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1.
Adv Mater ; : e2407199, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096075

RESUMEN

Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A-D-A-structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η = 67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground-state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2 -), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A-D-A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early-stage and advanced cervical cancer treatment.

2.
Adv Mater ; : e2409356, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39149770

RESUMEN

Delivery of proteins in plant cells can facilitate the design of desired functions by modulation of biological processes and plant traits but is currently limited by narrow host range, tissue damage, and poor scalability. Physical barriers in plants, including cell walls and membranes, limit protein delivery to desired plant tissues. Herein, a cationic high aspect ratio polymeric nanocarriers (PNCs) platform is developed to enable efficient protein delivery to plants. The cationic nature of PNCs binds proteins through electrostatic. The ability to precisely design PNCs' size and aspect ratio allowed us to find a cutoff of ≈14 nm in the cell wall, below which cationic PNCs can autonomously overcome the barrier and carry their cargo into plant cells. To exploit these findings, a reduction-oxidation sensitive green fluorescent protein (roGFP) is deployed as a stress sensor protein cargo in a model plant Nicotiana benthamiana and common crop plants, including tomato and maize. In vivo imaging of PNC-roGFP enabled optical monitoring of plant response to wounding, biotic, and heat stressors. These results show that PNCs can be precisely designed below the size exclusion limit of cell walls to overcome current limitations in protein delivery to plants and facilitate species-independent plant engineering.

3.
ACS ES T Eng ; 4(7): 1702-1711, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39021402

RESUMEN

Polyvinyl chloride (PVC) membrane-based ion-selective electrode (ISE) sensors are common tools for water assessments, but their development relies on time-consuming and costly experimental investigations. To address this challenge, this study combines machine learning (ML), Morgan fingerprint, and Bayesian optimization technologies with experimental results to develop high-performance PVC-based ISE cation sensors. By using 1745 data sets collected from 20 years of literature, appropriate ML models are trained to enable accurate prediction and a deep understanding of the relationship between ISE components and sensor performance (R 2 = 0.75). Rapid ionophore screening is achieved using the Morgan fingerprint based on atomic groups derived from ML model interpretation. Bayesian optimization is then applied to identify optimal combinations of ISE materials with the potential to deliver desirable ISE sensor performance. Na+, Mg2+, and Al3+ sensors fabricated from Bayesian optimization results exhibit excellent Nernst slopes with less than 8.2% deviation from the ideal value and superb detection limits at 10-7 M level based on experimental validation results. This approach can potentially transform sensor development into a more time-efficient, cost-effective, and rational design process, guided by ML-based techniques.

4.
J Orthop ; 57: 98-103, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39006207

RESUMEN

Background: Femoral neck fractures (FNF) are one of the most common fractures, with a projected increase in incidence with population growth and ageing. The Femoral Neck System (FNS) launched in 2019 was developed specifically for fixation of FNF with the purported advantages of providing both angular and rotational stability. We report our experience with the FNS and evaluate its effectiveness and associated complications. Methods: A retrospective case series of 50 patients who underwent surgical fixation for FNF from August 2020 to October 2021 using the FNS in two Singapore tertiary institutions with at least 2 years follow-up were included. Clinical data (patients' demographics, fracture classification, intra-operative and post-operative complications) were reviewed. Radiological analysis assessed the pre- and immediate post-operative garden alignment index (GAI) and presence of femoral neck shortening at 3 months. Results: The mean age was 63.5 years (SD 16.9, range 26-92). Five (10 %), 34 (68 %) and 11 (22 %) were ASA 1, 2 and 3 respectively. Twenty-four (48 %), 16 (32 %), 4 (8 %), and 6 (12 %) patients sustained Garden's 1, 2, 3 and 4 FNF respectively. The mean operative duration was 66.2 min (SD 20.5) and length of stay was 6.9 days (SD 4.6).The post-operative improvement in garden alignment index (GAI) was a mean of 9.1° (p < 0.001) on lateral view. The mean femoral neck shortening was 1.97 mm (SD 5.3) at 3 months. There were no intra-operative complications. Post-operatively, 1 (2 %) patient required blood transfusion, 1 (2 %) patient had implant cut-out and non-union managed non-operatively, 2 (4 %) patients developed avascular necrosis and required revision to total hip replacements. There were two (4 %) cases of 1-year mortality. Conclusion: The FNS achieved good outcomes with low rates of complications. The promising results justify its continued use and further evaluation in comparison to other devices.

