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1.
J Control Release ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662587

RESUMO

Detrimental tumor microenvironment (TME) relies on distorted tumor vasculature for further tumor expansion. Vascular normalization therapy partly improves TME through vessel repairing, while these therapies enter an unbreakable Möbius ring due to each attempt hindered by pro-angiogenic factors from TME, leading to limited duration and extent of normalization window. Here, we developed a nanosystem including FLG and MAR/MPA nanodrugs to dual-regulate tumor vasculature and TME. FLG nanodrugs were constructed by connecting VEGF/VEGFR2 inhibitory low molecular weight heparin and gambogic acid with F3 peptide decoration for directly regulating on vascular endothelial cells and inducing vascular normalization. Meanwhile, MAR/MPA nanodrugs encapsulating CCL5/CCR5 blocker maraviroc were designed to restrict pro-angiogenic and TME deteriorating cytokine functions, contributing to vasculature repairing and TME reconstruction. Our results demonstrated this combined nanosystem synergistically induced vascular normalization window lasting 9 days and restored vascular permeability and oxygen supply in Panc-1 tumor. Furthermore, in melanoma, our nanosystem achieved immune improvements with increased infiltration of CD4+ and CD8+T cells in a remodeled TME. The two nanodrugs assisting each other in terms of both vascular repairing and TME improvements successfully reversed the vicious crosstalk to a positive one, achieving overall TME remodeling and promoting therapeutic efficiency.

2.
Sci Total Environ ; 806(Pt 3): 150409, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34599953

RESUMO

This study focused on the resource recovery of sludge treatment by quantifying the environmental contributions, identifying the influential factors, and comparing different scenarios. Life cycle assessment (LCA) of sewage sludge treatment was carried out to estimate the environmental impacts of six scenarios: (1) co-digestion of sludge and food waste; (2) co-gasification of sludge and woody waste; (3) co-incineration of sludge and used oil; (4) landfilling; (5) incineration; and (6) anaerobic digestion combined with incineration. Results demonstrate that the resource recovery had a substantial contribution to the environmental performance of the sludge treatment, while the degree of contribution was largely affected by various treatment scenarios and diverse impact categories. To gain deep insight into the parameters related to resource recovery, sensitivity analysis was performed to investigate the influence of the parameters on the LCA results, including the organic content, conversion efficiency of organic matter to methane, and other energy conversion efficiencies. After integrating the inventory variation of those parameters into the decision process via the Monte Carlo simulation, results indicate that no obviously superior scenario could be identified. Conversely, when parameter uncertainty was not considered, co-gasification of sludge and woody waste exhibited the most preferable environmental performance. Overall, this study demonstrates that considering the parameter uncertainty of resource recovery will contribute to a more transparent evaluation process, but will inevitably increase the complexity of the decision-making process based on LCA results because it is difficult to determine a sludge treatment scenario that decisively outperforms the others.

3.
Microbes Environ ; 36(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34602537

RESUMO

The accessory nidamental gland (ANG) is part of the reproduction organ in the majority of female cephalopods, including the bigfin reef squid Sepioteuthis lessoniana, an economically important fishery product. Microbes in Alphaproteobacteria, Gammaproteobacteria, and Verrucomicrobia have been suggested to play a role in the maturation of the S. lessoniana ANG and are responsible for its color. However, the bacterial composition and dynamics of the different maturation stages of the ANG remain unclear. In the present study, we surveyed ANG-associated bacterial dynamics in wild-caught S. lessoniana at various developmental stages in different populations over 3 years. The results obtained showed that the ANG bacterial community shifted gradually and decreased in diversity throughout maturation. Verrucomicrobia occupied the ANG during the early stages in large numbers, and was replaced by Bacteroidia, Alphaproteobacteria, and Gammaproteobacteria in the later stages. Flavobacteriales and Alphaproteobacteria both appeared to contribute to pigmentation, while Bacteroidia, Alphaproteobacteria, and Gammaproteobacteria may be involved in enriching the heme biosynthesis pathway in the ANG with the maturation of S. lessoniana. The present results provide an open question of whether S. lessoniana actively selects the bacterial community in the ANG to adjust to its surrounding environment.

