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1.
J Surg Res ; 269: 249-259, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624724

RESUMO

BACKGROUND: Systemic inflammation status has been recognized as a sensitive marker associated with survival in cancers and anti-inflammatory treatment outcomes in inflammation-derived diseases. This study aimed to investigate the role of systemic inflammation status as a predictive marker for survival and anti-inflammatory treatment benefit in rectal cancer patients. METHODS: A total of 475 patients with stage I-III rectal cancer receiving curative resection were prospectively enrolled. The platelet-neutrophils to lymphocytes ratio (PNLR) that integrates neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios was applied to enable a comprehensive evaluation of systemic inflammation status and investigate its association with survival and nonsteroidal anti-inflammatory drugs (NSAIDs) benefit. Patients were grouped according to baseline PNLR and perioperative use of NSAIDs. RESULTS: The high-PNLR group had worse 5-y disease-free survival (DFS) compared with the low-PNLR group (61.2% versus 70.9%, P = 0.014). Multivariate analyses confirmed that PNLR was an independent predictor for DFS (hazard ratio [HR] 1.42, 95% CI: 1.03-1.97, P = 0.031). A nomogram including PNLR and other independent prognostic factors was developed and validated to predict DFS. In the high-PNLR subset, NSAIDs group had a 21.3% lower risk of recurrence than non-NSAIDs group (P = 0.009), and multivariate analysis confirmed the independently significant association of perioperative NSAIDs use with better DFS (hazard ratio 0.36, 95% CI 0.16-0.78, P = 0.010). However, this association was not significant in the low-PLR subset. CONCLUSIONS: Baseline PNLR could be used to predict DFS and NSAIDs benefit in rectal cancer patients. This study highlights the potential survival benefit from the anti-inflammatory treatment in the patients with elevated systemic inflammation status in cancer patients.

2.
Oncol Lett ; 22(5): 798, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630705

RESUMO

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide. Long non-coding RNA (lncRNA) NUT family member 2A antisense RNA 1 (NUTM2A-AS1) is dysregulated in LUAD; however, its role in this disease remains unclear. The present study aimed to identify the underlying molecular mechanism of the effect of lncRNA NUTM2A-AS1 in LUAD by exploring whether lncRNA NUTM2A-AS1 could affect LUAD cell proliferation and apoptosis through the microRNA (miR)-590-5p/methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3) axis. miR-590-5p was predicted and verified as the direct target of NUTM2A-AS1 using bioinformatics analysis and a dual luciferase reporter assay. The expression levels of NUTM2A-AS1 and miR-590-5p in lung cancer cells, and the effects of NUTM2A-AS1 on cell viability and apoptosis were determined using MTT assays and flow cytometry, respectively. Reverse transcription-quantitative PCR analysis revealed that the expression levels of NUTM2A-AS1 were significantly upregulated, while those of miR-590-5p were significantly downregulated, in lung cancer cells compared with the control epithelial cells. NUTM2A-AS1 knockdown inhibited NCI-H23 cell viability and induced apoptosis by upregulating miR-590-5p expression. Moreover, the function and regulatory mechanism of miR-590-5p in LUAD were also investigated. It was determined that miR-590-5p could interact with METTL3, and further analysis of the expression levels of METTL3 in lung cancer cells demonstrated that METTL3 was significantly upregulated in NCI-H23 and A549 cells compared with the control cells. In addition, miR-590-5p inhibited NCI-H23 cell viability and induced apoptosis by downregulating METTL3 expression. In conclusion, the findings of the present study suggested that NUTM2A-AS1 knockdown may inhibit LUAD progression by regulating the miR-590-5p/METTL3 axis. These results may provide insight into the mechanisms underlying the tumorigenesis of LUAD and offer a new treatment strategy for the disease.

