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1.
PLoS One ; 19(9): e0310889, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39321199

RESUMO

B-cell lymphoma, clinically, comprises a heterogeneous group of malignancies that encompass various subtypes. CD20 is an optimal target for therapeutic antibodies in B-cell lymphoma immunotherapy since approximately 90% of B-cell malignancies typically exhibit CD20 expression on their surface, while its presence is limited in normal tissues. In this study, we have developed a series of novel non-IgG-like T cell-dependent bispecific antibodies by constructing Fab-FabCH3, referred to as Tandem Antigen-binding Fragment 002 (TFAB002), which specifically target CD20 for the treatment of malignant B-cell lymphoma. TFAB002s display strong binding affinity with CD20 and moderate binding affinity with CD3, thereby triggering target-specific T-cell activation, cytokine release, and tumor cell lysis in vitro. Furthermore, TFAB002s exhibit potent cytotoxicity against B-cell malignancies that express varying levels of CD20. Besides, the TFAB002s show potent pharmacodynamic activity in vivo in the WIL2-S cells CDX mouse model. Collectively, these results underscore the potential of TFAB002s as a highly promising therapeutic approach for selectively depleting CD20-positive B cells, thereby warranting further clinical evaluation as a viable treatment option for CD20-expressing B-cell malignancies.


Assuntos
Anticorpos Biespecíficos , Antígenos CD20 , Fragmentos Fab das Imunoglobulinas , Linfoma de Células B , Linfócitos T , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Antígenos CD20/imunologia , Linfoma de Células B/imunologia , Linfoma de Células B/terapia , Linfoma de Células B/tratamento farmacológico , Camundongos , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Linfócitos T/imunologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Ativação Linfocitária/imunologia , Ativação Linfocitária/efeitos dos fármacos , Feminino
2.
Int J Environ Health Res ; 34(2): 1156-1167, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37158781

RESUMO

A retrospective analysis of birth data hospital-based obtained from 14 monitoring areas in the Huaihe River Basin from 2009 to 2019 was conducted. Trend in the total prevalence of birth defects (BDs) and subgroups were analyzed using the Joinpoint Regression model. The incidence of BDs increased gradually from 118.87 per 10,000 in 2009 to 241.18 per 10,000 in 2019 (AAPC = 5.91, P < 0.001). Congenital heart diseases were the most common subtype of BDs. The proportion of maternal age younger than 25 decreased but the age 25-40 years increased significantly (AAPC<20=-5.58; AAPC20-24=-6.38; AAPC25-29 = 5.15; AAPC30-35 = 7.07; AAPC35-40 = 8.27; All P < 0.05). Compared with the one-child policy period, the risk of BDs was greater for groups among maternal age younger than 40 years during the partial and universal two-child policy period (P < 0.001). The incidence of BDs and the proportion of women with advanced maternal age in Huaihe River Basin is increasing. There was an interaction between changes in birth policy and the mother's age on the risk of BDs.


Assuntos
Políticas , Humanos , Feminino , Adulto , Estudos Transversais , Estudos Retrospectivos , Idade Materna , China/epidemiologia
3.
Sci Rep ; 13(1): 16447, 2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37777594