4.
J Hazard Mater ; 424(Pt A): 127188, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34597936

RESUMO

Microbial carriers may co-transport polycyclic aromatic hydrocarbons (PAHs), but lack substantial experimental evidence. Cable bacteria use gliding or twitching motility to access sulfide; hence, they could be important microbial carriers in co-transporting PAHs from the sediment-water interface into suboxic zones. In this study, the effect of cable bacteria on pyrene migration was investigated by connecting or blocking the paths of cable bacteria to the suboxic zones. The results showed that downward migration of pyrene in the connecting groups were significantly higher (17.3-49.2%, p < 0.01) than those in the control groups. Meanwhile, significant downward migration of microbial communities in the connecting groups were also observed, including abundant filamentous-motile microorganisms, especially cable bacteria. The adsorption of surrounding particles by cable bacteria were morphologically evidenced. The biomechanical model based on the Peclet number indicated that filamentous-motile microorganisms demonstrated stronger adsorption ability for pyrene than other microorganisms. Supposedly, the downward migration of microbial communities, especially cable bacteria, significantly enhanced pyrene migration, thus influencing the distribution and ecological risk of pyrene in sediments. This study provides new insights into the important roles of motile microorganisms in the migration of PAHs in sediments, shedding lights on guidance for ecological risk assessment of PAHs.

5.
Magn Reson Imaging ; 85: 80-86, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34666158

RESUMO

OBJECTIVES: To develop and validate a radiomics nomogram for differentiating between malignant pulmonary nodules and benign nodules. METHODS: 56 benign and 51 malignant nodules from 96 patients were analyzed using manual segmentation of the T2-fBLADE-TSE, while the nodules signal intensity (SIlesion), lesion muscle ratio (LMR) and nodule size were all measured and recorded. The maximum relevance and minimum redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select nonzero coefficients and develop the model in pulmonary nodules diagnosis. The radiomics nomogram was also developed. The clinical prediction value was determined by the decision curve analysis (DCA). RESULTS: The nodule size, SIlesion and LMR of the benign group were 1.78 ± 0.57 cm, 227.50 ± 81.39 and 2.40 ± 1.27 respectively, in contrast to the 2.00 ± 0.64 cm, 232.87 ± 82.21 and 2.17 ± 0.91, respectively, in the malignant group (P = 0.09, 0.60 and 0.579). A total of 13 radiomics features were retained. The Rad-score of the benign nodules group was lower than that of the malignant nodules group (P < 0.001 & 0.049, training & test set). The AUC of radiomics signature for nodules diagnosis was 0.82 (95% CI, 0.73-0.91) in the training set and 0.71 (95% CI, 0.51-0.90) in the test set. A nomogram, consisting of 13 radiomics features and nodule size, produced good prediction in the training set (AUC, 0.82; 95% CI, 0.73-0.91), which was significantly better than that of T2-based quantitative parameters (AUC, 0.62; 95% CI, 0.50-0.75, P = 0.003). In the test set, the performance of radiomics nomogram (AUC, 0.70; 95% CI, 0.51-0.90) was also better than that of T2-based quantitative parameters (AUC, 0.46; 95% CI, 0.25-0.67) (P = 0.145). The DCA showed that radiomics nomogram and T2-based quantitative parameter had overall net benefits, while the performance of nomogram was better. CONCLUSION: We constructed and validated a T2-fBLADE-TSE-based radiomics nomogram that can help to differentiate between malignant pulmonary nodules and benign nodules.

