bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphatic Absorption of Microbial Plasmalogens in Rats
Authors: Sato Nana , Kanehama Aki , Kashiwagi Akiko , Yamada Miwa , Nishimukai Megumi
Published: March 2022

Plasmalogens, functional glycerophospholipids with biological roles in the human body, are associated with various diseases. Although a variety of saturated and/or unsaturated fatty acids in plasmalogens are presumed to have different functions in the human body, there are limited reports validating such functions of plasmalogens. In this study, we focused on the bacterial plasmalogen derived from Selenomonas ruminantium subsp. lactilytica (NBRC No. 103574) with different main species of hydrocarbon chains at the sn-1 position and shorter fatty acids at the sn-2 position than animal plasmalogens. Optimum culture conditions of S. ruminantium for high-yield production of plasmalogens, such as pH and the concentration of caproic acid, were investigated under anaerobic conditions using a 2-L scale jar fermenter. The obtained plasmalogen mainly consisted of the ethanolamine plasmalogen (PlsEtn). The molar ratios of PlsEtn species obtained from S. ruminantium, at sn-1/sn-2 positions, were p16:1/14:0 (68.4%), p16:1/16:1 (29.2%), p16:1/16:0 (0.7%), p16:1/15:0 (0.3%), and p17:1/14:0 (0.3%). Subsequently, duodenal infusion of the emulsion carrying the lipid extracted from S. ruminantium was carried out in lymph duct-cannulated rats. In the lymphatic plasmalogen of rats, the level of PlsEtns with molar ratios p16:1/14:0 and p16:1/16:1, the main species of plasmalogens from S. ruminantium, increased gradually until 3–4 h after lipid injection and then gradually decreased. In addition, the level of PlsEtns with p16:1/20:4 and p16:1/22:6 rapidly increased, peaking at 1–1.5 h and 1.5–2 h after lipid injection, respectively. The increase in the number of PlsEtns with p16:1/20:4 and p16:1/22:6 suggested that 20:4 and 22:6, the main fatty acids at the sn-2 position in the rat lymphatic plasmalogen, were preferentially re-esterified at the sn-2 position, regardless of the types of hydrocarbon chains at the sn-1 position. Thus, we showed that bacterial PlsEtns with “unnatural” structures against rats could be absorbed into the lymph. Our findings provide insights into the association between the chemical structure of plasmalogens and their biological functions in humans.
Osteogenesis-Related Long Noncoding RNA GAS5 as a Novel Biomarker for Osteonecrosis of Femoral Head
Authors: Liu Guanzhi , Luo Sen , Lei Yutian , Jiao Ming , Cao Ruomu , Guan Huanshuai , Tian Run , Wang Kunzheng , Yang Pei
Published: March 2022

Background: The lack of effective biomarkers makes it difficult to achieve early diagnosis and intervention for osteonecrosis of the femoral head (ONFH). Hence, we aimed to identify novel long noncoding RNA (lncRNA) biomarkers for ONFH.

Methods: High-throughput RNA sequencing was performed to detect lncRNA and mRNA expression levels in subchondral bone samples from three patients with ONFH and three patients with femoral neck fractures. Integrated bioinformatics analyses were conducted to identify lncRNAs associated with ONFH development and their potential functions and signaling pathways. A co-expression network was constructed based on the gene time-series expression data in GSE113253. After selecting lncRNA GAS5 as a novel biomarker for ONFH, bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation assays were performed to verify the association between lncRNA GAS5 and osteogenic differentiation. Alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to measure the osteogenic phenotype and lncRNA GAS5 expression. Finally, for further validation, ONFH rat models were established, and lncRNA GAS5 expression in subchondral bone was detected by RT-qPCR.

Results: We identified 126 and 959 differentially expressed lncRNAs and genes, respectively. lncRNA GAS5 expression level was significantly downregulated in patients with ONFH compared to the control group patients. The BMSC osteogenic differentiation assays showed that ALP activity increased gradually from days 3 to 7, while the lncRNA GAS5 expression level was significantly upregulated in the osteogenic differentiation induction groups. Furthermore, in vivo experiments suggested that the bone volume/tissue volume value and trabecular thickness significantly decreased in the ONFH rat model group compared to the control group, whereas the trabecular space significantly increased in the ONFH group compared to the control group. In addition, the lncRNA GAS5 expression level significantly decreased in the ONFH rat model group.

Conclusion: The lncRNA GAS5 expression level was highly associated with BMSC osteogenic differentiation and was significantly downregulated in both the subchondral trabecular bone tissue of ONFH patients and ONFH rat models. Therefore, lncRNA GAS5 can serve as an ONFH osteogenic biomarker to provide an effective target for early diagnosis and molecular therapy of ONFH.
The Mitochondria-Targeting Agent MitoQ Improves Muscle Atrophy, Weakness and Oxidative Metabolism in C26 Tumor-Bearing Mice
Authors: Pin Fabrizio , Huot Joshua R. , Bonetto Andrea
Published: March 2022

