bluuebunny/crossref_metadata_2025 huggingface dataset:
Cationic Polymer Brush-Modified Carbon Nanotube-Meditated eRNA LINC02569 Silencing Attenuates Nucleus Pulposus Degeneration by Blocking NF-κB Signaling Pathway and Alleviate Cell Senescence
Authors: Huang Yulin , Yang Jiaming , Liu Xizhe , Wang Xiaoshuai , Zhu Kai , Ling Zemin , Zeng Baozhu , Chen Ningning , Liu Shaoyu , Wei Fuxin
Published: January 2022

Enhancer RNAs (eRNAs) are noncoding RNAs that synthesized at active enhancers. eRNAs have important regulatory characteristics and appear to be significant for maintenance of cell identity and information processing. Series of functional eRNAs have been identified as potential therapeutic targets for multiple diseases. Nevertheless, the role of eRNAs on intervertebral disc degeneration (IDD) is still unknown yet. Herein, we utilized the nucleus pulposus samples of patients and identified a key eRNA (LINC02569) with the Arraystar eRNA Microarray. LINC02569 mostly locates in nucleus and plays an important role in the progress of IDD by activating nuclear factor kappa-B (NF-κB) signaling pathway. We used a cationic polymer brush coated carbon nanotube (oCNT-pb)-based siRNA delivery platform that we previously designed, to transport LINC02569 siRNA (si-02569) to nucleus pulposus cells. The siRNA loaded oCNT-pb accumulated in nucleus pulposus cells with lower toxicity and higher transfection efficiency, compared with the traditional siRNA delivery system. Moreover, the results showed that the delivery of si-02569 significantly alleviated the inflammatory response in the nucleus pulposus cells via inhibiting P65 phosphorylation and preventing its transfer into the nucleus, and meanwhile alleviated cell senescence by decreasing the expression of P21. Altogether, our results highlight that eRNA (LINC02569) plays important role in the progression of IDD and could be a potential therapeutic target for alleviation of IDD.
Gas–Liquid Slug Flow Studies in Microreactors: Effect of Nanoparticle Addition on Flow Pattern and Pressure Drop
Authors: Zong Jie , Yue Jun
Published: January 2022

Colloidal suspensions of nanoparticles (e.g., metals and oxides) have been considered as a promising working fluid in microreactors for achieving significant process intensification. Existing examples include their uses in microflow as catalysts for enhancing the reaction efficiency, or as additives to mix with the base fluid (i.e., to form the so-called nanofluids) for heat/mass transfer intensification. Thus, hydrodynamic characterization of such suspension flow in microreactors is of high importance for a rational design and operation of the system. In this work, experiments have been conducted to investigate the flow pattern and pressure drop characteristics under slug flow between N2 gas and colloidal suspensions in the presence of TiO2 or Al2O3 nanoparticles through polytetrafluoroethylene (PTFE) capillary microreactors. The base fluid consisted of water or its mixture with ethylene glycol. The slug flow pattern with nanoparticle addition was characterized by the presence of a lubricating liquid film around N2 bubbles, in contrast to the absence of liquid film in the case of N2-water slug flow. This shows that the addition of nanoparticles has changed the wall wetting property to be more hydrophilic. Furthermore, the measured pressure drop under N2-nanoparticle suspension slug flow is well described by the model of Kreutzer et al. (AIChE J 51(9):2428–2440, 2005) at the mixture Reynolds numbers ca. above 100 and is better predicted by the model of Warnier et al. (Microfluidics and Nanofluidics 8(1):33–45, 2010) at lower Reynolds numbers given a better consideration of the effect of film thickness and bubble velocity under such conditions in the latter model. Therefore, the employed nanoparticle suspension can be considered as a stable and pseudo single phase with proper fluid properties (e.g., viscosity and density) when it comes to the pressure drop estimation.
Highly Sensitive Water Detection Through Reversible Fluorescence Changes in a syn-Bimane Based Boronic Acid Derivative
Authors: Pramanik Apurba , Karmakar Joy , Grynszpan Flavio , Levine Mindy
Published: January 2022

Reported herein is a fluorometric and colorimetric sensor for the presence of trace amounts of water in organic solvents, using syn-bimane based boronate ester 1. This sensor responds to the presence of water with a highly sensitive turn-off fluorescence response, with detection limits as low as 0.018% water (v/v). Moreover, analogously high performance was observed when compound 1 was adsorbed on filter paper, with the paper-based sensor responding both to the presence of liquid water and to humid atmospheres. Reusability of the paper-based sensor up to 11 cycles was demonstrated, albeit with progressive decreases in the performance, and 1H NMR and mass spectrometry analyses were used to explain the observed, hydrolysis-based sensor response.
New Chitosan Polymer Scaffold Schiff Bases as Potential Cytotoxic Activity: Synthesis, Molecular Docking, and Physiochemical Characterization
Authors: Packialakshmi Ponnusamy , Gobinath Perumal , Ali Daoud , Alarifi Saud , Gurusamy Raman , Idhayadhulla Akbar , Surendrakumar Radhakrishnan
Published: January 2022

