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1.
ACS Omega ; 7(35): 31299-31308, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092568

RESUMO

Nanodrugs have attracted increasing interest in drug delivery and disease treatment. However, the cumbersome preparation process and the poor biocompatibility of nanodrugs obstruct their clinical translation. In this study, we utilized a self-assembly strategy to develop a low-toxicity, long-lasting nanodrug for the effective treatment and real-time monitoring of bladder tumors. The accurate self-assembly of compatible raw materials allowed for an encapsulation rate of 43.7% for insoluble erdafitinib. Interestingly, robust therapeutic effects and reduced side effects could be realized simultaneously using this nanodrug, enabling broader scenarios for the clinical application of erdafitinib. Furthermore, the nanodrug exhibited a significantly prolonged in vivo half-life (14.4 h) and increased bioavailability (8.0 µg/mL·h), which were 8.3 times and 5.0 times higher than those of its nonformulated counterpart. Also, it is worth mentioning that the introduction of a fluorescent protein module into the nanodrug brought up a novel possibility for real-time feedback on the therapeutic response. In conclusion, this research revealed a versatile technique for developing low-toxicity, long-acting, and multifunctional nanoformulations, paving the way for multidimensional therapy of malignant tumors.

2.
Neuron ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36113472

RESUMO

Rodents explore their environment through coordinated orofacial motor actions, including whisking. Whisking can free-run via an oscillator of inhibitory neurons in the medulla and can be paced by breathing. Yet, the mechanics of the whisking oscillator and its interaction with breathing remain to be understood. We formulate and solve a hierarchical model of the whisking circuit. The first whisk within a breathing cycle is generated by inhalation, which resets a vibrissa oscillator circuit, while subsequent whisks are derived from the oscillator circuit. Our model posits, consistent with experiment, that there are two subpopulations of oscillator neurons. Stronger connections between the subpopulations support rhythmicity, while connections within each subpopulation induce variable spike timing that enhances the dynamic range of rhythm generation. Calculated cycle-to-cycle changes in whisking are consistent with experiment. Our model provides a computational framework to support longstanding observations of concurrent autonomous and driven rhythmic motor actions that comprise behaviors.

3.
Rapid Commun Mass Spectrom ; : e9399, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114650

RESUMO

RATIONALE: To effectively separate unknown impurities and polymerized impurities in cefamandole nafate, reversed phase liquid chromatography (RP-HPLC) and high performance size exclusion chromatography (HPSEC) methods were developed. The liquid chromatography tandem ion trap/time-of-flight mass spectrometry was applied to characterize the structures of the impurities. Ultraviolet spectrum characteristics and mass spectrum characteristics of △3 -isomer and 7-epimer in cefamandole nafate were studied to distinguish the isomers. METHODS: Reversed phase liquid chromatography tandem ion trap/time-of-flight mass spectrometry (RPLC-IT-TOF MS) was used to characterize the structures of unknown impurities and polymerized impurities eluted from C18 column. On this basis, the two-dimensional high performance size exclusion chromatography tandem ion trap/time-of-flight mass spectrometry (2D HPSEC-IT-TOF MS) was used to confirm the structures of polymerized impurities eluted from TSK-gel G2000SWxl column. Complete fragmentation patterns of impurities were studied and used to obtain information about the structures of the impurities. RESULTS: The structures of nineteen unknown impurities in cefamandole nafate were elucidated based on the high resolution MSn data with both positive and negative modes, assisted by the UV spectra and stress testing, two of which were polymerized impurities. Cefamandole nafate produced a series of degradation impurities, and another principal component cefamandole acid also produced a series of similar degradation impurities. The disciplines between mass fragmentation pattern/ultraviolet spectrum and structure for △3 -isomer and 7-epimer were presented to distinguish their structures. CONCLUSIONS: The results from this study provided a scientific basis for the improvement of official monographs in pharmacopoeias to effectively control the impurities and ensure drug safety for the public. This study also revealed the forming mechanisms of degradation impurities in cefamandole nafate, which may guide industry to improve the manufacturing process and storage conditions to reduce the content of impurities in products.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36101483

