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1.
Front Oncol ; 12: 870741, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574368

RESUMO

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial. Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate. Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively. Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT. Trial registration: ClinicalTrial.gov NCT02301481.

2.
Front Microbiol ; 13: 860079, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558118

RESUMO

Heat stress induced by global warming has damaged the well-being of aquatic animals. The skin tissue plays a crucial role as a defense barrier to protect organism, however, little is known about the effect of heat stress on fish skin, particularly in cold-water fish species. Here, we investigated the effects of mild heat stress (24°C, MS) and high heat stress (28°C, HS) on Siberian sturgeon skin using RNA-seq, histological observation, and microbial diversity analysis. In RNA-seq, 8,819 differentially expressed genes (DEGs) in MS vs. C group and 12,814 DEGs in HS vs. C group were acquired, of which the MS vs. C and HS vs. C groups shared 3,903 DEGs, but only 1,652 DEGs were successfully annotated. The shared DEGs were significantly enriched in pathways associating with mucins synthesis. Histological observation showed that the heat stresses significantly reduced the number of skin mucous cells and induced the damages of epidermis. The microbial diversity analysis elicited that heat stress markedly disrupted the diversity and abundance of skin microbiota by increasing of potential pathogens (Vibrionimonas, Mesorhizobium, and Phyllobacterium) and decreasing of probiotics (Bradyrhizobium and Methylovirgula). In conclusion, this study reveals that heat stress causes adverse effects on sturgeon skin, reflecting in decreasing the mucus secretion and disordering the mucosal microbiota, which may contribute to develop the preventive strategy for heat stress caused by global warming.

3.
Comput Biol Med ; 146: 105583, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35533454

RESUMO

BACKGROUND: Invasively measured fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) are gold standards for the diagnosis of coronary artery disease (CAD) and coronary microcirculatory dysfunction (CMD). However, the interaction between CAD and CMD has not been comprehensively investigated. We aim to non-invasively investigate hemodynamic effect of CMD in nonobstructive CAD cases using computational fluid dynamics (CFD) simulation. METHOD: This study employed CFD simulations on six cases with nonobstructive CAD and CMD in left anterior descending artery (LAD) territories. Two microcirculatory situations were simulated: normal microcirculatory resistance (MR) situation; CMD situation where MR at the outlets of LAD branches were multiplied by the ratio of clinically measured IMR to the cutoff value. Blood flow, translesional pressure drop (Δptl), and simulated FFR (FFRCT) of LAD and non-culprit branches were compared between the two microcirculatory situations using Wilcoxon signed rank test. RESULTS: The results are in accordance with existing studies and clinical measurements. Compared with normal MR, there were significant decreases in outlet flow velocity and increases in FFRCT (p < 0.01 for both in Wilcoxon signed rank tests) in LAD branches with CMD, with minor decreases (0.63-5.64 mmHg) in Δptl. There was no significant influence on outlet flow velocity (< 2%) and FFRCT (< 0.02) in non-culprit branches (p > 0.05 for both). CONCLUSION: IMR-based CFD simulation could estimate hemodynamic effects of CMD. CMD in a coronary artery branch can decrease its blood flow and Δptl, increase its FFR, with little effect on non-culprit branches.

4.
J Phys Chem A ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35544770

RESUMO

Despite the long history of spectroscopic studies of the C2 molecule, fundamental questions about its chemical bonding are still being hotly debated. The complex electronic structure of C2 is a consequence of its dense manifold of near-degenerate, low-lying electronic states. A global multi-state diabatic model is proposed here to disentangle the numerous configuration interactions that occur within four symmetry manifolds of excited states of C2 (1Πg, 3Πg, 1Σu+ , and 3Σu+ ). The key concept of our model is the existence of two "valence-hole" configurations, 2σg22σu11πu33σg2 for 1,3Πg states and 2σg22σu11πu43σg1 for 1,3Σu+ states, that are derived from 3σg ← 2σu electron promotion. The lowest-energy state from each of the four C2 symmetry species is dominated by this type of valence-hole configuration at its equilibrium internuclear separation. As a result of their large binding energy (nominal bond order of 3) and correlation with the 2s22p2 + 2s2p3 separated-atom configurations, the presence of these valence-hole configurations has a profound impact on the global electronic structure and unimolecular dynamics of C2.

