bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of miR-379/miR-544 Cluster Resists High-Fat Diet-Induced Obesity and Prevents Hepatic Triglyceride Accumulation in Mice
Authors: Cao Congcong , Duan Peng , Li Wencun , Guo Yang , Zhang Jin , Gui Yaoting , Yuan Shuiqiao
Published: September 2021

Non-alcoholic fatty liver disease (NAFLD) affects obesity-associated metabolic syndrome, which exhibits hepatic steatosis, insulin insensitivity and glucose intolerance. Emerging evidence suggests that microRNAs (miRNAs) are essential for the metabolic homeostasis of liver tissues. Many hepatic miRNAs located in the miR-379/miR-544 cluster were significantly increased in leptin-receptor-deficient type 2 mice (db/db), a mouse model of diabetes. However, the function of the miR-379/miR-544 cluster in the process of hepatic steatosis remains unclear. Here, we report that the novel function of miR-379/miR-544 cluster in regulating obesity-mediated metabolic dysfunction. Genetical mutation of miR-379/miR-544 cluster in mice displayed resistance to high-fat diet (HFD)-induced obesity with moderate hepatic steatosis and hypertriglyceridemia.In vitrostudies revealed that silencing ofmiR-379in human hepatocellular carcinoma (HepG2) cells ameliorated palmitic acid-induced elevation of cellular triglycerides, and overexpression ofmiR-379had the opposite effect. Moreover,Igf1r(Insulin-like growth factor 1 receptor) andDlk1(Delta-like homolog 1) were directly targeted bymiR-379andmiR-329, respectively, and elevated in the livers of themiR-379/miR-544cluster knockout mice fed on HFD. Further transcriptome analyses revealed that the hepatic gene expressions are dysregulated inmiR-379/miR-544knockout mice fed with HFD. Collectively, our findings identify themiR-379/miR-544cluster as integral components of a regulatory circuit that functions under conditions of metabolic stress to control hepatic steatosis. Thus, this miRNA cluster provides potential targets for pharmacologic intervention in obesity and NAFLD.
Digitally Driven Aerosol Jet Printing to Enable Customisable Neuronal Guidance
Authors: Capel Andrew J. , Smith Matthew A. A. , Taccola Silvia , Pardo-Figuerez Maria , Rimington Rowan P. , Lewis Mark P. , Christie Steven D. R. , Kay Robert W. , Harris Russell A.
Published: September 2021

Digitally driven manufacturing technologies such as aerosol jet printing (AJP) can make a significant contribution to enabling new capabilities in the field of tissue engineering disease modeling and drug screening. AJP is an emerging non-contact and mask-less printing process which has distinct advantages over other patterning technologies as it offers versatile, high-resolution, direct-write deposition of a variety of materials on planar and non-planar surfaces. This research demonstrates the ability of AJP to print digitally controlled patterns that influence neuronal guidance. These consist of patterned poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) tracks on both glass and poly(potassium 3-sulfopropyl methacrylate) (PKSPMA) coated glass surfaces, promoting selective adhesion of SH-SY5Y neuroblastoma cells. The cell attractive patterns had a maximum height ≥0.2 μm, width and half height ≥15 μm, Ra = 3.5 nm, and RMS = 4.1. The developed biocompatible PEDOT:PSS ink was shown to promote adhesion, growth and differentiation of SH-SY5Y neuronal cells. SH-SY5Y cells cultured directly onto these features exhibited increased nuclei and neuronal alignment on both substrates. In addition, the cell adhesion to the substrate was selective when cultured onto the PKSPMA surfaces resulting in a highly organized neural pattern. This demonstrated the ability to rapidly and flexibly realize intricate and accurate cell patterns by a computer controlled process.
Normothermic ex vivo Heart Perfusion Combined With Melatonin Enhances Myocardial Protection in Rat Donation After Circulatory Death Hearts via Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis
Authors: Lu Jun , Xu Liwei , Zeng Zifeng , Xue Chuqing , Li Jiale , Chen Xiong , Zhou Pengyu , Lin Shaoyan , Liao Yuhui , Du Xianjin , Yang Ronghua , Zheng Shaoyi
Published: September 2021

Objective

The adoption of hearts from donation after circulatory death (DCD) is a promising approach for the shortage of suitable organs in heart transplantation. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies demonstrate that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis is a novel target to ameliorate myocardial IRI. Melatonin is shown to inhibit NLRP3 inflammasome-mediated pyroptosis. Therefore, this study is designed to verify the hypothesis that melatonin can protect the heart graft preserved with ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome-mediated pyroptosis in a rat model of DCD.

Methods

Donor-heart rats were randomly divided into three groups: (1) Control group: non-DCD hearts were harvested from heart-beating rats and immediately preserved with allogenic blood-based perfusate at constant flow for 105 min in the normothermic EVHP system; (2) DCD-vehicle group; and (3) DCD-melatonin group: rats were subjected to the DCD procedure with 25 min of warm ischemia injury and preserved by the normothermic EVHP system for 105 min. Melatonin (200 μmol/L) or vehicle was perfused in the cardioplegia and throughout the whole EVHP period. Cardiac functional assessment was performed every 30 min during EVHP. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis of heart grafts submitted to EVHP were evaluated.

