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1.
Food Chem ; 400: 134049, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36067689

RESUMO

Novel insecticide cyetpyrafen is frequently used in various crops, however, knowledge of its fate in crops and environments is largely unexplored. In this study, an effective method was firstly established for simultaneous determination of cyetpyrafen and its metabolites (M-309 and M-391) in 13 matrices (e.g., plants and soils) to explore their fate. Mean recoveries of the three compounds ranged from 73.1 % to 118.7 % with the relative standard deviations (RSDs) less than 17.9 %. Further, after 28 days of exposure in a field soil-strawberry system, cyetpyrafen and M-309 exhibited great accumulations in strawberry leaves by foliar spray while both compounds were predominately accumulated in roots by root irrigation, where cyetpyrafen was poorly translocated within plant. An equal amount of M-309 was measured in both strawberry plants and soils indicates the extensive transformation of cyetpyrafen in soil-strawberry system. Therefore, metabolism of cyetpyrafen in foods need to be considered for its better risk assessment.


Assuntos
Produtos Agrícolas/química , Fragaria , Praguicidas/análise , Solo/química , Água/análise , Produtos Agrícolas/metabolismo , Inseticidas/análise , Inseticidas/metabolismo , Praguicidas/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Água/metabolismo
2.
Bioengineering (Basel) ; 9(9)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36134979

RESUMO

Synthetic nanocarriers are a promising therapeutic delivery strategy. However, these systems are often hampered by inherent disadvantages such as strong biotoxicity and poor biocompatibility. To overcome these issues, biological carriers with commonly used chemotherapy drugs have been developed. In this work, engineered bacterial ghosts (BGs) originated from probiotic Escherichia coli Nissle 1917 (EcN) were devised to specifically target acidic extracellular environments of tumor tissue. To improve the production efficiency and safety, a novel lysis protein E from phage α3 was applied to produce EcN BGs under high growth densities in high quality. In addition, the acidity-triggered rational membrane (ATRAM) peptides were displayed in EcN BGs to facilitate specific cancer cell internalization within the acidic tumor microenvironment before drug release. In conclusion, the engineered EcN BGs offer a promising means for bionic bacteria construction for hepatocellular carcinoma therapy.

3.
Front Neurosci ; 16: 964904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148147

RESUMO

There are many factors that influence the academic achievements of medical students, but how personality and brain modulate the academic achievements of medical students remains unclear. The study collected the personality, brain imaging, and academic data from 448 medical students at Tianjin Medical University with admission time between 2008 and 2017. Four types of academic achievements, including behavioral and social sciences, clinical sciences and skills, basic biomedical sciences, and scientific methods, were assessed by the academic records of 58 courses. Personality was evaluated by Tridimensional Personality Questionnaire and Neuroticism Extraversion Openness Personality Inventory. Brain structural and functional properties, including gray matter volume, spontaneous brain activity and functional connectivity, were computed based on magnetic resonance imaging (MRI). Linear regression was used to evaluate the associations between personality and academic achievements. A voxel-wise correlation was used to identify areas of the brain where structural and functional properties were associated with academic achievements. Mediation analysis was used to test whether brain properties and personality independently contribute to academic achievements. Our results showed that novelty seeking (NS) was negatively correlated, and conscientiousness was positively correlated with all types of academic achievements. Brain functional properties showed negatively correlated with academic achievement in basic biomedical sciences. However, we did not find any mediation effect of the brain functional properties on the association between personality (NS and conscientiousness) and academic achievement in basic biomedical sciences, nor mediation effect of the personality (NS and conscientiousness) on the association between brain functional properties and academic achievement in basic biomedical sciences. These findings suggest that specific personality (NS and conscientiousness) and brain functional properties independently contribute to academic achievements in basic biomedical sciences, and that modulation of these properties may benefit academic achievements among medical students.

