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1.
Magn Reson Med ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34231258

RESUMO

PURPOSE: The assessment of cellular energy metabolism is crucial for understanding myocardial physiopathology. Here, we conducted a pilot study to develop an alternative imaging approach for the assessment of myocardial energy metabolism. METHODS: We developed a deuterium MRSI method to noninvasively monitor the accumulation of deuterated downstream metabolites and deuterated water in rat hearts infused with deuterated glucose or acetate substrate on a 16.4 Tesla animal scanner. RESULTS: We found that the deuterated water accumulation rate and isotopic turnover rate of deuterated glutamate/glutamine via the tricarboxylic acid cycle and exchange in rat hearts were much higher when infused with acetate compared to that with glucose, demonstrating the myocardium substrate preference for acetate over glucose. CONCLUSION: We demonstrated the feasibility of deuterium MRSI for noninvasive imaging and assessment of myocardial energy metabolism in vivo. Although the strong signal and large dynamics of myocardial deuterated water may provide a sensitive imaging biomarker, quantifying the metabolic rates still poses a challenge due to the confounding effects of blood recirculation, perfusion, and multiple deuterated water production pathways. In contrast, the deuterated glutamate/glutamine signal and change should directly reflect the metabolic activity of the myocardial tricarboxylic acid cycle, which can be used to study the metabolic shift in substance preference between acetate and glucose in the diseased state. Deuterium MRSI is noninvasive and robust and may have the potential to assess myocardial energy metabolism in human patients.

2.
Curr Alzheimer Res ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34259145

RESUMO

BACKGROUND: Calcium dysregulation has been proposed to play a causative role in the development of Alzheimer's disease pathology. Pregabalin is a compound already approved for human use, marketed as the prescription drug Lyrica. It binds the α2-δ subunit of P/Q-type voltage gated calcium channels, lowering calcium influx and providing effective treatment for epilepsy and neuropathic pain. OBJECTIVE: We hypothesize that increased resting calcium in neuronal processes near amyloid plaques plays a role in the development of neuritic dystrophies and further progression of amyloid pathology. METHODS: 5XFAD mice were treated orally for 12 weeks with pregabalin, then immunoblotting and immunofluorescent imaging were used to quantify neuritic dystrophy and amyloid deposition in pregabalin compared to placebo-treated mice. RESULTS: The treatment did not decrease markers of neuritic dystrophy or amyloid deposition. The image analysis of neuritic dystrophy on a plaque-by-plaque basis showed a small non-significant increase in the relative proportion of LAMP1 to Aß42 in plaques with areas of 50 -450 µm2 in the cortex of pregabalin-treated mice. In addition, there was a statistically significant positive correlation between the measured cerebral concentration of pregabalin and the relative levels of BACE1 and Aß in the cortex. This relationship was not observed in the hippocampus, and there was no increase in average Aß levels in pregabalin treated mice compared to placebo. We confirmed previous findings that smaller amyloid plaques are associated with a greater degree of neuritic dystrophy. CONCLUSION: Pregabalin may have an effect on Aß that merits further investigation, but our study does not suggest that pregabalin contributes substantially to amyloid pathology.

3.
BMC Pulm Med ; 21(1): 237, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266422

RESUMO

BACKGROUND: The mortality risk of chronic interstitial lung disease (ILD) is currently assessed using the ILD-GAP score. The present study evaluates whether the addition of cardiopulmonary ultrasound parameters to the ILD-GAP score can further improve the predictive value of ILD-GAP. METHODS: Medical records from 91 patients with ILD hospitalized from June 2015 to March 2016 were retrospectively examined. The Lung ultrasound (LUS) score, right ventricular (RV) function, and mechanics were obtained from the cardiopulmonary ultrasound. The ILD-GAP score was calculated from demographic characteristics and pulmonary function parameters. Patients were followed up with until May 2020. The primary endpoint was all-cause death. RESULTS: After exclusions, 74 patients with ILD were included in the analysis. During the follow-up period, 36 patients with ILD survived (ILDs), and 38 patients died (ILDd). Compared to ILDs, the ILDd cases exhibited a higher number of B-lines, LUS score, and RV end-diastolic base dimension (RVD), but lower RV function. In multivariate analysis, the ILD-GAP score (hazard ratio, 2.88; 95% CI 1.38-5.99, P = 0.005), LUS score (hazard ratio 1.13; 95% CI 1.04-1.24, P = 0.006), and RVD (hazard ratio 1.09, 95% CI 1.03-1.16, P = 0.004) were significantly related to the risk of death. Adding the LUS score and RVD to the ILD-GAP score significantly improved the predictive value compared to the ILD-GAP score alone (C statistics 0.90 vs 0.76, P = 0.018). CONCLUSION: We investigated the utility of a new prognostic model for ILD that includes both cardiopulmonary ultrasound parameters (LUS score and RVD) and the ILD-GAP score. This model better reflects the severity of pulmonary fibrosis and cardiac involvement, and has incremental predictive value over the ILD-GAP score alone.

