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Abstract Background The production of β-lactamases is the most prevalent resistance mechanism for β-lactam antibiotics in Gram-negative bacteria. Presently, over 4900 β-lactamases have been discovered, and they are categorized into hundreds of families. In each enzyme family, amino acid substitutions result in subtle changes to enzyme hydrolysis profiles; in contrast, certain conserved sequences retained by all of the family members can serve as important markers for enzyme family identification. Results The SHV family was chosen as the study object. First, a unique 10-mer peptide was identified as SHV family's epitope by an approach of protein fingerprint analysis. Then, an SHV-specific magnetic epitope-imprinted gel polymer (MEI-GP) was prepared by an epitope surface imprinting technique, and its sorption behavior and recognition mechanism for template epitope and SHV were both elaborated. Finally, the MEI-GP was successfully applied to selectively extract SHV from bacteria, and the extracted SHV was submitted to MALDI-TOF MS for specific determination. By following this strategy, other β-lactamase families can also be specifically detected. According to the molecular weight displayed in mass spectra, the kind of β-lactamase and its associated hydrolysis profile on β-lactams can be easily identified. Based on this, an initial drug option scheme can be quickly formulated for antimicrobial therapy. From protein extraction to medication guidance reporting, the mean time to detection (MTTD) was less than 2 h, which is much faster than conventional phenotype-based methods (at least 16–20 h) and gene-based techniques (usually about 8 h). Conclusions This enzyme-specific detection strategy combined the specificity of epitope imprinting with the sensitivity of mass spectrometry, enabling β-lactamase to be selectively extracted from bacteria and clearly presented in mass spectra. Compared with other drug resistance detection methods, this technique has good specificity, high sensitivity (≤ 15 mg of bacteria), a short MTTD (less than 2 h), and simple operation, and therefore has a broad application prospect in clinical medicine. Graphical Abstract

Abstract To improve the sensitivity measurement of temperature sensors, a fiber optic temperature sensor structure based on the harmonic Vernier effect with two parallel fiber Sagnac interferometers (FSIs) is designed, and theoretical analysis and experimental testing are conducted. The FSI consisting of two polarization maintaining fibers (PMFs) with lengths of 13.62 m and 15.05 m respectively is used to achieve the basic Vernier effect. Then by changing the length of one PMF to approximately i times that of the others, the FSI composed of two PMFs of 7.1 m and 15.05 m is used to achieve the first-order harmonic Vernier effect. Afterward, temperature sensing tests are conducted to observe the wavelength drift during temperature changes and ultimately achieve high sensitivity. The experimental results show that the temperature sensitivity of the sensor based on the first-order harmonic Vernier effect is −28.89 nm/°C, which is 17.09 times that of a single FSI structure (−1.69 nm/°C) and 1.84 times that of the sensitivity generated by the structure based on the basic Vernier effect (−15.69 nm/°C). The experimental results are consistent with the theoretical analysis. The structure proposed in this paper achieves drift measurement of 0.1 °C variation based on 1 °C drift, making the fiber optic temperature sensor applicable to related fields that require high precision temperature. The proposed temperature sensor has the simple structure, low production cost, high sensitivity, and broad application prospects.

Natural fractures are crucial factors influencing productivity and water invasion in the ultra-deep tight sandstone gas wells of the Keshen gas reservoir in the Kuqa Depression, Tarim Basin. Research on fractures is significant for understanding water invasion patterns and formulating effective water control strategies. This study investigated the development characteristics, distribution patterns, and water invasion characteristics of effective fractures using core samples, thin sections, conventional logging, imaging logging, production data, and well testing, as well as the influence of different fracture networks on water invasion. High-angle and nearly vertical shear fractures are the main fracture types. Vertically, the first member of Bashijiqike Formation (K1bs1) is predo-minantly characterized by completely filled fractures, which are ineffective fractures. Conversely, the second and third members of Bashijiqike Formation (K1bs2 and K1bs3) are mostly characterized by partially filled and unfilled fractures, which are effective fractures. Horizontally, the NNW-SSE striking effective fractures are concentrated in the western part of the gas reservoir and have larger average apertures. The eastern part has relatively deve-loped nearly E-W and NWW-SEE striking effective fractures with smaller average apertures. The more deve-loped and the larger the aperture of the effective fractures, the lower the initial water production from gas wells, with more production of condensate water. From production onset to water breakthrough, formation water is produced in various forms: sealed water, condensate water, movable water and pure formation water. The development stage, aperture and orientation of effective fractures are important factors affecting heterogeneous water invasion. Dense, highly effective fracture networks that are nearly parallel to the orientation of water invasion will accelerate the water invasion speed, resulting in significant water production and severely reducing gas well productivity. Integrating the development characteristics of effective fractures with individual well water invasion dynamics reveals three types of water invasion: rapid channeling along faults or dense fractures, slow coning along sparse fractures and slow uplift and invasion of edge-bottom water.

Abstract Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Osteoarthritis (OA) is a prevalent clinical condition affecting the entire joint, characterized by its multifactorial etiology and complex pathophysiology. The onset of OA is linked to inflammatory mediators produced by the synovium, cartilage, and subchondral bone, all of which are closely tied to cartilage degradation. Consequently, OA may also be viewed as a systemic inflammatory disorder. Emerging studies have underscored the significance of T cells in the development of OA. Notably, imbalances in Th1/Th2 and Th17/Treg immune cells may play a crucial role in the pathogenesis of OA. This review aims to compile recent advancements in understanding the role of T cells and their Th/Treg subsets in OA, examines the immune alterations and contributions of Th/Treg cells to OA progression, and proposes novel directions for future research, including potential therapeutic strategies for OA.

