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1.
Artigo em Inglês | MEDLINE | ID: mdl-38568772

RESUMO

The foundation model has recently garnered significant attention due to its potential to revolutionize the field of visual representation learning in a self-supervised manner. While most foundation models are tailored to effectively process RGB images for various visual tasks, there is a noticeable gap in research focused on spectral data, which offers valuable information for scene understanding, especially in remote sensing (RS) applications. To fill this gap, we created for the first time a universal RS foundation model, named SpectralGPT, which is purpose-built to handle spectral RS images using a novel 3D generative pretrained transformer (GPT). Compared to existing foundation models, SpectralGPT 1) accommodates input images with varying sizes, resolutions, time series, and regions in a progressive training fashion, enabling full utilization of extensive RS Big Data; 2) leverages 3D token generation for spatial-spectral coupling; 3) captures spectrally sequential patterns via multi-target reconstruction; 4) trains on one million spectral RS images, yielding models with over 600 million parameters. Our evaluation highlights significant performance improvements with pretrained SpectralGPT models, signifying substantial potential in advancing spectral RS Big Data applications within the field of geoscience across four downstream tasks: single/multi-label scene classification, semantic segmentation, and change detection.

2.
Diabetes Metab Syndr Obes ; 17: 1289-1299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505538

RESUMO

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes and can potentially develop into end-stage renal disease. Its pathogenesis is complex and not fully understood. Podocytes, glomerular endothelial cells (GECs), glomerular mesangial cells (GMCs) and renal tubular epithelial cells (TECs) play important roles in the normal function of glomerulus and renal tubules, and their injury is involved in the progression of DN. Although our understanding of the mechanisms leading to DN has substantially improved, we still need to find more effective therapeutic targets. Autophagy, pyroptosis and ferroptosis are programmed cell death processes that are associated with inflammation and are closely related to a variety of diseases. Recently, a growing number of studies have reported that autophagy, pyroptosis and ferroptosis regulate the function of podocytes, GECs, GMCs and TECs. This review highlights the contributions of autophagy, pyroptosis, and ferroptosis to DN injury in these cells, offering potential therapeutic targets for DN treatment.

3.
Neural Plast ; 2024: 5599046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529366

RESUMO

Low back pain (LBP) is a leading cause of global disabilities. Numerous molecular, cellular, and anatomical factors are implicated in LBP. Current issues regarding neurologic alterations in LBP have focused on the reorganization of peripheral nerve and spinal cord, but neural mechanisms of exactly what LBP impacts on the brain required further researches. Based on existing clinical studies that chronic pain problems were accompanying alterations in brain structures and functions, researchers proposed logical conjectures that similar alterations occur in LBP patients as well. With recent extensive studies carried out using noninvasive neuroimaging technique, increasing number of abnormalities and alterations has been identified. Here, we reviewed brain alterations including white matters, grey matters, and neural circuits between brain areas, which are involved in chronic LBP. Moreover, brain structural and functional connectivity abnormalities are correlated to the happening and transition of LBP. The negative emotions related to back pain indicate possible alterations in emotional brain regions. Thus, the aim of this review is to summarize current findings on the alterations corresponding to LBP in the brain. It will not only further our understanding of etiology of LBP and understanding of negative emotions accompanying with back pain but also provide ideas and basis for new accesses to the diagnosis, treatment, and rehabilitation afterward based on integral medicine.


