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1.
Biotechnol J ; 19(3): e2300637, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38472092

RESUMO

The aldo-keto reductase (AKR) KdAKR from Kluyvermyces dobzhanskii can reduce t-butyl 6-chloro-(5S)-hydroxy-3-oxohexanoate ((5S)-CHOH) to t-butyl 6-chloro-(3R,5S)-dihydroxyhexanoate ((3R,5S)-CDHH), which is the key chiral intermediate of rosuvastatin. Herein, a computer-aided design that combined the use of PROSS platform and consensus design was employed to improve the stability of a previously constructed mutant KdAKRM6 . Experimental verification revealed that S196C, T232A, V264I and V45L produced improved thermostability and activity. The "best" mutant KdAKRM10 (KdAKRM6 -S196C/T232A/V264I/V45L) was constructed by combining the four beneficial mutations, which displayed enhanced thermostability. Its T50 15 and Tm values were increased by 10.2 and 10.0°C, respectively, and half-life (t1/2 ) at 40°C was increased by 17.6 h. Additionally, KdAKRM10 demonstrated improved resistance to organic solvents compared to that of KdAKRM6 . Structural analysis revealed that the increased number of hydrogen bonds and stabilized hydrophobic core contributed to the rigidity of KdAKRM10 , thus improving its stability. The results validated the feasibility of the computer-aided design strategy in improving the stability of AKRs.


Assuntos
Aldeído Redutase , Caproatos , Aldo-Ceto Redutases/química , Aldo-Ceto Redutases/genética , Caproatos/química
2.
Sleep Med ; 117: 46-52, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38507976

RESUMO

BACKGROUND: The effect of sleep apnea treatment on reducing cardiovascular disease risk remains inconclusive. This study aims to assess if the effective apnea hypopnea index (eAHI), a measure of residual sleep apnea burden post-treatment, is a factor in determining blood pressure (BP) response to continuous positive airway pressure therapy. The eAHI integrates time on therapy, residual apnea, and % of sleep time untreated. METHODS: A secondary analysis of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a randomized, controlled, parallel group assessment of continuous positive airway pressure (CPAP), oxygen and sleep hygiene. The Delta-AHI (▲AHI) was defined as the difference between baseline AHI and effective AHI at 12 weeks. Logistic and linear regression models estimated the predictors for nocturnal systolic BP change following sleep apnea therapy. RESULTS: One hundred and sixty-nine subjects with a mean age of 62.82 ± 6.99 years were included in the final analysis. Fifty subjects had ▲AHI ≤8/hour of sleep and 119 subjects were higher. After adjustment, baseline mean nighttime systolic blood pressure (OR 1.036, 95% CI 1.015-1.058, p: 0.001) and ▲AHI ≥8/hour (OR 2.406, 95% CI 1.116-5.185, p:0.025) were independent predictors for mean nighttime systolic blood pressure change >3 mm Hg. The higher effective AHI was negatively related with BNP (ß: -2.564, SE: 1.167, p: 0.029) and positively related with troponin change (ß: 0.703, SE: 0.256, p: 0.007). CONCLUSION: The ▲AHI was an independent predictor of the blood pressure response to sleep apnea treatment. REGISTER NUMBER: NCT01086800.


Assuntos
Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Pessoa de Meia-Idade , Idoso , Pressão Sanguínea/fisiologia , Pressão Positiva Contínua nas Vias Aéreas , Síndromes da Apneia do Sono/terapia , Síndromes da Apneia do Sono/complicações , Oxigênio
3.
Int J Biochem Cell Biol ; 170: 106559, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499237

RESUMO

Yes-associated protein (YAP)-a major effector protein of the Hippo pathway- regulates cell proliferation, differentiation, apoptosis, and senescence. Amp-activated protein kinase (AMPK) is a key sensor that monitors cellular nutrient supply and energy status. Although YAP and AMPK are considered to regulate cellular senescence, it is still unclear whether AMPK is involved in YAP-regulated cellular senescence. Here, we found that YAP promoted AMPKα1 aggregation and localization around mitochondria by co-transfecting CFP-YAP and YFP-AMPKα1 plasmids. Subsequent live cell fluorescence resonance energy transfer (FRET) assay did not exhibit direct interaction between YAP and AMPKα1. FRET, Co-immunoprecipitation, and western blot experiments revealed that YAP directly bound to TEAD, enhancing the expression of AMPKα1 and p-AMPKα. Treatment with verteporfin inhibited YAP's binding to TEAD and reversed the elevated expression of AMPKα1 in the cells overexpressing CFP-YAP. Verteporfin also reduced the proportion of AMPKα1 puncta in the cells co-expressing CFP-YAP and YFP-AMPKα1. In addition, the AMPKα1 puncta were demonstrated to inhibit cell viability, autophagy, and proliferation, and ultimately promote cell senescence. In conclusion, YAP binds to TEAD to upregulate AMPKα1 and promotes the formation of AMPKα1 puncta around mitochondria under the condition of co-expression of CFP-YAP and YFP-AMPKα1, in which AMPKα1 puncta lead to cellular senescence.