Cancer cachexia is a debilitating syndrome characterized by skeletal muscle wasting, weakness and fatigue. Several pathogenetic mechanisms can contribute to these muscle derangements. Mitochondrial alterations, altered metabolism and increased oxidative stress are known to promote muscle weakness and muscle catabolism. To the extent of improving cachexia, several drugs have been tested to stimulate mitochondrial function and normalize the redox balance. The aim of this study was to test the potential beneficial anti-cachectic effects of Mitoquinone Q (MitoQ), one of the most widely-used mitochondria-targeting antioxidant. Here we show that MitoQ administration (25 mg/kg in drinking water, daily) in vivo was able to improve body weight loss in Colon-26 (C26) bearers, without affecting tumor size. Consistently, the C26 hosts displayed ameliorated skeletal muscle and strength upon treatment with MitoQ. In line with improved skeletal muscle mass, the treatment with MitoQ was able to partially correct the expression of the E3 ubiquitin ligases Atrogin-1 and Murf1. Contrarily, the anabolic signaling was not improved by the treatment, as showed by unchanged AKT, mTOR and 4EBP1 phosphorylation. Assessment of gene expression showed altered levels of markers of mitochondrial biogenesis and homeostasis in the tumor hosts, although only Mitofusin-2 levels were significantly affected by the treatment. Interestingly, the levels of Pdk4 and CytB, genes involved in the regulation of mitochondrial function and metabolism, were also partially increased by MitoQ, in line with the modulation of hexokinase (HK), pyruvate dehydrogenase (PDH) and succinate dehydrogenase (SDH) enzymatic activities. The improvement of the oxidative metabolism was associated with reduced myosteatosis (i.e., intramuscular fat infiltration) in the C26 bearers receiving MitoQ, despite unchanged muscle LDL receptor expression, therefore suggesting that MitoQ could boost β-oxidation in the muscle tissue and promote a glycolytic-to-oxidative shift in muscle metabolism and fiber composition. Overall, our data identify MitoQ as an effective treatment to improve skeletal muscle mass and function in tumor hosts and further support studies aimed at testing the anti-cachectic properties of mitochondria-targeting antioxidants also in combination with routinely administered chemotherapy agents.
Methotrexate-Lactoferrin Targeted Exemestane Cubosomes for Synergistic Breast Cancer Therapy
Authors: Mokhtar Sarah , Khattab Sherine N. , Elkhodairy Kadria A. , Teleb Mohamed , Bekhit Adnan A. , Elzoghby Ahmed O. , Sallam Marwa A.
Published: March 2022

While the treatment regimen of certain types of breast cancer involves a combination of hormonal therapy and chemotherapy, the outcomes are limited due to the difference in the pharmacokinetics of both treatment agents that hinders their simultaneous and selective delivery to the cancer cells. Herein, we report a hybrid carrier system for the simultaneous targeted delivery of aromatase inhibitor exemestane (EXE) and methotrexate (MTX). EXE was physically loaded within liquid crystalline nanoparticles (LCNPs), while MTX was chemically conjugated to lactoferrin (Lf) by carbodiimide reaction. The anionic EXE-loaded LCNPs were then coated by the cationic MTX–Lf conjugate via electrostatic interactions. The Lf-targeted dual drug-loaded LCNPs exhibited a particle size of 143.6 ± 3.24 nm with a polydispersity index of 0.180. It showed excellent drug loading with an EXE encapsulation efficiency of 95% and an MTX conjugation efficiency of 33.33%. EXE and MTX showed synergistic effect against the MCF-7 breast cancer cell line with a combination index (CI) of 0.342. Furthermore, the Lf-targeted dual drug-loaded LCNPs demonstrated superior synergistic cytotoxic activity with a combination index (CI) of 0.242 and a dose reduction index (DRI) of 34.14 and 4.7 for EXE and MTX, respectively. Cellular uptake studies demonstrated higher cellular uptake of Lf-targeted LCNPs into MCF-7 cancer cells than non-targeted LCNPs after 4 and 24 h. Collectively, the targeted dual drug-loaded LCNPs are a promising candidate offering combinational hormonal therapy/chemotherapy for breast cancer.
Synthesis and Modification of Tetrahedron Li10.35Si1.35P1.65S12via Elemental Doping for All-Solid-State Lithium Batteries
Authors: Lin Yuanzhong , Chen Jian , Yan Jiawei , Zhuang Yanhua , Lu Hengyi , Zhao Chenyang
Published: March 2022

Solid-state electrolyte (SSE), as the core component of solid-state batteries, plays a critical role in the performance of the batteries. Currently, the development of SSE is still hindered by its high price, low ionic conductivity, and poor interface stability. In this work, we report the tailored synthesis of a high ionic conductive and low cost sulfide SSE for all-solid-state lithium batteries. The Li10.35Si1.35P1.65S12 with favorable tetragonal structure was synthesis by increasing the concentration of Si4+, which shows an ionic conductivity of 4.28 × 10−3 S cm−1 and a wide electrochemical stability window of up to 5 V. By further modifying the composition of the electrolyte via ionic doping, the ionic conductivity of Li10.35Si1.35P1.65S12 can be further enhanced. Among them, the 1% Co4+-doped Li10.35Si1.35P1.65S12 shows the highest ionic conductivity of 6.91 × 10−3 S cm−1, 40% higher than the undoped one. This can be attributed to the broadened MS4− tetrahedrons and increased Li+ concentration. As a demonstration, an all-solid-state Li metal battery was assembled using TiS2 as the cathode and 1% Co4+-doped Li10.35Si1.35P1.65S12 as the electrolyte, showing capacity retention of 72% at the 110th cycle. This strategy is simple and can be easily extended for the construction of other high-performance sulfide SSEs.
Carbon Dioxide Solubility in Nonionic Deep Eutectic Solvents Containing Phenolic Alcohols
Authors: Alhadid Ahmad , Safarov Javid , Mokrushina Liudmila , Müller Karsten , Minceva Mirjana
Published: March 2022

