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1.
J Clin Med ; 10(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34768551

RESUMO

Serum vascular endothelial growth factor (VEGF) is involved in follicular vascularization, oxygenation, and consequently in oocyte maturation and embryo development. Unanswered questions remain regarding the relationship of intrafollicular VEGF level in preovulatory leading follicles to oocyte maturation and ovarian reserve during ovarian stimulation. We conducted this study to investigate the relationship of intrafollicular VEGF level in the fluid of single preovulatory leading follicles to ovarian reserve and oocyte maturation in patients receiving GnRH antagonist in vitro fertilization (IVF) protocol treatment. One hundred and eighty-five patients receiving IVF treatment were recruited and assigned to low-, normal-, and high-ovarian-reserve groups according to their serum anti-Müllerian hormone (AMH) level. Follicular fluid (FF) in preovulatory leading follicles, serum profiles, and clinical variables were collected for analysis. The result disclosed a significant among-group difference in FF VEGF concentration. Moreover, the serum AMH level was also negatively correlated with FF VEGF level. The oocyte maturation rate tended to be increased at higher AMH levels. FF VEGF concentration was significantly positively correlated with basal FSH level. In conclusion, FF VEGF concentration has a negative association with ovarian reserve level and oocyte maturation rate in patients undergoing GnRH antagonist IVF protocols.

2.
Front Plant Sci ; 12: 740936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721466

RESUMO

In recent years, deep-learning-based fruit-detection technology has exhibited excellent performance in modern horticulture research. However, deploying deep learning algorithms in real-time field applications is still challenging, owing to the relatively low image processing capability of edge devices. Such limitations are becoming a new bottleneck and hindering the utilization of AI algorithms in modern horticulture. In this paper, we propose a lightweight fruit-detection algorithm, specifically designed for edge devices. The algorithm is based on Light-CSPNet as the backbone network, an improved feature-extraction module, a down-sampling method, and a feature-fusion module, and it ensures real-time detection on edge devices while maintaining the fruit-detection accuracy. The proposed algorithm was tested on three edge devices: NVIDIA Jetson Xavier NX, NVIDIA Jetson TX2, and NVIDIA Jetson NANO. The experimental results show that the average detection precision of the proposed algorithm for orange, tomato, and apple datasets are 0.93, 0.847, and 0.850, respectively. Deploying the algorithm, the detection speed of NVIDIA Jetson Xavier NX reaches 21.3, 24.8, and 22.2 FPS, while that of NVIDIA Jetson TX2 reaches 13.9, 14.1, and 14.5 FPS and that of NVIDIA Jetson NANO reaches 6.3, 5.0, and 8.5 FPS for the three datasets. Additionally, the proposed algorithm provides a component add/remove function to flexibly adjust the model structure, considering the trade-off between the detection accuracy and speed in practical usage.

3.
Risk Manag Healthc Policy ; 14: 4545-4552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785963

RESUMO

Objective: The purpose of this study was to establish and verify a risk-scoring system for colorectal adenoma recurrence. Methods: A total of 359 patients with colorectal adenoma who underwent polypectomy from October 2017 to December 2018 were included in this retrospective study. Information including taking traditional Chinese medicine, demographic characteristics, adenoma characteristics were collected. The patients will review the colonoscopy one year after surgery. The patients were divided into a modeling cohort (216 cases) and a model validation cohort (143 cases) according to the ratio of 6:4. Modeling and model verification were performed by logistic regression, ROC curve, nomogram (calibration chart) and other methods. Results: After adjusting for confounding factors by logistic regression, it was found that taking Chinese medicine, the number, size, site, pathological type and morphology of adenoma were independent influencing factors for the recurrence of colorectal adenoma. The area under the ROC curve (AUC) in the model validation cohort of established risk scoring system was 0.771 (95% CI: 0.694-0.847), indicating that there was good consistency. Conclusion: The established risk prediction model of colorectal adenoma recurrence and its risk scoring system performed well and had high predictive value.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34626192

RESUMO

We investigated the efficacy of subxiphoid thoracoscopic thymectomy in patients with myasthenia gravis. The data of 37 consecutive cases were reviewed. 2 cases of postoperative myasthenia gravis crisis and 4 cases of residual mediastinal fat tissue were recorded. Moreover, 29 patients presented the neurological outcomes, and complete stable remission was achieved in 5 (17.2%) cases. Subxiphoid thymectomy is technically feasible. High-quality evidence is warranted before this approach can be recommended.

