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1.
Artigo em Inglês | MEDLINE | ID: mdl-38734818

RESUMO

The ventral subiculum (vSUB), the major output structure of the hippocampal formation, regulates motivation, stress integration, and anxiety-like behaviors that rely on heightened arousal. However, the roles and underlying neural circuits of the vSUB in wakefulness are poorly known. Using in vivo fiber photometry and multichannel electrophysiological recordings in mice, we found that the vSUB glutamatergic neurons exhibited high activities during wakefulness. Moreover, activation of vSUB glutamatergic neurons caused an increase in wakefulness and anxiety-like behaviors and induced a rapid transition from sleep to wakefulness. In addition, optogenetic stimulation of vSUB glutamatergic terminals and retrograde-targeted chemogenetic activation of vSUB glutamatergic neurons revealed that vSUB promoted arousal by innervating the lateral hypothalamus (LH), nucleus accumbens (NAc) shell, and prefrontal cortex (PFC). Nevertheless, local microinjection of dopamine D1 or D2/D3 receptor antagonist blocked the wake-promoting effect induced by chemogenetic activation of vSUB pathways. Finally, chemogenetic inhibition of vSUB glutamatergic neurons decreased arousal. Altogether, our findings reveal a prominent contribution of vSUB glutamatergic neurons to the control of wakefulness through several pathways.

2.
Cell Stem Cell ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38692273

RESUMO

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38700794

RESUMO

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-ß1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-ß/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.

4.
Int J Mol Sci ; 25(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38612919

RESUMO

Salvia miltiorrhiza is a prized traditional Chinese medicinal plant species. Its red storage roots are primarily used for the treatment of cardiovascular and cerebrovascular diseases. In this study, a transcription factor gene AtMYB2 was cloned and introduced into Salvia miltiorrhiza for ectopic expression. Overexpression of AtMYB2 enhanced salt stress resistance in S. miltiorrhiza, leading to a more resilient phenotype in transgenic plants exposed to high-salinity conditions. Physiological experiments have revealed that overexpression of AtMYB2 can decrease the accumulation of reactive oxygen species (ROS) during salt stress, boost the activity of antioxidant enzymes, and mitigate oxidative damage to cell membranes. In addition, overexpression of AtMYB2 promotes the synthesis of tanshinones and phenolic acids by upregulating the expression of biosynthetic pathway genes, resulting in increased levels of these secondary metabolites. In summary, our findings demonstrate that AtMYB2 not only enhances plant tolerance to salt stress, but also increases the accumulation of secondary metabolites in S. miltiorrhiza. Our study lays a solid foundation for uncovering the molecular mechanisms governed by AtMYB2 and holds significant implications for the molecular breeding of high-quality S. miltiorrhiza varieties.


Assuntos
Hidroxibenzoatos , Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Abietanos , Antioxidantes
5.
Respir Res ; 25(1): 164, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622598

RESUMO

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.


Assuntos
Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/terapia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Remodelação Ventricular , Ecocardiografia , Doença Crônica , Artéria Pulmonar/diagnóstico por imagem
6.
Cereb Cortex ; 34(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466114

RESUMO

It is important to explore causal relationships in functional magnetic resonance imaging study. However, the traditional effective connectivity analysis method is easy to produce false causality, and the detection accuracy needs to be improved. In this paper, we introduce a novel functional magnetic resonance imaging effective connectivity method based on the asymmetry detection of transfer entropy, which quantifies the disparity in predictive information between forward and backward time, subsequently normalizing this disparity to establish a more precise criterion for detecting causal relationships while concurrently reducing computational complexity. Then, we evaluate the effectiveness of this method on the simulated data with different level of nonlinearity, and the results demonstrated that the proposed method outperforms others methods on the detection of both linear and nonlinear causal relationships, including Granger Causality, Partial Granger Causality, Kernel Granger Causality, Copula Granger Causality, and traditional transfer entropy. Furthermore, we applied it to study the effective connectivity of brain functional activities in seafarers. The results showed that there are significantly different causal relationships between different brain regions in seafarers compared with non-seafarers, such as Temporal lobe related to sound and auditory information processing, Hippocampus related to spatial navigation, Precuneus related to emotion processing as well as Supp_Motor_Area associated with motor control and coordination, which reflects the occupational specificity of brain function of seafarers.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Entropia , Encéfalo/diagnóstico por imagem , Emoções , Cognição
7.
Brain Sci ; 14(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38539638