Results

Twenty five-minute warm ischemia injury resulted in a significant decrease in the developed pressure (DP), dP/dtmax, and dP/dtmin of left ventricular of the DCD hearts, while the treatment with melatonin significantly increased the DP, dP/dtmax of the left ventricular of DCD hearts compared with DCD-vehicle group. Furthermore, warm ischemia injury led to a significant increase in the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis in the hearts preserved with EVHP. However, melatonin added in the cardioplegia and throughout the EVHP period significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis compared with DCD-vehicle group.

Conclusion

EVHP combined with melatonin post-conditioning attenuates myocardial IRI in DCD hearts by inhibiting NLRP3 inflammasome-mediated pyroptosis, which might expand the donor pool by the adoption of transplantable DCD hearts.
miR-4732-3p in Extracellular Vesicles From Mesenchymal Stromal Cells Is Cardioprotective During Myocardial Ischemia
Authors: Sánchez-Sánchez Rafael , Gómez-Ferrer Marta , Reinal Ignacio , Buigues Marc , Villanueva-Bádenas Estela , Ontoria-Oviedo Imelda , Hernándiz Amparo , González-King Hernán , Peiró-Molina Esteban , Dorronsoro Akaitz , Sepúlveda Pilar
Published: September 2021

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are an emerging alternative to cell-based therapies to treat many diseases. However, the complexity of producing homogeneous populations of EVs in sufficient amount hampers their clinical use. To address these limitations, we immortalized dental pulp-derived MSC using a human telomerase lentiviral vector and investigated the cardioprotective potential of a hypoxia-regulated EV-derived cargo microRNA, miR-4732-3p. We tested the compared the capacity of a synthetic miR-4732-3p mimic with EVs to confer protection to cardiomyocytes, fibroblasts and endothelial cells against oxygen-glucose deprivation (OGD). Results showed that OGD-induced cardiomyocytes treated with either EVs or miR-4732-3p showed prolonged spontaneous beating, lowered ROS levels, and less apoptosis. Transfection of the miR-4732-3p mimic was more effective than EVs in stimulating angiogenesis in vitro and in vivo and in reducing fibroblast differentiation upon transforming growth factor beta treatment. Finally, the miR-4732-3p mimic reduced scar tissue and preserved cardiac function when transplanted intramyocardially in infarcted nude rats. Overall, these results indicate that miR-4732-3p is regulated by hypoxia and exerts cardioprotective actions against ischemic insult, with potential application in cell-free-based therapeutic strategies.
Four Novel d10 Metal-Organic Frameworks Incorporating Amino-Functionalized Carboxylate Ligands: Synthesis, Structures, and Fluorescence Properties
Authors: Xie Wang , Wu Jie , Hang Xiaochun , Zhang Honghai , shen Kang , Wang Zhoulu
Published: September 2021

By employment of amino-functionalized dicarboxylate ligands to react with d10 metal ions, four novel metal-organic frameworks (MOFs) were obtained with the formula of {[Cd(BCPAB)(μ2-H2O)]}n (1), {[Cd(BDAB)]∙2H2O∙DMF}n (2), {[Zn(BDAB)(BPD)0.5(H2O)]∙2H2O}n (3) and {[Zn(BDAB)(DBPB)0.5(H2O)]∙2H2O}n (4) (H2BCPAB = 2,5-bis(p-carbonylphenyl)-1-aminobenzene; H2BDAB = 1,2-diamino-3,6-bis(4-carboxyphenyl)benzene); BPD = (4,4′-bipyridine); DBPB = (E,E-2,5-dimethoxy-1,4-bis-[2-pyridin-vinyl]-benzene; DMF = N,N-dimethylformamide). Complex 1 is a three-dimensional (3D) framework bearing seh-3,5-Pbca nets with point symbol of {4.62}{4.67.82}. Complex 2 exhibits a 4,4-connected new topology that has never been reported before with point symbol of {42.84}. Complex 3 and 4 are quite similar in structure and both have 3D supramolecular frameworks formed by 6-fold and 8-fold interpenetrated 2D coordination layers. The structures of these complexes were characterized by single crystal X-ray diffraction (SC-XRD), thermal gravimetric analysis (TGA) and powder X-ray diffraction (PXRD) measurements. In addition, the fluorescence properties and the sensing capability of 2–4 were investigated as well and the results indicated that complex 2 could function as sensor for Cu2+ and complex 3 could detect Cu2+ and Ag+via quenching effect.
d-Glucose Adsorption on the TiO2 Anatase (100) Surface: A Direct Comparison Between Cluster-Based and Periodic Approaches
Authors: Butera Valeria , Massaro Arianna , Muñoz-García Ana B. , Pavone Michele , Detz Hermann
Published: September 2021