6.
Radiology ; : 210355, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546127

RESUMO

Background The long-term prognostic value of coronary CT angiography (CCTA) in asymptomatic adults with hepatic steatosis (HS) remains unknown. Purpose To evaluate the long-term prognostic value of CCTA in asymptomatic adults with HS. Materials and Methods Between January 2009 and December 2013, consecutive asymptomatic adults who underwent CCTA evaluation and unenhanced abdominal CT were prospectively enrolled. All participants were divided into two groups-with HS and without HS according to abdominal CT results. The primary end point was major adverse cardiovascular events (MACEs), defined as cardiac death, stroke, myocardial infarction, and angina requiring hospitalization. Multivariable Cox regression analysis and Kaplan-Meier analysis were used to compare survival rates. Results One thousand thirteen participants with HS and 1940 participants without HS who completed the follow-up were included (mean age, 66 years ± 10 [standard deviation] [range, 29-90 years]; 1940 men). During a median of 7.2 years of follow-up (interquartile range, 6.3-8.1), MACEs were observed in 96 of 1013 participants with HS (10%), whereas 80 of 1940 participants without HS (4%) had MACEs. In participants with a Coronary Artery Disease Reporting and Data System (CAD-RADS) category of 0, both participants with and without HS had a similar 8.8-year event-free survival rate (99.2% event-free survival rate in participants with HS vs 99.0% event-free survival rate in participants without HS, P = .77). As for participants with CAD-RADS categories 1 or 2 or 3-5, the 8.8-year event-free survival rate was lower in participants with HS than in those without HS (70.6% vs 85.2%, P < .001; 51.4% vs 71.7%, P = .03, respectively). The risk of MACEs was higher for participants with HS than for those without HS in CAD-RADS categories 1 and 2 (adjusted hazard ratio = 2.3; 95% CI: 1.4, 3.9; P < .001) and CAD-RADS categories 3-5 (adjusted HR = 2.1; 95% CI: 1.2, 3.6; P = .006) but not in the setting of CAD-RADS category 0 (adjusted HR = 5.1; 95% CI: 0.1, 398; P = .47). Conclusion Asymptomatic participants with hepatic steatosis (HS) had a worse prognosis than those without HS in the presence of coronary artery disease (CAD) at coronary CT angiography, whereas participants with HS and without CAD might have excellent clinical outcomes during a median follow-up of 7.2 years. © RSNA, 2021 Online supplemental material is available for this article.

7.
J Colloid Interface Sci ; 606(Pt 2): 1445-1456, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34492479

RESUMO

Hematite (α-Fe2O3) is a promising candidate for NH3 selective catalytic reduction (NH3-SCR) of NOx due to its good sulfur resistance. However, the activity of pure α-Fe2O3 is very low. In this work, α-Fe2O3 obtained excellent N2 selectivity and medium-high temperature activity via a simple surface sulfation method. The α-Fe2O3-350 (sulfated at 350 °C) sample showed an NO conversion rate of ~ 100% in the range of 275-350 °C and exhibited excellent H2O and SO2 resistance ability at 300 °C. Furthermore, pure α-Fe2O3 was used as a model catalyst to fully uncover the effect of sulfation on FeOx-based catalysts in NH3-SCR reactions. Structural characterization indicated that the degree of surface sulfation of the catalyst would be deepened with increasing temperature, and the states of sulfate species on α-Fe2O3 changed from surface sulfates to bulk-like sulfates. Although sulfation treatment reduced the redox properties of α-Fe2O3, it significantly increased its surface acidity and thus the activity. Excessive bulk-like sulfates induced a decrease in activity. Sulfation inhibited the adsorption of NOx on the α-Fe2O3 catalyst surface and reduced the thermal stability of nitrates at medium-high temperature. Thus, the Langmuir-Hinshelwood (L-H) mechanism was inhibited, and the reaction mainly followed the Eley-Rideal (E-R) mechanism.