3.
Front Microbiol ; 12: 707281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616376

RESUMO

Mitochondria are the major energy source for cell functions. However, for the plant fungal pathogens, mitogenome variations and their roles during the host infection processes remain largely unknown. Rhizoctonia solani, an important soil-borne pathogen, forms different anastomosis groups (AGs) and adapts to a broad range of hosts in nature. Here, we reported three complete mitogenomes of AG1-IA RSIA1, AG1-IB RSIB1, and AG1-IC, and performed a comparative analysis with nine published Rhizoctonia mitogenomes (AG1-IA XN, AG1-IB 7/3/14, AG3, AG4, and five Rhizoctonia sp. mitogenomes). These mitogenomes encoded 15 typical proteins (cox1-3, cob, atp6, atp8-9, nad1-6, nad4L, and rps3) and several LAGLIDADG/GIY-YIG endonucleases with sizes ranging from 109,017 bp (Rhizoctonia sp. SM) to 235,849 bp (AG3). We found that their large sizes were mainly contributed by repeat sequences and genes encoding endonucleases. We identified the complete sequence of the rps3 gene in 10 Rhizoctonia mitogenomes, which contained 14 positively selected sites. Moreover, we inferred a robust maximum-likelihood phylogeny of 32 Basidiomycota mitogenomes, representing that seven R. solani and other five Rhizoctonia sp. lineages formed two parallel branches in Agaricomycotina. The comparative analysis showed that mitogenomes of Basidiomycota pathogens had high GC content and mitogenomes of R. solani had high repeat content. Compared to other strains, the AG1-IC strain had low substitution rates, which may affect its mitochondrial phylogenetic placement in the R. solani clade. Additionally, with the published RNA-seq data, we investigated gene expression patterns from different AGs during host infection stages. The expressed genes from AG1-IA (host: rice) and AG3 (host: potato) mainly formed four groups by k-mean partitioning analysis. However, conserved genes represented varied expression patterns, and only the patterns of rps3-nad2 and nad1-m3g18/mag28 (an LAGLIDADG endonuclease) were conserved in AG1-IA and AG3 as shown by the correlation coefficient analysis, suggesting regulation of gene repertoires adapting to infect varied hosts. The results of variations in mitogenome characteristics and the gene substitution rates and expression patterns may provide insights into the evolution of R. solani mitogenomes.

4.
Opt Express ; 29(17): 26366-26374, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615073

RESUMO

The transverse mode instability (TMI) has been one of the main limitations for the power scaling of single mode fiber lasers. In this work, we report a 6 kW single mode monolithic fiber laser enabled by effective mitigation of the TMI. The fiber laser employs a custom-made wavelength-stabilized 981 nm pump source, which remarkably enhanced the TMI threshold compared with the wavelength of 976 nm. With appropriately distributing bidirectional pump power, the monolithic fiber laser is scaled to 6 kW with single mode beam quality (M2<1.3). The stability is verified in a continuous operation for over 2 hours with power fluctuation below 1%.

5.
Redox Biol ; 47: 102156, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34607159

RESUMO

OBJECTIVE: The disruption of mitochondrial redox homeostasis in endothelial cells (ECs) can cause chronic inflammation, a substantial contributor to the development of atherosclerosis. Chronic sympathetic hyperactivity can enhance oxidative stress to induce endothelial dysfunction. We determined if renal denervation (RDN), the strategy reducing sympathetic tone, can protect ECs by ameliorating mitochondrial reactive oxygen species (ROS)-induced inflammation to reduce atherosclerosis. METHODS AND RESULTS: ApoE deficient (ApoE-/-) mice were conducted RDN or sham operation before 20-week high-fat diet feeding. Atherosclerosis, EC phenotype and mitochondrial morphology were determined. In vitro, human arterial ECs were treated with norepinephrine to determine the mechanisms for RDN-inhibited endothelial inflammation. RDN reduced atherosclerosis, EC mitochondrial oxidative stress and inflammation. Mechanistically, the chronic sympathetic hyperactivity increased circulating norepinephrine and mitochondrial monoamine oxidase A (MAO-A) activity. MAO-A activation-impaired mitochondrial homeostasis resulted in ROS accumulation and NF-κB activation, thereby enhancing expression of atherogenic and proinflammatory molecules in ECs. It also suppressed mitochondrial function regulator PGC-1α, with involvement of NF-κB and oxidative stress. Inactivation of MAO-A by RDN disrupted the positive-feedback regulation between mitochondrial dysfunction and inflammation, thereby inhibiting EC atheroprone phenotypic alterations and atherosclerosis. CONCLUSIONS: The interplay between MAO-A-induced mitochondrial oxidative stress and inflammation in ECs is a key driver in atherogenesis, and it can be reduced by RDN.

