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1.
J Affect Disord ; 296: 189-197, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34607060

RESUMEN

BACKGROUND: The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. METHODS: Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. RESULTS: Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%-1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%-57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. LIMITATIONS: The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. CONCLUSIONS: Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

2.
Mol Med Rep ; 25(1)2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34779493

RESUMEN

To investigate the role of NEAT1 and the microRNA (miR)­377/fibroblast growth factor receptor 1 (FGFR1) axis in cervical cancer (CC), the expression levels of NEAT1, FGFR1 and miR­377 were detected in CC tissues and cell lines. NEAT1 or FGFR1 was knocked down by transfection with short hairpin RNA (sh)­NEAT1 or sh­FGFR1, and miR­377 was overexpressed by transfection with miR­377 mimics in HeLa and C33A cells. Cell viability and migration were measured using MTT and Transwell assays, respectively. Cell apoptosis was determined by flow cytometry. A dual luciferase reporter assay was performed to confirm the presence of binding sites between miR­377 and FGFR1. The results revealed that the expression levels of NEAT1 and FGFR1 were significantly elevated, whereas miR­377 expression was markedly decreased in CC tissues and cell lines. In HeLa and C33A cells, after NEAT1 knockdown, miR­377 expression was increased, cell viability and migration were inhibited, and apoptosis was induced. Similarly, silencing FGFR1 inhibited cell viability and migration, and induced apoptosis of HeLa and C33A cells. A dual luciferase reporter gene assay verified a targeting relationship between NEAT1 and miR­377. Inhibition of miR­377 or overexpression of FGFR1 reversed the effects of NEAT1 knockdown on cell function in HeLa and C33A cells. Moreover, a dual luciferase reporter assay confirmed that FGFR1 was a direct target of miR­377. In conclusion, suppression of NEAT1 inhibited cell viability and migration, and promoted apoptosis of CC cells, and these effects were achieved through regulation of the miR­377/FGFR1 axis.

3.
J Colloid Interface Sci ; 605: 624-636, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34352443

RESUMEN

A 3D α-MoO3 nanostructure for high-performance triethylamine (TEA) detection was synthesized via the facial oxidation of MoS2 nanoflowers (NFs) obtained by a hydrothermal process. The influence of the time of hydrothermal process in growing MoS2 on the morphologies of the final MoO3 obtained after calcination was investigated. As-obtained MoO3 and their precursors were systematically characterized by various techniques, such as X-ray diffraction, Raman, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and N2 adsorption-desorption isotherms. Results showed that MoO3 with a hierarchical layered nanostructure was successfully obtained. After hydrothermal treatment of the MoS2 precursor for 20 h, the typical MoO3-based sensor (called M20) exhibited a high response of 2.42 at a very low TEA concentration of only 0.1 ppm at 240 °C. The M20 sensor response to 50 ppm TEA was as high as 125 with a fast response/recovery time of 14/22 s. Moreover, the sensor had a high stability and reproducibility as well as a high selectivity against other interfering VOCs or gases. Due to the tendency of TEA to adsorb to active oxygen sites of MoO3, the enhanced sensing properties of MoO3 can be ascribed to the remarkable hierarchical structure and large surface area. MoO3 obtained after calcination of hydrothermally grown MoS2 is thus a promising sensing material for enhanced TEA gas detection.

4.
J Environ Manage ; 301: 113924, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34731947

RESUMEN

The present paper aimed to investigate the roles of quinones contained in wastewater and the enhanced effects on microbial fuel cells (MFCs) under different redox conditions. The feasibility of using wastewater rich in quinones to act as co-substrate and redox mediators (RMs) library to strengthen the synergistic removal of azo dye in MFCs was evaluated. The results demonstrated that quinones achieved enhanced effects on electricity generation and COD removal of MFC better at higher current intensity. The addition of pure quinone decreased electron transfer resistance (Rct) of MFCs from 4.76 Ω to 2.13 Ω under 1000 Ω resistance and 1.16 Ω-0.75 Ω under 50 Ω resistance. Meanwhile, higher coulombic efficiency was achieved. Compared with sodium acetate, using quinone-rich traditional Chinese medicine (TCM) wastewater as the co-substrate enhanced the synergistic removal of reactive red 2 (RR2) in MFCs from 79.58% to 92.45% during 24 h. RR2 was also degraded more thoroughly due to the accelerated electron transfer process mediated by RMs. Microbial community analysis demonstrated that the presence of quinone in TCM wastewater can enrich different exoelectrogens under varied redox conditions and thus influenced the enhanced effects on MFC. Metagenomic functional prediction results further indicated that the abundance of functional genes involved in carbohydrate metabolism, membrane transport metabolism, biofilm formation, and stress tolerance increased significantly in presence of RMs. Redundancy analyses revealed that RMs addition was the more important factor driving the variation of the microorganism community. This study revealed the potential effect of quinones as redox mediators on the bioelectrochemical system for pollutants removal.


