Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.296
Filtrar
1.
Front Oncol ; 12: 1040495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387250

RESUMO

Background: Many studies have shown that the peripheral blood inflammatory index and nutritional index, such as the platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI), are independent prognostic factors for tumors. The present study aimed to investigate the prognostic role of these peripheral blood indexes before treatment in locally advanced gastric cancer (LAGC) treated with adjuvant chemoradiotherapy after D2 dissection. Methods: A total of 89 patients with LAGC who underwent D2 gastrectomy and adjuvant chemoradiotherapy at our hospital from 2010-2018 were eligible. Systemic inflammatory indicators before treatment were evaluated. Receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and Cox regression were utilized for prognosis evaluation. Results: The median follow-up time was 29.1 (4.1-115.8) months. The overall survival at 3 years (OS) and the disease-free survival (DFS) were 78.9% and 59.1%, respectively. According to the ROC curve for 3-year DFS, the best cut-off values of pre-treatment NLR, PLR, LMR, SII, SIRI, PIV and PNI were 1.7, 109.3, 2.9, 369.2, 0.58, 218.7, and 48, respectively. Multivariate Cox regression analysis showed that NLR was an independent prognostic factor for DFS (HR 2.991, 95%CI 1.085-8.248, P = 0.034). Kaplan-Meier analysis showed that a higher NLR (>1.70) was significantly associated with a poorer OS (3-year OS: 68.8% vs 92.9%, P = 0.045) and DFS (3-year DFS: 47.5% vs 80.9%, P = 0.005). In terms of the free locoregional recurrence rate (LRR), the prognosis of patients with high NLR was also significantly worse than those with low NLR (70.2% vs 96.0%, P = 0.017). Paraaortic lymph nodes were the most common site of LRR (7/14 patients). The seven cases of paraaortic lymph node metastasis occurred in patients with high NLR. Conclusions: In our retrospective analysis, we found that pretreatment NLR could serve as a prognostic factor for survival in LAGC treated with adjuvant chemoradiotherapy after D2 dissection, especially for the prediction of LRR and paraaortic lymph node metastasis. Prospective studies are needed to confirm our findings.

2.
Int J Bioprint ; 8(4): 607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36404790

RESUMO

Precise and shape-matching osteotomy models are determinants of the experimental homogeneity in the assessment of orthopedic biomechanical properties. At present, however, publications on detailed description of osteotomy in bone biomechanical study are scanty. The purposes of this study were to design a new method of osteotomy-aided module production for bone biomechanical study with the help of three-dimensional (3D) printing and computer-aided design (CAD) and to test the accuracy of osteotomy. Fourteen fourth-generation composite femurs were analyzed. The composite bone was scanned using computed tomography (CT) scanner and loaded in Mimics for reconstruction and, then, imported into 3-Matic software to design intertrochanteric region, distal femur, and rotation control lever models. 3D printer was used to print each component. After assembling Sawbones and osteotomy modules, a horizontal band-saw was used to create fracture models. The volume and mass of intermediate fragments were calculated and analyzed. Satisfactory osteotomies of all composite Sawbones were achieved. The mean volume and mass of intermediate fragments were 21.0 ± 1.5 mm3 and 19.0 ± 1.2 g, respectively. Range of deviation from average of volumes was -1.9 - 2.8 mm3 and most of these deviations fall within the range of -1.4 - 2.1 mm3. Range of deviation from average of mass was -2.0 - 1.6 g and most of these deviations fall within the range of -1.4 - 1.6 g. One-dimensional histogram of deviation from average shows the precise and stable osteotomy performed based on the modules accordingly. A new method of osteotomy-aided module production for bone biomechanical study with the help of 3D printing and CAD was designed and the accuracy of osteotomy was verified. This method is expected to achieve homogeneity and standardization of osteotomy in bone biomechanical study.

