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1.
Clin Appl Thromb Hemost ; 27: 10760296211059500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34775859

RESUMO

To investigate the associations between soluble Lectin-like Oxidized Low-density lipoprotein receptor-1 (sLOX-1) and clinical prognosis, especially infarct volume in patients with acute atherosclerosis-related ischemic stroke. We recruited acute ischemic stroke patients within 3 days after onset. Patients were stratified into 3 groups by sLOX-1 level. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI by ITK-SNAP software. The clinical prognosis was evaluated by DWI volume, clinical response at discharge, and functional outcome at 90 days. Spearman rank correlation analysis was used to examine associations between circulating sLOX-1 levels and infarct volumes. Logistic regression was used to explore the relationship between sLOX-1 levels and clinical prognosis. A total of 207 patients were included in our study. The median DWI volume in the lowest sLOX-1 tertile was 1.98 cm3, smaller than 4.26 cm3 in the highest sLOX-1 group. The Spearman rank correlation coefficient between sLOX-1 levels and DWI volume was 0.47 (P < .01). Compared with the highest sLOX-1 tertiles, patients in the lowest sLOX-1 tertile had a higher risk of favorable functional outcome at 90 days (OR = 3.47, 95% CI, 1.21-9.96) after adjusting traditional risk factors. However, there was no difference between sLOX-1 level and clinical response at discharge. For patients with acute atherosclerosis-related ischemic stroke, circulating sLOX-1 level is correlated with DWI volume in the acute phase and favorable functional outcome at 90 days, but not with the clinical response at discharge.

2.
Aging Cell ; : e13514, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775673

RESUMO

Adiponectin (APN) deficiency has also been associated with Alzheimer-like pathologies. Recent studies have illuminated the importance of APN signaling in reducing Aß accumulation, and the Aß elimination mechanism remains rudimentary. Therefore, we aimed to elucidate the APN role in reducing Aß accumulation and its associated abnormalities by targeting autophagy and lysosomal protein changes. To assess, we performed a combined pharmacological and genetic approach while using preclinical models and human samples. Our results demonstrated that the APN level significantly diminished in the plasma of patients with dementia and 5xFAD mice (6 months old), which positively correlated with Mini-Mental State Examination (MMSE), and negatively correlated with Clinical Dementia Rating (CDR), respectively. APN deficiency accelerated cognitive impairment, Aß deposition, and neuroinflammation in 5xFAD mice (5xFAD*APN KO), which was significantly rescued by AdipoRon (AR) treatment. Furthermore, AR treatment also markedly reduced Aß deposition and attenuated neuroinflammation in APP/PS1 mice without altering APP expression and processing. Interestingly, AR treatment triggered autophagy by mediating AMPK-mTOR pathway signaling. Most importantly, APN deficiency dysregulated lysosomal enzymes level, which was recovered by AR administration. We further validated these changes by proteomic analysis. These findings reveal that APN is the negative regulator of Aß deposition and its associated pathophysiologies. To eliminate Aß both extra- and intracellular deposition, APN contributes via the autophagic/lysosomal pathway. It presents a therapeutic avenue for AD therapy by targeting autophagic and lysosomal signaling.

3.
Dalton Trans ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34752589

RESUMO

Photochromic materials coupled with photoswitchable luminescence functionalities are of particular interest due to their potential applications in switches and optical memory devices. However, the construction of such materials, especially those with two-color emission states, is still challenging. In this context, a rare Zn7 cluster-based host-guest MOF material, (bbmp)[Zn7(IPA)6(OH)4(H2O)2] (1) (H2IPA = isophthalic acid, bbmp·2I = 4,4'-([1,1'-biphenyl]-4,4'-diyl)bis(1-methylpyridin-1-ium) diiodide), was prepared by encapsulating an organic cation into an anionic MOF produced from zinc cations and isophthalic acid ligands, which exhibits reversible naked detectable photochromic properties varying from yellow to green upon UV-Vis light irradiation. The photoactive guest bbmp2+ and the short O⋯N+ distances between the oxygen atoms of the carboxylate groups and the pyridine ring play a crucial role in the photochromism of this compound. More interestingly, the luminescence color of this cluster-based host-guest material can be reversibly switched from green to blue upon irradiation, exhibiting photoswitchable luminescence properties.