Deep eutectic solvents (DES) are a new class of green solvents that have shown unique properties in several process applications. This study evaluates nonionic DES containing phenolic alcohols as solvents for carbon dioxide (CO2) capture applications. Potential phenolic alcohols and the molar ratio between DES constituents were preselected for experimental investigations based on the conductor-like screening model for realistic solvation (COSMO-RS). CO2 solubility was experimentally determined in two different DES, namely, L-menthol/thymol in 1:2 molar ratio and thymol/2,6-xylenol in 1:1 molar ratio, at various temperatures and pressures. CO2 solubility in the studied systems was higher than that reported in the literature for ionic DES and ionic liquids. This study demonstrates that nonionic DES containing phenolic alcohols can be excellent, inexpensive, and simple solvents for CO2 capture.
A LysR Transcriptional Regulator Manipulates Macrophage Autophagy Flux During Brucella Infection
Authors: Zhang Lu , Yu Siyuan , Ning Xinnuan , Fang Hui , Li Jie , Zhi Feijie , Li Junmei , Zhou Dong , Wang Aihua , Jin Yaping
Published: March 2022

Brucella, the intracellular bacteria, have evolved subtle strategies to efficiently survive and replicate in macrophages. However, the virulence effector proteins involved are still unclear. LysR-type transcriptional regulators (lttrs) are the largest regulator family with diverse function in prokaryotes. However, very little is known about the role of LysR regulators in the Brucella spp. Here, a BSS2_II0858 gene, encoded as one of the LysR-type regulators, was studied. We successfully constructed a BSS2_II0858 deletion mutant, Δ0858, and complementation strain CΔ0858 in Brucella suis S2. The cell apoptosis induced by B. suis S2 and its derivatives were detected by flow cytometry. The autophagy was then assessed by immunoblot analysis using the IL3I/II and p62 makers. In addition, the autophagy flux was evaluated by double fluorescent labeling method for autophagy marker protein LC3. Our studies demonstrated that B. suis S2 and its derivatives inhibited the programmed cell death in early stage and promoted apoptosis in the later stage during infection in RAW264.7 cells. The BSS2_II0858 gene was found to play no role during apoptosis according to these results. Compared with the wild-type strain, Δ0858 mutant can stimulate the conversion of LC3-I to LC3-II and markedly inhibited the autophagy flux at early stage leading to obvious autophagosome accumulation. This study explored the function of BSS2_II0858 gene and may provide new insights for understanding the mechanisms involved in the survival of Brucella in macrophages.
Semi-Quantitative Assay to Measure Urease Activity by Urinary Catheter-Associated Uropathogens
Authors: Duran Ramirez Jesus M. , Gomez Jana , Obernuefemann Chloe L. P. , Gualberto Nathaniel C. , Walker Jennifer N.
Published: March 2022

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is left untreated, the crystals can grow until they block the urinary catheter. Catheter blockage and subsequent failure reduces the quality of life for the chronically catheterized, as it requires frequent catheter exchanges and can promote more severe disease, including dissemination of the infection to the kidneys or bloodstream. Thus, understanding how urease contributes to catheter blockages and/or more severe disease among the broad range of urease-producing microbes may provide insights into better prevention or treatment strategies. However, clinical assays that detect urease production among clinical isolates are qualitative and prioritize the detection of urease from Proteus mirabilis, the most well-studied uropathogenic urease producer. While urease from other known urease producers, such as Morganella morganii, can also be detected with these methods, other uropathogens, including Staphylococcus aureus and Klebsiella pneumonia, are harder to detect. In this study, we developed a high throughput, semiquantitative assay capable of testing multiple uropathogens in a rapid and efficient way. We validated the assay using Jack Bean urease, the urease producing species: Proteus spp., M. morganii, K. pneumonia, and S. aureus strains, and the non-urease producer: Escherichia coli. This modified assay more rapidly detected urease-producing strains compared to the current clinical test, Christensen Urea Agar, and provided semiquantitative values that may be used to further investigate different aspects of urease regulation, production, or activity in these diverse species. Furthermore, this assay can be easily adapted to account for different environmental stimuli affecting urease production, including bacterial concentration, aeration, or addition of anti-urease compounds.
Introduction of the Rapid Deployment Aortic Valve System Use in Elderly Patients With Endocarditis
Authors: Öner Alper , Hemmer Christoph , Alozie Anthony , Löser Benjamin , Dohmen Pascal M.
Published: March 2022

Introduction

The rapid-deployment valve system (RDVS) was introduced to facility minimally invasive aortic valve replacement. In this study we evaluate the potential benefits of RDVS in elderly high-risk patients with endocarditis of the aortic valve.

Materials and Methods

Since the introduction of RDVS in our institution in December 2017 through October 2021, EDWARDS INTUITY rapid-deployment prosthesis (Model 8300A, Edwards Lifesciences, Irvine, CA, USA) has been implanted in a total of 115 patients for different indications by a single surgeon. Out of one-hundred and fifteen cases of RDVS implantation, seven patients with a median age of 77 yrs. (range 62–84yrs.), suffered from active infective endocarditis of the aortic valve. The median EuroSCORE II of these highly selected patient cohort was 77% (range 19–80%). Patient data were evaluated perioperatively including intra-operative data as well as in-hospital morbidity/mortality and follow-up after discharge from hospital.

