bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Roles and Delivery Strategies for Ions to Promote Osteogenic Induction
Authors: Bosch-Rué Elia , Diez-Tercero Leire , Giordano-Kelhoffer Barbara , Delgado Luis M. , Bosch Begoña M. , Hoyos-Nogués Mireia , Mateos-Timoneda Miguel Angel , Tran Phong A. , Gil Francisco Javier , Perez Roman A.
Published: January 2021

Bone is the most studied tissue in the field of tissue regeneration. Even though it has intrinsic capability to regenerate upon injury, several pathologies and injuries could hamper the highly orchestrated bone formation and resorption process. Bone tissue engineering seeks to mimic the extracellular matrix of the tissue and the different biochemical pathways that lead to successful regeneration. For many years, the use of extrinsic factors (i.e., growth factors and drugs) to modulate these biological processes have been the preferred choice in the field. Even though it has been successful in some instances, this approach presents several drawbacks, such as safety-concerns, short release profile and half-time life of the compounds. On the other hand, the use of inorganic ions has attracted significant attention due to their therapeutic effects, stability and lower biological risks. Biomaterials play a key role in such strategies where they serve as a substrate for the incorporation and release of the ions. In this review, the methodologies used to incorporate ions in biomaterials is presented, highlighting the osteogenic properties of such ions and the roles of biomaterials in controlling their release.
Minicircle Biopharmaceuticals–An Overview of Purification Strategies
Authors: Alves Cláudia P. A. , Prazeres Duarte Miguel F. , Monteiro Gabriel A.
Published: January 2021

Minicircles are non-viral delivery vectors with promising features for biopharmaceutical applications. These vectors are plasmid-derived circular DNA molecules that are obtained in vivo in Escherichia coli by the intramolecular recombination of a parental plasmid, which generates a minicircle containing the eukaryotic therapeutic cassette of interest and a miniplasmid containing the prokaryotic backbone. The production process results thus in a complex mixture, which hinders the isolation of minicircle molecules from other DNA molecules. Several strategies have been proposed over the years to meet the challenge of purifying and obtaining high quality minicircles in compliance with the regulatory guidelines for therapeutic use. In minicircle purification, the characteristics of the strain and parental plasmid used have a high impact and strongly affect the purification strategy that can be applied. This review summarizes the different methods developed so far, focusing not only on the purification method itself but also on its dependence on the upstream production strategy used.
Recent Progress in Designing Halide-Perovskite-Based System for the Photocatalytic Applications
Authors: Zhao Yizhou , Wang Lanning , Song Tinglu , Mudryi Alexander , Li Yujing , Chen Qi
Published: January 2021

The halide perovskite material has attracted vast attention as a versatile semiconductor in the past decade. With the unique advantages in physical and chemical properties, they have also shown great potential in photocatalytic applications. This review aims at the specific design principles triggered by the unique properties when employing halide-perovskite-based photocatalytic systems from the following perspectives: (I) Design of photoelectrocatalytic device structures including the n-i-p/p-i-n structure, photoelectrode device encapsulation, and electrolyte engineering. (II) The design of heterogeneous photocatalytic systems toward the hydrogen evolution reaction (HER) and CO2 reduction reaction, including the light management, surface/interface engineering, stability improvement, product selectivity engineering, and reaction system engineering. (III) The photocatalysts for the environmental application and organic synthesis. Based on the analyses, the review also suggests the prospective research for the future development of halide-perovskite-based photocatalytic systems.
The Mitochondrial Fission Regulator DRP1 Controls Post-Transcriptional Regulation of TNF-α
Authors: Gao Fushan , Reynolds Mack B. , Passalacqua Karla D. , Sexton Jonathan Z. , Abuaita Basel H. , O’Riordan Mary X. D.
Published: January 2021

The mitochondrial network plays a critical role in the regulation of innate immune signaling and subsequent production of proinflammatory cytokines such as IFN-β and IL-1β. Dynamin-related protein 1 (DRP1) promotes mitochondrial fission and quality control to maintain cellular homeostasis during infection. However, mechanisms by which DRP1 and mitochondrial dynamics control innate immune signaling and the proinflammatory response are incompletely understood. Here we show that macrophage DRP1 is a positive regulator of TNF-α production during sterile inflammation or bacterial infection. Silencing macrophage DRP1 decreased mitochondrial fragmentation and TNF-α production upon stimulation with lipopolysaccharide (LPS) or methicillin-resistantStaphylococcus aureus(MRSA) infection. The defect in TNF-α induction could not be attributed to changes in gene expression. Instead, DRP1 was required for post-transcriptional control of TNF-α. In contrast, silencing DRP1 enhanced IL-6 and IL-1β production, indicating a distinct mechanism for DRP1-dependent TNF-α regulation. Our results highlight DRP1 as a key player in the macrophage pro-inflammatory response and point to its involvement in post-transcriptional control of TNF-α production.
Columbite-Tantalite Group Mineral U-Pb Geochronology of Chaqiabeishan Li-Rich Granitic Pegmatites in the Quanji Massif, NW China: Implications for the Genesis and Emplacement Ages of Pegmatites
Authors: Pan Tong , Ding Qing-Feng , Zhou Xuan , Li Shan-Ping , Han Jie , Cheng Long
Published: January 2021

