bluuebunny/crossref_metadata_2025 huggingface dataset:
The Advances and Biomedical Applications of Imageable Nanomaterials
Authors: Xiang Xiaohong , Shi Doudou , Gao Jianbo
Published: July 2022

Nanomedicine shows great potential in screening, diagnosing and treating diseases. However, given the limitations of current technology, detection of some smaller lesions and drugs’ dynamic monitoring still need to be improved. With the advancement of nanotechnology, researchers have produced various nanomaterials with imaging capabilities which have shown great potential in biomedical research. Here, we summarized the researches based on the characteristics of imageable nanomaterials, highlighted the advantages and biomedical applications of imageable nanomaterials in the diagnosis and treatment of diseases, and discussed current challenges and prospects.
Emerging Role of Non-Coding RNAs in Senescence
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Baniahmad Aria , Branicki Wojciech , Taheri Mohammad , Eghbali Ahmad
Published: July 2022

Senescence is defined as a gradual weakening of functional features of a living organism. Cellular senescence is a process that is principally aimed to remove undesirable cells by prompting tissue remodeling. This process is also regarded as a defense mechanism induced by cellular damage. In the course of oncogenesis, senescence can limit tumor progression. However, senescence participates in the pathoetiology of several disorders such as fibrotic disorders, vascular disorders, diabetes, renal disorders and sarcopenia. Recent studies have revealed contribution of different classes of non-coding RNAs in the cellular senescence. Long non-coding RNAs, microRNAs and circular RNAs are three classes of these transcripts whose contributions in this process have been more investigated. In the current review, we summarize the available literature on the impact of these transcripts in the cellular senescence.
m6A Topological Transition Coupled to Developmental Regulation of Gene Expression During Mammalian Tissue Development
Authors: Li Shanshan , Yang Qing , Jiao Rui , Xu Pengfei , Sun Yazhou , Li Xin
Published: July 2022

N6-methyladenosine (m6A) is the most prevalent internal modification and reversible epitranscriptomic mark in messenger RNAs (mRNAs) and plays essential roles in a variety of biological processes. However, the dynamic distribution patterns of m6A and their significance during mammalian tissue development are poorly understood. Here, we found that based on m6A distribution patterns, protein-coding genes were classified into five groups with significantly distinct biological features and functions. Strikingly, comparison of the m6A methylomes of multiple mammalian tissues between fetal and adult stages revealed dynamic m6A topological transition during mammalian tissue development, and identified large numbers of genes with significant m6A loss in 5′UTRs or m6A gain around stop codons. The genes with m6A loss in 5′UTRs were highly enriched in developmental stage-specific genes, and their m6A topological transitions were strongly associated with gene expression regulation during tissue development. The genes with m6A gain around the stop codons were associated with tissue-specific functions. Our findings revealed the existence of different m6A topologies among protein-coding genes that were associated with distinct characteristics. More importantly, these genes with m6A topological transitions were crucial for tissue development via regulation of gene expression, suggesting the importance of dynamic m6A topological transitions during mammalian tissue development.
Chromatin Ubiquitination Guides DNA Double Strand Break Signaling and Repair
Authors: Kolobynina Ksenia G. , Rapp Alexander , Cardoso M. Cristina
Published: July 2022

Chromatin is the context for all DNA-based molecular processes taking place in the cell nucleus. The initial chromatin structure at the site of the DNA damage determines both, lesion generation and subsequent activation of the DNA damage response (DDR) pathway. In turn, proceeding DDR changes the chromatin at the damaged site and across large fractions of the genome. Ubiquitination, besides phosphorylation and methylation, was characterized as an important chromatin post-translational modification (PTM) occurring at the DNA damage site and persisting during the duration of the DDR. Ubiquitination appears to function as a highly versatile “signal-response” network involving several types of players performing various functions. Here we discuss how ubiquitin modifiers fine-tune the DNA damage recognition and response and how the interaction with other chromatin modifications ensures cell survival.
From Biomass-Derived p-Hydroxycinnamic Acids to Novel Sustainable and Non-Toxic Phenolics-Based UV-Filters: A Multidisciplinary Journey
Authors: Rioux Benjamin , Combes Jeanne , Woolley Jack M. , Rodrigues Natércia d. N. , Mention Matthieu M. , Stavros Vasilios G. , Allais Florent
Published: July 2022

Although organic UV-filters are extensively used in cosmetics to protect consumers from the deleterious effects of solar UV radiation-exposure, they suffer from some major drawbacks such as their fossil origin and their toxicity to both humans and the environment. Thus, finding sustainable and non-toxic UV-filters is becoming a topic of great interest for the cosmetic industry. A few years ago, sinapoyl malate was shown to be a powerful naturally occurring UV-filter. Building on these findings, we decided to design and optimize an entire value chain that goes from biomass to innovative biobased and non-toxic lignin-derived UV-filters. This multidisciplinary approach relies on: 1) The production of phenolic synthons using either metabolite extraction from biomass or their bioproduction through synthetic biology/fermentation/in stream product recovery; 2) their functionalization using green chemistry to access sinapoyl malate and analogues; 3) the study of their UV-filtering activity, their photostability, their biological properties; and 4) their photodynamics. This mini-review aims at demonstrating that combining biotechnology, green chemistry, downstream process and photochemistry is a powerful approach to transform biomass and, in particular lignins, into high value-added innovative UV-filters.
The Chemistry of HNO: Mechanisms and Reaction Kinetics
Authors: Michalski Radosław , Smulik-Izydorczyk Renata , Pięta Jakub , Rola Monika , Artelska Angelika , Pierzchała Karolina , Zielonka Jacek , Kalyanaraman Balaraman , Sikora Adam Bartłomiej
Published: July 2022