3.
Heliyon ; 8(11): e11530, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36406714

RESUMO

Background: The secondary preventive medical remedies used in the U.S. general population, particularly those with numerous co-morbidities, are poorly understood. We aimed to assess health outcomes and the extent of their adherence to guideline-based secondary prevention medications among U.S. coronary heart disease (CHD) patients. Methods: We analysed information from the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 on people in the United States aged 18 to 85 who had a personal history of coronary heart disease (CHD). Logistic regression analyses were used to identify characteristics related to healthcare access that were linked with not taking any indicated drugs among CHD and other co-morbidity patients in the U.S. Results: We gathered 4256 CHD patients aged 18 and above. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), statins, and antiplatelet medications were taken by 50.94%, 48.26%, 53.41 %, and 19.78% of the population, respectively. Surprising, not received recommended drugs was reached up to 21.12%, and taking all four drugs was only 7.64%. In conclusion, the logistic regression analysis revealed that the chance of not taking prescribed drugs increased with age (18-39), race (Hispanic and Non-Hispanic Black), low income, lack of insurance, and the absence of co-morbidities (hypertension, heart failure, and diabetes mellitus). Conclusions: The gap between the proposed secondary preventative measures and their actual execution remains sizable. In order to achieve 'Healthy Aging', a systematic approach for prevention of CHD is urgently needed.

4.
Front Immunol ; 13: 1027122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405747

RESUMO

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the highly infectious Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is an urgent need for biomarkers that will help in better stratification of patients and contribute to personalized treatments. We performed targeted proteomics using the Olink platform and systematically investigated protein concentrations in 350 hospitalized COVID-19 patients, 186 post-COVID-19 individuals, and 61 healthy individuals from 3 independent cohorts. Results revealed a signature of acute SARS-CoV-2 infection, which is represented by inflammatory biomarkers, chemokines and complement-related factors. Furthermore, the circulating proteome is still significantly affected in post-COVID-19 samples several weeks after infection. Post-COVID-19 individuals are characterized by upregulation of mediators of the tumor necrosis (TNF)-α signaling pathways and proteins related to transforming growth factor (TGF)-ß. In addition, the circulating proteome is able to differentiate between patients with different COVID-19 disease severities, and is associated with the time after infection. These results provide important insights into changes induced by SARS-CoV-2 infection at the proteomic level by integrating several cohorts to obtain a large disease spectrum, including variation in disease severity and time after infection. These findings could guide the development of host-directed therapy in COVID-19.


Assuntos
COVID-19 , Proteômica , Humanos , Proteoma , SARS-CoV-2 , Biomarcadores
5.
Nat Chem ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376388

RESUMO

Iodine is a reactive trace element in atmospheric chemistry that destroys ozone and nucleates particles. Iodine emissions have tripled since 1950 and are projected to keep increasing with rising O3 surface concentrations. Although iodic acid (HIO3) is widespread and forms particles more efficiently than sulfuric acid, its gas-phase formation mechanism remains unresolved. Here, in CLOUD atmospheric simulation chamber experiments that generate iodine radicals at atmospherically relevant rates, we show that iodooxy hypoiodite, IOIO, is efficiently converted into HIO3 via reactions (R1) IOIO + O3 → IOIO4 and (R2) IOIO4 + H2O → HIO3 + HOI + (1)O2. The laboratory-derived reaction rate coefficients are corroborated by theory and shown to explain field observations of daytime HIO3 in the remote lower free troposphere. The mechanism provides a missing link between iodine sources and particle formation. Because particulate iodate is readily reduced, recycling iodine back into the gas phase, our results suggest a catalytic role of iodine in aerosol formation.

