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Cancer nanomedicine treatment aims to achieve highly specific targeting and localization to cancer cells. Coating of nanoparticles with cell membranes endows them with homologous cellular mimicry, enabling nanoparticles to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused a human-derived HCT116 colon cancer cell membrane (cM) with a red blood cell membrane (rM) to fabricate an erythrocyte-cancer cell hybrid membrane (hM). Oxaliplatin and chlorin e6 (Ce6) co-encapsulated reactive oxygen species-responsive nanoparticles (NPOC) were camouflaged by hM and obtained a hybrid biomimetic nanomedicine (denoted as hNPOC) for colon cancer therapy. hNPOC exhibited prolonged circulation time and recognized homologous targeting ability in vivo since both rM and HCT116 cM proteins were maintained on the hNPOC surface. hNPOC showed enhanced homologous cell uptake in vitro and considerable homologous self-localization in vivo, producing effective synergistic chemophotodynamic therapy efficacy under irradiation with a homologous HCT116 tumor compared to that with a heterologous tumor. Together, the biomimetic hNPOC nanoparticles showed prolonged blood circulation and preferential cancer cell-targeted function in vivo to provide a bioinspired strategy for chemophotodynamic synergistic therapy of colon cancer.
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Neoplasias do Colo , Nanopartículas , Humanos , Biônica , Membrana Eritrocítica/metabolismo , Fototerapia , Neoplasias do Colo/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular TumoralRESUMO
Background: FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis. Methods: We report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome. Results: A total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150-380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1-1:32), while the median serum MOG antibody titer was 1:32 (1:10-1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike-slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses. Conclusion: FLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Recidiva Local de Neoplasia/complicações , Convulsões/complicações , Autoanticorpos , Imageamento por Ressonância MagnéticaRESUMO
Sound monitoring has been widely used in the field of the Internet of Things (IoT), in which the sensors are mainly powered by batteries with high power consumption and limited life. Here, a near-zero quiescent power sound wake-up and identification system based on a triboelectric nanogenerator (TENG) is proposed, in which the sound TENG (S-TENG) is used for ambient sound energy harvesting and system activation. Once the sound intensity is higher than 65 dB, the converted and stored electric energy by the S-TENG can wake up the system within 0.5 s. By integrating a deep learning technique, the system is used for identifying sound sources, such as drilling, child playing, dog barking, and street music. In the active mode, the sound signals are recorded by a microelectromechanical systems (MEMS) microphone and then sent to a remote computer for sound recognition through a wireless transmitter within 2.8 s. In the standby mode, the ambient sound is not enough to wake up the system, and the quiescent power consumption is only 55 nW. This work provides a triboelectric sensor-based ultralow quiescent power sound wake-up system, which has shown excellent application prospects in smart homes, unmanned monitoring, and the Internet of Things.
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OBJECTIVE: ovarian granulosa cell tumor (OGCT) is a kind of infrequent ovarian malignant tumor with limited epidemiological data available. we established a predictive nomograph to verify the clinical prognosis. METHODS: 1005 diagnosed with ovarian granulosa cell tumor (OGCT) were extracted from Surveillance, Epidemiology, and End Results (SEER) public database from 2000-2018. Kaplan-Meier analysis was applied to distinguish risk factors, univariate and multivariate Cox analyses were used to determine the independent prognostic factors for cancer-specific survival (CSS) of OGCT patients. The obtained prognostic variables were combined to construct a nomogram model for predicting CSS in OGCT patients. RESULTS: Model performance was detected and evaluated with ROC curves and calibration plots. Data collected from 1005 patients were divided into two groups: training cohort(n=703,70%) and validation cohort(n=302,30%). The multivariate Cox model identified five covariates including age, marital status, AJCC stages, surgery and chemotherapy as independent interfering factors of CSS. The nomogram has shown a promising and excellent accuracy in evaluating 3 -, 5 -, 8-year CSS in OGCT patients. In terms of the CSS of the training cohort, the AUC values of the 3 -, 5 -, 8-year ROC curves were 0.819,0.8,0.819, while in terms of the CSS of the validation cohort, the AUC values of the validation cohort were 0.822,0.84,0.823, respectively. All the calibration curves showed pleasant consistency between predicted and actual survival rates. The nomogram model established in the study can improve the veracity of prognosis prediction, thereby improving the accuracy of individualized survival risk assessment, and providing targeted and constructive recommendations for specific treatment options. CONCLUSION: Age, advanced clinical stage, widower and without surgery therapy are independent risk factors for poor prognosis and the nomogram we constructed can help clinicians efficiently recognize high-risk OGCT patients to guide targeted therapies and improve their outcomes.
