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1.
Cell Transplant ; 30: 963689720980367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33586472

RESUMO

The present study aimed to investigate the effect and possible mechanism of recombinant human thrombopoietin (rhTPO) on mouse 32D cells (a mouse myeloid progenitor cell line) treated with serum from patients with aplastic anemia and to elucidate the potential mechanism of rhTPO in the treatment of aplastic anemia. After treatment with aplastic anemia serum, the apoptotic rate of 32D cells was increased and the proliferation of 32D cells was significantly inhibited. rhTPO reduced the apoptotic rate and promoted the proliferation of 32D cells, while rhTPO failed to restore the cell proliferation of 32D cells from aplastic anemia serum group to the normal level as compared to that from the normal serum group. The phosphorylation level of STAT3 protein was higher, and the phosphorylation level of STAT5 protein was lower in 32D cells from aplastic anemia serum group than that in normal serum group. After rhTPO treatment, the phosphorylation level of STAT3 protein in aplastic anemia serum group was decreased and the phosphorylation level of STAT5 protein was increased. The expression levels of Survivin and Bcl-2 were significantly decreased in 32D cells from aplastic anemia serum group, which were significantly increased after rhTPO treatment. The expression level of Bax protein in 32D cells from the normal serum group after rhTPO treatment was significantly decreased; while the mRNA expression level of Bax was not affected by rhTPO. The expression levels of Bax mRNA and protein were significantly up-regulated in 32D cells from aplastic anemia serum group, which was significantly decreased by rhTPO treatment. In conclusion, our results indicated that aplastic anemia serum impaired proliferative potential and enhanced apoptosis of 32D cells. Further mechanistic studies revealed that rhTPO promoted cell proliferation and attenuated apoptosis of aplastic anemia serum-treated 32D cells via activating STAT3/STAT5 signaling pathway and modulating apoptosis-related mediators.

2.
J Org Chem ; 86(2): 1462-1470, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33410687

RESUMO

Nitidumpeptins A and B (1 and 2), two novel cyclic hexapeptides, were isolated from the herb Zanthoxylum nitidum var. tomentosum. Their planar structures were elucidated based on NMR and MS spectrometric analysis, and the absolute configurations were determined by the Marfey's method. Structurally, 1 is a unique peptide with a backbone bearing a pyrrolidine-2,5-dione unit, which is the first occurrence moiety specifically in a naturally occurring cyclohexapeptide. The total synthesis of 1 and 2 was achieved by solution-phase in parallel with solid-phase peptide synthesis, and their absolute configurations were further confirmed. The combination of 2 with gefitinib exhibited synergistic antiproliferative activity in acquired gefitinib-resistant non-small cell lung cancer cells (HCC827-gef). The underlying mechanism for the antiproliferative activity of 2 was in part associated with the suppression of YAP expression in HCC827-gef cells.

3.
Cell Death Dis ; 12(1): 46, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33414441

RESUMO

The rising of a highly aggressive subtype of castration-resistant prostate cancer (CRPC) named treatment-induced neuroendocrine prostate cancer (t-NEPC) after androgen deprivation therapy (ADT) is well known for its features of the neuroendocrine differentiation (NED) and androgen receptor (AR) independence. However, t-NEPC is still largely unknown. Here, we found that EHF is notably depressed in t-NEPC tumors, patient-derived xenografts, transgenic mice, and cell models. Results from cell lines uncovered that ADT represses EHF expression, which is required for the ADT-induced NED. Mechanism dissection revealed that ADT decreases the EHF transcription via relieving the AR binding to different androgen-responsive elements, which then promotes the expression and enzymatic activity of enhancer of zeste homolog 2 (EZH2), consequently catalyzing tri-methylation lysine 27 of histone H3 for transcriptional repression of its downstream genes to promote the NED. Furthermore, preclinical studies from cell and mice models proved that recovery of EHF expression or using EZH2 inhibitor can attenuate aggressive properties of CRPC cells, hinder the progression of t-NEPC, and promote the response of CPRC cells to enzalutamide. Together, we elucidate that the ADT/AR/EHF/EZH2 signaling is required for the ADT-enhanced NED and plays a critical role in the progression of t-NEPC.

