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ABSTRACTDoxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.

Abstract The manuscript proposes a fault diagnosis method based on graph neural network (GNN) with one-shot learning to effectively diagnose rolling bearings under variable operating conditions. In this proposed method, the convolutional neural network is utilized for feature extraction, reducing loss in the process. Subsequently, GNN applies an adjacency matrix to generate codes for one-shot learning. Experimental verification is conducted using open data from Case Western Reserve University Rolling Bearing Data Center, where four different working conditions with six types of typical faults are selected as input signals. The classification accuracy of the proposed method reaches 98.02%. To further validate its effectiveness, traditional single-learning neural networks such as Siamese, Matching Net, Prototypical Net and (Stacked Auto Encoder) SAE are introduced as comparisons. Simulation results that the proposed method outperforms all chosen methods.

BackgroundSepsis is a clinical syndrome with high mortality. Subtype identification in sepsis is meaningful for improving the diagnosis and treatment of patients. The purpose of this research was to identify subtypes of sepsis using RNA-seq datasets and further explore key genes that were deregulated during the development of sepsis.MethodsThe datasets GSE95233 and GSE13904 were obtained from the Gene Expression Omnibus database. Differential analysis of the gene expression matrix was performed between sepsis patients and healthy controls. Intersection analysis of differentially expressed genes was applied to identify common differentially expressed genes for enrichment analysis and gene set variation analysis. Obvious differential pathways between sepsis patients and healthy controls were identified, as were developmental stages during sepsis. Then, key dysregulated genes were revealed by short time-series analysis and the least absolute shrinkage and selection operator model. In addition, the MCPcounter package was used to assess infiltrating immunocytes. Finally, the dysregulated genes identified were verified using 69 clinical samples.ResultsA total of 898 common differentially expressed genes were obtained, which were chiefly related to increased metabolic responses and decreased immune responses. The two differential pathways (angiogenesis and myc targets v2) were screened on the basis of gene set variation analysis scores. Four subgroups were identified according to median expression of angiogenesis and myc target v2 genes: normal, myc target v2, mixed-quiescent, and angiogenesis. The genes CHPT1, CPEB4, DNAJC3, MAFG, NARF, SNX3, S100A9, S100A12, and METTL9 were recognized as being progressively dysregulated in sepsis. Furthermore, most types of immune cells showed low infiltration in sepsis patients and had a significant correlation with the key genes. Importantly, all nine key genes were highly expressed in sepsis patients.ConclusionThis study revealed novel insight into sepsis subtypes and identified nine dysregulated genes associated with immune status in the development of sepsis. This study provides potential molecular targets for the diagnosis and treatment of sepsis.

Abstract Treatment of infected wounds remains a challenge owing to antibiotic resistance; thus, developing smart biomaterials for the healing of infected wounds is urgently needed. In this study, a microneedle (MN) patch system with antimicrobial and immunomodulatory properties is developed to promote and accelerate infected wound healing. In the MN patch (termed PFG/M MNs), a nanoparticle with polydopamine (PDA)‐loaded iron oxide is grafted with glucose oxidase (GOx) and hyaluronic acid (HA) and then integrated into the tips, and amine‐modified mesoporous silica nanoparticles (AP‐MSNs) are incorporated into the bases. Results show that PFG/M MNs eradicate bacterial infections and modulate the immune microenvironment, combining the advantages of chemodynamic therapy, photothermal therapy, and M2 macrophage polarization from Fe/PDA@GOx@HA in the tips as well as anti‐inflammatory effect of AP‐MSNs from the MN bases. Thus, the PFG/M MN system is a promising clinical candidate for promoting infected wound healing.

Because of the harsh working environment, there is usually a lack of effective data from the gearboxes of wind turbines for fault classification. In this paper, a fault-diagnosis model based on graph neural networks and one-shot learning is proposed to solve the problem of fault classification with limited data. In the proposed method, the short-time Fourier transform is used to convert one-dimensional vibration signals into two-dimensional data, then feature vectors are extracted from the two-dimensional data, and small-sample learning is achieved. An experimental rig was built to simulate the real working scenario of a wind turbine, and the results indicate the high classification accuracy of the proposed method. Furthermore, its effectiveness is verified in comparisons with Siamese, matching and prototypical networks, with the proposed method outperforming all of them.

Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, their role in sepsis-related liver injury (SLI) in the elderly is unclear. This study assessed whether metformin could attenuate SLI by modulating gut microbiota in septic aged rats. Cecal ligation and puncture (CLP) was used to induce SLI in aged rats. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. The composition of gut microbiota was analyzed by 16S rRNA sequencing. Moreover, the liver and colon tissues were analyzed by histopathology, immunofluorescence, immunohistochemistry,and reverse transcription polymerase chain reaction (RT-PCR). Metformin improved liver damage, colon barrier dysfunction in aged SLI rats. Moreover, metformin improved sepsis-induced liver inflammation and damage under the presence of gut microbiota. Importantly, FMT assay showed that rats gavaged with feces from metformin-treated SLI rats displayed fewer-severe liver damage and colon barrier dysfunction than did rats gavaged with feces from SLI rats.The gut microbiota composition among the sham-operated, CLP-operated and metformin-treated SLI rats were different. In particular, the proportion of Klebsiella and Escherichia_Shigella was higher in SLI rats than sham-operated and metformin-treated SLI rats;while metformin could increased the proportion of Bifidobacterium, Muribaculaceae, Parabacteroides_distasonis and Alloprevitella in aged SLI rats. Additionally, Klebsiella and Escherichia_Shigella correlated positively with the inflammatory factors in the liver. Our findings suggest that metformin may improve the liver injury by regulating the gut microbiota and alleviating colon barrier dysfunction in septic aged rats, which may be an effective therapy for SLI.

BackgroundThe mortality rate associated with sepsis in elderly individuals is higher than that in younger individuals. The intestinal microbiota has been demonstrated to play an important role in the occurrence and development of sepsis. The purpose of this study was to investigate the differences in the intestinal microbiota between aged and adult mice with sepsis.MethodsThirty male C57BL mice were randomly divided into two groups: 15 in the adult group (AD group) and 15 in the age group (Age group). All the mice underwent caecal ligation and puncture to induce sepsis. Mice faeces were collected, and analysed using 16S rRNA sequencing. The liver and colon tissues were collected.ResultsThere were significant differences in intestinal microbiota composition between the two groups. Compared with adult sepsis mice, the diversity of intestinal microbiota in the aged group was significantly reduced and the structure of dominant intestinal microbiota was changed. In the Age group, the microbiota associated with inflammatory factors increased, and the microbiota associated with the production of SCFAs (Ruminiclostridium, Prevotellaceae_UCG-001, Rikenella, Parabacteroides, Oscillibacter, Odoribacter, Muribaculum, Lachnoclostridium, Intestinimonas, Faecalibaculum, Anaerotruncus, Alloprevotella and Absiella) decreased. The metabolic pathways related to the microbiota also changed. Moreover, the proportion of inflammatory factors in Age group was higher than that in AD group.ConclusionOur results showed that there were significant differences in the abundance and structure of microbiota between aged and adult sepsis mice, Aged sepsis mice have more severe intestinal microbiota destruction and liver tissue inflammation than adult sepsis mice.

Abstract Smart nanomaterials constitute a new approach toward safer and more effective combined anti‐cancer immunotherapy. In this study, polydopamine‐multiprotein conjugates (DmPCs) that can be used for targeted delivery of multiple proteins to cells, realize imaging and combine the advantages of multiple treatment methods (photothermal therapy, chemodynamic therapy, and immunotherapy) can be synthesized and characterized. Proteins, as biological agents, are frequently used in this context, given their low toxicity in vivo. To overcome protein instability and short half‐life in vivo, the use of several proteins in combination with selected nanomaterials to treat patients with melanoma is proposed. In addition to the synthesis and characterization of protein‐bound nanoparticles, it is further demonstrated that several proteins can be efficiently delivered to tumor sites. DmPCs have a wide range of potential adaptability, which provides new opportunities for proteins in the field of treatment and imaging.

The aim of this paper is to illustrate the impact of stress-sensitive permeability on productivity in naturally fracture carbonate reservoirs. First, stress sensitivity evaluation experiments were conducted on artificial cores with matrix, uncemented fracture, partially- cemented fracture and fully-cemented fracture by measuring their permeability in the process of increasing confining pressure. Then, a new mathematical model for productivity prediction in naturally fractured carbonate reservoir with consideration of stress-sensitive permeability is developed. Comparisons have been made between the new model prediction results and field measured data to verify the accuracy of the new model. Finally, based on the validated model, the detailed impact of permeability modulus on productivity is analysed. The experiment results show that the strength of stress sensitivity, evaluated by permeability modulus, of cores with uncemented fracture and partially-cemented fracture is generally an order of magnitude larger than that of cores with matrix and fully-cemented fracture. The results show the new model can be simplified to the classic model (Vogel equation) under the condition of the stress sensitivity being not taken into account, which means the class model is corresponding to a special case of this new model. Field application shows that the new model is reliable and correct. Moreover, with the help of the new model, it is found that the impact of stress-sensitive permeability on productivity increases with increasing permeability modulus and decreasing flow bottom hole pressure.