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The combination of PD-1 blockade with neoadjuvant chemotherapy (NAC) has achieved unprecedented clinical success in non-small cell lung cancer (NSCLC) compared to NAC alone, but the underlying mechanisms by which PD-1 blockade augments the effects of chemotherapy remain incompletely elucidated. Single-cell RNA sequencing was performed on CD45+ immune cells isolated from surgically resected fresh tumors of seven NSCLC patients receiving NAC or neoadjuvant pembrolizumab and chemotherapy (NAPC). Multiplex fluorescent immunohistochemistry was performed on FFPE tissues before and after NAC or NAPC from 65 resectable NSCLC patients, and results were validated with GEO dataset. NAC resulted in an increase only of CD20+ B cells, whereas NAPC increased the infiltration of CD20+ B cells, CD4+ T cells, CD4+CD127+ T cells, CD8+ T cells, CD8+CD127+ and CD8+KLRG1+ T cells. Synergistic increase in B and T cells promotes favorable therapeutic response after NAPC. Spatial distribution analysis discovered that CD8+ T cells and their CD127+ and KLRG1+ subsets were in closer proximity to CD4+ T/CD20+ B cells in NAPC versus NAC. GEO dataset validated that B-cell, CD4, memory, and effector CD8 signatures correlated with therapeutic responses and clinical outcomes. The addition of PD-1 blockade to NAC promoted anti-tumor immunity through T and B cells recruitment in the tumor microenvironment and induced tumor-infiltrating CD8+ T cells skewed toward CD127+ and KLRG1+ phenotypes, which may be assisted by CD4+ T cells and B cells. Our comprehensive study identified key immune cell subsets exerting anti-tumor responses during PD-1 blockade therapy and that may be therapeutically targeted to improve upon existing immunotherapies for NSCLC.
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Photodynamic therapy (PDT), as a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species, has been widely used for eliminating cancer cells under specific wavelength light irradiation. However, the low aqueous solubility of PSs and special tumor microenvironments (TME), such as high glutathione (GSH) and tumor hypoxia remain challenges towards PDT for hypoxic tumor treatment. To address these problems, we constructed a novel nanoenzyme for enhanced PDT-ferroptosis therapy by integrating small Pt nanoparticles (Pt NPs) and near-infrared photosensitizer CyI into iron-based metal organic frameworks (MOFs). In addition, hyaluronic acid was adhered to the surface of the nanoenzymes to enhance the targeting ability. In this design, MOFs act not only as a delivery vector for PSs, but also a ferroptosis inducer. Pt NPs stabilized by MOFs were functioned as an oxygen (O2) generator by catalyzing hydrogen peroxide into O2 to relieve tumor hypoxia and increase singlet oxygen generation. In vitro and in vivo results demonstrated that under laser irradiation, this nanoenzyme could effectively relive the tumor hypoxia and decrease the level of GSH, resulting in enhanced PDT-ferroptosis therapy against hypoxic tumor. The proposed nanoenzymes represent an important advance in altering TME for improved clinical PDT-ferroptosis therapy, as well as their potential as effective theranostic agents for hypoxic tumors.