Assuntos
Neoplasias , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Quinases Ativadas por AMP , Verteporfina , Senescência Celular , Diferenciação Celular , Proliferação de Células
4.
Elife ; 132024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251723

RESUMO

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites revealed that the acetylation status of Isw1K97 coordinates with its ubiquitination processes at Isw1K113 and Isw1K441 through modulating the interaction between Isw1 and Cdc4, an E3 ligase. Additionally, clinical isolates of C. neoformans overexpressing the degradation-resistant ISW1K97Q allele showed impaired drug-resistant phenotypes. Collectively, our studies revealed a sophisticated acetylation-Isw1-ubiquitination regulation axis that controls multidrug resistance in C. neoformans.


Assuntos
Criptococose , Cryptococcus neoformans , Proteínas de Saccharomyces cerevisiae , Humanos , Cromatina , Cryptococcus neoformans/genética , Saccharomyces cerevisiae/genética , Acetilação , Comportamento Imitativo , Adenosina Trifosfatases/metabolismo , Ubiquitinação , Resistência a Múltiplos Medicamentos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
5.
Nat Mater ; 23(1): 65-70, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37563291

RESUMO

Moiré superlattices host a rich variety of correlated electronic phases. However, the moiré potential is fixed by interlayer coupling, and it is dependent on the nature of carriers and valleys. In contrast, it has been predicted that twisted hexagonal boron nitride (hBN) layers can impose a periodic electrostatic potential capable of engineering the properties of adjacent functional layers. Here, we show that this potential is described by a theory of electric polarization originating from the interfacial charge redistribution, validated by its dependence on supercell sizes and distance from the twisted interfaces. This enables controllability of the potential depth and profile by controlling the twist angles between the two interfaces. Employing this approach, we further demonstrate how the electrostatic potential from a twisted hBN substrate impedes exciton diffusion in semiconductor monolayers, suggesting opportunities for engineering the properties of adjacent functional layers using the surface potential of a twisted hBN substrate.

6.
J Hazard Mater ; 464: 132971, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-37956562

RESUMO

Microplastic (MP) pollution has emerged as a pressing environmental concern due to its ubiquity and longevity. Biodegradation of MPs has garnered significant attention in combatting global MP contamination. This study focused on MPs within sediments near the sewage outlet of Shenzhen Bay. The objective was to elucidate the microbial communities in sediments with varying MPs, particularly those with high MP loads, and to identify microorganisms associated with MP degradation. The results revealed varying MP abundance, ranging from 211 to 4140 items kg-1 dry weight (d. w.), with the highest concentration observed near the outfall. Metagenomic analysis confirmed the enrichment of Psychrobacter species in sediments with high MP content. Psychrobacter accounted for ∼16.71% of the total bacterial community and 41.71% of hydrocarbon degrading bacteria at the S3 site, exhibiting a higher abundance than at other sampling sites. Psychrobacter contributed significantly to bacterial function at S3, as evidenced by the Kyoto Encyclopedia of Genes and Genomes pathway and enzyme analysis. Notably, 28 enzymes involved in MP biodegradation were identified, predominantly comprising oxidoreductases, hydrolases, transferases, ligases, lyases, and isomerases. We propose a putative mechanism for MP biodegradation, involving the breakdown of long-chain plastic polymers and subsequent oxidation of short-chain oligomers, ultimately leading to thorough mineralization.


