Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 99
Filtrar
1.
ACS Appl Mater Interfaces ; 16(15): 19379-19390, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38568698

RESUMEN

Photodriven chiral catalysis is the combination of photocatalysis and chiral catalysis and is considered one of the cleanest and most efficient methods for the synthesis of chiral compounds or drugs. Furthermore, due to the potential metal contamination associated with most metal-based catalysts, metal-free chiral photocatalysts are ideal candidates. In this work, we demonstrate that metal-free chiral carbon dots (CDs) exhibit size-dependent enantioselective photocatalytic activity. Using serine as the raw material, chiral CDs with well-defined structures and average sizes of 2.22, 3.01, 3.70, 4.77, and 7.21 nm were synthesized using the electrochemical method. These chiral CDs possess size-dependent band gaps and exhibit photoresponsive enantioselective catalytic activity toward the oxidation of dihydroxyphenylalanine (DOPA). Under light-assisted conditions, chiral CDs (L72, 500 µg/mL) exhibit high selectivity (selectivity factor: 2.07) and maintain a certain level of catalytic activity (1.34 µM/min) even at a low temperature of 5 °C. The high catalytic activity of the chiral CDs arises from their photoelectrons reducing O2 to generate O2-, as the active oxygen species for DOPA oxidation. The high enantioselectivity of the chiral CDs is attributed to their differential adsorption capabilities toward DOPA enantiomers. This study provides a new approach for designing metal-free chiral photocatalysts with high enantioselectivity.

2.
Acta Neuropathol ; 147(1): 65, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557897

RESUMEN

Human microglia are critically involved in Alzheimer's disease (AD) progression, as shown by genetic and molecular studies. However, their role in tau pathology progression in human brain has not been well described. Here, we characterized 32 human donors along progression of AD pathology, both in time-from early to late pathology-and in space-from entorhinal cortex (EC), inferior temporal gyrus (ITG), prefrontal cortex (PFC) to visual cortex (V2 and V1)-with biochemistry, immunohistochemistry, and single nuclei-RNA-sequencing, profiling a total of 337,512 brain myeloid cells, including microglia. While the majority of microglia are similar across brain regions, we identified a specific subset unique to EC which may contribute to the early tau pathology present in this region. We calculated conversion of microglia subtypes to diseased states and compared conversion patterns to those from AD animal models. Targeting genes implicated in this conversion, or their upstream/downstream pathways, could halt gene programs initiated by early tau progression. We used expression patterns of early tau progression to identify genes whose expression is reversed along spreading of spatial tau pathology (EC > ITG > PFC > V2 > V1) and identified their potential involvement in microglia subtype conversion to a diseased state. This study provides a data resource that builds on our knowledge of myeloid cell contribution to AD by defining the heterogeneity of microglia and brain macrophages during both temporal and regional pathology aspects of AD progression at an unprecedented resolution.


Asunto(s)
Enfermedad de Alzheimer , Animales , Humanos , Enfermedad de Alzheimer/patología , Proteínas tau/genética , Proteínas tau/metabolismo , Transcriptoma , Encéfalo/patología , Células Mieloides/patología , Microglía/patología , Péptidos beta-Amiloides/metabolismo
3.
Cureus ; 16(1): e52810, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38389613

RESUMEN

Rarely do patients with chronic graft-versus-host disease (cGVHD) experience vitiligo and alopecia areata. Nevertheless, the exact cause of vitiligo and alopecia areata is still not fully understood. The patient experienced a relapse of acute myeloid leukemia (AML) following a second complete remission after undergoing HLA-6/8 mismatched unrelated donor hematopoietic cell transplantation (HCT). Achieving full donor chimerism was successful during the initial stages of the transplant. Nevertheless, the molecular evidence of measurable residual disease remained, prompting the administration of donor lymphocyte infusions (DLI) following a dose-escalation protocol. After three cycles of DLI given at two-month intervals, the circulating blasts eventually vanished. After the third DLI dose, vitiligo developed despite achieving molecular remission. The dermatologist confirmed the presence of vitiligo and alopecia areata, along with cutaneous cGVHD. The outcome was the complete elimination of the molecular presence, and the patient experienced both clinical and molecular remission for a period of five years following DLI. Based on our observations, it was found that DLI could effectively eradicate molecular leukemia in cases of AML relapse after HCT. The development of vitiligo and alopecia areata was influenced by the destruction of melanocytes due to autoimmune reactions caused by cGVHD.