4.
Environ Int ; 169: 107522, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36137426

RESUMO

As new agrochemicals are continuously introduced into agricultural systems, it is essential to investigate their uptake and metabolism by plants to better evaluate their fate and accumulation in crops and the subsequent risks to human exposure. In this study, the uptake and elimination kinetics and transformation of a novel insecticide, cyetpyrafen, in two model crops (lettuce and rice) were first evaluated by hydroponic experiments. Cyetpyrafen was rapidly taken up by plant roots and reached a steady state within 24 h, and it was preferentially accumulated in root parts with root concentration factors up to 2670 mL/g. An uptake mechanism study suggested that root uptake of cyetpyrafen was likely to be dominated by passive diffusion and was difficult to transport via xylem and phloem. Ten phase I and three phase II metabolites of cyetpyrafen were tentatively identified in the hydroponic-plant system through a nontarget screening strategy. The structures of two main metabolites (M-309 and M-391) were confirmed by synthesized standards. The metabolic pathways were proposed including hydroxylation, hydrolysis, dehydrogenation, dehydration and conjugation, which were assumed to be regulated by cytochrome P450, carboxylesterase, glycosyltransferase, glutathione S-transferases and peroxidase. Cyetpyrafen and its main metabolites (M-409, M-309 and M-391) were estimated to be harmful/toxic toward nontarget organisms by theoretical calculation. The high bioaccumulation and extensive transformation of cyetpyrafen highlighted the necessity for systematically assessing the crop uptake and metabolism of new agrochemicals.

5.
Materials (Basel) ; 15(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36143750

RESUMO

Isothermal-compression tests of B4Cp/6063Al composites containing 20 vol.% B4C were performed using a Gleeble-3500 device, at strain rates ranging from 0.001 s-1 to 1 s-1 and deformation temperatures ranging from 723 K to 823 K. The results showed that the high-temperature flow stress of B4Cp/6063Al composites increases with the decrease in deformation temperature or the increase in the strain rate. After friction correction, the friction corrected stress was less than the original experimental stress. At the initial stage of deformation, the difference between the rheological stress after friction correction and the measured rheological stress is small, but with the continuous increase in the strain, the difference between the rheological stress after friction correction and the measured rheological stress is grows. Under the same strain, the difference between the rheological stress before and after friction correction becomes more significant with the decrease in the deformation temperature and the increase in the strain rate. Next, the material constants (i.e., α, ß, Q, A, n) of B4Cp/6063Al composites were calibrated based on the experimental data, and a constitutive equation was established based on Arrhenius theory. The experimental values and predicted values of the stress-strain curves are in good agreement with the stress-strain curves of the finite element simulation, and the validity of the constitutive equation was verified.

6.
Front Genet ; 13: 967688, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118902

RESUMO

Craniosynostosis (CRS) is a disease with prematurely fused cranial sutures. In the last decade, the whole-exome sequencing (WES) was widely used in Caucasian populations. The WES largely contributed in genetic diagnosis and exploration on new genetic mechanisms of CRS. In this study, we enrolled 264 CRS patients in China. After a 17-gene-panel sequencing designed in the previous study, 139 patients were identified with pathogenic/likely pathogenic (P/LP) variants according to the ACMG guideline as positive genetic diagnosis. WES was then performed on 102 patients with negative genetic diagnosis by panel. Ten P/LP variants were additionally identified in ten patients, increasing the genetic diagnostic yield by 3.8% (10/264). The novel variants in ANKH, H1-4, EIF5A, SOX6, and ARID1B expanded the mutation spectra of CRS. Then we designed a compatible research pipeline (RP) for further exploration. The RP could detect all seven P/LP SNVs and InDels identified above, in addition to 15 candidate variants found in 13 patients with worthy of further study. In sum, the 17-gene panel and WES identified positive genetic diagnosis for 56.4% patients (149/264) in 16 genes. At last, in our estimation, the genetic testing strategy of "Panel-first" saves 24.3% of the cost compared with "WES only", suggesting the "Panel-first" is an economical strategy.

