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With the increasing demand for energy and the climate challenges caused by the consumption of traditional fuels, there is an urgent need to accelerate the adoption of green and sustainable energy conversion and storage technologies. The integration of flexible thermoelectrics with other various energy conversion technologies plays a crucial role, enabling the conversion of multiple forms of energy such as temperature differentials, solar energy, mechanical force, and humidity into electricity. The development of these technologies lays the foundation for sustainable power solutions and promotes research progress in energy conversion. Given the complexity and rapid development of this field, this review provides a detailed overview of the progress of multifunctional integrated energy conversion and storage technologies based on thermoelectric conversion. The focus is on improving material performance, optimizing the design of integrated device structures, and achieving device flexibility to expand their application scenarios, particularly the integration and multi-functionalization of wearable energy conversion technologies. Additionally, we discuss the current development bottlenecks and future directions to facilitate the continuous advancement of this field.
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The coupled relationship between carrier and phonon scattering severely limits the thermoelectric performance of n-type GeTe materials. Here, we provide an efficient strategy to enlarge grains and induce vacancy clusters for decoupling carrier-phonon scattering through the annealing optimization of n-type GeTe-based materials. Specifically, boundary migration is used to enlarge grains by optimizing the annealing time, while vacancy clusters are induced through the aggregation of Ge vacancies during annealing. Such enlarged grains can weaken carrier scattering, while vacancy clusters can strengthen phonon scattering, leading to decoupled carrier-phonon scattering. As a result, a ratio between carrier mobility and lattice thermal conductivity of â¼492.8 cm3 V-1 s-1 W-1 K and a peak ZT of â¼0.4 at 473 K are achieved in Ge0.67Pb0.13Bi0.2Te. This work reveals the critical roles of enlarged grains and induced vacancy clusters in decoupling carrier-phonon scattering and demonstrates the viability of fabricating high-performance n-type GeTe materials via annealing optimization.
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Chiral mesoporous silica (mSiO2) nanomaterials have gained significant attention during the past two decades. Most of them show a topologically characteristic helix; however, little attention has been paid to the molecular-scale chirality of mSiO2 frameworks. Herein, we report a chiral amide-gel-directed synthesis strategy for the fabrication of chiral mSiO2 nanospheres with molecular-scale-like chirality in the silicate skeletons. The functionalization of micelles with the chiral amide gels via electrostatic interactions realizes the growth of molecular configuration chiral silica sols. Subsequent modular self-assembly results in the formation of dendritic large mesoporous silica nanospheres with molecular chirality of the silica frameworks. As a result, the resultant chiral mSiO2 nanospheres show abundant large mesopores (â¼10.1 nm), high pore volumes (â¼1.8 cm3·g-1), high surface areas (â¼525 m2·g-1), and evident CD activity. The successful transfer of the chirality from the chiral amide gels to composited micelles and further to asymmetric silica polymeric frameworks based on modular self-assembly leads to the presence of molecular chirality in the final products. The chiral mSiO2 frameworks display a good chiral stability after a high-temperature calcination (even up to 1000 °C). The chiral mSiO2 can impart a notable decline in ß-amyloid protein (Aß42) aggregation formation up to 79%, leading to significant mitigation of Aß42-induced cytotoxicity on the human neuroblastoma line SH-ST5Y cells in vitro. This finding opens a new avenue to construct the molecular chirality configuration in nanomaterials for optical and biomedical applications.
