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Background: Whether patients can benefit from three-field lymphadenectomy (3-FL) in minimally invasive esophagectomy (MIE) remains unclear. This study retrospectively compared short-term outcomes between 3-FL and two-field lymphadenectomy (2-FL) in MIE for patients with esophageal cancer (EC) and aimed to evaluate the clinical significance of 3-FL. Methods: There were 284 patients enrolled in the study (124 patients with 3-FL and 160 patients with 2-FL). The cases were matched based on their propensity scores using a matching ratio of 1:1, the nearest neighbor matching protocol, and a caliper of 0.02. Patients were propensity-score matched for sex, cancer location, Age-adjusted Charlson Comorbidity Index (ACCI), and neoadjuvant treatment. The short-term outcomes were postoperative complications, operation characteristics, pathology results and postoperative hospital stay. Results: There were no significant differences in intraoperative hemorrhage, postoperative hospital stay, or postoperative complications between the 2-FL and 3-FL groups. The operation time of the two groups was significantly different (227.1±46.2 vs. 248.5±45.9 min, P=0.001); the operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group. The number of lymphatic nodes (LNs) obtained in the 3-FL group was significantly higher than that in the 2-FL group (31.3±12.9 vs. 54.6±18.0, P<0.001). Pathological N stage was also significantly different (P=0.002); the 3-FL group was more advanced than the 2-FL group. Conclusions: Compared to 2-FL MIE, 3-FL MIE does not increase postoperative complications, can obtain more LNs, and improves the accuracy of tumor LN staging.
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BACKGROUND: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumors (TURBT) has emerged as a promising complementary tool to white light (WL) cystoscopy, potentially improving cancer detection and replacing conventional mapping biopsies. This study aimed to investigate the diagnostic accuracy of PDD by anatomical locations in mapping biopsies through lesion-based analysis. METHODS: PDD and WL findings were prospectively recorded in 102 patients undergoing mapping biopsies and PDD-assisted TURBT using oral 5-aminolevulinic acid. We evaluated 673 specimens collected from flat tumor or normal-looking lesions on WL cystoscopy, after excluding 98 specimens collected from papillary or nodular tumors. RESULTS: Among the 673 lesions, cancer was detected in 110 (16%) by lesion-based analysis. PDD demonstrated significantly higher sensitivity (65.5% vs. 46.4%, p < 0.001) and negative predictive value (92.5% vs. 89.5%, p < 0.001) compared to WL. The sensitivity of PDD findings varied by location: posterior (100%), right (78.6%), dome (73.3%), left (70.6%), trigone (58.8%), bladder neck (41.7%), anterior (40.0%), and prostatic urethra (25.0%). Incorporating targeted biopsies of specific locations (bladder neck, anterior, and prostatic urethra) into the PDD-guided biopsies, regardless of PDD findings, significantly increased the overall sensitivity from 65.5% to 82.7% (p = 0.001). CONCLUSIONS: This study first demonstrated the detection rate of location-specific mapping biopsies using PDD, revealing difficulties in accuracy assessment in areas susceptible to tangential fluorescence. While PDD-guided biopsy improves cancer detection compared to WL cystoscopy even for flat tumors or normal-looking lesions, more careful decisions, including mapping biopsies, may be beneficial for an assessment in these tangential areas.
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T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8-/- mice received DCPC daily by transiently inhaling 10% CO2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8-/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8-/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC.
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Introduction: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection in immunocompromised individuals. Immune checkpoint inhibitor (ICI) has brought significant survival benefit in lung cancer patients. Although the few studies showed there was high mortality in PJP patients with ICI use, these studies had no comparative control groups. Methods: A retrospective study was conducted to compare the mortality in PJP patients with lung cancer between those treated with ICI and a concurrent control group treated without ICI. Results: A total number of 20 non-human immunodeficiency virus (HIV) patients with confirmed PJP and co-existing lung cancer were included in the current study, and classified into ICI group (n=9) and non-ICI group (n=11).There was a clear trend to a shorter onset of PJP in ICI group than non-ICI group (118.9 ± 60.9 vs 253.0 ± 185.1 days), although without statistical significance (p=0.053). Bronchoscopic alveolar lavage fluid were collected from all patients and used to identify Pneumocystis jirovecii. In both groups, metagenomics next-generation sequencing (mNGS) were the most used diagnostic techniques. Within 28 days after the onset of PJP, mortality was significantly higher in the ICI group than non-ICI group (33.3% vs 0, p=0.042). Conclusion: Lung cancer patients with ICI use had a higher mortality rate after PJP infection than patients without ICI use. Prospective studies with larger sample size and a multi-center design are warranted to further verify the present results.
