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1.
Chemistry ; : e202401826, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747420

RESUMO

Reaction of a rare and well-characterized MnIII-superoxo species, Mn(BDPBrP)(O2•) (1, H2BDPBrP = 2,6-bis((2-(S)-di(4-bromo)phenylhydroxylmethyl-1-pyrrolidinyl)methyl)pyridine), with 4-dimethylaminophenol at -80 °C proceeds via concerted proton electron transfer (CPET) to produce a MnIII-hydroperoxo complex, Mn(BDPBrP)(OOH) (2), alongside 4-dimethylaminophenoxy radical; whereas, upon treatment with 4-nitrophenol, complex 1 undergoes a proton transfer process to afford a MnIV-hydroperoxo complex, [Mn(BDPBrP)(OOH)]+ (3). Intriguingly, the reactions of 1 with 4-chlorophenol and 4-methoxyphenol follow two routes of CPET and sequential proton and electron transfer to furnish complex 2 in the end. UV-vis and EPR spectroscopic studies coupled with DFT calculations provided support for this wide mechanistic spectrum of activating various phenol O-H bonds by a single MnIII-superoxo complex, 1.

2.
Mol Cell ; 83(23): 4239-4254.e10, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38065062

RESUMO

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.


Assuntos
Leucemia , Síndromes Mielodisplásicas , Neoplasias , Metilação de RNA , Fatores de Processamento de Serina-Arginina , Humanos , Leucemia/genética , Síndromes Mielodisplásicas/genética , Neoplasias/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Fatores de Processamento de Serina-Arginina/genética , Metilação de RNA/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-38082741

RESUMO

Three germ layer formation on micropatterns are extremely useful for quantitative analysis of hiPSC (human induced pluripotent stem cells) pluripotency. Spatial patterns of stem cells differentiated on the micropatterns will be formed from about 24 hours after differentiation induction and usually quantitated near 48 hours. To delineate the germ layer formation process, temporal changes in spatial patterning of germ layers should be analyzed by noninvasive microscopy. This study proposed a series of image processing methods combined with a U-net automatic segmentation to segment differentiated hiPSCs captured by bright-field microscopy. High segmentation accuracy (83.3%) for the test bright-field images compared with their concurrent Hoechst images (85%) was achieved. Tempo-spatial patterning and formation process of germ layers on the micropatterns can be visualized and quantified by segmenting time-lapse bright-field microscopy images using our method.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Microscopia/métodos , Imagem com Lapso de Tempo , Diferenciação Celular
4.
Sci Rep ; 13(1): 17595, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845277

RESUMO

In this study, we passively analyzed the near-field characteristics of thermally excited evanescent waves, which are radiation waves generated by the local dynamics of materials, including electron motions and lattice vibrations. The thermally excited evanescent waves on aluminium nitride (AlN) and gallium nitride (GaN) were measured using passive spectroscopic scattering-type scanning near-field optical microscopy (s-SNOM) in the wavelength ranges of 10.5-12.2 µm and 14.0-15.0 µm, which include the surface phonon-polariton (SPhP) wavelength of the studied dielectrics. We determined the unique decay characteristics of AlN and GaN, indicating a ten-fold increase in the probe area contributing to the scattering of waves near the SPhP wavelength compared to that in other wavelength ranges. The extended probe area correlated with the polariton decay lengths, indicating that the non-enhanced polaritons around K ~ ω/c were dominant in the scattered waves near the SPhP wavelength. In addition to the conventional passive detection mechanisms for metals, the proposed detection scheme will be a versatile passive detection model in the near future.

5.
Front Endocrinol (Lausanne) ; 14: 1216584, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37608795

RESUMO

Background: Risk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone. Methods: We retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle. Results: Following confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035-47.274). Group 1 (b = -12.72; 95% CI -20.9 to -4.55) and BMI (b = -0.25; 95% CI -0.5 to -0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS. Conclusions: The maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes.