Abstract City-scale traffic data, such as traffic flow, speed, and density on every road segment, are the foundation of modern urban research. However, accessing such data on a city scale is challenging due to the limited number of sensors and privacy concerns. Consequently, most of the existing traffic datasets are typically limited to small, specific urban areas with incomplete data types, hindering the research in urban studies, such as transportation, environment, and energy fields. It still lacks a city-scale traffic dataset with comprehensive data types and satisfactory quality that can be publicly available across cities. To address this issue, we propose a unified approach for producing city-scale traffic data using the classic traffic assignment model in transportation studies. Specifically, the inputs of our approach are sourced from open public databases, including road networks, traffic demand, and travel time. Then the approach outputs comprehensive and validated citywide traffic data on the entire road network. In this study, we apply the proposed approach to 20 cities in the United States, achieving an average correlation coefficient of 0.79 in average travel time and an average relative error of 5.16% and 10.47% in average travel speed when compared with the real-world data.

MAGUK p55 subfamily member 7, a part of the membrane palmitoylated protein subfamily, is an essential adapter that promotes epithelial cell polarity and has increasing significance in multiple cancers, including esophageal cancer, clear cell renal cell carcinoma, breast cancer, and pancreatic ductal adenocarcinoma. This paper aims to determine the effect of the MAGUK p55 subfamily member 7 in various tumor types using The Cancer Genome Atlas and Genotype-Tissue Expression database. A variety of software and web platforms, such as cBioPortal, GEPIA2, TIMER2, UALCAN, R, STRING, and DAVID, were used to obtain and analyze data. Notably, low expression of MAGUK p55 subfamily member 7 was observed in most cancers. In addition, low expression of MAGUK p55 subfamily member 7 predicted poor prognoses in cancer patients. Mutation was the most frequent genetic alteration type in MAGUK p55 subfamily member 7, with the phosphorylation sites identified as S412 and S490 in various cancers. Furthermore, expression of MAGUK p55 subfamily member 7 was associated with cancer-related fibroblasts and CD8+ T cells. Gene enrichment analysis indicated that MAGUK p55 subfamily member 7 influences cancer through the Rap1 signaling pathway. This paper elucidates the biological significance of MAGUK p55 subfamily member 7 in human pan-cancer prognosis and immune response.

PurposeTo enhance the accuracy of real-time four-dimensional cone beam CT (4D-CBCT) imaging by incorporating spatiotemporal correlation from the sequential projection image into the single projection-based 4D-CBCT estimation process.MethodsWe first derived 4D deformation vector fields (DVFs) from patient 4D-CT. Principal component analysis (PCA) was then employed to extract distinctive feature labels for each DVF, focusing on the first three PCA coefficients. To simulate a wide range of respiratory motion, we expanded the motion amplitude and used random sampling to generate approximately 900 sets of PCA labels. These labels were used to produce 900 simulated 4D-DVFs, which in turn deformed the 0% phase 4D-CT to obtain 900 CBCT volumes with continuous motion amplitudes. Following this, the forward projection was performed at one angle to get all of the digital reconstructed radiographs (DRRs). These DRRs and the PCA labels were used as the training data set. To capture the spatiotemporal correlation in the projections, we propose to use the convolutional LSTM (ConvLSTM) network for PCA coefficient estimation. For network testing, when several online CBCT projections (with different motion amplitudes that cover the full respiration range) are acquired and sent into the network, the corresponding 4D-PCA coefficients will be obtained and finally lead to a full online 4D-CBCT prediction. A phantom experiment is first performed with the XCAT phantom; then, a pilot clinical evaluation is further conducted.ResultsResults on the XCAT phantom and the patient data show that the proposed approach outperformed other networks in terms of visual inspection and quantitative metrics. For the XCAT phantom experiment, ConvLSTM achieves the highest quantification accuracy with MAPE(Mean Absolute Percentage Error), PSNR (Peak Signal-to-Noise Ratio), and RMSE(Root Mean Squared Error) of 0.0459, 64.6742, and 0.0011, respectively. For the patient pilot clinical experiment, ConvLSTM also achieves the best quantification accuracy with that of 0.0934, 63.7294, and 0.0019, respectively. The quantification evaluation labels that we used are 1) the Mean Absolute Error (MAE), 2) the Normalized Cross Correlation (NCC), 3)the Structural Similarity Index Measurement(SSIM), 4)the Peak Signal-to-Noise Ratio (PSNR), 5)the Root Mean Squared Error(RMSE), and 6) the Absolute Percentage Error (MAPE).ConclusionThe spatiotemporal correlation-based respiration motion modeling supplied a potential solution for accurate real-time 4D-CBCT reconstruction.

Hexokinase (HK) catalyzes the first irreversible rate-limiting step in glycolysis that converts glucose to glucose-6-phosphate. HK1 is ubiquitously expressed in the brain, erythrocytes, and other tissues where glycolysis serves as the major source of ATP production. Spermatogenic cell-specific type 1 hexokinase (HK1S) is expressed in sperm but its physiological role in male mice is still unknown. In this study, we generate Hk1s knockout mice using the CRISPR/Cas9 system to study the gene function in vivo. Hk1s mRNA is exclusively expressed in testes starting from postnatal day 18 and continuing to adulthood. HK1S protein is specifically localized in the outer surface of the sperm fibrous sheath (FS). Depletion of Hk1s leads to infertility in male mice and reduces sperm glycolytic pathway activity, yet they have normal motile parameters and ATP levels. In addition, by using in vitro fertilization (IVF), Hk1s deficient sperms are unable to fertilize cumulus-intact or cumulus-free oocytes, but can normally fertilize zona pellucida-free oocytes. Moreover, Hk1s deficiency impairs sperm migration into the oviduct, reduces acrosome reaction, and prevents capacitation-associated increases in tyrosine phosphorylation, which are probable causes of infertility. Taken together, our results reveal that HK1S plays a critical role in sperm function and male fertility in mice.

