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1.
Food Chem ; 367: 130727, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371276

RESUMO

An electrochemical sensor was fabricated by modifying nanoporous gold (NPG)-coated glassy carbon electrode (NPG/GCE) with functionalized graphene oxide /chitosan/ionic liquid nanocomposites (fGO/CS/IL). The introduction of ionic liquid (IL) and chitosan (CS) induced higher dispersibility of functionalized graphene oxide (fGO), and was beneficial for the combination of fGO/CS/IL with NPG/GCE. As a result of the synergistic effect of NPG and fGO/CS/IL, the resulted functionalized graphene oxide/chitosan/ionic liquid nanocomposites/nanoporous gold /glassy carbon electrode (fGO/CS/IL/NPG/GCE) showed the highest redox peak current response signal of Amaranth (E123) due to ultrahigh surface area, electronic conductivity as well as the improvement of the surface structure. Under optimized conditions, the enhanced peak currents represented excellent analytical performance for detection of Amaranth in the concentration range from 8.0 to 1200.0 nM. Meanwhile, the fGO/CS/IL/NPG/GCE presented satisfactory sensitivity and selectivity, excellent reproducibility, and long-time stability. For practical applications, the fGO/CS/IL/NPG/GCE was validated for the determination of Amaranth in three types of drinks with satisfactory results.

2.
Stem Cells Dev ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34470469

RESUMO

We previously reported that cytoprotective heme oxygenase-1 (HO-1) gene-modified human placenta-derived Mesenchymal stem cell (PMSC) improved placental vascularization in vitro. In the current study, we explored the protective benefit of HO-1-PMSC transplantation in a preeclampsia (PE)-like rat model. A model of PE was successfully constructed by intraperitoneal injection of N-nitro-L-arginine methyl ester (L-NAME). Blood pressure and urinary protein levels were measured. Doppler ultrasound was examined to understand uteroplacental perfusion. ELISA was used to examine the serum levels of VEGF, PlGF, sFlt-1, and sEng. The placentas and fetuses were weighed to verify the improvement in pregnancy outcome. Immunohistochemical and H&E staining was used to detect microvascular density (MVD) in placental tissues and kidney pathology, respectively. The distribution of GFP-labeled PMSC in the placenta were observed under fluorescence microscopy. Blood pressure and proteinuria were reduced and kidney damage improved. PE rat models treated with PMSC and HO-1-PMSC exhibited an increase in the quality of fetuses and placentas, MVD, VEGF, and PlGF expression, but substantially decreased expression of sFlt-1 and sEng. Doppler ultrasound showed that the placental perfusion improved. Green fluorescent tracing experiments verified that the cells were successfully transplanted into the placenta and distributed in the blood vessels, indicating that the cells might participate in the process of angiogenesis. These results indicate that therapy with HO-1-PMSC could improve placental vascular dysplasia, increase placental perfusion, control PE symptoms, and promote pregnancy outcome by regulating the balance of angiogenic and anti-angiogenic factors or directly participating in the repair of placental vessels in a PE-like rat model.

3.
Genet Epidemiol ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472134

RESUMO

The development of set-based genetic-survival association tests has been focusing on right-censored survival outcomes. However, interval-censored failure time data arise widely from health science studies, especially those on the development of chronic diseases. In this paper, we proposed a suite of set-based genetic association and interaction tests for interval-censored survival outcomes under a unified weighted-V-statistic framework. Besides dealing with interval censoring, the new tests can account for genetic effect heterogeneity and accommodate left truncation of survival outcomes. Simulation studies showed that the new tests perform well in terms of size and power under various scenarios and that the new interaction test is more powerful than the standard likelihood ratio test for testing gene-gene/gene-environment interactions. The practical utility of the developed tests was illustrated by a genome-wide association study of age to early childhood caries.

