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1.
Artigo em Inglês | MEDLINE | ID: mdl-34523905

RESUMO

Electron acceptors with nonfused aromatic cores (NCAs) have aroused increasing interest in organic solar cells due to the low synthetic complexity and flexible chemical modification, but the corresponding device performance still lags behind. Herein, we designed and synthesized two new quinoxaline-based NCAs, namely, QOC6-4H and QOC6-4Cl. Although both NCAs show good backbone coplanarity, QOC6-4Cl with chlorinated end groups exhibits higher extinction coefficient, enhanced crystallinity, and more compact π-π stacking, which is correlated with the stronger intermolecular interactions induced by chlorine atoms. Benefiting from the broader and stronger optical absorption, improved carrier mobilities, and suppressed charge recombination, a notable power conversion efficiency (PCE) of 12.32% with a distinctly higher short-current density (Jsc) of 22.91 mA cm-2 and a fill factor (FF) of 69.01% could be obtained for the PBDB-T:QOC6-4Cl-based device. The PCEs of PBDB-T:QOC6-4H were only lower than 8%, which could mainly be attributed to the unsymmetric charge transport. Our work proves that the chlorination of end groups is a facile and effective strategy to enhance the intermolecular interactions and thus the photovoltaic performance of NCAs, and a careful modulation of the intermolecular interactions plays a vital role in further developing both high-performance and low-cost organic photovoltaic materials.

2.
PLoS One ; 16(9): e0257207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34529731

RESUMO

Streptococcus pneumoniae (Spn) is a leading respiratory tract pathogen that colonizes the nasopharynx (NP) through adhesion to epithelial cells and immune evasion. Spn actively interacts with other microbiota in NP but the nature of these interactions are incompletely understood. Using 16S rRNA gene sequencing, we analyzed the microbiota composition in the NP of children with or without Spn colonization. 96 children were included in the study cohort. 74 NP samples were analyzed when children were 6 months old and 85 NP samples were analyzed when children were 12 months old. We found several genera that correlated negatively or positively with Spn colonization, and some of these correlations appeared to be influenced by daycare attendance or other confounding factors such as upper respiratory infection (URI) or Moraxella colonization. Among these genera, Corynebacterium showed a consistent inverse relationship with Spn colonization with little influence by daycare attendance or other factors. We isolated Corynebacterium propinquum and C. pseudodiphtheriticum and found that both inhibited the growth of Spn serotype 22F strain in vitro.

3.
Int J Cancer ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536292

RESUMO

Programmed death 1(PD-1) inhibitors are widely used for treatment of hepatocellular carcinoma (HCC). Hypothyroidism is commonly associated with this therapy, although the mechanism underlying this complication and effects on patient prognosis remain unclear. We retrospectively analysed the data of patients with HCC who received anti-PD-1 therapy at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 2018 and May 2020. Based on thyroid function evaluation, patients were categorised into hypothyroidism group and non-hypothyroidism group. Follow-up was completed on February 28, 2021. The primary endpoint of our study was progression free survival (PFS). The study included 74 patients, and the disease control rate was higher in hypothyroidism group (62.7%, 27/43) than in non-hypothyroidism group (36.4%, 11/31) (P=0.020). The PFS was longer in hypothyroidism group (7.44 months) than in non-hypothyroidism group (5.68 months) (P=0.006). Additionally, the PFS of patients with hypothyroidism before immunotherapy (6.27 months) was also longer than that in non-hypothyroidism group (5.68 months), although the difference was statistically nonsignificant (P=0.527). Cox regression analysis showed that the hazard ratios of hypothyroidism, Child-Pugh grade B at initial admission and serum gamma-glutamyl transferase levels >71U/L before immunotherapy were 0.404 (95% confidence interval [CI]: 0.207-0.791, P=0.008), 2.753 (95%CI:1.127-6.455, P=0.026) and 2.469 (95%CI:1.155-5.277, P=0.020), respectively. Hypothyroidism was associated with prognosis in patients with HCC treated with PD-1 inhibitors, and prognosis was more favourable in patients with hypothyroidism than in those without hypothyroidism. Hypothyroidism and the Child-Pugh grade at initial admission were independently associated with patient prognosis. This article is protected by copyright. All rights reserved.