4.
Water Res ; 191: 116791, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433334

RESUMO

Medetomidine has been authorized in ship hull paints as an antifouling biocide under the biocidal product regulation in Europe since 2016. Its release into marine systems causes concerns over persistence and toxicity. However, the environmental fate of medetomidine has not been fully investigated. In this study, the photodegradation of medetomidine under natural sunlight conditions was investigated using collected coastal and sea waters. In addition, the phototransformation of medetomidine with reactive species (i.e., singlet oxygen, excited triplet state organic matter, and hydroxyl radicals) under UVA light was examined. Photoproducts were isolated by high-performance liquid chromatography (HPLC), identified by a combination of nuclear magnetic resonance (NMR) spectroscopy and time-of-flight mass spectrometry (qTOF), and reaction mechanisms were proposed. The results show that medetomidine is a neutral base (pKa of protonated form = 7.2) that leads to two different protonation states in the aquatic environment. Photodegradation of neutral medetomidine was dominated by reaction with singlet oxygen, while protonated medetomidine was relatively photostable. The contribution of reactive species to the overall photodegradation of neutral medetomidine was calculated to provide an assessment of phototransformation of medetomidine. The half-live of medetomidine was < 1.5 days in natural waters (pHcoastal = 8.3; pHsea = 8.1) under sunlit near-surface conditions, suggesting that it is not persistent in the aquatic environment. Because medetomidine has a relatively short half-life in sunlit aquatic ecosystems, a number of products, such as 2-(2,3-dimethylphenyl)propanamide, can be formed by photochemical reactions of medetomidine, with unknown consequences for marine and coastal waters.


Assuntos
Medetomidina , Poluentes Químicos da Água , Ecossistema , Europa (Continente) , Cinética , Fotólise , Poluentes Químicos da Água/análise
5.
Aerosp Med Hum Perform ; 92(2): 92-98, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33468289

RESUMO

BACKGROUND: The effects of seasickness on working performance during motion exposure have been reported, while the aftereffects on working ability and life quality decline (WLD) still remain unclarified.METHODS: Two cohorts of healthy male Chinese subjects received either a single (SSV) or repeated (RSV) sea voyage training program on different vessels. A seasickness incidence (SSI) questionnaire was administered to assess the prevalence of seasickness symptoms (vomiting, nausea, other, or no symptoms). A WLD questionnaire was used to survey the general feeling of WLD (severe, moderate, slight, and none) by a 4-point score as well as the incidence rate (IR) of specific WLD items within 24 h after landing.RESULTS: The RSV cohort had lower overall IR of WLD than the SSV cohort (54.64% vs. 63.78%, N 657 for both cohorts). The landing ship trainees in both cohorts showed higher general WLD score and higher IRs of physical fatigue, sleep disorder, and spontaneous locomotion decrement than those trained on the small vessels. Subjects with vomiting or nausea had higher general WLD score and higher IRs of concentration distraction, physical fatigue, anorexia, and spontaneous locomotion decrement than those with no symptoms. Higher IRs of firing accuracy decline (SSV: 21.35% vs. 7.13%, 9.14%; RSV: 22.11% vs. 9.28%, 5.27%), equipment operation disturbance (SSV: 16.85% vs. 3.57%, 6.85%; RSV: 20.47% vs. 7.85%, 7.03%) were also observed in the vomiting subjects than those with other symptoms and no symptoms.DISCUSSION: Significant WLD after landing was associated with transportation types, seasickness severity, and habituation during sea voyage training.Qi R-R, Xiao S-F, Su Y, Mao Y-Q, Pan L-L, Li C-H, Lu Y-L, Wang J-Q, Cai Y-L. Sea voyage training and motion sickness effects on working ability and life quality after landing. Aerosp Med Hum Perform. 2021; 92(2):9298.


