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1.
Nano Lett ; 23(17): 8043-8049, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37592211

RESUMO

Recent studies have shown that the critical currents of several metallic superconducting nanowires and Dayem bridges can be locally tuned by using a gate voltage (Vg). Here, we report a gate-tunable Josephson junction structure constructed from a three-dimensional (3D) niobium nanobridge junction (NBJ) with a voltage gate on top. Measurements up to 6 K showed that the critical current of this structure can be tuned to zero by increasing Vg. The critical gate voltage was reduced to 16 V and may possibly be reduced further by reducing the thickness of the insulation layer between the gate and the NBJ. Furthermore, the flux modulation generated by Josephson interference of two parallel 3D NBJs can also be tuned by using Vg in a similar manner. Therefore, we believe that this gate-tunable Josephson junction structure is promising for superconducting circuit fabrication at high integration levels.

2.
Int J Mol Sci ; 25(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891819

RESUMO

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.


Assuntos
Nanopartículas Metálicas , Neoplasias , Terapia Fototérmica , Humanos , Terapia Fototérmica/métodos , Neoplasias/terapia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
3.
Sensors (Basel) ; 23(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36679578

RESUMO

Node localization in two-dimensional (2D) and three-dimensional (3D) space for wireless sensor networks (WSNs) remains a hot research topic. To improve the localization accuracy and applicability, we first propose a quantum annealing bat algorithm (QABA) for node localization in WSNs. QABA incorporates quantum evolution and annealing strategy into the framework of the bat algorithm to improve local and global search capabilities, achieve search balance with the aid of tournament and natural selection, and finally converge to the best optimized value. Additionally, we use trilateral localization and geometric feature principles to design 2D (QABA-2D) and 3D (QABA-3D) node localization algorithms optimized with QABA, respectively. Simulation results show that, compared with other heuristic algorithms, the convergence speed and solution accuracy of QABA are greatly improved, with the highest average error of QABA-2D reduced by 90.35% and the lowest by 17.22%, and the highest average error of QABA-3D reduced by 75.26% and the lowest by 7.79%.


Assuntos
Redes de Comunicação de Computadores , Tecnologia sem Fio , Simulação por Computador , Algoritmos
4.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38069279

RESUMO

Tumors are a major public health issue of concern to humans, seriously threatening the safety of people's lives and property. With the increasing demand for early and accurate diagnosis and efficient treatment of tumors, noninvasive optical imaging (including fluorescence imaging and photoacoustic imaging) and tumor synergistic therapies (phototherapy synergistic with chemotherapy, phototherapy synergistic with immunotherapy, etc.) have received increasing attention. In particular, light in the near-infrared second region (NIR-II) has triggered great research interest due to its penetration depth, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Nanomaterials with many advantages, such as high brightness, great photostability, tunable photophysical properties, and excellent biosafety offer unlimited possibilities and are being investigated for NIR-II tumor imaging-guided synergistic oncotherapy. In recent years, many researchers have tried various approaches to investigate nanomaterials, including gold nanomaterials, two-dimensional materials, metal sulfide oxides, polymers, carbon nanomaterials, NIR-II dyes, and other nanomaterials for tumor diagnostic and therapeutic integrated nanoplatform construction. In this paper, the application of multifunctional nanomaterials in tumor NIR-II imaging and collaborative therapy in the past three years is briefly reviewed, and the current research status is summarized and prospected, with a view to contributing to future tumor therapy.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Fototerapia/métodos , Polímeros/uso terapêutico , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Imagem Óptica , Nanomedicina Teranóstica/métodos
5.
J Environ Manage ; 317: 115318, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35623131

