RESUMO
Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.
Assuntos
Envelhecimento , Ferroptose , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Ferroptose/genética , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/genética , Ratos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Masculino , Envelhecimento/metabolismo , Envelhecimento/genética , Envelhecimento/patologia , Ratos Sprague-Dawley , Linhagem Celular , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismoRESUMO
BACKGROUND: Knee osteoarthropathy is one of the most common degenerative joint diseases in the elderly, total knee arthroplasty (TKA) is the most commonly used treatment for end-stage knee osteoarthropathy. Negative emotions such as anxiety have been extensively documented in knee osteoarthropathy patients. AIM: This study aimed to investigate the Emotional Contagion during hospitalization in patients undergoing TKA. METHODS: Eligible subjects were divided into three case groups according to their anxiety states and bed arrangement. All subjects underwent a unilateral, cemented TKA under general anesthesia. Post-operative recovery outcomes including pain, pain behavior and physical function were recorded pre-operation, 1-day, 1 week, 2-weeks, 1-month and 3-months post-operation. RESULTS: A total of 38 subjects were included in the final analysis. Subjects with anxiety had higher Visual Analogue Scale pain scores, PROMIS-Pain Behavior scores than subjects without anxiety in the Contagion Group preoperation (p ≤ .05). Non-anxiety subjects hospitalized in beds physically adjacent to anxiety subjects experienced more severe pain and poorer function (p ≤ .05). After discharge, all clinical outcomes gradually became lower than anxiety subjects in the Contagion Group, reaching levels similar to non-anxiety subjects in the No Contagion Group within 1 month (p>.05). CONCLUSIONS: This study showed that patients with anxiety may have an "Adjacent Bed Effect" on patients with TKA in the adjacent bed, which may be associated with poorer postoperative recovery, including pain and physical function. We speculate this phenomenon can be effectively avoided by the nursing team through accurately assessing psychological status and reasonable bed arrangements in the inpatient assessment phase.
Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Idoso , Resultado do Tratamento , Período Pós-Operatório , Dor/complicaçõesRESUMO
Different from three-dimensional bulk compounds, two-dimensional monolayer compounds exhibit much better thermoelectric performance on account of the quantum confinement and interface effect. Here, we present a systematic study on the electronic and thermal transport properties of bulk and monolayer Bi2Si2X6 (X = Se, Te) through theoretical calculations using density functional theory based on first-principles and Boltzmann transport theory. Monolayer Bi2Si2X6 are chemically, mechanically and thermodynamically stable semiconductors with suitable band gaps, and they have lower lattice thermal conductivity (κL) in the a/b direction than their bulk counterparts. The calculated κL of monolayer Bi2Si2Se6 (Bi2Si2Te6) is as low as 0.72 (0.95) W m-1 K-1 at 700 K. Moreover, monolayer Bi2Si2X6 exhibit a higher Seebeck coefficient compared with bulk Bi2Si2X6 owing to the sharper peaks in the electronic density of states (DOS). This results in a significant increase in power factor by dimensionality reduction. Combined with the synergetically suppressed thermal conductivity, the maximum ZT values for monolayer Bi2Si2Se6 and Bi2Si2Te6 are significantly enhanced up to 5.03 and 2.87 with p-type doping at 700 K, which are more than 2 times that of the corresponding bulk compounds. These results demonstrate the superb thermoelectric performance of monolayer Bi2Si2X6 for promising thermoelectric conversion applications.
