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1.
EBioMedicine ; 62: 103107, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33181461

RESUMO

BACKGROUND: High rates of recurrence after resection severely worsen hepatocellular carcinoma (HCC) prognosis. This study aims to explore whether circulating tumor cell (CTC) is helpful in determine the appropriate liver resection margins for HCC patients. METHODS: HCC patients who underwent liver resection were enrolled into training (n=117) or validation (n=192) cohorts, then classified as CTC-positive (CTC≥1) or CTC-negative (CTC=0). A standardized pathologic sampling method was used in the training cohort to quantify microvascular invasion (mVI) and the farthest mVI from the tumor (FMT). FINDINGS: CTC number positively correlated with mVI counts (r=0.655, P<0.001) and FMT (r=0.495, P<0.001). The CTC-positive group had higher mVI counts (P=0.032) and greater FMT P=0.008) than the CTC-negative group. In the CTC-positive group, surgical margins of >1 cm independently protected against early recurrence (training cohort, P=0.004; validation cohort, P=0.001) with lower early recurrence rates (training cohort, 20.0% vs. 65.1%, P=0.005; validation cohort, 36.4% vs. 65.1%, P=0.003) compared to surgical margins of ≤1 cm. No differences in postoperative liver function were observed between patients with margins >1 cm vs. ≤1 cm. Surgical margin size minimally impacted early postoperative HCC recurrence in CTC-negative patients when using 0.5 cm or 1 cm as the threshold. INTERPRETATIONS: Preoperative CTC status predicts mVI severity in HCC patients and is a potential factor for determining optimal surgical margin size to ensure disease eradication and conserve liver function. A surgical margin of >1 cm should be achieved for patients with positive CTC. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgement section.

2.
Liver Int ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205544

RESUMO

BACKGROUND & AIMS: Liver transplantation (LTx) is one of the most effective treatments for hepatocellular carcinoma (HCC); however, tumor recurrence after LTx often leads to poor outcomes. This study investigated the value of circulating tumor cells (CTCs) as a predictor of recurrence following LTx in patients with HCC. METHODS: This analysis included 193 patients with HCC who underwent LTx at our institute and accepted pre- and post-operative CTC detection; 38 were selected for serial CTC monitoring. The predictive value of CTCs for tumor recurrence in patients with HCC following LTx was evaluated. Single-cell whole genome sequencing was used to characterize CTCs. RESULTS: Overall, the CTC burden decreased after LTx (P <0.05). Postoperative CTC count ≥1 per 5 mL peripheral blood was identified as a potential biomarker for predicting tumor recurrence after LTx, especially in patients with no detectable CTCs prior to LTx and negative tumor serological biomarkers. The predictive value of postoperative CTC count ≥1 per 5 mL blood was retained in patients who did not meet the Milan criteria, University of California San Francisco (UCSF) criteria, or Fudan criteria (all P <0.05). Furthermore, postoperative serial CTC detection may be useful in postsurgical surveillance for HCC recurrence. CONCLUSIONS: CTCs may be a useful biomarker to evaluate recurrence risk following LTx in patients with HCC. Evaluation based on CTC detection may enhance the post-transplant management of HCC, and improve the therapeutic efficacy of LTx.

3.
Restor Neurol Neurosci ; 38(5): 385-393, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33185618

RESUMO

BACKGROUND: Escitalopram is one of the most commonly used SSRIs at present, which has the characteristics of quick onset, less interactions with other drugs, and relative safety. OBJECTIVE: This study aims to investigate the effects of escitalopram on neural functional prognoses and endothelial dysfunction after acute ischemic stroke. METHODS: One hundred eligible patients afflicted with acute ischemic stroke were randomized into two groups: control and treatment groups. Patients in the treatment group received escitalopram in addition to the basic therapies in the control group over a period of 90 days. Neurological deficits were quantified using the National Institutes of Health Stroke Scale (NIHSS) score and Barthel index (BI) score, cognitive impairment was determined using the Mini-Mental State Examination (MMSE) score, depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAMD). Furthermore, post-stroke depression (PSD) was defined based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a HAMD score ≥17. Flow-mediated vascular dilatation (FMD) of the brachial artery was use as a surrogate indicator for endothelial dysfunction assessment with ultrasound. RESULTS: The mean NIHSS and HAMD scores on day 90 after treatment were significantly lower in the treatment group than in the control group (2.17±0.36 vs. 4.24±0.85; 5.81±1.35 vs. 10.43±4.91; P < 0.01), while the mean BI score and FMD were significantly higher in the treatment group (93.08±6.23 vs. 79.64±7.56, P < 0.01; 8.71±2.35 vs. 5.83±1.21, P < 0.05) than in the control group. The improvement in MMSE score was not significantly different between the two groups. CONCLUSIONS: Treatment with escitalopram early after ischemic stroke can improve neural functional prognoses and endothelial dysfunction. Escitalopram had less side effects, which is worthy of clinical prophylactic application.

