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In the realm of reservoir development, the optimization of well placement constitutes a cornerstone challenge with significant implications that directly determine the recovery rate and economic benefits of oil and gas production. This research proposes a novel approach to optimizing well placement in reservoirs by integrating reservoir numerical simulations with intelligent optimization algorithms. The quintessence of this inquiry revolves around the strategic placing of wells amidst the complex geological fabric of reservoirs, where the objective function landscape often manifests with non-smooth, multimodal characteristics. To address those issues, the Weighted Mapping of Productivity Potential (WMPP) technique, fortified by the Simulated Annealing algorithm to judiciously ascertain specific weighting coefficients for the computation of WMPP across reservoirs is introduced in this study. Furthermore, an emblematic carbonate reservoir model serves to corroborate the adaptability and viability of WMPP for well placement optimization, underscoring its efficacy as a swift, economically viable instrument for the delineation of prospective reservoir zones and the guidance of drilling initiatives. The optimization results show that the well placement scheme guided by WMPP, which required 7 fewer wells than the oil initially in place (OOIP)-based scheme, improved 21.74% oil production over the twenty years production period. This comprehensive workflow proffers invaluable insights and benchmarks for the formulation of well placement strategies, with the proposed methodology, in its apparent simplicity, showcasing remarkable efficiency.

There is a growing body of literature on the demographic and socioeconomic distinctions between mobile-only and hybrid Internet users and how the two groups use the Internet differently. However, little is known about why people change their type of Internet access and the impact of this change. Relying on data from two waves of a nationally representative survey conducted in China, this study demonstrates that capital-enhancing Internet activities are positively correlated with the likelihood of switching from mobile-only access to hybrid access and negatively correlated with the likelihood of switching from hybrid access to mobile-only access. In addition, those who switch from mobile to hybrid access subsequently strengthen their capital-enhancing uses, thereby not only amplifying the divide between them and others who remain mobile-only but also creating a positive feedback loop. However, non-capital-enhancing uses, such as gaming, are irrelevant to changes in the type of access. It appears that mobile-only access has become a comparable substitute for computer-based Internet in terms of casual activities. However, for “serious” uses, a device divide still exists.

Constructing an accurate model with the capability to accurately forecast gas solubility in electrolyte solutions across diverse temperature, pressure, and salt concentration ranges holds significant relevance for carbon capture and storage (CCS). The model was modified by introducing the Debye–Hückel electrostatic term in the previously published CPA-MHV1 equation of state to account for the influence of salt on the gas solubility. The water–salt and gas–salt binary interaction parameters were optimized using experimental data, and the phase behavior of CO2and CH4was investigated in five salt solutions, NaCl, KCl, MgCl2, CaCl2, and Na2SO4. Furthermore, various association schemes for CO2were compared, revealing optimal simulation outcomes when modeling CO2as a nonself-associating molecule solvated in water. The average absolute relative deviation values of CO2and CH4obtained by this method in five single-salt solutions were 7.08 and 3.87%, respectively. The proposed model demonstrates a high degree of accuracy in simulating vapor–liquid equilibrium within water–gas–salt systems.

Relative permeability (RP) curves which provide fundamental insights into porous media flow behavior serve as critical parameters in reservoir engineering and numerical simulation studies. However, obtaining accurate RP curves remains a challenge due to expensive experimental costs, core contamination, measurement errors, and other factors. To address this issue, an innovative approach using deep learning strategy is proposed for the prediction of rock sample RP curves directly from mercury injection capillary pressure (MICP) measurements which include the mercury injection curve, mercury withdrawal curve, and pore size distribution. To capture the distinct characteristics of different rock samples' MICP curves effectively, the Gramian Angular Field (GAF) based graph transformation method is introduced for mapping the curves into richly informative image forms. Subsequently, these 2D images are combined into three-channel red, green, blue (RGB) images and fed into a Convolutional Long Short-Term Memory (ConvLSTM) model within our established self-supervised learning framework. Simultaneously the dependencies and evolutionary sequences among image samples are captured through the limited MICP-RP samples and self-supervised learning framework. After that, a highly generalized RP curve calculation proxy framework based on deep learning called RPCDL is constructed by the autonomously generated nearly infinite training samples. The remarkable performance of the proposed method is verified with the experimental data from rock samples in the X oilfield. When applied to 37 small-sample data spaces for the prediction of 10 test samples, the average relative error is 3.6%, which demonstrates the effectiveness of our approach in mapping MICP experimental results to corresponding RP curves. Moreover, the comparison study against traditional CNN and LSTM illustrated the great performance of the RPCDL method in the prediction of both Soand Swlines in oil–water RP curves. To this end, this method offers an intelligent and robust means for efficiently estimating RP curves in various reservoir engineering scenarios without costly experiments.

