil and gas resource development, but most tight reservoirs exhibit complex pore structures, strong non-homogeneity, and limited water drive development. Fracturing fluid imbibition is a critically important way to improve the recovery of tight reservoirs. In this paper, an NMR experimental device was used to conduct imbibition experiments in tight reservoirs, and the relationship between temperature, pressure, matrix permeability, and imbibition recovery was investigated. Based on the fracturing fluid imbibition recovery curve, the imbibition process is divided into the fast imbibition stage, slow imbibition stage, and imbibition equilibrium. In addition, based on the pore structure division, the recovery changes of each pore under different experimental conditions were quantitatively analyzed. The results indicate that the highest imbibition recovery is achieved at an experimental pressure of 5 MPa within the range of 0 MPa to 15 MPa. Increasing the experimental pressure can increase the imbibition rate but will not increase imbibition recovery. Within the investigated range in this paper, fracturing fluid imbibition increases with rising temperature and matrix permeability. Moreover, the recovery of each pore gradually increases with the experimental pressure ranging from 0 MPa to 5 MPa. The recovery of each pore is positively correlated with matrix permeability and temperature. During the experiment, micropores contributed the most to the recovery, while macropores contributed the least. The study in this paper guides the efficient development of tight reservoirs. [ABSTRACT FROM AUTHOR]

Objective: Efficacy and safety of perampanel monotherapy for treating focal‐onset seizures (FOS) has been barely studied in China. This observational study aimed to evaluate the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS. Methods: This single‐center, prospective, real‐world observational study enrolled patients aged ≥4 years with FOS who visited the Epilepsy Out‐Patient Clinic of Nanjing Brain Hospital affiliated to Nanjing Medical University from January 2020 to December 2021. All patients were treated with perampanel monotherapy. Seizure‐freedom rates after 6 and 12 months of treatment were calculated. Adverse events (AEs) were recorded. Results: Seventy patients with FOS were enrolled. The mean maintenance perampanel dose was 4.64 ± 1.55 mg/day. The 6‐ and 12‐month retention rates of perampanel monotherapy were 78.6% (55/70) and 70.0% (49/70), respectively. The 6‐ and 12‐month seizure‐freedom rates were 69.84% (44/63) and 65.08% (41/63), respectively. Patients with focal to bilateral tonic–clonic seizures had significantly higher 6‐month and numerically higher 12‐month seizure freedom rates than patients with focal impaired awareness seizures (P = 0.046 and P = 0.204, respectively). Twenty‐six (37.1%) patients experienced treatment‐emergent AEs, and the most common AE was dizziness. Four (5.7%) patients withdrew from the study due to AEs. No new safety concern was observed. Significance: This is the first prospective study on the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS, and perampanel monotherapy was effective and safe in treating Chinese patients aged ≥4 years with FOS up to 12 months. More multicenter, real‐world studies with large sample sizes and longer follow‐ups are needed to further evaluate the long‐term efficacy and safety of perampanel monotherapy. [ABSTRACT FROM AUTHOR]

Abstract: The circadian clock enables organisms to rapidly adapt to the ever‐changing environmental conditions that are caused by daily light/dark cycles. Circadian clock genes universally affect key agricultural traits, particularly flowering time. Here, we show that OsPRR37, a circadian clock gene, delays rice flowering time in an expression level‐dependent manner. Using high‐throughput mRNA sequencing on an OsPRR37 overexpressing transgenic line (OsPRR37‐OE5) and the recipient parent Guangluai4 that contains the loss‐of‐function Osprr37, we identify 14,992 genes that display diurnal rhythms, which account for 52.9% of the transcriptome. Overexpressing OsPRR37 weakens the transcriptomic rhythms and alters the phases of rhythmic genes. In total, 3,210 differentially expressed genes (DEGs) are identified, among which 1,863 rhythmic DEGs show a correlation between the change of absolute amplitudes and the mean expression levels. We further reveal that OsPRR37 functions as a transcriptional repressor to repress the expression levels and amplitudes of day‐phased clock genes. More importantly, OsPRR37 confers expanded regulation on the evening‐phased rhythmic DEGs by repressing the morning‐phased rhythmic DEGs. Further study shows that OsPRR37 expands its regulation on flowering pathways by repressing Ehd1. Thus, our results demonstrate an expanded regulation mechanism of the circadian clock on the diurnal rhythms of the transcriptome. [ABSTRACT FROM AUTHOR]