4.
Acta Pharmacol Sin ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253875

RESUMO

Diabetic kidney disease (DKD) is one of the microvascular complications of diabetes mellitus and a major cause of end-stage renal disease with limited treatment options. Wogonin is a flavonoid derived from the root of Scutellaria baicalensis Georgi, which has shown a potent renoprotective effect. But the mechanisms of action in DKD are not fully elucidated. In this study, we investigated the effects of wogonin on glomerular podocytes in DKD using mouse podocyte clone 5 (MPC5) cells and diabetic mice model. MPC5 cells were treated with high glucose (30 mM). We showed that wogonin (4, 8, 16 µM) dose-dependently alleviated high glucose (HG)-induced MPC5 cell damage, accompanied by increased expression of WT-1, nephrin, and podocin proteins, and decreased expression of TNF-α, MCP-1, IL-1ß as well as phosphorylated p65. Furthermore, wogonin treatment significantly inhibited HG-induced apoptosis in MPC5 cells. Wogonin reversed HG-suppressed autophagy in MPC5 cells, evidenced by increased ATG7, LC3-II, and Beclin-1 protein, and decreased p62 protein. We demonstrated that wogonin directly bound to Bcl-2 in MPC5 cells. In HG-treated MPC5 cells, knockdown of Bcl-2 abolished the beneficial effects of wogonin, whereas overexpression of Bcl-2 mimicked the protective effects of wogonin. Interestingly, we found that the expression of Bcl-2 was significantly decreased in biopsy renal tissue of diabetic nephropathy patients. In vivo experiments were conducted in STZ-induced diabetic mice, which were administered wogonin (10, 20, 40 mg · kg-1 · d-1, i.g.) every other day for 12 weeks. We showed that wogonin administration significantly alleviated albuminuria, histopathological lesions, and p65 NF-κB-mediated renal inflammatory response. Wogonin administration dose-dependently inhibited podocyte apoptosis and promoted podocyte autophagy in STZ-induced diabetic mice. This study for the first time demonstrates a novel action of wogonin in mitigating glomerulopathy and podocytes injury by regulating Bcl-2-mediated crosstalk between autophagy and apoptosis. Wogonin may be a potential therapeutic drug against DKD.

5.
J Clin Neurosci ; 90: 68-75, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275583

RESUMO

BACKGROUND: This study was performed to investigate the safety and outcome of one-stage hybrid endovascular and microsurgical treatment of intracranial hypervascular tumors. METHODS: The blood supply of the tumor was endovascularly embolized just before microsurgery in a one-stage fashion. Clinical data regarding the preoperative neurological status, tumor characteristics, hybrid treatment details and complications, intraoperative blood loss, and postoperative outcomes were collected prospectively and then analyzed. RESULTS: Beginning in July 2016, 13 patients (5 women, 8 men) with intracranial hypervascular tumors were enrolled in this study, with a mean age of 48.2 ± 10.9 years. The patients' tumors comprised seven hemangioblastomas, three hemangiopericytomas, two meningiomas, and one mesenchymal chondrosarcoma. The mean maximum tumor diameter was 54.9 ± 21.5 mm. No major procedural complications occurred except catheterization-related bleeding in one patient. The mean percentage of tumor devascularization was 65.0%±17.5%. Gross total resection was achieved in 12 patients (92.3%). The mean blood loss volume during microsurgical resection was 703.8 ± 886.8 mL (range, 150-3600 mL). Symptoms improved in three patients and remained stable in six patients. CONCLUSIONS: One-stage hybrid embolization before intracranial hypervascular tumor resection is a safe and effective procedure to decrease intraoperative blood loss. It can prevent or treat embolization-related complications in a timely manner and avoid the risk of multiple surgical procedures.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34279663