Smart heritage is still novel in heritage discourse, with a few relevant review articles. In this regard, a specific interpretation of smart architectural heritage and a framework for instructing its development is lacking. This article reviews the literature on smart heritage in sustainable development to fill the knowledge gap. As a methodology for this study, the integrative review approach and thematic analysis are adopted to review references located at the crossroads of historic, smart, and sustainable disciplines. The review and interpretation draw on literature from relevant fields to understand implementations, current states, and support to interpret smart heritage. Review outcomes indicate that smart heritage is becoming dynamic as technologies are increasingly applied to more detailed heritage branches. This article lists the factors that heritage should possess to be defined as smart, and it provides a framework that might be followed to achieve the aims of this discourse by stating that smart heritage discussions are relevant to smart cities, as they may have a mutual effect and interact to promote each other.

Abdominal wall defects are associated with abdominal wall surgery, infection and tumour resection. Polypropylene (PP) mesh, which has excellent mechanical strength, is currently the primary clinical repair material. In repairing the abdominal wall, the mesh can erode the bowel and cause other problems. Constructing a barrier that induces a weak inflammatory response and promotes rapid recovery of the peritoneum is important. We used electrospinning technology to construct a silk fibroin coating on the abdominal surface of a PP patch. A rat model was used to compare the inflammatory responses, regeneration of peritoneal tissue, and antiadhesion effects of electrospun regenerated silk fibroin (RSF) coatings, polycaprolactone (PCL) coatings, and noncoated PP meshes. The inflammatory responses, antiadhesion fractions, and areas of RSF and PCL were better than those of PP at 6 weeks. RSF was associated with complete peritoneal regeneration, in contrast to PCL. At 12 weeks, the structure of the PCL peritoneum was unstable, and the adhesion fraction and area were significantly higher than those of RSF. The intact peritoneum could not be effectively regenerated. The RSF group exhibited lower IL-6 levels than the PCL and PP groups but higher VEGF, IL-10 and TGF-β levels, making RSF more conducive to the regeneration of peritoneal and abdominal wall tissues.

Sepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammatory factors, and inflammatory pathways. We hypothesized that metformin may have an effect on microglia, which affects the prognosis of SAE. In this study, metformin treatment of mice with SAE induced by lipopolysaccharide (LPS) reduced the expression of microglia protein and related inflammatory factors. Poor prognosis of SAE is related to increased expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in brain tissues. Levels of inflammatory cytokines produced by LPS-induced SAE mouse microglia were significantly increased compared with those in the sham group. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes. In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5′-monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-κB). Metformin can partially reverse the severe prognosis caused by sepsis by blocking microglial proliferation and inhibiting the production of inflammatory factors.

Fractured carbonate reservoirs are different from conventional reservoirs and generally develop fractures. Conventional reservoir well test performance analysis can only obtain the formation parameters and discharge radius around a single well. For vertical wells in fractured carbonate reservoirs, we can establish a dual-porosity composite reservoir model for well testing interpretation and analysis based on the actual conditions of the reservoir and combined with geological knowledge. The model can be applied to formations with different reservoir properties in the near-well and far-well areas around a single well to analyze the fracture parameters (elastic reserve ratio and channeling coefficient) and the effective flow capacity of formation fluids in the two areas. On this basis, we use the interpretation of actual production wells to verify the accuracy of the model and analyze the influence of reservoir parameters and fracture parameters on the theoretical curve.