5.
Mol Nutr Food Res ; 65(21): e2100389, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34496124

RESUMO

SCOPE: The polyphenol xanthohumol (XN) improves dysfunctional glucose and lipid metabolism in diet-induced obesity animal models. Because XN changes intestinal microbiota composition, the study hypothesizes that XN requires the microbiota to mediate its benefits. METHODS AND RESULTS: To test the hypothesis, the study feeds conventional and germ-free male Swiss Webster mice either a low-fat diet (LFD, 10% fat derived calories), a high-fat diet (HFD, 60% fat derived calories), or a high-fat diet supplemented with XN at 60 mg kg-1 body weight per day (HXN) for 10 weeks, and measure parameters of glucose and lipid metabolism. In conventional mice, the study discovers XN supplementation decreases plasma insulin concentrations and improves Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). In germ-free mice, XN supplementation fails to improve these outcomes. Fecal sample 16S rRNA gene sequencing analysis suggests XN supplementation changes microbial composition and dramatically alters the predicted functional capacity of the intestinal microbiota. Furthermore, the intestinal microbiota metabolizes XN into bioactive compounds, including dihydroxanthohumol (DXN), an anti-obesogenic compound with improved bioavailability. CONCLUSION: XN requires the intestinal microbiota to mediate its benefits, which involves complex diet-host-microbiota interactions with changes in both microbial composition and functional capacity. The study results warrant future metagenomic studies which will provide insight into complex microbe-microbe interactions and diet-host-microbiota interactions.

6.
Risk Manag Healthc Policy ; 14: 3701-3709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512057

RESUMO

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Although there are many predictors of death for CAP, there are still some limitations. This study aimed to build a simple and accurate model based on available and common clinical-related feature variables for predicting CAP mortality by adopting machine learning techniques. Methods: This was a single-center retrospective study. The data used in this study were collected from all patients (≥18 years) with CAP admitted to research hospitals between January 2012 and April 2020. Each patient had 62 clinical-related features, including clinical diagnostic and treatment features. Patients were divided into two endpoints, and by using Tensorflow2.4.1 as the modeling framework, a three-layer fully connected neural network (FCNN) was built as a base model for classification. For a comprehensive comparison, seven classical machine learning methods and their integrated stacking patterns were introduced to model and compare the same training and test data. Results: A total of 3997 patients with CAP were included; 205 (5.12%) died in the hospital. After performing deep learning methods, this study established an ensemble FCNN model based on 12 FCNNs. By comparing with seven classical machine learning methods, the area under the curve of the ensemble FCNN was 0.975 when using deep learning algorithms to classify poor from good prognosis based on available and common clinical-related feature variables. The predicted outcome was poor prognosis if the ControlNet's poor prognosis score was greater than the cutoff value of 0.50. To confirm the scientificity of the ensemble FCNN model, this study analyzed the weight of random forest features and found that mainstream prognostic features still held weight, although the model is perfect after integrating other factors considered less important by previous studies. Conclusion: This study used deep learning algorithms to classify prognosis based on available and common clinical-related feature variables in patients with CAP with high accuracy and good generalizability. Every clinical-related feature is important to the model.

7.
Clin Lab ; 67(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34542977

RESUMO

BACKGROUND: With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS: Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS: There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS: The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.