Assuntos
Militares , Enjoo devido ao Movimento/fisiopatologia , Enjoo devido ao Movimento/psicologia , Qualidade de Vida , Navios , Adolescente , Adulto , China/epidemiologia , Humanos , Incidência , Masculino , Enjoo devido ao Movimento/epidemiologia , Prevalência , Inquéritos e Questionários
6.
Artigo em Inglês | MEDLINE | ID: mdl-33475683

RESUMO

Importance: During the novel coronavirus disease 2019 pandemic, telehealth has become a vital component of health care delivery. For otolaryngology evaluations, examination of the ear and oropharynx is important but difficult to achieve remotely. Objective: To assess the feasibility of patient use of low-cost digital videoscopes and smartphones for examination of the ear and oropharynx. Design, Setting, and Participants: A prospective quality improvement study was conducted in an academic adult otolaryngology clinic including 23 patients who presented for an in-person appointment and owned a smartphone device. The study was conducted from July 1 to 15, 2020. Interventions: Participants were asked to capture pictures and videos of their ear canals and oropharynx with digital videoscopes and their smartphones under real-time guidance over a telehealth platform. They were then surveyed about their experience. Main Outcomes and Measures: The primary outcomes were ratings by health care clinicians and a blinded otolaryngologist reviewer of image acceptability. Secondary outcomes included participant time to image acquisition and willingness to purchase digital videoscopes for telehealth use. Results: Of the 23 participants included, 14 were women (61%); mean age was 50 years (range, 21 to 80 years). Of the images obtained using the digital otoscope ear examination, 95% were considered acceptable by the health care clinicians and 91% were considered acceptable by the blinded reviewer; 16 participants (70%) reported that the otoscope was easy to use. The mean time to acquire images for both ears was 114 seconds (95% CI, 84-145 seconds). Twenty-one participants (91%) were willing to pay for a digital otoscope for telehealth use. For the oropharyngeal examination, a greater proportion of smartphone video examinations were considered acceptable by clinicians (63% acceptability) and the blinded reviewer (55%) compared with the digital endoscope (clinicians, 40%; blinded reviewer, 14%). The mean time required for the oropharyngeal examination smartphone video capture was shorter at 35 seconds compared with both the digital endoscope (difference, -27 seconds; 95% CI, -7 to -47 seconds) and smartphone photo capture (difference, -53 seconds; 95% CI, -20 to -87 seconds). Conclusions and Relevance: Digital otoscopes and smartphones apparently can facilitate remote head and neck physical examination in telehealth. Digital otoscopes were useful for ear examinations, and smartphone videos appeared to be the most useful for oropharyngeal examinations. Further studies are required to determine specific diagnostic capabilities in various telehealth practice settings.

7.
Appl Ergon ; 92: 103312, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33338973

RESUMO

Profile of cybersickness and balance disturbance induced by virtual ship motion alone and in combination with galvanic vestibular stimulation (GVS) remained unclear. Subjects were exposed to a ship deck vision scene under simulated Degree 5 or 3 sea condition using a head-mounted virtual reality display with or without GVS. Virtual ship motion at Degree 5 induced significant cybersickness with symptom profile: nausea syndrome > central (headache and dizziness) > peripheral (cold sweating) > increased salivation. During a single session of virtual ship motion exposure, GVS aggravated balance disturbance but did not affect most cybersickness symptoms except cold sweating. Repeated exposure induced cybersickness habituation which was delayed by GVS, while the temporal change of balance disturbance was unaffected. These results suggested that vestibular inputs play different roles in cybersickness and balance disturbance during virtual reality exposure. GVS might not serve as a potential countermeasure against cybersickness induced by virtual ship motion.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33381887

RESUMO

The reversibility of metal anode is a fundamental challenge to the lifetime of rechargeable batteries. Though being widely employed in aqueous energy storage systems, metallic zinc suffers from dendrite formation that severely hinders its applications. Here we report texturing Zn as an effective way to address the issue of zinc dendrite. An in-plane oriented Zn texture with preferentially exposed (002) basal plane is demonstrated via a sulfonate anion-induced electrodeposition, noting no solid report on (002) textured Zn till now. Anion-induced reconstruction of zinc coordination is revealed to be responsible for the texture formation. Benchmarking against its (101) textured-counterpart by the conventional sulphate-based electrolyte, the Zn (002) texture enables highly reversible stripping/plating at a high current density of 10 mA cm-2 , showing its dendrite-free characteristics. The Zn (002) texture-based aqueous zinc battery exhibits excellent cycling stability. The developed anion texturing approach provides a pathway towards exploring zinc chemistry and prospering aqueous rechargeable batteries.

