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Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential mediator of the IL-1R and TLR signaling pathways, both of which have been implicated in multiple autoimmune conditions. Hence, blocking the activity of IRAK4 represents an attractive approach for the treatment of autoimmune diseases. The activity of this serine/threonine kinase is dependent on its kinase and scaffolding activities; thus, degradation represents a potentially superior approach to inhibition. Herein, we detail the exploration of structure–activity relationships that ultimately led to the identification of KT-474, a potent, selective, and orally bioavailable heterobifunctional IRAK4 degrader. This represents the first heterobifunctional degrader evaluated in a nononcology indication and dosed to healthy human volunteers. This molecule successfully completed phase I studies in healthy adult volunteers and patients with atopic dermatitis or hidradenitis suppurativa. Phase II clinical trials in both of these indications have been initiated.

Super 13Cr, as an economy stainless steel (SS) for oil country tubular goods, needs stable corrosion resistance in high-pressure and high-temperature (HPHT) downhole medium. Severe plastic deformation (SPD) are the surface modification technology to improve mechanical properties, fatigue behavior and corrosion resistance of metals, and shot peening (SP) has been the most widely used SPD process. However, there are quite limited studies about the microsutructure evolution, residual stress, and high-temperature corrosion behavior of SP-treated martensitic SS. In this study, super 13Cr martensitic SS was treated by SP with various air pressures and nozzle speeds. The surface characteristics and high-temperature corrosion behaviour in 3.17 mol/L K2HPO4solution were investigated through finite element model analysis, characterization of residual stress and microstructure, as well as electrochemical and stress corrosion cracking (SCC) tests at 160 °C and 10 MPa. The results showed that SP-treated super 13Cr could generate high-level compressive residual stress and SPD microstucture, including nano-sized equiaxed grains, gradient lamellar structure and fragmented carbides. Increasing air pressure contributed to achieve uniform nanocrystalline, but tended to generate high dislocation density and surface defects. The improving effect of SP treatment at low air pressure of 0.15 MPa on passivation ability was limited, and high air pressure adversely impacted corrosion resistance. SP-treated specimens showed high SCC susceptibility, due to the introduction of more surface defects, high angle grain boundaries, and dislocations.

Developing therapies for the activated B-cell like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL) remains an area of unmet medical need. A subset of ABC DLBCL tumors is driven by activating mutations in myeloid differentiation primary response protein 88 (MYD88), which lead to constitutive activation of interleukin-1 receptor associated kinase 4 (IRAK4) and cellular proliferation. IRAK4 signaling is driven by its catalytic and scaffolding functions, necessitating complete removal of this protein and its escape mechanisms for complete therapeutic suppression. Herein, we describe the identification and characterization of a dual-functioning molecule, KT-413 and show it efficiently degrades IRAK4 and the transcription factors Ikaros and Aiolos. KT-413 achieves concurrent degradation of these proteins by functioning as both a heterobifunctional degrader and a molecular glue. Based on the demonstrated activity and safety of KT-413 in preclinical studies, a phase 1 clinical trial in B-cell lymphomas, including MYD88 mutant ABC DLBCL, is currently underway.

Immulina is a commercially available extract of Arthrospira platensis enriched with bacterial lipoproteins that acts as a potent Toll-like receptor 2 agonist. However, the immunostimulatory effect of Immulina is not well understood in vivo. Here, to devise an Immulina formulation suitable for in vivo oral gavage dosing, Immulina nanosuspension was prepared and freeze-dried to yield lyophilized nano-Immulina, which had an average particle size of around 300 nm and fully retained the bioactivity as a Toll-like receptor 2 agonist. Compared to the regular Immulina powder, lyophilized nano-Immulina notably accelerated the dissolution in aqueous media. Immulina nanosuspension was found to stimulate the production of proinflammatory cytokines in murine bone marrow-derived dendritic cells and macrophages. The immune response to Immulina was investigated in healthy mice by longitudinally monitoring the phagocytic activity of circulating neutrophils as a surrogate marker. Following daily oral ingestion of Immulina nanosuspension (10 mg/mouse/day), the phagocytic activity of circulating neutrophils was significantly elevated, suggesting an important mechanism for Immulina to enhance innate immunity. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this work is to evaluate the clinical efficacy and safety of sufentanil vs. remifentanil anesthesia in elderly patients undergoing curative resection for hepatocellular carcinoma (HCC). Methods: Medical records of elderly patients aged ≥ 65 years who received curative resection for HCC between January 2017 and December 2020 were retrospectively reviewed. The patients were divided into either the sufentanil group or the remifentanil group according to the method of analgesia used. Vital signs including mean arterial pressure (MAP), heart rate (HR), and arterial oxygen saturation (SpO2), distribution of T-cell subsets (CD3, CD4, and CD8 lymphocytes), distribution of the stress response index [cortisol (COR), interleukin (IL)-6, C-reactive protein (CRP), and glucose (GLU)] were recorded prior to anesthesia (T0), after induction of anesthesia (T1), at the end of surgery (T2), 24 h after surgery (T3), and 72 h after surgery (T4). Postoperative adverse events were collected. Results: Repeated measure analysis of variance (ANOVA) showed that after controlling for baseline patient demographic and treatment characteristics as covariates, both between- and within-group effects were significant (all P< 0.01), and the interaction between time and treatments was also significant (all P< 0.01) in the vital signs (MAP, HR, and SpO2), distribution of T-cell subsets (CD3, CD4, and CD8 lymphocytes), and distribution of the stress response index (COR, IL-6, CRP, and GLU), indicating that sufentanil led to stable hemodynamic and respiratory functions, lower reduction of T-lymphocyte subsets, and stable stress response indices compared to remifentanil. There is no significant difference in adverse reactions between the two groups (P= 0.72). Conclusions: Sufentanil was associated with improved hemodynamic and respiratory function, less stress response, less inhibition of cellular immunity, and similar adverse reactions compared with remifentanil.

