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1.
Nature ; 629(8014): 1091-1099, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38750363

RESUMO

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.


Assuntos
Adansonia , Filogenia , Adansonia/classificação , Adansonia/genética , Biodiversidade , Conservação dos Recursos Naturais , Ecologia , Espécies em Perigo de Extinção , Evolução Molecular , Genoma de Planta/genética , Madagáscar , Dinâmica Populacional , Elevação do Nível do Mar
2.
Proc Natl Acad Sci U S A ; 119(36): e2209630119, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36044552

RESUMO

The melting point is a fundamental property that is time-consuming to measure or compute, thus hindering high-throughput analyses of melting relations and phase diagrams over large sets of candidate compounds. To address this, we build a machine learning model, trained on a database of ∼10,000 compounds, that can predict the melting temperature in a fraction of a second. The model, made publicly available online, features graph neural network and residual neural network architectures. We demonstrate the model's usefulness in diverse applications. For the purpose of materials design and discovery, we show that it can quickly discover novel multicomponent materials with high melting points. These predictions are confirmed by density functional theory calculations and experimentally validated. In an application to planetary science and geology, we employ the model to analyze the melting temperatures of ∼4,800 minerals to uncover correlations relevant to the study of mineral evolution.

3.
Br J Cancer ; 131(1): 1-10, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38514762

RESUMO

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Neoplasias/radioterapia , Inteligência Artificial , Fenótipo , Dosagem Radioterapêutica
4.
Hum Brain Mapp ; 45(1): e26560, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38224536

RESUMO

OBJECTIVES: White matter hyperintensities (WMH) increase the risk of stroke and cognitive impairment. This study aims to determine the cross-sectional and longitudinal associations between adiposity and WMH. METHODS: Participants were enrolled from the UK Biobank cohort. Associations of concurrent, past, and changes in overall and central adiposity with WMH were investigated by linear and nonlinear regression models. The association of longitudinal adiposity and WMH volume changes was determined by a linear mixed model. Mediation analysis investigated the potential mediating effect of blood pressure. RESULTS: In 34,653 participants with available adiposity measures and imaging data, the concurrent obese group had a 25.3% (ß [95% CI] = 0.253 [0.222-0.284]) higher WMH volume than the ideal weight group. Increment in all adiposity measures was associated with a higher WMH volume. Among them, waist circumference demonstrated the strongest effect (ß [95% CI] = 0.113 [0.101-0.125]). Past adiposity also demonstrated similar effects. Among the subset of 2664 participants with available WMH follow-up data, adiposity measures were predictive of WMH change. Regarding changes of adiposity, compared with ideal weight stable group, those who turned from ideal weight to overweight/obese had a 8.1% higher WMH volume (ß [95% CI] = 0.081 [0.039-0.123]), while participants who turned from overweight/obese to ideal weight demonstrated no significant WMH volume change. Blood pressure partly meditates the associations between adiposity and WMH. CONCLUSIONS: Both concurrent and past adiposity were associated with a higher WMH volume. The detrimental effects of adiposity on WMH occurred throughout midlife and in the elderly and may still exist after changes in obesity status.


Assuntos
Substância Branca , Humanos , Idoso , Substância Branca/diagnóstico por imagem , Adiposidade , Sobrepeso/diagnóstico por imagem , Estudos Transversais , Imageamento por Ressonância Magnética , Obesidade/diagnóstico por imagem
5.
EMBO Rep ; 23(8): e54265, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35766227

RESUMO

The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis. Patients with low MTAP expression display worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduce the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. We identify vimentin as a dimethyl-protein whose dimethylation levels drop in response to MTAP deficiency. The sDMA modification on vimentin reduces its protein abundance but trivially affects its filamentous structure. In MTAP-deficient cells, lower sDMA modification prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin and contributing to cell invasion. MTAP and PRMT5 negatively correlate with vimentin in lung cancer samples. Taken together, we propose a mechanism for metastasis involving vimentin post-translational regulation.