RESUMO

Water scarcity tends to be aggravated by increase in water demand with the trend of socio-economic development. Thus, non-stationary characteristics of water demand should be identified in water resources allocation (WRA) to alleviate the potential influences from water shortages. In this study, a Copula-based interval linear programming model was established for regional WRA. Through combining correlation analysis and an interval linear programming model, this model can: 1) identify interactions between water demand and socio-economic development levels based on Copula functions, 2) explore variations in water shortage with consideration of multiple risk tolerance levels of decision-makers based on Copula sampling, and 3) obtain desired strategies for WRA through an interval linear programming model. Also, Dalian City in China was selected as a case study area to verify the effectiveness of the model for WRA to five water users (i.e., agricultural sector, industrial sector, public service sector, domestic residents, and ecological environment). Considering multiple tolerance levels of decision-makers to water shortage risk, three scenarios (i.e., S1 to S3), indicating 20%, 40%, and 60% of their low, medium, and high tolerance levels, were proposed. The results showed that the correlation between the amount of water demand and indicators of socio-economic development can be described by Clayton and Gaussian Copula functions. The total water supply of Dalian in 2030 would increase by 2.06%-2.65%, compared with the one in 2025. The allocation of water resources across districts was influenced by varied water demand, energy consumption, and risk tolerance levels. Compared with the amount of water allocation in 2025, the contribution of transferred water sources would increase by 6.71% and 7.04% under S1 and S2 in 2030, respectively, and decrease by 14.31% under S3. With the increase of risk tolerance levels of decision-makers, the amount of water supply in Dalian City would gradually decrease.


Assuntos
Recursos Hídricos , Água , China , Modelos Teóricos , Programação Linear , Alocação de Recursos , Incerteza , Abastecimento de Água
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(12): 1385-1389, 2022 Dec 10.
Artigo em Zh | MEDLINE | ID: mdl-36453964

RESUMO

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation and speech delay. METHODS: Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy. RESULTS: The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c.56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c.5314dupA variant of the KAT6A gene in the fetus. CONCLUSION: The heterozygous c.5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.


Assuntos
Deficiência Intelectual , Transtornos do Desenvolvimento da Linguagem , Criança , Humanos , Masculino , Gravidez , Histona Acetiltransferases , Deficiência Intelectual/genética , Linhagem
7.
Mol Cell Biochem ; 463(1-2): 45-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630283

RESUMO

Adipose tissue inflammation is closely associated with the development of obesity and insulin resistance. Free fatty acids (FFAs) are a major inducer of obesity-related insulin resistance. Previously, we reported that endoplasmic reticulum (ER) stress potentially mediated retinal inflammation in diabetic retinopathy. The unfolded protein response (UPR) protects cells against damage induced by oxidative stress. X-box binding protein 1 (XBP1) plays a major role in protecting cells by modulating the UPR. However, the link between ER stress and adipocyte inflammation has been poorly investigated. In the present study, we found that pretreatment of 3T3-L1 adipocytes with a low dose of ER stress inducer tunicamycin inhibited FFA-induced upregulated expression of inflammatory cytokines. In addition, FFAs induced phosphorylation of the p65 subunit of NF-κB was largely inhibited by pretreatment with tunicamycin in 3T3-L1 adipocytes. Knockdown of XBP1 by siRNA markedly mitigated the protective effects of preconditioning against inflammation. Conversely, overexpression of XBP1 alleviated FFA-induced phosphorylation of IκB-α, IKKα/ß, and NF-κB, which was accompanied by decreased inflammatory cytokine expression. Collectively, these results imply a beneficial role of ER stress preconditioning in protecting against FFA-induced 3T3-L1 adipocyte inflammation, which is likely mediated through inhibition of the IKK/NF-κB pathway via XBP1.


Assuntos
Adipócitos/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácidos Graxos/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Proteína 1 de Ligação a X-Box/metabolismo , Células 3T3-L1 , Adipócitos/patologia , Animais , Citocinas/metabolismo , Ácidos Graxos/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Células RAW 264.7 , Tunicamicina/farmacologia
8.
J Cardiovasc Pharmacol ; 75(2): 155-167, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31658172

