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1.
Curr Biol ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38663397

RESUMEN

Fungal biomineralization plays an important role in the biogeochemical cycling of metals in the environment and has been extensively explored for bioremediation and element biorecovery. However, the cellular and metabolic responses of fungi in the presence of toxic metals during biomineralization and their impact on organic matter transformations are unclear. This is an important question because co-contamination by toxic metals and organic pollutants is a common phenomenon in the natural environment. In this research, the biomineralization process and oxidative stress response of the geoactive soil fungus Aspergillus niger were investigated in the presence of toxic metals (Co, Cu, Mn, and Fe) and the azo dye orange II (AO II). We have found that the co-existence of toxic metals and AO II not only enhanced the fungal biomineralization of toxic metals but also accelerated the removal of AO II. We hypothesize that the fungus and in situ mycogenic biominerals (toxic metal oxalates) constituted a quasi-bioreactor, where the biominerals removed organic pollutants by catalyzing reactive oxygen species (ROS) generation resulting from oxidative stress. We have therefore demonstrated that a fungal/biomineral system can successfully achieve the goal of toxic metal immobilization and organic pollutant decomposition. Such findings inform the potential development of fungal-biomineral hybrid systems for mixed pollutant bioremediation as well as provide further understanding of fungal organic-inorganic pollutant transformations in the environment and their importance in biogeochemical cycles.

2.
J Orthop Surg Res ; 19(1): 162, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429811

RESUMEN

OBJECTIVE: The primary aim of the present study was to explore the potential correlation of serum / local CXCL13 expressions and disease severity in non-traumatic osteonecrosis of the femoral head (NT-ONFH). METHODS: In total, NT-ONFH patients (n = 130) together with healthy controls (HCs, n = 130) were included in this investigation. Radiographic progression was evaluated based on the imaging criteria outlined in the ARCO classification system. To assess the diagnostic value of serum CXCL13 in relation to radiographic progression, Receiver operating characteristic (ROC) curve analysis was conducted. Serum CXCL13 levels were quantified utilizing ELISA in all participants. Furthermore, local protein/mRNA expressions of CXCL13 were examined employing immunohistochemistry, western blot, as well as RT-PCR techniques. Clinical severity was appraised using the visual analogue scale (VAS), Harris Hip Score (HHS), and Western Ontario as well as McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The findings revealed a significant reduction in serum CXCL13 levels among NT-ONFH patients in contrast with HCs. Moreover, both mRNA and protein expressions of CXCL13 were markedly decreased in the necrotic area (NA) than the non-necrotic area (NNA) as well as the healthy femoral head tissues. Additionally, serum CXCL13 levels were substantially lower among patients classified as ARCO stage 4 than those at ARCO stage 3. The concentrations of CXCL13 in stage 3 patients were notably diminished relative to those at ARCO stage 2. Notably, serum CXCL13 levels demonstrated a negative association with ARCO grade. Furthermore, these levels were also inversely linked to VAS scores as well as WOMAC scores while displaying a positive association with HHS scores. The findings of ROC curve suggested that reduced serum CXCL13 levels could be an underlying indicator for ARCO stage. CONCLUSIONS: The reduced levels of either serum CXCL13 or local CXCL13 were intricately linked to disease severity for patients with NT-ONFH.


Asunto(s)
Necrosis de la Cabeza Femoral , Cabeza Femoral , Humanos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Gravedad del Paciente , Curva ROC , ARN Mensajero , Quimiocina CXCL13
3.
J Hazard Mater ; 469: 133968, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38452682

