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1.
Ultrasonics ; 119: 106632, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34717143

RESUMEN

Since the temperature has a great effect on the service behavior of the ultrasonic motor, high temperature will affect its mechanical characteristics and service life. This article is on a model of a piezoelectric driven three-stator multi-degree-of-freedom ultrasonic motor. Firstly, the motion mechanism is analyzed, and the main causes of temperature rise are determined to be friction heat generation and vibration heat generation. Then, the theoretical model of temperature rise is built, and the temperature rise characteristics of the ultrasonic motor are simulated and analyzed by establishing a three-dimensional transient temperature field model. Finally, it is verified by temperature test experiment. The results show that the simulation analyses are consistent with the experimental results, and this analysis can correctly reflect the temperature rise characteristics of the motor. It provides a reference for further seeking the effect of the body temperature rise on the service behavior of the ultrasonic motor and improving the operating characteristics of the ultrasonic motor.

2.
Environ Res ; 203: 111851, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34384752

RESUMEN

The 32-mile Detroit River and surrounding tributaries have been designated as a Great Lakes Area of Concern due to pollution from decades of municipal and industrial discharges, sewer overflows and urban development. The Agency for Toxic Substances and Disease Registry and the Michigan Department of Health and Human Services conducted a biomonitoring study to assess exposures to persistent toxic substances in Detroit urban shoreline anglers who may be at high exposure risk due to consumption of locally caught fish. Using a modified venue-based sampling approach, 287 adult shoreline anglers along the Detroit River were recruited and participated in the program. Study participants provided blood and urine specimens and completed a questionnaire interview. In this report, we examine percentile estimates for blood lead, blood manganese, urine arsenic, urine mercury, urine cadmium, organochlorine pesticides in serum (mirex, hexachlorobenzene, chlordane), and serum polybrominated biphenyl 153 (PBB 153) concentrations among study participants. Multiple linear regression was used to identify predictors of contaminant concentrations. The Detroit urban anglers' blood lead concentrations were 2 times higher than the general adult U.S. population (median (95% CI): 2.9 µg/dL (1.8-2.3) vs. 0.94 µg/dL (0.90-0.98)). PBB 153 levels were 1.8 times higher than the general adult U.S. population at the 95th percentile (95th percentile, 95% CI: 62.7 ng/g of lipid, 53.2-75.2 vs. 34.6 ng/g of lipid, 12.8-66.8). Percentile estimates of the other study pollutants were similar to background levels found in the general U.S. population. Eating more locally caught fish was not associated with increased body burdens for any of the contaminants examined in this report. Higher blood lead was associated with increased age, male sex, current smoking, residing in a home built before 1960, an annual income less than $25,000, and a work history of lead paint removal. Evidence of PBB exposure in our study cohort likely reflects the continued effect of a widespread contamination of livestock feed in 1973 among Michigan's lower peninsula population. These study results help determine if the pollutants examined warrant further consideration in subsequent population-based biomonitoring of frequent consumers of fish from the Detroit River and surrounding waterways. The biomonitoring data from this study also served to inform public health officials regarding the potential need for environmental public health actions to reduce harmful exposures.

3.
Support Care Cancer ; 30(1): 413-421, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34302546

RESUMEN

BACKGROUND: Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli-caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables. METHODS: A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor. RESULTS: Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk (< 10% mortality, 0-1 points), medium risk (10-20% mortality, 2 points), and high risk (> 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer-Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P < 0.01). CONCLUSIONS: Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality.