Assuntos
Staphylococcus aureus , Tato , Humanos , Meticilina , Pacientes Ambulatoriais , Staphylococcus
8.
J Cardiothorac Surg ; 16(1): 272, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565438

RESUMO

BACKGROUND: The optimal sequence of pulmonary vessel interruption during lung cancer resection remains controversial. This review aimed to elucidate the association of vein-first versus artery-first ligation and survival of the patients. METHODS: We searched PubMed, Web of Science, Scopus, Embase, Cochrane Library and Google Scholar from their inception to September 2021 for published articles that compared vein-first (the pulmonary vein was interrupted first) and artery-first procedure (the pulmonary artery was ligated first) during lung cancer surgery. RESULTS: Finally, a total of 13 full articles were obtained. First, 7 studies with survival information were included for meta-analyses. As compared with the artery-first ligation, vein-first approach did not decrease the risk of local recurrence (risk ratio [RR] 0.92 in favour of vein-first; 95% confidence interval [CI] 0.61-1.39, p = 0.68) or distant metastasis (RR 0.92; 95% CI 0.30-2.85, p = 0.89); but it was associated with better disease-free survival (RR 0.52; 95% CI 0.37-0.73, p < 0.01) as well as 5-year overall survival (RR 0.60; 95% CI 0.41-0.86, p < 0.01). In addition, the operative time, intraoperative blood loss, total complications, and length of postoperative stay were mainly comparable between the two groups. Second, 7 studies provided the data of tumor cells indicated by different biomarkers and detection methods; and 3 of these reports showed that vein-first ligation decreased the extent of intraoperative tumor dissemination. However, a quantitative meta-analysis was not possible due to the significant heterogeneity. CONCLUSION: Vein-first ligation in lung cancer surgery may be associated with improved survival of the patients, which might be ascribed to potentially lower risk of tumor cell dissemination. Well-designed, large-scale trials are warranted to clarify these occasional findings.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Ligadura , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia , Pneumonectomia , Artéria Pulmonar/cirurgia
9.
Am J Transl Res ; 13(7): 8150-8157, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377299

RESUMO

OBJECTIVE: To determine the clinical significance of serum Cortisol (Cor) levels and adrenal gland size in patients with chronic obstructive pulmonary disease (COPD). METHODS: We assigned 80 patients with COPD admitted to our hospital to an observation group, and 80 healthy individuals to a control group. Serum Cor, C-reactive protein (CRP) level, and adrenal gland size were measured. Patients with COPD were divided into several subgroups according to BODE (BMI, Obstruction, Dyspnea, Exercise capacity) indexes and forced expiratory volume in the first second (FEV1), and Cor levels and adrenal gland size were compared between subgroups. The Pearson Correlation was used to analyze correlations of adrenal gland size and Cor levels with partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), FEV1, forced vital capacity (FVC), and FEV1/FVC. After 30 days' follow-up, the patients were allocated into good-prognosis group and poor-prognosis group. The clinical value of Cor levels in predicting prognosis was estimated by the receiver operating characteristic (ROC) curve. RESULTS: Increased serum CRP levels were found in the observation group, while Cor levels and adrenal gland diameter were decreased (P<0.05 for each comparison). In the observation group, an increase in BODE index or decrease in FEV1 led to decreased Cor levels and adrenal gland diameter, as well as increased CRP levels (P<0.05, each comparison). Correlation analysis showed that adrenal gland diameter and Cor levels were positively correlated with PaO2, FEV1, FVC, and FEV1/FVC, but negatively correlated with PaCO2. The ROC curve indicated that Cor levels were valuable in predicting the prognosis (AUC>0.7, P<0.05). CONCLUSION: Cor levels and adrenal gland size are closely associated with the severity of COPD, and Cor levels are predictive of prognosis.

10.
J Asthma Allergy ; 14: 981-992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408443

RESUMO

Objective: This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma. Methods: Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients. Results: Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies. Conclusion: We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.