The corrosion behavior and mechanism of P110 steel tubing in in low CO2 particle pressure and high salinity formation water environment was investigated through high temperature and high pressure dynamic immersion tests, macro-morphology analysis, scanning electron microscopy(SEM) inspection, energy disperse spectroscopy(EDS) analysis and X-ray diffraction(XRD) analysis. The Results showed that the increasing of CO2 partial pressure accelerated the corrosion process of P110 tubing steel, and the corrosion rates of P110 tubing decreased with the increasing of temperature. Furthermore, the high content of Ca2+ in the formation water also had a big influence on the corrosion behavior of P110 tubing steel, for it could affect the precipitation quantity and morphology of CaCO3 at different temperature and CO2 particle pressure.

The corrosion behavior of 3Cr steel in simulated oilfield CO2 and formation water environment at different temperature and partial pressure of CO2 were investigated using dynamic immersion tests, scanning electron microscopy inspection and X-ray diffraction analysis. The result demonstrated that with an increasing of temperature, the corrosion rate of 3Cr steel decreased, and reached the maximum corrosion rate when the partial pressure of CO2 was 0.5MPa. The high content of Ca2+ in the formation water had also played an important role in the corrosion behavior of the 3Cr steel for it can lead to a deposition of the CaCO3 on the surface of the specimen.

In recent years, with the rapid development of modern petroleum industry, some conventional oil country tubular goods (OCTGs) have been unable to meet the requirements of ultra-deep oil and gas drilling and production. Titanium alloy OCTGs showed broad application prospects due to its high specific strength, Low elastic modulus and strong CO2+H2S+Cl- corrosion resistance. However, large-scale applications of titanium alloy OCTGs were seldom reported, which is mainly attributed to the lack of anti-corrosive resistance and mechanical performance of titanium alloy OCTGs in the working conditions. In the present work, the research progress on properties and application of titanium alloy OCTGs were reviewed. The resistance to uniform corrosion, stress corrosion cracking, pit and crevice corrosion, mechanical properties of the titanium alloy OCTGs in air and downhole corrosion media were comprehensively discussed. Application status and prospect of titanium alloy OCTGs in oil and gas exploration were also summarized.

Glioblastoma represents one of the most aggressive cancers, characterized by severely limited therapeutic options. Despite extensive investigations into this brain malignancy, cellular and molecular components governing its immunosuppressive microenvironment remain incompletely understood. Here, we identify a distinct neutrophil subpopulation, termed disease-specific suppressive granulocytes (DSSGs), present in human glioblastoma and lower-grade gliomas. DSSGs exhibit the concurrent expression of multiple immunosuppressive and immunomodulatory signals, and their abundance strongly correlates with glioma grades and poor clinical outcomes. Genetic disruption of neutrophil recruitment in immunocompetent mouse models of gliomas, achieved through Cxcl1knockout in glioma cells or host-specific Cxcr2deletion or diphtheria toxin A-mediated neutrophil depletion, can significantly enhance antitumor immunity and prolong survival. Further, we reveal that the skull bone marrow and meninges can be the primary sources of neutrophils and DSSGs in human and mouse glioma tumors. These findings demonstrate a critical mechanism underlying the establishment of the immunosuppressive microenvironment in gliomas.

Recently, airflow sensors have attracted great attention due to their unique characteristics. However, the preparation of high-performance airflow sensors viaextraordinarily simple, controllable and cost-effective methods remains a great challenge. Herein, inspired by the fluff system of the spider, an ultrasensitive fluffy-like airflow sensor with carbon fibers (CFs) uniformly and firmly planted on the surface of a polyvinyl alcohol (PVA) fibrous substrate has been easily fabricated using electrostatic flocking technology. The fluffy-like structure endows the airflow sensor with superior properties including ultra-sensitivity, fast response time (0.103 s), low airflow velocity detection limit (0.068 m s−1), ultra-sensitive detection in a wide airflow range (0.068–16 m s−1), and multi-directional consistent response to airflow. This sensor can be used to accurately recognize sound waves and voiceless speech and detect human and object motions in different postures and speeds. This work presents insights into designing and preparing high-performance airflow sensors on a large-scale for sound recognition, motion monitoring, and assisting the disabled.

