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Abstract Background Intramyocardial dissecting hematoma (IDH) is a rare mechanical complication following myocardial infarction (MI), and only a few isolated cases have been reported to date. IDH presents with diverse clinical manifestations, often resulting in missed or misdiagnosed cases due to limited physician understanding. The diagnosis and treatment of IDH is a major challenge. Case presentations We report a case of acute extensive anterior MI in a 73-year-old woman, who underwent percutaneous coronary intervention (PCI); the left ventricular intramyocardial dissecting hematoma (LVIDH) penetrated the right ventricular outflow tract (RVOT), resulting in thrombus formation and subsequent RVOT obstruction. Clinically insignificant IDH was detected by transthoracic echocardiography (TTE) at 3 days, 43 days, and 75 days post-PCI, with characteristic changes in the left ventricular wall ultrasound images. This unusual case highlights the important role of continuous transthoracic echocardiography in identifying this rare complication of LVIDH. After a detailed discussion with the patient, the choice between conservative or surgical management of IDH depends on factors such as the size of the hematomae, left ventricular systolic function, and the patient’s clinical and haemodynamic status. In this particular case, conservative management was chosen by the patient who declined surgery but unfortunately succumbed to cardiogenic shock. Conclusions This case describes a rare complication of acute myocardial infarction (AMI) and also focuses on the utility of TTE in the diagnosis of this rare complication. Whether LVIDH is treated conservatively or surgically requires careful evaluation to achieve the best prognosis for the patient.

Abstract Objectives This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. Methods Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. Results There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8–56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3–69.0). The prediction model was: probability = 1/(e‑Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer–Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. Conclusions There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

Abstract Clinical metagenomics (CMg) Nanopore sequencing can facilitate infectious disease diagnosis. In China, sub-lineages ST11-KL64 and ST11-KL47 Carbapenem-resistant Klebsiella pneumoniae (CRKP) are widely prevalent. We propose PathoTracker, a specially compiled database and arranged method for strain feature identification in CMg samples and CRKP traceability. A database targeting high-prevalence horizontal gene transfer in CRKP strains and a ST11-only database for distinguishing two sub-lineages in China were created. To make the database user-friendly, facilitate immediate downstream strain feature identification from raw Nanopore metagenomic data, and avoid the need for phylogenetic analysis from scratch, we developed data analysis methods. The methods included pre-performed phylogenetic analysis, gene-isolate-cluster index and multilevel pan-genome database and reduced storage space by 10-fold and random-access memory by 52-fold compared with normal methods. PathoTracker can provide accurate and fast strain-level analysis for CMg data after 1 h Nanopore sequencing, allowing early warning of outbreaks. A user-friendly page ( http://PathoTracker.pku.edu.cn/ ) was developed to facilitate online analysis, including strain-level feature, species identifications and phylogenetic analyses. PathoTracker proposed in this study will aid in the downstream analysis of CMg.

Abstract Hydrate formation in foam drainage gas recovery wells and the shut in accidents caused by plugging have become an important problem that restricts the safe production of natural gas. The blockage and accumulation of hydrates is a gradual problem. This research goes beyond predicting the formation of hydrates and delves deeper into examining the rate of hydrate formation and the degree of pipeline blockage at different wellbore locations. First, the temperature model, pressure model, multiphase flow model, and hydrate plugging model of hydrate formation process are established from the equations of mass conservation, energy conservation, and momentum conservation. Second, an iterative approach is employed to solve the model, with a maximum error of 6.86% in model validation. Finally, sensitivity analysis shows that wellhead temperature, wellhead pressure, and foam viscosity have different effects on hydrate formation, maximum plugging position, and plugging degree. At the same time, combined with the actual drainage and gas production process, and the characteristics of hydrate blockage, proposed hydrate prevention measures can be taken to achieve safe production of natural gas. The research results indicate that a decrease in temperature signifies an increase in undercooling, resulting in an accelerated rate of hydrate formation and an elevated risk of hydrate blockage. The decrease in wellhead pressure leads to a decrease in the rate of hydrate formation and an increase in production, which is beneficial for the hydrate prevention. However, larger pressure differences and gas production rates will put higher requirements on equipment such as well control devices. An increase in foam viscosity will lead to increased pressure, foam compression, reduced drainage capacity, and intensified hydrate generation. Therefore, foam viscosity should be kept as small as possible to keep the foam stable.

To further explore the metabolism of Lycium barbarum polysaccharides, the cell wall microstructure of Lycium barbarum fruits in different growth periods was observed by transmission electron microscopy, and the cell wall polysaccharide content and its degrading enzyme activity were extracted by chemical method. The changes of polysaccharide components in cell wall of Lycium barbarum fruits in different growth periods were analyzed by microcopolymer Raman spectroscopy. The correlation between the content of polysaccharide in cell wall and the activity of degrading enzyme was analyzed. The results showed that the changes of cell wall structure mainly occurred during 28~35 d, with the cell wall becoming significantly thinner, pectin degrading, and the cell wall structure gradually collapsing. Cell wall material (CWM) content increased first and then decreased, and water-soluble pectin (WSP) content increased significantly (P

Abstract Rationale: Quinolone antibiotics are extensively used clinically for human treatment and in agriculture. However, improper and excessive use can lead to the persistence of quinolone residues in animal tissues, potentially accumulating in the human body and posing health risks. Investigating the correlation between mass spectrometry cleavage patterns and molecular structural features enhances the analytical framework for detecting trace or unknown impurities in quinolones. Methods: To collect data, we employed triple quadrupole linear ion trap mass spectrometry in electrospray positive ion mode. Primary mass spectrometry scanning was utilized to confirm parent ions, while secondary mass spectrometry scanning enabled the observation of fragment ions. The cleavage characteristics and pathways of the compounds were inferred from accurate mass‐to‐charge ratios obtained from both primary and secondary mass spectrometry. Results: Under soft ionization conditions, the compounds generally exhibited characteristic fragment ions of [M+H−H2O]+, [M+H−CO]+, and [M+H−H2O−CO]+. Additionally, subtle variations were observed in each compound due to differences in modifying groups. For instance, upon deacidification, the piperazine ring structure underwent breakage and rearrangement, yielding fragment ion peaks devoid of neutral molecules such as C2H5N, C3H7N, or C4H8N. Notably, compounds featuring a cyclopropyl substituent group at the N‐1 position typically exhibited characteristic fragments resulting from the loss of the cyclopropyl radical (⋅C3H5). Moreover, substituents at the N‐1 and C‐8 positions, when linked to form a six‐membered carbocyclic ring, were prone to cleavage, releasing the neutral C3H6 molecule. Conclusion: Quinolone antibiotics share structural similarities in their parent nuclei, leading to partially similar cleavage pathways. Nevertheless, distinct cleavage patterns emerge due to variations in functional groups. According to the difference of mass spectrometry cleavage patterns, it can provide an identification basis for the measured detection of antibiotics.