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Enfermedad de Alzheimer , Nanosferas , Humanos , Nanosferas/química , Péptidos beta-Amiloides , Dióxido de Silicio/química , Micelas , Geles , AmidasRESUMEN
In this work, a LaB6 -alloying strategy is reported to effectively boost the figure-of-merit (ZT) of Ge0.92 Bi0.08 Te-based alloys up to ≈2.2 at 723 K, attributed to a synergy of La-dopant induced band structuring and structural manipulation. Density-function-theory calculations reveal that La dopant enlarges the bandgap and converges the energy offset between the sub-valence bands in cubic-structured GeTe, leading to a significantly increased effective mass, which gives rise to a high Seebeck coefficient of ≈263 µV K-1 and in turn a superior power factor of ≈43 µW cm-1 K-2 at 723 K. Besides, comprehensive electron microscopy characterizations reveal that the multi-scale phonon scattering centers, including a high density of planar defects, Boron nanoparticles in tandem with enhanced boundaries, dispersive Ge nanoprecipitates in the matrix, and massive point defects, contribute to a low lattice thermal conductivity of ≈0.67 W m-1 K-1 at 723 K. Furthermore, a high microhardness of ≈194 Hv is witnessed in the as-designed Ge0.92 Bi0.08 Te(LaB6 )0.04 alloy, derived from the multi-defect-induced strengthening. This work provides a strategy for developing high-performance and mechanical robust middle-temperature thermoelectric materials for practical thermoelectric applications.
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The long-standing popularity of thermoelectric materials has contributed to the creation of various thermoelectric devices and stimulated the development of strategies to improve their thermoelectric performance. In this review, we aim to comprehensively summarize the state-of-the-art strategies for the realization of high-performance thermoelectric materials and devices by establishing the links between synthesis, structural characteristics, properties, underlying chemistry and physics, including structural design (point defects, dislocations, interfaces, inclusions, and pores), multidimensional design (quantum dots/wires, nanoparticles, nanowires, nano- or microbelts, few-layered nanosheets, nano- or microplates, thin films, single crystals, and polycrystalline bulks), and advanced device design (thermoelectric modules, miniature generators and coolers, and flexible thermoelectric generators). The outline of each strategy starts with a concise presentation of their fundamentals and carefully selected examples. In the end, we point out the controversies, challenges, and outlooks toward the future development of thermoelectric materials and devices. Overall, this review will serve to help materials scientists, chemists, and physicists, particularly students and young researchers, in selecting suitable strategies for the improvement of thermoelectrics and potentially other relevant energy conversion technologies.
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BACKGROUND: Mechanical obstruction is the most common cause of shunt failure for hydrocephalic patients. However, the diagnosis is extremely challenging and often requires invasive testing methods. Thus, a simple and non-invasive technique is in urgent need to predict the intracranial pressure (ICP) of hydrocephalic patients during their post-surgical follow-up, which could help neurosurgeons to determine the conditions of the shunt system. MATERIALS AND METHODS: Two groups of patients were enrolled in the current study. In group I, patients were enrolled as they were diagnosed with high ICP hydrocephalus and received shunt surgery. The shunt valve pressures were taken for their post-surgical ICP. Meanwhile, the participants of group II exhibited abnormally increased lumbar puncture opening pressure (LPOP; from 180 to 400 mmH2O). Both the ICP and LPOP were used to match with their corresponding tympanic membrane temperature (TMT). RESULTS: When patients' ICP were in the normal range (group I, from 50 to 180 mmH2O), the TMT correlated with ICP in a linear regression model (R2 = 0.59, p < 0.001). Interestingly, when patients exhibited above-normal ICP (LPOP was from 180 to 400 mmH2O), their TMT fit well with the ICP in a third-order polynomial regression (R2 = 0.88). When the ICP was 287.98 mmH2O, the TMT approached the vertex, which was 38.54 °C. Based on this TMT-ICP algorithm, we invented a non-invasive ICP monitor system. Interestingly, a tight linear correlation was detected between the ICP data drawn from the non-invasive device and Codman ICP monitoring system (R2 = 0.93, p < 0.01). CONCLUSIONS: We believe the TMT-ICP algorithm (the Y-Jiang model) could be used for preliminary prediction of shunt malfunction as well as monitoring ICP changes.