In this work, we synthesize the sulfonated Schiff bases of the chitosan derivatives 2a-2j without the use of a catalyst in two moderately straightforward steps with good yield within a short reaction time. The morphology and chemical structure of chitosan derivatives were investigated using FT-IR, NMR (1H—13C), XRD, and SEM. Furthermore, our chitosan derivatives were tested for their anticancer activity against the MCF-7 cancer cell line, and doxorubicin was used as a standard. In addition, the normal cell lines of the breast cancer cell MCF-10A, and of the lung cell MRC-5 were tested. Compound 2 h, with a GI50 value of 0.02 µM for MCF-7, is highly active compared with the standard doxorubicin and other compounds. The synthesized compounds 2a-2j exhibit low cytotoxicity, with IC50 > 100 μg/ml, against normal cell lines MCF-10A, MRC-5. We also provide the results of an in-silico study involving the Methoxsalen protein (1Z11). Compound 2h exhibits a higher binding affinity for 1Z11 protein (−5.9 kcal/mol) and a lower binding affinity for Doxorubicin (−5.3 kcal/mol) than certain other compounds. As a result of the aforementioned findings, the use of compound 2h has an anticancer drug will be researched in the future.
Application of Fatty Liver Inhibition of Progression Algorithm and Steatosis, Activity, and Fibrosis Score to Assess the Impact of Non-Alcoholic Fatty Liver on Untreated Chronic Hepatitis B Patients
Authors: Huang Yan , Gan Qinyi , Lai Rongtao , Wang Weijing , Guo Simin , Sheng Zike , Chen Lu , Guo Qing , Cai Wei , Wang Hui , Zhao Gangde , Cao Zhujun , Xie Qing
Published: January 2022

Backgrounds and Purpose

Concurrent non-alcoholic fatty liver disease (NAFLD) in chronic hepatitis B (CHB) patients is a frequent and increasingly concerning problem because of the NAFLD pandemic. Admittedly, NAFLD can progress to non-alcoholic steatohepatitis (NASH) and severe fibrosis. Direct evidence of the fibrotic effect of NAFLD or NASH in chronic hepatitis B virus (HBV) infection remains lacking. We aimed to reveal the influence of concurrent histologically proven fatty liver diseases in fibrogenesis with chronic HBV infection.

Methods

We performed a retrospective cross-sectional study on a liver biopsy population of CHB patients without excessive alcohol intake to evaluate the prevalence of concurrent histologically proven NAFLD or NASH according to the fatty liver inhibition of progression (FLIP) algorithm and its association with the liver fibrosis stage.

Results

Among 1,081 CHB patients, concurrent NAFLD was found in 404 patients (37.4%), among whom 24.0% (97/404) have NASH. The presence of NASH was an independent predictor of significant fibrosis (odds ratio (OR), 2.53; 95% CI, 1.52–4.21; p < 0.001) and severe fibrosis (OR, 1.83; 95% CI, 1.09–3.09; p = 0.023) in all patients, as well as in patients with normal alanine aminotransferase (ALT) (predicting significant fibrosis, OR, 2.86, 95% CI, 1.34–6.10; p = 0.007). The presence of lobular inflammation (p < 0.001) or presence of cytological ballooning (p < 0.001), rather than presence of steatosis (p = 0.419), was related with severity of fibrosis in Spearman’s correlation analysis.

Conclusions

Concurrent NAFLD is common in CHB patients, and NASH is an independent risk factor potentiating significant fibrosis by 2.53-fold and severe fibrosis by 1.83-fold. While coping with chronic HBV infection, routine assessment of co-existing NAFLD or NASH is also important.
Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne’s Disease
Authors: Wherry Taylor L. T. , Dassanayake Rohana P. , Casas Eduardo , Mooyottu Shankumar , Bannantine John P. , Stabel Judith R.
Published: January 2022

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of ruminant enteritis, targets intestinal macrophages. During infection, macrophages contribute to mucosal inflammation and development of granulomas in the small intestine which worsens as disease progression occurs. Vitamin D3 is an immunomodulatory steroid hormone with beneficial roles in host-pathogen interactions. Few studies have investigated immunologic roles of 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in cattle, particularly cattle infected with MAP. This study examined the effects of exogenous vitamin D3 on immune responses of monocyte derived macrophages (MDMs) isolated from dairy cattle naturally infected with MAP. MDMs were pre-treated with ± 100 ng/ml 25(OH)D3 or ± 4 ng/ml 1,25(OH)2D3, then incubated 24 hrs with live MAP in the presence of their respective pre-treatment concentrations. Following treatment with either vitamin D3 analog, phagocytosis of MAP by MDMs was significantly greater in clinically infected animals, with a greater amount of live and dead bacteria. Clinical cows had significantly less CD40 surface expression on MDMs compared to subclinical cows and noninfected controls. 1,25(OH)2D3 also significantly increased nitrite production in MAP infected cows. 1,25(OH)2D3 treatment played a key role in upregulating secretion of pro-inflammatory cytokines IL-1β and IL-12 while downregulating IL-10, IL-6, and IFN-γ. 1,25(OH)2D3 also negatively regulated transcripts of CYP24A1, CYP27B1, DEFB7, NOS2, and IL10. Results from this study demonstrate that vitamin D3 compounds, but mainly 1,25(OH)2D3, modulate both pro- and anti-inflammatory immune responses in dairy cattle infected with MAP, impacting the bacterial viability within the macrophage.
Intestinal Epithelial Cell Exosome Launches IL-1β-Mediated Neuron Injury in Sepsis-Associated Encephalopathy
Authors: Xi Shaosong , Wang Yunguang , Wu Chenghao , Peng Weihua , Zhu Ying , Hu Wei
Published: January 2022

Background

Gut–microbiota–brain axis links the relationship between intestinal microbiota and sepsis-associated encephalopathy (SAE). However, the key mediators between them remain unclear.