RESUMO

BACKGROUND: Optimal penetration of anti-infectives in the female genital tract (FGT) is paramount in the treatment and prevention of infectious diseases. While exposure of anti-infectives in lower FGT tissues (e.g. cervix, vagina) has been described, little data exist on upper genital tissues (e.g. ovary, uterus). METHODS: Autopsies were performed and post-mortem tissues were collected within 24 h of death for female participants with advanced HIV in Uganda (n = 27). Tenofovir, lamivudine, efavirenz and fluconazole concentrations were measured using LC-MS/MS in plasma, ovarian, uterine, cervical and vaginal tissues. Tissue penetration was calculated as tissue-to-plasma concentration ratios (TPRs). RESULTS: TPRs of tenofovir, lamivudine and fluconazole were highest in vaginal tissue (medians 1.86, 1.83 and 0.94, respectively), while the TPR of efavirenz was highest in ovarian tissue (median 0.65). With cervix as a reference compartment, vaginal TPRs were significantly higher than cervical for all four drugs; TPRs of efavirenz in uterine and ovarian compartments were also significantly higher than cervical. Most of the post-mortem FGT samples had a TPR of greater than 1 for tenofovir and lamivudine, while less than 50% had a TPR of greater than 1 for both efavirenz and fluconazole. CONCLUSIONS: Penetration of anti-infectives was not homogeneous among the FGT compartments. Approximately 70% of FGT tissues had a TPR of greater than 1 for tenofovir and lamivudine, favouring the prevention of local HIV replication and transmission in the FGT.

5.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36077243

RESUMO

Glucose oxidase, which uses molecular oxygen as an electron acceptor to specifically catalyze the conversion of ß-d-glucose to gluconic acid and hydrogen peroxide (H2O2), has been considered an important enzyme in increasing environmental sustainability and food security. However, achieving the high yield, low price and high activity required for commercial viability remains challenging. In this review, we first present a brief introduction, looking at the sources, characteristics, catalytic process, and applications of glucose oxidase. Then, the predictive structures of glucose oxidase from two different sources are comparatively discussed. We summarize the inhibitors of glucose oxidase. Finally, we highlight how the production of glucose oxidase can be improved by optimizing the culture conditions and microbial metabolic engineering.


Assuntos
Glucose Oxidase , Peróxido de Hidrogênio , Catálise , Glucose/metabolismo , Glucose Oxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Oxigênio
6.
ACS Nano ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36075214

RESUMO

Plant biotic or abiotic stresses, such as pathogens, mechanical damage, or high temperature, can increase intracellular H2O2 concentration, damaging proteins, lipids, and DNA. Most current H2O2 detection methods require the separation or grinding of plant samples, inducing plant stresses, and the process is complicated and time-consuming. This paper constructed a metal-organic framework (MOF)-based biosensor for real-time, remote, and in situ detection of exogenous/endogenous H2O2 in plant organs through color-to-thermal signal conversion. By simply spraying horseradish peroxidase, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and the precursor of zeolite imidazolate frameworks-8 (ZIF-8), ZIF-8 biosensors were formed in situ on a plant root, petiole, or leaf. This biosensor could report sub-micromolar H2O2 in plants since the oxidation products, ABTS• +, emitted heat when they absorbed energy from near-infrared (NIR) light. Due to the plant's low absorption in the NIR region, the ZIF-8 biosensor allowed for remote thermal sensing of H2O2 transport or biotic/abiotic stresses in plants with a high signal-to-noise ratio combining NIR laser and thermometer. Our biosensor can be used for the future development of plant sensors for monitoring plant signaling pathways and metabolism that are nondestructive, minimally invasive, and capable of real-time, in situ analysis.