6.
J Med Chem ; 64(19): 14142-14152, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34606259

RESUMO

Hypercontractility of the cardiac sarcomere may be essential for the underlying pathological hypertrophy and fibrosis in genetic hypertrophic cardiomyopathies. Aficamten (CK-274) is a novel cardiac myosin inhibitor that was discovered from the optimization of indoline compound 1. The important advancement of the optimization was discovery of an Indane analogue (12) with a less restrictive structure-activity relationship that allowed for the rapid improvement of drug-like properties. Aficamten was designed to provide a predicted human half-life (t1/2) appropriate for once a day (qd) dosing, to reach steady state within two weeks, to have no substantial cytochrome P450 induction or inhibition, and to have a wide therapeutic window in vivo with a clear pharmacokinetic/pharmacodynamic relationship. In a phase I clinical trial, aficamten demonstrated a human t1/2 similar to predictions and was able to reach steady state concentration within the desired two-week window.

7.
Cell ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34644527

RESUMO

To secure phosphorus (P) from soil, most land plants use a direct phosphate uptake pathway via root hairs and epidermis and an indirect phosphate uptake pathway via mycorrhizal symbiosis. The interaction between these two pathways is unclear. Here, we mapped a network between transcription factors and mycorrhizal symbiosis-related genes using Y1H. Intriguingly, this gene regulatory network is governed by the conserved P-sensing pathway, centered on phosphate starvation response (PHR) transcription factors. PHRs are required for mycorrhizal symbiosis and regulate symbiosis-related genes via the P1BS motif. SPX-domain proteins suppress OsPHR2-mediated induction of symbiosis-related genes and inhibit mycorrhizal infection. In contrast, plants overexpressing OsPHR2 show improved mycorrhizal infection and are partially resistant to P-mediated inhibition of symbiosis. Functional analyses of network nodes revealed co-regulation of hormonal signaling and mycorrhizal symbiosis. This network deciphers extensive regulation of mycorrhizal symbiosis by endogenous and exogenous signals and highlights co-option of the P-sensing pathway for mycorrhizal symbiosis.

8.
Eur J Pharm Sci ; : 106047, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34687899

RESUMO

Nintedanib (BIBF) is a biopharmaceutical classification system II (BCS II) drug that has a good therapeutic effect for the treatment of nonsmall cell lung cancer; however, it shows poor oral bioavailability due to low dissolution and intestinal absorption. This study aims to fabricate rod-shaped nanocrystals to enhance oral bioavailability by improving the dissolution and absorption of BIBF in the intestine. By prescription screening, BIBF nanocrystals (BIBF-NCs) with a particle size of 325.30 ± 1.03 nm and zeta potential of 32.70 ± 1.24 mV were fabricated by an antisolvent precipitation-ultrasound approach with a stabilizer of sodium carboxyl methyl cellulose (CMC-Na). BIBF-NCs exhibited a rod-shaped morphology by transmission electron microscopy (TEM). The results of powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) showed that the crystal form of BIBF in BIBF-NCs was altered. The BIBF-NCs remarkably improved the saturation solubility and dissolution of BIBF compared with BIBF powder. According to the results of in situ single-pass intestinal perfusion (SPIP), BIBF-NCs showed improved absorption and membrane permeability, with Ka and Papp values in the jejunum of 0.21 ± 0.01 min-1 and (4.34 ± 0.11) × 10-4 cm/min, respectively. Further, the Ka and Papp values of BIBF-NCs were all reduced significantly after the addition of inhibitors colchicine, chlorpromazine and indomethacin, which demonstrated that BIBF-NCs could be absorbed by endocytosis mediated by caveolae and clathrin and micropinocytosis in the intestine. The cell evaluation results showed that BIBF-NCs could be taken up by macrophages and transported from Caco-2 monolayers. The in vivo pharmacokinetic results showed that the bioavailability of the BIBF-NCs was 2.51-fold higher than that of the BIBF solution (BIBF-Sol) after oral administration with a longer Tmax (4.50 ± 1.00 h vs. 2.60 ± 1.92 h). In summary, rod-shaped BIBF-NCs could significantly improve oral bioavailability through multiple intestinal absorption pathways.