This patient was an elderly patient with abdominal distension and shortness of breath. According to relevant examinations, his condition was initially considered to be related to cirrhosis, but pathological biopsy confirmed the diagnosis of noncirrhotic portal hypertension of unknown etiology. The portal vein pressure was significantly reduced after transjugular intrahepatic portosystemic shunt (TIPS). Nevertheless, the relief of the hydrothorax and ascites was not significant, and the numbness in both lower limbs gradually worsened. POEMS syndrome was ultimately diagnosed following a comprehensive examination. After two courses of bortezomib combined with dexamethasone, the patient died due to a systemic infection. The clinical symptoms of the patient were atypical, as was the presence of portal hypertension, which hindered the diagnosis of POEMS. Due to the patient’s advanced age, the diagnosis was delayed, and the prognosis was poor. This case reminds clinicians that POEMS patients can also have portal hypertension as the main manifestation.

Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital genitourinary abnormality defined by uterine didelphys, obstructed hemivagina, and ipsilateral urological anomalies. Accurate diagnosis and prompt commencement of therapy can be difficult owing to heterogeneous genitourinary malformation among different patients. This is a case report of a patient with rare HWWS with uterine didelphys, obstructed hemivagina, vagina-ureteral remnant fistula (Gartner's duct cyst), and ipsilateral kidney dysgenesis who complained of intermittent abdominal pain during menstruation. The right ureteral remnant of the patient was distinctive, with three portions. The upper section was connected to the right dysplastic kidney, the lower section formed the fistulous tract with the vagina and bladder, while the middle section communicated with Gartner's Duct Cyst, which merged with the vagina and opened to the posterior cavity of hemivagina. The lower section of the right ureter was excised and ligated during laparoscopic surgery, while the upper section was excised. The patient recovered after surgery. We presented this rare case and conducted a literature review to provide a more comprehensive understanding of HWWS. This could help gynecologists effectively reduce misdiagnosis and missed diagnosis, especially when combined with complicated urinary malformation.

Abstract Abnormal inflammatory states in the brain are associated with a variety of brain diseases. The dynamic changes in the number and function of immune cells in cerebrospinal fluid (CSF) are advantageous for the early prediction and diagnosis of immune diseases affecting the brain. The aggregated factors and cells in inflamed CSF may represent candidate targets for therapy. The physiological barriers in the brain, such as the blood‒brain barrier (BBB), establish a stable environment for the distribution of resident immune cells. However, the underlying mechanism by which peripheral immune cells migrate into the brain and their role in maintaining immune homeostasis in CSF are still unclear. To advance our understanding of the causal link between brain diseases and immune cell status, we investigated the characteristics of immune cell changes in CSF and the molecular mechanisms involved in common brain diseases. Furthermore, we summarized the diagnostic and treatment methods for brain diseases in which immune cells and related cytokines in CSF are used as targets. Further investigations of the new immune cell subtypes and their contributions to the development of brain diseases are needed to improve diagnostic specificity and therapy.

Abstract. Background:. The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients. Methods:. This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes. Results:. The optimal cut-off values of L3-SMI were 39.50 cm2/m2 for male patients and 33.06 cm2/m2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis (Wald = 6.347, P = 0.012). Conclusions:. This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

BackgroundSarcopenia is common in patients with liver cirrhosis and is an independent predictor of multiple clinical outcomes. Most studies to date have used a static assessment of sarcopenia. However, there is very limited data evaluating the temporal course of muscle area in cirrhosis. To bridge this gap in clinical studies, we performed a longitudinal analysis to evaluate the impact of changes in sarcopenia for cirrhotic patients.MethodsAdult patients with clinically diagnosed liver cirrhosis who underwent at least 2 abdominal computed tomography (CT) scans in the hospital were enrolled. The interval between the two abdominal scans was 6 ± 1 months. Patients were categorized into persistent non-sarcopenia, new-onset sarcopenia, sarcopenia to non-sarcopenia, and persistent sarcopenia based on changes in sarcopenia. Kaplan–Meier method and Log-rank tests were used to separately compare unadjusted survival curves by different statuses of sarcopenia. Cox regression analysis was performed to assess the associations between different states of sarcopenia and overall mortality. The association between persistent non-sarcopenia and new-onset sarcopenia was analyzed by multivariate logistic regression analysis.ResultsA total of 307 patients were included for analysis. At the second assessment, 10.10% (31/307) patients were new-onset sarcopenia, 27.69% (85/307) with persistent sarcopenia status, while 13.03% (40/307) patients with sarcopenia developed non-sarcopenia and 49.19% (151/307) with persistent non-sarcopenia status. The overall survival rate was significantly lower in the persistent sarcopenia and new-onset sarcopenia than in the non-sarcopenia group and sarcopenia to non-sarcopenia group (p

Science popularization work on earthquake prevention and disaster reduction should keep pace with the times, play a greater role in public opinion guidance, and take more responsibility in public opinion governance. In this paper we discuss that science popularization of earthquake prevention and disaster reduction plays an important role in guiding public opinion from two aspects. First, the hotspots of public opinion provide an opportunity for science popularization of earthquake prevention and disaster reduction. Second, the hotspots of public opinion provide contents for science popularization of earthquake prevention and disaster reduction. I put forward the public opinion guidance strategy of science popularization of earthquake prevention and disaster reduction from three aspects. First, reasonably set the science popularization agenda and take the initiative to guide public opinion; Second, consciously guide public opinion by means of new media communication technology; The third is to play a good “combination boxing” to form the greatest resultant force for public opinion guidance. In the hotspots of public opinion, we should actively do a good job of science popularization of earthquake prevention and disaster reduction, innovate communication forms and methods, skillfully set the agenda, cover the whole time and space, and participate in the whole society, build a benign public opinion field for the exchange of information between the government, the media and the public, enhance the public’s risk awareness and disaster prevention ability, and truly build a people’s defense line for risk prevention and control.