7.
Antioxidants (Basel) ; 11(9)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36139748

RESUMO

Basic leucine zipper (bZIP) transcription factors of the ABA-responsive element binding factor/ABA-responsive element binding proteins (ABF/AREB) subfamily have been implicated in abscisic acid (ABA) and abiotic stress responses in plants. However, the specific function of ABF/AREB transcription factors under saline-alkaline stress is unclear. Here, we identified four ABF/AREB transcription factors in tomato and found that SlAREB1 strongly responded to both ABA and saline-alkaline stress. To further explore the function of SlAREB1 under saline-alkaline stress, SlAREB1-overexpressing lines were constructed. Compared with wild-type plants, SlAREB1-overexpressing transgenic tomato plants showed reduced malondialdehyde content, increased the relative water content, and alleviated the degradation of chlorophyll under saline-alkaline stress. Importantly, SlAREB1 directly physically interacted with SlMn-SOD, which improved the activity of antioxidant enzymes and increased the scavenging of excess reactive oxygen species. Overall, the overexpression of SlAREB1 increased the antioxidant capacity of the transgenic tomato under saline-alkaline stress.

8.
Molecules ; 27(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36144486

RESUMO

Secoatractylohexone A (1), an unprecedented secoguaiane lactone glycoside featuring 6/7 cores and dihydroxy-9-guaine-3-one 11-O-ß-d-glucopyranoside (2), a 9,10-unsaturated guaiene-type glycoside possessing an uncommon scaffold, were isolated from the water-soluble portion of the ethanolic extract of Atractylodes lancea rhizomes together with five known compounds (3-7). The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic data and application of the CD technique. The potential biological activities of secoatractylohexone A were predicted by network pharmacology in silico, the result of which indicated that secoatractylohexone A may be used to treat type II diabetes.

9.
Bioresour Technol ; 363: 127888, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36070812

RESUMO

This study aimed to propose a novel air-lift multi-stage circulating integrated bioreactor (AMCIB) to treat urban sewage. The AMCIB combined the reaction zone and sedimentation zone, the alternating circulation of activated sludge in separate aerobic and anaerobic environments facilitates the enrichment of HN-AD bacteria. The preliminary study showed that AMCIB had high removal efficiencies for COD, NH4+-N, TN and TP under high dissolved oxygen (DO) concentration conditions, with average removal rates of 93.21 %, 96.04 %, 75.06 % and 94.30 %, respectively. IlluminaMiSeq sequencing results showed that the system successfully cultured heterotrophic nitrification-aerobic denitrification (HN-AD) functional bacteria (Pseudomonas, Acinetobacter, Aeromonas) that played a crucial role in sewage treatment, and Tetrasphaera was the central phosphorus removing bacteria in the system. Functional gene predictions showed that the HN-AD played a dominant role in the system.

10.
ACS Appl Mater Interfaces ; 14(37): 42454-42467, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36089739

RESUMO

Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte-liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers in vitro. Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood-brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. In vitro, the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. In vivo, apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, in vitro and in vivo studies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning.


Assuntos
Acetilcolinesterase , Compostos Organofosforados , Acetilcolinesterase/metabolismo , Antídotos/química , Antídotos/farmacologia , Antídotos/uso terapêutico , Arildialquilfosfatase , Inibidores da Colinesterase/farmacologia , Gangliosídeo G(M1) , Lipossomos , Paraoxon/análogos & derivados , Espécies Reativas de Oxigênio , Distribuição Tecidual
11.
Front Neurol ; 13: 952405, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062014

RESUMO

Objective: To use structural magnetic resonance imaging (3D-MRI) to evaluate the abnormal development of the cerebral cortex in infants with global developmental delay (GDD). Methods: The GDD group includes 67 infants aged between 112 and 699 days with global developmental delay and who underwent T1-weighted MRI scans in Shanxi Children's Hospital from December 2019 to March 2022. The healthy control (HC) group includes 135 normal developing infants aged between 88 and 725 days in Shanxi Children's Hospital from September 2020 to August 2021. Whole-brain T1-weighted MRI scans were carried out with a 3.0-T magnetic resonance scanner, which was later processed using InfantSurfer to perform MR image processing and cortical surface reconstruction. Two morphological features of the cortical surface of the 68 brain regions were computed, i.e., the cortical thickness (CT) and cortical surface area (SA), and compared between the GDD and HC groups. Results: With regard to the CT, the HC group showed a rapid decrease at first and then a slow increase after birth, and the CT of the GDD group decreased slowly and then became relatively stable. The GDD group showed bilaterally higher hemispherical average CT than those in the HC group. In detail, for the left hemisphere, except in the entorhinal and temporal poles in which the average CT values of the two brain regions were lower than those of the HC group, the CT of the 26 brain regions in the GDD group was higher than those of the HC group (p < 0.05). For the right hemisphere, the CT of the entorhinal in the GDD group was lower than that in the HC group. Otherwise, the CT of the remaining 28 brain regions was higher than those in the HC group (p < 0.05). With regard to the SA, both groups showed a rapid increase after birth till 23 months and remained quite stable afterward. The GDD group shows lower SA bilaterally than that in the HC group. In detail, SA in the GDD group was lower in most cortical regions of both hemispheres than in the HC group (p < 0.05), except for the right temporal pole and entorhinal. When testing for brain asymmetry, we found that the HC group showed obvious asymmetry of CT and SA, while only a few cortical regions in the GDD group showed asymmetry.