5.
ACS Nano ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35511445

RESUMO

The global rise of antimicrobial resistance (AMR) that increasingly invalidates conventional antibiotics has become a huge threat to human health. Although nanosized antibacterial agents have been extensively explored, they cannot sufficiently discriminate between microbes and mammals, which necessitates the exploration of other antibiotic-like candidates for clinical uses. Herein, two-dimensional boron nitride (BN) nanosheets are reported to exhibit antibiotic-like activity to AMR bacteria. Interestingly, BN nanosheets had AMR-independent antibacterial activity without triggering secondary resistance in long-term use and displayed excellent biocompatibility in mammals. They could target key surface proteins (e.g., FtsP, EnvC, TolB) in cell division, resulting in impairment of Z-ring constriction for inhibition of bacteria growth. Notably, BN nanosheets had potent antibacterial effects in a lung infection model by P. aeruginosa (AMR), displaying a 2-fold increment of survival rate. Overall, these results suggested that BN nanosheets could be a promising nano-antibiotic to combat resistant bacteria and prevent AMR evolution.

6.
Biomaterials ; 285: 121561, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35537337

RESUMO

Apoptosis dysregulation is an important mechanism responsible for the intrinsic and acquired resistance of melanoma, which necessitates the exploration of oncological treatments to activate nonapoptotic cell death. Herein, we developed nano-enabled photosynthesis in tumours to activate lipid peroxidation and ferroptosis to overcome melanoma resistance. Controlled photosynthesis was conducted in tumours to construct a hyperoxic microenvironment with photosynthetic microcapsules (PMCs), which were prepared by encapsulating cyanobacteria and upconversion nanoparticles in alginate microcapsules and driven by external near infrared photons. The combination of PMCs and X-rays evoked lipid peroxidation, Fe2+ release, glutathione peroxidase 4 suppression, glutathione reduction and ferroptosis in melanoma cells and xenografts. Consequently, the intrinsic and acquired resistance in melanoma could be overcome by the combined treatment, which further inhibited tumour metastases and improved the survival rate of melanoma-bearing mice. Overall, the development of nano-enabled photosynthesis in tumours will inspire the exploration of oncological treatments.

7.
Sci Rep ; 12(1): 7440, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523993

RESUMO

Single/multilayer graphene holds great promise in withstanding impact/penetration as ideal protective material. In this work, dynamic penetration behaviors of graphene has been explored using molecular dynamics simulations. The crashworthiness performance of graphene is contingent upon the number of layers and impact velocity. The variables including residual velocity and kinetic energy loss under different layers or different impact velocities have been monitored during the hypervelocity impact. Results show that there exists deviation from the continuum Recht-Ipson and Rosenberg-Dekel models, but these models tend to hold to reasonably predict the ballistic limit velocity of graphene with increasing layers. Besides, fractal theory has been introduced here and proven valid to quantitatively describe the fracture morphology. Furthermore, Forrestal-Warren rigid body model II still can well estimate the depth of penetration of multilayer graphene under a certain range of velocity impact. Finally, one modified model has been proposed to correlate the specific penetration energy with the number of layer and impact velocity.

8.
Front Endocrinol (Lausanne) ; 13: 873012, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399937

RESUMO

Background: Furin has been associated with diabetes but the underlying mechanisms are unclear. As a mediator linking fixed genome and dynamic environment, DNA methylation of its coding gene FURIN may be involved. Here, we aimed to examine the prospective association between DNA methylation in FURIN promoter and incident diabetes during 4 years of follow-up in Chinese adults. Methods: DNA methylation levels in FURIN promoter were quantified by target bisulfite sequencing using peripheral blood from 1836 participants in the Gusu cohort who were free of diabetes at baseline. To examine the association between DNA methylation levels in FURIN promoter and incident diabetes, we constructed a logistic regression model adjusting for the conventional factors. Multiple testing was controlled by adjusting for the total number of CpG sites assayed using the false-discovery rate approach. Results: Among the 1836 participants free of diabetes at baseline, 109 (5.94%) participants developed diabetes during the average of 4 years of follow-up. Hypermethylation at two of the eight CpG sites assayed in the FURIN promoter was associated with an increased risk of diabetes, after multivariable adjustment and multiple testing correction. Every 5% increment in methylation levels at CpG1 and CpG2 were associated with a 22% (OR=1.22, 95%CI: 1.05-1.43, P=0.009, q=0.038) and 39% (OR=1.39, 95%CI: 1.08-1.77, P=0.009, q=0.038) higher risk of incident diabetes, respectively. The gene-based association analysis revealed that DNA methylation at multiple CpG loci was jointly associated with incident diabetes (P<0.001). Using the average methylation level of the 8 CpG loci in FURIN promoter revealed a similar association (OR=1.28, 95% CI: 1.02-1.62, P=0.037). Conclusions: These results suggested that the hypermethylation levels in FURIN promoter were associated with an increased risk for incident diabetes in Chinese adults.


