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1.
Cell Signal ; 121: 111278, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38944257

RÉSUMÉ

Promyelocytic leukemia protein (PML), a tumor suppressor protein, plays a key role in cell cycle regulation, apoptosis, senescence and cellular metabolism. Here, we report that PML promotes apoptosis and ferroptosis. Our data showed that PML over-expression inhibited cell proliferation and migration. PML over-expression increased apoptotic cells, nuclear condensation and the loss of mitochondrial membrane potential, accompanied by regulation of Bcl-2 family proteins and reactive oxygen species (ROS) level, suggesting that PML enhanced apoptosis. Meanwhile, PML over-expression not only increased lipid ROS accumulation and Malondialdehyde (MDA) content but also downregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, indicating that PML enhanced ferroptosis. Additionally, knockdown of p53 attenuated the effect of PML on SLC7A11 and GPX4, and inhibited the increase of lipid ROS and ROS by PML over-expression. Moreover, translocation of PML from nucleus to cytoplasm not only promoted apoptosis and ferroptosis, but also inhibited cell proliferation. Taken together, PML promotes apoptosis and ferroptosis, in which the mediation of p53 and the nuclear export of PML play important roles.

2.
Microbiol Spectr ; : e0420223, 2024 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-38874428

RÉSUMÉ

The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as Cryptococcus neoformans, is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in C. neoformans. Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of C. neoformans at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting C. neoformans thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the set302∆ strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. set302∆ strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of C. neoformans.IMPORTANCECryptococcus neoformans is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in C. neoformans. Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of C. neoformans. Moreover, Set302 regulates the pathogenicity and colonization ability of C. neoformans in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in C. neoformans.

3.
Sleep Med ; 119: 432-437, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38781666

RÉSUMÉ

STUDY OBJECTIVES: To determine the clinical impact of sleep apnea-related hypoxic burden in pregnant women and neonates. METHODS: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) study. Hypoxia burden was calculated from the home sleep apnea test (HSAT) and defined as the total area under respiratory events. Logistic regression analysis assessed the relationship between hypoxia burden and pregnancy/neonatal outcomes. RESULTS: A total of 3006 subjects in the early term, and 2326 subjects in the middle term of pregnancy, had HSAT. A hypoxic burden greater than 6.8%min was present in 1740 at early term and associated with a higher risk of preeclampsia (odds ratio 1.297, 95 % confidence interval 1.032-1.630, p: 0.026) after adjusted by obstructive sleep apnea (OSA) severity. In the middle term, 1058 subjects had a hypoxia burden more than 11.8%min, which was a predictor for higher incidence of gestational diabetes (OR 1.795, 95 % CI 1.097-2.938, p: 0.020) and an Apgar <7 at 1 min (OR 1.446, 95 % CI 1.079-1.939, p: 0.012) after adjusted by obstructive sleep apnea (OSA) severity. After adjusted by oxygenation disturbance index, HB was not related with Apgar <7 at 1 min (p:0.565). CONCLUSIONS: The hypoxic burden is an independent predictor for preeclampsia and gestational diabetes and an Apgar <7 at 1 min.


Sujet(s)
Hypoxie , Pré-éclampsie , Issue de la grossesse , Humains , Grossesse , Femelle , Hypoxie/complications , Adulte , Nouveau-né , Issue de la grossesse/épidémiologie , Pré-éclampsie/épidémiologie , Complications de la grossesse/épidémiologie , Diabète gestationnel/épidémiologie , Syndrome d'apnées obstructives du sommeil/complications , Syndrome d'apnées obstructives du sommeil/épidémiologie , Facteurs de risque , Syndromes d'apnées du sommeil/complications , Syndromes d'apnées du sommeil/épidémiologie
4.
Sleep Med ; 117: 46-52, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38507976

RÉSUMÉ

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.


Sujet(s)
Syndromes d'apnées du sommeil , Syndrome d'apnées obstructives du sommeil , Humains , Adulte d'âge moyen , Sujet âgé , Pression sanguine/physiologie , Ventilation en pression positive continue , Syndromes d'apnées du sommeil/thérapie , Syndromes d'apnées du sommeil/complications , Oxygène
5.
Biotechnol J ; 19(3): e2300637, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38472092

RÉSUMÉ

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.


Sujet(s)
Aldose reductase , Caproates , Aldo-keto reductases/composition chimique , Aldo-keto reductases/génétique , Caproates/composition chimique
6.
Int J Biochem Cell Biol ; 170: 106559, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38499237

RÉSUMÉ

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.


Sujet(s)
Tumeurs , Facteurs de transcription , Facteurs de transcription/génétique , Facteurs de transcription/métabolisme , AMP-Activated Protein Kinases , Vertéporfine , Vieillissement de la cellule , Différenciation cellulaire , Prolifération cellulaire
7.
Elife ; 132024 Jan 22.
Article de Anglais | MEDLINE | ID: mdl-38251723

RÉSUMÉ

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.