7.
ACS Appl Mater Interfaces ; 14(37): 41834-41850, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36073504

RESUMO

Combining photodynamic therapy (PDT) with natural killer (NK) cell-based immunotherapy has shown great potential against cancers, but the shedding of NK group 2, member D ligands (NKG2DLs) on tumor cells inhibited NK cell activation in the tumor microenvironment. Herein, we assembled microenvironment-/light-responsive bio-nanosystems (MLRNs) consisting of SB-3CT-containing ß-cyclodextrins (ß-CDs) and photosensitizer-loaded liposomes, in which SB-3CT was considered to remodel the tumor microenvironment. ß-CDs and liposomes were linked by metalloproteinase 2 (MMP-2) responsive peptides, enabling sequential release of SB-3CT and chlorin e6 triggered by the MMP-2-abundant tumor microenvironment and 660 nm laser irradiation, respectively. Released SB-3CT blocked tumor immune escape by antagonizing MMP-2 and promoting the NKG2D/NKG2DL pathway, while liposomes were taken up by tumor cells for PDT. MLRN-mediated photo-immunotherapy significantly induced melanoma cell cytotoxicity (83.31%), inhibited tumor growth (relative tumor proliferation rate: 1.13% of that of normal saline) in the xenografted tumor model, and enhanced tumor-infiltrating NK cell (148 times) and NKG2DL expression (9.55 and 16.52 times for MICA and ULBP-1, respectively), achieving a synergistic effect. This study not only provided a simple insight into the development of new nanomedicine for programed release of antitumor drugs and better integration of PDT and immunotherapy but also a novel modality for clinical NK cell-mediated immunotherapy against melanoma.


Assuntos
Antineoplásicos , Inibidores Enzimáticos/farmacologia , Melanoma , beta-Ciclodextrinas , Linhagem Celular Tumoral , Compostos Heterocíclicos com 1 Anel , Humanos , Imunoterapia , Lipossomos , Metaloproteinase 2 da Matriz , Melanoma/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Solução Salina , Sulfonas , Triazenos , Microambiente Tumoral
8.
Int J Mol Sci ; 23(16)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36012653

RESUMO

Sublethal doses of insecticides have many impacts on pest control and agroecosystems. Insects that survive a sublethal dose of insecticide could adapt their physiological and behavioral functions and resist this environmental stress, which contributes to the challenge of pest management. In this study, the sublethal effects of thiamethoxam on gene expression were measured through RNA sequencing in the melon aphid Aphis gossypii. Genes regulating energy production were downregulated, while genes related to neural function were upregulated. To further address the function of genes related to neurotransmission, RNA interference (RNAi) was implemented by transdermal delivery of dsRNA targeting synapsin (syn), a gene regulating presynaptic vesicle clustering. The gene expression of synapsin was knocked down and the mortality of aphids was increased significantly over the duration of the assay. Co-delivery of syn-dsRNA and thiamethoxam reversed the upregulation of synapsin caused by low-dose thiamethoxam and resulted in lethality to melon aphids, suggesting that the decreased presynaptic function may contribute to this synergistic lethal effect. In addition, the nanocarrier star polycation, which could bind both dsRNA and thiamethoxam, greatly improved the efficacy of lethality. These results increase our knowledge of the gene regulation induced by sublethal exposure to neonicotinoids and indicated that synapsin could be a potential RNAi target for resistance management of the melon aphid.


Assuntos
Afídeos , Inseticidas , Animais , Afídeos/genética , Inseticidas/farmacologia , Nitrocompostos/farmacologia , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/farmacologia , Sinapsinas/genética , Transmissão Sináptica , Tiametoxam/farmacologia
9.
Inorg Chem ; 61(35): 13768-13774, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35998355

RESUMO

A new metal-organic framework (MOF) with tetrazole-derived triphenylamine (TPA) as the ligand, namely Mn-TPA, has been successfully prepared and thoroughly characterized via thermogravimetric analysis, IR spectroscopy, elemental analysis, UV-vis absorption, fluorescence analysis, bond valence sum calculations, and single-crystal and powder X-ray diffraction analysis. The undulating monolayer of Mn-TPA can hinder the interaction and tight stacking among analytes, which creates a bionic microenvironment for the electrochemical recognition process. Mn-TPA exhibits high specific surface area, stable film-forming capacity, excellent electrochemical activity, and good biocompatibility. Furthermore, the developed Mn-TPA-based immunosensing system exhibits an excellent limit of detection of 0.50 pg·mL-1 toward vomitoxin, which is more outstanding than that of the reported vomitoxin-sensing system. Thus, this work shows the great potential of a well-designed MOF as an easy-to-make and highly sensitive electrochemical platform for biosensing in food safety detection and other fields.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Técnicas Biossensoriais/métodos , Inspeção de Alimentos , Estruturas Metalorgânicas/química , Tetrazóis
10.
Cell Death Dis ; 13(8): 674, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927240