RESUMO
BACKGROUND: Right ventricular mass indexed to body surface area (RVMI) decreases and left ventricular mass index (LVMI) increases rapidly and substantially during early infancy. The relationship between these sizeable mass transformations and simultaneous electrocardiographic changes have not been previously delineated. METHODS: Normal term infants (#45 initially enrolled) were prospectively evaluated at 2 days and at 2-week, 2-month, and 4-month clinic visits. Ventricular masses were estimated with 2D echocardiographic methods. QRS voltages were measured in leads V1, V6, I and aVF. RESULTS: Mean QRS axis shifted from 135 (95%CI 124, 146) to 65 degrees (95%CI 49, 81) and correlated with both RVMI decrease and LVMI increase (R = 0.46â vs. 0.25, respectively. *p < 0.01, p < 0.05). As RVMI decreased from mean 28.1 (95%CI 27.1, 29.1) to 23.3 g/m2 (95%CI 21.4, 25.2) so did V1R and V6S voltages. RVMI changes correlated with V1R, V6S, and V1R + V6S voltages (R = 0.29*, 0.23 and 0.35*, respectively. *p < 0.01, p < 0.05) but not with V1R/S ratio. As LVMI increased from 44.6 (95%CI 42.9, 46.3) to 55.4 g/m2 (95%CI 52.3, 58.5) V6R and V6Q increased but V1S voltage did not. LVMI changes correlated with V6R, V6R-S, and V6(Q + R)-S voltages (R = 0.31*, 0.34*, and 0.38* respectively. *p < 0.01) but not with V1S or V6R/S (R = 0.01 and 0.18 respectively, p = NS). CONCLUSIONS: During early infancy the RVMI decrease correlates best with the QRS axis shift and V1R + V6S voltage, and the LVMI increase correlates best with V6R-S and V6(Q + R)-S voltages.
Assuntos
Ecocardiografia , Eletrocardiografia , Humanos , Lactente , Eletrocardiografia/métodosRESUMO
By using first-principles calculations, the sensing properties of pristine and transition metal (TM) atoms (Ti, V, and Co) embedded germanium selenide (GeSe) monolayer toward small gas molecules (H2, NH3, CO, O2, SO2, NO, and NO2) were investigated. The adsorption energies, electronic structure, optical properties, and recovery time of the adsorption systems were calculated and analyzed in detail. The results indicate that TM doped GeSe has stronger interaction with gas molecules compared with the pristine GeSe monolayer. Especially for Ti- and V-GeSe monolayer, the absolute value of adsorption energies are up to 2 eV for O2, NO, and NO2. The doping with TM atoms also changes the charge transfer and electronic structures of adsorption systems. Combined with the result of the calculated optical properties and recovery time, it can be concluded that Ti-GeSe monolayer has great potential for NH3 detection, while Co-GeSe monolayer can be very promising SO2 gas sensors.
RESUMO
Paenarthrobacter sp. TYUT067 is a soil bacterium that can degrade and use cyclohexylamine as the sole source of carbon and energy. However, the responsible enzymes involved in cyclohexylamine degradation by TYUT067 have not been cloned and characterized in detail yet. In this study, four possible cyclohexylamine degradation genes, one cyclohexylamine oxidase (Pachao), two cyclohexanone monooxygenases (Pachms) and one lactone hydrolase (Pamlh) were successfully cloned and heterologous expressed in Escherichia coli T7 host cells. The four enzymes were purified and characterized. The optimal pH and temperature of the purified enzymes toward their own substrates were 7.0 (PaCHAO), 8.0 (PaCHM1), 9.0 (PaCHM2 and PaMLH) and 30 °C (PaCHAO and PaMLH), 40 °C (PaCHM2) and 45 °C (PaCHM1), respectively, with KM of 1.1 mM (PaCHAO), 0.1 mM (PaCHM1), 0.1 mM (PaCHM2) and 0.8 mM (PaMLH), and yielding a catalytic efficiency kcat/KM of 16.1 mM-1 s-1 (PaCHAO), 1.0 mM-1 s-1 (PaCHM1), 5.0 mM-1 s-1 (PaCHM2) and 124.4 mM-1 s-1 (PaMLH). In vitro mimicking the cyclohexylamine degradation pathway was conducted by using the combined three cyclohexylamine degradation enzymes (PaCHAO, PaCHM2 and PaMLH) with 10-50 mM cyclohexylamine, 100% conversion of cyclohexylamine could be finished within 12 h without any detected intermediates. The current study confirmed the enzymes responsible for cyclohexylamine degradation in TYUT067 for the first time, provide basic information for further investigation and application of these specific enzymes in pollution control.
