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Emission characteristics of biogenic volatile organic compounds (BVOCs) from dominant tree species in the subtropical pristine forests of China are extremely limited. Here we conducted in situ field measurements of BVOCs emissions from representative mature evergreen trees by using dynamic branch enclosures at four altitude gradients (600-1690 m a.s.l.) in the Nanling Mountains of southern China. Composition characteristics as well as seasonal and altitudinal variations were analyzed. Standardized emission rates and canopy-scale emission factors were then calculated. Results showed that BVOCs emission intensities in the wet season were generally higher than those in the dry season. Monoterpenes were the dominant BVOCs emitted from most broad-leaved trees, accounting for over 70% of the total. Schima superba, Yushania basihirsuta and Altingia chinensis had relatively high emission intensities and secondary pollutant formation potentials. The localized emission factors of isoprene were comparable to the defaults in the Model of Emissions of Gases and Aerosols from Nature (MEGAN), while emission factors of monoterpenes and sesquiterpenes were 2 to 58 times of those in the model. Our results can be used to update the current BVOCs emission inventory in MEGAN, thereby reducing the uncertainties of BVOCs emission estimations in forested regions of southern China.
Subject(s)
Air Pollutants , Environmental Monitoring , Forests , Volatile Organic Compounds , Volatile Organic Compounds/analysis , China , Air Pollutants/analysis , Trees , SeasonsABSTRACT
BACKGROUND: While prior studies have explored the efficacy of Morinda officinalis oligosaccharides (MOs) as a treatment for patients with major depressive disorder (MDD), the mechanistic basis for the effects of MOs on brain function or the default-mode network (DMN) has yet to be characterized. The objective of this was to examine the effects of MOs treatment on functional connectivity in different regions of the DMN. METHODS: In total, 27 MDD patients and 29 healthy control subjects (HCs) underwent resting-state functional magnetic resonance imaging. The patients were then treated with MOs for 8 weeks, and scanning was performed at baseline and the end of the 8-week treatment period. Changes in DMN homogeneity associated with MOs treatment were assessed using network homogeneity (NH) analyses of the imaging data, and pattern classification approaches were employed to determine whether abnormal baseline NH deficits could differentiate between MDD patients and controls. The ability of NH abnormalities to predict patient responses to MOs treatment was also evaluated. RESULTS: Relative to HCs, patients exhibited a baseline reduction in NH values in the right precuneus (PCu). At the end of the 8-week treatment period, the MDD patients showed reduced and increased NH values in the right PCu and left superior medial frontal gyrus (SMFG), respectively. Compared to these patients at baseline, the 8-week MOs treatment was associated with reduced NH values in the right angular gyrus and increased NH values in the left middle temporal gyrus and the right PCu. Support vector machine (SVM) analyses revealed that NH abnormalities in the right PCu and left SMFG were the most accurate (87.50%) for differentiating between MDD patients and HCs. CONCLUSION: These results indicated that MOs treatment could alter default-mode NH in patients with MDD. The results provide a foundation for elucidation of the effects of MOs on brain function and suggest that the distinctive NH patterns observed in this study may be useful as imaging biomarkers for distinguishing between patients with MDD and healthy subjects.