4.
J Hazard Mater ; 423(Pt A): 127088, 2022 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-34482077

RESUMEN

Antibiotic resistance has become a global public health problem. Recently, various environmental pollutants have been reported to induce the proliferation of antibiotic resistance. However, the impact of multiple pollutants (e.g., heavy metals and antibiotics), which more frequently occur in practical environments, is poorly understood. Herein, one widely distributed heavy metal (Ag+) and one frequently detected antibiotic (tetracycline) were chosen to investigate their coexisting effect on the proliferation of antibiotic resistance in the activated sludge system. Results show that the co-occurrence of Ag+ and tetracycline at environmentally relevant concentrations exhibited no distinct inhibition in reactor performances. However, they inhibited the respiratory activity by 42%, destroyed the membrane structure by 218%, and increased membrane permeability by 29% compared with the blank control bioreactor. Moreover, the relative abundances of target antibiotic resistance genes (ARGs) (e.g., tetA, blaTEM-1, and sulII) in effluent after exposure of coexisting Ag+ and tetracycline were increased by 92-1983% compared with those in control reactor, which were 1.1-4.3 folds higher than the sum of the sole ones. These were possibly attributed to the enrichments of antibiotic-resistant bacteria. The results would illumine the coexisting effect of heavy metals and antibiotics on the dissemination of ARGs in activated sludge system.

5.
Talanta ; 236: 122866, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34635248

RESUMEN

Small molecular contaminants (such as mycotoxins, antibiotics, pesticide residues, etc.) in food and environment have given rise to many biological and ecological toxicities, which has attracted worldwide attention in recent years. Meanwhile, due to the advantages of aptamers such as high specificity and stability, easy synthesis and modification, as well as low cost and immunogenicity, various aptasensors for the detection of small molecular contaminants have been flourishing. An aptasensor as a whole is composed of an aptamer-based target recognizer and a signal transducer, which are fields of concentrated research. In the practical detection applications, in order to achieve the quantitative detection of small molecular contaminants at low abundance in real samples, a large number of signal enhancing strategies have been utilized in the development of aptasensors. Recent years is a vintage period for efficient signal enhancing strategies of aptasensors by the aid of nanomaterials and nucleic acid amplification that are applied in the elements for target recognition and signal conversion. Therefore, this paper meticulously reviews the signal enhancing strategies based on nanomaterials (including the (quasi-)zero-dimensional, one-dimensional, two-dimensional and three-dimensional nanomaterials) and nucleic acid amplification (including enzyme-assisted nucleic acid amplification and enzyme-free nucleic acid amplification). Furthermore, the challenges and future trends of the abovementioned signal enhancing strategies for application are also discussed in order to inspire the practitioners in the research and development of aptasensors for small molecular contaminants.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanoestructuras , Ácidos Nucleicos , Técnicas de Amplificación de Ácido Nucleico
6.
J Hazard Mater ; 421: 126709, 2022 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-34315021

RESUMEN

Nanoscale zero-valent iron nanoparticles (nZVI) have been used for groundwater remediation and wastewater treatment due to their high reactivity, high adsorption capacity and nontoxicity. However, side reactions generally occur in tandem with the target contaminants removal process, resulting in poor electron selectivity (ES) of nZVI, and subsequently restricting its commercial application. Major efforts to increase ES of nZVI have been made in recent years. This review's objective is to provide a progress report on the significant developments in nZVI's ES during the past decade. Firstly, the definition of ES and its quantification approaches were documented, and the intrinsic (i.e. particle size, crystallinity, and surface area) and extrinsic factors (i.e. solutions pH, target contaminant concentration, and presence of co-contaminants) affecting the ES of nZVI were reported. The latest techniques for increasing ES were summarized in detail, with reference made to sulfidation, magnetization, carbon loading and other features. Then the mechanisms of those strategies for ES enhancement were described. Finally, some constructive suggestions on future research directions concerning nZVI's ES in the future were proposed.


