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1.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35121660

RESUMEN

Multidrug Resistance Proteins (MRPs) are transporters that play critical roles in cancer even though the physiological substrates of these enigmatic transporters are poorly elucidated. In Caenorhabditis elegans, MRP5/ABCC5 is an essential heme exporter because mrp-5 mutants are unviable due to their inability to export heme from the intestine to extraintestinal tissues. Heme supplementation restores viability of these mutants but fails to restore male reproductive deficits. Correspondingly, cell biological studies show that MRP5 regulates heme levels in the mammalian secretory pathway even though MRP5 knockout (KO) mice do not show reproductive phenotypes. The closest homolog of MRP5 is MRP9/ABCC12, which is absent in C. elegans, raising the possibility that MRP9 may genetically compensate for MRP5. Here, we show that MRP5 and MRP9 double KO (DKO) mice are viable but reveal significant male reproductive deficits. Although MRP9 is highly expressed in sperm, MRP9 KO mice show reproductive phenotypes only when MRP5 is absent. Both ABCC transporters localize to mitochondrial-associated membranes, dynamic scaffolds that associate the mitochondria and endoplasmic reticulum. Consequently, DKO mice reveal abnormal sperm mitochondria with reduced mitochondrial membrane potential and fertilization rates. Metabolomics show striking differences in metabolite profiles in the DKO testes, and RNA sequencing shows significant alterations in genes related to mitochondrial function and retinoic acid metabolism. Targeted functional metabolomics reveal lower retinoic acid levels in the DKO testes and higher levels of triglycerides in the mitochondria. These findings establish a model in which MRP5 and MRP9 play a concerted role in regulating male reproductive functions and mitochondrial sufficiency.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Mitocondrias/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Reproducción/fisiología , Subfamilia B de Transportador de Casetes de Unión a ATP , Animales , Transporte Biológico/fisiología , Caenorhabditis elegans/metabolismo , Hemo/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Animales , Espermatozoides/metabolismo , Testículo/metabolismo
2.
Breast Cancer Res ; 26(1): 76, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745208

RESUMEN

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. METHODS: We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. RESULTS: We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA-protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. CONCLUSIONS: This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Proteogenómica , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Biomarcadores de Tumor/genética , Proteogenómica/métodos , Mutación , Captura por Microdisección con Láser , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Proteómica/métodos , Pronóstico
3.
Breast Cancer Res Treat ; 204(1): 15-26, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38038766

RESUMEN

PURPOSE: To explore the association of clinicopathologic and molecular factors with the occurrence of positive margins after first surgery in breast cancer. METHODS: The clinical and RNA-Seq data for 951 (75 positive and 876 negative margins) primary breast cancer patients from The Cancer Genome Atlas (TCGA) were used. The role of each clinicopathologic factor for margin prediction and also their impact on survival were evaluated using logistic regression, Fisher's exact test, and Cox proportional hazards regression models. In addition, differential expression analysis on a matched dataset (71 positive and 71 negative margins) was performed using Deseq2 and LASSO regression. RESULTS: Association studies showed that higher stage, larger tumor size (T), positive lymph nodes (N), and presence of distant metastasis (M) significantly contributed (p ≤ 0.05) to positive surgical margins. In case of surgery, lumpectomy was significantly associated with positive margin compared to mastectomy. Moreover, PAM50 Luminal A subtype had higher chance of positive margin resection compared to Basal-like subtype. Survival models demonstrated that positive margin status along with higher stage, higher TNM, and negative hormone receptor status was significant for disease progression. We also found that margin status might be a surrogate of tumor stage. In addition, 29 genes that could be potential positive margin predictors and 8 pathways were identified from molecular data analysis. CONCLUSION: The occurrence of positive margins after surgery was associated with various clinical factors, similar to the findings reported in earlier studies. In addition, we found that the PAM50 intrinsic subtype Luminal A has more chance of obtaining positive margins compared to Basal type. As the first effort to pursue molecular understanding of the margin status, a gene panel of 29 genes including 17 protein-coding genes was also identified for potential prediction of the margin status which needs to be validated using a larger sample set.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/metabolismo , Mastectomía , Márgenes de Escisión , Mama/patología , Mastectomía Segmentaria , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología
4.
Stem Cells ; 41(10): 971-985, 2023 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-37534584