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Hidrocefalia , Presión Intracraneal , Humanos , Invenciones , Hidrocefalia/diagnóstico , Hidrocefalia/cirugía , Monitoreo Fisiológico , Derivaciones del Líquido CefalorraquídeoRESUMEN
Mn alloying in thermoelectrics is a long-standing strategy for enhancing their figure-of-merit through optimizing electronic transport properties by band convergence, valley perturbation, or spin-orbital coupling. By contrast, mechanisms by which Mn contributes to suppressing thermal transports, namely thermal conductivity, is still ambiguous. A few precedent studies indicate that Mn introduces a series of hierarchical defects from the nano- to meso-scale, leading to effective phonon scattering scoping a wide frequency spectrum. Due to insufficient insights at the atomic level, the theory remains as phenomenological and cannot be used to quantitatively predict the thermal conductivity of Mn-alloyed thermoelectrics. Herein, by choosing the SnTe as a case study, aberration-corrected transmission electron microscopy (TEM)/scanning transmission electron microscopy (STEM) to characterize the lattice complexity of Sn1.02- x Mnx Te is employed. Mn as a "dynamic" dopant that plays an important role in SnTe with respect to different alloying levels or post treatments is revealed. The results indicate that Mn precipitates at x = 0.08 prior to reaching solubility (≈10 mol%), and then splits into MnSn substitution and γ-MnTe hetero-phases via mechanical alloying. Understanding such unique crystallography evolution, combined with a modified Debye-Callaway model, is critical in explaining the decreased thermal conductivity of Sn1.02- x Mnx Te with rational phonon scattering pathways, which should be applicable for other thermoelectric systems.
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BACKGROUND: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.
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Codón sin Sentido/genética , Hipertrigliceridemia/complicaciones , Lipoproteína Lipasa/genética , Pancreatitis/etiología , Pancreatitis/genética , Adulto , Heparina/farmacología , Heterocigoto , Humanos , Hipertrigliceridemia/sangre , Masculino , Pancreatitis/sangre , Pancreatitis/diagnóstico por imagen , Triglicéridos/sangreRESUMEN
In recent years, transplantation of mesenchymal stem cells (MSCs) has attracted much attention as a potential cell-based therapy for acute liver failure (ALF). As an inducible enzyme, heme oxygenase 1 (HO-1) has been reported to have cytoprotective, anti-apoptotic and immunoregulatory effects. Autophagy, a conserved catabolic process in cells, may be an important pathway for MSCs to treat ALF. In this study, we aimed to explore whether MSCs treat ALF by regulating autophagy and whether HO-1 was involved in the same pathway. Bone marrow-derived MSCs were isolated from Sprague-Dawley rats and cultured according to an established protocol. Co-culture systems of MSCs and hepatocytes were used to assess autophagy in the treatment of ALF. Meanwhile, MSCs were transplanted into rats with d-galactosamine (Gal)-induced ALF. Autophagy inhibitor (3-methyladenine, 3-MA), HO-1 inhibitor (zinc protoporphyrin, ZnPP) and PI3K specific inhibitor (LY294002) were employed in the study. Blood samples and liver tissues were collected before euthanasia. Survival rate, liver function, inflammatory factors, histology, Ki67 and TUNEL staining were determined. MSCs transplantation alleviated ALF both in vivo and in vitro. Autophagy and autophagy-related proteins were significantly up-regulated during MSCs treatment. 3-MA attenuated the therapeutic effect of MSCs. Administration of LY294002 before ALF induction inhibited hepatocyte autophagy. During the MSCs treatment, the HO-1 expression was increased, while inhibiting HO-1 attenuated the therapeutic effect of MSCs as well as hepatocyte autophagy. These findings suggested MSCs could alleviate ALF by increasing the HO-1 expression, which played an important role in activating autophagy through PI3K/AKT signaling pathway.
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Autofagia , Hemo-Oxigenasa 1/metabolismo , Fallo Hepático Agudo/enzimología , Fallo Hepático Agudo/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Animales , Autofagosomas/metabolismo , Autofagosomas/ultraestructura , Hepatocitos/patología , Hepatocitos/ultraestructura , Inflamación/patología , Hígado/lesiones , Hígado/patología , Fallo Hepático Agudo/patología , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Regulación hacia ArribaRESUMEN
BACKGROUND: Hypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG. METHODS: A Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes. RESULTS: The patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene. CONCLUSIONS: This is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.