4.
J Cell Mol Med ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469035

RESUMO

Patients with malignant glioma often suffered from depression, which leads to an increased risk of detrimental outcomes. Imipramine, an FDA-approved tricyclic antidepressant, has been commonly used to relieve depressive symptoms in the clinic. Recently, imipramine has been reported to participate in the suppression of tumour progression in several human cancers, including prostate cancer, colon cancer and lymphomas. However, the effect of imipramine on malignant glioma is largely unclear. Here, we show that imipramine significantly retarded proliferation of immortalized and primary glioma cells. Mechanistically, imipramine suppressed tumour proliferation by inhibiting yes-associated protein (YAP), a recognized oncogene in glioma, independent of Hippo pathway. In addition to inhibiting YAP transcription, imipramine also promoted the subcellular translocation of YAP from nucleus into cytoplasm. Consistently, imipramine administration significantly reduced orthotopic tumour progression and prolonged survival of tumour-bearing mice. Moreover, exogenous overexpression of YAP partially restored the inhibitory effect of imipramine on glioma progression. Most importantly, compared with imipramine or temozolomide (TMZ) monotherapy, combination therapy with imipramine and TMZ exhibited enhanced inhibitory effect on glioma growth both in vitro and in vivo, suggesting the synergism of both agents. In conclusion, we found that tricyclic antidepressant imipramine impedes glioma progression by inhibiting YAP. In addition, combination therapy with imipramine and TMZ may potentially serve as promising anti-glioma regimens, thus predicting a broad prospect of clinical application.

5.
Melanoma Res ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34524220

RESUMO

Retinopathy is a rare side effect of interferon α-2b treatment. The goal of this study was to prospectively investigate the clinical characteristics of Chinese patients with melanomas who developed retinopathy following high doses of interferon α-2b (HD-IFN) therapy. The study included 56 melanoma stage I-III patients that were treated with HD-IFN. Fourty-three patients developed HD-IFN-induced retinopathies. Forty-three melanoma patients (76%) developed retinopathy after being treated with HD-IFN. Among these patients, 49% had cotton-wool spots, 19% had retinal hemorrhage, and 30% had retinal hemorrhage. The median time of occurrence of retinopathy was 4 weeks after treatment, and the median time of duration was 4 weeks. No patient showed other symptoms except one who had blurred vision. A comparison of clinical characteristics (age, gender, primary site, stage, and ulceration) and laboratory examinations (white blood cell and platelet counts, hemoglobin, serum lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, triiodothyronine, thyroxine, thyroid-stimulating hormone, and lipid) between the HD-IFN-induced retinopathy patients and nonretinopathy patients did not show any significant differences (P > 0.05). Although all patients that developed retinopathy had diabetes or hypertension, an equal percentage of patients were without retinopathy had diabetes or hypertension. HD-IFN therapy in patients with melanomas may induce mild retinopathy. Our results; however, do not necessarily suggest to discontinue the HD-IFN treatment because retinopathy is a reversible disorder.

6.
Comput Intell Neurosci ; 2021: 6379469, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531910

RESUMO

Based on Salp Swarm Algorithm (SSA) and Slime Mould Algorithm (SMA), a novel hybrid optimization algorithm, named Hybrid Slime Mould Salp Swarm Algorithm (HSMSSA), is proposed to solve constrained engineering problems. SSA can obtain good results in solving some optimization problems. However, it is easy to suffer from local minima and lower density of population. SMA specializes in global exploration and good robustness, but its convergence rate is too slow to find satisfactory solutions efficiently. Thus, in this paper, considering the characteristics and advantages of both the above optimization algorithms, SMA is integrated into the leader position updating equations of SSA, which can share helpful information so that the proposed algorithm can utilize these two algorithms' advantages to enhance global optimization performance. Furthermore, Levy flight is utilized to enhance the exploration ability. It is worth noting that a novel strategy called mutation opposition-based learning is proposed to enhance the performance of the hybrid optimization algorithm on premature convergence avoidance, balance between exploration and exploitation phases, and finding satisfactory global optimum. To evaluate the efficiency of the proposed algorithm, HSMSSA is applied to 23 different benchmark functions of the unimodal and multimodal types. Additionally, five classical constrained engineering problems are utilized to evaluate the proposed technique's practicable abilities. The simulation results show that the HSMSSA method is more competitive and presents more engineering effectiveness for real-world constrained problems than SMA, SSA, and other comparative algorithms. In the end, we also provide some potential areas for future studies such as feature selection and multilevel threshold image segmentation.