RESUMEN

Pb2+ is a heavy metal ion pollutant that poses a serious threat to human health and ecosystems. The conventional methods for detecting Pb2+ have several limitations. In this study, we introduce a novel fluorescent probe that enables the detection of Pb2+ in the near-infrared region, free from interference from other common ions. A unique characteristic of this probe is its ability to rapidly and accurately identify Pb2+ through ratiometric measurements accompanied by a large Stokes shift of 201 nm. The limit of detection achieved by probe was remarkably low, surpassing the standards set by the World Health Organization, and outperforming previously reported probes. To the best of our knowledge, this is the first organic small-molecule fluorescent probe with both near-infrared emission and ratiometric properties for the detection of Pb2+. We present a triple-mode sensing platform constructed using a probe that allows for the sensitive and selective recognition of Pb2+ in common food items. Furthermore, we successfully conducted high-quality fluorescence imaging of Pb2+ in various samples from common edible plants, HeLa cells, Caenorhabditis elegans, and mice. Importantly, the probe-Pb2+ complex exhibited tumour-targeting capabilities. Overall, this study presents a novel approach for the development of fluorescent probes for Pb2+ detection.


Asunto(s)
Colorantes Fluorescentes , Plomo , Humanos , Animales , Ratones , Células HeLa , Ecosistema
4.
Dalton Trans ; 53(9): 4185-4193, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38323430

RESUMEN

Five new alkylaluminum complexes with different pyridinyl-substituted imines or cyclohexyl-substituted imines were synthesized and characterized successfully. The aluminum complex [FlCHNCH(CH3)Py]AlMe2(Py = 2-pyridyl) (1) was obtained by reacting 9-[2-pyridyl-CH(CH3)-NCH]Fl (Fl = fluorenyl) (L1) and equimolar AlMe3. The reactions of 9-(2-pyridyl-NCH)Fl (L2) and 9-[2-N(CH3)2-cyclohexyl-NCH]Fl (L3) with equimolar AlMe3 or AlEt3 afforded other alkylaluminum complexes [FlCHNPy]AlMe2(Py = 2-pyridyl) (2), [FlCHNPy]AlEt2 (Py = 2-pyridyl) (3), [FlCHNCyN(CH3)2]AlMe2 (Cy = 2-cyclohexyl) (4) and [FlCHNCyN(CH3)2]AlEt2 (Cy = 2-cyclohexyl) (5). All these complexes (1-5) were characterized using NMR spectroscopy, elemental analysis, and X-ray crystal structure analysis. The catalytic properties of these new alkylaluminum complexes for the hydrophosphonylation of aldimines were examined. Complex 5 showed the best catalytic performance under mild reaction conditions with a low catalyst loading (1 mol%), and 20 different substituents of aldimines were isolated with more than 90% yields.

5.
PeerJ ; 12: e16701, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38188175

RESUMEN

Rapid urbanization has drawn some aquatic environments into the urban texture from the outskirts of cities, and the composition and distribution of plant species in urban wetlands along the urban gradient have changed. Understanding the drivers of these changes will help in the conservation and utilization of urban wetlands. This study investigated the differences in plant diversity and associated influencing factors in three wetlands, Xixi wetland, Tongjian Lake wetland, and Qingshan Lake wetland, which are located in a core area, fringe area, and suburban area of Hangzhou City, respectively. The results showed that a total of 104 families, 254 genera, and 336 species of plants were recorded in the Xixi wetland; 179 species, 150 genera, and 74 families were found in the Qingshan Lake wetland; and 112 species, 96 genera, and 57 families were collected in the Tongjian Lake wetland. The main plant species and flora distribution of the three urban wetlands showed similarities. Indigenous spontaneous vegetation was highest in the Xixi wetland, while cultivated plant species were most abundant in the Tongjian Lake wetland. The introduction of cultivated plants decreased the distance attenuation effect of plant communities, which led to a certain degree of plant diversity convergence among the three wetlands. Eight endangered plants were preserved in the Xixi wetland by planting them in suitable habitats. Ellenberg's indicator values showed that the proportion of heliophilous plants was higher in the Qingshan Lake wetland, while the proportion of thermophilous plants and nitrogen-loving plants in the Tongjian Lake wetland was higher than in the other two wetlands. The importance of artificial interference factors affecting the differences in plant diversity was significantly higher than that of natural environmental factors in urban wetlands. The preservation of spontaneous plants and the introduction of cultivated plants had an importance of 25.73% and 25.38%, respectively. These were the main factors influencing the plant diversity of urban wetlands. The management mode that did not interfere with spontaneous vegetation and confined maintenance to cultivated plants in the Xixi wetland was beneficial for improving wetland plant diversity. Scientific plant reintroduction can also improve wetland plant diversity.