RESUMO

This study aimed to assess the accuracy of cortical bone trajectory (CBT) screws placement guided by a spinous process clamp (SPC) guide. A total of 32 patients who received single-level midline lumbar fusion (MIDLF) surgery between June 2019 and January 2020 were retrospectively analyzed and divided into free-hand (FH) and SPC-guided groups according to the surgical approach. In the FH group, CBT screws was implanted with the assistance of fluoroscopy, while in the SPC group, CBT screws was implanted using the SPC navigator hardwire. A total of 128 screws were assessed in this study, with higher rates of clinically acceptable screw placement (grades A and B) and grade A screws in the SPC group than in the FH guide group (92.2% vs. 79.7%, P = 0.042 and 54.7% vs. 35.9%, P = 0.033, respectively). Misplacement screws (grades C, D, and E) occurred more often in the FH group than in the SPC guide group (20.3% vs. 7.8%, P = 0.042). The incidence of proximal facet joint violation (FJV) was higher in the FH group than in the SPC group (15.6% vs. 3.1%, P = 0.030). The radiation dose and time in the SPC guide group were comparable to those in the FH group (P = 0.063 and P = 0.078). The average operative time was significantly longer in the SPC guide group than in the FH group (267.8 ± 45.5 min vs. 210.9 ± 44.5 min, P = 0.001). Other clinical parameters, such as the average bone mineral density (BMD), intraoperative blood loss, and postoperative hospital stay, were not significantly different. Oswestry disability index (ODI) and back pain visual analogue scale (VAS) scores were significantly improved in both groups compared with preoperatively. SPC guided screw placement was more accurate than the fluoroscopy-assisted FH technique for single-level MIDLF at L4/5. Patients undergoing SPC-guided screw placement can achieve similar clinical outcomes as the fluoroscopy-assisted FH technique.


Assuntos
Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Fusão Vertebral , Cirurgia Assistida por Computador , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Osso Cortical/diagnóstico por imagem , Osso Cortical/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos
4.
Phys Rev Lett ; 130(19): 193001, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37243630

RESUMO

Quantum liquid, in the form of a self-bound droplet, is stabilized by a subtle balance between the mean-field contribution and quantum fluctuations. While a liquid-gas transition is expected when such a balance is broken, it remains elusive whether liquid-gas critical points exist in the quantum regime. Here, we study the quantum criticality in a binary Bose mixture undergoing the liquid-gas transition. We show that, beyond a narrow stability window of the self-bound liquid, a liquid-gas coexistence persists, which eventually transits into a homogeneous mixture. Importantly, we identify two distinct critical points where the liquid-gas coexistence terminates. These critical points are characterized by rich critical behaviors in their vicinity, including divergent susceptibility, unique phonon-mode softening, and enhanced density correlations. The liquid-gas transition and the critical points can be readily explored in ultracold atoms confined to a box potential. Our work highlights the thermodynamic approach as a powerful tool in revealing the quantum liquid-gas criticality, and paves the way for further studies of critical phenomena in quantum liquids.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(2): 147-152, 2023 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-36854690

RESUMO

OBJECTIVES: To investigate the clinical characteristics and risk factors for early-onset necrotizing enterocolitis (NEC) in preterm infants with very/extremely low birth weight (VLBW/ELBW). METHODS: A retrospective analysis was performed on the medical data of 194 VLBW/ELBW preterm infants with NEC who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. These infants were divided into early-onset group (onset in the first two weeks of life; n=62) and late-onset group (onset two weeks after birth; n=132) based on their onset time. The two groups were compared in terms of perinatal conditions, clinical characteristics, laboratory examination results, and clinical outcomes. Sixty-two non-NEC infants with similar gestational age and birth weight who were hospitalized at the same period as these NEC preterm infants were selected as the control group. The risk factors for the development of early-onset NEC were identified using multivariate logistic regression analysis. RESULTS: Compared with the late-onset group, the early-onset group had significantly higher proportions of infants with 1-minute Apgar score ≤3, stage III NEC, surgical intervention, grade ≥3 intraventricular hemorrhage, apnea, and fever or hypothermia (P<0.05). The multivariate logistic regression analysis showed that feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, and hemodynamically significant patent ductus arteriosus were independent risk factors for the development of early-onset NEC in VLBW/ELBW preterm infants (P<0.05). CONCLUSIONS: VLBW/ELBW preterm infants with early-onset NEC have more severe conditions compared with those with late-onset NEC. Neonates with feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, or hemodynamically significant patent ductus arteriosus have a higher risk of early-onset NEC.