Azanone (HNO, also known as nitroxyl) is the protonated form of the product of one-electron reduction of nitric oxide (•NO), and an elusive electrophilic reactive nitrogen species of increasing pharmacological significance. Over the past 20 years, the interest in the biological chemistry of HNO has increased significantly due to the numerous beneficial pharmacological effects of its donors. Increased availability of various HNO donors was accompanied by great progress in the understanding of HNO chemistry and chemical biology. This review is focused on the chemistry of HNO, with emphasis on reaction kinetics and mechanisms in aqueous solutions.
Increased Interferon-Induced Protein With Tetracopeptides (IFITs) Reduces Mycobacterial Growth
Authors: Madhvi Abhilasha , Mishra Hridesh , Chegou Novel N. , Baker Bienyameen
Published: July 2022

Objectives

The host immune response towards Mycobacterium tuberculosis (M. tb) is known to vary with the virulence of mycobacterial species. While the majority of M. tb-exposed individuals develop latent TB infection (LTBI), a small proportion develops active TB disease. The milieu of understudied immune factors is believed to play an important role against host immune response towards mycobacteria. Here, we investigate the role of antiviral factors of the interferon-induced proteins with tetracopeptides (IFITs) family, which, in our previous research, have shown to be upregulated in response to pathogenic M. tb, but as yet have no established role in host response to bacterial infections.

Methods

We performed vector-driven overexpression and siRNA-mediated downregulation of IFITs in THP-1 cells infected with different mycobacterial species. Also, we investigated the mRNA levels of IFITs in the LTBI and active-TB cases.

Results

Overexpression of IFITs reduces CFUs by ~32% (30%–43%) [Median (IQR)] across three different mycobacterial strains, while knock-down increases CFUs by ~57% (41%–78%). Compared to IFN-γ, treatment of infected THP-1 cells with IFN-β significantly increases the expression of IFITs, while the overexpression of IFITs had higher mRNA expression of IFN-β than IFN-γ. Cytokines like IDO-1, IL-6, IL-23, and IFN- γ are observed to play key roles in mycobacterial survival upon IFITs intervention. mRNA expression levels of IFITs were higher in LTBI cases as compared to active TB.

Conclusion

Higher expression levels of IFITs reduce in vitro survival of different drug-susceptible and drug-resistant mycobacteria and correlates with latent TB infection in infected individuals, hence emerging as an immuno-therapeutic target against M. tb.
Miltefosine and Benznidazole Combination Improve Anti-Trypanosoma cruzi In Vitro and In Vivo Efficacy
Authors: Gulin Julián Ernesto Nicolás , Bisio Margarita María Catalina , Rocco Daniela , Altcheh Jaime , Solana María Elisa , García-Bournissen Facundo
Published: July 2022

Drug repurposing and combination therapy have been proposed as cost-effective strategies to improve Chagas disease treatment. Miltefosine (MLT), a synthetic alkylphospholipid initially developed for breast cancer and repositioned for leishmaniasis, is a promising candidate against Trypanosoma cruzi infection. This study evaluates the efficacy of MLT as a monodrug and combined with benznidazole (BZ) in both in vitro and in vivo models of infection with T. cruzi (VD strain, DTU TcVI). MLT exhibited in vitro activity on amastigotes and trypomastigotes with values of IC50 = 0.51 µM (0.48 µM; 0,55 µM) and LC50 = 31.17 µM (29.56 µM; 32.87 µM), respectively. Drug interaction was studied with the fixed-ration method. The sum of the fractional inhibitory concentrations (ΣFICs) resulted in ∑FIC= 0.45 for trypomastigotes and ∑FIC= 0.71 for amastigotes, suggesting in vitro synergistic and additive effects, respectively. No cytotoxic effects on host cells were observed. MLT efficacy was also evaluated in a murine model of acute infection alone or combined with BZ. Treatment was well tolerated with few adverse effects, and all treated animals displayed significantly lower mean peak parasitemia and mortality than infected non-treated controls (p<0.05). The in vivo studies showed that MLT led to a dose-dependent parasitostatic effect as monotherapy which could be improved by combining with BZ, preventing parasitemia rebound after a stringent immunosuppression protocol. These results support MLT activity in clinically relevant stages from T. cruzi, and it is the first report of positive interaction with BZ, providing further support for evaluating combined schemes using MLT and exploring synthetic alkylphospholipids as drug candidates.
Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium
Authors: Primessnig Uwe , Deißler Peter M. , Wakula Paulina , Tran Khai Liem , Hohendanner Felix , von Lewinski Dirk , Blaschke Florian , Knosalla Christoph , Falk Volkmar , Pieske Burkert , Grubitzsch Herko , Heinzel Frank R.
Published: July 2022

Background

Although the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan started a new era in heart failure (HF) treatment, less is known about the tissue-level effects of the drug on the atrial myocardial functional reserve and arrhythmogenesis.