Asunto(s)
Urbanización , Humedales , Humanos , Ciudades , China , Lagos
6.
Eur J Med Chem ; 265: 116070, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38134747

RESUMEN

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly. Contemporary treatments can only relieve symptoms but fail to delay disease progression. Curcumin is a naturally derived compound that has demonstrated significant therapeutic effects in AD treatment. Recently, molecular hybridization has been utilized to combine the pharmacophoric groups present in curcumin with those of other AD drugs, resulting in a series of novel compounds that enhance the therapeutic efficacy through multiple mechanisms. In this review, we firstly provide a concise summary of various pathogenetic hypotheses of AD and the mechanism of action of curcumin in AD, as well as the concept of molecular hybridization. Subsequently, we focus on the recent development of hybrid molecules derived from curcumin, summarizing their structures and pharmacological activities, including cholinesterase inhibitory activity, Aß aggregation inhibitory activity, antioxidant activity, and other activities. The structure-activity relationships were further discussed.


Asunto(s)
Enfermedad de Alzheimer , Curcumina , Enfermedades Neurodegenerativas , Humanos , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Curcumina/farmacología , Curcumina/uso terapéutico , Curcumina/química , Enfermedades Neurodegenerativas/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Relación Estructura-Actividad , Péptidos beta-Amiloides
7.
Front Immunol ; 14: 1264447, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38022581

RESUMEN

"Cytokine storm" is common in critically ill COVID-19 patients, however, mechanisms remain largely unknown. Here, we reported that overexpression of SARS-CoV-2 N protein in diabetic db/db mice significantly increased tubular death and the release of HMGB1, one of the damage-associated molecular patterns (DAMPs), to trigger M1 proinflammatory macrophage activation and production of IL-6, TNF-α, and MCP-1 via a Mincle-Syk/NF-κB-dependent mechanism. This was further confirmed in vitro that overexpression of SARS-CoV-2 N protein caused the release of HMGB1 from injured tubular cells under high AGE conditions, which resulted in M1 macrophage activation and production of proinflammatory cytokines via a Mincle-Syk/NF-κB-dependent mechanism. This was further evidenced by specifically silencing macrophage Mincle to block HMGB1-induced M1 macrophage activation and production of IL-6, TNF-α, and MCP-1 in vitro. Importantly, we also uncovered that treatment with quercetin largely improved SARS-CoV-2 N protein-induced AKI in db/db mice. Mechanistically, we found that quercetin treatment significantly inhibited the release of a DAMP molecule HMGB1 and inactivated M1 pro-inflammatory macrophage while promoting reparative M2 macrophage responses by suppressing Mincle-Syk/NF-κB signaling in vivo and in vitro. In conclusion, SARS-CoV-2 N protein-induced AKI in db/db mice is associated with Mincle-dependent M1 macrophage activation. Inhibition of this pathway may be a mechanism through which quercetin inhibits COVID-19-associated AKI.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Diabetes Mellitus , Proteína HMGB1 , Ratones , Animales , Humanos , FN-kappa B/metabolismo , Proteína HMGB1/metabolismo , SARS-CoV-2/metabolismo , Quercetina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Activación de Macrófagos , Interleucina-6/metabolismo , COVID-19/metabolismo , Macrófagos/metabolismo , Lesión Renal Aguda/metabolismo , Diabetes Mellitus/metabolismo
8.
World J Gastrointest Surg ; 15(10): 2351-2356, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37969708

