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Enhanced particle transport events are discovered and analyzed as the density limit of the J-TEXT tokamak is approached. Edge shear layer collapse is observed and the ratio of Reynolds power to turbulence production decreases. Simultaneously, the divergence of turbulence internal energy flux (i.e. turbulence spreading) increases, indicating that shear layer collapse triggers an outward spreading event. Studies of correlations show that the enhanced particle transport events are quasi-coherent, and manifested primarily in density fluctuations which exhibit positive skewness. Electron adiabaticity emerges as the critical parameter which signals transport event onset. For α < 0.35 as density approaches the Greenwald density, both turbulence spreading and density fluctuations rise rapidly. Taken together, these results elucidate the connections between edge shear layer, density fluctuations, particle transport events, turbulence spreading and plasma edge cooling as the density limit is approached.

Objective: β-Catenin is the key mediator of the Wnt signal and also a component of E-cadherin complexes at the intercellular adhering junction, which mediates cell-cell adhesion. We hypothesized that β-catenin might be involved in the long-lasting changed phenotype of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and could play a role in the pathogenesis of RA. In this study we investigated the expression of β-catenin in RA-FLS. Methods: Synovial tissues were obtained during joint replacement surgery or arthroscopy from six patients with RA, six patients with osteoarthritis (OA), and six patients with joint trauma (Trauma group). Immunohistochemical analysis of β-catenin was performed in the synovial tissues from the three groups. Synovial tissues from three patients in each group were selected at random for FLS isolation. Expression of β-catenin in FLS from the three groups was evaluated at the protein level by western blotting and at the mRNA level by reverse transcription polymerase chain reaction (RT-PCR). Results: Immunohistochemistry revealed that the expression of β-catenin in synovial lining cells of the RA samples was significantly greater than that of the OA or trauma samples (p < 0.01). Western blotting and RT-PCR showed that β-catenin expression was elevated in RA-FLS compared with that in OA-FLS or Trauma-FLS (p < 0.05) at the protein level but no difference was found at the mRNA level. Conclusions: Expression of β-catenin is elevated in RA-FLS, not only in vitro but also in vivo. The increase is due to activation of Wnt/β-catenin signalling. Wnt/β-catenin signalling is activated in RA-FLS, and contributes to the stable activation of RA-FLS. [ABSTRACT FROM AUTHOR]

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: As a currently incurable but preventable disease, the prevention and early diagnosis of Alzheimer's disease (AD) has long been a research hotspot. Amyloid deposition has been shown to be a major pathological feature of AD. Notably, not all the people with amyloid-beta (Aβ) pathology will have significant cognitive declines and eventually develop AD. Therefore, the aim of this study was to explore the risk factors for cognitive decline in Aβ-positive participants., Methods: We included 650 non-demented participants who were Aβ-positive at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Mixed effects and COX regression models were applied to assess 37 potential risk factors. Mixed effects models were employed to assess the temporal associations between potential risk factors and four cognitive assessment scales. COX regression models were used to assess the impact of potential risk factors on cognitive diagnosis conversion. Univariate and multivariate analyses were applied to the above models. Additionally, we used the Cochran-Armitage trend test to examine whether the incidence of cognitive decline increased with the number concurrent of risk factors., Results: Six factors (low diastolic pressure, low body mass index, retired status, a history of drug abuse, Parkinsonism, and depression) were the identified risk factors and four factors (a history of urinary disease, musculoskeletal diseases, no major surgical history, and no prior dermatologic-connective tissue diseases) were found to be suggestive risk factors. The incidence of cognitive decline in the Aβ-positive participants gradually increased as the number of concurrent risk factors increased (p for trend = 0.0005)., Conclusions: Our study may facilitate the understanding of the potential pathological processes in AD and provide novel targets for the prevention of cognitive decline among participants with Aβ positivity., (© 2024. The Author(s).)

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-β-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca 2+ inward flow in PC-12 cells., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 ., (© 2024. The Author(s).)

This study explored the associations between peripheral immunity with cerebral small vessel diseases. Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative were investigated. Peripheral blood was obtained, and magnetic resonance imaging was performed to measure cerebral microbleeds (CMB), lacunar infarctions (LI), and white matter hyperintensities (WMH). Multivariable-adjusted regression models, linear mixed-effects models, and the Spearman correlations were used to evaluate the associations. At baseline, individuals with greater neutrophils (odds ratio [OR] =1.10, 95% confidence interval [CI] 1.00-1.20, p=0.042) and monocytes (OR=1.12, 95% CI 1.02-1.22, p=0.016) had higher WMH volume. On the contrary, a higher lymphocyte-to-monocyte ratio (LMR) was related to lower WMH volume (OR=0.91, 95% CI 0.82-1.00, p=0.041). Longitudinally, higher neutrophils (ρ=0.084, p=0.049) and NLR (ρ=0.111, p=0.009) predicted accelerated progression of WMH volume, while a greater LMR (ρ=-0.101, p=0.018) was linked to slower growth of WMH volume. Nevertheless, associations between peripheral immunity with CMB or LI were not observed at baseline and follow-up. Our study found that peripheral immune indexes could serve as convenient noninvasive biomarkers of WMH., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning this article., (Copyright © 2024. Published by Elsevier Inc.)