Titanium dioxide (TiO2) has been extensively studied as a suitable material for a wide range of fields including catalysis and sensing. For example, TiO2-based nanoparticles are active in the catalytic conversion of glucose into value-added chemicals, while the good biocompatibility of titania allows for its application in innovative biosensing devices for glucose detection. A key process for efficient and selective biosensors and catalysts is the interaction and binding mode between the analyte and the sensor/catalyst surface. The relevant features regard both the molecular recognition event and its effects on the nanoparticle electronic structure. In this work, we address both these features by combining two first-principles methods based on periodic boundary conditions and cluster approaches (CAs). While the former allows for the investigation of extended materials and surfaces, CAs focus only on a local region of the surface but allow for using hybrid functionals with low computational cost, leading to a highly accurate description of electronic properties. Moreover, the CA is suitable for the study of reaction mechanisms and charged systems, which can be cumbersome with PBC. Here, a direct and detailed comparison of the two computational methodologies is applied for the investigation of d-glucose on the TiO2 (100) anatase surface. As an alternative to the commonly used PBC calculations, the CA is successfully exploited to characterize the formation of surface and subsurface oxygen vacancies and to determine their decisive role in d-glucose adsorption. The results of such direct comparison allow for the selection of an efficient, finite-size structural model that is suitable for future investigations of biosensor electrocatalytic processes and biomass conversion catalysis.
Green Synthesis of New Category of Pyrano[3,2-c]Chromene-Diones Catalyzed by Nanocomposite as Fe3O4@SiO2-Propyl Covalented Dapsone-Copper Complex
Authors: Zare Fekri Leila
Published: September 2021

Nanomagnetic dapsone-Cu supported on the silica-coated Fe3O4 (Fe3O4@SiO2-pr@dapsone-Cu) nanocomposite was synthesized and characterized by Fourier transform infrared (FT-IR), energy-dispersive X-ray (EDX), X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), zeta potential, vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). This newly synthesized nanocomposite was chosen to act as a green, efficient, and recyclable Lewis acid for the multicomponent synthesis of new derivatives of pyrano[3,2-c]chromene-diones through the reaction of aromatic aldehydes, indandione, and 4-hydroxycoumarin in water. All of the synthesized compounds are new and are recognized by FT-IR, NMR, and elemental analysis; this avenue is new and has advantages such as short reaction times, high productivity, economical synthesis, and use of green solvent, H2O, as a medium. The catalyst is magnetically recoverable and can be used after six runs without a decrease in the efficiency.
Self-Assembly Dipeptide Hydrogel: The Structures and Properties
Authors: Li Liangchun , Xie Li , Zheng Renlin , Sun Rongqin
Published: September 2021

Self-assembly peptide-based hydrogels are well known and popular in biomedical applications due to the fact that they are readily controllable and have biocompatibility properties. A dipeptide is the shortest self-assembling motif of peptides. Due to its small size and simple synthesis method, dipeptide can provide a simple and easy-to-use method to study the mechanism of peptides’ self-assembly. This review describes the design and structures of self-assembly linear dipeptide hydrogels. The strategies for preparing the new generation of linear dipeptide hydrogels can be divided into three categories based on the modification site of dipeptide: 1) COOH-terminal and N-terminal modified dipeptide, 2) C-terminal modified dipeptide, and 3) uncapped dipeptide. With a deeper understanding of the relationship between the structures and properties of dipeptides, we believe that dipeptide hydrogels have great potential application in preparing minimal biocompatible materials.
Analysis of Porcine Model of Fecal-Induced Peritonitis Reveals the Tropism of Blood Microbiome
Authors: Hyun Hwi , Lee Min Seok , Park Inwon , Ko Hwa Soo , Yun Seongmin , Jang Dong-Hyun , Kim Seonghye , Kim Hajin , Kang Joo H. , Lee Jae Hyuk , Kwon Taejoon
Published: September 2021

Recent studies have suggested the existence of a blood microbiome in the healthy host. However, changes in the blood microbiome upon bloodstream infection are not known. Here, we analyzed the dynamics of the blood microbiome in a porcine model of polymicrobial bacteremia induced by fecal peritonitis. Surprisingly, we detected bacterial populations in the bloodstream even before the infection, and these populations were maintained over time. The native blood microbiome was notably taxonomically different from the fecal microbiome that was used to induce peritonitis, reflecting microbial tropism for the blood. Although the population composition after the infection was similar to that of the native blood microbiome, new bacterial strains entered the bloodstream upon peritonitis induction as clinical symptoms relevant to sepsis developed. This indicates that the bacteria detected in the blood before peritonitis induction were derived from the blood rather than a contamination. Comparison of the functional pathways enriched in the blood and fecal microbiomes revealed that communication and stress management pathways are essential for the survival of the blood microbiome.
Symbiotic Interactions Between Mosquitoes and Mosquito Viruses
Authors: Altinli Mine , Schnettler Esther , Sicard Mathieu
Published: September 2021