Assuntos
Cicloexilaminas , Micrococcaceae , Clonagem Molecular , Cicloexilaminas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Hidrolases/genética , Micrococcaceae/metabolismoRESUMO
The thermoelectric properties of intrinsic n-type ß-Ga2O3 are evaluated by first-principles calculations combined with Boltzmann transport theory and relaxation time approximation. The electron mobility is predicted by considering polar optical phonon scattering in ß-Ga2O3. A temperature power law of T-0.67 is obtained for the intrinsic electron mobility. Due to the ultra-wide band gap of 4.7-4.9 eV, ß-Ga2O3 has a large Seebeck coefficient. As a result, a maximum power factor of 3.1 × 10-3 W m-1 K-2 is obtained at 1600 K. A clear anisotropy in lattice thermal conductivity is observed, with the highest thermal conductivity of 23.1 W m-1 K-1 at 300 K along the [010] direction, and a lower value of 13.2 and 12.2 W m-1 K-1 along the [001] and [100] directions, respectively. A high ZT value of 1.07 at 1600 K can be obtained at the optimal carrier concentration of 2.4 × 1019 cm-3, which is superior to that of most other oxides such as ZnO. In addition, the lattice thermal conductivity can be reduced by precisely adjusting the grain size, and the lattice thermal conductivity at 300 K (1600 K) can be reduced by 73% (39%) when the grain size is decreased to 10 nm. The excellent thermoelectric properties of ß-Ga2O3 have promoted its potential application in the field of high temperature thermoelectric conversion.
RESUMO
In this paper, hypercrosslinked polystyrene (HCLPS) networks were synthesized by radical bulk polymerization and Friedel-Crafts alkylation reactions using vinylbenzyl-co-divinylbenzene chloride (VBC-DVB) as the precursors. A series of HCLPS was prepared with varying content of DVB from 0 to 10% in the precursor. Both N2 adsorption and positron annihilation measurements reveal micropores in the HCLPS. Especially, the existence of ultramicropores with a size in the range of 0.63-0.7 nm is confirmed by positron lifetime measurements. With increasing DVB content from 0 to 10%, the number of ultramicropores shows a gradual increase. Both the H2 and CO2 adsorption capacity increase monotonously with the increase of the DVB content. With 10% DVB in the HCLPS, the H2 storage increases to 10.3 mmol g-1 (2.05 wt%) at 77 K and 1 bar and the CO2 capture reaches 2.81 mmol g-1 (12.4 wt%) at 273 K and 1 bar. The remarkable gas storage ability is ascribed to the existence of the ultramicropores, which result in a stronger affinity to the gas molecules. By using positrons as a new probe for the pores, our results provide convincing evidence of the role of ultramicropores in the gas adsorption performance in microporous organic polymers.
RESUMO
In this work, we study theoretically the electronic and phonon transport properties of heterojunction SnSe/SnS, bilayer SnSe and SnS. The energy filtering effect caused by the nano heterostructure in SnSe/SnS induces an increase in the Seebeck coefficient, causing a large power factor. We calculate the phonon relaxation time and lattice thermal conductivity κL for the three structures; the heterogeneous nanostructure could effectively reduce κL due to the enhanced phonon boundary scattering at interfaces. The average κL notably reduces from around 3.3 (3.2) W m-1 K-1 for bilayer SnSe (SnS) to nearly 2.2 W m-1 K-1 for SnSe/SnS at 300 K. As a result, the average ZT (ZTave in b and c directions) reaches 1.63 with temperature range around 300-800 K, which is improved by 63% (25%) compared with that of bilayer SnSe (SnS). Our theoretical results show that the heterogeneous nanostructure is an innovative approach for improving the Seebeck coefficient and significantly reducing κL, effectively enhancing thermoelectric properties.
RESUMO
In this paper, we performed comprehensive investigations of both the thermal and electrical transport properties of BiSbSe3 and BiSbS3 by using first-principles calculations and Boltzmann transport theory. Due to the repulsion between the lone-pair electrons of Sb and the p orbital of Se(S), both BiSbSe3 and BiSbS3 show strong anharmonicity with Grüneisen parameters of 1.90 and 1.79, respectively. As a result, these two materials possess extremely low lattice thermal conductivities. Meanwhile, both BiSbSe3 and BiSbS3 exhibit similar anisotropic thermal transport behaviors, which is due to the smaller phonon group velocities along the a axis. The predicted highest ZT values at 750 K are 2.9 for n-type BiSbSe3 and 1.2 for p-type BiSbS3. Our calculations provide insights into the origin of the extremely low thermal conductivity in BiSbSe3 and BiSbS3, which is meaningful for exploiting high performance thermoelectric materials with low thermal conductivity.