Surface hydroxyl groups commonly exist on the catalyst and present a significant role in the catalytic reaction. Considering the lack of systematical researches on the effect of the surface hydroxyl group on reactant molecule activation, the PtOx/TiO2and PtOx–y(OH)y/TiO2catalysts were constructed and studied for a comprehensive understanding of the roles of the surface hydroxyl group in the oxidation of volatiles organic compounds. The PtOx/TiO2formed by a simple treatment with nitric acid presented greatly enhanced activity for toluene oxidation in which the turnover frequency of toluene oxidation on PtOx/TiO2was around 14 times as high as that on PtOx–y(OH)y/TiO2. Experimental and theoretical results indicated that adsorption/activation of toluene and reactivity of oxygen atom on the catalyst determined the toluene oxidation on the catalyst. The removal of surface hydroxyl groups on PtOxpromoted strong electronic coupling of the Pt 5d orbital in PtOxand C 2p orbital in toluene, facilitating the electron transfers from toluene to PtOxand subsequently the adsorption/activation of toluene. Additionally, the weak Pt–O bond promoted the activation of surface lattice oxygen, accelerating the deep oxidation of activated toluene. This study clarifies the inhibiting effect of surface hydroxyl groups on PtOxin toluene oxidation, providing a further understanding of hydrocarbon oxidation.

Introduction Ocular immune-related adverse events (OirAEs) associated with novel cancer therapies of immune checkpoint inhibitors (ICIs) are emerging. Retrobulbar optic neuritis (ON) combined with optic perineuritis (OPN), associated with atezolizumab, has been rarely reported and has a unique clinical manifestation.Case Description A 67-year-old woman was diagnosed with small-cell lung cancer. As maintenance therapy, atezolizumab was administered continuously for 10 cycles for approximately 14 months. One week after the administration of the tenth dose of atezolizumab, the patient experienced a bilateral, successive painless visual decline. The fundus and the retinal nerve fiber layer revealed no abnormalities, but the ganglion cell of the macula disappeared loss. The concentric shrinking of the peripheral visual field of the left eye was noticed. Orbital MRI revealed bilateral optic nerve thickening and peripheral optic nerve sheath enhancement (“tram-track” and “doughnut” signs). Serology, cerebrospinal fluid results, and image examination ruled out common causes of vision decline, and the condition was identified as bilateral retrobulbar ON combined with OPN as a probable atezolizumab-related immune adverse event. Thereafter, atezolizumab was discontinued, and intravenous methylprednisolone pulse (IVMP) (160 mg/day for 5 days) plus intravenous immunoglobulin (20 g/day for 3 days) was administered. The patient's visual function considerably improved after three weeks.Conclusions Retrobulbar ON and OPN associated with atezolizumab are rare side effects that are easily overlooked. Immune-related ON has unique features and requires early identification. The primary treatment for optic nerve irAEs is corticosteroids, but this is not standardized and should be used with caution.

Curcumin is a natural phenylpropanoid compound with various biological activities and is widely used in food and pharmaceuticals. A de novocurcumin biosynthetic pathway was constructed in Escherichia coliBL21(DE3). Optimization of the curcumin biosynthesis module achieved a curcumin titer of 26.8 ± 0.6 mg/L. Regulating the metabolic fluxes of the β-oxidation pathway and fatty acid elongation cycle and blocking the endogenous malonyl-CoA consumption pathway increased the titer to 113.6 ± 7.1 mg/L. Knockout of endogenous curcumin reductase (curA) and intermediate product detoxification by heterologous expression of the solvent-resistant pump (srpB) increased the titer to 137.5 ± 3.0 mg/L. A 5 L pilot-scale fermentation, using a three-stage pH alternation strategy, increased the titer to 696.2 ± 20.9 mg/L, 178.5-fold higher than the highest curcumin titer from de novobiosynthesis previously reported, thereby laying the foundation for efficient biosynthesis of curcumin and its derivatives.