The present study measured serum levels of vitamin A (VA) and vitamin D (VD) in children with chronic tic disorders (CTD) and investigated their potential association with CTD and comorbidity of attention deficit hyperactivity disorder (ADHD) and the association of their co-insufficiencies or deficiencies with CTD symptoms. A total of 176 children (131 boys and 45 girls, median age of 9 years) with CTD were recruited as the CTD group. During the same period, 154 healthy children were selected as the healthy control (HC) cohort. Circulating retinol and 25-hydroxyvitamin D (25[OH]D) levels were measured for all participants using high-performance liquid chromatography (HPLC) and tandem mass spectrometry. The Yale Global Tic Severity Scale (YGTSS) was employed for the assessment of tic status and CTD impairment. The Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were used to evaluate comorbidity symptoms. CTD pediatric participants exhibited markedly diminished circulating retinol and 25(OH)D levels compared to HCs. Moreover, VA and VD deficiencies and their co-insufficiencies/deficiencies were more prevalent in CTD participants than HCs. Circulating 25(OH)D levels were inversely proportional to the YGTSS motor tic scores. YGTSS scores in CTD children with only VA or VD insufficiency or deficiency or with VA and VD co-insufficiency/deficiency did not differ from those in CTD children with normal VA and VD. CTD children with comorbid ADHD displayed reduced circulating retinol and 25(OH)D concentrations and elevated prevalence of VD deficiency compared to CTD participants without comorbid ADHD. Lower serum retinol content was intricately linked to the presence of elevated CTD and comorbid ADHD. VA and VD deficiencies and their co-insufficiencies/deficiencies were markedly enhanced in CTD pediatric participants compared to HCs. Lower VA concentration was linked to the presence of enhanced CTD and comorbid ADHD. Therefore, children with CTD, especially with comorbid ADHD, may be at a higher risk of VA or VD deficiency, which may prompt the clinicians to consider whether blood tests for VA and VD in CTD children would be helpful for clinical care., (© 2023. The Author(s).)

Our previous studies have suggested that spastin, which aggregates on spindle microtubules in oocytes, may promote the assembly of mouse oocyte spindles by cutting microtubules. This action may be related to CRMP5, as knocking down CRMP5 results in reduced spindle microtubule density and maturation defects in oocytes. In this study, we found that, after knocking down CRMP5 in oocytes, spastin distribution shifted from the spindle to the spindle poles and errors in microtubule-kinetochore attachment appeared in oocyte spindles. However, CRMP5 did not interact with the other two microtubule-severing proteins, katanin-like-1 (KATNAL1) and fidgetin-like-1 (FIGNL1), which aggregate at the spindle poles. We speculate that, in oocytes, due to the reduction of spastin distribution on chromosomes after knocking down CRMP5, microtubule-kinetochore errors cannot be corrected through severing, resulting in meiotic division abnormalities and maturation defects in oocytes. This finding provides new insights into the regulatory mechanisms of spastin in oocytes and important opportunities for the study of meiotic division mechanisms.

Synergistic bioassay-guided isolation of the extracts of Artemisia rupestris L, which belongs to the family Asteraceae, afforded two acetylenic spiroketal enol ethers, namely rupesdiynes A ( 1 ) and B ( 2 ). Their structures were determined based on spectroscopic analysis and experimental and calculated ECD investigations. The two compounds exhibited synergistic activity and were able to reduce the minimum inhibitory concentration (MIC) of oxacillin four-fold, with a fractional inhibitory concentration index (FICI) of 0.5 in combination with oxacillin against the oxacillin-resistant EMRSA-16. Biofilm formation inhibitory and Ethidium bromide (EtBr) efflux assay were further employed to verify the possible mechanism of the synergistic antibacterial effect. Additionally, molecular docking studies were conducted to investigate the binding affinities of the two compounds with penicillin-binding protein 2a (PBP2a) of EMRSA-16. Taken together, rupesdiynes A ( 1 ) and rupesdiyne B ( 2 ) showed moderate synergistic activity against EMRSA-16 with oxacillin via inhibiting biofilm formation and efflux pump activity, respectively.

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate-methanol-water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1'S)-1'-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1-6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1 H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lipofuscin accumulation has been observed in human coronary arteries but whether or not myocardial tissue can release lipofuscin generated within cardiomyocytes must be clarified, as this may provide indicators for future anti-ageing research. The hearts of Sprague Dawley rats, aged 6-24 months, were embedded in resin and ultrathin sections cut for electron microscopy. Lipofuscin granules were abundant in cardiomyocytes. Cardiomyocytes were seen to release lipofuscin granules into the myocardial interstitium as cytoplasmic fragments with irregular protrusions on the sarcolemma surface. The cytoplasmic fragments entering the stroma fused directly with the endothelial cells of adjacent capillaries, delivering lipofuscin to the vessel wall. These fragments were also seen to be engulfed by stromal macrophages or fused with fibroblasts, which then combined with capillary endothelial cells to deliver lipofuscin to the vessel wall. Some cytoplasmic fragments disaggregated and formed membrane-like waste, which travelled to the vessel wall from the myocardial stroma as soluble fine particles via diffusion or pinocytosis of capillary endothelial cells. Lipofuscin entered the vascular wall and endothelial cells, forming large and small protrusions or folds that transported the lipofuscin to the vascular lumen and bloodstream., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Multidrug-resistant Staphylococcus aureus , a Gram-positive bacterium that causes several difficult-to-treat human infections, is a considerable threat to global healthcare. We hypothesize that there exist inner responsive molecules (IRMs) which can function synergistically with antibiotics to restore the sensitivity of resistant bacteria to existing antibiotics without inducing new antibiotic resistance. An investigation of the extracts of the Chinese medicinal herb Piper betle L. led to the isolation of six benzoate esters, BO-1 - BO-6 . Among these, BO-1 as a distinct IRM displayed considerable synergism by potentiating antibacterial activity against five antibiotic-resistant S. aureus strains. Mechanistic studies demonstrated that BO-1 acted as a suppressing drug resistance IRM via inhibiting efflux activity. A combination of BO-1 with ciprofloxacin significantly inhibited resistance to this antibiotic and reversed its resistance in the S. aureus strain. Furthermore, BO-1 effectively enhanced the activity of ciprofloxacin against the efflux fluoroquinolone-resistant S. aureus strain SA1199B that caused infection in two animal models and significantly decreased the inflammatory factors IL-6 and C-reactive protein of the infected mice, thereby showing the practice utility of this approach.