RESUMO

Transmembrane of coiled-coil domains 1 (TMCO1) plays an important role in maintaining homeostasis of calcium (Ca2+) stores in the endoplasmic reticulum (ER). TMCO1-defect syndrome shares multiple features with human cerebro-facio-thoracic (CFT) dysplasia, including abnormal corpus callosum (CC). Here, we report that TMCO1 is required for the normal development of CC through sustaining Ca2+ homeostasis. Tmco1-/- mice exhibit severe agenesis of CC with stalled white matter fiber bundles failing to pass across the midline. Mechanistically, the excessive Ca2+ signals caused by TMCO1 deficiency result in upregulation of FGFs and over-activation of ERK, leading to an excess of glial cell migration and overpopulated midline glia cells in the indusium griseum which secretes Slit2 to repulse extension of the neural fiber bundles before crossing the midline. Supportingly, using the clinical MEK inhibitors to attenuate the over-activated FGF/ERK signaling can significantly improve the CC formation in Tmco1-/- brains. Our findings not only unravel the underlying mechanism of abnormal CC in TMCO1 defect syndrome, but also offer an attractive prevention strategy to relieve the related agenesis of CC in patients.


Assuntos
Corpo Caloso , Deficiência Intelectual , Animais , Canais de Cálcio/metabolismo , Corpo Caloso/metabolismo , Retículo Endoplasmático/metabolismo , MAP Quinases Reguladas por Sinal Extracelular , Homeostase , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Neurogênese
11.
Neuroimage ; 260: 119436, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35788043

RESUMO

Pain is subjective and perceived differently in different people. However, individual differences in pain-elicited brain activations are largely overlooked and often discarded as noises. Here, we used a brain-activation-based individual identification procedure to investigate the uniqueness of the activation patterns within the whole brain or brain regions elicited by nociceptive (laser) and tactile (electrical) stimuli in each of 62 healthy participants. Specifically, brain activation patterns were used as "fingerprints" to identify each individual participant within and across sensory modalities, and individual identification accuracy was calculated to measure each individual's identifiability. We found that individual participants could be successfully identified using their brain activation patterns elicited by nociceptive stimuli, tactile stimuli, or even across modalities. However, different participants had different identifiability; importantly, the within-pain, but not within-touch or cross-modality, individual identifiability obtained from three brain regions (i.e., the left superior frontal gyrus, the middle temporal gyrus and the insular gyrus) were inversely correlated with the scores of Pain Vigilance and Awareness Questionnaire (i.e., how a person is alerted to pain) across participants. These results suggest that each individual has a unique pattern of brain responses to nociceptive stimuli which contains both modality-nonspecific and pain-specific information and may be associated with pain-related behaviors shaped by his/her own personal experiences and highlight the importance of a transition from group-level to individual-level characterization of brain activity in neuroimaging studies.


Assuntos
Percepção do Tato , Tato , Encéfalo , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Dor , Tato/fisiologia , Percepção do Tato/fisiologia
12.
Cell ; 185(15): 2623-2625, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35868266

RESUMO

Technological advances in a variety of scientific disciplines are being applied in the life sciences leading to an increase in the number scientists who see themselves or are classed as being multidisciplinary. Although their diverse skills are celebrated and needed to understand the immense complexity of life, being a multidisciplinary researcher can pose unique challenges. We asked multidisciplinary researchers and the director of an institute that fosters multidisciplinary research for their thoughts on what they see as the challenges or obstacles that multidisciplinary scientists can often face.