Assuntos
Dor Lombar , Humanos , Encéfalo/diagnóstico por imagem , Emoções , Medula Espinal
4.
Front Pharmacol ; 15: 1268464, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464713

RESUMO

Scopoletin is a coumarin synthesized by diverse medicinal and edible plants, which plays a vital role as a therapeutic and chemopreventive agent in the treatment of a variety of diseases. In this review, an overview of the pharmacology, pharmacokinetics, and toxicity of scopoletin is provided. In addition, the prospects and outlook for future studies are appraised. Scopoletin is indicated to have antimicrobial, anticancer, anti-inflammation, anti-angiogenesis, anti-oxidation, antidiabetic, antihypertensive, hepatoprotective, and neuroprotective properties and immunomodulatory effects in both in vitro and in vivo experimental trials. In addition, it is an inhibitor of various enzymes, including choline acetyltransferase, acetylcholinesterase, and monoamine oxidase. Pharmacokinetic studies have demonstrated the low bioavailability, rapid absorption, and extensive metabolism of scopoletin. These properties may be associated with its poor solubility in aqueous media. In addition, toxicity research indicates the non-toxicity of scopoletin to most cell types tested to date, suggesting that scopoletin will neither induce treatment-associated mortality nor abnormal performance with the test dose. Considering its favorable pharmacological activities, scopoletin has the potential to act as a drug candidate in the treatment of cancer, liver disease, diabetes, neurodegenerative disease, and mental disorders. In view of its merits and limitations, scopoletin is a suitable lead compound for the development of new, efficient, and low-toxicity derivatives. Additional studies are needed to explore its molecular mechanisms and targets, verify its toxicity, and promote its oral bioavailability.

5.
Front Public Health ; 12: 1295433, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371232

RESUMO

Background: One of the biggest challenges facing older adults is cognitive decline and social participation has always been considered a protective factor. However, it is not clear whether social participation predicts cognitive function in this population, rather than depressive symptoms, self-reported health, and activities of daily life, with sufficient capacity to detect unique effects. Methods: This study included adults aged 45 and above in China (N = 5,258) who participated in a large national older adult health survey and provided data from 2011, 2013, 2015, and 2018. The unique associations between the predictors of social participation and cognitive function over time and context were evaluated in the Latent Growth Model (LGM). Results: Among the 5,258 participants in our study, an overall cognitive decline was observed. Social participation predicts two dimensions of cognitive function, with a degree of impact comparable to depressive symptoms, self-reported health, and activities of daily life. Among them, social participation exhibits a noteworthy prognostic impact on episodic memory during the same period. The regression coefficient is approximately 0.1 (p < 0.05) after controlling other mixed variables (depressive symptoms, self-reported health, and activities of daily life). In contrast, social participation is also a significant predictor of mental intactness in the same period, with a regression coefficient of 0.06 (p < 0.05), even if all mixed variables are controlled. Conclusion: Over time, the correlation strength of social participation is comparable to other recognized cognitive function prediction indicators, indicating that promoting social participation among middle-aged and older Chinese adults is a meaningful way to improve cognitive function degradation, which has important policy and practical significance.


Assuntos
Disfunção Cognitiva , Participação Social , Pessoa de Meia-Idade , Humanos , Idoso , Participação Social/psicologia , Estudos Longitudinais , Envelhecimento/psicologia , Cognição , Disfunção Cognitiva/epidemiologia
6.
Int Immunopharmacol ; 130: 111755, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38408417

RESUMO

A growing amount of epidemiological evidence proposes diabetes mellitus (DM) to be an independent risk factor for osteoarthritis (OA). Sirtuin 3 (SIRT3), which is mainly located in mitochondria, belongs to the family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases and is involved in the physiological and pathological processes of cell regulation. The aim of this study was to investigate the effects of SIRT3 on diabetic OA and underlying mechanisms in the prevention of type 2 DM (T2DM)-induced articular cartilage damage. High-fat and high-sugar diets combined with streptozotocin (STZ) injection were used for establishing an experimental T2DM rat model. The destabilization of medial meniscus (DMM) surgery was applied to induce the rat OA model. Primary rat chondrocytes were cultivated with a concentration of gradient glucose. Treatment with intra-articular injection of SIRT3 overexpression lentivirus was achieved in vivo, and intervention with SIRT3 knockdown was performed using siRNA transfection in vitro. High glucose content was found to activate inflammatory response, facilitate apoptosis, downregulate autophagy, and exacerbate mitochondrial dysfunction in a dose-dependent manner in rat chondrocytes, which can be deteriorated by SIRT3 knockdown. In addition, articular cartilage damage was found to be more severe in T2DM-OA rats than in DMM-induced OA rats, which can be mitigated by the intra-articular injection of SIRT3 overexpression lentivirus. Targeting SIRT3 is a potential therapeutic strategy for the alleviation of diabetic OA.


