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1.
Artigo em Inglês | MEDLINE | ID: mdl-34981548

RESUMO

PURPOSE: To determine the effect of low-intensity, long-wavelength red light therapy (LLRT) on the inhibition of myopia progression in children. METHODS: A retrospective study was conducted. One hundred and five myopic children (spherical equivalent refractive error [SER] -3.09 ± 1.74 dioptres [D]; mean age, 9.19 ± 2.40 years) who underwent LLRT treatment (power 0.4 mW, wavelength 635 nm) twice per day for 3 min each session, with at least a 4-h interval between sessions, and a control group of 56 myopic children (SER -3.04 ± 1.66 D; mean age, 8.62 ± 2.45 years) were evaluated. Both groups wore single-vision distance spectacles. Each child returned for a follow-up examination every 3 months after the initial measurements for a total of 9 months. RESULTS: At 9 months, the mean SER in the LLRT group was -2.87 ± 1.89 D, significantly greater than that of the control group (-3.57 ± 1.49 D, p < 0.001). Axial length (AL) changes were -0.06 ± 0.19 mm and 0.26 ± 0.15 mm in the LLRT group and control group (p < 0.001), respectively. The subfoveal choroidal thickness changed by 45.32 ± 30.88 µm for children treated with LLRT at the 9-month examination (p < 0.001). Specifically, a substantial hyperopic shift (0.31 ± 0.24 D and 0.20 ± 0.14 D, respectively, p = 0.02) was found in the 8-14 year olds compared with 4-7 year old children. The decrease in AL in subjects with baseline AL >24 mm was -0.08 ± 0.19 mm, significantly greater than those with a baseline AL ≤24 mm (-0.04 ± 0.18 mm, p = 0.03). CONCLUSIONS: Repetitive exposure to LLRT therapy was associated with slower myopia progression and reduced axial growth after short durations of treatment. These results require further validation in randomised controlled trials.

2.
DNA Cell Biol ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981960

RESUMO

A large variety of long noncoding RNAs (lncRNAs) have been discovered through high-throughput sequencing technology and some have been demonstrated to play important roles in lipid metabolism regulation. In our study, we found a highly expressed lncRNA (lnc-LLMA, liver lipid metabolism-associated lncRNA) in the liver of Duroc pigs, which was enriched in the nucleus. It displays potent tissue specificity among different pig breeds. Overexpression of lnc-LLMA can cause a decline in intracellular triglyceride (TG) levels and increases in ATP and mitochondrial DNA levels in pig primary hepatocytes and HepG2 cells. In addition, the expression levels of MTTP, APOB, CPT1α, and other genes were increased by overexpression of lnc-LLMA. It downregulated expression of G6Pase and SREBP1 genes. Chromatin isolation by RNA purification (ChRIP) experiments demonstrated that microsomal triglyceride transfer protein (MTTP) and glycogen synthase 2 (GYS2) were the potential interacting proteins of lnc-LLMA. The overexpression of the GYS2 gene rescued the decreasing intracellular TG levels caused by the increase of lnc-LLMA. Similarly, overexpression of MTTP was also able to save the lnc-LLMA-induced decrease in intracellular TG. Our study demonstrated that this novel lncRNA was closely related to lipid metabolism and affected lipid transport and mitochondrial function through MTTP and GYS2. Our results provided a new direction for further studying the effect of lncRNA on lipid metabolism regulation.