5.
Water Res ; 262: 122107, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39038424

RESUMEN

To address the increasing issue of antibiotic wastewater, this study applied a static magnetic field (SMF) to the activated sludge process to increase the efficiency of tetracycline (TC) removal from swine wastewater and to reveal its enhanced mechanisms. The results demonstrated that the SMF-modified activated sludge process could achieve almost complete TC removal at sludge loading rates of 0.3 mg TC/g MLSS/d. Analysis of zeta potential and extracellular polymeric substances composition of the activated sludge revealed that SMF increased electrostatic interactions between TC and activated sludge and made activated sludge has much more binding sites, finally resulting in the increased TC biosorption. Metagenomic analysis showed that SMF promoted the enrichment of ammonia-oxidizing bacteria, TC-degrading bacteria, and aromatic compounds-degrading bacteria; it also enhanced ammonia monooxygenase- and cytochrome P450-mediated TC metabolism while upregulating functional genes associated with oxidase, reductase, and dehydrogenase - all contributing to increased TC biodegradation. Additionally, SMF mitigated the enrichment and spread of antibiotic resistance genes (ARGs) by decreasing the abundance of potential hosts of ARGs and inhibiting the upregulation of genes encoding ABC transporters and putative transposase. Based on these findings, this study demonstrates that magnetic field is an enhancement strategy with great potential to relieve the harmful impacts of the growing antibiotic wastewater problem on human health and the ecosystem.


Asunto(s)
Farmacorresistencia Microbiana , Campos Magnéticos , Aguas del Alcantarillado , Tetraciclina , Tetraciclina/farmacología , Farmacorresistencia Microbiana/genética , Antibacterianos/farmacología , Aguas Residuales/química , Animales , Eliminación de Residuos Líquidos/métodos , Bacterias/genética , Bacterias/metabolismo , Biodegradación Ambiental , Porcinos
6.
Mater Horiz ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946704

RESUMEN

Contrary to previous results, a unique anti-correlation effect of the alkyl chain size on the photovoltaic performance of acceptors was observed. For a centrally-extended acceptor, replacing linear alkyl chains (n-undecyl for CH-BBQ) on the thienothiophene unit with branched ones (2-butyloctyl for CH-BO) leads to a plunge in the power conversion efficiency of organic solar cells (18.12% vs. 11.34% for binary devices), while the largely shortened ones (n-heptyl for CH-HP) bring a surge in performance (18.74%/19.44% for binary/ternary devices). Compared with CH-BO, the more compact intermolecular packing of CH-HP facilitates carrier transport. The characterization of organic field effect transistors and carrier dynamics also echoes the above results. Molecular dynamics simulations indicate that the encounter of the branched alkyl chains and the extended central core hinders the effective interfacial interaction of polymer donors and acceptors, thus deteriorating the device performance. This work suggests that the conventional strategy for alkyl chain engineering of Y-series acceptors might need to be reconsidered in other molecular systems.

7.
J Am Chem Soc ; 146(27): 18771-18780, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38935700

RESUMEN

Chiral three-dimensional (3D) perovskites exhibit exceptional optoelectronic characteristics and inherent chiroptical activity, which may overcome the limitations of low-dimensional chiral optoelectronic devices and achieve superior performance. The integrated chip of high-performance arbitrary polarized light detection is one of the aims of chiral optoelectronic devices and may be achieved by chiral 3D perovskites. Herein, we first fabricate the wafer-scale integrated full-Stokes polarimeter by the synergy of unprecedented chiral 3D perovskites (R/S-PyEA)Pb2Br6 and one-step capillary-bridge assembly technology. Compared with the chiral low-dimensional perovskites, chiral 3D perovskites present smaller exciton binding energies of 57.3 meV and excellent circular dichroism (CD) absorption properties, yielding excellent circularly polarized light (CPL) photodetectors with an ultrahigh responsivity of 86.7 A W-1, an unprecedented detectivity exceeding 4.84 × 1013 Jones, a high anisotropy factor of 0.42, and high-fidelity CPL imaging with 256 pixels. Moreover, the anisotropic crystal structure also enables chiral 3D perovskites to have a large linear-polarization response with a polarized ratio of 1.52. The combination of linear-polarization and circular-polarization discrimination capabilities guarantees the achievement of a full-Stokes polarimeter. Our study provides new research insights for the large-scale patterning wafer integration of high-performance chiroptical devices.