Purpose of Review: Nerve blocks constitute an integral portion in the management of chronic pain. The widespread use of ultrasound imaging opened the door to a flood of newer blocks especially truncal plane nerve blocks. We reviewed the current medical literature for studies and case reports utilizing the two most common truncal plane nerve blocks, transversus abdominis plane and erector spinae plane blocks, to manage chronic pain., Recent Findings: We found some evidence, mostly in case reports and retrospective observational studies, that supports the use of transversus abdominis plane and erector spinae plane nerve blocks, usually with steroids, as a safe and valuable part of interdisciplinary management of chronic abdominal and chest walls pain. Ultrasound-guided truncal fascial plane nerve blocks are safe, easy to learn, and proven to help with post-operative acute pain management. Although limited, our current review provides evidence from the current medical literature regarding the utility of these blocks to manage some of the challenging chronic and cancer-related pain conditions of the trunk region., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The low maturation rate of oocytes is an important reason for female infertility and failure of assisted pregnancy. The germinal vesicle breakdown (GVBD) is a landmark event of oocyte maturation. In our previous studies, we found that zona pellucida 3 (ZP3) was strongly concentrated in the nuclear region of germinal vesicle (GV) oocytes and interacted with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) and lamin A to promote GVBD. In the current study, we found that lamin A is mainly concentrated in the nuclear membrane. When ZP3 is knocked down, lamin A will be partially transferred to the nucleus of oocytes. The prelamin A is increased in both the nuclear membrane and nucleus, while phosphorylated lamin A (p-lamin A) is significantly reduced. AIPL1 was also proved to accumulate in the GV region of oocytes, and ZP3 deletion can significantly inhibit the aggregation of AIPL1 in the nuclear region. Similar to ZP3 knockdown, the absence of AIPL1 resulted in a decrease in the occurrence of GVBD, an increase in the amount of prelamin A, and a significant decrease in p-lamin A in oocytes developed in vitro . Finally, we propose the hypothesis that ZP3 can stabilize farnesylated prelamin A on the nuclear membrane of AIPL1, and promote its further processing into mature lamin A, therefore promoting the occurrence of GVBD. This study may be an important supplement for the mechanism of oocyte meiotic resumption and provide new diagnostic targets and treatment clues for infertility patients with oocyte maturation disorder.

Roflumilast is a phosphodiesterase-4 inhibitor which treats chronic obstructive pulmonary disease (COPD). Roflumilast N-oxide is the major metabolite of roflumilast with a similar mechanism of action to roflumilast. Although racial differences in roflumilast drug disposition have been observed, the necessity of dose adjustment is subject to debate. This study compares the pharmacokinetics of a single 500 μg dose of roflumilast in healthy Chinese and Caucasian subjects under uniform conditions. Chinese subjects were found to have longer t 1/2 and higher AUC 0-t and C max than Caucasian subjects. The point estimates on the geometric mean of AUC 0-t in Chinese subjects were 22% higher for roflumilast and 46% higher for roflumilast N-oxide. Point estimates on the geometric mean of C max were 9% and 24% higher for roflumilast and roflumilast N-oxide, respectively. Total phosphodiesterase-4 (PDE4) inhibitory (tPDE4i) activity, a theoretical parameter that describes the combined contribution to PDE4 inhibitory activity of roflumilast and roflumilast N-oxide, was 44% higher in Chinese subjects than in Caucasian subjects. With about a 10-fold higher plasma AUC compared to the parent roflumilast and a much longer observed half-life, roflumilast N-oxide has been estimated to contribute about 90% of tPDE4i, with 10% attributed to the parent compound roflumilast. Following body weight normalization, these figures were lower but remained significant. Safety analysis showed signs of reduced tolerance or different pharmacodynamic response to roflumilast in Chinese recipients than in Caucasians. Our results suggest that Chinese patients should receive a dose of roflumilast lower than 500 μg daily during future clinical trials., (© 2022 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Ischemic stroke (IS) has become a cerebrovascular disease of widespread concern. Overexpression of circUCK2 alleviates neuronal damage in IS. However, the specific regulatory mechanisms of circUCK2 are not fully understood. In this study, we found that circUCK2 and HECT domain E3 ubiquitin ligase 1 (HECTD1) were downregulated in IS models in vitro and in vivo. Overexpression of circUCK2 or HECTD1 inhibited endothelial-mesenchymal transition (EndoMT) and protected the blood-brain barrier (BBB) in transient middle cerebral artery occlusion mice from damage. It was further discovered that circUCK2 regulated HECTD1 expressions by interacting with fused in sarcoma (FUS). Moreover, FUS overexpression partially restored the effect of circUCK2 on EndoMT, and overexpression of HECTD1 weakened the effect of FUS on EndoMT. Collectively, circUCK2 upregulates the expression of HECTD1 by combining with FUS and inhibits EndoMT to alleviate BBB damage in IS both in vivo and in vitro., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

There is an unmet need for novel and efficacious therapeutics for regenerating injured articular cartilage in progressive osteoarthritis (OA) and/or trauma. Mesenchymal stem cells (MSCs) are particularly promising for their chondrogenic differentiation, local healing environment modulation, and tissue- and organism-specific activity; however, despite early in vivo success, MSCs require further investigation in highly-translatable models prior to disseminated clinical usage. Large animal models, such as canine, porcine, ruminant, and equine models, are particularly valuable for studying allogenic and xenogenic human MSCs in a human-like osteochondral microenvironment, and thus play a critical role in identifying promising approaches for subsequent clinical investigation. In this mini-review, we focus on [1] considerations for MSC-harnessing studies in each large animal model, [2] source tissues and organisms of MSCs for large animal studies, and [3] tissue engineering strategies for optimizing MSC-based cartilage regeneration in large animal models, with a focus on research published within the last 5 years. We also highlight the dearth of standard assessments and protocols regarding several crucial aspects of MSC-harnessing cartilage regeneration in large animal models, and call for further research to maximize the translatability of future MSC findings., Competing Interests: XZ is a founder of Bone Biologics Inc./Bone Biologics Corp., which sublicenses Nell-1 patents from the UC Regents, which also hold equity in the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Ha, Xiao, Kim, Jensen, Easley, Yao and Zhang.)