9.
Small ; : e2103695, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623728

RESUMO

Blocking liquid penetration in porous materials is a key function for several applications including chemical protective clothing (CPC), wound healing, and hygiene products. Enormous efforts are made to prevent liquid penetration through porous media by the modification of materials. CPC is used as an example to demonstrate the effect of the synergistic effect on liquid penetration. A common strategy to achieve liquid protection is the use of liquid-repellent surfaces with the aid of a liquid absorption liner layer. However, this strategy demonstrates limited success for low surface energy liquids. Herein, a novel approach is reported to prevent the permeation of liquid across porous materials by a synergistic effect. Both fabrics are individually susceptible to be wetted by low surface tension liquids. However, when they are assembled, they can prevent low surface tension liquids from penetrating because of the wettability gap between the two fabrics. The fabric assembly demonstrates an increase in the liquid prevention capacity by 70-1000 times compared with a commercial CPC material. This novel synergistic effect may offer a breakthrough in the development of various applications including protective clothing baby nappies, hygiene products, food preparation, soil water retention, and sporting/camping/ski equipment and clothing.

10.
Environ Int ; 158: 106919, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634623

RESUMO

BACKGROUND: Chronic diseases have become main killers affecting the health of human, and environmental pollution is a major health risk factor that cannot be ignored. It has been reported that exogenous chemical residues including pesticides, herbicides, fungicides, veterinary drugs and persistent organic pollutants are associated with chronic diseases. However, the evidence for their relationship is equivocal and the underlying mechanisms are unclear. OBJECTIVES: We aim to investigate the linkages between serum exogenous chemical residues and 5 main chronic diseases including obesity, hyperuricemia, hypertension, diabetes and dyslipidemia, and further reveal the metabolic perturbations of chronic diseases related to exogenous chemical residue exposure, then gain potential mechanism insight at the metabolic level. METHODS: LC-MS-based targeted and nontargeted methods were respectively performed to quantify exogenous chemical residues and acquire metabolic profiling of 496 serum samples from chronic disease patients. Non-parametric test, correlation and regression analyses were carried out to investigate the association between exogenous chemical residues and chronic diseases. Metabolome-wide association study combined with the meeting-in-the-middle strategy and mediation analysis was performed to reveal and explain exposure-related metabolic disturbances and their risk to chronic diseases. RESULTS: In the association analysis of 106 serum exogenous chemical residues and 5 chronic diseases, positive associations of serum perfluoroalkyl substances (PFASs) with hyperuricemia were discovered while other associations were not significant. 240 exposure markers of PFASs and 84 disease markers of hyperuricemia were found, and 47 of them were overlapped and considered as putative effective markers. Serum uric acid, amino acids, cholesterol, carnitines, fatty acids, glycerides, glycerophospholipids, ceramides, and a part of sphingolipids were positively correlated with PFASs and associated with increased risk for hyperuricemia. Creatine, creatinine, glyceryl monooleate, phosphatidylcholine 36:6, phosphatidylethanolamine 40:6, cholesterol and sphingolipid 36:1;2O were significant markers which mediated the associations of the residues with hyperuricemia. CONCLUSIONS: Our study demonstrated a significantly positive association between PFASs exposure and hyperuricemia. The most significant metabolic abnormality was lipid metabolism which not only was positively associated with PFASs, but also increased the risk of hyperuricemia.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34574428