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OBJECTIVE: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC. METHODS: The INMARC database was queried for T1aN0M0 RCC. Patients were stratified into groups based on recurrence. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed for factors associated with recurrence, cancer-specific (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) assessed survival by histology and grade. Subset analysis for time to recurrence was conducted for grade and histologic groups and compared with recent AUA follow-up guidelines [low-risk (AUA-LR), intermediate-risk (AUA-IR), high-risk (AUA-HR), and very-high risk (AUA-VHR) groups]. RESULTS: We analyzed 1,878 patients (median follow-up 35.2 months); 101 (5.4%) developed recurrence. MVA for recurrence demonstrated increasing age (Pâ¯=â¯0.026), male sex (Pâ¯=â¯0.043), diabetes (Pâ¯=â¯0.007), high/unclassified grade (P < 0.001-0.007), and variant histology (Pâ¯=â¯0.017) as independent risk factors for increased risk, while papillary (Pâ¯=â¯0.016) and chromophobe (Pâ¯=â¯0.049) were associated with decreased risk. MVA identified high/unclassified grade (Pâ¯=â¯0.003-0.004) and pT3a upstaging (Pâ¯=â¯0.043) as predictive factors for worsened risk of CSM while papillary (Pâ¯=â¯0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (Pâ¯=â¯0.022), variant histology (Pâ¯=â¯0.049), recurrence (Pâ¯=â¯0.004), and eGFR<45 at last follow-up (P < 0.001) to be independent risk factors. KMA comparing clear cell, chromophobe, papillary, and variant RCC revealed significant differences for 5-year CSS (Pâ¯=â¯0.018) and RFS (P < 0.001), but not OS (Pâ¯=â¯0.34). Median time to recurrence was 23.8 months for low-grade (AUA-LR), 17.3 months for high-grade (AUA-IR), 18 months for pT3a upstaging (AUA-HR), and 12 months for variant histology (AUA-VHR; P < 0.001). CONCLUSION: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. Our findings support recently promulgated AUA follow-up guidelines for low-grade and variant histology pT1a RCC, but call for consolidation of follow-up protocols for high-grade pT1a and pT3a upstaged patients, with intensification of frequency of imaging follow-up in pT1a high-grade RCC.
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Carcinoma de Células Renales , Bases de Datos Factuales , Neoplasias Renales , Recurrencia Local de Neoplasia , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Masculino , Femenino , Recurrencia Local de Neoplasia/patología , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Persona de Mediana Edad , Anciano , Pronóstico , Factores de Riesgo , Estadificación de NeoplasiasRESUMEN
The novel multifunctional active packaging composite film with antimicrobial, antioxidant, water-vapor and UV-barrier, and corrosion resistance properties was successfully prepared from waste biomass. In this study, waste poplar sawdust was pretreated using green liquor to extract black liquor (BL). BL was then mixed with polyvinyl alcohol (PVA) solution for synthesizing silver nanoparticles (AgNPs). PVA-BL-AgNPs film was fabricated by solution casting method, and the microstructure characterization and macroscopic performance testing of the composite film were conducted. The results revealed that PVA-BL-AgNPs film exhibited inhibitory effects against Staphylococcus aureus (inhibition zone: 33.6 mm), Pseudomonas aeruginosa (inhibition zone: 31.6 mm), and Escherichia coli (inhibition zone: 32.0 mm). It could eliminate over 99 % of 2,2-diazodi (3-ethyl-benzothiazol-6-sulfonic acid) (ABTS) free radicals and provided 100 % UV-blocking, reducing light-induced food damage. It exhibited the improvement of water-vapor barrier properties and corrosion resistance. In vitro cytotoxicity assays demonstrated that no significant impact occurred on cell proliferation, confirming the safety of the film. Packaging experiments showed that PVA-BL-AgNPs film effectively inhibited milk spoilage and prolonged the shelf-life of bread and bananas. Therefore, PVA-BL-AgNPs film might extend the shelf-life of food and offer significant opportunities in addressing the issues of low safety and environmental pollution associated with traditional packaging films.
