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1.
Sci Total Environ ; 954: 176382, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39304155

RESUMO

The capacitive deionization (CDI) has emerged as a robust technology due to its effective performance in removing and recovering phosphate in wastewater. However, there are still challenges in achieving fast charge transfer and high capacity phosphorus storage simultaneously. In this study, a layered double hydroxide-polyaniline-carbon nanotubes composite material (ZnFe-PANI/CNT) with heterojunction and pseudocapacitive characteristics was fabricated via a simple and effective precipitation strategy. The existence of heterojunction and pseudocapacitance of ZnFe-PANI/CNT was confirmed through material performance testing Moreover, with its fast charge transfer and high ion storage performance, it was achieved high phosphate adsorption efficiency (94 %) and sustainable electrode regeneration in low concentration phosphate wastewater. Ultraviolet photoelectron spectroscopy (UPS) and density functional theory revealed the ability to accelerate charge transfer, which was contributed by the heterojunction ZnFe-PANI/CNT. In addition, it was found that the synergies of electrostatic attraction, ligand exchange and surface complexation contributed to the high phosphate capture ability in the acidic environments. The binuclear bidentate or mononuclear bidentate structures dominated the surface configuration of phosphate adsorption at pH 4-9.

2.
iScience ; 27(9): 110732, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39310775

RESUMO

Global warming significantly impacts amphibian populations globally, and modeling helps understand these effects. Here, we used MaxEnt and MigClim models to predict the impact of climate change on habitat suitability for Hoplobatrachus chinensis. Our results indicate that temperature is a key factor affecting H. chinensis distribution. Increasing temperatures positively correlated with habitat suitability, with suitable habitat expanding northward by 2060 while maintaining suitability in the southern parts of the range. We found a 25.18% overlap between the current potential suitable habitat of H. chinensis and agricultural wetlands. Our model indicated that H. chinensis might be able to track shifts in suitable habitats under climate change given a 15 km dispersal ability per generation. Climate change will likely expand suitable habitat for H. chinensis. Our predictions offer important guidance for the conservation of the species, especially for the integrated role of natural and agricultural wetlands such as rice paddies.

3.
medRxiv ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39314940

RESUMO

Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). Their detection is paramount in the clinical management of those with AMD, yet they remain challenging to reliably identify. We thus developed a deep learning (DL) model to segment RPD from 9,800 optical coherence tomography B-scans, and this model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC]=0·76 [95% confidence interval [CI] 0·71-0·81]) than the agreement amongst the specialists (DSC=0·68, 95% CI=0·63-0·73; p <0·001). In five external test datasets consisting of 1,017 eyes from 812 individuals, the DL model detected RPD with a similar level of performance as two retinal specialists (area-under-the-curve of 0·94 [95% CI=0·92-0·97], 0·95 [95% CI=0·92-0·97] and 0·96 [95% CI=0·94-0·98] respectively; p ≥0·32). This DL model enables the automatic detection and quantification of RPD with expert-level performance, which we have made publicly available.

4.
Ophthalmol Sci ; 4(6): 100551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161750

RESUMO

Purpose: To understand the spatial relationship between local rod-mediated visual function and reticular pseudodrusen (RPD) in eyes with large drusen. Design: Retrospective cross-sectional study. Participants: One eye with large drusen (>125 µm) each from 91 individuals with intermediate age-related macular degeneration, with and without RPD. Methods: All participants underwent dark adaptation testing using a dark-adapted chromatic perimeter, where visual sensitivities were measured over 30 minutes of dark adaptation after photobleach. The rod intercept time (RIT; a measure of dynamic rod function) and pointwise sensitivity difference (PWSD; a relative measure of rod- compared with cone-mediated function) was determined at multiple retinal locations, and their association with the overall (central 20° × 20° region) and local (2° diameter region centered on the location tested) extent of RPD and drusen (quantified using multimodal imaging) was examined. Main Outcome Measures: Association between overall and local extent of RPD and drusen with RIT and PWSD at each retinal location tested. Results: In a multivariable analysis, delayed RIT was associated with an increasing overall (P < 0.001), but not local (P = 0.884), extent of RPD. In contrast, the increasing local (P < 0.001), but not overall (P = 0.475), extent of drusen was associated with delayed RIT. Furthermore, only an increasing overall extent of RPD (P < 0.001) was associated with reduced PWSD (or worse rod compared with cone function), but not the local extent of RPD and drusen, or overall extent of drusen (P ≥ 0.344). Conclusions: Local rod-mediated function was associated with the overall, rather than local, extent of RPD in eyes with large drusen, suggesting that there may be widespread pathologic changes in eyes with RPD that account for this. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