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Ferroptose , Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Estruturas Metalorgânicas/farmacologia , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes , Neoplasias/tratamento farmacológico , Oxigênio , Peróxido de Hidrogênio/farmacologia , Microambiente TumoralRESUMO
OBJECTIVE: Treatment with adrenocorticotropic hormone (ACTH) or a corticosteroid is the first choice for infantile spasms (IS), and vigabatrin is the first choice for children with tuberous sclerosis. Although corticosteroids may be also effective against IS and IS-related Lennox-Gastaut syndrome (LGS), the use of dexamethasone (DEX), a kind of corticosteroid, for these diseases has been rarely reported. This retrospective study aimed to evaluate the efficacy and tolerability of DEX for the treatment of IS and IS-related LGS. METHODS: Patients diagnosed as having IS (including patients whose condition evolved to LGS after the failure of early treatment) in our hospital between May 2009 and June 2019 were treated with dexamethasone after failure of prednisone treatment. The oral dose of DEX was 0.15-0.3 mg/kg/d. Thereafter, the clinical efficacy, electroencephalogram (EEG) findings, and adverse effects were observed every 4-12 weeks depending on the individual patient's response. Then, the efficacy and safety of DEX in the treatment of IS and IS-related LGS were retrospectively evaluated. RESULTS: Among 51 patients (35 cases of IS; 16 cases of IS-related LGS), 35 cases (68.63%) were identified as responders to DEX treatment, comprising 20 cases (39.22%) and 15 cases (29.41%) with complete control and obvious control, respectively. To discuss the syndromes individually, complete control and obvious control were achieved in 14/35 and 9/35 IS cases and in 6/16 and 6/16 IS-related LGS cases, respectively. During DEX withdrawal, 11 of the 20 patients with complete control relapsed (9/14 IS; 2/6 LGS). The duration of dexamethasone treatment (including weaning) in most of the 35 responders was less than 1 year. However, 5 patients were treated with prolonged, low-dose maintenance therapy, which continued for more than 1.5 years. These 5 patients showed complete control, and 3 patients had no recurrence. Except for one child who died of recurrent asthma and epileptic status 3 months after stopping DEX, there were no serious or life-threatening adverse effects during DEX treatment. CONCLUSION: Oral DEX is effective and tolerable for IS and IS-related LGS. all LGS patients were evolved from IS in this study. The conclusion may not apply to patients with other etiology and courses of LGS. Even when prednisone or ACTH is failed, DEX may still be considered as a treatment option. For children who respond to DEX but do not show complete control after 6 months of treatment, prolonged treatment with low-dose DEX administered in the morning might be considered.
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Síndrome de Lennox-Gastaut , Espasmos Infantis , Criança , Humanos , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/diagnóstico , Síndrome de Lennox-Gastaut/tratamento farmacológico , Síndrome de Lennox-Gastaut/diagnóstico , Estudos Retrospectivos , Prednisona/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêutico , Corticosteroides/uso terapêutico , Eletroencefalografia , Dexametasona/efeitos adversos , Anticonvulsivantes/uso terapêuticoRESUMO
Background: Mechanical lithotripsy produces stone fragments that are not easily detected by cholangiography and is a potential cause of recurrence of common bile duct stones (CBDS). This study aims to clarify whether 100 ml saline irrigation after mechanical lithotripsy reduces the recurrent rate of CBDS. Methods: In this randomized controlled trial performed at the Surgical Endoscopy Center, the First Hospital of Lanzhou University between May 10, 2019, and Dec 31, 2020, patients undergoing endoscopic mechanical lithotripsy were randomly assigned to receive saline irrigation (study group) or no irrigation (control group). The saline irrigation was given 100 ml saline pulse irrigation after cholangiography showed no residual stones. Patients were followed up for at least 24 months after endoscopic stone removal to assess the recurrence of CBDS. This study was registered with ClinicalTrials.gov (NCT03937037). Findings: During the median follow-up period of 35.6 months (interquartile range, 26.0-40.7), 43 of the 180 patients had stone recurrence (24%). The frequency of recurrence of CBD stones was 12.22% in the saline irrigation group and 35.56% in the control group, with a difference of 23.33% between the two groups (95% confidence interval [CI], 11.35%-35.32%, p < 0.001). Multivariable Cox proportional hazards analyses showed that constipation (hazard risk [HR] 2.42; 95% CI, 1.22-4.80, p = 0.012), periampullary diverticulum (PAD) (HR 3.06; 95% CI, 1.62-5.79, p < 0.001), and total to direct bilirubin ratio (HR 1.48; 95% CI, 1.21-1.81, p < 0.001) were independent risk factors for the recurrence of CBDS. Saline irrigation was the only preventive factor for the recurrence of CBDS (HR 0.22; 95% CI, 0.11-0.44, p < 0.001). Interpretation: For patients with CBDS requiring mechanical lithotripsy, 100 ml saline irrigation effectively reduces the recurrent rate of CBDS after endoscopic stone removal. Funding: This work was supported by National Natural Science Foundation of China (32160255); Natural Science Foundation of Gansu Province (22JR5RA898, 20JR10RA676); Science and Technology Planning Project of Chengguan District in Lanzhou (2020JSCX0043).