4.
Sci Robot ; 9(87): eadh2479, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38381840

RESUMEN

Cerebral aneurysms and brain tumors are leading life-threatening diseases worldwide. By deliberately occluding the target lesion to reduce the blood supply, embolization has been widely used clinically to treat cerebral aneurysms and brain tumors. Conventional embolization is usually performed by threading a catheter through blood vessels to the target lesion, which is often limited by the poor steerability of the catheter in complex neurovascular networks, especially in submillimeter regions. Here, we propose magnetic soft microfiberbots with high steerability, reliable maneuverability, and multimodal shape reconfigurability to perform robotic embolization in submillimeter regions via a remote, untethered, and magnetically controllable manner. Magnetic soft microfiberbots were fabricated by thermal drawing magnetic soft composite into microfibers, followed by magnetizing and molding procedures to endow a helical magnetic polarity. By controlling magnetic fields, magnetic soft microfiberbots exhibit reversible elongated/aggregated shape morphing and helical propulsion in flow conditions, allowing for controllable navigation through complex vasculature and robotic embolization in submillimeter regions. We performed in vitro embolization of aneurysm and tumor in neurovascular phantoms and in vivo embolization of a rabbit femoral artery model under real-time fluoroscopy. These studies demonstrate the potential clinical value of our work, paving the way for a robotic embolization scheme in robotic settings.


Asunto(s)
Neoplasias Encefálicas , Aneurisma Intracraneal , Procedimientos Quirúrgicos Robotizados , Robótica , Animales , Conejos , Procedimientos Quirúrgicos Robotizados/métodos , Aneurisma Intracraneal/terapia , Fenómenos Magnéticos
5.
ACS Nano ; 18(6): 5029-5039, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38286031

RESUMEN

Clarifying the structure-reactivity relationship of non-noble-metal electrocatalysts is one of the decisive factors for the practical application of water electrolysis. In this field, the anodic oxygen evolution reaction (OER) with a sluggish kinetic process has become a huge challenge for large-scale production of high-purity hydrogen. Here we synthesize a layered quasi-nevskite metastable-phase cobalt oxide (LQNMP-Co2O3) nanosheet via a simple molten alkali synthesis strategy. The unit-cell parameters of LQNMP-Co2O3 are determined to be a = b = 2.81 Šand c = 6.89 Šwith a space group of P3̅m1 (No. 164). The electrochemical results show that the LQNMP-Co2O3 electrocatalyst enables delivering an ultralow overpotential of 266 mV at a current density of 10 mA cmgeo-2 with excellent durability. The operando XANES and EXAFS analyses clearly reveal the origin of the OER activity and the electrochemical stability of the LQNMP-Co2O3 electrocatalyst. Density functional theory (DFT) simulations show that the energy barrier of the rate-determining step (RDS) (from *O to *OOH) is significantly reduced on the LQNMP-Co2O3 electrocatalyst by comparing with simulated monolayered CoO2 (M-CoO2).

6.
Eur J Pharmacol ; 965: 176315, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38176636

RESUMEN

Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and pERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and pERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation.


Asunto(s)
Hipertensión Pulmonar , MicroARNs , Hipertensión Arterial Pulmonar , Humanos , Ratas , Animales , Hipertrofia Ventricular Derecha , Hipertensión Arterial Pulmonar/complicaciones , Ácido Butírico/farmacología , Ácido Butírico/uso terapéutico , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar Primaria Familiar , MicroARNs/genética , MicroARNs/metabolismo , Factor I del Crecimiento Similar a la Insulina
7.
Small ; 20(7): e2305873, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37803396

RESUMEN

N-doped carbon (NC)-encapsulated transition metal (TM) nanocomposites are considered as alternatives to Pt-based hydrogen evolution reaction (HER) electrocatalysts; however, their poor electron transfer and mass diffusion capability at high current densities hinder their practical application. Herein, an oriented coupling strategy for the in situ grafting of ultrafine Co nanoparticle-embedded hollow porous C polyhedra onto Si nanowires (Co/NC-HP@Si-NWs) is proposed to address this concern. Experimental investigations reveal that the intimate coupling between the Si-NW and Co/NC nanocage forms a multithreaded conductive network, lowering the energy barrier for internal electron transfer. When functionalized as an HER electrocatalyst in 0.5 m H2 SO4 , Co/NC-HP@Si-NWs deliver overpotentials as low as 57 and 440 mV at 10 and 500 mA cm-2 , respectively, which are much better than those of the pristine Co/NC-HP. Moreover, Co/NC-HP@Si-NWs show an outstanding cycle durability of 24 h at 10 and 500 mA cm-2 . The findings of this study are expected to inspire revolutionary work on the development of Si-mediated TM-based electrocatalysts for the HER.