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Antibacterianos , Antioxidantes , Embalaje de Alimentos , Lignina , Nanopartículas del Metal , Plata , Rayos Ultravioleta , Antibacterianos/farmacología , Antibacterianos/química , Antioxidantes/química , Antioxidantes/farmacología , Lignina/química , Corrosión , Embalaje de Alimentos/métodos , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Frutas/química , Alcohol Polivinílico/química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Bone defects arising from diverse causes, such as traffic accidents, contemporary weapon usage, and bone-related disorders, present significant challenges in clinical treatment. Prolonged treatment cycles for bone defects can result in complications, impacting patients' overall quality of life. Efficient and timely repair of bone defects is thus a critical concern in clinical practice. OBJECTIVE: This study aims to assess the scientific progress and achievements of magnesium phosphate bone cement (MPC) as an artificial bone substitute material. Additionally, the research seeks to explore the future development path and clinical potential of MPC bone cement in addressing challenges associated with bone defects. METHODS: The study comprehensively reviews MPC's performance, encompassing e.g. mechanical properties, biocompatibility, porosity, adhesion and injectability. Various modifiers are also considered to broaden MPC's applications in bone tissue engineering, emphasizing drug-loading performance and antibacterial capabilities, which meet clinical diversification requirements. RESULTS: In comparison to alternatives such as autogenous bone transplantation, allograft, polymethyl methacrylate (PMMA), and calcium phosphate cement (CPC), MPC emerges as a promising solution for bone defects. It addresses limitations associated with these alternatives, such as immunological rejection and long-term harm to patients. MPC can control heat release during the curing process, exhibits superior mechanical strength, and has the capacity to stimulate new bone growth. CONCLUSION: MPC stands out as an artificial bone substitute with appropriate mechanical strength, rapid degradation, non-toxicity, and good biocompatibility, facilitating bone repair and regeneration. Modification agents can enhance its clinical versatility. Future research should delve into its mechanical properties and formulations, expanding clinical applications to create higher-performing and more medically valuable alternatives in bone defect repair.
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Cementos para Huesos , Sustitutos de Huesos , Compuestos de Magnesio , Fosfatos , Cementos para Huesos/química , Cementos para Huesos/uso terapéutico , Humanos , Fosfatos/química , Compuestos de Magnesio/química , Compuestos de Magnesio/uso terapéutico , Sustitutos de Huesos/uso terapéutico , Sustitutos de Huesos/química , Animales , Regeneración Ósea/efectos de los fármacos , Porosidad , Ensayo de Materiales , Huesos/efectos de los fármacosRESUMEN
The secretory glutaminyl cyclase (sQC) and Golgi-resident glutaminyl cyclase (gQC) are responsible for N-terminal protein pyroglutamation and associated with various human diseases. Although several sQC/gQC inhibitors have been reported, only one inhibitor, PQ912, is currently undergoing clinic trials for the treatment of Alzheimer's disease. We report an X-ray crystal structure of sQC complexed with PQ912, revealing that the benzimidazole makes "anchor" interactions with the active site zinc ion and catalytic triad. Structure-guided design and optimization led to a series of new benzimidazole derivatives exhibiting nanomolar inhibition for both sQC and gQC. In a MPTP-induced Parkinson's disease (PD) mouse model, BI-43 manifested efficacy in mitigating locomotor deficits through reversing dopaminergic neuronal loss, reducing microglia, and decreasing levels of the sQC/gQC substrates, α-synuclein, and CCL2. This study not only offers structural basis and new leads for drug discovery targeting sQC/gQC but also provides evidence supporting sQC/gQC as potential targets for PD treatment.