Assuntos
Neoplasias Pulmonares , Purina-Núcleosídeo Fosforilase , Humanos , Neoplasias Pulmonares/genética , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Purina-Núcleosídeo Fosforilase/metabolismo , Vimentina/genética
6.
Macromol Rapid Commun ; : e2400059, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538294

RESUMO

Many crucial components inside electronic devices are made from non-renewable, non-biodegradable, and potentially toxic materials, leading to environmental damage. Finding alternative green dielectric materials is mandatory to align with global sustainable goals. Carboxymethyl cellulose (CMC) is a bio-polymer derived from cellulose and has outstanding properties. Herein, citric acid, dextrin, and CMC based hydrogels are prepared, which are biocompatible and biodegradable and exhibit rubber-like mechanical properties, with Young modulus values of 0.89 MPa. Hence, thin film CMC-based hydrogel is explored as a suitable green high-k dielectric candidate for operation at low voltages, demonstrating a high dielectric constant of up to 78. These fabricated transistors reveal stable high capacitance (2090 nF cm-2) for ≈±3 V operation. Using a polyelectrolyte-type approach and poly-(2-vinyl anthracene) (PVAn) surface modification, this study demonstrates a thin dielectric layer (d ≈30 nm) with a small voltage threshold (Vth ≈-0.8 V), moderate transconductance (gm ≈65 nS), and high ON-OFF ratio (≈105). Furthermore, the dielectric layer exhibits stable performance under bias stress of ± 3.5 V and 100 cycles of switching tests. The modified CMC-based hydrogel demonstrates desirable performance as a green dielectric for low-voltage operation, further highlighting its biocompatibility.

7.
Neurol Sci ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943019

RESUMO

Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. 18F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.

8.
J Appl Clin Med Phys ; 25(2): e14154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37683120

RESUMO

BACKGROUND: Tolerance limit is defined on pre-treatment patient specific quality assurance results to identify "out of the norm" dose discrepancy in plan. An out-of-tolerance plan during measurement can often cause treatment delays especially if replanning is required. In this study, we aim to develop an outlier detection model to identify out-of-tolerance plan early during treatment planning phase to mitigate the above-mentioned risks. METHODS: Patient-specific quality assurance results with portal dosimetry for stereotactic body radiotherapy measured between January 2020 and December 2021 were used in this study. Data were divided into thorax and pelvis sites and gamma passing rates were recorded using 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria. Statistical process control method was used to determine six different site and criterion-specific tolerance and action limits. Using only the inliers identified with our determined tolerance limits, we trained three different outlier detection models using the plan complexity metrics extracted from each treatment field-robust covariance, isolation forest, and one class support vector machine. The hyperparameters were optimized using the F1-score calculated from both the inliers and validation outliers' data. RESULTS: 308 pelvis and 200 thorax fields were used in this study. The tolerance (action) limits for 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria in the pelvis site are 99.1% (98.1%), 95.8% (91.1%), and 91.7% (86.1%), respectively. The tolerance (action) limits in the thorax site are 99.0% (98.7%), 97.0% (96.2%), and 91.5% (87.2%). One class support vector machine performs the best among all the algorithms. The best performing model in the thorax (pelvis) site achieves a precision of 0.56 (0.54), recall of 1.0 (1.0), and F1-score of 0.72 (0.70) when using the 2%/2 mm (2%/1 mm) criterion. CONCLUSION: The model will help the planner to identify an out-of-tolerance plan early so that they can refine the plan further during the planning stage without risking late discovery during measurement.


Assuntos
Radiocirurgia , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Algoritmos , Pelve , Radiometria/métodos , Radioterapia de Intensidade Modulada/métodos , Garantia da Qualidade dos Cuidados de Saúde
9.
J Appl Clin Med Phys ; 25(7): e14348, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38561975

RESUMO

INTRODUCTION: Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3. METHODS: A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread-out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented. RESULTS: The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of ± 3 % $ \pm 3\% $ are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of ± 1 mm $ \pm 1\ {\mathrm{mm}}$ is used. Four diodes at ± 10 cm $ \pm 10\ {\mathrm{cm}}$ from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A 1.5 mm $1.5\ {\mathrm{mm}}$ tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries. CONCLUSION: With the proposed approach, we can perform four QA items in the TG224 within 10 min.