RESUMO

The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, plays an important role in the inflammatory mechanisms of the pathophysiology and progression of acute ischemic stroke (AIS). The aim of this study was to identify the potential factors associated with functional prognosis in AIS. A total of 303 AIS patients were enrolled in this study; baseline information of each participant, including demographic characteristics, medical history, laboratory data, and 90-day functional outcome, was collected. Multivariate logistic regression analysis revealed that NLR, systolic blood pressure (SBP) and National Institutes of Health Stroke Scale (NIHSS) score were found to be independent factors for poor functional outcomes. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive value of the NLR for 90-day functional outcome, with the best predictive cutoff value being 3.06. In the multivariate logistic regression analysis, three models were constructed: Model 1, adjusted for age, sex, SBP, and TOAST classification (AUC = 0.694); Model 2, further adjusted for the NIHSS score at admission (AUC = 0.826); and Model 3, additionally adjusted for the NLR (AUC = 0.829). The NLR at admission was an independent predictor of 90-day prognosis in patients with AIS. The risk factors related to poor 90-day functional outcomes were higher SBP, higher NLR, and a greater NIHSS score.

8.
Int J Cardiol Heart Vasc ; 51: 101363, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38445233

RESUMO

Background: Balloon pulmonary angioplasty (BPA) is an established treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its efficacy in CTEPH patients with a pulmonary comorbidity has not been well-studied. Here, we compared post-BPA outcomes between CTEPH patients with and without chronic pulmonary disease at baseline and analyzed predictors of BPA success. Methods: From August 2017 to October 2022, 62 patients with inoperable CTEPH who underwent BPA were consecutively enrolled and grouped based on the presence of a pulmonary comorbidity at baseline. All patients underwent transthoracic echocardiography, pulmonary function tests, and right heart catheterization. Pre- and post-BPA data were evaluated to identify factors that influence the success of BPA. Results: Among the 62 CTEPH patients, BPA was considered successful in 50 patients and unsuccessful in 12 patients. Responders to BPA had better exercise capacity and right heart function at baseline, but no differences in hemodynamic or respiratory function were detected between the groups. In CTEPH patients with chronic pulmonary disease (n = 14), BPA significantly improved mean pulmonary arterial pressure, pulmonary vascular resistance and right heart function parameters. Only CTEPH patients without chronic pulmonary disease (n = 48) exhibited significant improvement in 6-minute walk distance and respiratory function. Multivariate logistic regression analysis showed that pulmonary comorbidity at baseline was independently associated with the efficacy of BPA. Conclusions: BPA provided significantly improvements in hemodynamics and right heart function in CTEPH patients, independent of pulmonary comorbidity at baseline. However, pulmonary comorbidity can negatively impact post-BPA outcomes.