Summary: Background: The global spread of the plasmid-mediated mcr (mobilized colistin resistance) gene family presents a significant threat to the efficacy of colistin, a last-line defense against numerous Gram-negative pathogens. The mcr-9 is the second most prevalent variant after mcr-1. Methods: A dataset of 698 mcr-9-positive isolates from 44 countries is compiled. The historical trajectory of the mcr-9 gene is reconstructed using Bayesian analysis. The effective reproduction number is used innovatively to study the transmission dynamics of this mobile-drug-resistant gene. Findings: Our investigation traces the origins of mcr-9 back to the 1960s, revealing a subsequent expansion from Western Europe to the America and East Asia in the late 20th century. Currently, its transmissibility remains high in Western Europe. Intriguingly, mcr-9 likely emerged from human-associated Salmonella and exhibits a unique propensity for transmission within the Enterobacter. Our research provides a new perspective that this host preference may be driven by codon usage biases in plasmids. Specifically, mcr-9-carrying plasmids prefer the nucleotide C over T compared to mcr-1-carrying plasmids among synonymous codons. The same bias is seen in Enterobacter compared to Escherichia (respectively as their most dominant genus). Furthermore, we uncovered fascinating patterns of coexistence between different mcr-9 subtypes and other resistance genes. Characterized by its low colistin resistance, mcr-9 has used this seemingly benign feature to silently circumnavigate the globe, evading conventional detection methods. However, colistin-resistant Enterobacter strains with high mcr-9 expression have emerged clinically, implying a strong risk of mcr-9 evolving into a global “true-resistance-gene”. Interpretation: This study explores the mcr-9 gene, emphasizing its origin, adaptability, and dissemination potential. Given the high mcr-9 expression colistin-resistant strains was observed in clinically the prevalence of mcr-9 poses a significant challenge to drug resistance prevention and control within the One Health framework. Funding: This work was partially supported by the National Natural Science Foundation of China (Grant No. 32141001 and 81991533).

Background/Aims: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third leading cause of cancer-related mortality. Extensive literature suggests that long noncoding RNAs play a role in the progression of HCC and hold potential as diagnostic biomarkers for this disease. Materials and Methods: We examined the serum levels of HOX antisense intergenic RNA (HOTAIR) in 49 hepatitis patients, 31 liver cirrhosis (LC), and 37 HCC patients using quantitative real-time polymerase chain reaction. Correlations between serum HOTAIR levels and clinical data were evaluated in HCC patients. The receiver operating characteristic curve was utilized to analyze the diagnostic potency of HOTAIR. Results: The HOTAIR levels in serum were significantly higher in HCC patients compared to those with hepatitis (P = .003) and LC patients (P = .048). There was a significant association between the serum levels of HOTAIR and positivity of hepatitis B e antigen (HBeAg) (P = .039) as well as portal vein tumor thrombus (P = .040) in HCC patients. The area under the curve (AUC) for HOTAIR for distinguishing HCC from hepatitis and LC was 0.697. The combined AUC for HOTAIR, HBeAg, and alpha-fetoprotein (AFP) was 0.777. Conclusion: Serum HOTAIR functions as a potential diagnostic marker for hepatitis B virus-related HCC. Combining HOTAIR with clinical data and AFP can reinforce the diagnostic precision on HCC.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a prevalent issue in China, with its spread primarily attributed to the presence of the plasmid-borne carbapenemase genes, blaKPC and blaNDM. However, instances of plasmids containing both blaKPC-2 and blaNDM-1have never been reported. Methods: In this study, the genomic and microbiological characteristics of hybrid plasmids containing both blaKPC-2 and blaNDM-1 were identified in Chinese clinical CRKP isolates by Illumina combined with ONT nanopore sequencing technology. Results: The newly identified plasmid was formed via IS26-mediated recombination and has been shown to be transferable to Escherichia coli. It substantially elevates the minimum inhibitory concentration (MIC) of meropenem by 4000-fold in E. coli, surpassing the MIC values observed in E. coli strains that carry either blaKPC-2 and blaNDM-1 alone, as previously demonstrated in our study. Notably, the co-occurrence of the KPC–NDM fusion plasmid and a pLVPK-like virulence plasmid was observed in these organisms. In vivo experiments revealed that the isolates harbouring the pLVPK-like virulence plasmid exhibited a significantly higher lethality rate in Galleria mellonella. Conclusions: The increased antibiotic resistance brought by this novel fusion plasmid and its accompanying virulence factors pose a serious potential threat to human health and deserve our vigilance.

Abstract The social network is an important way to promote subjective poverty alleviation. Based on China Labor Dynamics Survey (CLDS) data from 2014, 2016, and 2018, this paper analyzes the action mechanism of social networks on the subjective poverty of Chinese residents. The results find that social network acts on subjective poverty through social support and reference groups. Specifically, social networks provide emotional and instrumental social support for individuals, which can effectively alleviate subjective poverty. In addition, when the social network members serve as the reference group, the higher the status of individuals in the network, the weaker the subjective poverty. Secondly, objective poverty is the mediating path between the social support function of social networks and subjective poverty. Finally, objective poverty is a regulator of the effect of social networks as a reference group on subjective poverty. When individuals are objectively poor, the alleviating effect of social networks as a reference group on subjective poverty is weakened. In summary, placing social networks’ social support and reference group functions under the same framework helps fully grasp social networks’ social benefits. As a result, consolidating China’s poverty reduction achievements and focusing on the informal social insurance role of social networks are conducive to alleviating subjective poverty.

Abstract The utilization of diverse energy storage devices is imperative in the contemporary society. Taking advantage of solar power, a significant environmentally friendly and sustainable energy resource, holds great appeal for future storage of energy because it can solve the dilemma of fossil energy depletion and the resulting environmental problems once and for all. Recently, photo‐assisted energy storage devices, especially photo‐assisted rechargeable metal batteries, are rapidly developed owing to the ability to efficiently convert and store solar energy and the simple configuration, as well as the fact that conventional Li/Zn‐ion batteries are widely commercialized. Considering many puzzles arising from the rapid development of photo‐assisted rechargeable metal batteries, this review commences by introducing the fundamental concepts of batteries and photo‐electrochemistry, followed by an exploration of the current advancements in photo‐assisted rechargeable metal batteries. Specifically, it delves into the elucidation of device components, operating principles, types, and practical applications. Furthermore, this paper categorizes, specifies, and summarizes several detailed examples of photo‐assisted energy storage devices. Lastly, it addresses the challenges and bottlenecks faced by these energy storage systems while providing future perspectives to facilitate their transition from laboratory research to industrial implementation.

Summary: Klebsiella pneumoniae carbapenemase (KPC) poses a major public health risk. Understanding its transmission dynamics requires examining the epidemiological features of related plasmids. Our study compiled 15,660 blaKPC-positive isolates globally over the past two decades. We found extensive diversity in the genetic background of KPC, with 23 Tn4401-related and 341 non-Tn4401 variants across 163 plasmid types in 14 genera. Intra-K. pneumoniae and cross-genus KPC transmission patterns varied across four distinct periods. In the initial periods, plasmids with narrow host ranges gradually established a survival advantage. In later periods, broad-host-range plasmids became crucial for cross-genera transmission. In total, 61 intra-K. pneumoniae and 66 cross-genus transmission units have been detected. Furthermore, phylogenetic reconstruction dated the origin of KPC transmission back to 1991 and revealed frequent exchanges across countries. Our research highlights the frequent and transient spread events of KPC mediated by plasmids across multiple genera and offers theoretical support for high-risk plasmid monitoring.