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Codón sin Sentido , Hipertrigliceridemia/complicaciones , Proteínas de la Membrana/genética , Obesidad Mórbida/genética , Pancreatitis/genética , Fumar/genética , Adulto , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Hipertrigliceridemia/genética , Estilo de Vida , Masculino , Pancreatitis/etiologíaRESUMEN
As yet, there was no effective pharmacological therapy approved for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to evaluate the therapeutic potential of puerarin against NAFLD and explored the underlying mechanisms. C57BL/6J mice were fed with a high-fat high-sucrose (HFHS) diet with or without puerarin coadministration intragastrically. The levels of hepatocellular injury, steatosis, fibrosis, and mitochondrial and metabolism alteration were detected. First, puerarin ameliorated histopathologic abnormalities due to HFHS. We observed a marked increase in hepatic lipid content, inflammation, and fibrosis level, which were attenuated by puerarin. Possible mechanisms were related to puerarin-mediated activation of PI3K/AKT pathway and further improvement in fatty acid metabolism. Puerarin restored the NAD+ content and beneficially affected the hepatic mitochondrial function, which attenuated HFHS-induced steatosis and metabolic disturbances. Finally, hepatic PARP-1 was activated due to excessive fat intake. Puerarin attenuated the PARP-1 expression in HFHS-fed mice, and PJ34, the PARP inhibitor, could mimic these protections of puerarin. However, pharmacological inhibition of PI3K disabled the protection of puerarin or PJ34 toward NAD+ refilling and mitochondrial homeostasis. In conclusion, our findings indicated that puerarin could be a promising and practical therapeutic strategy in NAFLD through modulating PARP-1/PI3K/AKT signaling pathway and further facilitating mitochondrial function.
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Dieta Alta en Grasa/efectos adversos , Isoflavonas/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sacarosa/efectos adversos , Vasodilatadores/uso terapéutico , Animales , Humanos , Isoflavonas/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Vasodilatadores/farmacologíaRESUMEN
OBJECTIVE: Delayed neurological deficit was often observed in patients underwent craniectomy, which could be improved by cranioplasty. Little is known about hemodynamic improvement before and after cranioplasty. METHODS: Cerebral blood perfusion, tympanic membrane temperature (TMT), neuropsychological and cognitive function were assessed in eleven craniectomy patients before and after cranioplasty. RESULTS: Before cranioplasty, the cerebral blood volume (CBV) on the decompressed side was significantly lower than that of the contralateral side. The cranioplasty led to instant improvement (7 days after cranioplasty) of cerebral perfusion at the cranioplasty side in the frontal lobe, parietal lobe, temporal lobe, mesencephalon, basal ganglia and thalamus, but not the occipital lobe and epencephalon. Interestingly, CBV of the thalamus and basal ganglia gradually decreased to pre-surgical status 6 months later while the frontal lobe, parietal lobe, temporal lobe, mesencephalon remained well perfused. Meanwhile, the TMT changes acquired positive correlation with the perfusion of temporal lobe and mesencephalon as well as the GCS and MMSE score. CONCLUSION: The cranioplasty remarkably improves neurological and cognitive function by ameliorating cerebral perfusion in certain regions. The TMT could be used as a non-invasive method to monitor the cerebral perfusion improvement after the cranioplasty.