The Chaqiabeishan area is characterized by small Li-rich granitic pegmatites in the Quanji Massif (QM), northwest China. In this study, the columbite-tantalite group minerals (CGMs) from a typical Li-rich pegmatite dike were analyzed for major element contents using an EMPA (electron microprobe analyzer), for trace element contents using LA-ICP-MS (laser ablation-inductively coupled plasma mass spectrometry), and for ages using LA-ICP-MS U-Pb dating, respectively. The CGMs from the sample can be divided into two types, i.e., magmatic Type 1 and metasomatic Type 2. Although these two types of CGMs do not exhibit distinct major and trace element variations from core to rim within an individual grain, the Ta# values, Mn# values, and some trace element contents (such as Zr, Hf, W, and Sr) of Type 1 CGMs are distinct from those of Type 2 CGMs. The overall compositional changes from Type 1 CGMs to Type 2 CGMs are consistent with the typical evolutionary trend described for many lithium-cesium-tantalum (LCT) pegmatites and the complex spodumene trend described by Černý and Ercit (Bull. Mineral., 1989, 108, 499–532). The Type 2 CGMs have formed later and must be a metasomatic product of Type 1 CGMs. Eighteen Type 1 CGMs yielded a weighted mean 206Pb/238U age of 240.6 ± 1.5 Ma. The slight oscillatory zoning and/or sector zoning suggest that the dated Type 1 columbites have a magmatic origin. Thus, the crystallization ages of Type 1 columbites represent the emplacement ages of Li-rich pegmatites. One of the Type 2 CGMs yielded a 206Pb/238U age of 211.0 ± 4.7 Ma, which is hardly interpreted to be an age representing the later hydrothermal metasomatism, because one dataset has no apparent statistical significance. Therefore, our dating results can only indicate that the Li-rich pegmatite-forming melts were emplaced at approximately 240.6 Ma. Based on these results and previous studies of the 240–254 Ma granitoids in the QM, we conclude that the 240.6 Ma Li-rich granitic pegmatites, as well as 240–254 Ma granitoids in the QM, were both emplaced during the southward subduction of the Zongwulong Ocean Plate in the Late Permian to Middle Triassic.
The Effect of Forbush Decreases on the Polar-Night HOx Concentration Affecting Stratospheric Ozone
Authors: Mironova Irina , Karagodin-Doyennel Arseniy , Rozanov Eugene
Published: January 2021

It is well-known that energetic particle precipitations during solar proton events increase ionization rates in the middle atmosphere enhancing the production of hydrogen oxide radicals (HOx) involved in the catalytic ozone destruction cycle. There are many studies where the contribution of energetic particles to the formation of hydrogen oxide radicals and ozone loss has been widely investigated. However, until now, there was no solid evidence that the reduction in galactic cosmic ray fluxes during a magnetic storm, known as Forbush-effect, directly and noticeably affects the polar-night stratospheric chemistry. Here, the impact of the Forbush decrease on the behavior of hydrogen oxide radicals was explored using the chemistry-climate model SOCOLv2. We found that hydrogen oxide radical lost about half of its concentration over the polar boreal night stratosphere owing to a reduction in ionization rates caused by Forbush decreases after solar proton events occurred on 17 and 20 of January 2005. The robust response in ozone was not found. There is not any statistically significant response in (NOx) on Forbush decrease events as well as over summer time in the southern polar region. The results of this study can be used to increase the veracity of ozone loss estimation if stronger Forbush events can have place.
Comparing the Effects of a Different Social Partner (Social Robot vs. Human) on Children's Social Referencing in Interaction
Authors: Tolksdorf Nils F. , Crawshaw Camilla E. , Rohlfing Katharina J.
Published: January 2021

Social robots have emerged as a new digital technology that is increasingly being implemented in the educational landscape. While social robots could be deployed to assist young children with their learning in a variety of different ways, the typical approach in educational practices is to supplement the learning process rather than to replace the human caregiver, e.g., the teacher, parent, educator or therapist. When functioning in the role of an educational assistant, social robots will likely constitute a part of a triadic interaction with the child and the human caregiver. Surprisingly, there is little research that systematically investigates the role of the caregiver by examining the ways in which children involve or check in with them during their interaction with another partner—a phenomenon that is known as social referencing. In the present study, we investigated social referencing in the context of a dyadic child–robot interaction. Over the course of four sessions within our longitudinal language-learning study, we observed how 20 pre-school children aged 4–5 years checked in with their accompanying caregivers who were not actively involved in the language-learning procedure. The children participating in the study were randomly assigned to either an interaction with a social robot or a human partner. Our results revealed that all children across both conditions utilized social referencing behaviors to address their caregiver. However, we found that the children who interacted with the social robot did so significantly more frequently in each of the four sessions than those who interacted with the human partner. Further analyses showed that no significant change in their behavior over the course of the sessions could be observed. Findings are discussed with regard to the caregiver's role during children's interactions with social robots and the implications for future interaction design.
Japanese Schoolteachers' Attitudes and Perceptions Regarding Inclusive Education Implementation: The Interaction Effect of Help-Seeking Preference and Collegial Climate
Authors: Maeda Kaede , Hashimoto Hirofumi , Sato Kosuke
Published: January 2021

