The innate hypoxic microenvironment of most solid tumors has a major influence on tumor growth, invasiveness, and distant metastasis. Here, a hypoxia‐activated self‐immolative prodrug of paclitaxel ...(PTX2‐Azo) was synthesized and encapsulated by a peptide copolymer decorated with the photosensitizer chlorin e6 (Ce6) to prepare light‐boosted PTX nanoparticle (Ce6/PTX2‐Azo NP). In this nanoparticle, PTX2‐Azo prevents premature drug leakage and realizes specific release in hypoxic tumor microenvironment and the photosensitizer Ce6 not only efficiently generates singlet oxygen under light irradiation but also acts as a positive amplifier to promote the release of PTX. The combination of photodynamic therapy (PDT) and chemotherapy results in excellent antitumor efficacy, demonstrating the great potential for synergistic cancer therapy.
A light‐boosted hypoxia‐activated self‐immolative paclitaxel prodrug nanosystem was designed for synergistic photodynamic therapy and chemotherapy. Upon irradiation, severe hypoxia occurred and amplified the specific release of paclitaxel from prodrug bridged with azobenzene. The nanoparticle showed superior antitumor efficacy with little toxicity to other organs.
Solar and radiative warming are smart approaches to maintaining the human body at a metabolically comfortable temperature in both indoor and outdoor scenarios. Nevertheless, existing warming textiles ...are ineffective in frigid climates because the solar absorption of selective absorbing coating is significantly reduced when coated on rough textile surface. Herein, for the first time, high‐entropy nitrides based spectrally selective film (SSF) is introduced on common cotton through a one‐step magnetron sputtering method. The well‐designed refractive index gradient enables destructive interference effects, offering a roughness‐insensitive high solar absorptance (92.8%) and low thermal emittance (39.2%). Impressively, the solar absorptance is 9.1% higher than the reported best‐performing selective nanofilm‐based textile. As a result, such a textile achieves a record‐high photothermal conversion efficiency (82.2% under 0.6 suns, at 0 °C). This textile yields a 3.5 °C drop in the set‐point of indoor air‐conditioner temperature. Besides, in a winter morning with an air temperature of 7.5 °C, it warms up the human skin by as large as 12 °C under weak sunlight (350 W m−2). More importantly, such a superior radiative warming performance is achieved by engineering the widely used cotton without compromising its breathability and durability, showing great potential for practical applications.
High‐entropy engineering is adapted to the design of high‐efficiency solar warming textile. The high‐entropy coating offers both roughness‐insensitive high solar absorption and low IR emissivity even coated on cotton. The coating is prepared by a facile one‐step sputtering method, yielding outstanding adhesion and anti‐oxidation properties. All these merits make it suitable for solar and radiative warming without compromising its wearability.
Reduction of expression and activity of sirtuin 3 (SIRT3) contributes to the pathogenesis of cardiomyopathy via inducing mitochondrial injury and energy metabolism disorder. However, development of ...effective ways and agents to modulate SIRT3 remains a big challenge. In this study we explored the upstream suppressor of SIRT3 in angiotensin II (Ang II)-induced cardiac hypertrophy in mice. We first found that SIRT3 deficiency exacerbated Ang II-induced cardiac hypertrophy, and resulted in the development of spontaneous heart failure. Since miRNAs play crucial roles in the pathogenesis of cardiac hypertrophy, we performed miRNA sequencing on myocardium tissues from Ang II-infused Sirt3
and wild type mice, and identified microRNA-214 (miR-214) was significantly up-regulated in Ang II-infused mice. Similar results were also obtained in Ang II-treated neonatal mouse cardiomyocytes (NMCMs). Using dual-luciferase reporter assay we demonstrated that SIRT3 was a direct target of miR-214. Overexpression of miR-214 in vitro and in vivo decreased the expression of SIRT3, which resulted in extensive mitochondrial damages, thereby facilitating the onset of hypertrophy. In contrast, knockdown of miR-214 counteracted Ang II-induced detrimental effects via restoring SIRT3, and ameliorated mitochondrial morphology and respiratory activity. Collectively, these results demonstrate that miR-214 participates in Ang II-induced cardiac hypertrophy by directly suppressing SIRT3, and subsequently leading to mitochondrial malfunction, suggesting the potential of miR-214 as a promising intervention target for antihypertrophic therapy.
Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers, including both hematological and solid tumors. However, the serious cardiotoxic effect restricted its clinical ...application. We previously have illuminated the protective role of canonical Wnt/β-catenin signaling in Dox-induced cardiotoxicity. Secreted frizzled-related protein 1 (sFRP1) is one of the endogenous inhibitors of both canonical and noncanonical Wnt signaling. In this study, we investigated the relationship between sFRP1 and noncanonical Wnt/PCP-JNK (Wnt/planar cell polarity-c-Jun N-terminal kinase) pathway in Dox-induced cardiotoxicity in vitro and in vivo. We showed that treatment of H9c2 cardiac myoblasts with Dox (1 μM) time-dependently suppressed cell viability accompanied by significantly decreased sFRP1 protein level and increased Wnt/PCP-JNK signaling. Pretreatment with SP600125, the Wnt/PCP-JNK signaling inhibitor, attenuated Dox-induced apoptosis of H9c2 cells. Overexpression of sFRP1 protected H9c2 cells from Dox-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway. After intraperitoneal injection of a cumulative dose of 15 mg/kg Dox, rats displayed significant cardiac dysfunction; their heart showed inhibited Wnt/β-catenin signaling and activated Wnt/PCP-JNK signaling. These results suggest that sFRP1 may be a novel target for Dox-induced cardiotoxicity.
Hydrocarbon CO2-philes are of great interest for use in expanding CO2 applications as a green solvent. In this work, multiscale molecular modeling and dissolution behavior measurement were both ...applied to explore CO2-philicity of the poly(vinyl acetate) (PVAc)-based copolymer. Introduction of a favorable comonomer, i.e., vinyl ethyl ether (VEE), could significantly reduce the polymer–polymer interaction on the premise that the polymer–CO2 interaction was not weakened but enhanced. The ab initio calculated interaction of the model molecules with CO2 demonstrated that the ether group in VEE or VBE was the suitable CO2-philic segment. From the molecular dynamics (MD) simulations of polymer/CO2 systems, the interaction energy and Flory–Huggins parameter (χ12) of poly(VAc-alt-VEE)/CO2 supported that poly(VAc-alt-VEE) possessed better CO2-philicity than PVAc. The dissolution behaviors of the synthesized poly(VAc-co-alkyl vinyl ether) copolymers in CO2 showed the best CO2-phile had the VEE content of about 34 mol %. The MD simulations also indicated that the interaction of random poly(VAc-co-VEE) containing about 30 mol % VEE with CO2 was the strongest and the χ12 was the smallest in these polymer/CO2 systems. Not only could the VEE monomer reduce the polymer–polymer interaction, but it could also enhance the polymer–CO2 interaction with an optimized composition. Introducing a suitable comonomer with a certain composition might be a promising strategy to form the synergistic effect of polymer–polymer interaction and polymer–CO2 interaction for screening the hydrocarbon CO2-philes.
Recent advances in high-entropy ceramic nanofilms have unlocked new possibilities for preparing high-performance solar-thermal conversion materials. Due to their species diversity and structure ...distinctiveness, these materials provide huge room to exploit more appropriate compositions for boosting solar-thermal performance. Herein, we report a spectrally selective absorber based on high-entropy ZrNbMo-Cr-N ceramic nanofilm prepared by magnetron co-sputtering. Enabled by interface interference and intrinsic absorption effects, the as-deposited absorber exhibits a high solar absorptance of 96.3%, suppressed thermal emittance of 18.8%@400 ºС, and solar-thermal conversion efficiency of 85.4% under 400 ºС and 100 suns. Besides, due to the high configuration entropy of the absorption layers, the absorber exhibits superior thermal robustness after annealing at 400 ºС for 7 days. Further, the absorber can be well deposited on various substrates, including flexible cotton. Radiated by simulated sunlight, those absorber shows a good temperature response; in particular, the surface temperature of the absorber on cotton readily increases to 80 ºС with 50 s under 1 sun. Featured with those competitive merits, the high-entropy ceramic nanofilm absorber empowers a distinct paradigm to investigate solar-thermal conversion, rendering it attractive for various solar-thermal applications.
