Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.256
Filtrar
1.
J Healthc Eng ; 2021: 9998427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211684

RESUMO

AR/VR technology can fuse the clinical imaging data and information to build an anatomical environment combining virtual and real, which is helpful to improve the interest of teaching and the learning initiative of medical students, and then improve the effect of clinical teaching. This paper studies the application and learning effect of the VR/AR system in human anatomy surgery teaching. This paper first shows the learning environment and platform of the VR/AR system, then explains the interface and operation of the system, and evaluates the teaching situation. This paper takes the VR/AR operation simulation system of an Irish company as an example and evaluates the learning effect of 41 students in our hospital. Research shows that the introduction of the feature reweighting module in the VR/AR surgery simulation system improves the accuracy of bone structure segmentation (IOU value increases from 79.62% to 83.56%). For real human ultrasound image data, the IOU value increases from 80.21% to 82.23% after the feature reweighting module is introduced. Therefore, the dense convolution module and feature reweighting module improve the learning ability of the network for bone structure features in ultrasound images from two aspects of feature connection and importance understanding and effectively improve the performance of bone structure segmentation.

2.
BMC Infect Dis ; 21(1): 631, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210280

RESUMO

BACKGROUND: COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients. METHODS: Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients. RESULTS: Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4+ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). For severe patients, the counts of T cell, CD4+ T cell, CD8+ T cell gradually decreased with the increased delayed hospitalization (p = 0.001, 0.03, and <  0.001, respectively). The proportions of T cell, CD8+ T cell gradually decreased with the increased delayed hospitalization (both p <  0.001), but the proportions of NK cell, B cell gradually increased with the increased delayed hospitalization (p = 0.007, and 0.002, respectively). For mild patients, only the NK cell count was gradually decreased with the increased delayed hospitalization (p = 0.012). CONCLUSION: T lymphocyte and its subset negatively correlated with disease severity, CT manifestation and delayed hospitalization. The counts of lymphocyte subset were changed more profound than their proportions.


Assuntos
COVID-19/diagnóstico por imagem , COVID-19/patologia , Subpopulações de Linfócitos , SARS-CoV-2 , Adulto , Linfócitos B , Testes Diagnósticos de Rotina , Citometria de Fluxo , Hospitalização , Humanos , Células Matadoras Naturais , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
3.
JACC Cardiovasc Interv ; 14(13): 1450-1462, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34238555

RESUMO

OBJECTIVES: The aim of the present study was to evaluate the safety and efficacy of thinner strut Firesorb (100/125 µm) sirolimus-eluting bioresorbable scaffolds (BRS) versus cobalt-chromium everolimus-eluting stents (CoCr-EES) in patients with coronary artery disease. BACKGROUND: First-generation thicker strut BRS were associated with unexpected device-related adverse outcomes at long-term follow-up. METHODS: Eligible patients with 1 or 2 de novo noncomplex coronary lesions were randomized to the Firesorb BRS group or CoCr-EES group in a 1:1 ratio. The primary endpoint was 1-year angiographic in-segment late loss (LL), powered for noninferiority testing. The key secondary endpoint was the 1-year proportion of covered struts assessed on optical coherence tomography, powered for noninferiority and subsequent superiority testing. RESULTS: A total of 433 participants from 28 Chinese centers were randomized to the Firesorb BRS group (n = 215) or CoCr-EES group (n = 218). Patient-level 1-year in-segment LL was 0.17 ± 0.27 mm in the Firesorb BRS group and 0.18 ± 0.37 mm in the CoCr-EES group (difference -0.01 mm; 95% confidence interval [CI]: -0.07 to 0.06; pnoninferiority < 0.0001) in the intention-to-treat population and was 0.17 ± 0.27 mm in the Firesorb BRS group and 0.19 ± 0.37 mm in the CoCr-EES group (difference -0.005 mm; 95% CI: -0.07 to 0.06; pnoninferiority < 0.0001) in the per-protocol set. The proportion of covered struts was 99.3% in the Firesorb BRS group and 98.8% in the CoCr-EES group (difference 0.8%; 95% CI: -0.5% to 2.1%; pnoninferiority < 0.0001; psuperiority = 0.21). One-year clinical outcomes were similar between groups. CONCLUSIONS: The thinner strut Firesorb BRS was noninferior to the CoCr-EES for the primary endpoint of 1-year angiographic in-segment LL and the key secondary endpoint of 1-year proportion of covered struts by optical coherence tomography. (A Trial of Firesorb in Patients With Coronary Artery Disease: FUTURE-II [FUTURE-II]; NCT02890160).