Zeolitic imidazolate framework-67 (ZIF67) derivatives are considered as promising active materials for energy storage owing to the possible formation of cobalt oxide and N-doped graphite. Cobalt oxide has multiple redox states for generating redox reactions for charge storage, while N-doped graphite can provide high electrical conductivity for charge transfer. In this study, it is the first time to synthesize binder-free electrodes composed of cobalt oxide and N-doped graphite derived from ZIF67 on carbon cloth (CC) for supercapacitor (SC). Successive oxidation and carbonization along with additional coverage of ZIF67 derivatives are applied to synthesize ZIF67 derivatives composed of cobalt oxide, N-doped graphite and cobalt oxide/N-doped graphite composites with different layer compositions. The highest specific capacitance (C F ) of 90.0F/g at 20 mV/s is obtained for the oxidized ZIF67/carbonized ZIF67/carbon cloth (O67/C67/CC) electrode, due to the large surface area and high electrical conductivity benefitted from preferable morphology and growing sequence of Co 3 O 4 and N-doped graphite. The symmetric SC composed of O67/C67/CC electrodes shows the maximum energy density of 2.53 Wh/kg at the power density of 50 W/kg. Cycling stability with C F retention of 70% and Coulombic efficiency of 65% after 6000 times repeatedly charge/discharge process is also obtained for this symmetric SC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to identify brain regions with local, structural, and functional abnormalities in dementia with Lewy bodies (DLB) and uncover the differences between DLB and Alzheimer's disease (AD). The neural networks involved in the identified abnormal brain regions were further described., Methods: PubMed, Web of Science, OVID, Science Direct, and Cochrane Library databases were used to identify neuroimaging studies that included DLB versus healthy controls (HCs) or DLB versus AD. The coordinate-based meta-analysis and functional meta-analytic connectivity modeling were performed using the activation likelihood estimation algorithm., Results: Eleven structural studies and fourteen functional studies were included in this quantitative meta-analysis. DLB patients showed a dysfunction in the bilateral inferior parietal lobule and right lingual gyrus compared with HC patients. DLB patients showed a relative preservation of the medial temporal lobe and a tendency of lower metabolism in the right lingual gyrus compared with AD. The frontal-parietal, salience, and visual networks were all abnormally co-activated in DLB, but the default mode network remained normally co-activated compared with AD., Conclusions: The convergence of local brain regions and co-activation neural networks might be potential specific imaging markers in the diagnosis of DLB. This might provide a pathway for the neural regulation in DLB patients, and it might contribute to the development of specific interventions for DLB and AD., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The purpose of this study was to reveal the patterns of reorganization of rich club organization in brain functional networks in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The study found that the rich club node shifts from sensory/somatomotor network to fronto-parietal network in DLB. For AD, the rich club nodes switch between the temporal lobe with obvious structural atrophy and the frontal lobe, parietal lobe and cerebellum with relatively preserved structure and function. In addition, compared with healthy controls, rich club connectivity was enhanced in the DLB and AD groups. The connection strength of DLB patients was related to cognitive assessment. In conclusion, we revealed the different functional reorganization patterns of DLB and AD. The conversion and redistribution of rich club members may play a causal role in disease-specific outcomes. It may be used as a potential biomarker to provide more accurate prevention and treatment strategies., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China., Methods: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world., Results: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million., Conclusions: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

A phytochemical investigation of an extract of the leaves of Piper betle , guided by a synergistic antibacterial screen, led to the isolation and structural elucidation of 10 new neolignans, Pibeneolignan A-J ( 1 - 10 ), together with 11 known compounds. The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic data, single-crystal X-ray diffraction analysis, and experimental and calculated ECD investigations. Compounds 1 and 2 are new naturally occurring neolignan skeletons, based on the cyclohept-2-ene-1,4-dione framework. We propose that these natural products are biosynthetically formed from bicyclic [3.2.1] neolignans by oxidative cleavage and ring opening at C-1' and C-2'. Among these compounds, 9 , 13 , 15 , and 16 , in combination with norfloxacin against an effluxing S. aureus strain (SA1199B), exhibited significant synergistic activity with fractional inhibitory concentration indices (FICIs) of 0.078, 0.156, 0.125, and 0.25, respectively. Bacterial growth curves, ethidium bromide (EtBr) efflux, and qRt-PCR were further employed to verify their synergistic antibacterial mechanism. Furthermore, computational molecular modeling suggested the binding of compounds 14 - 17 and 19 to the active site of the modeled structure of the NorA efflux pump, which is the main efflux pump in SA1199B.