RESUMO

Oxidative low-density lipoprotein (ox-LDL) induces endothelium senescence and promotes atherosclerosis. Ginsenoside Rb1 (gRb1) has been proved to protect human umbilical vein cells (HUVECs), but its effect on ox-LDL-induced endothelium senescence and the underlying mechanism remains unknown. This study is to explore the involvement of the SIRT1/Beclin-1/autophagy axis in the effect of gRb1 on protecting endothelium against ox-LDL-induced senescence. Hyperlipidemia of Sprague Dawley rats was induced by high-fat diet, and gRb1 was intraperitoneal injected. A senescence model of HUVECs induced by ox-LDL was also established. The results showed that gRb1 alleviated hyperlipidemia-induced endothelium senescence and ox-LDL-induced HUVECs senescence. GRb1 also restored the reductions in SIRT1 and autophagy, which were involved in the anti-senescence effects. Beclin-1 acetylation was reduced, and the correlation between SIRT1 and Beclin-1 was increased by gRb1. Results of our study demonstrated the anti-senescence function of gRb1 against hyperlipidemia in the endothelium, and the underlying mechanism involves the SIRT1/Beclin-1/autophagy axis.


Assuntos
Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Senescência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Ginsenosídeos/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Lipoproteínas LDL/toxicidade , Sirtuína 1/metabolismo , Acetilação , Animais , Células Cultivadas , Dieta Hiperlipídica , Modelos Animais de Doenças , Células Endoteliais/enzimologia , Células Endoteliais/ultraestrutura , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/enzimologia , Hiperlipidemias/patologia , Masculino , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuína 1/genética
9.
Genet Med ; 21(6): 1330-1338, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30405208

RESUMO

PURPOSE: To determine the role of mosaicism in the pathogenesis and inheritance of Rett and Rett-like disorders. METHODS: We recruited 471 Rett and Rett-like patients. Panel-sequencing targeting MECP2, CDKL5, and FOXG1 was performed. Mosaicism was quantified in 147 patients by a Bayesian genotyper. Candidates were validated by amplicon sequencing and digital PCR. Germline mosaicism of 21 fathers with daughters carrying pathogenic MECP2 variants was further quantified. RESULTS: Pathogenic variants of MECP2/CDKL5/FOXG1 were found in 324/471 (68.7%) patients. Somatic MECP2 mosaicism was confirmed in 5/471 (1.1%) patients, including 3/18 males (16.7%) and 2/453 females (0.4%). Three of the five patients with somatic MECP2 mosaicism had mosaicism at MECP2-Arg106. Germline MECP2 mosaicism was detected in 5/21 (23.8%) fathers. CONCLUSION: This is the first systematic screening of somatic and paternal germline MECP2 mosaicism at a cohort level. Our findings indicate that somatic MECP2 mosaicism contributes directly to the pathogenicity of Rett syndrome, especially in male patients. MECP2-Arg106 might be a mosaic hotspot. The high proportion of paternal germline MECP2 mosaicism indicates an underestimated mechanism underlying the paternal origin bias of MECP2 variants. Finally, this study provides an empirical foundation for future studies of genetic disorders caused by de novo variations of strong paternal origin.


Assuntos
Proteína 2 de Ligação a Metil-CpG/genética , Mosaicismo , Síndrome de Rett/genética , Adulto , Teorema de Bayes , Pré-Escolar , Estudos de Coortes , Bases de Dados Genéticas , Pai , Feminino , Fatores de Transcrição Forkhead/genética , Genômica , Genótipo , Mutação em Linhagem Germinativa/genética , Hereditariedade , Humanos , Masculino , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas Serina-Treonina Quinases/genética , Síndrome de Rett/fisiopatologia
10.
Genet Med ; 21(9): 2162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30783265

RESUMO

The second author Jiarui Li is now listed as a co-first author according to her contribution to this paper. The list of authors who contributed equally now reads: Qingping Zhang, Xiaoxu Yang, Jiaping Wang, and Jiarui Li. This has now been corrected in both the PDF and HTML versions of the Article.