Abstract The staged and layered fracturing technology plays an important role in unconventional tight reservoirs. And the gas well fracturing and completion integration is the core component to realize the fracturing and completion integration process, which can realize the integration of acid fracturing and later drainage production so as to reduce the secondary pollution to the reservoir. The packer rubber barrel’s performance directly affects the long-term effective sealing reliability itself in high temperature and high pressure environment. In this paper, the constitutive model of rubber tested from high temperature and high pressure curing kettle to simulate the high-temperature and highly corrosive environment of the formation. On this basis, the structure of the packer’s shoulder and the protective ring of the rubber barrels are optimized through Abaqus to reduce its stress failure under high pressure, and its corrosion resistance is improved by improving the rubber material. The sealing performance of the packer rubber cylinder under the field underground requirements is tested through laboratory evaluation test and field test. The results show that the protective ring and rubber tube shoulder at 30° angle are a reasonable result of optimization, and the optimized packer can meet the requirements of 154 °C temperature resistance, 79 MPa pressure bearing and long-term effective sealing. The successful development of packer rubber and the integrated analysis process can lay a solid foundation for the realization of integrated fracturing and completion process for exploration and development of deep volcanic or carbonate reservoirs.

In order to study the distribution characteristics of the “three zones” of coal spontaneous combustion in the goaf of double cut roof retained roadway, taking the working face 4502 of Shaqu No.1 Mine as the engineering background, a combination of on-site monitoring and numerical simulation was adopted to study the air leakage law and the distribution characteristics of the “three zones” of coal spontaneous combustion in the goaf of the working face 4502 with double cut roof retained roadway. The results show that the main air leakage areas in the goaf of the double cut roof retaining roadway are the corners of the working face and the retaining roadways on both sides. The air flow mainly leaks into the goaf from the corners on both sides, and there is air exchange between the goaf and the retaining roadways on both sides. There is a slender oxidation zone on the side of the double retaining roadway, and the oxidation zone is distributed in a U-shaped throughout the goaf. At different stages of mining, there are significant differences in the distribution of the “three zones” of coal spontaneous combustion in the working face with double cut roof retaining roadway. In the initial stage of mining, it is necessary to strengthen the prevention and control of coal spontaneous combustion within a range of 5 m on the side of the double cut roof retaining roadway and 32-65 m in the middle of the goaf. In the middle and later stages of mining, it is necessary to strengthen the prevention and control of coal spontaneous combustion within a range of 2.5 m on the side of the transportation retaining roadway, within a range of 12 m after 38 m from the track retaining roadway, and within a range of 30-80 m in the middle of the goaf.

The tight oil reservoirs of Fuyang and Gaotaizi in the Daqing Oilfield exhibit characteristics such as thin layers and distributed barriers, which pose challenges for maintaining drilling accuracy within the desired geological sweet spot. Hydraulic fracturing has emerged as the optimal method to connect production wells with target layers effectively. Understanding the behavior of hydraulic fracture propagation in multiple thin layers with significant differences in mechanical properties is crucial for assessing the extent of effective drainage. In this study, a finite element numerical simulation model incorporating cohesive elements is employed to investigate and quantify the effects of stress differences and rock mechanical parameters on fracture penetration. The results indicate that the stress difference between the reservoir and barrier layers plays a key role in controlling hydraulic fracture penetration and height. Moreover, the flow rate and viscosity of the fracturing fluid have a noticeable impact on fracture progression. Hydraulic fractures tend to propagate along the interface of layers with low flow rate and fluid viscosity, thereby hampering the penetration performance in those layers. To achieve a comparable penetrated fracture length in low permeability reservoirs, it is necessary to increase the volume of fracturing fluid in high permeability reservoirs. Furthermore, the barriers layers, which possess relatively weaker mechanical properties, can constrain the width development of hydraulic fractures. This limitation may result in the risk of excessive liquid without sufficient proppant (commonly known as “over liquid but no sand”). Therefore, appropriate measures should be implemented to increase the net pressure and avoid encountering this complex situation.

The aim of this study was to solve the problems associated with the sealing and tearing failure of rubber packer cylinders during CO2 downhole injection. Using Comsol Multiphysics 6.0 software, a rubber cylinder model in a supercritical CO2 (SC–CO2) environment was established. The thermal analogy method was used to simulate the CO2 diffusion and rubber cylinder swelling process. We analyzed the deformation and stress of the rubber cylinder that was caused by temperature and pressure, with CO2 as the swelling agent. The results show that in the SC–CO2 environment, under the influence of CO2 diffusion and the consequent swelling, the rubber cylinder body is prone to large deformations, and the maximum shear stress is significantly increased, leading to the shear failure of the rubber cylinder. Reducing the initial seating pressure can alleviate the impact of deformation, whereas reducing the maximum contact pressure can cause the rubber cylinder to lose its seal. We also analyzed the influence of various factors on the maximum contact stress of the rubber cylinder, providing a theoretical basis and technical support for improving the sealing performance of rubber packer cylinders in an SC–CO2 environment.

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs’ dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly.

Abstract Background Blood–brain barrier (BBB) is a crucial but dynamic structure that functions as a gatekeeper for the central nervous system (CNS). Managing sufficient substances across the BBB is a major challenge, especially in the development of therapeutics for CNS disorders. Methods To achieve an efficient, fast and safe strategy for BBB opening, an acoustofluidic transwell (AFT) was developed for reversible disruption of the BBB. The proposed AFT was consisted of a transwell insert where the BBB model was established, and a surface acoustic wave (SAW) transducer realized using open-source electronics based on printed circuit board techniques. Results In the AFT device, the SAW produced acousto-mechanical stimulations to the BBB model resulting in decreased transendothelial electrical resistance in a dose dependent manner, indicating the disruption of the BBB. Moreover, SAW stimulation enhanced transendothelial permeability to sodium fluorescein and FITC-dextran with various molecular weight in the AFT device. Further study indicated BBB opening was mainly attributed to the apparent stretching of intercellular spaces. An in vivo study using a zebrafish model demonstrated SAW exposure promoted penetration of sodium fluorescein to the CNS. Conclusions In summary, AFT effectively disrupts the BBB under the SAW stimulation, which is promising as a new drug delivery methodology for neurodegenerative diseases. Graphical Abstract

This paper reviews the multiple rounds of upgrades of the hydraulic fracturing technology used in the Gulong shale oil reservoirs and gives suggestions about stimulation technology development in relation to the production performance of Gulong shale oil wells. Under the control of high-density bedding fractures, fracturing in the Gulong shale results in a complex fracture morphology, yet with highly suppressed fracture height and length. Hydraulic fracturing fails to generate artificial fractures with sufficient lengths and heights, which is a main restraint on the effective stimulation in the Gulong shale oil reservoirs. In this regard, the fracturing design shall follow the strategy of “controlling near-wellbore complex fractures and maximizing the extension of main fractures”. Increasing the proportions of guar gum fracturing fluids, reducing perforation clusters within one fracturing stage, raising pump rates and appropriately exploiting stress interference are conducive to fracture propagation and lead to a considerably expanded stimulated reservoir volume (SRV). The upgraded main hydraulic fracturing technology is much more applicable to the Gulong shale oil reservoirs. It accelerates the oil production with a low flowback rate and lifts oil cut during the initial production of well groups, which both help to improve well production. It is suggested to optimize the hydraulic fracturing technology in six aspects, namely, suppressing propagation of near-wellbore microfractures, improving the pumping scheme of CO2, managing the perforating density, enhancing multi-proppant combination, reviewing well pattern/spacing, and discreetly applying fiber-assisted injection, so as to improve the SRV, the distal fracture complexity and the long-term fracture conductivity.