3.
ACS Nano ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040625

RESUMO

External-stimuli-driven soft actuators overcome several limitations inherent in traditional mechanical-driven technology considering the coming age of flexible robots, which might face harsh working conditions and rigorous multifunctional requirements. However, how to achieve multi-external-stimuli response, fast speed, and precise control of the position and angle of the actuator, especially working in a toxic liquid or vapor environment, still requires long-term efforts. Here, we report a multi-external-stimuli-driven sandwich actuator with aligned carbon nanotubes as the constructive subject, which can respond to various types of liquids (organic solvents), vapor, and solar light. The actuator has an ultrafast response speed (<10 ms) and can accurately adjust the bending angle range from 0° to 180°. Through manipulating the stimuli positions, actuators can be wound into varied turns when simulating a flexible robotic arm. Hence, liquid/vapor/light-driven actuators are able to support diverse programmable motions, such as periodic blooming, gesture variations, caterpillar crawling, toxic surface evading, and bionic phototaxis. We believe that this multifunctional actuator is promising in supporting a complex scenario to complete a variety of tasks in the fields of healthcare, bioengineering, chip technology, and mobile sensors.

4.
Phytochemistry ; 196: 113077, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34990976

RESUMO

A total of twelve highly oxygenated isoryanodane (also known as cinncassiol D-type) diterpenoids including nine undescribed ones, named cinnacassins A-I, were isolated from the leaves of Cinnamomum cassia. Their chemical structures were elucidated by extensive spectrometric and spectroscopic techniques including HRESIMS, 1D and 2D NMR, single-crystal X-ray diffraction analysis, calculated 13C-NMR DP4+ analysis, and chemical methods. The absolute configuration of cinnacassin A was unambiguously delineated by single-crystal X-ray diffraction analysis. Cinnacassin H represents the first example of 16-O-glucosylated isoryanodane diterpenoid, and cinnacassin I is the first isoryanod-13(18)-ene diterpenoid. The relationship of the configuration C-18 and the chemical shifts of H2-19 and C-20 in the 19-hydroxy-isoryanodane diterpenoids was discussed, and the 18S-configuration of three known 19-hydroxy-isoryanodane diterpenoids, cinncassiol D1, 19-O-ß-D-glucopyranosyl-cinncassiol D1, and cinncassiol D3 was assigned. All the isolated isoryanodane diterpenoids were evaluated for their immunomodulatory effects in vitro, and cinnacassin A and cinncassiol D1 enhanced the proliferation of Con A-induced murine T cells with enhancement rates ranging from 17.9% to 45.4%, which were more potent than the positive control, thymosin α1. In addition, cinncassiol D1 significantly promoted the proliferation of LPS-induced murine B cells with an enhancement rate up to 116.1%, two-fold more potent than thymosin α1 at a concentration of 1.5625 µM.

5.
Environ Pollut ; 295: 118714, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34942291

RESUMO

The objective of this work was to evaluate the adsorption capacity of alkylated modified porous biochar prepared by esterification and etherification (PSAC-2) for low concentrate volatile organic compounds (VOCs, toluene and ethyl acetate) in high humidity environment by experiments and theoretical calculations. Results showed that PSAC-2 has a large specific surface area and weak surface polarity, at 80% relative humidity, its capacities for toluene and ethyl acetate adsorption could be maintained at 92% and 87% of the initial capacities (169.9 mg/g and 96.77 mg/g). The adsorption behaviors of toluene, ethyl acetate, and water vapor were studied by adsorption isotherms, and isosteric heat was obtained. The desorption activation energy was obtained by temperature programmed desorption experiment. The outcomes manifested that the PSAC-2 can achieve strong adsorption performance for weakly polar molecules. Through density functional theory (DFT) simulations, owing to the interaction of hydrogen bonds, oxygen-containing groups became a significant factor influencing the adsorption of VOCs in humid environments. These results could provide an important reference for VOCs control in a high humidity environment.