Asunto(s)
Restauración y Remediación Ambiental , Agua Subterránea , Contaminantes Químicos del Agua , Purificación del Agua , Electrones , Hierro , Contaminantes Químicos del Agua/análisis
7.
Gene ; 807: 145948, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-34481002

RESUMEN

BACKGROUNDS: To investigate associations of genetic and environmental factors with coronary artery disease (CAD), we collected medical reports, lifestyle details, and blood samples of 2113 individuals, and then used the polymerase chain reaction (PCR)-ligase detection reaction (LDR) to genotype the targeted 102 SNPs. METHODS: We adopted elastic net algorithm to build an association model that considered simultaneously genetic and lifestyle/clinical factors associated with CAD in Chinese Han population. RESULTS: In this study, we developed an all covariates-based model to explain the risk of CAD, which incorporated 8 lifestyle/clinical factors and a gene-score variable calculated from 3 significant SNPs (rs671, rs6751537 and rs11641677), attaining an area under the curve (AUC) value of 0.71. It was found that, in terms of genetic variants, the AA genotype of rs671 in the additive (adjusted odds ratio (OR) = 2.51, p = 0.008) and recessive (adjusted OR = 2.12, p = 0.021) models, the GG genotype of rs6751537 in the additive (adjusted OR = 3.36, p = 0.001) and recessive (adjusted OR = 3.47, p = 0.001) models were associated with increased risk of CAD, while GG genotype of rs11641677 in additive model (adjusted OR = 0.39, p = 0.044) was associated with decreased risk of CAD. In terms of lifestyle/clinical factors, the history of hypertension (unadjusted OR = 2.37, p < 0.001) and dyslipidemia (unadjusted OR = 1.82, p = 0.007), age (unadjusted OR = 1.07, p < 0.001) and waist circumference (unadjusted OR = 1.02, p = 0.05) would significantly increase the risk of CAD, while height (unadjusted OR = 0.97, p = 0.006) and regular intake of chicken (unadjusted OR = 0.78, p = 0.008) reduced the risk of CAD. A significantinteraction was foundbetween rs671 and dyslipidemia (the relative excess risk due to interaction (RERI) = 3.36, p = 0.05). CONCLUSION: In this study, we constructed an association model and identified a set of SNPs and lifestyle/clinical risk factors of CAD in Chinese Han population. By considering both genetic and non-genetic risk factors, the built model may provide implications for CAD pathogenesis and clues for screening tool development in Chinese Han population.


Asunto(s)
Adenilil Ciclasas/genética , Aldehído Deshidrogenasa Mitocondrial/genética , Enfermedad de la Arteria Coronaria/genética , beta-Caroteno 15,15'-Monooxigenasa/genética , Adenilil Ciclasas/metabolismo , Anciano , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Algoritmos , Área Bajo la Curva , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , China/epidemiología , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hipertensión/genética , Estilo de Vida , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo Genético/genética , Factores de Riesgo , Circunferencia de la Cintura/genética , beta-Caroteno 15,15'-Monooxigenasa/metabolismo
8.
Rob Auton Syst ; 148: 103917, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34720413

RESUMEN

The coronavirus disease 2019 (COVID-19) outbreak has increased mortality and morbidity world-wide. Oropharyngeal swabbing is a well-known and commonly used sampling technique for COVID-19 diagnose around the world. We developed a robot to assist with COVID-19 oropharyngeal swabbing to prevent frontline clinical staff from being infected. The robot integrates a UR5 manipulator, rigid-flexible coupling (RFC) manipulator, force-sensing and control subsystem, visual subsystem and haptic device. The robot has strength in intrinsically safe and high repeat positioning accuracy. In addition, we also achieve one-dimensional constant force control in the automatic scheme (AS). Compared with the rigid sampling robot, the developed robot can perform the oropharyngeal swabbing procedure more safely and gently, reducing risk. Alternatively, a novel robot control schemes called collaborative manipulation scheme (CMS) which combines a automatic phase and teleoperation phase is proposed. At last, comparative experiments of three schemes were conducted, including CMS, AS, and teleoperation scheme (TS). The experimental results shows that CMS obtained the highest score according to the evaluation equation. CMS has the excellent performance in quality, experience and adaption. Therefore, the proposal of CMS is meaningful which is more suitable for robot-sampling.