Ovarian cancer is a highly heterogeneous and lethal malignancy with limited treatment options. Over the past decade, single-cell sequencing has emerged as an advanced biological technology capable of decoding the landscape of ovarian cancer at the single-cell resolution. It operates at the level of genes, transcriptomes, proteins, epigenomes, and metabolisms, providing detailed information that is distinct from bulk sequencing methods, which only offer average data for specific lesions. Single-cell sequencing technology provides detailed insights into the immune and molecular mechanisms underlying tumor occurrence, development, drug resistance, and immune escape. These insights can guide the development of innovative diagnostic markers, therapeutic strategies, and prognostic indicators. Overall, this review provides a comprehensive summary of the diverse applications of single-cell sequencing in ovarian cancer. It encompasses the identification and characterization of novel cell subpopulations, the elucidation of tumor heterogeneity, the investigation of the tumor microenvironment, the analysis of mechanisms underlying metastasis, and the integration of innovative approaches such as organoid models and multi-omics analysis.

Abstract Chemodynamic therapy of cancer is limited by insufficient endogenous H2O2 generation and acidity in the tumor microenvironment (TME). Herein, we developed a biodegradable theranostic platform (pLMOFePt-TGO) involving composite of dendritic organosilica and FePt alloy, loaded with tamoxifen (TAM) and glucose oxidase (GOx), and encapsulated by platelet-derived growth factor-B (PDGFB)-labeled liposomes, that effectively uses the synergy among chemotherapy, enhanced chemodynamic therapy (CDT), and anti-angiogenesis. The increased concentration of glutathione (GSH) present in the cancer cells induces the disintegration of pLMOFePt-TGO, releasing FePt, GOx, and TAM. The synergistic action of GOx and TAM significantly enhanced the acidity and H2O2 level in the TME by aerobiotic glucose consumption and hypoxic glycolysis pathways, respectively. The combined effect of GSH depletion, acidity enhancement, and H2O2 supplementation dramatically promotes the Fenton-catalytic behavior of FePt alloys, which, in combination with tumor starvation caused by GOx and TAM-mediated chemotherapy, significantly increases the anticancer efficacy of this treatment. In addition, T2-shortening caused by FePt alloys released in TME significantly enhances contrast in the MRI signal of tumor, enabling a more accurate diagnosis. Results of in vitro and in vivo experiments suggest that pLMOFePt-TGO can effectively suppress tumor growth and angiogenesis, thus providing an exciting potential strategy for developing satisfactory tumor theranostics.

A double Sagnac interferometer (DSI) and vernier effect sensor for relative humidity (RH) is proposed and experimentally implemented, in which two single Sagnac interferometers (SI1 and SI2) cascaded in parallel to construct the structure of the sensor. Owing to the approximate free spectral range (FSR) of the SI1 and SI2, the proposed sensor can produce fundamental and harmonic vernier effect. Theoretical analysis shows that the RH sensitivity of the sensor is only related to the lengths of polarization-maintaining fibers (PMFs). The experimental results show that in the range of 30∼80%RH, the RH sensitivities of the spectral envelope can reach −0.48 nm/%RH, which is 60 times higher than that measured by the single Sagnac interferometer sensor (8 pm/%RH). The experimental results are consistent with the theoretical analysis. The proposed sensor has the superiorities of high sensitivity, good repeatability, simple fabrication, and compact size, and it has potential applications in the areas of biopharmaceuticals, environmental monitoring, food processing, and microbial sensing.

Abstract Background and aims To investigate the usefulness of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), protein C (PC), and thromboelastography (TEG) to serve as a predictor of portal vein thrombosis (PVT) in patients with liver cirrhosis. Additionally, we examined the clinical significance of the above indicators in terms of disease progression. Methods A total of 123 patients with liver cirrhosis were recruited from May 2021 to December 2021, according to the imaging findings. They were divided into the PVT group (n = 52) and the non-PVT group (n = 71). Furthermore, patients with PVT were divided into plasma transfusion groups (n = 13) and non-plasma transfusion groups (n = 39). The basic general information, past medical history, laboratory, and imaging examination data were collected and analyzed. Results In univariate analysis, there was no significant difference between the two groups in IL-6, PC, reaction time (R), alpha angle (Angle), maximum amplitude, or coagulation index (CI) (P > 0.05). TNF-α in the PVT group was significantly lower than that in the non-PVT group (P = 0.001). K-time (K) in the PVT group was significantly higher than that in the non-PVT group (P = 0.031). There was no significant difference in IL-6, TNF-α, PC, or TEG between different Child–Pugh classification groups (P > 0.05). There were no significant differences in TEG between the plasma transfusion group and the non-plasma transfusion group. In Binary logistic regression analysis, TNF-α (OR = 0.9881, 95%CI = 0.971, 0.990, P