8.
BMC Genomics ; 22(1): 668, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525971

RESUMO

OBJECTIVE: From genome-wide association studies, brain-derived neurotrophic factor (BDNF) locus on chromosome 11 was the only SNP associated with both smoking and body mass index (BMI) in European, African and Asian population. This study aims to explore the unique genetic predisposition to obesity in former smokers by examining the effects of BDNF on BMI and waist circumference (WC). METHODS: The study design is case-control study with a cohort validation in supplementary. We included 15,072 ethnic Chinese participants in the Guangzhou Biobank Cohort Study (GBCS) with data of four BDNF SNPs related to both BMI and smoking behavior. We used baseline smoke exposure data in 2003-2007 and follow-up outcomes of general obesity (by BMI) and central obesity (WC) in 2008-2012. Odds ratios (ORs) and 95% confidence intervals (CIs) for general obesity and central obesity associated with these SNPs were derived from logistic regression. RESULTS: Of 15,072 participants (3169 men and 11,903 women), 1664 (11.0%) had general and 7868 (52.2%) had central obesity. In 1233 former smokers, the rs6265 GG, versus AA, genotype was associated with higher risks of general obesity (OR = 1.79, 95% CI = 1.06-3.01) and central obesity (OR = 2.08, 95% CI = 1.47-2.92) after adjustment. These associations were not significant in never or current smokers. In former heavy (≥20 cigarettes/day) smokers, the rs6265 GG genotype showed a higher odds for general obesity (OR = 2.15, 95% CI = 1.05-4.40), while no association was found in former light (1-9 cigarettes/day) smokers. Similar results were found for the association of rs6265 with central obesity and for the associations of other two BDNF SNPs (rs4923457 and rs11030104) with both general and central obesity. CONCLUSIONS: We firstly identified the genetic predisposition (BDNF SNPs) to general and central obesity in former smokers, particularly in former heavy smokers. The different associations of the SNPs for general/central obesity in different smoke exposure groups may be related to the competitive performance of the sites and epigenetic modification, which needs further study.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Estudo de Associação Genômica Ampla , Índice de Massa Corporal , Fator Neurotrófico Derivado do Encéfalo/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Obesidade/genética , Fumantes
9.
ACS Appl Mater Interfaces ; 13(37): 44497-44508, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34506122

RESUMO

As a secondary Li-ion battery with high energy density, lithium-sulfur (Li-S) batteries possess high potential development prospects. One of the important ingredients to improve the safety and energy density in Li-S batteries is the solid-state electrolyte. However, the poor ionic conductivity largely limits its application for the commercial market. At present, the gel electrolyte prepared by combining the electrolyte or ionic liquid with the all-solid electrolyte is an effective method to solve the low ion conductivity of the solid electrolyte. We present a cross-linked gel polymer electrolyte with fluoroethylene carbonate (FEC) as a solid electrolyte interface (SEI) film formed for Li-S quasi-solid-state batteries, which can be simply synthesized without initiators. This gel polymer electrolyte with FEC as an additive (GPE@FEC) possesses high ionic conductivity (0.830 × 10-3 S/cm at 25 °C and 1.577 × 10-3 S/cm at 85 °C) and extremely high Li-ion transference number (tLi+ = 0.674). In addition, the strong ability toward anchoring polysulfides resulting in the high electrochemical performance of Li-S batteries was confirmed in GPE@FEC by the diffusion experiment, X-ray photoelectron spectroscopy analysis (XPS), and scanning electron microscopy (SEM) mapping of the S element. Such a high ion conductivity (IC) gel polymer electrolyte enables a competitive specific capacity of 940 mAh/g at 0.2C and supreme cycling performance for 180 cycles at 0.5C, which is far beyond that of conventional poly(ethylene oxide)-based quasi-solid-state Li-S batteries.

10.
J Hazard Mater ; 416: 126222, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492977

RESUMO

Plastic biodegradation by mealworm is regarded as an emerging strategy for plastic disposal. In this study, the polystyrene (PS) and low density polyethylene (LDPE) degradation efficiency by yellow mealworms (Tenebrio molitor larvae) supplemented with bran and the effects of plastics on the gut core microbiome were explored to construct a circular and continuous reactor for plastic biodegradation in the future. The gut microbiome was also investigated with dietary shift to explore the relationship between specific diets and gut microbes. The bran plus plastic (7:1 ratio, w/w) co-diet contributed to the mealworm survival and growth. The formation of -CË­O-/-C-O- groups in the plastic-fed mealworms frass represented the oxidation process of plastic biodegradation in the mealworm gut. The changes in molecular weights (Mw, Mn and Mz) of residual PS and LDPE in mealworms frass compared with that of PS and PE feedstock confirmed the plastic depolymerization and biodegradation. Lactobacillus and Mucispirillum were significantly associated with PE + bran diet compared to bran diet and PE diet, representing the response of mealworm gut microbiome to the bran and plastic mixture was distinguished from either bran or plastics alone. The gut microbiome changed substantially with the diet shift, indicating that microbial community assembly was a stochastic process and diverse plastic-degrading bacteria might occur in the mealworm gut.