Methods and Results

Right atrial (RA) biopsies were retrieved from patients (n = 42) undergoing open-heart surgery, and functional experiments were conducted in muscle strips (n = 101). B-type natriuretic peptide (BNP) did not modulate systolic developed force in human myocardium during β-adrenergic stimulation, but it significantly reduced diastolic tension (p < 0.01) and the probability of arrhythmias (p < 0.01). In addition, patient's plasma NTproBNP positively correlated with isoproterenol-induced contractile reserve in atrial tissue in vitro (r = 0.65; p < 0.01). Sacubitrilat+valsartan (Sac/Val) did not show positive inotropic effects on atrial trabeculae function but reduced arrhythmogeneity. Atrial and ventricular biopsies from patients with end-stage HF (n = 10) confirmed that neprilysin (NEP) is equally expressed in human atrial and ventricular myocardium. RA NEP expression correlates positively with RA ejection fraction (EF) (r = 0.806; p < 0.05) and left ventricle (LV) NEP correlates inversely with left atrial (LA) volume (r = −0.691; p < 0.05).

Conclusion

BNP ameliorates diastolic tension during adrenergic stress in human atrial myocardium and may have positive long-term effects on the inotropic reserve. BNP and Sac/Val reduce atrial arrhythmogeneity during adrenergic stress in vitro. Myocardial NEP expression is downregulated with declining myocardial function, suggesting a compensatory mechanism in HF.
Risk Factors and Outcomes of Acute Myocardial Infarction in a Cohort of Antiphospholipid Syndrome
Authors: Gan Yuzhou , Zhao Yawei , Li Gongming , Ye Hua , Zhou Yunshan , Hou Chang , Wang Lan , Guo Jianping , Li Chun
Published: July 2022

Background

Antiphospholipid syndrome (APS) is a disorder associated with thromboembolic diseases, including acute myocardial infarction (AMI). Given that AMI is a relatively common condition with poor prognostic features, identification of risk factors for AMI in APS is important.

Methods

A retrospective cohort study was performed consisting of 332 patients with APS, and 239 patients with thrombotic APS were finally included. Patients were followed up in the outpatient department for 5 years. Clinical data and laboratory parameters were analyzed to identify the risk factors for AMI in APS. The primary and secondary clinical outcomes were all-cause mortality and recurrence of thrombosis, respectively.

Results

AMI was observed in 12.1% (29/239) of patients with APS. Compared to patients without AMI, patients with AMI had multiple organ thrombosis (55.1 vs. 34.3%, p = 0.029), recurrent thrombosis (58.6 vs. 34.3%, p = 0.011), a higher incidence of atherosclerosis (62.1 vs. 23.8%, p < 0.001), higher neutrophil count (×109/L) [4.68 (3.25, 8.17) vs. 3.71 (2.64, 5.80), p = 0.036], longer QT interval (ms) [438 ms (423, 454) vs. 425 ms (410, 446), p = 0.016], and fewer venous thrombosis events (27.6 vs. 63.3%, p < 0.001). Multivariate logistic regression analysis (adjusted for age and gender) identified several factors that were positively associated with AMI, including multiple organ thrombosis [odds ratio (OR) 8.862, 95% confidence interval (CI): 1.817–43.212, p = 0.007), atherosclerosis (OR 5.397, 95%CI: 1.943–14.994, p = 0.001), and elevated neutrophil count (>6.3 ×109/L) (OR 3.271, 95%CI: 1.268–8.440, p = 0.014). The venous thrombosis was negatively associated with AMI (OR 0.106, 95%CI: 0.036–0.314, p < 0.001). Kaplan–Meier analysis revealed that the recurrence rates of arterial thrombosis differed significantly between patients with AMI and those without AMI [hazard ratio (HR) = 3.307, p = 0.038].

Conclusion

Atherosclerosis, multiple organ thrombosis, an increased number of neutrophils are variables positively associated with AMI in APS, and venous thrombosis had a negative association with AMI. AMI only predicts the subsequent recurrence of arterial thrombosis. These findings suggest that distinct pathophysiological mechanisms may exist and contribute to the development of venous or arterial thrombotic APS.
Estrogen Mediates an Atherosclerotic-Protective Action via Estrogen Receptor Alpha/SREBP-1 Signaling
Authors: Xie Fei , Li Xiandong , Xu Yue , Cheng Dongliang , Xia Xianru , Lv Xi , Yuan Guolin , Peng Chunyan
Published: July 2022