9.
Pediatr Pulmonol ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331678

RESUMO

PURPOSE: Comparing the efficacy of a deep-learning model in classifying the etiology of pneumonia on pediatric chest X-rays (CXRs) with that of human readers. METHODS: We built a clinical-pediatric CXR set containing 4,035 patients to exploit a deep-learning model called Resnet-50 for differentiating viral from bacterial pneumonia. The dataset was split into training (80%) and validation (20%). Model performance was assessed by receiver operating characteristic curve and area under the curve (AUC) on the first test set of 400 CXRs collected from different studies. For the second test set composed of 100 independent examinations obtained from the daily clinical practice at our institution, the kappa coefficient was selected to measure the inter-rater agreement in a pair-wise fashion for the reference standard, all reviewers and the model. Gradient-weighted class activation mapping (Grad-CAM) was used to visualize the significant areas contributing to the model prediction. RESULTS: On the first test set, the best-performing classifier achieved an AUC of 0.919 (P < 0.001), with a sensitivity of 79.0% and specificity of 88.9%. On the second test set, the classifier achieved a performance similar to that of human experts, which resulted in a sensitivity of 74.3% and specificity of 90.8%, positive and negative likelihood ratios of 8.1 and 0.3 respectively. Contingence tables and kappa values further revealed that expert reviewers and model reached substantial agreements on differentiating the etiology of pediatric pneumonia. CONCLUSIONS: This study demonstrated that the model performed similarly as human reviewers and recognized the regions of pathology on CXRs. This article is protected by copyright. All rights reserved.

10.
ACS Nano ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33350807

RESUMO

Plasmonic metal nanoparticles exhibit large dipole moments upon photoexcitation and have the potential to induce electronic transitions in nearby materials, but fast internal relaxation has to date limited the spatial range and efficiency of plasmonic mediated processes. In this work, we use photo-electrochemistry to synthesize hybrid nanoantennas comprised of plasmonic nanoparticles with photoconductive polymer coatings. We demonstrate that the formation of the conductive polymer is selective to the nanoparticles and that polymerization is enhanced by photoexcitation. In situ spectroscopy and simulations support a mechanism in which up to 50% efficiency of nonradiative energy transfer is achieved. These hybrid nanoantennas combine the unmatched light-harvesting properties of a plasmonic antenna with the similarly unmatched device processability of a polymer shell.

11.
Acta Physiol (Oxf) ; : e13602, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33315278

RESUMO

AIM: Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, exerts multiple protective effects against cardiovascular diseases, including cardiac hypertrophy. However, the molecular mechanism underlying its anti-hypertrophic effect has not been clarified. This study revealed that EGCG could inhibit pressure overload-induced cardiac hypertrophy by regulating the PSMB5/Nmnat2/SIRT6-dependent signalling pathway. METHODS: Quantitative real-time polymerase chain reaction and western blotting were used to determine the expression of mRNA and protein respectively. A fluorometric assay kit was used to determine the activity of SIRT6, a histone deacetylase. Luciferase reporter gene assay and electrophoretic mobility shift assay were employed to measure transcriptional activity and DNA binding activity respectively. RESULTS: EGCG could significantly increase Nmnat2 protein expression and enzyme activity in cultured neonatal rat cardiomyocytes stimulated with angiotensin II (Ang II) and heart tissues from rats subjected to abdominal aortic constriction. Nmnat2 knockdown by RNA interference attenuated the inhibitory effect of EGCG on cardiac hypertrophy. EGCG blocked NF-κB DNA binding activity induced by Ang II, which was dependent on Nmnat2 and the subsequent SIRT6 activation. Moreover the activation of PSMB5 (20S proteasome subunit ß-5, chymotrypsin-like) was required for EGCG-induced Nmnat2 protein expression. Additionally, we demonstrated that EGCG might interact with PSMB5 and inhibit the activation of the proteasome. CONCLUSIONS: These findings serve as the first evidence that the effect of EGCG against cardiac hypertrophy may be, at least partially, attributed to the modulation of the PSMB5/Nmnat2-dependent signalling pathway, suggesting the therapeutic potential of EGCG in the prevention and treatment of cardiac hypertrophy.

