bluuebunny/crossref_metadata_2025 huggingface dataset:
Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices
Authors: Vasiliu Tudor , Mocci Francesca , Laaksonen Aatto , Engelbrecht Leon De Villiers , Perepelytsya Sergiy
Published: February 2022

Polyamines have important roles in the modulation of the cellular function and are ubiquitous in cells. The polyamines putrescine2+, spermidine3+, and spermine4+ represent the most abundant organic counterions of the negatively charged DNA in the cellular nucleus. These polyamines are known to stabilize the DNA structure and, depending on their concentration and additional salt composition, to induce DNA aggregation, which is often referred to as condensation. However, the modes of interactions of these elongated polycations with DNA and how they promote condensation are still not clear. In the present work, atomistic molecular dynamics (MD) computer simulations of two DNA fragments surrounded by spermidine3+ (Spd3+) cations were performed to study the structuring of Spd3+ “caged” between DNA molecules. Microsecond time scale simulations, in which the parallel DNA fragments were constrained at three different separations, but allowed to rotate axially and move naturally, provided information on the conformations and relative orientations of surrounding Spm3+ cations as a function of DNA-DNA separation. Novel geometric criteria allowed for the classification of DNA-Spd3+ interaction modes, with special attention given to Spd3+ conformational changes in the space between the two DNA molecules (caged Spd3+). This work shows how changes in the accessible space, or confinement, around DNA affect DNA-Spd3+ interactions, information fundamental to understanding the interactions between DNA and its counterions in environments where DNA is compacted, e.g. in the cellular nucleus.
Glutathione-Sensitive Mesoporous Organosilica-Coated Gold Nanorods as Drug Delivery System for Photothermal Therapy-Enhanced Precise Chemotherapy
Authors: Song Hui , Peng Tingwei , Wang Xue , Li Beibei , Wang Yufang , Song Dianhai , Xu Tianzhao , Liu Xinghui
Published: February 2022

The combination of photothermal therapy (PTT) and chemotherapy can remarkably improve the permeability of the cell membrane and reduce the concentration of chemotherapy agents that not only kill the tumor cells effectively but also have adverse effects on normal tissues. It is of great meaning to construct nanomaterials that could be simultaneously applied for tumor eradication with PTT and chemotherapy. In this work, we developed a novel gold nanorod coated with mesoporous organosilica nanoparticles (oMSN-GNR), which presented as an optimal photothermal contrast agent. Moreover, after doxorubicin loading (oMSN-GNR–DOX), the organosilica shell exhibited biodegradable properties under high glutathione in the tumor microenvironment, resulting in massively releasing doxorubicin to kill tumor cells. More importantly, the hyperthermia effect of GNR cores under near-infrared light provided promising opportunities for localized photothermal ablation in vivo. Therefore, the combination of precise chemotherapy and highly effective PTT successfully inhibited tumor growth in liver tumor-bearing mice. This versatile synergistic therapy with local heating and chemotherapeutics precise release opens up the potential clinical application of PTT and chemotherapy therapeutics for malignant tumor eradication.
Involvement of Abnormal Gut Microbiota Composition and Function in Doxorubicin-Induced Cardiotoxicity
Authors: Huang Jie , Wei Shanshan , Jiang Chuanhao , Xiao Zijun , Liu Jian , Peng Weijun , Zhang Bikui , Li Wenqun
Published: February 2022

Objectives

Doxorubicin (Dox), a chemotherapeutic anthracycline agent for the treatment of a variety of malignancies, has a limitation in clinical application for dose-dependent cardiotoxicity. The purpose of this study was to explore the relationship between the composition/function of the gut microbiota and Dox-induced cardiotoxicity (DIC).