5.
Clin Exp Ophthalmol ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39089690

RESUMO

BACKGROUND: Nocturnal hypoxia is common, under-diagnosed and is found in the same demographic at risk of age-related macular degeneration (AMD). The objective of this study was to determine any association between nocturnal hypoxia and AMD, its severity, and the high-risk sub-phenotype of reticular pseudodrusen (RPD). METHODS: This cross-sectional study included participants aged ≥50 years with AMD, or normal controls, exclusive of those on treatment for obstructive sleep apnoea. All participants had at home, overnight (up to 3 nights) pulse oximetry recordings and multimodal imaging to classify AMD. Classification of Obstructive Sleep Apnea (OSA) was determined based on oxygen desaturation index [ODI] with mild having values of 5-15 and moderate-to-severe >15. RESULTS: A total of 225 participants were included with 76% having AMD, of which 42% had coexistent RPD. Of the AMD participants, 53% had early/intermediate AMD, 30% had geographic atrophy (GA) and 17% had neovascular AMD (nAMD). Overall, mild or moderate-to-severe OSAwas not associated with an increased odds of having AMD nor AMD with RPD (p ≥ 0.180). However, moderate-to-severe OSA was associated with increased odds of having nAMD (odds ratio = 6.35; 95% confidence interval = 1.18 to 34.28; p = 0.032), but not early/intermediate AMD or GA, compared to controls (p ≥ 0.130). Mild OSA was not associated with differences in odds of having AMD of any severity (p ≥ 0.277). CONCLUSIONS: There was an association between nocturnal hypoxia as measured by the ODI and nAMD. Hence, nocturnal hypoxia may be an under-appreciated important modifiable risk factor for nAMD.

6.
Ophthalmol Sci ; 4(6): 100566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139546

RESUMO

Objective: Recent developments in artificial intelligence (AI) have positioned it to transform several stages of the clinical trial process. In this study, we explore the role of AI in clinical trial recruitment of individuals with geographic atrophy (GA), an advanced stage of age-related macular degeneration, amidst numerous ongoing clinical trials for this condition. Design: Cross-sectional study. Subjects: Retrospective dataset from the INSIGHT Health Data Research Hub at Moorfields Eye Hospital in London, United Kingdom, including 306 651 patients (602 826 eyes) with suspected retinal disease who underwent OCT imaging between January 1, 2008 and April 10, 2023. Methods: A deep learning model was trained on OCT scans to identify patients potentially eligible for GA trials, using AI-generated segmentations of retinal tissue. This method's efficacy was compared against a traditional keyword-based electronic health record (EHR) search. A clinical validation with fundus autofluorescence (FAF) images was performed to calculate the positive predictive value of this approach, by comparing AI predictions with expert assessments. Main Outcome Measures: The primary outcomes included the positive predictive value of AI in identifying trial-eligible patients, and the secondary outcome was the intraclass correlation between GA areas segmented on FAF by experts and AI-segmented OCT scans. Results: The AI system shortlisted a larger number of eligible patients with greater precision (1139, positive predictive value: 63%; 95% confidence interval [CI]: 54%-71%) compared with the EHR search (693, positive predictive value: 40%; 95% CI: 39%-42%). A combined AI-EHR approach identified 604 eligible patients with a positive predictive value of 86% (95% CI: 79%-92%). Intraclass correlation of GA area segmented on FAF versus AI-segmented area on OCT was 0.77 (95% CI: 0.68-0.84) for cases meeting trial criteria. The AI also adjusts to the distinct imaging criteria from several clinical trials, generating tailored shortlists ranging from 438 to 1817 patients. Conclusions: This study demonstrates the potential for AI in facilitating automated prescreening for clinical trials in GA, enabling site feasibility assessments, data-driven protocol design, and cost reduction. Once treatments are available, similar AI systems could also be used to identify individuals who may benefit from treatment. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

7.
Acta Neuropathol Commun ; 12(1): 117, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014393

RESUMO

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.