Assuntos
Microbioma Gastrointestinal , Tenebrio , Animais , Dieta , Polietileno , Poliestirenos
11.
Front Mol Biosci ; 8: 729350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485387

RESUMO

LuxR, a bacterial quorum sensing-related transcription factor that responds to the signaling molecule 3-oxo-hexanoyl-homoserine lactone (3OC6-HSL). In this study, we employed molecular dynamics simulation and the Molecular Mechanics Generalized Born Surface Area (MM-GB/SA) method to rationally identify residues in Vibrio fischeri LuxR that are important for its interaction with 3OC6-HSL. Isoleucine-46 was selected for engineering as the key residue for interaction with 3OC6-HSL-LuxR-I46F would have the strongest binding energy to 3OC6-HSL and LuxR-I46R the weakest binding energy. Stable wild-type (WT) LuxR, I46F and I46R variants were produced in Escherichia coli (E. coli) in the absence of 3OC6-HSL by fusion with maltose-binding protein (MBP). Dissociation constants for 3OC6-HSL from MBP-fusions of WT-, I46F- and I46R-LuxR determined by surface plasmon resonance confirmed the binding affinity. We designed and constructed a novel whole-cell biosensor on the basis of LuxR-I46F in E. coli host cells with a reporting module that expressed green fluorescent protein. The biosensor had high sensitivity in response to the signaling molecule 3OC6-HSL produced by the target bacterial pathogen Yersinia pestis. Our work demonstrates a practical, generalizable framework for the rational design and adjustment of LuxR-family proteins for use in bioengineering and bioelectronics applications.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34585040

RESUMO

PURPOSE: Strict clinical criteria used by Medicare for germline testing for Lynch syndrome (LS) could lead to missed diagnoses of hereditary cancer syndromes given variable individual and family phenotypes. The aim of this study was to compare rates and spectrum of pathogenic or likely pathogenic (P/LP) variants in LS and other hereditary cancer genes on the basis of meeting Medicare LS testing criteria. METHODS: Retrospective review of Medicare beneficiaries who had multigene panel testing with an indication of personal or family history of colorectal cancer (CRC) was performed. Ordering providers determined if Medicare LS criteria were met. The results of genetic testing were compared on the basis of whether or not Medicare testing criteria were met. RESULTS: Among 639 Medicare beneficiaries, 495 (77.5%) met testing criteria. Overall rates of P/LP variant identification were similar between those meeting and not meeting testing criteria (18.4% v 11.8%; P = .06). LS was diagnosed more frequently among those meeting testing criteria (10.1% v 4.9%; P = .05). No statistical differences were found in rates of P/LP variant identification for non-LS CRC genes (5.3% v 5.6%; P = .89) or non-CRC genes (4.2% v 2.1%; P = .23). PMS2, MUTYH, and ATM P/LP variants were found at higher rates among those outside of criteria. CONCLUSION: Among Medicare beneficiaries undergoing genetic testing for suspected LS, rates of P/LP variants in actionable cancer genes were similar regardless of whether testing criteria were met. Current testing criteria fail to identify individuals with P/LP variants in PMS2 and other actionable cancer genes. Relaxing LS testing criteria could improve identification of individuals with hereditary cancer syndromes among Medicare beneficiaries.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34468782

RESUMO

BACKGROUND: To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. METHODS: The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. RESULTS: PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p < 0.001; 88.0% vs. 81.1%, p < 0.001; 0.863 vs. 0.796, p < 0.05) in diagnosing lymph nodes. Accordingly, MRI-staged T3N0-3M0 patients showed nondifferent survival rates, as they were the same T3N1M0 if staged by PET/CT. In addition, patients staged by PET/CT and MRI showed higher survival rates than those staged by MRI alone (p < 0.05), regardless of the Epstein-Barr virus DNA load. Interestingly, SUVmax-N, nodal necrosis, and extranodal extension were highly predictive of survival. The radiologic score model based on these factors performed well in risk stratification with a C-index of 0.72. Finally, induction chemotherapy showed an added benefit (p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). CONCLUSION: PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment.