12.
Aging (Albany NY) ; 122020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33231563

RESUMO

In this study, we performed bioinformatics analysis to identify the competing endogenous RNAs (ceRNAs) that regulate bladder cancer (BCa) progression. RNA-sequencing data analysis identified 2451 differentially expressed mRNAs, 174 differentially expressed lncRNAs, and 186 microRNAs (miRNAs) in BCa tissues (n=414) compared to the normal urothelial tissues (n=19) from the TGCA database. CeRNA network analysis of the differentially expressed lncRNAs and mRNAs showed strong positive correlation between lncRNA MAGI2-AS3 and Tensin 1 (TNS1) mRNA in BCa tissues. Bioinformatics analysis also showed that both MAGI2-AS3 and TNS1 mRNA sequences contain miR-31-5p binding sites. Furthermore, we observed significantly lower MAGI2-AS3 and TNS1 mRNA expression and higher miR-31-5p expression in the BCa tissues and cell lines (T24 and J82) compared with their corresponding controls. Functional and biochemical experiments in BCa cell lines including luciferase reporter assays showed that MAGI2-AS3 upregulated TNS1 by sponging miR-31-5p. Transwell assays showed that the MAGI2-AS3/miR-31-5p/TNS1 axis regulated migration and invasion ability of BCa cell lines. Moreover, immunohistochemical staining of paired BCa and normal urothelial tissues showed that low expression of TNS1 correlated with advanced tumor (T) stages and lymph node metastasis in BCa. In conclusion, our study demonstrates that the MAGI2-AS3/miR-31-5p/TNS1 axis regulates BCa progression.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33146832

RESUMO

PURPOSE: To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months. METHODS: Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12. RESULTS: At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P < 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 µm at baseline to 308.73 ± 106.80 µm (P < 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mm3 at baseline to 8.32 ± 0.84 mm3 at end-point (P < 0.001). The mean volume of pigment epithelial detachment (PED) decreased from 0.73 ± 0.97 mm3 at baseline to 0.48 ± 0.71 mm3 (P < 0.05) at month 3. At month 12, the mean volume of PED was 0.57 ± 0.80 mm3 (P > 0.05 compared to baseline). After the 3-monthly loading injections, 6 eyes (20.0%) showed complete polyp regression, whereas a total of 19 eyes (63.5%) showed complete regression at month 12. The average injections given per subject were 7.70 ± 1.81. CONCLUSION: Intravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

15.
Kidney Int Rep ; 5(10): 1679-1689, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33102960

RESUMO

Introduction: Prior cross-sectional studies suggest that health-related quality of life (HRQOL) worsens with more severe glomerular disease. This longitudinal analysis was conducted to assess changes in HRQOL with changing disease status. Methods: Cure Glomerulonephropathy (CureGN) is a cohort of patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA vasculitis, or IgA nephropathy. HRQOL was assessed at enrollment and follow-up visits 1 to 3 times annually for up to 5 years with the Patient-Reported Outcomes Measurement Information System (PROMIS). Global health, anxiety, and fatigue domains were measured in all; mobility was measured in children; and sleep-related impairment was measured in adults. Linear mixed effects models were used to evaluate HRQOL responsiveness to changes in disease status. Results: A total of 469 children and 1146 adults with PROMIS scores were included in the analysis. HRQOL improved over time in nearly all domains, though group-level changes were modest. Edema was most consistently associated with worse HRQOL across domains among children and adults. A greater number of symptoms also predicted worse HRQOL in all domains. Sex, age, obesity, and serum albumin were associated with some HRQOL domains. The estimated glomerular filtration rate (eGFR) was only associated with fatigue and adult physical health; proteinuria was not associated with any HRQOL domain in adjusted models. Conclusion: HRQOL measures were responsive to changes in disease activity, as indicated by edema. HRQOL over time was not predicted by laboratory-based markers of disease. Patient-reported edema and number of symptoms were the strongest predictors of HRQOL, highlighting the importance of the patient experience in glomerular disease. HRQOL outcomes inform understanding of the patient experience for children and adults with glomerular diseases.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33095455