Assuntos
Metilação de DNA , Glândula Pineal , Pinealoma , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pinealoma/genética , Pinealoma/patologia , Adolescente , Adulto Jovem , Criança , Glândula Pineal/patologia , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Pré-Escolar , Variações do Número de Cópias de DNA
8.
Food Chem X ; 23: 101548, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38974200

RESUMO

Granaticins are natural pigments derived from microorganisms with promising bioactivity. However, their practical applications have been restricted due to inherent instability. To improve the stability of granaticins from the novel strain Streptomyces vilmorinianum YP1, microcapsules were prepared using gum Arabic (GA) by a freeze-drying method. The optimal parameters for microencapsulation were determined using response surface methodology. Under the optimal conditions (GA 9.2% (v/v), a wall/-core ratio 4.8 (w/w), encapsulating temperature 29 °C), the maximum encapsulation efficiency achieved was 93.64%. The microcapsules were irregular single crystals with an average particle size of 206.37 ± 2.51 nm. Stability testing indicated improved stability of the microencapsulated granaticins. Notably, granaticnic B retention increased by 17.0% and 6.6% after exposure to sunlight and storage at 4 °C, respectively. These finding suggest that GA as a well material significantly enhances the stability of granaticins from S. vilmorinianum YP1, facilitating their potential applications.

9.
Invest Ophthalmol Vis Sci ; 65(8): 30, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39028907

RESUMO

Purpose: Investigating the sequence of morphological changes preceding outer plexiform layer (OPL) subsidence, a marker preceding geographic atrophy, in intermediate AMD (iAMD) using high-precision artificial intelligence (AI) quantifications on optical coherence tomography imaging. Methods: In this longitudinal observational study, individuals with bilateral iAMD participating in a multicenter clinical trial were screened for OPL subsidence and RPE and outer retinal atrophy. OPL subsidence was segmented on an A-scan basis in optical coherence tomography volumes, obtained 6-monthly with 36 months follow-up. AI-based quantification of photoreceptor (PR) and outer nuclear layer (ONL) thickness, drusen height and choroidal hypertransmission (HT) was performed. Changes were compared between topographic areas of OPL subsidence (AS), drusen (AD), and reference (AR). Results: Of 280 eyes of 140 individuals, OPL subsidence occurred in 53 eyes from 43 individuals. Thirty-six eyes developed RPE and outer retinal atrophy subsequently. In the cohort of 53 eyes showing OPL subsidence, PR and ONL thicknesses were significantly decreased in AS compared with AD and AR 12 and 18 months before OPL subsidence occurred, respectively (PR: 20 µm vs. 23 µm and 27 µm [P < 0.009]; ONL, 84 µm vs. 94 µm and 98 µm [P < 0.008]). Accelerated thinning of PR (0.6 µm/month; P < 0.001) and ONL (0.8 µm/month; P < 0.001) was observed in AS compared with AD and AR. Concomitant drusen regression and hypertransmission increase at the occurrence of OPL subsidence underline the atrophic progress in areas affected by OPL subsidence. Conclusions: PR and ONL thinning are early subclinical features associated with subsequent OPL subsidence, an indicator of progression toward geographic atrophy. AI algorithms are able to predict and quantify morphological precursors of iAMD conversion and allow personalized risk stratification.