4.
Am J Nephrol ; : 1-17, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753140

RESUMO

BACKGROUND: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington's disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. SUMMARY: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

5.
Clin Kidney J ; 14(11): 2371-2376, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34754432

RESUMO

Background: Chronic kidney disease (CKD) is common among people with type 2 diabetes (T2D), and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length (LTL) is associated with CKD in patients with T2D. We previously reported single-nucleotide polymorphisms (SNPs) associated with LTL in an Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using the Mendelian randomization (MR) approach. Methods: The cross-sectional association of 16 LTL SNPs with CKD, defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2, was assessed among 4768 (1628 cases and 3140 controls) participants in the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in T2D and Diabetic Nephropathy cohorts. MR analysis was performed using the random-effect inverse-variance weighted (IVW) method, the weighted median, MR-Egger and Radial MR adjusted for age and sex-stratified by cohorts and ethnicity (Chinese and Malays), then meta-analyzed. Results: Genetically determined shorter LTL was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio = 1.51, 95% confidence interval 1.12-2.12, P = 0.007, Phet = 0.547). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (ß = 0.010, P = 0.751). Conclusions: Our findings suggest that genetically determined LTL is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.

6.
China CDC Wkly ; 3(12): 243-246, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-34594858
7.
China CDC Wkly ; 3(2): 21-24, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34594898

RESUMO

What is already known about this topic?: The World Health Organization has estimated the impact of reductions in the performance of global tuberculosis (TB) detection and care on TB deaths. However, the actual impact of COVID-19 pandemic on TB deaths in China remains unclear. What is added by this report?: The stringent public interventions to fight COVID-19 including lockdown led to more than 20% decrease of TB detection in China. It was predicted that the reduction of TB detection might result in 11,700 excess deaths based on assumption of no detection rebound. Based on the prediction the total deaths will be 51,100 in 2020 which might surpass the deaths in 2011. What are the implications for public health practice?: Rapid restoration of TB diagnosis and care services is critical for minimizing the potential effects on TB-related deaths and bringing TB burden back to control. It is urgent to ramp up case detection including active case finding and to provide an uninterrupted supply of quality-assured treatment and care for TB cases in post-COVID-19 outbreak.

8.
China CDC Wkly ; 3(26): 553-556, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34594934

RESUMO

What is already known on this topic? The coronavirus disease 2019 (COVID-19) pandemic has disrupted the tuberculosis (TB) service system. However, the impact on TB patients in China remains unknown. What is added by this report? This report firstly addressed the impact of COVID-19 on TB patients in China. About half of TB patients did not revisit the hospital due to personal reasons. The reasons for irregular medication and postponing or cancelling examination after full treatment course were different. What are the implications for public health practice? Health education and risk communication should be strengthened for better TB patient management and treatment adherence, especially in light of the COVID-19 pandemic.

10.
Plant Dis ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645309

RESUMO

Wheat pathogens, especially those causing powdery mildew and stripe rust, seriously threaten yield worldwide. Utilizing newly identified disease resistance genes from wheat relatives is an effective strategy to minimize disease damage. In this study, chromosome-specific molecular markers for the 3Sb and 7Sb chromosomes of Aegilops bicornis were developed using PCR-based landmark unique gene (PLUG) primers for screening wheat-Ae. bicornis progenies. Fluorescence in situ hybridization (FISH) was performed to further identify wheat-Ae. bicornis progenies using oligonucleotides probes Oligo-pSc119.2-1, Oligo-pTa535-1, and Oligo-(GAA)8. After establishing Ae. bicornis 3Sb and 7Sb chromosome-specific FISH markers, Holdfast (common wheat)-Ae. bicornis 3Sb addition, 7Sb addition, 3Sb(3A) substitution, 3Sb(3B) substitution, 3Sb(3D) substitution, 7Sb(7A) substitution, and 7Sb(7B) substitution lines were identified by the molecular and cytological markers. Stripe rust and powdery mildew resistance, along with agronomic traits were investigated to evaluate the breeding potential of these lines. Holdfast and Holdfast-Ae. bicornis progenies were all highly resistant to stripe rust, indicating that the stripe rust resistance might derive from Holdfast. However, Holdfast-Ae. bicornis 3Sb addition, 3Sb(3A) substitution, 3Sb(3B) substitution, and 3Sb(3D) substitution lines showed high resistance to powdery mildew while Holdfast was highly susceptible, indicating that chromosome 3Sb of Ae. bicornis carries previously unknown powdery mildew resistance gene(s). Additionally, the transfer of the 3Sb chromosome from Ae. bicornis to wheat significantly increased tiller number, but chromosome 7Sb has a negative effect on agronomic traits. Therefore, wheat germplasm containing Ae. bicornis chromosome 3Sb has potential to contribute to improving powdery mildew resistance and tiller number during wheat breeding.