11.
BMC Med Genet ; 19(1): 191, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376817

RESUMO

BACKGROUND: MEF2C (Myocyte-specific enhancer factor 2C) has been associated with neurodevelopmental disorders. This study aimed at delineating the clinical profiles of MEF2C gene mutations. METHODS: In total, 112 Chinese patients with intellectual disability (ID) were recruited, including 44 patients presented with Rett syndrome (RTT) or RTT-like syndrome, and 68 patients with non-syndromic ID. Targeted next-generation sequencing (NGS) was performed. Detailed clinical information was collected. RESULTS: Five heterozygous MEF2C gene mutations were identified, of which three were novel. The MEF2C mutant rate was 4.5% (5/112) in total, and 6.8% (3/44) in the RTT (-like) cohort. All patients with MEF2C gene mutation presented with cognitive impairment, gross motor delay, speech disorder and autistic features. Four patients had epilepsy, which responded well to antiepileptic drugs. One female was diagnosed with classical RTT, two females with RTT-like syndrome, and two males with non-syndromic ID. Generally, the phenotype of two males with relatively downstream mutations (c.565C > T, p.Arg 189*; c.766C > T, p.Arg 256*) was milder than that of three females with upstream mutations (c.48C > G, p.Asn16Lys; c.334G > T, p.Glu112* and c.403-1G > T). CONCLUSIONS: Our findings expanded the current understanding of the consequences of MEF2C dysfunctions, especially MEF2C point mutations. MEF2C mutations are associated with a broad clinical spectrum, ranged from classical RTT to non-syndromic ID. Through our study, it can be inferred that there is correlation between the phenotype and MEF2C-genotype, the mutation site. Overall, the MEF2C gene mutational analysis should be performed in ID cohort, especially in patients with features overlapped with RTT.


Assuntos
Estudos de Associação Genética , Deficiência Intelectual/genética , Mutação Puntual , Síndrome de Rett/genética , Adolescente , Povo Asiático , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Expressão Gênica , Genótipo , Heterozigoto , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etnologia , Deficiência Intelectual/fisiopatologia , Fatores de Transcrição MEF2/genética , Masculino , Fenótipo , Síndrome de Rett/diagnóstico , Síndrome de Rett/etnologia , Síndrome de Rett/fisiopatologia , Índice de Gravidade de Doença
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(4): 484-488, 2018 Aug 10.
Artigo em Zh | MEDLINE | ID: mdl-30098239

RESUMO

OBJECTIVE: To delineate the clinical and genetic characteristics of patients with Allan-Herndon-Dudley syndrome (AHDS). METHODS: Genetic testing was carried out by next generation sequencing on 117 patients featuring intellectual disability and developmental delay. Clinical information including clinical manifestation, brain magnetic resonance imaging(MRI), thyroid hormone levels, and electrocardiogram was collected for those with SLC16A2 mutations. RESULTS: Five male patients with SLC16A2 gene mutations were identified, including 2 affected brothers and 3 sporadic cases. The ages of the patients ranged from 8 months to 8 years. All patients presented with severe intellectual disability and developmental delay including poor head control, inability to sit independently, no speech, and poor response to external stimuli. All patients presented with hypotonia, dystonia, and positive pyramidal signs. Three patients had sinus tachycardia. All patients had abnormal thyroid hormone levels with elevated free triiodothyronine (FT3), decreased free tetraiodothyronine(FT4), and normal thyroid stimulating hormone (TSH). Brain MRI on 3 patients showed delayed myelination. Among the 3 sporadic patients, 2 carried de novo mutations including c.61G to T(p.E21X) and c.695_699delATGGT(p.N232SfsX7), respectively, 1 carried a c.42delC(p.W15GfsX69)mutation, which was inherited from his heterozygous mother. A nonsense mutation (c.916C to T, p.Q306X) was discovered in the two brothers, for which their mother was heterozygous. CONCLUSION: AHDS is characterized by severe psychomotor developmental delay as well as congenital hypotonia, dystonia and positive pyramidal signs. Affected males may present with distinctive thyroid hormone abnormalities including increased FT3 and low FT4 accompanied by normal TSH. Delayed meylination of white matter is common. It is an X-linked mental retardation caused by SLC16A2 gene mutations.