RESUMEN

Recent studies suggest that chromosomal cohesin complex proteins are important in regulating hematopoiesis and may contribute to myeloid malignancies. To investigate the effects of perturbing the cohesin subunit protein RAD21 on normal hematopoiesis, we used conditional knockout (cKO) mouse models. While cohesin is vital for hematopoietic stem cell (HSC) function, Rad21 haploinsufficiency (Rad21Δ/+) led to distinct hematopoietic phenotypes. Our findings revealed that Rad21Δ/+ cells exhibited decreased hematopoietic reconstitution in competitive bone marrow transplantation assays. This reduction in peripheral blood chimerism was specifically observed in the lymphoid compartment, while the chimerism in the myeloid compartment remained unaffected. Rad21 haploinsufficiency also resulted in changes in the hematopoietic stem and progenitor cells (HSPC) and myeloid progenitor compartments, with a significant accumulation of granulocyte-macrophage progenitors in the bone marrow. We observed differential gene expression in Rad21Δ/+ LSK (Lin- Sca1-Kit+) cells, including genes required for HSPC function and differentiation, such as Setdb1, Hmga2, Ncor1, and Myb. In addition, we observed a notable decrease in the expression of genes related to the interferon response and a significant reduction in the expression of genes involved in the IL2-STAT5 signaling pathways. Our studies suggest that RAD21 protein and level of its post-translational modifications in the bone marrow cells may play a potential role in hematopoiesis. Overall, Rad21 haploinsufficiency impairs hematopoietic differentiation and increases HSC self-renewal.


Asunto(s)
Proteínas Cromosómicas no Histona , Trasplante de Células Madre Hematopoyéticas , Ratones , Animales , Diferenciación Celular , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Células Madre Hematopoyéticas/metabolismo , Hematopoyesis/genética , Ratones Endogámicos C57BL , Co-Represor 1 de Receptor Nuclear/metabolismo , Cohesinas
5.
FEMS Yeast Res ; 242024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38444195

RESUMEN

In this study, we explored the sphingolipid (SL) landscape in Candida auris, which plays pivotal roles in fungal biology and drug susceptibility. The composition of SLs exhibited substantial variations at both the SL class and molecular species levels among clade isolates. Utilizing principal component analysis, we successfully differentiated the five clades based on their SL class composition. While phytoceramide (PCer) was uniformly the most abundant SL class in all the isolates, other classes showed significant variations. These variations were not limited to SL class level only as the proportion of different molecular species containing variable number of carbons in fatty acid chains also differed between the isolates. Also a comparative analysis revealed abundance of ceramides and glucosylceramides in fluconazole susceptible isolates. Furthermore, by comparing drug-resistant and susceptible isolates within clade IV, we uncovered significant intraclade differences in key SL classes such as high PCer and low long chain base (LCB) content in resistant strains, underscoring the impact of SL heterogeneity on drug resistance development in C. auris. These findings shed light on the multifaceted interplay between genomic diversity, SLs, and drug resistance in this emerging fungal pathogen.


Asunto(s)
Antifúngicos , Candida , Antifúngicos/farmacología , Candida auris , Esfingolípidos , Farmacorresistencia Fúngica , Pruebas de Sensibilidad Microbiana
6.
Langmuir ; 40(10): 5040-5059, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38419155