8.
Adv Mater ; 36(33): e2405921, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38932651

RESUMEN

Enhancing stability while maintaining high efficiency is among the primary challenges in the commercialization of perovskite solar cells (PSCs). Here, a crystal growth technique assisted by in situ generated 2D perovskite phases has been developed to construct high-quality 2D/3D perovskite films. The in situ generated 2D perovskite serve as templates for regulating the nucleation and oriented crystal growth in the α-FAPbI3-rich film. This led to a high film quality with much reduced trap density and an ultralong carrier lifetime. The obtained perovskite film shows excellent stability under extreme environment conditions (T = 200 °C, RH = 75 ± 5%). The corresponding PSC achieved an efficiency of 26.16% (certified 25.84%), along with excellent operational stability (T93 > 1300 h, T ≅ 50 °C) as well as outstanding high and low temperature cycle stability.

9.
Foods ; 13(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38890931

RESUMEN

Recent research has demonstrated the positive impact of herbal tea consumption on postprandial blood glucose regulation. This study conducts a comparative analysis of aqueous and ethanol extractions on four herbal teas (Mallotus, Cyclocarya, Rubus, and Vine) to assess their phytochemical profiles and functional attributes. Phytochemical contents, antioxidant activities, α-glucosidase inhibitory activities, and chemical compositions are investigated via colorimetric analyses and UPLC-Q-Orbitrap HRMS/MS, respectively. Results indicate that Vine, among the teas studied, exhibits the most pronounced glucose-regulating effects under both extraction methods. While ethanol extractions yield higher phytochemical content overall, the compositions vary. Conversely, aqueous extracts demonstrate unexpectedly potent antioxidant activities and comparable α-glucosidase inhibitory activities to ethanol extracts. Phytochemical contents correlate positively with antioxidant activities and α-glucosidase inhibitory activities. However, antioxidant activities exhibit a weak positive correlation with α-glucosidase inhibitory activities. These findings provide evidence that aqueous extracts from herbal teas contain valuable phytochemical compositions beneficial for antioxidants and individuals with hyperglycemia, suggesting their potential as functional ingredients to enhance the nutritional value of herbal food products.

10.
J Cereb Blood Flow Metab ; 44(8): 1298-1305, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38820447

RESUMEN

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.508, p = 0.031) and the SvO2 (r = -0.498, p = 0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS. .


Asunto(s)
Venas Cerebrales , Disfunción Cognitiva , Imagen por Resonancia Magnética , Oxígeno , Humanos , Masculino , Femenino , Adulto , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Venas Cerebrales/diagnóstico por imagen , Venas Cerebrales/metabolismo , Oxígeno/metabolismo , Oxígeno/sangre , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/psicología , Circulación Cerebrovascular/fisiología , Consumo de Oxígeno , Saturación de Oxígeno
11.
J Am Chem Soc ; 146(20): 14287-14296, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38718348

RESUMEN

PEDOT: PSS has been widely used as a hole extraction layer (HEL) in organic solar cells (OSCs). However, their acidic nature can potentially corrode the indium tin oxide (ITO) electrode over time, leading to adverse effects on the longevity of the OSCs. Herein, we have developed a class of biphosphonic acid molecules with tunable dipole moments for self-assembled monolayers (SAMs), namely, 3-BPIC(i), 3-BPIC, and 3-BPIC-F, which exhibit an increasing dipole moment in sequence. Compared to centrosymmetric 3-BPIC(i), the axisymmetric 3-BPIC and 3-BPIC-F exhibit higher adsorption energies (Eads) with ITO, shorter interface spacing, more uniform coverage on ITO surface, and better interfacial compatibility with the active layer. Thanks to the incorporation of fluorine atoms, 3-BPIC-F exhibits a deeper highest occupied molecular orbital (HOMO) energy level and a larger dipole moment compared to 3-BPIC, resulting in an enlarged work function (WF) for the ITO/3-BPIC-F substrate. These advantages of 3-BPIC-F could not only improve hole extraction within the device but also lower the interfacial impedance and reduce nonradiative recombination at the interface. As a result, the OSCs using SAM based on 3-BPIC-F obtained a record high efficiency of 19.71%, which is higher than that achieved from the cells based on 3-BPIC(i) (13.54%) and 3-BPIC (19.34%). Importantly, 3-BPIC-F-based OSCs exhibit significantly enhanced stability compared to that utilizing PEDOT:PSS as HEL. Our work offers guidance for the future design of functional molecules for SAMs to realize even higher performance in organic solar cells.