Assuntos
Algoritmos , Benchmarking , Simulação por Computador , Mutação
7.
Cell Rep ; 36(10): 109674, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34496236

RESUMO

Tumor-initiating stem cells (TSCs) are critical for drug resistance and immune escape. However, the mutual regulations between TSC and tumor microenvironment (TME) remain unclear. Using DNA-label retaining, single-cell RNA sequencing (scRNA-seq), and other approaches, we investigated intestinal adenoma in response to chemoradiotherapy (CRT), thus identifying therapy-resistant TSCs (TrTSCs). We find bidirectional crosstalk between TSCs and TME using CellPhoneDB analysis. An intriguing finding is that TSCs shape TME into a landscape that favors TSCs for immunosuppression and propagation. Using adenoma-organoid co-cultures, niche-cell depletion, and lineaging tracing, we characterize a functional role of cyclooxygenase-2 (Cox-2)-dependent signaling, predominantly occurring between tumor-associated monocytes and macrophages (TAMMs) and TrTSCs. We show that TAMMs promote TrTSC proliferation through prostaglandin E2 (PGE2)-PTGER4(EP4) signaling, which enhances ß-catenin activity via AKT phosphorylation. Thus, our study shows that the bidirectional crosstalk between TrTSC and TME results in a pro-tumorigenic and immunosuppressive contexture.

8.
BMC Infect Dis ; 21(1): 977, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544384

RESUMO

BACKGROUND: Multidrug-resistant (MDR) Klebsiella pneumoniae infections, from pancreatic infections to bloodstream infections, influence the mortality of patients with acute pancreatitis (AP) on the condition of limited antibiotic choices. The aim of this study was to investigate the predictor of mortality among AP patients complicated with MDR-K. pneumoniae infections. METHODS: Seventy-one AP patients who occurred MDR-K. pneumoniae infections from August 1st, 2016 to August 1st, 2020 were enrolled. MDR-K. pneumoniae was defined as the K. pneumoniae strain non-susceptible to at least one agent in three or more antimicrobial categories. MDR-K. pneumoniae isolates were confirmed by Vitek-2 system. Antibiotic susceptibility test was carried out using a micro broth dilution method. Clinical characteristics and drug-resistance rates were retrospectively reviewed, and the predictors of mortality were evaluated by univariate and multivariate analyses. RESULTS: The mortality rate of AP patients complicated with MDR-K. pneumoniae infections reached 46.5% (33 of 71), and pancreas (n = 53) was the most common site of MDR-K pneumoniae strains. The drug resistance rates of MDR-K. pneumoniae were high to 11 of 12 common antibiotics (more than 50.0%) except of tigecycline (23.9%). The predictor independently associated with mortality was septic shock (hazard ratio 2.959, 95% confidence intervals 1.396 - 6.272, P = 0.005). CONCLUSIONS: More attention should be paid for pancreatic MDR-K. pneumoniae infections among AP patients The predictor for mortality of AP patients complicated with MDR-K. pneumoniae infection is septic shock. Therefore, further clinical investigations should focus on areas against septic shock.