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Aminoaciltransferasas , Bencimidazoles , Inhibidores Enzimáticos , Animales , Aminoaciltransferasas/antagonistas & inhibidores , Aminoaciltransferasas/metabolismo , Bencimidazoles/química , Bencimidazoles/farmacología , Bencimidazoles/síntesis química , Cristalografía por Rayos X , Ratones , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/uso terapéutico , Relación Estructura-Actividad , Modelos Animales de Enfermedad , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Humanos , Ratones Endogámicos C57BL , Descubrimiento de Drogas , Masculino , Modelos MolecularesRESUMEN
The excessive usage and emissions of triclosan (TCS) pose a serious threat to aquatic environments. Iron-based bimetallic particles (Pd/Fe, Ni/Fe, and Cu/Fe, etc.) were widely used for the degradation of chlorophenol pollutants. This study proposed a novel synthesis method for the preparation of Ni/Fe bimetallic particles (Ni-Febm) by ball milling microscale zero valent iron ZVI (mZVI) and NiSO4. Ball-milling conditions such as ball-milling time, ball-milling speed and ball-to-powder ratio were optimized to prepare high activity Ni-Febm bimetallic particles. During the ball-milling process, Ni2+ was reduced to Ni0 and formed a coupled structure with ZVI. The amount of Ni0 on ZVI significantly affected the activity of Ni-Febm bimetallic particles. The highest activity Ni-Febm bimetallic particles with Ni/Fe ratio of 0.03 were synthesized under optimized conditions, which could remove 86.56% of TCS (10 µM) in aerobic aqueous solution within 60 min. In addition, higher particle dosage, lower pH condition and higher reaction temperature were more conducive for TCS degradation. The higher corrosion current and lower electron transfer impedance of Ni-Febm bimetallic particles were the main reasons for its high activity. The hydrogen atom (â¢H) on the surface of Ni-Febm bimetallic particles was mainly contributed to the removal of TCS, as reductive transformation products of TCS were detected by LC-TOF-MS. Notably, a small amount of oxidation products were discovered. The total dechlorination rate of TCS was calculated to be 39.67%. After eight reaction cycles, the residual Ni-Febm bimetallic particles could still degrade 28.34% of TCS within 6 h. Low Ni2+ leaching during reaction indicated that Ni-Febm bimetallic particles did not pose potential environmental risks. The prepared environmental-friendly Ni-Febm bimetallic particles with high activity have great potential in the degradation of other chlorinated organic compounds in wastewater.
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Hierro , Níquel , Triclosán , Contaminantes Químicos del Agua , Triclosán/química , Níquel/química , Hierro/química , Contaminantes Químicos del Agua/química , PolvosRESUMEN
Tamoxifen (TAM) is a classical anti-estrogenic drug that antagonizes estrogen by competitively binding to estrogen receptor α (ERα). However, drug resistance to TAM remains a significant challenge in breast cancer treatment. In this study, we aimed to design an actively targeted drug delivery system to enhance the proliferation inhibitory effects of TAM on ER positive breast cancer cells. Herein, chitosan (CS) was modified with genistein (GEN) to obtain the actively targeted GEN-CS. The TAM-loaded nanoparticles (TAM-GEN-CS-NPs) were constructed using an ionic-crosslinking method, with GEN-CS as the carrier material and sodium tripolyphosphate (TPP) as the crosslinking agent. As a result, TAM-GEN-CS-NPs exhibited a spherical morphology with an average size of 299.8 nm. The encapsulation efficiency and drug loading content were 85.77% and 14.13 µg/mg, respectively. Compared with free TAM, TAM-GEN-CS-NPs displayed obvious slow-release performance. In vitro cellular assays demonstrated that TAM-GEN-CS-NPs had active targeting and proliferation inhibitory effects on MCF-7 cells. The IC50 of TAM and TAM-GEN-CS-NPs were 10.25 µg/mL and 7.22 µg/mL, respectively. More importantly, the combination index (CI) value of TAM and GEN was less than 1, indicating synergistic effects. Therefore, TAM-GEN-CS-NPs hold the potential to enhance TAM therapy for breast cancer through active targeting and synergistic treatment strategies.