4.
Biomed Res Int ; 2021: 9972560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195289

RESUMO

Passive movement is an important mean of rehabilitation for stroke survivors in the early stage or with greater paralysis. The upper extremity robot is required to assist therapists with passive movement during clinical rehabilitation, while customizing is one of the crucial issues for robot-assisted upper extremity training, which fits the patient-centeredness. Robot-assisted teaching training could address the need well. However, the existing control strategies of teaching training are usually commanded by position merely, having trouble to achieve the efficacy of treatment by therapists. And deficiency of flexibility and compliance comes to the training trajectory. This research presents a novel motion control strategy for customized robot-assisted passive neurorehabilitation. The teaching training mechanism is developed to coordinate the movement of the shoulder and elbow, ensuring the training trajectory correspondence with human kinematics. Furthermore, the motion trajectory is adjusted by arm strength to realize dexterity and flexibility. Meanwhile, the torque sensor employed in the human-robot interactive system identifies movement intention of human. The goal-directed games and feedbacks promote the motor positivity of stroke survivors. In addition, functional experiments and clinical experiments are investigated with a healthy adult and five recruited stroke survivors, respectively. The experimental results present that the suggested control strategy not only serves with safety training but also presents rehabilitation efficacy.

5.
Molecules ; 26(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201677

RESUMO

A novel turn-on fluorescence probe L has been designed that exhibits high selectivity and sensitivity with a detection limit of 9.53 × 10-8 mol/L for the quantification of Zn2+. 1H-NMR spectroscopy and single crystal X-ray diffraction analysis revealed the unsymmetrical nature of the structure of the Schiff base probe L. An emission titration experiment in the presence of different molar fractions of Zn2+ was used to perform a Job's plot analysis. The results showed that the stoichiometric ratio of the complex formed by L and Zn2+ was 1:1. Moreover, the molecular structure of the mononuclear Cu complex reveals one ligand L coordinates with one Cu atom in the asymmetric unit. On adding CuCl2 to the ZnCl2/L system, a Cu-Zn complex was formed and a strong quenching behavior was observed, which inferred that the Cu2+ displaced Zn2+ to coordinate with the imine nitrogen atoms and hydroxyl oxygen atoms of probe L.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34213304

RESUMO

Doping engineering of two-dimensional (2D) semiconductors is vital for expanding their device applications, but has been limited by the inhomogeneous distribution of doping atoms in such an ultrathin thickness. Here, we report the controlled doping of Sn heteroatoms into 2D MoS2 crystals through a single-step deposition method to improve the photodetection ability of MoS2 flakes, whereas the host lattice has been well reserved without the random aggregation of the introduced atoms. Atomic-resolution and spectroscopic characterizations provide direct evidence that Sn atoms have been substitutionally doped at Mo sites in the MoS2 lattice and the Sn dopant leads to an additional strain in the host lattice. The detection performance of Sn-doped MoS2 flakes exhibits an order of magnitude improvement (up to Rλ ≈ 29 A/W, EQE ≈ 7.8 × 103%, D* ≈ 1011 Jones@470 nm) as compared with that of pure MoS2 flakes, which is associated with electrons released from Sn atoms. Such a substitutional doping process in TMDs provides a potential platform to tune the on-demand properties of these 2D materials.