Mosquitoes not only transmit human and veterinary pathogens called arboviruses (arthropod-borne viruses) but also harbor mosquito-associated insect-specific viruses (mosquito viruses) that cannot infect vertebrates. In the past, studies investigating mosquito viruses mainly focused on highly pathogenic interactions that were easier to detect than those without visible symptoms. However, the recent advances in viral metagenomics have highlighted the abundance and diversity of viruses which do not generate mass mortality in host populations. Over the last decade, this has facilitated the rapid growth of virus discovery in mosquitoes. The circumstances around the discovery of mosquito viruses greatly affected how they have been studied so far. While earlier research mainly focused on the pathogenesis caused by DNA and some double-stranded RNA viruses during larval stages, more recently discovered single-stranded RNA mosquito viruses were heavily studied for their putative interference with arboviruses in female adults. Thus, many aspects of mosquito virus interactions with their hosts and host-microbiota are still unknown. In this context, considering mosquito viruses as endosymbionts can help to identify novel research areas, in particular in relation to their long-term interactions with their hosts (e.g. relationships during all life stages, the stability of the associations at evolutionary scales, transmission routes and virulence evolution) and the possible context-dependent range of interactions (i.e. beneficial to antagonistic). Here, we review the symbiotic interactions of mosquito viruses considering different aspects of their ecology, such as transmission, host specificity, host immune system and interactions with other symbionts within the host cellular arena. Finally, we highlight related research gaps in mosquito virus research.
Specific Gut Microbiome and Serum Metabolome Changes in Lung Cancer Patients
Authors: Zhao Feng , An Rui , Wang Liqian , Shan Jikang , Wang Xianjun
Published: September 2021

Background

Lung cancer (LC) is one of the most aggressive, prevalent and fatal malignancies. Gut microbes and their associated metabolites are thought to cause and modulate LC development, albeit influenced by the host genetic make-up and environment. Herein, we identified and classified gut microbiota and serum metabolites associated with LC.

Methods

Stool samples were collected from 41 LC patients and 40 healthy volunteers. The gut microbiota was analyzed using 16S rRNA gene sequencing. Serum samples were collected from the same LC patients (n=30) and healthy volunteers (n=30) and serum metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). Microbiome and metabolome data were analyzed separately and integrated for combined analysis using various bioinformatics methods.

Results

Serum metabolomics uncovered 870 metabolites regulated in 76 metabolic pathways in both groups. Microbial diversity analyses identified 15967 operational taxonomic units (OTUs) in groups. Of these, the abundance of 232 OTUs was significantly different between HC and LC groups. Also, serum levels of glycerophospholipids (LysoPE 18:3, LysoPC 14:0, LysoPC 18:3), Imidazopyrimidines (Hypoxanthine), AcylGlcADG 66:18; AcylGlcADG (22:6/22:6/22:6) and Acylcarnitine 11:0 were substantially different between HC and LC groups. Combined analysis correlated LC-associated microbes with metabolites, such as Erysipelotrichaceae_UCG_003, Clostridium and Synergistes with glycerophospholipids.

Conclusions

There is an intricate relationship between gut microbiome and levels of several metabolites such as glycerophospholipids and imidazopyrimidines. Microbial-associated metabolites are potential diagnostic biomarkers and therapeutic targets for LC.
Skew Surge and Storm Tides of Tropical Cyclones in the Delaware and Chesapeake Bays for 1980–2019
Authors: Callahan John A. , Leathers Daniel J. , Callahan Christina L.
Published: September 2021

Coastal flooding poses the greatest threat to human life and is often the most common source of damage from coastal storms. From 1980 to 2020, the top 6, and 17 of the top 25, costliest natural disasters in the U.S. were caused by coastal storms, most of these tropical systems. The Delaware and Chesapeake Bays, two of the largest and most densely populated estuaries in the U.S. located in the Mid-Atlantic coastal region, have been significantly impacted by strong tropical cyclones in recent decades, notably Hurricanes Isabel (2003), Irene (2011), and Sandy (2012). Current scenarios of future climate project an increase in major hurricanes and the continued rise of sea levels, amplifying coastal flooding threat. We look at all North Atlantic tropical cyclones (TC) in the International Best Track Archive for Climate Stewardship (IBTrACS) database that came within 750 km of the Delmarva Peninsula from 1980 to 2019. For each TC, skew surge and storm tide are computed at 12 NOAA tide gauges throughout the two bays. Spatial variability of the detrended and normalized skew surge is investigated through cross-correlations, regional storm rankings, and comparison to storm tracks. We find Hurricanes Sandy (2012) and Isabel (2003) had the largest surge impact on the Delaware and Chesapeake Bay, respectively. Surge response to TCs in upper and lower bay regions are more similar across bays than to the opposing region in their own bay. TCs that impacted lower bay more than upper bay regions tended to stay offshore east of Delmarva, whereas TCs that impacted upper bay regions tended to stay to the west of Delmarva. Although tropical cyclones are multi-hazard weather events, there continues to be a need to improve storm surge forecasting and implement strategies to minimize the damage of coastal flooding. Results from this analysis can provide insight on the potential regional impacts of coastal flooding from tropical cyclones in the Mid-Atlantic.
Physicality in Postcolonialism: Tensions at the Asian Rural Institute
Authors: Senda-Cook Samantha
Published: September 2021