4.
Nano Lett ; 21(18): 7569-7578, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34472343

RESUMO

Selective amplification of reactive oxygen species (ROS) generation in tumor cells has been recognized as an effective strategy for cancer therapy. However, an abnormal tumor metabolism, especially the mitochondrial glutaminolysis, could promote tumor cells to generate high levels of antioxidants (e.g., glutathione) to evade ROS-induced damage. Here, we developed a tumor-targeted nanoparticle (NP) platform for effective breast cancer therapy via combining inhibition of mitochondrial glutaminolysis and chemodynamic therapy (CDT). This NP platform is composed of bovine serum albumin (BSA), ferrocene, and purpurin. After surface decoration with a tumor-targeting aptamer and then intravenous administration, this NP platform could target tumor cells and release ferrocene to catalyze hydrogen peroxide (H2O2) into the hydroxyl radical (·OH) for CDT. More importantly, purpurin could inhibit mitochondrial glutaminolysis to concurrently prevent the nutrient supply for tumor cells and disrupt intracellular redox homeostasis for enhanced CDT, ultimately leading to the combinational inhibition of tumor growth.

5.
Cell Signal ; 87: 110141, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34487815

RESUMO

Myocardial ischemia/reperfusion(I/R) injury elicits an inflammatory response that drives tissue damage and cardiac remodeling. The trafficking and recruitment of inflammatory cells are controlled by C-X-C motif chemokine ligands and their receptors. CXCL16, a hallmark of acute coronary syndromes, is responsible for the recruitment of macrophages, monocytes and T lymphocytes. However, its role in cardiac I/R injury remains poorly characterized. Here we reported that CXCL16-mediated cardiac infiltration of CD11b+Ly6C+ cells played a crucial role in IL-18-induced myocardial inflammation, apoptosis and left ventricular(LV) dysfunction during I/R. Treatment with CXCL16 shRNA attenuated I/R-induced cardiac injury, LV remodeling and cardiac inflammation by reducing the recruitment of inflammatory cells and the release of TNFα, IL-17 and IFN-γ in the heart. We found that I/R-mediated NLRP3/IL-18 signaling pathway triggered CXCL16 transcription in cardiac vascular endothelial cells(VECs). Two binding sites of FOXO3 were found at the promoter region of CXCL16. By luciferase report assay and ChIP analysis, we confirmed that FOXO3 was responsible for endothelial CXCL16 transcription. A pronounced reduction of CXCL16 was observed in FOXO3 siRNA pretreated-VECs. Further experiments revealed that IL-18 activated FOXO3 by promoting the phosphorylation of STAT3 but not STAT4. An interaction between FOXO3 and STAT3 enhanced the transcription of CXCL16 induced by FOXO3. Treatment with Anakinra or Stattic either effectively inhibited IL-18-mediated nuclear import of FOXO3 and CXCL16 transcription. Our findings suggested that IL-18 accelerated I/R-induced cardiac damage and dysfunction through activating CXCL-16 and CXCL16-mediated cardiac infiltration of the CD11b+Ly6C+ cells. CXCL16 might be a novel therapeutic target for the treatment of I/R-related ischemic heart diseases.

6.
Med Image Anal ; 74: 102207, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34487982

RESUMO

The assessment of myocardial perfusion has become increasingly important in the early diagnosis of coronary artery disease. Currently, the process of perfusion assessment is time-consuming and subjective. Although automated methods by threshold processing have been proposed, they cannot obtain an accurate perfusion assessment. Thus, there is a great clinical demand to obtain a rapid and accurate assessment of myocardial perfusion through a standard procedure using an automated algorithm. In this work, we present a spatio-temporal multi-task network cascade (ST-MNC) to provide an accurate and robust assessment of myocardial perfusion. The proposed network captures patch-based spatio-temporal representations for each pixel through a spatio-temporal encoder-decoder network. Then the multi-task network cascade uses spatio-temporal representations as shared features to predict various perfusion parameters and myocardial ischemic regions. Extensive experiments on CT images of 232 subjects demonstrate ST-MNC could produce a good approximation for perfusion parameters and an accurate classification for ischemic regions. These results show that our proposed method can provide a fast and accurate assessment of myocardial perfusion.