11.
BMC Womens Health ; 21(1): 317, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454485

RESUMO

BACKGROUND: To analyze the characteristics of basal thyroid hormone levels in infertile women consulting for assisted reproductive technology (ART) treatment. METHODS: This was a retrospective study. Serum TSH, FT3 and FT4 levels of women seeking ART consultation were tested routinely. Analyses were performed based on age and sampling time. One-way ANOVA or Kruskal-Wallis rank sum test was used to compare the continuous data among the groups, and the chi-square test or Fisher's exact test was used to compare categorical data where appropriate. RESULTS: A total of 6426 women were initially included in the study. After exclusion criteria were applied, the remaining 4126 women were categorized into different groups. The prevalence of subclinical hypothyroidism significantly decreased with age and sampling time, from 21.09 to 11.91% and from 28.57 to 10.67%, respectively (P < 0.001, respectively). Mean serum TSH, FT3, and FT4 levels decreased significantly with age (P = 0.017, < 0.001, < 0.001, respectively). In the context of sampling time, TSH levels from early in the morning were significantly higher (P < 0.001), while FT4 and FT3 levels were similar in different groups (P = 0.258, 0.300, respectively). CONCLUSIONS: The prevalence of subclinical hypothyroidism significantly decreased with increasing age and sampling time, as did the serum TSH levels. Even though, the establishment of reference interval of TSH level based on age or sampling time was not recommended. Full consideration of age and sampling time should be carefully taken before initiation of treatment.


Assuntos
Infertilidade Feminina , Feminino , Humanos , Infertilidade Feminina/epidemiologia , Estudos Retrospectivos , Tireotropina , Tiroxina , Tri-Iodotironina
12.
Nano Lett ; 21(13): 5874-5880, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34197120

RESUMO

The magnetic structures of MnBi2Te4(Bi2Te3)n can be manipulated by tuning the interlayer coupling via the number of Bi2Te3 spacer layers n, while the intralayer ferromagnetic (FM) exchange coupling is considered too robust to control. By applying hydrostatic pressure up to 3.5 GPa, we discover opposite responses of magnetic properties for n = 1 and 2. MnBi4Te7 stays at A-type antiferromagnetic (AFM) phase with a decreasing Néel temperature and an increasing saturation field. In sharp contrast, MnBi6Te10 experiences a phase transition from A-type AFM to a quasi-two-dimensional FM state with a suppressed saturation field under pressure. First-principles calculations reveal the essential role of intralayer exchange coupling from lattice compression in determining these magnetic properties. Such magnetic phase transition is also observed in 20% Sb-doped MnBi6Te10 because of the in-plane lattice compression.

13.
Iran J Immunol ; 18(2): 150-157, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34190696

RESUMO

The role of anti-programmed cell death protein-1 (PD-1) antibody camrelizumab in brain metastases (BMs) from lung adenocarcinoma is uncertain. Herein, for the first time, we report the efficacy of camrelizumab in a patient with chemotherapy-refractory BMs from lung adenocarcinoma. A 49-year-old male non-smoker was admitted with cough and back pain. Primary lung adenocarcinoma with brain and spinal metastases was diagnosed. The specimen from CT-guided lung biopsy showed a positive expression of PD-L1 (~20%).The BMs were enlarged after first-line intravenous pemetrexed/cisplatin and zoledronic acid; whereas second-line camrelizumab demonstrated impressive complete remission of the BMs. The intracranial progression-free survival and overall survival of the patients since the start of the immunotherapy plan prolonged to more than 12 months and 20 months, respectively. In addition, we searched PubMed for relevant studies from inception to May 2020, and a total of 23 reports enrolling 1187 patients also indicated the promising efficacy of immunotherapy for BMs from lung cancer. However, more and better evidence is still needed before a definite conclusion could be drawn.

14.
Biomed Res Int ; 2021: 5525710, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124244

RESUMO

As a powerful antioxidant in the human body, uric acid (UA) has been the subject of increasing research that focused on its influence on Alzheimer's disease (AD) in recent years. The latest literature was gathered to describe the influence of serum uric acid (SUA) level on the onset and progression of AD and to analyze the possibility that SUA is a biomarker of Alzheimer's disease. A large number of existing studies suggested that the SUA level was lower or tended to decrease in patients with AD, and increased SUA level may have a protective effect in AD, which could reduce the risk of onset and slowing the course of the disease. However, some Mendelian randomization analyses suggested that genetically determined uric acid was not associated with AD risk. Existing research results are contradictory due to the high inconsistency of the studies, the selection of subjects, and other factors. UA also showed a strong association with cognitive function, and there appeared to be a gender-selective neuroprotective action. Due to its potent antioxidant properties, the low uric acid level may contribute to oxidative stress to accelerate disease progression. But some preclinical data showed a possibility that in some special cases, UA had a prooxidant properties. The possibility was raised in the discussion of the underlying mechanism that both the low uric acid level and the rapidly progressive course of the disease were the consequence of malnutrition. This paper reviews recent advances in the study of SUA and AD which offers the possibility of new biomarker, new prevention, and treatment strategies for Alzheimer's disease.