Assuntos
Condrócitos , Osteoartrite , Sirtuína 3 , Animais , Ratos , Apoptose , Autofagia , Cartilagem Articular/patologia , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Osteoartrite/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo
7.
Endocrine ; 84(2): 646-655, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38175390

RESUMO

PURPOSE: Accurate preoperative diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains an unsolved problem. This study aimed to construct a nomogram and scoring system for predicting LNM based on the clinical characteristics of patients with PTC. METHODS: 1400 patients with PTC who underwent thyroidectomy and lymph node dissection at the First Affiliated Hospital of Sun Yat-sen University were retrospectively enrolled and randomly divided into training and internal testing sets. Furthermore, 692 patients with PTC from three other medical centers were collected as external testing sets. Least absolute shrinkage and selection operator (LASSO) was used to screen the predictors, and a nomogram was constructed. In addition, a scoring system was constructed using 10-fold cross-validation. The performances of the two models were verified among datasets and compared with preoperative ultrasound (US). RESULTS: Six independent predictors were included in the multivariate logistic model: age, sex, US diagnosis of LNM, tumor diameter, location, and thyroid peroxidase antibody level. The areas under the receiver operating characteristic curve (AUROC) (95% confidence interval) of this nomogram in the training, internal testing, and three external testing sets were 0.816 (0.791-0.840), 0.782 (0.727-0.837), 0.759 (0.699-0.819), 0.749 (0.667-0.831), and 0.777 (0.726-0.828), respectively. The AUROC of the scoring system were 0.810 (0.785-0.835), 0.772 (0.718-0.826), 0.736 (0.675-0.798), 0.717 (0.635-0.799) and 0.756 (0.704-0.808), respectively. The prediction performances were both significantly superior to those of preoperative US (P < 0.001). CONCLUSION: The nomogram and scoring system performed well in different datasets and significantly improved the preoperative prediction of LNM than US alone.


Assuntos
Metástase Linfática , Nomogramas , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Feminino , Masculino , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Adulto , Estudos Retrospectivos , Linfonodos/patologia , Tireoidectomia , Pescoço/patologia , Adulto Jovem , Idoso , Excisão de Linfonodo
9.
Angew Chem Int Ed Engl ; 63(12): e202318784, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38291557

RESUMO

Plitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75 mg/L. Next, we developed two straightforward chemical strategies to convert didemnin B into plitidepsin, one of which involved a one-step synthetic route giving over 90 % overall yield. Furthermore, we synthesized 13 new didemnin derivatives and three didemnin probes, enabling research into structure-activity relationships and interactions between didemnin and proteins. Our study highlights the synergistic potential of biosynthesis and chemical synthesis in overcoming the challenge of producing complex natural products sustainably and at scale.


Assuntos
Antineoplásicos , Depsipeptídeos , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/metabolismo , Depsipeptídeos/farmacologia , Antineoplásicos/farmacologia , Relação Estrutura-Atividade
10.
J Environ Manage ; 351: 119978, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38169258

RESUMO

Global climate change exerts a significant impact on sustainable horticultural crop production and quality. Rising Global temperatures have compelled the agricultural community to adjust planting and harvesting schedules, often necessitating earlier crop cultivation. Notably, climate change introduces a suite of ominous factors, such as greenhouse gas emissions (CGHs), including elevated temperature, increased carbon dioxide (CO2) concentrations, nitrous oxide (N2O) and methane (CH4) ozone depletion (O3), and deforestation, all of which intensify environmental stresses on crops. Consequently, climate change stands poised to adversely affect crop yields and livestock production. Therefore, the primary objective of the review article is to furnish a comprehensive overview of the multifaceted factors influencing horticulture production, encompassing fruits, vegetables, and plantation crops with a particular emphasis on greenhouse gas emissions and environmental stressors such as high temperature, drought, salinity, and emission of CO2. Additionally, this review will explore the implementation of novel horticultural crop varieties and greenhouse technology that can contribute to mitigating the adverse impact of climate change on agricultural crops.


Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Mudança Climática , Dióxido de Carbono/análise , Agricultura , Produtos Agrícolas , Horticultura , Óxido Nitroso/análise , Metano/análise , Solo
11.
Chem Biol Interact ; 390: 110890, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38278314

RESUMO

Osteoarthritis (OA) is the most common type of arthritis and is an age-related joint disease that is particularly prevalent in subjects over 65 years old. The chronic rise of senescent cells has a close correlation with age-related diseases such as OA, and the senescence-associated secretory phenotype (SASP) is implicated in OA cartilage degeneration pathogenesis. Sirtuin 6 (SIRT6) is likely to be a key senescence-related regulator. Fisetin (FST) is a natural flavonol of the flavonoid family that is recommended as a senolytic drug to extend health and lifespan. However, the potential chondroprotective effects of FST on OA rats are largely unclarified. The aim of this study is to investigate the ameliorative effects of FST on OA joint cartilage and the relationship with SIRT6 and the detailed mechanisms from anti-inflammatory and anti-senescent perspectives. Rats were subjected to destabilization of the medial meniscus (DMM) surgery as a means of inducing the experimental OA model in vivo. Chondrocytes treated with IL-1ß were utilized for mimicking the OA cell model in vitro. Intra-articular injection of FST, OSS_128,167 (OSS, SIRT6 inhibitor), and MDL800 (MDL, SIRT6 agonist) in vivo or administering them in IL-1ß-induced rat chondrocytes in vitro were performed in order to determine the effects FST has on OA and the link with SIRT6. This study found SIRT6 level to be negatively correlated with OA severity. SIRT6 downregulation was validated in the joint cartilages of DMM rats and IL-1ß-treated chondrocytes. It was also notably demonstrated that FST can activate SIRT6. Both the administration of FST and activation of SIRT6 using MDL were found to rescue cartilage erosion, decrease extracellular matrix (ECM) degradation, prevent cartilage from apoptosis, and improve detrimental senescence-related phenotype. The alleviative effects of FST against inflammation, ECM degradation, apoptosis, and senescence in IL-1ß-stimulated chondrocytes were also confirmed. SIRT6 loss occurs in articular cartilage in OA pathogenesis, which is linked to aging. FST attenuates injury-induced aging-related phenotype changes in chondrocytes through the targeting of SIRT6.


Assuntos
Cartilagem Articular , Osteoartrite , Sirtuínas , Humanos , Ratos , Animais , Idoso , Condrócitos , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Flavonóis/farmacologia , Flavonóis/metabolismo , Interleucina-1beta/metabolismo , Cartilagem Articular/metabolismo , Sirtuínas/metabolismo , Senescência Celular
12.
J Alzheimers Dis ; 97(2): 687-695, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38143359