9.
Environ Sci Pollut Res Int ; 31(16): 24220-24234, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38436849

RESUMO

Two natural adsorbent materials, potassium humate (KHA) and montmorillonite (MMT), were successfully prepared by embedding them in sodium alginate (SA) gel spheres through physical cross-linking with CaCl2. And CaCO3 was used as a porogenic agent to prepare the porous composites, KHA/SA/MMT. The materials were characterized by using XRD, TGA, SEM, and N2 adsorption/desorption equipment. The results showed that MMT and KHA were successfully embedded in the SA gel; the introduction of MMT increased the thermal stability of the composites and the embedding of MMT, and the porogenic effect of CaCO3 increased the specific surface area of the composites substantially, which provided favorable conditions for adsorption and treatment of pollutants. In addition, a one-way exploratory experiment yielded a higher removal rate of Rhodamine B (RhB) at D = 0.6 g/L, pH = 5, C0 = 100 mg/L, and t = 360 min. The adsorption kinetics and adsorption isotherm conformed to the secondary kinetic model and Langmuir model, respectively, and the maximum adsorption of RhB by KHA/SA/MMT could reach up to 884.96 mg/g at 303 K. The adsorption mechanism for RhB was shown by FT-IR and XPS analyses to be possibly bound by non-covalent bonding forces. After seven consecutive adsorption-desorption cycles, the adsorption of RhB by KHA/SA/MMT still reached 80.75%. Therefore, the prepared gel spheres have the advantages of easy regeneration and efficient reuse and great potential for application in purifying RhB from wastewater.


Assuntos
Rodaminas , Poluentes Químicos da Água , Poluentes Químicos da Água/química , Adsorção , Alginatos , Espectroscopia de Infravermelho com Transformada de Fourier , Cinética , Concentração de Íons de Hidrogênio
10.
Angew Chem Int Ed Engl ; 63(14): e202401228, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38354230

RESUMO

Functional thin films, being fabricated by incorporating discrete supramolecular architectures, have potential applications in research areas such as sensing, energy storage, catalysis, and optoelectronics. Here, we have determined that an anion-coordinated triple helicate can be solution-processed into a functional thin film by incorporation into a polymethyl methacrylate (PMMA) matrix. The thin films fabricated by the incorporation of the anion-coordinated triple helicate show multiple optical properties, such as fluorescence, CD, and CPL. In addition, the film has the ability to recognize choline and choline derivatives in a water system. The successful recognition of Ch+ by the film represents the first example of utilizing 'aniono'-supramolecular architectures for biomolecule detection in aqueous solution and opens up a new route for designing biocompatible functional materials.

11.
J Exp Clin Cancer Res ; 42(1): 334, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057879

RESUMO

BACKGROUND: With the advancements in bioinformatic technology, an increasing number of circular RNAs (circRNAs) have been discovered and their crucial roles in the development and progression of various malignancies have been confirmed through multiple pathways. However, the specific mechanisms involving protein-binding circRNAs in colorectal cancer (CRC) remain largely unexplored. METHODS: Differential circRNA expression was assessed using a human circRNA microarray in five CRC tissue and paired normal samples. CircGPRC5A expression was then confirmed in the CRC tissues and paired normal samples using qRT-PCR. The biological function of circGPRC5A in CRC were studied in vitro and in vivo. Western blotting, fluorescence in situ hybridization, immunofluorescence, RNA pulldown, mass spectrometry, immunoprecipitation, quantitative phosphoproteomics, and RNA-binding protein immunoprecipitation assays were used to study circGPRC5A. RESULTS: Our analysis revealed that circGPRC5A expression was higher in CRC tissues compared to normal tissues and was associated with tumor size, tumor stage and lymph node status. CircGPRC5A promoted CRC cell proliferation, migration, and metastasis in vitro and in vivo. CircGPRC5A could stabilize PPP1CA protein by inhibiting the binding between UBA1 and PPP1CA, and increasing YAP dephosphorylation. CONCLUSIONS: Our study revealed that circGPRC5A plays an essential function in CRC progression by stabilizing PPP1CA protein and enhancing YAP dephosphorylation. CircGPRC5A could act as a novel and potential target for CRC.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Hibridização in Situ Fluorescente , MicroRNAs/genética , Proteína Fosfatase 1/metabolismo , RNA/genética , RNA Circular/genética , RNA Circular/metabolismo
12.
Plant Cell Rep ; 43(1): 18, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38148416