Asunto(s)
Fuentes de Energía Bioeléctrica , Compuestos Azo , Electricidad , Electrodos , Oxidación-Reducción , Quinonas , Aguas Residuales
5.
J Environ Manage ; 301: 113857, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34626946

RESUMEN

A new type of binder was developed by grafting casein and ß-glucan to investigate its effect on tailings erosion and plant growth. 6% casein and 2% ß-glucan were recommended as the best ratio of the new biopolymer binder, which had the best effect on the soil utilization of iron tailings. The infrared analysis of the new binder demonstrated that casein and ß-glucan reacted adequately as raw materials. The results of physichemical properties and loss prevention of iron tailings showed that the binder-treated soils demonstrated lower erodibility compared with untreated iron tailings. The particle size of the tailings was increased after the addition of the binder. In treated soil, the content of soil organic matter increased significantly, which provided sufficient nutrients for the plants growing. Compared with natural tailings without binder, plant height, fresh weight, chlorophyll content, and enzyme activity (POD and SOD) were also significantly increased. This study overcame the current defects of biopolymer in soil improvement and provided an environmentally friendly method to prevent the loss of iron tailings and promote its soil utilization efficiency.


Asunto(s)
Contaminantes del Suelo , Biopolímeros , Hierro/análisis , Desarrollo de la Planta , Suelo , Contaminantes del Suelo/análisis
6.
Chemosphere ; 287(Pt 2): 132242, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34826929

RESUMEN

In this study, a multi-wavelength spectrophotometric method for simultaneous determination of peracetic acid (PAA) and coexistent hydrogen peroxide (H2O2) was presented. This method was based on the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) with the assistance of Fe2+/KI to produce a stable green radical (ABTS●+), which could be determined at four characteristic peaks (i.e., 415 nm, 650 nm, 732 nm, and 820 nm). The absorbances of ABTS●+ at four peaks were well linear (R2 > 0.999) with concentrations of both total peroxides (PAA + H2O2) and PAA in the range of 0-40 µM under optimized conditions. The sensitivities for determining total peroxides at 415 nm, 650 nm, 732 nm and 820 nm were determined to be 4.248 × 104 M-1 cm-1, 1.682 × 104 M-1 cm-1, 2.132 × 104 M-1 cm-1, and 1.928 × 104 M-1 cm-1, respectively. For determining PAA, the corresponding sensitivities were 4.622 × 104 M-1 cm-1, 1.895 × 104 M-1 cm-1, 2.394 × 104 M-1 cm-1 and 2.153 × 104 M-1 cm-1, respectively. The concentration of coexistent H2O2 was gained by deducting PAA concentration from total peroxides concentration. The ABTS method was accurate enough to determine PAA concentration in natural water samples. Moreover, the ABTS method was successfully used to determine the changes of PAA and coexistent H2O2 and to distinguish their role on naproxen degradation in heat-activated PAA process. Overall, the ABTS method could be used as an alternative method for the convenient, rapid and sensitive determination of PAA and the coexistent H2O2 in water samples.

7.
EMBO Rep ; : e53166, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34779554

RESUMEN

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.