While the special needs education system in Japan has shifted from a segregated approach to a more inclusive one, the actual implementation of this approach may be less than ideal. The implementation of inclusive education faces several challenges, such as difficulty in meeting individual needs and lack of medical support systems in general school settings. With this in mind, we conducted a web-based survey of Japanese schoolteachers to empirically examine their attitudes and perceptions regarding inclusive education. We also sought to determine the socio-environmental and individual factors that affect the attitudes and perceptions of Japanese elementary and junior high school teachers regarding the implementation of inclusive education. Survey results showed that schoolteachers regard the idea of inclusive education as desirable, but not feasible. However, we found that schoolteachers' perceptions of the feasibility of inclusive education implementation were positively associated with their help-seeking preference if they perceived their climate as being sufficiently collegial. Based on these findings, we discuss the educational environment in which inclusive education could be successfully implemented.
Cancer Treatment by Caryophyllaceae-Type Cyclopeptides
Authors: Houshdar Tehrani Mohammad Hassan , Gholibeikian Mohammadreza , Bamoniri Abdolhamid , Mirjalili Bi Bi Fatemeh
Published: January 2021

Cancer is one of the leading diseases, which, in the most cases, ends with death and, thus, continues to be a major concern in human beings worldwide. The conventional anticancer agents used in the clinic often face resistance among many cancer diseases. Moreover, heavy financial costs preclude patients from continuing treatment. Bioactive peptides, active in several diverse areas against man’s health problems, such as infection, pain, hypertension, and so on, show the potential to be effective in cancer treatment and may offer promise as better candidates for combating cancer. Cyclopeptides, of natural or synthetic origin, have several advantages over other drug molecules with low toxicity and low immunogenicity, and they are easily amenable to several changes in their sequences. Given their many demanded homologues, they have created new hope of discovering better compounds with desired properties in the field of challenging cancer diseases. Caryophyllaceae-type cyclopeptides show several biological activities, including cancer cytotoxicity. These cyclopeptides have been discovered in several plant families but mainly are from the Caryophyllaceae family. In this review, a summary of biological activities found for these cyclopeptides is given; the focus is on the anticancer findings of these peptides. Among these cyclopeptides, information about Dianthins (including Longicalycinin A), isolated from different species of Caryophyllaceae, as well as their synthetic analogues is detailed. Finally, by comparing their structures and cytotoxic activities, finding the common figures of these kinds of cyclopeptides as well as their possible future place in the clinic for cancer treatment is put forward.
Cumulative Live Birth Rate and Cost-Effectiveness Analysis of Gonadotropin Releasing Hormone-Antagonist Protocol and Multiple Minimal Ovarian Stimulation in Poor Responders
Authors: Liu Yuan , Su Rongjia , Wu Yu
Published: January 2021

Background

The overall cumulative live birth rate (CLBR) of poor ovarian responders (POR) is extremely low. Minimal ovarian stimulation (MOS) provides a relatively realistic solution for ovarian stimulation in POR. Our study aimed to investigate whether multiple MOS strategies resulted in higher CLBR compared to conventional gonadotropin releasing hormone (GnRH) antagonists in POR.

Methods

This retrospective study included 699 patients (1,058 cycles) from one center, who fulfilled the Bologna criteria between 2010 and 2018. Overall, 325 women (325 cycles) were treated with one-time conventional GnRH antagonist ovarian stimulation (GnRH-antagonist). Another 374 patients (733 cycles) were treated with multiple MOS including natural cycles. CLBR and time-and-cost-benefit analyses were compared between these two groups of women.

Results

GnRH antagonists provided more retrieved oocytes, meiosis II oocytes, fertilized oocytes, and more viable embryos compared to both the first MOS (p < 0.001) and the cumulative corresponding numbers in multiple MOSs (p < 0.001). For the first in vitro fertilization (IVF) cycle, GnRH antagonists resulted in higher CLBR than MOS [12.92 versus 4.54%, adjusted OR (odds ratio) 2.606; 95% CI (confidence interval) 1.386, 4.899, p = 0.003]. The one-time GnRH-antagonist induced comparable CLBR (12.92 versus 7.92%, adjusted OR 1.702; 95% CI 0.971, 2.982, p = 0.063), but a shorter time to live birth [9 (8, 10.75) months versus 11 (9, 14) months, p = 0.014] and similar financial expenditure compared to repeated MOS [20,838 (17,953, 23,422) ¥ versus 21,261.5 (15,892.5, 35,140.25) ¥, p = 0.13].

Conclusion

Both minimal ovarian stimulation (MOS) and GnRH-antagonists provide low chances of live birth in poor responders. The GnRH antagonist protocol is considered a suitable choice for PORs with comparable CLBR, shorter times to live birth, and similar financial expenditure compared to repeated MOS.
Type 2 Diabetes and Glycemic Traits Are Not Causal Factors of Osteoarthritis: A Two-Sample Mendelian Randomization Analysis
Authors: Cui Zhiyong , Feng Hui , He Baichuan , Xing Yong , Liu Zhaorui , Tian Yun
Published: January 2021

Background

It remains unclear whether an increased risk of type 2 diabetes (T2D) affects the risk of osteoarthritis (OA).

Methods

Here, we used two-sample Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on hip and knee OA. We identified single-nucleotide polymorphisms (SNPs) strongly associated with T2D, fasting glucose (FG), and 2-h postprandial glucose (2hGlu) from genome-wide association studies (GWAS). We used the MR inverse variance weighted (IVW), the MR–Egger method, the weighted median (WM), and the Robust Adjusted Profile Score (MR.RAPS) to reveal the associations of T2D, FG, and 2hGlu with hip and knee OA risks. Sensitivity analyses were also conducted to verify whether heterogeneity and pleiotropy can bias the MR results.