Assuntos
Psychrobacter , Poluentes Químicos da Água , Microplásticos/análise , Plásticos/análise , Psychrobacter/genética , Baías , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Biodegradação Ambiental , China , Bactérias/genética , Sedimentos Geológicos/microbiologia
7.
J Sex Res ; : 1-17, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37676778

RESUMO

The present study describes changes in young adults' sexual behaviors during the early COVID-19 pandemic. Latent class growth analyses (LCGAs) conducted with four waves of data collected between July 2019 to May 2020 in N = 775 college students (Mage = 18.61, SD = 0.33; 50.3% female, 90.2% White) revealed the presence of high- and low-risk classes in separate models for oral, vaginal, and anal sexual risk taking. As anticipated, vaginal and oral risk taking declined in spring 2020. Membership in high-risk trajectories was attributable to high COVID-19-related financial problems, early sexual debut, low self-control, and being in a romantic relationship. Other COVID-19 factors and demographic control variables were not linked to trajectory membership. Thus, while many young adults' sexual risk taking changed during the early pandemic, their perceptions of and experiences with COVID-19 were not predictive of sexual risk trajectory membership.

8.
Emerg Microbes Infect ; 12(2): 2244087, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37526401

RESUMO

Systemic infection with Cryptococcus neoformans, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of C. neoformans virulence. C. neoformans prm1Δ cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, prm1Δ cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed prm1Δ cells was found to facilitate the host immunological defence against infection with wild-type C. neoformans. Further investigation demonstrated that prm1Δ cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that C. neoformans Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.


Assuntos
Criptococose , Cryptococcus neoformans , Animais , Camundongos , Temperatura Alta , Criptococose/prevenção & controle , Cryptococcus neoformans/genética , Vacinação , Imunização
9.
J Adolesc ; 95(7): 1365-1376, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37345900

RESUMO

PURPOSE: This study aims to investigate the goal selection patterns among adolescents and examines the extent to which goals focused on oneself, relationships, and the larger community were associated with variability of daily purpose and mean level sense of purpose in life. METHODS: Participants were 213 high school students with an average age of 15.18 years in an urban public school district in the Northeast United States. Students were asked to select their three most important goals one time and report on their sense of purpose once a day for 3 weeks in spring of 2022. Latent class analysis was used to classify students by the type of goals selected. Differences in the overall sense of purpose and its subscales by class were examined. RESULTS: A model with four classes (Self and Inner Circle, Inner Circle, Other-Oriented, and Self-Oriented) best fits the data. There were no statistical group differences in the variability of daily purpose and overall sense of purpose. Only one pairwise comparison was significant and indicated that students in the Other-Oriented group perceived their purpose as more meaningful than students in the Self and Inner Circle group. CONCLUSIONS: Findings from this study provide a lens into goal prioritization patterns among adolescents. Further, although students who were more likely to select other-oriented goals had somewhat higher perceptions of sense of purpose, findings support the concept of equifinality by suggesting that a sense of purpose may be actualized through a diverse set of specific goals.


Assuntos
Objetivos , Estudantes , Humanos , Adolescente , Análise de Classes Latentes , Instituições Acadêmicas
10.
Micromachines (Basel) ; 14(5)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37241534

RESUMO

In this work, a N/P polySi thermopile-based gas flow device is presented, in which a microheater distributed in a comb-shaped structure is embedded around hot junctions of thermocouples. The unique design of the thermopile and the microheater effectively enhances performance of the gas flow sensor leading to a high sensitivity (around 6.6 µV/(sccm)/mW, without amplification), fast response (around 35 ms), high accuracy (around 0.95%), and mood long-term stability. In addition, the sensor has the advantages of easy production and compact size. With such characteristics, the sensor is further used in real-time respiration monitoring. It allows detailed and convenient collection of respiration rhythm waveform with sufficient resolution. Information such as respiration periods and amplitudes can be further extracted to predict and alert of potential apnea and other abnormal status. It is expected that such a novel sensor could provide a new approach for respiration monitoring related noninvasive healthcare systems in the future.