RESUMEN

Polluted water has become a concern for the scientific community as it causes many severe threats to living beings. Detection or removal of contaminants present in wastewater and attaining purity of water that can be used for various purposes are a primary responsibility. Different treatment methods have already been used for the purification of sewage. There is a need for low-cost, highly selective, and reusable materials that can efficiently remove pollutants or purify contaminated water. In this regard, MOFs have shown significant potential for applications such as supercapacitors, drug delivery, gas storage, pollutant adsorption, etc. The outstanding structural diversity, substantial surface areas, and adjustable pore sizes of MOFs make them superior candidates for wastewater treatment. This Review provides an overview of the interaction science and engineering (kinetic and thermodynamic aspects with interactions) underpinning MOFs for water purification. First, fundamental strategies for the synthesis methods of MOFs, different categories, and their applicability in wastewater treatment are summarized, followed by a detailed explanation of various interaction mechanisms. Finally, current challenges and future outlooks for research on MOF materials toward the adsorption of hazardous components are discussed. A new avenue for modifying their structural characteristics for the adsorption and separation of hazardous materials, which will undoubtedly direct future work, is also summarized.

7.
Langmuir ; 40(21): 11023-11029, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38748850

RESUMEN

The bolometer is developed using single-walled carbon nanotubes (SWCNT) anchored with semiconductor nanoparticles of cadmium sulfide, stannous disulfide, and zinc oxide (ZnO). The bolometric responses were recorded at varying temperatures from 10 K to room temperature. The anchored SWCNTs provided a higher temperature coefficient of resistance (TCR) than pristine SWCNTs. The largest TCR is recorded from SWCNTs/ZnO (-0.11%/K) at room temperature, which is 200% higher than pristine SWCNTs. The largest photoresponsivities of SWCNTs/ZnO under near-infrared (NIR) and wide wavelength source (200-1200 nm) illuminations are 5.06 and 37.51 mV/W, respectively. The extraordinary performance of SWCNTs/ZnO stands out at ∼17 × 104% under IR illumination. The study presents a significant advancement in the development of high-performance SWCNT bolometric materials by anchoring with semiconductor nanoparticles.

8.
EMBO Rep ; 23(2): e54022, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-34866326

RESUMEN

PfCDPK7 is an atypical member of the calcium-dependent protein kinase (CDPK) family and is crucial for the development of Plasmodium falciparum. However, the mechanisms whereby PfCDPK7 regulates parasite development remain unknown. Here, we perform quantitative phosphoproteomics and phospholipid analysis and find that PfCDPK7 promotes phosphatidylcholine (PC) synthesis by regulating two key enzymes involved in PC synthesis, phosphoethanolamine-N-methyltransferase (PMT) and ethanolamine kinase (EK). In the absence of PfCDPK7, both enzymes are hypophosphorylated and PMT is degraded. We further find that PfCDPK7 interacts with 4'-phosphorylated phosphoinositides (PIPs) generated by PI4-kinase. Inhibition of PI4K activity disrupts the vesicular localization PfCDPK7. P. falciparum PI4-kinase, PfPI4K is a prominent drug target and one of its inhibitors, MMV39048, has reached Phase I clinical trials. Using this inhibitor, we demonstrate that PfPI4K controls phospholipid biosynthesis and may act in part by regulating PfCDPK7 localization and activity. These studies not only unravel a signaling pathway involving PfPI4K/4'-PIPs and PfCDPK7 but also provide novel insights into the mechanism of action of a promising series of candidate anti-malarial drugs.


Asunto(s)
Malaria Falciparum , Plasmodium falciparum , Humanos , Fosfolípidos/metabolismo , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Transducción de Señal
9.
Int Microbiol ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38342794