14.
Appl Microbiol Biotechnol ; 105(18): 6691-6706, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34463799

RESUMO

Natural water-soluble Monascus pigments (WSMPs) have been in increasing demand but have not been able to achieve industrial production due to the low production rate. This study aimed to improve the biosynthesis and secretion of extracellular yellow pigments (EYPs) through submerged fermentation with Monascus ruber CGMCC 10,910 supplemented with sodium starch octenyl succinate (OSA-SNa). The results demonstrated that the yield was 69.68% and 48.89% higher than that without OSA-SNa in conventional fermentation (CF) and extractive fermentation (EF), respectively. The mainly increased EYP components were Y3 and Y4 in CF, but they were mainly Y1 and Y2 as well as secreted intracellular pigments, including Y5, Y6, O1, and O2, in EF. Scanning electron microscopy analysis revealed that the mycelium presented an uneven surface profile with obvious wrinkles and small fragments with OSA-SNa. It was found that a higher unsaturated/saturated fatty acids ratio in the cell membrane resulted in increased permeability and facilitated the export of intracellular yellow pigments into the broth with OSA-SNa treatment. In addition, a higher NAD+/NADH ratio and glucose-6-phosphate dehydrogenase activity provided a reducing condition for yellow pigment biosynthesis. Gene expression analysis showed that the expression levels of the key genes for yellow pigment biosynthesis were significantly upregulated by OSA-SNa. This study provides an effective strategy to promote the production of WSMPs by microparticle-enhanced cultivation using OSA-SNa. KEY POINTS: • OSA-SNa addition facilitated the production of Monascus yellow pigments. • Mycelial morphology and membrane permeability were affected by OSA-SNa. • The key gene expression of yellow pigments was upregulated.


Assuntos
Monascus , Fermentação , Monascus/metabolismo , Pigmentos Biológicos/metabolismo , Sódio , Amido , Succinatos , Água
15.
Lancet Reg Health West Pac ; 9: 100110, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34379708

RESUMO

Background: A universally applicable approach that provides standard HALE measurements for different regions has yet to be developed because of the difficulties of health information collection. In this study, we developed a natural language processing (NLP) based HALE estimation approach by using individual-level electronic medical records (EMRs), which made it possible to calculate HALE timely in different temporal or spatial granularities. Methods: We performed diagnostic concept extraction and normalisation on 13•99 million EMRs with NLP to estimate the prevalence of 254 diseases in WHO Global Burden of Disease Study (GBD). Then, we calculated HALE in Chongqing, 2017, by using the life table technique and Sullivan's method, and analysed the contribution of diseases to the expected years "lost" due to disability (DLE). Findings: Our method identified a life expectancy at birth (LE0) of 77•9 years and health-adjusted life expectancy at birth (HALE0) of 71•7 years for the general Chongqing population of 2017. In particular, the male LE0 and HALE0 were 76•3 years and 68•9 years, respectively, while the female LE0 and HALE0 were 80•0 years and 74•4 years, respectively. Cerebrovascular diseases, cancers, and injuries were the top three deterioration factors, which reduced HALE by 2•67, 2•15, and 1•19 years, respectively. Interpretation: The results demonstrated the feasibility and effectiveness of EMRs-based HALE estimation. Moreover, the method allowed for a potentially transferable framework that facilitated a more convenient comparison of cross-sectional and longitudinal studies on HALE between regions. In summary, this study provided insightful solutions to the global ageing and health problems that the world is facing. Funding: National Key R and D Program of China (2018YFC2000400).