7.
Huan Jing Ke Xue ; 42(7): 3263-3271, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212652

RESUMO

Increased loads of biogenic and terrestrial natural organic matter into freshwater lakes are projected to be a major consequence of global climate change and cyanobacterial blooms. In this study, the effects of phytoplankton-derived organic matter (POM) and terrestrial humic acid (HA) on the activity, composition, and function of the microbial community in Lake Taihu sediments were investigated. Fluorescent spectra demonstrated that POM with high chemodiversity was composed of labile protein-like components (50%) and recalcitrant humic-like components (50%), while humic-like substances accounted for 97% of HA. Over two-month periods, the organic carbon mineralization in sediments was enhanced owing to increasing NOM concentrations; however, the carbon consumption in POM-amended sediments was significantly higher than that in sediments amended with the same concentrations of HA. Analysis of extracellular polymeric substances indicated that NOM input improved the microbial secretion of proteins and polysaccharides, increasing the aggregation and stability of the microbial community. The amendment of POM also stimulated the activity of organic matter metabolic enzymes, promoting microbial activity. Moreover, 16S rRNA gene sequencing suggested that the mineralization of NOM (especially POM) increased the diversity of the microbial community, favored the survival of Proteobacteria and Bacteroidetes, and upregulated the function genes of organic matter metabolism. These results suggest that the composition and function of microbial community in sediments were associated with the origin, composition, and concentration of NOM input.


Assuntos
Cianobactérias , Microbiota , Sedimentos Geológicos , Substâncias Húmicas/análise , Lagos , RNA Ribossômico 16S
8.
Exp Anim ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34234081

RESUMO

Myocardial infarction (MI) is a common cardiovascular disease with high morbidity and mortality. In this study, we explored the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in MI. MI was induced by ligation of the left anterior descending coronary artery. Lentivirus-mediated RNA interference of IFIT3 expression was performed by tail vein injection 72 hours before MI modeling. Cardiac injury indexes and inflammatory response were examined 3 days after MI. Cardiac function indexes, infarct size, and cardiac fibrosis were assessed 4 weeks after MI. IFIT3 expression was upregulated in myocardial tissues at both 3 days and 4 weeks after MI. Knockdown of IFIT3 significantly relieved the myocardial injury, as evidenced by the decrease in serum levels of cTnI and CK-MB. In addition, IFIT3 knockdown significantly reduced the number of CD68+ macrophages and the levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-α, indicating that the inflammatory response was relieved. Moreover, IFIT3 silencing also significantly improved cardiac function and reduced infarct size, myocardial fibrosis, and collagen content in mice with MI. Mechanically, the present study showed that the activation of the MAPK pathway was observed in myocardial tissues of MI mice, which was blocked by IFIT3 knockdown, as indicated by the decreased phosphorylation of JNK, p-38, and ERK. Collectively, our results revealed the role of IFIT3 in the inflammatory response and myocardial fibrosis after MI, indicating that IFIT3 might be a potential target for MI treatment.

9.
Adv Sci (Weinh) ; : e2100629, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236760

RESUMO

MicroRNAs are potential candidates for lung cancer prevention and therapy. A major limitation is the lack of an efficient delivery system to directly deliver miRNA to cancer cells while limiting systemic exposure. The delivery of miRNA via inhalation is a potential strategy for lung cancer prevention in high-risk individuals. In this study, the authors investigate the efficacy of aerosolized let-7b miRNA treatment in lung cancer prevention. Let-7b shows significant inhibition of B[a]P-induced lung adenoma with no detectable side effects. Single-cell RNA sequencing of tumor-infiltrating T cells from primary tumors reveals that Let-7b post-transcriptionally suppresses PD-L1 and PD-1 expression in the tumor microenvironment, suggesting that let-7b miRNAs may promote antitumor immunity in vivo. Let-7b treatment decreases the expression of PD-1 in CD8+ T cells and reduces PD-L1 expression in lung tumor cells. The results suggest that this aerosolized let-7b mimic is a promising approach for lung cancer prevention, and that the in vivo tumor inhibitory effects of let-7b are mediated, at least in part, by immune-promoting effects via downregulating PD-L1 in tumors and/or PD-1 on CD8+ T cells. These changes potentiate antitumor CD8+ T cell immune responses, and ultimately lead to tumor inhibition.