Sujet(s)
Cryptococcose , Cryptococcus neoformans , Protéines de Saccharomyces cerevisiae , Humains , Chromatine , Cryptococcus neoformans/génétique , Saccharomyces cerevisiae/génétique , Acétylation , Comportement d'imitation , Adenosine triphosphatases/métabolisme , Ubiquitination , Multirésistance aux médicaments , Protéines de liaison à l'ADN/métabolisme , Protéines de Saccharomyces cerevisiae/métabolisme
8.
Nat Mater ; 23(1): 65-70, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-37563291

RÉSUMÉ

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.

9.
J Hazard Mater ; 464: 132971, 2024 02 15.
Article de Anglais | MEDLINE | ID: mdl-37956562

RÉSUMÉ

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.


Sujet(s)
Psychrobacter , Polluants chimiques de l'eau , Microplastiques/analyse , Matières plastiques/analyse , Psychrobacter/génétique , Baies (géographie) , Polluants chimiques de l'eau/analyse , Surveillance de l'environnement , Dépollution biologique de l'environnement , Chine , Bactéries/génétique , Sédiments géologiques/microbiologie
10.
J Sex Res ; : 1-17, 2023 Sep 07.
Article de Anglais | MEDLINE | ID: mdl-37676778

RÉSUMÉ

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.

11.
Emerg Microbes Infect ; 12(2): 2244087, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37526401

RÉSUMÉ

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.


Sujet(s)
Cryptococcose , Cryptococcus neoformans , Animaux , Souris , Température élevée , Cryptococcose/prévention et contrôle , Cryptococcus neoformans/génétique , Vaccination , Immunisation
12.
J Adolesc ; 95(7): 1365-1376, 2023 10.
Article de Anglais | MEDLINE | ID: mdl-37345900

RÉSUMÉ

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.


Sujet(s)
Objectifs , Étudiants , Humains , Adolescent , Analyse de structure latente , Établissements scolaires
13.
Sleep Med ; 107: 137-148, 2023 07.
Article de Anglais | MEDLINE | ID: mdl-37178545

RÉSUMÉ

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.


Sujet(s)
Syndromes d'apnées du sommeil , Syndrome d'apnées obstructives du sommeil , Mâle , Humains , Adulte d'âge moyen , Sujet âgé , Femelle , Acétazolamide/pharmacologie , Acétazolamide/usage thérapeutique , Syndrome d'apnées obstructives du sommeil/traitement médicamenteux , Études rétrospectives , Syndromes d'apnées du sommeil/traitement médicamenteux , Respiration , Ventilation en pression positive continue
14.
Micromachines (Basel) ; 14(5)2023 Apr 23.
Article de Anglais | MEDLINE | ID: mdl-37241534

RÉSUMÉ

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.

15.
Sleep Med ; 106: 42-51, 2023 06.
Article de Anglais | MEDLINE | ID: mdl-37044000

RÉSUMÉ

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.


Sujet(s)
Ventilation en pression positive continue , Syndrome d'apnées obstructives du sommeil , Humains , Études prospectives , Respiration , Polysomnographie
16.
Heart Lung ; 58: 223-228, 2023.
Article de Anglais | MEDLINE | ID: mdl-36638763

RÉSUMÉ

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.


Sujet(s)
Pneumopathies interstitielles , Ventilation artificielle , Mâle , Humains , Sujet âgé , Études rétrospectives , Unités de soins intensifs , Poumon , Mortalité hospitalière
17.
Clin Colorectal Cancer ; 22(1): 111-119, 2023 03.
Article de Anglais | MEDLINE | ID: mdl-36473779

RÉSUMÉ

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.


Sujet(s)
Tumeurs colorectales , Tumeurs du foie , Tumeurs du pancréas , Tumeurs du péritoine , Humains , Tumeurs du péritoine/traitement médicamenteux , Score de propension , Tumeurs colorectales/anatomopathologie , Perfusions artérielles , Tumeurs du pancréas/traitement médicamenteux , Tumeurs du pancréas/anatomopathologie , Tumeurs du foie/secondaire , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Artère hépatique/anatomopathologie , Tumeurs du pancréas
18.
Environ Sci Pollut Res Int ; 30(3): 6262-6274, 2023 Jan.
Article de Anglais | MEDLINE | ID: mdl-35994150

RÉSUMÉ

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.


Sujet(s)
Oxydes , Polluants chimiques de l'eau , Oxydes/composition chimique , Titane/composition chimique , Oxydoréduction , Électrodes , Polluants chimiques de l'eau/analyse
19.
Micromachines (Basel) ; 13(10)2022 Oct 11.
Article de Anglais | MEDLINE | ID: mdl-36296070

RÉSUMÉ

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.

20.
Nat Commun ; 13(1): 5407, 2022 09 15.
Article de Anglais | MEDLINE | ID: mdl-36109512

RÉSUMÉ

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.


Sujet(s)
Cryptococcus neoformans , Cystéine , Cryptococcus neoformans/génétique , Cryptococcus neoformans/métabolisme , Cystéine/métabolisme , ADN/métabolisme , Homéostasie , Mitochondries/génétique , Mitochondries/métabolisme , Espèces réactives de l'oxygène/métabolisme
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