Plant architecture directly affects biomass in higher plants, especially grain yields in agricultural crops. In this study, we characterized a recessive mutant, plant architecture determinant ( pad), derived from the Oryza sativa ssp. indica cultivar MH86. The mutant exhibited severe dwarf phenotypes, including shorter and stunted leaves, fewer secondary branches during both the vegetative and reproductive growth stages. Cytological studies revealed that pad mutant growth defects are primarily due to the inhibition of cell expansion. The PAD gene was isolated using a map-based cloning strategy. It encodes a plasma membrane protein OsMCA1 and a SNP responsible for a single amino acid change was found in the mutant. PAD was universally expressed in rice tissues from the vegetative to reproductive growth stages, especially in seedlings, nodes and rachillae. Quantitative real-time PCR analysis revealed that the most of the genes responding to gibberellin (GA) metabolism were up-regulated in pad mutant internodes. The endogenous GA content measurement revealed that the levels of GA were significantly decreased in the third internode of pad mutants. Moreover, a GA response assay suggested that OsMCA1/PAD might be involved in the regulation of GA metabolism and signal transduction. Our results revealed the pad is a loss-of-function mutant of the OsMCA1/PAD, leading to upregulation of genes related to GA deactivation, which decreased bioactive GA levels. [ABSTRACT FROM AUTHOR]

Aims Arsenic trioxide (ATO), an effective therapeutic agent for acute promyelocytic leukaemia, can cause sudden cardiac death due to long QT syndrome (LQTS). The present study was designed to determine whether ATO could induce cardiac fibrosis and explore whether cardiac fibroblasts (CFs) are involved in the development of LQTS by ATO. Methods and results ATO treatment of guinea pigs caused substantial interstitial myocardial fibrosis and LQTS, which was accompanied by an increase in transforming growth factor β1(TGF-β1) secretion and a decrease in ether-à-go-go-related gene (HERG) and inward rectifying potassium channel (IK1) subunit Kir2.1 protein levels. ATO promoted collagen production and TGF-β1 expression and secretion in cultured CFs. Whole-cell patch clamp and western blotting showed that treatment with TGF-β1 markedly reduced HERG and IK1 current densities and downregulated HERG and Kir2.1 protein expression in HEK293 cells stably transfected with the human recombinant HERG channel and in cardiomyocytes (CMs). These changes were completely reversed by treatment with the protein kinase A (PKA) antagonist, H89. CM and CF co-cultures showed that ATO significantly increased TGF-β1 levels in the culture medium, whereas markedly reduced HERG and Kir2.1 protein levels were observed in CMs compared with ATO-treated CMs not co-cultured with CFs. Finally, in vivo administration of LY364947, a pharmacological antagonist of TGF-β signalling, dramatically prevented interstitial fibrosis and LQTS and abolished aberrant expression of TGF-β1, HERG, and Kir2.1 in ATO-treated guinea pigs. Conclusion ATO-induced TGF-β1 secretion from CFs aggravates QT prolongation, suggesting that modulation of TGF-β signalling may provide a novel strategy for the treatment of drug-induced LQTS. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor-1 alpha (HIF-1α) is a central transcriptional regulator of hypoxic response. The present study was designed to investigate the role of HIF-1α in mild hypoxia-induced cardiomyocytes hypertrophy and its underlying mechanism. Mild hypoxia (MH, 10% O2) caused hypertrophy in cultured neonatal rat cardiac myocytes, which was accompanied with increase of HIF-1α mRNA and accumulation of HIF-1α protein in nuclei. Transient receptor potential canonical (TRPC) channels including TRPC3 and TRPC6, except for TRPC1, were increased, and Ca2+-calcineurin signals were also enhanced in a time-dependent manner under MH condition. MH-induced cardiomyocytes hypertrophy, TRPC up-regulation and enhanced Ca2+-calcineurin signals were inhibited by an HIF-1α specific blocker, SC205346 (30 μM), whereas promoted by HIF-1α overexpression. Electrophysiological voltage-clamp demonstrated that DAG analogue, OAG (30 μM), induced TRPC current by as much as 170% in neonatal rat cardiomyocytes overexpressing HIF-1α compared to negative control. These results implicate that HIF-1α plays a key role in development of cardiac hypertrophy in responses to hypoxic stress. Its mechanism is associated with up-regulating TRPC3, TRPC6 expression, activating TRPC current and subsequently leading to enhanced Ca2+-calcineurin signals. [ABSTRACT FROM AUTHOR]

To study the impact of the fractures on development in the ultra-low permeability sandstone reservoir of the Yangchang Formation of the Upper Triassic in the Ordos Basin, data on outcrops, cores, slices, well logging and experiments are utilized to analyze the cause of the formation of the fractures, their distribution rules and the control factors and discuss the seepage flow effect of the fractures. In the studied area developed chiefly high-angle tectonic fractures and horizontal bedding fractures, intergranular fractures and grain boundary fractures as well. Grain boundary fractures and intragranular fractures serve as vital channels linking intragranular pores and intergranular solution pores in the reservoir matrix, thus providing a good connectivity between the pores in the ultra-low permeability sandstone reservoir. The formation of fractures and their distribution are influenced by such external and internal factors as the palaeo-tectonic stress field, the reservoir lithological character, the thickness of the rock layer and the anisotropy of a layer. The present-day stress field influences the preservative state of fractures and their seepage flow effect. Under the tectonic effect of both the Yanshan and Himalayan periods, in this region four sets of fractures are distributed, respectively assuming the NE-SW, NW-SE, nearly E-W and nearly S-N orientations, but, due to the effect of the rock anisotropy of the rock formation, in some part of it two groups of nearly orthogonal fractures are chiefly distributed. Under the effect of the present-day stress field, the fractures that assume the NE-SW direction have a good connectivity, big apertures, a high permeability and a minimum starting pressure, all of which are main advantages of the seepage fractures in this region. With the development of oilfields, the permeability of the fractures of different directions will have a dynamic change. [ABSTRACT FROM AUTHOR]