Here, we demonstrate the applicability of self‐assembling linear‐dendritic block copolymers (LDBCs) and their nanoaggregates possessing varied surfaces as therapeutic nanocarriers. These LDBCs are comprised of a hydrophobic, linear polyester chemically coupled to a hydrophilic dendron polyamidoamine (PAMAM)—the latter of which acts as the surface of the self‐assembled nanoaggregate in aqueous media. To better understand how surface charge density affects the overall operability of these nanomaterials, we modified the nanoaggregate surface to yield cationic (NH3+), neutral (OH), and anionic (COO−) surfaces. The effect of these modifications on the physicochemical properties (i.e., size, morphology, and surface charge density), colloidal stability, and cellular uptake mechanism of the polymeric nanocarrier were investigated. This comparative study demonstrates the viability of nanoaggregates formed from PDLLA‐PAMAM LDBCs to serve as nanocarriers for applications in drug delivery.

Deep learning is applied to many complex tasks in the field of wireless communication, such as modulation recognition of spectrum waveforms, because of its convenience and efficiency. This leads to the problem of a malicious third party using a deep learning model to easily recognize the modulation format of the transmitted waveform. Some existing works address this problem directly using the concept of adversarial examples in the computer vision field without fully considering the characteristics of the waveform transmission in the physical world. Therefore, we propose two low‐interception waveforms (LIWs) generation methods, the LIW and ULIW algorithms, which can reduce the probability of the modulation being recognized by a third party without affecting the reliable communication of the friendly party. Among them, ULIW improves LIW algorithm by simulating channel noise during training cycle, and substantially reduces the perturbation magnitude while maintaining low interception accuracy. Our LIW and ULIW exhibit significant low‐interception performance in both numerical simulations and hardware experiments. Define the low‐interception question, and give the mathematical model, application scenarios, and evaluation criteriaPropose the ULIW algorithm based on our LIW algorithm, which substantially reduces perturbation while maintaining low interception accuracyVerify the low‐interception performance of LIW and ULIW in both the digital and physical worlds Define the low‐interception question, and give the mathematical model, application scenarios, and evaluation criteria Propose the ULIW algorithm based on our LIW algorithm, which substantially reduces perturbation while maintaining low interception accuracy Verify the low‐interception performance of LIW and ULIW in both the digital and physical worlds

This paper gives a thorough investigation on the fracture failure of the blowout preventer (BOP) ram. Through appearance inspection, magnetic powder inspection, physicochemical inspection, metallographic inspection and scanning electron microscope (SEM), the main fracture reason of the BOP ram is that there was some original cracks in the BOP ram before fracture, during the service process the bop ram is subjected to impact load, therefore brittle fracture occurs due to the high brittleness of the gate material (which is caused by large internal structure) and low anti-crack propagation ability. Key words: Blowout preventer (BOP) ram; Fatigue break; Brittle fracture; Failure analysis

The mains reasons for internal corrosion failure and cracking of the tee in shale gas transportation platform have been proposed based on macroscopic analysis, physical and chemical property test, metallographic examination, Scanning Electron Microscope analysis, X-ray spectroscopy analysis and service condition analysis. The results show that corrosion occurring in the inner wall of tee was caused by the combined impacts of CO2 corrosion, sulfate-reducing bacteria (SRB) corrosion and erosion corrosion. The crack in the weld of the inner wall was mainly due to the Sulfate-reducing Bacteria Induced cracking.

With the increasingly harsh conditions of complex oil and gas wells such as high-temperature and high-pressure deep wells and long-distance horizontal well, the integrity of casing string puts forward higher requirements for compression performance of premium thread connections. The requirements of high compression resistance of connection is complicated, including ensuring the integrity of structure and sealability for thread at the same time under high compression load being equal to the bearing capacity of casing body, and considering the structural fatigue, environmental fracture and seal failure caused by the weakening of thread bearing performance under cyclic load. Based on the failure cases of some casing connections, laboratory tests and finite element analysis results, this paper discusses the key technical points in the above mentioned problems, and provides the suggestions for the performance optimization of high-performance casing premium connections based on failure prevention.

Coronavirus disease 2019 (COVID-19) has emerged as a pandemic with serious clinical manifestations including death. A pandemic at the large-scale like COVID-19 places extraordinary demands on the world's health systems, dramatically devastates vulnerable populations, and critically threatens the global communities in an unprecedented way. While tremendous efforts at the frontline are placed on detecting the virus, providing treatments and developing vaccines, it is also critically important to examine the technologies and systems for tackling disease emergence, arresting its spread and especially the strategy for diseases prevention. The objective of this article is to review enabling technologies and systems with various application scenarios for handling the COVID-19 crisis. The article will focus specifically on 1) wearable devices suitable for monitoring the populations at risk and those in quarantine, both for evaluating the health status of caregivers and management personnel, and for facilitating triage processes for admission to hospitals; 2) unobtrusive sensing systems for detecting the disease and for monitoring patients with relatively mild symptoms whose clinical situation could suddenly worsen in improvised hospitals; and 3) telehealth technologies for the remote monitoring and diagnosis of COVID-19 and related diseases. Finally, further challenges and opportunities for future directions of development are highlighted.