Assuntos
Hormônio Liberador de Gonadotropina , Oócitos , Feminino , Humanos , Gravidez , Coeficiente de Natalidade , Hormônio Liberador de Gonadotropina/agonistas , Estudos Retrospectivos
6.
Proc Natl Acad Sci U S A ; 120(32): e2307323120, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37523554

RESUMO

The complex and heterogeneous nature of the lignin macromolecule has presented a lasting barrier to its utilization. To achieve high lignin yield, the technical lignin extraction process usually severely modifies and condenses the native structure of lignin, which is a critical drawback for its utilization in conversion processes. In addition, there is no method capable of separating lignin from plant biomass with controlled structural properties. Here, we developed an N-heterocycle-based deep eutectic solvent formed between lactic acid and pyrazole (La-Py DES) with a binary hydrogen bonding functionality resulting in a high affinity toward lignin. Up to 93.7% of lignin was extracted from wheat straw biomass at varying conditions from 90 °C to 145 °C. Through careful selection of treatment conditions as well as lactic acid to pyrazole ratios, lignin with controlled levels of ether linkage content, hydroxyl group content, and average molecular weight can be generated. Under mild extraction conditions (90 °C to 120 °C), light-colored native-like lignin can be produced with up to 80% yield, whereas ether linkage-free lignin with low polydispersity can be obtained at 145 °C. Overall, this study offers a new strategy for native lignin extraction and generating lignin with controlled structural properties.

7.
J Biomed Sci ; 30(1): 25, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37069555

RESUMO

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a clinically critical pathogen that causes severe infection. Due to improper antibiotic administration, the prevalence of CRKP infection has been increasing considerably. In recent years, the utilization of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has enabled the identification of bacterial isolates at the families and species level. Moreover, machine learning (ML) classifiers based on MALDI-TOF MS have been recently considered a novel method to detect clinical antimicrobial-resistant pathogens. METHODS: A total of 2683 isolates (369 CRKP cases and 2314 carbapenem-susceptible Klebsiella pneumoniae [CSKP]) collected in the clinical laboratories of Taipei Medical University Hospital (TMUH) were included in this study, and 80% of data was split into the training data set that were submitted for the ML model. The remaining 20% of data was used as the independent data set for external validation. In this study, we established an artificial neural network (ANN) model to analyze all potential peaks on mass spectrum simultaneously. RESULTS: Our artificial neural network model for detecting CRKP isolates showed the best performance of area under the receiver operating characteristic curve (AUROC = 0.91) and of area under precision-recall curve (AUPRC = 0.90). Furthermore, we proposed the top 15 potential biomarkers in probable CRKP isolates at 2480, 4967, 12,362, 12,506, 12,855, 14,790, 15,730, 16,176, 16,218, 16,758, 16,919, 17,091, 18,142, 18,998, and 19,095 Da. CONCLUSIONS: Compared with the prior MALDI-TOF and machine learning studies of CRKP, the amount of data in our study was more sufficient and allowing us to conduct external validation. With better generalization abilities, our artificial neural network model can serve as a reliable screening tool for CRKP isolates in clinical practice. Integrating our model into the current workflow of clinical laboratories can assist the rapid identification of CRKP before the completion of traditional antimicrobial susceptibility testing. The combination of MADLI-TOF MS and machine learning techniques can support physicians in selecting suitable antibiotics, which has the potential to enhance the patients' outcomes and lower the prevalence of antimicrobial resistance.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Redes Neurais de Computação , Lasers
8.
Cancer Discov ; 13(7): 1678-1695, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37098965

RESUMO

Inflammation is strongly associated with pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy. Dysregulated RNA splicing factors have been widely reported in tumorigenesis, but their involvement in pancreatitis and PDAC is not well understood. Here, we report that the splicing factor SRSF1 is highly expressed in pancreatitis, PDAC precursor lesions, and tumors. Increased SRSF1 is sufficient to induce pancreatitis and accelerate KRASG12D-mediated PDAC. Mechanistically, SRSF1 activates MAPK signaling-partly by upregulating interleukin 1 receptor type 1 (IL1R1) through alternative-splicing-regulated mRNA stability. Additionally, SRSF1 protein is destabilized through a negative feedback mechanism in phenotypically normal epithelial cells expressing KRASG12D in mouse pancreas and in pancreas organoids acutely expressing KRASG12D, buffering MAPK signaling and maintaining pancreas cell homeostasis. This negative feedback regulation of SRSF1 is overcome by hyperactive MYC, facilitating PDAC tumorigenesis. Our findings implicate SRSF1 in the etiology of pancreatitis and PDAC, and point to SRSF1-misregulated alternative splicing as a potential therapeutic target. SIGNIFICANCE: We describe the regulation of splicing factor SRSF1 expression in the context of pancreas cell identity, plasticity, and inflammation. SRSF1 protein downregulation is involved in a negative feedback cellular response to KRASG12D expression, contributing to pancreas cell homeostasis. Conversely, upregulated SRSF1 promotes pancreatitis and accelerates KRASG12D-mediated tumorigenesis through enhanced IL1 and MAPK signaling. This article is highlighted in the In This Issue feature, p. 1501.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite , Animais , Camundongos , Processamento Alternativo , Carcinogênese/genética , Carcinoma Ductal Pancreático/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Inflamação , Neoplasias Pancreáticas/patologia , Pancreatite/genética , Pancreatite/complicações , Pancreatite/patologia , Fatores de Processamento de RNA/genética , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Humanos
9.
Tzu Chi Med J ; 35(1): 58-61, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36866341