11.
Nat Commun ; 12(1): 5960, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645822

RESUMO

Non-noble transition metal oxides are abundant in nature. However, they are widely regarded as catalytically inert for hydrogen evolution reaction (HER) due to their scarce active electronic states near the Fermi-level. How to largely improve the HER activity of these kinds of materials remains a great challenge. Herein, as a proof-of-concept, we design a non-solvent strategy to achieve phosphate substitution and the subsequent crystal phase stabilization of metastable ß-NiMoO4. Phosphate substitution is proved to be imperative for the stabilization and activation of ß-NiMoO4, which can efficiently generate the active electronic states and promote the intrinsic HER activity. As a result, phosphate substituted ß-NiMoO4 exhibits the optimal hydrogen adsorption free energy (-0.046 eV) and ultralow overpotential of -23 mV at 10 mA cm-2 in 1 M KOH for HER. Especially, it maintains long-term stability for 200 h at the large current density of 1000 mA cm-2 with an overpotential of only -210 mV. This work provides a route for activating transition metal oxides for HER by stabilizing the metastable phase with abundant active electronic states.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34682557

RESUMO

Rapid urbanization of China has brought lifestyle changes resulting in a continuous decline in children's physical fitness (PF) and out-of-school physical activity (PA). To date, studies have been focused on correlates of PF and out-of-school PA, and patterns and trends based on geographic diversity and urban-rural contrasts. Western China, with a large rural population, has substantial urban-rural differences, but little work has been done to compare its children's physical fitness (PF) and out-of-school physical activity (PA) at a county level. A total of 715 primary school students (grades 3-6) were surveyed from one urban school (n = 438) and four rural schools (n = 277) in a county-level administrative unit, Yangling District, Shaanxi, in western China. Physical fitness index (PFI) was measured and calculated based on the revised Chinese Student Physical Fitness Standards. Out-of-school PA and other variables of demographics, behavior and perception were collected using questionnaires. Statistical analyses explored urban-rural differences and correlates of PFI and out-of-school PA. We found that the PFI (72.86 vs. 79.67) and weekly moderate-to-vigorous physical activity (MVPA) duration (167.57 vs. 220.08) of urban students were significantly lower than those of rural students. Weekly MVPA duration had the largest positive impact on PFI. Perceived availability of PA spaces was positively associated with both the urban and rural students' PF and PA, while screen time was negatively associated with PF and PA, especially for rural students. Facilitators of PA frequency include the perceived availability of PA time and parental educational level. Parents' PA habits had a positive impact on urban students' PA. No association between active school commuting and PF or PA was found. Our findings revealed that PF and out-of-school PA of urban students were clearly lower than among rural students. The health of rural children at the county level in western China should be paid much more attention during the process of rapid urbanization.


Assuntos
Aptidão Física , População Rural , Criança , China , Exercício Físico , Humanos , Instituições Acadêmicas , Estudantes
14.
15.
Aging (Albany NY) ; 13(20): 23739-23756, 2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34689137

RESUMO

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease threatening the health of the elderly, but the available therapeutic and preventive drugs remain suboptimal. Loganin, an iridoid glycoside extracted from Cornus officinalis, is reported to have anti-inflammatory and memory-enhancing properties. This study is aimed to explore the influence of loganin on cognitive function in 3xTg-AD mice and the underlying mechanism associated with its neuroprotection. According to the results of behavioral tests, we found that administration of loganin could significantly alleviate anxiety behavior and improve memory deficits of 3xTg-AD mice. Furthermore, immunohistochemical analysis displayed that there were decreased Aß deposition in the hippocampus and cortex of 3xTg-AD mice treated with loganin compared with the control mice. Importantly, the Aß-related pathological change was mainly involved in altering APP expression and processing. And loganin was also found to reduce the levels of phosphorylated tau (i.e. pTauS396 and pTauS262) in 3xTg-AD mice. By performing 2D-DIGE combined with MALDI-TOF-MS/MS, we revealed 28 differentially expressed proteins in the 3xTg-AD mice treated with loganin compared with the control mice. Notably, 10 proteins largely involved in energy metabolism, synaptic proteins, inflammatory response, and ATP binding were simultaneously detected in 3xTg-AD mice compared to WT mice. The abnormal changes of energy metabolism (PAGM1 and ENO1), synaptic proteins (SYN2 and Cplx2), inflammatory response (1433Z) were verified by western blot. Overall, our study suggested that loganin could be used as a feasible candidate drug to ameliorate molecular deficits, pathologies and cognitive impairment for prevention and treatment of AD.