Results

Three patients underwent previous cardiac surgery. Concomitant procedures were performed in six patients including, ascending aorta replacement (n = 3), mitral valve repair (n = 1), pulmonary valve replacement (n = 1), bypass surgery (n = 1), left atrial appendix resection (n = 1) and anterior mitral valve repair (n = 1). Median aortic cross-clamp and cardiopulmonary bypass time was 56 min (range 29–122 min) and 81 min (range 45–162 min.), respectively. Post-operative complications in these elderly high-risk patients were atrial fibrillation (n = 3) and re-exploration for pericardial effusion (n = 1). One pacemaker implantation was required on postoperative day 6 due to sick sinus syndrome. There was one in-hospital death (14%) and one during follow-up (14%).

Conclusion

Rapid-deployment aortic valve system seems to be a viable option with acceptable morbidity and mortality in elderly high-risk patients with active infective endocarditis of the aortic valve.
Formation and Maintenance of the Natural Bypass Vessels of the Brain
Authors: Perovic Tijana , Harms Christoph , Gerhardt Holger
Published: March 2022

Ischemic diseases are the leading cause of death and disability worldwide. The main compensatory mechanism by which our body responds to reduced or blocked blood flow caused by ischemia is mediated by collateral vessels. Collaterals are present in many healthy tissues (including brain and heart) and serve as natural bypass vessels, by bridging adjacent arterial trees. This review focuses on: the definition and significance of pial collateral vessels, the described mechanism of pial collateral formation, an overview of molecular players and pathways involved in pial collateral biology and emerging approaches to prevent or mitigate risk factor-associated loss of pial collaterals. Despite their high clinical relevance and recent scientific efforts toward understanding collaterals, much of the fundamental biology of collaterals remains obscure.
Occlusion of Bilobulated Left Atrial Appendage Using the Dual-Watchman Technique: A Long-Term Follow-Up Study
Authors: Chen Tao , Wang Qing-song , Liu Ge , Lu Xu , Song Ting-ting , Shi Ming-yuan , Zhu Hang , Mu Yang , Guo Jun , Chen Yun-dai
Published: March 2022

Background

Percutaneous left atrial appendage (LAA) occlusion has been considered an efficient alternative to oral anticoagulation to prevent embolic events in patients with non-valvular atrial fibrillation (NVAF). Due to the complexities and heterogeneous anatomy of the LAA structure, the single-device approach may not always fit a large bilobulated LAA. This study aimed to evaluate the feasibility and safety of one-stop dual Watchman implantation for patients with bilobulated LAA.

Methods

Included in the analysis were patients who underwent complete LAA closure with dual Watchman devices between December 2015 and December 2021. The anatomic morphology, procedure characteristics, procedure safety, and procedural complications were analyzed. Cardiac CT or transesophageal ultrasound was obtained at 7 days, 6 months, 1 year, and 2 years post-operatively to evaluate the effect of occlusion.

Results

Among the 330 patients who underwent LAA occlusion during the study period, 7 (2.1%) patients were occluded with one-stop implantation of the double Watchman strategy. Successful occlusion was achieved in all patients. One patient had the double-access sheath strategy for implantation, and 6 patients had only a single-access sheath strategy for implantation. Pericardial effusion occurred in one case during the 7-day perioperative period. There was no device embolization, thrombosis, or obvious peridevice leakage (≥l mm) during the 2-year follow-up, with the exception of two cases with 2 mm of incomplete LAA sealing.

Conclusion

The one-stop implantation of a dual Watchman is feasible and safe and might provide a strategy to occlude a large bilobulated LAA when incomplete closure is inevitable with a single device.
Candida albicans and Early Childhood Caries
Authors: Menon Leena U. , Scoffield Jessica A. , Jackson Janice G. , Zhang Ping
Published: March 2022

Early childhood caries (ECC) is a highly prevalent and costly chronic oral infectious disease in preschool children. Candida albicans has been frequently detected in children and has demonstrated cariogenic traits. However, since ECC is a multifactorial infectious disease with many predisposing non-microbial factors, it remains to be elucidated whether the presence and accumulation of C. albicans in ECC is merely a consequence of the adaptation of C. albicans to a cariogenic oral environment, or it plays an active role in the initiation and progression of dental caries. This review aims to summarize the current knowledge on C. albicans and the risk of ECC, with a focus on its synergistic relationship with the cariogenic pathogen Streptococcus mutans. We also highlight recent advances in the development of approaches to disrupt C. albicans-S. mutans cross-kingdom biofilms in ECC prevention and treatment. Longitudinal clinical studies, including interventional clinical trials targeting C. albicans, are necessary to ascertain if C. albicans indeed contributes in a significant manner to the initiation and progression of ECC. In addition, further work is needed to understand the influence of other bacteria and fungi of oral microbiota on C. albicans-S. mutans interactions in ECC.
Fluid Inclusion, Isotopic, and Elemental Geochemistry Studies of Cave-Filling Calcite in the Lower–Middle Ordovician Yingshan Formation of Tahe Oilfield, NW China: Implication for Karstification in Non-exposed Limestone
Authors: Zhang Yongmei , Zhang Shaonan , Huang Baiwen , Lu Ziye , Ye Ning , Zhu Bei , Hou Xianhai , Xie Fei , Bai Xiaoliang , Zhang Xinyan
Published: March 2022