Assuntos
Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Deficiência Intelectual Ligada ao Cromossomo X/genética , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/genética , Atrofia Muscular/diagnóstico , Atrofia Muscular/genética , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Transportadores de Ácidos Monocarboxílicos/genética , Simportadores , Hormônios Tireóideos/sangue
13.
BMC Med Genet ; 18(1): 104, 2017 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-28923014

RESUMO

BACKGROUND: SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. This study aimed to broaden the phenotypic-spectrum of disease related with SCN8A mutations. METHODS: To identify the pathogenic gene of a Chinese family, in which six members suffered from epilepsy, whole-exome sequencing was performed. In addition, target next-generation sequencing (NGS) was performed on 178 sporadic patients, who had epilepsy of unknown etiology within 6 months after birth. A detailed clinical history was obtained. RESULTS: A heterozygous missense mutation of SCN8A was identified in the Chinese family. Six de novo mutations of SCN8A were detected in 6 sporadic patients with epilepsy. In the family, six members developed seizures within a few years after birth. Five of them had milder clinical performance, that they had normal cognition and developmental milestones, and seizure-free was achieved by mono-therapy. The other one affected member presented with refractory epilepsy and developmental regression. She died from sudden unexpected death in epilepsy (SUDEP) at 17-year-old. Clinical features of six sporadic patients with SCN8A mutations were diverse, ranging from severe epileptic encephalopathy to benign epilepsy with normal cognition. Seizures started at the mean age of 3.9 months (from 2 months to 6 months). Seizure-free was achieved in four of them by mono- or multi-antiepileptic drugs. Five of them demonstrated mild or severe psychomotor retardation, whereas the other one was normal in development and intelligence. CONCLUSIONS: Our findings extend the spectrum of SCN8A mutations and the clinical features of patients with SCN8A mutations. The majority of SCN8A mutations were de novo, inherited mutations from the heterozygous parents can also occur. The phenotypic spectrum of SCN8A mutation varied largely. Most affected patients manifested as refractory epilepsy and severe intellectual disability, only a small number of patients presented with milder clinical patterns. Additionally, our study confirmed that the same mutation can lead to different phenotypes.


Assuntos
Povo Asiático/genética , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Convulsões/genética , Espasmos Infantis/genética , Adolescente , Adulto , Sequência de Aminoácidos , Criança , Pré-Escolar , Morte Súbita , Feminino , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Pessoa de Meia-Idade , Linhagem , Análise de Sequência de DNA
14.
Biomed Pharmacother ; 171: 116071, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183741

RESUMO

Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is of importance in understanding the neuropathological progression of Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular deposits of the amyloid ß-peptide (Aß) and intraneuronal aggregates of the microtubule-associated protein tau. Critical roles of Aß oligomer deposited and ganglioside GM1 could be formed as "seed" from insoluble GAß polymer in initiating the pathogenic process, while tau might also mediate SPLs and their toxicity. The interaction between ceramide and α-Synuclein (α-Syn) accelerates the aggregation of ferroptosis and exacerbates the pathogenesis of AD. For instance, reducing the levels of SPLs can mitigate α-Syn accumulation and inhibit AD progression. Meanwhile, loss of SPLs may inhibit the expression of APOE4 and confer protection against AD, while the loss of APOE4 expression also disrupts SPLs homeostasis. Moreover, the heightened activation of sphingomyelinase promotes the ferroptosis signaling pathway, leading to exacerbated AD symptoms. Ferroptosis plays a vital role in the pathological progression of AD by influencing Aß, tau, APOE, and α-Syn. Conversely, the development of AD also exacerbates the manifestation of ferroptosis and SPLs. We are compiling the emerging techniques (Derivatization and IM-MS) of sphingolipidomics, to overcome the challenges of AD diagnosis and treatment. In this review, we examined the intricate neuro-mechanistic interactions between SPLs and Aß, tau, α-Syn, APOE, and ferroptosis, mediating the onset of AD. Furthermore, our findings highlight the potential of targeting SPLs as underexplored avenue for devising innovative therapeutic strategies against AD.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4 , Esfingolipídeos , Proteínas tau/metabolismo , Ceramidas
15.
Water Res ; 250: 121034, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38157602