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Temperatura Corporal/fisiología , Circulación Cerebrovascular/fisiología , Craniectomía Descompresiva/métodos , Membrana Timpánica/cirugía , Lesiones Encefálicas/cirugía , Femenino , Estudios de Seguimiento , Lateralidad Funcional , Escala de Consecuencias de Glasgow , Humanos , Masculino , Pruebas Neuropsicológicas , Resultado del Tratamiento , Membrana Timpánica/fisiologíaRESUMEN
The chronic presence of viral Ags can induce T cell exhaustion, which is characterized by upregulation of coinhibitory receptors and loss of T cell function. We studied whether a similar phenomenon occurs after liver transplantation (LTx), when there is continuous exposure to alloantigen. Expression of coinhibitory receptors on circulating CD4(+) and CD8(+) T cells was analyzed longitudinally in 19 patients until 6 mo after LTx and cross-sectionally in 38 patients late (1-12 y) after LTx. Expression of the coinhibitory receptors CD160 and CD244 on circulating CD8(+) T cells was already higher 6 mo after LTx compared with pre-LTx, and the elevated expression was sustained late after LTx, with CD244 showing the more prominent increase. The strongest upregulation of CD244 on circulating CD8(+) T cells was observed in patients who experienced CMV infection after LTx. CMV infection also was associated with reduced CD8(+) T cell proliferation and cytotoxic degranulation in response to alloantigen late after LTx. Purified CD244(+)CD8(+) T cells from LTx patients showed lower proliferative responses to alloantigen, as well as to polyclonal stimulation, than did their CD244(-) counterparts. In addition, the CD244(+)CD8(+) T cell population contained the majority of CMV peptide-loaded MHC class I tetramer-binding cells. In conclusion, CMV infection after LTx, rather than persistence of alloantigen, induces the accumulation of dysfunctional CD244(+)CD8(+) T cells in the circulation that persist long-term, resulting in reduced frequencies of circulating alloreactive CD8(+) T cells. These results suggest that CMV infection restrains CD8(+) T cell alloresponses after LTx.
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Antígenos CD/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Expresión Génica , Isoantígenos/inmunología , Trasplante de Hígado , Receptores Inmunológicos/genética , Adulto , Estudios Transversales , Femenino , Proteínas Ligadas a GPI/genética , Humanos , Trasplante de Hígado/efectos adversos , Estudios Longitudinales , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
BACKGROUND & AIMS: Co-inhibitory receptor-ligand interactions fine-tune immune responses by negatively regulating T cell functions. Our aim is to examine the involvement of co-inhibitory receptor-ligand pair PD-1/PD-L1 in regulating rejection after liver transplantation (LT) in humans. METHODS: PD-L1/PD-1 expression in liver allograft was determined by immunohistochemistry or flow cytometry, and the effect of blockade was studied using graft-infiltrating T cells ex vivo. Five single nucleotide polymorphisms within PD-1 and PD-L1 genes were genotyped in 528 LT recipients and 410 donors, and associations with both early (⩽6months) and late (>6months) acute rejection were analyzed using Cox proportional-hazards regression model. The effect of PD-L1 rs4143815 on PD-L1 expression was analyzed using donor hepatic leukocytes. RESULTS: PD-L1 was expressed by hepatocytes, cholangiocytes and along the sinusoids in post-transplant liver allografts, and PD-1 was abundantly expressed on allograft-infiltrating T cells. PD-L1 blockade enhanced allogeneic proliferative responses of graft-infiltrating T cells. In the genetic association analysis, donor PD-L1 rs4143815 (CC/CG vs. GG; HR=0.230; p=0.002) and recipient PD-1 rs11568821 (AA/AG vs. GG; HR=3.739; p=0.004) were associated with acute rejection late after LT in multivariate analysis. Recipients carrying the PD-1 rs11568821 A allele who were transplanted with liver grafts of PD-L1 rs4143815 GG homozygous donors showed the highest risk for late acute rejection. PD-L1 rs4143815 is associated with differential PD-L1 expression on donor hepatic dendritic cells upon IFN-γ stimulation. CONCLUSION: Our data suggest that interplay between donor PD-L1 and recipient PD-1 counter-regulates rejection activity against liver grafts in humans.