The Asian Rural Institute (ARI) is a transnational NGO that has a unique model of education and was founded in response to Japan’s role as a colonizer. It invites participants from around the world to learn sustainable agriculture, servant leadership, and community advocacy at their campus in Tochigi, Japan. Postcolonial studies has a strong foundation of analyzing physical elements such as bodies and space and their role in both controlling colonized people and resisting colonizers. I argue that the complications of postcolonial and racial relationships manifest physically through movement and shared space at ARI, both of which operate as tensions that support (and sometimes undermine) self-determination and survivance, key characteristics of decolonization. This analysis contributes to postcolonial scholarship by providing another means of conceptualizing movement and linking space to consubstantiation.
Coronary Artery Disease: Optimal Lipoprotein(a) for Survival—Lower Is Better? A Large Cohort With 43,647 Patients
Authors: Liu Jin , Liu Liwei , Wang Bo , Chen Shiqun , Liu Buyun , Liang Jingjing , Huang Haozhang , Li Qiang , Lun Zhubin , Ying Ming , Chen Guanzhong , Huang Zhidong , Xu Danyuan , Yan Xiaoming , Zhu Tingting , Tadesse Girmaw Abebe , Tan Ning , Chen Jiyan , Liu Yong
Published: September 2021

Background: A high level of lipoprotein(a) can lead to a high risk of cardiovascular events or mortality. However, the association of moderately elevated lipoprotein(a) levels (≥15 mg/dL) with long-term prognosis among patients with coronary artery disease (CAD) is still uncertain. Hence, we aim to systematically analyzed the relevance of baseline plasma lipoprotein(a) levels to long-term mortality in a large cohort of CAD patients.

Methods: We obtained data from 43,647 patients who were diagnosed with CAD and had follow-up information from January 2007 to December 2018. The patients were divided into two groups (<15 and ≥15 mg/dL). The primary endpoint was long-term all-cause death. Kaplan–Meier curve analysis and Cox proportional hazards models were used to investigate the association between moderately elevated baseline lipoprotein(a) levels (≥15 mg/dL) and long-term all-cause mortality.

Results: During a median follow-up of 5.04 years, 3,941 (18.1%) patients died. We observed a linear association between lipoprotein(a) levels and long-term all-cause mortality. Compared with lipoprotein(a) concentrations <15 mg/dL, lipoprotein(a) ≥15 mg/dL was associated with a significantly higher risk of all-cause mortality [adjusted hazard ratio (aHR) 1.10, 95%CI: 1.04–1.16, P-values = 0.001). Similar results were found for the subgroup analysis of non-acute myocardial infarction, non-percutaneous coronary intervention, chronic heart failure, diabetes mellitus, or non-chronic kidney diseases.

Conclusion: Moderately elevated baseline plasma lipoprotein(a) levels (≥15 mg/dL) are significantly associated with higher all-cause mortality in patients with CAD. Our finding provides a rationale for testing the lipoprotein(a)-reducing hypothesis with lower targets (even <15 mg/dL) in CAD outcome trials.
Cardioprotecive Properties of Known Agents in Rat Ischemia-Reperfusion Model Under Clinically Relevant Conditions: Only the NAD Precursor Nicotinamide Riboside Reduces Infarct Size in Presence of Fentanyl, Midazolam and Cangrelor, but Not Propofol
Authors: Xiao Yang , Phelp Philippa , Wang Qian , Bakker Diane , Nederlof Rianne , Hollmann Markus W. , Zuurbier Coert J.
Published: September 2021

Background: Cardioprotective strategies against ischemia-reperfusion injury (IRI) that remain effective in the clinical arena need to be developed. Therefore, maintained efficacy of cardioprotective strategies in the presence of drugs routinely used clinically (e.g., opiates, benzodiazepines, P2Y12 antagonist, propofol) need to be identified in preclinical models.

Methods: Here, we examined the efficacy of promising cardioprotective compounds [fingolimod (Fingo), empagliflozin (Empa), melatonin (Mela) and nicotinamide riboside (NR)] administered i.v. as bolus before start ischemia. Infarct size as percentage of the area of risk (IS%) was determined following 25 min of left ascending coronary (LAD) ischemia and 2 h of reperfusion in a fentanyl-midazolam anesthetized IRI rat model. Plasma lactate dehydrogenase (LDH) activity at 30 min reperfusion was determined as secondary outcome parameter. Following pilot dose-response experiments of each compound (3 dosages, n = 4–6 animals per dosage), potential cardioprotective drugs at the optimal observed dosage were subsequently tested alone or in combination (n = 6–8 animals per group). The effective treatment was subsequently tested in the presence of a P2Y12 antagonist (cangrelor; n = 6/7) or propofol aesthesia (n = 6 both groups).

Results: Pilot studies suggested potential cardioprotective effects for 50 mg/kg NR (p = 0.005) and 500 μg/kg melatonin (p = 0.12), but not for Empa or Fingo. Protection was subsequently tested in a new series of experiments for solvents, NR, Mela and NR+Mela. Results demonstrated that only singular NR was able to reduce IS% (30 ± 14 vs. 60 ± 16%, P = 0.009 vs. control). Mela (63 ± 18%) and NR+Mela (47 ± 15%) were unable to significantly decrease IS%. NR still reduced IS in the presence of cangrelor (51 ± 18 vs. 71 ± 4%, P = 0.016 vs. control), but lost protection in the presence of propofol anesthesia (62 ± 16 vs. 60 ± 14%, P = 0.839 vs. control). LDH activity measurements supported all IS% results.