16.
Huan Jing Ke Xue ; 42(9): 4481-4488, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414748

RESUMO

Soil archaeal communities play an essential role in the biogeochemical cycles of agricultural ecosystems. However, the response and mechanisms of soil archaeal community structure and assembly processes to heavy metal pollution remain poorly understood. This study examined the archaeal community composition and assembly process and their relationships with environmental factors in arable soils around high geological background areas, metal enterprises, and mining areas, based on high-throughput sequencing. The arable soils within the study area exhibited high spatial heterogeneity of heavy metal content, as well as severe cadmium pollution. The ecological risk levels were high in some soil samples from mining areas, but low to moderate in other soil samples. Crenarchaeota (62.7%-98.3%) was the dominant phyla in all soil samples, followed by Halobacterota (1.1%-23.2%). The pH, organic matter, arsenic, and lead contents of the soil were significantly correlated with the archaeal community (P<0.05), making them the main driving factors of archaeal community structure. The null-model analysis showed that the assembly process of the archaeal community was mainly influenced by heterogeneous processes, including heterogeneous selection (deterministic process) and dispersal limitation (stochastic process). Heterogeneous selection played a vital role in our study areas, while homogeneous selection only occurred in samples around the metal enterprises. Therefore, environmental selection was the ultimate driver of the archaeal community assembly process in this study, and its relative importance varied according to habitat type. Environmental heterogeneity increased the contribution of heterogeneous selection to community assembly, thus enhancing the community's resistance to environmental stress, and contributing to the stability and sustainability of the agricultural ecosystem.


Assuntos
Metais Pesados , Solo , Archaea/genética , Ecossistema , Microbiologia do Solo
17.
Sci Rep ; 11(1): 14024, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234229

RESUMO

Mounting evidence suggests that microbiota dysbiosis caused by antibiotic administration is a risk factor for cancer, but few research reports focus on the relationships between antibiotics and chemotherapy efficiency. We evaluated the influence of antibiotic administration on neoadjuvant therapy efficacy in patients with breast cancer (BC) in the present study. BC patients were stratified into two groups: antibiotic-treated and control based on antibiotic administration within 30 days after neoadjuvant therapy initiation. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analyses. The pathologic complete response rate of the control group was significantly higher than that of the antibiotic-treated group (29.09% vs. 10.20%, p = 0.017). Further univariate analysis with Kaplan-Meier calculations demonstrated that antibiotic administration was strongly linked with both reduced DFS (p = 0.04) at significant statistical levels and OS (p = 0.088) at borderline statistical levels. Antibiotic administration was identified as a significant independent prognostic factor for DFS [hazard ratio (HR) 3.026, 95%, confidence interval (CI) 1.314-6.969, p = 0.009] and OS (HR 2.836, 95% CI 1.016-7.858, p = 0.047) by Cox proportional hazards model analysis. Antibiotics that initiated reduced efficiency of chemotherapy were more noticeable in the HER2-positive subgroup for both DFS (HR 5.51, 95% CI 1.77-17.2, p = 0.003) and OS (HR 7.0395% CI 1.94-25.53, p = 0.003), as well as in the T3-4 subgroup for both DFS (HR 20.36, 95% CI 2.41-172.07, p = 0.006) and OS (HR 13.45, 95% CI 1.39-130.08, p = 0.025) by stratified analysis. Antibiotic administration might be associated with reduced efficacy of neoadjuvant therapy and poor prognosis in BC patients. As a preliminary study, our research made preparations for further understanding and large-scale analyses of the impact of antibiotics on the efficacy of neoadjuvant therapy.

18.
BMC Cancer ; 21(1): 860, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315423

RESUMO

BACKGROUND: The psychometric properties of the simplified Chinese version of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) have not been assessed. Therefore, we aimed to assess its validity, reliability, and responsiveness. PATIENTS AND METHODS: A Chinese version of the PRO-CTCAE and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) were distributed to 1580 patients from four cancer hospitals in China. Validity assessments included construct validity, measured by Pearson's correlations and confirmatory factor analysis (CFA), and known-groups validity, measured by t-tests. The assessment of reliability included internal consistency, measured by Cronbach's ɑ, and test-retest reliability, measured by the intraclass correlation (ICC). Responsiveness was assessed by standardized response means (SRMs). RESULTS: Data from 1555 patients who completed the instruments were analyzed. The correlations were high between PRO-CTCAE items and parallel QLQ-C30 symptom scales (r > 0.60, p < 0.001), except for fatigue (severity: r = 0.49). Moreover, CFA showed the PRO-CTCAE structure was a good fit with the data (Root Mean Square Error of Approximation = 0.046). Known-groups validity was also confirmed. Cronbach's ɑ of all item clusters were greater than 0.9 and the median test-retest reliability coefficients of the 38 items were 0.85 (range = 0.71-0.91). In addition, the SRMs of PRO-CTCAE items were greater than 0.8, indicating strong responsiveness. CONCLUSION: The simplified Chinese version of the PRO-CTCAE showed good reliability, validity, and responsiveness.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
19.
J Magn Reson Imaging ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254384