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Panoramic ghost imaging (PGI) is a novel method by only using a curved mirror to enlarge the field of view (FOV) of ghost imaging (GI) to 360°, making GI a breakthrough in the applications with a wide FOV. However, high-resolution PGI with high efficiency is a serious challenge because of the large amount of data. Therefore, inspired by the variant-resolution retina structure of human eye, a foveated panoramic ghost imaging (FPGI) is proposed to achieve the coexistence of a wide FOV, high resolution and high efficiency on GI by reducing the resolution redundancy, and further to promote the practical applications of GI with a wide FOV. In FPGI system, a flexible variant-resolution annular pattern structure via log-rectilinear transformation and log-polar mapping is proposed to be used for projection, which can allocate the resolution of the region of interest (ROI) and the other region of non-interest (NROI) by setting related parameters in the radial and poloidal directions independently to meet different imaging requirements. In addition, in order to reasonably reduce the resolution redundancy and avoid the loss of the necessary resolution on NROI, the variant-resolution annular pattern structure with a real fovea is further optimized to keep the ROI at any position in the center of 360° FOV by flexibly changing the initial position of the start-stop boundary on the annular pattern structure. The experimental results of the FPGI with one fovea and multiple foveae demonstrate that, compared to the traditional PGI, the proposed FPGI not only can improve the imaging quality on the ROIs with a high resolution and flexibly remain a lower-resolution imaging on the NROI with different required resolution reduction; but also reduce the reconstruction time to improve the imaging efficiency due to the reduction of the resolution redundancy.
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The purpose of this study was to assess the effects of psychological interventions on the pregnancy rates of infertile women undergoing assisted reproductive technology (ART). Using the electronic databases PubMed, EM Base, Cochrane Library, WOS, CNKI, WanFang Data, CSTJ, and CBM, a systematic literature search was conducted in the second week of August 2019. Randomized controlled trials (RCTs) on the effect of psychological interventions on the pregnancy rate of infertile women undergoing assisted reproductive technology were collected. There is no time limit for this search setting. The language is limited to Chinese or English. Two investigators independently screened the literature, extracted data, and assessed the risk of bias of the included studies, and then used Revman5.3 and STATA16.0 software for meta-analysis. A total of 25 randomized controlled trials were included in this meta-analysis, including 2098 patients in the experimental group and 2075 patients in the control group. There was a significant difference in the pregnancy rate between the two groups [RR=1.31, 95%CI(1.22,1.40)]. Subgroup analysis showed that this is also true of infertile women of different nationalities, different intervention timing and format. However, different psychological interventions may indeed have different effects. Current evidence suggests that psychological interventions may improve pregnancy rates in infertile women undergoing assisted reproductive technology. Limited by the quantity and quality of included studies, the above conclusions need to be verified by more high-quality studies. Our PROSPERO registration number is: CRD42019140666.
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Stream sediments from mine area are a converging source of water and soil pollution. The risk and development trends of metal(loid)s pollution in sediments from an abandoned arsenic-containing mine were studied using modelling techniques. The results showed that the combined techniques of geographic information system (GIS), random forest (RF), and numerical simulation (NS) could identify risk sources and diffusion trends of metal(loid)s in mine sediments. The median values of As, Cd, Hg, and Sb in sediments were 5.01, 3.02, 5.67, and 3.20 times of the background values of stream sediments in China, respectively. As (14.09%) and Hg (18.64%) pollution in mine stream sediments were severe while As is the main potential risk source with a strong spatial correlation. High-risk blocks were concentrated in the landfill area, with the surrounding pollution shows a decreasing trend of "step-type" pollution. The risk correlation between Hg and As (55.37%) in the landfill area is high. As a case of arsenic, the diffusion capacity of As within 500m is strong and stabilizes at 1 km when driven by the flows of 0.05, 0.5, and 5 m3/s, respectively. With the worst-case scenario flow (86 m3/s), it would take only 147 days for the waters within 3 km to become highly polluted. The high pollution levels in a stream under forecast of different distance intervals (500, 1500, 2000 m) within 6.5 km is arrived at approximate 344, 357, and 384 days, respectively. The study suggested the combined technique of GIS, RF, and NS can serve the risk source identification of contaminated sites and risk forecast of toxic element diffusion in emergency situations.