Assuntos
Permeabilidade do Canal Arterial , Enterocolite Necrosante , Doenças do Recém-Nascido , Doenças do Prematuro , Criança , Lactente , Feminino , Gravidez , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Enterocolite Necrosante/etiologia , Estudos Retrospectivos , Doenças do Prematuro/etiologia , Fatores de Risco
6.
Int J Med Robot ; 19(2): e2484, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36413096

RESUMO

BACKGROUND: The purpose of this study was to access the accuracy of cortical bone trajectory screw placement guided by spinous process clamp (SPC). METHODS: Eight formalin-treated cadaveric lumbar specimens with T12-S1 were used. A total of 96 screws were implanted in eight lumbar specimens. RESULTS: In the freehand (FH) group, clinically acceptable placement (grade A and B) was 40 screws (83.3%), meanwhile 44 screws (91.7%) in the SPC guide group (p = 0.217). The grade A screws in the SPC guide group were much more than that in the FH group (n = 40 vs. n = 31, p = 0.036). The misplacement screws (grade C, D, and E) and proximal facet joint violation (FJV) in the SPC group was comparable to the FH group. CONCLUSIONS: This cadaveric study demonstrate that implanting CBT screws guided by SPC guide was more accuracy and reduces severe deviations in important directions.


Assuntos
Procedimentos Ortopédicos , Parafusos Pediculares , Fusão Vertebral , Humanos , Vértebras Lombares/cirurgia , Osso Cortical/cirurgia , Cadáver
7.
BMC Surg ; 22(1): 384, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348354

RESUMO

BACKGROUND AND OBJECTIVE: The Cortical Bone Trajectory (CBT) technique provides an alternative method for fixation in the lumbar spine in patients with osteoporosis. An accuracy CBT screw placement could improve mechanical stability and reduce complication rates. PURPOSE: The purpose of this study is to explore the accuracy of cortical screw placement with the application of implanted spinous process clip (SPC) guide. METHODS AND MATERIALS: Four lumbar specimens with T12-S1 were used to access the accuracy of the cortical screw. The SPC-guided planning screws were compared to the actual inserted screws by superimposing the vertebrae and screws preoperative and postoperative CT scans. According to preoperative planning, the SPC guide was adjusted to the appropriate posture to allow the K-wire drilling along the planned trajectory. Pre and postoperative 3D-CT reconstructions was used to evaluate the screw accuracy according to Gertzbein and Robbins classification. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to examine SPC-guided agreements for CBT screw placement. RESULTS: A total of 48 screws were documented in the study. Clinically acceptable trajectory (grades A and B) was accessed in 100% of 48 screws in the planning screws group, and 93.8% of 48 screws in the inserted screws group (p = 0.242). The incidence of proximal facet joint violation (FJV) in the planning screws group (2.1%) was comparable to the inserted screws group (6.3%) (p = 0.617). The lateral angle and cranial angle of the planned screws (9.2 ± 1.8° and 22.8 ± 5.6°) were similar to inserted screws (9.1 ± 1.7° and 23.0 ± 5.1°, p = 0.662 and p = 0.760). Reliability evaluated by intraclass correlation coefficients and Bland-Altman showed good consistency in cranial angle and excellent results in lateral angle and distance of screw tip. CONCLUSIONS: Compared with preoperative planning screws and the actually inserted screws, the SPC guide could achieve reliable execution for cortical screw placement.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Reprodutibilidade dos Testes , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Cadáver
8.
Transpl Immunol ; 71: 101556, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35202801