Background: Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. The development of immunotherapy greatly improves the patient prognosis but there are some exceptions. Thus, screening for better biomarkers for prognostic evaluation could contribute to the treatment of DLBCL patients., Aim: To screen the novel mediators involved in the development of DLBCL., Methods: The GSE60 dataset was applied to identify the differentially expressed genes (DEGs) in DLBCL, and the principal components analysis plot was used to determine the quality of the included samples. The protein-protein interactions were analyzed by the STRING tool. The key hub genes were entered into to the GEPIA database to determine their expressions in DLBCL. Furthermore, these hub gene alterations were analyzed in cBioportal. The UALCAN portal was employed to analyze the expression of the hub genes in different stages of DLBCL. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Score was conducted to evaluate the correlation between the gene expression and tumor purity. The gene-gene correlation analysis was conducted in the GEPIA. The stromal score analysis was conducted in TIMER to confirm the correlation between the gene expression and infiltrated stromal cells. The correlation between the indicated genes and infiltration level of cancer-associated fibroblasts (CAFs) was also completed in TIMER with two methods, MCP-Counter and Tumor immune dysfunction and exclusion. The correlation between fibronectin (FN1) protein level and secreted protein acidic and cysteine-rich (SPARC) messenger ribonucleic acid expression was confirmed in the cBioportal., Results: The top 20 DEGs in DLBCL were identified, and the principal components analysis plot confirmed the quality of the significant DEGs. The pairwise correlation coefficient analysis among all samples showed that these DEGs have a certain co-expression pattern. The DEGs were subjected to STRING to identify the hub genes, alpha-2-macroglobulin ( A2M ), cathepsin B ( CTSB ), FN1 , matrix metallopeptidase 9 ( MMP9 ), and SPARC . The five hub genes were confirmed to be overexpressed in DLBCL. The cBioportal portal detected these five hub genes that had gene alteration, including messenger ribonucleic acid high amplification and missense mutation, and the gene alteration percentages of A2M , FN1 , CTSB , MMP9 , and SPARC were 5%, 8%, 5%, 2.7%, and 5%, respectively. Furthermore, the five hub genes had a potential positive correlation with tumor stage. The correlation analysis between the five genes and tumor purity confirmed that the five genes were overexpressed in DLBCL and had a positive correlation with the development of DLBCL. More interestingly, the five genes had a significant correlation with the stromal infiltration scores. The correlation analysis between the fives genes and CAFs also showed a significant value, among which the top two genes, FN1 and SPARC , had a remarkable co-expression pattern., Conclusion: The top DEGs were identified, and the five hub genes were overexpressed in DLBCL. Furthermore, the gene alterations were confirmed and the positive correlation with tumor purity revealed the overexpression of the five genes and close association with the development of DLBCL. More interestingly, the five genes were positively correlated with stromal infiltration, especially in CAFs. The top two genes, FN1 and SPARC , showed a co-expression pattern, which indicates their potential as novel therapeutic targets for DLBCL., Competing Interests: Conflict-of-interest statement: All authors declare having no conflict of interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Prometryne is a widely used herbicide in China to control annual grasses and broadleaf weeds. However, the stability of prometryne makes it difficult to be degraded, which poses a threat to human health. This study presents a bacterial strain isolated from soil samples with a prometryne application history, designated strain DY-1. Strain DY-1, identified as Pseudomonas sp., is capable of utilizing prometryne as a sole carbon source for growth and degrading 100% of prometryne within 48 h from an initial concentration of 50 mg L -1 . To further optimize the degradation of prometryne, the prometryne concentration, temperature, pH, and salt concentration were examined. The optimal conditions for degradation of prometryne by strain DY-1 were an initial prometryne concentration of 50 mg L -1 , 30 °C, pH 7-8, and NaCl concentration of 200 mg L -1 . The same strain also degraded other s-triazine herbicides, including simetryne, ametryne, desmetryne, and metribuzin, under the same conditions. The biodegradation pathway of prometryne was established by isolating sulfoxide prometryne as the first metabolite and by the identification of sulfone prometryne and 2-hydroxy prometryne by liquid chromatography-mass spectrometry (LC-MS/MS). The results illustrated that strain DY-1 achieved the removal of prometryne by gradually oxidizing and hydrolyzing the methylthio groups. A bioremediation trial with contaminated soil and pot experiments showed that after treating the prometryne-contaminated soil with strain DY-1, the content of prometryne was significantly reduced (P < 0.05). This study provides an efficient bacterial strain and approach that could be potentially useful for detoxification and bioremediation of prometryne analogs.