Menopause is associated with dyslipidemia and an increased risk of cardiovascular disease, the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen. In this study, we find that estrogen mediates an atherosclerotic-protective action via estrogen receptor alpha/SREBP-1 signaling. Increased lipid accumulation and low-density lipoprotein (LDL)-uptake in HepG2 cells and THP-1 macrophages were induced by treatment of mixed hyperlipidemic serum from postmenopausal women; 17β-estradiol [estrogen (E2)] (10 nM) administration significantly improved hyperlipidemic profiles, relieved fatty-liver damage and attenuated the plaque area in the heart chamber of high-fat diet (HFD)-fed ovariectomized (OVX) ApoE–/– mice. Expression of sterol regulatory element-binding protein (SREBP)-1 mRNA of circulating leukocytes in postmenopausal women was strongly correlated to the serum E2 level. Exploration of data from the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that expression of SREBP-1 protein correlated to expression of estrogen receptor (ESR)α protein in the liver, blood and in normal tissue. Genetic overexpression/inhibition of ESRα resulted in increased/decreased SREBP-1 expression as well as attenuated/deteriorated lipid deposition in vitro. An inhibitor of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway, AZD8055, abolished ESRα-induced SREBP-1 expression in HepG2 cells. Moreover, E2 and statin co-treatment significantly reduced lipid accumulation in vitro and hindered the progression of atherosclerosis and fatty-liver damage in OVX ApoE–/– mice. Collectively, our results suggest that estrogen could exerted its atherosclerotic-protective action via ESRα/SREBP-1 signaling. E2 might enhance the cellular sensitivity of statins and could be used as a novel therapeutic strategy against atherosclerotic disorders in postmenopausal women.
Correlation Between Non-insulin-Based Insulin Resistance Indices and Increased Arterial Stiffness Measured by the Cardio–Ankle Vascular Index in Non-hypertensive Chinese Subjects: A Cross-Sectional Study
Authors: Zhang Xin , Ye Runyu , Yu Chaoping , Liu Tianhu , Chen Xiaoping
Published: July 2022

Data are limited on the relationship between the cardio–ankle vascular index (CAVI) and non-insulin-based insulin resistance (IR) indices, including the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), fasting triglyceride and glucose index (TyG), and metabolic score for IR (METS-IR). In this study, we explored the relationship between TG/HDL-C, TyG, METS-IR, and the risk of increased arterial stiffness (CAVI ≥ 8.0) and compared their ability to detect arterial stiffness in the non-hypertensive Chinese population. A total of 3,265 non-hypertensive subjects were included. Spearman’s and partial correlation analyses were used to assess the relationship between non-insulin-based IR indices and CAVI. The correlation between these indices and the risk of a CAVI ≥ 8.0 was explored by multiple logistic regression analysis. The area under the receiver-operating characteristic curve was used to compare the ability of TG/HDL-C, TyG, and METS-IR to detect a CAVI ≥ 8.0. After adjustment for confounding factors, linear regression analysis showed that the CAVI changed by 0.092 [95% confidence interval (CI) 0.035–0.149] per standard deviation increase in TyG. While, this linear relationship was not found when analyzing TG/HDL-C and METS-IR. Multiple logistic regression analysis showed that the proportion of patients with CAVI ≥ 8.0 in the fourth quartile of TG/HDL-C [Q4 vs. Q1: odds ratio (OR) 2.434, 95% CI 1.489–3.975], TyG (Q4 vs. Q1: OR 2.346, 95% CI 1.413–3.896), and METS-IR (Q4 vs. Q1: OR 2.699, 95% CI 1.235–5.897) was significantly higher than that in the lowest quartile. The area under the curve that could discriminate CAVI ≥ 8.0 was 0.598 (95% CI 0.567–0.629) for TG/HDL-C, 0.636 (95% CI 0.606–0.667) for TyG, and 0.581 (95% CI 0.550–0.613) for METS-IR. In this study, we demonstrated a significant association between increased arterial stiffness and non-insulin-based IR indices. Among them, TyG showed better discriminatory ability than TG/HDL-C or METS-IR.
Changes in the Runoff of Urumqi Glacier No. 1 Under Climate Change: From Historical Observation to Future Prediction
Authors: Jiang Pei , Wang Zemin , Yan Boya , Ai Songtao , Jin Shuang
Published: July 2022