Assuntos
Terapia com Prótons , Garantia da Qualidade dos Cuidados de Saúde , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Terapia com Prótons/métodos , Terapia com Prótons/normas , Humanos , Garantia da Qualidade dos Cuidados de Saúde/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Neoplasias/radioterapia , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/normas , Imagens de Fantasmas , Algoritmos , Radiometria/métodos
10.
Zhongguo Zhong Yao Za Zhi ; 49(1): 185-196, 2024 Jan.
Artigo em Zh | MEDLINE | ID: mdl-38403351

RESUMO

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Proteína de Ligação a GTP rhoC/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Metaloproteinase 9 da Matriz/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Sorafenibe , Camundongos Nus , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Movimento Celular , Proliferação de Células
11.
J Cell Physiol ; 238(10): 2228-2242, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37682901

RESUMO

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

12.
J Cell Physiol ; 238(11): 2586-2599, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37795636

RESUMO

Adolescent idiopathic scoliosis (AIS) is a complex disease characterized by three-dimensional structural deformities of the spine. Its pathogenesis is associated with osteopenia. Bone-marrow-derived mesenchymal stem cells (BMSCs) play an important role in bone metabolism. We detected 1919 differentially expressed mRNAs and 744 differentially expressed lncRNAs in BMSCs from seven patients with AIS and five patients without AIS via high-throughput sequencing. Multiple analyses identified bone morphogenetic protein-6 (BMP6) as a hub gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS. BMP6 expression was found to be decreased in AIS and its knockdown in human BMSCs significantly altered the degree of osteogenic differentiation. Additionally, CAP1-217 has been shown to be a potential upstream regulatory molecule of BMP6. We showed that CAP1-217 knockdown downregulated the expression of BMP6 and the osteogenic differentiation of BMSCs. Simultaneously, knockout of BMP6 in zebrafish embryos significantly increased the deformity rate. The findings of this study suggest that BMP6 is a key gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS via the CAP1-217/BMP6/RUNX2 axis.


Assuntos
Doenças Ósseas Metabólicas , Escoliose , Humanos , Adolescente , Animais , Escoliose/genética , Escoliose/patologia , Osteogênese/genética , Peixe-Zebra/genética , Coluna Vertebral/metabolismo , Diferenciação Celular/genética , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Células Cultivadas , Células da Medula Óssea/metabolismo , Proteína Morfogenética Óssea 6/genética
13.
J Neurochem ; 166(2): 414-423, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37222503

RESUMO

White matter hyperintensities (WMH) are the most compelling risk factors of stroke, dementia, and early mortality. We aimed to investigate the associations between WMH and circulating metabolites. We studied up to 8190 individuals from the UK Biobank, who have both measurements of 249 plasma metabolites and WMH volume. Linear regression models were applied in pooled samples, and age-stratified and sex-stratified subsamples to estimate the associations between WMH and metabolomic measures. We conducted three analytic models. In the basic model, we identified 45 metabolomic measures associated with WMH after multiple testing correction (p < 0.0022), 15 of which remained significant in additional adjustments, but no metabolites passed the full adjustment in pooled samples. The 15 WMH-related metabolites were subfractions of various sizes of high-density lipoprotein (HDL), fatty acids, and glycoprotein acetyls. Among them, one fatty acid metabolite and 12 HDL-related traits showed significant negative associations with WMH. Higher glycoprotein acetyls were associated with large WMH. Strong age and sex specificities were observed indicating distinct metabolomic features accompany WMH in different samples. More metabolites were identified in males and adults under 50 years old. Circulating metabolites showed remarkably widespread associations with WMH. Population specificities may shed light on the different pertinent implications of WMH.


Assuntos
Acidente Vascular Cerebral , Substância Branca , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/complicações , Fatores de Risco
14.
Small ; 19(1): e2205316, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36394201

RESUMO

Recently, flexible stretchable sensors have been gaining attention for their excellent adaptability for electronic skin applications. However, the preparation of stretchable strain sensors that achieve dual-mode sensing while still retaining ultra-low detection limit of strain, high sensitivity, and low cost is a pressing task. Herein, a high-performance dual-mode stretchable strain sensor (DMSSS) based on biomimetic scorpion foot slit microstructures and multi-walled carbon nanotubes (MWCNTs)/graphene (GR)/silicone rubber (SR)/Fe3 O4 nanocomposites is proposed, which can accurately sense strain and magnetic stimuli. The DMSSS exhibits a large strain detection range (≈160%), sensitivity up to 100.56 (130-160%), an ultra-low detection limit of strain (0.16% strain), and superior durability (9000 cycles of stretch/release). The sensor can accurately recognize sign language movement, as well as realize object proximity information perception and whole process information monitoring. Furthermore, human joint movements and micro-expressions can be monitored in real-time. Therefore, the DMSSS of this work opens up promising prospects for applications in sign language pose recognition, non-contact sensing, human-computer interaction, and electronic skin.