8.
Front Pharmacol ; 12: 760331, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34803702

RESUMEN

Lagotis brachystachya Maxim is a characteristic herb commonly used in Tibetan medicine. Tibetan medicine records it as an important medicine for the clinical treatment of "Yellow Water Disease," the symptoms of which are similar to that of arthritis. Our previous study showed that the flavonoid fraction extracted from L. brachystachya could attenuate hyperuricemia. However, the effects of the active flavonoids on gouty arthritis remain elusive, and the underlying mechanism is not understood. In the present study, the effects of the active flavonoids were evaluated in rats or Raw264.7 cells with gouty arthritis induced by monosodium urate (MSU) crystal, followed by the detection of TLR4, MyD88, pNF-κB, and NLR family pyrin domain-containing 3 (NLRP3) expression. The swelling of the ankle joint induced by MSU crystal began to be relieved 6 h post the administration with the active flavonoids. In addition, the active flavonoids not only alleviated MSU crystal-induced inflammation in synovial tissues by histopathological examination but also reduced tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels in the joint tissue fluid of MSU crystal-induced rats. Furthermore, Western blot analysis indicated that the active flavonoids reduced the production of these cytokines by inhibiting the TLR4/MyD88/NF-κB pathway and decreasing NLRP3 expression in synovial tissues of rats. More importantly, the inhibition of TLR4/MyD88/NF-κB pathway and NLRP3 expression was also confirmed in MSU-induced Raw264.7 cells. In conclusion, these results indicated that the active flavonoids from L. brachystachya could effectively attenuate gouty arthritis induced by MSU crystal through the TLR4/MyD88/NF-κB pathway and NLRP3 expression in vivo and in vitro, suggesting several potential candidates for the treatment of gouty arthritis.

9.
Front Physiol ; 12: 733979, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34803728

RESUMEN

Background and Aims: Precancerous lesions of gastric cancer (PLGC) are the most important pathological phase with increased risk of gastric cancer (GC) and encompass the key stage in which the occurrence of GC can be prevented. In this study, we found that the gut microbiome changed significantly during the process of malignant transformation from chronic gastritis to GC in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) multiple factors-induced rat model. Accumulating evidence has shown that alterations in gut microbiota and metabolism are potentially linked to chronic inflammation and cancer of the gastrointestinal tract. However, the correlation of gut microbiota and metabolites, inflammatory factors, and the potential mechanism in the formation of PLGC have not yet been revealed. Methods: In this study, multiple factors including MNNG, sodium salicylate drinking, ranitidine feed, and irregular diet were used to establish a PLGC rat model. The pathological state of the gastric mucosa of rats was identified through HE staining and the main inflammatory cytokine levels in the serum were detected by the Luminex liquid suspension chip (Wayen Biotechnologies, Shanghai, China). The microbial composition and metabolites in the stool samples were tested by using 16S ribosomal RNA (rRNA) gene sequencing and non-targeted metabolomics. The correlation analysis of gut microbiota and inflammatory cytokines in the serum and gut microbiota and differential metabolites in feces was performed to clarify their biological function. Results: The results showed that compared to the control group, the gastric mucosa of the model rats had obvious morphological and pathological malignant changes and the serum levels of inflammatory cytokines including interleukin-1ß (IL-1ß), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and macrophage colony-stimulating factor (M-CSF) increased significantly, while the level of chemokine (C-X-C motif) ligand 1 (CXCL1) in serum reduced significantly. There were significant differences in the composition of the gut microbiota and fecal metabolic profiles between the model and control rats. Among them, Lactobacillus and Bifidobacterium increased significantly, while Turicibacter, Romboutsia, Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-005, and Ruminococcus_1 reduced significantly in the model rats compared to the control rats. The metabolites related to the lipid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway have also undergone significant changes. In addition, there was a significant correlation between the changes of the differential inflammatory cytokines in the serum, fecal metabolic phenotypes, and gut microbial dysbiosis in model rats. Conclusion: The activation of the inflammatory response, disturbance of the gut microbiota, and changes in the fecal metabolic phenotype could be closely related to the occurrence of PLGC. This study provides a new idea to reveal the mechanism of risk factors of chronic gastritis and GC from the perspective of inflammation-immune homeostasis, gut microbiota, and metabolic function balance.