RESUMEN

BACKGROUND: Few reports have described living foreign bodies in the human body. The current manuscript demonstrates that computed tomography (CT) is an effective tool for accurate preoperative evaluation of living foreign bodies in clinic. The three-dimensional (3D) reconstruction technology could clearly display anatomical structures, lesions and adjacent organs, improving diagnostic accuracy and guiding the surgical decision-making process. CASE SUMMARY: Herein we describe a 68-year-old man diagnosed with digestive tract perforation and acute peritonitis caused by a foreign body of Monopterus albus. The patient presented to the emergency department with complaints of dull abdominal pain, profuse sweating and a pale complexion during work. A Monopterus albus had entered the patient's body through the anus two hours ago. During hospitalization, the 3D reconstruction technology revealed a perforation of the middle rectum complicated with acute peritonitis and showed a clear and complete Monopterus albus bone morphology in the abdominal and pelvic cavities, with the Monopterus albus biting the mesentery. Laparoscopic examination detected a large (diameter of about 1.5 cm) perforation in the mid-rectum. It could be seen that a Monopterus albus had completely entered the abdominal cavity and had tightly bitten the mesentery of the small intestine. During the operation, the dead Monopterus albus was taken out. CONCLUSION: The current manuscript demonstrates that CT is an effective tool for accurate preoperative evaluation of living foreign bodies in clinic.

9.
BMC Pregnancy Childbirth ; 23(1): 641, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37674133

RESUMEN

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) was demonstrated to be superior to conventional IVF in reducing the incidence of miscarriage and abnormal offspring after the first embryo transfer (ET). PGT-A requires several embryo trophectoderm cells, but its negative impacts on embryo development and long-term influence on the health conditions of conceived children have always been a concern. As an alternative, noninvasive PGT-A (niPGT-A) approaches using spent blastocyst culture medium (SBCM) achieved comparable accuracy with PGT-A in several pilot studies. The main objective of this study is to determine whether noninvasive embryo viability testing (niEVT) results in better clinical outcomes than conventional IVF after the first embryo transfer. Furthermore, we further investigated whether niEVT results in higher the live birth rate between women with advanced maternal age (AMA, > 35 years old) and young women or among patients for whom different fertilization protocols are adopted. METHODS: This study will be a double-blind, multicenter, randomized controlled trial (RCT) studying patients of different ages (20-43 years) undergoing different fertilization protocols (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). We will enroll 1140 patients at eight reproductive medical centers over 24 months. Eligible patients should have at least two good-quality blastocysts (better than grade 4 CB). The primary outcome will be the live birth rate of the first embryo transfer (ET). Secondary outcomes will include the clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, cumulative live birth rate, ectopic pregnancy rate, and time to pregnancy. DISCUSSION: In this study, patients who undergo noninvasive embryo viability testing (niEVT) will be compared to women treated by conventional IVF. We will determine the effects on the pregnancy rate, miscarriage rate, and live birth rate and adverse events. We will also investigate whether there is any difference in clinical outcomes among patients with different ages and fertilization protocols (IVF/ICSI). This trial will provide clinical evidence of the effect of noninvasive embryo viability testing on the clinical outcomes of the first embryo transfer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2100051408. 9 September 2021.


Asunto(s)
Aborto Espontáneo , Tasa de Natalidad , Niño , Femenino , Embarazo , Humanos , Adulto , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Inyecciones de Esperma Intracitoplasmáticas , Índice de Embarazo , Aneuploidia , Fertilización In Vitro , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
10.
Heliyon ; 9(7): e17996, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37483760