16.
Biomaterials ; 278: 121172, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34653935

RESUMO

Silicon, a highly biocompatible and ubiquitous chemical element in living systems, exhibits great potentials in biomedical applications. However, the silicon-based nanomaterials such as silica and porous silicon have been largely limited to only serving as carriers for delivery systems, due to the lack of intrinsic functionalities of silicon. This work presents the facile construction of a two-dimensional (2D) hydrogen-bonded silicene (H-silicene) nanosystem which is highlighted with tunable bandgap and selective degradability for tumor-specific photodynamic therapy facilely by surface covalent modification of hydrogen atoms. Briefly, the H-silicene nanosheet material is selectively degradable in normal neutral tissues but rather stable in the mildly acidic tumor microenvironment (TME) for achieving efficient photodynamic therapy (PDT). Such a 2D hydrogen-bonded silicene nanosystem featuring the tunable bandgap and tumor-selective degradability provides a new paradigm for the application of multi-functional two-dimensional silicon-based biomaterials towards the diagnosis and treatments of cancer and other diseases.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Hidrogênio , Neoplasias/tratamento farmacológico , Silício , Microambiente Tumoral
17.
Toxicol Ind Health ; : 7482337211022223, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706592

RESUMO

Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.

18.
J Pineal Res ; 71(4): e12774, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34617321

RESUMO

While melatonin is known to have protective effects in mitochondria-related diseases, aging, and neurodegenerative disorders, there is poor understanding of the effects of melatonin treatment on mitophagy in Alzheimer's disease (AD). We used proteomic analysis to investigate the effects and underlying molecular mechanisms of oral melatonin treatment on mitophagy in the hippocampus of 4-month-old wild-type mice versus age-matched 5 × FAD mice, an animal model of AD. 5 × FAD mice showed disordered mitophagy and mitochondrial dysfunction as revealed by increased mtDNA, mitochondrial marker proteins and MDA production, decreased electron transport chain proteins and ATP levels, and co-localization of Lamp1 and Tomm20. Melatonin treatment reversed the abnormal expression of proteins in the signaling pathway of lysosomes, pathologic phagocytosis of microglia, and mitochondrial energy metabolism. Moreover, melatonin restored mitophagy by improving mitophagosome-lysosome fusion via Mcoln1, and thus, ameliorated mitochondrial functions, attenuated Aß pathology, and improved cognition. Concurrent treatment with chloroquine and melatonin blocked the positive behavioral and biochemical effects of administration with melatonin alone. Taken in concert, these results suggest that melatonin reduces AD-related deficits in mitophagy such that the drug should be considered as a therapeutic candidate for the treatment of AD.

19.
Arch Gynecol Obstet ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34694432

RESUMO

PURPOSE: Previous epidemiological data linking the C677T and A1298C MTHFR polymorphisms to gestational diabetes risk have been mixed and controversial. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship between MTHFR polymorphisms and this pregnancy disorder. METHODS: A systematic literature search for original epidemiological studies was performed in the CNKI, WanFang, Cochrane Library, PubMed, and Web of Science databases. R language-based programs were employed for all statistical analyses. Odds ratios and corresponding 95% confidence intervals were calculated to estimate the effects of the variant allele on gestational diabetes risk. RESULTS: A summary of the estimates for the C677T polymorphism showed that the exposure cohorts were prone to gestational diabetes by a greater magnitude than the control groups. Further subgroup analysis by ethnicity showed that the Asians carrying the variant T allele were more susceptible to this pregnancy disorder. However, the pathogenic effect was not evident in the non-Asian subgroup. For the A1298C polymorphism, no statistical significance could be detected. CONCLUSION: This meta-analysis suggests that the T allele of the MTHFR gene C677T polymorphism tends to increase gestational diabetes susceptibility, especially for Asians. However, the A1298C polymorphism is not associated with an increased risk of this crippling pregnancy disorder.

20.
Nanomaterials (Basel) ; 11(9)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34578659

RESUMO

Bound states in the continuum (BICs) have attracted much attention due to their infinite Q factor. However, the realization of the analogue of electromagnetically induced transparency (EIT) by near-field coupling with a dark BIC in metasurfaces remains challenging. Here, we propose and numerically demonstrate the realization of a high-quality factor EIT by the coupling of a bright electric dipole resonance and a dark toroidal dipole BIC in an all-dielectric double-layer metasurface. Thanks to the designed unique one-dimensional (D)-two-dimensional (2D) combination of the double-layer metasurface, the sensitivity of the EIT to the relative displacement between the two layer-structures is greatly reduced. Moreover, several designs for widely tunable EIT are proposed and discussed. We believe the proposed double-layer metasurface opens a new avenue for implementing BIC-based EIT with potential applications in filtering, sensing and other photonic devices.

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