7.
BMC Med ; 20(1): 454, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36424578

RESUMO

BACKGROUND: Previous studies have reported that maternal smoking during pregnancy and breastfeeding may affect the occurrence of hypertension, but whether early life factors modify the impact of the offspring's genetic risk on hypertension is still unknown. The aim of this study was to investigate the relationships among maternal smoking and breastfeeding with adult-onset hypertension and the modified impact of offspring genetic susceptibility. METHODS: This study included 437,185 participants from the UK Biobank who were initially free of hypertension and provided a prospective cohort of individuals aged 40 to 69 years. The association of maternal smoking during pregnancy and breastfeeding with hypertension was examined by using the Cox regression model. Then, a polygenic risk score (PRS) for hypertension was used to test the gene-environmental interaction on hypertension. RESULTS: During a median follow-up period of 8.7 years, a total of 68,148 cases of hypertension were identified in this study. The hazard ratios (HRs) and 95% confidence intervals (CIs) of hypertension for maternal smoking and breastfeeding were 1.11 (1.09, 1.13) and 0.96 (0.94, 0.98), respectively. However, no evidence of an interaction between maternal smoking and breastfeeding was observed. Across all levels of genetic risk, including high genetic risk, maternal smoking and nonbreastfeeding had higher hypertension hazards than nonmaternal smoking and breastfeeding, respectively. The adjusted HRs (95% CIs) of hypertension were 1.80 (1.73, 1.87) in those who had high genetic predisposition plus maternal smoking and 1.67 (1.60-1.74) in those with nonbreastfeeding and high genetic risk. There were significant additive interactions between maternal smoking or breastfeeding and genetic factors on the incidence of hypertension. CONCLUSIONS: Maternal smoking and nonbreastfeeding were associated with a higher risk of hypertension in adulthood and may attenuate the risk of hypertension related to genetic factors. These results suggested that adherence to nonmaternal smoking and breastfeeding was associated with a lower risk of hypertension among participants with all gradients of genetic risk.

8.
Adv Mater ; : e2208553, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36427459

RESUMO

Checkpoint immunotherapy holds great potential to treat malignancies via blocking the immunosuppressive signaling pathways, which however suffers from inefficiency and off-target adverse effects. We herein report checkpoint nano-proteolysis targeting chimeras (nano-PROTACs) in combination with photodynamic tumor regression and immunosuppressive protein degradation to block checkpoint signaling pathways for activatable cancer photo-immunotherapy. These nano-PROTACs are composed of a photosensitizer (protoporphyrin IX, PpIX) and an Src homology 2 domain-containing phosphatase 2 (SHP2)-targeting PROTAC peptide (aPRO) via a caspase 3-cleavable segment. aPRO is activated by the increased expression of caspase 3 in tumor cells after phototherapeutic treatment and induces targeted degradation of SHP2 via the ubiquitin-proteasome system. The persistent depletion of SHP2 blocks the immunosuppressive checkpoint signaling pathways (CD47/SIRPα and PD-1/PD-L1), thus reinvigorating antitumor macrophages and T cells. Such a checkpoint PROTAC strategy synergizes immunogenic phototherapy to boost antitumor immune response. Thus, this study represents a generalized PROTAC platform to modulate immune-related signaling pathways for improved anticancer therapy. This article is protected by copyright. All rights reserved.

9.
Nanoscale ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36413063

RESUMO

LL-37, the only human host cathelicidin peptide, is proposed to be able to induce host cell apoptosis through mitochondrial membrane permeabilization (MMP). Detailed pathways of the LL-37-triggered MMP are however still disputed. It is generally believed that cationic peptides permeate a membrane mostly in conditions of micromolar peptide concentrations and negatively charged membranes, which are not usually satisfied in the mitochondrial circumstance. Herein, using a variety of single-molecule techniques, we show that nanomolar LL-37 specifically induces permeability of a phosphoethanolamine (PE)-rich biomimetic mitochondrial membrane in a protein-independent manner. The insertion dynamics of single LL-37 molecules exhibit different metastable states in bilayers composed of different lipids. Moreover, the PE lipids significantly facilitate adsorption and accumulation of LL-37 on the PE-rich bilayer, and produce deeper insertion of peptide oligomers, especially tetramers, into the bilayer. This work offers an alternative pathway of the LL-37-triggered MMP and apoptosis.