7.
Cell Chem Biol ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34499862

RESUMO

While there are hundreds of predicted E3 ligases, characterizing their applications for targeted protein degradation has proved challenging. Here, we report a chemical biology approach to evaluate the ability of modified recombinant E3 ligase components to support neo-substrate degradation. Bypassing the need for specific E3 ligase binders, we use maleimide-thiol chemistry for covalent functionalization followed by E3 electroporation (COFFEE) in live cells. We demonstrate that electroporated recombinant von Hippel-Lindau (VHL) protein, covalently functionalized at its ligandable cysteine with JQ1 or dasatinib, induces degradation of BRD4 or tyrosine kinases, respectively. Furthermore, by applying COFFEE to SPSB2, a Cullin-RING ligase 5 receptor, as well as to SKP1, the adaptor protein for Cullin-RING ligase 1 F box (SCF) complexes, we validate this method as a powerful approach to define the activity of previously uncharacterized ubiquitin ligase components, and provide further evidence that not only E3 ligase receptors but also adaptors can be directly hijacked for neo-substrate degradation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34515533

RESUMO

Objective: To study the associations of a single nucleotide polymorphisms (SNP) of the myosin heavy chain 6 (MYH6) gene with the risk of atrial fibrillation (AF) and warfarin anticoagulation therapy. Methods: Sanger sequencing was employed to analyze the genotypes of the MYH6 gene's rs28730771, rs365990, and rs2277473 loci in 243 AF patients and 243 non-AF patients (control group) selected according to the age and sex of AF patients at a 1:1 ratio. Multiple logistic regression was used to analyze the risk factors in AF. SHEsis was adopted to analyze the association between rs28730771, rs365990, rs2277473 haplotypes and susceptibility to AF. The average weekly dose of warfarin administered to AF patients with different genotypes was compared. Results: The T allele at rs28730771 of the MYH6 gene (odds ratio [OR] = 2.82, 95% confidence interval [CI]: 1.73-4.59, p < 0.01), the G allele at rs365990 (OR = 1.65, 95% CI: 1.22-2.24, p < 0.01) and the T allele at rs2277473 (OR = 1.91, 95% CI: 1.25-2.91, p < 0.01) were significantly associated with an elevated risk of AF. The results of a logistic regression analysis demonstrated that hypertension, smoking, drinking, family history of stroke, as well as the genotypes at the rs28730771, rs365990, and rs2277473 loci were all risk factors in AF (p < 0.05). The CAG haplotype for the three SNPs was associated with a reduced risk of AF susceptibility (OR = 0.61, 95% CI: 0.46-0.81, p < 0.01), and the CGG haplotype was related to an increased risk of AF (OR = 1.49, 95% CI: 1.07-2.06, p = 0.02). The doses of warfarin used in AF patients with different genotypes at the MYH6 rs28730771, rs365990, and rs2277473 were significantly different (p < 0.05). Conclusion: The three SNPs (rs28730771, rs365990, and rs2277473) of the MYH6 gene loci were significantly associated with the risk of AF susceptibility and the dose of warfarin anticoagulant therapy.

9.
Sci Total Environ ; 792: 148454, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34465049

RESUMO

Nano zero-valent iron particles (nZVI, 0.09 wt%), micro zero-valent iron particles (mZVI, 0.09 wt%), granular activated carbon (GAC, 3.03 wt%), GAC supported nZVI (nZVI/GAC, 3.12 wt%) and nZVI&GAC (nZVI 0.09 wt%, GAC 3.03 wt%) were evaluated for their effects on polychlorinated biphenyls (PCBs) anaerobic reductive dechlorination, detoxification, as well as microbial community structure in Taihu Lake (China) sediment microcosms. The results showed that all of these five materials could stimulate PCBs reductive dechlorination, especially for dioxin-like PCB congeners, and nZVI&GAC had the best removal effect on PCBs. The reduction of total PCBs increased from 13.5% to 33.2%. H2 generated by zero-valent iron corrosion was utilized by organohalide-respiring bacteria (OHRB) to enhance the dechlorination of PCBs predominantly via meta chlorine removal in the short term. The addition of ZVI had little impact on the total bacterial abundance and the microbial community structure. The adsorption of GAC and potential bioremediation properties of attached biofilm could promote the long-term removal of PCBs. GAC, nZVI/GAC, nZVI&GAC had different influences on the microbial structure. These findings provide insights into the biostimulation technique for in situ remediations of PCBs contaminated sediments.