Methods

Memory test was determined by Water maze. Intestinal flora was measured by 16S RNA sequencing. Neurotransmitter was detected by high-performance liquid chromatography (HPLC). Histopathology was determined by H&E, immunofluorescence (IF), and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. Flow cytometry was employed to determine the proportion of macrophages.

Results

Fecal microbiota transplantation (FMT) relieved hippocampus impairment of SAE rats by inhibiting inflammation cytokine secretion, the expression of IBA-1 and neurotransmitter disturbance, and cell apoptosis and autophagy, accompanied by the reduced M1 polarization and M1 pro-inflammation factors produced by macrophages in mesenteric lymph nodes (MLNs). Actually, M1 polarization in SAE rats depended on intestinal epithelial cell (IEC)-derived exosome. GW4869-initiated inhibition of exosome secretion notably abolished M1 polarization and the secretion of IL-1β. However, GW4869-mediated improvement of hippocampus impairment was counteracted by the delivery of recombinant interleukin (IL)-1β to hippocampus. Mechanistically, IEC-derived exosome induced the excessive circulating IL-1β produced by CP-R048 macrophages, which subsequently induced damage and apoptosis of hippocampal neurons H19-7 in an autophagy-dependent manner. And reactivation of autophagy facilitates intestinal IL-1β-mediated hippocampal neuron injury.

Conclusion

Collectively, intestinal flora disturbance induced the exosome release of IECs, which subsequently caused M1 polarization in MLNs and the accumulation of circulating IL-1β. Circulating IL-1β promoted the damage and apoptosis of neurons in an autophagy-dependent manner. Possibly, targeting intestinal flora or IEC-derived exosome contributes to the treatment of SAE.
Micrococcal Nuclease stimulates Staphylococcus aureus Biofilm Formation in a Murine Implant Infection Model
Authors: Forson Abigail M. , Rosman Colin W. K. , van Kooten Theo G. , van der Mei Henny C. , Sjollema Jelmer
Published: January 2022

Advancements in contemporary medicine have led to an increasing life expectancy which has broadened the application of biomaterial implants. As each implant procedure has an innate risk of infection, the number of biomaterial-associated infections keeps rising. Staphylococcus aureus causes 34% of such infections and is known as a potent biofilm producer. By secreting micrococcal nuclease S. aureus is able to escape neutrophil extracellular traps by cleaving their DNA-backbone. Also, micrococcal nuclease potentially limits biofilm growth and adhesion by cleaving extracellular DNA, an important constituent of biofilms. This study aimed to evaluate the impact of micrococcal nuclease on infection persistence and biofilm formation in a murine biomaterial-associated infection-model with polyvinylidene-fluoride mesh implants inoculated with bioluminescent S. aureus or its isogenic micrococcal nuclease deficient mutant. Supported by results based on in-vivo bioluminescence imaging, ex-vivo colony forming unit counts, and histological analysis it was found that production of micrococcal nuclease enables S. aureus bacteria to evade the immune response around an implant resulting in a persistent infection. As a novel finding, histological analysis provided clear indications that the production of micrococcal nuclease stimulates S. aureus to form biofilms, the presence of which extended neutrophil extracellular trap formation up to 13 days after mesh implantation. Since micrococcal nuclease production appeared vital for the persistence of S. aureus biomaterial-associated infection, targeting its production could be a novel strategy in preventing biomaterial-associated infection.
Gut Microbiota: A Key Regulator in the Effects of Environmental Hazards on Modulates Insulin Resistance
Authors: Huang Ruixue
Published: January 2022

Insulin resistance is a hallmark of Alzheimer’s disease (AD), type II diabetes (T2D), and Parkinson’s disease (PD). Emerging evidence indicates that these disorders are typically characterized by alterations in the gut microbiota composition, diversity, and their metabolites. Currently, it is understood that environmental hazards including ionizing radiation, toxic heavy metals, pesticides, particle matter, and polycyclic aromatic hydrocarbons are capable of interacting with gut microbiota and have a non-beneficial health effect. Based on the current study, we propose the hypothesis of “gut microenvironment baseline drift”. According to this “baseline drift” theory, gut microbiota is a temporarily combined cluster of species sharing the same environmental stresses for a short period, which would change quickly under the influence of different environmental factors. This indicates that the microbial species in the gut do not have a long-term relationship; any split, division, or recombination may occur in different environments. Nonetheless, the “baseline drift” theory considers the critical role of the response of the whole gut microbiome. Undoubtedly, this hypothesis implies that the gut microbiota response is not merely a “cross junction” switch; in contrast, the human health or disease is a result of a rich palette of gut-microbiota-driven multiple-pathway responses. In summary, environmental factors, including hazardous and normal factors, are critical to the biological impact of the gut microbiota responses and the dual effect of the gut microbiota on the regulation of biological functions. Novel appreciation of the role of gut microbiota and environmental hazards in the insulin resistance would shed new light on insulin resistance and also promote the development of new research direction and new overcoming strategies for patients.
Novel Insights Into the Interactions Between the Gut Microbiome, Inflammasomes, and Gasdermins During Colorectal Cancer
Authors: Privitera Giuseppe , Rana Nitish , Scaldaferri Franco , Armuzzi Alessandro , Pizarro Theresa T.
Published: January 2022