12.
Front Genet ; 13: 881051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081986

RESUMO

Background: Aging is characterized by the gradual loss of physiological integrity, resulting in impaired function and easier death. This deterioration is a major risk factor for major human pathological diseases, including cancer, diabetes, cardiovascular disease and neurodegenerative diseases. It is very important to find biomarkers that can prevent aging. Methods: Q-Exactive-MS was used for proteomic detection of young and senescence fibroblast. The key senescence-related molecules (SRMs) were identified by integrating transcriptome and proteomics from aging tissue/cells, and the correlation between these differentially expressed genes and well-known aging-related pathways. Next, we validated the expression of these molecules using qPCR, and explored the correlation between them and immune infiltrating cells. Finally, the enriched pathways of the genes significantly related to the four differential genes were identified using the single cell transcriptome. Results: we first combined proteomics and transcriptome to identified four SRMs. Data sets including GSE63577, GSE64553, GSE18876, GSE85358, and qPCR confirmed that ETF1, PLBD2, ASAH1, and MOXD1 were identified as SRMs. Then the correlation between SRMs and aging-related pathways was excavated and verified. Next, we verified the expression of SRMs at the tissue level and qPCR, and explored the correlation between them and immune infiltrating cells. Finally, at the single-cell transcriptome level, we verified their expression and explored the possible pathway by which they lead to aging. Briefly, ETF1 may affect the changes of inflammatory factors such as IL-17, IL-6, and NFKB1 by indirectly regulating the enrichment and differentiation of immune cells. MOXD1 may regulate senescence by affecting the WNT pathway and changing the cell cycle. ASAH1 may affect development and regulate the phenotype of aging by affecting cell cycle-related genes. Conclusion: In general, based on the analysis of proteomics and transcriptome, we identified four SRMs that may affect aging and speculated their possible mechanisms, which provides a new target for preventing aging, especially skin aging.

13.
Crit Rev Food Sci Nutr ; : 1-19, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094452

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic and continuing emergence of viral mutants, there has been a lack of effective treatment methods. Zinc maintains immune function, with direct and indirect antiviral activities. Zinc nutritional status is a critical factor in antiviral immune responses. Importantly, COVID-19 and zinc deficiency overlap in high-risk population. Hence, the potential effect of zinc as a preventive and adjunct therapy for COVID-19 is intriguing. Here, this review summarizes the immune and antiviral function of zinc, the relationship between zinc levels, susceptibility, and severity of COVID-19, and the effect of zinc supplementation on COVID-19. Existing studies have confirmed that zinc deficiency was associated with COVID-19 susceptibility and severity. Zinc supplementation plays a potentially protective role in enhancing immunity, decreasing susceptibility, shortening illness duration, and reducing the severity of COVID-19. We recommend that zinc levels should be monitored, particularly in COVID-19 patients, and zinc as a preventive and adjunct therapy for COVID-19 should be considered for groups at risk of zinc deficiency to reduce susceptibility and disease severity.