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Ultrasonic extraction of Osmanthus fragrans was used for reducing Ag+ to prepare AgNPs, which were further loaded on barley distiller's grains shell biochar. By supplementary of sodium alginate and tannic acid, composite gel beads were prepared. The physical properties of biochar-based AgNPssodium alginate-tannic acid composite gel beads (C-Ag/SA/TA) were characterized. SEM, FTIR, and XRD showed that biochar-based AgNPs were compatible with sodium alginate-tannic acid. CAg greatly improved the dissolution, swelling, and expansion of gel beads. Through the analysis by the agar diffusion method, C-Ag/SA/TA gel beads had high antibacterial activity (inhibition zone: 22 mm against Escherichia coli and 20 mm against Staphylococcus aureus). It was observed that C-Ag/SA/TA composite gel beads had high antioxidant capacity and the free radical scavenging rate reached 89.0 %. The dye adsorption performance of gel beads was studied by establishing a kinetic model. The maximum adsorption capacities of C-Ag/SA/TA gel beads for methylene blue and Congo red were 166.57 and 318.06 mg/g, respectively. The removal rate of Cr(VI) reached 96.4 %. These results indicated that the prepared composite gel beads had a high adsorption capacity for dyes and metal ions. Overall, C-Ag/SA/TA composite gel beads were biocompatible and had potential applications in environmental pollution treatment.
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Alginatos , Antibacterianos , Antioxidantes , Carbón Orgánico , Cromo , Nanopartículas del Metal , Plata , Taninos , Plata/química , Carbón Orgánico/química , Alginatos/química , Taninos/química , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Antioxidantes/química , Antioxidantes/farmacología , Adsorción , Cromo/química , Geles/química , Colorantes/química , Cinética , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Contaminantes Químicos del Agua/química , PolifenolesRESUMEN
AIM: To compare endovascular coiling and surgical clipping for the evaluation of clinical outcomes in patients with unruptured intracranial aneurysms. MATERIAL AND METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and three Chinese domestic electronic databases, namely, Wanfang, CNKI and VIP for studies published between January 1990 and January 2018. We included controlled clinical studies comparing clinical outcomes between surgical clipping and endovascular coiling treatments. Two researchers extracted the data and assessed the quality of the studies, and a meta-analysis was performed using RevMan 5 software. RESULTS: We analysed a total of 23 controlled clinical studies including 117,796 cases. Meta-analysis demonstrated similar ischaemia rates between clipping and coiling with an odds ratio [OR] of 1.36 (95% CI: 0.77?2.40). The occlusion rate and bleeding risk were higher with clipping than coiling; the pooled ORs were 5.31 (95% CI: 3.07?9.19) and 2.39 (95% CI: 1.82?3.13), respectively. In addition, clipping resulted in a longer hospital stay (OR = 2.90, 95% CI: 2.14?3.65) than coiling did. Patients who underwent clipping had a higher short-term mortality (OR = 1.99, 95% CI: 1.70?2.33) and neurological deficit rate (OR = 2.05, 95% CI: 1.73? 2.44) compared with those who underwent coiling. However, 1 year mortality and deficit rate were similar for both clipping and coiling, with pooled ORs of 0.75 (95% CI: 0.41?1.38) and 0.94 (95% CI: 0.53?1.67), respectively. Funnel plots did not demonstrate a publication bias, with the exception of ischaemic outcome, and sensitivity analysis showed consistent results. CONCLUSION: Our study demonstrates that coiling is associated with a lower rate of occlusion, shorter hospital stay, lower bleeding risk and lower short-term mortality and morbidity compared with clipping. In terms of ischaemic risk, 1 year mortality and morbidity, coiling and clipping bear a similar risk. In addition, we speculate that surgical clipping may have a better outcome than endovascular coiling in the long term especially in young patients. Further research is needed to confirm our conclusion.