Assuntos
Pesquisa Interdisciplinar , Pesquisadores , Humanos
13.
Reprod Biol Endocrinol ; 20(1): 96, 2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780124

RESUMO

Myostatin (MSTN) is member of the transforming growth factor ß (TGF-ß) superfamily and was originally identified in the musculoskeletal system as a negative regulator of skeletal muscle growth. The functional roles of MSTN outside of the musculoskeletal system have aroused researchers' interest in recent years, with an increasing number of studies being conducted in this area. Notably, the expression of MSTN and its potential activities in various reproductive organs, including the ovary, placenta, and uterus, have recently been examined. Numerous studies published in the last few years demonstrate that MSTN plays a critical role in human reproduction and fertility, including the regulation of follicular development, ovarian steroidogenesis, granule-cell proliferation, and oocyte maturation regulation. Furthermore, findings from clinical samples suggest that MSTN may play a key role in the pathogenesis of several reproductive disorders such as uterine myoma, preeclampsia (PE), ovary hyperstimulation syndrome (OHSS), and polycystic ovarian syndrome (PCOS). There is no comprehensive review regarding to MSTN related to the female reproductive system in the literature. This review serves as a summary of the genes in reproductive medicine and their potential influence. We summarized MSTN expression in different compartments of the female reproductive system. Subsequently, we discuss the role of MSTN in both physiological and several pathological conditions related to the female fertility and reproduction-related diseases.


Assuntos
Fertilidade , Miostatina , Reprodução , Feminino , Fertilidade/genética , Humanos , Miostatina/genética , Miostatina/metabolismo , Ovário/metabolismo , Reprodução/genética , Fator de Crescimento Transformador beta
14.
Stem Cell Res Ther ; 13(1): 270, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729659

RESUMO

Stem and progenitor cells (SPCs) possess self-remodeling ability and differentiation potential and are responsible for the regeneration and development of organs and tissue systems. However, the precise mechanisms underlying the regulation of SPC biology remain unclear. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) acts on miscellaneous cells via binding to fibroblast growth factor-inducible 14 (Fn14) and exerts pleiotropic functions in the regulation of divergent stem cell fates. TWEAK/Fn14 signaling can regulate the proliferation, differentiation, and migration of multiple SPCs as well as tumorigenesis in certain contexts. Although TWEAK's roles in modulating multiple SPCs are sparsely reported, the systemic effector functions of this multifaceted protein have not been fully elucidated. In this review, we summarized the fate decisions of TWEAK/Fn14 signaling on multiple stem cells and characterized its potential in stem cell therapy.


Assuntos
Receptores do Fator de Necrose Tumoral , Transdução de Sinais , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo , Receptor de TWEAK/genética , Receptor de TWEAK/metabolismo , Fator de Necrose Tumoral alfa
15.
Pharmaceutics ; 14(6)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35745695

RESUMO

(1) Background: Acute ischemic stroke (IS) is one of the main causes of human disability and death. Therefore, multifunctional nanosystems that effectively cross the blood-brain barrier (BBB) and efficiently eliminate reactive oxygen species (ROS) are urgently needed for comprehensive neuroprotective effects. (2) Methods: We designed a targeted transferrin (Tf)-based manganese dioxide nanozyme (MnO2@Tf, MT) using a mild biomimetic mineralization method for rebalancing ROS levels. Furthermore, MT can be efficiently loaded with edaravone (Eda), a clinical neuroprotective agent, to obtain the Eda-MnO2@Tf (EMT) nanozyme. (3) Results: The EMT nanozyme not only accumulates in a lesion area and crosses the BBB but also possesses satisfactory biocompatibility and biosafety based on the functional inheritance of Tf. Meanwhile, EMT has intrinsic hydroxyl radical-scavenging ability and superoxide-dismutase-like and catalase-like nanozyme abilities, allowing it to ameliorate ROS-mediated damage and decrease inflammatory factor levels in vivo. Moreover, the released Mn2+ ions in the weak acid environment of the lesion area can be used for magnetic resonance imaging (MRI) to monitor the treatment process. (4) Conclusions: Our study not only paves a way to engineer alternative targeted ROS scavengers for intensive reperfusion-induced injury in ischemic stroke but also provides new insights into the construction of bioinspired Mn-based nanozymes.