In this paper, a copper-based bond emery wheel was prepared by vacuum hot pressing sintering through powder metallurgy. The effects of various bond contents on the grinding performance of the copperbased bond grinding wheel were studied using a self-made experimental device; the friction coefficients between the friction pairs and roughness of the grinded rail surface were also obtained. The results show that the grinding wheel had the best grinding performance when the content of the copper-based bond was at 35 wt.-%, the friction coefficient 0.29, the grinding ratio 81.34, and the surface roughness 7.191 μm, which meet the roughness requirements of rail grinding. The microstructure of the rail surface and debris after grinding were studied by scanning electron microscope and energy spectrum analysis. Adhesive wear, abrasive wear, oxidation wear and delamination wear occurred during the friction and wear process. The grinding behavior of grinding wheels was analyzed in accordance with the experimental results.

Supplemental Digital Content is available in the text.Major histocompatibility complex (MHC) class II regulatory genes play a paramount role in immune response that can exert a predominant influence on clinical outcome of Epstein–Barr virus infection consistently assumed as the main pathogenetic factor for nasopharyngeal carcinoma. To elucidate the relationship between allelic variants of MHCclass II regulatory genes and susceptibility to nasopharyngeal carcinoma, a total of 28 polymorphic loci at MHCclass II regulatory genes, involving CIITA, CREB1, RFXfamily genes (RFX5, RFXAP,and RFXANK), and NFYfamily genes (NFYA, NFYB, and NFYC), were genotyped by multiplex SNaPshot minisequencing in 137 patients with nasopharyngeal carcinoma and 107 healthy controls from the southern Chinese population. Allelic analysis disclosed that rs7404873, rs6498121, rs6498126, and rs56074043 shared correlations with nasopharyngeal carcinoma (Ptrend< 0.05). Further, rs6498126 on CIITAwas independently associated with the risk of developing nasopharyngeal carcinoma (CC vs. GG, odds ratio: 7.386, 95% confidence interval: 1.934–28.207, Ptrend< 0.01). Conversely, rs7404873 on CIITAand rs56074043 on NFYBmanifested epistatic interaction to decreased susceptibility of nasopharyngeal carcinoma (rs7404873, TT vs. GG, odds ratio: 0.256, 95% confidence interval: 0.088–0.740, Ptrend< 0.05; rs56074043, AA vs. AG, odds ratio: 0.341, 95% confidence interval: 0.129–0.900, Ptrend< 0.05). Additionally, bioinformatics analysis revealed that the three variants were transcriptional regulatory in function and might impact the expression of nearby genes. The findings suggested genetic variants on MHCclass II regulatory genes contributed to nasopharyngeal carcinoma susceptibility and might provide new insights for screening high-risk population.

In this paper, a novel decentralised robust state feedback sliding mode control is presented to stabilise a class of nonlinear interconnected systems with matched uncertainty and unknown interconnections. A composite sliding surface is designed, and a set of conditions are developed to guarantee that the corresponding sliding motion is uniformly asymptotically stable. Then, a decentralised state feedback sliding mode control is proposed to drive interconnected systems to the designed sliding surface in finite time, and sliding motion occurs thereafter. The bounds on the uncertainties and interconnections are known nonlinear functions, which are employed in the control design to reject the effects of uncertainties and unknown interconnections to enhance the robustness. Finally, a numerical simulation example is given to demonstrate the effectiveness of the proposed control strategy.

A microfluidic device integrated with a microchannel stacked by two kinds of microbeads with different sizes and a capillary microchannel array was designed and fabricated. When whole blood sample flowed through these channels, blood cells were filtered and adsorbed by the stacked microbeads, and plasma could be separated rapidly. The microbeads were introduced into the channel by negative pressure and thus stacked compactly. Protein blocking solution was used to improve the hydrophilicity of the bead surface. Then the microchip was dried and cooled before 20 μL of blood was dropped in the inlet. Driven by capillary force, the blood proceeded in the channel. The influences of microbeads with different sizes and a locally widened microchannel were investigated. Experimental results showed that when microbeads with a diameter of 10 μm were filled in the locally widened microchannel, the separation rate of plasma was the fastest. The collection rate of plasma could reach up to 0.16 μL min−1in this case, which could meet the requirement of most clinical applications. On the chip device, collected plasma was used to carry out the agglutination test, and the blood group could be determined quickly, which verified the usefulness of this method.

Complement factor D (FD), a highly specific S1 serine protease, plays a central role in the amplification of the alternative complement pathway (AP) of the innate immune system. Dysregulation of AP activity predisposes individuals to diverse disorders such as age-related macular degeneration, atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II, and paroxysmal nocturnal hemoglobinuria. Previously, we have reported the screening efforts and identification of reversible benzylamine-based FD inhibitors (1and 2) binding to the open active conformation of FD. In continuation of our drug discovery program, we designed compounds applying structure-based approaches to improve interactions with FD and gain selectivity against S1 serine proteases. We report herein the design, synthesis, and medicinal chemistry optimization of the benzylamine series culminating in the discovery of 12, an orally bioavailable and selective FD inhibitor. 12demonstrated systemic suppression of AP activation in a lipopolysaccharide-induced AP activation model as well as local ocular suppression in intravitreal injection-induced AP activation model in mice expressing human FD.