Hydraulic fracturing technology is an effective way to develop tight sandstone reservoirs with low porosity and permeability. The tight sandstone reservoir is heterogeneous and the heterogeneity characteristics has an important influence on fracture propagation. To investigate hydraulic fracture performance in heterogeneous tight reservoir, the X-ray diffraction experiments are carried out, the Weibull distribution method and finite element method are applied to establish the uniaxial compression model and the hydraulic fracture propagation model of heterogeneous tight sandstone. Meanwhile, the sensitivity of different heterogeneity characterization factors and the multi-fracture propagation mechanism during hydraulic fracture propagation is analyzed. The results indicate that the pressure transfer in the heterogeneous reservoir is non-uniform, showing a multi-point initiation fracture mode. For different heterogeneity characterization factors, the heterogeneity characteristics based on elastic modulus are the most sensitive. The multi-fracture propagation of heterogeneous tight sandstone reservoir is different from that of homogeneous reservoir, the fracture propagation morphology is more complex. With the increase of stress difference, the fracture propagation length increases. With the increase of injection rate, the fracture propagation length increases. With the increase of cluster spacing, the propagation length of multiple fractures tends to propagate evenly. This study clarifies the influence of heterogeneity on fracture propagation and provides some guidance for fracturing optimization of tight sandstone reservoirs.

Nucleotides (NTs), important biomolecules involved in numerous cellular processes, have been proposed as potential candidates for anti-aging interventions. However, whether nucleotides can act as an anti-aging supplement in older adults remains unclear. TALENTs is a randomized, double-blinded, placebo-controlled trial that evaluates the efficacy and safety of NTs as an anti-aging supplement in older adults by exploring the effects of NTs on multiple dimensions of aging in a rigorous scientific setting. Eligible community-dwelling adults aged 60–70 years were randomly assigned equally to two groups: nucleotides intervention group and placebo control group. Comprehensive geriatric health assessments were performed at baseline, 2-months, and 4-months of the intervention. Biological specimens were collected and stored for age-related biomarker testing and multi-omics sequencing. The primary outcome was the change from baseline to 4 months on leukocyte telomere length and DNA methylation age. The secondary aims were the changes in possible mechanisms underlying aging processes (immunity, inflammatory profile, oxidative stress, gene stability, endocrine, metabolism, and cardiovascular function). Other outcomes were changes in physical function, body composition and geriatric health assessment (including sleep quality, cognitive function, fatigue, frailty, and psychology). In the RCT, 301 participants were assessed for eligibility and 122 were enrolled. Participants averaged 65.65 years of age, and were predominately female (67.21%). All baseline characteristics were well-balanced between groups, as expected due to randomization. The majority of participants were pre-frailty and had at least one chronic condition. The mean scores for physical activity, psychological, fatigue and quality of life were within the normal range. However, nearly half of the participants still had room for improvement in cognitive level and sleep quality. This TALENTs trial will represent one of the most comprehensive experimental clinical trials in which supplements are administered to elderly participants. The findings of this study will contribute to our understanding of the anti-aging effects of NTs and provide insights into their potential applications in geriatric healthcare.

Vortex drainage gas recovery has been used to carry liquid from gas wells. However, the traditional vortex tools in gas wells cannot produce long effective distance spiral flow at a low gas flow rate, and their operating mechanism has not been thoroughly analyzed. In this paper, the venturi acceleration vortex tool for a horizontal gas well is designed to improve drainage performance. The tube drainage, the vortex tool, and the venturi accelerated vortex tool were applied in a horizontal tube to investigate their drainage capacities by a horizontal well multiphase flow experimental device. The influence of different gas flow rates and liquid flow rates on the length of the spiral flow and pressure drop produced by the three tools was analyzed. The results show that the vortex tool can convert the gas–liquid mixing flow into the gas–liquid separation flow, that is, the liquid flows spirally along the wall and the gas flows in the center of the horizontal tube. Compared with the vortex tool, the venturi accelerated vortex tool can form a longer and more stable spiral flow. The laminar spiral flow reduces the total pressure drop in the tube. The length of the spiral flow increases with the increase in the gas flow rate. With the increase in the liquid flow rate, the spiral flow is not clear because of the turbulent flow. The length of the spiral flow and the pressure drop for the venturi accelerated vortex tool with different gas and liquid flow rates are analyzed to guide the application of the tool. This study provides a new means for the drainage of a horizontal gas well and further clarifies the working mechanism of the vortex drainage tool.

Objective: This study aims to determine the drug concentration of etomidate, remifentanil, and rocuronium bromide for general anesthesia in fetus as well as the placental transport rate between term and preterm delivery, twins, and singleton.Study design: Sixty parturients with 72 fetuses undergoing cesarean section under general anesthesia were included. According to whether the fetus was a twin or premature, parturients were divided into Group I (term singleton), Group II (premature singleton), Group III (term twins), and Group IV (premature twins). The preoperative demographic characteristics and laboratory examination of parturients, hemodynamic indicators, the Apgar score of neonates at 1, 5, and 10 min after delivery and at specific assigned values, umbilical artery blood gas analysis results, neonatal weight, and resuscitative measures were recorded. Anesthetic drug concentrations in maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood were detected by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS).Result: No significant differences were observed in the concentrations of etomidate, remifentanil, and rocuronium bromide in MA, UV, and UA blood, or in the UV/MA and UA/UV ratios between term and preterm infants, twins, and singletons. Moreover, there was no variation in the anesthetic drug concentration among each pair of twins. Additionally, no correlation was found between the neonatal weight and the plasma concentrations of anesthetic drugs in UV and UA blood, except for remifentanil in UA blood.Conclusion: Preterm or twin deliveries do not affect the neonatal concentration of etomidate, remifentanil, and rocuronium bromide used in general anesthesia for cesarean sections.Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR2100046547

ABSTRACT: The compound 3-nitrooxypropanol (3-NOP) is a promising methane inhibitor, which performs well in inhibiting methane emission and does not affect animal feed intake and digestibility. However, it causes a significant increase in hydrogen production while suppressing methane emission, resulting in a waste of feed energy. Vitamin B12 is a key factor in the propionate production pathway and thus plays an important role in regulating the hydrogen utilization pathway. In this study, the effects of 3-NOP combined with vitamin B12 supplementation on rumen fermentation and microbial compositional structure in dairy cattle were investigated by simulating rumen fermentation in vitro. Experiments were performed using a 2 × 2-factorial design: two 3-NOP levels (0 or 2 mg/g dry matter) and 2 vitamin B12 levels (0 or 2 mg/g dry matter). Three experiments were performed, each consisting of 4 treatments, 4 replicates, and 4 blanks containing only inoculum. The combined supplementation of 3-NOP and vitamin B12 reduced methane emission by 12% without affecting dry matter digestibility. The combined addition of 3-NOP and vitamin B12 significantly increased the concentration of propionate and reduced the concentration of acetate and the acetate to propionate ratio. At the bacterial level, 3-NOP increased the relative abundances of Christensenellaceae_R-7_group and Lachnospiraceae_NK3A20_group. Vitamin B12 increased the relative abundances of unclassified_f__Prevotellaceae and Prevotellaceae_UCG-003 and decreased the relative abundance of Lachnospiraceae_NK3A20_group. At the archaeal level, the combination of 3-NOP and vitamin B12 increased the relative abundances of Methanobrevibacter_ sp._ Abm4, OTU1125, and OTU95 and decreased the relative abundances of uncultured_methanogenic_archaeon_g__Methanobrevibacter, OTU1147, OTU1056, and OTU55. The results indicated that 3-NOP combined with vitamin B12 could alleviate rumen hydrogen emission and enhance the inhibition of methane emission compared with 3-NOP alone.