Astrocytes are integral components of synaptic transmission, and their dysfunction leads to neuropsychiatric disorders such as anxiety and depression. Liver X receptor β (LXRβ) is expressed in astrocytes, and LXRβ global knockout mice shows impaired synaptic formation. In order to define the role of LXRβ in astrocytes, we used a conditional Cre-loxP system to specifically remove LXRβ from astrocytes. We found that this deletion caused anxiety-like but not depressive-like behaviors in adult male mice. This behavioral phenotype could be completely reproduced by selective deletion of LXRβ in astrocytes in the medial prefrontal cortex (mPFC). Pyramidal neurons in layer V of mPFC are involved in mood behaviors. We found that there was an increased spontaneous excitatory synaptic transmission in layer V pyramidal neurons of the mPFC of these mice. This was concurrent with increased dendritic complexity, despite normal appearance and number of dendritic spines. In addition, gene ontology analysis of RNA sequencing revealed that deletion of astrocytic LXRβ led to the enrichment of the process of synaptic transmission in mPFC. Finally, we also confirmed that renormalized excitatory synaptic transmission in layer V pyramidal neurons alleviated the anxiety in mice with astrocytic LXRβ deletion in mPFC. Together, our findings reveal that astrocytic LXRβ in mPFC is critical in the regulation of synaptic transmission, and this provides a potential new target for treatment of anxiety-like behavior.

The immunoglobulin E (IgE) response to Angiostrongylus cantonensisinfection increases in the host. This study analyzed the IgG and IgE responses detected in different body fluids of A. cantonensis-infected mice.

Both layered- and rocksalt-type Li-rich cathode materials are drawing great attention due to their enormous capacity, while the individual phases have their own drawbacks, such as great volume change for the layered phase and low electronic and ionic conductivities for the rocksalt phase. Previously, we have reported the layered/rocksalt intergrown cathodes with nearly zero-strain operation, while the use of precious elements hinders their industrial applications. Herein, low-cost 3d Mn4+ions are utilized to partially replace the expensive Ru5+ions, to develop novel ternary Li-rich cathode material Li1+x[RuMnNi]1–xO2. The as-designed Li1.15Ru0.25Mn0.2Ni0.4O2is revealed to have a layered/rock salt intergrown structure by neutron diffraction and transmission electron microscopy. The as-designed cathode exhibits ultrahigh lithium-ion reversibility, with 0.86 (231.1 mAh g–1) out of a total Li+inventory of 1.15 (309.1 mAh g–1). The X-ray absorption spectroscopy and resonant inelastic X-ray scattering spectra further demonstrate that the high Li+storage of the intergrown cathode is enabled by leveraging cationic and anionic redox activities in charge compensation. Surprisingly, in situ X-ray diffraction shows that the intergrown cathode undergoes extremely low-strain structural evolution during the charge–discharge process. Finally, the Mn content in the intergrown cathodes is found to be tunable, providing new insights into the design of advanced cathode materials for high-energy Li-ion batteries.

Hydroxytyrosol is a natural polyphenolic compound widely used in the food and drug industries. The current commercial production of hydroxytyrosol relies mainly on plant extracts, which involve long extraction cycles and various raw materials. Microbial fermentation has potential value as an environmentally friendly and low-cost method. Here, a de novobiosynthetic pathway of hydroxytyrosol has been designed and constructed in an Escherichia colistrain with released tyrosine feedback inhibition. By introduction of hpaBCfrom E. coliand ARO10and ADH6from Saccharomyces cerevisiae, the de novobiosynthesis of hydroxytyrosol was achieved. An important finding in cofactor engineering is that the introduction of L-amino acid deaminase (LAAD) promotes not only cofactor regeneration but also metabolic flow redistribution. To further enhance the hydroxylation process, different 4-hydroxyphenylacetate 3-monooxygenase (hpaB) mutants and HpaBC proteins from different sources were screened. Finally, after optimization of the carbon source, pH, and seed medium, the optimum engineered strain produced 9.87 g/L hydroxytyrosol in a 5 L bioreactor. This represents the highest titer reported to date for de novobiosynthesis of hydroxytyrosol in microorganisms.