RESUMO

CONTEXT: The interaction of glycated hemoglobin A1c (HbA1c) and glycemic variability in relation to diabetes-related outcomes remains unknown. OBJECTIVE: To evaluate the relationship between HbA1c and all-cause mortality across varying degrees of glycemic variability in patients with type 2 diabetes. DESIGN, SETTING, AND PATIENTS: This was a prospective study conducted in a single referral center. Data of 6090 hospitalized patients with type 2 diabetes was analyzed. Glucose coefficient of variation (CV) was obtained as the measure of glycemic variability by using continuous glucose monitoring (CGM) for 3 days. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs for all-cause mortality. RESULTS: During a median follow-up of 6.8 years, 815 patients died. In patients with the lowest and middle tertiles of glucose CV, HbA1c ≥8.0% was associated with 136% (95%CI 1.46-3.81) and 92% (95%CI 1.22-3.03) higher risks of all-cause mortality as compared with HbA1c 6.0-6.9%, respectively, after adjusting for confounders. However, a null association of HbA1c with mortality was found in patients with the highest tertile of glucose CV. CONCLUSIONS: HbA1c may not be a robust marker of all-cause mortality in patients with high degree of glycemic variability. New metrics of glycemic control may be needed in these individuals to achieve better diabetes management.

7.
J Chemother ; : 1-12, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34286671

RESUMO

The miRNA-302 family plays a critical role in carcinogenesis. As an enzyme that regulates the N6-methyladenosine modification, methyltransferase-like 3 (METTL3) plays important roles in the development and progression of various tumours. However, the upstream regulatory mechanisms of METTL3 in melanoma have not yet been fully investigated. Herein, we investigated the functions of miR-302a-3p and its target RNA METTL3 on proliferation, apoptosis, and invasion of melanoma. Quantitative real-time PCR and immunofluorescence staining were used to measure the expression of METTL3 mRNA and protein level after transfection. miR-302a-3p expression was determined by quantitative reverse transcription-PCR. The cell proliferation, cell cycle progression, apoptosis, colony formation, migration, and cell invasion ability were determined using MTT assay, propidium iodide (PI) staining, Annexin V/PI flow cytometry, plate clone assay, and Transwell migration and invasion assays, respectively. Melanoma cell metastasis was also evaluated using an in vivo model. The effect of METTL3 on the phosphorylation of PI3K and AKT was measured with western blot analysis. Our results showed that miR-302a-3p was significantly downregulated in melanoma and exerted a tumour suppressive role against melanoma progression. We identified METTL3 as a direct target of miR-302a-3p in melanoma cells using bioinformatics analysis and luciferase assay. Furthermore, the enforced overexpression of METTL3 promoted the proliferation, cell cycle progression, cell invasion, migration, expression of epithelial-to-mesenchymal transition markers, and the PI3K-AKT signalling pathway as well as suppressed the apoptosis of melanoma cells. Meanwhile, silencing the expression of METTL3 with specific shRNA demonstrated reverse outcomes of the above phenotypes in melanoma cells. By rescue experiments, we found that the restoration of METTL3 expression in miR-302a-3p-overexpressing melanoma cells successfully recovered the miR-302a-3p-mediated melanoma suppression. The in vivo results also showed that miR-302a-3p substantially inhibited melanoma cell growth and metastasis. In summary, this study demonstrated that miR-302a-3p targets METTL3 and plays tumour suppressive roles in the proliferation, apoptosis, invasion, and migration of melanoma cells.