10.
Nat Commun ; 12(1): 4210, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244522

RESUMO

Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor angiotensin-converting enzyme-2 (ACE2) in binding to RBD. Site-directed mutagenesis confirms these common binding features although some minor differences are found. One representative antibody, P5A-3C8, demonstrates extraordinarily protective efficacy in a golden Syrian hamster model against SARS-CoV-2 infection. However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies. The discovery of public antibodies and shared escape mutation highlight the intricate relationship between antibody response and SARS-CoV-2, and provide critical reference for the development of antibody and vaccine strategies to overcome the antigenic variation of SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Receptores Virais/imunologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Sítios de Ligação/imunologia , COVID-19/imunologia , Cricetinae , Modelos Animais de Doenças , Epitopos/imunologia , Feminino , Humanos , Masculino , Testes de Neutralização , Receptores de Antígenos de Linfócitos B/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
11.
BMC Genomics ; 22(1): 558, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284723

RESUMO

BACKGROUND: Breeding for new maize varieties with propitious root systems has tremendous potential in improving water and nutrients use efficiency and plant adaptation under suboptimal conditions. To date, most of the previously detected root-related trait genes in maize were new without functional verification. In this study, seven seedling root architectural traits were examined at three developmental stages in a recombinant inbred line population (RIL) of 179 RILs and a genome-wide association study (GWAS) panel of 80 elite inbred maize lines through quantitative trait loci (QTL) mapping and genome-wide association study. RESULTS: Using inclusive composite interval mapping, 8 QTLs accounting for 6.44-8.83 % of the phenotypic variation in root traits, were detected on chromosomes 1 (qRDWv3-1-1 and qRDW/SDWv3-1-1), 2 (qRBNv1-2-1), 4 (qSUAv1-4-1, qSUAv2-4-1, and qROVv2-4-1), and 10 (qTRLv1-10-1, qRBNv1-10-1). GWAS analysis involved three models (EMMAX, FarmCPU, and MLM) for a set of 1,490,007 high-quality single nucleotide polymorphisms (SNPs) obtained via whole genome next-generation sequencing (NGS). Overall, 53 significant SNPs with a phenotypic contribution rate ranging from 5.10 to 30.2 % and spread all over the ten maize chromosomes exhibited associations with the seven root traits. 17 SNPs were repeatedly detected from at least two growth stages, with several SNPs associated with multiple traits stably identified at all evaluated stages. Within the average linkage disequilibrium (LD) distance of 5.2 kb for the significant SNPs, 46 candidate genes harboring substantial SNPs were identified. Five potential genes viz. Zm00001d038676, Zm00001d015379, Zm00001d018496, Zm00001d050783, and Zm00001d017751 were verified for expression levels using maize accessions with extreme root branching differences from the GWAS panel and the RIL population. The results showed significantly (P < 0.001) different expression levels between the outer materials in both panels and at all considered growth stages. CONCLUSIONS: This study provides a key reference for uncovering the complex genetic mechanism of root development and genetic enhancement of maize root system architecture, thus supporting the breeding of high-yielding maize varieties with propitious root systems.


Assuntos
Plântula , Zea mays , Estudo de Associação Genômica Ampla , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Plântula/genética , Zea mays/genética
12.
Aging (Albany NY) ; 13(undefined)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34297698

RESUMO

Research on association between programmed cell death ligand 1 (PD-L1) expression in cancer cells and prognosis of esophageal squamous cell carcinoma (ESCC) has been controversial and has focused on patients with surgical resection. We aimed to investigate impact of PD-L1 on treatment response and prognostic value in ESCC and analyze which subset of patients may benefit from immunotherapy. The PD-L1 expression was evaluated by immunohistochemical analysis in all patients. Stratification analysis was performed according to whether surgery was performed. There were no significant correlations between PD-L1 expression with 3-year overall survival (OS) and progression-free survival (PFS) in 81 ESCC patients. Then stratification analysis was performed. Among these 44 patients without surgery, disease control rate (DCR) in negative PD-L1 expression group (78%) was significantly better than those (42%) in positive PD-L1 expression group (P = 0.032). There were no significant correlations between PD-L1 expression with 3-year OS and PFS in 37 ESCC patients receiving surgery. However, in 44 ESCC patients without surgery, the Kaplan-Meier method showed that 3-year OS and PFS in negative PD-L1 expression group were significantly better than those in positive PD-L1 expression group. In Cox univariate and multivariate model, PD-L1 was an independent prognosticator for inferior OS (p = 0.011; p = 0.017). Our research revealed prognostic role of PD-L1 expression in cancer cells may be variable in different treatment methods. Consequently, PD-L1 may serve as an independent prognostic factor and provide a theoretical basis for combining conventional therapy with immunotherapy targeting PD-L1 to achieve better treatment outcome in ESCC patients without esophagectomy.