Assuntos
Pistacia , Compostos Orgânicos Voláteis , Adsorção , Alquilação , Carvão Vegetal , Umidade
6.
J Colloid Interface Sci ; 608(Pt 1): 90-102, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626999

RESUMO

Defect engineering through induction of dislocations is an efficient strategy to design and develop an electrode material with enhanced electrochemical performance in energy storage technology. Yet, synthesis, comprehension, identification, and effect of dislocation in electrode materials for lithium-ion batteries (LIBs) are still elusive. Herein, we propose an ethanol-thermal method mediated with surfactant-template and subsequent annealing under air atmosphere to induce dislocation into titanium niobium oxide (Ti2Nb14O39), resultant nanoscale-dislocated-Ti2Nb14O39 (Nano-dl-TNO). High-resolution transmission electron microscope (HRTEM), fast Fourier transform (FFT), and Geometrical phase analysis (GPA) denote that the high dislocation density engraved with stacking faults forms into the Ti2Nb14O39 lattice. The presence of dislocation could offer an additional active site for lithium-ion storage and tune the electrical and ionic properties of the Ti2Nb14O39. The resultant Nano-dl-TNO delivers superior rate capability, high specific capacity, better cycling stability, and making Ti2Nb14O39 a suitable candidate among fast-charging anode materials for lithium-ion batteries. Moreover, In-situ High-resolution transmission electron microscope (HRTEM) and Geometrical phase analysis (GPA) evinces that the removal of the dislocated area in the Nano-dl-TNO leads to the contraction of the lattice, alleviation of the total volume expansion, causing the symmetrization and preserves structural stability. The present findings and designed approach reveal the rose-colored perspective of dislocation engineering into mixed transition metal oxides as next-generation anodes for advanced lithium-ion batteries and all-solid-state lithium-ion batteries.

7.
Sci Total Environ ; 810: 152263, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896510

RESUMO

Estuaries are resistome hotspots owing to resistome accumulation and propagation at these locations from surrounding rivers, yet the large-scale biogeographic pattern of resistome, especially biocide and metal resistance genes (BMRGs) and its driving mechanisms in estuarine waters remains to be elucidated. Here, a metagenomics-based approach was firstly used to investigate resistome and mobilome profiles in waters from 30 subtropical estuaries, South China. The Pearl River estuaries had a higher diversity and abundance of antibiotic resistance genes (ARGs), BMRGs, and mobile genetic elements (MGEs) when compared with estuaries from east and west regions. Genes resistant to multiple antibiotics, metals, and biocides were the most abundant gene types in the resistome. The abundance of MGEs (e.g., intI1, IS91, and tnpA) was highly associated with the total abundance of resistance genes, suggesting their utility as potential indicators for quantitative estimations of the resistome contamination. Further, MGEs contributed more than bacterial communities in shaping the resistome in subtropical estuaries. Physicochemical factors (e.g., pH) regulated MGE composition and stochastic assembly, which mediated the co-selection of ARGs and BMRGs via horizontal gene transfer. Our findings have important implications and provide a reference on the management of ARGs and BMRGs in subtropical estuarine ecosystems.

8.
Bioact Mater ; 7: 98-111, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34466720

RESUMO

Injectable biomaterial-based treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury (SCI) by bridging cavity spaces. However, there are limited reports of injectable, electroconductive hydrogels with self-healing properties being employed for the treatment of traumatic SCI. Hence, a natural extracellular matrix (ECM) biopolymer (chondroitin sulphate and gelatin)-based hydrogel containing polypyrrole, which imparted electroconductive properties, is developed for traumatic SCI repair. The resulting hydrogels showed mechanical (~928 Pa) and conductive properties (4.49 mS/cm) similar to natural spinal cord tissues. Moreover, the hydrogels exhibited shear-thinning and self-healing abilities, which allows it to be effectively injected into the injury site and to fill the lesion cavity to accelerate the tissue repair of traumatic SCI. In vitro, electroconductive ECM hydrogels promoted neuronal differentiation, enhanced axon outgrowth, and inhibited astrocyte differentiation. The electroconductive ECM hydrogel activated endogenous neural stem cell neurogenesis in vivo (n = 6), and induced myelinated axon regeneration into the lesion site via activation of the PI3K/AKT and MEK/ERK pathways, thereby achieving significant locomotor function restoration in rats with spinal cord injury (p < 0.001, compared to SCI group). Overall, the injectable self-healing electroconductive ECM-based hydrogels developed in this study are ideal biomaterials for treatment of traumatic SCI.