RESUMO

BACKGROUND: Alzheimer's disease (AD) and related dementias are progressive neurological disorders with stage-specific clinical features and challenges. An important knowledge gap is the "window of time" within which patients transition from mild cognitive impairment or mild AD to moderate or severe AD. Better characterization/establishment of transition times would help clinicians initiating treatments, including anti-amyloid therapy. OBJECTIVE: To describe cognitive test score-based AD stage transitions in Veterans with AD in the US Veterans Affairs Healthcare System (VAHS). METHODS: This retrospective analysis (2010-2019) identified Veterans with AD from the VAHS Electronic Health Record (EHR) notes. AD stage was based on Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), or Saint Louis University Mental Status (SLUMS) Examination scores in the EHR. RESULTS: We identified 296,519 Veterans with cognitive test-based AD staging. Over the 10-year study, the proportion of veterans with MMSE scores declined from 24.9% to 9.5% while those with SLUMS rose from 9.0% to 17.8%; and MoCA rose from 5.0% to 25.4%. The average forward transition times between each stage were approximately 2-4 years, whether assessed by MMSE, MoCA, or SLUMS. CONCLUSION: The average transition time for cognitive test-based assessments of initial cognitive decline, early-stage AD, and moderate/severe AD in the VAHS is 2-4 years. In view of the short window for introducing disease-modifying therapy and the significant benefits of early treatment of AD, our data suggest a critical need for treatment guidelines in the management of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Veteranos , Humanos , Estados Unidos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Estudos Retrospectivos , Entrevista Psiquiátrica Padronizada , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos
13.
Small ; : e2310612, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087883

RESUMO

The biological system realizes the unity of action and perception through the muscle tissue and nervous system. Correspondingly, artificial soft actuators realize the unity of sensing and actuating functions in a single functional material, which will have tremendous potential for developing intelligent and bionic soft robotics. This paper reports the design of a laser-induced graphene (LIG) electrothermal actuator with self-sensing capability. LIG, a functional material formed by a one-step direct-write lasing procedure under ambient air, is used as electrothermal conversion materials and piezoresistive sensing materials. By transferring LIG to a flexible silicone substrate, the design ability of the LIG-based actuator unit is enriched, along with an effectively improved sensing sensitivity. Through the integration of different types of well-designed LIG-based actuator units, the transformations from multidimensional precursors to 2D and 3D structures are realized. According to the piezoresistive effect of the LIG units during the deformation process, the visual synchronous deformation state feedback of the LIG-based actuator is proposed. The multimodal crawling soft robotics and the switchable electromagnetic shielding cloak serve as the demonstrations of the self-sensing LIG-based actuator, showing the advantage of the design in remote control of the soft robot without relying on the assistance of visual devices.

14.
Pestic Biochem Physiol ; 197: 105651, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38072526

RESUMO

Solenopsis invicta is a main issue in southern China and is causing significant damage to the local ecological environment. The extensive use of insecticides has resulted in the development of tolerance in S. invicta. In our study, ten S. invicta colonies from Sichuan Province exhibited varying degrees of tolerance against flonicamid, with LC50 values from 0.49 mg/L to 8.54 mg/L. The sensitivity of S. invicta to flonicamid significantly increased after treatment with the P450 enzyme inhibitor piperonyl butoxide (PBO). Additionally, the activity of P450 in S. invicta was significantly enhanced after being treated with flonicamid. Flonicamid induced the expression levels of CYP4aa1, CYP9e2, CYP4C1, and CYP6A14. The expression levels of these P450 genes were significantly higher in the tolerant colonies compared to the sensitive colonies, and the relative copy numbers of CYP6A14 in the tolerant colonies were 2.01-2.15 fold. RNAi feeding treatment effectively inhibited the expression of P450 genes, thereby reducing the tolerance of S. invicta against flonicamid. In addition, the overexpression of CYP6A14 in D. melanogaster resulted in reduced sensitivity to flonicamid. Our investigations revealed hydrophobic interactions between flonicamid and seven amino acid residues of CYP6A14, along with the formation of a hydrogen bond between Glu306 and flonicamid. Our findings suggest that flonicamid can effectively control S. invicta and P450 plays a pivotal role in the tolerance of S. invicta against flonicamid. The overexpression of CYP6A14 also increased tolerance to flonicamid.


