bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early targeting of endoneurial macrophages alleviates the neuropathy and affects abnormal Schwann cell differentiation in a mouse model of Charcot‐Marie‐Tooth 1A
Authors: Klein Dennis , Groh Janos , Yuan Xidi , Berve Kristina , Stassart Ruth , Fledrich Robert , Martini Rudolf 
Published: February 2022

AbstractWe have previously shown that targeting endoneurial macrophages with the orally applied CSF‐1 receptor specific kinase (c‐FMS) inhibitor PLX5622 from the age of 3 months onwards led to a substantial alleviation of the neuropathy in mouse models of Charcot‐Marie‐Tooth (CMT) 1X and 1B disease, which are genetically‐mediated nerve disorders not treatable in humans. The same approach failed in a model of CMT1A (PMP22‐overexpressing mice, line C61), representing the most frequent form of CMT. This was unexpected since previous studies identified macrophages contributing to disease severity in the same CMT1A model. Here we re‐approached the possibility of alleviating the neuropathy in a model of CMT1A by targeting macrophages at earlier time points. As a proof‐of‐principle experiment, we genetically inactivated colony‐stimulating factor‐1 (CSF‐1) in CMT1A mice, which resulted in lower endoneurial macrophage numbers and alleviated the neuropathy. Based on these observations, we pharmacologically ablated macrophages in newborn CMT1A mice by feeding their lactating mothers with chow containing PLX5622, followed by treatment of the respective progenies after weaning until the age of 6 months. We found that peripheral neuropathy was substantially alleviated after early postnatal treatment, leading to preserved motor function in CMT1A mice. Moreover, macrophage depletion affected the altered Schwann cell differentiation phenotype. These findings underscore the targetable role of macrophage‐mediated inflammation in peripheral nerves of inherited neuropathies, but also emphasize the need for an early treatment start confined to a narrow therapeutic time window in CMT1A models and potentially in respective patients.
Changes in serum hepatitis B surface and e antigen, interferon‐inducible protein 10, and aminotransferase levels during combination therapy of immune‐tolerant chronic hepatitis B
Authors: Perrillo Robert , Lin Hsing‐Hua S. , Schwarz Kathleen B. , Rosenthal Philip , Lisker‐Melman Mauricio , Chung Raymond T. , Prokunina‐Olsson Ludmila , Cloherty Gavin , Feld Jordan ,   for the Hepatitis B Research Network (HBRN)
Published: February 2022

Abstract

Background and Aims
Treatment of immune‐tolerant (IT) children and adults with combined peginterferon alfa‐2a and entecavir results in a decline in serum HBeAg and HBsAg concentrations but rarely results in loss of HBeAg or sustained off‐treatment response. Factors associated with declines in these viral antigens during treatment remain unexplored.

Approach and Results
We investigated the pattern of virologic and biochemical response in 86 participants (59 children, 27 adults) by serial quantitative measurement of HBsAg (qHBsAg), quantitative HBeAg (qHBeAg), HBV RNA, interferon‐inducible protein (IP‐10), IL‐18, and alanine aminotransferase (ALT). Each individual had previously been treated with 8 weeks of entecavir followed by 40 weeks of combined peginteferon and entecavir. We defined the interrelationships between these parameters and virologic response measured as nadir declines from baseline for HBeAg and HBsAg. The patterns of HBsAg and HBeAg decline were similar in pediatric and adult participants. Higher levels of IP‐10 were observed during treatment in participants with greater ALT elevations and greater reductions of qHBsAg and qHBeAg. Individuals with peak ALT values exceeding three times the upper limit of normal were significantly more likely to have >1 log10 decline in both viral antigens. HBV DNA became undetectable in 21 of 86 (24%) and HBV RNA in 4 of 77 (5%) during therapy, but both markers remained negative only in those who became HBsAg negative, all of whom also had ALT elevations.