Halogens and other volatiles are widely recycled into the deep mantle by subduction and are key components to metasomatize the sub-continental lithospheric mantle (SCLM). Lamprophyres are well known to be rich in volatiles and are important for understanding the halogen characteristics of the metasomatized SCLM and/or the mobilization of halogens during the ascent of such volatile-rich, low-degree partial melts. The North China Craton (NCC) hosts lamprophyre dikes coeval with extensive thinning of the eastern NCC in the Mesozoic and generated from lithosphere metasomatized by multiple-stage subduction components. Here we report bulk-rock heavy halogens (Cl, Br, and I) of 16 lamprophyres from the eastern NCC. The bulk-rock halogen concentrations are overall very low (Cl = 58–170 μg/g, Br = 285–559 ng/g, and I <5 ng/g), comparable with depleted Mid-Ocean ridge basalts (N-MORBs). Volatile-rich minerals (e.g., amphibole and biotite) are abundant (20–30 vol%) in these lamprophyres, however, electron probe microanalyses (EPMA) data indicate that amphiboles are mainly rich in OH and F but display very low Cl concentrations (0.01–0.04 wt%). The bulk rock and amphibole data consistently indicate low abundances of heavy halogens in the lamprophyres, which is dificult to reconcile with the remarkable enrichment of fluid-mobile large ion lithophile elements such as Ba, Rb, and K. Based on low Cl/Nb and Br/Nb but high Ba/Nb and K/Nb ratios, the low halogen concentrations likely resulted from extensive volatile loss (>90%) during melt ascent. The low Cl concentrations in early-stage amphiboles (Mg# 60–64) further indicate that such loss would have occurred before amphibole crystallization at a depth of ~15 km. We thus propose that crystallization of early olivines and pyroxenes and reaction with surrounding mantle rocks likely induced volatile saturation and exsolution, leading to strong partitioning of the halogens into the exsolved aqueous volatile phases and thus the extensive loss of halogens from the rising melt. These results reveal that significant volatile loss of halogens not only occurs during surficial low-pressure eruption but also at much deeper levels in the crust, as also identified for some kimberlites. Consequently, it would be dificult to constrain the primitive halogen components of the mantle sources via lamprophyres or similar magmas.

Chlorogenic acid is a natural phenolic compound widely used in the food and daily chemical industries. Compared to plant extraction, microbial cell factories provide a green and sustainable production method for the production of chlorogenic acid. However, complex metabolic flux distribution and potential byproducts limited the biosynthesis of chlorogenic acid in microorganisms. A de novobiosynthesis pathway for chlorogenic acid was constructed in Escherichia colivia modular engineering. Increasing the shikimate pathway flux greatly promoted chlorogenic acid production, and the influence of pyruvate metabolism on chlorogenic acid synthesis was also explored. The supply of cofactors for the key enzymes quinate/shikimate 5-dehydrogenase (YdiB) and 4-hydroxyphenylacetate 3-monooxygenase (HpaBC) was enhanced by a cofactor regeneration system. Furthermore, mutants of YdiB were verified for chlorogenic acid production in vivo. Chlorogenic acid browning occurred when the buffer pH of the buffer exceeded 6.0, but two-stage pH control achieved a chlorogenic acid titer of 2789.2 mg/L in a 5 L fermenter, the highest reported to date. This study provided a strategy for the efficient production of chlorogenic acid from simple carbon sources.

Gas-solid fluidized beds are widely applied in chemical and process engineering. It is of significance to establish a reasonable and effective mathematical model to explore the hydrodynamics of gas-particle system for industrial applications. As a less computationally demanding alternative to the discrete descriptions, two-fluid model considering kinetic theory of granular flow is often adopted to describe the fluidized behaviors of particles, but it cannot characterize the rotation of particles and its influence on the fluidized behaviors. In this study, to address the rotation effect of the fluidized particles, a two-fluid model combining the classical fluid and micropolar fluid is established, namely CMTFM. In the CMTFM, classical fluid is used to describe the motion of gas phase, while micropolar fluid is adopted to describe the motion of particle phase, and the rotation of particles and its influence on the hydrodynamics of the gas-particle system are characterized by the degree of freedom of microrotation and the improved drag force based on micropolar viscosities. In the calculation of the gas-solid bubbling fluidized bed, we investigated the influence of the microstructure parameters, particle-particle collision restitution coefficient and inlet velocity, and the results are compared to those from TFM model and experiments. Through the analysis, it manifests that pressure drop and expansion height of the fluidized bed under the consideration of the microrotation effect are closer to the experiments, which demonstrates the feasibility and advantage of the classical-micropolar two-fluid model.

•Spinal PAR1 plays an important role in the genesis of chronic pain in MRL/lpr mice.•Activation of PAR1 and suppression of AMPK activity in MRL/lpr mice with chronic pain.•Blockade of PAR1 or AMPK activation attenuated chronic pain in MRL/lpr mice.•Targeting the PAR1 and AMPK pathways may be a potent approach for treating chronic pain caused by SLE.

An urgent demand for lowering bonding temperature has been put forward by advanced flip-chip integration such as micro-LED packaging and heterogeneous integration of semiconductor devices. Indium microbump with low-melting point has attracted attention for its potential use as the interconnection intermediate, and the development of its fabrication process is therefore of great attraction. To reveal the critical process factors for successfully fabricating a high-density In microbump array, this paper investigated a simple process flow of In patterning and reflow and detailed the flux-assisted wet reflow process. Critical process conditions, including the patterned In volume, alignment accuracy, reflow reagent liquidity, and temperature profile, were described, with a particular emphasis on the role of surface tension of molten indium film during the formation of spherical microbumps. A high-density indium ball array with an overall yield greater than 99.7% can be obtained, which suggests that the In patterning and wet-reflow processes are robust and that a high-quality microbump array could be readily formed with low equipment requirements. Furthermore, the interfacial reaction characteristics between In microbump and Au adhesion layer were investigated under thermal aging conditions, which revealed lateral intermetallic growth of AuIn2compound and well-retained interfacial strength even after prolonged aging.