Assuntos
Doença de Alzheimer/sangue , Disfunção Cognitiva/sangue , Ácido Úrico/sangue , Doença de Alzheimer/patologia , Doença de Alzheimer/prevenção & controle , Biomarcadores/sangue , Disfunção Cognitiva/patologia , Disfunção Cognitiva/prevenção & controle , Humanos , Fatores de Risco
15.
Cell Biosci ; 11(1): 92, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016172

RESUMO

BACKGROUND: Cigarette smoke (CS) exposure increases corticosteroid insensitive asthma related to increased Th17 phenotype, and new treatment strategies are needed for CS-associated asthma. Histone deacetylase 2 (HDAC2), found in the airway epithelium, is critical for ameliorating glucocorticoids insensitivity. We recently demonstrated the anti-inflammatory effects of CpG oligodeoxynucleotides (CpG-ODNs) on CS-exposure asthma. However, the effects of CpG-ODNs on HDAC2 expression and enzymatic activity remain unclear. This study aimed to assess whether CpG-ODNs protect against excessive Th17 immune responses in CS-induced asthma through HDAC2-dependent mechanisms and compared their effects with those of corticosteroids. METHODS: The effects of CpG-ODNs alone and in combination with budesonide (BUD) on airway inflammation and Th2/Th17-related airway immune responses were determined using an in vivo model of CS-induced asthma and in cultured bronchial epithelial (HBE) cells administered ovalbumin (OVA) and/or cigarette smoke extract (CSE). HDAC2 and retinoid-related orphan nuclear receptor γt (RORγt) expression were also assessed in mouse lung specimens and HBE cells. RESULTS: CpG-ODNs and BUD synergistically attenuated CS exposure asthmatic responses in vivo by modulating the influx of eosinophils and neutrophils, airway remodeling, Th2/Th17 associated cytokine and chemokine production, and airway hyperresponsiveness and blocking RORγt-mediated Th17 inflammation through induced HDAC2 expression/activity. In vitro, CpG-ODNs synergized with BUD to inhibit Th17 cytokine production in OVA- and CSE-challenged HBE cells while suppressing RORγt and increasing epithelial HDAC2 expression/activity. CONCLUSIONS: CpG-ODNs reversed CS-induced HDAC2 downregulation and enhanced the sensitivity of CS-exposed asthmatic mice and CSE-induced HBE cells to glucocorticoid treatment. This effect may be associated with HDAC2 restoration via RORγt/IL-17 pathway regulation, suggesting that CpG-ODNs are potential corticosteroid-sparing agents for use in CS-induced asthma with Th17-biased immune conditions.

16.
Reprod Sci ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33973147

RESUMO

The role of high-normal thyroid-stimulating hormone levels has been of great concern recently. However, the conclusions of different studies are inconsistent. To assess whether high-normal conditions have an impact on reproductive and obstetric outcomes in euthyroid women undergoing ART treatment, a systematic review and meta-analysis was performed. Eligible studies published up to December 30, 2020, were searched from the PubMed, EMBASE, COCHRANE, and CNKI databases. Quality assessment of the included studies, data extraction, and synthesis were performed separately. RevMan 5.2 was used to carry out the meta-analysis. A total of 23 studies that included 25,143 patients were included. We observed similar clinical pregnancy rates (RR = 1.01, 95% CI: 0.99-1.05), miscarriage rates (RR = 0.95, 95% CI: 0.84-1.08), live birth rates (RR = 1.04, 95% CI: 0.99-1.09), birth weights (SMD = 0.07, 95% CI: -0.02 to 0.16), and gestational ages (SMD = 0.07, 95% CI: -0.02 to 0.16) between the high-normal TSH group and low TSH group. Subgroup analysis showed similar results. High-normal TSH levels were associated with similar clinical pregnancy rates, live birth rates, and miscarriage rates to those of women with low TSH levels. The results suggested that preconceptional TSH levels, regardless of potentially being affected by the controlled ovarian stimulation process, had little impact on reproductive and obstetric outcomes and should not be of great concern.