Objective: To evaluate the efficacy of Tian dan shu gan rehabilitation exercise in improving the short-term survival quality of patients after percutaneous coronary intervention (PCI) and explore whether patients’ symptoms, physical function, cognitive function, and psychosocial function are improved after this exercise.

ABSTRACT: Objectives: This study aims to explore the high-risk factors of carbapenem-resistant Enterobacteriaceae (CRE) infection of hospitalised patients in high-risk departments. Methods: This study is a multicentre, retrospective study. CRE screening positive patients from 1 January 2016 to 31 December 2018 of high-risk departments in five tertiary first-class teaching hospitals in Beijing collect the patients’ CRE test specimen information, CRE infection information and outcomes. The patients were divided into a colonisation group and an infection group for comparative analysis. A logistic regression model was established to explore the risk factors of CRE infection. Subgroup analysis was conducted according to invasive procedures and the type of the infection. Results: In total, 344 patients were included in this study, including 85 (24.71%) colonisation and 259 (75.29%) infection; 36.09% CRE colonisation converted to infection, and the mean conversion time from colonisation to infection was 6.5 (4.0, 18.8) days. Renal disease, granulocytosis, invasive procedures and the time from hospital stay to positive CRE were the risk factors for CRE infection. The subgroup analysis showed that the rate of CRE infection in the invasive group was higher than in the non-invasive group (P < 0.001), and the rate of exacerbation or death in the invasive group was also higher than in the non-invasive group (P = 0.019). The average length of ICU and hospitalisation in the healthcare-associated infection group were significantly higher than those in the community infection group, but there was no difference in the proportion of final exacerbation or death between them (P = 0.727). Conclusion: Kidney disease, granulocytosis, invasive procedures and CRE detection time are the risk factors for CRE infection. Carrying out CRE screening in patients as early as possible and taking effective intervention measures in time to avoid adverse consequences is all important.

In the process of constructing deep natural gas wells in Sichuan and Chongqing, gas wells encounter various technical challenges such as high temperature, high pressure, and a corrosive environment containing H2S and CO2. The corrosion of rubber materials in these acidic environments can easily lead to seal failure in downhole tools. To better investigate the corrosion resistance of rubber materials in acidic environments, we utilized a dynamic cyclic corrosion experimental device capable of simulating the service conditions experienced by downhole tools under high-temperature, high-pressure multiphase flow. Corrosion-resistance tests were conducted on fluororubbers (FKM) 1, 2, 3, and HNBR (hydrogenated nitrile-butadiene rubber) under acidic conditions (80 °C and 160 °C), along with sealing corrosion tests on O-rings. These tests aimed to analyze the mechanical properties, hardness, and corrosion resistance before and after exposure to acid media as well as the sealing performance of O-rings. Ultimately, our goal was to identify suitable rubber materials for acidic pressure environments. Experimental results revealed that all four types of rubber exhibited decreased elongation at break after undergoing corrosion testing; however, fluororubber 3 demonstrated significant susceptibility to temperature effects while the other three types showed minimal impact from temperature variations. Fluororubber 1 and fluororubber 3 displayed substantial deformation levels whereas mechanical properties greatly deteriorated for fluororubber 2. Overall, HNBR showcased superior comprehensive performance.

Dietary assessments hold significant importance within the field of public health. However, the current methods employed for dietary assessments face certain limitations and challenges that necessitate improvement. The aim of our study was to develop a reliable and practical dietary assessment tool known as photo-assisted dietary intake assessment (PAD). In order to evaluate its validity, we conducted an analysis on a sample of 71 college students’ dinners at a buffet in a canteen. We compared estimates of food weights obtained through the 24-h recall (24 HR) or PAD method with those obtained through the weighing method; we also evaluated the feasibility of PAD for recording dinner intakes among a sample of college students (n = 76) and elderly individuals (n = 121). In addition, we successfully identified the dietary factors that have a significant impact on the bias observed in weight estimation. The findings of the study indicated that the PAD method exhibited a higher level of consistency with the weighing method compared to the 24 HR method. The discrepancy in D% values between cereals (14.28% vs. 40.59%, P < 0.05), vegetables (17.67% vs. 44.44%, P < 0.05), and meats (14.29% vs. 33.33%, P < 0.05) was clearly apparent. Moreover, a significant proportion of the food mass value acquired through the PAD method fell within the limits of agreement (LOAs), in closer proximity to the central horizontal line. Furthermore, vegetables, cereals, eggs, and meats, for which the primary importance lies in accuracy, exhibited a considerably higher bias with the 24 HR method compared to the PAD method (P < 0.05), implying that the PAD method has the potential to mitigate the quality bias associated with these food items in the 24 HR method. Additionally, the PAD method was well received and easily implemented by the college students and elderly individuals. In conclusion, the PAD method demonstrates a considerable level of accuracy and feasibility as a dietary assessment method that can be effectively employed across diverse populations.

Abstract When public health emergencies occur, relevant information containing different topics, sentiments, and emotions spread rapidly on social media. From the cognitive and emotional dimensions, this paper explores the relationship between information attributes and information dissemination behavior. At the same time, the moderating role of the media factor (user influence) and the time factor (life cycle) in information attributes and information transmission is also discussed. The results confirm differences in the spread of posts under different topic types, sentiment types, and emotion types on social media. At the same time, the study also found that posts published by users with a high number of followers and users of a media type are more likely to spread on social media. In addition, the study also found that posts with different information attributes are easier to spread on social media during the outbreak and recurrence periods. The driving effect of life cycles is more obvious, especially for topics of prayer and fact, negative sentiment, emotions of fear, and anger. Relevant findings have specific contributions to the information governance of public opinion, the development of social media theory, and the maintenance of network order, which can further weaken the negative impact of information epidemic in the occurrence of public health emergencies, maintain normal social order, and thus create favorable conditions for the further promotion of global recovery.

Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic effects of NSC transplantation are limited by the low survival and differentiation rates of NSCs due to the harsh environment in the brain after ischemic stroke. Here, we employed NSCs derived from human induced pluripotent stem cells together with exosomes extracted from NSCs to treat cerebral ischemia induced by middle cerebral artery occlusion/reperfusion in mice. The results showed that NSC-derived exosomes significantly reduced the inflammatory response, alleviated oxidative stress after NSC transplantation, and facilitated NSCs differentiation in vivo. The combination of NSCs with exosomes ameliorated the injury of brain tissue including cerebral infarction, neuronal death, and glial scarring, and promoted the recovery of motor function. To explore the underlying mechanisms, we analyzed the miRNA profiles of NSC-derived exosomes and the potential downstream genes. Our study provided the rationale for the clinical application of NSC-derived exosomes as a supportive adjuvant for NSC transplantation after stroke.