Methods

C57BL/6J mice were injected intraperitoneally with 15 mg/kg of Dox, with or without antibiotics (Abs) administration. The M-mode echocardiograms were performed to assess cardiac function. The histopathological analysis was conducted by H&E staining and TUNEL kit assay. The serum levels of creatine kinase (CK), CK-MB (CK-MB), lactic dehydrogenase (LDH), and cardiac troponin T (cTnT) were analyzed by an automatic biochemical analyzer. 16S rRNA gene and metagenomic sequencing of fecal samples were used to explore the gut microbiota composition and function.

Key Findings

Dox caused left ventricular (LV) dilation and reduced LV contractility. The levels of cardiomyocyte apoptosis and myocardial enzymes were elevated in Dox-treated mice compared with the control (Con) group. 16S rRNA gene sequencing results revealed significant differences in microbial composition between the two groups. In the Dox group, the relative abundances of Allobaculum, Muribaculum, and Lachnoclostridium were significantly decreased, whereas Faecalibaculum, Dubosiella, and Lachnospiraceae were significantly increased compared with the Con group at the genus level. Functional enrichment with Cluster of orthologous groups of proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the Dox mice displayed different clusters of cellular processes and metabolism from the Con mice. The different species and their functions between the two groups were associated with the clinical factors of cardiac enzymes. Moreover, depletion of the gut microbiota could alleviate Dox-induced myocardial injury and cardiomyocyte apoptosis.

Conclusions

The study here shows that composition imbalance and functional changes of the gut microbiota can be one of the etiological mechanisms underlying DIC. The gut microbiota may serve as new targets for the treatment of cardiotoxicity and cardiovascular diseases.
Some Good and Some Bad: Sand Fly Salivary Proteins in the Control of Leishmaniasis and in Autoimmunity
Authors: Aoki Valeria , Abdeladhim Maha , Li Ning , Cecilio Pedro , Prisayanh Phillip , Diaz Luis A. , Valenzuela Jesus G.
Published: February 2022

Sand flies are hematophagous insects responsible for the transmission of vector-borne diseases to humans. Prominent among these diseases is Leishmaniasis that affects the skin and mucous surfaces and organs such as liver and spleen. Importantly, the function of blood-sucking arthropods goes beyond merely transporting pathogens. The saliva of vectors of disease contains pharmacologically active components that facilitate blood feeding and often pathogen establishment. Transcriptomic and proteomic studies have enumerated the repertoire of sand fly salivary proteins and their potential use for the control of Leishmaniasis, either as biomarkers of vector exposure or as anti-Leishmania vaccines. However, a group of specific sand fly salivary proteins triggers formation of cross-reactive antibodies that bind the ectodomain of human desmoglein 1, a member of the epidermal desmosomal cadherins. These cross-reactive antibodies are associated with skin autoimmune blistering diseases, such as pemphigus, in certain immunogenetically predisposed individuals. In this review, we focus on two different aspects of sand fly salivary proteins in the context of human disease: The good, which refers to salivary proteins functioning as biomarkers of exposure or as anti-Leishmania vaccines, and the bad, which refers to salivary proteins as environmental triggers of autoimmune skin diseases.
Combination Therapies for Biofilm Inhibition and Eradication: A Comparative Review of Laboratory and Preclinical Studies
Authors: Hawas Sophia , Verderosa Anthony D. , Totsika Makrina
Published: February 2022

Microbial biofilms are becoming increasingly difficult to treat in the medical setting due to their intrinsic resistance to antibiotics. To combat this, several biofilm dispersal agents are currently being developed as treatments for biofilm infections. Combining biofilm dispersal agents with antibiotics is emerging as a promising strategy to simultaneously disperse and eradicate biofilms or, in some cases, even inhibit biofilm formation. Here we review studies that have investigated the anti-biofilm activity of some well-studied biofilm dispersal agents (e.g., quorum sensing inhibitors, nitric oxide/nitroxides, antimicrobial peptides/amino acids) in combination with antibiotics from various classes. This review aims to directly compare the efficacy of different combination strategies against microbial biofilms and highlight synergistic treatments that warrant further investigation. By comparing across studies that use different measures of efficacy, we can conclude that treating biofilms in vitro and, in some limited cases in vivo, with a combination of an anti-biofilm agent and an antibiotic, appears overall more effective than treating with either compound alone. The review identifies the most promising combination therapies currently under development as biofilm inhibition and eradication therapies.
Control of Jump Markov Uncertain Linear Systems With General Probability Distributions
Authors: Flüs Patrick , Stursberg Olaf
Published: February 2022