8.
Mol Vis ; 27: 354-364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220183

RESUMO

Purpose: Proper aqueous humor (AH) dynamics is crucial for maintaining the intraocular pressure (IOP) in the eye. This study aims to investigate the function of Piezo2, a newly discovered mechanosensitive ion channel, in regulating AH dynamics. Methods: Immunohistochemistry (IHC) analysis and western blotting were performed to detect Piezo2 expression. The Cre-lox system was applied to create a conditional knockout model of Piezo2. IOP and aqueous humor outflow facility in live animals were recorded with a Tonometer and a syringe-pump system for up to 2 weeks. Results: We first detected Piezo2 with robust expression in the human trabecular meshwork (TM), Schlemm's canal (SC), the ciliary body's epithelium, and ciliary muscle. In addition, we found Piezo2 in human retinal ganglion cells (RGCs) and astrocytes in the optic nerve head (ONH). Through the Cre-lox system, Piezo2 can be successfully downregulated in mouse iridocorneal angle tissues. However, Piezo2 downregulation cannot significantly influence the IOP and outflow facility through the conventional pathway. Instead, we observed an effect of downregulated Piezo2 on decreasing the intercept in the flow rate versus pressure plot. According to the Goldmann equation, Piezo2 may function in regulating unconventional outflow, AH production, and episcleral venous pressure. Conclusions: These findings, for the first time, demonstrate that Piezo2 acts as an essential mechanosensor in maintaining the proper aqueous humor dynamics in the eye.

9.
J Anat ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34268788

RESUMO

Describing osteological development is of great importance for understanding vertebrate phenotypic variations, form-functional transitions and ecological adaptations. Anurans exhibit dramatic changes in their morphology, habitat preferences, diet and behaviour between the tadpole and frog stages. However, the anatomical details of their cranial and postcranial development have not been extensively studied, especially in Microhylidae. In this work, we studied the microhylid Microhyla fissipes, commonly known as the ornamented pygmy frog, a small-sized frog with fast metamorphosis. Its osteological development was comprehensively described based on 120 cleared and stained specimens, including six tadpoles for each stage between 28 and 45, six juveniles and six adults. Additionally, 22 osteological traits of these specimens involved in food acquisition, respiration, audition and locomotion were selected and measured to reflect the changes in tadpole ecological functions during metamorphosis. Our study provides the first detailed qualitative and quantitative developmental information about these structures. Our results have confirmed that skeletal elements (viz., neopalatines, omosternum, clavicles and procoracoids) absent in adults are not detected during development. Our data reveal that morphologically, radical transformations of the cranial structures related to feeding and breathing are completed within stages 42-45 (72 h), but the relative length and width of these skeletons have changed in earlier stages. The postcranial skeletons correlated with locomotion are well developed before stage 42 and approach the adult morphology at stage 45. Indeed, the relative length of the pectoral girdle and forelimb reaches the adult level at stage 42 and stage 45, respectively, whereas that of the vertebral column, pelvic girdle and hind limbs increases from their appearance until reaching adulthood. Based on published accounts of 19 species from Neobatrachia, Mesobatrachia and Archaeobatrachia, cranial elements are among the first ossified skeletons in most studied species, whereas sphenethmoids, neopalatines, quadratojugals, mentomeckelians, carpals and tarsals tend to ossify after metamorphosis. These results will help us to better understand the ecomorphological transformations of anurans from aquatic to terrestrial life. Meanwhile, detailed morphological and quantitative accounts of the osteological development of Microhyla fissipes will provide a foundation for further study.