16.
J Immunother Cancer ; 10(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35738798

RESUMO

BACKGROUND: Although anti-programmed cell death protein 1 (PD-1) immunotherapy is greatly effective in melanoma treatment, low response rate and treatment resistance significantly hinder its efficacy. Tumor cell ferroptosis triggered by interferon (IFN)-γ that is derived from tumor-infiltrating CD8+ T cells greatly contributes to the effect of immunotherapy. However, the molecular mechanism underlying IFN-γ-mediated ferroptosis and related potentially promising therapeutic strategy warrant further clarification. MicroRNAs (miRNAs) participate in ferroptosis execution and can be delivered systemically by multiple carriers, which have manifested obvious therapeutic effects on cancer. METHODS: MiRNAs expression profile in IFN-γ-driven ferroptosis was obtained by RNA sequencing. Biochemical assays were used to clarify the role of miR-21-3p in IFN-γ-driven ferroptosis and the underlying mechanism. MiR-21-3p-loaded gold nanoparticles were constructed and systemically applied to analyze the role of miR-21-3p in anti-PD-1 immunotherapy in preclinical transplanted tumor model. RESULTS: MiRNAs expression profile of melanoma cells in IFN-γ-driven ferroptosis was first obtained. Then, upregulated miR-21-3p was proved to facilitate IFN-γ-mediated ferroptosis by potentiating lipid peroxidation. miR-21-3p increased the ferroptosis sensitivity by directly targeting thioredoxin reductase 1 (TXNRD1) to enhance lipid reactive oxygen species (ROS) generation. Furthermore, miR-21-3p overexpression in tumor synergized with anti-PD-1 antibody by promoting tumor cell ferroptosis. More importantly, miR-21-3p-loaded gold nanoparticles were constructed, and the systemic delivery of them increased the efficacy of anti-PD-1 antibody without prominent side effects in preclinical mice model. Ultimately, ATF3 was found to promote miR-21-3p transcription in IFN-γ-driven ferroptosis. CONCLUSIONS: MiR-21-3 p upregulation contributes to IFN-γ-driven ferroptosis and synergizes with anti-PD-1 antibody. Nanoparticle delivery of miR-21-3 p is a promising therapeutic approach to increase immunotherapy efficacy without obvious systemic side effects.


Assuntos
Ferroptose , Melanoma , Nanopartículas Metálicas , MicroRNAs , Animais , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Ouro , Humanos , Imunoterapia , Melanoma/tratamento farmacológico , Melanoma/genética , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo
17.
J Hazard Mater ; 437: 129394, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35749899

RESUMO

Microplastics (MPs), as emerging contaminant detected in dyeing sludge (DS), inevitably affected the subsequent treatment and disposal of DS. However, the effect of MPs on the predominant disposal path (incineration) of DS remains far from explicit. This study used thermogravimetry-mass spectrometry (TG-MS) method to explore the effect of representative MPs, polyethylene terephthalate (PET) and polyvinyl chloride (PVC), on combustion characteristics, gas evolution and kinetics on DS combustion. Results showed that PET inhibited the whole combustion of DS by physical barrier. Relatively, PVC delayed the combustion of light volatile but promoted heavy volatile and char reaction due to HCl catalyst. Generally, MPs deteriorated the combustibility, burnout performance and combustion stability of DS. MPs aggravated HCl and gaseous N emissions. Noticeably, the interactions between DS and PVC accelerated the emissions of gaseous pollutants, especially under high dose condition. DAEM and FWO models could well describe the combustion kinetic of DS containing MPs. MPs led to an increase in activation energy of DS, namely, it deteriorated the combustion efficiency of DS. The combustion mechanisms could be divided into two stages: (1) diffusion (D3) stage: melted MPs blocked the gas channels, (2) chemical reaction (F3): the residual chars were thermally stable.