This study explores the ice volumes of Urumqi Glacier No. 1 from 2013 to 2112 to examine the changes in the runoff of the glacier. Based on the Sixth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC), the changes of the glacier were predicted under three hypothetical climate scenarios: SSP1-1.9, SSP2-4.5, and SSP5-8.5 scenarios. The results derived from the Elmer/Ice ice-flow model showed increasing runoff till 2040 in the SSP2-4.5 and SSP5-8.5 scenarios and gradually decreasing runoff in the SSP1-1.9 scenario. The glacier areas and ice volumes of the two branches will keep declining under all the climate scenarios, including fast reductions until 2080 and slow reductions by the end of the ablation period. Moreover, the east branch (EB) will disappear at the end of the 21st century under the SSP2-4.5 and SSP5-8.5 scenarios. With much mass loss of the EB under all the climate scenarios, the runoff will increase in the early 100-year period and decrease until it is being infinitely close to the precipitation, which is similar with that of the west branch (WB). Since 2070, the ice volumes of the WB will contribute more than 50% of the whole glacier volumes under all the climate scenarios. The WB ice volume percentage will reach 100% in 2080 for the disappearance of the EB under the SSP5-8.5 scenario. As the fast retreat of the EB before 2080, the variations of the total runoff will be consistent with that of the EB runoff, and the EB runoff will account for more than 60% of the total runoff before 2070 under all the climate scenarios. Even if the meltwater of Urumqi Glacier No. 1 is stable from the late 21st century (after 2090), it will decline to approximately 15% of that in 2013. It will greatly influence the runoff of Urumqi River, hence human life and biodiversity.
Associations Between Asthma and Polycystic Ovary Syndrome: Current Perspectives
Authors: Xu Yue , Zhou Zhi-Yang , Pan Jie-Xue , Huang He-Feng
Published: July 2022

A potential correlation between polycystic ovary syndrome (PCOS) and asthma, used to be identified as diseases originating from two independent systems, has been supported by increasing evidence. From an epidemiological perspective, mounting studies have confirmed that women suffering from PCOS exhibit increased susceptibility to asthma. Meanwhile, PCOS and asthma seem to share several mutual pathological conditions, such as metabolic disorders, hormonal fluctuation, proinflammatory state, etc. Here, we further elucidate the correlation between asthma and PCOS by focusing on the internal common pathophysiology and adverse influences on women’s health. Understanding the internal connection between PCOS and asthma may shed light on developing new prevention and control strategies to fight against these conditions.
The Energy Storage System Integration Into Photovoltaic Systems: A Case Study of Energy Management at UTFPR
Authors: Mariano Juliana D’Angela , Urbanetz Jr Jair
Published: July 2022

Energy storage system integration can reduce electricity costs and provide desirable flexibility and reliability for photovoltaic (PV) systems, decreasing renewable energy fluctuations and technical constraints. In this sense, this study aimed to propose energy management strategies through this integration, aiming to improve the demand profile of a university commercial consumer for compensation during peak hours. To achieve the objectives of this research, a pilot project was installed which included a 10 kWp grid-tie PV system (GTPVS), bidirectional inverters, and battery bank, as part of a research and development (R&D) project implemented in the Federal University of Technology–Paraná (UTFPR) Curitiba campus at Neoville headquarters. The methodology consisted of the analysis of variables that interfere with the operation of this system, such as a detailed university profile of demand and consumption, local energy pricing, PV generation profile as well as the interaction between PV generator and the energy storage system, and the variation in power fluctuations throughout the year. Additionally, a technical feasibility study was carried out aimed to determine this consumer’s optimal size through the Homer Grid software. The detailed demand profile allowed us to know in depth the peak values were above 80 kW, for university working days. Furthermore, the daily analysis of the PV generation profile confirmed that although the PV source is quite variable, the scheduled dispatch operation is not interfered by the variability and intermittency of the solar source, as the system was designed and programmed to operate in parallel with the electrical network. Regarding the energy consumed at the university, very significant values were obtained, in which the month of July presented the highest consumption for the base year 2019, with a total monthly value of 48,670 kWh. The established operating strategy for the battery bank with a 10% discharge depth resulted in a life cycle of 2,500 cycles which can extend its useful life by approximately 9.5 years. The results obtained by the simulation show different levels of energy contribution with percentages of 60.0, 33.6, and 2.7%, respectively.
Seagull Optimization Algorithm–Based Fractional-Order Fuzzy Controller for LFC of Multi-Area Diverse Source System With Realistic Constraints
Authors: Naga Sai Kalyan CH. , Goud B. Srikanth , Reddy Ch. Rami , Udumula Ramanjaneya Reddy , Bajaj Mohit , Sharma Naveen Kumar , Elgamli Elmazeg , Shouran Mokhtar , Kamel Salah
Published: July 2022

This study initiates the implementation of fractional-order (FO) fuzzy (F) PID (FOFPID) controller fine-tuned using a seagull optimization algorithm (SOA) for the study of load frequency control (LFC). Initially, the SOA-tuned FOFPID regulator is implemented on the widely utilized model of dual-area reheat-thermal system (DARTS), named test system-1 in this work for a perturbation of 10% step load (10% SLP) on area-1. Dynamical analysis of the DARTS system reveals the viability of the SOA-tuned FOFPID control scheme in regulating frequency deviations effectively compared to other control schemes covered in the literature. Later, the presented regulator is implemented on the multi-area diverse sources (MADS) system possessing realistic constraints in this study, termed test system-2. The sovereignty of the presented FOFPID controller is once again evidenced with controllers of PID/FOPID/FPID fine-tuned with the SOA approach. Moreover, the effect of considering practical realistic nonlinearity constraints such as communication time delays (CTDs) on MADS system performance is visualized and the necessity of its consideration is demonstrated. Furthermore, AC-DC lines are incorporated with the MADS system to enhance the performance under heavy-load disturbances and the robustness of the proposed regulatory mechanism is deliberated.
A Systematic Review and Analysis of MPPT Techniques for TEG Systems Under Nonuniform Temperature Distribution
Authors: Zhang Dan , Song Lan , Wang Long , Li Xiang , Chang Xucheng , Wu Peng
Published: July 2022