Assuntos
Microbiota , Bifenilos Policlorados , Biodegradação Ambiental , Catálise , Cloro , Sedimentos Geológicos , Ferro , Lagos , Bifenilos Policlorados/análise
10.
J Environ Sci (China) ; 108: 96-106, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34465441

RESUMO

Hydrodechlorination is a promising technology for the remediation of water body contaminated with trichloroethylene (TCE). In this work, the liquid-phase hydrogenation of TCE by Raney Ni (R-Ni) and Pd/C under an open system have been studied, in which nascent H2 (Nas-H2) generated in situ from the cathode acted as a hydrogen source. Experimental results showed that TCE was completely eliminate from the solution through the synergistic effects of hydrodechlorination and air flotation due to the formation of continuous micro/nano-sized Nas-H2 bubbles from the cathode. Furthermore, the effects of inorganic anions and organic solvents on R-Ni and Pd/C hydrogenation activity were investigated, respectively. The results showed that NO3- and acetonitrile can form a competitive reaction with TCE; Sulfur with lone-pair electrons will cause irreversible poisoning to these two catalysts, and have a stronger inhibitory effect on Pd/C. This work helps to realize the separation of volatile halogenated compounds from water environment and provides certain data support for the choice of catalyst in the actual liquid-phase hydrogenation system.


Assuntos
Tricloroetileno , Catálise , Hidrogenação , Solventes , Enxofre
11.
Cancer Med ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477306

RESUMO

BACKGROUND: Artificial intelligence (AI) assistance has been considered as a promising way to improve colonoscopic polyp detection, but there are limited prospective studies on real-time use of AI systems. METHODS: We conducted a prospective, multicenter, randomized controlled trial of patients undergoing colonoscopy at six centers. Eligible patients were randomly assigned to conventional colonoscopy (control group) or AI-assisted colonoscopy (AI group). AI assistance was our newly developed AI system for real-time colonoscopic polyp detection. Primary outcome is polyp detection rate (PDR). Secondary outcomes include polyps per positive patient (PPP), polyps per colonoscopy (PPC), and non-first polyps per colonoscopy (PPC-Plus). RESULTS: A total of 2352 patients were included in the final analysis. Compared with the control, AI group did not show significant increment in PDR (38.8% vs. 36.2%, p = 0.183), but its PPC-Plus was significantly higher (0.5 vs. 0.4, p < 0.05). In addition, AI group detected more diminutive polyps (76.0% vs. 68.8%, p < 0.01) and flat polyps (5.9% vs. 3.3%, p < 0.05). The effects varied somewhat between centers. In further logistic regression analysis, AI assistance independently contributed to the increment of PDR, and the impact was more pronounced for male endoscopists, shorter insertion time but longer withdrawal time, and elderly patients with larger waist circumference. CONCLUSION: The intervention of AI plays a limited role in overall polyp detection, but increases detection of easily missed polyps; ChiCTR.org.cn number, ChiCTR1800015607.

12.
Mol Cancer ; 20(1): 114, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496888

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated. METHODS: Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC-MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis. RESULTS: We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice. CONCLUSIONS: The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.

13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1111-1118, 2021 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-34523275