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Antígeno B7-H1/fisiología , Rechazo de Injerto/etiología , Trasplante de Hígado/efectos adversos , Receptor de Muerte Celular Programada 1/fisiología , Adolescente , Adulto , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Femenino , Genotipo , Humanos , Interferón gamma/farmacología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Linfocitos T/inmunología , Adulto JovenRESUMEN
BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) has been regarded as a potential treatment for acute liver failure (ALF), but the optimal route was unknown. The present study aimed to explore the most effective MSCs transplantation route in a swine ALF model. METHODS: The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection (InP group), hepatic intra-arterial injection (AH group), peripheral intravenous injection (PV group) and intrahepatic injection (IH group). The living conditions and survival time were recorded. Blood samples before and after MSCs transplantation were collected for the analysis of hepatic function. The histology of liver injury was interpreted and scored in terminal samples. Hepatic apoptosis was detected by TUNEL assay. Apoptosis and proliferation related protein expressions including cleaved caspase-3, survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) were analyzed by Western blotting. RESULTS: The average survival time of each group was 10.7+/-1.6 days (InP), 6.0+/-0.9 days (AH), 4.7+/-1.4 days (PV), 4.3+/-0.8 days (IH), respectively, when compared with the average survival time of 3.8+/-0.8 days in the D-Gal group. The survival rates between the InP group and D-Gal group revealed a statistically significant difference (P<0.01). Pathological and biochemical analysis showed that liver damage was the worst in the D-Gal group, while less injury in the InP group. Histopathological scores revealed a significant decrease in the InP group (3.17+/-1.04, P<0.01) and AH group (8.17+/-0.76, P<0.05) as compared with that in the D-Gal group (11.50+/-1.32). The apoptosis rate in the InP group (25.0%+/-3.4%, P<0.01) and AH group (40.5%+/-1.0%, P<0.05) was lower than that in the D-Gal group (70.6%+/-8.5%). The expression of active caspase-3 was inhibited, while the expression of survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) was elevated in the InP group. CONCLUSIONS: Intraportal injection was superior to other pathways for MSC transplantation. Intraportal MSC transplantation could improve liver function, inhibit apoptosis and prolong the survival time of swine with ALF. The transplanted MSCs may participate in liver regeneration via promoting cell proliferation and suppressing apoptosis during the initial stage of ALF.
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Apoptosis , Proliferación Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/cirugía , Fallo Hepático Agudo/prevención & control , Regeneración Hepática , Hígado/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Western Blotting , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Galactosamina , Hígado/metabolismo , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Pruebas de Función Hepática , Fenotipo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Porcinos , Porcinos Enanos , Factores de TiempoRESUMEN
BACKGROUND: Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). METHODS: Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. RESULTS: 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. CONCLUSIONS: FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis.
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Biopsia , Próstata/patología , Neoplasias de la Próstata/diagnóstico , ARN Largo no Codificante/orina , Anciano , Biomarcadores de Tumor/orina , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/orinaRESUMEN
A method of ionic liquid salt aqueous two-phase extraction coupled with high-performance liquid chromatography has been developed for the analysis of seven rare ginsenosides including Rg6 , F4 , 20(S)-Rg3 , 20(R)-Rg3 , Rk3 , Rk1 , and Rg5 in Xue-Sai-Tong injection. The injection was mixed with ionic liquid 1-butyl-3-methylimidazolium bromide aqueous solution, and a mixture was obtained. With the addition of sodium dodecyl sulfate and dipotassium phosphate into the mixture, the aqueous two-phase mixture was formed after ultrasonic treatment and centrifuged. Rare ginsenosides were extracted into the upper phase. To obtain a high extraction factors, various influences were considered systematically, such as the volume of ionic liquid, the category and amount of salts, the amount of sodium dodecyl sulfate, the pH value of system, and the time of ultrasonic treatment. Under the optimal condition, rare ginsenosides in Xue-Sai-Tong injection were enriched and detected, the recoveries of seven rare ginsenosides ranged from 90.05 to 112.55%, while relative standard deviations were lower than 2.50%. The developed method was reliable, rapid and sensitive for the determination of seven rare ginsenosides in the injections.