Assuntos
Formigas , Inseticidas , Animais , Formigas Lava-Pés , Drosophila melanogaster , Inseticidas/toxicidade
15.
ACS Appl Mater Interfaces ; 15(46): 53746-53754, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37920991

RESUMO

Excellent energy-absorbing structures have been highly sought after in engineering applications to improve devices and personal safety. The ideal energy absorption mechanism should exhibit characteristics such as lightweight, high energy absorption capacity, and efficient reusability. To address this demand, a novel three-dimensional (3D) chiral lattice structure with compression-twist coupling deformation is fabricated by combining the left and right chiral units. The proposed structure was fabricated in NiTi shape memory alloys (SMAs) by using laser powder bed fusion technology. The compression experiment result indicates that the shape recovery ratio is as high as 94% even when the compression strain is over 80%. Additionally, the platform strain reaches as high as 66%, offering high-level specific energy absorption, i.e., 213.02 J/g. The obtained results are of great significance for basic research and engineering applications of energy-absorbing structures with high deformation recovery ratios.

16.
Injury ; 54(12): 111132, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37883840

RESUMO

OBJECTIVE: The concept of enhanced recovery after surgery (ERAS) has been proposed in recent years, which indeed bring about evident convenience for the patients. This prospective cohort study was aimed to investigate the impact of ERAS on the clinical outcome of patients who undergoing total hip arthroplasty due to displaced femoral neck fractures. METHODS: Patients in two periods were included in our research, before ERAS (n = 194) and after ERAS (n = 65). The clinical outcome, such as patient statistics, details of perioperative management, length of stay (LOS), pain, Harris hip score, in-hospital complications, and interim postoperative survival were collected. This retrospective observational study addressed confounding bias using propensity score matching (PSM) analysis. RESULTS: With PSM, 55 pairs of well-matched patients were generated for comparison (conventional vs. ERAS). LOS decreased to 13.0 ± 3.2 days for the ERAS group, compared to 15.7 ± 3.5 days in the conventional group. VAS pain scores decreased significantly in both groups, and the decrease in the ERAS group was more significant than that in the conventional group at 3, 7, and 14 days postoperatively. The Harris scores of both groups significantly improved, but were better for the ERAS group than the conventional group at 7 and 14 days and 1 month postoperatively. However, no significant difference was observed at 6 months postoperatively. Additionally, the incidence of complications during hospitalization was lower in the ERAS group than that in the conventional group. No significant difference was observed in the medium-term survival between the two groups. CONCLUSIONS: ERAS apparently benefit patients in early rehabilitation by reducing complications and shortening hospital stays but not for the long-term hip function or survival.


Assuntos
Artroplastia de Quadril , Recuperação Pós-Cirúrgica Melhorada , Fraturas do Colo Femoral , Humanos , Artroplastia de Quadril/efeitos adversos , Estudos Prospectivos , Pontuação de Propensão , Fraturas do Colo Femoral/complicações , Estudos Retrospectivos , Tempo de Internação , Dor/etiologia , Complicações Pós-Operatórias/cirurgia
17.
Neurol Ther ; 12(6): 2067-2078, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37747662

RESUMO

BACKGROUND: Early identification of individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a clinical and research imperative. Use of diagnostic codes for MCI and AD identification has limitations. We used clinical notes to supplement diagnostic codes in the Veterans Affairs Healthcare System (VAHS) electronic health records (EHR) to identify and establish cohorts of Veterans recorded with MCI or AD. METHODS: Targeted keyword searches for MCI ("Mild cognitive impairment;" "MCI") and AD ("Alz*") were used to extract clinical notes from the VAHS EHR from fiscal year (FY) 2010 through FY 2019. Iterative steps of inclusion and exclusion were applied until searches achieved a positive predictive value ≥ 80%. MCI and AD cohorts were identified via clinical notes and/or diagnostic codes (i.e., including Veterans recorded by "Notes Only," "Notes + Code," or "Codes Only"). RESULTS: A total of 2,134,661 clinical notes from 339,007 Veterans met the iterative search criteria for MCI due to any cause and 4,231,933 notes from 572,063 Veterans met the iterative search criteria for AD. Over the 10-year study period, the number of clinical notes recording AD was generally stable, whereas the number for MCI more than doubled. More Veterans were identified for the MCI or AD cohorts via clinical notes than by diagnostic codes, particularly in the AD cohort. Among Veterans identified by having "Notes + Code" for MCI, the number first recorded by a code was lower than the number first recorded by a note until FY 2015 and then gradually became comparable after FY 2015. Among Veterans identified by having "Notes + Code" for AD, the number first recorded by a note was more than double the number first recorded by a code AD in each of the FYs. CONCLUSIONS: Clinical note-based identification captured more Veterans recorded with MCI and AD than diagnostic code-based identification.