11.
Sleep Med ; 107: 137-148, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37178545

RESUMO

BACKGROUND: The acute effect during positive pressure titration and long term efficacy of acetazolamide (AZT) in high loop gain sleep apnea (HLGSA) is inadequately assessed. We predicted that AZT may improve HLGSA in both conditions. METHODS: A retrospective analysis of polysomnograms from patients with presumed HLGSA and residual respiratory instability administered AZT (125 or 250 mg) about 3 h into an initially drug-free positive pressure titration. A responder was defined as ≥ 50% reduction of the apnea hypopnea index(AHI 3% or arousal) before and after AZT. A multivariable logistic regression model estimated responder predictors. Long term efficacy of AZT was assessed by comparing both auto-machine (aREIFLOW) and manually scored respiratory events (sREIFLOW) extracted from the ventilator, prior to and after 3 months of AZT, in a subset. RESULTS: Of the 231 participants (median age of 61[51-68] years) and 184 (80%) males in the acute effect testing: 77 and 154 patients were given 125 mg and 250 mg AZT. Compared to PAP alone, PAP plus AZT was associated with a lower breathing related arousal index (8 [3-16] vs. 5 [2-10], p < 0.001), and AHI3% (19 [7-37] vs. 11 [5-21], p < 0.001); 98 patients were responders. The non-rapid eye movement sleep (NREM) AHI3% (OR 1.031, 95%CI [1.016-1.046], p < 0.001) was a strong predictor for responder status with AZT exposure. In the 109 participants with 3-month data, both aREIFLOW and sREIFLOWwere significantly reduced after AZT. CONCLUSIONS: AZT acutely and chronically reduced residual sleep apnea in presumed HLGSA; NREM AHI3% is a response predictor. AZT was well tolerated and beneficial for at least 3 months.


Assuntos
Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Acetazolamida/farmacologia , Acetazolamida/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Estudos Retrospectivos , Síndromes da Apneia do Sono/tratamento farmacológico , Respiração , Pressão Positiva Contínua nas Vias Aéreas
12.
Sleep Med ; 106: 42-51, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37044000

RESUMO

STUDY OBJECTIVES: Determine the risk factors for, and consequences of, residual apnea during long-term positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA). METHODS: A prospective cohort study of 195 subjects after a split-night polysomnogram. Estimation of residual respiratory events on PAP were done by both automated and manual scoring of data in EncoreAnywhere™. Clinical and polysomnographic predictors of residual apnea were estimated. RESULTS: There were 166 and 101 patients still on PAP at the 3 and 12 months, respectively. Seventy four (44.6%) and 46 (45.5%) had a residual scored respiratory event index-flow (sREIFLOW) ≥ 15/hour of use and 46 (45.5%) at the 3rd and 12th month, respectively. Treatment phase central apnea hypopnea index (TCAHI), a surrogate of high loop gain, was the main predictor for residual sREIFLOW (ß = 0.345, p: 0.025) at the 3rd and 12th month (ß = 0.147, p: 0.020). TCAHI also predicted unstable breathing (U) %. The body mass index (hazard ratio [HR] 1.034, 95% CI 1.008-1.062, p: 0.012) and effective sREIFLOW>15/hour in the first month (HR 2.477, 95% CI 1.510-4.065, p < 0.001) were the key predictors for drop out of PAP use at the 12th month. Effective sREIFLOW>15/hour in the first month was also a predictor for median usage duration >4 h for 70% of the night at both the 3rd month (odds ratio [OR] 0.947, 95% CI 0.909-0.986, p: 0.008) and 12th month (OR 0.973, 95% CI 0.951-0.994, p: 0.014). CONCLUSIONS: Treatment-phase CAHI predicts long-term residual apnea on PAP. High residual disease adversely impacts adherence.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Humanos , Estudos Prospectivos , Respiração , Polissonografia
13.
Heart Lung ; 58: 223-228, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36638763

RESUMO

BACKGROUND: Ventilatory ratio (VR) is a simple bedside index of ventilatory efficiency. Interstitial lung disease (ILD) is a diverse group of diseases that causes fibrosis or inflammation of the pulmonary parenchyma, and the main clinical manifestation is hypoxemia. To date, no study has explored ventilation efficiency in patients with ILD. OBJECTIVES: This study aimed to explore the features of VR in mechanically ventilated patients with ILD and their relationship with intensive care unit (ICU) mortality. METHODS: In this retrospective analysis, we included mechanically ventilated patients with ILD in the ICU of West China Hospital, Sichuan University, from 2013 to 2021. Demographic data and mechanical ventilation (MV) parameters within 24 h of intubation were collected. The characteristics of VR and their relationships with ICU mortality were also analyzed. RESULTS: 224 patients were included in the final analysis. There were 146 males (53.9%), and the median age was 65 years (interquartile range [IQR]54∼74). The mean value of VR was 2.22, and VR was significantly higher in nonsurvivors than in survivors (1.79 vs 2.32, P < 0.001). A high VR value was an independent risk factor for ICU mortality (odds ratio=1.602, P = 0.038) after adjustment. A high value of VR was associated with a shorter survival time after admission to ICU (hazard ratio=1.485, P = 0.006) CONCLUSIONS: VR in patients with ILD on MV was increased, and the VR of nonsurvivors within 24 h of intubation was higher than that of survivors. The high VR value within 24 h of intubation was an independent risk factor for ICU mortality after adjusting for other factors.