10.
Minerva Urol Nephrol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263744

RESUMO

BACKGROUND: To establish a model that predicts postoperative fever and enables decision-making regarding optimal antibiotic therapy duration for asymptomatic bacteriuria or pyuria prior to retrograde intrarenal surgery (RIRS). METHODS: We retrospectively investigated 667 consecutive patients with asymptomatic bacteriuria or pyuria who underwent RIRS between September 2016 and December 2019. We constructed a predictive nomogram for risk quantification of postoperative infection. A preoperative score model was used for risk stratification. The effect of antibiotic therapy duration (short-course [2-3 days] vs. long-course [≥4 days]) was evaluated. RESULTS: Infections occurred in 113 (16.9%) patients. The incidence of fever was marginally lower in long-course group than in short-course group (15% vs. 19%, p=0.173). Hydronephrosis, stone size, multi-drug resistant bacteriuria, and degree of pyuria were used to construct a preoperative score model (the H-SMP score). Using the H-SMP score, the patients were stratified into low- and high-risk groups based on varying incidence rates of postoperative fever (11.0% vs. 29.9%, p<0.001). Significant reduction in fever occurred only among high-risk patients in the long-course group (23.5% vs. 38.0%, p=0.022), and no such reduction in postoperative fever rates occurred in low-risk patients (10.4% vs. 11.5%, p=0.712). Even after propensity score matching, the low-risk group showed no improvement in postoperative fever incidence with long-course antibiotic therapy (7.5% vs. 10.0%, p=0.419). CONCLUSIONS: Based on the newly developed H-SMP score, we concluded that long-course antibiotics (≥4 days) recommended in high-risk patients may not bring in more benefit in low-risk patients for treating asymptomatic bacteriuria or pyuria prior to RIRS.

11.
Rev Sci Instrum ; 92(4): 044904, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243481

RESUMO

The nitrogen-vacancy center in diamond has been broadly applied in quantum sensing since it is sensitive to different physical quantities. Meanwhile, it is difficult to isolate disturbances from unwanted physical quantities in practical applications. Here, we present a fiber-based quantum thermometer by tracking the sharp-dip in the zero-field optically detected magnetic resonance spectrum in a high-density nitrogen-vacancy ensemble. Such a scheme can not only significantly isolate the magnetic field and microwave power drift but also improve the temperature sensitivity. Thanks to its simplicity and compatibility in implementation and robustness, this quantum thermometer is then applied to the surface temperature imaging of an electronic chip with a sensitivity of 18mK/Hz. It thus paves the way to high sensitive temperature measurements in ambiguous environments.

12.
Neurochem Int ; 149: 105123, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34224804

RESUMO

This study explored the role of succinate accumulation in the oxidative stress and iron accumulation in both pentylenetetrazol (PTZ)-induced epileptogenesis and kainic acid (KA)-induced status epilepticus (SE). The levels of succinate, oxidative stress, iron content, iron-related protein expression, and the severity of neuronal injury and seizures were measured in both models. We found that increased concentrations of succinate were associated with increased levels of oxidative stress, iron content, iron regulator protein, and iron importer divalent metal transporter 1, as well as decreased levels of iron exporter ferropotin 1. Aggravated neuronal injury was observed in the hippocampi and cortices of both models. The cell-permeable molecule dimethyl malonate (DM), a competitive inhibitor of succinate dehydrogenase (SDH), significantly attenuated succinate accumulation, reduced the oxidative stress and iron levels, and mitigated the severity of the seizures and neuronal injury. Our results thus indicate that the accumulation of succinate due to the reverse catalysis of SDH may exacerbate oxidative stress and thus induce iron accumulation and neuronal injury in both models. Targeting succinate accumulation may achieve neuroprotective and anti-seizure effects.

13.
Nucleic Acids Res ; 49(13): 7554-7570, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34197606

RESUMO

Polo-like kinase 1 (PLK1) is a master kinase that regulates cell cycle progression. How its enzymatic activity is regulated in response to DNA damage is not fully understood. We show that PLK1 is enriched at double strand breaks (DSBs) within seconds of UV laser irradiation in a PARP-1-dependent manner and then disperses within 10 min in a PARG-dependent manner. Poly(ADP-)ribose (PAR) chains directly bind to PLK1 in vitro and inhibit its enzymatic activity. CHK1-mediated PLK1 phosphorylation at S137 prevents its binding to PAR and recruitment to DSBs but ensures PLK1 phosphorylation at T210 and its enzymatic activity toward RAD51 at S14. This subsequent phosphorylation event at S14 primes RAD51 for CHK1-mediated phosphorylation at T309, which is essential for full RAD51 activation. This CHK1-PLK1-RAD51 axis ultimately promotes homologous recombination (HR)-mediated repair and ensures chromosome stability and cellular radiosensitivity. These findings provide biological insight for combined cancer therapy using inhibitors of PARG and CHK1.