IMPORTANCE: Cardiovascular disease (CVD) is a leading cause of death among patients with end-stage renal disease (ESRD). Young adult (ages 22-29 years) have risks for ESRD-associated CVD that may vary from other ages. OBJECTIVE: To test the hypothesis that young adult–onset ESRD is associated with higher cardiovascular (CV) hospitalizations and mortality with different characteristics than childhood-onset disease. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used the US Renal Data System to categorize patients who initiated ESRD care between 2003 and 2013 by age at ESRD onset (1-11, 12-21, and 22-29 years). Cardiovascular hospitalizations were identified via International Classification of Diseases, Ninth Revision discharge codes and CV mortality from the Centers for Medicare & Medicaid ESRD Death Notification Form. Patients were censored at death from non-CVD events, loss to follow-up, recovery, or survival to December 31, 2014. Adjusted proportional hazard models (95% CI) were fit to determine risk of CV hospitalization and mortality by age group. Data analysis occurred from May 2016 and December 2017. EXPOSURES: Onset of ESRD. MAIN OUTCOMES AND MEASURES: Cardiovascular mortality and hospitalization. RESULTS: A total of 33 156 patients aged 1 to 29 years were included in the study population. Young adults (aged 22-29 years) had a 1-year CV hospitalization rate of 138 (95% CI, 121-159) per 1000 patient-years. Young adults had a higher risk for CV hospitalization than children (aged 1-11 years; hazard ratio [HR], 0.41 [95% CI, 0.26-0.64]) and adolescents (aged 12-21 years; HR, 0.86 [95% CI, 0.77-0.97]). Of 4038 deaths in young adults, 1577 (39.1%) were owing to CVD. Five-year cumulative incidence of mortality in this group (7.3%) was higher than in younger patients (adolescents, 4.0%; children, 1.7%). Adjusted HRs for CV mortality were higher for young adults with all causes of ESRD than children (cystic, hereditary, and congenital conditions: HR, 0.22 [95% CI, 0.11-0.46]; P &lt; .001; glomerulonephritis: HR, 0.21 [95% CI, 0.10-0.44]; P &lt; .001; other conditions: HR, 0.33 [95% CI, 0.23-0.49]; P &lt; .001). Adolescents had a lower risk for CV mortality than young adults for all causes of ESRD except glomerulonephritis (cystic, hereditary, and congenital conditions: HR, 0.45 [95% CI, 0.27-0.74]; glomerulonephritis: HR, 0.99 [95% CI, 0.76-1.11]; other: HR, 0.47 [95% CI, 0.40-0.57]). Higher risks for CV hospitalization and mortality were associated with lack of preemptive transplant compared with hemodialysis (hospital: HR, 14.24 [95% CI, 5.92-34.28]; mortality: HR, 13.64 [95% CI, 8.79-21.14]) and peritoneal dialysis [hospital: HR, 8.47 [95% CI, 3.50-20.53]; mortality: HR, 7.86 [95% CI, 4.96-12.45]). Nephrology care before ESRD was associated with lower risk for CV mortality (HR, 0.77 [95% CI, 0.70-0.85]). CONCLUSIONS AND RELEVANCE: Cardiovascular disease accounted for nearly 40% of deaths in young adults with incident ESRD in this cohort. Identified risk factors may inform development of age-appropriate ESRD strategies to improve the CV health of this population.

A noninvasive topical ocular therapy for the treatment of neovascular or “wet” age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in vivo models of choroidal neovascularization (CNV) as the primary means of developing SAR related to efficacy from topical administration. Ultimately, this effort led to the discovery of acrizanib (LHA510), a small-molecule VEGFR-2 inhibitor with potency and efficacy in rodent CNV models, limited systemic exposure after topical ocular administration, multiple formulation options, and an acceptable rabbit ocular PK profile.

Supplemental Digital Content is available in the text.

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 109, which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

Tuberous sclerosis complex (TSC) is a rare disease that causes multisystem benign neoplasm, induced by dysregulation of the mammalian target of the rapamycin pathway (mTOR). This study aimed to examine the effects of continuous low-dose everolimus, a potent and selective inhibitor of mTOR, on the treatment of TSC-associated renal angiomyolipoma (AML). Between July 2013 and August 2017, 11 patients with TSC-AML were enrolled for an everolimus therapy protocol. An oral everolimus dose starting at 2.5?mg daily was gradually increased to 5.0?mg daily. All patients were evaluated using MRI or CT scanning at baseline, 12, 24, 36 and 48 months after the start of treatment for measuring changes of renal AML mass volume. Everolimus therapy resulted in significant shrinkage of TSC-AML volume after 48 months follow-up. Serum levels of everolimus were subdivided into group I (<8?ng/mL, n=6) and group II (>8?ng/mL, n=5). The volume reduction rates were 10.6%–65.2% in group I and 42.5%–70.6% in group II. To evaluate the response to treatment, three of six (50%) were responders in group I, and all the patients in group II (5/5, 100%) were responders. The differences in AML volume reduction between the groups were statistically significant at 12 months (p=0.011), 24 months (p=0006), 36 months (p=0.014) and 48 months (p=0.05). These results suggest that continuous low-dose everolimus therapy (2.5–5?mg daily) might be effective in shrinking TSC-AML volume and minimizes adverse effects and subsequent reducing medical costs.