Background: Psoriasis is a common chronic inflammatory skin disease with 2% to 3% prevalence worldwide and a heavy social-psychological burden for patients and their families. As the exact pathogenesis of psoriasis is still unknown, the current treatment is far from satisfactory. Thus, there is an urgent need to find a more effective therapy for this disease. Keratin 17 (K17), a type I intermediate filament, is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis. Therefore, we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis. This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA (siRNA) on mice with imiquimod (IMQ)-induced psoriasis-like dermatitis., Methods: Eight-week-old female BALB/c mice were administered a 5% IMQ cream on both ears to produce psoriatic dermatitis. On day 3, K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days. The right ears of the mice were treated in parallel with negative control (NC) siRNA. Inflammation was evaluated by gross ear thickness, histopathology, the infiltration of inflammatory cells (CD3+ T cells and neutrophils) using immunofluorescence, and the expression of cytokine production using real-time quantitative polymerase chain reaction. The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance., Results: The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears, as evidenced by the alleviated ear inflammation phenotype, including decreased ear thickness, infiltration of inflammatory cells (CD3+ T cells and neutrophils), and inflammatory cytokine/chemokine expression levels (interleukin 17 [IL-17], IL-22, IL-23, C-X-C motif chemokine ligand 1, and C-C motif chemokine ligand 20) (P < 0.05 vs. the Blank or NC siRNA groups). Compared to the NC siRNA treatment, the K17 siRNA treatment resulted in increased K1 and K10 expression, which are characteristic of keratinocyte differentiation (vs. NC siRNA, K17 siRNA1 group: K1, t = 4.782, P = 0.0050; K10, t = 3.365, P = 0.0120; K17 siRNA2 group: K1, t = 4.104, P = 0.0093; K10, t = 4.168, P = 0.0042; siRNA Mix group: K1, t = 3.065, P = 0.0221; K10, t = 10.83, P < 0.0001), and decreased K16 expression, which is characteristic of keratinocyte proliferation (vs. NC siRNA, K17 siRNA1 group: t = 4.156, P = 0.0043; K17 siRNA2 group: t = 2.834, P = 0.0253; siRNA Mix group: t = 2.734, P = 0.0250)., Conclusions: Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis. Thus, gene therapy targeting K17 may be a potential treatment approach for psoriasis., (Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Labor induction is commonly used for achieving successful vaginal delivery. This study aimed to compare the effectiveness of dinoprostone and Cook's balloon as labor-inducing agents in primipara women at term. A retrospective cohort study among primipara women was conducted in Hubei Maternity and Child Health Hospital. Basic clinical characteristics were collected. The main outcomes were vaginal delivery rate, cesarean section rate and forceps delivery rate. Obstetric and perinatal outcomes were also compared. Univariate and multivariate analyses were further performed to evaluate the predictors for vaginal delivery within 24 h. A total of 845 eligible primipara women undergoing labor induction were recruited. Of them, 141 women were induced with dinoprostone (dinoprostone group, DG), and 704 with Cook's balloon (Cook's balloon group, CG). Groups were homogeneous except more women with premature rupture of membranes in DG, with gestational hypertension in CG (P<0.05). The vaginal delivery rate within 12 h was 1.98% and 16.52% in CG and DG respectively (P=0.0001). Besides, the vaginal delivery rate within 24 h was 37.62% and 52.26% in CG and DG respectively (P=0.0079). DG showed the lower rate of oxytocin augmentation, artificial rupture of membrane and postpartum hemorrhage and the shorter interval from insertion to active labor than CG (P<0.05). Multivariate regression analysis revealed that abortion history, oxytocin augmentation, artificial rupture of membrane, and obstetric analgesia were independent predictors for vaginal delivery within 24 h. In conclusion, dinoprostone was more effective than Cook's balloon to induce labor and achieve vaginal birth in the sample of primipara women at term.

Development of Keap1-Nrf2 interaction inhibitors is a promising strategy for the discovery of therapeutic agents against oxidative stress-mediated diseases. Two motifs of Nrf2, ETGE and DLG motif, are responsible for Keap1-Nrf2 binding. Previously, ETGE peptide or ETGE-derived peptide-based approaches were used to detect Keap1-Nrf2 interaction; however, these approaches are not able to monitor Keap1-DLG motif binding. We first report here a novel Enzyme-linked Immunosorbent Assay (ELISA) approach to detect the protein-protein interaction of full length Keap1 and Nrf2. In our assay, the test compounds can target either ETGE or DLG binding site, therefore facilitating the exploration of diverse Keap1-Nrf2 inhibitors. Three FDA-approved drugs, zafirlukast, dutasteride and ketoconazole, were found to inhibit the Keap1-Nrf2 interaction with IC 50 of 5.87, 2.81 and 1.67 μM, respectively. Additionally, these three drugs also activated Nrf2 pathway in neuroblasts and lipopolysaccharide (LPS)-challenged mice. The results presented here indicate that the ELISA approach has the capacity to identify Keap1-Nrf2 inhibitors., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypericum L. is a genus of the family Hypericaceae within the dicotyledones. The constituents of Hypericum species are valued for their important biological properties. Their use is in the treatment of depression and as antibacterial agents has been well documented in the primary literature and in ethnobotanical reports. The present contribution gives a comprehensive summary of the chemical constituents of members of the genus Hypericum and their biological effects. A detailed account of the chemical constituents, including phloroglucinol derivatives, xanthones, dianthrones, and flavonoids, is included. These compounds show a diverse range of biological activities that include antimicrobial, cytotoxic, antidepressant-like, and antinociceptive effects.

Dementia with Lewy bodies (DLB) is characterized by the transient fluctuating cognition and recurrent visual hallucinations, which may be caused by disorders of the intrinsic brain network dynamics. However, little is known regarding the dynamic features of the brain network behind these symptoms in DLB. In the present study, the intra- and inter-brain network dynamics were explored on a time scale in 17 DLB and 20 healthy controls (HC) applying a sliding-window method followed by k -means clustering analysis. To further evaluate the impact of network dynamics on brain performance, the local and global efficiency of the brain network was calculated. Compared with HC, the dynamic functional connectivity variation matrix in DLB patients was represented by a mixed change of intra-network increase and inter-network decrease. DLB patients devoted more time to a negative connectivity pattern, which represents a state of functional separation. Furthermore, the local efficiency of DLB patients was significantly lower compared with HC. These observations indicate an altered dynamic variability and disorders to the time allocation of state sequences in DLB, which might result in a disturbance of the intricate brain network dynamic properties, thereby leading to a lack of integration and flexibility and an ineffective brain function. In conclusion, dynamic functional connectivity analysis could identify differences between DLB and HC, providing evidences for DLB diagnosis and contributing to the understanding of the widespread clinical features and complex treatment strategies in DLB patients., (Copyright © 2019 Ma, Yao, Hu, Xiao, Shi and Chen.)

