Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 90
Filter
1.
ACS Nano ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38934514

ABSTRACT

Precise synthesis of all-inorganic lead halide perovskite nanowire heterostructures and superlattices with designable modulation of chemical compositions is essential for tailoring their optoelectronic properties. Nevertheless, controllable synthesis of perovskite nanostructure heterostructures remains challenging and underexplored to date. Here, we report a rational strategy for wafer-scale synthesis of one-dimensional periodic CsPbCl3/CsPbI3 superlattices. We show that the highly parallel array of halide perovskite nanowires can be prepared roughly as horizontally guided growth on an M-plane sapphire. A periodic patterning of the sapphire substrate enables position-selective ion exchange to obtain highly periodic CsPbCl3/CsPbI3 nanowire superlattices. This patterning is further confirmed by micro-photoluminescence investigations, which show that two separate band-edge emission peaks appear at the interface of a CsPbCl3/CsPbI3 heterojunction. Additionally, compared with the pure CsPbCl3 nanowires, photodetectors fabricated using these periodic heterostructure nanowires exhibit superior photoelectric performance, namely, high ION/IOFF ratio (104), higher responsivity (49 A/W), and higher detectivity (1.51 × 1013 Jones). Moreover, a spatially resolved visible image sensor based on periodic nanowire superlattices is demonstrated with good imaging capability, suggesting promising application prospects in future photoelectronic imaging systems. All these results based on the periodic CsPbCl3/CsPbI3 nanowire superlattices provides an attractive material platform for integrated perovskite devices and circuits.

2.
bioRxiv ; 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38853824

ABSTRACT

Recent findings indicate a correlation between the peripheral adaptive immune system and neuroinflammation in Alzheimer's disease (AD). To characterize the composition of adaptive immune cells in the peripheral blood of AD patients, we utilized single-cell mass cytometry (CyTOF) to profile peripheral blood mononuclear cells (PBMCs). Concurrently, we assessed the concentration of proteins associated with AD and neuroinflammation in the plasma of the same subjects. We found that the abundance of proinflammatory CXCR3 + CD127 + Type 1 T helper (Th1) cells in AD patients was negatively correlated with the abundance of neurofilament light chain (NfL) protein. This correlation is apolipoprotein E (ApoE) ε4-dependent. Analyzing public single-cell RNA-sequencing (scRNA-seq) data, we found that, contrary to the scenario in the peripheral blood, the cell frequency of CXCR3 + CD127 + Th1 cells in the cerebrospinal fluid (CSF) of AD patients was increased compared to healthy controls (HCs). Moreover, the proinflammatory capacity of CXCR3 + CD127 + Th1 cells in the CSF of AD patients was further increased compared to HCs. These results reveal an association of a peripheral T-cell change with neuroinflammation in AD and suggest that dysregulation of peripheral adaptive immune responses, particularly involving CXCR3 + CD127 + Th1 cells, may potentially be mediated by factors such as ApoE ε4 genotype. One sentence summary: An apolipoprotein E (ApoE) ε4-dependent alteration of CD4 T cell subpopulation in peripheral blood is associated with neuroinflammation in patients with Alzheimer's disease.

3.
Endocrine ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834859

ABSTRACT

PURPOSE: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery. METHODS: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307). CONCLUSION: Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted.

4.
J Alzheimers Dis ; 99(3): 1065-1075, 2024.
Article in English | MEDLINE | ID: mdl-38788073

ABSTRACT

Background: Diagnostic codes can be instrumental for case identification in Alzheimer's disease (AD) research; however, this method has known limitations and cannot distinguish between disease stages. Clinical notes may offer more detailed information including AD severity and can complement diagnostic codes for case identification. Objective: To estimate prevalence of mild cognitive impairment (MCI) and AD using diagnostics codes and clinical notes available in the electronic healthcare record (EHR). Methods: This was a retrospective study in the Veterans Affairs Healthcare System (VAHS). Health records from Veterans aged 65 years or older were reviewed during Fiscal Years (FY) 2010-2019. Overall, 274,736 and 469,569 Veterans were identified based on a rule-based algorithm as having at least one clinical note for MCI and AD, respectively; 201,211 and 149,779 Veterans had a diagnostic code for MCI and AD, respectively. During FY 2011-2018, likely MCI or AD diagnosis was defined by≥2 qualifiers (i.e., notes and/or codes)≥30 days apart. Veterans with only 1 qualifier were considered as suspected MCI/AD. Results: Over the 8-year study, 147,106 and 207,225 Veterans had likely MCI and AD, respectively. From 2011 to 2018, yearly MCI prevalence increased from 0.9% to 2.2%; yearly AD prevalence slightly decreased from 2.4% to 2.1%; mild AD changed from 22.9% to 26.8%, moderate AD changed from 26.5% to 29.1%, and severe AD changed from 24.6% to 30.7. Conclusions: The relative distribution of AD severities was stable over time. Accurate prevalence estimation is critical for healthcare resource allocation and facilitating patients receiving innovative medicines.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Veterans , Humans , Alzheimer Disease/epidemiology , Alzheimer Disease/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/diagnosis , United States/epidemiology , Aged , Male , Female , Prevalence , Veterans/statistics & numerical data , Retrospective Studies , Aged, 80 and over , Electronic Health Records , United States Department of Veterans Affairs
5.
Materials (Basel) ; 17(10)2024 May 13.
Article in English | MEDLINE | ID: mdl-38793377