As a waste heat recovery power generation technology, the thermoelectric generation (TEG) system is popular and promising for its high reliability and environmental benefits. However, because of its low conversion efficiency, it has not been in large-scale use. To raise the efficiency of the TEG system, maximum power point tracking (MPPT) techniques are effective ways to gain the maximum power of the TEG system. But in practical engineering scene, TEG usually works under nonuniform temperature distribution (NTD) conditions; this will bring some difficulties on MPPT controlling, such as local maximum power point (LMPP) and oscillations around the maximum power point (MPP). For this reason, many intelligent MPPT algorithms have been emerged to solve aforementioned problems. In this article, the mathematical model and NTD condition will be introduced. Then, the latest research on classical and intelligent MPPT technologies will be reviewed, which includes a comparison of complexity, economy, efficiency, adaptive ability, and other aspects of these methods, in which researchers can obtain information in related fields.
Influence of Inlet Groove on Flow Characteristics in Stall Condition of Full-Tubular Pump
Authors: Shi Lijian , Jiang Yuhang , Cai Yiping , Chen Beishuai , Tang Fangping , Xu Tian , Zhu Jun , Chai Yao
Published: July 2022

The full-tubular pump is a new type of pump with a narrow range of stable operation. In order to improve the internal flow characteristics of the full-tubular pump under small flow conditions and improve the safe and stable operating range of the pump, this paper conducts numerical simulation of the full-tubular pump model based on the Reynolds time-averaged N-S equation and the SST k-ω turbulence model. The improvement mechanism of the parameters of the inlet grooves on the stall area of the full-tubular pump is studied, and the reliability of the numerical simulation of the full-tubular pump is verified by model tests. The research results show that the inlet groove can improve the head and efficiency of the full-tubular pump in the small flow area, and the head at the deep stall condition is increased by nearly 1.61 m. The inlet groove increases the pressure difference of the impeller, which increases the head and improves the hump. At the same time, the increase in the pressure difference of the impeller increases the backflow flow in the gap between the stator and the rotor. The groove can reduce the vortex strength and backflow range at the inlet pipe wall near the stall operating, and also improve the flow field at the impeller inlet. In terms of pressure pulsation, the groove can effectively suppress the low-frequency pressure pulsation at the inlet of the impeller of the full-tubular pump under stall conditions, and effectively reduce the amplitude of the main frequency pressure pulsation and improve the internal flow. The research in this paper can provide a reference for improving the flow characteristics in the stall condition of the full-tubular pump.
Relationship Between Foreign Direct Investment, Industrial Structure Optimization, and Green Full-Factor Productivity: Empirical Evidence From Changjiang Economic Area
Authors: Zhang Huaping , Ren Yuanyuan
Published: July 2022

By setting up an evaluation indicator system (EIS) containing bad outcomes for green full-factor productivity (GFFP), this work utilizes the super epsilon-based measure (Super EBM) model to assess the GFFPs of 11 regional-level administrative regions (regions) in the Changjiang Economic Area (CEA) from 2005 to 2019, and goes on to analyze the regional difference and spatial correlation between the regional GFFPs. On this basis, spatial measurement models were adopted to analyze how GFFP is affected by foreign direct investment (FDI), industrial structure optimization (ISO), and their cross term. The results show that: During the sample period, the GFFPs in the CEA exhibited large regional differences. Shanghai’s GFFP fell on the efficient frontier. This state was not achieved by any other region in the CEA, leaving a room for improvement. In general, most regions in the lower basin of the CEA had satisfactory GFFPs, while those in the middle and upper basin had general GFFPs. Besides, the GFFP trends were similar in the upper, middle, and lower basin of the CEA. Before 2010, the GFFPs in all three regions did not change significantly. After that year, the GFFPs in the three regions began to decline. During the sample period, the Global Moran’s I values of CEA GFFPs remained positive, and went through the test of significance in most years. Thus, the GFFPs were clustered prominently in space. Considering the results of spatial measurement models, the CEA GFFPs were significantly inhibited by FDI, and promoted by ISO; the cross term between FDI and ISO positively affected GFFP. Among the control parameters, economic growth and environment regulation clearly promote GFFP, urbanization level strongly inhibits GFFP, and energy structure does not significantly affect GFFP. The research results disclose the internal correlations between FDI and ISO in the transformation to green development: the benign interaction between FDI and regional ISO paves the way to green development for the CEA.
Patterns of Fungal Community Assembly Across Two Culex Mosquito Species
Authors: Tawidian Patil , Jumpponen Ari , Michel Kristin
Published: July 2022