9.
Bioact Mater ; 7: 333-340, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34466736

RESUMO

The treatment of malignant bone tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment, and thus calls for the development of new therapeutic options. Here, we reported a bone-targeted protein nanomedicine for this purpose. Saporin, a toxin protein, was co-assembled with a boronated polymer for intracellular protein delivery, and the formed nanoparticles were further coated with an anionic polymer poly (aspartic acid) to shield the positive charges on nanoparticles and provide the bone targeting function. The prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo, and could reverse the surface charge property from negative to positive after locating at tumor site triggered by tumor extracellular acidity. The boronated polymer in the de-shielded nanoparticles further promote intracellular delivery of saporin into tumor cells, exerting the anticancer activity of saporin by inactivation of ribosomes. As a result, the bone-targeted and saporin-loaded nanomedicine could kill cancer cells at a low saporin dose, and efficiently prevented the progression of osteosarcoma xenograft tumors and bone metastatic breast cancer in vivo. This study provides a facile and promising strategy to develop protein-based nanomedicines for the treatment of malignant bone tumors.

10.
Environ Pollut ; 294: 118655, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896220

RESUMO

As a promising amendment, biochar has excellent characteristics and can be used as a remediation agent for diverse types of soil pollution. Biochar is mostly made from agricultural wastes, forestry wastes, and biosolids (eg, sewage sludge), but not all the biochar has the same performance in the improvement of soil quality. There is a lack of guidelines devoted to the selection of biochar to be used for different types of soil pollution, and this can undermine the remediation efficiency. To shed light on this sensitive issue, this review focus on the following aspects, (i) how feedstocks affect biochar properties, (ii) the effects of biochar on heavy metals and organic pollutants in soil, and (iii) the impact on greenhouse gas emissions from soil. Generally, the biochars produced from crop residue and woody biomass which are composed of lignin, cellulose, and hemicellulose are more suitable for organic pollution remediation and greenhouse gas emission reduction, while biochar with high ash content are more suitable for cationic organic pollutant and heavy metal pollution (manure and sludge, etc.). Additionally, the effect of biochar on soil microorganisms shows that gram-negative bacteria in soil tend to use WB biochar with high lignin content, while biochar from OW (rich in P, K, Mg, and other nutrients) is more able to promote enzyme activity. Finally, our recommendations on feedstocks selection are presented in the form of a flow diagram, which is precisely intended to be used as a support for decisions on the crucial proportioning conditions to be selected for the preparation of biochar having specific properties and to maximize its efficiency in pollution control.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Carvão Vegetal , Metais Pesados/análise , Solo , Poluentes do Solo/análise
11.
Ann N Y Acad Sci ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850398

RESUMO

The test for the cancer stem cell (CSC) hypothesis is to find a target expressed on all, and only CSCs in a patient tumor, then eliminate all cells with that target that eliminates the cancer. That test has not yet been achieved, but CSC diagnostics and targets found on CSCs and some other cells have resulted in a few clinically relevant therapies. However, it has become apparent that eliminating the subset of tumor cells characterized by self-renewal properties is essential for long-term tumor control. CSCs are able to regenerate and initiate tumor growth, recapitulating the heterogeneity present in the tumor before treatment. As great progress has been made in identifying and elucidating the biology of CSCs as well as their interactions with the tumor microenvironment, the time seems ripe for novel therapeutic strategies that target CSCs to find clinical applicability. On May 19-21, 2021, researchers in cancer stem cells met virtually for the Keystone eSymposium "Cancer Stem Cells: Advances in Biology and Clinical Translation" to discuss recent advances in the understanding of CSCs as well as clinical efforts to target these populations.