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Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/análisis , Ginsenósidos/análisis , Extractos Vegetales/análisis , Extracción en Fase Sólida/métodos , Cloruros/química , Ginsenósidos/química , Concentración de Iones de Hidrógeno , Imidazoles/química , Líquidos Iónicos , Límite de Detección , Modelos Lineales , Extracción Líquido-Líquido , Panax notoginseng , Reproducibilidad de los Resultados , Saponinas/análisis , Saponinas/química , Dodecil Sulfato de Sodio , Espectrofotometría Ultravioleta , UltrasonidoRESUMEN
BACKGROUND: A novel hybrid bioartificial liver (HBAL) was constructed using an anionic resin adsorption column and a multi-layer flat-plate bioreactor containing porcine hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs). This study aimed to evaluate the microbiological safety of the HBAL by detecting the transmission of porcine endogenous retroviruses (PERVs) into canines with acute liver failure (ALF) undergoing HBAL. METHODS: Eight dogs with ALF received a 6-hour HBAL treatment on the first day after the modeling by D-galactosamine administration. The plasma in the HBAL and the whole blood in the dogs were collected for PERV detection at regular intervals until one year later when the dogs were sacrificed to retrieve the tissues of several organs for immunohistochemistry and Western blotting for the investigation of PERV capsid protein gag p30 in the tissue. Furthermore, HEK293 cells were incubated to determine the in vitro infectivity. RESULTS: PERV RNA and reverse transcriptase activity were observed in the plasma of circuit 3, suggesting that PERV particles released in circuit 3. No positive PERV RNA and reverse transcriptase activity were detected in other plasma. No HEK293 cells were infected by the plasma in vitro. In addition, all PERV-related analyses in peripheral blood mononuclear cells and tissues were negative. CONCLUSION: No transmission of PERVs into ALF canines suggested a reliable microbiological safety of HBAL based on porcine hepatocytes.
Asunto(s)
Proteínas de la Cápside/metabolismo , Retrovirus Endógenos/aislamiento & purificación , Hepatocitos/virología , Fallo Hepático Agudo/terapia , Hígado Artificial/virología , ARN Viral/análisis , Proteínas de los Retroviridae/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Animales , Modelos Animales de Enfermedad , Perros , Células HEK293/virología , Humanos , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/metabolismo , ADN Polimerasa Dirigida por ARN/análisis , Porcinos , Virosis/transmisiónRESUMEN
Increasing numbers of studies have shown that tumor cells prefer fermentative glycolysis over oxidative phosphorylation to provide a vast amount of energy for fast proliferation even under oxygen-sufficient conditions. This metabolic alteration not only favors tumor cell progression and metastasis but also increases lactate accumulation in solid tumors. In addition to serving as a byproduct of glycolytic tumor cells, lactate also plays a central role in the construction of acidic and immunosuppressive tumor microenvironment, resulting in therapeutic tolerance. Recently, targeted drug delivery and inherent therapeutic properties of nanomaterials have attracted great attention, and research on modulating lactate metabolism based on nanomaterials to enhance antitumor therapy has exploded. In this review, the advanced tumor therapy strategies based on nanomaterials that interfere with lactate metabolism are discussed, including inhibiting lactate anabolism, promoting lactate catabolism, and disrupting the "lactate shuttle". Furthermore, recent advances in combining lactate metabolism modulation with other therapies, including chemotherapy, immunotherapy, photothermal therapy, and reactive oxygen species-related therapies, etc., which have achieved cooperatively enhanced therapeutic outcomes, are summarized. Finally, foreseeable challenges and prospective developments are also reviewed for the future development of this field.
Asunto(s)
Nanoestructuras , Neoplasias , Humanos , Estudios Prospectivos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Glucólisis , Lactatos/uso terapéutico , Microambiente TumoralRESUMEN
Thermoelectric technology, which enables a direct and pollution-free conversion of heat into electricity, provides a promising path to address the current global energy crisis. Among the broad range of thermoelectric materials, silver copper chalcogenides (AgCuQ, Q = S, Se, Te) have garnered significant attention in thermoelectric community in light of inherently ultralow lattice thermal conductivity, controllable electronic transport properties, excellent thermoelectric performance across various temperature ranges, and a degree of ductility. This review epitomizes the recent progress in AgCuQ-based thermoelectric materials, from the optimization of thermoelectric performance to the rational design of devices, encompassing the fundamental understanding of crystal structures, electronic band structures, mechanical properties, and quasi-liquid behaviors. The correlation between chemical composition, mechanical properties, and thermoelectric performance in this material system is also highlighted. Finally, several key issues and prospects are proposed for further optimizing AgCuQ-based thermoelectric materials.