4.
Curr Org Synth ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167843

RESUMO

AIM AND OBJECTIVE: Benzoxazoles are valuable bicyclic aromatic compounds, the construction of benzoxazoles via C-O cross-coupling reactions has attracted more and more attention. MATERIALS AND METHODS: The best condition of C-O bond formation from o-haloanilides was carried out taking Cu(OTf)2 (5 mol%) and vasicine (10 mol%) as the catalyst in EtOH in present of K2CO3 (2 eq.) for 12 h at 90oC. RESULTS: A series of 2-substituted benzoxazoles have been prepared in high yields from 2-bromoanilides and 2-iodioanilides under mild conditions. CONCLUSION: We have developed an efficient Cu-vasicine catalytic system for intramolecular C-O bond formation. This strategy is applicable to synthesis of a wide variety of 2-substituted benzoxazoles by intramolecular O-arylation of o-haloanilides.

5.
Transl Res ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33129993

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. Reduced progesterone levels are associated with luteal phase deficiency in women with PCOS. The levels of C-X-C motif chemokine ligand-14 (CXCL14) were previously reported to be decreased in human-luteinized granulosa (hGL) cells derived from PCOS patients. However, the function of CXCL14 in hGL cells and whether CXCL14 affects the synthesis of progesterone in hGL cells remain unclear. In the present study, the levels of CXCL14 were reduced in follicular fluid and hGL cells in PCOS patients, accompanied by decreased progesterone levels in follicular fluid and decreased steroidogenic acute regulatory (STAR) expression in hGL cells. CXCL14 administration partially reversed the low progesterone production and STAR expression in hGL cells obtained from PCOS patients. In primary hGL cells, CXCL14 upregulated STAR expression and progesterone production. CXCL14 activated the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and CREB inhibitor attenuated the modulation of StAR expression by CXCL14. P38 and Jun N-terminal kinase (JNK) pathways were also activated by CXCL14 and inhibition of p38 and JNK attenuated the increase of phosphorylation of CREB, STAR expression and progesterone production caused by CXCL14. Our findings revealed the novel role of CXCL14 in upregulation of STAR expression and progesterone synthesis through CREB phosphorylation via activation of p38 and JNK pathways in hGL cells. This is likely contributing to the dysfunction in steroidogenesis in granulosa cells from PCOS patients.

6.
Nanotechnology ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217749

RESUMO

Recently emerging spintronic terahertz (THz) emitters, featuring many appreciable merits such as low-cost, high efficiency, ultrabroadband, and ease of integration, offer multifaceted capabilities not only in understanding the fundamental ultrafast magnetism physics but also for exploring multifarious practical applications. Integration of various flexible and tunable functions at the source such as polarization manipulation, amplitude tailoring, phase modulation, and radiation beam steering with the spintronic THz emitters and their derivatives can yield more compact and elegant devices. Here, we demonstrate a monolithic metamaterial integrated onto a W/CoFeB/Pt THz nanoemitter for a purpose-designed functionality of the electromagnetically induced transparency analog. Through elaborate engineering the asymmetry degree and geometric parameters of the metamaterial structure, we successfully verified the feasibility of monolithic modulations for the radiated THz waves. The integrated device was eventually compared with a set of stand-alone metamaterial positioning scenarios, and the negligible frequency difference between two of the positioning schemes further manifests almost an ideal realization of the proposed monolithic integrated metamaterial device with a spintronic THz emitter. We believe that such adaptable and scalable devices may make valuable contributions to the designable spintronic THz devices with pre-shaping THz waves and enable chip-scale spintronic THz optics, sensing, and imaging.