ABSTRACT

Hot-rolled backup rolls are widely used in steel rolling and usually need to be repaired by arc hardfacing after becoming worn. However, a corrugated-groove defect commonly occurs on the roll surface due to the uneven hardness distribution in the hardfacing layers, affecting the proper usage of the roll. Accordingly, a new swing-arc submerged arc welding (SA-SAW) process is proposed to attempt to solve this drawback. The microstructure and hardness are then investigated experimentally for both SAW and SA-SAW hardfacing layers. It is revealed that a self-tempering effect occurs in the welding pass bottom and the welding pass side neighboring the former pass for both processes, refining the grain in the two areas. In all the zones, including the self-tempering zone (STZ), heat-affected zone (HAZ), and not-heat-affected zone in the welding pass, both SAW and SA-SAW passes crystallize in a type of columnar grain, where the grains are the finest in STZ and the coarsest in HAZ. In addition, the arc swing improves the microstructure homogeneity of the hardfacing layers by obviously lowering the tempering degree in HAZ while promoting the even distribution of the arc heat. Accordingly, the hardness of the SA-SAW bead overall increases and distributes more uniformly with a maximum difference of < 80 HV0.5 along the horizontal direction of the bead. This hardness difference in SA-SAW is accordingly decreased by ~38.5% compared to that of the SAW bead, further indicating the practicability of the new process.

6.
Article in English | MEDLINE | ID: mdl-38568772

ABSTRACT

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.

7.
Front Pharmacol ; 15: 1268464, 2024.
Article in English | MEDLINE | ID: mdl-38464713

ABSTRACT

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.

8.
Diabetes Metab Syndr Obes ; 17: 1289-1299, 2024.
Article in English | MEDLINE | ID: mdl-38505538

ABSTRACT

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.

9.
Neural Plast ; 2024: 5599046, 2024.
Article in English | MEDLINE | ID: mdl-38529366

ABSTRACT

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.


Subject(s)
Low Back Pain , Humans , Brain/diagnostic imaging , Emotions , Spinal Cord
10.
Front Public Health ; 12: 1295433, 2024.
Article in English | MEDLINE | ID: mdl-38371232

ABSTRACT

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.


Subject(s)
Cognitive Dysfunction , Social Participation , Middle Aged , Humans , Aged , Social Participation/psychology , Longitudinal Studies , Aging/psychology , Cognition , Cognitive Dysfunction/epidemiology
11.
Int Immunopharmacol ; 130: 111755, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38408417

ABSTRACT

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.


Subject(s)
Chondrocytes , Osteoarthritis , Sirtuin 3 , Animals , Rats , Apoptosis , Autophagy , Cartilage, Articular/pathology , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Osteoarthritis/metabolism , Sirtuin 3/genetics , Sirtuin 3/metabolism
12.
J Environ Manage ; 351: 119978, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38169258

ABSTRACT

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.


Subject(s)
Greenhouse Gases , Greenhouse Gases/analysis , Climate Change , Carbon Dioxide/analysis , Agriculture , Crops, Agricultural , Horticulture , Nitrous Oxide/analysis , Methane/analysis , Soil
14.
Endocrine ; 84(2): 646-655, 2024 May.
Article in English | MEDLINE | ID: mdl-38175390

ABSTRACT

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.


Subject(s)
Lymphatic Metastasis , Nomograms , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Female , Male , Lymphatic Metastasis/pathology , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Middle Aged , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/surgery , Adult , Retrospective Studies , Lymph Nodes/pathology , Thyroidectomy , Neck/pathology , Young Adult , Aged , Lymph Node Excision
15.
Angew Chem Int Ed Engl ; 63(12): e202318784, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38291557

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Depsipeptides , Peptides, Cyclic/pharmacology , Peptides, Cyclic/metabolism , Depsipeptides/pharmacology , Antineoplastic Agents/pharmacology , Structure-Activity Relationship
16.
Chem Biol Interact ; 390: 110890, 2024 Feb 25.
Article in English | MEDLINE | ID: mdl-38278314

ABSTRACT

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.


Subject(s)
Cartilage, Articular , Osteoarthritis , Sirtuins , Humans , Rats , Animals , Aged , Chondrocytes , Osteoarthritis/drug therapy , Osteoarthritis/pathology , Flavonols/pharmacology , Flavonols/metabolism , Interleukin-1beta/metabolism , Cartilage, Articular/metabolism , Sirtuins/metabolism , Cellular Senescence
17.
J Alzheimers Dis ; 97(2): 687-695, 2024.
Article in English | MEDLINE | ID: mdl-38143359

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Veterans , Humans , United States , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Retrospective Studies , Mental Status Schedule , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Neuropsychological Tests
18.
Pestic Biochem Physiol ; 197: 105651, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38072526

ABSTRACT

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.


Subject(s)
Ants , Insecticides , Animals , Fire Ants , Drosophila melanogaster , Insecticides/toxicity
19.
Small ; : e2310612, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38087883

ABSTRACT

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.

20.
ACS Appl Mater Interfaces ; 15(46): 53746-53754, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37920991

ABSTRACT

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.

SELECTION OF CITATIONS
SEARCH DETAIL
...