Results

We did not find statistically significant causal effects of genetically increased T2D risk, FG, and 2hGlu on hip and knee OA (e.g., T2D and hip OA, MR–Egger OR = 1.1708, 95% CI 0.9469–1.4476, p = 0.1547). It was confirmed that horizontal pleiotropy was unlikely to bias the causality (e.g., T2D and hip OA, MR–Egger, intercept = −0.0105, p = 0.1367). No evidence of heterogeneity was found between the genetic variants (e.g., T2D and hip OA, MR–Egger Q = 30.1362, I2 < 0.0001, p = 0.6104).

Conclusion

Our MR study did not support causal effects of a genetically increased T2D risk, FG, and 2hGlu on hip and knee OA risk.
Detecting the Multiomics Signatures of Factor-Specific Inflammatory Effects on Airway Smooth Muscles
Authors: Zhang Yu-Hang , Li Zhandong , Zeng Tao , Chen Lei , Li Hao , Huang Tao , Cai Yu-Dong
Published: January 2021

Smooth muscles are a specific muscle subtype that is widely identified in the tissues of internal passageways. This muscle subtype has the capacity for controlled or regulated contraction and relaxation. Airway smooth muscles are a unique type of smooth muscles that constitute the effective, adjustable, and reactive wall that covers most areas of the entire airway from the trachea to lung tissues. Infection with SARS-CoV-2, which caused the world-wide COVID-19 pandemic, involves airway smooth muscles and their surrounding inflammatory environment. Therefore, airway smooth muscles and related inflammatory factors may play an irreplaceable role in the initiation and progression of several severe diseases. Many previous studies have attempted to reveal the potential relationships between interleukins and airway smooth muscle cells only on the omics level, and the continued existence of numerous false-positive optimal genes/transcripts cannot reflect the actual effective biological mechanisms underlying interleukin-based activation effects on airway smooth muscles. Here, on the basis of newly presented machine learning-based computational approaches, we identified specific regulatory factors and a series of rules that contribute to the activation and stimulation of airway smooth muscles by IL-13, IL-17, or the combination of both interleukins on the epigenetic and/or transcriptional levels. The detected discriminative factors (genes) and rules can contribute to the identification of potential regulatory mechanisms linking airway smooth muscle tissues and inflammatory factors and help reveal specific pathological factors for diseases associated with airway smooth muscle inflammation on multiomics levels.
A Density Peak-Based Method to Detect Copy Number Variations From Next-Generation Sequencing Data
Authors: Xie Kun , Tian Ye , Yuan Xiguo
Published: January 2021

Copy number variation (CNV) is a common type of structural variations in human genome and confers biological meanings to human complex diseases. Detection of CNVs is an important step for a systematic analysis of CNVs in medical research of complex diseases. The recent development of next-generation sequencing (NGS) platforms provides unprecedented opportunities for the detection of CNVs at a base-level resolution. However, due to the intrinsic characteristics behind NGS data, accurate detection of CNVs is still a challenging task. In this article, we propose a new density peak-based method, called dpCNV, for the detection of CNVs from NGS data. The algorithm of dpCNV is designed based on density peak clustering algorithm. It extracts two features, i.e., local density and minimum distance, from sequencing read depth (RD) profile and generates a two-dimensional data. Based on the generated data, a two-dimensional null distribution is constructed to test the significance of each genome bin and then the significant genome bins are declared as CNVs. We test the performance of the dpCNV method on a number of simulated datasets and make comparison with several existing methods. The experimental results demonstrate that our proposed method outperforms others in terms of sensitivity and F1-score. We further apply it to a set of real sequencing samples and the results demonstrate the validity of dpCNV. Therefore, we expect that dpCNV can be used as a supplementary to existing methods and may become a routine tool in the field of genome mutation analysis.
Myeloid-Derived Suppressor Cell Differentiation in Cancer: Transcriptional Regulators and Enhanceosome-Mediated Mechanisms
Authors: Fultang Norman , Li Xinyuan , Li Ting , Chen Youhai H.
Published: January 2021

Myeloid-derived Suppressor Cells (MDSCs) are a sub-population of leukocytes that are important for carcinogenesis and cancer immunotherapy. During carcinogenesis or severe infections, inflammatory mediators induce MDSCsviaaberrant differentiation of myeloid precursors. Although several transcription factors, including C/EBPβ, STAT3, c-Rel, STAT5, and IRF8, have been reported to regulate MDSC differentiation, none of them are specifically expressed in MDSCs. How these lineage-non-specific transcription factors specify MDSC differentiation in a lineage-specific manner is unclear. The recent discovery of the c-Rel−C/EBPβ enhanceosome in MDSCs may help explain these context-dependent roles. In this review, we examine several transcriptional regulators of MDSC differentiation, and discuss the concept of non-modular regulation of MDSC signature gene expression by transcription factors such as c-Rel and C/EBPß.
Multiple Fetal Nutritional Patterns Before Parturition in Viviparous Fish Sebastes schlegelii (Hilgendorf, 1880)
Authors: Tengfei Du , Yongshuang Xiao , Haixia Zhao , Li Zhou , Qinghua Liu , Xueying Wang , Jun Li , Shihong Xu , Yanfeng Wang , Jiachen Yu , Lele Wu , Yunong Wang , Guang Gao
Published: January 2021