BackgroundThere is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this study is to investigate whether abandonment of intravenous volume expansion after PXB administration is associated with intraoperative hemodynamic instability.Methods83 Patients with pheochromocytoma received surgical treatment in the Department of Urology, Handan First Hospital, between October 2014 and July 2022. All patients were subclassified into either the hemodynamic stability group (HS group) or the hemodynamic instability group (HU group) according to whether intraoperative hemodynamic instability occurred, with 51 cases in HS group and 32 cases in HU group. Differences in data between the two groups were examined, and the risk factors for intraoperative hemodynamic instability were analyzed using logistic regression.ResultsThe results of the analysis showed no statistically significant differences in age, sex, location of the tumor, surgical method, body mass index (BMI) ≥ 24 kg/m2, blood and urine catecholamine test results, preoperative oral PXB followed by combined intravenous volume expansion, proportion of patients with hypertension or diabetes mellitus or coronary heart disease between the two groups (P>0.05). The size of the tumor in the HS group was smaller than that in the HU group (5.3 ± 1.9 cm vs 6.2 ± 2.4 cm P=0.010). Multivariate analyses demonstrated that abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability. Only the tumor size (P=0.025) was an independent risk factor for intraoperative hemodynamic instability.ConclusionThe purpose of general preoperative intravenous fluid expansion is to prevent hypotension after the tumor has been resected. In the current study, we indicated that preoperative management of pheochromocytomas using the α-blocker PXB in combination with intravenous volume expansion does not further reduce the risk of intraoperative hemodynamic instability or postoperative complications compared with oral PXB alone. Therefore, our study supports preoperative management of pheochromocytoma with a single α-blocker, PXB, as sufficient.

We report a case of a man in his early 50 s who was admitted to our hospital for anorexia. An imaging examination led to a preoperative diagnosis of a gastrointestinal stromal tumor and gallbladder stones. He underwent treatment by laparoscopic cholecystectomy and distal partial gastrectomy with lymph node dissection. The final histopathological diagnosis was gastric schwannoma and tubular adenoma of the gallbladder. Gastric schwannoma accounts for only 0.2% of all gastric tumors, and tubular adenoma constitutes only 2.2% of gallbladder tumors. This report describes the diagnosis and treatment process for this combination of tumors, thus providing a reference for similar cases.

In this paper, the stereoselective degradation and quantitative identification of chiral pesticide etoxazole in organisms with different classes of organisms (soil, chlorella algal fluid and mice) were carried out by compound-specific isotope analysis (CSIA). The degradation behavior and stable isotope fractionation effect of etoxazole in soil, chlorella and mice were investigated. The R-etoxazole degraded faster than S-etoxazole in different classes of organisms. The metabolites M1, M2 and M3 were detected in all three substrates. Biodegradation is the main factor for the change of stable isotope ratio of chiral pesticide etoxazole. Furthermore, the relationship between fractionation value of carbon isotope and residual concentration of etoxazole is established by Rayleigh equation, and the biodegradation rate of etoxazole could be calculated by using CSIA without measuring the concentration of etoxazole. Therefore, the use of CSIA can accurately assess the degradation behavior of pesticide pollution in the environment and provide a certain scientific evidence and technical support in the process of environmental remediation.

Abstract Greenhouse-grown cucumbers were monitored over two successive growing seasons to investigate the effects of successive application of ZJ0712, a new quinone outside inhibitor (QoI) fungicide, on the development of resistance in cucumber powdery mildew (Podosphaera xanthii). Resistant P. xanthii isolates were detected after nine successive applications of ZJ0712, although the control efficacy of this fungicide against cucumber powdery mildew at that time was still higher than 80%. Seven ZJ0712-resistant P. xanthii isolates with resistance factor values greater than 180 were obtained, which exhibited a stable resistance to ZJ0712. These resistant P. xanthii isolates had similar pathogenicity to the wild-type isolate on cucumber plants. The ZJ0712 showed significant cross-resistance with azoxystrobin, enostrobilurin, or chlorothalonil, but not with the azole fungicide triadimefon. Furthermore, the most commonly reported G143A mutation in Cyt b associated with QoI resistance was found in five of the seven resistant isolates. These findings suggest that there is a high risk of resistance development associated with using ZJ0712 for controlling cucumber powdery mildew under greenhouse conditions, and the underlying resistance mechanisms in different P. xanthii isolates are not consistent and need to be further unraveled.

More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients.

Abstract Immunosuppressive tumor microenvironment is a crucial factor that impedes the success of tumor immunotherapy, and tumor-associated macrophages (TAMs) are essential for the formation of tumor immunosuppressive microenvironment. Hyaluronic acid (HA) is highly important brick for glioblastoma microenvironment, but whether it contributes to TAM polarization and glioblastoma immunosuppressive microenvironment is less well known. In our study, we observed that disrupting glioblastoma HA synthesis or blocking HA binding to its receptor CD44 on macrophages increased the proportion of M1 macrophages by upregulating SIRPα in macrophages, the underlying mechanism was elevated SIRPα enhanced STAT1 phosphorylation and suppressed STAT3 phosphorylation in macrophages. Subsequently, the induced macrophages could inhibit glioblastoma growth via a feedback effect. In addition, 4-methylumbelliferone (4MU), a cholecystitis drug, can disrupt the CD47/SIRPα axis by disturbing glioblastoma HA synthesis. Collectively, these findings indicated that HA plays a crucial role in macrophages polarization and CD47/SIRPα signaling between glioblastoma cells and macrophages, and suppressing the HA pathway may be a new immunotherapeutic approach for glioblastoma.

Morels (Morchella) are one of the most popular edible fungi in the world, especially known for their rich nutrition and delicious taste. Earlier research indicates that the production of fruiting bodies can be affected by the growth of mycelium. To investigate the molecular mechanisms underlying mycelium growth in Morchella importuna, we performed transcriptome analysis and metabolomics analysis of three growth stages of the hypha of M. importuna. As a result, 24 differentially expressed genes, such as transketolase (tktA), glucose-6-phosphate dehydrogenase (G6PDH), fructose-diphosphate aldolase (Fba), and ribose-5-phosphate isomerase (rpiA), as well as 15 differentially accumulated metabolites, including succinate and oxaloacetate, were identified and considered as the key genes and metabolites to mycelium growth in M. importuna. In addition, guanosine 3′,5′-cyclic monophosphate (cGMP), guanosine-5′-monophosphate (GMP), and several small peptides were found to differentially accumulate in different growth stages. Furthermore, five pathways, namely, starch and sucrose metabolism, pentose and glucuronate interconversions, fructose and mannose metabolism, tyrosine metabolism, and purine nucleotides, enriched by most DEGs, existed in the three compared groups and were also recognized as important pathways for the development of mycelium in morels. The comprehensive transcriptomics and metabolomics data generated in our study provided valuable information for understanding the mycelium growth of M. importuna, and these data also unveiled the key genes, metabolites, and pathways involved in mycelium growth. This research provides a great theoretical basis for the stable production and breeding of morels.