14.
Nature ; 609(7927): 560-568, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36045290

RESUMO

Central oscillators are primordial neural circuits that generate and control rhythmic movements1,2. Mechanistic understanding of these circuits requires genetic identification of the oscillator neurons and their synaptic connections to enable targeted electrophysiological recording and causal manipulation during behaviours. However, such targeting remains a challenge with mammalian systems. Here we delimit the oscillator circuit that drives rhythmic whisking-a motor action that is central to foraging and active sensing in rodents3,4. We found that the whisking oscillator consists of parvalbumin-expressing inhibitory neurons located in the vibrissa intermediate reticular nucleus (vIRtPV) in the brainstem. vIRtPV neurons receive descending excitatory inputs and form recurrent inhibitory connections among themselves. Silencing vIRtPV neurons eliminated rhythmic whisking and resulted in sustained vibrissae protraction. In vivo recording of opto-tagged vIRtPV neurons in awake mice showed that these cells spike tonically when animals are at rest, and transition to rhythmic bursting at the onset of whisking, suggesting that rhythm generation is probably the result of network dynamics, as opposed to intrinsic cellular properties. Notably, ablating inhibitory synaptic inputs to vIRtPV neurons quenched their rhythmic bursting, impaired the tonic-to-bursting transition and abolished regular whisking. Thus, the whisking oscillator is an all-inhibitory network and recurrent synaptic inhibition has a key role in its rhythmogenesis.


Assuntos
Parvalbuminas , Vibrissas , Animais , Tronco Encefálico/fisiologia , Mamíferos , Camundongos , Movimento/fisiologia , Neurônios/fisiologia , Vibrissas/fisiologia
15.
Nano Lett ; 22(17): 7136-7143, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36018249

RESUMO

Single-beam super-resolution microscopy, also known as superlinear microscopy, exploits the nonlinear response of fluorescent probes in confocal microscopy. The technique requires no complex purpose-built system, light field modulation, or beam shaping. Here, we present a strategy to enhance this technique's spatial resolution by modulating excitation intensity during image acquisition. This modulation induces dynamic optical nonlinearity in upconversion nanoparticles (UCNPs), resulting in variations of nonlinear fluorescence response in the obtained images. The higher orders of fluorescence response can be extracted with a proposed weighted finite difference imaging algorithm from raw fluorescence images to generate an image with higher resolution than superlinear microscopy images. We apply this approach to resolve single nanoparticles in a large area, improving the resolution to 132 nm. This work suggests a new scope for the development of dynamic nonlinear fluorescent probes in super-resolution nanoscopy.


Assuntos
Corantes Fluorescentes , Nanopartículas , Algoritmos , Microscopia Confocal/métodos
16.
Ther Clin Risk Manag ; 18: 799-812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992228

RESUMO

Purpose: Selective serotonin reuptake inhibitors (SSRIs) are the preferred treatments for depression. The most common adverse drug reactions are symptoms involving the digestive system, leading to low compliance in patients with depression. Therefore, it is important to assess the safety of SSRIs with respect to the digestive system. Several meta-analyses have compared the risks of digestive side effects of SSRIs and other antidepressants. We aimed to compare the risks of various SSRIs (fluoxetine, escitalopram, citalopram, paroxetine, and sertraline) for adverse reactions of the digestive system. Methods: Systematic searches returned 30 randomized controlled trials (n = 5004) of five antidepressants and placebos. Results: Fluoxetine had the lowest probability of digestive side effects, ranking fifth at 0.548. Sertraline had the highest probability of digestive side effects, with a probability of 0.611. For gastrointestinal tolerability, escitalopram was better than paroxetine (odds ratio [OR] =0.62, 95% confidence interval [CI] 0.43-0.87) and sertraline (OR=0.56, 95% CI 0.32-0.99). Conclusion: Fluoxetine exhibited distinct advantages compared to other SSRIs, while sertraline had the greatest likelihood of digestive system side effects. These findings will help doctors understand the relative advantages of various antidepressants.

17.
Natl Sci Rev ; 9(8): nwac044, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35992235

RESUMO

Uncertainties in ocean-mixing parameterizations are primary sources for ocean and climate modeling biases. Due to lack of process understanding, traditional physics-driven parameterizations perform unsatisfactorily in the tropics. Recent advances in the deep-learning method and the new availability of long-term turbulence measurements provide an opportunity to explore data-driven approaches to parameterizing oceanic vertical-mixing processes. Here, we describe a novel parameterization based on an artificial neural network trained using a decadal-long time record of hydrographic and turbulence observations in the tropical Pacific. This data-driven parameterization achieves higher accuracy than current parameterizations, demonstrating good generalization ability under physical constraints. When integrated into an ocean model, our parameterization facilitates improved simulations in both ocean-only and coupled modeling. As a novel application of machine learning to the geophysical fluid, these results show the feasibility of using limited observations and well-understood physical constraints to construct a physics-informed deep-learning parameterization for improved climate simulations.