Colorectal cancer (CRC) is one of the most prevalent and deadly forms of cancer in Western countries. Inflammation is a well-known driver of colonic carcinogenesis; however, its role in CRC extends beyond colitis-associated cancer. Over the last decades, numerous associations between intestinal dysbiosis and CRC have been identified, with more recent studies providing mechanistic evidence of a causative relationship. Nonetheless, much remains to be discovered regarding the precise implications of microbiome alterations in the pathogenesis of CRC. Research confirms the importance of a bidirectional crosstalk between the gut microbiome and the mucosal immune system in which inflammasomes, multiprotein complexes that can sense “danger signals,” serve as conduits by detecting microbial signals and activating innate immune responses, including the induction of microbicidal activities that can alter microbiome composition. Current evidence strongly supports an active role for this “inflammasome–microbiome axis” in the initiation and development of CRC. Furthermore, the gasdermin (GSDM) family of proteins, which are downstream effectors of the inflammasome that are primarily known for their role in pyroptosis, have been recently linked to CRC pathogenesis. These findings, however, do not come without controversy, as pyroptosis is reported to exert both anti- and protumorigenic functions. Furthermore, the multi-faceted interactions between GSDMs and the gut microbiome, as well as their importance in CRC, have only been superficially investigated. In this review, we summarize the existing literature supporting the importance of the inflammasome–microbiota axis, as well as the activation and function of GSDMs, to gain a better mechanistic understanding of CRC pathogenesis.
Infant Pneumococcal Carriage in Belgium Not Affected by COVID-19 Containment Measures
Authors: Willen Laura , Ekinci Esra , Cuypers Lize , Theeten Heidi , Desmet Stefanie
Published: January 2022

Streptococcus pneumoniae is an important and frequently carried respiratory pathogen that has the potential to cause serious invasive diseases, such as pneumonia, meningitis, and sepsis. Young children and older adults are among the most vulnerable to developing serious disease. With the arrival of the COVID-19 pandemic and the concomitant restrictive measures, invasive disease cases caused by respiratory bacterial species, including pneumococci, decreased substantially. Notably, the stringency of the containment measures as well as the visible reduction in the movement of people appeared to coincide with the drop in invasive disease cases. One could argue that wearing protective masks and adhering to social distancing guidelines to halt the spread of the SARS-CoV-2 virus, also led to a reduction in the person-to-person transmission of respiratory bacterial species. Although plausible, this conjecture is challenged by novel data obtained from our nasopharyngeal carriage study which is performed yearly in healthy daycare center attending children. A sustained and high pneumococcal carriage rate was observed amid periods of stringent restrictive measures. This finding prompts us to revisit the connection between nasopharyngeal colonization and invasion and invites us to look closer at the nasopharyngeal microbiome as a whole.
Phytoprevention of Heavy Metal Contamination From Terrestrial Enhanced Weathering: Can Plants Save the Day?
Authors: Suhrhoff Tim Jesper
Published: January 2022

Enhanced weathering is a promising approach to remove carbon dioxide from the atmosphere. However, it may also pose environmental risks through the release of heavy metals, in particular nickel and chromium. In this perspective article I explore the potential role of plants in modulating these heavy metal fluxes. Agricultural basaltic soils may be valuable study sites in this context. However, the effect of biomass harvesting on the accumulation of heavy metals is currently not well studied. Mostly caused by different parent rock concentrations, there is a large variability of heavy metal concentrations in basaltic and ultramafic soils. Hence, to minimize environmental risks of enhanced weathering, basalts with low heavy metal concentrations should be favored. Existing phytoremediation strategies may be used to “phytoprevent” the accumulation of nickel and chromium released from enhanced weathering in soils. As a result, elevated nickel and chromium concentrations in rocks must not preclude enhanced weathering in all settings. In particular, hyperaccumulating plants could be used as part of a crop rotation to periodically remove heavy metals from soils. Enhanced weathering could also be employed on fields or forests of (non-hyper) accumulating plants that have a high primary production of biomass. Both approaches may have additional synergies with phytomining or bioenergy carbon capture and storage, increasing the total amount of carbon dioxide drawdown and at the same time preventing heavy metal accumulation in soils.
Uncertainty in Health Emergencies: Communicating Risks During COVID-19 Response
Authors: Logar Silvia , Bednarova Rym , Rizzardo Alessandro , Miceli Luca
Published: January 2022

The world’s fragmented response to the COVID-19 pandemic created fertile ground for mixed messages and inconsistency. The authors analyzed Google-trending insights from five countries (Italy, Spain, the United States, the United Kingdom, and France) across three-week time (1–23 March 2020) to document trends in population health anxiety in response to the initial global spreading of the outbreak. The results are expressed in the form of Uncertainty Index (UI), which reflects the total number of Google searches/COVID-19 prevalence and standardized per million inhabitants. The United Kingdom experienced the highest level of health anxiety (UI = 11.5), followed by France (UI = 4.6) and Spain (UI = 3.2). The United States suffered the highest rate of uncertainty in the early stage of the pandemic; the Italian population experienced a balanced level of anxiety. Institutionalizing risk communication during COVID-19 should represent an integral part of the country emergency response.
Detecting Fear of Heights Response to a Virtual Reality Environment Using Functional Near-Infrared Spectroscopy
Authors: de With Luciënne A. , Thammasan Nattapong , Poel Mannes
Published: January 2022