Assuntos
Nanocompostos , Nanotubos de Carbono , Humanos , Nanotubos de Carbono/química , Movimento , Fenômenos Físicos , Fenômenos Magnéticos
15.
J Transl Med ; 21(1): 768, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904154

RESUMO

BACKGROUND: Early prevention of Alzheimer's disease (AD) is a feasible way to delay AD onset and progression. Information on AD prediction at the individual patient level will be useful in AD prevention. In this study, we aim to develop risk models for predicting AD onset at individual level using optimal set of predictors from multiple features. METHODS: A total of 487 cognitively normal (CN) individuals and 796 mild cognitive impairment (MCI) patients were included from Alzheimer's Disease Neuroimaging Initiative. All the participants were assessed for clinical, cognitive, magnetic resonance imaging and cerebrospinal fluid (CSF) markers and followed for mean periods of 5.6 years for CN individuals and 4.6 years for MCI patients to ascertain progression from CN to incident prodromal stage of AD or from MCI to AD dementia. Least Absolute Shrinkage and Selection Operator Cox regression was applied for predictors selection and model construction. RESULTS: During the follow-up periods, 139 CN participants had progressed to prodromal AD (CDR ≥ 0.5) and 321 MCI patients had progressed to AD dementia. In the prediction of individual risk of incident prodromal stage of AD in CN individuals, the AUC of the final CN model was 0.81 within 5 years. The final MCI model predicted individual risk of AD dementia in MCI patients with an AUC of 0.92 within 5 years. The models were also associated with longitudinal change of Mini-Mental State Examination (p < 0.001 for CN and MCI models). An Alzheimer's continuum model was developed which could predict the Alzheimer's continuum for individuals with normal AD biomarkers within 3 years with high accuracy (AUC = 0.91). CONCLUSIONS: The risk models were able to provide personalized risk for AD onset at each year after evaluation. The models may be useful for better prevention of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Sintomas Prodrômicos , Progressão da Doença , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/patologia , Biomarcadores
16.
Mol Biol Rep ; 50(5): 4375-4384, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36944863

RESUMO

The plant COBRA protein family plays an important role in secondary cell wall biosynthesis and the orientation of cell expansion. The COBRA gene family has been well studied in Arabidopsis thaliana, maize, rice, etc., but no systematic studies were conducted in wheat. In this study, the full-length sequence of TaCOBLs was obtained by homology cloning from wheat, and a conserved motif analysis confirmed that TaCOBLs belonged to the COBRA protein family. qRT-PCR results showed that the TaCOBL transcripts were induced by abiotic stresses, including cold, drought, salinity, and abscisic acid (ABA). Two haplotypes of TaCOBL-5B (Hap5B-a and Hap5B-b), harboring one indel (----/TATA) in the 5' flanking region (- 550 bp), were found on chromosome 5BS. A co-dominant marker, Ta5BF/Ta5BR, was developed based on the polymorphism of the two TaCOBL-5B haplotypes. Significant correlations between the two TaCOBL-5B haplotypes and cold resistance were observed under four environmental conditions. Hap5B-a, a favored haplotype acquired during wheat polyploidization, may positively contribute to enhanced cold resistance in wheat. Based on the promoter activity analysis, the Hap5B-a promoter containing a TATA-box was more active than that of Hap5B-b without the TATA-box under low temperature. Our study provides valuable information indicating that the TaCOBL genes are associated with cold response in wheat.