Sebastes schlegeliiis a commercially important fish with a special viviparous reproductive system that is cultured in near-shore seawater net cages in East Asia. In the gonadal development of the species, the gonad of males mature before those of females, which mature after mating. Mating in male/female fishes occurs in October of each year. Then, females undergoing oocyte maturation complete fertilization using stored sperm in March of the following year. The pregnancy is completed when larvae are produced in the ovary. It has been reported that embryonic nutrient supply originates entirely from the female viviparous reproductive systems. However, until now, the nutritional patterns and the processes of nutrient provision inS. schlegeliibefore parturition have not been clear. The goal of this research was to study the embryos, larvae and juveniles ofS. schlegeliiduring pregnancy. Anatomical observations, light microscopy and scanning electron microscopy were used to study the developmental characteristics of early embryos and larvae and the connecting structures between the mother and the fetus. The results showed the following: (1) Placental-like structures were found during the process of embryonic development inS. schlegelii, and these placental-like structures proliferated after fertilization. (2) The embryos ofS. schlegeliiwere encased by a saclike structure composed of blood vessels, connective tissue, and surface epithelial cells. The vessels near the embryo existed in the thecal layer. Vascularized proliferation was detected following embryonic development. (3) Starting in the gastrula stage, connections between the embryo and surrounding cells loosened, and ovarian fluid became abundant. In addition, a large number of small holes and cristae were observed on the surface of the embryo. We speculate that embryos may be able to absorb nutrients from the ovarian fluid. (4) Yolk was present throughout embryo development. (5) Two types of nutritional modes were observed, lecithotrophic and matrotrophic during embryonic development. Three forms of placental analogs may exist inS. schlegelii: (1) external epithelial absorptive surfaces; (2) trophonemata, with modifications of the ovarian epithelia for absorbing the histotroph; and (3) a follicular pseudoplacenta, with close apposition between follicle cells and embryonic absorptive epithelia.
COVID-19–Related Fatalities and Intensive-Care-Unit Admissions by Age Groups in Europe: A Meta-Analysis
Authors: Cohen Jérémie F. , Korevaar Daniël A. , Matczak Soraya , Chalumeau Martin , Allali Slimane , Toubiana Julie
Published: January 2021

Objectives: Precise international estimates of the age breakdown of COVID-19–related deaths and intensive-care-unit (ICU) admissions are lacking. We evaluated the distribution of COVID-19–related fatalities and ICU admissions by age groups in Europe.

Materials and methods: On April 6, 2020, we systematically reviewed official COVID-19–related data from 32 European countries. We included countries that provided data regarding more than 10 COVID-19–related deaths stratified by age according to pre-specified age groups (i.e., <40, 40–69, ≥70 years). We used random-effects meta-analysis to summarize the data.

Results: Thirteen European countries were included in the review, for a total of 31,864 COVID-19–related deaths (range: 27–14,381 per country). In the main meta-analysis (including data from Germany, Hungary, Italy, The Netherlands, Portugal, Spain, Switzerland; 21,522 COVID-19–related fatalities), the summary proportions of individuals <40, 40–69, and ≥70 years old among all COVID-19–related deaths were 0.1% (0.0–0.2; I2 28.6%), 13.0% (10.8–15.4; I2 91.5%), and 86.6% (84.2–88.9; I2 91.5%), respectively. ICU data were available for four countries (France, Greece, Spain, Sweden). The summary proportions of individuals around <40–50, around 40–69, and around ≥60–70 years old among all COVID-19–related ICU admissions were 5.4% (3.4–7.8; I2 89.0%), 52.6% (41.8–63.3; I2 98.1%), and 41.8% (32.0–51.9; I2 99%), respectively.

Conclusions: People under 40 years old represent a small fraction of most severe COVID-19 cases in Europe. These results may help health authorities respond to public concerns and guide future physical distancing and mitigation strategies. Specific measures to protect older people should be considered.
Correlates of Early-Stage Frailty—Sleep, Fitness, Oxidative Stress, and BMI
Authors: Netz Yael , Ben-Zaken Sigal , Zeev Aviva , Dunsky Ayelet
Published: January 2021

Frailty reflects a decreased reserve in multiple systems resulting from cumulative decline. Frailty markers should be identified as early as possible to attenuate the loss of reserve. The aim of this study was to identify potentially modifiable correlates of frailty in relatively healthy older adults. Volunteers (n = 122) were recruited from local councils and, based on gender and age, were divided into one group of men aged 77.0 (±5.3), and two groups of women, aged 68.8 (±3.6) and aged 78.4 (±3.4). Frailty was assessed by a Frailty Index. The examined correlates were: physical activity, physical fitness (predicted peak VO2), sleep quality, oxidative stress (hydrogen peroxide—H2O2) and depression. Both groups of women had poor scores on physical fitness compared to women's norms. In order to examine the contribution of each of the potential correlates to explaining the variance of frailty, stepwise regressions were performed for each group separately. Based on the results, none of the suggested correlates significantly explained the variability of frailty in the men. In the younger-aged women, predicted peak VO2 and sleep quality explained 22.4% of the variability of frailty. In the older women, Body Mass Index (BMI), oxidative stress and sleep quality explained 34.9% of the variance. It is possible that increased aerobic fitness and interventions for improving sleep quality in older, seemingly healthy women will slow down the frailty process. Further research is needed to assess potential correlates of frailty, and to initiate suitable interventions to mitigate the signs of frailty at an early stage.
Allocation of the “Already” Limited Medical Resources Amid the COVID-19 Pandemic, an Iterative Ethical Encounter Including Suggested Solutions From a Real Life Encounter
Authors: Alhalaseh Yazan Nedal , Elshabrawy Hatem A. , Erashdi Madiha , Shahait Mohammed , Abu-Humdan Abdulrahman Mohammad , Al-Hussaini Maysa
Published: January 2021