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Arsênio , Mercúrio , Metais Pesados , Poluentes do Solo , Poluentes Químicos da Água , Arsênio/análise , Rios , Metais Pesados/análise , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Sedimentos Geológicos , Poluentes Químicos da Água/análise , China , Medição de RiscoRESUMO
BACKGROUND: Impaired liver regeneration in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients is closely related to prognosis; however, the mechanisms are not yet defined. Liver-derived extracellular vesicles (EVs) may be involved in the dysregulation of liver regeneration. Clarifying the underlying mechanisms will improve the treatments for HBV-ACLF. METHODS: EVs were isolated by ultracentrifugation from liver tissues of HBV-ACLF patients (ACLF_EVs) after liver transplantation, and their function was investigated in acute liver injury (ALI) mice and AML12 cells. Differentially expressed miRNAs (DE-miRNAs) were screened by deep miRNA sequencing. The lipid nanoparticle (LNP) system was applied as a carrier for the targeted delivery of miRNA inhibitors to improve its effect on liver regeneration. RESULTS: ACLF_EVs inhibited hepatocyte proliferation and liver regeneration, with a critical role of miR-218-5p. Mechanistically, ACLF_EVs fused directly with target hepatocytes and transferred miR-218-5p into hepatocytes, acting by suppressing FGFR2 mRNA and inhibiting the activation of ERK1/2 signaling pathway. Reducing the level of miR-218-5p expression in the liver of ACLF mice partially restored liver regeneration ability. CONCLUSION: The current data reveal the mechanism underlying impaired liver regeneration in HBV-ACLF that promotes the discovery of new therapeutic approaches.
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Supercapacitors are widely used in various fields due to their high power density, fast charging and discharging speeds, and long service life. However, with the increasing demand for flexible electronics, integrated supercapacitors in devices are also facing more challenges, such as extensibility, bending stability, and operability. Despite many reports on stretchable supercapacitors, challenges still exist in their preparation process, which involves multiple steps. Therefore, we prepared stretchable conducting polymer electrodes by depositing thiophene and 3-methylthiophene on patterned 304 stainless steel (SS 304) through electropolymerization. The cycling stability of the prepared stretchable electrodes could be further improved by protecting them with poly(vinyl alcohol)/sulfuric acid (PVA/H2SO4) gel electrolyte. Specifically, the mechanical stability of the polythiophene (PTh) electrode was improved by 2.5%, and the stability of the poly(3-methylthiophene (P3MeT) electrode was improved by 7.0%. As a result, the assembled flexible supercapacitors maintained 93% of their stability even after 10,000 cycles of strain at 100%, which indicates potential applications in flexible electronics.
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AIMS: LDL cholesterol (LDL-C) is a well-established risk factor for coronary artery disease (CAD). However, the optimal LDL-C level with regard to efficacy and safety remains unclear. We aimed to investigate the causal relationships between LDL-C and efficacy and safety outcomes. METHODS: We analyzed 353,232 British from the UK Biobank and 41,271 Chinese from the China-PAR project. Linear and non-linear Mendelian randomization (MR) analyses were performed to evaluate the causal relation between genetically proxied LDL-C and CAD, all-cause mortality, and safety outcomes (including hemorrhagic stroke, diabetes mellitus, overall cancer, non-cardiovascular death, and dementia). RESULTS: No significant non-linear associations were observed for CAD, all-cause mortality, and safety outcomes (Cochran Q P > 0.25 in British and Chinese) with LDL-C levels above the minimum values of 50â mg/dL and 20â mg/dL in British and Chinese, respectively. Linear MR analyses demonstrated a positive association of LDL-C with CAD (British: odds ratio [OR] per unit mmol/L increase, 1.75, P = 7.57 × 10-52; Chinese: OR, 2.06, P = 9.10 × 10-3). Furthermore, stratified analyses restricted to individuals with LDL-C levels less than the guidelines-recommended 70â mg/dL demonstrated lower LDL-C levels were associated with a higher risk of adverse events, including hemorrhagic stroke (British: OR, 0.72, P = 0.03) and dementia (British: OR, 0.75, P = 0.03). CONCLUSION: In British and Chinese populations, we confirmed a linear dose-response relationship of LDL-C with CAD and found potential safety concerns at low LDL-C levels, providing recommendations for monitoring adverse events in people with low LDL-C in the prevention of cardiovascular disease.