Assuntos
Ácido Abscísico , Proteínas de Plantas , Ácido Abscísico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas/genética , Plantas Geneticamente Modificadas/genética , Temperatura Baixa
17.
Macromol Rapid Commun ; 44(22): e2300420, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37775102

RESUMO

Tactile sensing is required for electronic skin and intelligent robots to function properly. However, the dielectric layer's poor structural compressibility in conventional pressure sensors results in a limited pressure sensing range and low sensitivity. To solve this issue, a flexible pressure sensor with a crocodile-inspired fillable gradient structure is provided. The fillable gradient structure and grooves in the pressure sensor accommodate the deformed microstructure that permits the enhancement of the media layer compressibility via COMSOL finite element simulation and optimization. The pressure sensor exhibits a high sensitivity of up to 0.97 k Pa-1 (0-4 kPa), a wide pressure detection range (7 Pa-380 kPa), and outstanding repeatability. The sensor can detect Morse code, robotic grabbing, and human motion monitoring. As a result, flexible sensors with a bionic fillable gradient structure pave the way for wearable devices and offer a novel method for achieving highly precise tactile perception.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos , Pressão , Biônica/métodos
18.
BMC Psychiatry ; 23(1): 174, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927467

RESUMO

BACKGROUND: We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. METHODS: We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. RESULTS: Children with ASD had a shorter breastfeeding duration in infancy (8 (3-12) months vs. 10 (6-14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4-6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance. CONCLUSIONS: Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than TD children. These feeding patterns may be related to the symptoms and growth of children with ASD. The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms and that infants who have difficulty introducing complementary foods should be followed up for neurodevelopment. TRIAL REGISTRATION: The ethics committee of the Children's Hospital of Chongqing Medical University approved the study. Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194, registered on 23/03/2020).


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Lactente , Transtorno do Espectro Autista/psicologia , Transtorno Autístico/complicações , Suplementos Nutricionais , Comportamento Alimentar
19.
Am J Primatol ; 85(4): e23468, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36691713

RESUMO

The gut microbiota plays an integral role in the metabolism and immunity of animal hosts, and provides insights into the health and habitat assessment of threatened animals. The skywalker hoolock gibbon (Hoolock tianxing) is a newly described gibbon species, and is considered an endangered species. Here, we used 16S rRNA amplicon sequencing to describe the fecal bacterial community of skywalker hoolock gibbons from different habitats and in captivity. Fecal samples (n = 5) from two captive gibbons were compared with wild populations (N = 6 gibbons, n = 33 samples). At the phylum level, Spirochetes, Proteobacteria, Firmicutes, Bacteroidetes dominated in captive gibbons, while Firmicutes, Bacteroidetes, and Tenericutes dominated in wild gibbons. At the genus level, captive gibbons were dominated by Treponema-2, followed by Succinivibrio and Cerasicoccus, while wild gibbons were dominated by Anaeroplasma, Prevotellaceae UCG-001, and Erysipelotrichaceae UCG-004. Captive rearing was significantly associated with lower taxonomic alpha-diversity, and different relative abundance of some dominant bacteria compared to wild gibbons. Predicted Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that captive gibbons have significantly lower total pathway diversity and higher relative abundance of bacterial functions involved in "drug resistance: antimicrobial" and "carbohydrate metabolism" than wild gibbons. This study reveals the potential influence of captivity and habitat on the gut bacterial community of gibbons and provides a basis for guiding the conservation management of captive populations.


Assuntos
Microbioma Gastrointestinal , Hylobatidae , Animais , Hylobates , RNA Ribossômico 16S/genética , Hylobatidae/genética , Ecossistema , Bactérias/genética
20.
Skeletal Radiol ; 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37712982

RESUMO

We reported a case of atypical spinal tuberculosis on the posterior elements of lumbar spine in a 52-year-old female. It was easy to be misdiagnosed as spinal tumor due to its imaging characteristics. We performed puncture biopsy to initially consider tuberculosis, and then the patient was accepted surgical treatment. The intraoperative removed specimen was sent to pathological examination, microbial culture, Xpert MTB/RIF and metagenomic next-generation sequencing (mNGS) and then the diagnosis of neural arch tuberculosis was confirmed. After operation, the patient obtained stable effect by anti-tuberculosis drug treatment. In a word, the uncommon case had an important reference significance for the diagnosis of atypical spine tuberculosis and differentiation from spinal tumors. It is critical to make right preliminary diagnosis by appropriate examination as it determined the next diagnosis and treatment in special and rare clinical cases.

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