9.
Chemphyschem ; 2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34850511

RESUMEN

Thiol etching reaction of gold is still suffering from a lack of deep understandings on the reaction kinetics and mechanism. Herein, by using the sensor of quartz crystal microbalance (QCM) as the sacrificial probe, the etching reaction of gold has been studied in employing cysteamine (CS) as a typical thiol etchant. The etching reaction is verified as diffusion-controlled and shows a half-order reaction kinetics. It is demonstrated that intact thiol and amino on CS are both crucial for its etching ability to gold. Applied potentials can affect the electron transferring and hence can be used to regulate the etching of gold. Our results also reveal that only two carbon atoms of the spacer between thiol and amino on CS are very critical to the excellent etching ability. This work exhibits a new route to explore the thiol etching reaction of gold and well elucidates the reaction kinetics and mechanism.

10.
Chem Biodivers ; 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34862731

RESUMEN

Hepatocellular carcinoma (HCC),a common malignancy worldwide, has a high mortality rate and limited effective therapeutic options. In this work, a series of quinazolinone compounds ( 6a-t and 7a-i ) were synthesized as potential anti-HCC agents. Among them, compound 7b more potently inhibited HepG2, HUH7 and SK-Hep-1 cells proliferation than classical anti-HCC drug sorafenib, indicating its potential anti-HCC effect. Interestingly, 7b could dose-dependently decrease Cyclin D1 and CDK2 levels, and increase p21 protein expression, thus inducing HepG2 cells cycle arrest at G0/G1 phase. In addition, 7b also displayed potent apoptosis-induced effect on HepG2 cells by interfering Bad, Bax, Bcl-2 and Bcl-xl proteins expression. Notably, 7b could efficiently block the activity of PI3K pathway by dose-dependently reducing the phosphorylation of PI3K (Y607) and AKT (S473). Moreover, predicted ADME properties indicated that 7b possessed a good pharmacokinetic profile. Collectively, compound 7b might be a promising lead to the development of novel therapeutic agents towards HCC.

11.
Neuroradiology ; 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34860278

RESUMEN

PURPOSE: To develop and validate a dual-energy CT (DECT)-based radiomics nomogram from multicenter trials for predicting the histological differentiation of head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 178 patients (112 in the training and 66 in the validation cohorts) from eight institutions with histologically proven HNSCCs were included in this retrospective study. Radiomics-signature models were constructed from features extracted from virtual monoenergetic images (VMI) and iodine-based material decomposition images (IMDI), reconstructed from venous-phase DECT images. Clinical factors were also assessed to build a clinical model. Multivariate logistic regression analysis was used to develop a nomogram combining the radiomics signature models and clinical model for predicting poorly differentiated HNSCC and moderately well-differentiated HNSCC. The predictive performance of the clinical model, radiomics signature models, and nomogram was compared. The calibration degree of the nomogram was also assessed. RESULTS: The tumor location, VMI-signature, and IMDI-signature were associated with the degree of HNSCC differentiation, and areas under the ROC curves (AUCs) were 0.729, 0.890, and 0.833 in the training cohort and 0.627, 0.859, and 0.843 in the validation cohort, respectively. The nomogram incorporating tumor location and two radiomics-signature models yielded the best performance in training (AUC = 0.987) and validation (AUC = 0.968) cohorts with a good calibration degree. CONCLUSION: The nomogram that integrated the DECT-based radiomics-signature models and tumor location showed good performance in predicting histological differentiation degree of HNSCC, providing a novel combination for predicting HNSCC differentiation.