RESUMEN

This study was to evaluate whether Intracytoplasmic sperm injection (ICSI) can improve the quality of embryo in patients with poor-quality embryos in the previous In-vitro fertilization (IVF) cycle, which was cancelled before transfer. This was a retrospective cohort study of 178 IVF and 158 ICSI cycles for patients with poor-quality embryos in the previous IVF cycle in the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University from March 2016 to June 2022. The 2 PN rate, oocyte utilization rate , high-quality embryo rate and clinical pregnancy rate were compared between the two groups. Furthermore, the implantation rate, miscarriage rate and cycle cancelation rate were measured and compared. ICSI resulted in a comparable 2 PN rate, oocyte utilization rate and cycle cancelation rate with IVF. The high-quality embryo rate of ICSI group was significantly higher than that of IVF group (5.56% vs. 2.60%, P < 0.05). Eventually, a total of 239 patients performed embryo transfer. ICSI resulted in a significantly higher clinical pregnancy rate (55.56% vs. 40.98%, P < 0.05) compared with IVF, however, there were no notable differences in miscarriage rate and implantation rate. The present study suggested that ICSI significantly improved the high-quality embryo rate and clinical pregnancy of the patients with poor-quality embryos in the previous IVF cycle. Prospective randomized controlled trials are needed to further verify.

12.
Natl Sci Rev ; 10(4): nwac180, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37089193

RESUMEN

The invention of laser cooling has fundamentally influenced the research frontier of atomic physics and quantum physics, and recently an intense focus has been on the studies of cold atom physics in microgravity environments. Herein, we report the results of our laser cooling experiment in TianGong-2 space lab, which operated for 34 consecutive months in orbit. Over such an extended operation time, the quality of laser cooling did not experience any significant decline, while the properties of laser cooling in orbital microgravity were systematically studied. In particular, we demonstrate magneto-optical trapping and polarization-gradient cooling in orbit and carefully examine their performances. A comparison of the in-orbit and on-ground results indicates that a higher cooling efficiency exists in microgravity, including a smaller loss rate during the trapping and cooling process and lower ultimate temperature of laser-cooled atoms. Our progress has laid the technical foundations for future applications of cold atoms in space missions with operation times of the order of years.

13.
J Xray Sci Technol ; 31(4): 713-729, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37092210

RESUMEN

BACKGROUND: Chest CT scan is an effective way to detect and diagnose COVID-19 infection. However, features of COVID-19 infection in chest CT images are very complex and heterogeneous, which make segmentation of COVID-19 lesions from CT images quite challenging. OBJECTIVE: To overcome this challenge, this study proposes and tests an end-to-end deep learning method called dual attention fusion UNet (DAF-UNet). METHODS: The proposed DAF-UNet improves the typical UNet into an advanced architecture. The dense-connected convolution is adopted to replace the convolution operation. The mixture of average-pooling and max-pooling acts as the down-sampling in the encoder. Bridge-connected layers, including convolution, batch normalization, and leaky rectified linear unit (leaky ReLU) activation, serve as the skip connections between the encoder and decoder to bridge the semantic gap differences. A multiscale pyramid pooling module acts as the bottleneck to fit the features of COVID-19 lesion with complexity. Furthermore, dual attention feature (DAF) fusion containing channel and position attentions followed the improved UNet to learn the long-dependency contextual features of COVID-19 and further enhance the capacity of the proposed DAF-UNet. The proposed model is first pre-trained on the pseudo label dataset (generated by Inf-Net) containing many samples, then fine-tuned on the standard annotation dataset (provided by the Italian Society of Medical and Interventional Radiology) with high-quality but limited samples to improve performance of COVID-19 lesion segmentation on chest CT images. RESULTS: The Dice coefficient and Sensitivity are 0.778 and 0.798 respectively. The proposed DAF-UNet has higher scores than the popular models (Att-UNet, Dense-UNet, Inf-Net, COPLE-Net) tested using the same dataset as our model. CONCLUSION: The study demonstrates that the proposed DAF-UNet achieves superior performance for precisely segmenting COVID-19 lesions from chest CT scans compared with the state-of-the-art approaches. Thus, the DAF-UNet has promising potential for assisting COVID-19 disease screening and detection.


Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico por imagen , Tomografía Computarizada por Rayos X
14.
Mol Ther ; 31(2): 344-361, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36514292

RESUMEN

Increasing evidence shows that SARS-CoV-2 can infect kidneys and cause acute kidney injury (AKI) in critically ill COVID-19 patients. However, mechanisms through which COVID-19 induces AKI are largely unknown, and treatment remains ineffective. Here, we report that kidney-specific overexpressing SARS-CoV-2 N gene can cause AKI, including tubular necrosis and elevated levels of serum creatinine and BUN in 8-week-old diabetic db/db mice, which become worse in those with older age (16 weeks) and underlying diabetic kidney disease (DKD). Treatment with quercetin, a purified product from traditional Chinese medicine (TCM) that shows effective treatment of COVID-19 patients, can significantly inhibit SARS-CoV-2 N protein-induced AKI in diabetic mice with or without underlying DKD. Mechanistically, quercetin can block the binding of SARS-CoV-2 N protein to Smad3, thereby inhibiting Smad3 signaling and Smad3-mediated cell death via the p16-dependent G1 cell-cycle arrest mechanism in vivo and in vitro. In conclusion, SARS-CoV-2 N protein is pathogenic and can cause severe AKI in diabetic mice, particularly in those with older age and pre-existing DKD, via the Smad3-dependent G1 cell-cycle arrest mechanism. Importantly, we identify that quercetin may be an effective TCM compound capable of inhibiting COVID-19 AKI by blocking SARS-CoV-2 N-Smad3-mediated cell death pathway.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Diabetes Mellitus Experimental , Ratones , Animales , SARS-CoV-2 , COVID-19/complicaciones , Quercetina/farmacología , Diabetes Mellitus Experimental/complicaciones , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Ratones Endogámicos , Puntos de Control del Ciclo Celular
15.
J Fluoresc ; 33(2): 731-737, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36512144

RESUMEN

In this paper, the novel fluorescence probe XP based on Schiff-base was designed, synthesized and characterized, which could detect Y3+selectively and sensitively. The recognition mechanism of XP toward Y3+ was studied by Job's plot and HRMS. It was investigated that stoichiometric ratio of the probe XP conjugated with Y3+ was 1:2. And the detection limit was calculated as 0.30 µM. In addition, Y3+ was recognized by the test paper made from XP. And the probe XP could detect  Y3+ selectively in Caenorhabditis elegans and the main organs of mice. Thus, XP was considered to have some potential for application in bioimaging.


Asunto(s)
Colorantes Fluorescentes , Itrio , Ratones , Animales , Espectrometría de Fluorescencia/métodos , Bases de Schiff
16.
Beilstein J Nanotechnol ; 13: 1011-1019, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36225850

RESUMEN

To explain the phenomenon of all-optical modulation of quantum cascade laser (QCL), and explore the physics in QCL's gain medium which consists of multiple of dielectric nanostructures with high refractive index under light injection, we modified the 1½-period model to calculate values of electron population and lifetime in each subband which is separated by the nanostructures, optical gain, current and number of photons in the cavity of a mid-infrared QCL modulated with near-infrared optical injection. The results were consistent with an experiment, where the injected light increases the electron population and lifetime, but does not affect the optical gain obviously. Our study can be helpful for optimizing its use and dielectric nanostructure design.

17.
Anal Chem ; 94(32): 11298-11306, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35926081

RESUMEN

Herein, a novel strategy was proposed for identifying carbon monoxide (CO), which plays a crucial part in living systems. For the first time, we have managed to design, synthesize, and characterize successfully this new Cu2+-assisted fluorescent probe (DPHP) in detecting CO. Compared with the commonly adopted Pd0-mediated Tsuji-Trost reaction recognition method, such a new strategy did not engage costly palladium (II) salt and generated no leaving group, indicating a satisfactory anti-interference ability. The recognition mechanism was confirmed by IR, 1H NMR titration, HR-MS, cyclic voltammetry, X-ray photoelectron spectroscopy, electron paramagnetic resonance, and optical properties. Surprisingly, it was found that the new method achieved high selectivity and rapid identification of CO with a lower limit of detection (1.7 × 10-8 M). More intriguingly, it could recognize endogenous and exogenous CO in HeLa cells. The cytotoxicity of this new method was so low that it allowed the detection of CO in mice and zebrafish. Basically, our results trigger a novel viewpoint of rationally designing and synthesizing advanced materials for CO detection with unique features, impelling new research in detection chemistry.