10.
Front Bioeng Biotechnol ; 9: 727643, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34805105

RESUMEN

Objective: Osteoarthritis (OA) is a common degenerative joint disease, and animal models have proven pivotal in investigating this disease. This study aimed to develop a primate model of OA that may be more relevant to research studies on OA in humans. Method: Twelve female rhesus macaques were randomly divided into three groups. Four animals were untreated (Control group); four were subjected to the modified Hulth method, involving cutting of the anterior and posterior cruciate ligaments, and transecting the meniscus (Hulth group); and four were subjected to the modified Hulth method combined with cartilage defect (MHCD group). Each primate was subjected to motor ability tests, and underwent arthroscopic, radiographic, morphological, and pathological observation of the knee joints at various times for up to 180 days. Results: Motor ability on Day 180 was significantly lower in the MHCD group than in the Control (p<0.01) and Hulth (p<0.05) groups. Radiographic and morphological examination showed that the severity of knee joint deformity and articular cartilage injury were greater in the MHCD group than in the other groups. Pathological examination showed that cartilage thickness was significantly lower in the MHCD group than in the other groups at the same time points. The Mankin score on Day 180 was markedly higher in the MHCD group than in the Hulth (p<0.05) and Control (p<0.001) groups. Conclusion: The MHCD model of OA closely resembles the pathophysiological processes of spontaneous knee OA in humans. The time required to develop knee OA is shorter using the MHCD model than using the Hulth method.

11.
Chem Commun (Camb) ; 2021 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-34812801

RESUMEN

The construction of heteroporous covalent organic frameworks (COFs) is still a challenge. Herein, a series of 2D COFs with hexagonal and quadrilateral pores were constructed via in situ salphen or metal salphen formation. Metallized salphen-based COFs can be used as electrocatalysts towards water oxidation with an overpotential of 266 mV at 10 mA cm-2.

12.
Phys Chem Chem Phys ; 23(45): 25658-25666, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34755164

RESUMEN

Molecular dynamics simulations are carried out to study impact-induced coalescence behaviors for the first time. When the droplets possess different impact velocities, the big difference between them could induce unconventional coalescence behaviors that exhibit non-synchronous spreading and retraction processes, and thus produce non-coalescence behaviors. At the same impact velocity, the distance of two impacting droplets plays a vital role in their coalescing dynamics. We here present the lower and upper critical values of distance in a map to determine whether two droplets after impacting can coalesce or not, which are highly dependent on the impact velocity. Moreover, simulation studies show that the upper critical value is 2(Rmax - R), while the lower critical distance increases with the increase of impact velocity. This work not only helps advance our understanding of the effect of impact dynamics on the coalescence behaviors, but also shows the critical conditions for coalescence and non-coalescence behaviors, which could be considered as a new strategy to control the coalescence by tuning the impact parameters, and are expected to be used for some potential applications.

13.
Zootaxa ; 5023(2): 273-283, 2021 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-34810963

RESUMEN

Two new species of Alcochera (Ichneumonidae, Ctenopelmatinae, Mesoleiini), Alcochera flavoclypeata Sheng Sun, sp. nov. collected from Labagoumen Natural Reserve, Huairou, Beijing, and A. truncata Sheng Sun, sp. nov. from Wugongshan Natural Reserve, are described and illustrated. An updated taxonomic key to world species of Alcochera is provided.


Asunto(s)
Himenópteros , Animales , China
14.
Front Psychol ; 12: 711578, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34721157

RESUMEN

Early childhood interventions can improve self-regulation, but there are few economic evaluations of such interventions. This study analyzed the cost-effectiveness of an early childhood self-regulation intervention (Red Light Purple Light!; RLPL), comparing three different models of implementation across stages of intervention development: (Model 1) trained research assistants (RAs; graduate students) directly delivered the RLPL intervention to children; (Model 2) RAs trained trainers (e.g., program coaches), who then trained teachers to implement RLPL with children (e.g., train-the-trainer); and (Model 3) program faculty trained teachers to deliver the RLPL intervention to children. We implemented a cost-effectiveness analysis by calculating the incremental cost-effectiveness ratio. We also conducted a series of sensitivity analyses to adjust for parameter uncertainty. Our base-case analysis suggests that Model 2 was the most cost-effective strategy, in that a cost of $23 per child was associated with a one-unit increase of effect size on self-regulation scores. The "train-the-trainer" model remained the optimal strategy across scenarios in our sensitivity analysis. This study fills an important gap in cost-effectiveness analyses on early childhood self-regulation interventions. Our process and results can serve as a model for future cost-effectiveness analyses of early childhood intervention programs and may ultimately inform decisions related to intervention adoption that optimize resource allocation and improve program design.