Introduction: We evaluate the effectiveness and safety of transdermal acupuncture by needles for smoking cessation., Methods: A literature search for randomized controlled trials (RCTs) was performed in seven electronic databases from inception to February 2017. Meta-analysis was conducted using Revman 5.3.0 software. We used either a random effects model (REM) or a fixed effects model (FEM) for pooling data according to the result of a heterogeneity test (defined as significant if I 2 >75%). Trial sequential analysis (TSA) was applied by TSA 0.9.5.10 Beta software., Results: Twenty-four trials involving 3984 participants were included. The methodological quality was generally low. With regard to smoking abstinence, meta-analysis showed acupuncture was more effective compared to no intervention/waiting list for short-term (4 weeks) cessation (1 trial, RR=2.37, 95% 1.41, 3.97) and long-term (longer than 6 months) (2 trials, RR=2.66, 95% CI: 1.50, 4.70). Compared to acupuncture/auricular acupressure alone, acupuncture plus auricular acupressure showed more benefit for short-term cessation (3 trials, RR=1.52, 95% CI: 1.03, 2.25). Acupuncture plus auricular acupressure was more effective compared to sham acupuncture plus sham auricular acupressure for short-term cessation (3 trials, RR=2.50, 95% CI: 1.44, 4.33) and long-term (2 trials, RR=3.61, 95% CI: 1.37, 9.48). Acupuncture in combination with counseling, educational smoking cessation program or moxibustion had more benefit compared to acupuncture for short-term cessation (3 trials, RR=0.75, 95% 0.63, 0.91) and long-term (2 trials, RR=0.77, 95% CI: 0.56, 1.05), and TSA illustrated the cumulative Z-curve of this comparison for long-term across the traditional boundary of 5% significance and monitoring boundaries. No serious adverse events occurred., Conclusions: Acupuncture combined with counseling, educational smoking cessation program or moxibustion was more effective than acupuncture as monotherapy with regard to long-term smoking cessation. Further, high quality trials are needed to confirm the result., Competing Interests: Authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported.

Aims: To determine the value of a monoclonal antibody panel against a C-terminal conserved sequence polypeptide of human papillomavirus (HPV) L1 (a major capsid protein) for the detection of HPV in cervical exfoliated cells, as well as the potential of this antibody panel to be developed into an assay kit for the clinical screening of cervical cancer., Methods: Cervical exfoliated cells were collected at a gynecology clinic. One part of each sample was sent to the Department of Pathology for HPV genotyping, and the other part was sent to the Department of Pathology for cytologic testing and then to the laboratory for immunological histological chemistry (IHC) assay in which an HPV L1 C-terminal conserved sequence polypeptide-induced mouse monoclonal antibody panel was used to detect HPV L1., Results: Cervical cell samples were collected from 514 patients at the gynecology clinic; of these, 339 samples were sent for HPV genotyping, and 220 were HPV positive (64.90%, 220/339). Moreover, the duplicate samples from these 339 patients were sent for IHC assay, and 229 samples were positive (67.55%, 229/339). The IHC result was concordant with that obtained by HPV genotyping (Kappa = 0.743, p < 0.001)., Conclusion: This study showed that use of the HPV L1 C-terminal conserved sequence polypeptide-induced mouse monoclonal antibody panel was of great value for the detection of HPV in cervical cells; the resulting detection rate was comparable to that obtained using the commercial HPV genotyping kit that is currently in use in clinical practice., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To explore the expression of microRNA-106b (miRNA-106b) in nonsmall cell lung cancer (NSCLC)., Settings and Design: miRNAs are short regulatory RNAs that negatively modulate gene expression at the posttranscriptional level, and are deeply involved in the pathogenesis of several types of cancer. miRNA-106b has been shown to play an oncogenic role in tumor progression. The expression of miRNA-106b is detected in this study., Subjects and Methods: Quantitative reverse transcription polymerase chain reaction and Northern blotting were used to detect the expression level of miRNA-106b in 200 NSCLC samples., Statistical Analysis Used: All statistical analyses were performed using SPSS 16.0 software. Results were statistically evaluated using the Kruskal-Wallis test and Mann-Whitney U-test. Survival curves were estimated by the Kaplan-Meier method and P < 0.05 was considered to be statistically significant., Results: miRNA-106b expression is increased in NSCLC tissues. Statistical analysis showed that overexpression of miRNA-106b was strongly associated with lymph node metastasis, stage of tumor node metastasis classification, and poor prognosis. Moreover, there was a significant difference in the miRNA-106b expression levels between smoking and nonsmoking patients. Multivariate Cox regression analysis showed that miRNA-106b was an independent prognostic factor for NSCLC patients., Conclusions: These data suggest that aberrantly expressed miRNA-106b may contribute to the development of NSCLC., Competing Interests: There are no conflicts of interest

Background: Plasma extracellular RNAs have recently garnered interest as biomarkers in heart failure (HF). Most studies in HF focus on single extracellular RNAs related to phenotypes and outcomes, and few describe their functional roles. We hypothesized that clusters of plasma microRNAs (miRNAs) associated with left ventricular (LV) remodeling in human HF would identify novel subsets of genes involved in HF in animal models., Methods and Results: We prospectively measured circulating miRNAs in 64 patients with systolic HF (mean age, 64.8 years; 91% men; median LV ejection fraction, 26%) with serial echocardiography (10 months apart) during medical therapy. We defined LV reverse remodeling as a 15% reduction in LV end-systolic volume index. Using principal components analysis, we identified a component associated with LV reverse remodeling (odds ratio=3.99; P =0.01) that provided risk discrimination for LV reverse remodeling superior to a clinical model (C statistic, 0.58 for a clinical model versus 0.71 for RNA-based model). Using network bioinformatics, we uncovered genes not previously widely described in HF regulated simultaneously by >2 miRNAs. We observed increased myocardial expression of these miRNAs during HF development in animals, with downregulation of target gene expression, suggesting coordinate miRNA-mRNA regulation. Target mRNAs were involved in autophagy, metabolism, and inflammation., Conclusions: Plasma miRNAs associated with LV reverse remodeling in humans are dysregulated in animal HF and target clusters of genes involved in mechanisms implicated in HF. A translational approach integrating human HF, bioinformatics, and model systems may uncover novel pathways involved in HF., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00351390., (© 2018 American Heart Association, Inc.)