RESUMO

Objective: To compare the effectiveness of the femoral neck system (FNS) and inverted triangle cannulated screws (ITCS) for the treatment of Pauwels type Ⅲ femoral neck fractures. Methods: The clinical data of 59 patients with Pauwels type Ⅲ femoral neck fractures treated between May 2019 and November 2020 were retrospectively analysed. The patients were divided into FNS group (28 cases) and ITCS group (31 cases) according to the different internal fixation. There was no significant difference in gender, age, affected side, body mass index, cause of injury, smoking history, alcohol abuse history, Pauwels angle, Garden classification, AO/Orthopaedic Trauma Association (AO/OTA) classification, and time from injury to operation between the two groups ( P>0.05). The operation time, incision length, intraoperative blood loss, extra assisted reduction procedures (Kirschner wire prying reduction or open reduction), hospitalization stay, and early complications were recorded and compared between the two groups. Garden index and Haidukewych score were used to evaluate fracture reduction. Fracture healing time, lateral thigh irritation, time of partial or total weight-bearing postoperatively, shortening length and degree of femoral neck, change of caput-collum-diaphysis (CCD) angle (the difference of CCD angle between immediate after operation and last follow-up), incidence of osteonecrosis of femoral head and revision surgery were recorded and compared between the two groups. Hip joint function were evaluated by Harris score. Results: The operation time of FNS group was significantly shorter than ITCS group, and the incision length was significantly longer than ITCS group ( P<0.05). There was no significant difference in intraoperative blood loss, assisted reduction, Garden index, Haidukewych score, and hospitalization stay between the two groups ( P>0.05). All the incisions healed by first intention. There were 2 deep vein thrombosis in the FNS group and 1 pulmonary infection and 1 deep vein thrombosis in the ITCS group. No significant difference was found in the incidence of early postoperative complications (7.1% vs. 6.5%) between the two groups ( P=1.000). Patients in both groups were followed up 3-14 months, and there was no significant difference in follow-up time between the two groups ( t=-0.553, P=0.582). The fracture healing time, Harris score, and the partial weight-bearing time after operation of the FNS group were significantly better than those of the ITCS group ( P<0.05). However, there was no significant difference in total weight-bearing time between the two groups ( Z=-1.298, P=0.194). No lateral thigh irritation was found in the FNS group, while 10 patients in the ITCS group had lateral thigh irritation, and the incidence between the two groups (0 vs. 32.3%) was significant ( P=0.001). At last follow-up, the shortening length and degree of femoral neck and the change of CCD angle in FNS group were significantly less than those in ITCS group ( P<0.05). There was no patient with osteonecrosis of femoral head or reoperation in the FNS group, while 4 patients in the ITCS group underwent reoperation (including 2 cases of osteonecrosis of the femoral head). However, the incidences (0 vs. 6.5%; 0 vs.12.9%) between the two groups were not significant ( P=0.493; P=0.114). Conclusion: Using FNS to treat Pauwels type Ⅲ femoral neck fracture is simple as well as able to reduce the shortening of the femoral neck and the change of the CCD angle. Also, FNS is conducive to the recovery of hip joint function, which should be considered as a new choice for the treatment of young femoral neck fracture patients.


Assuntos
Fraturas do Colo Femoral , Parafusos Ósseos , Fraturas do Colo Femoral/cirurgia , Colo do Fêmur , Fixação Interna de Fraturas , Humanos , Estudos Retrospectivos , Resultado do Tratamento
14.
Anim Biosci ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34530508

RESUMO

Objective: The growth differentiation factor 8 (GDF8) gene plays a key role in bone formation, resorption, and skeletal muscle development in mammals. Here, we studied the genetic variants of GDF8 and their contribution to body conformation traits in Chinese Dabieshan cattle. Methods: Single nucleotide polymorphisms were identified in the bovine GDF8 gene by DNA sequencing. Phylogenetic analysis, motif analysis, and genetic diversity analysis were conducted using bioinformatics software. Association analysis between five SNPs, haplotype combinations, and body conformation traits was conducted in 380 individuals. Results: GDF8 was highly conserved in seven species, and the GDF8 sequence of cattle was most similar to the sequences of sheep and goat based on the phylogenetic analysis. The motif analysis showed that there were 12 significant motifs in GDF8. Genetic diversity analysis indicated that the polymorphism information content of the five studied SNPs was within 0.25 to 0.5. Haplotype analysis revealed a total of 12 different haplotypes and those with a frequency of < 0.05 were excluded. Linkage disequilibrium analysis showed a strong linkage (r2 > 0.330) between the following SNPs: g.5070C > A, g.5076T > C, and g.5148A > C. Association analysis indicated these five SNPs were associated with some of the body conformation traits (p < 0.05), and the animals with haplotype combination H1H1 (-GGGGCCTTAA-) had greater wither height, hip height, heart girth, abdominal girth, and pin bone width than the other (p < 0.05) Dabieshan cattle. Conclusion: Overall, our results indicate that the genetic variants of GDF8 affected the body conformation traits of Chinese Dabieshan cattle, and the GDF8 gene could make a strong candidate gene in Dabieshan cattle breeding programs.