Assuntos
Aprendizado Profundo , Atrofia Geográfica , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Feminino , Masculino , Idoso , Atrofia Geográfica/diagnóstico , Pessoa de Meia-Idade , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/diagnóstico por imagem , Seguimentos , Progressão da Doença , Idoso de 80 Anos ou mais , Drusas Retinianas/diagnóstico , Atrofia
10.
Invest Ophthalmol Vis Sci ; 65(8): 44, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39078733

RESUMO

Purpose: To understand the microperimetry response characteristics of regions with a truly nonresponding location, which will be useful when considering criteria for end-stage atrophic age-related macular degeneration (AMD). Methods: A simulation model was developed using data from 128 participants with bilateral large drusen at baseline seen over 36 months at 6-month intervals. One hundred thousand pairs of real-world microperimetry testing results were simulated separately with and without one truly nonresponding location, where the sensitivity of one randomly selected location for the former group was derived from the distribution of responses from a truly nonresponding location at the optic nerve head from 60 healthy participants. Results: Only 60% of the simulated test pairs with a truly nonresponding location had ≥1 location that was <0 decibel (dB) on both tests. In contrast, 91% of the simulated test pairs had ≥1 location that was ≤10 dB on both tests, and 87% had ≥1 location that was ≤10 dB on both tests and <0 dB for one of the tests. Of the simulated test pairs without a truly nonresponding location, there were 0.04%, 1.4%, and 0.4% that met these three above criteria, respectively. Conclusions: Regions with a truly nonresponding test location do not almost always show a repeatable absolute scotoma (<0 dB), but instead, much more often a deep visual sensitivity defect (≤10 dB), with or without having an absolute scotoma on one of the tests. These findings are crucial if functional criteria are to be considered as part of a definition of end-stage atrophic AMD.


Assuntos
Degeneração Macular , Testes de Campo Visual , Campos Visuais , Humanos , Testes de Campo Visual/métodos , Campos Visuais/fisiologia , Feminino , Masculino , Idoso , Degeneração Macular/fisiopatologia , Degeneração Macular/diagnóstico , Atrofia Geográfica/fisiopatologia , Atrofia Geográfica/diagnóstico , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Idoso de 80 Anos ou mais
11.
J Hazard Mater ; 475: 134924, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38880045

RESUMO

Nanofiltration (NF) is a promising technology in the treatment of microelectronic wastewater. However, the treatment of concentrate derived from NF system remains a substantial technical challenge, impeding the achievement of the zero liquid discharge (ZLD) goal in microelectronic wastewater industries. Herein, a ZLD system, coupling a two-stage NF technology with anaerobic biotechnology was proposed for the treatment of tetramethylammonium hydroxide (TMAH)-contained microelectronic wastewater. The two-stage NF system exhibited favorable efficacy in the removal of conductivity (96 %), total organic carbon (TOC, 90 %), and TMAH (96 %) from microelectronic wastewater. The membrane fouling of this system was dominated by organic fouling, with the second stage NF membrane experiencing a more serious fouling compared to the first stage membrane. The anaerobic biotechnology achieved a near-complete removal of TMAH and an 80 % reduction in TOC for the first stage NF concentrate. Methyloversatilis was the key genus involved in the anaerobic treatment of the microelectronic wastewater concentrate. Specific genes, including dmd-tmd, mtbA, mttB and mttC were identified as significant players in mediating the dehydrogenase and methyl transfer pathways during the process of TMAH biodegradation. This study highlights the potential of anaerobic biodegradation to achieve ZLD in the treatment of TMAH-contained microelectronic wastewater by NF system.


Assuntos
Biodegradação Ambiental , Filtração , Compostos de Amônio Quaternário , Águas Residuárias , Águas Residuárias/química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/metabolismo , Anaerobiose , Eliminação de Resíduos Líquidos/métodos , Membranas Artificiais , Purificação da Água/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismo , Reatores Biológicos , Resíduo Eletrônico , Nanotecnologia
12.
Transl Vis Sci Technol ; 13(6): 7, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38874975

RESUMO

Purpose: The subsidence of the outer plexiform layer (OPL) is an important imaging biomarker on optical coherence tomography (OCT) associated with early outer retinal atrophy and a risk factor for progression to geographic atrophy in patients with intermediate age-related macular degeneration (AMD). Deep neural networks (DNNs) for OCT can support automated detection and localization of this biomarker. Methods: The method predicts potential OPL subsidence locations on retinal OCTs. A detection module (DM) infers bounding boxes around subsidences with a likelihood score, and a classification module (CM) assesses subsidence presence at the B-scan level. Overlapping boxes between B-scans are combined and scored by the product of the DM and CM predictions. The volume-wise score is the maximum prediction across all B-scans. One development and one independent external data set were used with 140 and 26 patients with AMD, respectively. Results: The system detected more than 85% of OPL subsidences with less than one false-positive (FP)/scan. The average area under the curve was 0.94 ± 0.03 for volume-level detection. Similar or better performance was achieved on the independent external data set. Conclusions: DNN systems can efficiently perform automated retinal layer subsidence detection in retinal OCT images. In particular, the proposed DNN system detects OPL subsidence with high sensitivity and a very limited number of FP detections. Translational Relevance: DNNs enable objective identification of early signs associated with high risk of progression to the atrophic late stage of AMD, ideally suited for screening and assessing the efficacy of the interventions aiming to slow disease progression.


Assuntos
Degeneração Macular , Redes Neurais de Computação , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Idoso , Feminino , Masculino , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Atrofia Geográfica/diagnóstico por imagem , Atrofia Geográfica/diagnóstico , Progressão da Doença , Retina/diagnóstico por imagem , Retina/patologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
13.
Opt Express ; 32(11): 20230-20241, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859138

RESUMO

A low-complexity multi-subcarrier pulse generation scheme is proposed to suppress the interference fading in a phase-sensitive optical time-domain reflectometer (Φ-OTDR) based distributed acoustic sensor (DAS) with heterodyne coherent detection. The multi-subcarrier pulse is generated in the digital domain based on the proper clipping operation of a sine signal. The localization and recovery of the disturbance signal are realized by the spectrum extraction and rotated vector sum (SERVS) method. The experimental results show that the occurrences of interference fading can be significantly reduced. The intensity fluctuation is reduced from ∼75 dB to ∼25 dB. Multiple disturbance signals are successfully demodulated to verify the effectiveness of the proposed method.

14.
J Liposome Res ; : 1-12, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733152

RESUMO

Neogambogic acid (NGA), which possesses a variety of anticancer activities, is visualized as an anticancer bioactive ingredient. However, the huge vascular stimulation, poor aqueous solubility, and short half-life restricted its clinical use. In this work, an effective nanocarrier was explored to reduce toxicity and enhance the tumor-targeted delivery. Two liposomal formulations, neogambogic acid liposomes (NGA-L), and hyaluronic acid-coated neogambogic acid liposomes (HA-NGA-L) were prepared and characterized with high encapsulation efficiency, slow pattern of drug release, narrow size distribution and higher stability. The cytotoxicity and cellular uptake of HA-NGA-L were higher than those of NGA-L in MDA-MB-231 cells (high CD44 expression), while no obvious differences in MCF-7 cells with (low CD44 expression), suggesting the CD44-mediated cellular internalization of hyaluronic acid-modified liposomes enhanced the cytotoxicity. Mechanistically, elevation of Bax and caspase-3 as well as downregulation of Bcl-2 led to cell apoptosis. Besides, the vascular stimulation and the hemolysis test indicated good safety of HA-NGA-L. In addition, HA-NGA-L was the effective nanocarrier to repress tumor proliferation in MDA-MB-231 tumor xenograft mouse through CD44 mediated active targeting without any obvious histopathological abnormities on major organs. Immunohistochemistry analysis revealed the enhanced elevation of Bax and caspase-3, and reduced expression of Bcl-2 contribute to apoptosis in tumors. Meanwhile, HA-NGA-L increased the AUC and t1/2 by 5.34-fold and 3.94-fold, respectively. In summary, the present study shows that HA-NGA-L may be safe and effective for the tumor-targeted delivery of neogambogic acid.