Experiments were performed to study the transformation, migration and outcome of residual bodies (RBs) in the seminiferous tubules of the rat testes. One part of the testes from adult Sprague-Dawley rats was used to generate paraffin sections to observe RBs and RB precursors through specific staining, and the other part of the testes was used to generate ultrathin sections to observe RBs under a transmission electron microscope. Deep blue particles of different sizes were observed in some seminiferous tubules through specific staining for RBs and RB precursors. These particles first appeared in the seminiferous tubules at stage I of the spermatogenic cycle, and after spermiation, the particles travelled rapidly towards the deeper region of the seminiferous epithelium and soon appeared close to the basement membrane of the seminiferous tubule. All of the particles in the tubules disappeared at stage IX. Using transmission electron microscopy, components of different electron densities were observed in the RBs on the surface of the seminiferous epithelium, all of which gradually formed in the cytoplasm of spermatozoon in later stages of spermiogenesis. After the spermatozoa were released, the RBs in the epithelium travelled quickly to the edge of the tube and were gradually transformed into lipid inclusions. These lipid inclusions ultimately became lipidlike particles. The lipidlike particles were discharged into the interstitial tissue. RBs initiate their own digestive process before their formation during spermiation in the rat testes. After spermiation, the RBs transform into lipid inclusions and finally into lipidlike particles. These lipidlike particles can be eliminated from the seminiferous tubules., (© 2017 Blackwell Verlag GmbH.)

Purpose: It is critical and difficult to accurately discriminate between high- and low-grade gliomas preoperatively. This study aimed to ascertain the role of several scalar measures in distinguishing high-grade from low-grade gliomas, especially the axial diffusivity (AD), radial diffusivity (RD), planar tensor (Cp), spherical tensor (Cs), and linear tensor (Cl) derived from diffusion tensor imaging (DTI). Materials and Methods: Fifty-three patients with pathologically confirmed brain gliomas (21 low-grade and 32 high-grade) were included. Contrast-enhanced T1-weighted images and DTI were performed in all patients. The AD, RD, Cp, Cs, and Cl values in the tumor zone, peritumoral edema zone, white matter (WM) adjacent to edema and contralateral normal-appearing white matter (NAWM) were calculated. The DTI parameters and tumor grades were statistically analyzed, and receiver operating characteristic (ROC) curve analysis was also performed. Results: The DTI metrics in the affected hemisphere showed significant differences from those in the NAWM, except for the AD values in the tumor zone and the RD values in WM adjacent to edema in the low-grade groups, as well as the Cp values in WM adjacent to edema in the high-grade groups. AD in the tumor zone as well as Cs and Cl in WM adjacent to edema revealed significant differences between the low- and high-grade gliomas. The areas under the curve (Az) of all three metrics were greater than 0.5 in distinguishing low-grade from high-grade gliomas by ROC curve analysis, and the best DTI metric was Cs in WM adjacent to edema (Az: 0.692). Conclusion: AD in the tumor zone as well as Cs and Cl in WM adjacent to edema will provide additional information to better classify gliomas and can be used as non-invasive reliable biomarkers in glioma grading.

Background: To investigate the effects of S-phase kinase protein 2 (SKP2) expression on the radiation induced bystander effect (RIBE) in esophageal cancer (EC) cells., Materials and Methods: Western blot was used to detect the levels of SKP2, Rad51, and Ku70 in EC cells. Positive transfection, RNAi, micronucleus (MN), and γ-H2AX focus formation assay were used to investigate the effects of SKP2 on RIBE induced by irradiated cells., Results: We found a significant negative correlation between SKP2 expression and MN frequency ( p < 0.05) induced by RIBE. The results were further confirmed by positive transfection, RNAi, and rescue experiments.γ-H2AX focus formation assay results indicated that overexpression of SKP2 in the irradiated cells inhibited the DNA damage of RIBE cells. However, when SKP2 expression decreased in irradiated cells, the DNA damage of RIBE cells increased. Increased or decreased expression levels of SKP2 had effects on Rad51 expression under the conditions of RIBE., Conclusions: These results showed, for the first time, that SKP2 expression can inhibit RIBE of EC cells. The mechanism may function, at least partly, through the regulation of Rad51 in the ability to repair DNA damage.

Objective: To investigate the expression of mir-106b in esophageal squamous cell carcinoma (ESCC) tissue and analyze its correlation with the clinicopathologic features of ESCC., Methods: A total of 200 fresh surgical specimens of ESCC and adjacent tissues collected between 2001 and 2007 were examined for expressions of mir-106b using real-time PCR (RT-PCR). Northern blot analysis for mir-106b was performed in 4 pairs of samples to confirm the RT-PCR results. The relationship between mir-106b expression and clinicopathological features and prognosis of the patients were analyzed., Results: Mir-106b was expressed at significantly higher levels in ESCC tissues than in the paired adjacent tissues. Overexpression of mir-106b was associated with lymph node metastasis, stage of TNM classification and smoking (P<0.05). The survival rate of patients with low mir-106b expression was higher than that of patients with high mir-106b expression (60 vs 37 months, P=0.024). Cox regression analysis indicated that the expression of mir-106b, lymph node metastasis and smoking were independent prognostic factors for ESCC (P<0.05)., Conclusion: Mir-106b is overexpressed in ESCC tumors, and its overexpression is strongly associated with lymph node metastasis and a poor prognosis. Mir-106b expression is an independent prognostic factor for ESCC and can serve as a biomarker for diagnosis and prognostic evaluation of ESCC.