To enable virtual reality exposure therapy (VRET) that treats anxiety disorders by gradually exposing the patient to fear using virtual reality (VR), it is important to monitor the patient's fear levels during the exposure. Despite the evidence of a fear circuit in the brain as reflected by functional near-infrared spectroscopy (fNIRS), the measurement of fear response in highly immersive VR using fNIRS is limited, especially in combination with a head-mounted display (HMD). In particular, it is unclear to what extent fNIRS can differentiate users with and without anxiety disorders and detect fear response in a highly ecological setting using an HMD. In this study, we investigated fNIRS signals captured from participants with and without a fear of height response. To examine the extent to which fNIRS signals of both groups differ, we conducted an experiment during which participants with moderate fear of heights and participants without it were exposed to VR scenarios involving heights and no heights. The between-group statistical analysis shows that the fNIRS data of the control group and the experimental group are significantly different only in the channel located close to right frontotemporal lobe, where the grand average oxygenated hemoglobin Δ[HbO] contrast signal of the experimental group exceeds that of the control group. The within-group statistical analysis shows significant differences between the grand average Δ[HbO] contrast values during fear responses and those during no-fear responses, where the Δ[HbO] contrast values of the fear responses were significantly higher than those of the no-fear responses in the channels located towards the frontal part of the prefrontal cortex. Also, the channel located close to frontocentral lobe was found to show significant difference for the grand average deoxygenated hemoglobin contrast signals. Support vector machine-based classifier could detect fear responses at an accuracy up to 70% and 74% in subject-dependent and subject-independent classifications, respectively. The results demonstrate that cortical hemodynamic responses of a control group and an experimental group are different to a considerable extent, exhibiting the feasibility and ecological validity of the combination of VR-HMD and fNIRS to elicit and detect fear responses. This research thus paves a way toward the a brain-computer interface to effectively manipulate and control VRET.
The Disconnect Between Short- and Long-Term Population Projections for Plant Reintroductions
Authors: Bialic-Murphy Lalasia , Knight Tiffany M. , Kawelo Kapua , Gaoue Orou G.
Published: January 2022

The reintroduction of rare species in natural preserves is a commonly used restoration strategy to prevent species extinction. An essential first step in planning successful reintroductions is identifying which life stages (e.g., seeds or large adults) should be used to establish these new populations. Following this initial establishment phase, it is necessary to determine the level of survival, growth, and recruitment needed to maintain population persistence over time and identify management actions that will achieve these goals. In this 5-year study, we projected the short- and long-term population growth rates of a critically endangered long-lived shrub, Delissea waianaeensis. Using this model system, we show that reintroductions established with mature individuals have the lowest probability of quasi-population extinction (10 individuals) and the highest increase in population abundance. However, our results also demonstrate that short-term increases in population abundances are overly optimistic of long-term outcomes. Using long-term stochastic model simulations, we identified the level of natural seedling regeneration needed to maintain a positive population growth rate over time. These findings are relevant for planning future reintroduction efforts for long-lived species and illustrate the need to forecast short- and long-term population responses when evaluating restoration success.
Event-Based Resilient Control of Multi-Agent Systems in Non-Ideal Communication Networks
Authors: Lyu Jianting , Sun Lianghui , Wang Xin , Gao Dai
Published: January 2022

This article focuses on the consensus problem of linear multi-agent systems under denial-of-service attacks and directed switching topologies. With only intermittent communication, the leader-following consensus can be preserved by fully distributed event-triggered strategies. Theoretical analysis shows that the proposed event-triggered resilient controller guarantees the exponential convergence in the presence of denial-of-service attacks and the exclusion of Zeno behavior. Compared to the existing studies where continuous communication between neighboring agents is required, the event-triggered data reduction scheme is provided to tackle the effects of denial-of-service attacks on directed switching topology as well as to avoid continuous communication and reduce energy consumption. The obtained results can be extended to the scenario without a leader. Numerical simulations are finally given to illustrate the effectiveness of the proposed method.
Left Ventricular Mechanics Differ in Subtypes of Aortic Stenosis Following Transcatheter Aortic Valve Replacement
Authors: Wani Adil , Harland Daniel R. , Bajwa Tanvir K. , Kroboth Stacie , Ammar Khawaja Afzal , Allaqaband Suhail Q. , Duval Sue , Khandheria Bijoy K. , Tajik A. Jamil , Jain Renuka
Published: January 2022

Background

Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). We hypothesized that there would be differences in myocardial mechanics, measured by global longitudinal strain (GLS) recovery in patients with four subtypes of severe AS after transcatheter aortic valve replacement (TAVR), stratified based upon flow and gradient.