9.
J Magn Reson Imaging ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487595

RESUMO

BACKGROUND: Corticospinal tract (CST) injury has been shown to exert a major influence on functional recovery after ischemic stroke. PURPOSE: To evaluate the prognostic value of CST injury estimated using a recent developed tractometry-based method. STUDY TYPE: Prospective. POPULATION: Forty-eight patients with CST damage induced by stroke lesion who underwent brain magnetic resonance imaging within 7 days from onset. SEQUENCE: Diffusion-weighted imaging (b = 1000 seconds/mm2 ) and diffusion kurtosis imaging (DKI) spin-echo echo-planar sequence with three b-values (0, 1250, and 2500 seconds/mm2 ) at 3.0 T. ASSESSMENT: A recently developed approach that combines tract segmentation and orientation mapping was used for CST-specific tractography and tractometry. CST injury was estimated using the proposed method with diffusion metrics extracted from DKI sequence and with the first principal component (PC1) of the metrics. We also calculated the weighted lesion load (wLL) for comparison. Clinical evaluation included the National Institutes of Health Stroke Score in the acute phase and the modified Rankin scale at 3 months post-stroke. The correlations between CST injury and initial motor impairment, as well as the prognostic values of CST injury for functional outcomes were evaluated. STATISTICAL TESTS: Pearson correlation and logistic regression. Area under the receiver operating characteristic curve. P < 0.05 was considered statistically significant. RESULTS: CST injury calculated with diffusion metrics except fractional anisotropy all showed significant correlations with initial motor impairment. PC1 achieved the largest correlation coefficient (R = 0.65) compared with wLL and other diffusion metrics. In addition to wLL, DKI_AK, AFD_total, and PC1 maximum all showed predictive values for functional outcomes. DATA CONCLUSION: Structural injury to CST is important for the assessment of the extent of injury and the prediction of functional outcome. The method proposed in our study could provide an imaging indicator to quantify the CST injury after ischemic stroke. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

10.
Plant Methods ; 17(1): 93, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479588

RESUMO

BACKGROUND: Ploidy manipulation is effective in seedless loquat breeding, in which flesh color is a key agronomic and economic trait. Few techniques are currently available for detecting the genotypes of polyploids in plants, but this ability is essential for most genetic research and molecular breeding. RESULTS: We developed a system for genotyping by quantitative PCR (qPCR) that allowed flesh color genotyping in multiple tetraploid and triploid loquat varieties (lines). The analysis of 13 different ratios of DNA mixtures between two homozygous diploids (AA and aa) showed that the proportion of allele A has a high correlation (R2 = 0.9992) with parameter b [b = a1/(a1 + a2)], which is derived from the two normalized allele signals (a1 and a2) provided by qPCR. Cluster analysis and variance analysis from simulating triploid and tetraploid hybrids provided completely correct allelic configurations. Four genotypes (AAA, AAa, Aaa, aaa) were found in triploid loquats, and four (AAAA, AAAa, AAaa, Aaaa; absence of aaaa homozygotes) were found in tetraploid loquats. DNA markers analysis showed that the segregation of flesh color in all F1 hybrids conformed to Mendel's law. When tetraploid B431 was the female parent, more white-fleshed triploids occurred among the progeny. CONCLUSIONS: qPCR can detect the flesh color genotypes of loquat polyploids and provides an alternative method for analyzing polyploid genotype and breeding, dose effects and allele-specific expression.

11.
Chem Commun (Camb) ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498624

RESUMO

Direct thiocyanations of benzylic compounds have been implemented. Here, a new strategy, involving a free radical reaction pathway initiated by AIBN, was used to construct the benzylic sp3 C-SCN bond. In this way, the disadvantage of other strategies involving introducing leaving groups in advance to synthesize benzyl thiocyanate compounds was overcome. The currently developed protocol also involved the use of readily available raw materials and resulted in high product yields (up to 100%), both being great advantages for synthesizing benzyl thiocyanates.

12.
J Neurosci Res ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498762

RESUMO

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole-brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18 F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region-of-interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo- and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34469096

RESUMO

In this study, we present a wavelength sensor that is capable of distinguishing the spectrum in the range from ultraviolet (UV) to near-infrared (NIR) light. The filterless device is composed of two horizontally stacking PdSe2/20 µm Si/PdSe2 heterojunction photodetectors with a photovoltaic (PV) behavior, which makes it possible for the device to work at 0 bias voltage. Due to the relatively small thickness of Si and the wavelength-dependent absorption coefficient, the two PdSe2/20 µm Si/PdSe2 photodetectors according to theoretical simulation display a sharp contrast in distribution of the photoabsorption rate. As a result, the photocurrents of both photodetectors evolve in completely different ways with increasing wavelengths, leading to a monotonic decrease in the photocurrent ratio from 6800 to 22 when the wavelength gradually increases from 265 to 1050 nm. The corresponding relationship between both the photocurrent ratio and wavelength can be easily described by the monotonic function, which can help to precisely determine the wavelength in the range from 265 to 1050 nm, with an average relative error less than ±1.6%. It is also revealed that by slightly revising the monotonic function, the wavelength in other different temperatures can also be estimated.