RESUMO
The topological phase transition and thermoelectric performance of LaPtBi under hydrostatic pressure up to 34.6 GPa have been systematically investigated using first-principles calculations based on density functional theory. The results indicate that the band structure can be tuned by applying hydrostatic pressure. As the energy band gap is opened under the hydrostatic pressure, a topological phase transition occurs in this material, changing from a topologically nontrivial semimetal to a trivial semiconductor. In addition, the hydrostatic pressure also has a remarkable effect on the thermoelectric properties of the topological half-Heusler compound LaPtBi. Though the lattice thermal conductivity shows a continuous increase with increasing hydrostatic pressure, the power factor is greatly enhanced due to the increase of the Seebeck coefficient. As a result, a maximum ZT value of 1.74 at 1000 K is achieved in n-type LaPtBi under pressure of 21.0 GPa. It is obvious that the thermoelectric figure of merit of LaPtBi is far beyond that of state-of-the-art half-Heusler thermoelectric materials, such as ZrNiSn, FeNbSb and TiCoSb. The realization of high thermoelectric performance in the half-Heusler compound LaPtBi under hydrostatic pressure could provide a new way to further explore other topological thermoelectric materials.
RESUMO
Pluripotent stem cell (PSC) cultures form an integral part of biomedical and medical research due to their capacity to rapidly proliferate and differentiate into hundreds of highly specialized cell types. This makes them a highly useful tool in exploring human physiology and disease. Genomic editing of PSC cultures is an essential method of attaining answers to basic physiological functions, developing in vitro models of human disease, and exploring potential therapeutic strategies and the identification of drug targets. Achieving reliable and efficient genomic editing is an important aspect of using large-scale PSC cultures. The CRISPR/Cas9 genomic editing tool has facilitated highly efficient gene knockout, gene correction, or gene modifications through the design and use of single-guide RNAs which are delivered to the target DNA via Cas9. CRISPR/Cas9 modification of PSCs has furthered the understanding of basic physiology and has been utilized to develop in vitro disease models, to test therapeutic strategies, and to facilitate regenerative or tissue repair approaches. In this review, we discuss the benefits of the CRISPR/Cas9 system in large-scale PSC cultures.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Técnicas de Inativação de Genes , Genômica/métodos , Células-Tronco Pluripotentes/fisiologia , Humanos , Células-Tronco Pluripotentes/citologiaRESUMO
First-principles calculations are used to study the structural, electronic, transport and optical properties of buckled bismuthene with the adsorption of various gas molecules such as CO, O2, H2O, NH3, SO2, NO and NO2. By considering the van der Waals interactions between the gas molecules and buckled bismuthene, we find that the buckled bismuthene shows superior gas sensing performance to other 2D materials such as graphene and MoS2. The adsorption of CO, O2, H2O and NH3 molecules is physisorption, whereas SO2, NO and NO2 are chemisorbed on the buckled bismuthene with large charge transfer and strong adsorption energy. After adsorption, charges are transferred from buckled bismuthene to the molecules and the quantum conductance is changed by the adsorbed molecules. Furthermore, the work function of buckled bismuthene is changed with the adsorption of different molecules. Our results show that the electronic, transport and optical properties of buckled bismuthene are sensitive to the adsorption of gas molecules, which suggests that buckled bismuthene holds great potential for application in gas sensors.
RESUMO
For the purpose of providing new insights for high-efficiency radiochemotherapy of hepatoma, a radioimmunotherapy and chemotherapy combinatorial therapy albumin nanospheres 131 I-antiAFPMcAb-DOX-BSA-NPs was designed and prepared. It was obtained in a high radiolabeling yield approximately 65% with the radiochemical purity of over 98%. The transmission electron microscope showed that the nanospheres obtained in good monodispersion with a diameter of approximately 230 nm. The doxorubicin (DOX) loading capacity of the DOX-BSA-NPs nanoparticles was determined to be approximately 180 µg/mg and 95.79 ± 3.89%. DOX was released gradually in 6 days. In vivo tumor-growth inhibition experiments showed that after treating with 131 I-antiAFPMcAb-DOX-BSA-NPs for 14 days, the tumor volume decreased more obvious than that of other 2 time points and the control groups. All the results indicated that the radiolabeled immune albumin nanospheres 131 I-antiAFPMcAb-DOX-BSA-NPs could significantly inhibit the hepatoma tumor growth with the strategy of combinatorial radioimmunotherapy and chemotherapy.
