Effect of proppant sizes and injection modes on proppant transportation and distribution in the tortuous fracture model

Particle-fluid transport and placement mechanism in tortuous fracture played a crucial role in uncon-ventional reservoirs.Currently,most studies focused on mono-size proppant with fluid transport pro-cesses in tortuous fractures.However,the mixture-size proppant with fluid movement mechanism in tortuous fracture was still uncommon.Therefore,this study designed and applied a series of experiments with a physical analog model of a tortuous fracture with 120°and 90°-angled bends and combined high-speed camera-based equipment.This experimental system was used to track different-mixture-sized proppant particle motion trajectories for a series of proppant injection schemes;The following conclu-sions were drawn from this study:1.The pile-up processes mechanism in all investigated schemes were similar and could be reduced to four main stages.2.The packing structure at both sides of the fracture wall had different variation rates,which were controlled by the mix ratio(change from 1∶1-1∶5)of proppant size.3.Some new packing patterns,such as Zebra Stripe,had occurred,controlled by the different proppant injection sequences.4.Small-sized mono-proppant(30/50 mesh)had the highest transport efficiency in the tortuous fracture,followed by the mixed-sized multi-proppant(10/20 mesh:30/50 mesh),large-sized proppant(10/20 mesh)was the worst.5.An optimized alternating in-jection mode was recommended as injecting small-sized proppant first(30/50 mesh)and followed by mixed-sized multi-proppant(10/20 mesh:30/50 mesh),which could contribute to obtaining the optimal both proppant packing height and travel distance in tortuous fracture.6.Two correlations were devel-oped for predicting the proppant packing height and transportation distance.

FTO-mediated m6A modification alleviates autoimmune uveitis by regulating microglia phenotypes via the GPC4/TLR4/NF-κB signaling axis

Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclear.N6-methyladenosine(m^(6)A)modification has been proven to be involved in the immune response.Therefore,we in this work aimed to identify the potentially crucial m^(6)A regulators of microglia in uveitis.Through the single-cell sequencing(scRNA-seq)analysis and experimental verification,we found a significant decrease in the expression of fat mass and obesity-associated protein(FTO)in retinal microglia of uveitis mice and human microglia clone 3(HMC3)cells with inflammation.Additionally,FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia.Mechanistically,the RNA-seq data and rescue experiments showed that glypican 4(GPC4)was the target of FTO,which regulated microglial inflammation mediated by the TLR4/NF-κB pathway.Moreover,RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m^(6)A“reader”YTH domain family protein 3(YTHDF3).Finally,the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis(EAU)inflammation by promoting the GPC4/TLR4/NF-κB signaling axis,and this could be attenuated by the TLR4 inhibitor TAK-242.Collectively,a decreased FTO could facilitate microglial inflammation in EAU,suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis.

Assessment of non-target toxicity effects of synthetic estradiol, quinestrol, in chickens

Fertility control agents for the management of rodent populations are developing and maturing.Investigating the impacts on non-target species of consumption of these agents is essential.The present study assessed the non-target toxicity effects of quinestrol,a synthetic estrogen-based antifertility agent for managing rodent populations.Various quinestrol doses administered to male and female(n=60 each)chickens through single oral gavage were 0(A),10(B),50(C),and 150(D)mg/kg body weight.Chickens were assessed for effect on body weight,weight of vital and reproductive organs,reproductive hormones,histology of reproductive organs and egg laying rates after 15,30,and 135 days of treatment.Quinestrol did not induce mortality in chickens and its effects were time and dose dependent.The 90%egg-laying rates were delayed by 30,60 for groups B and C compared with the control group,and group D did not reach the 90%egg-laying rate by 135 days.Reproductive organs in males and females returned to normal levels within 30 and 135 days,respectively.With the exception of the FSH concentration in group D,reproductive hormones of both sexes were similar to controls by 30 days.No other significant effects were found.The present research demonstrated the safety of quinestrol on non-target species and facilitates recommendations for the general administration of quinestrol for rodent pest management.

Ceramic membrane fouling mechanisms and control for water treatment

Membrane separation, as an important drinking water treatment technology, has wide applications. The remarkable advantages of ceramic membranes, such as chemical stability, thermal stability, and high mechanical strength, endow them with broader prospects for development. Despite the importance and advantages of membrane separation in water treatment, the technique has a limitation: membrane fouling, which greatly lowers its effectiveness. This is caused by organics, inorganic substances, and microorganisms clogging the pore and polluting the membrane surface. The increase in membrane pollution greatly lowers purification effectiveness. Controlling membrane fouling is critical in ensuring the efficient and stable operation of ceramic membranes for water treatment. This review analyzes four mechanisms of ceramic membrane fouling, namely complete blocking, standard blocking, intermediate blocking, and cake filtration blocking. It evaluates the mechanisms underlying ceramic membrane fouling and summarizes the progress in approaches aimed at controlling it. These include ceramic membrane pretreatment, ceramic membrane surface modification, membrane cleaning, magnetization, ultrasonics, and nanobubbles. This review highlights the importance of optimizing ceramic membrane preparation through further research on membrane fouling and pre-membrane pretreatment mechanisms. In addition, combining process regulations with ceramic membranes as the core is an important research direction for ceramic membrane-based water treatment.