We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment.

With the rapid growth of the automotive industry, a huge amount of tires have been produced, which inevitably led to the accumulation of scrap tires. A typical disposal routine is using scrap tires as a partial substitute for fine aggregate in concrete, producing so-called rubber concrete. However, the detrimental effects of rubber particles on concrete properties have been identified, which, to some content, hinders their broader application. The discrete fiber addition is shown to be effective in minimizing this detrimental effect, and this paper has therefore attempted to introduce macro fiber produced from waste glass fiber reinforced polymer (GFRP) into the rubber concrete system. Three series of specimens for compression, splitting, and flexural testing were tested. The test variables include concrete type (i.e., normal concrete, rubber concrete, and modified rubber concrete); and macro fiber content (i.e., 0–2 %). In addition, the inverse analysis is performed to transform the flexural test response into the tensile constitutive law of the fiber-reinforced concrete (FRC). The test results revealed macro fibers have little effect on the compressive strength of normal concrete and rubber concrete and a detrimental effect on that of modified rubber concrete. Incorporated fibers notably improve the splitting and flexural performance of normal concrete and rubber concrete. In addition, the cost and environmental impact analysis revealed that the addition of recycling products increases the concrete cost and results in a maximum reduction of carbon emissions by 17.3 % and embodied energy emissions by 80 %.

In recent years, substantial research has been conducted on molecular mechanisms and inhibitors targeting bromodomains (BRDs) and extra-terminal (BET) family proteins. On this basis, non-BET BRD is gradually becoming a research hot spot. BRDs are abundant in histone acetyltransferase (HAT)-associated activating transcription factors, and BRD-containing HATs have been linked to cancer, inflammation, and viral replication. Therefore, the development of BRD-containing HATs as chemical probes is useful for understanding the specific biological roles of BRDs in diseases and drug discovery. Several types of BRD-containing HATs, including CBP/P300, PCAF/GCN5, and TAF1, are discussed in this context in terms of their structures, functions, and small-molecule inhibitors. Additionally, progress in BRD inhibitors/chemical probes and proteolysis targeting chimeras in terms of drug design, biological activity, and disease application are summarized. These findings provide insights into the development of BRD inhibitors as potential drug candidates for various diseases.

Hydrophones are generally calibrated in acoustic fields with temporally localized (short pulse) or long duration (tone burst) signals. Free-field conditions are achieved by time gating any reflections from the hydrophone body, mounting structures, and surrounding water tank boundaries arriving at the active sensing element. Consequently, the sensitivity response of the hydrophone is a result of direct waves incident on its active element, free from any contaminating effects of reflections. However, when using tone bursts below 400 kHz to calibrate hydrophones, it may not be possible to isolate the direct wave from reflection artifacts. This means that the sensitivity responses derived at these frequencies using short pulse and tone burst signals might not be comparable as they can be characteristic of the acoustic field interaction with either/both the hydrophone active element alone or the hydrophone active element and body. Therefore, there is a need to consider an appropriate calibration method for a given hydrophone type, depending on whether the eventual application employs short pulse or tone burst acoustic fields. This article presents the findings from a short study comprising four needle-type hydrophones of active element diameters in the range of 1–4 mm. These hydrophones were calibrated from 30 kHz to 1.6 MHz using established calibration methodologies within the underwater acoustics (UWA) and ultrasound (US) areas employed at the National Physical Laboratory (NPL), Teddington, U.K. In UWA tone, burst acoustic fields are used, while in US, it is short pulses. The 2- and 4-mm-diameter needle hydrophones showed the largest variation at the overlapping frequencies, in which the maximum disagreement of UWA calibration was 30% relative to US calibration. For the 4-mm hydrophone, UWA calibration exhibited resonant sensitivity structure between 100 and 450 kHz, but which was absent in US calibration. This observed behavior was further investigated theoretically by using a validated acoustic wave solver to confirm the resonant sensitivity structure seen in the case of UWA calibration. The work contained within illustrates the need to ensure that the method of calibration is carefully considered in the context of the duration of the acoustic signals for which the hydrophone is intended.