7.
Adv Mater ; : e2005268, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185295

RESUMO

Kesterite-based Cu2 ZnSn(S,Se)4 semiconductors are emerging as promising materials for low-cost, environment-benign, and high-efficiency thin-film photovoltaics. However, the current state-of-the-art Cu2 ZnSn(S,Se)4 devices suffer from cation-disordering defects and defect clusters, which generally result in severe potential fluctuation, low minority carrier lifetime, and ultimately unsatisfactory performance. Herein, critical growth conditions are reported for obtaining high-quality Cu2 ZnSnSe4 absorber layers with the formation of detrimental intrinsic defects largely suppressed. By controlling the oxidation states of cations and modifying the local chemical composition, the local chemical environment is essentially modified during the synthesis of kesterite phase, thereby effectively suppressing detrimental intrinsic defects and activating desirable shallow acceptor Cu vacancies. Consequently, a confirmed 12.5% efficiency is demonstrated with a high VOC of 491 mV, which is the new record efficiency of pure-selenide Cu2 ZnSnSe4 cells with lowest VOC deficit in the kesterite family by Eg /q-Voc. These encouraging results demonstrate an essential route to overcome the long-standing challenge of defect control in kesterite semiconductors, which may also be generally applicable to other multinary compound semiconductors.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33057772

RESUMO

PURPOSE: To develop and validate a clinico-biological features and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) radiomic-based nomogram via machine learning for the pretherapy prediction of discriminating between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in non-small cell lung cancer (NSCLC). METHODS: A total of 315 NSCLC patients confirmed by postoperative pathology between January 2017 and June 2019 were retrospectively analyzed and randomly divided into the training (n = 220) and validation (n = 95) sets. Preoperative clinical factors, serum tumor markers, and PET, and CT radiomic features were analyzed. Prediction models were developed using the least absolute shrinkage and selection operator (LASSO) regression analysis. The performance of the models was evaluated and compared by the area under receiver-operator characteristic (ROC) curve (AUC) and DeLong test. The clinical utility of the models was determined via decision curve analysis (DCA). Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: In total, 122 SCC and 193 ADC patients were enrolled in this study. Four independent prediction models were separately developed to differentiate SCC from ADC using clinical factors-tumor markers, PET radiomics, CT radiomics, and their combination. The DeLong test and DCA showed that the Combined Model, consisting of 2 clinical factors, 2 tumor markers, 7 PET radiomics, and 3 CT radiomic parameters, held the highest predictive efficiency and clinical utility in predicting the NSCLC subtypes compared with the use of these parameters alone in both the training and validation sets (AUCs (95% CIs) = 0.932 (0.900-0.964), 0.901 (0.840-0.957), respectively) (p < 0.05). A quantitative nomogram was subsequently constructed using the independently risk factors from the Combined Model. The calibration curves indicated a good consistency between the actual observations and nomogram predictions. CONCLUSION: This study presents an integrated clinico-biologico-radiological nomogram that can be accurately and noninvasively used for the individualized differentiation SCC from ADC in NSCLC, thereby assisting in clinical decision making for precision treatment.

9.
Braz J Med Biol Res ; 53(11): e8930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053113

RESUMO

This study aimed to investigate whether the routine administration of escitalopram for three months would improve the prognosis of patients with ischemic stroke and decrease the plasma copeptin level. A total of 97 patients with acute cerebral infarction were randomly allocated to receive escitalopram (5-10 mg once per day, orally; n=49) or not to receive escitalopram (control group; n=48) for 12 weeks starting at 2-7 days after the onset of stroke. Both groups received conventional treatments, including physiotherapy and secondary prevention of stroke. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the disability of patients at the initial evaluation and at the monthly follow-up visits for three months. Impairment in the daily activities was assessed using the Barthel Index (BI), while cognitive impairment was assessed using Mini-Mental State Examination (MMSE) score. The psychiatric assessment included the administration of the Present State Examination modified to identify Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms of depression. The severity of depression was measured using the 17-item Hamilton Rating Scale for Depression (HAMD). During the 3-month follow-up period, 95 patients were included in the analysis (two patients withdrew from the escitalopram group). NIHSS and BI improvement at the 90th day were significantly greater in the escitalopram group (P<0.05), while HAMD and plasma copeptin levels significantly decreased, compared to the control group (P<0.01). In patients with acute ischemic stroke, the earlier administration of escitalopram for three months may improve neurological functional prognosis and decrease copeptin level.