18.
Nat Commun ; 12(1): 3136, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035291

RESUMO

Structural degradation in manganese oxides leads to unstable electrocatalytic activity during long-term cycles. Herein, we overcome this obstacle by using proton exchange on well-defined layered Li2MnO3 with an O3-type structure to construct protonated Li2-xHxMnO3-n with a P3-type structure. The protonated catalyst exhibits high oxygen reduction reaction activity and excellent stability compared to previously reported cost-effective Mn-based oxides. Configuration interaction and density functional theory calculations indicate that Li2-xHxMnO3-n has fewer unstable O 2p holes with a Mn3.7+ valence state and a reduced interlayer distance, originating from the replacement of Li by H. The former is responsible for the structural stability, while the latter is responsible for the high transport property favorable for boosting activity. The optimization of both charge states to reduce unstable O 2p holes and crystalline structure to reduce the reaction pathway is an effective strategy for the rational design of electrocatalysts, with a likely extension to a broad variety of layered alkali-containing metal oxides.

19.
J Alzheimers Dis ; 83(4): 1521-1536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33843675

RESUMO

BACKGROUND: Given that there is no specific drug to treat Alzheimer's disease, non-pharmacologic interventions in people with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are one of the most important treatment strategies. OBJECTIVE: To clarify the efficacy of blue-green (500 nm) light therapy on sleep, mood, and physiological parameters in patients with SCD and aMCI is an interesting avenue to explore. METHODS: This is a monocentric, randomized, and controlled trial that will last for 4 weeks. We will recruit 150 individuals aged 45 years or older from memory clinics and divide them into 5 groups: SCD treatment (n = 30), SCD control (n = 30), aMCI treatment (n = 30), aMCI control (n = 30), and a group of healthy adult subjects (n = 30) as a normal control (NC). RESULTS: The primary outcome is the change in subjective and objective cognitive performance between baseline and postintervention visits (4 weeks after baseline). Secondary outcomes include changes in performance assessing from baseline, postintervention to follow-up (3 months after the intervention), as well as sleep, mood, and physiological parameters (including blood, urine, electrophysiology, and neuroimaging biomarkers). CONCLUSION: This study aims to provide evidence of the impact of light therapy on subjective and objective cognitive performance in middle-aged and older adults with SCD or aMCI. In addition, we will identify possible neurophysiological mechanisms of action underlying light therapy. Overall, this trial will contribute to the establishment of light therapy in the prevention of Alzheimer's disease.

20.
Nat Chem ; 13(5): 451-457, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33875818

RESUMO

Recent advances in end-to-end continuous-flow synthesis are rapidly expanding the capabilities of automated customized syntheses of small-molecule pharmacophores, resulting in considerable industrial and societal impacts; however, many hurdles persist that limit the number of sequential steps that can be achieved in such systems, including solvent and reagent incompatibility between individual steps, cumulated by-product formation, risk of clogging and mismatch of timescales between steps in a processing chain. To address these limitations, herein we report a strategy that merges solid-phase synthesis and continuous-flow operation, enabling push-button automated multistep syntheses of active pharmaceutical ingredients. We demonstrate our platform with a six-step synthesis of prexasertib in 65% isolated yield after 32 h of continuous execution. As there are no interactions between individual synthetic steps in the sequence, the established chemical recipe file was directly adopted or slightly modified for the synthesis of twenty-three prexasertib derivatives, enabling both automated early and late-stage diversification.


Assuntos
Técnicas de Química Sintética/métodos , Pirazinas/uso terapêutico , Pirazóis/uso terapêutico , Técnicas de Síntese em Fase Sólida/métodos , Humanos , Pirazinas/farmacologia , Pirazóis/farmacologia
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