14.
Braz J Med Biol Res ; 54(11): e11295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495248

RESUMO

This study aimed to investigate the diagnostic value of heparin-binding protein (HBP) in the cerebrospinal fluid of children with purulent meningitis (PM). This study included 118 children with PM diagnosed at our hospital from January 2018 to January 2020, 110 children with viral meningitis (VM) and 80 children with suspected meningitis who were ruled out by cerebrospinal fluid (CSF) analysis during the same period. HBP and white blood cell (WBC) count in the CSF, and inflammatory factors, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and procalcitonin (PCT), were measured. Receiver-operator characteristic curves were used to analyze the predictive value of HBP, CRP, PCT, and TNF-α levels in the diagnosis of PM by CSF analysis. HBP levels in the CSF of children with PM were higher, while the CRP and serum PCT and TNF-α levels were elevated in all groups (P<0.05). In addition, HBP levels in the CSF were more accurate for the diagnosis of PM than traditional diagnostic indexes. HBP levels in the CSF can be used as an important reference for early diagnosis of PM.


Assuntos
Meningites Bacterianas , Meningite Viral , Peptídeos Catiônicos Antimicrobianos , Proteínas Sanguíneas , Proteína C-Reativa , Criança , Humanos , Meningites Bacterianas/diagnóstico , Pró-Calcitonina
15.
Bioengineered ; 12(1): 6713-6723, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34519634

RESUMO

Long non-coding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) was reported to exert critical roles in multiple cancers. The current work aimed to determine the role of FGD5-AS1 in cisplatin (DDP) resistance of hepatocellular carcinoma (HCC). The levels of FGD5-AS1, miR-153-3p, and twinfilin actin binding protein 1 (TWF1) were analyzed using RT-qPCR. CCK-8, colony formation, Transwell, and TUNEL assays were used to examine the IC50 value of DDP, cell viability, invasion, and apoptosis. The interaction between miR-153-3p and TWF1 or FGD5-AS1 was determined by luciferase reporter and RIP assays. In our study, we found that FGD5-AS1 level was elevated in DDP-resistant HCC tissues and cell lines. FGD5-AS1 silencing improved the sensitivity of HCC cells to DDP. Moreover, FGD5-AS1 directly bound to miR-153-3p and FGD5-AS1 addition neutralized the inhibitory impacts of miR-153-3p supplementation on DDP resistance in the HCC cells. In addition, knockdown of TWF1 inhibited DDP resistance of HCC cells, which was reversed by miR-153-3p deletion. Lastly, FGD5-AS1 interference decreased TWF1 expression level, which was rescued by miR-153-3p inhibition. Our study exhibited that FGD5-AS1 promoted DDP resistance through modulating the miR-153-3p/TWF1 axis in HCC cells. This could be an effective treatment strategy for HCC patients.

16.
Nat Commun ; 12(1): 5236, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475399

RESUMO

New drugs are urgently needed to combat the global TB epidemic. Targeting simultaneously multiple respiratory enzyme complexes of Mycobacterium tuberculosis is regarded as one of the most effective treatment options to shorten drug administration regimes, and reduce the opportunity for the emergence of drug resistance. During infection and proliferation, the cytochrome bd oxidase plays a crucial role for mycobacterial pathophysiology by maintaining aerobic respiration at limited oxygen concentrations. Here, we present the cryo-EM structure of the cytochrome bd oxidase from M. tuberculosis at 2.5 Å. In conjunction with atomistic molecular dynamics (MD) simulation studies we discovered a previously unknown MK-9-binding site, as well as a unique disulfide bond within the Q-loop domain that defines an inactive conformation of the canonical quinol oxidation site in Actinobacteria. Our detailed insights into the long-sought atomic framework of the cytochrome bd oxidase from M. tuberculosis will form the basis for the design of highly specific drugs to act on this enzyme.