•The well-designed ZrNbMo-Cr-N HECN SSA embraces a high solar absorptance of 96.3% and low thermal emittance of 18.8%@400 ºС as well as a direction-independent absorption.•The ZrNbMo-Cr-N SSA shows superior thermal robustness, no significant optical performance attenuation is observed even after annealing at 800 °C for 2 h, which is capable of diverse temperature solar-thermal applications.•FDTD simulation proves that the collective effects of destructive interference and intrinsic absorption of ZrNbMo-Cr-N HECN boost sunlight harvesting ability.•Upon 1.5 sun (1.5 kW m−2) irradiation, the high surface temperature of more than 100 °C is captured, suggesting great potential in solar interface evaporation-related applications.
This study investigated the influence of
extract (CAext) on intestinal microbiota composition of mice fed a high-fat diet (HFD). Kun Ming (KM) mice were fed either a normal chow diet or a HFD for six ...weeks. At the seventh week, HFD-fed mice were gavaged daily with saline, or a different dose of CAext for four weeks, respectively. Then, the composition of the gut microbiota was analyzed by high-throughput sequencing technology. Analysis of fecal microbial populations, grouped by phyla, showed significant increases of
and
, but a decrease of
in all CAext-fed mice. Particularly, CAext gavage in a low dose or a medium dose caused a significant increase in the proportion of
. These findings suggested that CAext can alter the gut microbiota composition of HFD-fed mice, and had a potential prebiotic effects on
.
Stacked graphene (GE) membranes with cascading nanoslits can be synthesized economically compared to monolayer nanoporous GE membranes, and have potential for molecular separation. This study focuses ...on investigating the seawater desalination performance of these stacked GE layers as forward osmosis (FO) membranes by using molecular dynamics simulations. The FO performance is evaluated in terms of water flux and salt rejection and is explained by analysing the water density distribution and radial distribution function. The water flow displays an Arrhenius type relation with temperature and the activation energy for the stacked GE membrane is estimated to be 8.02 kJ mol
−1
, a value much lower than that of commercially available FO membranes. The study reveals that the membrane characteristics including the pore width, offset, interlayer separation distance and number of layers have significant effects on the desalination performance. Unlike monolayer nanoporous GE membranes, at an optimum layer separation distance, the stacked GE membranes with large pore widths and completely misaligned pore configuration can retain complete ion rejection and maintain a high water flux. Findings from the present study are helpful in developing GE-based membranes for seawater desalination
via
FO.
A slit-pore stacked graphene membrane shows promising forward osmosis performance with high water flux and ion rejection.
Background and purpose
Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus ...DBS (STN‐DBS) on motor and non‐motor symptoms in patients with primary Meige syndrome.
Methods
Thirty patients who underwent bilateral STN‐DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health‐related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation.
Results
The Burke−Fahn−Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke−Fahn−Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow‐up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported.
Conclusions
Bilateral STN‐DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.
Inspired by the clinically approved albumin based PTX formulation (Abraxane) and high-drug-loading dimeric prodrug tactics, herein we report a theranostic “Abraxane-like” prodrug formulation, which ...is comprised of human serum albumin (HSA), a paclitaxel (PTX) dimer bridged with thioether liner (PTX
2
-S), and photosensitizer IR780 iodide. Nanoparticles (NPs) with PTX
2
-S and IR780 as the core and HSA as the stealth shell are formed. Compared with HSA-based PTX clinical formulation (Abraxane), the dimeric molecules not only constitute the bulk structure of the particles, but also act as crossing agent, thus realizing drug loading content increasing from 6.6 wt.% to 48.7 wt.% with high loading efficiency (> 90%) and excellent stability in biological conditions. Importantly, the thioether linkage dually responds to the tumor redox heterogeneity and the NPs gradually releases the parent drug PTX for chemotherapy. Meanwhile, PTX
2
-S facilitates the encapsulation of IR780 iodide due to their π-π stacking interaction and IR780 iodide generates spatio-temporal hyperthermia under light irradiation to kill cancer cells for photothermal therapy. The described craft integrates the biomimetic trait of HSA, high drug loading, tumor redox heterogeneity-initiated on-demand drug release, and combination therapy into one formulation and the developed nanoparticles are promising for cancer treatment.
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