Assuntos
Metilação de DNA , Diabetes Mellitus , Furina , Regiões Promotoras Genéticas , Adulto , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Furina/genética , Humanos
9.
Clin Epidemiol ; 14: 463-473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431582

RESUMO

Objective: Although elevated uric acid is associated with obesity and considered a predictor of hypertension, the causal linkage between the three metabolic conditions is not very clear. We aim to examine whether elevated uric acid mediates the effects of obesity on hypertension development. Methods: A total of 1984 participants (mean aged 53 years, 62.10% female) with repeated measurements of obesity, blood pressure, and uric acid 4 years apart in the Gusu cohort were included. We first applied cross-lagged panel analysis and bidirectional association analysis to delineate the temporal association between obesity and hyperuricemia. Then, a causal mediation model was constructed to further examine the causal role of hyperuricemia in the linkage between obesity and hypertension. Age, sex, education, cigarette smoking, alcohol consumption, fasting blood glucose, and lipids were adjusted. Results: The cross-lagged panel analysis demonstrated that the relationship from baseline obesity to follow-up hyperuricemia was stronger than that from baseline hyperuricemia to follow-up obesity (ß: 0.09 vs 0.06, P<0.01 for BMI, ß: 0.13 vs 0.07, P<0.01 for WC). Bidirectional association analysis found that baseline obesity predicted the risk of incident hyperuricemia (OR = 1.09, P<0.01 for BMI, OR = 1.05, P<0.01 for WC), but the other directional association was not statistically significant (all P>0.05). The causal mediation analysis found that hyperuricemia partially mediated the association of baseline BMI (mediate proportion: 3.09%, 95% CI: 0.97%~6.00% for SBP, 3.74%, 95% CI: 1.55%~7.00% for DBP) and baseline WC (mediate proportion: 5.56%, 95% CI: 2.01%~11.00% for SBP, 5.81%, 95% CI: 2.59%~10.00% for DBP) with follow-up blood pressures. Conclusion: Obesity preceded hyperuricemia and the latter partially mediated the relationship between obesity and hypertension, independent of behavioral and other metabolic factors.

10.
Front Oncol ; 12: 841460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425711

RESUMO

Background: This study aimed to explore the predictive value of quantitative dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters for the response to neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (LAGC) patients, and the relationship between the prediction results and patients' prognosis, so as to provide a basis for clinical individualized precision treatment. Methods: One hundred twenty-nine newly diagnosed LAGC patients who underwent IVIM-DWI and DCE-MRI pretreatment were enrolled in this study. Pathological tumor regression grade (TRG) served as the reference standard of NCT response evaluation. The differences in DCE-MRI and IVIM-DWI parameters between pathological responders (pR) and pathological non-responders (pNR) groups were analyzed. Univariate and multivariate logistic regressions were used to identify independent predictive parameters for NCT response. Prediction models were built with statistically significant quantitative parameters and their combinations. The performance of these quantitative parameters and models was evaluated using receiver operating characteristic (ROC) analysis. Clinicopathological variables, DCE-MRI and IVIM-DWI derived parameters, as well as the prediction model were analyzed in relation to 2-year recurrence-free survival (RFS) by using Cox proportional hazards model. RFS was compared using the Kaplan-Meier method and the log-rank test. Results: Sixty-nine patients were classified as pR and 60 were pNR. Ktrans, kep, and ve values in the pR group were significantly higher, while ADCstandard and D values were significantly lower than those in the pNR group. Multivariate logistic regression analysis demonstrated that Ktrans, kep, ve, and D values were independent predictors for NCT response. The combined predictive model, which consisted of DCE-MRI and IVIM-DWI, showed the best prediction performance with an area under the curve (AUC) of 0.922. Multivariate Cox regression analysis showed that ypStage III and NCT response predicted by the IVIM-DWI model were independent predictors of poor RFS. The IVIM-DWI model could significantly stratify median RFS (52 vs. 15 months) and 2-year RFS rate (72.3% vs. 21.8%) of LAGC. Conclusion: Pretreatment DCE-MRI quantitative parameters Ktrans, kep, ve, and IVIM-DWI parameter D value were independent predictors of NCT response for LAGC patients. The regression model based on baseline DCE-MRI, IVIM-DWI, and their combination could help RFS stratification of LAGC patients.