Assuntos
Albuminas/química , Quimiorradioterapia/métodos , Doxorrubicina/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Nanosferas/química , Neoplasias Experimentais/terapia , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Doxorrubicina/administração & dosagem , Feminino , Células Hep G2 , Humanos , Radioisótopos do Iodo/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , alfa-Fetoproteínas/imunologiaRESUMO
In this paper we show the preliminary evidence that the formation of positronium depends on the electrical conductivity of porous materials. Porous nano γ-Al2O3 was chosen as the base material, and it was filled with carbon of different allotropes (commercial graphite, carbon black, carbon nanotubes and home-made ordered mesoporous carbon) by a mechanical mixing method. The positron lifetime and Doppler broadening of the annihilation radiation were measured for these composites. In the pure γ-Al2O3 sample, there are two long positron lifetime components τ3 (3.5 ns) and τ4 (101.3 ns) with intensities of 1.0% and 24.6%, which indicates the formation and annihilation of positronium in small and large pores, respectively. In the carbon filled γ-Al2O3 samples, the longest lifetime τ4 and its intensity I4 both show a continuous decrease with increasing carbon content. The Doppler broadening S parameter shows a similar tendency to τ4 and I4. This suggests that carbon has a quenching effect on positronium and also inhibits the formation of positronium. Among these four carbon allotropes, carbon nanotubes have the strongest quenching and inhibition effect, while graphite has the weakest effect. A detailed study further reveals that the decreasing rate of τ4 and I4 as well as the S parameter depend on the electrical conductivity of the carbon filled γ-Al2O3 and also the specific surface area of the filled carbon. Our results suggest that the formation and annihilation of positronium are strongly affected by the electrical conductivity of the materials.
RESUMO
INTRODUCTION: Accurate placement of pedicle screws in spine surgery is a challenge for surgeons. Patient-specific template techniques have the potential for improving the accuracy of screw placement. The target of this analysis was to investigate differences in terms of accuracy of pedicle screw insertion between patient-specific template assistance and the conventional free-hand method for reconstruction of spinal stability. MATERIALS: The Cochrane Library, Ovid, Web of Science, PubMed, EMBASE and CNKI database were searched until February 2017 for a systematic review, and several comparative studies were screened for comparisons of accuracies of pedicle screw insertion with patient-specific assistance and conventional methods. Primary outcomes extracted from papers that met the selection criterion were expressed as odds ratios for dichotomous outcomes with a 95% confidence interval. A χ 2 test and I 2 statistics were used to evaluate heterogeneity. RESULTS: A total of ten RCTs and two prospective cohort studies were finally chosen for the analysis of accuracy rates. Study quality was assessed using the Cochrane Collaboration's Tool and Newcastle-Ottawa Quality Assessment Scale. There were obvious differences between them, and the accuracy rate of screw implantation among a patient-specific template assistance set was statistically significantly higher than the conventional free-hand set (OR 95% CI 3.78-6.41, P < 0.01); in vitro: OR 95% CI 3.93-7.42, P < 0.01; in vivo: OR 95% CI 2.49-6.44, P < 0.01. CONCLUSIONS: The template-assisted technique is superior to the conventional method for the reduction of pedicle violation. The template-assisted technique is a promising technique that should be considered as another available navigation tool for surgeons to improve the accuracy of pedicle screw placement. As an available technique for emerging applications in spine surgeries, this technique will face challenges but ultimately prove successfully.
Assuntos
Procedimentos Ortopédicos/métodos , Planejamento de Assistência ao Paciente , Parafusos Pediculares , Cuidados Pré-Operatórios/métodos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Humanos , Tomografia Computadorizada por Raios XRESUMO
Solar cells containing upconversion nanoparticles (UCNPs) used as a power source in biomedical nanosystems have attracted great interest. However, such solar cells further need to be developed because their substrate materials should be biocompatible, flexible and highly luminescent. Here, we report that freestanding silk fibroin (SF) films containing a mesh of silver nanowires (AgNWs) and ß-NaYF4:Yb,Er nanocrystals with metal-enhanced fluorescence behavior can be fabricated. The freestanding composite films exhibit properties such as good optical transparency, conductivity and flexibility. Furthermore, they show significantly enhanced upconversion fluorescence due to surface plasmon polaritons (SPPs) of AgNWs compared to the SF-UCNP films without AgNWs. The freestanding composite films with metal-enhanced fluorescence behavior show great promise for future applications in self-powered nanodevices such as cardiac pacemakers, biosensors and nanorobots.