RESUMEN

Quorum sensing (QS) is pivotal in coordinating virulence factors and biofilm formation in various pathogenic bacteria, making it a prime target for disrupting bacterial communication. Pseudomonas aeruginosa is a member of the "ESKAPE" group of bacterial pathogens known for their association with antimicrobial resistance and biofilm formation. The current antibiotic arsenal falls short of addressing biofilm-related infections effectively, highlighting the urgent need for novel therapeutic agents. In this study, we explored the anti-QS and anti-biofilm properties of theophylline against two significant pathogens, Chromobacterium violaceum and P. aeruginosa. The production of violacein, pyocyanin, rhamnolipid, and protease was carried out, along with the evaluation of biofilm formation through methods including crystal violet staining, triphenyl tetrazolium chloride assay, and fluorescence microscopy. Furthermore, computational analyses were conducted to predict the targets of theophylline in the QS pathways of P. aeruginosa and C. violaceum. Our study demonstrated that theophylline effectively inhibits QS activity and biofilm formation in C. violaceum and P. aeruginosa. In P. aeruginosa, theophylline inhibited the production of key virulence factors, including pyocyanin, rhamnolipid, protease, and biofilm formation. The computational analyses suggest that theophylline exhibits robust binding affinity to CviR in C. violaceum and RhlR in P. aeruginosa, key participants in the QS-mediated biofilm pathways. Furthermore, theophylline also displays promising interactions with LasR and QscR in P. aeruginosa. Our study highlights theophylline as a versatile anti-QS agent and offers a promising avenue for future research to develop novel therapeutic strategies against biofilm-associated infections.

10.
J Pediatr Gastroenterol Nutr ; 78(3): 471-487, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38314925

RESUMEN

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.


Asunto(s)
Enterocolitis Necrotizante , Sepsis Neonatal , Sepsis , Recién Nacido , Humanos , Femenino , Embarazo , Sepsis Neonatal/prevención & control , Calostro , Recien Nacido Prematuro , Sepsis/prevención & control , Enterocolitis Necrotizante/prevención & control , Enterocolitis Necrotizante/epidemiología
11.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): A73-A82, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437435

RESUMEN

In recent years, optical information processing has become increasingly important due to its ability to handle large amounts of data efficiently. Amplitude, phase, spatial frequency, wavelength, and polarization are the physical dimensions used for information encoding into the light beam. Information encoding using orbital angular momentum (OAM) carried by a vortex beam is gaining interest in this regard. Such beams provide high-dimensional orthogonal states for encoding and have shown more stability in turbulent media than Gaussian beams, especially in the case of free space propagation. This study demonstrates an image encryption method utilizing an array of OAM light modes. The approach uses a non-interferometric intensity recording-based encoding scheme, which offers ease of implementation. Quick response codes have been utilized for encoding to avoid information loss from non-uniform distribution of light and aberrations. The encryption scheme is highly secure because the encrypted light beam contains only partial information about the object, preventing complete information retrieval without proper key information.

12.
Lett Appl Microbiol ; 77(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38845375

RESUMEN

This study explores the eco-friendly synthesis of silver nanoparticles (AgNPs) using soil bacteria, Pseudomonas otitidis. The bio-synthesized AgNPs were characterized using various techniques, including UV-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). UV-visible spectroscopy revealed a distinct broad absorption band in the range of 443 nm, indicating the reduction of silver nitrate to AgNPs. XRD analysis provided evidence of the crystalline nature of the particles, with sharp peaks confirming their crystallinity and an average size of 82.76 nm. FTIR spectroscopy identified extracellular protein compounds as capping agents. SEM examination revealed spherical agglomeration of the crystalline AgNPs. The antimicrobial assay by a disc diffusion method, minimum inhibitory concentration, and minimum bactericidal concentration testing revealed that the biosynthesized AgNPs showed moderate antibacterial activity against both pathogenic Gram-negative (Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) and Gram-positive (Bacillus cereus, Staphylococcus aureus, and Streptococcus mutans) bacterial strains. Furthermore, the AgNPs significantly disrupted the biofilm of P. aeruginosa, as confirmed by crystal violet assay and fluorescent microscopy. Overall, this study underscores the potential of microbial-synthesized nanoparticles in biomedical applications, particularly in combating pathogenic bacteria, offering a promising avenue for future research and development.