11.
Toxins (Basel) ; 14(4)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35448881

RESUMO

A highly selective and sensitive aptasensor for detecting patulin (PAT) was constructed based on the fluorescence quenching of fullerenol quantum dots (FOQDs) towards carboxytetramethylrhodamine (TAMRA) through PET mechanism. The π-π stacking interaction between PAT aptamer and FOQDs closed the distance between TAMRA and FOQDs and the fluorescence of TAMRA was quenched with maximum quenching efficiency reaching 85%. There was no non-specific fluorescence quenching caused by FOQDs. In the presence of PAT, the PAT aptamer was inclined to bind with PAT and its conformation was changed. Resulting in the weak π-π stacking interaction between PAT aptamer and FOQDs. Therefore, the fluorescence of TAMRA recovered and was linearly correlated to the concentration of PAT in the range of 0.02-1 ng/mL with a detection limit of 0.01 ng/mL. This PAT aptasensor also performed well in apple juice with linear dynamic range from 0.05-1 ng/mL. The homogeneous fluorescence aptasensor shows broad application prospect in the detection of various food pollutants.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Malus , Patulina , Pontos Quânticos , Técnicas Biossensoriais/métodos , Fulerenos , Limite de Detecção , Patulina/análise
12.
Rev Sci Instrum ; 93(4): 044702, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489911

RESUMO

In the field of time domain measurement, with increasing complexity of measured signals, the periodic stationarity of signals is destroyed and the transient non-stationarity starts to stand out, specifically manifested as frequent presence of transient abnormal signals, such as burrs, harmonics, noises, and modulating waves in the periodic signals. By applying the entropy estimation of signals to the field of time domain measurement, this paper designs a transient abnormal signal acquisition system based on approximate entropy (ApEn) and sample entropy (SampEn). In the process of data acquisition, the ApEn and SampEn of sampled data are computed in real time and the complexities of measured signals are differentiated, thus realizing abnormal signal detection. The experimental results demonstrate that SampEn generally has a higher sensitivity and wider application than ApEn in the detection process of transient abnormal signals. The study can provide a new method for the design of a time-domain measuring instrument with abnormal signal detection ability.


Assuntos
Entropia
14.
ACS Appl Mater Interfaces ; 14(17): 19889-19896, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35437993

RESUMO

Encapsulation for carbon-based electronic devices against oxidation can enhance their long-term working stability. Graphene glass fiber fabric (GGFF), as an advanced flexible electrothermal material, also struggles with graphene oxidation. The flexible, full-surface, conformal encapsulation for each fiber in the large-area fabric puts forward high requirements for encapsulating materials and techniques. Herein, the nanometer-thick h-BN layer was in situ grown on cambered surfaces of each fiber in GGFF with the chemical vapor deposition method. Stable heating duration (500 °C) of h-BN-encapsulated GGFF (h-BN/GGFF) was increased by 1 order of magnitude without compromising the electrothermal performances and flexibility. Theoretical simulations revealed that the enhanced oxidation resistance of h-BN/GGFF was attributed to the decreased interaction and adsorption life of oxygen. The proposed flexible, full-surface, conformal encapsulation technique targeting the fiber-shaped graphene electrothermal device is scalable and can be extended to the other carbon materials, even devices with intricate shapes, which will promote the development of flexible electronics.

15.
Ultramicroscopy ; 237: 113519, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35378371

RESUMO

The characterization of geometrically necessary dislocation (GND) is central to understanding the plastic deformation in materials. Currently, fast and accurate determination of GND density via Electron Backscatter Diffraction (EBSD) remains a challenge. Here, a multi-modal deep learning approach is proposed to predict GND density in terms of electron backscatter patterns (EBSPs) and dislocation configurations. The proposed multi-modal architecture consists of two separated convolutional neural network (CNN) processing streams. One CNN stream aims at extracting pattern shifts from EBSPs, and the other CNN stream focuses on learning suitable representations of dislocation configurations. We also introduce a specific data augmentation strategy termed neighboring pairs generating strategy for the GND prediction task. Taking the GND density from dictionary indexing-based analysis as the target property, high accuracy is achieved on several aluminum samples. Also, our networks are robust to various forms of noise, and the prediction speed is as fast as modern EBSD scanning rates, enabling real-time GND density analysis possible.