The shortage of healthcare providers is well-documented in low-income countries (LIC) prior to COVID-19, due to various causes including the migration to developed countries, scarcity of supplies, poor healthcare infrastructure, limited ICU facilities, and lack of access to guidelines and protocols. One of the important hitches in LIC is the insufficient testing capacity that precluded accurate assessment of disease burden and subsequently resource allocations. Trying to adhere to the principles of bioethics including respect to others, beneficence, and justice should be applied on the ground in the particular setting of the LIC. Solutions should be tailored to the tangible needs and possibility of implementation in real life in the face of the “already” limited resources by making use of simple, yet plausible, measures. Implementing guidelines and frameworks that were set to work in the better-resourced nations is a call for futility. The adoption of novel solutions to overcome the unique challenges in the LIC is exigent. These include the use of automated screening algorithms and virtual video clinics. Moreover, integrating electronic intensive care unit (e-ICU) software may allow for remote monitoring of multiple patients simultaneously. Telemedicine could help in getting consultations worldwide. It can also enhance healthcare workers' knowledge and introduce new skills through teleconferences, e-workshops, and free webinars. Healthcare workers can be remotely trained to enhance their skills. Agencies, such as the WHO, should develop comprehensive programs to tackle different health issues in LIC in collaboration with major institutions and experts around the world.
A Culturally Responsive Curricular Revision to Improve Engagement and Learning in an Undergraduate Microbiology Lab Course
Authors: Fuller Karla S. , Torres Rivera Camila
Published: January 2021

We seek to increase student engagement and success to subsequently lead to increased retention and degree attainment for students at our Hispanic-serving institution. We hypothesized that using a culturally responsive approach in an undergraduate microbiology lab would increase engagement and learning gains. Using a culturally responsive approach allowed students to start their learning from their own place of understanding—centering students’ lived experiences. Students interviewed family members to learn about “home remedies,” and then devised experiments to test whether those home remedies affected growth of bacteria commonly implicated in gastrointestinal distress (Staphylococcus aureus, Bacillus cereus, and Escherichia coli) or sore throat (Neisseria gonorrhoeae, Streptococcus pyogenes, and Mycoplasma pneumoniae). As a final assessment, students generated project posters which they presented at a class symposium. Implementation of a culturally responsive research experience focused on the gut microbiome resulted in increased learning gains as evidenced by movement up Bloom’s Revised Taxonomy Scale. Student feedback indicated increased engagement, increased confidence in communicating science and a deeper understanding and appreciation for microbiology. Taken together, the results indicate that students appreciate a more culturally responsive and student-centered approach to learning in microbiology and encourages expansion of this approach to other modules in the course. This paper includes responsive data to support this claim, as well as a sample course calendar and supplementary learning material to support the human microbiome approach to microbiology.
Enhanced Metabolic Potentials and Functional Gene Interactions of Microbial Stress Responses to a 4,100-m Elevational Increase in Freshwater Lakes
Authors: Li Huabing , Zeng Jin , Ren Lijuan , Yan Qingyun , Wu Qinglong L.
Published: January 2021

Elevation has a strong influence on microbial community composition, but its influence on microbial functional genes remains unclear in the aquatic ecosystem. In this study, the functional gene structure of microbes in two lakes at low elevation (ca. 530 m) and two lakes at high elevation (ca. 4,600 m) was examined using a comprehensive functional gene array GeoChip 5.0. Microbial functional composition, but not functional gene richness, was significantly different between the low- and high-elevation lakes. The greatest difference was that microbial communities from high-elevation lakes were enriched in functional genes of stress responses, including cold shock, oxygen limitation, osmotic stress, nitrogen limitation, phosphate limitation, glucose limitation, radiation stress, heat shock, protein stress, and sigma factor genes compared with microbial communities from the low-elevation lakes. Higher metabolic potentials were also observed in the degradation of aromatic compounds, chitin, cellulose, and hemicellulose at higher elevations. Only one phytate degradation gene and one nitrate reduction gene were enriched in the high-elevation lakes. Furthermore, the enhanced interactions and complexity among the co-occurring functional genes in microbial communities of lakes at high elevations were revealed in terms of network size, links, connectivity, and clustering coefficients, and there were more functional genes of stress responses mediating the module hub of this network. The findings of this study highlight the well-developed functional strategies utilized by aquatic microbial communities to withstand the harsh conditions at high elevations.
Genome Sequencing Analysis of Scleromitrula shiraiana, a Causal Agent of Mulberry Sclerotial Disease With Narrow Host Range
Authors: Lv Zhiyuan , He Ziwen , Hao Lijuan , Kang Xin , Ma Bi , Li Hongshun , Luo Yiwei , Yuan Jianglian , He Ningjia
Published: January 2021