10.
Cell Death Dis ; 11(10): 895, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093445

RESUMO

Accumulating evidence indicates that hepatocellular carcinoma (HCC) tumorigenesis, recurrence, metastasis, and therapeutic resistance are strongly associated with liver cancer stem cells (CSCs), a rare subpopulation of highly tumorigenic cells with self-renewal capacity and differentiation potential. Previous studies identified B cell leukemia/lymphoma-11b (BCL11B) as a novel tumor suppressor with impressive capacity to restrain CSC traits. However, the implications of BCL11B in HCC remain unclear. In this study, we found that low BCL11B expression was an independent indicator for shorter overall survival (OS) and time to recurrence (TTR) for HCC patients with surgical resection. In vitro and in vivo experiments confirmed BCL11B as a tumor suppressor in HCC with inhibitory effects on proliferation, cell cycle progression, apoptosis, and mobility. Furthermore, BCL11B could suppress CSC traits, as evidenced by dramatically decreased tumor spheroid formation, self-renewal potential and drug resistance. A Cignal Finder Array and dual-luciferase activity reporter assays revealed that BCL11B could activate the transcription of P73 via an E2F1-dependent manner. Thus, we concluded that BCL11B is a strong suppressor of retaining CSC traits in HCC. Ectopic expression of BCL11B might be a promising strategy for anti-HCC treatment with the potential to cure HBV-related HCC regardless of P53 mutation status.

11.
BMJ Open ; 10(10): e036252, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33033011

RESUMO

INTRODUCTION: Pregnancy loss (PL) is an adverse life event, and there is no proven effective treatment for recurrent PL (RPL). Preimplantation genetic screening (PGS) can be performed to reduce the risks of PL; however, there is still no solid scientific evidence that PGS improves outcomes for couples experiencing RPL. Comprehensive chromosome screening (PGS2.0) has become a routine practice in in vitro fertilisation (IVF) clinics. Previous studies based on PGS1.0 with a focus on RPL couples where the female is of advanced maternal age have reported contradictory results. Hence, a multicentre randomised trial is needed to provide evidence for the clinical benefits of PGS2.0 treatment for RPL couples. METHODS AND ANALYSIS: Overall, 268 RPL couples undergoing IVF cycles will be enrolled. Couples will be randomised according to a unique grouping number generated by a random digital software into (1) PGS2.0 group and (2) non-PGS (conventional embryo morphology evaluation) group. This study aims to investigate whether the live birth rate (LBR) per initiated cycle after PGS2.0 is superior to the LBR per initiated cycle after conventional embryo evaluation (non-PGS group). Live birth will be defined as a live baby born after a gestation period of >28 weeks, with a birth weight of more than 1000 g. A multivariate logistic regression model will be used to adjust for confounding factors. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ethics Committee of Obstetrics and Gynecology Hospital, Fudan University and the participating hospitals. Written informed consent will be obtained from each couple before any study procedure is performed. Data from this study will be stored in the Research Electronic Data Capture. The results of this trial will be presented and published via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT03214185; Pre-results.

12.
J Clin Neurosci ; 79: 154-159, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33070887

RESUMO

Schizophrenic patients often experience visual hallucinations (VHs) and auditory hallucinations (AHs); however, brain aberrations associated with combined VH and AH in schizophrenic patients remains poorly documented. Changes to the brain and cognition during the first episode of untreated schizophrenic patients (FUSCH) with both VHs and AHs (FUSCHVA) were evaluated. One-hundred and fifty-seven patients were enrolled that had FUSCH (1) with VHs but not AHs (FUSCHV), and (2) with AHs but not VHs (FUSCHA), plus FUSCHVA and healthy controls (n = 30). Gray matter volume (GMV) and MATRICS Consensus Cognitive Battery (MCCB) was measured to reflect impairments to the brain and cognition, respectively. FUSCHVA patients had the severest cognitive impairment for all components of the MCCB, followed by FUSCHV and FUSCHA patients. Compared to healthy patients, FUSCHVA patients had reduced GMV in the occipital, parietal, frontal, and temporal cortex, and increased GMV in the hippocampus and striatum. Compared to FUSCHV patients, FUSCHVA patients had reduced GMV in the occipital cortex and postcentral gyrus, and increased GMV in the posterio-parietal lobe. Compared to patients with FUSCHA, the GMV in patients with FUSCHVV was reduced in the occipital cortex and posterio parietal lobe. In conclusion, visual and auditory hallucinations appear to deteriorate reciprocally in FUSCHVA patients, accompanied with sever cognitive impairments. Compared to AHs, VHs might be accompanied with severe GMV impairment in the brain, especially in the primary visual cortex and higher perception integration cortex (posterio parietal lobe) in patients with FUSCH.