16.
Andrology ; 2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35466583

RESUMO

OBJECTIVE: To investigate the effect of low androgen status on mitochondria-associated membranes (MAMs) and its relationship with erectile function. METHODS: A total of 36 eight-week-old male Sprague-Dawley rats were randomly divided into six groups: the control (sham-operated) group, the castration group, the castration + testosterone (cast + T) group, the control + siRNA group, the cast + siRNA group, and the cast + empty vector group. Testosterone propionate (3 mg/kg) was subcutaneously injected into the rats in the cast + T group every other day starting from the second day after the surgery. Four weeks later, lentiviral vectors carrying phosphofurin acidic cluster sorting protein 2 (PACS-2) gene-specific siRNA (1 × 108 TU/ml, 10 µl) were injected into the rats in the siRNA groups. At the sixth week of castration, the ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the levels of nitric oxide (NO), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), fatty acid-CoA ligase 4 (FACL-4), PACS-2, and inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in the penile corpus cavernosum were determined. RESULTS: The FACL-4, PACS-2, and IP3R1 were primarily localized in the cytoplasm of endothelial cells and part of smooth muscle cells in the corpus cavernosum. The level of NO, the ratio of ICPmax/MAP, and p-eNOS/eNOS were decreased significantly in the castration group compared with the control group (p < 0.01). The expressions of FACL-4, PACS-2, and IP3R1 were increased significantly in the castration group compared with the control group (p < 0.01). The level of NO, the ratios of ICPmax/MAP, and the ratio of p-eNOS/eNOS were increased significantly in the cast + siRNA group compared with the castration group (p < 0.01). The expressions of FACL-4 and PACS-2 were decreased significantly in the cast + siRNA group compared with the castration group (p < 0.01). CONCLUSION: Low androgen status upregulated the expressions of patients in MAMs (FACL-4, PACS-2, and IP3R1) in the corpus cavernosum and inhibited the eNOS/NO/cGMP signaling pathway, resulting in impaired erectile function in rats. Erectile function may be improved by inhibiting the high expression of PACS-2 in the corpus cavernosum under low androgen state.

17.
Small ; : e2201352, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35429134

RESUMO

Bi2 Te3 -related alloys dominate the commercial thermoelectric market, but the layered crystal structure leads to the dissociation and intrinsic brittle fracture, especially for single crystals that may worsen the practical efficiency. In this work, point defect configuration by S/Te/I defects engineering is engaged to boost thermoelectric and mechanical properties of n-type Bi2 Te3 alloy, which, coupled with p-type BiSbTe, shows a competitive conversion efficiency for the fabricated module. First, as S alloying suppresses the intrinsic B i T e , antisite defects and forms a donor-like effect, electronic transport properties are optimized, associated with the decreased thermal conductivity due to the point defect scattering. The periodide compound TeI4 is afterward adopted to further tune carrier concentration for the realization of an optimal ZT. Finally, an advanced average ZT of 1.05 with ultra-high compressive strength of 230 MPa is achieved for Bi2 Te2.9 S0.1 (TeI4 )0.0012 . Based on this optimum composition, a fabricated 17-pair module demonstrates a maximum conversion efficiency of 5.37% under the temperature difference of 250 K, rivaling the current state-of-the-art Bi2 Te3 modules. This work reveals the novel mechanism of point defect reconfiguration in synergistic enhancement of thermoelectric and mechanical properties for durably commercial application, which may be applicable to other thermoelectric systems.