Abstract Background Due to its high expression capability, recombination of Escherichia coli and pET vector has become the bioengineering preferred expression system. Because β-lactamases mediate bacterial antimicrobial resistance, these enzymes have a substantial clinical impact. Using the E. coli expression system, several kinds of β-lactamases have been produced. However, previous studies have been focused on characterizing target β-lactamases, and the effects of cultivation and induction conditions on the expression efficiency of target enzymes were not addressed. Results Using pET-28a as the cloning vector and E. coli BL21(DE3) as the expression host, this study originally elucidated the effects of IPTG concentration, culture temperature, induction time, and restriction sites on recombinant β-lactamase expression. Moreover, the effects of the target protein length and the 6 × His-tag fusion position on enzyme purification were also explored, and consequently, this study yielded several important findings. (i) Only the signal peptide–detached recombinant β-lactamase could exist in a soluble form. (ii) Low-temperature induction was beneficial for soluble β-lactamase expression. (iii) The closer to the rbs the selected restriction site was, the more difficult it was to express soluble β-lactamase. (iv) The short-chain recombinant protein and the protein with His-tag fused at its C-terminus showed high affinity to the Ni2+ column. Conclusions Based on our findings, researchers can easily design an effective program for the high production of soluble recombinant β-lactamases to facilitate other related studies.

In order to construct unconditionally secure one-vote veto protocol, a primitive protocol of secure multiparty computations was defined, i.e., secure multiparty disjunction.Furthermore, by introducing a quantum cloud, a quantum secure multiparty disjunction (QSMD) protocol was proposed.BB84 states were took as quantum resources and only single-photon operations and measurements were needed.To avoid the flaws of infeasibility, i.e., most of existing quantum voting protocols need to perform operations and measurements in high-dimensional Hilbert space, a quantum anonymous one-vote veto protocol with a quantum cloud (QAOVC) was designed by using the QSMD protocol.In addition, to decentralize, a quantum anonymous one-vote veto (QAOV) protocol without any third party was presented.Compared with related protocols, the proposed protocols require less quantum resources and simpler operations, so they have better feasibility.Under the semi-honest model, quantum perfect encryption and classical one-time pad can ensure the unconditional security of the proposed protocols, i.e., it can completely meet secure requirements of one-vote veto and perfectly protect the privacy of the voters.Finally, simulation experiments are implemented on IBM Qiskit, and the experimental results show that the protocols are correct and feasible.

Abstract The application of chemodynamic therapy (CDT) for cancer is a serious challenge owing to the low efficiency of the Fenton catalyst and insufficient H2O2 expression in cells. Herein, we fabricated a PDGFB targeting, biodegradable FePt alloy assembly for magnetic resonance imaging (MRI)-guided chemotherapy and starving-enhanced chemodynamic therapy for cancer using PDGFB targeting, pH-sensitive liposome-coated FePt alloys, and GOx (pLFePt-GOx). We found that the Fenton-catalytic activity of FePt alloys was far stronger than that of traditional ultrasmall iron oxide nanoparticle (UION). Upon entry into cancer cells, pLFePt-GOx nanoliposomes degraded into many tiny FePt alloys and released GOx owing to the weakly acidic nature of the tumor microenvironment (TME). The released GOx-mediated glucose consumption not only caused a starvation status but also increased the level of cellular H2O2 and acidity, promoting Fenton reaction by FePt alloys and resulting in an increase in reactive oxygen species (ROS) accumulation in cells, which ultimately realized starving-enhanced chemodynamic process for killing tumor cells. The anticancer mechanism of pLFePt-GOx involved ROS-mediated apoptosis and ferroptosis, and glucose depletion-mediated starvation death. In the in vivo assay, the systemic delivery of pLFePt-GOx showed excellent antitumor activity with low biological toxicity and significantly enhanced T2-weighted magnetic resonance imaging (MRI) signal of the tumor, indicating that pLFePt-GOx can serve as a highly efficient theranostic tool for cancer. This work thus describes an effective, novel multi-modal cancer theranostic system.

Abstract Background Mesenchymal stem cells (MSCs) therapy is showing potential therapeutic effects on liver function improvement in patients with chronic liver disease; however, the consensus on efficacy and safety of MSCs has not been reached. Methods We performed this systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of MSCs therapy for patients with chronic liver disease. A detailed search of the Cochrane Library, MEDLINE, Web of Science, and EMBASE databases was conducted to find studies published prior to September 15, 2021. The outcome measures were survival rate, model of end-stage liver disease (MELD) score, albumin, total bilirubin, coagulation function, and aminotransferase. Results A literature search resulted in 892 citations. Of these, 12 studies met the inclusion criteria. It was found that compared with conventional treatment, MSCs therapy was associated with improved liver function including the MELD score, albumin levels, and coagulation function. However, it had no obvious beneficial effects on survival rate and aminotransferase levels. Subgroup analyses indicated that MSCs therapy had therapeutic effects on patients with both acute on chronic liver failure (ACLF) and cirrhosis. BM-MSCs and UC-MSCs treatment had similar efficacy to improve liver function. The effectiveness varied slightly between the peripheral intravenous injection and hepatic arterial injection. Five studies reported that the only adverse event of the MSCs therapy was fever, and no serious adverse events and side effects were reported. Analysis on clinical symptoms showed that encephalopathy and gastrointestinal hemorrhage events were reduced after MSCs therapy. Conclusions In conclusion, this study suggested that MSCs therapy could be a potential therapeutic alternative for patients with chronic liver disease in clinical practice.