RESUMO

Objectives: The influence of chronic liver disease (CLD) on emergent neurosurgical outcomes in patients with spontaneous intracerebral hemorrhage (ICH) remains unclear. CLD is usually associated with coagulopathy and thrombocytopenia, which contribute to a high rebleeding rate and poor prognosis after surgery. This study aimed to confirm the outcomes of spontaneous intracranial hemorrhage in patients with CLD after emergent neurosurgery. Materials and Methods: We reviewed the medical records of all patients with spontaneous ICH from February 2017 to February 2018 at the Buddhist Tzu Chi Hospital, Hualien, Taiwan. This study was approved by the Review Ethical Committee/Institutional Board Review of Hualien Buddhist Tzu Chi Hospital (IRB111-051-B). Patients with aneurysmal subarachnoid hemorrhage, tumors, arteriovenous malformations, and those younger than 18 years were excluded. Duplicate electrode medical records were also removed. Results: Among the 117 enrolled patients, 29 had CLD and 88 did not. There were no significant differences in essential characteristics, comorbidities, biochemical profile, Glasgow coma scale (GCS) score at admission, or ICH sites. The length of hospital stay (LOS) and length of intensive care unit stay (LOICUS) are significantly longer in the CLD group (LOS: 20.8 vs. 13.5 days, P = 0.012; LOICUS: 11 vs. 5 days, P = 0.007). There was no significant difference in the mortality rate between the groups (31.8% vs. 28.4%, P = 0.655). The Wilcoxon rank-sum test for liver and coagulation profiles between survivors and the deceased revealed significant differences in the international normalized ratio (P = 0.02), including low platelet counts (P = 0.03) between survivors and the deceased. A multivariate analysis of mortality found that every 1 mL increase in ICH at admission increased the mortality rate by 3.9%, and every reduction in GCS at admission increased the mortality rate by 30.7%. In our subgroup analysis, we found that the length of ICU stay and LOS are significantly longer in patients with CLD who underwent emergent neurosurgery: 17.7 ± 9.9 days versus 7.59 ± 6.68 days, P = 0.002, and 27.1 ± 7.3 days versus 16.36 ± 9.08 days, P = 0.003, respectively. Conclusions: From our study's perspective, emergent neurosurgery is encouraged. However, there were more prolonged ICU and hospital stays. The mortality rate of patients with CLD who underwent emergent neurosurgery was not higher than that of patients without CLD.

10.
Rev Sci Instrum ; 94(2): 023701, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859006

RESUMO

Passive scattering-type, scanning near-field optical microscopy (s-SNOM) has been employed to study localized, long-wavelength infrared (LWIR) surface waves without external illumination. Here, we develop a cryogenic passive s-SNOM instrument in a vacuum chamber with 4 K liquid-helium cooling. Notably, the extremely low-temperature environment inside the chamber enables the realization of passive near-field detection with low background thermal noise. The technique mainly utilizes a highly sensitive LWIR confocal optical system and a tuning fork-based atomic force microscope, and the near-field detection was performed at a wavelength of 10.2 ± 0.9 µm. In this paper, we discuss the cryogenic s-SNOM implementation in detail and report the investigation of thermally excited surface electromagnetic fields on a self-heated NiCr wire deposited on SiO2 at a temperature of 5 K. The origin of the surface electromagnetic fields was established to be the thermally excited fluctuating charges of the conduction electrons. The cryogenic s-SNOM method presented herein shows significant promise for application in a variety of spheres, including hot-carrier dissipation in ballistic conductors.