Scleromitrula shiraiana is a necrotrophic fungus with a narrow host range, and is one of the main causal pathogens of mulberry sclerotial disease. However, its molecular mechanisms and pathogenesis are unclear. Here, we report a 39.0 Mb high-quality genome sequence for S. shiraiana strain SX-001. The S. shiraiana genome contains 11,327 protein-coding genes. The number of genes and genome size of S. shiraiana are similar to most other Ascomycetes. The cross-similarities and differences of S. shiraiana with the closely related Sclerotinia sclerotiorum and Botrytis cinerea indicated that S. shiraiana differentiated earlier from their common ancestor. A comparative genomic analysis showed that S. shiraiana has fewer genes encoding cell wall-degrading enzymes (CWDEs) and effector proteins than that of S. sclerotiorum and B. cinerea, as well as many other Ascomycetes. This is probably a key factor in the weaker aggressiveness of S. shiraiana to other plants. S. shiraiana has many species-specific genes encoding secondary metabolism core enzymes. The diversity of secondary metabolites may be related to the adaptation of these pathogens to specific ecological niches. However, melanin and oxalic acid are conserved metabolites among many Sclerotiniaceae fungi, and may be essential for survival and infection. Our results provide insights into the narrow host range of S. shiraiana and its adaptation to mulberries.
Niche Differentiation of Comammox Nitrospira in the Mudflat and Reclaimed Agricultural Soils Along the North Branch of Yangtze River Estuary
Authors: Wang Xinxin , Lu Lu , Zhou Xue , Tang Xiufeng , Kuang Lu , Chen Junhui , Shan Jun , Lu Huijie , Qin Hua , Adams Jonathan , Wang Baozhan
Published: January 2021

The discovery of complete ammonia oxidation (comammox), oxidizing ammonia to nitrate via nitrite in a single organism, has redefined the traditional recognition of the two-step nitrification driven by two functional groups (ammonia-oxidizing and nitrite-oxidizing microorganisms). However, the understanding of the distribution and niche differentiation of comammox Nitrospira in the estuarine mudflats and their reclaimed agricultural soils is still limited. Here, we investigated the abundance, diversity and community structures of comammox Nitrospira in the mudflats and the reclaimed agricultural soils in the northern Yangtze River estuary. Quantitative PCR showed the abundances of amoA genes of comammox were lower than that of ammonia-oxidizing bacteria (AOB) in nearly all samples. Amplicon sequencing of amoA genes revealed that the community structures of comammox Nitrospira were significantly (P < 0.001) different between the original mudflats and the reclaimed agricultural soils, indicating niche differentiation among comammox Nitrospira clades (clade A.1, clade A.2, and clade B). The clade A.1 was the dominant group of comammox Nitrospira in the mudflats, while clade B predominated in the agricultural soils. However, the members of clade A.2 could be clearly divided into two groups, the mudflat-preferred and agricultural soil-preferred groups, suggesting more complicated ecological preferences within this sub-clade. Furthermore, it was demonstrated that salinity, organic matter (OM) and NO3–-N had a significantly influence on the distribution of comammox Nitrospira in the estuarine environment. Clade A.1 and nearly half members of clade A.2 were positively correlated with salinity, and negatively correlated with the concentrations of OM and NO3–-N. In contrast, the clade B and the other half members of clade A.2 showed the exact opposite pattern: a negative correlation with salinity and positive correlation with OM and NO3–-N. The co-occurrence network demonstrated that the operational taxonomic units (OTUs) within the same (sub-)clade were mostly positively correlated, indicating the similar niche preferences among the members from the same (sub-)clade of comammox Nitrospira. Taken together, our results revealed the niche differentiation of comammox Nitrospira in estuarine ecosystems where salinity and OM were the primary factors responsible for the distinct ecological distribution patterns.
Transcriptome Profiling of Staphylococcus aureus Associated Extracellular Vesicles Reveals Presence of Small RNA-Cargo
Authors: Joshi Bishnu , Singh Bhupender , Nadeem Aftab , Askarian Fatemeh , Wai Sun Nyunt , Johannessen Mona , Hegstad Kristin
Published: January 2021

Bacterial extracellular vesicles (EVs) have a vital role in bacterial pathogenesis. However, to date, the small RNA-cargo of EVs released by the opportunistic pathogen Staphylococcus aureus has not been characterized. Here, we shed light on the association of small RNAs with EVs secreted by S. aureus MSSA476 cultured in iron-depleted bacteriologic media supplemented with a subinhibitory dosage of vancomycin to mimic infection condition. Confocal microscopy analysis on intact RNase-treated EVs indicated that RNA is associated with EV particles. Transcriptomic followed by bioinformatics analysis of EV-associated RNA revealed the presence of potential gene regulatory small RNAs and high levels of tRNAs. Among the EV-associated enriched small RNAs were SsrA, RsaC and RNAIII. Our finding invites new insights into the potential role of EV-associated RNA as a modulator of host-pathogen interaction.
Long Non-coding RNAMALAT1 Knockdown Alleviates Cerebral Ischemia/Reperfusion Injury of Rats Through Regulating the miR-375/PDE4D Axis
Authors: Zhang Guangjian , Wang Qingdong , Su Daoqing , Xie Yingliang
Published: January 2021

Objectives: Cerebral ischemic/reperfusion injury (CI/RI) is the clinical manifestation of cerebral ischemic stroke, which severely affects the health and life of the patients. We aimed to investigate the regulatory mechanism of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on CI/RI in this study.