ObjectiveCorticosteroids are a common option used in sepsis treatment. However, the efficacy and potential risk of corticosteroids in septic patients have not been well assessed. This review was performed to assess the efficacy and safety of corticosteroids in patients with sepsis.MethodsPubMed, Embase, and Cochrane library databases were searched from inception to March 2021. Randomized controlled trials (RCTs) that evaluated the effect of corticosteroids on patients with sepsis were included. The quality of outcomes in the included articles was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The data were pooled by using risk ratio (RR) and mean difference (MD). The random-effects model was used to evaluate the pooled MD or RR and 95% confidence intervals (CIs).ResultsFifty RCTs that included 12,304 patients with sepsis were identified. Corticosteroids were not associated with the mortality in 28-day (RR, 0.94; 95% CI, 0.87–1.02; evidence rank, moderate) and long-term mortality (>60 days) (RR, 0.96; 95% CI, 0.88–1.05) in patients with sepsis (evidence rank, low). However, corticosteroids may exert a significant effect on the mortality in the intensive care unit (ICU) (RR, 0.9; 95% CI, 0.83–0.97), in-hospital (RR, 0.9; 95% CI, 0.82–0.99; evidence rank, moderate) in patients with sepsis or septic shock (evidence rank, low). Furthermore, corticosteroids probably achieved a tiny reduction in the length of hospital stay and ICU. Corticosteroids were associated with a higher risk of hypernatremia and hyperglycemia; furthermore, they appear to have no significant effect on superinfection and gastroduodenal bleeding.ConclusionsCorticosteroids had no significant effect on the 28-day and long-term mortality; however, they decreased the ICU and hospital mortality. The findings suggest that the clinical corticosteroids may be an effective therapy for patients with sepsis during the short time.Systematic Review Registrationhttps://inplasy.com/wp-content/uploads/2021/05/INPLASY-Protocol-1074-4.pdf

The carboniferous carbonate reservoirs in the North Truva Oilfield have undergone complex sedimentation, diagenesis and tectonic transformation. Various reservoir spaces of pores, caves and fractures, with strong reservoir heterogeneity and diverse pore structures, have been developed. As a result, a quantitative description of the pore structure is difficult, and the accuracy of logging identification and prediction is low. These pose a lot of challenges to reservoir classification and evaluation as well as efficient development of the reservoirs. This study is based on the analysis of core, thin section, scanning electron microscope, high-pressure mercury injection and other data. Six types of petrophysical facies, PG1, PG2, PG3, PG4, PG5, and PG6, were divided according to the displacement pressure, mercury removal efficiency, and median pore-throat radius isobaric mercury parameters, combined with the shape of the capillary pressure curve. The petrophysical facies of the wells with mercury injection data were divided accordingly, and then the machine learning method was applied. The petrophysical facies division results of two mercury injection wells were used as training samples. The artificial neural network (ANN) method was applied to establish a training model of petrophysical facies recognition. Subsequently, the prediction for the petrophysical facies of each well in the oilfield was carried out, and the petrophysical facies division results of other mercury injection wells were applied to verify the prediction. The results show that the overall coincidence rate for identifying petrophysical facies is as high as 89.3%, which can be used for high-precision identification and prediction of petrophysical facies in non-coring wells.

Thiol-containing natural products possess a wide range of bioactivities. The burst of synthetic biology technology facilitates the discovery of new thiol-containing active ingredients. Herein, we report a sensitive, quick, and robust surface-enhanced Raman scattering technology for specific and multiplex detection of thiol-containing compounds without purification requirements and also indicating the thiols with different chemical environments. Using this platform, we successfully demonstrated the simultaneous detection of thiol-containing compounds from as low as 1 μM of analytes spiked in complex culture matrices.

Abstract Background Drug resistance of paclitaxel (TAX), the first-line chemotherapy drug for breast cancer, was reported to develop in 90% of patients with breast cancer, especially metastatic breast cancer. Investigating the mechanism of TAX resistance of breast cancer cells and developing the strategy improving its therapeutic efficiency are crucial to breast cancer cure. Methods and Results We here report an elegant nanoparticle (NP)-based technique that realizes efficient breast cancer treatment of TAX. Using lentiviral vector-mediated gene knockdown, we first demonstrated that TAX therapeutic efficiency was closely correlated with metadherin (MTDH) gene expression in breast cancer cell lines. This finding was also supported by efficacy of TAX treatment in breast cancer patients from our clinical studies. Specifically, TAX treatment became more effective when MTDH expression was decreased in MCF-7 cancer cells by the blocking nuclear factor-kappa B (NF-κB) pathway. Based on these findings, we subsequently synthesized a polymeric NP that could co-deliver MTDH-small interfering RNA (MTDH–siRNA) and TAX into the breast cancer tumors in tumor-bearing mice. The NPs were composed of a cationic copolymer, which wrapped TAX in the inside and adsorbed the negatively charged siRNA on their surface with high drug-loading efficiency and good stability. Conclusions NP-based co-delivery approach can effectively knock down the MTDH gene both in vitro and in vivo, which dramatically inhibits breast tumor growth, achieving effective TAX chemotherapy treatment without overt side effects. This study provides a potential therapeutic strategy for the treatment of a wide range of solid tumors highly expressing MTDH.