In the aquatic environment, mosquito larvae encounter bacteria and fungi that assemble into bacterial and fungal communities. The composition and impact of mosquito-associated bacterial community has been reported across larvae of various mosquito species. However, knowledge on the composition of mosquito-associated fungal communities and the drivers of their assembly remain largely unclear, particularly across mosquito species. In this study, we used high throughput sequencing of the fungal Internal transcribed spacer 2 (ITS2) metabarcode marker to identify fungal operational taxonomic units (OTUs) and amplicon sequence variants (ASVs) associated with field-collected Culex restuans and Culex pipiens larvae and their breeding water. Our analyses identified diverse fungal communities across larval breeding sites collected on a fine geographic scale. Our data show that the larval breeding site is the major determinant of fungal community assembly in these mosquito species. We also identified distinct fungal communities in guts and carcasses within each species. However, these tissue-specific patterns were less evident in Cx. restuans than in Cx. pipiens larvae. The broad ecological patterns of fungal community assembly in mosquito larvae did not vary between OTU and ASV analyses. Together, this study provides the first insight into the fungal community composition and diversity in field collected Cx. restuans and Cx. pipiens larvae using OTUs and ASVs. While these findings largely recapitulate our previous analyses in Aedes albopictus larvae, we report minor differences in tissue-specific fungal community assembly in Cx. restuans larvae. Our results suggest that while the fungal community assembly in mosquito larvae may be generalized across mosquito species, variation in larval feeding behavior may impact fungal community assembly in the guts of mosquito larvae.
Optimizing CRISPR/Cas9 Editing of Repetitive Single Nucleotide Variants
Authors: Usher Inga , Ligammari Lorena , Ahrabi Sara , Hepburn Emily , Connolly Calum , Bond Gareth L. , Flanagan Adrienne M. , Cottone Lucia
Published: July 2022

CRISPR/Cas9, base editors and prime editors comprise the contemporary genome editing toolbox. Many studies have optimized the use of CRISPR/Cas9, as the original CRISPR genome editing system, in substituting single nucleotides by homology directed repair (HDR), although this remains challenging. Studies describing modifications that improve editing efficiency fall short of isolating clonal cell lines or have not been validated for challenging loci or cell models. We present data from 95 transfections using a colony forming and an immortalized cell line comparing the effect on editing efficiency of donor template modifications, concentration of components, HDR enhancing agents and cold shock. We found that in silico predictions of guide RNA efficiency correlated poorly withactivity in cells. Using NGS and ddPCR we detected editing efficiencies of 5–12% in the transfected populations which fell to 1% on clonal cell line isolation. Our data demonstrate the variability of CRISPR efficiency by cell model, target locus and other factors. Successful genome editing requires a comparison of systems and modifications to develop the optimal protocol for the cell model and locus. We describe the steps in this process in a flowchart for those embarking on genome editing using any system and incorporate validated HDR-boosting modifications for those using CRISPR/Cas9.
Combining Single-Cell and Transcriptomic Data Revealed the Prognostic Significance of Glycolysis in Pancreatic Cancer
Authors: Chen Liang , Lin Yunhua , Wei Wei , Wang Yue , Li Fangyue , Du Wang , Yang Zhonghua , Hu Yiming , Ying Xiaomei , Tang Qikai , Xie Jiaheng , Yu Hongzhu
Published: July 2022

Background: Pancreatic cancer (PC), the most common fatal solid malignancy, has a very dismal prognosis. Clinical computerized tomography (CT) and pathological TNM staging are no longer sufficient for determining a patient’s prognosis. Although numerous studies have suggested that glycolysis is important in the onset and progression of cancer, there are few publications on its impact on PC.

Methods: To begin, the single-sample gene set enrichment analysis (ssGSEA) approach was used to quantify the glycolysis pathway enrichment fraction in PC patients and establish its prognostic significance. The genes most related to the glycolytic pathway were then identified using weighted gene co-expression network analysis (WGCNA). The glycolysis-associated prognostic signature in PC patients was then constructed using univariate Cox regression and lasso regression methods, which were validated in numerous external validation cohorts. Furthermore, we investigated the activation of the glycolysis pathway in PC cell subtypes at the single-cell level, performed a quasi-time series analysis on the activated cell subtypes and then detected gene changes in the signature during cell development. Finally, we constructed a decision tree and a nomogram that could divide the patients into different risk subtypes, according to the signature score and their different clinical characteristics and assessed the prognosis of PC patients.

Results: Glycolysis plays a risky role in PC patients. Our glycolysis-related signature could effectively discriminate the high-risk and low-risk patients in both the trained cohort and the independent externally validated cohort. The survival analysis and multivariate Cox analysis indicated this gene signature to be an independent prognostic factor in PC. The prognostic ROC curve analysis suggested a high accuracy of this gene signature in predicting the patient prognosis in PC. The single-cell analysis suggested that the glycolytic pathway may be more activated in epithelial cells and that the genes in the signature were also mainly expressed in epithelial cells. The decision tree analysis could effectively identify patients in different risk subgroups, and the nomograms clearly show the prognostic assessment of PC patients.