13.
Bioresour Technol ; 337: 125454, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34198243

RESUMO

Dual selective pressure was applied as the driving condition to cultivate an enhanced aerobic granular sludge (AGS) with Fe(0)-based biochemical cycle galvanic-cells (BCGC) as the core. The BCGC-AGS coupled micro-electrolysis with synergistic autotrophic-heterotrophic denitrification to enhance nitrogen removal. COD and total nitrogen removal of 91.8% and 95.9% were achieved, respectively. The formation of circulation channel between Fe3+ and Fe2+ provided a solid foundation for the biochemical cycle of galvanic-cells with low consumption. The existence of micro-electrolysis selective pressure in BCGC-AGS was also confirmed. Facultative aerobic bacteria Methylocystis and Azospirillum were the most abundant genera. Facultative iron redox bacteria and autotrophic denitrifying bacteria Geobacter, Thiobacillus, Aquabacterium, Thauera and Azospirillum showed high abundance, affirming the success culture of EAGS system. Load shock test verified BCGC-AGS possessed excellent load shock resistance. Obtaining the advantages of fast-cultivation, high-efficiency and low galvanic-cells consumption, BCGC-AGS showed significant potential for practical application.

14.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209804

RESUMO

Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8-12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.

15.
Small ; : e2102550, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314097

RESUMO

Despite the boom in the water-triggered electric power generation technologies, few attempts have been made with a broader horizonyielding the electricity from sweat, which is of great value for low-power-consumption wearable electronics. Here, an electromechanical coupling and humidity-actuated two-in-one humidity actuator-driven piezoelectric generator (HAPG) are reported, that can yield continuous electric power from fluctuations in the ambient humidity. It is composed of polyvinyl alcohol (PVA)-wrapped highly aligned dopamine (DA)/polyvinylidene fluoride (PVDF) shell/core nanofibers (PVA@DA/PVDF NFs). As-received PVA@DA/PVDF NFs can exchange water with the ambient humidity to perform expansion and contraction and convert them into electric power. An all-fiber-based portable HAPG is fabricated and tested on human palm skin. The devices show high sensitivity and accuracy for converting the mental sweating-derived continuous moisture fluctuations into electric power. This electric power can be stored in capacitors, which is expected to power micro- and nano-electronic devices or be used in electrotherapy such as electrical stimulation to promote wound healing. Beyond this, the obtained voltage profiles exhibit unique features that can reflect the typical sweat damping oscillation curve features.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 262: 120134, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34271238

RESUMO

Studies have shown that changes in the redox state of cells might be closely related to pathological and physiological processes. Sulfur dioxide and hydrogen peroxide, as a significant redox couple in living cells, are endogenously produced by cells. Here, we report a long-wavelength fluorescent probe to reversibly monitor sulfur dioxide and hydrogen peroxide. This probe (NBD) displayed high selectivity and sensitivity, which could be accumulated in mitochondria for real-time imaging of SO2/H2O2. These results indicated that NBD would be an ideal tool for monitoring the redox cycle state in living cells.