RESUMO

KEY MESSAGE: Editing ZmGA20ox3 can achieve the effect similar to applying Cycocel, which can reduce maize plant height and enhance stress resistance. Drought stress, a major plant abiotic stress, is capable of suppressing crop yield performance severely. However, the trade-off between crop drought tolerance and yield performance turns out to be significantly challenging in drought-resistant crop breeding. Several phytohormones [e.g., gibberellin (GA)] have been reported to play a certain role in plant drought response, which also take on critical significance in plant growth and development. In this study, the loss-of-function mutations of GA biosynthesis enzyme ZmGA20ox3 were produced using the CRISPR-Cas9 system in maize. As indicated by the result of 2-year field trials, the above-mentioned mutants displayed semi-dwarfing phenotype with the decrease of GA1, and almost no yield loss was generated compared with wild-type (WT) plants. Interestingly, as revealed by the transcriptome analysis, differential expressed genes (DEGs) were notably enriched in abiotic stress progresses, and biochemical tests indicated the significantly increased ABA, JA, and DIMBOA levels in mutants, suggesting that ZmGA20ox3 may take on vital significance in stress response in maize. The in-depth analysis suggested that the loss function of ZmGA20ox3 can enhance drought tolerance in maize seedling, reduce Anthesis-Silking Interval (ASI) delay while decreasing the yield loss significantly in the field under drought conditions. The results of this study supported that regulating ZmGA20ox3 can improve plant height while enhancing drought resistance in maize, thus serving as a novel method for drought-resistant genetic improvement in maize.


Assuntos
Resistência à Seca , Edição de Genes , Zea mays/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Melhoramento Vegetal , Secas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética
13.
Int J Mol Sci ; 24(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37958490

RESUMO

Transcription factors play crucial roles in regulating plant abiotic stress responses and physiological metabolic processes, which can be used for plant molecular breeding. In this study, an R2R3-MYB transcription factor gene, AtMYB12, was isolated from Arabidopsis thaliana and introduced into Salvia miltiorrhiza under the regulation of the CaMV35S promoter. The ectopic expression of AtMYB12 resulted in improved salt tolerance in S. miltiorrhiza; transgenic plants showed a more resistant phenotype under high-salinity conditions. Physiological experiments showed that transgenic plants exhibited higher chlorophyll contents, and decreased electrolyte leakage and O2- and H2O2 accumulation when subjected to salt stress. Moreover, the activity of reactive oxygen species (ROS)-scavenging enzymes was enhanced in S. miltiorrhiza via the overexpression of AtMYB12, and transgenic plants showed higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities compared with those of the wild type (WT) under salt stress, coupled with lower malondialdehyde (MDA) levels. In addition, the amount of salvianolic acid B was significantly elevated in all AtMYB12 transgenic hair roots and transgenic plants, and qRT-PCR analysis revealed that most genes in the phenolic acid biosynthetic pathway were up-regulated. In conclusion, these results demonstrated that AtMYB12 can significantly improve the resistance of plants to salt stress and promote the biosynthesis of phenolic acids by regulating genes involved in the biosynthetic pathway.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Salvia miltiorrhiza , Arabidopsis/metabolismo , Salvia miltiorrhiza/metabolismo , Tolerância ao Sal/genética , Peróxido de Hidrogênio/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética , Antioxidantes , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
14.
Opt Lett ; 48(22): 5847-5850, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966734

RESUMO

Wavefront coding (WFC) combines phase mask design and image restoration algorithm to extend the depth of field (DOF) for various applications. However, discrete design limits finding globally optimal solutions, increasing the complexity of system design, and affecting the accuracy and robustness of image restoration. An end-to-end imaging system design has emerged to break through these limitations by integrating optical design and image processing algorithms. In this study, we propose an algorithm that synchronously optimizes the optical elements and decoding algorithm in WFC using ray-tracing simulation. We also derive formulas for the optical layer's forward and backward propagation for joint optimization of the optical layer and decoding algorithm. Experimental verification demonstrates the algorithm's effectiveness in optimizing the WFC system and offers improved performance under a unified design framework.