18.
Clin Epigenetics ; 14(1): 102, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974349

RESUMO

BACKGROUND: Noninvasive diagnostic markers that are capable of distinguishing patients with colorectal cancer (CRC) from healthy individuals or patients with other cancer types are lacking. We report the discovery and validation of a panel of methylation-based markers that specifically detect CRC. METHODS: This was a large-scale discovery study based on publicly available datasets coupled with a validation study where multiple types of specimens from six cohorts with CRC, other cancer types, and healthy individuals were used to identify and validate the tissue-specific methylation patterns of CRC and assess their diagnostic performance. RESULTS: In the discovery and validation cohort (N = 9307), ten hypermethylated CpG sites located in three genes, C20orf194, LIFR, and ZNF304, were identified as CRC-specific markers. Different analyses have suggested that these CpG sites are CRC-specific hypermethylated and play a role in transcriptional silencing of corresponding genes. A random forest model based on ten markers achieved high accuracy rates between 85.7 and 94.3% and AUCs between 0.941 and 0.970 in predicting CRC in three independent datasets and a low misclassification rate in ten other cancer types. In the in-house validation cohort (N = 354), these markers achieved consistent discriminative capabilities. In the cfDNA pilot cohort (N = 14), hypermethylation of these markers was observed in cfDNA samples from CRC patients. In the cfDNA validation cohort (N = 155), the two-gene panel yielded a sensitivity of 69.5%, specificity of 91.7%, and AUC of 0.806. CONCLUSIONS: Hypermethylation of the ten CpG sites is a CRC-specific alteration in tissue and has the potential use as a noninvasive cfDNA marker to diagnose CRC.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ácidos Nucleicos Livres/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Ilhas de CpG , Metilação de DNA , Humanos
19.
Front Public Health ; 10: 920233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979472

RESUMO

The deterioration of the living environment caused by the earthquake is the main migration motivation of residents in the area of the secondary earthquake disaster, and their migration intention is one of the most important factors affecting residents' happiness. This paper uses 957 effective survey samples from 12 secondary geological disaster areas after the Wenchuan earthquake to research the migration intention of residents and its influencing factors. It can be found that 45.2% of residents are willing to migrate, which means they have an instinctive reaction to profit-seeking and harm-avoiding, but it has not become a realistic choice. Investigation facts and research results show that the instinctive response of profit-seeking and harm-avoiding drives residents to make different choices. The migration of residents in areas where secondary geological disasters occur is affected not only by disasters such as debris flow, landslides, and collapse, but also by many factors such as life convenience, family income, expectations for future life, gender, education level, psychological feeling. The improved life and the optimization of the economic conditions brought about by the success of post-disaster reconstruction have made the vast majority of people more confident in the future of the disaster-stricken areas, which made most people choose to stay in those areas. This paper will provide policy suggestions for residents' migration and the reconstruction of the local social governance system in secondary geological disaster areas, which is helpful to improve ecological livability and residents' happiness in the Wenchuan earthquake-stricken area.


Assuntos
Desastres , Terremotos , Humanos , Renda , Intenção , Inquéritos e Questionários
20.
ACS Omega ; 7(33): 29483-29494, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36033726

RESUMO

As a supervised machine learning algorithm, conditional random fields are mainly used for fault classification, which cannot detect new unknown faults. In addition, faulty variable location based on them has not been studied. In this paper, conditional random fields with a linear chain structure are utilized for modeling multimode processes with transitions. A linear chain conditional random field model is trained by normal data with mode label. This model is able to distinguish transitions from stable modes well. After mode identification, the expectation of state feature function is developed for fault detection and faulty variable location. Case studies on the Tennessee Eastman process and continuous stirred tank reactor (CSTR) testify the effectiveness of the proposed approach.

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