Assuntos
Doenças Pulmonares Intersticiais , Respiração Artificial , Masculino , Humanos , Idoso , Estudos Retrospectivos , Unidades de Terapia Intensiva , Pulmão , Mortalidade Hospitalar
14.
Environ Sci Pollut Res Int ; 30(3): 6262-6274, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35994150

RESUMO

The anode material plays a crucial role in the process of electrochemical oxidation. Herein, a TiO2 nanotube arrays (TiO2-NTA) intermediate layer and La-PbO2 catalytic layer were synthesized on a Ti surface by the electrochemical anodic oxidation and electrochemical deposition technology, respectively. The prepared Ti/TiO2-NTA/La-PbO2 electrode was used as an electrocatalytic oxidation anode for pollutant degradation. Scanning electron microscopy (SEM) analysis showed that the TiO2-NTA layer possessed a highly ordered and well-aligned nanotube array morphology, and the La-PbO2 layer with angular cone cluster was uniform and tightly bonded. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis indicated that the intermediate layer primarily consisted of the anatase crystal structure of TiO2 and the catalyst layer was made of La-PbO2. Electrochemical analysis revealed that Ti/TiO2-NTA/La-PbO2 electrode exhibited higher oxidation peak current, electrochemical active surface area, and oxygen evolution potential (OEP, 1.64 V). Using methyl orange and 4-nitrophenol as model pollutants, electrocatalytic properties of the prepared Ti/TiO2-NTA/La-PbO2 electrode were systematically investigated under different conditions, and the electrochemical degradation fitted well with the pseudo-first-order kinetics model. Efficient anodic oxidation of model pollutants was mainly attributed to the indirect oxidation mediated by hydroxyl radicals (•OH). The total organic carbon (TOC) removal efficiency of methyl orange and 4-nitrophenol was 70.2 and 72.8%, and low energy consumption (2.50 and 1.89 kWh g-1) was achieved after 240 min of electrolysis under the conditions of initial concentration of model pollutant, electrode spacing, and electrolyte concentration were 50 mg L-1, 2 cm, and 0.1 mol L-1, respectively. This work provided a new strategy to develop the high-efficiency electrode for refractory pollutants degradation.


Assuntos
Óxidos , Poluentes Químicos da Água , Óxidos/química , Titânio/química , Oxirredução , Eletrodos , Poluentes Químicos da Água/análise
15.
Clin Colorectal Cancer ; 22(1): 111-119, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36473779

RESUMO

BACKGROUND: The significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM. PATIENT AND METHODS: The PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed. RESULTS: The main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor. CONCLUSION: Our findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Pancreáticas , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/tratamento farmacológico , Pontuação de Propensão , Neoplasias Colorretais/patologia , Infusões Intra-Arteriais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Hepáticas/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artéria Hepática/patologia , Neoplasias Pancreáticas
16.
Micromachines (Basel) ; 13(10)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36296070

RESUMO

The response time is an important parameter for thermopiles sensors, which reflects the response speed of the device. The accurate measurement of response time is extremely important to evaluate device characteristics for using them in suitable scenarios. In this work, to accurately measure the response time of thermopile sensors, an Al microheater is integrated in a MEMS thermopile as an in situ heat source. Compared with the traditional chopper measurement method for response time, this approach avoids mechanical delay induced by chopper blades. Accordingly, based on this approach, the response time of the device is measured to be 6.9 ms, while that is 12.7 ms when a chopping system is used, demonstrating that an error of at least 5.8 ms is avoided. Such an approach is quite simple to realize and provides a novel route to accurately measure the response time.

17.
Nat Commun ; 13(1): 5407, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109512

RESUMO

Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.