15.
Brain Imaging Behav ; 17(5): 530-540, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37433970

RESUMO

OBJECTIVES: The alterations in cerebellar activity that occur in vascular mild cognitive impairment remain largely unexplored. This study aimed to investigate potential associations between abnormal cerebellar functional connectivity (FC) and changes in cognitive function by examining intracerebellar and cerebellar-cerebral FC. METHODS: MRI data were collected from seventy-two patients with vascular mild cognitive impairment (VMCI), comprising 38 patients with small vessel mild cognitive impairment (SVMCI) and 34 with poststroke mild cognitive impairment (PSMCI), and from 43 demographically matched healthy controls (HCs). Changes in FC between subregions within the cerebellum and from each cerebellar subregion to the selected cerebral seed points in VMCI patients were calculated, and the association of these changes with cognitive function was examined. RESULTS: Compared with HCs, we found that VMCI patients had 11 cerebellar subregions showing significant differences (mainly decreases) in FC with brain regions in the default-mode network (DMN), sensory-motor network (SMN), and frontoparietal network (FPN). In the intracerebellar FC analysis, 47 (8%) cerebellar connections had significant intergroup differences, mainly a reduced magnitude of FC in VMCI patients. In the correlation analysis, higher Montreal Cognitive Assessment (MoCA) scores were correlated with stronger intracerebellar FC (left crus II-right lobule VI, left crus II-right lobule VIIb) and cerebellar-cerebral FC (right lobule X-left precuneus, vermal lobule IX-right inferior parietal lobule) in both the SVMCI and PSMCI groups. CONCLUSION: These findings suggest prominent intracerebellar and cerebellar-cerebral FC abnormalities in VMCI patients, contributing evidence for a possible role of the cerebellum in cognitive processes.


Assuntos
Disfunção Cognitiva , Imageamento por Ressonância Magnética , Humanos , Cerebelo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Lobo Parietal , Disfunção Cognitiva/diagnóstico por imagem
16.
Front Aging Neurosci ; 15: 1224525, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37416325

RESUMO

Background and objective: This study aims to examine the role of neurovascular coupling (NVC) in vascular cognitive impairment (VCI) by investigating the relationship between white matter lesion (WML) burden, NVC, and cognitive deficits. Additionally, we aim to explore the potential of NVC as a tool for understanding the neural mechanisms underlying VCI. Methods: This study included thirty-eight small vessel disease cognitive impairment (SVCI) patients, 34 post-stroke cognitive impairment (PSCI) patients, and 43 healthy controls (HC). Comprehensive assessments, including neuroimaging and neuropsychological testing, were conducted to evaluate cognitive function. WML burden was measured and correlated with NVC coefficients to examine the relationship between white matter pathology and NVC. Mediation analysis was employed to explore the link relationship between NVC, WML burden, and cognitive function. Results: The present study showed that NVC was significantly reduced in the SVCI and PSCI groups compared with HCs at both whole-brain and brain region level. The analysis revealed notable findings regarding NVC in relation to WML burden and cognitive function in VCI patients. Specifically, reduced NVC coefficients were observed within higher order brain systems responsible for cognitive control and emotion regulation. Mediation analysis demonstrated that NVC played a mediating role in the relationship between WML burden and cognitive impairment. Conclusion: This study reveals the mediating role of NVC in the relationship between WML burden and cognitive function in VCI patients. The results demonstrate the potential of the NVC as an accurate measure of cognitive impairment and its ability to identify specific neural circuits affected by WML burden.

17.
bioRxiv ; 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37293038

RESUMO

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The synthetic niche reprograms differentiated nephron cells into NPC state, recapitulating the plasticity of developing nephron in vivo. Scalability and ease of genome-editing in the cultured NPCs allow for genome-wide CRISPR screening, identifying novel genes associated with kidney development and disease. A rapid, efficient, and scalable organoid model for polycystic kidney disease was derived directly from genome-edited NPCs, and validated in drug screen. These technological platforms have broad applications to kidney development, disease, plasticity, and regeneration.