17.
Commun Biol ; 4(1): 906, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34302042

RESUMO

Expressed on cells of the myeloid and lymphoid lineages, V-domain Ig Suppressor of T cell Activation (VISTA) is an emerging target for cancer immunotherapy. Blocking VISTA activates both innate and adaptive immunity to eradicate tumors in mice. Using a tripeptide small molecule antagonist of VISTA CA170, we found that it exhibited potent anticancer efficacy on carcinogen-induced mouse lung tumorigenesis. Remarkably, lung tumor development was almost completely suppressed when CA170 was combined with an MHCII-directed KRAS peptide vaccine. Flow cytometry and single-cell RNA sequencing (scRNA-seq) revealed that CA170 increased CD8+ T cell infiltration and enhanced their effector functions by decreasing the tumor infiltration of myeloid-derived suppressor cells (MDSCs) and Regulatory T (Treg) cells, while the Kras vaccine primarily induced expansion of CD4+ effector T cells. VISTA antagonism by CA170 revealed strong efficacy against lung tumorigenesis with broad immunoregulatory functions that influence effector, memory and regulatory T cells, and drives an adaptive T cell tumor-specific immune response that enhances the efficacy of the KRAS vaccine.

18.
Small ; : e2101665, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34278716

RESUMO

Owing to the urgent need for electrochemical analysis and sensing of trace target molecules in various fields such as medical diagnosis, agriculture and food safety, and environmental monitoring, signal amplification is key to promoting analysis and sensing performance. The nanoconfinement effect, derived from nanoconfined spaces and interfaces with sizes approaching those of target molecules, has witnessed rapid development for ultra-sensitive analyzing and sensing. In this review, the two main types of nanoconfinement systems - confined nanochannels and planes - are assessed and recent progress is highlighted. The merits of each nanoconfinement system, the nanoconfinement effect mechanisms, and applications for electrochemical analysis and sensing are summarized and discussed. This review aims to help deepen the understanding of nanoconfinement devices and their effects in order to develop new analysis and sensing applications for researchers in various fields.

19.
BMC Pulm Med ; 21(1): 233, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256743

RESUMO

BACKGROUND: To explore the long-term trajectories considering pneumonia volumes and lymphocyte counts with individual data in COVID-19. METHODS: A cohort of 257 convalescent COVID-19 patients (131 male and 126 females) were included. Group-based multi-trajectory modelling was applied to identify different trajectories in terms of pneumonia lesion percentage and lymphocyte counts covering the time from onset to post-discharge follow-ups. We studied the basic characteristics and disease severity associated with the trajectories. RESULTS: We characterised four distinct trajectory subgroups. (1) Group 1 (13.9%), pneumonia increased until a peak lesion percentage of 1.9% (IQR 0.7-4.4) before absorption. The slightly decreased lymphocyte rapidly recovered to the top half of the normal range. (2) Group 2 (44.7%), the peak lesion percentage was 7.2% (IQR 3.2-12.7). The abnormal lymphocyte count restored to normal soon. (3) Group 3 (26.0%), the peak lesion percentage reached 14.2% (IQR 8.5-19.8). The lymphocytes continuously dropped to 0.75 × 109/L after one day post-onset before slowly recovering. (4) Group 4 (15.4%), the peak lesion percentage reached 41.4% (IQR 34.8-47.9), much higher than other groups. Lymphopenia was aggravated until the lymphocytes declined to 0.80 × 109/L on the fourth day and slowly recovered later. Patients in the higher order groups were older and more likely to have hypertension and diabetes (all P values < 0.05), and have more severe disease. CONCLUSIONS: Our findings provide new insights to understand the heterogeneous natural courses of COVID-19 patients and the associations of distinct trajectories with disease severity, which is essential to improve the early risk assessment, patient monitoring, and follow-up schedule.

20.
Mol Cancer Ther ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253595

RESUMO

Dual bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4 and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of GI toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain (BD2) of the four BET family proteins. In contrast to the broad antiproliferative activities observed with DbBi, ABBV-744 displayed significant antiproliferative activities largely although not exclusively in cancer cell lines derived from AML and androgen receptor (AR) positive prostate cancer. Studies in AML xenograft models demonstrated anti-tumor efficacy for ABBV-744 that was comparable to the pan-BET inhibitor ABBV-075 but with an improved therapeutic index. Enhanced anti-tumor efficacy was also observed with the combination of ABBV-744 and the BCL-2 inhibitor, venetoclax compared to monotherapies of either agent alone. These results collectively support the clinical evaluation of ABBV-744 in AML (Clinical Trials.gov identifier: NCT03360006).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...