10.
Environ Pollut ; 316(Pt 1): 120560, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36328287

RESUMO

Benzotriazole ultraviolet stabilizers (BUVSs) have been reported to induce inflammatory responses which may promote cholesterol accumulation and to downregulate the expression of genes involved in cholesterol biosynthesis; hence, we speculated whether BUVSs promote foam cell formation, which plays a key role in all stages of atherosclerosis. Herein, we used high-content imaging to screen all available BUVSs; of all the 17 candidates, 6 of them could promote foam cell formation at 10 µM. Further analyses showed that one BUVS UV-234 markedly increased the foam cell staining intensity by 15.0%-55.9% in the 0.5-10 µM exposure groups in a dose-dependent manner. Cholesterol influx was markedly enhanced by 21.0%-24.5% in the 5-10 µM exposure groups and cholesterol efflux was downregulated by 21.2%-59.3% in the 0.5-10 µM exposure groups, indicating that cholesterol efflux may play a major role in foam formation considering cholesterol efflux was downregulated at a relatively low concentration. Gene expression of ABCA1 and ABCG1 which regulate the cholesterol efflux were also decreased at 0.5-10 µM. The degradation of hypoxia-inducible factor 1α (HIF1α) via the ubiquitin-proteasome system was observed at 0.5-10 µM, probably contributing to the downregulated expression of the genes encoding liver X receptors (LXR) α/ß and their targets, ABCA1 and ABCG1. Thus, our study revealed that BUVSs frequently detected in the environment can promote foam cell formation in macrophages, contributing to the risk of atherosclerosis in humans.

11.
Curr Psychol ; : 1-14, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36340895

RESUMO

This study aimed to explore the relationship between parenting styles and the social adjustment of university students as well as the mediating effects of attachment avoidance and friendship quality. We further examined the moderating role of gender. This study used convenience sampling to recruit 501 Chinese university students to complete the Chinese version of the Negative Parenting subscale of EMBU, Attachment Avoidance Scale, Friendship Quality Questionnaire, and Social Adjustment Scale. SPSS 24.0 and the Process 3.5 macro program were used to carry out descriptive statistical and correlation analyses and mediating effect and moderated chain-mediating effect tests on the data. The analyses revealed that negative parenting styles significantly negatively predicted social adjustment in university students. Attachment avoidance mediated the relationship between negative parenting styles and social adjustment in university students, and friendship quality mediated the relationship between negative parenting styles and social adjustment in university students. Attachment avoidance and friendship quality played a chain-mediating role in the relationship between negative parenting styles and university students' social adjustment. Gender moderated the effect of negative parenting style on friendship quality among university students. These results show how negative parenting styles affect college students' social adjustment and its underlying mechanisms in the context of China's collectivist culture and high power distance and further reveal the gender differences involved, providing insights to better understand the factors influencing college students' social adjustment.

12.
Front Oncol ; 12: 997894, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324593

RESUMO

Background: Single-incision laparoscopy surgery (SILS) is a new laparoscopic technique that has emerged in the past decade. Whether it has advantages over conventionl laparoscopy surgery (CLS) is inconclusive. This article aimed to compare the short- and long-term outcomes of single-incision laparoscopic surgery and conventional laparoscopic surgery for colorectal cancer through high-quality literature text mining and meta-analysis. Methods: Relevant articles were searched on the PubMed, Embase, and Cochrane Library databases from January 2012 to November 2021. All data was from randomized controlled trials (RCTs) in order to increase the confidence of the analytical results.The main outcomes were intraoperative and postoperative complications. Results: A total of 10 RCTs were included, involving 1609 patients. The quality of the included studies was generally high. No significant difference was found between SILS and CLS in the postoperative complications, operation time, postoperative hospital stay, number of lymph nodes removed, readmission, reoperation, complication level I- II, complication level IIIa, complication level IIIb, prolonged Ileus, blood loss, infection, anastomotic leakage and operation time. The results showed that SILS group had a higher rate of intraoperative complications, but it had lower incision length and better cosmetic effects. Conclusion: These results indicate that SILS did not have a comprehensive and obvious advantage over the CLS. On the contrary, SILS has higher intraoperative complications, which may be related to the more difficulty of SILS operation, but SILS still has better cosmetic effects, which is in line with the concept of surgical development. Therefore, the SILS needs to be selected in patients with higher cosmetic requirements and performed by more experienced surgeons.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36343000