18.
Environ Sci Pollut Res Int ; 30(32): 78933-78947, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37277589

RESUMO

Groundwater contaminant source identification (GCSI) has practical significance for groundwater remediation and liability. However, when applying the simulation-optimization method to precisely solve GCSI, the optimization model inevitably encounters the problems of high-dimensional unknown variables to identify, which might increase the nonlinearity. In particular, to solve such optimization models, the well-known heuristic optimization algorithms might fall into a local optimum, resulting in low accuracy of inverse results. For this reason, this paper proposes a novel optimization algorithm, namely, the flying foxes optimization (FFO) to solve the optimization model. We perform simultaneous identification of the release history of groundwater pollution sources and hydraulic conductivity and compare the results with those of the traditional genetic algorithm. In addition, to alleviate the massive computational load caused by the frequent invocation of the simulation model when solving the optimization model, we utilized the multilayer perception (MLP) to establish a surrogate model of the simulation model and compared it with the method of backpropagation algorithm (BP). The results show that the average relative error of the results of FFO is 2.12%, significantly outperforming the genetic algorithm (GA); the surrogate model of MLP can replace the simulation model for calculation with fitting accuracy of more than 0.999, which is better than the commonly used surrogate model of BP.


Assuntos
Quirópteros , Água Subterrânea , Animais , Modelos Teóricos , Simulação por Computador , Algoritmos , Redes Neurais de Computação
19.
Heart Lung Circ ; 32(9): 1080-1088, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37355431

RESUMO

OBJECTIVES: This study examined the echocardiographic characteristics of patients with pulmonary artery intimal sarcoma (PAIS) and compared the results with those from computed tomographic pulmonary angiography (CTPA). METHOD: Twenty-six (26) patients were diagnosed with PAIS at the current institution during the study period, and 23 were eligible for analysis. Echocardiography and CTPA examinations were performed in all enrolled patients. RESULTS: The echocardiography results showed that most lesions had expansive growth in the left pulmonary artery (PA); the right PA; or a combination of the left PA, right PA, and main PA, with extension to the pulmonary valve and/or right ventricular outflow tract. These lesions also had distinctive sieve-like echogenic signals. Echocardiography also showed that some lesions had lobulated shapes, were nearly round and echolucent or with calcifications, and moved during imaging. The lesion distribution was similar in CTPA and echocardiography (p=0.361), but CTPA was more sensitive in detection of the complete shape (p=0.023). CONCLUSIONS: The unique echocardiographic characteristics of PAIS, especially the "sieve sign", could help in the diagnosis of this cancer. Transthoracic echocardiography is a non-invasive technique that appears effective in detecting PAIS.


Assuntos
Neoplasias Pulmonares , Embolia Pulmonar , Sarcoma , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Pulmão , Sarcoma/diagnóstico por imagem , Ecocardiografia/métodos , Embolia Pulmonar/diagnóstico
20.
J Cardiothorac Surg ; 18(1): 178, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170135

RESUMO

Pulmonary artery sarcoma (PAS) is a sporadic malignant tumor that mainly originates from the pulmonary arteries. However, PAS may also involve the right ventricular outflow tract (RVOT) and lead to obstruction, syncope, or sudden death. Early diagnosis and complete surgical resection are essential to prolong survival and improve the quality of life of patients with PAS. Herein, we report a case of a young female patient admitted for pulmonary malignancy and acute pulmonary embolism. The patient had a mass in the RVOT, which was detected by transthoracic echocardiography. Computed tomography and magnetic resonance imaging revealed the invasion depth and extent of the lesions. Surgical resection improved hemodynamics, while pathological and immunohistochemical tests confirmed the diagnosis of a pulmonary artery sarcoma. Local recurrence was detected in the adjacent tissues about two months after the surgery. Given the potential risk of reoperation, the patient was suggested to undergo conservative treatment.


Assuntos
Neoplasias Pulmonares , Sarcoma , Obstrução do Fluxo Ventricular Externo , Humanos , Feminino , Artéria Pulmonar/diagnóstico por imagem , Qualidade de Vida , Sarcoma/diagnóstico , Sarcoma/cirurgia , Sarcoma/patologia , Ecocardiografia/métodos , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/cirurgia
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