Subject(s)
Default Mode Network , Depressive Disorder, Major , Magnetic Resonance Imaging , Morinda , Oligosaccharides , Humans , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/physiopathology , Male , Female , Adult , Oligosaccharides/therapeutic use , Default Mode Network/diagnostic imaging , Default Mode Network/physiopathology , Default Mode Network/drug effects , Middle Aged , Brain/drug effects , Brain/diagnostic imaging , Brain/physiopathology , Young AdultABSTRACT
Exposure to environmental pollutants, including nanomaterials, has a significant impact on tumor progression. The increased demand for black phosphorus nanosheets (BPNSs), driven by their exceptional properties, raises concerns about potential environmental contamination. Assessing their toxicity on tumor growth is essential. Herein, we employed a range of biological techniques, including cytotoxicity measurement, bioinformatics tools, proteomics, target gene overexpression, Western blot analysis, and apoptosis detection, to investigate the toxicity of BPNSs across A549, HepG-2, MCF-7, and Caco-2 cell lines. Our results demonstrated that BPNSs downregulated the expression of ADIPOQ and its associated downstream pathways, such as AMP-activated protein kinase (AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2), and other unidentified pathways. These downregulated pathways ultimately led to mitochondria-dependent apoptosis. Notably, the specific downstream pathways involved varied depending on the type of tumors. These insightful findings not only confirm the consistent inhibitory effects of BPNSs across different tumor cells, but also elucidate the cytotoxicity mechanisms of BPNSs in different tumors, providing valuable information for their safe application and health risk assessment.
Subject(s)
Adiponectin , Apoptosis , Cell Proliferation , Down-Regulation , Nanostructures , Phosphorus , Signal Transduction , Humans , Phosphorus/chemistry , Cell Proliferation/drug effects , Adiponectin/metabolism , Down-Regulation/drug effects , Signal Transduction/drug effects , Nanostructures/chemistry , Nanostructures/toxicity , Apoptosis/drug effects , Cell Line, Tumor , AMP-Activated Protein Kinases/metabolism , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/geneticsABSTRACT
Formaldehyde (HCHO) is one of the key indicators of severe photochemical pollution and strong atmospheric oxidation capacity in southern China. However, current information on the origins of regional HCHO and the impacts of polluted air masses remains scarce and unclear. In this study, an intensive observation of HCHO was conducted at a mountainous background site in southern China during typical photochemical pollution episodes. The concentrations of HCHO reached up to 6.14 ppbv and averaged at 2.68 ± 1.11 ppbv. Source appointment using a photochemical age-based parameterization method revealed significant contributions of secondary formation (50 %) and biomass burning (42 %). Meanwhile, under the influence of the East Asian Winter Monsoon, polluted air masses from central and western China can significantly increase the regional HCHO levels. The simulation results adopting the Rapid Adaptive Optimization Model for Atmospheric Chemistry model further demonstrated that the intrusion of active anthropogenic pollutants (e.g., small-molecule alkenes) can accelerate the net production rate of HCHO, particularly through BVOC-oxidation pathways. This study suggests a potential enhanced mechanism of HCHO production resulting from anthropogenic-biogenic interactions. It highlights that polluted air masses carrying abundant HCHO from upwind areas may facilitate severe photochemical pollution in the Greater Bay Area.
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Open biomass burning (OBB) is one of the largest primary emission sources for atmospheric carbonyl compounds, key precursors for ozone and secondary organic aerosol pollution. To clarify the carbonyl emissions, the comprehensive characteristics of C1-C10 carbonyl compounds from open burning of seven typical subtropical biomass in China were investigated in this study, which included subtropical plants and agricultural residues. Total 27 carbonyl compounds were detected. The total EFs were 2824 mg kg-1 with 95% confidence interval (CI) [2418, 3322] for burning subtropical plants and 4080 mg kg-1 with 95% CI [3446, 4724] for burning agriculture residues, respectively. The EFs were 2-3 orders of magnitude larger than previous values in China. Aliphatic aldehydes were the largest group of carbonyl groups, with acetaldehyde, as the most abundant carbonyl species (about 30% contribution). Formaldehyde, acetone, acrolein, glyoxal, methylglyoxal, butanone, isovaleraldehyde, and m-tolualdehyde were also found to be abundant and varying with the types of biomass burnt. Formaldehyde emission ratios to acetonitrile and CO were lower than those in previous studies both for burning plants and agricultural residues. There were significant variabilities in the emission ratios and factors among different types of OBBs. Strong positive correlations were found between carbonyl emissions and CO emissions and water content in biomass; furthermore, total carbonyl concentrations measured in the flaming stage were higher than those in the smoldering one. This study provides important fundamental measurement data on carbonyl emissions from burning typical subtropical plants and agricultural residues, which will help improve the quality of emission inventories and better understand the potential impacts of OBB on regional air quality in southern China.