Conclusion: Our study developed a glycolysis-related signature, which contributes to the risk subtype assessment of patients with PC and to the individualized management of patients in the clinical setting.
CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood
Authors: Egri Natalia , Olivé Victoria , Hernández-Rodríguez José , Castro Pedro , De Guzman Catherine , Heredia Libertad , Segura Ana Castellet , Fernandez M. Dolores , de Moner Noemi , Torradeflot María , Ballús Judit , Martinez Robert , Vazquez Mario , Costa Marta Vidal , Dobaño Carlota , Mazza Massimiliano , Mazzotti Lucia , Pascal Mariona , Juan Manel , González-Navarro Europa Azucena , Calderón Hugo
Published: July 2022

Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell’s role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-γ ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.
Munronoid I Ameliorates DSS-Induced Mouse Colitis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Via Modulation of NLRP3
Authors: Ma Xingyu , Di Qianqian , Li Xiaoli , Zhao Xibao , Zhang Ruihan , Xiao Yue , Li Xunwei , Wu Han , Tang Haimei , Quan Jiazheng , Wu Zherui , Xiao Weilie , Chen Weilin
Published: July 2022

Inflammatory bowel diseases (IBDs) are increasingly common diseases characterized by chronic and relapsing inflammation of the gastrointestinal tract. NLRP3 might be a crucial regulator of the homeostatic balance of the intestine, but its upregulation leads to pyroptosis. Munronoid I is extracted and purified from Munronia sinica, which has shown an anti-inflammatory effect, but the efficacy of Munronoid I in IBD remains unproven. In this study, we attempted to determine the effect of Munronoid I on NLRP3 to regulate the inflammasome activation and pyroptosis in IBD. Our data demonstrated that Munronoid I treatment attenuated DSS-induced body weight loss, pathological injury of the colon, the production of IL-1β and IL-18, and the expression of pyroptosis-associated proteins in colon tissue in mice. Moreover, Munronoid I inhibited LPS/ATP-induced pyroptosis in mouse peritoneal macrophages, MODE-K cells, and DSS-induced pyroptosis in mouse colonic epithelial cells, and decreased the release of inflammatory cytokines IL-1β and IL-18 in mouse peritoneal macrophages. Mechanically, Munronoid I could suppress the NLRP3 inflammasome activation and pyroptosis by promoting the K48-linked ubiquitination and NLRP3 degradation. It is suggested that Munronoid I might be a potential therapeutic candidate for IBD.
gC1qR/C1qBP/HABP-1: Structural Analysis of the Trimeric Core Region, Interactions With a Novel Panel of Monoclonal Antibodies, and Their Influence on Binding to FXII
Authors: Zhang Ying , Vontz Alexander J. , Kallenberger Ethan M. , Xu Xin , Ploscariu Nicoleta T. , Ramyar Kasra X. , Garcia Brandon L. , Ghebrehiwet Berhane , Geisbrecht Brian V.
Published: July 2022

The protein gC1qR/C1qBP/HABP-1 plays an essential role in mitochondrial biogenesis, but becomes localized at the cellular surface in numerous pathophysiological states. When this occurs on endothelial cells, surface-exposed gC1qR activates the classical pathway of complement. It also promotes assembly of a multi-protein complex comprised of coagulation factor XII (FXII), pre-kallikrein (PK), and high-molecular weight kininogen (HMWK) that activates the contact system and the kinin-generating system. Since surface-exposed gC1qR triggers intravascular inflammatory pathways, there is interest in identifying molecules that block gC1qR function. Here we further that objective by reporting the outcome of a structure/function investigation of gC1qR, its interactions with FXII, and the impact of a panel of monoclonal anti-gC1qR antibodies on FXII binding to gC1qR. Although deletion mutants have been used extensively to assess gC1qR function, none of these proteins have been characterized structurally. To that end, we determined a 2.2 Å resolution crystal structure of a gC1qR mutant lacking both of its acidic loops, but which retained nanomolar-affinity binding to FXII and FXIIa. This structure revealed that the trimeric gC1qR assembly was maintained despite loss of roughly thirty residues. Characterization of a novel panel of anti-gC1qR monoclonal antibodies identified several with biochemical properties distinct from previously described antibodies, as well as one which bound to the first acidic loop of gC1qR. Intriguingly, we found that each of these antibodies could partly inhibit binding of FXII and FXIIa to gC1qR. Based on these results and previously published studies, we offer new perspectives for developing gC1qR inhibitors.
Pathogen-Derived Nucleases: An Effective Weapon for Escaping Extracellular Traps
Authors: Liao Chengshui , Mao Fuchao , Qian Man , Wang Xiaoli
Published: July 2022

Since the 2004 publication of the first study describing extracellular traps (ETs) from human neutrophils, several reports have shown the presence of ETs in a variety of different animals and plants. ETs perform two important functions of immobilizing and killing invading microbes and are considered a novel part of the phagocytosis-independent, innate immune extracellular defense system. However, several pathogens can release nucleases that degrade the DNA backbone of ETs, reducing their effectiveness and resulting in increased pathogenicity. In this review, we examined the relevant literature and summarized the results on bacterial and fungal pathogens and parasites that produce nucleases to evade the ET-mediated host antimicrobial mechanism.