12.
Plant Biotechnol J ; 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34861095

RESUMEN

Humans have domesticated diverse species from across the plant kingdom, however our current understanding of plant domestication is largely founded on major cereal crops. Here, we examine the evolutionary processes and genetic basis underlying the domestication of water caltrop (Trapa spp., Lythraceae), a traditional, yet presently-underutilized non-cereal crop that sustained early Chinese agriculturalists. We generated a chromosome-level genome assembly of tetraploid T. natans, and then divided the allotetraploid genome into two subgenomes. Based on resequencing data from 57 accessions, representing cultivated diploid T. natans, wild T. natans (2x and 4x) and diploid T. incisa, we showed that water caltrop was likely first domesticated in the Yangtze River Valley as early as 6,300 yr BP, and experienced a second improvement c. 800 years ago. We also provided strong support for an allotetraploid origin of T. natans within the past 230,000-310,000 years. By integrating selective sweep and transcriptome profiling analyses, we identified a number of genes potentially selected and/or differentially expressed during domestication, some of which likely contributed not only to larger fruit sizes but also to a more vigorous root system, facilitating nutrient uptake, environmental stress response, and underwater photosynthesis. Our results shed light on the evolutionary and domestication history of water caltrop, one of the earliest domesticated crops in China. This study has implications for genomic-assisted breeding of this presently underutilized aquatic plant, and improves our general understanding of plant domestication.

13.
J Agric Food Chem ; 69(45): 13568-13577, 2021 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-34730357

RESUMEN

To improve the reactivity and enrich the functionality of lignin for valorization, kraft lignin was depolymerized and demethylated via cleaving aryl and alkyl ether bonds in acidic lithium bromide trihydrate (∼60% LiBr aqueous solution). It was found that the cleavage of the ether bonds followed the order of ß-O-4 ether > aryl alkyl ether in phenylcoumaran > dialkyl ether in resinol > methoxyl (MeO). The depolymerization via ß-O-4 cleavage occurred under mild conditions (e.g., <0.5 M HCl at 110 °C), while sufficient demethylation of the lignin needed harsher conditions (>1.5 M HCl). Both depolymerization and demethylation generated new aromatic hydroxyl (ArOH). With 2.4 M HCl, MeO content dropped from 4.85 to 0.95 mmol/g lignin, and ArOH content increased from 2.78 to 5.09 mmol/g lignin. The depolymerized and demethylated kraft lignin showed excellent antioxidant activity and Cr(VI)-scavenging capacity, compared with original kraft lignin and tannins.


Asunto(s)
Antioxidantes , Lignina , Desmetilación , Éteres , Lignina/metabolismo
14.
Opt Express ; 29(23): 38027-38043, 2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34808863

RESUMEN

Raman microscopy with resolution below the diffraction limit is demonstrated on sub-surface nanostructures. Unlike most other modalities for nanoscale measurements, our approach is able to image nanostructures buried several microns below the sample surface while still extracting details about the chemistry, strain, and temperature of the nanostructures. In this work, we demonstrate that combining polarized Raman microscopy adjusted to optimize edge enhancement effects and nanostructure contrast with fast computational deconvolution methods can improve the spatial resolution while preserving the flexibility of Raman microscopy. The cosine transform method demonstrated here enables significant computational speed-up from O(N3) to O(Nlog N) - resulting in computation times that are significantly below the image acquisition time. CMOS poly-Si nanostructures buried below 0.3 - 6 µm of complex dielectrics are used to quantify the performance of the instrument and the algorithm. The relative errors of the feature sizes, the relative chemical concentrations and the fill factors of the deconvoluted images are all approximately 10% compared with the ground truth. For the smallest poly-Si feature of 230 nm, the absolute error is approximately 25 nm.

15.
Artículo en Inglés | MEDLINE | ID: mdl-34811702

RESUMEN

Recently, it has been irrefutably discovered that brown adipocytes dissipate energy as heat and protect against obesity. Researchers make great efforts to explore approaches for its activation. Lipoxin A4 (LXA4) has been proven to reverse adipose tissue inflammation and improve insulin resistance, but its function on brown adipocyte differentiation has been poorly understood, which therefore to be investigated in the present study. Mouse embryonic fibroblasts (MEFs) were induced and differentiated to model brown adipocytes, and treated with LXA4 at 0, 1, 5, and 10 nM for 0-14 d. Afterwards, Oil Red O staining detected lipid droplets. In differentiated MEFs with or without LXA4 (10 nM) treatment, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assessed adipocyte browning marker uncoupling protein 1 (UCP-1), and brown adipogenesis markers peroxisome proliferator-activated receptor gamma (PPARγ), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), cyclooxygenase-2 (COX-2), and positive regulation domain containing 16 (PRDM16) as well as lipogenic genes of stearoyl-CoA desaturase 1 (SCD1), fatty acid synthase (FASN), glucose transporter type 4 (GLUT4), and carbohydrate response element binding protein (ChREBP). The induced differentiation of MEFs toward brown adipocytes was successful. LXA4 promoted intracellular accumulation of lipid droplets of induced cells and increased UCP-1 expression in a dose- or time-dependent manner. Under the administration of LXA4, brown adipogenesis markers and lipogenic genes were further upregulated. LXA4 made a contribution to induce differentiation of MEFs to brown adipocytes, which could be regarded a new drug target for obesity management.