8.
J Formos Med Assoc ; 123(1): 98-105, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37365098

RESUMEN

BACKGROUND/PURPOSE: Encapsulating peritoneal sclerosis (EPS) is a rare and potential lethal complication of peritoneal dialysis characterized by bowel obstruction. Surgical enterolysis is the only curative therapy. Currently, there are no tools for predicting postsurgical prognosis. This study aimed to identify a computed tomography (CT) scoring system that could predict mortality after surgery in patients with severe EPS. METHODS: This retrospective study enrolled patients with severe EPS who underwent surgical enterolysis in a tertiary referral medical center. The association of CT score with surgical outcomes including mortality, blood loss, and bowel perforation was analyzed. RESULTS: Thirty-four patients who underwent 37 procedures were recruited and divided into a survivor and non-survivor group. The survivor group had higher body mass indices (BMIs, 18.1 vs. 16.7 kg/m2, p = 0.035) and lower CT scores (11 vs. 17, p < 0.001) than the non-survivor group. The receiver operating characteristic curve revealed that a CT score of ≥15 could be considered a cutoff point to predict surgical mortality, with an area under the curve of 0.93, sensitivity of 88.9%, and specificity of 82.1%. Compared with the group with CT scores of <15, the group with CT scores of ≥15 had a lower BMI (19.7 vs. 16.2 kg/m2, p = 0.004), higher mortality (4.2% vs. 61.5%, p < 0.001), greater blood loss (50 vs. 400 mL, p = 0.007), and higher incidence of bowel perforation (12.5% vs. 61.5%, p = 0.006). CONCLUSION: The CT scoring system could be useful in predicting surgical risk in patients with severe EPS receiving enterolysis.


Asunto(s)
Perforación Intestinal , Fibrosis Peritoneal , Humanos , Fibrosis Peritoneal/diagnóstico por imagen , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/cirugía , Estudios Retrospectivos , Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Esclerosis/complicaciones
9.
ACS Nano ; 17(21): 21539-21552, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37843009

RESUMEN

The occurrence and development of inflammatory bowel diseases (IBDs) are inextricably linked to the excessive production of reactive oxygen species (ROS). Thus, there is an urgent need to develop innovative tactics to combat IBDs and scavenge excess ROS from affected areas. Herein, silicon hydrogen nanoparticles (SiH NPs) with ROS-scavenging ability were prepared by etching Si nanowires (NWs) with hydrogen fluoride (HF) to alleviate the symptoms associated with IBD by orally targeting the inflamed colonic sites. The strong reductive Si-H bonds showed excellent stability in the gastric and intestinal fluids, which exhibited efficient ROS-scavenging effects to protect cells from high oxidative stress-induced death. After oral delivery, the negatively charged SiH NPs were specifically adsorbed to the positively charged inflammatory epithelial tissues of the colon for an extended period via electrostatic interactions to prolong the colonic residence time. SiH NPs exhibited significant preventive and therapeutic effects in dextran sodium sulfate-induced prophylactic and therapeutic mouse models by inhibiting colonic shortening, reducing the secretion of pro-inflammatory cytokines, regulating macrophage polarization, and protecting the colonic barrier. As determined using 16S rDNA high-throughput sequencing, the oral administration of SiH NPs treatment led to changes in the abundance of the intestinal microbiome, which improved the bacterial diversity and restored the relative abundance of beneficial bacteria after the inflamed colon. Overall, our findings highlight the broad application of SiH-based anti-inflammatory drugs in the treatment of IBD and other inflammatory diseases.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Nanoestructuras , Silicio , Animales , Ratones , Antiinflamatorios/uso terapéutico , Bacterias , Colon , Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Especies Reactivas de Oxígeno , Silicio/farmacología , Silicio/uso terapéutico
10.
Nano Lett ; 23(20): 9515-9521, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37830516

RESUMEN

Two-dimensional (2D) van der Waals single crystals with long-range magnetic order are the precondition and urgent task for developing a 2D spintronics device. In contrast to graphene and transition metal dichalcogenides, the study of 2D single-crystal metal oxides with intrinsic ferromagnetic properties remains a huge challenge. Here, we report a large-size trigonal single-crystal rhodium oxide (SC-Tri-RhO2), with crystal parameters of a = b = 3.074 Å, c = 6.116 Å, and a space group of P3̅m1 (164), exhibiting strong ferromagnetism (FM) at a rather high temperature. Furthermore, theoretical calculations suggest that the ferromagnetism in SC-Tri-RhO2 originates from spin splitting near the Fermi level, and the total magnetic moment is contributed mainly by the Rh atom.