14.
Exp Eye Res ; 210: 108702, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34270977

RESUMO

Retinal vein occlusion (RVO) is the second most common retinal vascular disorders and causes visual damage in a large population. Neutrophil extracellular traps (NETs) formation (NETosis) is an important cause of vascular diseases, however, the association between NETs related biomarkers and RVO development remained unclear. In this pilot study, a total of 77 RVO cases and 48 controls were included between Jan 2020 and July 2020. Besides, the circulating levels of three NETs related markers, cell-free DNA (cfDNA), myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit), were detected in all the participants and thus the association between NETosis and RVO incidence was analyzed. Advanced assays were conducted to investigate the inflammation and thrombosis related biomarkers in RVO cases with higher or lower NETs biomarkers. When the results were considered, it was found that NETs biomarkers, including cfDNA, MPO-DNA and H3Cit, were increased in the RVO cases comparing with the controls (P < 0.05). Through the receiver operating characteristic (ROC) analyses, we found that circulating NETs related biomarkers demonstrated potential diagnostic effects for RVO and the AUCs of plasma cfDNA, MPO-DNA and H3Cit were 0.859, 0.871 and 0.928, respectively (P < 0.001). Through analyzing the correlations between circulating NETs markers and RVO stages and durations, inflammatory markers as well as thrombotic indexes, it was found that NETs were related with the RVO subtypes, inflammatory status and thrombus formation. In conclusion, the plasma NETs remnants are significantly increased in RVO cases. Besides, advanced studies demonstrate that inflammation as well as thrombus formation might be involved in this association.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34224981

RESUMO

Corticosterone (CORT)-mediated adaptive plasticity improves animal fitness in stressful environments. Although it brings ecological benefits, the cost potentially constrains its expression and evolution. Revealing the factors affecting plasticity costs is of great ecological and evolutionary significance. Evidence indicates that both CORT and background colour can induce metabolic changes in animals, which in turn determine phenotypic plasticity. However, whether and/or how CORT and background colour jointly act on plastic responses has not been studied. Here, this question has been investigated in amphibian tadpoles (Microhyla fissipes) exposed to CORT at different background colours (white or black) using integrated morphological, histological, and transcriptomic analyses. The results showed that CORT exposure increased relative tail length, immune function, and metabolic maintenance (i.e., transcription of substrate catabolism and oxidative phosphorylation) at the expense of reduction in growth rate and skin melanin level. The black background also increased relative tail length and metabolic maintenance (i.e., transcription of oxidative phosphorylation) at the cost of reduction in growth rate, but increased skin melanin level. The expression of critical pigmentation genes indicated that black background activated a distinct and opposite pigmentation regulating route to CORT. Although there was no interactive effect of background colour and CORT on phenotypic and metabolic variations, their additive effects further impact the trade-off between somatic growth, metabolic maintenance, and pigmentation in terms of resource allocation. In conclusion, the individual and additive effects of background colour and CORT exposure on tadpole plasticity were revealed. These results likely provide new insights into the environmental adaptation of animals.

16.
Math Biosci Eng ; 18(4): 3755-3780, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-34198411

RESUMO

Computer vision technologies have been widely implemented in the defect detection. However, most of the existing detection methods generally require images with high quality, and they can only process code characters on simple backgrounds with high contrast. In this paper, a defect detection approach based on deep learning has been proposed to efficiently perform defect detection of code characters on complex backgrounds with a high accuracy. Specifically, image processing algorithms and data enhancement techniques were utilized to generate a large number of defect samples to construct a large data set featuring a balanced positive and negative sample ratio. The object detection network called BBE was build based on the core module of EfficientNet. Experimental results show that the mAP of the model and the accuracy reach 0.9961 and 0.9985, respectively. Individual character detection results were screened by setting relevant quality inspection standards to evaluate the overall quality of the code characters, the results of which have verified the effectiveness of the proposed method for industrial production. Its accuracy and speed are high with high robustness and transferability to other similar defect detection tasks. To the best of our knowledge, this report describes the first time that the BBE has been applied to defect inspections for real plastic container industry.