12.
J Magn Reson Imaging ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587279

RESUMEN

BACKGROUND: The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP. PURPOSE: To investigate the sub-structural characteristics of the ChP, particularly the vascular compartment using high-resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super-paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels. STUDY TYPE: Prospective. SUBJECTS: Forty-nine subjects without neurological disorders (age: 21-80 years; 42 ± 17 years; 20 females). FIELD STRENGTH/SEQUENCE: 7-T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR. ASSESSMENT: The vascular and stromal compartments of the ChP were segmented using K-means clustering on post-contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Volvessel/VolChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE-derived susceptibility-weighted imaging and quantitative susceptibility mapping, respectively. STATISTICAL TESTS: Independent t-test, Mann-Whitney U test, and Chi-square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra-class coefficient was calculated for inter-observer agreement. A P value <0.05 was considered statistically significant. RESULTS: 2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = -0.48, and r = -0.45). DATA CONCLUSION: Ferumoxytol-enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

13.
Environ Sci Technol ; 58(19): 8587-8596, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38683942

RESUMEN

Water scarcity has driven the demand for water production from unconventional sources and the reuse of industrial wastewater. Pressure-driven membranes, notably thin-film composite (TFC) membranes, stand as energy-efficient alternatives to the water scarcity challenge and various wastewater treatments. While pressure drives solvent movement, it concurrently triggers membrane compaction and flux deterioration. This necessitates a profound comprehension of the intricate interplay among compressive modulus, structural properties, and transport efficacy amid the compaction process. In this study, we present an all-encompassing compaction model for TFC membranes, applying authentic structural and mechanical variables, achieved by coupling viscoelasticity with Monte Carlo flux calculations based on the resistance-in-series model. Through validation against experimental data for multiple commercial membranes, we evaluated the influence of diverse physical parameters. We find that support polymers with a higher compressive modulus (lower compliance), supports with higher densities of "finger-like" pores, and "sponge-like" pores with optimum void fractions will be preferred to mitigate compaction. More importantly, we uncover a trade-off correlation between steady-state permeability and the modulus for identical support polymers displaying varying porosities. This model holds the potential as a valuable guide in shaping the design and optimization for further TFC applications and extending its utility to biological scaffolds and hydrogels with thin-film coatings in tissue engineering.


Asunto(s)
Membranas Artificiales , Porosidad , Permeabilidad , Polímeros/química
14.
Front Neurosci ; 18: 1374948, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38686326

RESUMEN

Introduction: Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear. Methods: In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins. Results: Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all p < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all p < 0.05). Conclusion: The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.

15.
J Biochem Mol Toxicol ; 38(4): e23689, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38613465

RESUMEN

Renal cell carcinoma (RCC) is the most common kidney cancer with high mortality rate. Pazopanib has been approved for the treatment of RCC. However, the underlying mechanism is not clear. Here, we report a novel finding by showing that treatment with Pazopanib could promote cellular senescence of the human RCC cell line ACHN. Cells were stimulated with 5, 10, and 20 µM Pazopanib, respectively. Cellular senescence was measured using senescence-associated ß-galactosidase (SA-ß-Gal) staining. Western blot analysis and real-time polymerase chain reaction were used to measure the mRNA and protein expression of nuclear factor E2-related factor 2 (Nrf2), γH2AX, human telomerase reverse transcriptase (hTERT), telomeric repeat binding factor 2 (TERF2), p53 and plasminogen activator inhibitor (PAI). First, we found that exposure to Pazopanib reduced the cell viability of ACHN cells. Additionally, Pazopanib induced oxidative stress  by increasing the production of reactive oxygen species, reducing the levels of glutathione peroxidase, and promoting nuclear translocation of Nrf2. Interestingly, Pazopanib exposure resulted in DNA damage by increasing the expression of γH2AX. Importantly, Pazopanib increased cellular senescence and reduced telomerase activity. Pazopanib also reduced the gene expression of hTERT but increased the gene expression of TERF2. Correspondingly, we found that Pazopanib increased the expression of p53 and PAI at both the mRNA and protein levels. To elucidate the underlying mechanism, the expression of Nrf2 was knocked down by transduction with Ad- Nrf2 shRNA. Results indicate that silencing of Nrf2 in ACHN cells abolished the effects of Pazopanib in stimulating cellular senescence and reducing telomerase activity. Consistently, knockdown of Nrf2 restored the expression of p53 and PAI in ACHN cells. Based on these results, we explored a novel mechanism whereby which Pazopanib displays a cytotoxicity effect in RCC cells through promoting cellular senescence mediated by Nrf2.