All-inorganic lead halide perovskite has emerged as an attractive semiconducting material due to its unique optoelectronic properties. However, its poor environmental stability restricts its broad application. Here, a simple method for the fabrication of CsPb2Br5/TiO2 is investigated. The introduction of p-aminobenzoic acid, which has two functional groups, is critical for the capping of amorphous TiO2 on CsPb2Br5. After calcination at 300 °C, amorphous TiO2 crystallizes into the anatase phase. The CsPb2Br5/TiO2 NCs show high long-term stability in water and enhanced stability against ultraviolet radiation and heat treatment, owing to the chemical stability of TiO2. More importantly, photo-electrochemical characterizations indicate that the formation of TiO2 shells can increase the charge separation efficiency. Hence, CsPb2Br5/TiO2 exhibits improved photoelectric activity owing to the electrical conductivity of the TiO2 in water. This study provides a new route for the fabrication of optoelectronic devices and photocatalysts based on perovskite NCs in the aqueous phase. Furthermore, the present results demonstrate that CsPb2Br5/TiO2 NCs has considerable potential to be used as a photoelectric material in optical sensing and monitoring.

Introduction: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective way to improve portal hypertension, however, the role of anticoagulation or antiplatelet therapy following TIPS remains controversial. We conducted this study to evaluate the efficacy and safety of anticoagulation or antiplatelet therapy following TIPS.Methods: A literature search was conducted on anticoagulation or antiplatelet therapy after TIPS using Pubmed, Web of Science, EMBASE, and Cochrane. The retrieval period was from the earliest accessible date in the database to 31 October 2022. We collected information on the incidence of stent dysfunction, bleeding, hepatic encephalopathy, the new occurrence of portal vein thrombosis, and the survival rate. Stata was analyzed in RevMan.Results: 1. Four studies received anticoagulation or antiplatelet therapy after TIPS without control groups. According to the single-group rate meta-analysis, stent dysfunction occurred at 27% [95% CI (0.19, 0.38)], bleeding occurred at 21% [95% CI (0.14, 0.29)], new portal vein thrombosis occurred at 17% [(95%CI(0.04.0.71)], hepatic encephalopathy occurred at 47% [95%CI (0.34, 0.63)], and death occurred at 31% [95% CI (0.22, 0.42)]. 2. Eight studies, including 1025 patients, compared anticoagulation and antiplatelet therapy after TIPS to TIPS alone. In terms of stent dysfunction, bleeding, and hepatic encephalopathy, there were no significant differences between the two groups. The use of anticoagulation or antiplatelet therapy may result in a significant decrease in the incidence of new portal vein thrombosis and mortality over 1 year.Discussion: Anticoagulant or antiplatelet therapy may not improve the patency rate of TIPS, but may effectively prevent new portal vein thrombosis after TIPS. Following TIPS, the use of anticoagulants or antiplatelet drugs does not lead to an increase in bleeding or death.

Taking the Qinling-Huaihe River as the boundary, this paper divides the Chinese service industry into north and south regions. The current study calculates the green total factor productivity of the Chinese service industry from 2003 to 2019 by using the DEA-Malmquist productivity index method. The influencing factors of the service industry in the north and south of China are tested by the Moran index and the spatial Durbin model. The results show that the green total factor productivity of the Chinese service industry shows great regional heterogeneity. The average green total factor productivity of northern China is 1.4 percentage points lower than that of southern China. The leading factor for the growth of green total factor productivity in southern China is technological progress, while TFP in northern China mainly depends on technical efficiency improvement. The results of spatial econometric regression show that the intensive level of producer services plays a significant role in promoting the green development of the service industry. The transportation infrastructure can significantly promote the green development level of the service industry. Finally, some suggestions are provided to narrow the gap between the north and south of the Chinese service industry.

Abstract Background Fc gamma receptor IIb (FcγRIIb) is an important inhibitory receptor that plays vital roles in regulating various immune response processes and the pathogenesis of many infectious diseases. The purpose of our research was to evaluate FcγRIIb expression in serum and liver biopsy specimens from hepatitis B virus (HBV)-infected patients and to explore the association of FcγRIIb with chronic HBV infection. Methods Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum FcγRIIb levels in 119 HBV-infected patients and 24 healthy controls. An immunohistochemical method was then employed to identify FcγRIIb expression in biopsy specimens from patients with chronic hepatitis B (CHB). The integrated optical density (IOD) value was measured to represent FcγRIIb expression levels. Results Serum FcγRIIb levels were decreased in CHB patients compared to controls (P

The service industry has become the driving force of Chinese economic development. Promoting the green and high-quality development of the service industry is of great significance to the realization of the “dual carbon” goal. The current studies use the DEA-Malmquist index method to measure the green total factor productivity of the service industry in 31 provinces and cities in China from 2009 to 2019. The spatial correlation characteristics and contributing factors to the green development of the service industry are analyzed through the social network analysis method. Our results show that the added value of the service industry accounts for a high proportion of GDP. However, the service industries are not green enough due to their large low added value and high energy consumption sections. The green development of the service industry shows complex spatial correlation characteristics, and the service industry in the eastern province is the core of the spatial network. The bridge mediating effect of green development of the service industry in the southern region is significant. The green development of the service sector has a significant spatial spillover effect, and no region can be good alone in green development. Provinces should cooperate to promote green development in the service industry.