Zhanazhol is a weakly volatile reservoir of fractured pore carbonate. The reservoir has poor physical properties and strong heterogeneity. During injection development, the pressure of injection wells is severe and the effect of water injection is not obvious. Making full use of abundant associated gas resources for gas injection development is the best way to stabilize and restore formation pressure and improve oilfield development effectiveness. In order to clarify the impact of different geological characteristics and development parameters on the gas injection development effect of fractured pore carbonate reservoirs, an orthogonal test method was used to analyze the main influencing factors of gas injection development. Studies have shown that the order of the influence of various parameters on gas injection development from high to low is injection-production ratio, well spacing, oil production rate, gas injection timing, matrix permeability, formation dip angle, fracture volume density, net pay thickness, ratio of horizontal permeability to vertical permeability. The research results provide support for formulating gas injection development technology policies and improving oilfield development effect.

The pressure balance between gas cap and oil ring is likely to be broken during their concurrent production in gas cap reservoirs. In order to increase the whole development efficiency of the concurrent production of gas cap and oil ring, the Zhanzhol gas cap reservoir of Kazakhstan was taken as example to carry out the research, a three-dimensional visualization physical model was established based on the similarity criterion of oil phase, gas phase and water phase, and a reservoir engineering model of fluid interface moving rate was also set up according to the material balance principle. The calculation results of reservoir engineering model tally with the results of physical simulation experiment and reservoir dynamic test data. The moving rate template of fluid interface under three development modes, depletion development, barrier water injection development and barrier plus pattern water injection development have been also established by reservoir engineering method. The main controlling factors under different development modes have been figured out: for depletion development, the main controlling factors on the stabilization of oil-gas contact are oil recovery rate and gas recovery rate; for barrier water injection development, the main controlling factors are oil recovery rate, gas recovery rate and production-injection ratio; and for barrier plus pattern water injection development, the main controlling factors are oil recovery rate, gas recovery rate, production-injection ratio and the ratio of barrier water injection to pattern water injection. Key words: Zhanzhol oil field, gas cap reservoir, concurrent production of gas cap and oil ring, fluid interface, moving rule

Reservoir Γ north, which belongs to Zhanzhol, Kazakhstan, a fracture-pore typed carbonate oilfield, has a variety of reservoir types. According to the combination pattern of different voids and the relationship between porosity and permeability, carbonate reservoirs are classified into four types which are fracture-cavity-pore typed (referred to as composite typed here after), fracture-pore typed, pore typed and fracture typed, and the identification of which by well logging data is realized. There is a little difference in the producing degree within the same reservoir type for composite typed and fracture typed reservoirs. However, there are large differences in the producing degree for fracture-pore typed and pore typed reservoirs. In order to appraise the producing degree of reservoirs more exactly, key parameters affecting the producing degree of fracture-pore typed and pore typed reservoirs are selected separately, which, for the fracture-pore typed are reservoir quality index (RQI), pore throat radius at mercury saturation of 50% (R50), total permeability (Kf+Km), and the ratio of fracture permeability to matrix permeability (Kf/Km), and for the pore typed are RQI, R50, and matrix permeability (Km). With the integrated consideration of matrix and fracture, a flow unit classification method for dual medium reservoir is established, and taking these parameters as clustering variants, four types of reservoirs are further divided into six kinds of reservoir flow units by the means of neural network clustering technology. Based on reservoir flow unit modeling, a numerical simulation model is built with each type of reservoir flow units adopting its corresponding relative permeability curve, based on which, the distribution regularity of remaining oil of reservoir Γ north is studied and demonstrated. Eight new wells are designed according to the research result, and put into production in 2013 with the initial daily oil production rate being 2.3 times that of nearby old wells. Key words: carbonate oil reservoir, reservoir type, reservoir flow unit, neural network clustering technology, reservoir flow unit model, remaining oil