RESUMO

The unclear mechanism that ischemia-reperfusion injury (IRI) contributes to the development of primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) remains a major issue in lung transplantation. Differentially expressed PGD-related genes and CLAD-related genes during IRI (IRI-PGD common genes and IRI-CLAD common genes) were identified using GEO datasets (GSE127003, GSE8021, GSE9102) and GeneCards datasets. Enrichment analysis and four network analyses, namely, protein-protein interaction, microRNA (miRNA)-gene, transcription factor (TF)-gene, and drug-gene networks, were then performed. Moreover, GSE161520 was analyzed to identify the differentially expressed core miRNAs during IRI in rats. Finally, Pearson correlation analysis and ROC analysis were performed. Eight IRI-PGD common genes (IL6, TNF, IL1A, IL1B, CSF3, CXCL8, SERPINE1, and PADI4) and 10 IRI-CLAD common genes (IL1A, ICAM1, CCL20, CCL2, IL1B, TNF, PADI4, CXCL8, GZMB, and IL6) were identified. Enrichment analysis showed that both IRI-PGD and IRI-CLAD common genes were significantly enriched in "AGE-RAGE signaling pathway in diabetic complication" and "IL-17 signaling pathway". Among the core miRNAs, miR-1-3p and miR-335 were differentially expressed in IRI rats. Among core TFs, CEBPB expression had a significant negative correlation with P/F ratio (r = -0.33, P = 0.021). In the reperfused lung allografts, the strongest positive correlation was exhibited between PADI4 expression and neutrophil proportion (r = 0.76, P < 0.001), and the strongest negative correlation was between PADI4 expression and M2 macrophage proportion (r = -0.74, P < 0.001). In lung allografts of PGD recipients, IL6 expression correlated with activated dendritic cells proportion (r = 0.86, P < 0.01), and IL1B expression correlated with the neutrophils proportion(r = 0.84, P < 0.01). In whole blood of CLAD recipients, GZMB expression correlated with activated CD4+ memory T cells proportion (r = 0.76, P < 0.001).Our study provides the novel insights into the molecular mechanisms by which IRI contributes to PGD and CLAD and potential targets for therapeutic intervention.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Pulmão , MicroRNAs , Disfunção Primária do Enxerto , Traumatismo por Reperfusão , Aloenxertos/metabolismo , Animais , Interleucina-6 , Pulmão/metabolismo , MicroRNAs/genética , Disfunção Primária do Enxerto/genética , Ratos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Transcriptoma
9.
Res Vet Sci ; 136: 416-421, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33812284

RESUMO

Reliability of canine plasma amino acid analysis depends on sample stability which can be influenced by pre-analytical handling techniques, storage temperature, storage time, and deproteinization status. Extrapolating data to dogs from research in other species is limited given discordant methodology and interspecies differences. The present study investigated the effects of deproteinization status (non-deproteinized or deproteinized) and storage temperature (at -20 °C or - 80 °C) on the concentration of 22 canine plasma amino acids during a 300-day storage period. Storage time had a significant effect (p < 0.05) of overall declining concentration of most amino acids. Compared to non-deproteinized samples, deproteinization contributed to overall higher concentrations of cyst(e)ine and glutamic acid, and consistently modified the effect of storage time and temperature on cyst(e)ine, glutamic acid, and glutamine. Compared to -20 °C, storage at -80 °C contributed to a higher concentration of cyst(e)ine and glutamic acid, and modified the effect of storage time on arginine, glutamic acid, glutamine, and tryptophan. Storage time had a consistent, significant effect on amino acid concentrations in canine plasma samples. Although sample deproteinization and low storage temperature modified the effect of storage time, these interactions were variable among analyzed amino acids. Therefore, timely sample analysis is recommended. If delayed sample analysis is inevitable, deproteinization should be performed prior to sample banking to preserve amino acid stability.


Assuntos
Aminoácidos/sangue , Preservação de Sangue/veterinária , Proteínas Sanguíneas , Animais , Proteínas Sanguíneas/química , Cães , Feminino , Masculino , Plasma/química , Reprodutibilidade dos Testes , Temperatura , Fatores de Tempo
10.
Sleep Breath ; 25(4): 1969-1976, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33619665