11.
Eur J Pharmacol ; 959: 176077, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37820784

RESUMEN

Pulmonary artery smooth muscle cells (PASMCs) phenotypic switching and pulmonary artery endothelial cells (PAECs) endothelial-mesenchymal transition (EndMT) are important in promoting pulmonary hypertension (PH)-pulmonary vascular remodeling (PVR). Resveratrol can efficiently inhibit the proliferation of PASMCs, but its application is limited due to its low bioavailability and solubility. In this study, we modified resveratrol to assess the role of A ring N(CH3)2-based derivatives of resveratrol (Res4) in PVR-PASMCs phenotypic switching and PVR-PAECs EndMT. Chemical methods were used for the preparation of Res4; NMRS and HPLC were used to authenticate Res4. Mice developed PVR after 4 weeks of hypoxia (10% O2). Res4 (50 mg/kg/d) attenuated right ventricular systolic pressure, right ventricular hypertrophy, and PVR. PASMCs developed phenotypic switching and PAECs developed EndMT after 2 days of hypoxia (3% O2). Res4 (10 µM) could inhibit PASMCs and PAECs viability. Res4 could decrease proliferating cell nuclear antigen (PCNA) and osteopontin (OPN) expression, and increase α-smooth muscle actin (α-SMA) and vimentin expression in PASMCs. It could also decrease PCNA, α-SMA, vimentin expression and increase platelet endothelial cell adhesion molecule (CD31) expression in PAECs. Notably, Res4 inhibited the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated protein kinase (ERK), Jun-N-terminal kinase (JNK), and p38 kinase in hypoxia-treated PASMCs and PAECs, indicating MAPK pathway may be involved in Res4-induced inhibition of PASMCs phenotypic switching and PAECs EndMT. Our data demonstrated that Res4 exerts antiproliferative effects by regulating PASMCs phenotypic switching and PAECs EndMT. Res4 may be potentially used as a drug against PH-PVR.


Asunto(s)
Hipertensión Pulmonar , Ratones , Animales , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Resveratrol/farmacología , Resveratrol/metabolismo , Vimentina/metabolismo , Células Endoteliales/metabolismo , Remodelación Vascular , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Arteria Pulmonar , Miocitos del Músculo Liso , Proliferación Celular , Células Cultivadas
12.
Nat Commun ; 14(1): 5365, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37666815

RESUMEN

The oxygen evolution reactions in acid play an important role in multiple energy storage devices. The practical promising Ru-Ir based catalysts need both the stable high oxidation state of the Ru centers and the high stability of these Ru species. Here, we report stable and oxidative charged Ru in two-dimensional ruthenium-iridium oxide enhances the activity. The Ru0.5Ir0.5O2 catalyst shows high activity in acid with a low overpotential of 151 mV at 10 mA cm-2, a high turnover frequency of 6.84 s-1 at 1.44 V versus reversible hydrogen electrode and good stability (618.3 h operation). Ru0.5Ir0.5O2 catalysts can form more Ru active sites with high oxidation states at lower applied voltages after Ir incorporation, which is confirmed by the pulse voltage induced current method. Also, The X-ray absorption spectroscopy data shows that the Ru-O-Ir local structure in two-dimensional Ru0.5Ir0.5O2 solid solution improved the stability of these Ru centers.