The high pressure in some gas wells, such as those in the Xushen gas field in Daqing, China, makes them susceptible to freezing and hydrate blockages. Downhole throttling technology is widely used to reduce costs during well construction, however, due to the limitations of temperature, pressure and depth structure, this technology is sometime applied independently in some gas wells in which freezing and blockages are a frequent problem that can seriously affect production capacity. Moreover, artificial alcohol injection of 'passive plugging' to prevent hydrate formation not only consumes significant amounts of methanol but its efficiency is also dependent on factors such as weather, personnel and equipment, so it is not a continuous solution. In order to solve the above problems, the mechanism of hydrate formation was analyzed in this study, from which a combined mechanical and chemical hydrate control process was developed. OLGA software was used to design the process parameters of the novel mechanical and chemical inhibition technology for hydrate prevention and control, and also to simulate and analyze the wellhead temperature, pressure and hydrate generation once the process was implemented. Based on the results of the parameters calculation, the downhole throttle and hydrate inhibitor automatic filling device are used to realize the functions of downhole throttle depressurization and hydrate inhibitor continuous filling, reduce the wellhead pressure and hydrate generation temperature, and ensure the continuous production of gas well. This novel combination process was subsequently tested in three wells in the Daqing gas oilfield. Measurements showed that the average daily gas increase from a single well was 0.5×104m3, methanol consumption was reduced from the original maximum daily amount of 1750 kg to just 60 kg, the manual maintenance workload was reduced by 80%, and the rate of the well openings was increased from 45% to 100%. These results proved that this technology is feasible and efficient for applications in gas wells with high downhole pressure and low wellhead temperature, and, thus, provides important technical support for the prevention of gas hydrate and improvement of gas well production.

With the development of economy and society, the consumption of fossil energy is gradually increasing. In order to solve the current energy dilemma, Natural gas hydrate (NGH) is considered as an ideal alternative energy. At the same time, solid fluidization exploitation is an ideal method. However, in the process of that, sand and hydrate ore bodies enter the closed pipeline together, which will block the pipeline and increase the difficulty of exploitation. Therefore, the pre-separation of sand by hydrocyclone plays an important role in solid fluidization exploitation. In this study, the numerical simulation method was used to study the internal flow field characteristics of the hydrocyclone, and the effects of different flow rate, different flow ratio, different sand content and different particle diameter on the phase distribution were investigated. The results show that: at the same axial position, the increase of flow rate and sand content makes the sand phase more distributed at the edge of the flow field. Under the same working conditions, the sand gradually migrates to the center of the flow field with the increase of the axial distance. By calculation, it is obtained that under the optimum working condition of the flow rate is 4.83m3/h, the flow ratio is 20%, the sand content is 20%, and sand diameter is 80μm, the maximum Es is 22.1% and the minimum is 86.1%. Finally, a comprehensive analysis of the hydrocyclone in this study shows that this hydrocyclone is only applicable to rough pre-separation of sand in the process of solid fluidization exploitation. Through the study of the internal flow field characteristics and phase distribution law of the hydrocyclone, this study provides a reference for the practical engineering application of sand phase pre-separation in the solid fluidization exploitation of NGH.

Rock brittleness index is an important parameter that affects the volume fracturing effect of an unconventional reservoir. The higher the brittleness index, the larger the communication area of fracture network formed under volume fracturing. However, rock brittleness has strong heterogeneity, which seriously affects the propagation of volume fracture network. Most existing rock brittleness characterization methods start from macro brittleness and cannot analyze the influence of heterogeneity on reservoir brittleness. The mineral composition analysis method can characterize the heterogeneity of a reservoir by analyzing the influence of mineral composition on brittleness, but this is limited to qualitative analysis on different minerals, resulting in large errors. In this study, the relationship between macro mechanical properties and micro mineral composition of rocks was analyzed using multiple linear regression analysis and a large number of experimental core parameters on the Shahejie Formation to understand the quantitative characterization of rock brittleness distribution in a heterogeneous reservoir. The results showed that quartz, plagioclase, analcite, siderite, and pyrite were high brittle minerals while clay minerals were low brittle minerals. This method provides a new focus for the analysis of brittle distribution of heterogeneous reservoirs and an additional method to study rock fracture law.

IntroductionNegative energy balance (NEB) is the pathological basis of metabolic disorders in early lactation dairy cows. Rumen-protected glucose (RPG) is a feed additive to relieve NEB of cows in early lactation. The aims of the current study were to evaluate the impact of different doses of RPG supply on fecal microbiota and metabolome in early lactation dairy cows, and their correlation with each other.MethodsA total of 24 multiparous Holstein dairy cows in early lactation were randomly assigned to one of four treatments for the first 35 days of the early lactation period, as follows: control group, a basal diet without RPG (CON); low RPG, a basal diet plus 200 g/d RPG (LRPG); medium RPG, a basal diet plus 350 g/d RPG (MRPG); or HRPG, high RPG, a basal diet plus 500 g/d RPG (HRPG). After 35 days, fecal samples were obtained from cows in all groups individually and using 16S rRNA gene sequencing to evaluate their microbiotas, while their metabolites were evaluated through metabolomics.ResultsAs expected, Firmicutes and Bacteroidetes were the core bacteria phyla. After RPG supplementation, there were an increase in Firmicutes and a decrease in Bacteroidetes. MRPG increased the relative abundance of cellulolytic bacteria, including Ruminococcaceae_UCG-005, Lachnospiraceae_UCG-008, Lachnospiraceae_FCS020_group, and Ruminiclostridium_9, while it decreased the relative abundance of Alistipes, Prevotellaceae_UCG-003, and Dorea. RPG supplementation could regulate the carbohydrate metabolism and amino acid metabolism pathway significantly and relieve lipolysis in dairy cows. Correlation analysis of fecal microbiome and metabolome showed that some major differential bacteria were the crucial contributors to differential metabolites.ConclusionIn conclusion, RPG supplementation can affect the fecal microbial components and microbial metabolism, and 350 g RPG might be the ideal dose as a daily supplement.

The non-natural mineralization of CaCO3 with special structures or morphologies is generated during the migration of crude oil and is the main form of scale in alkaline/surfactant/polymer (ASP) flooding in oilfields, adversely affecting oil recovery and causing environmental pollution. To date, the mineralization of aragonite superstructures and the role of heavy alkyl-benzene sulfonate (HABS) in mineralization are still unclear. In this work, aragonite-based superstructures of CaCO3 crystals were obtained in an O/W emulsion with HABS to help deepen the understanding of the diversified growth of CaCO3 scaling in oilfields. As a result, rosette-like, bouquet-like, and dumbbell-shaped CaCO3 crystals with vaterite–aragonite, aragonite, and calcite–aragonite phases were formed with 200 mg/L HABS concentration at 45 °C for 60 min and spherical vaterite phase stabilized at a high HABS concentration (800 mg/L and 1000 mg/L). Rhombohedral calcite content experienced a fluctuation of about 40% as the HABS concentration varied. Needle-like and bundle-like aragonite precipitates were generated with increasing temperatures from 65 °C to 85 °C. Thus, HABS affects the nucleation and growth of the precipitated CaCO3 solid, leading to modifications in the structure and morphology of the crystals. The synergistic effect between HABS and temperature can regulate ion pairs with the calcium ions and block sites that are essential to the incorporation of new solutes into the crystal lattice, which leads to the heterogeneous nucleation of vaterite and aragonite on calcite, forming aragonite-based superstructures in kerosene emulsion. This work may enrich the understanding of CaCO3 mineralization in oilfields, and also provide a novel strategy for manufacturing organic–inorganic composites.