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Procedimientos Endovasculares , Aneurisma Intracraneal , Instrumentos Quirúrgicos , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/terapia , Procedimientos Endovasculares/métodos , Resultado del Tratamiento , Procedimientos Neuroquirúrgicos/métodos , Embolización Terapéutica/métodos , Embolización Terapéutica/instrumentaciónRESUMEN
Sulfidated zero valent iron (ZVI) is a popular material for the reductive degradation of halogenated organic pollutants. Simple and economic synthesis of this material is highly demanded. In this study, sulfidated micro/nanostructured ZVI (MNZVI) particles were prepared by simply heating MNZVI particles and sulfur elements (S0) in pure water (50â). The iron oxides on the surface of MNZVI particles were conducive to sulfidation reaction, indicating the formation of iron-sulphide minerals (FeSx) on the surface of MNZVI particles might not be from the direct reaction of Fe0 with S0 (Fe0 and S0 acted as reductant and oxidant, respectively). As an important reductant, hydrogen atom (Hâ¢) can be generated from the reduction of H+ by MNZVI particles and participate in the formation of FeSx. Quenching experiment and cyclic voltammetry analysis proved the existence of H⢠on the surface of MNZVI particles. DFT calculation found that the potential barrier of Hâ¢/S0 and Fe0/S0 were 1.91 and 7.24 eV, respectively, indicating that S0 would preferentially react with H⢠instead of Fe0. The formed H⢠can quickly react with S0 to generate hydrogen sulfide (H2S), which can further react with iron oxides such as α-Fe2O3 on the surface of MNZVI particles to form FeSx. In addition, the H2 partial pressure in water significantly affected the amount of H⢠generated, thereby affecting the sulfidation efficiency. For TCE degradation, as the sulfur loading of sulfidated MNZVI particles increased, the contribution of H⢠significantly decreased while the contribution of direct electron transfer increased. This study provided new insights into the synthesis mechanism of sulfidated ZVI in water.
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Hidrógeno , Hierro , Hidrógeno/química , Hierro/química , Oxidación-ReducciónRESUMEN
BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Humanos , Masculino , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Nomogramas , Próstata/diagnóstico por imagen , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Distribución AleatoriaRESUMEN
Landing on unmanned surface vehicles (USV) autonomously is a critical task for unmanned aerial vehicles (UAV) due to complex environments. To solve this problem, an autonomous landing method is proposed based on a multi-level marker and linear active disturbance rejection control (LADRC) in this study. A specially designed landing board is placed on the USV, and ArUco codes with different scales are employed. Then, the landing marker is captured and processed by a camera mounted below the UAV body. Using the efficient perspective-n-point method, the position and attitude of the UAV are estimated and further fused by the Kalman filter, which improves the estimation accuracy and stability. On this basis, LADRC is used for UAV landing control, in which an extended state observer with adjustable bandwidth is employed to evaluate disturbance and proportional-derivative control is adopted to eliminate control error. The results of simulations and experiments demonstrate the feasibility and effectiveness of the proposed method, which provides an effective solution for the autonomous recovery of unmanned systems.
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Flexible solid-state batteries fabricated by printing techniques are promising integrated power supplies for miniaturized and customized electronic devices. While typically these batteries use polymer solid electrolytes, a flexible Li2S cathode with sulfide solid electrolyte is spray-printed in this work, by using solvated Li3PS4 nanoparticles as inorganic ion-conductive binder. This benefits from a novel low-temperature-sintering property of these nanoparticles, which can be pressure-free densified, along with the desolvation process, and thus bind the cathode at 250 °C. The battery can be stably charged and discharged for 300 cycles with no stacking pressure, and the capacity maintains at 840 mA h gLi2 S-1. We believe this low-temperature-sintering phenomenon of solid electrolyte nanoparticles will open a new path toward the application of sulfide solid electrolytes in printed solid-state batteries.
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PURPOSE: To established an AI system to make the pathological diagnosis of prostate cancer. METHODS: Prostate histopathological whole mount (WM) sections from patients underwent robot-assisted laparoscopic prostatectomy were prepared. All the prostate WM pathological sections were converted to digital image data and marked with different colors on the basis of the ISUP Gleason grade group. The image was then fed into a segmentation algorithm. We chose modified U-Net as our fundamental network architecture. RESULTS: 172 patients were involved in this study. 896 pieces of prostate WM pathological sections from 160 patients, in which 826 pieces of WM sections from 148 patients were assigned to the training set randomly. After image segmentation there were totally 2,138,895 patches, of which 1,646,535 patches were valid for training. The other WM section was arranged for testing. Based on the whole image testing, AI and pathologists presented the same answers among 21 of 22 pieces of sections. To evaluate the diagnostic results at the pixel level, we anticipated correct cancer or non-cancer diagnose from this AI system. The area under the ROC curve as 96.8%. The value of pixel accuracy of three methods (binary analysis, clinically oriented analysis and analysis for different ISUP Gleason grade) were 96.93%, 95.43% and 93.88%, respectively. The value of frequency weighted IoU were 94.32%, 92.13% and 90.21%, respectively. CONCLUSIONS: This AI system is able to assist pathologists to make a final diagnosis, indicating the great potential and a wide-range of applications of AI in the medical field.