11.
Nature ; 617(7959): 147-153, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36949200

RESUMO

Pancreatic ductal adenocarcinoma (PDA) is characterized by aggressive local invasion and metastatic spread, leading to high lethality. Although driver gene mutations during PDA progression are conserved, no specific mutation is correlated with the dissemination of metastases1-3. Here we analysed RNA splicing data of a large cohort of primary and metastatic PDA tumours to identify differentially spliced events that correlate with PDA progression. De novo motif analysis of these events detected enrichment of motifs with high similarity to the RBFOX2 motif. Overexpression of RBFOX2 in a patient-derived xenograft (PDX) metastatic PDA cell line drastically reduced the metastatic potential of these cells in vitro and in vivo, whereas depletion of RBFOX2 in primary pancreatic tumour cell lines increased the metastatic potential of these cells. These findings support the role of RBFOX2 as a potent metastatic suppressor in PDA. RNA-sequencing and splicing analysis of RBFOX2 target genes revealed enrichment of genes in the RHO GTPase pathways, suggesting a role of RBFOX2 splicing activity in cytoskeletal organization and focal adhesion formation. Modulation of RBFOX2-regulated splicing events, such as via myosin phosphatase RHO-interacting protein (MPRIP), is associated with PDA metastases, altered cytoskeletal organization and the induction of focal adhesion formation. Our results implicate the splicing-regulatory function of RBFOX2 as a tumour suppressor in PDA and suggest a therapeutic approach for metastatic PDA.


Assuntos
Processamento Alternativo , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Processamento Alternativo/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Animais , Metástase Neoplásica , Adesões Focais
12.
Environ Sci Pollut Res Int ; 30(3): 6146-6158, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35987852

RESUMO

This study aimed to investigate the characteristics of, exposure to, and factors influencing gas-phase and PM2.5-bound phthalates (PAEs) in nail salons. Data on both indoor and outdoor gas-phase and PM2.5-bound PAEs, carbon dioxide (CO2), temperature, and relative humidity were collected in nail salons. We also used questionnaires to survey building characteristics and occupants' behaviors. The average total gas-phase and PM2.5-bound PAE concentrations indoors were higher than those outdoors by 6 and 3 times, respectively. Diethyl phthalate, diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di-(2-ethylhexyl) phthalate (DEHP) were the predominant compounds among both the gas-phase and PM2.5-bound PAEs in indoor air. The volume of the salon's space or the difference of indoor and outdoor CO2 concentrations (dCO2) was significantly associated with indoor PAE concentrations. The ratios of PM2.5-bound to gas-phase PAEs, especially high-molecular-weight PAEs, were positively associated with the dCO2 concentrations. Higher ratios of indoor to outdoor PM2.5-bound DiBP, DnBP, and DEHP concentrations were discovered when more clients visited each day. Building characteristics, ventilation conditions, and occupants' activities have influences on the gas-phase and particle-phase PAEs. The study identifies the characteristics of gas-phase and PM2.5-bound PAEs in nail salons and their influencing factors.


Assuntos
Poluição do Ar em Ambientes Fechados , Dietilexilftalato , Ácidos Ftálicos , Humanos , Poluição do Ar em Ambientes Fechados/análise , Dióxido de Carbono , Ácidos Ftálicos/análise , Material Particulado/análise , Ésteres/análise , China
13.
Nano Lett ; 22(20): 8137-8142, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36200986

RESUMO

Loading quantum information deterministically onto a quantum node is an important step toward a quantum network. Here, we demonstrate that coherent-state microwave photons with an optimal temporal waveform can be efficiently loaded onto a single superconducting artificial atom in a semi-infinite one-dimensional (1D) transmission-line waveguide. Using a weak coherent state (the number of photons (N) contained in the pulse ≪1) with an exponentially rising waveform, whose time constant matches the decoherence time of the artificial atom, we demonstrate a loading efficiency of 94.2% ± 0.7% from 1D semifree space to the artificial atom. The high loading efficiency is due to time-reversal symmetry: the overlap between the incoming wave and the time-reversed emitted wave is up to 97.1% ± 0.4%. Our results open up promising applications in realizing quantum networks based on waveguide quantum electrodynamics.