Assuntos
Incineração , Esgotos , Corantes , Gases , Microplásticos , Plásticos , Cloreto de Polivinila , Esgotos/química
18.
J Biomed Nanotechnol ; 18(3): 837-848, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35715898

RESUMO

Minimally invasive photodynamic therapy, destroying lesions with a light-activated photosensitizer, has been increasingly performed since it is highly efficiency, safe, synergistically compatible, repeatable, and minimally-invasive, with few adverse reactions. However, the most present photosensitizer or nanodrug delivery system containing a photosensitizer can target tumor cells but rarely cell nuclei. In this regard, the nucleus-targeting drug delivery system has been developed aiming impair tumor cells in an efficient and direct manner. In this study, the cationic liposome (Clip) drug delivery system integrated with low dose nucleus-targeting chemotherapeutic drug Doxorubicin (DOX) and photosensitizer AlPcS4 (Clip-AlPcS4@DOX) was synthesized. Among them, Clip was used to efficiently load drugs into cells almost at the same time, low dose DOX was used to open the channel for the materials to enter the nucleus on the premise of ensuring low cytotoxicity and then introduced photosensitizer into the nucleus, AlPcS4 photosensitizer was used to damage directly and efficiently through the photodynamic therapy (PDT) effect after entering the nucleus. In summary, a nucleus-targeting nanodrug delivery system (Clip-AlPcS4@DOX) was designed and synthesized and could be induced cell apoptosis more quickly and efficiently. Therefore, it could be a promising nucleus-targeting nanosized reagent integrating the PDT and chemotherapy for gastric therapy.


Assuntos
Fotoquimioterapia , Linhagem Celular Tumoral , Núcleo Celular , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Lipossomos , Fármacos Fotossensibilizantes/farmacologia
19.
iScience ; 25(5): 104249, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35521536

RESUMO

L3MBTL2 is a crucial component of ncPRC1.6 and has been implicated in transcriptional repression and chromatin compaction. However, the repression mechanism of L3MBTL2 and its biological functions are largely undefined. Here, we found that L3MBTL2 plays a distinct oncogenic role in tumor development. We demonstrated that L3MBTL2 repressed downstream CGA through an H2AK119ub1-dependent mechanism. Importantly, the binding of the MGA/MAX heterodimer to the E-box on the CGA promoter enhanced the specific selective repression of CGA by L3MBTL2. CGA encodes the alpha subunit of glycoprotein hormones; however, we showed that CGA plays an individual tumor suppressor role in PDAC. Moreover, CGA-transcript1 (T1) was identified as the major transcript, and the tumor suppression function of CGA-T1 depends on its own glycosylation. Furthermore, glycosylated CGA-T1 inhibited PDAC, partly by repression of autophagy through multiple pathways, including PI3K/Akt/mTOR and TP53INP2 pathways. These findings reveal the important roles of L3MBTL2 and CGA in tumor development.

20.
Biomedicines ; 10(5)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35625884

RESUMO

Bone morphogenetic protein (BMP) signaling has been shown to be intimately associated with adult neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ). Adult neurogenesis declines in aging rodents and primates. However, the role of BMP signaling in the age-related neurogenesis decline remains elusive and the effect of BMP4 on adult SVZ neurogenesis remains controversial. Here, the expression of BMP4 and its canonical effector phosphorylated-Smad1/5/8 (p-Smad1/5/8) in the murine SVZ and SGZ were found to be increased markedly with age. We identified Id3 as a major target of BMP4 in neuronal stem cells (NSCs) of both neurogenic regions, which exhibited a similar increase during aging. Intracerebroventricular infusion of BMP4 activated Smad1/5/8 phosphorylation and upregulated Id3 expression, which further restrained NeuroD1, leading to attenuated neurogenesis in both neurogenic regions and defective differentiation in the SGZ. Conversely, noggin, a potent inhibitor of BMP4, demonstrated opposing effects. In support of this, BMP4 treatment or lentiviral overexpression of Id3 resulted in decreased NeuroD1 protein levels in NSCs of both neurogenic regions and significantly inhibited neurogenesis. Thus, our findings revealed that the increased BMP4 signaling with age inhibited adult neurogenesis in both SVZ and SGZ, which may be attributed at least in part, to the changes in the Id3-NeuroD1 axis.

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