15.
Front Microbiol ; 12: 754245, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34721359

RESUMEN

"Candidatus Liberibacter asiaticus" (CLas) is an unculturable phloem-limited α-proteobacterium associated with citrus Huanglongbing (HLB; yellow shoot disease). HLB is currently threatening citrus production worldwide. Understanding the CLas biology is critical for HLB management. In this study, a novel single-stranded DNA (ssDNA) phage, CLasMV1, was identified in a CLas strain GDHZ11 from Guangdong Province of China through a metagenomic analysis. The CLasMV1 phage had a circular genome of 8,869 bp with eight open reading frames (ORFs). While six ORFs remain uncharacterized, ORF6 encoded a replication initiation protein (RIP), and ORF8 encoded a major capsid protein (MCP). Based on BLASTp search against GenBank database, amino acid sequences of both MCP and RIP shared similarities (coverage > 50% and identity > 25%) to those of phages in Microviridae, an ssDNA phage family. Phylogenetic analysis revealed that CLasMV1 MCP and RIP sequences were clustered with genes from CLas and "Ca. L. solanacearum" (CLso) genomes and formed a unique phylogenetic lineage, designated as a new subfamily Libervirinae, distinct to other members in Microviridae family. No complete integration form but partial sequence (∼1.9 kb) of CLasMV1 was found in the chromosome of strain GDHZ11. Read-mapping analyses on additional 15 HiSeq data sets of CLas strains showed that eight strains harbored complete CLasMV1 sequence with variations in single-nucleotide polymorphisms (SNPs) and small sequence insertions/deletions (In/Dels). PCR tests using CLasMV1-specific primer sets detected CLasMV1 in 577 out of 1,006 CLas strains (57%) from southern China. This is the first report of Microviridae phage associated with CLas, which expands our understanding of phage diversity in CLas and facilitates current research in HLB.

16.
J Cell Physiol ; 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34724217

RESUMEN

Mechanical forces can modulate the immune response, mostly described as promoting the activation of immune cells, but the role and mechanism of pathological levels of mechanical stress in lymphocyte activation have not been focused on before. By an ex vivo experimental approach, we observed that mechanical stressing of murine spleen lymphocytes with 50 mmHg for 3 h induced the nuclear localization of NFAT1, increased C-Jun, and increased the expression of early activation marker CD69 in resting CD8+ cells. Interestingly, 50 mmHg mechanical stressing induced the nuclear localization of NFAT1; but conversely decreased C-Jun and inhibited the expression of CD69 in lymphocytes under lipopolysaccharide or phorbol 12-myristate 13-acetate/ionomycin stimulation. Additionally, we observed similar changes trends when comparing RNA-seq data of hypertensive and normotensive COVID-19 patients. Our results indicate a biphasic effect of mechanical stress on lymphocyte activation, which provides insight into the variety of immune responses in pathologies involving elevated mechanical stress.

17.
Bioresour Technol ; 344(Pt A): 126225, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34737161

RESUMEN

Coupling chemical induction and abiotic stresses is a beneficial strategy for astaxanthin (Asta) induction in Haematococcus pluvialis. The combined application of melatonin (MT) and putrescine (Put) induced Asta and lipid biosynthesis in H. pluvialis under adverse conditions. Under MT and Put inductions, the highest Asta and lipid contents were 3.64% and 55.84%, which were 1.71- and 1.17-times higher than the control group, respectively. The combination of MT and Put also enhanced the expression of carotenogenic, lipogenic and antioxidant enzyme genes. Additionally, this combined treatment increased the endogenous Put content while decreasing the reactive oxygen species (ROS) and γ-aminobutyric acid (GABA) levels. Further results proved that endogenous Put promoted Asta production and alleviated oxidative stress by regulating carotenogenesis and GABA and ROS signaling. This study describes a potential process for stimulating Asta and lipid coproduction and highlights the connections among MT, Put, signaling molecules, Asta and lipid synthesis in H. pluvialis.