13.
Adv Healthc Mater ; 9(21): e2000650, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000919

RESUMO

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), reveals a limited therapeutic effect due to a lack of selectivity and evident drug resistance. In the present study, bismuth-based mesoporous nanomaterial (NBOF) is loaded with SOR and then coated with polyethylene glycol and folic acid conjugates (P-FA) to form an NBOF@SOR-P-FA nanocarrier system. The system achieves significantly enhanced anti-cancer efficacy by combining chemotherapy with radiotherapy. To evaluate the effect of synergistic treatment, cytotoxicity detection, Live/Dead staining, apoptotic assay, and Western blot analysis are performed. The results suggest that NBOF@SOR-P-FA significantly inhibits HCC cell proliferation and promotes cell apoptosis. Also, the NBOF@SOR-P-FA exhibits excellent biocompatibility by hemolysis and serum biochemical tests and produces a substantially enhanced contrast efficiency as compared to iohexol by computed tomography imaging. More importantly, the profound suppression of tumor growth and potentiation of apoptosis are observed in a mouse subcutaneous tumor model. Collectively, these results indicate that the bismuth-based nanotheranostic platform could enhance the therapeutic effect of sorafenib and serve as an innovative method for HCC treatment.

14.
Acta Biomater ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33122146

RESUMO

Phototherapy, including photodynamic and photothermal therapies, is a non-invasive photo-triggered tumor treatment. Combination therapy and new synergistic therapeutic reagents may hold promise for improving these treatments. Herein, we report an amphiphilic iridium-based photosensitizer (C14-IP2000) loaded with a hydrophobic photo-thermal drug (ZnPc) to form nano-micelles (ZNPs) for dual-light triggered tumor phototherapy. The C14-IP2000 was contained within ZNPs consisting of an iridium complex core decorated with hydrophilic polyethylene glycol chains to extend the time in blood circulation, and two hydrophobic carbon chains to enhance the loading capacity and the hydrophobic interaction with the loaded reagent. The designed ZNPs showed effective blood circulation, passive tumor targeting ability, remarkable photodynamic conversion ability, and good photothermal conversion capability, and therefore may be used for combined tumor ablation. Our results demonstrated that the amphipathic bionic structure of ZNPs not only enables self-assembled reagent fabrication with prolonged circulation time and favorable metabolic characteristics for tumor combination therapy, but also provides a nanostructure strategy for the modification of functionalized reagents.

15.
Eur J Dent Educ ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967058

RESUMO

OBJECTIVE: To summarize the lessons learned from implementing a dental undergraduate research program over the past eleven years and identify key elements to guarantee the success of dental undergraduate research in the future. MATERIAL AND METHODS: An overview of 80 research projects from 2007 to 2017 was provided, consisting of 239 participating undergraduates and 47 faculty advisors. Students' academic performance was compared between participating and non-participating undergraduates. An anonymous questionnaire was designed and distributed to participants, with VAS satisfaction assessment, Likert-scale items and open-ended questions. Questions focused on overall satisfaction, motivation, benefits to student career development, and essential elements for the dental undergraduate research program in the future. RESULTS: The undergraduate participants had significantly better scores of GPAs (3.41 vs 3.21; p < 0.0001), obtained more awards on the honor rolls (0.53 vs 0.30; p = 0.0171) and published more peer-reviewed articles (1.62 vs 1.31; p = 0.0253) than non-participants. Seventy-two undergraduates (75.79%) and thirty-eight advisors (80.85%) responded to the questionnaire. The overall satisfaction was scored as 78.18/100 and 72.36/100 among advisors and students, respectively. Interest was considered the best motivation for participation by students (3.81/5.00) and advisors (4.00/5.00). The research program was beneficial to students' overall career development. Essential roles played by the dental school, faculty and undergraduates were suggested to improve the research environment. CONCLUSION: The dental undergraduate research program has positive effects on students' academic performance. The support of the dental school, the engagement of qualified faculty, the interest and autonomy of students, and camaraderie among these three key elements are essential for the research program in the future.