Subject(s)
Air Pollutants , Air Pollutants/analysis , Biomass , Open Waste Burning , China , Formaldehyde , Environmental Monitoring , Particulate Matter/analysisABSTRACT
Layered black phosphorus (LBP) is drawing increasing attention because of its excellent potential in biomedical applications. Properties and bioeffects of LBP depend on its layer number (LN). However, the variation of LN during applications, especially in organisms, is largely unknown. Herein, LBP is found to be exfoliated by human serum albumin (HSA) after the formation of protein coronas. The sorption of HSA on LBP exhibits multiple intermediate equilibrium and size-dependent capacity and is distinguished from traditional multilayer sorption. The loss of LN for LBP increases with the increase of HSA concentrations, e.g., 2, 4, and 6 layers of LBP are exfoliated at 35, 135, and 550 mg/L HSA, respectively. The energy distribution shows that at low HSA concentrations, exfoliation is mainly driven by electrostatic and hydrogen bond interactions. With middle or high HSA concentrations, exfoliation is mainly driven by p-π or hydrophobic interactions, respectively. Layer exfoliation causes the continuous emergence of an unsaturated LBP surface available for adsorbing further HSA, breaking previous sorption saturations. The complete exfoliation of LBP weakens cytotoxicity and promotes internalization to the A-549 cell line compared with pristine or less exfoliated LBP. This finding unveils the exfoliation mechanism of proteins toward LBP and is of benefit to evaluating application performance and biosafety of LBP.
Subject(s)
Phosphorus , Serum Albumin, Human , Humans , Serum Albumin, Human/chemistryABSTRACT
Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
Subject(s)
Antimalarials , Artemisinins , Cardiovascular Diseases , Heart Failure , Malaria, Cerebral , Quinolines , Child , Adult , Humans , Antimalarials/pharmacology , Cardiovascular Diseases/drug therapy , Artemisinins/pharmacology , Malaria, Cerebral/drug therapy , Heart Failure/drug therapy , Arrhythmias, Cardiac/drug therapyABSTRACT
Anthropogenic aromatics play a key role in photochemical pollution and pose a serious threat to human health. Current knowledge on source characteristics of aromatics in the urban region of the Tibetan Plateau (TP), the "Third Pole" and ecologically sensitive area, remains limited. In this study, an intensive observation of 17 aromatic hydrocarbons was conducted in Lhasa, the cultural and economic center of TP, during the second Tibetan Plateau Scientific Expedition and Research in summer 2020. The results showed that the average concentration of aromatics in Lhasa (7.6 ± 7.4 ppbv) was unexpectedly higher than those in megacities such as Beijing, Shanghai, and Guangzhou. Tripled concentrations and corresponding ozone formation potential during pollution episodes were recorded. Further source apportionment using positive matrix factorization revealed that solvent usage (60.0 %) was the dominant source, which may be due to the extremely low atmospheric pressure. Vehicle exhaust (15.4 %), industrial emissions (12.8 %), fuel evaporation (6.2 %), and burning emissions (5.7 %) were also important sources. The concentration weighted trajectory analysis revealed that the observed high levels of aromatics were mainly driven by local anthropogenic emissions, rather than the regional transport by the Indian summer monsoon. Long-term exposure to aromatics in Lhasa was assessed to pose carcinogenic risks to the population, with the risks of benzene and ethylbenzene 5 times the criteria. Our results suggest that, given the magnified emissions of aromatics in this extreme environment (low atmospheric pressure and strong solar radiation), the implementation of targeted pollution controls is urgently needed to mitigate the aromatic-related photochemical pollution and health threats in TP.