Methods

We retrospectively evaluated 204 patients with severe AS who underwent TAVR and were followed post-TAVR at our institution for clinical outcomes. Speckle-tracking transthoracic echocardiography was performed pre- and post-TAVR. Patients were classified as: (1) normal-flow and high-gradient, (2) normal-flow and high-gradient with reduced LV ejection fraction (LVEF), (3) classical low-flow and low-gradient, or (4) paradoxical low-flow and low-gradient.

Results

Both GLS (−13.9 ± 4.3 to −14.8 ± 4.3, P < 0.0001) and LVEF (55 ± 15 to 57 ± 14%, P = 0.0001) improved immediately post-TAVR. Patients with low-flow AS had similar improvements in LVEF (+2.6 ± 9%) and aortic valve mean gradient (−23.95 ± 8.34 mmHg) as patients with normal-flow AS. GLS was significantly improved in patients with normal-flow (−0.93 ± 3.10, P = 0.0004) compared to low-flow AS. Across all types of AS, improvement in GLS was associated with a survival benefit, with GLS recovery in alive patients (mean GLS improvement of −1.07 ± 3.10, P < 0.0001).

Conclusions

LV mechanics are abnormal in all patients with subtypes of severe AS and improve immediately post-TAVR. Recovery of GLS was associated with a survival benefit. Patients with both types of low-flow AS showed significantly improved, but still impaired, GLS post-TAVR, suggesting underlying myopathy that does not correct post-TAVR.
The Regulation Mechanisms and Clinical Application of MicroRNAs in Myocardial Infarction: A Review of the Recent 5 Years
Authors: Wu Chan , Liu Binghong , Wang Ruiying , Li Gang
Published: January 2022

Myocardial infarction (MI) is the most frequent end-point of cardiovascular pathology, leading to higher mortality worldwide. Due to the particularity of the heart tissue, patients who experience ischemic infarction of the heart, still suffered irreversible damage to the heart even if the vascular reflow by treatment, and severe ones can lead to heart failure or even death. In recent years, several studies have shown that microRNAs (miRNAs), playing a regulatory role in damaged hearts, bring light for patients to alleviate MI. In this review, we summarized the effect of miRNAs on MI with some mechanisms, such as apoptosis, autophagy, proliferation, inflammatory; the regulation of miRNAs on cardiac structural changes after MI, including angiogenesis, myocardial remodeling, fibrosis; the application of miRNAs in stem cell therapy and clinical diagnosis; other non-coding RNAs related to miRNAs in MI during the past 5 years.
Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death
Authors: Antoniak Silvio , Phungphong Sukanya , Cheng Zhaokang , Jensen Brian C.
Published: January 2022

Anthracycline antineoplastic agents such as doxorubicin are widely used and highly effective component of adjuvant chemotherapy for breast cancer and curative regimens for lymphomas, leukemias, and sarcomas. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that typically manifests as cardiomyopathy and can progress to the potentially fatal clinical syndrome of heart failure. Decades of pre-clinical research have explicated the complex and multifaceted mechanisms of anthracycline-induced cardiotoxicity. It is well-established that oxidative stress contributes to the pathobiology and recent work has elucidated important central roles for direct mitochondrial injury and iron overload. Here we focus instead on emerging aspects of anthracycline-induced cardiotoxicity that may have received less attention in other recent reviews: thrombosis, myocardial atrophy, and non-apoptotic programmed cell death.
Trends in Diabetes Mortality in Urban and Rural China, 1987–2019: A Joinpoint Regression Analysis
Authors: Su Binbin , Wang Yiran , Dong Yanhui , Hu Gang , Xu Yike , Peng Xiaobo , Wang Qianyun , Zheng Xiaoying
Published: January 2022

Purpose

Diabetes mellitus is emerging as an epidemic worldwide, and the incidence and prevalence of diabetes have drastically changed in China over the past 30 years, but data on its mortality rate are scarce. This study aimed to analyze the time trends of mortality rates among patients with diabetes in the rural and urban population in China between 1987 and 2019.

Methods

The research data come from China’s annual report on national health statistics and the Chinese Health Statistics Yearbook. Age-standardized mortality rates were calculated by using the direct method based on the World Standard Population from the WHO. Joinpoint regression analysis was employed to estimate the annual percent change and average annual percentage changes of mortality rates of diabetes mellitus.

Results

An overall trend for increment in diabetes mortality was observed. The crude mortality rates and age-standardized mortality rates of diabetes for urban and rural residents in China showed a significant increasing trend between 1987 and 2019. Mortality due to diabetes in urban areas has been higher than in rural areas for 30 years. However, due to the rapid increase of rural diabetes mortality in the past decade, the gap between the two gradually narrowed. The age-standardized mortality rates of diabetes increased by about 38.5% in urban areas and 254.9% in rural areas over the whole study period. In addition, the age-standardized mortality rate of females with diabetes was higher than that of males, but this pattern began to change in urban areas in 2012. Finally, the age-standardized mortality rates in the elderly population in China are higher with a faster growth rate, especially in rural areas.