Nuclear factor-Y mediates pancreatic β-cell compensation by repressing reactive oxygen species-induced apoptosis under metabolic stress

Background:Pancreaticβ-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions.Deficits inβ-cell compensatory capacity result in hyperglycemia and type 2 diabetes(T2D).However,the mechanism in the regulation ofβ-cell compensative capacity remains elusive.Nuclear factor-Y(NF-Y)is critical for pancreatic islets’homeostasis under physiological conditions,but its role inβ-cell compensatory response to insulin resistance in obesity is unclear.Methods:In this study,using obese(ob/ob)mice with an absence of NF-Y subunit A(NF-YA)inβ-cells(ob,Nf-yaβKO)as well as rat insulinoma cell line(INS1)-based models,we determined whether NF-Y-mediated apoptosis makes an essential contribution toβ-cell compensation upon metabolic stress.Results:Obese animals had markedly augmented NF-Y expression in pancreatic islets.Deletion ofβ-cell Nf-ya in obese mice worsened glucose intolerance and resulted inβ-cell dysfunction,which was attributable to augmentedβ-cell apoptosis and reactive oxygen species(ROS).Furthermore,primary pancreatic islets from Nf-yaβKO mice were sensitive to palmitate-inducedβ-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response,which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase(JNK)and cleaved caspase-3.These detrimental effects were completely relieved by ROS scavenger.Ultimately,forced overexpression of NF-Y in INS1β-cell line could rescue palmitate-inducedβ-cell apoptosis,dysfunction,and mitochondrial impairment.Conclusion:Pancreatic NF-Y might be an essential regulator ofβ-cell compensation under metabolic stress.

A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing

Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.

生物多样性相关传统知识研究热点与前沿的可视化分析

传统知识研究目前已经成为生物多样性保护研究的热点领域,并对生态系统服务管理、社区可持续发展等领域产生了重要影响。本文以Web of Science (WoS)数据库为数据源,应用WoS自带的统计分析功能和可视化分析软件CiteSpace Ⅲ,采用关键词共现分析、突现词分析、文献共被引分析等方法对传统知识的研究态势、研究热点以及知识演进进行系统分析。研究发现,传统知识研究的文献数量呈逐年上升趋势;中国科学院、墨西哥国立自治大学、印度农业研究理事会、加州大学系统等研究机构在该领域表现出较强的科研实力;非洲、南美洲的巴西、玻利维亚以及亚洲的印度等地区为传统知识研究的热点区域;Albuquerque UP、Singh R、薛达元在该领域发表的学术论文最多;Berkes F、Drew JA、Gómez-Baggethun E等学者发表的论文为该领域知识基础的构建及相关研究的推进奠定了坚实的基础。与生物资源管理、生物多样性保护、生态系统服务和人类福祉、政策管理等相关的传统知识研究是未来该领域的重要方向。

武夷山试点经验及改进建议:南方集体林区国家公园保护的困难和改革的出路

国家公园体制试点在2015年1月国家发展和改革委员会等十三部委印发《建立国家公园体制试点方案》后正式开启,并在中央办公厅、国务院办公厅2017年印发《建立国家公园体制总体方案》(以下简称《总体方案》)指导下形成普遍规范, 2020年基本完成(臧振华等, 2020)。2020年是国家公园体制试点收官之年,在2021年初总结试点经验,旨在为国家公园体制试点收尾,迎接国家公园正式运行。福建省是4个国家级生态文明试验区之一,森林覆盖率多年全国第一,生态文明指数全国第一(http://49.5.6.212/html/2019-04/24/content82971.ht m)。福建武夷山国家公园是10个体制试点区之一。

生态系统完整性在管理层面的体现方式: 以跨省国家公园统一管理的体制机制为例

生态系统完整性保护是国家公园的重要管理目标,但学术上的完整性如何体现为管理上的完整性需要基于科学概念进行体制设计。从管理层面体现生态系统完整性需要突破原有的属地化要素管理模式,把国家公园作为国土空间用途管制的独立单元,将“山水林田湖草”统筹起来一体化管理,但这种管理往往因为不同行政区不同的“权、钱”相关制度引发的激励不相容而难以实现,尤其在国家公园跨省的情况下。可以首先实现跨省国家公园不同省的管理机构“权、钱”相关制度统一,再构建协调机制或组建类似资产管理的协调机构,以实现激励相容。在这样的体制机制下,今后的国家公园划界也易于突破省界藩篱,更好体现科学概念上的完整性。

Fabrication of Open-cell Al Foam Core Sandwich by Vibration Aided Liquid Phase Bonding Method and Its Mechanical Properties

The open-cell Al foam core sandwiches（AFCSs） were successfully fabricated by using a specially designed Zn-Al-Cu based filler alloy via vibration aided liquid phase bonding method.The effects of the vibration on the bonding seam were investigated and the bonding strength between Al foam core and solid Al alloy face sheet was tested by shearing tests.The results show that vibration can significantly improve the quality of the bonding and the shearing strength of the bonding seam,which implies that this joining method has a good potential in practical applications.

Obstructive Jaundice Caused by Mucinous Cystic Tumor of Gallbladder:A Case Report and Literature Review

Mucinous cystic tumor of the gallbladder is an extremely rare benign tumor,with potential for malignant degeneration.Mucinous cystic tumors of the cystic duct are divided into mucinous cystadenoma and mucinous cystadenocarcinoma.Currently,cystadenoma is generally considered to be a precancerous lesion of cystadenocarcinoma.At present,there are few cases reported worldwide,and there are no relevant guidelines for diagnosis and treatment of this disease.This article presents the collected clinical data of a patient with mucinous cystic tumor of the gallbladder who was admitted to the First Affiliated Hospital of Hunan Normal University,with the characteristics of the disease summarized in combination with a focused literature review.