14.
Nucleic Acids Res ; 50(2): 731-749, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35018432

RESUMO

Intronic splicing enhancers and silencers (ISEs and ISSs) are two groups of splicing-regulatory elements (SREs) that play critical roles in determining splice-site selection, particularly for alternatively spliced introns or exons. SREs are often short motifs; their mutation or dysregulation of their cognate proteins frequently causes aberrant splicing and results in disease. To date, however, knowledge about SRE sequences and how they regulate splicing remains limited. Here, using an SMN2 minigene, we generated a complete pentamer-sequence library that comprises all possible combinations of 5 nucleotides in intron 7, at a fixed site downstream of the 5' splice site. We systematically analyzed the effects of all 1023 mutant pentamers on exon 7 splicing, in comparison to the wild-type minigene, in HEK293 cells. Our data show that the majority of pentamers significantly affect exon 7 splicing: 584 of them are stimulatory and 230 are inhibitory. To identify actual SREs, we utilized a motif set enrichment analysis (MSEA), from which we identified groups of stimulatory and inhibitory SRE motifs. We experimentally validated several strong SREs in SMN1/2 and other minigene settings. Our results provide a valuable resource for understanding how short RNA sequences regulate splicing. Many novel SREs can be explored further to elucidate their mechanism of action.


Assuntos
Íntrons , Precursores de RNA/genética , Splicing de RNA , Sequências Reguladoras de Ácido Ribonucleico , Processamento Alternativo , Composição de Bases , Sequência de Bases , Biologia Computacional/métodos , Éxons , Biblioteca Gênica , Células HEK293 , Humanos , Motivos de Nucleotídeos , Matrizes de Pontuação de Posição Específica , Sítios de Splice de RNA , Análise de Sequência de RNA , Proteína 2 de Sobrevivência do Neurônio Motor/genética
15.
Sci Total Environ ; 806(Pt 4): 151472, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742808

RESUMO

Airborne microplastic particles (MPs) are emerging contaminants. Although some studies have investigated the characteristics of indoor MPs in homes or offices, information regarding MPs in nail salons with potentially higher MP pollution is unavailable. In this study, we collected indoor and outdoor air samples from nail salons to analyze the concentrations, physical characteristics, and polymers of MPs and further assessed the exposure through inhalation and influencing factors. Our data displayed that the average indoor MP concentration was 46 ± 55 MPs/m3. The estimated average annual exposure to indoor MPs was 67,567 ± 81,782 MPs/year. The predominant shape and size of indoor MPs were fragment and <50 µm, respectively. The predominant polymer in indoor air was acrylic (27%), followed by rubber (21%), and polyurethane (13%). Air conditioner, nail treatment, ceiling and flooring with plastic materials, and number of occupants were factors affecting indoor MP concentrations. We concluded that MP pollution was more severe in nail salons and the physical characteristics and polymer compositions differed between nail salons and other indoor spaces reported in other studies. Air conditioner usage induced higher MP emission, and higher MP concentrations were observed in nail salons with plastic ceiling and flooring or more occupants.


Assuntos
Poluição do Ar em Ambientes Fechados , Microplásticos , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Poluição Ambiental , Unhas , Plásticos
16.
Cancer Res ; 82(5): 900-915, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34921016

RESUMO

The M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in regulation of the Warburg effect, which is characterized by the preference for aerobic glycolysis over oxidative phosphorylation for energy metabolism. PKM2 is an alternative-splice isoform of the PKM gene and is a potential therapeutic target. Antisense oligonucleotides (ASO) that switch PKM splicing from the cancer-associated PKM2 to the PKM1 isoform have been shown to induce apoptosis in cultured glioblastoma cells when delivered by lipofection. Here, we explore the potential of ASO-based PKM splice switching as a targeted therapy for liver cancer. A more potent lead constrained-ethyl (cEt)/DNA ASO induced PKM splice switching and inhibited the growth of cultured hepatocellular carcinoma (HCC) cells. This PKM isoform switch increased pyruvate-kinase activity and altered glucose metabolism. In an orthotopic HCC xenograft mouse model, the lead ASO and a second ASO targeting a nonoverlapping site inhibited tumor growth. Finally, in a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis, without observable toxicity. These results lay the groundwork for a potential ASO-based splicing therapy for HCC. SIGNIFICANCE: Antisense oligonucleotides are used to induce a change in PKM isoform usage in hepatocellular carcinoma, reversing the Warburg effect and inhibiting tumorigenesis.