Conclusions
Induction of IP‐10 during peginterferon treatment in adults and children in the IT phase of chronic HBV infection is associated with ALT elevations and decline in viral antigens, suggesting a degree of interferon‐inducible viral control.
Ponicidin attenuates streptozotocin‐induced diabetic nephropathy in rats via modulating hyperlipidemia, oxidative stress, and inflammatory markers
Authors: An Shuqiang , Li Yang , Jia Xiaojing , Yang Yaqin , Jia Xiaojuan , Jia Xiaozhao , Xue Wujun 
Published: February 2022

AbstractThe present research work was proposed to discover the beneficial roles of ponicidin against the streptozotocin (STZ)‐induced diabetic nephropathy (DN) in rats via modulating the oxidative stress and inflammation. The DN was initiated to the Wistar rats via administering 45 mg/kg of STZ and then diabetic animals were supplemented with 50 mg/kg of ponicidin and 150 mg/kg of metformin (standard drug) for 8 weeks. The body weight and food intake of animals were checked every week. The glucose, insulin, and homeostasis model assessment– insulin resistance (HOMA‐IR) levels in the serum were assessed using kits. The levels of reactive oxygen species (ROS) accumulation, oxidative stress and antioxidant markers, and pro‐inflammatory cytokines were examined using assay kits. The levels of lipid profiles and renal function markers were investigated using respective kits. The renal tissues were analyzed microscopically to detect the histological alterations. The ponicidin treatment effectively decreased the body weight, food intake, HOMA‐IR, and HbAlc levels in the DN animals. The levels of ROS and MDA were decreased and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were improved by the ponicidin. The ponicidin also reduced the blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and kidney injury molecule (KIM‐1) levels. The levels of low‐density lipoprotein (LDL), very‐low‐density lipoprotein (VLDL), free fatty acid (FFA), and total cholesterol (TC) were decreased and the high‐density lipoprotein (HDL) level was improved by the ponicidin treatment to the DN rats. The tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), nuclear factor‐kappa B (NF‐κB), and IL‐6 levels were appreciably attenuated by the ponicidin. The ponicidin also ameliorated the DM‐provoked histological alterations in the renal tissues. In conclusion, this study work evidenced that ponicidin has the therapeutic action in ameliorating the development of DN via averting oxidative stress, inflammation, and renal injury. It could be a promising therapeutic agent to treat DN in the future.
Synthesis, anti‐TB activities, and molecular docking studies of 4‐(1,2,3‐triazoyl)arylmethanone derivatives
Authors: Turkmen Yunus , Yagiz Erdemir Güler , Yuksel Mayda Pelin , Akdemir Atilla , Gunaydin Akyildiz Aysenur , Altundas Aliye 
Published: February 2022

AbstractInfectious diseases such as tuberculosis (TB) are leading causes of human death. Antibiotics are effective molecules to combat bacterial infections by affecting the processes required for bacterial cell growth and proliferation. The development of new antibiotics has become an important issue as overdosed or incorrect use of antibiotic lead to the development of antibiotic resistance. In this study, a new series of 4‐(1,2,3‐triazoyl)arylmethanone derivatives has been synthesized using the one‐pot Copper‐​Catalyzed Oxidative Cross‐​Dehydrogenative Coupling​/Oxidative Cycloaddition strategy to overcome the aforementioned problems. New compounds were characterized by using spectroscopic techniques (1H, 13C‐APT‐NMR, FT‐IR, and HRMS‐TOF). In vitro antimycobacterial activities of the arylmethanone derivatives against the Mycobacterium tuberculosis H37Rv standard strain were examined using the resazurin microplate method in the presence of streptomycin and rifampycin as standard medicines. Bioactive assays demonstrated promising results that some of the synthesized 4‐(1,2,3‐triazoyl)arylmethanone derivatives exhibited good anti‐TB activities. Notably, compounds 6b, 6f, and 6g gave the most potent efficiency with minimum inhibitory concentration values of 4 μg/ml (12.8, 11.7, and 12.8 μΜ, respectively). Among the synthesized compounds, the cytotoxicity measurements of the 6b, 6f, 6g, 6d, and 6v derivatives were screened and it was found that the 6f derivative did not show any cytotoxicity. Molecular docking analyses are utilized to identify the binding mode and the key interactions between target compounds and the ligand‐binding site of M. tuberculosis enoyl‐acyl carrier protein reductase enzyme (MtInhA, EC 1.3.1.9). The docking results were in agreement with the in vitro results, which confirm the synthesized ligands bind to MtInha with moderate to low affinity.
Molecular docking study and molecular dynamics simulation of ethyl 3,5‐diphenyl‐1H‐pyrrole‐2‐carboxylate and (Z)‐ethyl‐2‐(3‐oxo‐1,3‐diphenylprop‐1‐enylamino)acetate
Authors: Kurbanova Malahat , Maharramov Abel , Safarova Aytan , Ahmad Sajjad , El Bakri Youness 
Published: February 2022