RESUMO

BACKGROUND: Sleep deprivation (SD) has become a serious concern worldwide. This study aimed to identify key modules and candidate hub genes correlated with diseases caused by SD, using co-expression analysis. METHODS: The weighted gene co-expression network analysis was performed to construct a co-expression network of hub genes correlated with SD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to search for signaling pathways. The protein-protein interaction network analysis of central genes was performed to recognize the interactions among central genes. Molecular Complex Detection, a plugin in Cytoscape, was used to discover the hub gene clusters involved in SD. RESULTS: A total of 564 genes in the yellow module were identified based on the results of topological overlap measure-based clustering. The yellow module showed a pivotal correlation with SD. Six hub gene clusters prominently associated with SD were identified. Heat shock protein family and circadian clock genes among them may be the hub genes involved in SD. CONCLUSIONS: These genes and pathways might become therapeutic targets with clinical usefulness in the future.


Assuntos
Perfilação da Expressão Gênica , Redes Reguladoras de Genes/genética , Transdução de Sinais/genética , Privação do Sono/genética , Humanos
11.
Am Heart J ; 234: 101-110, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33465369

RESUMO

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.


Assuntos
Angiografia Coronária/métodos , Doença das Coronárias/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Causas de Morte , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/etiologia , Revascularização Miocárdica , Estudos Prospectivos
12.
Phys Rev Lett ; 125(5): 055301, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32794831

RESUMO

For pseudospin-half bosons with interspin attraction and intraspin repulsion, the normal phase and Bose condensed phase can coexist at finite temperature. The homogeneous system is unstable against the spinodal decomposition within a medium density interval, and, consequently, a normal-superfluid phase separation takes place. The isothermal equation of state shows a characteristic plateau in the P-V (pressure-volume) diagram, which is reminiscent of a classical gas-liquid transition, although, unlike the latter, the coexistence lines never terminate at a critical point as temperature increases. In a harmonic trap, the phase separation can be revealed by the density profile of the atomic cloud, which exhibits a sudden jump across the phase boundary.

14.
Oncoimmunology ; 9(1): 1726168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117591

RESUMO

Oncolytic viruses represent a promising therapeutic modality, but they have yet to live up to their therapeutic potential. Safety and efficacy concerns impel us to identify least toxic oncolytic agents that would generate durable and multifaceted anti-tumor immune responses to disrupt the tumors. Here we describe a rational engineered oncolytic herpes virus (OVH) that is a selective killer for targeting tumors, has strong safety records, induces complete regression of tumors in multiple tumor models, and elicits potent antitumor immunity. By far, the potential of OVs in promoting the tumor antigen-specific humoral immune responses remains obscure. In this study, we found that effective treatment by OVH induced immunogenic cell death, which facilitates to elicit humoral immune responses. Depletion experiments revealed that B cells were required for maximal antitumor efficacy of oncolytic immunotherapy. Both serum transfer and antibody treatment experiments revealed that endogenous oncolysis-induced antigen-targeting therapeutic antibodies can lead to systemic tumor regression. Our data demonstrate that tumor-targeting immune modulatory properties confer oncolytic OVH virotherapy as potent immunotherapeutic cancer vaccines that can generate specific and efficacious antitumor humoral responses by eliciting endogenous tumor antigen-targeting therapeutic antibodies in situ, resulting in an efficacious and tumor-specific therapeutic effect.


Assuntos
Vacinas Anticâncer , Terapia Viral Oncolítica , Vírus Oncolíticos , Antígenos de Neoplasias , Imunoterapia , Vírus Oncolíticos/genética
15.
Cancer Immunol Res ; 8(5): 632-647, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32127389

RESUMO

Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II IFNs. To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage-associated molecular patterns, promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted in antitumor T-cell activity that led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSC), resulting in significantly higher percentages of CD155+ granulocytic-MDSCs (G-MDSC) and monocytic-MDSCs (M-MDSC) in tumors. In combination with TIGIT blockade, this virus enhanced tumor-specific immune responses in mice with implanted subcutaneous tumors or invasive tumors. These findings highlighted that intratumoral immunomodulation with an OV expressing aMPD-1 scFv could be an effective stand-alone strategy to treat cancers or drive maximal efficacy of a combination therapy with other immune checkpoint inhibitors.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Herpesvirus Humano 1/imunologia , Células Supressoras Mieloides/imunologia , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Receptores Imunológicos/antagonistas & inibidores , Anticorpos de Cadeia Única/farmacologia , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Imunomodulação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Nanoscale Res Lett ; 15(1): 46, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076846