Asunto(s)
Antibacterianos , Biopelículas , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Pseudomonas , Plata , Plata/farmacología , Plata/química , Biopelículas/efectos de los fármacos , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Pseudomonas/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Pseudomonas aeruginosa/efectos de los fármacos
13.
PLoS Genet ; 17(3): e1009441, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33739968

RESUMEN

Biallelic mutations in DONSON, an essential gene encoding for a replication fork protection factor, were linked to skeletal abnormalities and microcephaly. To better understand DONSON function in corticogenesis, we characterized Donson expression and consequences of conditional Donson deletion in the mouse telencephalon. Donson was widely expressed in the proliferation and differentiation zones of the embryonic dorsal and ventral telencephalon, which was followed by a postnatal expression decrease. Emx1-Cre-mediated Donson deletion in progenitors of cortical glutamatergic neurons caused extensive apoptosis in the early dorsomedial neuroepithelium, thus preventing formation of the neocortex and hippocampus. At the place of the missing lateral neocortex, these mutants exhibited a dorsal extension of an early-generated paleocortex. Targeting cortical neurons at the intermediate progenitor stage using Tbr2-Cre evoked no apparent malformations, whereas Nkx2.1-Cre-mediated Donson deletion in subpallial progenitors ablated 75% of Nkx2.1-derived cortical GABAergic neurons. Thus, the early telencephalic neuroepithelium depends critically on Donson function. Our findings help explain why the neocortex is most severely affected in individuals with DONSON mutations and suggest that DONSON-dependent microcephaly might be associated with so far unrecognized defects in cortical GABAergic neurons. Targeting Donson using an appropriate recombinase is proposed as a feasible strategy to ablate proliferating and nascent cells in experimental research.


Asunto(s)
Proteínas de Ciclo Celular/genética , Diferenciación Celular , Corteza Cerebral/metabolismo , Neuronas GABAérgicas/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células-Madre Neurales/metabolismo , Neuronas/metabolismo , Proteínas Nucleares/genética , Animales , Apoptosis/genética , Diferenciación Celular/genética , Corteza Cerebral/citología , Neuronas GABAérgicas/citología , Hipocampo/metabolismo , Ratones , Neocórtex , Células-Madre Neurales/citología , Neurogénesis/genética , Neuronas/citología , Telencéfalo/citología , Telencéfalo/metabolismo
14.
Luminescence ; 39(3): e4703, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38433325

RESUMEN

Transition metal dichalcogenides (TMDCs) are versatile two-dimensional (2D) nanomaterials used in biosensing applications due to their excellent physical and chemical properties. Due to biomaterial target properties, biosensors' most significant challenge is improving their sensitivity and stability. In environmental analysis, TMDCs have demonstrated exceptional pollutant detection and removal capabilities. Their high surface area, tunable electronic properties, and chemical reactivity make them ideal for sensors and adsorbents targeting various contaminants, including heavy metals, organic pollutants, and emerging contaminants. Furthermore, their unique electronic and optical properties enable sensitive detection techniques, enhancing our ability to monitor and mitigate environmental pollution. In the food analysis, TMDCs-based nanomaterials have shown remarkable potential in ensuring food safety and quality. These nanomaterials exhibit high specificity and sensitivity for detecting contaminants, pathogens, and adulterants in various food matrices. Their integration into sensor platforms enables rapid and on-site analysis, reducing the reliance on centralized laboratories and facilitating timely interventions in the food supply chain. In biomedical studies, TMDCs-based nanomaterials have demonstrated significant strides in diagnostic and therapeutic applications. Their biocompatibility, surface functionalization versatility, and photothermal properties have paved the way for novel disease detection, drug delivery, and targeted therapy approaches. Moreover, TMDCs-based nanomaterials have shown promise in imaging modalities, providing enhanced contrast and resolution for various medical imaging techniques. This article provides a comprehensive overview of 2D TMDCs-based biosensors, emphasizing the growing demand for advanced sensing technologies in environmental, food, and biomedical analysis.