RESUMO

As the continuous changes in environmental regulations have a non-negligible impact on the innovation activities of micro subjects, and economic policy uncertainty has become one of the important influencing factors to be considered in the development of enterprises. Therefore, based on the panel data of Chinese high-tech enterprises from 2012-2017, this paper explores the impact of heterogeneous environmental regulations on firms' green innovation from the perspective of economic policy uncertainty as a moderating variable. The empirical results show that, first, market-incentivized environmental regulation instruments have an inverted U-shaped relationship with innovation output, while voluntary environmental regulation produces a significant positive impact. Second, the U-shaped relationship between market-based environmental regulation and innovation output becomes more pronounced when economic policy uncertainty is high. However, it plays a negative moderating role in regulating the relationship between voluntary-based environmental regulation and innovation output. This paper not only illustrates the process of technological innovation by revealing the intrinsic mechanism of environmental regulation on firm innovation, but also provides insights for government in environmental governance from the perspective of economic policy uncertainty as well.

12.
Lab Chip ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581377

RESUMO

Reconstruction of 3D vascularized microtissues within microfabricated devices has rapidly developed in biomedical engineering, which can better mimic the tissue microphysiological function and accurately model human diseases in vitro. However, the traditional PDMS-based microfluidic devices suffer from the microfabrication with complex processes and usage limitations of either material properties or microstructure design, which drive the demand for easy processing and more accessible devices with a user-friendly interface. Here, we present an open microfluidic device through a rapid prototyping method by laser cutting in a cost-effective manner with high flexibility and compatibility. This device allows highly efficient and robust hydrogel patterning under a liquid guiding rail by spontaneous capillary action without the need for surface treatment. Different vascularization mechanisms including vasculogenesis and angiogenesis were performed to construct a 3D perfusable microvasculature inside a tissue chamber with various shapes under different microenvironment factors. Furthermore, as a proof-of-concept we have created a vascularized spheroid by placing a monoculture spheroid into the central through-hole of this device, which formed angiogenesis between the spheroid and microvascular network. This open microfluidic device has great potential for mass customization without the need for complex microfabrication equipment in the cleanroom, which can facilitate studies requiring high-throughput and high-content screening.

13.
Front Genet ; 12: 684905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484289

RESUMO

Background: Diaphyseal and metaphyseal modeling defects lead to severe changes in bone mass and shape, which are common features in osteoporosis that linked to non-vertebral fractures. Original mechanism of diaphyseal and metaphyseal modeling defects has proved elusive. Studying rare syndromes can elucidate mechanisms of common disorders and identify potential therapeutic targets. Methods: We evaluated a family pedigree with craniometadiaphyseal dysplasia (CRMDD, OMIM 269300), a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and absent of normal metaphyseal flaring and diaphyseal constriction. Systemic radiographic examination and serum hormone test were made for this rare disease. One patient and her two normal parents were examined by means of whole-exome sequencing (WES) to identify the candidate pathogenic gene and rule out mucopolysaccharidosis and Prader-Willi Syndrome by means of Sanger sequencing. Results: There are several conspicuous radiographic characteristics: (1) bullet-shaped phalanges, (2) long and narrow pelvic inlet, absent of supra-acetabular constriction, (3) round rod-shaped long tubular bones, (4) prominent aiploic mastoid, (5) bending-shaped limb, genua varus and genu varum, and (6) congenital dislocation of elbow. Here, we did not find any wormian bones, and there are several typical clinical characteristics: (1) macrocephaly and wide jaw, (2) Avatar elf-shaped ears, pointed and protruding ears, (3) hypertrophy of limbs, (4) flat feet and giant hand phenomenon, (5) nail dystrophy, (6) limb deformity, (7) high-arched palate, (8) superficial hemangiomas, (9) tall stature, and intellectual disability. In this patient, we found biallelic frameshift deletion mutations in WRAP53, and those two mutations were transmitted from her parents respectively. Conclusions: We describe her clinical and radiological findings and presented a new subtype without wormian bones and with a tall stature. Our study showed that craniometadiaphyseal dysplasia was caused by a deficiency of WRAP53 with autosomal recessive inheritance.