12.
Front Pharmacol ; 12: 764191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867388

RESUMO

Three type III secretion system (T3SS) inhibitors (compounds 5, 19, and 32) were identified by virtual screening and biological evaluation. These three compounds were evaluated against a panel of Salmonella species strains including S. enteritidis, S. typhi, S. typhimurium, S. paratyphi, and S. abortus equi, and their minimum inhibitory concentrations ranged from 1 to 53 µg/ml. Especially, these compounds showed comparable activity as the of the positive control gatifloxacin towards S. abortus equi. The present results suggest that these new T3SS inhibitors could be used as a potential lead molecule for drug development of anti-Salmonella.

13.
Front Nutr ; 8: 751405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869525

RESUMO

Galangal essential oil is obtained from the rhizomes of galangal with proven anti-inflammatory, antioxidant, antiviral, and antimicrobial properties, which are valuable in the food industry. To explore the effect of galangal essential oil on the quality of pineapple juice, 0.05, 0.1, 0.2, and 0.4% galangal essential emulsion were added, and their influence on the physical stability, physicochemical properties, microbial quantity, and aroma profiles of cloudy pineapple juice were evaluated. The essential oil emulsion of galangal is a milky white liquid with a strong aroma of galangal. The pH values of emulsion increased from 4.35 to 5.05 with the increase in essential oil concentration, and there was no significant difference in the particle size of the pineapple juice. The results showed that the galangal essential oil emulsion was stable and the stability of the cloudy pineapple juice was significantly enhanced by the essential oil emulsion determined using LUMiSizer. The cloudy pineapple juice with a 0.2% essential oil emulsion showed the most stability during storage. The lightness of the cloudy pineapple juice increased instantly with the essential oil emulsion addition. In addition, the microbial quantity of the cloudy pineapple juice was decreased by the individual essential oil emulsion or combined with thermal treatment to hold a longer shelf life. The microbial counts in pineapple juice treated by 0.4% essential oil emulsion and thermal treatment only increased from 1.06 to 1.59 log CFU/ml after 4 days of storage at 25°C. Additionally, the pH and total soluble solids showed a slightly increasing trend; however, the value of titratable acidity, free radical scavenging capacity, and ascorbic acid content of the cloudy pineapple juice showed no significant change. Finally, the results of the electronic nose showed that the aroma components of the pineapple juice were changed by the essential oil emulsion and thermal treatment, and the difference was especially evident in the content of the sulfur, sulfur organic, and aromatics compounds. Consequently, the results indicated that galangal essential oil emulsion can be used as juice additives to improve the quality attributes and extend the shelf-life of cloudy pineapple juice.

15.
Front Neurol ; 12: 790941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880829

RESUMO

Introduction: The phenomenon of coexisting autoimmune diseases (ADs) in patients with myasthenia gravis (MG) has attracted considerable attention. However, few studies have investigated the burden and potential clinical associations of ADs in Chinese MG cohorts. Methods: In this retrospective cross-sectional study, we reviewed the records of 1,132 patients with MG who were admitted to Huashan Hospital Fudan University from August 2013 to August 2020. Patients were excluded if they had incomplete medical records (n = 336). Results: Comorbid ADs were found in 92 of 796 Chinese patients with MG (11.6%), among which, hyperthyroidism (6.7%), hypothyrosis (2.6%), and vitiligo (0.8%) were predominant. Patients with MG with ADs were predominantly female, younger at the onset of MG symptoms, and had a lower frequency of thymoma. Compared to the general population, we found a significantly higher percentage of hyperthyroidism (8.5-fold increase, p < 0.001), hypothyrosis (2.6-fold increase, p < 0.001), vitiligo (1.3-fold increase, p < 0.001), rheumatoid arthritis (1.4-fold increase, p < 0.001), immune thrombocytopenic purpura (193.1-fold increase, p < 0.001), autoimmune hemolytic anemia (7.4-fold increase, p < 0.001), autoimmune hepatitis (5.1-fold increase, p < 0.001), and polymyositis (11.5-fold increase, p < 0.001) in patients with MG with ADs. Patients with MG with ADs presented a lower proportion of previous history of MC (0 vs. 5.6%, p < 0.05) than those without ADs. The proportion of MGFA Class I at onset in patients with MG with ADs was significantly higher than that in patients with MG without ADs (77.0 vs. 52.7%, p < 0.05). The proportion of MuSK-positive in patients with MG with ADs was significantly lower than that in patients with MG without ADs (0 vs. 4.8%, p < 0.05). Conclusion: In conclusion, we observed a higher frequency of concurrent ADs in a Chinese MG cohort. Furthermore, MG combined with ADs tended to have mild clinical presentation.