Conclusion: This observational study suggests that NR is a promising cardioprotective agent to target cardiac ischemia-reperfusion injury in clinical conditions employing opioid agonists, benzodiazepines and platelet P2Y12 inhibitors, but not propofol.
Angiogenic Secretion Profile of Valvular Interstitial Cells Varies With Cellular Sex and Phenotype
Authors: Nelson Victoria , Patil Vaidehi , Simon LaTonya R. , Schmidt Kelsey , McCoy Chloe M. , Masters Kristyn S.
Published: September 2021

Angiogenesis is a hallmark of fibrocalcific aortic valve disease (CAVD). An imbalance of pro- and anti-angiogenic factors is thought to play a role in driving this disease process, and valvular interstitial cells (VICs) may act as a significant source of these factors. CAVD is also known to exhibit sexual dimorphism in its presentation, and previous work suggested that VICs may exhibit cellular-scale sex differences in the context of angiogenesis. The current study sought to investigate the production of angiogenesis-related factors by male and female VICs possessing quiescent (qVIC) or activated (aVIC) phenotypes. Production of several pro-angiogenic growth factors was elevated in porcine aVICs relative to qVICs, with sex differences found in both the total amounts secreted and their distribution across media vs. lysate. Porcine valvular endothelial cells (VECs) were also sex-separated in culture and found to behave similarly with respect to metabolic activity, viability, and tubulogenesis, but male VECs exhibited higher proliferation rates than female VECs. VECs responded to sex-matched media conditioned by VICs with increased tubulogenesis, but decreased proliferation, particularly upon treatment with aVIC-derived media. It is likely that this attenuation of proliferation resulted from a combination of decreased basic fibroblast growth factor and increased thrombospondin-2 (TSP2) secreted by aVICs. Overall, this study indicates that VICs regulate angiogenic VEC behavior via an array of paracrine molecules, whose secretion and sequestration are affected by both VIC phenotype and sex. Moreover, strong sex differences in TSP2 secretion by VICs may have implications for understanding sexual dimorphism in valve fibrosis, as TSP2 is also a powerful regulator of fibrosis.
The Child Is Capable: Anishinaabe Pedagogy of Land and Community
Authors: Peltier Sharla Mskokii
Published: September 2021

Situated within a post-Truth and Reconciliation Commission Canadian context, educators are seeking Wisdom to create space in schools for Indigenous Knowledges, perspectives, languages, and histories. An Anishinaabe scholar invites readers to make meaningful connections to knowledge from experience that centers the child within the context of an Anishinaabe summer harvest camp, a competition powwow, and a smokehouse. The storyteller takes an inward turn, exploring features of the communal learning process conducive to the learning spirit, self-evaluation, and participation in learning and teaching that matches one’s readiness and skill. The story is powerful for connecting the heart and mind, stimulating receptivity to assessment-making opportunities for teachers that are relevant to Indigenous student community teaching-learning traditions. True to the storytelling method, the stories here are meant to stimulate remembering, reflection, and a process of deep knowing. The author invites educators to think with the stories for inspiration toward personal possibilities of praxis. Positive educational transformation is set into motion as teachers connect with Indigenous peoples to honor the diversity of children, co-create a relational curriculum inclusive of family and community to embrace Indigenous Knowledge that comes from the Land, and create space to generate and transmit new knowledge through story.
Osteoporosis-Related Randomized Clinical Trials With Middle-Aged and Older Adults Registered on the International Clinical Trials Registry Platform
Authors: Lai Fenghua , Pei Ling , Chen Xinwen , Li Jin
Published: September 2021

Background

A better understanding of the current features of osteoporosis-related randomized clinical trials (RCTs) is important for improving clinical trial designs and promoting the translatability of results into benefits for patients. However, there is a lack of thorough evaluation of osteoporosis-related RCTs in middle-aged and older populations. Therefore, this study aimed to investigate the characteristics of registered RCTs on osteoporosis among middle-aged and older adults on the International Clinical Trials Registry Platform (ICTRP).

Methods

Osteoporosis-related RCTs registered on the ICTRP were searched on December 31, 2020. The main features of eligible RCTs were assessed. We searched PubMed, Google scholar, Medline, and Embase databases for the publication status of completed RCTs.

Results

A total of 537 osteoporosis-related RCTs were identified for analysis. The number of registered RCTs increased rapidly in 2005 (N = 47). Of these, 346 (64.4%) RCTs involved only women and 275 (51.2%) were retrospectively registered. Most RCTs were of open-label design (61.3%). The most common primary purpose of osteoporosis-related RCTs was treatment (72.3%). Intervention investigated was mainly focused on medication (62.8%), followed by lifestyle or education (19.0%), and dietary supplement (10.4%). After trial completion, the results of only 140 (35.5%) RCTs were available on the ICTRP, and the publication rate after trial completion was 30.5%.