Assuntos
Processamento Alternativo , Carcinoma Hepatocelular , Neoplasias Hepáticas , Piruvato Quinase , Animais , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Glicólise/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Camundongos , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/farmacologia , Isoformas de Proteínas/genética , Piruvato Quinase/genética , Piruvato Quinase/metabolismo
18.
ACS Appl Mater Interfaces ; 13(18): 21914-21923, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33942616

RESUMO

The past decade has witnessed a significant development of droplet microfluidics for applications such as directed evolution and single-cell analysis. While the stability and manipulation of droplets are part of the prerequisites to further their applications, most of the currently available surfactants serve solely as stabilizers between the interfaces of water and oil. In this study, we present a novel type of photo-responsive fluorosurfactant based on fluorinated plasmonic nanoparticles (NPs). The demonstration by fluorinated gold-silica core-shell NPs (f-Au@SiO2) has been shown to be effective in stabilizing the water-in-fluorocarbon oil droplets. More importantly, the photothermal response enabled by the f-Au@SiO2 has been shown to be promising for the movement of droplets as well as the alteration of interfacial stability. The unique photo-responsiveness provided by the plasmonic NPs is expected to gear up the droplet microfluidics with an "active" surfactant for reconfigurable optical manipulation.

19.
Sci Rep ; 11(1): 4118, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602951

RESUMO

Single incision laparoscopic surgery (SILS) has emerged as least invasive interventions for gynecologic disease. However, SILS is slow to gain in popularity due to difficulties in triangulation and instrument crowding. Besides, the costly instruments may influence patients' will to have this procedure, and limit other medical expense as well. To optimize outcome and reduce cost, the objective of this study is to evaluate the feasibility and safety for patients undergoing adnexal surgeries using conventional laparoscopic instruments with SILS (SILS-C), and to compare with those of patients subject to TP using conventional laparoscopic instruments (TP-C). This is a retrospective case-control study. The data dated from April 2011 to April 2018. Patients who received concomitant multiple surgeries, were diagnosed with suspected advanced stage ovarian malignancy, or required frozen sections for intraoperative pathologic diagnosis were excluded. Demographic data, including the age, body weight, height, previous abdominal surgery were obtained. The surgical outcomes were compared using conventional statistical methods. 259 patients received SILS-C. The operating time was 63.83 ± 25.31 min. Blood loss was 2.38 ± 6.09 c.c. 58 patients (24.38%) needed addition of port to complete surgery. 384 patients received TP-C. Compared with SILS-C, the operating time was shorter (57.32 ± 26.38 min, OR = 0.984, CI = 0.975-0.992). The patients were further divided into unilateral or bilateral adnexectomy, and unilateral or bilateral cystectomy. Other than the operating time in unilateral cystectomy (66.12 ± 19.5 vs. 58.27 ± 23.92 min, p = .002), no statistical differences were observed in the subgroup analysis. Single incision laparoscopic surgery using conventional laparoscopic instruments is feasible and safe as initial approach to adnexal lesions. In complex setting as unilateral cystectomy or pelvic adhesions, two-port access may be considered.


Assuntos
Laparoscopia/métodos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Tempo de Internação , Masculino , Duração da Cirurgia , Estudos Retrospectivos , Ferida Cirúrgica/cirurgia , Aderências Teciduais/cirurgia , Resultado do Tratamento
20.
Macromol Rapid Commun ; 42(9): e2000723, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33543553

RESUMO

Ordered arrays of polymer nanostructures have been widely investigated because of their promising applications such as solar-cell devices, sensors, and supercapacitors. It remains a great challenge, however, to manipulate the shapes of individual nanostructures in arrays for tailoring specific properties. In this study, an effective strategy to prepare anisotropic polymer nanopillar arrays via photo-fluidization is presented. Azobenzene-containing polymers (azopolymers) are first infiltrated into the nanopores of ordered anodic aluminum oxide (AAO) templates. After the removal of the AAO templates using weak bases, azopolymer nanopillar arrays can be prepared. Upon exposure of linearly polarized lights, azobenzene groups in the azopolymers undergo trans-cis-trans photoisomerization, causing mass migration and elongation of the nanopillar along with the polarization directions. As a result, anisotropic nanopillar arrays can be fabricated, of which the deformation degrees are controlled by the illumination times. Furthermore, patterned nanopillar arrays can also be constructed with designed photomasks. This work presents a practical and versatile strategy to fabricate arrays of anisotropic nanostructures for future technical applications.


Assuntos
Óxido de Alumínio , Nanoporos , Eletrodos , Lasers , Polímeros
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