Asunto(s)
Contaminantes Ambientales , Nanoestructuras , Materiales Biocompatibles , Sistemas de Liberación de Medicamentos , Electrónica
15.
J Xray Sci Technol ; 32(3): 725-734, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38189739

RESUMEN

BACKGROUND: To reduce radiation dose and subsequent risks, several legislative documents in different countries describe the need for Diagnostic Reference Levels (DRLs). Spinal radiography is a common and high-dose examination. Therefore, the aim of this work was to establish the DRL for Computed Tomography (CT) examinations of the spine in healthcare institutions across Jordan. METHODS: Data was retrieved from the picture archiving and communications system (PACS), which included the CT Dose Index (CTDI (vol) ) and Dose Length Product (DLP). The median radiation dose values of the dosimetric indices were calculated for each site. DRL values were defined as the 75th percentile distribution of the median CTDI (vol)  and DLP values. RESULTS: Data was collected from 659 CT examinations (316 cervical spine and 343 lumbar-sacral spine). Of the participants, 68% were males, and the patients' mean weight was 69.7 kg (minimum = 60; maximum = 80, SD = 8.9). The 75th percentile for the DLP of cervical and LS-spine CT scans in Jordan were 565.2 and 967.7 mGy.cm, respectively. CONCLUSIONS: This research demonstrates a wide range of variability in CTDI (vol)  and DLP values for spinal CT examinations; these variations were associated with the acquisition protocol and highlight the need to optimize radiation dose in spinal CT examinations.


Asunto(s)
Dosis de Radiación , Columna Vertebral , Tomografía Computarizada por Rayos X , Humanos , Jordania , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/normas , Masculino , Femenino , Adulto , Persona de Mediana Edad , Columna Vertebral/diagnóstico por imagen , Anciano , Benchmarking , Niveles de Referencia para Diagnóstico , Adolescente , Adulto Joven , Niño , Anciano de 80 o más Años
16.
J Neuroinflammation ; 20(1): 8, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36631780

RESUMEN

BACKGROUND: The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. METHODS: We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood-brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. RESULTS: Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood-brain barrier is essential for NK cells and NKp46+ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. CONCLUSIONS: This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood-brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke.


Asunto(s)
Quimiocina CXCL12 , Accidente Cerebrovascular Isquémico , Células Asesinas Naturales , Animales , Ratones , Encéfalo/metabolismo , Encéfalo/patología , Quimiocina CXCL12/metabolismo , Células Endoteliales , Inmunidad Innata , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Células Asesinas Naturales/metabolismo , Linfocitos
17.
Chemistry ; 29(27): e202300250, 2023 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-36958938

RESUMEN

In this study, a highly air stable and eco-friendly methyl ammonium bismuth iodide (MA3 Bi2 I9 ) perovskite-like material has been prepared. After physiochemical characterizations, the synthesized MA3 Bi2 I9 was utilized as photo-catalyst towards hydrogen production. It is important to design and synthesize lead (Pb)-free perovskite-like material (MA3 Bi2 I9 ) for photo-catalytic hydrogen-production applications. The synthesized MA3 Bi2 I9 exhibits excellent photo-catalytic hydrogen generation with a production rate of 11.43 µmolg-1 h-1 . In the presence of a platinum co-catalyst, the hydrogen production rate further increases to 172.44 µmolg-1 h-1 . The MA3 Bi2 I9 photo-catalyst also demonstrates excellent cyclic stability.