15.
J Med Chem ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519507

RESUMO

Mitogen-activated protein kinase FgGpmk1 plays vital roles in the development and virulence of Fusarium graminearum (F. graminearum), the causative agent of Fusarium head blight (FHB). However, to date, the druggability of FgGpmk1 still needs verification, and small molecules targeting FgGpmk1 have never been reported. Here, we reported the discovery of a novel inhibitor 94 targeting FgGpmk1. First, a novel hit (compound 21) with an EC50 value of 13.01 µg·mL-1 against conidial germination of F. graminearum was identified through virtual screening. Then, guided by molecular modeling, compound 94 with an EC50 value of 3.46 µg·mL-1 was discovered, and it can inhibit the phosphorylation level of FgGpmk1 and influence the nuclear localization of its downstream FgSte12. Moreover, 94 can inhibit deoxynivalenol biosynthesis without any damage to the host. This study reported a group of FgGpmk1 inhibitors with a novel scaffold, which paves the way for the development of potent fungicides to FHB management.

16.
Lab Chip ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498019

RESUMO

Flexible diffraction gratings that can be dynamically tuned in terms of both diffraction efficiency and diffraction angles are very important components for various applications, and fundamentally can be tuned through varying the modulation depth, duty cycle and grating period. However, dynamic and continuous tuning of a grating in all three aspects is difficult and has never been demonstrated hitherto. We propose and successfully fabricate a laminar-flow-based microfluidic grating in which all the three parameters can be dynamically tuned by simply varying flow rates into several liquid inlets. A 32-period liquid grating is generated by using ethanol and benzyl alcohol as alternate liquid lamellae. The total diffraction efficiency is tuned between 0 and 99%, and the maximum diffraction efficiency of the first order is ∼27%. The duty cycle of the grating is dynamically tuned from 7.6% to 91.5%. The grating period is compressed from more than 22 µm to less than 4 µm, leading to tuning of the first order diffraction angle from 1.7° to 9.2°.

17.
BMC Genomics ; 22(1): 678, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548021

RESUMO

BACKGROUND: Genomic regions with a high frequency of runs of homozygosity (ROH) are related to important traits in farm animals. We carried out a comprehensive analysis of ROH and evaluated their association with production traits using the BovineHD (770 K) SNP array in Chinese Simmental beef cattle. RESULTS: We detected a total of 116,953 homozygous segments with 2.47Gb across the genome in the studied population. The average number of ROH per individual was 99.03 and the average length was 117.29 Mb. Notably, we detected 42 regions with a frequency of more than 0.2. We obtained 17 candidate genes related to body size, meat quality, and reproductive traits. Furthermore, using Fisher's exact test, we found 101 regions were associated with production traits by comparing high groups with low groups in terms of production traits. Of those, we identified several significant regions for production traits (P < 0.05) by association analysis, within which candidate genes including ECT2, GABRA4, and GABRB1 have been previously reported for those traits in beef cattle. CONCLUSIONS: Our study explored ROH patterns and their potential associations with production traits in beef cattle. These results may help to better understand the association between production traits and genome homozygosity and offer valuable insights into managing inbreeding by designing reasonable breeding programs in farm animals.

18.
Chem Res Toxicol ; 34(9): 2125-2134, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34428026

RESUMO

Polybrominated diphenyl ethers (PBDEs) are used worldwide in brominated flame retardants. Although due to the forbiddance of their application, PBDEs continuously exist in the environment due to their persistence. Therefore, it is important to expand the understanding of their potential toxicities and human risks. The underlying cardiovascular toxicological mechanisms of PBDEs are still largely unknown. Our previous studies indicated that PBDE quinone-type metabolite (PBDEQ) exposure causes reactive oxygen species (ROS)-driven cytotoxicity and various types of programmed cell death. Here, we first reported PBDEQ exposure induces atherosclerosis progression in bone marrow-derived macrophages (BMDMs) isolated from wild-type C57BL/6 or CD36-/- mice and J774A.1 macrophage models. First, we found that PBDEQ exposure induced lipid accumulation in oxidized low-density lipid (Ox-LDL)-treated J774A.1 macrophages. Consistently, in J774A.1 macrophages, PBDEQ exposure resulted in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis. CD36, a scavenger receptor responsible for the mediation of Ox-LDL uptake, was upregulated upon PBDEQ treatment. On the contrary, genetic knockout of CD36 or CD36 silencing by small interfering RNA efficiently attenuates PBDEQ-promoted lipid accumulation in BMDMs and J774A.1 macrophages. These findings highlight the effect of CD36 on the cardiovascular toxicity of PBDEs, which provides a better understanding of the pro-atherosclerosis effect of PBDEs.