RESUMO

Photorealistic multiview face synthesis from a single image is a challenging problem. Existing works mainly learn a texture mapping model from the source to the target faces. However, they rarely consider the geometric constraints on the internal deformation arising from pose variations, which causes a high level of uncertainty in face pose modeling, and hence, produces inferior results for large pose variations. Moreover, current methods typically suffer from undesired facial details loss due to the adoption of the de-facto standard encoder-decoder architecture without any skip connections (SCs). In this article, we directly learn and exploit geometric constraints and propose a fully deformable network to simultaneously model the deformations of both landmarks and faces for face synthesis. Specifically, our model consists of two parts: a deformable landmark learning network (DLLN) and a gated deformable face synthesis network (GDFSN). The DLLN converts an initial reference landmark to an individual-specific target landmark as delicate pose guidance for face rotation. The GDFSN adopts a dual-stream structure, with one stream estimating the deformation of two views in the form of convolution offsets according to the source pose and the converted target pose, and the other leveraging the predicted deformation offsets to create the target face. In this way, individual-aware pose changes are explicitly modeled in the face generator to cope with geometric transformation, by adaptively focusing on pertinent regions of the source face. To compensate for offset estimation errors, we introduce a soft-gating mechanism for adaptive fusion between deformable features and primitive features. Additionally, a pose-aligned SC (PASC) is tailored to propagate low-level input features to the appropriate positions in the output features for further enhancing the facial details and identity preservation. Extensive experiments on six benchmarks show that our approach performs favorably against the state-of-the-arts, especially with large pose changes. Code is available at https://github.com/cschengxu/FDFace.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36342505

RESUMO

PURPOSE: This study aims to study the depth of artery wall tumour invasion in patients undergoing surgery for pancreatic ductal adenocarcinoma. METHODS: Specimens from 47 pancreatic cancer patients with major arterial (splenic, SA; celiac, CA; common hepatic, CHA) invasion were examined: 45 left (distal) pancreatectomies, including 11 celiac artery resections, and two total pancreatectomies. Dissection of tumour-invaded arteries in 25 fresh specimens was attempted ex vivo using the sub-adventitial dissection technique (SDT). Tumour invasion of 66 arteries was graded using the tumour-free distance (TFD) from the external elastic lamina (EEL): 0 = no arterial invasion; I = TFD ≥ 1 mm; II = TFD < 1 mm; and grade III = EEL invasion. RESULTS: AJCC TNM staging was IA = 1 (2%), IB = 4 (9%), IIA = 5 (11%), IIB = 17(36%) and III = 20 (43%). Grade III tumour invasion was found in 17/47(36%) SAs, in 5/11 (45%) CAs and in 1/8 (13%) CHAs (p = 0.318). Attempted ex vivo SDT undertaken in 33 arteries from 25 specimens was complete in 16 and incomplete in 17 arteries. The median (IQR) TFD was 0.97 (0.11-2.54) mm in dissected and 0.14 (0.10, 0.14) mm in non-dissected SAs (p = 0.034). EEL tumour invasion occurred in 0/12 (0%) dissected compared to 7/13 (54%) non-dissected SAs (p = 0.005). Grades 0, I, II and III invasion were found in four (33%), two (17%) and six (50%), respectively, of 12 dissected SAs and grades II and III in six 6 (46%) and seven (54%), respectively, of 13 non-dissected SAs (p = 0.002). CONCLUSIONS: The grading system described may form the basis for classification to further develop arterial dissection techniques for pancreatic cancer.