RESUMO

We propose a new method for regulating valley pseudomagnetoresistance in ballistic graphene-based valley field-effect transistors by taking into account the Y-shaped Kekulé lattice distortion and electric barrier. The device involves valley injection and valley detection by ferromagnetic-strain source and drain. The valley manipulation in the channel is achieved via the Y-shaped Kekulé lattice distortion and electric barrier. The central mechanism of these devices lies on Y-shaped Kekulé lattice distortion in graphene can induce a valley precession, thus controlling the valley orientation of channel electrons and hence the current collected at the drain. We found that the tuning external bias voltage makes the valley pseudomagnetoresistance oscillate between positive and negative values and colossal tunneling valley pseudomagnetoresistance of over 30,000% can be achieved. Our results suggest that the synergy of valleytronics and digital logics may provide new paradigms for valleytronic-based information processing and reversible computing.

17.
Mol Nutr Food Res ; 64(3): e1901019, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31860939

RESUMO

SCOPE: Dietary advanced glycation products (dAGEs) have been reported to induce cognitive impairment while quercetin possesses potential neuroprotective effects. The aim is to explore whether dAGEs would induce similar cognitive impairment from both young and aged ICR mice, and the protective effects of quercetin. METHODS AND RESULTS: A total of 32 aged ICR mice (15-month-old) and 16 young ICR mice (3-month-old) are randomly assigned into the following six groups: Young mice control group, young mice fed with AGEs diet group, old mice control group, old mice fed with AGEs diet group, old mice with quercetin supplemented diet group, old mice fed with AGE diet supplemented with quercetin group. Dietary AGEs induced cognitive impairment only in aged, but not in young, ICR mice, while quercetin intervention is capable of reversing dAGEs-induced cognitive dysfunction. This may be since quercetin 1) increased miR-219, miR-15a, and miR-132 expression, inhibited p-ERK1/2, and tau phosphorylation; and 2) improved gut microbiota richness and diversity, inhibited phylum Tenericutes and Proteobacteria, and elevated butyric acid from cecum. CONCLUSION: Prolonged application of quercetin may be beneficial in the elderly, especially for those with high consumption of dAGEs.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Produtos Finais de Glicação Avançada/toxicidade , Quercetina/farmacologia , Fatores Etários , Peptídeos beta-Amiloides/metabolismo , Animais , Ceco/metabolismo , Envelhecimento Cognitivo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos ICR , MicroRNAs , Teste do Labirinto Aquático de Morris , Fármacos Neuroprotetores/farmacologia , RNA Ribossômico 16S , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
18.
Mol Ther Oncolytics ; 15: 153-165, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31720372

RESUMO

As a clinical setting in which novel treatment options are urgently needed, hepatocellular carcinoma (HCC) exhibits intriguing opportunities for oncolytic virotherapy. Here we report the rational generation of a novel herpes simplex virus type 1 (HSV-1)-based oncolytic vector for targeting HCC, named Ld0-GFP, which was derived from oncolytic ICP0-null virus (d0-GFP), had a fusogenic phenotype, and was a novel killer against HCC as well as other types of cancer cells. Compared with d0-GFP, Ld0-GFP exhibited superior cancer cell-killing ability in vitro and in vivo. Ld0-GFP targets a broad spectrum of HCC cells and can result in significantly enhanced immunogenic tumor cell death. Intratumoral and intravenous injections of Ld0-GFP showed effective antitumor capabilities in multiple tumor models, leading to increased survival. We speculated that more active cell-killing capability of oncolytic virus and enhanced immunogenic cell death may lead to better tumor regression. Additionally, Ld0-GFP had an improved safety profile, showing reduced neurovirulence and systemic toxicity. Ld0-GFP virotherapy could offer a potentially less toxic, more effective option for both local and systemic treatment of HCC. This approach also provides novel insights toward ongoing efforts to develop an optimal oncolytic vector for cancer therapy.