18.
J Mol Cell Cardiol ; 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34774547

RESUMEN

Effects of hypertrophic challenge on small-conductance, Ca2+-activated K+(SK2) channel expression were explored in intact murine hearts, isolated ventricular myocytes and neonatal rat cardiomyocytes (NRCMs). An established experimental platform applied angiotensin II (Ang II) challenge in the presence and absence of reduced p21-activated kinase (PAK1) (PAK1cko vs. PAK1f/f, or shRNA-PAK1 interference) expression. SK2 current contributions were detected through their sensitivity to apamin block. Ang II treatment increased such SK2 contributions to optically mapped action potential durations (APD80) and their heterogeneity, and to patch-clamp currents. Such changes were accentuated in PAK1cko compared to PAK1f/f, intact hearts and isolated cardiomyocytes. They paralleled increased histological and echocardiographic hypertrophic indices, reduced cardiac contractility, and increased SK2 protein expression, changes similarly greater with PAK1cko than PAK1f/f. In NRCMs, Ang II challenge replicated such increases in apamin-sensitive SK patch clamp currents as well as in real-time PCR and western blot measures of SK2 mRNA and protein expression and cell hypertrophy. Furthermore, the latter were enhanced by shRNA-PAK1 interference and mitigated by the PAK1 agonist FTY720. Increased CaMKII and CREB phosphorylation accompanied these effects. These were rescued by both FTY720 as well as the CaMKII inhibitor KN93, but not its inactive analogue KN92. Such CREB then specifically bound to the KCNN2 promoter sequence in luciferase assays. These findings associate Ang II induced hypertrophy with increased SK2 expression brought about by a CaMKII/CREB signaling convergent with the PAK1 pathway thence upregulating the KCNN2 promoter activity. SK2 may then influence cardiac electrophysiology under conditions of cardiac hypertrophy and failure.

19.
Sci Total Environ ; : 151270, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34756902

RESUMEN

The widespread application of metal-based nanoparticle (MNPs)/reduced graphene oxide (rGO) composites inevitably leads to their release into soils. However, we lack a detailed understanding of the bacterial community response to MNPs-rGO exposure in farmland soils. Here, we conducted a soil microcosm experiment to analyze the potential impact of MNPs-rGO on bacterial communities in two field soils via high-throughput sequencing. The change in alpha diversity of bacterial communities was more susceptible to Ag-rGO and ZnO-rGO treatments than CuO-rGO. In both soils, MNPs-rGO significantly changed the bacterial community structure even at a low dose (1 mg kg-1). The bacterial community structure was most strongly affected by Ag-rGO at 30 days, but the greatest changes occurred in ZnO-rGO at 60 days. The differences in soil properties could shape bacterial communities to MNPs-rGO exposure. Distance-based redundancy analysis and functional annotation of prokaryotic taxa showed that some bacterial species associated with nitrogen cycling were greatly influenced by Ag-rGO and ZnO-rGO exposure. In sum, Ag-rGO and ZnO-rGO may potentially affect bacterial communities and nitrogen turnover under long-term realistic field exposure. These findings present a perspective on the response of bacterial communities to MNPs-rGO and provide a fundamental basis for estimating the ecological behavior of MNPs-rGO.

20.
ACS Appl Mater Interfaces ; 13(45): 53671-53682, 2021 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-34730938

RESUMEN

Ferroptosis is a new form of regulated cell death depending on elevated iron (Fe2+) and lipid peroxidation levels. Myocardial ischemia/reperfusion (I/R) injury has been shown to be closely associated with ferroptosis. Therefore, antiferroptosis agents are considered to be a new strategy for managing myocardial I/R injury. Here, we developed polydopamine nanoparticles (PDA NPs) as a new type of ferroptosis inhibitor for cardioprotection. The PDA NPs features intriguing properties in inhibiting Fe2+ accumulation and restoring mitochondrial functions in H9c2 cells. Subsequently, we demonstrated that administration of PDA NPs effectively reduced Fe2+ deposition and lipid peroxidation in a myocardial I/R injury mouse model. In addition, the myocardial I/R injury in mice was alleviated by PDA NPs treatment, as demonstrated by reduced infarct size and improved cardiac functions. The present work indicates the therapeutic effects of PDA NPs against myocardial I/R injury via preventing ferroptosis.

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