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The production scalability and increasing demand for nano-black phosphorus materials (nano-BPs) inevitably lead to their environmental leakage, thereby raising the risk of human exposure through inhalation, ingestion, dermal, and even intravenous pathways. Consequently, a systematic evaluation of their potential impacts on human health is necessary. This Review outlines recent progress in the understanding of various biological responses to nano-BPs. Attention is particularly given to the inconsistent toxicological findings caused by a wide variation of nano-BPs' physicochemical properties, toxicological testing methods, and cell types examined in each study. Additionally, cellular uptake and intracellular trafficking, cell death modes, immunological effects, and other biologically relevant processes are discussed in detail, providing evidence for the potential health implications of nano-BPs. Finally, we address the remaining challenges related to the health risk evaluation of nano-BPs and propose a broader range of applications for these promising nanomaterials.
Subject(s)
Nanostructures , Phosphorus , Humans , Phosphorus/chemistry , Nanostructures/toxicity , Biological TransportABSTRACT
Mountainous background areas are typically considered to have a clean atmosphere where peroxyacetyl nitrate (PAN) can be decomposed. This study demonstrated that PAN was photochemically formed with a simulated production rate of 0.28 ± 0.06 ppbv h-1 in the Nanling mountains (1690 m a.s.l.) of South China and that net PAN formation was dependent on both volatile organic compounds (VOCs) and NOx precursors (transition regime). In contrast to dominated acetaldehyde oxidation in previous urban and rural research, PAN at Nanling was primarily formed by methylglyoxal (38%), acetaldehyde (28%), radicals (20%), and other oxygenated volatile organic compounds (OVOCs) (13%). Moreover, when polluted air masses invaded the Nanling mountains, the PAN production rate was altered, primarily because anthropogenic aromatics intensified PAN formation via the oxidized pathways of methylglyoxal, other OVOCs, and radicals. Finally, net PAN formation at Nanling reduced the hydroxyl radical level by consuming NOx, impaired local radical cycling, and thereby suppressed local O3 production. This suppressing effect was exacerbated on polluted days. The findings of this study deepen our understanding of PAN photochemistry and the impact of anthropogenic intrusions on the background atmosphere of mountainous regions.
Subject(s)
Air Pollutants , Environmental Pollutants , Ozone , Volatile Organic Compounds , Air Pollutants/analysis , Volatile Organic Compounds/analysis , Pyruvaldehyde , China , Atmosphere/chemistry , Acetaldehyde , Ozone/analysis , Environmental MonitoringABSTRACT
In this paper, a variety of 2D materials on the surface plasmon resonance sensor based on Al-Ni bimetallic layer are compared. Simulation results indicate that lateral position shift, which is calculated according to the real and imaginary parts of the refractive index of material, can be used as an effective parameter to optimize the sensitivity. By using the parameters for optimizing the SPR structures, the results show that the multiple layer models of Al(40 nm)-Ni(22 nm)-black phosphorus (BP)(1 L) and Al(40 nm)-Ni(22 nm)-blue phosphorus (BlueP)/WS2(1 L) exhibit average angular sensitivities of 507.0 °/RIU and 466 °/RIU in the refractive index range of 1.330-1.335, and maximum sensitivity of 542 °/RIU and 489 °/RIU at the refractive index of 1.333, respectively. We expect more applications can be explored based on the highly sensitive SPR sensor in different fields of optical sensing.