19.
Aging (Albany NY) ; 11(14): 5192-5205, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31343412

RESUMO

OBJECTIVE: Recently, the effect of long non-coding RNAs (lncRNAs) in hypertension (HTN) has been identified. This study aims to explore the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HTN and its role in vascular lesion and remodeling of HTN rats. RESULTS: LncRNA MALAT1 expression was up-regulated in HTN patients, and lncRNA MALAT1 could be an effective index of HTN diagnosis. Down-regulated MALAT1 and inhibited Notch-1 could reduce relative factor expression, including inflammation-related factors, endothelial function-related factors and oxidative stress-related factors, and inhibit apoptosis of aortic endothelial cells of HTN rats. METHODS: LncRNA MALAT1 expression in HTN patients and healthy controls was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Angiotensin II (Ang II)-induced HTN rat models were injected with MALAT1-siRNA, empty lentivirus vector, Notch pathway inhibitor (DAPT) and dimethyl sulphoxide (DMSO) via caudal vein. After three-week treatment, changes of blood pressure, inflammatory factor levels, endothelial function-related factors, oxidative stress indices and apoptosis of vascular endothelial cells were determined by a series of assays. CONCLUSION: This study revealed that down-regulated lncRNA MALAT1 could alleviate the vascular lesion and remodeling of HTN rats, the mechanism may be related to the inhibited activation of Notch signaling pathway.


Assuntos
Células Endoteliais/citologia , Hipertensão/genética , RNA Longo não Codificante/genética , Remodelação Vascular , Adulto , Idoso , Animais , Apoptose , Regulação para Baixo , Feminino , Humanos , Hipertensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno , Ratos , Receptor Notch1/metabolismo , Transdução de Sinais
20.
World Neurosurg ; 130: e933-e940, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302276

RESUMO

OBJECTIVE: To assess outcomes in obese patients with chronic obstructive pulmonary disease (COPD) who sustained an osteoporotic vertebral compression fracture (OVCF) treated by percutaneous vertebroplasty (PVP) in the improved prone position and right lateral position. METHODS: Between January 2015 and May 2016, a total of 60 patients were enrolled in this randomized controlled study. Patients in group A were placed in the improved prone position for a bilateral transpedicular technique, and those in group B were placed in the right lateral position for a left transverse process-pedicle approach. Clinical and radiologic outcomes were assessed and compared between the 2 groups during the 12-month follow-up period. RESULTS: All operations were successfully completed without any serious sequelae. The operation time, fluoroscopic time, scores for respiratory condition during the operation, intravertebral cement volume, and incidence of cement leakage were significantly greater in group A compared with group B (P < 0.01). During the follow-up period, all patients in both groups experienced significant improvement in pain relief. Satisfactory functional improvement was obtained at 3 months postoperatively. CONCLUSIONS: Treatment of obese patients with COPD suffering from painful OVCF by PVP in both the improved prone position with a bilateral technique and the right lateral position with a unilateral technique was relatively safe and effective. However, unilateral PVP in the right lateral position was associated with a shorter operation time, limited fluoroscopic time, and minimal cement leakage.


Assuntos
Fraturas por Compressão/cirurgia , Obesidade/cirurgia , Fraturas por Osteoporose/cirurgia , Posicionamento do Paciente/métodos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Idoso , Feminino , Seguimentos , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/epidemiologia , Humanos , Masculino , Obesidade/diagnóstico por imagem , Obesidade/epidemiologia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Dor/diagnóstico por imagem , Dor/epidemiologia , Dor/cirurgia , Manejo da Dor/métodos , Decúbito Ventral , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Resultado do Tratamento
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