13.
Aging (Albany NY) ; 15(15): 7583-7592, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37531210

RESUMEN

N1-methyladenosine (m1A) is an essential chemical modification of RNA. Dysregulation of RNA m1A modification and m1A-related regulators is detected in several adult tumors. Whether aberrant RNA m1A modification is involved in hepatoblast carcinogenesis has not been reported. tRNA methyltransferase 61B (TRMT61B) is responsible for mitochondrial RNA m1A modification. Some evidence has shown that genetic variants of TRMT61B might contribute to cancer susceptibility; however, its roles in hepatoblastoma are unknown. This study attempted to discover novel hepatoblastoma susceptibility loci. With the TaqMan method, we examined genotypes of the TRMT61B rs4563180 G>C polymorphism among germline DNA samples from 313 cases and 1446 controls. The association of the rs4563180 G>C polymorphism with hepatoblastoma risk was estimated based on odds ratios (ORs) and 95% confidence intervals (CIs). We found that the TRMT61B rs4563180 G>C polymorphism correlated significantly with a reduction in hepatoblastoma risk (GC vs. GG: adjusted OR=0.65, 95% CI=0.49-0.85, P=0.002; GC/CC vs. GG: adjusted OR=0.66, 95% CI=0.51-0.85, P=0.002). In stratified analysis, significant associations were detected in children younger than 17 months old, girls, and subgroups with stage I+II or III+IV tumors. False-positive report probability analysis validated that children with the GC or CC genotype, particularly in those <17 months of age, had a decreased risk of hepatoblastoma. The rs4563180 G>C polymorphism also correlated with expression of TRMT61B and the nearby gene PPP1CB. We identified a high-quality biomarker measuring hepatoblastoma susceptibility, which may contribute to future screening programs.


Asunto(s)
Hepatoblastoma , Neoplasias Hepáticas , Femenino , Humanos , Hepatoblastoma/genética , Predisposición Genética a la Enfermedad/genética , Estudios de Casos y Controles , ARN , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple
14.
Nat Commun ; 14(1): 1248, 2023 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-36871002

RESUMEN

Metastable metal oxides with ribbon morphologies have promising applications for energy conversion catalysis, however they are largely restricted by their limited synthesis methods. In this study, a monoclinic phase iridium oxide nanoribbon with a space group of C2/m is successfully obtained, which is distinct from rutile iridium oxide with a stable tetragonal phase (P42/mnm). A molten-alkali mechanochemical method provides a unique strategy for achieving this layered nanoribbon structure via a conversion from a monoclinic phase K0.25IrO2 (I2/m (12)) precursor. The formation mechanism of IrO2 nanoribbon is clearly revealed, with its further conversion to IrO2 nanosheet with a trigonal phase. When applied as an electrocatalyst for the oxygen evolution reaction in acidic condition, the intrinsic catalytic activity of IrO2 nanoribbon is higher than that of tetragonal phase IrO2 due to the low d band centre of Ir in this special monoclinic phase structure, as confirmed by density functional theory calculations.

15.
Angew Chem Int Ed Engl ; 62(20): e202218924, 2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-36932034

RESUMEN

Electrochemical two-electron oxygen reduction reaction (2 e- ORR) to produce hydrogen peroxide (H2 O2 ) is a promising alternative to the energetically intensive anthraquinone process. However, there remain challenges in designing 2 e- ORR catalysts that meet the application criteria. Here, we successfully adopt a microwave-assisted mechanochemical-thermal approach to synthesize hexagonal phase SnO2 (h-SnO2 ) nanoribbons with largely exposed edge structures. In 0.1 M Na2 SO4 electrolyte, the h-SnO2 catalysts achieve the excellent H2 O2 selectivity of 99.99 %. Moreover, when employed as the catalyst in flow cell devices, they exhibit a high yield of 3885.26 mmol g-1 h-1 . The enhanced catalytic performance is attributed to the special crystal structure and morphology, resulting in abundantly exposed edge active sites to convert O2 to H2 O2 , which is confirmed by density functional theory calculations.

16.
Nat Prod Res ; 37(13): 2243-2247, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35147448

RESUMEN

A new antifungal butenolide irperide (1) along with five known compounds were isolated from the co-culture of endophyte Irpex lacteus and pathogenic Nigrospora oryzae. The structure of 1, including the absolute configuration, was elucidated by analysis of NMR, HR-ESI-MS data and ECD spectra. Compounds 1, 4 and 6 exhibited significant antifungal activity against Aspergillus fumigatus, with MIC values of 1, 2 and 1 µg/mL, respectively.


Asunto(s)
Antifúngicos , Ascomicetos , Antifúngicos/farmacología , Antifúngicos/química , Ascomicetos/química
17.
Eur J Pharmacol ; 934: 175301, 2022 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-36191631

RESUMEN

In this study we aimed to reduce tau pathology, a hallmark of Alzheimer's Disease (AD), by activating mTOR-dependent autophagy in a transgenic mouse model of tauopathy by long-term dosing of animals with mTOR-inhibitors. Rapamycin treatment reduced the burden of hyperphosphorylated and aggregated pathological tau in the cerebral cortex only when applied to young mice, prior to the emergence of pathology. Conversely, PQR530 which exhibits better brain exposure and superior pharmacokinetic properties, reduced tau pathology even when the treatment started after the onset of pathology. Our results show that dosing animals twice per week with PQR530 resulted in intermittent, rather than sustained target engagement. Nevertheless, this pulse-like mTOR inhibition followed by longer intervals of re-activation was sufficient to reduce tau pathology in the cerebral cortex in P301S tau transgenic mice. This suggests that balanced therapeutic dosing of blood-brain-barrier permeable mTOR-inhibitors can result in a disease-modifying effect in AD and at the same time prevents toxic side effects due to prolonged over activation of autophagy.