Asunto(s)
Carcinoma de Células Renales , Indazoles , Neoplasias Renales , Pirimidinas , Sulfonamidas , Telomerasa , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Factor 2 Relacionado con NF-E2 , Telomerasa/genética , Proteína p53 Supresora de Tumor/genética , Neoplasias Renales/tratamiento farmacológico , ARN Mensajero
16.
Small ; 20(32): e2401054, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38488748

RESUMEN

2D conjugated extension on central units of small molecular acceptors (SMAs) has gained great successes in reaching the state-of-the-art organic photovoltaics. Whereas the limit size of 2D central planes and their dominant role in constructing 3D intermolecular packing networks are still elusive. Thus, by exploring a series of SMAs with gradually enlarged central planes, it is demonstrated that, at both single molecular and aggerated levels, there is an unexpected blue-shift for their film absorption but preferable reorganization energies, exciton lifetimes and binding energies with central planes enlarging, especially when comparing to their Y6 counterpart. More importantly, the significance of well-balanced molecular packing modes involving both central and end units is first disclosed through a systematic single crystal analysis, indicating that when the ratio of central planes area/end terminals area is no more than 3 likely provides a preferred 3D intermolecular packing network of SMAs. By exploring the limit size of 2D central planes, This work indicates that the structural profiles of ideal SMAs may require suitable central unit size together with proper heteroatom replacement instead of directly overextending 2D central planes to the maximum. These results will likely provide some guidelines for future better molecular design.

17.
Angew Chem Int Ed Engl ; 63(17): e202400303, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38444055

RESUMEN

Solid-state lithium metal batteries (LMBs), constructed through the in situ fabrication of polymer electrolytes, are considered a critical strategy for the next-generation battery systems with high energy density and enhanced safety. However, the constrained oxidation stability of polymers, such as the extensively utilized polyethers, limits their applications in high-voltage batteries and further energy density improvements. Herein, an in situ fabricated fluorinated and crosslinked polyether-based gel polymer electrolyte, FGPE, is presented, exhibiting a high oxidation potential (5.1 V). The fluorinated polyether significantly improves compatibility with both lithium metal and high-voltage cathode, attributed to the electron-withdrawing -CF3 group and the generated LiF-rich electrolyte/electrode interphase. Consequently, the solid-state Li||LiNi0.6Co0.2Mn0.2O2 batteries employing FGPE demonstrate exceptional cycling performances of 1000 cycles with 78 % retention, representing one of the best results ever reported for polymer electrolytes. Moreover, FGPE enables batteries to operate at 4.7 V, realizing the highest operating voltage of polyether-based batteries to date. Notably, our designed in situ FGPE provides the solid-state batteries with exceptional cycling stability even at practical conditions, including high cathode loading (21 mg cm-2) and industry-level 18650-type cylindrical cells (1.3 Ah, 500 cycles). This work provides critical insights into the development of oxidation-stable polymer electrolytes and the advancement of practical high-voltage LMBs.