RESUMO

OBJECTIVES: Nutrition status is of great significance to the clinical outcome after major abdominal surgery. However, the effect of preoperative short-term parenteral nutrition (PN) support among gastric cancer (GC) patients remains unknown and was evaluated in the current study. METHODS: We retrospectively analyzed 455 nutritionally at-risk GC patients after radical resection from 2010 to 2016. We matched patients with 3-7 days of PN support to those without PN support. χ2 And Mann-Whitney U tests were used to compare differences between the PN and control groups. RESULTS: The propensity-matched sample included 368 GC patients (PN group, n = 184; control group, n = 184). The PN and control groups did not differ regarding postoperative complications (P = .528). The incidence of anastomotic leakage in the PN group was lower than in the control group (P = .011), whereas other complications were not found to differ between the groups. The hospitalization cost of the PN group was significantly higher than that of the control group (P < .001), whereas other outcome indicators were similar. Subgroup analysis showed that short-term PN support may have an improved benefit for patients with serum albumin level <35 g/L, but not at the level of statistical significance (P = .17). CONCLUSION: Short-term PN support did not significantly improve the short-term clinical outcomes of nutritionally at-risk GC patients, with the exception of a lower incidence of anastomotic leakage. Considering that short-term PN support increases economic burden, PN should not be the preferred method among these patients.

17.
Front Psychiatry ; 11: 576135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33088278

RESUMO

Objective: This study investigated the effects of acute or chronic ketamine administration on learning and memory function as well as levels of brain-derived neurotrophic factor (BDNF) in the hippocampus and blood in order to explore the potential correlation between learning-memory dysfunction and ketamine. Methods: Rats were treated with 25 mg/kg ketamine for 3 d (n = 20) or 14 d (n = 20). Saline-treated rats were used as controls. The Morris water maze test was used to evaluate spatial learning and memory after 10 d of withdrawal. The level of BDNF in serum and the hippocampus were measured by ELISA. Results: The number of platform crossings and residence time in the target platform quadrant were significantly reduced in ketamine 3 d and 14 d groups than in the saline controls (both p < 0.05). In addition, the average escape latency of ketamine 3 d and 14 d groups were significantly longer than that of the saline 3 d and 14 d groups (p < 0.0001), respectively. Further examination found that only serum samples from ketamine 14 d group showed significantly decreased BDNF level compared to that from saline 14 d groups (p < 0.05). However, no differences were detected in hippocampus samples. Conclusion: Chronic ketamine exposure (25 mg/kg) causes spatial learning and memory deficits in SD rats, which may be associated with decreased serum BDNF levels.

18.
Exp Neurol ; 334: 113490, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33007295

RESUMO

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) have a common pathology. Both diseases are characterized by local deposition of amyloid proteins in the brain or islet organ, but their phenotypes and clinical manifestation vary widely. Although the sources of islet amyloid polypeptide (IAPP) and amyloid beta (Aß) are independent, their fibrillar sequences are highly homologous. The prevalence of AD in T2DM populations is considerably higher than that in the normal population, but a mechanistic linkage remains elusive. Therefore, the present study aimed to explore the effects of Aß42 deposition in the brain on the persistently expression of human IAPP (hIAPP). Additionally, cognitive ability, synaptic plasticity, the state of neural stem cells and mitochondrial function were evaluated at 2 or 6 months after stereotaxically injected the oligomer Aß1-42 into the dentate gyrus of hIAPP (-/+) mice or the wild-type littermates. We found that Aß42 and amylin were co-located in hippocampus and Aß42 levels increased when Aß1-42 was injected in hIAPP transgenic mice compared with that of the wild-type littermates. Furthermore, at 6 months after Aß1-42 injection in hIAPP (-/+) mice, it exhibits exacerbated AD-related pathologies including Aß42 deposition, cognitive impairment, synapse reduction, neural stem cells exhaustion and mitochondrial dysfunction. Our present study suggested that hIAPP directly implicated the Aß42 production and deposition as an important linkage between T2DM and AD.