15.
Eur J Prev Cardiol ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317303

RESUMO

AIMS: To identify metabolites associated with a healthy lifestyle and explore the possible mechanisms of lifestyle in CAD. METHODS AND RESULTS: The NMR metabolomics platform was applied to perform metabolomic profiling of baseline plasma samples from a randomly selected subset of 121,733 UK Biobank participants. Cox proportional hazards models with covariate adjustments were used to investigate the associations between validated lifestyle-associated metabolites and incident CAD and to estimate the accuracy of the inclusion of metabolites to predict CAD compared with traditional prediction models. The discriminatory ability of each model was evaluated using Harrell's C statistic, integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) indexes. During a median of 8.6 years of follow-up, 5,513 incident CAD cases were documented. Among the 111 lifestyle-associated metabolites, 65 were significantly associated with incident CAD after multivariate adjustment (Bonferroni P < 3.11 × 10-04). The addition of these metabolites to classic risk prediction models (Framingham Risk Score [FRS] using lipids; FRS using body mass index) improved CAD prediction accuracy as assessed by the C statistic (increasing to 0.739 [95% CI, 0.731-0.747] and 0.752 [95% CI, 0.746-0.758]), respectively; continuous NRI (0.274 [0.227-0.325] and 0.266 [0.223-0.317]) and IDI (0.003 [0.002-0.004] and 0.003 [0.002-0.004]). CONCLUSIONS: Healthy lifestyle-associated metabolites are associated with the incidence of CAD and may help improve the prediction of CAD risk. The use of metabolite information combined with the FRS model warrants further investigation before clinical implementation.

16.
Nutr Neurosci ; : 1-15, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36370050

RESUMO

The seed embryo of Nelumbo nucifera Gaertn. is a famous traditional Chinese medicine and food which is considered conducive to the prevention of Alzheimer's disease (AD). In this study, the effect and mechanism of TASENN (total alkaloids from the seed embryo of Nelumbo nucifera Gaertn.) on AD mice and amyloid-ß (Aß) injured PC12 cells were evaluated. HPLC-UV analysis showed that the extracted TASENN (purity = 95.6%) mainly contains Liensinine, Isoliensinine, and Neferine (purity was 23.01, 28.02, and 44.57%, respectively). In vivo, oral treatment with TASENN (50 mg/kg/day for 28 days) improved the learning and memory functions of APP/PS1 transgenic mice, ameliorated the histopathological changes of cortical and hippocampal neurons, and inhibited neuronal apoptosis. We found that TASENN reduced the phosphorylation of Tau and the formation of neurofibrillary tangles (NFTs) in APP/PS1 mouse brain. Moreover, TASENN down-regulated the expression of APP and BACE1, ameliorated Aß deposition, and inhibited microglial proliferation and aggregation. The elevated protein expression of CaM and p-CaMKII in APP/PS1 mouse brain was also reduced by TASENN. In vitro, TASENN inhibited the apoptosis of PC12 cells injured by Aß25-35 and increased the cell viability. Aß25-35-induced increase of cytosolic free Ca2+ level and high expression of CaM, p-CaMKII, and p-Tau were decreased by TASENN. Our findings indicate that TASENN has a potential therapeutic effect on AD mice and a protective effect on PC12 cells. The anti-AD activity of TASENN may be closely related to its negative regulation of the CaM pathway.