15.
Gene ; 923: 148561, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-38754570

RESUMO

Intermuscular bones, which are present in numerous economically significant fish species, have a negative impact on the development of aquaculture. The Asb15b gene, primarily expressed in skeletal muscle, plays a crucial role in regulating protein turnover and the development of muscle fibers. It stimulates protein synthesis and controls the differentiation of muscle fibers. In this study, we employed CRISPR/Cas9 technology to generate homozygous zebrafish strains with 7 bp and 49 bp deletions in the Asb15b gene. Subsequent analyses using skeleton staining demonstrated a substantial reduction in the number of intermuscular bones in adult Asb15b-/- -7 bp and Asb15b-/- -49 bp mutants compared to the wild-type zebrafish, with decreases of 30 % (P < 0.001) and 40 % (P < 0.0001), respectively. Histological experiments further revealed that the diameter and number of muscle fibers in adult Asb15b-/- mutants did not exhibit significant changes when compared to wild-type zebrafish. Moreover, qRT-PCR experiments demonstrated significant differences in the expression of bmp6 and runx2b genes, which are key regulators of intermuscular bone development, during different stages of intermuscular bone development in Asb15b-/- mutants. This study strongly suggests that the Asb15b gene plays a crucial role in regulating intermuscular bone development in fish and lays the groundwork for further exploration of the role of the Asb15b gene in zebrafish intermuscular bone development.


Assuntos
Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Osso e Ossos/metabolismo , Desenvolvimento Ósseo/genética , Sistemas CRISPR-Cas , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Músculo Esquelético/metabolismo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Repetição de Anquirina
16.
Stem Cell Rev Rep ; 20(6): 1569-1586, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38713406

RESUMO

Although stem/progenitor cell therapy shows potential for myocardial infarction repair, enhancing the therapeutic efficacy could be achieved through additional genetic modifications. HCLS1-associated protein X-1 (HAX1) has been identified as a versatile modulator responsible for cardio-protective signaling, while its role in regulating stem cell survival and functionality remains unknown. In this study, we investigated whether HAX1 can augment the protective potential of Sca1+ cardiac stromal cells (CSCs) for myocardial injury. The overexpression of HAX1 significantly increased cell proliferation and conferred enhanced resistance to hypoxia-induced cell death in CSCs. Mechanistically, HAX1 can interact with Mst1 (a prominent conductor of Hippo signal transduction) and inhibit its kinase activity for protein phosphorylation. This inhibition led to enhanced nuclear translocation of Yes-associated protein (YAP) and activation of downstream therapeutic-related genes. Notably, HAX1 overexpression significantly increased the pro-angiogenic potential of CSCs, as demonstrated by elevated expression of vascular endothelial growth factors. Importantly, implantation of HAX1-overexpressing CSCs promoted neovascularization, protected against functional deterioration, and ameliorated cardiac fibrosis in ischemic mouse hearts. In conclusion, HAX1 emerges as a valuable and efficient inducer for enhancing the effectiveness of cardiac stem or progenitor cell therapeutics.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proliferação de Células , Via de Sinalização Hippo , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Proteínas de Sinalização YAP , Animais , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Camundongos , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Proliferação de Células/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Humanos , Infarto do Miocárdio/terapia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Neovascularização Fisiológica , Células-Tronco/metabolismo , Células-Tronco/citologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Transplante de Células-Tronco , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento de Hepatócito/genética , Proteínas Proto-Oncogênicas
17.
Clin Exp Ophthalmol ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38812454