RESUMO

Remote sensing monitoring of particulate organic carbon (POC) concentration is essential for understanding phytoplankton productivity, carbon storage, and water quality in global lakes. Some algorithms have been proposed, but only for regional eutrophic lakes. Based on in-situ data (N = 1269) in 49 lakes across China, we developed a blended POC algorithm by distinguishing Type-I and Type-II waters. Compared to Type-I, Type-II waters had higher reflectance peak around 560 nm (>0.0125 sr-1) and mean POC (4.65 ± 4.11 vs. 2.66 ± 3.37 mg/L). Furthermore, because POC was highly related to algal production (r = 0.85), a three-band index (R2 = 0.65) and the phytoplankton fluorescence peak height (R2 = 0.63) were adopted to estimate POC in Type-I and Type-II waters, respectively. The novel algorithm got a mean absolute percent difference (MAPD) of 35.93 % and outperformed three state-of-the-art formulas with MAPD values of 40.56-76.42 %. Then, the novel algorithm was applied to OLCI/Sentinel-3 imagery, and we first obtained a national map of POC in 450 Chinese lakes (> 20 km2), which presented an apparent spatial pattern of "low in the west and high in the east". In brief, water classification should be considered when remotely monitoring lake POC concentration over a large area. Moreover, a process-oriented method is required when calculating water column POC storage from satellite-derived POC concentrations in type-II waters. Our results contribute substantially to advancing the dynamic observation of the lake carbon cycle using satellite data.


Assuntos
Monitoramento Ambiental , Lagos , Monitoramento Ambiental/métodos , Carbono , Qualidade da Água , Fitoplâncton , China
16.
Pharmaceutics ; 16(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38794265

RESUMO

Sonodynamic therapy (SDT) has attracted significant attention in recent years as it is an innovative approach to tumor treatment. It involves the utilization of sound waves or ultrasound (US) to activate acoustic sensitizers, enabling targeted drug release for precise tumor treatment. This review aims to provide a comprehensive overview of SDT, encompassing its underlying principles and therapeutic mechanisms, the applications of nanomaterials, and potential synergies with combination therapies. The review begins by introducing the fundamental principle of SDT and delving into the intricate mechanisms through which it facilitates tumor treatment. A detailed analysis is presented, outlining how SDT effectively destroys tumor cells by modulating drug release mechanisms. Subsequently, this review explores the diverse range of nanomaterials utilized in SDT applications and highlights their specific contributions to enhancing treatment outcomes. Furthermore, the potential to combine SDT with other therapeutic modalities such as photothermal therapy (PTT) and chemotherapy is discussed. These combined approaches aim to synergistically improve therapeutic efficacy while mitigating side effects. In conclusion, SDT emerges as a promising frontier in tumor treatment that offers personalized and effective treatment options with the potential to revolutionize patient care. As research progresses, SDT is poised to play a pivotal role in shaping the future landscape of oncology by providing patients with a broader spectrum of efficacious and tailored treatment options.

17.
Nat Med ; 30(2): 584-594, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177850

RESUMO

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.


Assuntos
Aprendizado Profundo , Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Cegueira
18.
Arterioscler Thromb Vasc Biol ; 32(9): 2131-40, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22772755

RESUMO

OBJECTIVE: Although the connection of oxidative stress and inflammation has been long recognized in diabetes mellitus, the underlying mechanisms are not fully elucidated. This study defined the role of 26S proteasomes in promoting vascular inflammatory response in early diabetes mellitus. METHODS AND RESULTS: The 26S proteasome functionality, markers of autophagy, and unfolded protein response were assessed in (1) cultured 26S proteasome reporter cells and endothelial cells challenged with high glucose, (2) transgenic reporter (Ub(G76V)-green fluorescence protein) and wild-type (C57BL/6J) mice rendered diabetic, and (3) genetically diabetic (Akita and OVE26) mice. In glucose-challenged cells, and also in aortic, renal, and retinal tissues from diabetic mice, enhanced 26S proteasome functionality was observed, evidenced by augmentation of proteasome (chymotrypsin-like) activities and reduction in 26S proteasome reporter proteins, accompanied by increased nitrotyrosine-containing proteins. Also, whereas inhibitor of the nuclear factor κ-light-chain-enhancer of activated B cells α proteins were decreased, an increase was found in nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) nucleus translocation, which enhanced the NF-κB-mediated proinflammatory response, without affecting markers of autophagy or unfolded protein response. Importantly, the alterations were abolished by MG132 administration, small interfering RNA knockdown of PA700 (proteasome activator protein complex), or superoxide scavenging in vivo. CONCLUSIONS: Early hyperglycemia enhances 26S proteasome functionality, not autophagy or unfolded protein response, through peroxynitrite/superoxide-mediated PA700-dependent proteasomal activation, which elevates NF- ĸB-mediated endothelial inflammatory response in early diabetes mellitus.