16.
J Hazard Mater ; 425: 127949, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34883372

RESUMO

Series of B-doped perovskite-like materials CeCu0.5Co0.5O3 (B-C3O) were fabricated with unique ferromagnetic property due to partial substitution of non-magnetic 2p-impurities boron in the lattice. Then, B-C3O was used for activating peroxymonosulfate (PMS) for the degradation of norfloxacin (NOR), one kind of emerging pollutants with the concentration level up to mg/L in wastewaters. The results indicated that 5.0% B-C3O exhibited stable catalytic ability at pH 3.0-9.0 and high degradation efficiency in co-existing inorganic Cl-, SO42-, NO3-, H2PO4- and organic humic acid. Non-radical 1O2, radicals •OH and SO4•-, as well as ClO- were detected with synergy effect for NOR degradation. By quantifying free radicals, •OH with 0.52 µM and SO4•- with 10.91 µM were obtained at 180 min, verifying the leading role of SO4•-. The degradation process involved the defluorination and decarboxylation, as well as opening of quinolone and piperazinyl rings. Adopting alfalfa as the model plant, the toxicity effect before and after NOR degradation was finally evaluated with seed germination rate and chlorophyll content as the physiological indicators. In summary, non-metal B-doping not only provides a creative strategy for the development of ferromagnetic perovskite-like materials, but also affords excellent catalysts for aiding the advanced oxidation technology for removal of emerging pollutants in wastewaters.

17.
ACS Sens ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34886660

RESUMO

Neuroblastoma is a metastatic tumor almost exclusively plaguing young children. To provide an early warning for timely medical interference that may prevent such tragedies from happening, we mimic the biomolecular pathology of this disease and have obtained an assay without using costly biomolecules such as antibodies and enzymes but can still sensitively detect trace level metal ions and metastatic marker proteins in the cerebrospinal fluid of neuroblastoma-bearing children in a one-step and reagentless fashion. Specifically, a surface-tethered "open bridge"-like molecular machine is designed. This probe, after interacting with cupric ions, can form an electrochemically active peroxidase-like artificial enzyme. Its activity first opens the probe, freeing the Bcl-2-targeting sequence of the probe to adopt the most favorable conformation, forming a noncovalent complex with Bcl-2. Then, the peroxidase-like activity of the probe induces the formation a robust fluorescence covalent linkage with the target protein. This fluorescence and electrochemical dual detection allows an analytical performance not inferior to the commercially available methods, pointing to possible clinical application in the early screening of pediatric metastatic conditions in the near future.

18.
Avian Pathol ; : 1-23, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859725

RESUMO

ABSTRACTNumerous studies have shown that viruses can utilize or manipulate ribosomal proteins to achieve viral protein biosynthesis and replication. In our recent studies using proteomics analysis of virus-infected cells, we found that ribosomal protein L18 (RPL18) was the highest up-regulated differentially expressed protein, which was along with the increasingly expressed viral proteins later in Newcastle disease virus (NDV) infection. However, the association of RPL18 with viral protein biosynthesis and NDV replication remains unclear. In this study, we found that the expression and transcription levels of RPL18 was reduced early in NDV infection but increased later in NDV infection. In addition, the presence of cytoplasmic NDV matrix (M) protein was responsible for the increased expression of RPL18 in both virus-infected cells and plasmid-transfected cells. Moreover, cytoplasmic M protein increased RPL18 expression in a dose-dependent manner, even though they did not interact with each other. Furthermore, siRNA-mediated knockdown of RPL18 or overexpression of RPL18 dramatically reduced or enhanced NDV replication by decreasing or increasing viral protein translation rather than viral RNA synthesis and transcription. Taken together, these results suggested that the increased expression of RPL18 might be associated with the physical clumping together of the M protein, which in turn promoted viral protein biosynthesis and NDV replication, thus revealing for the first time the association of RPL18 with NDV M protein was important for viral translation and replication.