14.
J Hazard Mater ; 416: 126192, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492956

RESUMO

The marine applicability of adsorbents intended for recovering uranium from seawater is crucial. For such applicability, the materials must exhibit anti-biofouling properties, seawater pH adaptability (pH~8), and salt tolerance. Extracting uranium from seawater is a long-term project; hence, biofouling, high salt concentrations, and weak alkaline environments negatively affect the adsorption of uranium and damage the recovered materials. Most studies on the extraction of uranium from seawater focus on increasing the adsorption capacity of the employed adsorbent, while its marine applicability is neglected. In the present study, three types of guanidine polymer (GP)-modified acrylic fibers were prepared to investigate the impact of the introduced structure on the marine applicability of the fibers. After screening, the introduction of polyhexamethylene biguanidine (PHMB) is observed to produce PAO-PHMB-A, characterized by excellent marine applicability. The enhanced properties include high antimicrobial activity (109 CFU/mL, 99.71%), good salt tolerance, and optimal adsorption at a pH of 8. Owing to the synergistic effect of its functional groups, the PAO-PHMB-A material exhibits excellent adsorption performance (525.89 mg/g), as well as high selectivity and durability. More importantly, long-term marine tests revealed that PAO-PHMB-A shows a remarkable uranium adsorption capacity (30 d, 3.19 mg/g) and excellent antibacterial activity. Considering its excellent marine applicability and good adsorption performance, the PAO-PHMB-A material developed in this work could serve as a potential adsorbent for engineering applications associated with uranium recovery from seawater.


Assuntos
Incrustação Biológica , Urânio , Adsorção , Polímeros , Água do Mar
15.
Obesity (Silver Spring) ; 29(10): 1708-1718, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34490739

RESUMO

OBJECTIVE: A Mendelian randomization (MR) framework was applied to disentangle the causal effect of branched-chain amino acids (BCAAs) and overweight/obesity in Chinese adolescents. METHODS: Circulating BCAA levels were measured by liquid chromatography coupled with mass spectrometry. A total of 7 BCAAs and 12 BMI-associated common variants identified from released genome-wide association study results were genotyped. Furthermore, a bidirectional MR approach was undertaken to disentangle the causal effect of BCAAs and overweight/obesity, using two-stage regression. RESULTS: Using the inverse variance-weighted strategy and the weighted genetic scoring instruments, the estimated odds ratio per 1-arbitrary-unit increase in the total BCAA level on overweight and obesity odds after adjusting for age and sex was 2.40 (95% CI: 1.38 to 3.42, p < 0.001) and 2.55 (95% CI: 1.35 to 4.82, p = 0.004), respectively. Furthermore, additional MR tests were undertaken using a reversed model, testing the causal effect of increasing BMI variants on total BCAA level. By contrast, no evidence that increased BMI was causally associated with the total BCAA level (estimated ß associated with 1-kg/m2 increase in BMI = 0.05, 95% CI: -0.17 to 0.28, p = 0.642) was observed. CONCLUSIONS: In summary, BCAAs may be causally associated with overweight/obesity or, rather, a congenital dysmetabolism of BCAAs could be a cause of overweight/obesity in adolescents.