18.
Neuroimage ; 291: 120588, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38537765

RESUMEN

BACKGROUND: Parkinson's disease (PD) is associated with the loss of neuromelanin (NM) and increased iron in the substantia nigra (SN). Magnetization transfer contrast (MTC) is widely used for NM visualization but has limitations in brain coverage and scan time. This study aimed to develop a new approach called Proton-density Enhanced Neuromelanin Contrast in Low flip angle gradient echo (PENCIL) imaging to visualize NM in the SN. METHODS: This study included 30 PD subjects and 50 healthy controls (HCs) scanned at 3T. PENCIL and MTC images were acquired. NM volume in the SN pars compacta (SNpc), normalized image contrast (Cnorm), and contrast-to-noise ratio (CNR) were calculated. The change of NM volume in the SNpc with age was analyzed using the HC data. A group analysis compared differences between PD subjects and HCs. Receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculations were used to evaluate the diagnostic performance of NM volume and CNR in the SNpc. RESULTS: PENCIL provided similar visualization and structural information of NM compared to MTC. In HCs, PENCIL showed higher NM volume in the SNpc than MTC, but this difference was not observed in PD subjects. PENCIL had higher CNR, while MTC had higher Cnorm. Both methods revealed a similar pattern of NM volume in SNpc changes with age. There were no significant differences in AUCs between NM volume in SNpc measured by PENCIL and MTC. Both methods exhibited comparable diagnostic performance in this regard. CONCLUSIONS: PENCIL imaging provided improved CNR compared to MTC and showed similar diagnostic performance for differentiating PD subjects from HCs. The major advantage is PENCIL has rapid whole-brain coverage and, when using STAGE imaging, offers a one-stop quantitative assessment of tissue properties.


Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Negra/diagnóstico por imagen , Porción Compacta de la Sustancia Negra , Imagen por Resonancia Magnética/métodos , Melaninas
19.
Small ; 20(24): e2311561, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38546001

RESUMEN

Balancing the rigid backbones and flexible side chains of light-harvesting materials is crucially important to reach optimized intermolecular packing, micromorphology, and thus photovoltaic performance of organic solar cells (OSCs). Herein, based on a distinctive CH-series acceptor platform with 2D conjugation extended backbones, a series of nonfullerene acceptors (CH-6F-Cn) are synthesized by delicately tuning the lengths of flexible side chains from n-octyl to n-amyl. A systemic investigation has revealed that the variation of the side chain's length can not only modulate intermolecular packing modes and crystallinity but also dramatically improve the micromorphology of the active layer and eventual photovoltaic parameters of OSCs. Consequently, the highest PCE of 18.73% can be achieved by OSCs employing D18:PM6:CH-6F-C8 as light-harvesting materials.

20.
Neuroscience ; 545: 158-170, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38513765

RESUMEN

Thioredoxin-reductase 2 (Txnrd2) belongs to the thioredoxin-reductase family of selenoproteins and is a key antioxidant enzyme in mammalian cells to regulate redox homeostasis. Here, we reported that Txnrd2 exerted a major influence in brain damage caused by Intracerebral hemorrhage (ICH) by suppressing endoplasmic reticulum (ER) stress oxidative stress and via Trx2/Prx3 pathway. Furthermore, we demonstrated that pharmacological selenium (Se) rescued the brain damage after ICH by enhancing Txnrd2 expression. Primarily, expression and localization of Txnrd2, Trx2 and Prx3 were determined in collagenase IV-induced ICH model. Txnrd2 was then knocked down using siRNA interference in rats which were found to develop more severe encephaledema and neurological deficits. Mechanistically, we observed that loss of Txnrd2 leads to increased lipid peroxidation levels and ER stress protein expression in neurons and astrocytes. Additionally, it was revealed that Se effectively restored the expression of Txnrd2 in brain and inhibited both the activity of ER stress protein activity and the generation of reactive oxygen species (ROS) by promoting Trx2/Prx3 kilter when administrating sodium selenite in lateral ventricle. This study shed light on the effect of Txnrd2 in regulating oxidative stress and ER stress via Trx2/Prx3 pathway upon ICH and its promising potential as an ICH therapeutic target.


Asunto(s)
Hemorragia Cerebral , Estrés del Retículo Endoplásmico , Estrés Oxidativo , Ratas Sprague-Dawley , Tiorredoxina Reductasa 2 , Tiorredoxinas , Animales , Masculino , Ratas , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/patología , Lesiones Encefálicas/metabolismo , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico/fisiología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Peroxiredoxina III/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Selenio/farmacología , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Tiorredoxina Reductasa 2/metabolismo , Tiorredoxinas/metabolismo
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