19.
Br J Pharmacol ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862596

RESUMO

BACKGROUND AND PURPOSE: Nonalcoholic fatty liver disease (NAFLD) affects over 25% of the general population and lacks an effective treatment. Recent evidence implicates disrupted mitochondrial calcium homeostasis in the pathogenesis of hepatic steatosis. EXPERIMENTAL APPROACH: In this study, mitochondrial calcium uniporter (MCU) was inhibited through classical genetic approaches, viral vectors or small molecule inhibitors in vivo to study its role in hepatic steatosis induced by HFD. In vitro, MCU was overexpressed or inhibited to change mitochondrial calcium homeostasis; endoplasmic reticulum-mitochondrial linker was adopted to increase mitochondria-associated membranes (MAM); and MICU1-EF hand mutant was used to decrease the sensitivity of mitochondrial calcium uptake 1 (MICU1) to calcium and block MCU channel. KEY RESULTS: Here we found that inhibition of liver MCU by AAV virus and classical genetic approaches can alleviate HFD-induced liver steatosis. MCU regulates mitochondrial calcium homeostasis and affects lipid accumulation in liver cells. In addition, a HFD in mice enlarged the MAM. The high calcium environment produced by MAM invalidated the function of MICU1 and led to persistent open of MCU channels. Therefore, it caused mitochondrial calcium overload and liver fat deposition. Inhibition of MAM and MCU alleviated HFD-induced hepatic steatosis. MCU inhibitors (Ru360 and mitoxantrone) can block MCU channels and reduce mitochondrial calcium levels. Intraperitoneal injection of MCU inhibitors (0.01 µM/kg bodyweight) can alleviate HFD-induced hepatic steatosis. CONCLUSION AND IMPLICATIONS: These findings provide molecular insights into the way HFD disrupts mitochondrial calcium homeostasis and identified MCU as a promising drug target for the treatment of hepatic steatosis.

20.
Sci Total Environ ; 808: 152098, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34863764

RESUMO

Polystyrene nanoplastics (PS-NPs) can impair antioxidant, immune, and nervous system functions as well as growth and development in aquatic organisms. At present, however, little is known about the effects and underlying mechanisms of PS-NPs on the digestive system of marine fish. Here, we studied the effects of these plastics on the intestinal health and growth performance of juvenile orange-spotted groupers (Epinephelus coioides). Based on histopathological analysis, we found that the liver and intestines can uptake PS-NPs at exposure concentrations of 300 and 3000 µg/ml, respectively. After 14 d of exposure, the activities of digestive enzymes lipase (LPS), trypsin (TRS), and lysozyme (LZM) were reduced, indicating that PS-NPs negatively affected digestive function in juvenile groupers. The PS-NPs also altered microbial community composition, resulting in a decrease in diversity and simplification of network relationships in the intestinal microbiota, but a significant increase in certain harmful bacteria, especially Vibrio and Aliivibrio. In addition, community assembly changed from being driven primarily by deterministic processes (68.89% for control group) to stochastic processes (73.33% and 51.11% for 300 and 3000 µg/ml PS-NP exposure groups, respectively). Furthermore, the specific growth rate (SGR) of the juvenile orange-spotted groupers decreased significantly with increasing PS-NP exposure concentrations (0.158% ± 0.032%, 0.095% ± 0.020%, and 0.074% ± 0.016% for 0, 300, and 3000 µg/L PS-NP groups, respectively). These results suggest that marine PS-NPs are harmful to the digestive system of juvenile fish and highlight the importance of evaluating the long-term impact of NPs in reshaping marine populations.

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