Improving the recognition of paleo-fluid circulation history is of great significance to reconstruct pore evolution during carbonate diagenesis. Integrated petrography, fluid inclusion, isotopic and elemental geochemistry (laser ablation inductively coupled plasma mass spectrometry) studies, calcites generated in paleocaves, and fractures were investigated. This study aims to reveal the paleo-fluid origin and karstification event within the nonexposed limestone of the Lower–Middle Ordovician Yingshan Formation in the Tarim Basin. The only generation of blocky calcite growing along the karst paleocave and fracture walls [cave-filling calcite (CFC)] crosscuts burial stylolites. The secondary fluid inclusions obtained from CFC are characterized by the coexistence of liquid-only and liquid-dominated aqueous inclusions with low salinities values (0–2.4 wt%), suggesting that the CFC has experienced a low-temperature environment (<50°C). The depleted δ18O values (−15.32‰ to 12.45‰), seawater-like yttrium and rare earth element patterns, and low ΣREE (<0.65 ppm) have recorded the major episode of meteoric water leaching the Yingshan limestone. This view was further confirmed by the calculated δ18Owater values of parent fluids (−14.3‰ to 2.2‰). The relatively higher 87Sr/86Sr ratios (0.70942–0.70994) are interpreted as the result of meteoric water interacting with the overlying Silurian detrital rock when percolated downward. The geochemical evidence recorded by CFC indicates that the karstification event for Yingshan nonexposed limestone possibly took place in the Early Hercynian period during the late Devonian. Therefore, meteoric water percolating downward along the fractures penetrating insoluble strata and/or migrating laterally along the permeable strata is deemed responsible for the karstification event, although the overlying thick insoluble strata in the coverage area.
Modeling and Simulation of Large-Scale Wind Power Base Output Considering the Clustering Characteristics and Correlation of Wind Farms
Authors: Zhao Mingzhe , Wang Yimin , Wang Xuebin , Chang Jianxia , Zhou Yong , Liu Tao
Published: March 2022

The rapid development of renewable energy improves the requirements of renewable energy output simulation. The clustering characteristics and correlation of renewable energy would improve the accuracy of power output simulation. To clarify the typical power output process of a large-scale wind power base, a novel method is proposed for wind power output scene simulation in this paper. Firstly, the genetic algorithm (GA) Kmeans is used to divide the wind farm clusters. The wind power output of each cluster is calculated by the wind turbine model. Then, the Copula principle is used to describe the correlation characteristic of wind farm clusters. Finally, the power output scenes are simulated by the Markov chain Monte Carlo (MCMC) method. To verify the effectiveness of proposed method, the wind power base in the downstream Yalong River basin is taken as the case study. The results show that the 65 wind farms should be divided into 6 clusters. The five typical power output scenes in winter–spring and summer–autumn seasons are simulated respectively based on the clustering characteristics and correlation of wind farms. This study provides a valuable reference for other large-scale renewable power bases all over the world.
Large-Eddy Simulation of the Boundary Layer Development in a Low-Pressure Turbine Cascade With Passive Flow Control
Authors: Yang Pengcheng , Chen Shaowen , Li Weihang , Zeng Cong
Published: March 2022

The boundary layer development on a low-pressure turbine blade surface modified by recessed dimples, U-grooves, and rectangular grooves has been investigated through the large-eddy simulations. The simulations are performed at a Reynolds number of 50,000 (based on the inlet velocity and axial chord length) and extremely low freestream turbulence conditions. The characteristic parameters of the boundary layer are used to estimate the development of the boundary layer, and spectral analysis has also been performed to identify the dominant frequency of shedding vortices. The results of simulations indicate that three surface modifications all reduce the profile losses by restraining the separation bubble size. However, the grooves and dimples show different mechanisms in inhibiting laminar separation. Grooves tend to promote the formation of spanwise vortices, which is more difficult to break into turbulence. A high-speed shedding vortex is induced by the particular 3D structure of dimple, and its shedding frequency is nearly twice the Kelvin–Helmholtz (K-H) instability frequency. The interaction between the shedding vortices and the K-H vortices promotes the breakdown process of the spanwise vortices, which leads to an earlier transition of the boundary layer at a low disturbance level. The current study reveals the different mechanisms of dimples and grooves and shows the great potential of dimples for flow control in low-pressure turbines. Besides, the flow structures inside the dimples with adverse pressure gradients are also explored.
CLCC1 c. 75C>A Mutation in Pakistani Derived Retinitis Pigmentosa Families Likely Originated With a Single Founder Mutation 2,000–5,000 Years Ago
Authors: Ma Yan , Wang Xun , Shoshany Nadav , Jiao Xiaodong , Lee Adrian , Ku Gregory , Baple Emma L. , Fasham James , Nadeem Raheela , Naeem Muhammad Asif , Riazuddin Sheikh , Riazuddin S. Amer , Crosby Andrew H. , Hejtmancik J. Fielding
Published: March 2022

Background: A CLCC1 c. 75C > A (p.D25E) mutation has been associated with autosomal recessive pigmentosa in patients in and from Pakistan. CLCC1 is ubiquitously expressed, and knockout models of this gene in zebrafish and mice are lethal in the embryonic period, suggesting that possible retinitis pigmentosa mutations in this gene might be limited to those leaving partial activity. In agreement with this hypothesis, the mutation is the only CLCC1 mutation associated with retinitis pigmentosa to date, and all identified patients with this mutation share a common SNP haplotype surrounding the mutation, suggesting a common founder.