17.
Environ Int ; 170: 107562, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36228550

RESUMO

BACKGROUND: Limited studies have examined the association between air pollutants and osteoporosis incidence; however, the results are conflicting. We aimed to quantify the effects of selected air pollutants on osteoporosis risk and explore the modifying effect of genetic predisposition. METHODS: A total of 422,955 subjects who did not have osteoporosis at baseline in the UK Biobank were included from 2006 to 2010. We conducted a Cox proportional hazards model with adjustment for covariates to examine the association between air pollutant scores and individual air pollutants and incident osteoporosis. Furthermore, a polygenic risk score (PRS) of osteoporosis was built and examined to determine whether genetic susceptibility modified the effect of air pollutants on osteoporosis. The relationship between air pollutants and osteoporosis was examined by using a restricted cubic spline (RCS) method. RESULTS: After confounder adjustment, the results showed a remarkable increase in the risk of osteoporosis with each 10 unit increase in exposure to air pollution (hazard ratio: 1.06, 95 % confidence interval: 1.03-1.08), PM2.5 (1.94, 1.52-2.48), NO2 (1.06, 1.02-1.10), and NOX (1.03, 1.01-1.04). However, no significant association was observed between PM10 or PM2.5-10 exposure and osteoporosis. Subjects with high air pollutant exposure levels and a high PRS had a noteworthy increase in osteoporosis risk compared to those with low air pollutant exposure levels and a low PRS. Air pollutants and genetic variants exerted additive effects on the risk of osteoporosis. Positive correlations were observed between osteoporosis and PM2.5 (P < 0.001), NO2 (P = 0.001), and NOx (P = 0.002) exposure. CONCLUSIONS: Exposure to PM2.5, NO2 and NOx was associated with an increase in osteoporosis risk, and this effect was more pronounced in populations with high genetic risk. The association between PM2.5, NO2 and NOx exposure and osteoporosis is modified by genetic variations.

18.
Cell Rep Med ; 3(10): 100774, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36195094

RESUMO

"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV and SARS-CoV-2 infection in vivo. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Mechanistic assays show that H84T-BanLec targets virus entry. High-speed atomic force microscopy depicts real-time multimolecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modeling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the drug compound's broad-spectrum antiviral activity and the lack of resistant mutants.


Assuntos
COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , SARS-CoV-2 , Lectinas/farmacologia , Manose/farmacologia , Enzima de Conversão de Angiotensina 2 , Glicoproteína da Espícula de Coronavírus/farmacologia , Antivirais/farmacologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-36279344

RESUMO

This article presents a novel efficient experience-replay-based adaptive dynamic programming (ADP) for the optimal control problem of a class of nonlinear dynamical systems within the Hamiltonian-driven framework. The quasi-Hamiltonian is presented for the policy evaluation problem with an admissible policy. With the quasi-Hamiltonian, a novel composite critic learning mechanism is developed to combine the instantaneous data with the historical data. In addition, the pseudo-Hamiltonian is defined to deal with the performance optimization problem. Based on the pseudo-Hamiltonian, the conventional Hamilton-Jacobi-Bellman (HJB) equation can be represented in a filtered form, which can be implemented online. Theoretical analysis is investigated in terms of the convergence of the adaptive critic design and the stability of the closed-loop systems, where parameter convergence can be achieved under a weakened excitation condition. Simulation studies are investigated to verify the efficacy of the presented design scheme.

20.
Small ; : e2205033, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36285776

RESUMO

Transition metal-nitrogen-carbon (TM-N-C) catalysts have been intensely investigated to tackle the sluggish oxygen reduction reactions (ORRs), but insufficient accessibility of the active sites limits their performance. Here, by using solid ZIF-L nanorods as self-sacrifice templates, a ZIF-phase-transition strategy is developed to fabricate ZIF-8 hollow nanorods with open cavities, which can be subsequently converted to atomically dispersed Fe-N-C hollow nanorods (denoted as Fe1 -N-C HNRs) through rational carbonization and following fixation of iron atoms. The microstructure observation and X-ray absorption fine structure analysis confirm abundant Fe-N4 active sites are evenly distributed in the carbon skeleton. Thanks to the highly accessible Fe-N4 active sites provided by the highly porous and open carbon hollow architecture, the Fe1 -N-C HNRs exhibit superior ORR activity and stability in alkaline and acidic electrolytes with very positive half-wave potentials of 0.91 and 0.8 V versus RHE, respectively, both of which surpass those of commercial Pt/C. Remarkably, the dynamic current density (JK ) of Fe1 -N-C HNRs at 0.85 V versus RHE in alkaline media delivers a record value of 148 mA cm-2 , 21 times higher than that of Pt/C. The assembled Zn-air battery using Fe1 -N-C HNRs as cathode catalyst exhibits a high peak power density of 208 mW cm-2 .

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...