Conclusions

RCTs on osteoporosis among middle-aged and older adults were dominated by retrospectively registered and open-label trials. Most trials lacked available results and associated publications. More awareness of prospective registration and blinding design in osteoporosis-related RCTs is needed. Further, publication and dissemination of RCTs results should be promoted.
Intrauterine Hyperglycemia Alters the Metabolomic Profile in Fetal Mouse Pancreas in a Gender-Specific Manner
Authors: Zhu Hong , Luo Si-Si , Cheng Yi , Yan Yi-Shang , Zou Ke-Xin , Ding Guo-Lian , Jin Li , Huang He-Feng
Published: September 2021

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition.
Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control
Authors: Zhang Dongxiao , Yamaguchi Satoshi , Zhang Xinhao , Yang Boxuan , Kurooka Naoko , Sugawara Ryosuke , Albuayjan Haya Hamed H. , Nakatsuka Atsuko , Eguchi Jun , Hiyama Takeshi Y. , Kamiya Atsunori , Wada Jun
Published: September 2021

In obesity and type 2 diabetes, numerous genes are differentially expressed, and microRNAs are involved in transcriptional regulation of target mRNAs, but miRNAs critically involved in the appetite control are not known. Here, we identified upregulation of miR-342-3p and its host gene Evl in brain and adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir342 (-/-) mice fed with HFHS chow were protected from obesity and diabetes. The hypothalamic arcuate nucleus neurons co-express Mir342 and EVL. The percentage of activated NPY+pSTAT3+ neurons were reduced, while POMC+pSTAT3+ neurons increased in Mir342 (-/-) mice, and they demonstrated the reduction of food intake and amelioration of metabolic phenotypes. Snap25 was identified as a major target gene of miR-342-3p and the reduced expression of Snap25 may link to functional impairment hypothalamic neurons and excess of food intake. The inhibition of miR-342-3p may be a potential candidate for miRNA-based therapy.
Long-Term Colony Dynamics and Fitness in a Colonial Tent-Web Spider Cyrtophora citricola
Authors: Yip Eric C. , Smith Deborah R. , Lubin Yael
Published: September 2021

Social animals are expected to experience a positive effect of conspecific number or density on fitness (an Allee effect) because of the benefits of group living. However, social animals also often disperse to live either solitarily or in small groups, so to understand why social animals leave their groups it is necessary to understand how group size affects both average fitness and the expected fitness outcomes of individuals. We examined the relationships between group size and fitness in the colonial spiderCyrtophora citricolausing long-term observations of colony demographics. We censused colonies, recording the number of juveniles, large females, and egg sacs, approximately every 2 months for 2 years. We also recorded the substrates supporting colony webs, including plant species and size, and the azimuth the colony occupied on the plant. Colonies in all regions showed cyclical patterns of growth and decline; however, regions were not synchronized, and seasonal effects differed between years. Colonies with fewer individuals at the initial observation were less likely to survive over the course of observations, and extinction rates were also influenced by an interaction between region and plant substrate. Small colonies were more likely to be extinct by the next census, but if they survived, they were more likely to have high growth rates compared to larger colonies. Despite the potential for high growth rates, high extinction rates depressed the average fitness of small colonies so that population growth rates peaked at intermediate colony sizes. Variance in egg sac production also peaked at intermediate colony sizes, suggesting that competitive interactions may increase the uneven distribution of resources in larger groups. Even if average fitness is high, if spiders can anticipate poor outcomes in large colonies, they may disperse to live solitarily or in smaller, less competitive groups.
Metabarcoding Analysis of Pollen Species Foraged by Osmia excavata Alfken (Hymenoptera: Megachilidae) in China
Authors: Lu Huanhuan , Dou Feiyue , Hao Youjin , Li Yue , Zhang Ke , Zhang Huan , Zhou Zeyang , Zhu Chaodong , Huang Dunyuan , Luo Arong
Published: September 2021

To meet the pollination need of economic crops, Osmia excavata has been successfully used to improve the pollination efficiency of Rosaceae and Brassicaceae plants. As a widely used pollinator of economic crops, a systematic study of flower-visiting species and diversities of O. excavata stocked in China was not found. To investigate the foraging pollen species and diversities of O. excavata, beebread from 20 experimental plots in China was collected by the trap-nesting method and analyzed by DNA metabarcoding technology. A total of 26 pollen plants in 14 genera and nine families were identified. A further analysis showed that the richness and abundance of the wild flowering plants in orchards and farmlands were lower than those in the nearby semi-natural habitats. The favorite pollen comes from economic crops apple and rape and wild flowering plants Juncus interior, Rosa gymnocarpa, and Rosa laevigata. Through a diversity index analysis, it was found that the Anhui region has the highest pollen plant diversity, while the Liaoning region has the lowest. Our results can provide a basis for flower-visiting species and diversities of O. excavata.
Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk
Authors: Lu Ye , Corradi Chiara , Gentiluomo Manuel , López de Maturana Evangelina , Theodoropoulos George E. , Roth Susanne , Maiello Evaristo , Morelli Luca , Archibugi Livia , Izbicki Jakob R. , Sarlós Patricia , Kiudelis Vytautas , Oliverius Martin , Aoki Mateus Nóbrega , Vashist Yogesh , van Eijck Casper H. J. , Gazouli Maria , Talar-Wojnarowska Renata , Mambrini Andrea , Pezzilli Raffaele , Bueno-de-Mesquita Bas , Hegyi Péter , Souček Pavel , Neoptolemos John P. , Di Franco Gregorio , Sperti Cosimo , Kauffmann Emanuele F. , Hlaváč Viktor , Uzunoğlu Faik G. , Ermini Stefano , Małecka-Panas Ewa , Lucchesi Maurizio , Vanella Giuseppe , Dijk Frederike , Mohelníková-Duchoňová Beatrice , Bambi Franco , Petrone Maria Chiara , Jamroziak Krzysztof , Guo Feng , Kolarova Katerina , Capretti Giovanni , Milanetto Anna Caterina , Ginocchi Laura , Loveček Martin , Puzzono Marta , van Laarhoven Hanneke W. M. , Carrara Silvia , Ivanauskas Audrius , Papiris Konstantinos , Basso Daniela , Arcidiacono Paolo G. , Izbéki Ferenc , Chammas Roger , Vodicka Pavel , Hackert Thilo , Pasquali Claudio , Piredda Maria L. , Costello-Goldring Eithne , Cavestro Giulia Martina , Szentesi Andrea , Tavano Francesca , Włodarczyk Barbara , Brenner Hermann , Kreivenaite Edita , Gao Xin , Bunduc Stefania , Vermeulen Roel C. H. , Schneider Martin A. , Latiano Anna , Gioffreda Domenica , Testoni Sabrina G. G. , Kupcinskas Juozas , Lawlor Rita T. , Capurso Gabriele , Malats Núria , Campa Daniele , Canzian Federico
Published: September 2021