18.
Biosci Rep ; 42(5)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35441668

RESUMO

Accumulated genetic mutations are an important cause for the development of acute myeloid leukemia (AML), but abnormal changes in the inflammatory microenvironment also have regulatory effects on AML. Exploring the relationship between inflammatory response and pathological features of AML has implications for clinical diagnosis, treatment and prognosis evaluation. We analyzed the expression variation landscape of inflammatory response-related genes (IRRGs) and calculated an inflammatory response score for each sample using the gene set variation analysis (GSVA) algorithm. The differences in clinical- and immune-related characteristics between high- and low-inflammatory response groups were further analyzed. We found that most IRRGs were highly expressed in AML samples, and patients with high inflammatory response had poor prognosis and were accompanied with highly activated chemokine-, cytokine- and adhesion molecule-related signaling pathways, higher infiltration ratios of monocytes, neutrophils and M2 macrophages, high activity of type I/II interferon (IFN) response, and higher expression of immune checkpoints. We also used the Genomics of Drug Sensitivity in Cancer (GDSC) database to predict the sensitivity of AML samples with different inflammatory responses to common drugs, and found that AML samples with low inflammatory response were more sensitive to cytarabine, doxorubicin and midostaurin. SubMap algorithm also demonstrated that high-inflammatory response patients are more suitable for anti-PD-1 immunotherapy. Finally, we constructed a prognostic risk score model to predict the overall survival (OS) of AML patients. Patients with higher risk score had significantly shorter OS, which was confirmed in two validation cohorts. The analysis of inflammatory response patterns can help us better understand the differences in tumor microenvironment (TME) of AML patients, and guide clinical medication and prognosis prediction.

19.
J Phys Chem B ; 126(16): 2979-2989, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35438983

RESUMO

It is generally believed that a protein's sequence uniquely determines its structure, the basis for a protein to perform biological functions. However, as a representative metamorphic protein, RfaH can be encoded by a single amino acid sequence into two distinct native state structures. Its C-terminal domain (CTD) either takes an all-α-helical configuration to pack tightly with its N-terminal domain (NTD), or the CTD disassociates from the NTD, transforms into an all-ß-barrel fold, and further attaches to the ribosome, leaving the NTD exposed to bind RNA polymerases. Therefore, the RfaH protein couples transcription and translation processes. Although previous studies have provided a preliminary understanding of its function, the full course of the conformational change of RfaH-CTD at the atomic level is elusive. We used teDA2, a feature space-based enhanced sampling protocol, to explore the transformation of RfaH-CTD. We found that it undergoes a large-scale structural rearrangement, with characteristic spectra as the fingerprint, and a global unfolding transition with a tighter and energetically moderate molten globule-like nucleus formed in between. The formation of this nucleus limits the possible intermediate conformations, facilitates the formation of secondary and tertiary structures, and thus ensures the efficiency of transformation. The key features along the transition path disclosed from this work are likely associated with the evolution of RfaH, such that encoding a single sequence into multiple folds with distinct biological functions is energetically unhindered.


Assuntos
Proteínas de Escherichia coli , Fatores de Alongamento de Peptídeos , Proteínas de Escherichia coli/química , Simulação de Dinâmica Molecular , Fatores de Alongamento de Peptídeos/química , Dobramento de Proteína , Transativadores/química
20.
Sci Total Environ ; : 155117, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35398425

RESUMO

Greenness could theoretically increase the impact of physical activity (PA) and reduce the adverse effects of air pollution on overweight/obesity. However, no evidence systematically compares these two pathways, especially in longitudinal studies of children and adolescent's cohort. Greenness, PA, and air pollution were assessed by Normalized Difference Vegetation Index (NDVI), International Physical Activity Short Form, and 7 pollutants (PM1, PM2.5, PM10, SO2, NO2, CO, and O3). Each exposure was divided into low-/high-level groups based on the 50% quantile. Proportional hazards and logistic regression model were used to assess the associations of greenness, PA, pollutants with overweight/obesity. The incidence of overweight/obesity was 1.98% in the national survey, and the cumulative incidence and incidence density were 12.76% and 3.43 per 100 person-year in the dynamic cohort, separately. An increase of 0.1 units in NDVI was associated with a 12% lower risk of overweight/obesity, but no significant link between PA and incidence was observed. The HRs of the high-level of PM1, PM2.5, PM10, SO2, NO2, CO, and O3 on the risk of overweight/obesity were 2.21, 2.63, 1.88, 2.38, 1.33, 2.43, and 1.33 in the low-level of greenness, which was higher than those in the high-level of greenness. The AFs of PM1, PM2.5, PM10, SO2, NO2, CO, and O3 were 25.58%, 44.37%, 22.96%, 29.15%, 11.55%, 29.50%, and 10.92% in the low-level of greenness, which simultaneously was higher than those in the high-level of greenness. Moreover, the risk of overweight/obesity associated with high-level of greenness in the high-level of PM10, SO2, CO were 0.83, 0.81, and 0.83 respectively. Our findings confirmed that greenness has a moderating effect on the effects of air pollutants on childhood overweight/obesity especially in heavy-industry areas where PM10, SO2, and CO are the major pollutants, although it did not influence the association between PA and overweight/obesity risks.

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