Conclusion

The mortality rate of diabetes is on the rise in China. The rapid growth of the mortality rate of diabetes in rural areas leads to the reduction of the urban–rural gap. Male mortality rates in urban areas have surpassed those of women. At the same time, the mortality rate of diabetes showed obvious elder-group orientation. As China’s population ages, the burden of death and disability caused by diabetes and its complications will continue to increase. These results indicate that diabetes has become a significant public health problem in China. Such an effect increases the demand for strategies aimed at the prevention and treatment of diabetes mellitus. In addition to the prevention and intervention of diabetes in high-risk groups, it is also necessary to establish diabetes screening networks to identify patients with mild symptoms. Early detection and timely intervention can effectively reduce the incidence and mortality of diabetes.
Climate Overrides Effects of Fertilizer and Straw Management as Controls of Nitrous Oxide Emissions After Oilseed Rape Harvest
Authors: Köbke Sarah , He Hongxing , Böldt Matthias , Wang Haitao , Senbayram Mehmet , Dittert Klaus
Published: January 2022

Oilseed rape (Brassica napusL.) is an important bioenergy crop that contributes to the diversification of renewable energy supply and mitigation of fossil fuel CO2emissions. Typical oilseed rape crop management includes the use of nitrogen (N) fertilizer and the incorporation of oilseed rape straw into soil after harvest. However, both management options risk increasing soil emissions of nitrous oxide (N2O). The aim of this 2-years field experiment was to identify the regulating factors of N cycling with emphasis on N2O emissions during the post-harvest period. As well as the N2O emission rates, soil ammonia (NH4+) and nitrate (NO3−) contents, crop residue and seed yield were also measured. Treatments included variation of fertilizer (non-fertilized, 90 and 180 kg N ha−1) and residue management (straw remaining, straw removal). Measured N2O emission data showed large intra- and inter-annual variations ranging from 0.5 (No-fert + str) to 1.0 kg N2O-N ha−1(Fert-180 + str) in 2013 and from 4.1 (Fert-90 + str) to 7.3 kg N2O-N ha−1(No-fert + str) in 2014. Cumulative N2O emissions showed that straw incorporation led to no difference or slightly reduced N2O emissions compared with treatments with straw removal, while N fertilization has no effect on post-harvest N2O emissions. A process-based model, CoupModel, was used to explain the large annual variation of N2O after calibration with measured environmental data. Both modeled and measured data suggest that soil water-filled pore space and temperature were the key factors controlling post-harvest N2O emissions, even though the model seemed to show a higher N2O response to the N fertilizer levels than our measured data. We conclude that straw incorporation in oilseed rape cropping is environmentally beneficial for mitigating N2O losses. The revealed importance of climate in regulating the emissions implies the value of multi-year measurements. Future studies should focus on new management practices to mitigate detrimental effects caused by global warming, for example by using cover crops.
Decarbonized Energies and the Wealth of Three European Nations: A Comparative Nexus Study Using Granger and Toda-Yamamoto Approaches
Authors: Simionescu Mihaela , Schneider Nicolas , Gavurova Beata
Published: January 2022

Considering the actual debate nuclear vs renewable that divides the green transition of the EU member states, this paper investigates the dynamic interactions between two sources of decarbonized energy (renewables and nuclear) and economic growth for three distinct economies: France, Spain, and Germany, all differing in their respective long-run nuclear planning. A complex methodological framework is employed to consider stationary (Augmented Dickey-Fuller test, Phillips-Perron test, Dickey-Fuller test, Elliott-Rothenberg-Stock test, Kwiatkowski-Phillips-Schmidt-Shin test, Zivot and Andrews test with structural break), cointegration (Johansen and Juselius test of cointegration, Gregory and Hansen cointegration test with breaks based on regime-trend shifts), long-run convergence (Vector Error Correction Model), causality (Granger causality test, Toda-Yamamoto non-causality test, and variance analysis (Impulse Response Functions) Empirical results for the period 1983–2019 fail to support the existence of statistical causality between renewable energy use and economic growth in France and Spain, which is congruent with the “neutral hypothesis”. Besides, while a weak one-way link is revealed from renewable energy use to GDP in Germany only, economic growth is found to substantially trigger nuclear energy consumption in Spain but not vice versa, thus corroborating the “growth hypothesis”. Accordingly, country-specific insights are provided to deploy low-carbon sectoral facilities in Spain, enhance the channels of radioactive waste treatment in France, and secure the nuclear phase-out in Germany.
Wintering Town: Individual Quality of Migratory Warblers Using Green Urban Areas in a Neotropical City
Authors: Pacheco-Muñoz Rodrigo , Ceja-Madrigal Adrián , Pérez-Negrón Edgar , Ortiz-Asbun A. Karen , Schondube Jorge E.
Published: January 2022