Methods: SNPs were genotyped by a combination of WGS and Sanger sequencing. The original founder haplotype, and recombination pathways were delineated by examination to minimize recombination events. Mutation age was estimated by four methods including an explicit solution, an iterative approach, a Bayesian approach and an approach based solely on ancestral segment lengths using high density SNP data.

Results: All members of each of the nine families studied shared a single autozygous SNP haplotype for the CLCC1 region ranging from approximately 1–3.5 Mb in size. The haplotypes shared by the families could be derived from a single putative ancestral haplotype with at most two recombination events. Based on the haplotype and Gamma analysis, the estimated age of the founding mutation varied from 79 to 196 generations, or approximately 2,000–5,000 years, depending on the markers used in the estimate. The DMLE (Bayesian) estimates ranged from 2,160 generations assuming a population growth rate of 0–309 generations assuming a population growth rate of 2% with broad 95% confidence intervals.

Conclusion: These results provide insight into the origin of the CLCC1 mutation in the Pakistan population. This mutation is estimated to have occurred 2000–5,000 years ago and has been transmitted to affected families of Pakistani origin in geographically dispersed locations around the world. This is the only mutation in CLCC1 identified to date, suggesting that the CLCC1 gene is under a high degree of constraint, probably imposed by functional requirements for this gene during embryonic development.
Extracellular HMGB1 Impairs Macrophage-Mediated Efferocytosis by Suppressing the Rab43-Controlled Cell Surface Transport of CD91
Authors: Wang Yao , Zhang Wen , Xu Yu , Wu Di , Gao Zhan , Zhou Jianchun , Qian Hang , He Binfeng , Wang Guansong
Published: March 2022

High-mobility group box 1 (HMGB1) protein can impair phagocyte function by suppressing the macrophage-mediated clearance of apoptotic cells (ACs), thereby delaying inflammation resolution in the lungs and allowing the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the precise mechanism underlying this HMGB1-mediated inhibition of efferocytosis remains unknown. The aim of this study was to determine the effect of HMGB1 on macrophage-mediated efferocytosis. We discovered that HMGB1 prevented efferocytosis by bone marrow-derived macrophages (BMDMs) and suppressed the expression of Ras-related GTP-binding protein 43 (Rab43), a member of the Ras-associated binding (Rab) family. The downregulation of Rab43 expression resulted in impaired clearance of apoptotic thymocytes by BMDMs. Subsequent analysis of HMGB1-treated and Rab43-deficient BMDMs revealed the inhibited transport of cluster of differentiation 91 (CD91), a phagocyte recognition receptor, from the cytoplasm to the cell surface. Notably, Rab43 directly interacted with CD91 to mediate its intercellular trafficking. Furthermore, Rab43 knockout delayed the inflammation resolution and aggravated the lung tissue damage in mice with ALI. Therefore, our results provide evidence that HMGB1 impairs macrophage-mediated efferocytosis and delays inflammation resolution by suppressing the Rab43-regulated anterograde transport of CD91, suggesting that the restoration of Rab43 levels is a promising strategy for attenuating ALI and ARDS in humans.
Cancer Metabolism: The Role of Immune Cells Epigenetic Alteration in Tumorigenesis, Progression, and Metastasis of Glioma
Authors: Kanwore Kouminin , Kanwore Konimpo , Adzika Gabriel Komla , Abiola Ayanlaja Abdulrahman , Guo Xiaoxiao , Kambey Piniel Alphayo , Xia Ying , Gao Dianshuai
Published: March 2022

Glioma is a type of brain and spinal cord tumor that begins in glial cells that support the nervous system neurons functions. Age, radiation exposure, and family background of glioma constitute are risk factors of glioma initiation. Gliomas are categorized on a scale of four grades according to their growth rate. Grades one and two grow slowly, while grades three and four grow faster. Glioblastoma is a grade four gliomas and the deadliest due to its aggressive nature (accelerated proliferation, invasion, and migration). As such, multiple therapeutic approaches are required to improve treatment outcomes. Recently, studies have implicated the significant roles of immune cells in tumorigenesis and the progression of glioma. The energy demands of gliomas alter their microenvironment quality, thereby inducing heterogeneity and plasticity change of stromal and immune cells via the PI3K/AKT/mTOR pathway, which ultimately results in epigenetic modifications that facilitates tumor growth. PI3K is utilized by many intracellular signaling pathways ensuring the proper functioning of the cell. The activation of PI3K/AKT/mTOR regulates the plasma membrane activities, contributing to the phosphorylation reaction necessary for transcription factors activities and oncogenes hyperactivation. The pleiotropic nature of PI3K/AKT/mTOR makes its activity unpredictable during altered cellular functions. Modification of cancer cell microenvironment affects many cell types, including immune cells that are the frontline cells involved in inflammatory cascades caused by cancer cells via high cytokines synthesis. Typically, the evasion of immunosurveillance by gliomas and their resistance to treatment has been attributed to epigenetic reprogramming of immune cells in the tumor microenvironment, which results from cancer metabolism. Hence, it is speculative that impeding cancer metabolism and/or circumventing the epigenetic alteration of immune cell functions in the tumor microenvironment might enhance treatment outcomes. Herein, from an oncological and immunological perspective, this review discusses the underlying pathomechanism of cell-cell interactions enhancing glioma initiation and metabolism activation and tumor microenvironment changes that affect epigenetic modifications in immune cells. Finally, prospects for therapeutic intervention were highlighted.
Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation
Authors: Papp Alexandra , Papp Krisztián , Uzonyi Barbara , Cserhalmi Marcell , Csincsi Ádám I. , Szabó Zsóka , Bánlaki Zsófia , Ermert David , Prohászka Zoltán , Erdei Anna , Ferreira Viviana P. , Blom Anna M. , Józsi Mihály
Published: March 2022

Components of the extracellular matrix (ECM), when exposed to body fluids may promote local complement activation and inflammation. Pathologic complement activation at the glomerular basement membrane and at the Bruch’s membrane is implicated in renal and eye diseases, respectively. Binding of soluble complement inhibitors to the ECM, including factor H (FH), is important to prevent excessive complement activation. Since the FH-related (FHR) proteins FHR1 and FHR5 are also implicated in these diseases, our aim was to study whether these FHRs can also bind to ECM components and affect local FH activity and complement activation. Both FH and the FHRs showed variable binding to ECM components. We identified laminin, fibromodulin, osteoadherin and PRELP as ligands of FHR1 and FHR5, and found that FHR1 bound to these ECM components through its C-terminal complement control protein (CCP) domains 4-5, whereas FHR5 boundviaits middle region, CCPs 3-7. Aggrecan, biglycan and decorin did not bind FH, FHR1 and FHR5. FHR5 also bound to immobilized C3b, a model of surface-deposited C3b,viaCCPs 3-7. By contrast, soluble C3, C3(H2O), and the C3 fragments C3b, iC3b and C3d bound to CCPs 8-9 of FHR5. Properdin, which was previously described to bindviaCCPs 1-2 to FHR5, did not bind in its physiologically occurring serum forms in our assays. FHR1 and FHR5 inhibited the binding of FH to the identified ECM proteins in a dose-dependent manner, which resulted in reduced FH cofactor activity. Moreover, both FHR1 and FHR5 enhanced alternative complement pathway activation on immobilized ECM proteins when exposed to human serum, resulting in the increased deposition of C3-fragments, factor B and C5b-9. Thus, our results identify novel ECM ligands of FH family proteins and indicate that FHR1 and FHR5 are competitive inhibitors of FH on ECM and, when bound to these ligands, they may enhance local complement activation and promote inflammation under pathological conditions.
Construction and Validation of a Novel Pyroptosis-Related Four-lncRNA Prognostic Signature Related to Gastric Cancer and Immune Infiltration
Authors: Wang Zhengguang , Cao Lei , Zhou Sitong , Lyu Jin , Gao Yang , Yang Ronghua
Published: March 2022

Increasing evidence has demonstrated that pyroptosis, a type of inflammatory programmed cell death, plays an important role in the pathogenesis and progression of gastric cancer. However, it remains unclear whether pyroptosis-related long non-coding RNAs (lncRNAs) can be used to predict the diagnosis and prognosis of gastric adenocarcinoma. This study aimed to evaluate and test the role of the lncRNA signature associated with pyroptosis as a prognostic tool for stomach adenocarcinoma (STAD) and to ascertain their immune value. Relative RNA-sequencing data were extracted from The Cancer Genome Atlas database (TCGA), and data preprocessing was performed for STAD. Pearson correlation analysis was used to determine whether lncRNAs were significantly correlated with pyroptosis based on 23 genes related to pyroptosis. Univariate Cox regression and least absolute shrinkage and selection operator(LASSO) analyses were both adopted to select features and establish the pyroptosis-related lncRNA (PRL) prognostic signature. Kaplan–Meier(KM) survival analysis of the different risk groups was conducted according to the risk scores. We further examined the functional enrichment, tumor microenvironment, and landscape of mutation status among the different risk groups, and these analyses further explained the reasons for the differences in the prediction as well as survival value of the different risk groups. Four lncRNAs, including HAND2-AS1, LINC01354, RP11-276H19.1, and PGM5-AS1, were involved in the PRL signature and used to split STAD patients into two risk groups. Overall survival time(OS) was significantly higher in the low-risk group than in the high-risk group in both the training and validation groups. Functional enrichment analysis was further employed to analyze differentially expressed genes in high- and low-risk groups to identify potential molecular functions and pathways associated with pyroptosis in the gastric cancer microenvironment. Protein-protein interaction (PPI) and Friends analysis identified hub genes that may play a key role in differentially expressed genes in high- and low-risk groups. In addition, there were remarkable discrepancies between the different risk groups in the tumor stage (P < 0.01) and histologic grade (P < 0.05). Furthermore, drug-susceptibility testing indicated potential sensitive chemotherapeutic drugs for each risk group. This study is the first to establish and validate STAD-associated PRLs that can effectively guide the prognosis and the immune microenvironment in STAD patients and provide evidence for the development of molecularly targeted therapies related to pyroptosis.
Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish
Authors: Wang Zixuan , Xu Jing , Feng Jianhua , Wu Kaizheng , Chen Kangyong , Jia Zhao , Zhu Xiaozhen , Huang Wenji , Zhao Xin , Liu Qin , Wang Bangjie , Chen Xinhua , Wang Junya , Zou Jun
Published: March 2022

Teleost type I interferons (IFNs) are categorized into group I and II subgroups that bind to distinct receptors to activate antiviral responses. However, the interaction between ifn ligands and receptors has not fully been understood. In this study, the crystal structure of grass carp [Ctenopharyngodon idella (Ci)] IFNa has been solved at 1.58Å and consists of six helices. The CiIFNa displays a typical structure of type I IFNs with a straight helix F and lacks a helix element in the AB loop. Superposition modeling identified several key residues involved in the interaction with receptors. It was found that CiIFNa bound to cytokine receptor family B (CRFB) 1, CRFB2, and CRFB5, and the three receptors could form heterodimeric receptor complexes. Furthermore, mutation of Leu27, Glu103, Lys117, and His165 markedly decreased the phosphorylation of signal transducer and activator of transcription (STAT) 1a induced by CiIFNa in the Epithelioma papulosum cyprini (EPC) cells, and Glu103 was shown to be required for the CiIFNa-activated antiviral activity. Interestingly, wild-type and mutant CiIFNa proteins did not alter the phosphorylation levels of STAT1b. Our results demonstrate that fish type I IFNs, although structurally conserved, interact with the receptors in a manner that may differ from mammalian homologs.
Controlled Synthesis of Small Water-Soluble Hybrid Gold Nanoparticles: An Optimized Strategy for Stable Nano-Dispersion and Towards Cellular Uptake
Authors: Bouyon Yenda Tracy , Jiguet-Jiglaire Carine , Khichane Imene , Gobert Quentin , Prabhakaran Rathinasabapathi , De Nonneville Alexandre , Djenizian Thierry , Salas Sébastien , Dallemer Frédéric
Published: March 2022

The development of effective drug delivery systems is one of the major challenges in the fight against cancer. Gold nanoparticles could effectively harness cancer therapies by improving their potency while reducing toxic side effects. In this work, we describe a high-yield one-step synthesis of small water-soluble gold nanoparticles (AuNPs). Efficient purification was monitored, and discrete structure was fully characterized by combining molecular analytical technics (UV-visible and NMR spectroscopies) and solid-state analyses (thermal gravimetric analysis and transmission electron microscopy). These AuNPs have good dispersibility in various biocompatible media and can be used without any additives. Preliminary study with in vitro treatment of IB115 human cancer cells showed massive cellular uptake associated to moderate intrinsic cytotoxicity. The high control of the synthesis and the small size of these AuNPs are offering fine surface properties control, crucial for challenging biological nano-dispersion issues. Thus, limitation of the agglomeration of nanoparticles and improvement of interaction with the surface of cell should open new leads for vectorization of drugs or imaging probes for diagnosis.
Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell Inner Plexiform Layer in Progressive Myopia and Glaucoma Among Adolescents
Authors: Xiao Hui , Zhong Yimin , Ling Yunlan , Xu Xiaoyu , Liu Xing
Published: March 2022

Purpose

This study aimed to investigate the differences in longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) caused by progressive myopia and glaucoma among adolescents.

Design

This was a retrospective observational study.

Methods

A total of forty-seven and 25 eyes of 47 and 25 adolescents with myopia progression (MP) and glaucoma progression (GP), respectively, who were followed up at the Zhongshan Ophthalmic Center for at least 3 years, were included in the study. The pRNFL and GCIPL that measured at the initial and last visits were analyzed.

Results

The median follow-up period was 5 years for both two groups. During follow-up, the whole, superior, and inferior pRNFL decreased in both the MP and GP groups, (p < 0.001). Nasal pRNFL decreased in the MP group (p < 0.001) but had no significant difference in the GP group (p = 0.19). Temporal pRNFL was increased in the MP group (p < 0.001) but decreased in the GP group (p < 0.001). The average and sectoral GCIPL decreased in both groups (p < 0.001). The annual change rate of temporal pRNFL and pRNFL at 10-, 8-, 9-, and 7-clock-hour sectors and the inferotemporal GCIPL has better diagnostic value to differentiate glaucoma from myopia (the area under the receiver operating characteristic curve, AUC > 0.85).

Conclusion

Glaucoma and MP could cause loss of the pRNFL and GCIPL in adolescents; however, the loss patterns were different between the two groups. The temporal quadrant and 7-, 8-, 9-, and 10-clock-hour sector pRNFL and the inferotemporal GCIPL can help distinguish pRNFL and GCIPL loss caused by glaucoma or MP.
Changes in Influenza Activity and Circulating Subtypes During the COVID-19 Outbreak in China
Authors: Zheng Luyan , Qi Jinjin , Wu Jie , Zheng Min
Published: March 2022

Background

Non-pharmaceutical interventions (NPIs) to mitigate COVID-19 can impact the circulation of influenza viruses. There is a need to describe the activity of influenza and its subtypes during the COVID-19 pandemic to aid in the development of influenza prevention and control measures in the next influenza season.

Method

Data from pathogenic surveillance performed by the Chinese National Influenza Center from January 2016 to August 2021 were extracted and stratified by type and subtype for northern China and southern China. The distribution of influenza activity and circulating subtypes were described during the COVID-19 pandemic, and data from 2016 to 2019 were used for comparisons.

Results

Influenza activity declined rapidly and then rose slowly during the COVID-19 pandemic in China. The distribution of influenza subtypes changed from A-dominant to B/Victoria-dominant after the COVID-19 outbreak.

Discussion

Whether the B/Yamagata lineage has disappeared from China deserves more attention in future virologic monitoring programs. The influenza vaccination campaign in the 2021–2022 season is an important means by which to reduce the proportion of susceptible people and limit the damage that potentially greater and earlier circulation of the virus could cause.