16.
J Immunother Cancer ; 9(9)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34548385

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC). METHODS: A CD8+ MeTIL signature score was constructed by using CD8+ T cell-specific differentially methylated positions (DMPs) that were identified from Illumina EPIC methylation arrays. Immune cells, colon epithelial cells, and two CRC cohorts (n=282 and 335) were used to develop a PCR-based assay for quantitative analysis of DNA methylation at single-base resolution (QASM) to determine CD8 + MeTIL signature score. RESULTS: Three CD8+ T cell-specific DMPs were identified to construct the CD8+ MeTIL signature score, which showed a dramatic discriminability between CD8+ T cells and other cells. The QASM assay we developed for CD8+ MeTIL markers could measure CD8+ TILs distributions in a fully quantitative, accurate, and simple manner. The CD8+ MeTIL score determined by QASM assay showed a strong association with histopathology-based CD8+ TIL counts and a gene expression-based immune marker. Furthermore, the low CD8+ MeTIL score (enriched CD8+ TILs) was associated with MSI-H tumors and predicted better survival in CRC cohorts. CONCLUSIONS: This study developed a quantitative DNA methylation-based signature that was reliable to evaluate CD8+ TILs and prognosis in CRC. This approach has the potential to be a tool for investigations on CD8+ TILs and a biomarker for therapeutic approaches, including immunotherapy.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34465138

RESUMO

URFs are more likely developed among HIV-1 infections through MSM because of multiple subtypes co-circulation. In this study, two novel URFs deriving from two HIV-positive subjects (HB010014, HB010063) were identified in Shijiazhuang, Hebei province, China, and two sequences formed a distinct monophyletic cluster. The further recombination analysis showed that of two new URFs were consisted of CRF01_AE and CRF07_BC. The subregion phylogenetic analysis indicated that CRF01_AE segments were traced back to cluster 4 of CRF01_AE strains, which were prevalent among HIV-1 infections through MSM in China. New URFs being developing gradually and spreading released that more and more novel recombinant strains of HIV-1 could be developed, which means that the past prevention strategies need to be adjusted.

18.
Quant Imaging Med Surg ; 11(9): 3920-3931, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34476178

RESUMO

Background: The 4-dimensional automated left atrial quantification (4D Auto LAQ) tool is a new software for analysis of the structure and function of the left atrium (LA). This study aimed to evaluate the relationship between LA strain (LAS) as measured by 4D Auto LAQ echocardiography and thromboembolism risk in patients with non-valvular atrial fibrillation (NVAF). Methods: Eight-five patients with NVAF were recruited from the cardiovascular center of our hospital, including 39 patients at high risk and 46 patients at low risk of thromboembolism. The study participants were assessed by routine echocardiography; 4D images were obtained, after which 4D Auto LAQ assessment was performed. Results: In the thromboembolism high-risk group, the rates of impaired LA reservoir strain, LA contraction strain, LA reservoir circumferential strain, LA conduit circumferential strain, and LA contraction circumferential strain were found to be significantly higher than in the low-risk group. However, there was no significant difference in volume at onset of LA contraction or LA ejection fraction (LAEF) between the 2 groups. LA contraction circumferential strain was found to be an independent high risk factor for thromboembolism [odds ratio (OR): 2.52; P=0.008]. LA contraction circumferential strain >-4.5% was the cut-off for differentiating between participants with high and low risk of thromboembolism, with an area under the curve (AUC) of 0.95 (P<0.0001), a sensitivity of 0.872, and a specificity of 0.978. Sequential analysis revealed that LA contraction circumferential strain had a high diagnostic efficacy for stroke, as well as a specified accuracy in the diagnosis of hypertension and diabetes in patients aged ≥65 years old. However, it was not found to be effective in the diagnosis of heart failure and vascular diseases. Conclusions: LAS is a useful index for the dynamic evaluation of LA function in patients with non-valvular AF, with higher sensitivity and accuracy than LA volume. LA contraction circumferential strain is an independent high risk factor for thromboembolism, and LA contraction circumferential strain >-4.5% is a valuable cut-off to guide the use of anticoagulant therapy in patients with non-valvular AF.

19.
Front Immunol ; 12: 723585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489974

RESUMO

Objectives: Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods: COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results: A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions: Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Citocinas/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , COVID-19/classificação , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
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