The global greenhouse effect makes carbon dioxide (CO2) emission reduction an important task for the world, however, CO2 can be used as injected fluid to develop shale oil reservoirs. Conventional water injection and gas injection methods cannot achieve desired development results for shale oil reservoirs. Poor injection capacity exists in water injection development, while the time of gas breakthrough is early and gas channeling is serious for gas injection development. These problems will lead to insufficient formation energy supplement, rapid energy depletion, and low ultimate recovery. Gas injection huff and puff (huff-n-puff), as another improved method, is applied to develop shale oil reservoirs. However, the shortcomings of huff-n-puff are the low sweep efficiency and poor performance for the late development of oilfields. Therefore, this paper adopts firstly the method of Allied In-Situ Injection and Production (AIIP) combined with CO2 huff-n-puff to develop shale oil reservoirs. Based on the data of Shengli Oilfield, a dual-porosity and dual-permeability model in reservoir-scale is established. Compared with traditional CO2 huff-n-puff and depletion method, the cumulative oil production of AIIP combined with CO2 huff-n-puff increases by 13,077 and 17,450 m3 respectively, indicating that this method has a good application prospect. Sensitivity analyses are further conducted, including injection volume, injection rate, soaking time, fracture half-length, and fracture spacing. The results indicate that injection volume, not injection rate, is the important factor affecting the performance. With the increment of fracture half-length and the decrement of fracture spacing, the cumulative oil production of the single well increases, but the incremental rate slows down gradually. With the increment of soaking time, cumulative oil production increases first and then decreases. These parameters have a relatively suitable value, which makes the performance better. This new method can not only enhance shale oil recovery, but also can be used for CO2 emission control. [ABSTRACT FROM AUTHOR]

A long non-coding RNA (lncRNA), named myocardial infarction associated transcript (MIAT), has been documented to confer risk of myocardial infarction (MI). The aim of this study is to elucidate the pathophysiological role of MIAT in regulation of cardiac fibrosis. In a mouse model of MI, we found that MIAT was remarkably up-regulated, which was accompanied by cardiac interstitial fibrosis. MIAT up-regulation in MI was accompanied by deregulation of some fibrosis-related regulators: down-regulation of miR-24 and up-regulation of Furin and TGF-β1. Most notably, knockdown of endogenous MIAT by its siRNA reduced cardiac fibrosis and improved cardiac function and restored the deregulated expression of the fibrosis-related regulators. In cardiac fibroblasts treated with serum or angiotensin II, similar up-regulation of MIAT and down-regulation of miR-24 were consistently observed. These changes promoted fibroblasts proliferation and collagen accumulation, whereas knockdown of MIAT by siRNA or overexpression of miR-24 with its mimic abrogated the fibrogenesis. Our study therefore has identified MIAT as the first pro-fibrotic lncRNA in heart and unraveled the role of MIAT in the pathogenesis of MI. These findings also promise that normalization of MIAT level may prove to be a therapeutic option for the treatment of MI-induced cardiac fibrosis and the associated cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Artificial selection of high yield crops and better livestock is paramount importance in breeding programs. Selection of elite parents with preferred traits from a phalanx of inbred lines is extremely laborious, time-consuming and highly random. General combining ability (GCA) was proposed and has been widely used for the evaluation of parents in hybrid breeding for more than half a century. However, the genetic and molecular basis of GCA has been largely overlooked. Here, we present two pleotropic QTLs are accounting for GCA of days to heading (DTH), plant height (PH) and spikelet per panicle (SPP) using an F2-based NCII design, the BC3F2 population as well as a set of nearly isogenic lines (NILs) with five testers. Both GCA1 and GCA2 were loss-of-function gene in low-GCA parent and gain-of-function gene in high-GCA parent, encoding the putative Pseudo-Response Regulators, OsPRR37 and Ghd7, respectively. Overexpression of GCA1 in low-GCA parent significantly increases GCA effects in three traits. Our results demonstrate that two GCA loci associate with OsPRR37 and Ghd7 and reveal that the genes responsible for important agronomic traits could simultaneously account for GCA effects. [ABSTRACT FROM AUTHOR]