19.
Gene ; 807: 145919, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34454034

RESUMO

The application of CRISPR/Cas9 system for gene editing, as a technical coup for biotechnology, is worldwide and encompasses multiple of species. The inactivation of catalytical site in Cas9 (dCas9) has been reprogrammed as an effective approach to regulate the transcriptional level of target genes, especially for the functionally essential genes and redundant genes. Here, we exploited the CRISPR/dCas9 system to manipulate the transcriptional level of target genes in common wheat. To improve target gene's expression, we generated transcriptional activator by fusing 6×TAL-VP128 activation domain to the C-terminus of dCas9 in frame. For target gene's repressing expression transcriptionally, 3×SRDX repression domain was conjugated to the C-terminus of dCas9 in frame. Our results showed that dCas9 fused activation or repression domain could increase or decrease the transcriptional level of target gene effectively in stable transgenic lines of wheat. The study on the tRNA-processing system in CRISPR/dCas9 based transcriptional regulation system demonstrated that this robust multiplex targeted tool can be incorporated to the CRISPR/dCas9 system to facilitate the target regulation of several genes' transcriptional level. Our data broaden the application of CRISPR/dCas9 based transcriptional regulation and provide great opportunities to investigate the function of essential genes in common wheat.

20.
J Magn Reson Imaging ; 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34369030

RESUMO

BACKGROUND: Late gadolinium enhancement (LGE) is absent in many patients with suspected myocarditis and preserved left ventricular ejection fraction (LV-EF), which poses difficulties in diagnosis and risk stratification. PURPOSE: To investigate the diagnostic and prognostic value of ventricular myocardial strain in patients with suspected myocarditis, preserved LV-EF, and negative Lake Louis Criteria (LLC) by comparing the findings in LGE negative and LGE positive patients. STUDY TYPE: Retrospective. POPULATION: A total of 108 patients with clinically suspected myocarditis who did not satisfy LLC were divided into LGE negative (N = 65) and LGE positive (N = 43) groups. A control group consisted of 50 healthy volunteers. FIELD STRENGTH/SEQUENCE: Steady-state free precession cine and phase-sensitive inversion recovery segmented gradient echo LGE sequences at 3.0 T. ASSESSMENT: Myocardial strain of the ventricles was evaluated by feature tracking, major adverse cardiovascular events (MACE) were assessed during follow-up since the date of magnetic resonance examination. STATISTICAL TESTS: Independent-samples t test, Mann-Whitney U test, receiver operating characteristic curve analysis, and Cox proportional hazard regression were performed. A P-value <0.05 was considered statistically significant. RESULTS: Cardiac function and myocardial deformability were impaired in all patients relative to controls. Left ventricular-global radial (LV-GRS), circumferential (LV-GCS), and longitudinal (LV-GLS) strain had diagnostic value, even in LGE negative patients (sensitivity = 0.446, 0.523, and 0.662; specificity = 0.92, 0.80, and 0.64; AUC = 0.685, 0.675, and 0.648, respectively). After a median follow-up of 530.5 (interquartile range: 168.5-969.25) days, MACE occurred in 18 (16.67%) patients. Right ventricular GLS showed prognostic value in all patients and in LGE negative patients, both in univariable analysis (hazard ratio [HR] 1.049, 95% confidence interval [CI] 1.001-1.099 and HR 1.068, 95% CI 1.011-1.127, respectively) and in multivariable Cox survival analysis. LV-GLS was associated with MACE in LGE positive patients in multivariable Cox survival analysis. DATA CONCLUSION: Myocardial strain provides diagnostic and prognostic value in suspected myocarditis with preserved LV-EF, even in the absence of LGE. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: 2.

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