Methods: The expression of lncRNA MALAT1 and miR-375 was detected by qRT-PCR. MTT was utilized to measure the viability of PC-12 cells. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and reactive oxygen species (ROS) were detected by LDH assay, SOD assay, and ROS assay, respectively. The apoptosis rate of PC-12 cells was measured by flow cytometry analysis. Through enzyme-linked immunosorbent assay, the levels of NF-α, IL-1β, and IL-6 were determined. The interactions between miR-375 and MALAT1/PDE4D were predicted by Starbase/Targetscan software and verified by the dual-luciferase reporter assay. Western blot assay was performed to determine the protein expression of Bcl-2, Caspase-3, and PDE4D.

Results: LncRNA MALAT1 expression was highly upregulated in the middle cerebral artery occlusion (MCAO)/reperfusion (R) model of rats. Both MALAT1 downregulation and miR-375 upregulation reversed the inhibitory effect of oxygen and glucose deprivation (OGD)/R on cell viability and the promoting effects on LDH level, cell apoptosis, and inflammatory factors levels. MALAT1 targeted miR-375, whereas miR-375 targeted PDE4D. Overexpression of miR-375 attenuated OGD/R-induced injury in PC-12 cells by targeting PDE4D. Both the low expression of miR-375 and high expression of PDE4D reversed the promoting effect of MALAT1 knockdown on SOD level and the inhibitory effects on ROS level, inflammatory factor levels, and cell apoptosis.

Conclusion: Suppression of MALAT1 alleviates CI/RI of rats through regulating the miR-375/PDE4D axis. This study provides a possible therapeutic strategy for human CI/RI in clinic.
Case Report: Filling Defect in Posterior Semicircular Canal on MRI With Balanced Steady-State Gradient-Echo Sequences After Labyrinthine Ischemia in the Common Cochlear Artery Territory as an Early Sign of Fibrosis
Authors: Castellucci Andrea , Pepponi Emanuela , Bertellini Annalisa , Senesi Caterina , Bettini Margherita , Botti Cecilia , Martellucci Salvatore , Malara Pasquale , Delmonte Silvia , Crocetta Francesco Maria , Fornaciari Martina , Lusetti Francesca , Bianchin Giovanni , Ghidini Angelo
Published: January 2021

We describe a rare case of posterior semicircular canal (PSC) fibrosis following acute labyrinthine ischemia in the territory supplied by the common cochlear artery (CCA) and review the relevant literature. A 71-year-old man with multiple vascular risk factors presented 12 days after the onset of acute vertigo and profound left-sided hearing loss. Right-beating spontaneous nystagmus with downbeat components elicited by mastoid vibrations and headshaking was detected. The video head impulse test (vHIT) revealed an isolated hypofunction of the left PSC, whereas vestibular evoked myogenic potentials (VEMPs) showed ipsilateral saccular loss. The clinical presentation and instrumental picture were consistent with acute ischemia in the territory supplied by left CCA. Compared to previous imaging, a new MRI of the brain with 3D-FIESTA sequences highlighted a filling defect in the left PSC, consistent with fibrosis. Hearing function exhibited mild improvement after steroid therapy and hyperbaric oxygen sessions, whereas vHIT abnormalities persisted over time. To the best of our knowledge, this is the only case in the literature reporting a filling defect on MRI, consistent with semicircular canal fibrosis following acute labyrinthine ischemia. Moreover, PSC fibrosis was related with poor functional outcome. We therefore suggest using balanced steady-state gradient-echo sequences a few weeks following an acute lesion of inner ear sensors to detect signal loss within membranous labyrinth consistent with post-ischemic fibrosis. Besides addressing the underlying etiology, signal loss might also offer clues on the functional behavior of the involved sensor over time. In cases of acute loss of inner ear function, a careful bedside examination supplemented by instrumental assessments, including vHIT and VEMPs, of vestibular receptors and afferents may be completed by MRI with balanced steady-state gradient-echo sequences at a later time to confirm the diagnosis and address both etiology and functional outcome.
The Potential of Multi-Biomarker Panels in Nutrition Research: Total Fruit Intake as an Example
Authors: McNamara Aoife E. , Walton Janette , Flynn Albert , Nugent Anne P. , McNulty Breige A. , Brennan Lorraine
Published: January 2021

Dietary and food intake biomarkers offer the potential of improving the accuracy of dietary assessment. An extensive range of putative intake biomarkers of commonly consumed foods have been identified to date. As the field of food intake biomarkers progresses toward solving the complexities of dietary habits, combining biomarkers associated with single foods or food groups may be required. The objective of this work was to examine the ability of a multi-biomarker panel to classify individuals into categories of fruit intake. Biomarker data was measured using 1H NMR spectroscopy in two studies: (1) An intervention study where varying amounts of fruit was consumed and (2) the National Adult Nutrition Survey (NANS). Using data from an intervention study a biomarker panel (Proline betaine, Hippurate, and Xylose) was constructed from three urinary biomarker concentrations. Biomarker cut-off values for three categories of fruit intake were developed. The biomarker sum cut-offs were ≤ 4.766, 4.766–5.976, >5.976 μM/mOsm/kg for <100, 101–160, and >160 g fruit intake. The ability of the biomarker sum to classify individuals into categories of fruit intake was examined in the cross-sectional study (NANS) (N = 565). Examination of results in the cross-sectional study revealed excellent agreement with self-reported intake: a similar number of participants were ranked into each category of fruit intake. The work illustrates the potential of multi-biomarker panels and paves the way forward for further development in the field. The use of such panels may be key to distinguishing foods and adding specificity to the predictions of food intake.