16.
Bioorg Med Chem ; 51: 116505, 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34781081

RESUMEN

Lipidation of microtubule associated protein 1 light chain 3 (LC3) is the critical step in autophagosome formation, numerous efforts have been made to design and develop small molecules that trigger LC3 lipidation to activate autophagy. In this study, we discovered a series of andrographolide derivatives as potent antagonists of vitamin D receptor (VDR) by luciferase reporter assay. Structure-activity-relationship study revealed that andrographolide derivative ZAV-12 specifically inhibited VDR signaling but not NF-κB or STAT3 activation. Western blot analysis indicates that ZAV-12 markedly triggered lipidation of LC3 in MPP+-induced Parkinsonism in vitro in an mTOR-independent manner. The ZAV-12 triggered lipidation was mediated through SREBP2 activation instead of changing expression levels of lipid synthesis genes. Furthermore, ZAV-12 treatment increased the ratio of LC3-II/LC3-I and oligomerization of A53T α-synuclein (SNCA) in SNCA triggered neurotoxicity. Taken together, these results demonstrate the therapeutic potential of VDR antagonist as novel drug candidate for neurodegenerative diseases.

17.
Artículo en Inglés | MEDLINE | ID: mdl-34816324

RESUMEN

INTRODUCTION: Medial unicompartmental knee arthroplasty (mUKA) requires full-thickness cartilage in the lateral compartment, but slight damage of the cartilage surface can be ignored. However, as this statement lacks literature support, we investigated whether slight cartilage damages in the weight-bearing area of the lateral femoral condyle would affect the outcome of mUKAs. MATERIALS AND METHODS: Outerbridge grading was performed on the cartilage in the weight-bearing area of the lateral femoral condyle intraoperatively. The patients, grouped as normal or as having lateral condyle cartilage of Outerbridge grade 1-2 (slight cartilage damage), underwent mUKA. Full-length lower extremity radiographs were taken and hip-knee-ankle angles (HKAAs) were measured both preoperatively and postoperatively. Using magnetic resonance imaging, the lateral meniscal extrusion distance was also measured. In addition, the Oxford Knee Score (OKS) was assessed preoperatively and at the last follow-up, in addition to the patient satisfaction assessment. RESULTS: We enrolled 152 knees of 142 patients proposed for mUKAs. The mean age of participants was 69.5 years (51-89 years) and they were followed up for a mean of 25.4 months (15-44 months). There was no significant difference in preoperative (p = 0.746) and postoperative (p = 0.202) mean OKS between the normal, Outerbridge grade 1 and Outerbridge grade 2 groups. While the normal group had a higher change in OKS than the group with cartilage damage, this difference was not significant (p = 0.910). The UKA corrected the patients' mean HKAA from 171.1° (preoperatively) to 176.1° (postoperatively). From all patients, only four had slight lateral meniscus extrusion with MEDs of ≤ 0.25 mm. With the exception of one patient with a poor outcome in normal group, the rest were satisfied with the outcome of mUKA. No patients had prosthesis-related complications or revision surgery. CONCLUSIONS: Cartilage damage of Outerbridge grade 1 and grade 2 in the weight-bearing area of the lateral femoral condyle will not compromise the short-term outcome of medial mobile-bearing UKA.