Migratory birds can be familiar winter visitors of Neotropical cities. However, of the regional migrant species bird pool, only a few species are abundant in urban areas. Their presence inside cities has been positively related to green urban areas with high tree cover. However, urban elements like artificial lights can also attract them to cities. Habitat quality that enables energetic refueling for migrant birds is crucial in all their annual migratory stages. While some Nearctic cities offer a high-quality refueling habitat for migrant birds, we lack this information for Neotropical cities where migratory birds winter. In this study, we evaluate whether the urban green areas of a Neotropical city act as high-quality habitats for two abundant species of migratory warblers:Setophaga coronataandLeiothlypis ruficapilla.We assessed this by capturing birds inside three urban green areas and comparing their abundances, population structure, and individual quality (scaled-mass index—SMI) with individuals spending winter in natural vegetation habitats outside the city. We found that both species do not show differences in SMI between urban and non-urban sites. We also found thatSetophaga coronatahad a higher capture rate in urban than non-urban sites, whileLeiothlypis ruficapillahad similar capture rates in both habitats. Our findings indicate that the urban green areas of cities can act as suitable quality habitat during winter for two abundant migrant birds. Our results indicate that cities can have a higher conservation potential for a declining and sensitive group such as the Nearctic-Neotropical migratory birds than previously thought. We also point out the need to acknowledge that migratory species can be urban dwellers.
Novel Immune-Related Gene-Based Signature Characterizing an Inflamed Microenvironment Predicts Prognosis and Radiotherapy Efficacy in Glioblastoma
Authors: Ji Hang , Zhao Hongtao , Jin Jiaqi , Liu Zhihui , Gao Xin , Wang Fang , Dong Jiawei , Yan Xiuwei , Zhang Jiheng , Wang Nan , Du Jianyang , Hu Shaoshan
Published: January 2022

Effective treatment of glioblastoma (GBM) remains an open challenge. Given the critical role of the immune microenvironment in the progression of cancers, we aimed to develop an immune-related gene (IRG) signature for predicting prognosis and improving the current treatment paradigm of GBM. Multi-omics data were collected, and various bioinformatics methods, as well as machine learning algorithms, were employed to construct and validate the IRG-based signature and to explore the characteristics of the immune microenvironment of GBM. A five-gene signature (ARPC1B, FCGR2B, NCF2, PLAUR, and S100A11) was identified based on the expression of IRGs, and an effective prognostic risk model was developed. The IRG-based risk model had superior time-dependent prognostic performance compared to well-studied molecular pathology markers. Besides, we found prominent inflamed features in the microenvironment of the high-risk group, including neutrophil infiltration, immune checkpoint expression, and activation of the adaptive immune response, which may be associated with increased hypoxia, epidermal growth factor receptor (EGFR) wild type, and necrosis. Notably, the IRG-based risk model had the potential to predict the effectiveness of radiotherapy. Together, our study offers insights into the immune microenvironment of GBM and provides useful information for clinical management of this desperate disease.
Identification of a Ubiquitin Related Genes Signature for Predicting Prognosis of Prostate Cancer
Authors: Song Guoda , Zhang Yucong , Li Hao , Liu Zhuo , Song Wen , Li Rui , Wei Chao , Wang Tao , Liu Jihong , Liu Xiaming
Published: January 2022

Background: Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. However, the biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear.

Methods: The transcriptome data and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), which was served as training cohort. The GSE21034 dataset was used to validate. The two datasets were removed batch effects and normalized using the “sva” R package. Univariate Cox, LASSO Cox, and multivariate Cox regression were performed to identify a URGs prognostic signature. Then Kaplan-Meier curve and receiver operating characteristic (ROC) curve analyses were used to evaluate the performance of the URGs signature. Thereafter, a nomogram was constructed and evaluated.

Results: A six-URGs signature was established to predict biochemical recurrence (BCR) of PCa, which included ARIH2, FBXO6, GNB4, HECW2, LZTR1 and RNF185. Kaplan-Meier curve and ROC curve analyses revealed good performance of the prognostic signature in both training cohort and validation cohort. Univariate and multivariate Cox analyses showed the signature was an independent prognostic factor for BCR of PCa in training cohort. Then a nomogram based on the URGs signature and clinicopathological factors was established and showed an accurate prediction for prognosis in PCa.

Conclusion: Our study established a URGs prognostic signature and constructed a nomogram to predict the BCR of PCa. This study could help with individualized treatment and identify PCa patients with high BCR risks.
Genome-Wide Investigation of the Zinc Finger-Homeodomain Family Genes Reveals Potential Roles in Apple Fruit Ripening
Authors: Zheng Xian-bo , Wu Yao , Wang Hao , Song Shang-wei , Bai Tuan-hui , Jiao Jian , Song Chun-hui , Pang Hong-guang , Wang Miao-miao
Published: January 2022

Zinc finger-homeodomain (ZF-HD) transcription factors play an important role in the regulation of plant growth and development, as well as the regulation of stress responses. Studies on the ZF-HD family genes have been conducted in many plants, however, the characteristics of this family in apple (Malus domestica) fruit remains to be poorly understood. In this study, we identified nineteen ZF-HD family genes in apple at the whole-genome scale, which were unevenly located on ten chromosomes. These MdZF-HD genes were phylogenetically divided into two subfamilies: zinc finger-homeodomain (ZHD) and MINI ZINC FINGER (MIF), and the ZHD subfamily was further classified into five groups (ZHDI–ZHDV). Analysis of the gene structures showed that most MdZF-HD genes lack introns. Gene expression analysis indicated that nine selected MdZF-HD genes were differentially responsive to 1-MCP (1-methylcyclopropene) treatment during the postharvest storage of “Qinguan” apple fruit. Moreover, the transcripts of six genes were further validated in “Golden Delicious” apple fruit, and five genes (MdZHD1/2/6/10/11) were significantly repressed and one gene (MdZHD7) was slightly induced by ethylene treatment. These results indicated that these six MdZF-HD genes may involve in the regulation of ethylene induced ripening process of postharvest apple fruit. These findings provide new clues for further functional investigation of ZF-HD genes, such as their roles in the regulation of fruit ripening.