RESUMO

BACKGROUND: To examine whether the clinical performance of predicting late age-related macular degeneration (AMD) development is improved through using multimodal imaging (MMI) compared to using colour fundus photography (CFP) alone, and how this compares with a basic prediction model using well-established AMD risk factors. METHODS: Individuals with AMD in this study underwent MMI, including optical coherence tomography (OCT), fundus autofluorescence, near-infrared reflectance and CFP at baseline, and then at 6-monthly intervals for 3-years to determine MMI-defined late AMD development. Four retinal specialists independently assessed the likelihood that each eye at baseline would progress to MMI-defined late AMD over 3-years with CFP, and then with MMI. Predictive performance with CFP and MMI were compared to each other, and to a basic prediction model using age, presence of pigmentary abnormalities, and OCT-based drusen volume. RESULTS: The predictive performance of the clinicians using CFP [AUC = 0.75; 95% confidence interval (CI) = 0.68-0.82] improved when using MMI (AUC = 0.79; 95% CI = 0.72-0.85; p = 0.034). However, a basic prediction model outperformed clinicians using either CFP or MMI (AUC = 0.85; 95% CI = 0.78-91; p ≤ 0.002). CONCLUSIONS: Clinical performance for predicting late AMD development was improved by using MMI compared to CFP. However, a basic prediction model using well-established AMD risk factors outperformed retinal specialists, suggesting that such a model could further improve personalised counselling and monitoring of individuals with the early stages of AMD in clinical practice.

18.
19.
Environ Sci Technol ; 58(21): 9416-9426, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38662937

RESUMO

The polyamide (PA) nanofiltration (NF) membrane has the potential to remove endocrine-disrupting compounds (EDCs) from water and wastewater to prevent risks to both the aquatic ecosystem and human health. However, our understanding of the EDC removal-water permeance trade-off by the PA NF membrane is still limited, although the salt selectivity-water permeance trade-off has been well illustrated. This constrains the precise design of a high-performance membrane for removing EDCs. In this study, we manipulated the PA nanostructures of NF membranes by altering piperazine (PIP) monomer concentrations during the interfacial polymerization (IP) process. The upper bound coefficient for EDC selectivity-water permeance was demonstrated to be more than two magnitudes lower than that for salt selectivity-water permeance. Such variations were derived from the different membrane-solute interactions, in which the water/EDC selectivity was determined by the combined effects of steric exclusion and the hydrophobic interaction, while the electrostatic interaction and steric exclusion played crucial roles in water/salt selectivity. We further highlighted the role of the pore number and residual groups during the transport of EDC molecules across the PA membrane via molecular dynamics (MD) simulations. Fewer pores decreased the transport channels, and the existence of residual groups might cause steric hindrance and dynamic disturbance to EDC transport inside the membrane. This study elucidated the trade-off phenomenon and mechanisms between EDC selectivity and water permeance, providing a theoretical reference for the precise design of PA NF membranes for effective removal of EDCs in water reuse.


Assuntos
Disruptores Endócrinos , Filtração , Membranas Artificiais , Nylons , Poluentes Químicos da Água , Disruptores Endócrinos/química , Nylons/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Água/química , Nanoestruturas/química
20.
Food Microbiol ; 120: 104486, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38431331

RESUMO

Auricularia auricula fermentation was performed to reduce anti-nutritional factors, improve nutritional components, and enhance biological activity of soybean. Results showed that the contents of raffinose, stachyose, and trypsin inhibitor were significantly decreased from initial 1.65 g L-1, 1.60 g L-1, and 284.67 µg g-1 to 0.14 g L-1, 0.35 g L-1, and 4.52 µg g-1 after 144 h of fermentation, respectively. Simultaneously, the contents of polysaccharide, total phenolics, and total flavonoids were increased, and melanin was secreted. The isoflavone glycosides were converted to their aglycones, and the contents of glyctin and genistin were decreased from initial 1107.99 µg g-1 and 2852.26 µg g-1 to non-detection after 72 h of fermentation, respectively. After 96 h of fermentation, the IC50 values of samples against DPPH and ABTS radicals scavenging were decreased from 17.61 mg mL-1 and 3.43 mg mL-1 to 4.63 mg mL-1 and 0.89 mg mL-1, and those of samples inhibiting α-glucosidase and angiotensin I-converting enzyme were decreased from 53.89 mg mL-1 and 11.27 mg mL-1 to 18.24 mg mL-1 and 6.78 mg mL-1, respectively, indicating the significant increase in these bioactivities. These results suggested A. auricula fermentation can enhance the nutritional quality and biological activity of soybean, and the fermented soybean products have the potential to be processed into health foods/food additives.


Assuntos
Antioxidantes , Auricularia , Glycine max , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fermentação , Fungos/metabolismo
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