The 110 Ksi tubing failed in use when reservoir acidification reconstruction and production testing were performed in an oil well, which were longitudinal cracking of coupling. Failure analysis was conducted on the coupling. The failure zone was studied by means of macroscopic analysis, metallographic, scanning electronic microscope,energy dispersive spectrometer and X-ray diffraction analysis etc. The results indicated that the failure of the coupling is caused by stress corrosion cracking (SCC). SCC initiated from the exterior surface of coupling and displayed the fracture feature of intergranular crack propagation. The corrosion products at the grain boundaries were found to be mainly some oxides. The failure was in connection with the completion fluid composition, which are mainly nitrates.

Purpose The purpose of this study is to reveal the lead–lag structure between international crude oil price and stock markets.Design/methodology/approach The methods used for this study are as follows: empirical mode decomposition; shift-window-based Pearson coefficient and thermal causal path method.Findings The fluctuation characteristic of Chinese stock market before 2010 is very similar to international crude oil prices. After 2010, their fluctuation patterns are significantly different from each other. The two stock markets significantly led international crude oil prices, revealing varying lead–lag orders among stock markets. During 2000 and 2004, the stock markets significantly led international crude oil prices but they are less distinct from the lead–lag orders. After 2004, the effects changed so that the leading effect of Shanghai composite index remains no longer significant, and after 2012, S&P index just significantly lagged behind the international crude oil prices.Originality/value China and the US stock markets develop different pattens to handle the crude oil prices fluctuation after finance crisis in 1998. [ABSTRACT FROM AUTHOR]

Abstract

Purpose Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that has been shown to affect many cellular functions, such as cell growth, proliferation, and metabolism. However, there has been minimal focus on the expression of mTOR in pterygium. The purpose of this study was to investigate the expression of mTOR and the correlation between the levels of mTOR and α-smooth muscle actin (α-SMA, a marker of transdifferentiation) in pterygium.Methods Primary pterygium samples from 28 patients and normal conjunctival samples from 16 patients were surgically removed and analyzed. The expression levels of mTOR and α-SMA in the excised specimens were assessed using immunohistochemistry and Western blotting. Furthermore, correlations between the mTOR and α-SMA expression levels were studied.Results The expression of mTOR and α-SMA was significantly higher in the pterygium tissues than in normal conjunctiva tissues. A significant positive correlation was detected between the number of mTOR-immunopositive fibroblasts and the number of α-SMA-immunopositive fibroblasts (ρ = 0.463, p = 0.0078). Additionally, mTOR expression was significantly correlated with α-SMA expression (ρ = 0.269, p = 0.031) in pterygium.Conclusions There was an increased expression of mTOR in pterygium samples compared to that in normal conjunctival tissues, with a positive correlation with α-SMA expression. These findings might be involved in the pathogenesis of pterygium.

The main objective of this study was to evaluate the efficacy and safety of Lactobacillus rhamnosusin children aged 4–48 months with atopic dermatitis.

In recent years, chiral guanidines have attracted considerable interest in organic synthesis because of their unique structural features and strongly basic properties. Compounds belonging to this structural class can act as not only Brønsted bases but also through a hydrogen bond activation mode either of the nucleophile or of the electrophile, and have consequently been widely used in asymmetric organic catalysis, delivering high levels of selectivity and activity. The Michael reaction is one of the most common methods of forming C-C and C-H bonds and has been used in many successful cases as an important transformation of industrial production of several bioactive molecules. In this review, series of classical chiral guanidines with “privileged” scaffolds were summarized, and recent reports describing the usage of chiral guanidines as organocatalysts in enatioselctive Michael reactions of carbon and hetero-nucleophiles to different olefins were described. Furthermore, the transition state models to elucidate how these chiral guanidines affect stereoselectivities in the conjugate additions were demonstrated, and the potential industrial applications of these methodologies were discussed as well.

Modernizations in the chemical and construction industries have made it possible to create novel curing techniques. Many studies have been conducted to determine the effectiveness of curing and how it impacts the properties of concrete. In this paper, a class of Ordinary Portland Cement (OPC) type-I Iranian Qayen is utilized to prepare for the Compound Curing Agent (CCA) and the Water Base Curing (WBC) concrete specimens. This paraffin-based water emulsion is adopted to protect fresh concrete against the rapid evaporation of mixing water. The findings from an experimental investigation conducted according to the ASTM standards to determine the compressive strength of mortar cylinders are summarized. After mixing, the slump test is used to determine the mixing efficiency. Then, the concrete specimens are prepared with an altering water/binder ratio of 0.47, utilizing ASTM-graded sand and OPC, and cured with WBC and CCA for 7 days, 14 days, 21 days, and 28 days for compressive strength testing. The influence of structural grade mortar mixing with cement on the concrete strength is investigated, the compressive strengths of different curing procedures are compared, and the technical effectiveness of concrete protection using the curing compounds in Kabul is examined. The experiment results show that the compressive strength of the concrete specimens is determined to be slightly larger in concrete specimens cured with water than in specimens cured with a curing compound. In contrast, the reliability of compressive strength data of the compound-cured concrete specimens is better than that of the water-cured ones. Finally, various hardening models are used to fit the compressive strength test results of the concrete specimens. The estimated findings show that the asymptotic model can more precisely reflect the hardening behaviour of concrete during the curing process when compared to the bilinear and broken line models.