17.
J Cell Physiol ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34224586

RESUMO

Age-related diseases such as cardiovascular diseases portend disability, increase health expenditures, and cause late-life mortality. Synthetic agonists of growth hormone-releasing hormone (GHRH) exhibit several favorable effects on heart function and remodeling. Here we assessed whether GHRH agonist MR409 can modulate heart function and systemic parameters in old mice. Starting at the age of 15 months, mice were injected subcutaneously with MR409 (10 µg/day, n = 8) or vehicle (n = 7) daily for 6 months. Mice treated with MR409 showed improvements in exercise activity, cardiac function, survival rate, immune function, and hair growth in comparison with the controls. More stem cell colonies were grown out of the bone marrow recovered from the MR409-treated mice. Mitochondrial functions of cardiomyocytes (CMs) from the MR409-treated mice were also significantly improved with more mitochondrial fusion. Fewer ß-gal positive cells were observed in endothelial cells after 10 passages with MR409. In Doxorubicin-treated H9C2 cardiomyocytes, cell senescence marker p21 and reactive oxygen species were significantly reduced after cultured with MR409. MR409 also improved cellular ATP production and oxygen consumption rate in Doxorubicin-treated H9C2 cells. Mitochondrial protein OPA1 long isoform was significantly increased after treatment with MR409. The effects of MR409 were mediated by GHRH receptor and protein kinase A (PKA). In short, GHRH agonist MR409 reversed the aging-associated changes with respect of heart function, mobility, hair growth, cellular energy production, and senescence biomarkers. The improvement of heart function may be related to a better mitochondrial functions through GHRH receptor/cAMP/PKA/OPA1 signaling pathway and relieved cardiac inflammation.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34227191

RESUMO

Stimulated Raman scattering (SRS) microscopy in combination with innovative tagging strategies offers great potential as a universal high-throughput biomedical imaging tool. Here, we report on rationally tailored small molecular monomers containing triple-bond units with large Raman scattering cross-sections, which can be polymerized at the nanoscale for enhancement of SRS contrast with smaller but brighter optical nanotags with artificial 'fingerprint' output. From this, a class of triple-bond rich polymer nanoparticles (NPs) was engineered by regulating the relative dosages of three chemically different triple-bond monomers in co-polymerization. The suggested bonding strategy allowed for 15 spectrally distinguishable triple-bond combinations. These accurately structured nano molecular aggregates, rather than long-chain macromolecules, could establish a universal method for generating small-sized biological SRS imaging tags with high-sensitivity for high-throughput multi-color biomedical imaging.

19.
NPJ Precis Oncol ; 5(1): 63, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215841

RESUMO

Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements. Here, we present extensive validation studies of the xF assay using reference standards, cell lines, and patient samples that establish high sensitivity, specificity, and accuracy in variant detection. The Tempus xF assay is highly concordant with orthogonal methods, including ddPCR, tumor tissue-based NGS assays, and another commercial plasma-based NGS assay. Using matched samples, we developed a dynamic filtering method to account for germline mutations and clonal hematopoiesis, while significantly decreasing the number of false-positive variants reported. Additionally, we calculated accurate circulating tumor fraction estimates (ctFEs) using the Off-Target Tumor Estimation Routine (OTTER) algorithm for targeted-panel sequencing. In a cohort of 1,000 randomly selected cancer patients who underwent xF testing, we found that ctFEs correlated with disease burden and clinical outcomes. These results highlight the potential of serial testing to monitor treatment efficacy and disease course, providing strong support for incorporating liquid biopsy in the management of patients with advanced disease.

20.
Open Biol ; 11(6): 210047, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34129782

RESUMO

SIRT7 is a class III histone deacetylase that belongs to the sirtuin family. The past two decades have seen numerous breakthroughs in terms of understanding SIRT7 biological function. We now know that this enzyme is involved in diverse cellular processes, ranging from gene regulation to genome stability, ageing and tumorigenesis. Genomic instability is one hallmark of cancer and ageing; it occurs as a result of excessive DNA damage. To counteract such instability, cells have evolved a sophisticated regulated DNA damage response mechanism that restores normal gene function. SIRT7 seems to have a critical role in this response, and it is recruited to sites of DNA damage where it recruits downstream repair factors and directs chromatin regulation. In this review, we provide an overview of the role of SIRT7 in DNA repair and maintaining genome stability. We pay particular attention to the implications of SIRT7 function in cancer and ageing.

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