Assuntos
Grupo dos Citocromos b/química , Grupo dos Citocromos d/química , Complexo de Proteínas da Cadeia de Transporte de Elétrons/química , Mycobacterium tuberculosis/enzimologia , Proteínas de Bactérias/química , Sítios de Ligação , Microscopia Crioeletrônica , Simulação de Dinâmica Molecular , Oxirredutases/química , Conformação Proteica , Subunidades Proteicas , Vitamina K 2/análogos & derivados , Vitamina K 2/química
17.
Food Chem ; 369: 130896, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34482239

RESUMO

As a typical representative of polymethoxylated flavones, nobiletin (NOB) is beneficial to health but hard to be processed, stored, and absorbed, due to its hydrophobicity and crystallinity. Herein, we developed a stabilization system based on an efficient manufacturing procedure of NOB nanocrystal by anti-solvent method combined with ultrasonic treatment. Metal-phenolic networks composed of tannic acid and metal ions were introduced to conformally coat on formed nanocrystal for further stabilization. From the results, the size and morphology of the prepared particles could be altered by the amount, ratio, and kind of the coating materials. The optimized samples could be redispersed after centrifugation, and keep stable at 4 ℃ for at least 120 days. Moreover, they possessed higher acid stability and more effective release than the control sample during the in vitro digestion experiment. Therefore, this work provided a promising idea for overcoming storage and delivery obstacle of hydrophobic crystalline bioactive components.

18.
Front Cell Infect Microbiol ; 11: 706252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513728

RESUMO

The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don't know how specific SARS-CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis via interacting with both M and PDK1, therefore strengthening M-mediated attenuation of PDK1-PKB/Akt interaction. Furthermore, when the M-N interaction was disrupted via certain rationally designed peptides, the PDK1-PKB/Akt signaling was restored, and the boosting activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which expands our understanding of the two key proteins of SARS-CoV-2 and sheds light on the pathogenicity of this life-threatening virus.


Assuntos
COVID-19 , SARS-CoV-2 , Apoptose , Humanos , Glicoproteínas de Membrana , Proteínas do Nucleocapsídeo , Glicoproteína da Espícula de Coronavírus
19.
Int J Med Sci ; 18(15): 3380-3388, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522164

RESUMO

Lung cancer remains a global challenge due to high morbidity and mortality rates and poor response to treatment, and there are still no effective strategies to solve it. The bispecific antibody (BsAb) is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. In this study, we combined two BsAbs to achieve a dual-target therapy strategy of EpCAM+ and MUC-1+ with high affinity and specificity. The results showed that the combination of two BsAbs against EpCAM and MUC-1 could inhibit the growth of lung cancer more effectively in cell lines and primary tumors. The superior antitumor effect of two BsAbs could be attributable to enhanced CTL and increased production of type I IFNs. At the same time, the combination of EpCAM/CD3 BsAb and MUC-1/CD3 BsAb significantly regulated T population in the TDLNs. Therefore, we have found a potential immunotherapeutic strategy, which was the combination therapy with EpCAM/CD3 BsAb and MUC-1/CD3 BsAb for the treatment of non-small cell lung cancer.

20.
Food Funct ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528647

RESUMO

A novel anticoagulant peptide (IEELEEELEAER) derived from oyster (Crassostrea gigas) was discovered by combining the emerging bioinformatics with the classical enzymolysis approach. The anticoagulant peptide drastically reduced the extrinsic clotting activity (49% residual PT activity) and impaired the intrinsic clotting activity (77% residual PT activity). Consistent with the clotting data, the thrombin peak height reduced to 88.7 from 123.4 nM, and the thrombin generation time delayed to 5.32 from 4.42 min when an extrinsic trigger was applied. The inhibitory kinetics of FXIa, FIXa, FXa, FIIa, and APC in a purified component system rationally explained the reduction of the extrinsic clotting activity and impairment of thrombin generation. Besides the inhibition of FXa and FIIa activity, the activation processes of FX and FII by an intrinsic/extrinsic tenase complex and prothrombinase were also damaged. The anticoagulant activity in the plasma system was the result of comprehensive inhibition of various factors. The research provided a frame for anticoagulant evaluation and inhibitory mechanism of bioactive peptides from food products.

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