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With the extensive production and application of black phosphorus (BP) nanosheets, release to the environment is inevitable, which raises concerns about the fate and effects of this two-dimensional (2D) material on sensitive receptors such as environmental microbes. Although the bacterial toxicity of BP nanosheets has been demonstrated, whether the biological response differs in pathogenic and nonpathogenic strains of a microorganism is unknown. Here, enteropathogenic Escherichia coli (EPEC) and nonpathogenic Escherichia coli DH5α (E. coli DH5α), Escherichia coli k12 (E. coli k12), and Bacillus tropicus (B. tropicus) are used to comparatively study the microbial toxicity of BP nanosheets. Upon exposure to BP nanosheets across a range of doses from 10 to 100 µg mL-1 for 12 h, EPEC experienced enhanced growth and E. coli DH5α and E. coli k12 were not affected, whereas B. tropicus exhibited clear toxicity. By combining transcriptome sequencing, proteome analysis, and other sensitive biological techniques, the mechanism of BP-induced growth promotion for EPEC was uncovered. Briefly, BP nanosheets activate the antioxidation system to resist oxidative stress, promote protein synthesis and secretion to attenuate membrane damage, enhance the energy supply, and activate growth-related pathways. None of these impacts were evident with nonpathogenic strains. By describing the mechanism of strain-dependent microbial effects, this study not only highlights the potential risks of BP nanosheets to the environment and to human health but also calls attention to the importance of model strain selection when evaluating the hazard and toxicity of emerging nanomaterials.
Subject(s)
Enteropathogenic Escherichia coli , Escherichia coli Proteins , Humans , Carrier Proteins , Enteropathogenic Escherichia coli/genetics , Enteropathogenic Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Gene Expression Profiling , Phosphorus , NanostructuresABSTRACT
The remarkable progress of applied black phosphorus nanomaterials (BPNMs) is attributed to BP's outstanding properties. Due to its potential for applications, environmental release and subsequent human exposure are virtually inevitable. Therefore, how BPNMs impact biological systems and human health needs to be considered. In this comprehensive Minireview, the most recent advancements in understanding the mechanisms and regulation factors of BPNMs' endogenous toxicity to mammalian systems are presented. These achievements lay the groundwork for an understanding of its biological effects, aimed towards establishing regulatory principles to minimize the adverse health impacts.
Subject(s)
Nanostructures , Phosphorus , Animals , Humans , Nanostructures/toxicity , MammalsABSTRACT
Two-dimensional (2D) organic-inorganic perovskites have great potential for the fabrication of next-generation photodetectors owing to their outstanding optoelectronic features, but their utilization has encountered a bottleneck in anisotropic carrier transportation induced by the unfavorable continuity of the thin films. We propose a facile approach for the fabrication of 0D ZnO quantum dot (QD)/2D (PEA)2PbI4 nanosheet hybrid photodetectors under the atmospheric conditions associated with the ZnO QD chloroform antisolvent. Profiting from the antisolvent, the uniform morphology of the perovskite thin films is obtained owing to the significantly accelerated nucleation site formation and grain growth rates, and ZnO QDs homogeneously decorate the surface of (PEA)2PbI4 nanosheets, which spontaneously passivate the defects on perovskites and enhance the carrier separation by the well-matched band structure. By varying the ZnO QD concentration, the Ion/Ioff ratio of the photodetectors radically elevates from 78.3 to 1040, and a 12-fold increase in the normalized detectivity is simultaneously observed. In addition, the agglomeration of perovskite grains is governed by the annealing temperature, and the photodetector fabricated at a relatively low temperature of 120 °C exhibits excellent stability after a 50-cycle test in the air condition without any encapsulation.