AIM: To detect the relative expression levels of microRNA-27a(miR-27a)and nuclear factor erythroid-2-related factor 2(NRF2)in serum of patients with age-related macular degeneration(ARMD)bleeding, and to explore the correlation between the expression levels and the prognosis of ARMD bleeding. METHODS: A retrospective case series observation was carried out.From June 2018 to October 2019, 80 patients with ARMD bleeding who were treated in our hospital were selected as ARMD bleeding group, and 80 healthy people who had routine examination in our hospital were selected as control group. The relative expression levels of miR-27a and NRF2 were detected by real-time fluorescent quantitative PCR(qRT-PCR), the diagnostic value of serum miR-27a and NRF2 expression for ARMD bleeding was evaluated by receiver operating characteristic curve(ROC). The incidence of poor prognosis was analyzed; in addition, Logistic regression was used to analyze the influencing factors of poor prognosis in patients with ARMD bleeding. RESULTS: The relative expression level of miR-27a in serum of ARMD bleeding group was significantly higher than that of control group(P

ObjectiveThis study aims to evaluate the impact of the inferior petrosal veins (IPVs) on operational exploration and to analyze related anatomic features.MethodsA total of 317 patients were retrospectively studied. Surgical outcomes and postoperative complications were analyzed, and patients were divided into two groups according to whether the IPV was sacrificed or preserved. The diameter of the IPV was also recorded during operation. Furthermore, the position where the IPV drained into the jugular bulb was recorded in each patient, and the influence of different injection points on the operation was analyzed.ResultsIPVs were conclusively identified in 242/317 (76.3%) of patients, with 110/242 (45.5%) of patients categorized as “IPV sacrifice” versus 132/242 (54.5%) categorized as “IPV preservation.” IPV diameter was observed to be 1 mm in 39 cases (16.2%). The position of IPV drainage into the jugular bulb was at the level of the accessory nerve in 163 cases (67.3%), the level of the vagus nerve in 42 cases (17.4%), and the level of the glossopharyngeal nerve or above in 37 cases (15.3%). The diameters of IPV in the sacrifice group were mainly less than 1 mm (94.5% vs. 75%, P 1 mm.

Abstract Flumorph is a carboxylic acid amide (CAA) fungicide with high activity against oomycetes. However, evolution to CAAs from low resistance to high resistance has never been reported. This study investigated the basis of resistance evolution of flumorph in Phytophthora sojae. Total of 120 P. sojae isolates were collected and their sensitivity to flumorph was evaluated. Although no spontaneous resistance was found among the field isolates, adaptation on flumorph‐amended media resulted in the selection of five stable mutant types exhibiting varying degrees of resistance to CAAs. Type I, which exhibited the lowest resistance level, was obtained when the wild‐type isolate was exposed to a low concentration of flumorph, but no resistant mutants were obtained by direct exposure to higher concentrations. However, the more resistant types (Type II, III, IV and V) were obtained when Type I were exposed to higher concentrations of flumorph. Similar results were obtained when the entire screening process was repeated, which implied that evolution of resistance to flumorph in P. sojae could be a two‐step process, where high resistance phenotypes could develop gradually from low resistance ones. Further investigation into molecular mechanism strongly confirmed that evolution of isolates highly resistant to flumorph occurs in a stepwise process with Type I as intermediary, through accumulation of mutations in their target protein of CAAs (CesA3). Together, our findings indicate that application of low rates of flumorph in field could result in selection of low resistance Type I isolates, but that raising dosage to maintain comparable levels of control could elicit rapid evolution of more resistant Type II, III, IV and V isolates with stepwise accumulation of mutations in CesA3, which would render flumorph ineffective as a control method. Precautionary resistance management strategy should be implemented. The phenomenon described in the study could have broader biological significance.

Induced pluripotent stem cells (iPSCs) have become the leading research object in the clinical application of restorative medicine. They are easily generated from diverse cell sources and functionally indistinguishable from embryonic stem cells without the accompanying ethical issues. To date, the use of iPSC-derived neural stem cells and their progeny in the treatment of neurodegenerative and injurious diseases has achieved good results, with great potential in cell drug development. However, because of some unique biological properties and differences from traditional drug production processes, cell drug research and development has many problems that can hinder clinical applications. Given this situation, the Chinese Association of Neurorestoratology (Preparatory) and China Committee of the International Association of Neurorestoratology have organized relevant professional experts to formulate the standard presented here. Overall, the aim was to promote the clinical application of neural stem cells (NSCs) and their further derived neural cells from iPSC sources and promote cell drugs’ production and development. This standard refers to the latest research results, quality evaluation criteria for traditional medicines, and the regulatory framework for cellular treatments. The standard considers general biological properties of cells, including cell morphology, cell cycle, karyotype, and cell viability. The specific biological properties of NSCs, such as cell surface markers and differentiation ability, general drug standards, such as aseptic testing, endotoxins, human virus detection, and cell-related drug standards, such as telomerase activity and tumorigenicity, are also considered. This standard will serve as a reference for physicians and scientists who focus on clinical nervous cell applications and studies related to iPSCs.

During public policy information diffusion, policy interpretation on government microblogs and public attention interact, but there are certain differences. We construct a research framework for the heterogeneous diffusion of public policy information on government microblogs. An empirical study is conducted based on the Network Agenda Setting (NAS) model. First, a combination of topic mining and content analysis is used to identify the issues discussed by government microblogs and citizens. Then, we use the importance of nodes in Degree Structure (DS) and Flow Structure (FS) entropy to measure their attention to different issues. Finally, the Quadratic Assignment Procedure (QAP) correlation and regression analysis explore the degree of heterogeneity and causal relationship between government microblog agenda networks (GMANs) and public agenda networks (PANs). We find that GMANs influence PANs and the degree of heterogeneity between them is relatively low at the beginning of policy implementation. However, as government microblogs reveal positive effects of policy implementation, they fail to influence PANs effectively, and there is a greater degree of heterogeneity between them. Moreover, PANs do not significantly affect GMANs. The dynamic leading relationship between GMANs and PANs in public policy diffusion is clarified, helping to shape the image of digital government in public opinion.

AIM: To investigate the efficacy of dexamethasone implant injection in the treatment of persistent diabetic macular edema(DME).METHODS: The clinical data of 30 DME patients(30 eyes)after anti-vascular endothelial growth factor(anti-VEGF)agents from June 2019 to January 2020 were retrospectively analyzed. All patients had underwent intravitreal injection of DEX. Best corrected visual acuity(BCVA), intraocular pressure(IOP), central macular thickness(CMT)and adverse events were recorded.RESULTS:BCVA(LogMAR)was significantly improved from(0.86±0.47)to(0.57±0.53, 0.42±0.48, 0.43±0.26, 0.45±0.66 and 0.51±0.37)at 1, 2, 3, 4 and 6mo after treatment. CMT improved significantly from baseline(495.64±107.23)μm to(412.57±74.55, 370.21±23.83, 371.53±52.66, 373.28±68.49, 389.35±95.61)μm 1, 2, 3, 4 and 6mo post-injection. The drug reached its peak efficacy 2mo after administration. 4 eyes were given repeated injection at 3mo, 5 eyes were given at 5mo and 2 eyes were given at 6mo following the primary injection. Cataract progression was showed in 1 case. 4 patients demonstrated IOP levels above 22mmHg and were mostly controllable by IOP-lowering medications. None of patients showed any adverse events at 6mo of follow-up.CONCLUSION: Dexamethasone implant injection showed significant BCVA and CMT improvement. DEX injection may be utilized as an effective DME therapy for patients who are persistent after anti-VEGF treatment.