18.
Biomaterials ; 279: 121180, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34768152

RESUMEN

Cancer stem cells (CSCs) present grand challenges for triple-negative breast cancer (TNBC). Conventional chemotherapy drugs, including Camptothecin (CPT), not only cannot eradicate CSCs but also foster a suppressive immune microenvironment for the initiation and proliferation of CSCs. Herein, we report a novel prodrug CPT-SS-NLG919 (CN) and its nanoformulation CN@PLA-HES-FA (CN@PHF), which potently suppress CSCs by regulating CSCs niche in murine TNBC 4T1 tumors. Via inducing immunogenic cell death (ICD) and simultaneous inhibiting indoleamine 2, 3-dioxygenase (IDO), CN and CN@PHF promote DC maturation, decrease Treg cells, mitigate tryptophan consumption, and reduce the amount of IL-6, IL-13, and TGF-ß, converting CSCs niche to a hostile condition for CSCs to live in and eliminating CSCs efficiently, thereby inducing efficient tumor inhibition in 4T1 tumor models. Our work represents a new paradigm of eliminating CSCs by regulating tumor immune microenvironment and suggests that CN and its nanoformulation CN@PHF are promising candidates for the treatment of intractable TNBC.

19.
Bioengineered ; 12(2): 11169-11187, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34783629

RESUMEN

Conventionally, Rho guanine nucleotide exchange factors (GEFs) are known activators of Rho guanosine triphosphatases (GTPases) that promote tumorigenesis. However, the role of Rho GEFs in non-small cell lung cancer (NSCLC) remains largely unknown. Through the screening of 81 Rho GEFs for their expression profiles and correlations with survival, four of them were identified with strong significance for predicting the prognosis of NSCLC patients. The four Rho GEFs, namely ABR, PREX1, DOCK2 and DOCK4, were downregulated in NSCLC tissues compared to normal tissues. The downregulation of ABR, PREX1, DOCK2 and DOCK4, which can be attributfed to promoter methylation, is correlated with poor prognosis. The underexpression of the four key Rho GEFs might be related to the upregulation of MYC signaling and DNA repair pathways, leading to carcinogenesis and poor prognosis. Moreover, overexpression of ABR was shown to have a tumor-suppressive effect in PC9 and H1703 cells. In conclusion, the data reveal the unprecedented role of ABR as tumor suppressor in NSCLC. The previously unnoticed functions of Rho GEFs in NSCLC will inspire researchers to investigate the distinct roles of Rho GEFs in cancers, in order to provide critical strategies in clinical practice.

20.
J Evol Biol ; 2021 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-34792226

RESUMEN

Artemisia frigida is a temperate grassland species that has the largest natural range among its genus, with occurrences across the temperate grassland biomes of Eurasia and North America. Despite its wide geographic range, we know little about the species' distribution history. Hence, we conducted a phylogeographical study to test the hypothesis that the species' distribution pattern is related to a potential historical migration over the 'Bering land bridge'. We applied two molecular approaches: genotyping-by-sequencing (GBS) and Sanger sequencing of the plastid intergenic spacer region (rpl32 - trnL) to investigate genetic differentiation and relatedness among 21 populations from North America, Middle Asia, Central Asia and the Russian Far East. Furthermore, we identified the ploidy level of individuals based on GBS data. Our results indicate that A. frigida originated in Asia, spread northwards to the Far East and then to North America across the Bering Strait. We found a pronounced genetic structuring between Middle and Central Asian populations with mixed ploidy levels, tetraploids in the Far East, and nearly exclusively diploids in North America except for one individual. According to phylogenetic analysis, two populations of Kazakhstan (KZ2 and KZ3) represent the most likely ancestral diploids that constitute the basally branching lineages, and subsequent polyploidization has occurred on several occasions independently. Mantel tests revealed weak correlations between genetic distance and geographical distance and climatic conditions, which indicates that paleoclimatic fluctuations may have more profoundly influenced A. frigida's spatial genetic structure and distribution than the current environment.

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