We used the Mendelian randomization method to estimate the causal relationships between LDL-C and efficacy and safety outcomes in the UK Biobank and the China-PAR project. We found a linear rather than a non-linear relationship between genetically proxied LDL cholesterol and coronary artery disease. There are potential safety concerns (including hemorrhagic stroke and dementia) for people who have low LDL-C levels.
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OBJECTIVE: To develop and validate a model to predict whether patients undergoing ureteroscopy (URS) will receive a stent. METHODS: Using registry data obtained from the Michigan Urological Surgery Improvement Collaborative Reducing Operative Complications from Kidney Stones initiative, we identified patients undergoing URS from 2016 to 2020. We used patients' age, sex, body mass index, size and location of the largest stone, current stent in place, history of any kidney stone procedure, procedure type, and acuity to fit a multivariable logistic regression model to a derivation cohort consisting of a random two-thirds of episodes. Model discrimination and calibration were evaluated in the validation cohort. A sensitivity analysis examined urologist variation using generalized mixed-effect models. RESULTS: We identified 15,048 URS procedures, of which 11,471 (76%) had ureteral stents placed. Older age, male sex, larger stone size, the largest stone being in the ureteropelvic junction, no prior stone surgery, no stent in place, a planned procedure type of laser lithotripsy, and urgent procedure were associated with a higher risk of stent placement. The model achieved an area under the receiver operating characteristic curve of 0.69 (95% CI 0.67, 0.71). Incorporating urologist-level variation improved the area under the receiver operating characteristic curve to 0.83 (95% CI 0.82, 0.84). CONCLUSION: Using a large clinical registry, we developed a multivariable regression model to predict ureteral stent placement following URS. Though well-calibrated, the model had modest discrimination due to heterogeneity in practice patterns in stent placement across urologists.
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The ranging accuracy of pulsed time-of-flight (TOF) lidar is affected by walk error and jitter error. To solve the issue, the balanced detection method (BDM) based on fiber delay optic lines (FDOL) is proposed. The experiments are carried out to prove the performance improvement of BDM over the conventional single photodiode method (SPM). The experimental results show that BDM can suppress common mode noise and simultaneously shift the signal to high frequency, which reduces the jitter error by approximately 52.4% and maintains the walk error at less than 300 ps with a non-distorted waveform. The BDM can be further applied to silicon photomultipliers.
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Refined and automatic retinal vessel segmentation is crucial for computer-aided early diagnosis of retinopathy. However, existing methods often suffer from mis-segmentation when dealing with thin and low-contrast vessels. In this paper, a two-path retinal vessel segmentation network is proposed, namely TP-Net, which consists of three core parts, i.e. main-path, sub-path, and multi-scale feature aggregation module (MFAM). Main-path is to detect the trunk area of the retinal vessels, and the sub-path to effectively capture edge information of the retinal vessels. The prediction results of the two paths are combined by MFAM, obtaining refined segmentation of retinal vessels. In the main-path, a three-layer lightweight backbone network is elaborately designed according to the characteristics of retinal vessels, and then a global feature selection mechanism (GFSM) is proposed, which can autonomously select features that are more important for the segmentation task from the features at different layers of the network, thereby, enhancing the segmentation capability for low-contrast vessels. In the sub-path, an edge feature extraction method and an edge loss function are proposed, which can enhance the ability of the network to capture edge information and reduce the mis-segmentation of thin vessels. Finally, MFAM is proposed to fuse the prediction results of main-path and sub-path, which can remove background noises while preserving edge details, and thus, obtaining refined segmentation of retinal vessels. The proposed TP-Net has been evaluated on three public retinal vessel datasets, namely DRIVE, STARE, and CHASE DB1. The experimental results show that the TP-Net achieved a superior performance and generalization ability with fewer model parameters compared with the state-of-the-art methods.