19.
Planta ; 252(5): 88, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057902

RESUMO

MAIN CONCLUSION: Xanthomonas campestris pv. campestris 8004 secretes several effector proteins that interfere with plant phosphorylation. Xanthomonas campestris pv. campestris (Xcc) can infect cruciferous plants and cause black rot. The strain Xcc8004 secretes effector proteins that interfere with plant cellular processes into host cells using a type III secretion (T3S) system. Several of the 24 predicted T3S effectors in the Xcc8004 genome have been implicated in the suppression of the Arabidopsis thaliana pattern-triggered immunity (PTI) response. We used an A. thaliana mesophyll protoplast-based assay to identify Xcc8004 T3S effectors that effectively interfere with PTI signalling induced by the bacterial peptide flg22. 11 of the 24 tested effector proteins (XopK, XopQ, HrpW, XopN, XopAC, XopD, XopZ1, XopAG, AvrBs2, XopL and XopX-1) inhibited expression of the flg22-inducible gene FRK1, and five effectors (XopK, XopG, XopQ, XopL and XopX-1) inhibited the expression of the flg22-inducible gene WRKY33. Therefore, there are 12 effector proteins that can inhibit the expression of relevant flg22-inducible genes. It was further investigated whether the 12 effector proteins affect the phosphorylation activation of mitogen-activated protein (MAP) kinases MPK3/MPK6, and four effector proteins (XopK, XopQ, XopZ1 and XopX-1) were found to markedly inhibit MPK3/MPK6 activation. Moreover, a subcellular localisation analysis revealed that the tested effectors were localised within various subcellular compartments. These results indicate that multiple T3S effectors in the Xcc8004 genome interfere with flg22-induced PTI signalling via various molecular mechanisms.

20.
Medicine (Baltimore) ; 99(40): e21668, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019384

RESUMO

BACKGROUND: One of the major challenges in nursing and medical education is to foster the critical thinking ability and autonomous learning ability for students. But the effect of different teaching methods on these abilities of nursing or medical students has not been conclusive, and few studies have directly compared the differences in the effects of different teaching methods. As a result, it is necessary for students to evaluate the impact of different teaching methods on critical thinking ability and autonomous learning ability. METHODS: A systematic search will be performed using Chinese National Knowledge Infrastructure, Wanfang Data (Chinese database), VIP Information (Chinese database), Chinese Biomedical Literature, and English language databases, including PubMed and Embase, Web of Science, CINAHL Complete (EBSCO0, Cochrane library to identify relevant studies from inception to July 10, 2020. We will include random controlled trials that evaluated the different teaching methods. The Quality Assessment of Diagnostic Accuracy Studies 2 quality assessment tool will be used to assess the risk of bias in each study. Standard pairwise meta-analysis and network meta-analysis will be performed using STATA V.12.0, MetaDiSc 1.40, and R 3.4.1 software to compare the diagnostic efficacy of different hormonal biomarkers. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will summarize the direct and indirect evidence to determine the effectiveness of different teaching methods for medical or nursing students and attempt to find the most effective teaching method. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required, because this study is a meta-analysis based on published studies. INPLASY REGISTRATION NUMBER: INPLASY202070017.


Assuntos
Educação Médica/métodos , Educação em Enfermagem/métodos , Currículo , Educação Médica/normas , Educação em Enfermagem/normas , Humanos , Metanálise em Rede , Aprendizagem Baseada em Problemas/métodos , Revisões Sistemáticas como Assunto , Pensamento
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