Electrolytic reduction technology plays a significant role in industrial metal production. In present work, cyclic voltammetry (CV) and square wave voltammetry (SWV) were applied to study the electrochemical behaviors of ZnO cathode in the CaCl2-NaCl melt at 873 K. During the experiment, we found that the dissolution-electrodeposition mechanism (ZnO = Zn2++ O2−, Zn2++ 2e−= Zn) dominates the electrolytic reduction of ZnO, and the contribution of the direct-reduction from solid phase (ZnO + 2e−= Zn + O2−) is small. Furthermore, the electro-reduction of ZnO was conducted by potentiostatic electrolysis. The peak potential of ZnO to Zn was −0.48 V vs Ag/Ag+. Therefore, the metallic Zn can be obtained at an applied potential of −0.80 V (vs Ag/Ag+). When the applied potential increased to −2.00 V (vs Ag/Ag+), the Zn and CaZn3alloy were formed simultaneously. The electrolytic products were confirmed by X-ray diffraction (XRD) analysis. This study proved the feasibility of electro-reduction technology to prepare Zn metal through the reduction of ZnO material.

The electrochemical behaviors of Gd2O3, ZnO and Gd2O3-ZnO in NaCl-CaCl2molten salt was studied by cyclic voltammetry and square wave voltammetry, and the corresponding constant potential electrolysis and XRD analysis indicated that the reduction processes were in agreement with the process that 3PI (metal∣oxide∣electrolyte three-phase interline) expanded with time from surface to interior of the cathode. Moreover, the addition of ZnO could promote the electrochemical reduction of Gd2O3. According to the electrochemical behavior (CV) and the characterization (XRD and SEM-EDS) of electrolytic product, the intermetallic compounds, GdZn12, Gd2Zn17and Gd13Zn58, were generated during the electrolysis of Gd2O3-ZnO cathode without dendritic deposits.

Purpose This paper aims to capture tail dependence between sentiment index and Shanghai composite index (SCI) by proposing a sentiment index based on text mining.Design/methodology/approach Online text mining and the Copula model were used in this study.Findings First, the paper finds herding effect in the expression of investors’ sentiment from online text data, and the usage occurrence frequency of most vocabulary is less correlative with SCI. Second, given these two features, the paper uses weighted divide-and-conquer algorithm to construct a sentiment index. Finally, because of multivariate non-Gaussian joint distribution between them, the paper uses the Copula model to detect their tail dependences, and finds that both upper and lower tail dependences could have a significant influence between positive sentiment and SCI, with a higher probability on the upper one. Additionally, only the upper tail dependence exhibits the significant influence between negative sentiment and SCI.Originality/value This paper proposes a framework of constructing investment sentiment index with the weighted conquer-and-divide algorithm, and characterizes tail dependence between sentiment index and SCI. The implication can measure the environment of investment market of China and provide an empirical ground for bandwagon effect and bargain shopper effect. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) and nocturnal enuresis are common disorders with extensive psychosocial suffering in affected children, and healthcare burden on parents. Whether the childhood psychological disorders and nocturnal enuresis are factors contributing to ADHD have not been clearly established. This study conducted a population-based case–control study using data sets from the National Health Research Insurance database, and identified 14 900 children diagnosed with ADHD. Risk factors that have been associated with or possibly related to ADHD development were included in this study. Performance of in groups of ADHD with enuresis was compared with controls. With adjustment for potential covariates, participants with enuresis exhibited a 2.24-fold greater risk of subsequent ADHD development compared with controls (95% CI 1.84 to 2.73). Participants with enuresis and comorbidity had a significantly greater risk of ADHD than those with no enuresis and no comorbidity (adjusted OR=8.43, 95% CI 4.38 to 16.2). Children who are assessed for ADHD should be evaluated for the presence of enuresis or other neurobehavioral comorbidities. Multidisciplinary treatment may benefit children with ADHD and minimize psychological burden on parents.