Background: Knee osteoarthritis (KOA), a chronic degenerative disease, is mainly characterized by destruction of articular cartilage and inflammatory reactions. At present, there is a lack of economical and effective clinical treatment. Zhuifeng Tougu (ZFTG) capsules have been clinically approved for treatment of OA as they relieve joint pain and inflammatory manifestations. However, the mechanism of ZFTG in KOA remains unknown.Purpose: This study aimed to investigate the effect of ZFTG on the TLR4/MyD88/NF-κB signaling pathway and its therapeutic effect on rabbits with KOA.Study design:In vivo, we established a rabbit KOA model using the modified Videman method. In vitro, we treated chondrocytes with IL-1β to induce a pro-inflammatory phenotype and then intervened with different concentrations of ZFTG. Levels of IL-1β, IL-6, TNF-α, and IFN-γ were assessed with histological observations and ELISA data. The effect of ZFTG on the viability of chondrocytes was detected using a Cell Counting Kit-8 and flow cytometry. The protein and mRNA expressions of TLR2, TLR4, MyD88, and NF-κB were detected using Western blot and RT-qPCR and immunofluorescence observation of NF-κB p65 protein expression, respectively, to investigate the mechanism of ZFTG in inhibiting inflammatory injury of rabbit articular chondrocytes and alleviating cartilage degeneration.Results: The TLR4/MyD88/NF-κB signaling pathway in rabbits with KOA was inhibited, and the levels of IL-1β, IL-6, TNF-α, and IFN-γ in blood and cell were significantly downregulated, consistent with histological results. Both the protein and mRNA expressions of TLR2, TLR4, MyD88, NF-κB, and NF-κB p65 proteins in that nucleus decreased in the ZFTG groups. Moreover, ZFTG promotes the survival of chondrocytes and inhibits the apoptosis of inflammatory chondrocytes.Conclusion: ZFTG alleviates the degeneration of rabbit knee joint cartilage, inhibits the apoptosis of inflammatory chondrocytes, and promotes the survival of chondrocytes. The underlying mechanism may be inhibition of the TLR4/MyD88/NF-kB signaling pathway and secretion of inflammatory factors.

In the gear shifting process of a clutchless automated mechanical transmission (AMT), the potential collision between sleeve and dog gear may increase both vehicle jerk and gear changing duration. Therefore, the gear shifting process's mechanism analysis and dynamic modeling are the essential prerequisites to improve gear shifting quality. This paper analyzes the potential collision between the sleeve and the dog gear which both with concave-convex profiles, the tooth-side chamfer considered. To model the collision process, a fast-determining collision face method based on an intersection map is proposed, and the Monte Carlo method and equivalent depth are employed to calculate the collision stiffness. Then, the stiffness-damping model of the collision process and an 8-degree-of-freedom dynamic model of the gear-shifting system are established. Finally, taking a two-speed clutchless and non-synchronizer automated mechanical transmission (NSAMT) as an example, the established dynamic model of the gear-shifting system is applied, and simulation verification is performed in Matlab/Simulink. The simulation results show that the established model can accurately reflect the changes of forces, speeds, and displacements of sleeve and dog gears during the collision and effectively reflect processes of the disengagement of the sleeve, the speed changes in active synchronization, the engagement of sleeve and gear keeping. Besides, the results also show that the tooth-side chamfer will increase the disengagement time, while it is conducive to gear keeping, and that unloading the drive motor can decrease the disengagement time due to the existence of the tooth-side chamfer.

A new type of electro-mechanical brake-by-wire system based on wedge transmission is proposed for driverless vehicle，and the optimal design method of wedge transmission angle is proposed too. The parameters design and three-dimensional modeling of the braking system are carried out，and the joint simulation virtual prototype model is built in Matlab/Simulink and Adams. The simulation results show that the tracking control performance of the new braking system is good. Under the emergency braking condition，the brake coordination time is 0.19 s，the brake unloading time is 0.3 s，the steady state control error is 1.2%. Compared with the national and industrial standards，and traditional hydraulic brake system by wire，the new brake has a large lead in loading and unloading speed，good follow-up performance，and is suitable for the use of the chassis system controlled by wire.

As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.

The Lower Jurassic Ahe Formation is an important exploration target for deep clastic reservoirs in the eastern Kuqa Depression. The Ahe Formation sandstones show heterogeneous porosity and permeability petrophysical properties. These properties have been poorly understood, limiting forecast of petroleum accumulations and making it difficult to develop the reservoirs. Based on cores, thin sections, SEM, and fluid inclusions, this study examined sandstone composition and texture and diagenetic heterogeneity at the core scale. The aim was to understand the influence of variations in detrital composition and texture on diagenetic and reservoir quality evolution. The Ahe Formation sandstones are dominantly fine- to coarse-grained litharenites, with minor feldspathic litharenites. In fining-up sand beds, detrital grain size determines the degree of mechanical compaction and, consequently, the abundance of porosity through ductile grains and muddy matrix. Local complete calcite cementation is a noticeable exception to this general trend. Three sandstone petrofacies have been defined based on texture and framework composition, detrital matrix, diagenesis, and pore types: (1) ductile-lean sandstone, (2) ductile-rich sandstone, and (3) tightly calcite-cemented sandstone. Different petrofacies experienced contrasting diagenetic and porosity evolution pathways. Ductile-lean sandstones underwent lower degree of compaction relative to ductile-rich sandstones during the eodiagenesis stage, and extensive grain dissolution occurred. The petrofacies remained relatively porous and permeable before early oil arrival. With continued burial, the porosity and permeability in the sandstones were further reduced by cementation. The petrofacies still had moderate porosity and permeability and were substantially charged when late petroleum migrated into the reservoirs. Thus, ductile-lean sandstones constitute effective reservoir rocks in deep reservoirs. By translating petrofacies to signatures of well logs, the effective properties of the reservoir rocks can be forecasted at the well scale.