AbstractThe present analysis has been performed in the wet‐lab and computational environments. First, the synthesis of the latest heterocyclic compounds containing the alkyl organic compound fragment of acetate and glycine acid were obtained and then their crystal structure and biological activity were studied. (Z)‐ethyl‐2‐(3‐oxo‐1,3‐diphenylprop‐1‐enylamino) acetate (1) was initially retrieved on the supported reaction of dibenzene gas with glycine alkyl organic compound‐complex within the presence of Y(OTF)3 catalyst in liquid medium. At an identical time, ethyl‐3,5‐diphenyl‐1H‐pyrrole‐2‐carboxylate (2) was synthesized from the interaction of amino alkane with tert‐BuOK in the presence of tert‐BuOH/DMFA solvent. The structure of the latest compounds has been studied by 1H, 13C NMR. Additionally, the crystal structure of ethyl‐3,5‐diphenyl‐1H‐pyrrole‐2‐carboxylate (2) is conferred. Moreover, computational drug‐likeness and pharmacokinetics indicated the compounds' good drug‐like molecules and friendly pharmacokinetics, making the compound valuable candidates to be explored for additional structural modification to act as a potential inhibitor of AChE and α‐glycosidase enzymes.
DACT3 has a tumor‐inhibiting role in acute myeloid leukemia via the suppression of Wnt/β‐catenin signaling by DVL2
Authors: Gao Qiuying , Hou Limin , Wang Hui , Xun Liru 
Published: February 2022

AbstractDapper antagonist of catenin‐3 (DACT3) is a new tumor‐related protein associated with a diverse set of tumors. However, whether DACT3 plays a role in acute myeloid leukemia (AML) is not fully understood. Our findings showed low DACT3 level in AML tissue, which was corrected with shorter survival rates. Upregulation of DACT3 effectively repressed cellular proliferation, and promoted cell cycle arrest and apoptosis of AML cells. Upregulation of DACT3 decreased levels of Dishevelled2 (DVL2), phospho‐glycogen synthase kinase‐3β (GSK‐3β), and active β‐catenin, which collectively suppressed Wnt/β‐catenin‐mediated transcriptional activity. Overexpression of DVL2 reversed DACT3‐mediated suppression of Wnt/β‐catenin pathway. Reactivation of Wnt/β‐catenin abrogated DACT3‐upregulation‐evoked tumor‐suppression in AML cells. Overexpression of DACT3 impeded the formation and growth of AML‐derived xenograft tumor. Collectively, our work reveals a tumor‐suppressive role of DACT3, a protein that negatively adjusts Wnt/β‐catenin pathway via downregulation of DVL2 in AML.
Coping, COVID knowledge, communication, and HBCU student's emotional well‐being: Mediating role of perceived control and social connectedness
Authors: Huang Hsuan Yuan , Li Huijun , Hsu Ying‐Chia 
Published: February 2022

AbstractThe pandemic has disproportionately affected African American college students, who have experienced significant work‐related, academic, financial, and socio‐emotional challenges due to COVID‐19. The purpose of the study is to investigate how African American students cope with the severe impact of COVID‐19 on their emotional well‐being leveraging the benefits of self‐care coping measures, COVID‐19 knowledge, and communication with others to enhance perceived control and social connectedness. A structural equation modeling and a path analysis of 254 responses from a Historically Black College and University showed that emotional well‐being was positively predicted by self‐care coping strategies, feelings of being in control in life, and social connectedness. In addition, respondents who adopted mind−body balance coping strategies, those who are knowledgeable about COVID‐19, and those in more constant communication with others attained a strong sense of being in control, and in turn the empowerment increased their emotional well‐being.
Running of the feathertail glider (Acrobates pygmaeus) on level ground: Kinematics
Authors: Panyutina Aleksandra A. , Makarov Viktor A. 
Published: February 2022