RESUMO
Tumor-infiltrating lymphocytes (TILs) that test positive for forkhead box P3 (FOXP3) and elevated preoperative serum albumin levels have been positively associated with survival in colorectal cancer (CRC). This study aimed to investigate correlations among FOXP3+ TILs, preoperative serum albumin, overall survival, and other clinicopathological features of CRC patients. Surgical specimens from 340 stage II-III CRC patients were stained immunohistochemically for the presence of FOXP3+ TILs. Serum albumin levels were determined using an automatic biochemistry analyzer. Associations between various clinicopathological features and patient survival were analyzed via a Cox proportional hazards regression model. The correlation between FOXP3+ TILs and preoperative serum albumin was assessed using Pearson's correlation analysis. Survival curves were constructed by the Kaplan-Meier method. A high FOXP3+ TIL density (>15/five high-power fields), elevated preoperative serum albumin (≥35 g/L), and proximal colon carcinoma were significantly associated with better survival, and high FOXP3+ TIL number and elevated preoperative serum albumin were independent predictors of better survival. The correlation between the number of FOXP3+ TILs and preoperative serum albumin level was significant but neither of these correlated with gender, age, tumor size, tumor differentiation, mucinous tumor, T4 stage, postoperative chemotherapy, or tumor location. Our findings suggest that increased FOXP3+ TILs and high preoperative serum albumin levels are independent prognostic markers for improved survival in CRC patients. Furthermore, the number of FOXP3+ TILs correlates with preoperative serum albumin levels in these patients.
Assuntos
Neoplasias Colorretais/genética , Fatores de Transcrição Forkhead/biossíntese , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Albumina SéricaRESUMO
The cytosolic conversion of therapeutically relevant nucleosides into bioactive triphosphates is often hampered by the inefficiency of the first kinase-mediated step. Nucleoside monophosphate prodrugs can be used to bypass this limitation. Herein we describe a novel cyclic-disulfide class of nucleoside monophosphate prodrugs with a cytosol-specific, reductive release trigger. The key event, a charge-dissipating reduction-triggered cyclodeesterification leads to robust cytosolic production of the cyclic 3',5'-monophosphate for downstream enzymatic processing. The antiviral competence of the platform was demonstrated with an O-benzyl-1,2-dithiane-4,5-diol ester of 2'-C-methyluridine-3',5'-phosphate. Both in vitro and in vivo comparison with the clinically efficacious ProTide prodrug of 2'-deoxy-2'-α-fluoro-ß-C-methyluridine is provided. The cytosolic specificity of the release allows for a wide range of potential applications, from tissue-targeted drug delivery to intracellular imaging.
Assuntos
Citosol/química , Dissulfetos/química , Sistemas de Liberação de Medicamentos , Pró-Fármacos/química , Conformação MolecularRESUMO
Bismuth telluride-based materials have been widely used in commercial thermoelectric applications due to their excellent thermoelectric performance in the near-room-temperature range, yet further improvement of their thermoelectric properties is still necessary. Moreover, the narrow band gap of these materials results in a bipolar effect at elevated temperatures, which causes severe degradation of the thermoelectric performance. In this work, the commercial Bi0.4Sb1.6Te3 was alloyed with AgSbTe2 by using high-energy ball milling method combined with spark plasma sintering. It was found that ball milling can effectively reduce the lattice thermal conductivity of the samples. The alloying of AgSbTe2 leads to a gradual increase in hole carrier concentration, resulting in an enhanced electrical conductivity and optimized power factor. Additionally, the bipolar effect is also weakened due to the increased hole carrier concentration. Furthermore, the substitution of Ag in the Bi/Sb sublattice causes further reduction in the lattice thermal conductivity. Ultimately, the sample alloyed with 0.15 wt % AgSbTe2 demonstrates its best thermoelectric performance with a maximum zT of 1.35 at 393 K, showing a 20.5% improvement compared to the commercial sample. Besides, its average zT reaches a high value of 1.25 between 303 and 483 K, with a 27.6% improvement compared to that of the commercial sample.