Hepatocellular carcinoma (HCC) is one of the important types of liver cancer. LncRNA is an important regulatory factor that regulates many biological processes such as tumor cells during tumorigenesis and metastasis. LINC00346 has been associated with various types of liver cancer, but its role and regulatory mechanism in HCC remain unclear. In our study, we found the LINC00356-miR-199a-3p-CDK1/CCNB1 axis through bioinformatics analysis. The expressions of LINC00356, miR-199a-3p, CDK1, and CCNB1 in HCC and normal hepatocytes were determined by qRT-PCR and WB. The results showed that LINC00356, CDK1 and CCNB1 were highly expressed in HCC, while miR-199a-3p was lowly expressed. Dual luciferase reporter gene assay, RIP and RNA-pull down assays demonstrated the targeted binding relationship of LINC00346-miR-199a-3p-CDK1/CCNB1. Overexpressing LINC00460 and silencing miR-199a-3p promoted cell invasion, inhibited apoptosis of HCC, and arrested the cell cycle in S phase while opposite results were obtained when silencing LINC00346, CDK1, and CCNB1. LINC00346 indirectly affects liver cancer by promoting the expression of CDK1/CCNB1 through competitive adsorption of miR-199a-3p. In addition, the study also demonstrated that overexpression of LINC00346 indirectly inhibited the expression of p53 and p21 proteins by promoting CDK1/CCNB1 expressions, thereby blocking the p53 signaling pathway. These results proved that LINC00346 could regulate the expression of CDK1/CCNB1 through the competitive adsorption of miR-199a-3p, thereby affecting the p53 signaling pathway and finally regulating the apoptosis, invasion and cell cycle of HCC cells. In conclusion, LINC00346 can be used as a tumor promoter and potential therapeutic target for HCC metastasis and prognosis.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a systemic conductive herbicide widely used across the world. With the large-scale and continuous use of 2,4-D, its possible harm to the environment and non-target organisms has attracted increasing attention, and the construction of a stable rapid on-site detection method is particularly important. In order to achieve on-site rapid detection of 2,4-D, we developed a gold nanoparticle immunochromatographic strip method with the visual elimination value was 50 ng/mL, and a quantitative detection limit of 11 ng/mL based on a nanobody. By combing with the color snap, the immunochromatographic strip could quantitatively analyze the amounts of 2,4-D. Meanwhile, a colorimetric card based on the true color of the test strips was developed for the qualitative analysis of 2,4-D on-site. The samples (water, fruits and vegetables) with and without 2,4-D were detected by the immunochromatographic strips, and the results showed the accuracy and reliability. Thus, this assay is a rapid and simple on-site analytical tool to detect and quantify 2,4-D levels in environmental samples, and the analytical results can be obtained in about ten minutes. In addition, the nanobody technology used in this study provides an inexhaustible supply of a relatively stable antibodies that can be archived as a nanobody, plasmid or even its sequence.

Threatening sounds can elicit a series of defensive behavioral reactions in animals for survival, but the underlying neural substrates are not fully understood. Here, we demonstrate a previously unexplored neural pathway in mice that projects directly from the auditory cortex (ACx) to the lateral periaqueductal gray (lPAG) and controls noise-evoked defensive behaviors. Electrophysiological recordings showed that the lPAG could be excited by a loud noise that induced an escape-like behavior. Trans-synaptic viral tracing showed that a great number of glutamatergic neurons, rather than GABAergic neurons, in the lPAG were directly innervated by those in layer V of the ACx. Activation of this pathway by optogenetic manipulations produced a behavior in mice that mimicked the noise-evoked escape, whereas inhibition of the pathway reduced this behavior. Therefore, our newly identified descending pathway is a novel neural substrate for noise-evoked escape and is involved in controlling the threat-related behavior.

This study proposes an electric vehicle (EV) aggregator operation mechanism in a residential community. The EV charging and discharging operation behaviours are scheduled to maximise the EV aggregator revenue, while EV aggregator provides reserve service for the grid. This study not only considers the energy and information interactions between three stakeholders: EV aggregator, EV owners, and power grids, but also the economic interests of aggregator and owners are considered. The aggregator-owner economic inconsistency issue (EV owners get higher charging cost in aggregator scheduling than self-scheduling) is presented. In order to mediate this issue, a rebate factor is proposed. In the first stage, the objective is to minimise the day-ahead (DA) charging cost of EV owners. Then the second stage is to maximise DA aggregator revenue with different rebate values. Finally, in the third stage, a real-time scheduling strategy is proposed to maximise aggregator revenue using the optimal rebate value. In addition, the battery degradation in influencing scheduling is formulated. Scheduling results show the effectiveness of the proposed strategy, e.g. economic inconsistency of different parties can be mediated. Significant reduction of EV owners’ cost from self-scheduling can be achieved while the revenue of EV aggregator is maximised under the proposed strategy.

In electric vehicles (EVs), bidirectional DC/DC(Bi-DC/DC) is installed between the battery pack and the DC bus to step up the voltage. In the process of mode switching under step signal, the Bi-DC/DC will be affected by a large current inrush which threatens the safety of the circuit. In this paper, a Bi-DC/DC mode switching method based on the optimized Bézier curve is proposed. The Boost and Buck modes can be switched based on the proposed method with fast and non-overshoot switching performance. The experimental results show that the mode switching can be finished in 4 ms without overshoot based on the optimal switching curve.

OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5%) with acute thrombosis, 5 patients (1.8%) with subacute thrombosis, 17 patients (6.2%) with stroke, and 2 death (0.7%) in low-dose aspirin group, compared with no patient (0%) with acute thrombosis, 2 patient (2.1%) with subacute thrombosis, 6 patients (6.2%) with stroke, and 2 death (2.1%) in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.