AbstractA complete kinematic analysis of the trunk and limbs was performed for the smallest gliding mammal, the feathertail glider (Acrobates pygmaeus). To compare the running technique of the glider with that of terrestrial mammals, only movement on horizontal substrate was studied. Kinematic analysis was performed separately for bound with extended suspension and bound with both suspensions. Terrestrial locomotion of the feathertail glider was classified as primitive ricochet, which is distinguished from true gallop by the absence of a delay in protraction of the hindlimbs after their take‐off. The kinematic analysis showed significant impacts of gliding adaptation on the quadrupedal running, the most striking of which are the extremely sprawling position of the limbs, in particular, the wide stance of the forelimbs, and consequently, the absence of crossing of the fore‐ and hindlimbs in gathered stage of the cycle. The degree of limbs' sprawling in the feathertail glider is closer to the reptilian condition than to the mammalian parasagittal state. The sprawling condition of the feathertail glider is secondary and therefore is designated as “deparasagittalization.”
How well do embryo development rate models derived from laboratory data predict embryo development in sea turtle nests?
Authors: Booth David T. , Turner Alysabeth G. , Laloë Jacques‑Olivier , Limpus Colin J. 
Published: February 2022

AbstractDevelopment rate of ectothermic animals varies with temperature. Here we use data derived from laboratory constant temperature incubation experiments to formulate development rate models that can be used to model embryonic development rate in sea turtle nests. We then use a novel method for detecting the time of hatching to measure the in situ incubation period of sea turtle clutches to test the accuracy of our models in predicting the incubation period from nest temperature traces. We found that all our models overestimated the incubation period. We hypothesize three possible explanations which are not mutually exclusive for the mismatch between our modeling and empirically measured in situ incubation period: (1) a difference in the way the incubation period is calculated in laboratory data and in our field nests, (2) inaccuracies in the assumptions made by our models at high incubation temperatures where there is no empirical laboratory data, and (3) a tendency for development rate in laboratory experiments to be progressively slower as temperature decreases compared with in situ incubation.
Lead exposure does not affect baseline and induced innate immunity in quails
Authors: Melhado Gabriel , Pedrobom L. Jorge Henrique , Menegário Amauri A. , Herrera Montalvo Luis Gerardo , Cruz‐Neto Ariovaldo P. 
Published: February 2022

AbstractLead (Pb) is one of the most common metals found in ecosystems in elevated concentrations derived mainly from anthropogenic activities. Pb toxicity is of special concern in birds due to its capacity for bioaccumulation in the liver, bones, and kidneys causing physiological disruptions. Such disruptions can be lethal in a few days after Pb acute intoxication and they are associated with several million deaths of birds. Moreover, Pb may work as an immunosuppressant as it affects the cell‐mediated and humoral immune responses, including components of the acute‐phase response (APR). We (1) examined the effects of Pb contamination on the innate immune system, body mass, and food intake of Japanese quails (Coturnix coturnix japonica), and (2) evaluated the effects of Pb on its APR after exposing the animals to Pb acetate in drinkable water during 7 days. We found that Pb contamination increased the number of circulating white blood cells (WBCs), but no effect was found on body mass, food intake, the heterophil/lymphocyte (H/L) ratio, and haptoglobin (Hp) concentration. When Pb‐exposed birds were injected with lipopolysaccharide from Escherichia coli to activate the APR, they had a negative body mass ratio, reduced food intake, and increased the number of WBCs, the H/L ratio, and the Hp concentration. We conclude that Pb exposure at this dose did not affect baseline values of the constitutive response and that it did not affect the APR of quails, but commend for further studies testing the effect of different Pb doses.
A curious case of cyclin-dependent kinases in neutrophils
Authors: Syahirah Ramizah , Hsu Alan Y , Deng Qing 
Published: February 2022