Assuntos
Diabetes Mellitus Experimental/enzimologia , Endotélio Vascular/enzimologia , Mediadores da Inflamação/metabolismo , Inflamação/enzimologia , Estresse Oxidativo , Complexo de Endopeptidases do Proteassoma/metabolismo , Animais , Glicemia/metabolismo , Células Cultivadas , Inibidores de Cisteína Proteinase/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/imunologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/imunologia , Ativação Enzimática , Sequestradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Células Endoteliais da Veia Umbilical Humana/enzimologia , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Inflamação/sangue , Inflamação/genética , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Peroxinitroso/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Inibidores de Proteassoma , Interferência de RNA , Fatores de Tempo , Tirosina/análogos & derivados , Tirosina/metabolismo , Ubiquitinação
19.
Environ Pollut ; 335: 122219, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37479168

RESUMO

Riverine organic carbon (OC) transport plays a role in regulating terrestrial and marine carbon pools and deteriorating coastal water quality. However, long-term OC transport in Asian rivers and its diffusion in marginal seas have remained unreported. This study reported the spatiotemporal variations in OC resources for Hong Kong waters, China, based on monthly monitoring data collected at 82 river stations and 94 ocean sites during 1986-2020. The station-based riverine OC varied spatially and was generally high, with a mean value of 1.4-52.0 mg/L. Moreover, along with improving water quality, OC at 97.6% of the river stations decreased during 1986-2020; overall, sewage treatment accounted for 83.4% of the exponential decrease in riverine OC (R2 = 0.68, p < 0.01). However, the reduction in riverine OC accounted for only 10.4% of the reduction in the marine five-day biochemical oxygen demand (BOD5), which occurred at 70.2% of the ocean sites, especially those closest to the shore. The linear reduction in the marine BOD5 (R2 = 0.24, p < 0.01) was mainly attributed to reduced OC input from the adjacent Pearl River (61.9%) and decreases in phytoplankton growth (19.0%). These results indicated that sewage treatment improved water quality and decreased OC resources in Hong Kong waters, which can serve as a sustainable development model for other coastal cities. This study has important implications for mitigating organic pollution in the context of human efforts to manage the water environment.


Assuntos
Carbono , Esgotos , Humanos , Hong Kong , Carbono/análise , Oceanos e Mares , China , Rios , Monitoramento Ambiental
20.
Water Res ; 245: 120622, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37716299

RESUMO

Rivers connect terrestrial and aquatic ecosystems and export approximately 55.47 % of the net terrestrial carbon fixation. However, due to unavailable high-frequency monitoring data, litter is known about diurnal variation in riverine carbon transport on a national scale. Based on daily measurements between March 2021 and February 2022 at 1491 stations across China, this study clarified the spatiotemporal variations in riverine organic matter indicated by chemical oxygen demand (COD). Spatially, COD content showed a spatial pattern with high values in the northwest (p < 0.05), and COD flux was determined by water discharge (84.01 %). Human activities explained 73.20 % of the spatial variations in riverine COD content; in particular, agricultural planting significantly elevated riverine COD (r = 0.73, p < 0.01). Seasonally, 95.53 % of stations showed significant seasonal variations in COD contents (p < 0.05); 69.72 % (25.81 %) were identified as Type II (III) typically had the maximum (minimum) COD in summer (autumn). Moreover, except for human activities (41.08 ± 22.94 %), natural factors also contributed 47.41 ± 24.04 % to the seasonal variations. In summer, high temperatures increased COD by promoting algal proliferation at Type II stations; however, heavy precipitation diluted COD contents at Type III stations. In these cases, seasonal measurements were essential for estimating riverine organic matter transport, especially the values measured in spring and winter. This study has significant implications for managing the aquatic environment, estimating riverine organic matter transport, and balancing the global carbon budget.

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