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Background: Long non-coding RNAs (lncRNAs) have become potential therapeutic targets or promising prognostic biomarkers in cancers. However, individual gene does not show sufficient prognostic value for clear cell renal cell carcinoma (ccRCC). Therefore, this study aims to develop a combined prognostic lncRNA signature to the prognosis of ccRCC. Methods: The transcriptome profiling data for confirmed ccRCC cases were obtained from The Cancer Genome Atlas (TCGA; https://portal.gdc.cancer.gov/). The prognostic significance, survival time and diagnostic effectiveness of the lncRNAs in ccRCC was evaluated using Kaplan-Meier method, the log-rank test and receiver operating characteristic (ROC) curves, respectively. The area under the ROC curve (AUC) of the 4 lncRNAs was also performed. The expression of mitotically-associated lncRNA (MANCR) was measured in ccRCC cells or tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Both Colony formation assays and Cell Counting Kit-8 (CCK-8) assay was conducted to detect the proliferation of both 786-O and SN12C cells. For apoptosis detection, flow cytometry in both 786-O and SN12C cells was performed. For migration of 786-O and SN12C cells detection, wound healing and transwell assays were performed. Results: A total of 1,567 differentially expressed lncRNAs in ccRCC were discerned with 1,340 upregulation and 227 downregulation. Furthermore, a 4-lncRNA signature (FIRRE, MANCR, AC103706.1, and AC018648.1) model was obtained that showed good performance in the prognosis of ccRCC. Gene Ontology (GO) analysis showed that these protein-coding genes (PCGs) were mainly enriched in ATPase activity, catalytic activity, and acting on RNA protein serine/threonine kinase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that PCGs were mainly involved in endocytosis, oocyte meiosis and spliceosome. In addition, we revealed that MANCR was highly expressed in ccRCC cells and tissues and downregulation of MANCR inhibited cell proliferation and migration. In contrast, apoptosis of 786-O and SN12C cells was promoted with MANCR suppression. Conclusions: A 4-lncRNA prognostic model that presented good performance for prognosis of ccRCC patients was established. Knockdown of MANCR inhibited cell proliferation and migration, and promoted apoptosis of 786-O and SN12C cells, suggesting that a 4-lncRNA signature model might be an essential for ccRCC prognosis.
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The acousto-optic interaction is strongly modified and different in subwavelength confinement. Here, the optical propagation and acoustic propagation in a subwavelength-diameter fiber (SDF) have been investigated through adopting a two-layer fiber model of air-coated silica rod. Theoretical investigation indicates that SDF with a diameter below 1.2 µm supports the single mode of light propagation, and various Brillouin acoustic modes with well-spaced spectral distribution can be also excited. Due to the light propagation with the outer environment as the cladding layer, the surrounding medium will greatly affect Brillouin scattering of SDFs. Both the simulation and experiment results indicate a relatively good linear relationship between the Brillouin frequency shift of the lower acoustic modes and surrounding environmental refractive index (RI), and the higher RI sensitivity in finer SDFs can be obtained. In addition, hybrid acoustic waves have shown higher sensitivity and stability than surface acoustic modes. A RI sensitivity of about 5.1 GHz/RIU has been achieved in a 1.1 µm SDF, demonstrating its potential application in RI sensing.
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This study presents underwater explosion tests with three different TNT charge weights to investigate the dynamic responses of a fixed steel sheet. A finite element model was established and benchmarked by comparing the bubble development and deformation distribution from the tests. The steel sheet shows a deformation process of hogging, sagging, and hogging again, due to the actions of shock waves, bubble expansion, bubble collapse, and bubble pulsation. The air may be sucked into the bubble during the hogging process, making the bubble collapse earlier and resulting in a relatively lower sagging deformation for large charge weights of TNT. The deformation caused by bubble pulsation is larger than that by the shock waves, owing to the large time duration of bubble pulsation. A parametric analysis was conducted to study the influence of steel grade, plate thickness, detonation distance, and the shape and position of charges on the dynamic behavior of steel plates subjected to underwater explosions. It shows that the damage to the steel plate gradually decreases, with the increase in steel strength, plate thickness, and detonation distance. The influence of the shape and position of charges is limited. The largest deformation is observed when the detonation distance increases to bubble radius.