RESUMO

BACKGROUND: 3.0 T non-contrast-enhanced nitroglycerin (NTG)-assisted whole-heart coronary magnetic resonance angiography (MRA) employing Dixon water-fat separation and compressed SENSE (CS-SENSE) acceleration is a promising method for diagnosing coronary artery disease (CAD). PURPOSE: To evaluate the diagnostic performance of this technique for detecting clinically-relevant (≥50% diameter reducing) CAD and to evaluate the difference in NTG-induced coronary vasodilation between patients with and without clinically-relevant CAD. STUDY TYPE: Prospective. POPULATION: Sixty-six patients with suspected CAD. FIELD STRENGTH/SEQUENCE: 3.0 T; CSSENSE, Dixon water-fat separation, three-dimensional segmented turbo field gradient-echo sequence for whole-heart coronary MRA. ASSESSMENT: Overall image quality of coronary MRA was calculated on the basis of all visible coronary segments. The diagnostic performance of coronary MRA for detecting a ≥50% reduction in coronary artery diameter with and without NTG was compared using X-ray coronary angiography (CAG) as the reference. According to CAG, patients were divided into a non-clinically-relevant CAD group and clinically-relevant CAD group, and the difference in NTG-induced vasodilation between the groups was evaluated. STATISTICAL TESTS: Unpaired/paired Student's t-test, Mann-Whitney U test, paired Wilcoxon signed-rank test, χ2 test, McNemar test. A two-tailed P value <0.05 was considered significant. RESULTS: Overall image quality was increased significantly in the coronary MRA images after NTG. The diagnostic performance of the non-NTG vs. NTG-assisted coronary MRA was as follows on a per-patient basis: sensitivity 94.3% vs. 94.3%, specificity 64.5% vs. 83.9%, positive predictive value 75.0% vs. 86.8%, negative predictive value 90.9% vs. 92.9%, and accuracy 80.3% vs. 89.4%, respectively. NTG-induced vasodilation was significantly lower in the clinically-relevant CAD group than in the non-clinically-relevant CAD group (13.7 ± 8.1% vs. 24.1 ± 16.3%). DATA CONCLUSION: Non-contrast Dixon water-fat separation CS-SENSE coronary MRA at 3.0 T can noninvasively detect clinically-relevant CAD and sublingual NTG improved performance. Combining pre- and post-NTG coronary MRA may provide a simple noninvasive and nonionizing test to evaluate coronary vasodilation function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

20.
Am J Hum Genet ; 108(7): 1283-1300, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214447

RESUMO

Most rare clinical missense variants cannot currently be classified as pathogenic or benign. Deficiency in human 5,10-methylenetetrahydrofolate reductase (MTHFR), the most common inherited disorder of folate metabolism, is caused primarily by rare missense variants. Further complicating variant interpretation, variant impacts often depend on environment. An important example of this phenomenon is the MTHFR variant p.Ala222Val (c.665C>T), which is carried by half of all humans and has a phenotypic impact that depends on dietary folate. Here we describe the results of 98,336 variant functional-impact assays, covering nearly all possible MTHFR amino acid substitutions in four folinate environments, each in the presence and absence of p.Ala222Val. The resulting atlas of MTHFR variant effects reveals many complex dependencies on both folinate and p.Ala222Val. MTHFR atlas scores can distinguish pathogenic from benign variants and, among individuals with severe MTHFR deficiency, correlate with age of disease onset. Providing a powerful tool for understanding structure-function relationships, the atlas suggests a role for a disordered loop in retaining cofactor at the active site and identifies variants that enable escape of inhibition by S-adenosylmethionine. Thus, a model based on eight MTHFR variant effect maps illustrates how shifting landscapes of environment- and genetic-background-dependent missense variation can inform our clinical, structural, and functional understanding of MTHFR deficiency.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Análise Mutacional de DNA , Diploide , Biblioteca Gênica , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Metilenotetra-Hidrofolato Redutase (NADPH2)/fisiologia , Saccharomyces cerevisiae/genética
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