Purpose – The purpose of this paper is to provide the possible and better selection for pedestrian flow evacuation. Design/methodology/approach – Simulation. Findings – First, according to the model with self-decision agents, the paper figures out that the effect of evacuation guided by the random-walk mechanism exceeds that guided by the inertial mechanism, and specifically, the effect of evacuation could significantly improve if random-walk agents restraint the probability of random walk under 0.4. Besides, on neighborhood reference mechanism, individuals who take neighbors’ average direction as reference tend to achieve better effect of evacuation than that of following majority rule. Furthermore, this paper proposes that an optimal ratio of the proportion of clever individuals and system density exists for evacuation effect improvement. Finally, the evacuating effect with barrier locating in different space is also studied in our research. Originality/value – The effect of evacuation could significantly improve if random-walk agents restraint the probability of random walk under 0.4. On neighborhood reference mechanism, individuals who take neighbors’ average direction as reference tend to achieve better effect of evacuation than that of following majority rule. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ) is considered a first line chemotherapy drug for glioblastoma (GBM). Unfortunately, the GBM without methylation of O6-methylguanine-DNA methyltransferase (MGMT), accounting for about 70% of all GBM, shows an inherent resistance to TMZ treatment. Aberrant accumulation of neutral lipids, primarily triglycerides (TGs) and cholesteryl esters (CEs), in lipid droplets (LDs) has been recognized as metabolic vulnerability for GBM therapy. However, it is not known whether MGMT methylation affects lipid accumulation in GBM. Herein, we employed label-free Raman spectromicroscopy, which integrated stimulated Raman scattering (SRS) microscopy and confocal Raman spectroscopy, to quantitatively analyze both the amount and composition of intracellular LDs in intact GBM tissues obtained from patients who had undergone resection surgery. Our results showed significant reductions in both the LD amount and the CE percentage in MGMT unmethylated GBMs (MGMT methylation < 15%) compared to MGMT methylated ones (MGMT methylation ≥ 15%). Due to a big variation of lipid accumulation in the MGMT methylated GBMs, these patients were further divided into hypermethylated group (MGMT methylation ≥ 50%) and intermediate-methylated group (MGMT methylation 15∼50%), according to the significantly different median survival rates of these two groups. Remarkable differences in LD amount, CE percentage, and also lipid saturation degree were found between the hypermethylated group and the other two groups, but not between the unmethylated and intermediate-methylated groups. To elucidate the possible underlying mechanism, we analyzed the differential expression of lipid metabolism-related genes in GBM with different levels of MGMT methylation using The Cancer Genome Atlas Program (TCGA) dataset. It was shown that the genes related to lipid oxidation and lipid efflux were upregulated, and the genes related to lipid synthesis were downregulated in unmethylated group. These findings unravel the relationship between MGMT methylation and lipid accumulation in GBM, which may offer new opportunities for the diagnosis and treatment of TMZ-resistant GBM.

The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019–2020 were assessed.

The electrochemical behavior of Eu(III)/Eu(II) (CEu total= 2.34 × 10−5 mol g−1) in LiF-BeF2(FLiBe) molten salt is studied by cyclic voltammetry (CV), square wave voltammetry (SWV), chrono potentiometry (CP) and linear polarization (LP) in the temperature range of 773 to 973 K. The coexistence of Eu(III) and Eu(II) and the ratio of Eu(III)/Eu(II) are determined by SWV test. The redox reaction of Eu(III)/Eu(II) couple on an inert tungsten electrode is demonstrated to be a quasi-reversible process with diffusion controlled mass transfer. The diffusion coefficient and diffusion activation energy of Eu(III) and Eu(II) are obtained by CP method at different temperature. The thermodynamic and kinetic characteristics of the redox reaction of Eu(III)/Eu(II) couple are investigated by various electrochemical methods. With the obtained data, the thermodynamic data ΔG0(−1046.1 KJ mol−1), ΔH0(−1218.2 KJ mol−1), ΔS0(−0.197 KJ mol−1), and E0EuF2/Eu(−0.799 V vs E0BeF2/Be) for EuF2are calculated at 873 K and the possibility of the application of the Eu(III)/Eu(II) couple as redox buffering species or salt potential indicator is evaluated.

Electro-deoxidation technology plays an important role in both industrial production and spent fuel reprocessing. In this work, the cyclic voltammetry (CV), square wave voltammetry (SWV) and open circuit chronopotentiometry (OCP) were applied to study the electrochemical behavior of U3O8and MoO3cathode in the CaCl2-NaCl melt at 873 K. The electrolytic reduction of U3O8-MoO3was conducted at −2.38 V (vs Ag/AgCl) for 3.8 h, and the reduced production of metallic U and Mo was successfully confirmed by XRD analysis.

The extraction of rare earth element neodymium (Nd) from LiF-NaF-KF (FLiNaK) molten salt by electrochemical reduction was introduced in this paper. Cyclic voltammetry (CV) and square wave voltammetry (SWV) results showed that Nd(III) can be reduced to Nd(0) by a one-step three electrons process: Nd(III) + 3e−→ Nd(0), and the diffusion coefficient (D), the transfer coefficient (α) and the rate constant of standard reaction (k0) of Nd (III) in FLiNaK melt at 823 K were calculated by CV and sem-integral analysis of the CV curves. The deposits of Nd on Pt cathode were confirmed by the potentiostatic electrolysis and characterized by SEM, EDS and XRD. The electrolytic products were composed mainly of Nd metal and two intermetallic compounds NdPt2and NdPt. All of these results demonstrated the feasibility of electrolytic separation of Nd(III) on Pt cathode in FLiNaK molten salt.