18.
Appl Opt ; 62(17): 4543-4550, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37707150

RESUMO

It is important to determine the ideal combination of housing materials, groups of refractive materials, and their optical powers for athermalizing achromatic and apochromatic optical systems. This study proposes a combined design approach that utilizes three or more glass types to resolve thermal aberrations and defocus achromatic and apochromatic optical systems. It selects a suitable glass type using a 3D glass chart and calculates the optical power analytically. Furthermore, a temperature-insensitive optical system with a 450-750 nm band based on refractive materials (CDGM Glass Co., Ltd.) is designed, with the modular transfer function value of the center field of view decreasing by less than 0.024 in the temperature range of -40∘ C to +80∘ C and the secondary spectrum aberration decreasing by over three times and being maintained within 0.08 mm.

19.
Chem Biol Interact ; 384: 110724, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37741535

RESUMO

OBJECTIVE: Osteoarthritis (OA) is a common joint disease characterized by inflammation and cartilage degeneration. Accumulating evidences support that endoplasmic reticulum (ER) stress induced OA chondrocytes apoptosis. The hypoglycemic and anti-inflammatory properties render Dapagliflozin (DAPA) effective in reducing ER stress on cells. However, its impact and potential mechanisms on the OA pathology are still obscure. The present study aimed to investigate whether DAPA attenuates ER stress in chondrocytes by activating sirt1 and delays the progression of OA. METHODS: In vitro, we first investigated the effect of DAPA on chondrocytes viability with IL-1ß or not for 24 or 48 h. Then, chondrocytes were treated with 10 ng/ml IL-1ß and 10 µM dapagliflozin with10 µM thapsigargin, 5 µM SRT1460 or not. Chondrocytes apoptosis in each group were detected by Tunel staining and flow cytometric. Immunofluorescence staining was applied to quantify the expression levels of cleaved caspase-3, Sirt1 and CHOP in chondrocytes. Inhibition of ER stress in chondrocytes associated with sirt1 activation were verified by PCR and western blotting. In addition, the effects of DAPA on cartilage were validated by a series of experiments in OA rat model, such as micro-CT, histological and immunohistochemical assay. RESULTS: The data demonstrated that DAPA alleviates IL-1ß induced ER stress related chondrocytes apoptosis, and PCR and western blotting data confirmed that DAPA inhibits the PERK-eIF2α-CHOP pathway by activating Sirt1. Besides, immunohistochemical results showed that DAPA enhanced the expression of Sirt1 and Collagen II in OA rats, and inhibited the expression of CHOP and cleaved caspase-3. Meanwhile, histological staining and micro-CT photography also confirmed that DAPA alleviated inflammation and cartilage degeneration in OA rat. CONCLUSIONS: The study demonstrated the relationship of ER stress and inflammation in the progression of OA, and verified that DAPA could inhibit PERK-eIF2α-CHOP axis of the ER stress response by activating Sirt1 in IL-1ß treated rat chondrocytes and potentially prevent the OA development.

20.
Beilstein J Org Chem ; 19: 998-1007, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404799

RESUMO

Five new eudesmane-type sesquiterpenoids (aquisinenoids F-J (1-5)) and five known compounds (6-10) were isolated from the agarwood of Aquilaria sinensis. Their structures, including absolute configurations, were identified by comprehensive spectroscopic analyses and computational methods. Inspired by our previous study on the same kinds of skeletons, we speculated that the new compounds have anticancer and anti-inflammatory activities. The results did not show any activity, but they revealed the structure-activity relationships (SAR).

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