Asunto(s)
Monóxido de Carbono , Colorantes Fluorescentes , Animales , Colorantes Fluorescentes/química , Colorantes Fluorescentes/toxicidad , Células HeLa , Humanos , Ratones , Imagen Óptica/métodos , Pez Cebra
18.
Mol Ther ; 30(9): 3017-3033, 2022 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-35791881

RESUMEN

Clopidogrel, a P2Y12 inhibitor, is a novel anti-fibrosis agent for chronic kidney disease (CKD), but its mechanisms remain unclear, which we investigated by silencing P2Y12 or treating unilateral ureteral obstruction (UUO) in LysM-Cre/Rosa Tomato mice with clopidogrel in vivo and in vitro. We found that P2Y12 was significantly increased and correlated with progressive renal fibrosis in CKD patients and UUO mice. Phenotypically, up to 82% of P2Y12-expressing cells within the fibrosing kidney were of macrophage origin, identified by co-expressing CD68/F4/80 antigens or a macrophage-lineage-tracing marker Tomato. Unexpectedly, more than 90% of P2Y12-expressing macrophages were undergoing macrophage-to-myofibroblast transition (MMT) by co-expressing alpha smooth muscle actin (α-SMA), which was also confirmed by single-cell RNA sequencing. Functionally, clopidogrel improved the decline rate of the estimated glomerular filtration rate (eGFR) in patients with CKD and significantly inhibited renal fibrosis in UUO mice. Mechanistically, P2Y12 expression was induced by transforming growth factor ß1 (TGF-ß1) and promoted MMT via the Smad3-dependent mechanism. Thus, silencing or pharmacological inhibition of P2Y12 was capable of inhibiting TGF-ß/Smad3-mediated MMT and progressive renal fibrosis in vivo and in vitro. In conclusion, P2Y12 is highly expressed by macrophages in fibrosing kidneys and mediates renal fibrosis by promoting MMT via TGF-ß/Smad3 signaling. Thus, P2Y12 inhibitor maybe a novel and effective anti-fibrosis agent for CKD.


Asunto(s)
Enfermedades Renales , Insuficiencia Renal Crónica , Obstrucción Ureteral , Animales , Clopidogrel/metabolismo , Clopidogrel/farmacología , Clopidogrel/uso terapéutico , Fibrosis , Riñón , Enfermedades Renales/etiología , Enfermedades Renales/genética , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Miofibroblastos/metabolismo , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Transducción de Señal , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/tratamiento farmacológico , Obstrucción Ureteral/genética
19.
Inorg Chem ; 61(23): 8746-8751, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35642949

RESUMEN

A stable 3d-4f heterometallic cluster, namely, {Dy4Ni5L10(NO3)4(CO3)4(CH3OH)2}·CH3CN (Dy4Ni5, HL = 8-hydroxyquinoline), has been solvothermally synthesized and structurally characterized. The compound exhibits an interesting structure in which a tetrahedron based on 4f ions interpenetrates with a square pyramid based on 3d ions. Besides, a unique intermolecular interaction was found in Dy4Ni5, giving rise to its high stability not only when it is in the solid state but also when it dissolves in organic solvents. In addition, the magnetic behavior of solid Dy4Ni5 and the magneto-optical activity of the Dy4Ni5 solution were also studied.

20.
Kidney Int ; 102(4): 828-844, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35752325

RESUMEN

The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.


Asunto(s)
Lesión Renal Aguda , Inhibidor Tisular de Metaloproteinasa-2 , Adenosina Difosfato Ribosa , Animales , Biomarcadores , Cisplatino/toxicidad , Inflamación , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/genética , Lipopolisacáridos , Ratones , Ratones Noqueados , Ubiquitina-Proteína Ligasas/metabolismo
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