Asunto(s)
Enfermedad de Alzheimer , Animales , Ratones , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Proteínas tau/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Ratones Transgénicos , Encéfalo , Sirolimus/farmacología , Modelos Animales de Enfermedad
18.
Nat Commun ; 13(1): 5828, 2022 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-36192414

RESUMEN

Designing well-ordered nanocrystal arrays with subnanometre distances can provide promising materials for future nanoscale applications. However, the fabrication of aligned arrays with controllable accuracy in the subnanometre range with conventional lithography, template or self-assembly strategies faces many challenges. Here, we report a two-dimensional layered metastable oxide, trigonal phase rhodium oxide (space group, P-3m1 (164)), which provides a platform from which to construct well-ordered face-centred cubic rhodium nanocrystal arrays in a hexagonal pattern with an intersurface distance of only 0.5 nm. The coupling of the well-ordered rhodium array and metastable substrate in this catalyst triggers and improves hydrogen spillover, enhancing the acidic hydrogen evolution for H2 production, which is essential for various clean energy-related devices. The catalyst achieves a low overpotential of only 9.8 mV at a current density of -10 mA cm-2, a low Tafel slope of 24.0 mV dec-1, and high stability under a high potential (vs. RHE) of -0.4 V (current density of ~750 mA cm-2). This work highlights the important role of metastable materials in the design of advanced materials to achieve high-performance catalysis.

19.
Small Methods ; 6(12): e2200914, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36287097

RESUMEN

As a unique carbon-based nano material, carbon dots (CDs) have attracted great attention because of their special structures and properties, and have been widely used in various fields, such as bio-imaging technology, catalyst design, pollutant degradation, chemical analysis, clean energy development and so on. CDs are used as catalysts or cocatalysts for multiple energy conversion reactions due to their advantages of valid visible light utilization, fast transmission of charge carriers, excellent catalytic activity, and good electrical conductivity. This review first summarizes the basic structure and properties of CDs. The advance and critical functions of energetic CDs in carbon dioxide photo/electroreduction reactions are discussed in detail. Due to the excellent optical absorption, electron transfer properties and good conductivity of CDs, they can enhance catalytic activity and stability effectively. In the end, the existing problems and future development opportunities of CDs-based catalysts in CO2 reduction reaction are proposed and outlined.

20.
Animals (Basel) ; 12(18)2022 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-36139273

RESUMEN

Porcine circovirus 2 (PCV2) is the main pathogen of porcine circovirus-associated disease (PCVAD), which can cause considerable economic loss to the pig industry. The diagnosis of PCVAD is complicated and requires a series of clinical, pathological, and virological methods. Therefore, a rapid, highly sensitive, on-site, and visual diagnostic approach would facilitate dealing with the spread of PCV2. In this study, we intended to establish a new and effective PCV2 detection method through combining the no specific equipment requirement advantage of loop-mediated isothermal amplification (LAMP) with the property of clustered regular interspaced short palindromic repeats (CRISPR)/Cas12a system possessing the huLbCas12a collateral cleavage activity able to cleave single-stranded DNA fluorophore quencher probe sensor (designed as LAPM-CRISPR). Following a series of optimizations of its reaction conditions, this LAMP-CRISPR-based PCV2 detection could be conducted in constant temperature equipment, with the result reflected in a direct visual readout way. This established PCV2 detection approach presented fine sensitivity, rapidity, specificity, and reliability, as demonstrated by a low detectable limit of 1 copy/µL, completed within an hour, no cross-reaction with main porcine DNA or RNA viruses like PCV1, PCV3, and PEDV, and a 100% coincidence rate with that of the quantitative PCR (qPCR) method in the evaluation of 30 clinical blood samples, respectively. Therefore, this novel method makes rapid, on-site, visual, highly sensitive, and specific detection of PCV2 possible, facilitating the prevention of this pathogen in the field.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA