bluuebunny/crossref_metadata_2025 huggingface dataset:
Signaling Modulation by miRNA-221-3p During Tooth Morphogenesis in Mice
Authors: Aryal Yam Prasad , Kim Tae-Young , Lee Eui-Seon , An Chang-Hyeon , Kim Ji-Youn , Yamamoto Hitoshi , Lee Sanggyu , Lee Youngkyun , Sohn Wern-Joo , Neupane Sanjiv , Kim Jae-Young
Published: August 2021

miRNAs are conserved short non-coding RNAs that play a role in the modulation of various biological pathways during tissue and organ morphogenesis. In this study, the function of miRNA-221-3p in tooth development, through its loss or gain in function was evaluated. A variety of techniques were utilized to evaluate detailed functional roles of miRNA-221-3p during odontogenesis, including in vitro tooth cultivation, renal capsule transplantation, in situ hybridization, real-time PCR, and immunohistochemistry. Two-day in vitro tooth cultivation at E13 identified altered cellular events, including cellular proliferation, apoptosis, adhesion, and cytoskeletal arrangement, with the loss and gain of miRNA-221-3p. qPCR analysis revealed alterations in gene expression of tooth-related signaling molecules, including β-catenin, Bmp2, Bmp4, Fgf4, Ptch1, and Shh, when inhibited with miRNA-221-3p and mimic. Also, the inhibition of miRNA-221-3p demonstrated increased mesenchymal localizations of pSMAD1/5/8, alongside decreased expression patterns of Shh and Fgf4 within inner enamel epithelium (IEE) in E13 + 2 days in vitro cultivated teeth. Moreover, 1-week renal transplantation of in vitro cultivated teeth had smaller tooth size with reduced enamel and dentin matrices, along with increased cellular proliferation and Shh expression along the Hertwig epithelial root sheath (HERS), within the inhibitor group. Similarly, in 3-week renal calcified teeth, the overexpression of miRNA-221-3p did not affect tooth phenotype, while the loss of function resulted in long and slender teeth with short mesiodistal length. This study provides evidence that a suitable level of miRNA-221-3p is required for the modulation of major signaling pathways, including Wnt, Bmp, and Shh, during tooth morphogenesis.
Using Latent Class Analysis to Identify Different Risk Patterns for Patients With Masked Hypertension
Authors: Fu Ming , Hu Xiangming , Yi Shixin , Sun Shuo , Zhang Ying , Feng Yingqing , Geng Qingshan , Zhou Yingling , Dong Haojian
Published: August 2021

Background: There is controversy whether masked hypertension (MHT) requires additional intervention. The aim of this study is to evaluate whether MHT accompanied with high-risk metabolic syndrome (MetS), as the subphenotype, will have a different prognosis from low-risk MetS.

Methods: We applied latent class analysis to identify subphenotypes of MHT, using the clinical and biological information collected from High-risk Cardiovascular Factor Screening and Chronic Disease Management Programme. We modeled the data, examined the relationship between subphenotypes and clinical outcomes, and further explored the impact of antihypertensive medication.

Results: We included a total of 140 patients with MHT for analysis. The latent class model showed that the two-class (high/low-risk MetS) model was most suitable for MHT classification. The high-risk MetS subphenotype was characterized by larger waist circumference, lower HDL-C, higher fasting blood glucose and triglycerides, and prevalence of diabetes. After four years of follow-up, participants in subphenotype 1 had a higher non-major adverse cardiovascular event (MACE) survival probability than those in subphenotype 2 (P = 0.016). There was no interaction between different subphenotypes and the use of antihypertensive medications affecting the occurrence of MACE.

Conclusions: We have identified two subphenotypes in MHT that have different metabolic characteristics and prognosis, which could give a clue to the importance of tracing the clinical correlation between MHT and metabolic risk factors. For patients with MHT and high-risk MetS, antihypertensive therapy may be insufficient.
Shexiang Baoxin Pills Inhibited Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells via PI3K/AKT/mTOR Pathway
Authors: Hua Lei , Zhou Yaqing , Hou Can , Chen Jiaxin , Wang Yanjun , Zhang Sheng , Zhou Hanxiao , He Shu , Jia Enzhi
Published: August 2021

Background: Proliferation and migration of smooth muscle cells in the coronary artery contribute to the deterioration of coronary artery disease (CAD).

Aim: This research was designed to study the function of Shexiang Baoxin pills (SBPs) on the proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) and their mechanism.

Methods: Oxidized low-density lipoprotein (ox-LDL) was applied to stimulate the proliferation and migration of HCASMCs. The function of ox-LDL and SBP on HCASMCs was evidenced by the cell counting kit-8 assay, cell cycle, and Transwell assay. Network pharmacology was employed to predict the potential targets and pathways of SBP on CAD. Western blot assay and molecular docking were conducted to validate the potential targets and pathways.

Results: The current research revealed that 2.5 mg/L SBP significantly inhibited the proliferation and migration of HCASMCs. Besides, network pharmacology revealed 11 candidate targets. Molecular docking and Western blot assay validated that the activation of the top 2 targets STAT3 and MAPK14 was associated with the inhibition of HCASMCs. Moreover, the Western blot assay also detected that HCASMCs treated with ox-LDL promoted the phosphorylation of the PI3K/AKT/mTOR pathway, and SBP inhibited the activation of the PI3K/AKT/mTOR pathway in HCASMCs stimulated by ox-LDL.

Conclusion: This study demonstrated that the treatment of CAD using SBP may result from the suppression of the proliferation and migration of HCASMCs. The mechanism of this function partly resulted from relieving the phosphorylation of targets STAT3 and MAPK14 and the PI3K/AKT/mTOR pathway. This study enhanced our comprehension of SBP and provides new targets for the treatment of CAD.
Anti-inflammatory Therapies for Coronary Heart Disease: A Systematic Review and Meta-Analysis
Authors: Wang Haiming , Jiang Min , Li Xin , Zhao Yunzhang , Shao Junjie , Liu Zifan , Lin Lejian , Xu Qiang , Wang Lin , Lu Xuechun , Zhang Haomin , Chen Yundai , Zhang Ran
Published: August 2021

Background: Anti-inflammatory therapy has been proposed as a promising treatment for coronary heart disease (CHD) that could reduce residual inflammation risk (RIR) and therefore major adverse cardiovascular events. We implemented a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the clinical benefits of anti-inflammatory agents in patients with CHD based on secondary cardiovascular prevention.

Methods: We systemically searched the PubMed, Embase, and Cochrane Library databases for RCTs (published between Jan 1, 1950, and June 1, 2021; no language restrictions) that focused on anti-inflammatory therapy for coronary heart disease. Our primary end points of interest were a composite of all-cause death, recurrent myocardial infarction and stroke. We processed pooled data using a random-effects model.

Results: Of 1497 selected studies, 18 studies with 67,449 participants met our inclusion criteria and were included in the present meta-analysis. Comparing anti-inflammatory agents with placebo, there was no significant decrease in risk of primary end points, secondary end points, all-cause mortality, cardiac mortality, recurrent myocardial infarction, stroke or revascularization. Further subgroup analysis indicated that anti-inflammatory agents led to a significant reduction in secondary end points (OR 0.87, CI 0.77–0.99; P = 0.03), recurrent myocardial infarction (OR 0.86, CI 0.78–0.95; P = 0.003) and revascularization (OR 0.81, CI 0.70–0.92; P = 0.001) in patients with stable CHD compared with placebo. Moreover, stable CHD patients had a lower propensity for recurrent myocardial infarction than acute coronary syndrome (ACS) patients when using anti-inflammatory agents (P = 0.03). The colchicine subgroup analysis showed that colchicine yielded a promising reduction in the primary end points (OR 0.81, CI 0.70–0.95; P = 0.009) compared with placebo. Anti-inflammatory agents were associated with a higher risk of infection (OR 1.13, CI 1.03–1.23; P = 0.007) and negligible effects on cancers (OR 0.98, CI 0.90–1.06; P = 0.61).

Conclusion: Anti-inflammatory agents appear to have beneficial effects in reducing the risk of recurrent myocardial infarction in patients with stable CHD, albeit at the cost of increased infection. Notably, colchicine demonstrates a promising cardioprotective effect with a lower incidence of major cardiovascular events and thus is a potential therapeutic strategy for stable CHD patients.

Systematic Review Registration: PROSPERO, identifier CRD42021245514.
A Bibliometric Analysis of Exosomes in Cardiovascular Diseases From 2001 to 2021
Authors: Ma Dan , Guan Baoyi , Song Luxia , Liu Qiyu , Fan Yixuan , Zhao Lin , Wang Tongxin , Zhang Zihao , Gao Zhuye , Li Siming , Xu Hao
Published: August 2021

Background: Exosomes in cardiovascular diseases (CVDs) have become an active research field with substantial value and potential. Nevertheless, there are few bibliometric studies in this field. We aimed to visualize the research hotspots and trends of exosomes in CVDs using a bibliometric analysis to help understand the future development of basic and clinical research.

Methods: The articles and reviews regarding exosomes in the CVDs were culled from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace and VOSviewer software.

Results: A total of 1,039 articles were included. The number of exosome articles in the CVDs increased yearly. These publications came from 60 countries/regions, led by the US and China. The primary research institutions were Shanghai Jiao Tong University and Nanjing Medical University. Circulation Research was the journal and co-cited journal with the most studies. We identified 473 authors among which Lucio Barile had the most significant number of articles and Thery C was co-cited most often. After analysis, the most common keywords are myocardium infarction, microRNA and mesenchymal stem cells. Ischemic heart disease, pathogenesis, regeneration, stem cells, targeted therapy, biomarkers, cardiac protection, and others are current and developing areas of study.

Conclusion: We identified the research hotspots and trends of exosomes in CVDs using bibliometric and visual methods. Research on exosomes is flourishing in the cardiovascular medicine. Regenerative medicine, exosome engineering, delivery vehicles, and biomarkers will likely become the focus of future research.
Improving Geospatial Agreement by Hybrid Optimization in Logistic Regression-Based Landslide Susceptibility Modelling
Authors: Sun Deliang , Wen Haijia , Xu Jiahui , Zhang Yalan , Wang Danzhou , Zhang Jialan
Published: August 2021

This study aims to develop a logistic regression model of landslide susceptibility based on GeoDetector for dominant-factor screening and 10-fold cross validation for training sample optimization. First, Fengjie county, a typical mountainous area, was selected as the study area since it experienced 1,522 landslides from 2001 to 2016. Second, 22 factors were selected as the initial conditioning factors, and a geospatial database was established with a grid of 30 m precision. Factor detection of the geographic detector and the stepwise regression method included in logistic regression were used to screen out the dominant factors from the database. Then, based on the sample dataset with a 1:10 ratio of landslides and nonlandslides, 10-fold cross validation was used to select the optimized sample to train the logistic regression model of landslide susceptibility in the study area. Finally, the accuracy and efficiency of the two models before and after screening out the dominant factors were evaluated and compared. The results showed that the total accuracy of the two models was both more than 0.9, and the area under the curve value of the receiver operating characteristic curve was more than 0.8, indicating that the models before and after screening factor both had high reliability and good prediction ability. Besides, the screened factors had an active leading role in the geospatial distribution of the historical landslide, indicating that the screened dominant factors have individual rationality. Improving the geospatial agreement between landslide susceptibility and actual landslide-prone by the screening of dominant factors and the optimization of the training samples, a simple, efficient, and reliable logistic-regression–based landslide susceptibility model can be constructed.
Design of Decentralized Adaptive Sliding Mode Controller for the Islanded AC Microgrid With Ring Topology
Authors: Jiang He , Wei Mofan , Zhao Yan , Han Ji
Published: August 2021

Sliding mode control can restrain the perturbations generated from the intermittence of the renewable energy generation and the randomness of local loads when microgrids are operating in islanded mode. However, the microgrid consists of several subsystems and the interactions among them will cause the chattering problems under the overall sliding mode control. In this paper, the chattering restraint issues for voltage control of the islanded microgrid with a ring topology structure are investigated based on the decentralized adaptive sliding mode control strategies. Firstly, we construct a tracking error system with interconnections considering the power transmission among subsystems and nominal values of system states. Secondly, we design linear matrix inequalities (LMIs) according to the H∞ attenuation performance of the system external disturbances. Then, the tracking error performance and the control precision are guaranteed via the asymptotic stabilities of integral sliding mode surfaces. Adaptive laws are utilized to address the chattering problems of the sliding mode control. Finally, simulation results verify the effectiveness of the proposed decentralized control methods.
Integration of Algal Biofuels With Bioremediation Coupled Industrial Commodities Towards Cost-Effectiveness
Authors: Nagi Gurpreet Kaur , Minhas Amritpreet Kaur , Gaur Suchitra , Jain Priyanshu , Mandal Shovon
Published: August 2021

Microalgae offer a great potential to contribute significantly as renewable fuels and documented as a promising platform for algae-based bio refineries. They provide solutions to mitigate the environmental concerns posed by conventional fuel sources; however, the production of microalgal biofuels in large scale production system encounters few technical challenges. High quantity of nutrients requirements and water cost constrain the scaling up microalgal biomass to large scale commercial production. Crop protection against biomass losses due to grazers or pathogens is another stumbling block in microalgal field cultivation. With our existing technologies, unless coupled with high-value or mid-value products, algal biofuel cannot reach the economic target. Many microalgal industries that started targeting biofuel in the last decade had now adopted parallel business plans focusing on algae by-products application as cosmetic supplements, nutraceuticals, oils, natural color, and animal feed. This review provides the current status and proposes a framework for key supply demand, challenges for cost-effective and sustainable use of water and nutrient. Emphasis is placed on the future industrial market status of value added by products of microalgal biomass. The cost factor for biorefinery process development needs to be addressed before its potential to be exploited for various value-added products with algal biofuel.
The Temporal-Spatial Variations and Potential Causes of Dust Events in Xinjiang Basin During 1960–2015
Authors: Mu Lamei , Su Jing , Mo Xinyue , Peng Nan , Xu Ying , Wang Meihua , Wang Jinyan
Published: August 2021

Dust events not only cause local ecosystem degradation and desertification, but also have profound impacts on regional and global climate system, as well as air quality and human health. Dust events in Xinjiang Basin, as the important dust source of Eastern Asia, have undergone a significant change under the global warming background and may be in a new active period after 2000, which is worthy of study. This study provides the temporal and spatial variations of dust events in the Xinjiang Basin based on surface meteorological station observation data during 1960–2015. The results show that Southern Xinjiang is the main dust occurrence region where dust events are significantly more than that in the Northern Xinjiang, and each year more than 73% of dust events occurred in spring and summer. The dust index (DI), which is defined to represent the large-scale variation of dust event, shows a significant downward trend during the past 56 years with a linear decreasing rate −8.2 years−1in Southern Xinjiang. The DI is positively correlated to surface wind speed with a mean correlation coefficient of 0.79. The declining trend of surface wind speed could explain dust events variation during 1960–2000. But in the new active period after 2000, the increase of DI is not consistent with the rising wind speed with the correlation coefficient decreasing to 0.34. It is found that, compared with 1960–1999, the average annual precipitation and frequency increased by 17.4 and 13% during 2000–2015, respectively, and the NDVI also increased at the same time, which indicates that the surface condition changes induced by the increase of precipitation might suppress the occurrence of dust. Moreover, the analysis of high-altitude wind field shows that the variation of the East Asian general circulation’s intensity, dominating the upper-level wind fields in the Xinjiang basin, will change the surface wind speed and precipitation, and further affect the occurrence of dust events.
A New Field Protocol for Monitoring Forest Degradation
Authors: Wheeler Charlotte E. , Mitchard Edward T. A. , Nalasco Reyes Hugo E. , Iñiguez Herrera Gloria , Marquez Rubio Jose Isaac , Carstairs Harry , Williams Mathew
Published: August 2021

Forest degradation leads to the gradual reduction of forest carbon stocks, function, and biodiversity following anthropogenic disturbance. Whilst tropical degradation is a widespread problem, it is currently very under-studied and its magnitude and extent are largely unknown. This is due, at least in part, to the lack of developed and tested methods for monitoring degradation. Due to the relatively subtle and ongoing changes associated with degradation, which can include the removal of small trees for fuelwood or understory clearance for agricultural production, it is very hard to detect using Earth Observation. Furthermore, degrading activities are normally spatially heterogeneous and stochastic, and therefore conventional forest inventory plots distributed across a landscape do not act as suitable indicators: at best only a small proportion of plots (often zero) will actually be degraded in a landscape undergoing active degradation. This problem is compounded because the metal tree tags used in permanent forest inventory plots likely deter tree clearance, biasing inventories toward under-reporting change. We have therefore developed a new forest plot protocol designed to monitor forest degradation. This involves a plot that can be set up quickly, so a large number can be established across a landscape, and easily remeasured, even though it does not use tree tags or other obvious markers. We present data from a demonstration plot network set up in Jalisco, Mexico, which were measured twice between 2017 and 2018. The protocol was successful, with one plot detecting degradation under our definition (losing greater than 10% AGB but remaining forest), and a further plot being deforested for Avocado (Persea americana) production. Live AGB ranged from 8.4 Mg ha–1 to 140.8 Mg ha–1 in Census 1, and from 0 Mg ha–1 to 144.2 Mg ha–1 Census 2, with four of ten plots losing AGB, and the remainder staying stable or showing slight increases. We suggest this protocol has great potential for underpinning appropriate forest plot networks for degradation monitoring, potentially in combination with Earth Observation analysis, but also in isolation.
A Multiplex Thyroid-Specific Assay for Quantification of Circulating Thyroid Cell-Free RNA in Plasma of Thyroid Cancer Patients
Authors: Yang Samantha Peiling , Koh Lian Chye Winston , Kong Kiat Whye , Parameswaran Rajeev , Loke Kelvin Siu Hoong , Ngiam Kee Yuan , Tan Wee Boon , Loh Thomas , Ng David Chee Eng , Goh Boon Cher , Ngeow Joanne , Tai E. Shyong
Published: August 2021

Background

The standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long half-life, and might be undetectable in 12% of structural disease patients. It detects recurrence with a sensitivity of 19–40%, mainly attributed to issue of TG antibody interference with TG immunometric assay. We hypothesise that the quantity of thyroid-specific cell-free RNA (cfRNA) is indicative of amount of thyroid tissues, and that during thyroid surgery, cfRNA levels decrease accordingly.

Methods

We identified 11 biologically significant and highly expressed thyroid-specific targets from Human Protein Atlas and literature. To assess for a fall in thyroid-specific cfRNA level, we recruited 16 patients undergoing thyroid surgery or RAI for malignant or benign thyroid disease, and tracked longitudinal trend of cfRNA. To assess the utility of cfRNA in detecting metastatic thyroid cancer, cfRNA of 11 patients at intermediate to high risk of recurrence was measured during surveillance and at time of clinical recurrence.

Results

The multiplex assay was capable of amplifying and quantifying multiple thyroid-specific genes in a single reaction. The selected targets were amplified successfully from RNA extracted directly from the thyroid (positive control), indicating that they were highly expressed within thyroid tissue. These cfRNAs were present in plasma, in amounts quantifiable using qRT-PCR. Four cfRNA transcripts (TPO, GFRA2, IVD, TG) fell post-treatment in more than 50% of cohort. The thyroid peroxidase (TPO) cfRNA fell post-therapy in 63% of cohort by 80%, as early as 1 day post-treatment, supporting the potential role as early indicator of remnant thyroid tissue volume. We demonstrated the clinical relevance of circulating TPO cfRNA by tracking temporal changes in setting of peri-treatment, recurrence, and TG Ab positive state.

Conclusion

Using a multiplex pre-amplification approach, the TPO cfRNA was a potential biomarker that can track residual thyroid mass. It can be further optimised for quantification of thyroid volume to guide RAI doses and for detection of thyroid cancer recurrence.
Heat and Hypoxia Exposure Mediates Circadian Rhythms Response via Methylation Modification in Apostichopus japonicas
Authors: Wu Jiong , Zhang Weiwei , Li Chenghua
Published: August 2021

As global warming progresses, heat and hypoxia are gradually becoming important factors threatening the survival, reproduction, and development of marine organisms. To determine the effect of heat and hypoxia on Apostichopus japonicus, whole genome methylation of the respiratory tree was determined under heat, hypoxia, and heat-hypoxia conditions [designed as heat stress treatment (HT), hypoxia treatment (LO), and heat-hypoxia combined treatment (HL) groups]. The number of differentially methylated regions (DMRs) under three treatments was determined based on the Venn diagram. The network of the DMRs associated with promoters that were co-existed under the three conditions showed that circadian rhythm was involved based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Circadian rhythm-related genes, CRY1a, CRY1b, CLC, and TIM, decreased in LO and HL groups, while CRY1a, CRY1b, and BMAL1 increased in the HT group. Bisulfite sequencing PCR (BSP) showed that the methylation levels of CpG island regions in the promoters of CRY1a and CRY1b were upregulated in HT, LO, and HL groups, leading to the decreased promoter activity of CRY1a and CRY1b. RNAi of CRY1a and CRY1b led to increased enzyme activities of two energy-related enzymes, pyruvate kinase (PK) catalyzing the rate-limiting step in glycolysis, and ATPase hydrolyzing ATP to ADP, which were also increased under the three tested conditions. Thus, it was concluded that A. japonicus may respond to the heat, hypoxia, and heat-hypoxia stresses via the DNA methylation of heat, hypoxia, and heat-hypoxia stresses via the DNA methylation of CpG islands of circadian rhythm-related genes, which increased the activity of energy-related enzymes.
A Novel Piezoceramic-Based Sensing Technology Combined With Visual Domain Networks for Timber Damage Quantification
Authors: Xiong Haibei , Chen Lin , Yuan Cheng , Kong Qingzhao
Published: August 2021

Early detection of timber damage is essential for the safety of timber structures. In recent decades, wave-based approaches have shown great potential for structural damage assessment. Current damage assessment accuracy based on sensing signals in the time domain is highly affected by the varied boundary conditions and environmental factors in practical applications. In this research, a novel piezoceramic-based sensing technology combined with a visual domain network was developed to quantitatively evaluate timber damage conditions. Numerical and experimental studies reveal the stress wave propagation properties in different cases of timber crack depths. Through the spectrogram visualization process, all sensing signals in the time domain were transferred to images which contain both time and frequency features of signals collected from different crack conditions. A deep neural network (DNN) was adopted for image training, testing, and classification. The classification results show high efficiency and accuracy for identifying crack conditions for timber structures. The proposed technology can be further integrated with a fielding sensing system to provide real-time monitoring of timber damage in field applications.
Holographic Near-Eye 3D Display Method Based on Large-Size Hologram
Authors: Liu Su-Juan , Ma Ning-Tao , Li Ping-Ping , Wang Di
Published: August 2021

In this paper, we propose a holographic near-eye 3D display method based on large-size computer-generated hologram (CGH). The reconstructed image with a large viewing angle is obtained by using a time multiplexing and spatial tiling system. The large-size CGHs are generated and they record the information of the 3D object from different angles. The CGHs are reproduced at different moments. For a certain reconstructed moment, three spatial light modulators (SLMs) spatially spliced into a linear structure are used to load a single CGH. The diffraction boundary angle of the reconstructed light forming each image point is equal to the maximum diffraction angle of the SLM, so the viewing angle of the image generated by the CGH is enlarged. For different CGHs, the incident angle of reconstructed light is changed. Through time multiplexing, the reconstructed images of the CGHs are combined into a reconstructed image whose viewing angle is further enlarged. Due to the large viewing angle of the reconstructed image, the proposed method has unique advantages in near-eye display. The feasibility of the proposed method is proved by experimental results.
Efficiency and Safety of the Selective Relaxant Binding Agent Adamgammadex Sodium for Reversing Rocuronium-Induced Deep Neuromuscular Block: A Single-Center, Open-Label, Dose-Finding, and Phase IIa Study
Authors: Zhao Yanhua , Chen Sifan , Huai Xiaorong , Yu Zhangjie , Qi Youmiao , Qing Jie , Yu Weifeng , Su Diansan
Published: August 2021

Background: Rapid reversal of neuromuscular block after surgery and anesthesia is often necessary. Here, we reported the primary efficacy and safety data from a phase IIa study on adamgammadex sodium, a newly developed modified γ-cyclodextrin derivative.

Methods: This was a phase IIa, single-center, randomized, open-label, and dose-finding study that enrolled 35 patients under general anesthesia who received the neuromuscular blocking agent rocuronium for induction and maintenance of neuromuscular blockade. The subjects were randomized to one of the five adamgammadex dose groups (2, 4, 6, 8, and 10 mg kg−1) and to the 4 mg kg−1 sugammadex group. Pharmacological efficacy was the recovery time from the start of adamgammadex or sugammadex administration to train-of-four (TOF) ratio ≥0.9, 0.8, and 0.7 among the different dose groups. Adverse events were recorded throughout the study.

Results: The efficacy in reversing deep neuromuscular block was the same between 4 mg kg−1 sugammadex and adamgammadex. However, in the lowest dose groups of 2 and 4 mg kg−1 adamgammadex, adequate reversal could not be achieved in all subjects. The recovery time of TOF ratio to 0.9, 0.8, and 0.7 was shorter in the adamgammadex 10 mg kg−1 group than in the sugammadex 4 mg kg−1 group. The average values of the TOF ratio after 3 min of administration of adamgammadex 8 and 10 mg kg−1 and sugammadex 4 mg kg−1 were >90%. There were no serious adverse events after the use of adamgammadex, and no subjects had to be withdrawn from the trial.

Conclusions: Adamgammadex enabled quick, predictable, and tolerable reversion of rocuronium-induced deep neuromuscular block in a dose-dependent manner. Adamgammadex doses of 6–10 mg kg−1 might be the recommended dose range for further exploration of efficacy. Clinical Trial Registration: This study was registered at chictr.org.cn, identifier: ChiCTR2000038391.
Implementation and Access to Pre-exposure Prophylaxis for Human Immunodeficiency Virus by Men Who Have Sex With Men in Europe
Authors: Sepodes Bruno , Rocha João , Batista Jorge , Figueira Maria-Eduardo , Dráfi František , Torre Carla
Published: August 2021

Pre-exposure prophylaxis (PrEP) is a significant public health intervention with proven efficacy and safety in the prevention of human immunodeficiency virus (HIV) infection, which has taken a considerable amount of time to reach Europe in relation to their transatlantic counterparts, namely, the United States of America (USA). There, it is perceived as being an essential prevention tool to be integrated within existing medical, behavioral and structural interventions in place for the management and containment of HIV infection in men who have sex with men (MSM). In a region such as Europe, with approximately double the USA population, it is estimated that not even 10% have proper access to PrEP, and given the lack of coordination with healthcare, taking PrEP has to be at their own expense. Here, we identify the reasons behind the 4-year lag in the approval of PrEP in the European Union/European Economic Area (and Europe in general) and explore the efficacy and effectiveness of PrEP needed to be confirmed with some implementation or demonstration studies conducted in the region. Independent of the data gathered, access of MSM to PrEP is far from ideal in Europe and much still needs to be done. The demonstration of the cost-effectiveness of PrEP alongside other social and behavioral factors needs to be addressed, while the clear populations within MSM that will benefit from this intervention are properly identified and make use of the latest recommendations of the World Health Organization that consider not only daily PrEP but also event-driven PrEP. The momentum for the proper implementation of PrEP in the EU is not lost, and with the existence of generics and even new formulations, there is a renewed opportunity for unleashing the public health benefits arising from this pharmacological tool with other interventions in place (e.g., condoms, testing, and counseling).
Diagnostic Classification of Bruch's Membrane Opening-Minimum Rim Width and Retinal Nerve Fiber Layer Thickness in Myopic Eyes by Optical Coherence Tomography
Authors: Wang Geng , Zhen Miaoru , Liu Shasha , Qiu Kunliang , Liu Cui , Wang Ji , Zhang Mingzhi
Published: August 2021

Purpose: This study was conducted in order to compare the diagnostic classification of Bruch's membrane opening-minimum rim width (BMO-MRW) and RNFL thickness in normal myopic subjects by using optical coherence tomography (OCT).

Methods: This cross-sectional study involved 75 healthy myopic subjects [spherical equivalent (SE) ≤ −0.5D] from April 2019 to January 2020. One eye of each subject was randomly selected for examination. BMO-MRW and peripapillary RNFL thickness were measured by spectral-domain OCT (Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany). All the subjects were divided into three groups: low myopic group (SE > −3D), moderate myopic group (−6D < SE ≤ −3D), and high myopic group (SE ≤ −6D). A nonparametric test was used to analyze the difference among groups. Linear regression was used to analyze the relationship between BMO-MRW/RNFL thickness and axial length/spherical equivalent. McNemar test was used to compare the diagnostic classification between BMO-MRW and RNFL thickness.

Results: The RNFL thickness classified a significantly higher percentage of eyes as outside normal limits/borderline in at least 1 quadrant (BMO-MRW, 4%; RNFL thickness, 34.67%; p < 0.01). There was no significant correlation between BMO-MRW/RNFL thickness and AL/SE. The low myopia (SE > −3D) had a significantly lower percentage of eyes classified as outside normal limits/borderline in at least 1 quadrant than the moderate myopia (−6D < SE ≤ −3D) and high myopia (SE ≤ −6D) (low myopia, 12.5%; moderate/high myopia, 42.42%/50%; p < 0.05).

Conclusion: BMO-MRW had a lower percentage of eyes classified as outside normal limits/borderline in at least 1 quadrant than RNFL thickness in normal myopic subjects. When referring to the diagnostic classification of RNFL thickness in myopic subjects, caution should be exercised in interpreting positive results. Further studies are needed to compare the diagnostic accuracy of these two measurements in myopic glaucoma patients.
Characterization of Erwinia gerundensis A4, an Almond-Derived Plant Growth-Promoting Endophyte
Authors: Saldierna Guzmán J. Paola , Reyes-Prieto Mariana , Hart Stephen C.
Published: August 2021

The rapidly increasing global population and anthropogenic climate change have created intense pressure on agricultural systems to produce increasingly more food under steadily challenging environmental conditions. Simultaneously, industrial agriculture is negatively affecting natural and agricultural ecosystems because of intensive irrigation and fertilization to fully utilize the potential of high-yielding cultivars. Growth-promoting microbes that increase stress tolerance and crop yield could be a useful tool for helping mitigate these problems. We investigated if commercially grown almonds might be a resource for plant colonizing bacteria with growth promotional traits that could be used to foster more productive and sustainable agricultural ecosystems. We isolated an endophytic bacterium from almond leaves that promotes growth of the model plant Arabidopsis thaliana. Genome sequencing revealed a novel Erwinia gerundensis strain (A4) that exhibits the ability to increase access to plant nutrients and to produce the stress-mitigating polyamine spermidine. Because E. gerundensis is known to be able to colonize diverse plant species including cereals and fruit trees, A4 may have the potential to be applied to a wide variety of crop systems.
Effects of Vanillic Acid on Dynamic Fermentation Parameter, Nitrogen Distribution, Bacterial Community, and Enzymatic Hydrolysis of Stylo Silage
Authors: He Liwen , Li Sen , Wang Cheng , Chen Xiaoyang , Zhang Qing
Published: August 2021

Vanillic acid (VA) is a phenolic acid derivative commonly found in plants and foods, with a pleasant creamy odor and pharmacologic activities, which is hypothesized to help improve silage fermentation. The silage profile of stylo silage ensiled with addition of VA was evaluated. The results showed that VA addition resulted in the decrease of pH value (5.22 vs. 4.33), dry matter loss (5.37 vs. 2.51% DM), and ammonia-N proportion (14.57 vs. 1.51% CP) of stylo silage as well as the increase of lactic acid concentration (0.51 vs. 1.17% DM), true protein proportion (51.18 vs. 58.47% CP), and saccharification yield (113.64 vs. 126.40 mg/g DM). Meanwhile, bacterial community of stylo silage was altered, where the relative abundance of Enterobacter, Clostridium, and Kosakonia decreased and that of Commensalibacter and Methylobacterium increased. In conclusion, it is suggested that VA could be used as a novel silage additive to improve silage fermentation and nutrient preservation of stylo silage.
The Role of Arabinogalactan Type II Degradation in Plant-Microbe Interactions
Authors: Villa-Rivera Maria Guadalupe , Cano-Camacho Horacio , López-Romero Everardo , Zavala-Páramo María Guadalupe
Published: August 2021

Arabinogalactans (AGs) are structural polysaccharides of the plant cell wall. A small proportion of the AGs are associated with hemicellulose and pectin. Furthermore, AGs are associated with proteins forming the so-called arabinogalactan proteins (AGPs), which can be found in the plant cell wall or attached through a glycosylphosphatidylinositol (GPI) anchor to the plasma membrane. AGPs are a family of highly glycosylated proteins grouped with cell wall proteins rich in hydroxyproline. These glycoproteins have important and diverse functions in plants, such as growth, cellular differentiation, signaling, and microbe-plant interactions, and several reports suggest that carbohydrate components are crucial for AGP functions. In beneficial plant-microbe interactions, AGPs attract symbiotic species of fungi or bacteria, promote the development of infectious structures and the colonization of root tips, and furthermore, these interactions can activate plant defense mechanisms. On the other hand, plants secrete and accumulate AGPs at infection sites, creating cross-links with pectin. As part of the plant cell wall degradation machinery, beneficial and pathogenic fungi and bacteria can produce the enzymes necessary for the complete depolymerization of AGs including endo-β-(1,3), β-(1,4) and β-(1,6)-galactanases, β-(1,3/1,6) galactanases, α-L-arabinofuranosidases, β-L-arabinopyranosidases, and β-D-glucuronidases. These hydrolytic enzymes are secreted during plant-pathogen interactions and could have implications for the function of AGPs. It has been proposed that AGPs could prevent infection by pathogenic microorganisms because their degradation products generated by hydrolytic enzymes of pathogens function as damage-associated molecular patterns (DAMPs) eliciting the plant defense response. In this review, we describe the structure and function of AGs and AGPs as components of the plant cell wall. Additionally, we describe the set of enzymes secreted by microorganisms to degrade AGs from AGPs and its possible implication for plant-microbe interactions.
Imaging Voltage with Microbial Rhodopsins
Authors: Zhang Xiao Min , Yokoyama Tatsushi , Sakamoto Masayuki
Published: August 2021

Membrane potential is the critical parameter that reflects the excitability of a neuron, and it is usually measured by electrophysiological recordings with electrodes. However, this is an invasive approach that is constrained by the problems of lacking spatial resolution and genetic specificity. Recently, the development of a variety of fluorescent probes has made it possible to measure the activity of individual cells with high spatiotemporal resolution. The adaptation of this technique to image electrical activity in neurons has become an informative method to study neural circuits. Genetically encoded voltage indicators (GEVIs) can be used with superior performance to accurately target specific genetic populations and reveal neuronal dynamics on a millisecond scale. Microbial rhodopsins are commonly used as optogenetic actuators to manipulate neuronal activities and to explore the circuit mechanisms of brain function, but they also can be used as fluorescent voltage indicators. In this review, we summarize recent advances in the design and the application of rhodopsin-based GEVIs.
Urinary 8-OxoGsn as a Potential Indicator of Mild Cognitive Impairment in Frail Patients With Cardiovascular Disease
Authors: Yao Si-Min , Zheng Pei-Pei , He Wei , Cai Jian-Ping , Wang Hua , Yang Jie-Fu
Published: August 2021

Oxidative RNA damage has been found to be associated with age-related diseases and 8-oxo-7,8-dihydroguanosine (8-oxoGsn) is a typical marker of oxidative modification of RNA. Urine tests are a feasible non-invasive diagnostic modality. The present study aimed to assess whether the measurement of urinary 8-oxoGsn could represent a potential early maker in mild cognitive impairment (MCI) of frail patients with cardiovascular disease (CVD). In this cross-sectional study performed in China from September 2018 to February 2019. Urinary 8-oxoGsn was measured in frail (Fried phenotype: 3–5) in patients with CVD and was adjusted by urinary creatinine (Cre) levels. Cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (MMSE) and participants were classified into non-MCI (≥24) and MCI (<24) groups. Univariate and multivariate logistic regression models were used to determine the relationship between 8-oxoGsn/Cre and MCI. Receiver operating characteristic (ROC) curve analysis was used to assess the 8-oxoGsn/Cre ratio in relation to MCI in frail patients with CVD. A total of 106 elderly patients were enrolled in this study. The mean age of participants was 77.9 ± 6.8 years, the overall prevalence of MCI was 22.6% (24/106), and 57.5% (61/106) of participants were women. In the multivariate logistic regression analysis, urinary 8-oxoGsn/Cre was independently associated with MCI (odds ratio [OR] = 1.769, 95% confidence interval [CI] = 1.234–2.536, P = 0.002), after adjusting for age, sex, education level, marital status, and serum prealbumin levels. The area under the ROC curve was 0.786 (0.679–0.893) (P < 0.001), and the optimal cut-off value was 4.22 μmol/mol. The urinary 8-oxoGsn/Cre ratio showed a sensitivity of 87.5% and a specificity of 69.5%. The present study suggests the urinary 8-oxoGsn/Cre ratio may be a useful indicator for the early screening of MCI in frail patients with CVD.

Clinical Trial Registration

ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.
Cognitive Trajectories and Dementia Risk: A Comparison of Two Cognitive Reserve Measures
Authors: Gallo Federico , Kalpouzos Grégoria , Laukka Erika J. , Wang Rui , Qiu Chengxuan , Bäckman Lars , Marseglia Anna , Fratiglioni Laura , Dekhtyar Serhiy
Published: August 2021

Background and Objectives

Cognitive reserve (CR) is meant to account for the mismatch between brain damage and cognitive decline or dementia. Generally, CR has been operationalized using proxy variables indicating exposure to enriching activities (activity-based CR). An alternative approach defines CR as residual variance in cognition, not explained by the brain status (residual-based CR). The aim of this study is to compare activity-based and residual-based CR measures in their association with cognitive trajectories and dementia. Furthermore, we seek to examine if the two measures modify the impact of brain integrity on cognitive trajectories and if they predict dementia incidence independent of brain status.

Methods

We used data on 430 older adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 12 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white-matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Cognition was assessed with a composite of perceptual speed, semantic memory, letter-, and category fluency. Dementia was clinically diagnosed in accordance with DSM-IV criteria. Linear mixed models were used for cognitive change analyses. Interactions tested if reserve measures modified the association between brain-integrity and cognitive change. Cox proportional hazard models, adjusted for brain-integrity index, assessed dementia risk.

Results

Both reserve measures were associated with cognitive trajectories [β × time (top tertile, ref.: bottom tertile) = 0.013; 95% CI: –0.126, –0.004 (residual-based) and 0.011; 95% CI: –0.001, 0.024, (activity-based)]. Residual-based, but not activity-based reserve mitigated the impact of brain integrity on cognitive decline [β (top tertile × time × brain integrity) = –0.021; 95% CI: –0.043, 0.001] and predicted 12-year dementia incidence, after accounting for the brain-integrity status [HR (top tertile) = 0.23; 95% CI: 0.09, 0.58].

Interpretation

The operationalization of reserve based on residual cognitive performance may represent a more direct measure of CR than an activity-based approach. Ultimately, the two models of CR serve largely different aims. Accounting for brain integrity is essential in any model of reserve.
Two-Dimensional Van Der Waals Materials for Spin-Orbit Torque Applications
Authors: Tian Mingming , Zhu Yonghui , Jalali Milad , Jiang Wei , Liang Jian , Huang Zhaocong , Chen Qian , Zeng Zhongming , Zhai Ya
Published: August 2021

Spin-orbit torque (SOT) provides an efficient approach to control the magnetic state and dynamics in different classes of materials. Recent years, the crossover between two-dimensional van der Waals (2D vdW) materials and SOT opens a new prospect to push SOT devices to the 2D limit. In this mini-review, we summarize the latest progress in 2D vdW materials for SOT applications, highlighting the comparison of the performance between devices with various structures. It is prospected that the large family of 2D vdW materials and numerous combinations of heterostructures will widely extend the material choices and bring new opportunities to SOT devices in the future.
Deletion of C1ql1 Causes Hearing Loss and Abnormal Auditory Nerve Fibers in the Mouse Cochlea
Authors: Qi Yue , Xiong Wei , Yu Shukui , Du Zhengde , Qu Tengfei , He Lu , Wei Wei , Zhang Lingjun , Liu Ke , Li Yi , He David Z. , Gong Shusheng
Published: August 2021

Complement C1q Like 1 (C1QL1), a secreted component of C1Q-related protein, is known to play an important role in synaptic maturation, regulation, and maintenance in the central nervous system.C1ql1is expressed in adult cochlear inner and outer hair cells (IHCs and OHCs) with preferential expression in OHCs. We generatedC1ql1null mice to examine the role of C1QL1 in the auditory periphery.C1ql1-null mice exhibited progressive hearing loss with elevated thresholds of auditory brainstem response and distortion product otoacoustic emission. Confocal microscopy showed that the number of nerve fibers innervating both IHCs and OHCs was significantly reduced. However, spiral ganglion neurons appeared to be normal under electron microscopy. IHC development and survival were not affected by deletion ofC1ql1.Voltage-clamp recording and immunocytochmistry combined with confocal microscopy showedC1ql1-null IHCs showed no significant reduction of pre-synaptic proteins and synaptic vesicle release. This is in contrast to significant OHC loss in the KO mice. Our study suggests thatC1ql1is essential for development of hair cell innervation and OHC survival. But maturation of presynaptic machinery in IHCs does not depend on C1QL1.