Fracture aperture of a fractured reservoir can be affected by both matrix elasticity and fracture compressibility when the reservoir pressure decreases, namely stress sensitivity. An elasticity parameter coupling Young’s modulus and Poisson’s ratio was introduced to reflect this geomechanical behavior, and a new model incorporating geomechanics was developed to analyze the flow behavior of a horizontal well in a naturally fractured reservoir. Pressure solutions for two cases—uniform-flux and infinite-conductivity—were derived, respectively. For the uniform-flux case, the effect of dimensionless elasticity parameter on the pressure-drop profile becomes stronger with continuing production, and the profile may be like a bow. Nine flow regimes can be observed on the transient response of the infinite-conductivity case. Stress sensitivity mainly affects the late-flow period and a larger dimensionless elasticity parameter causes a greater pressure drop. Due to stress sensitivity, the pressure derivative curve exhibits an upward tendency in the pseudo-radial flow regime, and the slope is greater than “1” in the pseudo-steady flow regime. For KT-I formation in the North Truva field, its elasticity parameter decreases with the increase of Young’s modulus or Poisson’s ratio and ranges from 8 × 10−8 Pa−1 to 1.1 × 10−7 Pa−1. Meanwhile, the transient response of H519 has a slight negative correlation with Young’s modulus and Poisson’s ratio in the pseudo-steady flow regime.

The central layer Yu-III in Akshabulak oilfield is a sandstone reservoir with strong edge water, whose major development characteristics are high oil recovery rate and heterogeneous water invasion. Aiming at this problem, the development policy chart of concurrent displacement of natural water and injected water is established on the basis of material balance principle. Injection-production ratio and oil recovery rate are the main controlling factors for the concurrent displacement of natural water and injected water. Each injection-production ratio corresponds with only one rational oil recovery rate, and the rational oil recovery rate increases with the injection-production ratio. When the actual injection-production ratio of the central Yu-III reservoir is 0.9, the rational oil recovery rate should be 4%.

Real-time monitoring of chemical reactions is still challenging as well as important to study reaction mechanisms and reaction kinetics. Herein, we demonstrated the real-time monitoring of o-phenylenediamine (OPD) oxidation on the surface of gold nanoparticles by surface-enhanced Raman spectroscopy (SERS). The oxidation mechanism and the reaction kinetics were investigated on the basis of the SERS spectrum variation and the related density functionalized theory calculation. It was shown that the oxidation of OPD in the presence of copper ions was a two-step process of the deprotonation of the amino group on the aromatic rings and the rearrangement of the electron cloud to a π-conjugated system, which may open a new door to comprehensively understand the reaction process.

The M2 subtype Acute Myeloid Leukemia (AML-M2) with t(8;21) represents an unmet challenge because of poor clinical outcomes in a sizable portion of patients. In this study,we report that FTY720 (Fingolimod), a sphingosine analogue and an FDA approved drug for treating of multiple sclerosis, shows antitumorigenic activity against the Kasumi-1 cell line, xenograft mouse models and leukemic blasts isolated from AML-M2 patients with t(8;21) translocation. Primary investigation indicated that FTY720 caused cell apoptosis through caspases and protein phosphatase 2A (PP2A) activation. Transcriptomic profiling further revealed that FTY720 treatment could upregulate AML1 target genes and interfere with genes involved in ceramide synthesis. Treatment with FTY720 led to the elimination of AML1-ETO oncoprotein and caused cell cycle arrest. More importantly, FTY720 treatment resulted in rapid and significant increase of pro-apoptotic ceramide levels, determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry based lipidomic approaches. Structural simulation model had also indicated that the direct binding of ceramide to inhibitor 2 of PP2A (I2PP2A) could reactivate PP2A and cause cell death. This study demonstrates, for the first time, that accumulation of ceramide plays a central role in FTY720 induced cell death of AML-M2 with t(8;21). Targeting sphingolipid metabolism by using FTY720 may provide novel insight for the drug development of treatment for AML-M2 leukemia.

In the research presented herein, low-valent-tungsten-catalyzed hydroboration of esters and nitriles was investigated. Aromatic and aliphatic substrates were smoothly reduced to corresponding alcohol derivatives and N,N-diborylamines in the presence of W(CO)4(NCMe)2. Valuable derivatives were conveniently accessed by introducing a further functionalization process to crude hydroboration mixtures in one pot. [ABSTRACT FROM AUTHOR]