16.
Biomater Sci ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32960197

RESUMO

Infections involving methicillin-resistant Staphylococcus aureus present great challenges, especially when biofilms and persister cells are involved. In this work, an α/ß chimeric polypeptide molecular brush (α/ß CPMB) is reported to show excellent performance in inhibiting the formation of biofilms and eradicating established biofilms. Additionally, the polymer brush efficiently killed metabolically inactive persister cells that are antibiotic-insensitive. Antimicrobial mechanism studies showed that α/ß CPMB causes membrane disturbance and a substantial increase in reactive oxygen species (ROS) levels to kill bacteria, and mesosome-like structure formation was also observed. Furthermore, the polymer brush was able to kill clinically isolated multidrug resistant Gram-positive bacteria with no risk of antimicrobial resistance. The α/ß CPMB has demonstrated great potential in addressing the great challenge of eradicating multidrug resistant Gram-positive bacterial infections.

17.
Fish Shellfish Immunol ; 106: 833-843, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32891790

RESUMO

Liver-expressed antimicrobial peptide-2 (LEAP-2) is a member of the antimicrobial peptides family. Research has demonstrated that LEAP-2 contains a number of cations and plays a key role in the innate immune system of organism. In this study, we cloned and identified TroLEAP-2, from the golden pompano (Trachinotus ovatus), and analyzed its functions in vivo and in vitro. Results showed that TroLEAP-2 contains a 321 bp open reading frame (ORF) that encodes 106 putative amino acids with a molecular weight of 11.65 kDa. The mature TroLEAP-2 peptide possesses four conserved cysteine residues, which can form a core structure with two disulfide bonds between the cysteine residues in the relative 1-3 (Cys 77 and Cys 88) and 2-4 (Cys 83 and Cys 93) positions. It has a high amino acid sequence similarity (38.68%-83.02%) with the liver-expressed antimicrobial peptide -2 of other teleosts. Phylogenetic analysis showed that TroLEAP-2 clustered with the LEAP-2 of Paralichthys olivaceus and Miichthy milluy. TroLEAP-2 was most abundantly expressed in the liver, spleen, and kidney, and was significantly upregulated during Edwardsiella tarda and Streptococcus agalactiae infection. Purified recombinant TroLEAP-2 (rTroLEAP-2) could significantly inhibit the in vitro growth of E. tarda and S. agalactiae. Overexpression of TroLEAP-2 in vivo was shown to significantly reduce E. tarda and S. agalactiae colonization of tissues, whereas its knockdown resulted in an increase of bacteria in fish tissues. We also saw that TroLEAP-2 overexpression significantly improved macrophage activation in vivo. Moreover, TroLEAP-2 can induce the expression of nonspecific immune-related genes. These results showed that it might play a significant role in the innate immune system of golden pompano. In conclusion, our results indicate that TroLEAP-2 plays an important role in antibacterial immunity and provides a new avenue for protection against pathogenic infections in golden pompano.

18.
Nutrients ; 12(9)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872103

RESUMO

BACKGROUND: The effect of obesity in early adulthood and weight loss on incident hypertension in older age has not been well characterized. This study aimed to examine the association of weight loss from young adulthood to midlife with risk of incident hypertension later in life. METHODS: We performed a retrospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES). Five weight change groups were categorized: stable normal, weight loss, weight gain, maximum overweight and stable obese. The hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between weight change and risk of hypertension in later life were estimated using Cox regression models. RESULTS: Compared with participants who maintained normal weight, the stable obese, weight gain, maximum overweight and weight loss groups exhibited significantly higher risks of incident hypertension, with HR of 3.28 (95% CI = 2.71 to 3.96), 2.93 (95% CI = 2.62 to 3.28), 1.76 (95% CI = 1.55 to 2.00) and 1.97 (95% CI = 1.17 to 3.31), respectively. We also observed a lower risk among those in the weight loss group (HR = 0.60, 95% CI = 0.35 to 1.02) compared with those who were stable obese. CONCLUSIONS: Weight loss from early to middle adulthood was associated with lower risk of incident hypertension as compared to those who stayed obese and higher risk of incident hypertension as compared to those who maintained normal weight. Thus, maintaining normal weight throughout adulthood may be important for the primary prevention of hypertension.