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The PI3K/AKT signaling pathway plays essential roles in multiple cellular processes, which include cell growth, survival, metabolism, and motility. In response to internal and external stimuli, the PI3K/AKT signaling pathway co-opts other signaling pathways, cellular components, and cytoskeletal proteins to reshape individual cells. The cytoskeletal network comprises three main components, which are namely the microfilaments, microtubules, and intermediate filaments. Collectively, they are essential for many fundamental structures and cellular processes. In cancer, aberrant activation of the PI3K/AKT signaling cascade and alteration of cytoskeletal structures have been observed to be highly prevalent, and eventually contribute to many cancer hallmarks. Due to their critical roles in tumor progression, pharmacological agents targeting PI3K/AKT, along with cytoskeletal components, have been developed for better intervention strategies against cancer. In our review, we first discuss existing evidence in-depth and then build on recent advances to propose new directions for therapeutic intervention.
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BACKGROUND: Synovial mesenchymal stem cells (SMSCs) have been discussed as promising tools for protecting chondrocytes from loss and inhibiting osteoarthritis (OA). This work infocuses on the function of SMSC-derived extracellular vesicles (EVs) in chondrocytes during OA and the molecular mechanism. METHODS: EVs were extracted from SMSCs and identified. Chondrocytes were treated with interleukin (IL)-1ß to induce an OA-like condition in vitro and then treated with EVs. The proliferation, apoptosis, migration, extracellular matrix (ECM) degradation and inflammation in chondrocytes were examined. Key microRNAs (miRNAs) carried by EVs were screened using a microarray analysis, and the downstream molecules involved were explored using bioinformatic analysis. Rescue experiments were performed to validate the involvements of these molecules in EV-mediated events. RESULTS: EVs restored proliferation and migration while reduced apoptosis, ECM degradation and the secretion of pro-inflammatory cytokines in chondrocytes induced by IL-1ß. miR-130b-3p was significantly elevated in chondrocytes after EVs treatment. Knockdown of miR-130b-3p blocked the protective roles of EVs against IL-1ß-induced damage to chondrocytes. miR-130b-3p was found to target LDL receptor related protein 12 (LRP12) mRNA in chondrocytes. Overexpression of LRP12 counteracted the effects of EVs as well and activated the AKT/ß-catenin signaling pathway. CONCLUSION: This study provided evidence that EVs alleviate chondrocyte damage during OA through miR-130b-3p-mediated inhibition of the LRP12/AKT/ß-catenin axis. This study may offer novel thoughts into the protection of chondrocytes and the management of OA.
Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , Osteoarthritis , beta Catenin , Apoptosis , Chondrocytes , Extracellular Vesicles/metabolism , Humans , Interleukin-1beta/metabolism , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Osteoarthritis/metabolism , Osteoarthritis/therapy , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolismABSTRACT
Glyoxal (Gly) and methylglyoxal (Mgly) are the intermediate products of several volatile organic compounds (VOCs) as well as the precursors of brown carbon and may play key roles in photochemical pollution and regional climate change in the Tibetan Plateau (TP). However, their sources and atmospheric behaviors in the TP remain unclear. During the second Tibetan Plateau Scientific Expedition and Research in the summer of 2020, the concentrations of Gly (0.40 ± 0.30 ppbv) and Mgly (0.57 ± 0.16 ppbv) observed in Lhasa, the most densely populated city in the TP, had increased by 20 and 15 times, respectively, compared to those measured a decade previously. Owing to the strong solar radiation, secondary formations are the dominant sources of both Gly (71%) and Mgly (62%) in Lhasa. In addition, primary anthropogenic sources also play important roles by emitting Gly and Mgly directly and providing abundant precursors (e.g., aromatics). During ozone pollution episodes, local anthropogenic sources (industries, vehicles, solvent usage, and combustion activities) contributed up to 41% and 45% in Gly and Mgly levels, respectively. During non-episode periods, anthropogenic emissions originating from the south of Himalayas also have non-negligible contributions. Our results suggest that in the previous decade, anthropogenic emissions have elevated the levels of Gly and Mgly in the TP dramatically. This study has important implications for understanding the impact of human activities on air quality and climate change in this ecologically fragile area.