18.
Pediatr Res ; 94(6): 2033-2039, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37479747

RESUMEN

BACKGROUND: To develop a simple scoring system to predict either any or severe IVH in VLBW infants. METHODS: In this retrospective cohort study, 923 VLBW infants were randomly divided into derivation (n = 431) and validation (n = 492) cohorts. After stepwise multivariable logistic regression analyses, a risk score was assigned to independent predictors. RESULTS: The overall rates of any and severe IVH were 22.9% and 9.9%. Gestational age, maternal race, location of birth and sex were independent predictors of any IVH (AUC 0.75 in derivation cohort and 0.69 for validation cohort). Birth weight, Apgar score at 1 minute, location of birth and sex were independent predictors of severe IVH (AUC 0.84 in derivation cohort and 0.77 for validation cohort). For any IVH, infants in the high-risk category (total score 4 or 5) had > 50% likelihood of any IVH with a negative predictive value of 82.6%. For severe IVH, the total risk score ranged from 0-8, and infants in high-risk category (total score 6-8) had 30% likelihood of severe IVH with a negative predictive value of 94.9%. CONCLUSION: We report an easy to calculate, validated scoring system with a high NPV to identify VLBW infants at highest risk of IVH. IMPACT: We report a simple validated scoring system with a high NPV for prediction of IVH in VLBW infants. The variables in the proposed model are available at birth and unlikely to be influenced by provider bias. This scoring system can identify infants at risk of any and severe IVH, while most previous models predict only severe IVH. This scoring system does not require access to web-based resources. This scoring system can help in employing prevention strategies only for infants at highest risk of IVH and thus eliminate the risks of interventions in a large majority of VLBW infants.


Asunto(s)
Hemorragia Cerebral , Enfermedades del Prematuro , Recién Nacido , Lactante , Humanos , Estudios Retrospectivos , Recién Nacido de muy Bajo Peso , Peso al Nacer , Edad Gestacional , Factores de Riesgo
19.
Soft Matter ; 19(35): 6743-6753, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37623699

RESUMEN

We perform computer simulations to explore the escape dynamics of a self-propelled (active) nanorod from circular confinements with narrow opening(s). Our results clearly demonstrate how the persistent and directed motion of the nanorod helps it to escape. Such escape events are absent if the nanorod is passive. To quantify the escape dynamics, we compute the radial probability density function (RPDF) and mean first escape time (MFET) and show how the activity is responsible for the bimodality of RPDF, which is clearly absent if the nanorod is passive. Broadening of displacement distributions with activity has also been observed. The computed mean first escape time decreases with activity. In contrast, the fluctuations of the first escape times vary in a non-monotonic way. This results in high values of the coefficient of variation and indicates the presence of multiple timescales in first escape time distributions and multimodality in uniformity index distributions. We hope our study will help in differentiating activity-driven escape dynamics from purely thermal passive diffusion in confinement.

20.
J Nucl Cardiol ; 30(3): 1147-1157, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36474068

RESUMEN

BACKGROUND: Routine use of cardiac sympathetic imaging in HF has been limited by the lower availability/sensitivity of radiotracers. This study was aimed to assess the feasibility of 18F-FDOPA (commonly available PET-radiotracer) in assessment of cardiac autonomic dysfunction. METHODS: Twenty-four controls (46.5 ± 11.1 years, 16men) and 24 patients (43.5 ± 11.0 years, 18men) with diagnosed HF (Framingham-Criteria) underwent cardiac-PET/CT. Region(s) Of Interest were drawn over entire left ventricular myocardium (LV), individual walls, and mediastinum (M). Coefficient of Variation (CV) was calculated from individual wall counts. RESULTS: HF patients had significantly lower myocardial 18F-FDOPA uptake (P < .001, independent t test) than controls [32.4% ± 9.5% global reduction; highest in apex (39.9% ± 7.0%)]. A cut-off of LV/M ≤ 1.68 could differentiate patients from controls with sensitivity and specificity of 100% and 95.8%, respectively. LV/M correlated positively with EF (Pearson coefficient = 0.460, P .031). During follow-up, 3 patients were lost to follow-up, 4 died (survival-20.5 ± 4 months), 2 worsened, and 15 remained stable/showed mild improvement. Patients who worsened/died during follow-up had higher CV than those with stable/improving symptoms [0.16 ± 0.05 vs 0.11 ± 0.05, P value .069 (independent t test); Cox regression P = .084]. CONCLUSION: Myocardial 18F-FDOPA uptake in patients with HF is significantly reduced. Higher reduction is seen in those with lower EF. CV, a maker of regional heterogeneity, is a potential prognostic marker.


Asunto(s)
Cardiopatías , Insuficiencia Cardíaca , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Proyectos Piloto , Corazón
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