Assuntos
Cryptococcus neoformans , Cisteína , Cryptococcus neoformans/genética , Cryptococcus neoformans/metabolismo , Cisteína/metabolismo , DNA/metabolismo , Homeostase , Mitocôndrias/genética , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
18.
ACS Omega ; 7(30): 26549-26559, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35936473

RESUMO

Hydraulic fracturing combined with horizontal drilling is widely used to develop shale gas resources, and huge amounts of fracturing fluid are injected into shale reservoirs. However, the fracturing fluid is ineluctably retained in reservoir rocks after fracturing, resulting in the alteration of shale pore systems and further affecting the hydrocarbons production efficiency. In this work, two types of shales with different pyrite contents, namely, pyrite rich (PR, Niutitang Formation) and pyrite poor (PP, Xiamaling Formation), were emphasized to illustrate the effect of pyrite oxidation on pore structure after fracturing operation. Slickwater fracturing fluid was used to treat the shale samples for a period of 3 days, under the condition of 100 °C and 50 MPa. The field emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD) were utilized to determine the surface morphology and mineral composition. The low-temperature N2 adsorption was performed to quantify the pore structure. The results showed that the pyrite oxidation induced the dissolution of both the pyrite and calcite and generated many dissolution pores for the pyrite-rich shale after slickwater treatment. The mineral dissolution led to an increase in the number of mesopores, enlarged the total specific surface area (TSSA) and total pore volume (TPV), and strengthened the pore-structure complexity. On the other hand, the pyrite-poor shale only experienced clay swelling after slickwater treatment. Its pore surface roughness and pore-structure complexity degraded with the loss of nanopores and the reductions in TSSA and TPV. The results of this study enhance the understanding of the impact of pyrite oxidation on the pore structure and provide new insight into the optimization of fracturing operation conditions based on shale's mineral composition characteristics.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 281: 121623, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35872426

RESUMO

Diethylenetriamine pentamethylene phosphonic acid (DTPMP) is one of the most commonly used amino organic phosphonates. The existing methods for DTPMP detection are complicated, time-consuming, and cannot detect trace DTPMP in the natural environment. In the present work, the Fe-based 3,5-dimethyl pyrazole fluorescent sensor (Fe-DP) was constructed. The addition of Fe3+ to DP solution can greatly decrease the fluorescent intensity of DP, while the addition of different concentrations of DTPMP will restore the fluorescence intensity of DP to different degrees, to achieve quantitative detection of DTPMP, and the detection limit (LOD) of DTPMP was lower as 0.105 µΜ. The Fe-DP fluorescent sensor exhibited excellent anti-interference ability and good stability. Moreover, the fluorescence quenching mechanism of DP by Fe3+ was revealed by UV absorption spectrum and Multiwfn wavefunction analysis based on density function theory (DFT). The results revealed that the excitation of DP belonged to local excitation, in which the electrons were donated primarily by the N atom with double bond and redistributed within the pyrazole ring.The fluorescence quenching of adding Fe3+ was not caused by resonance energy transfer or charge transfer, which did not belong to dynamic quenching, but due to the ground state complex formed by the coordination of Fe3+ and the double bond N atom on the DP pyrazole ring.


Assuntos
Corantes Fluorescentes , Poliaminas , Corantes Fluorescentes/química , Ácidos Fosforosos , Pirazóis
20.
J Pers Oriented Res ; 8(1): 10-23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720437

RESUMO

Executive functioning (EF) is a series of fundamental goal-directed cognitive abilities that enable effective learning. Differences in daily sleep quality may covary with fluctuations in EF among youth. Most studies linking sleep to EF rely on between-person differences and average effects for the sample. This study employed an intensive longitudinal design and examined the within-person relations between self-reported prior night's sleep quality and next day's EF. Students from Grades 4 to 12 (M age= 14.60, SD = 2.53) completed three behavioral EF tasks repeatedly across approximately one semester. The final analytic sample included 2898 observations embedded in 73 participants. Although, on average, sleep did not significantly covary with EF, there was heterogeneity in within-person sleep-EF relations. Moreover, individuals' average sleep quality moderated within-person effects. For individuals with low mean sleep quality, a better-than-usual sleep quality was linked to better EF performance. However, for individuals with high mean sleep quality, better-than-usual sleep quality was linked to worse EF performance. Understanding person-specific relations between sleep and EF can help educators optimize EF and learning on a daily basis and produce positive academic outcomes across longer time periods.

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