19.
Biosens Bioelectron ; 169: 112572, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916610

RESUMO

Convalescent serum with a high abundance of neutralization IgG is a promising therapeutic agent for rescuing COVID-19 patients in the critical stage. Knowing the concentration of SARS-CoV-2 S1-specific IgG is crucial in selecting appropriate convalescent serum donors. Here, we present a portable microfluidic ELISA technology for rapid (15 min), quantitative, and sensitive detection of anti-SARS-CoV-2 S1 IgG in human serum with only 8 µL sample volume. We first identified a humanized monoclonal IgG that has a high binding affinity and a relatively high specificity towards SARS-CoV-2 S1 protein, which can subsequently serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. We then measured the abundance of anti-SARS-CoV-2 S1 IgG in 16 convalescent COVID-19 patients. Due to the availability of the calibration standard and the large dynamic range of our assay, we were able to identify "qualified donors" for convalescent serum therapy with only one fixed dilution factor (200 ×). Finally, we demonstrated that our technology can sensitively detect SARS-CoV-2 antigens (S1 and N proteins) with pg/mL level sensitivities in 40 min. Overall, our technology can greatly facilitate rapid, sensitive, and quantitative analysis of COVID-19 related markers for therapeutic, diagnostic, epidemiologic, and prognostic purposes.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/virologia , Ensaio de Imunoadsorção Enzimática/instrumentação , Imunoglobulina G/sangue , Técnicas Analíticas Microfluídicas/instrumentação , Pneumonia Viral/virologia , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Antígenos Virais/sangue , Antígenos Virais/imunologia , Técnicas Biossensoriais/economia , Técnicas Biossensoriais/instrumentação , Infecções por Coronavirus/terapia , Ensaio de Imunoadsorção Enzimática/economia , Desenho de Equipamento , Humanos , Imunização Passiva , Imunoglobulina G/imunologia , Limite de Detecção , Medições Luminescentes/economia , Medições Luminescentes/instrumentação , Técnicas Analíticas Microfluídicas/economia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Fatores de Tempo , Adulto Jovem
20.
Lab Chip ; 20(20): 3815-3823, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32926039

RESUMO

Stimulus-responsive optical polymers, especially gels, are enabling new-concept energy-transducing "smart" optics. Full exploitation of their molecule-derived tuning and integration with traditional micro/nano-optics/optoelectronics rely on the implementation of devices by advanced "intelligent" micro/nano-manufacturing technologies, especially photolithographies with wide compatibility. In light of the increasing need for an organic combination of smart optical materials and digital micro/nano-manufacturing, novel "smart" optical micro-switches, namely, stimulus-actuated Mach-Zehnder interferometers as a proof-of-concept demonstration, were prototyped with protein-based hydrogels via aqueous multiphoton femtosecond laser direct writing (FsLDW). Protein-based Mach-Zehnder-interferometric smart optical devices here display a morphological quality sufficient for optical applications (average surface roughness ≤∼20 nm), nano-precision three-dimensional (3D) geometry of these millimeter-scale devices and purposely structured distribution of photo-crosslinking degree. Moreover, the device configuration was customized with unbalanced branches in which meticulous stimulus-responsive ability can be realized by simply tuning the surrounding chemical stimuli (i.e., Na2SO4 concentration here). The "heterogeneous" configuration with unbalanced branches (i.e., different optical and stimulus-responsive features) exhibits as-designed "smart" switching of propagated near-infrared light (∼808 nm). These capabilities, along with total biodegradation, indicate the application promise of this gel-based optic construction strategy towards novel "intelligent", bio/eco-friendly, self-tuning or sensing photonic integrated systems like optofluidics.

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