AbstractNeutrophils are terminally differentiated, short-lived white blood cells critical for innate immunity. Although cyclin-dependent kinases (CDKs) are typically related to cell cycle progression, increasing evidence has shown that they regulate essential functions of neutrophils. This review highlights the roles of CDKs and their partners, cyclins, in neutrophils, outside of cell cycle regulation. CDK1-10 and several cyclins are expressed in neutrophils, albeit at different levels. Observed phenotypes associated with specific inhibition or genetic loss of CDK2 indicate its role in modulating neutrophil migration. CDK4 and 6 regulate neutrophil extracellular traps (NETs) formation, while CDK5 regulates neutrophil degranulation. CDK7 and 9 are critical in neutrophil apoptosis, contributing to inflammation resolution. In addition to the CDKs that regulate mature neutrophil functions, cyclins are essential in hematopoiesis and granulopoiesis. The pivotal roles of CDKs in neutrophils present an untapped potential in targeting CDKs for treating neutrophil-dominant inflammatory diseases and understanding the regulation of the neutrophil life cycle.
Magnetic Resonance Imaging Quantification of Accumulation of Epicardial Adipose Tissue Adds Independent Risks for Diastolic Dysfunction among Dialysis Patients
Authors: Zhou Hang , An Dong‐Aolei , Ni Zhaohui , Xu Jianrong , Zhou Yan , Fang Wei , Lu Renhua , Ying Liang , Huang Jiaying , Yao Qiuying , Li Dawei , Hu Jiani , Chen Binghua , Shen Jianxiao , Jin Haijiao , Wei Yuehan , Fahmy Lara M. , Jing Du , Ye Jing , Xu Lei , Wu Lian‐Ming , Mou Shan 
Published: February 2022

BackgroundDiastolic dysfunction (DD) frequently occurs in dialysis patients; however, the risk factors of DD remain to be further explored in such a population. Epicardial adipose tissue (EAT) volume has proven to be an independent clinical risk factor for multiple cardiac disorders.PurposeTo assess whether EAT volume is an independent risk factor for DD in dialysis patients.Study TypeCase–control study.PopulationA total of 113 patients (mean age: 54.5 ± 14.4 years; 41 women) who had underwent dialysis for at least 3 months due to uremia.Field StrengthA 3 T, steady‐state free precession (SSFP) sequence for cine imaging, modified Look–Locker imaging (MOLLI) for T1 mapping and gradient‐recalled‐echo for T2*.AssessmentAll participants were performed cardiac magnetic resonance imaging (MRI) and echocardiogram. For MRI images analysis, borders of the EAT were manually delineated, as well as, pericardial adipose tissue (PeAT) and paracardial adipose tissue (PaAT), T1 mapping, T2* mapping, global longitudinal strain (GLS), and left atrial strain. For echocardiogram assessments, the thickness of PaAT, e' velocity, E velocity, E/e ratio, A velocity, and deceleration time were measured.Statistical testsUnivariate and multivariate logistic regressions were performed to explore the independent risk factors for DD. P value less than 0.05 was considered as significant.ResultsCompared with the DD(−) group, the DD(+) group had significantly more epicardial tissue fat (18.5 ± 1.3 vs. 30.9 ± 2.3) In addition, EAT volumes increased significantly with the grades of DD (grade 1 vs. grade 2 and 3: 27.9 ± 15.9 vs. 35.4 ± 13.1). Moreover, EAT had significant correlations with T1 mapping, T2* mapping, GLS, left atrial strain, e' velocity, and E/e ratio. EAT accumulation added an independent risk for DD (Odds Ratio = 1.03) over conventional clinical risk factors including age, diabetes mellitus, and hemodialysis.Data ConclusionEAT was associated with diastolic function, and its accumulation may be an independent risk factor for DD among dialysis patients.Evidence Level2Technical EfficacyStage 2
Coupling of brain activity and structural network in multiple sclerosis: A graph frequency analysis study
Authors: Ye Chenfei , Huang Jing , Liang Li , Yan Zehong , Qi Zhigang , Kang Xiong , Liu Zheng , Dong Huiqing , Lv Haiyan , Ma Ting , Lu Jie 
Published: February 2022

AbstractThe brain activities and the underlying wiring diagrams are vulnerable in multiple sclerosis (MS). Also, it remains unknown whether the complex coupling between these functional and structural brain properties would be affected. To address this issue, we adopted graph frequency analysis to quantify the high‐order structural‐functional interactions based on a combination of brain diffusion and functional MRI data. The structural‐functional decoupling index was proposed to measure how much brain regional functional activity with different graph frequency was organized atop the underlying wiring diagram in MS. The identified patterns in MS included (1) disruption of inherent structural‐functional coupling in the somatomotor network (β = 0.05, p = 0.03), and (2) excessive decrease of decoupling in the subcortical (β = −0.10, p = 0.02), visual (β = −0.04, p = 0.01), and dorsal attention networks (β = −0.12, p = 0.03). Besides, this structural‐functional coupling signature in the somatomotor network was associated with cognitive worsening of MS patients (β = −24.31, p = 0.006). Overall, our study unveiled a unique signature of brain structural‐functional reorganization in MS.