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case–Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07–1.17, p = 3.03 × 10−6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.
Tumor Expression Profile Analysis Developed and Validated a Prognostic Model Based on Immune-Related Genes in Bladder Cancer
Authors: Dong Bingqi , Liang Jiaming , Li Ding , Song Wenping , Zhao Shiming , Ma Yongkang , Song Jinbo , Zhu Mingkai , Yang Tiejun
Published: September 2021

Background: Bladder cancer (BLCA) ranks 10th in incidence among malignant tumors and 6th in incidence among malignant tumors in males. With the application of immune therapy, the overall survival (OS) rate of BLCA patients has greatly improved, but the 5-year survival rate of BLCA patients is still low. Furthermore, not every BLCA patient benefits from immunotherapy, and there are a limited number of biomarkers for predicting the immunotherapy response. Therefore, novel biomarkers for predicting the immunotherapy response and prognosis of BLCA are urgently needed.

Methods: The RNA sequencing (RNA-seq) data, clinical data and gene annotation files for The Cancer Genome Atlas (TCGA) BLCA cohort were extracted from the University of California, Santa Cruz (UCSC) Xena Browser. The BLCA datasets GSE31684 and GSE32894 from the Gene Expression Omnibus (GEO) database were extracted for external validation. Immune-related genes were extracted from InnateDB. Significant differentially expressed genes (DEGs) were identified using the R package “limma,” and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for the DEGs were performed using R package “clusterProfiler.” Least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the signature model. The infiltration level of each immune cell type was estimated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The performance of the model was evaluated with receiver operating characteristic (ROC) curves and calibration curves.

Results: In total, 1,040 immune-related DEGs were identified, and eight signature genes were selected to construct a model using LASSO regression analysis. The risk score of BLCA patients based on the signature model was negatively correlated with OS and the immunotherapy response. The ROC curve for OS revealed that the model had good accuracy. The calibration curve showed good agreement between the predictions and actual observations.

Conclusions: Herein, we constructed an immune-related eight-gene signature that could be a potential biomarker to predict the immunotherapy response and prognosis of BLCA patients.
PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role
Authors: Hu Xi’e , Jia Jintong , Yang Zhenyu , Chen Songhao , Xue Jingyi , Duan Sensen , Yang Ping , Peng Shujia , Yang Lin , Yuan Lijuan , Bao Guoqiang
Published: September 2021

Background

Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 (PLCE1) single-nucleotide polymorphisms (SNPs) and GC susceptibility, but its relationship with GC prognosis lacked exploration, and the specific mechanisms were not elaborated fully yet. This study aimed to further explore the possible mechanism of the association between PLCE1 polymorphisms and GC.

Materials and Methods

A case-control study, including 588 GC patients and 703 healthy controls among the Chinese Han population, was performed to investigate the association between SNPs of PLCE1 and GC risk by logistic regression in multiple genetic models. The prognostic value of PLCE1 in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of PLCE1, various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations.

Results

Rs3765524 C > T, rs2274223 A > G and rs3781264 T > C in PLCE1 were associated with the increased risk of GC. The overall survival and progression-free survival of patients with high expression of PLCE1 were significantly lower than those with low expression [HR (95% CI) = 1.38 (1.1–1.63), P < 0.01; HR (95% CI) = 1.4 (1.07–1.84), P = 0.01]. Bioinformatic analysis revealed that PLCE1 was associated with protein phosphorylation and played a crucial role in the calcium signal pathway. Two important functional domains, catalytic binding pocket and calcium ion binding pocket, were found by homology modeling of PLCE1 protein; rs3765524 polymorphism could change the efficiency of the former, and rs2274223 polymorphism affected the activity of the latter, which may together play a potentially significant role in the tumorigenesis and prognosis of GC.

Conclusion

Patients with high expression of PLCE1 had a poor prognosis in GC, and SNPs in PLCE1 were associated with GC risk, which might be related to the changes in spatial structure of the protein, especially the variation of the efficiency of PLCE1 in the calcium signal pathway.