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Laparoscopía , Neoplasias de la Próstata , Humanos , Masculino , Algoritmos , Redes Neurales de la Computación , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugíaRESUMEN
Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy. Developed lipid cubosomes showed a particle size of around 300 nm and possessed an internal ordered inverse primitive cubic phase, a high conjugation efficiency of Ang2 to the particle surface, and an encapsulation efficiency of more than 70% of CDDP and TMZ. In vitro models, including BBB hCMEC/D3 cell tight monolayer, 3D BBB cell spheroid, and microfluidic BBB/GBM-on-a-chip models with cocultured BBB and glioblastoma cells, were employed to study the efficiency of the developed cubosomes to cross the BBB and showed that Ang2-functionalized cubosomes can penetrate the BBB more effectively. Furthermore, Ang2-functionalized cubosomes showed significantly higher uptake by U87 glioblastoma cells, with a 3-fold increase observed in the BBB/GBM-on-a-chip model as compared to that of the bare cubosomes. Additionally, the in vivo biodistribution showed that Ang2 modification could significantly enhance the brain accumulation of cubosomes in comparison to that of non-functionalized particles. Moreover, CDDP-loaded Ang2-functionalized cubosomes presented an enhanced toxic effect on U87 spheroids. These findings suggest that the developed Ang2-cubosomes are prospective for improved BBB crossing and enhanced delivery of therapeutics to glioblastoma and are worth pursuing further as a potential application of nanomedicine for GBM treatment.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Péptidos , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Barrera Hematoencefálica/patología , Distribución Tisular , Estudios Prospectivos , Línea Celular Tumoral , Temozolomida , Neoplasias Encefálicas/patología , Nanopartículas/uso terapéutico , Lípidos/uso terapéuticoRESUMEN
A hybrid energy harvester based on magnetic levitation is inspired by the structure of the flapping wing, which consists of two parts: one is a flapping wing structure mounted with a piezoelectric sheet, which can achieve piezoelectric energy harvesting; the other is an intermediate muscle unit, which is vertically arranged by three groups of permanent magnets to achieve magnetic levitation electromagnetic energy harvesting. An electromechanical-electromagnetic coupling model of this harvester is established based on electromechanical coupling characteristics. The simulation analysis can evaluate the magnetic field distribution and nonlinear magnetic properties and also analyze its effects on the output performance. Several experiments are designed to verify the effectiveness of the hybrid energy harvesting structure and to check the influence of the number of magnets on the output power. The maximum output power of the proposed structure can generate 13.61 mW at 4.5 Hz excitation.
RESUMEN
CONTEXT: Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF). OBJECTIVE: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined. DESIGN: Population-based case-cohort study. SETTING: The Danish National Healthcare system maintains longitudinal records of medication use, healthcare utilization, and x-ray images. PARTICIPANTS: Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010-2015 (n = 4,973) were identified and compared to a random sample (n = 37,021). PREDICTORS: Bisphosphonate use was collected from 1995-2015. MAIN OUTCOME MEASURES: Fracture radiographs (n = 4,769) were reviewed by blinded study radiologists to identify AFFs (n = 181) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10. RESULTS: Compared to <1 year of BP use, 5-7 years of use was associated with a 7-fold increase in AFF [adjusted HR = 7.29 (CI: 3.07,17.30)]; the risk of AFF fell quickly after discontinuation. The 5-year number-needed-to-harm for one AFF was 1,424, while the 5-year number-needed-to-treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure. CONCLUSIONS: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.