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Glycogen synthase kinase-3 (GSK3) is one of the important serine/threonine protein kinases and has two isoforms, namely, GSK3α and GSK3ß. GSK3 inhibits glycogen synthase activity through phosphorylation. It plays a key role in various pathophysiological processes, such as differentiation, immunity, metabolism, cell death, and cell survival. Therefore, GSK3 has evolved as an important therapeutic target for treating neurological diseases, inflammatory diseases, and cancer. In addition, GSK3 regulates inflammatory processes through NF-κB-induced expression of various cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6. Moreover, GSK3 is reported to participate in many signaling pathways related to disease pathology, including PI3K/Akt, Wnt, Hedgehog, cyclic adenosine monophosphate, mitogen-activated protein kinase, and transforming growth factor-ß (TGF-ß). GSK3 has become a therapeutic target against some inflammatory diseases, including the inclusion body myositis, sepsis, and inflammatory bowel disease. Hence, several GSK3 inhibitors have been under evaluation as new therapeutic strategies in recent years. Two drugs targeting GSK3 have already entered clinical studies, including tideglusib and lithium carbonate. In this study, we analyzed nearly 30 different small-molecule GSK3 inhibitors reported in the past 4 years and classified them into four categories (thiazole, pyridine, F-substituted benzene, and others) according to their structure to conduct further literature research. Moreover, we summarized the optimal compounds and described the process of transformation from the lead compound to the optimal compound. In addition, we aimed to summarize the role of GSK3 in the pathogenesis of inflammatory diseases, with insights into the recent progress in the discovery of GSK3 inhibitors.
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BACKGROUND: Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that are important mediators of intercellular communication. Arthropods transport nutrients, signaling molecules, waste and immune factors to all areas of the body via the hemolymph. Little is known about tick hemolymph EVs. METHODS: Hemolymph was collected from partially fed Rhipicephalus haemaphysaloides and Hyalomma asiaticum ticks by making an incision with a sterile scalpel in the middle (between the femur and metatarsus) of the first pair of legs, which is known as leg amputation. EVs were isolated from hemolymph by differential centrifugation and characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Proteins extracted from the hemolymph EVs were analyzed by 4D label-free proteomics. The EVs were also examined by western blot and immuno-electron microscopy analysis. Intracellular incorporation of PHK26-labeled EVs was tested by adding labeled EVs to tick salivary glands and ovaries, followed by fluorescence microscopy. RESULTS: In this study, 149 and 273 proteins were identified by 4D label-free proteomics in R. haemaphysaloides and H. asiaticum hemolymph EVs, respectively. TEM and NTA revealed that the sizes of the hemolymph EVs from R. haemaphysaloides and H. asiaticum were 133 and 138 nm, respectively. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses of identified proteins revealed pathways related to binding, catalytic and transporter activity, translation, transport and catabolism, signal transduction and cellular community. The key EV marker proteins RhCD9, RhTSG101, Rh14-3-3 and RhGAPDH were identified using proteomics and western blot. The presence of RhFerritin-2 in tick hemolymph EVs was confirmed by western blot and immuno-electron microscopy. We demonstrated that PKH26-labeled hemolymph EVs are internalized by tick salivary glands and ovary cells in vitro. CONCLUSIONS: The results suggest that tick EVs are secreted into, and circulated by, the hemolymph. EVs may play roles in the regulation of tick development, metabolism and reproduction.
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Vesículas Extracelulares , Rhipicephalus , Animais , Feminino , Ovário , Proteômica/métodos , Hemolinfa , Vesículas Extracelulares/química , Proteínas/metabolismo , Glândulas SalivaresRESUMO
[This corrects the article DOI: 10.3389/fimmu.2022.875407.].