This paper introduces a method to control a class of jump Markov linear systems with uncertain initialization of the continuous state and affected by disturbances. Both types of uncertainties are modeled as stochastic processes with arbitrarily chosen probability distributions, for which however, the expected values and (co-)variances are known. The paper elaborates on the control task of steering the uncertain system into a target set by use of continuous controls, while chance constraints have to be satisfied for all possible state sequences of the Markov chain. The proposed approach uses a stochastic model predictive control approach on moving finite-time horizons with tailored constraints to achieve the control goal with prescribed confidence. Key steps of the procedure are (i) to over-approximate probabilistic reachable sets by use of the Chebyshev inequality, and (ii) to embed a tightened version of the original constraints into the optimization problem, in order to obtain a control strategy satisfying the specifications. Convergence of the probabilistic reachable sets is attained by suitable bounding of the state covariance matrices for arbitrary Markov chain sequences. The paper presents the main steps of the solution approach, discusses its properties, and illustrates the principle for a numeric example.
Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors: A Real-World Pharmacovigilance Study
Authors: Zhai Yinghong , Ye Xiaofei , Hu Fangyuan , Xu Jinfang , Guo Xiaojing , Lin Zhen , Zhou Xiang , Guo Zhijian , Cao Yang , He Jia
Published: February 2022

Background

Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.

Methods

This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.

Results

In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8–491] days, with the shortest median time of 42 days (IQR: 2–277 days) for esomeprazole, and the longest time of 389 days (IQR: 0–525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = −0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.

Conclusions

PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.
Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis
Authors: Hemilä Harri , Chalker Elizabeth , de Man Angelique M. E.
Published: February 2022

Background

Vitamin C deprivation can lead to fatigue, dyspnea, oedema and chest pain, which are also symptoms of heart failure (HF). In animal studies vitamin C has improved contractility and mechanical efficiency of the heart. Compared with healthy people, patients with HF have lower vitamin C levels, which are not explained by differences in dietary intake levels, and more severe HF seems to be associated with lower plasma vitamin C levels. This meta-analysis looks at the effect of vitamin C on left ventricular ejection fraction (LVEF).

Methods

We searched for trials reporting the effects of vitamin C on LVEF. We assessed the quality of the trials, and pooled selected trials using the inverse variance, fixed effect options. We used meta-regression to examine the association between the effect of vitamin C on LVEF level and the baseline LVEF level.

Results

We identified 15 trials, three of which were excluded from our meta-analysis. In six cardiac trials with 246 patients, vitamin C increased LVEF on average by 12.0% (95% CI 8.1–15.9%; P < 0.001). In six non-cardiac trials including 177 participants, vitamin C increased LVEF on average by 5.3% (95% CI 2.0–8.5%; P = 0.001). In meta-regression analysis we found that the effect of vitamin C was larger in trials with the lowest baseline LVEF levels with P = 0.001 for the test of slope. The meta-regression line crossed the null effect level at a baseline LVEF level close to 70%, with progressively greater benefit from vitamin C with lower LVEF levels. Some of the included trials had methodological limitations. In a sensitivity analysis including only the four most methodologically sound cardiac trials, the effect of vitamin C was not substantially changed.

Conclusions

In this meta-analysis, vitamin C increased LVEF in both cardiac and non-cardiac patients, with a strong negative association between the size of the vitamin C effect and the baseline LVEF. Further research on vitamin C and HF should be carried out, particularly in patients who have low LVEF together with low vitamin C intake or low plasma levels. Different dosages and different routes of administration should be compared.
Myocardial Segmentation of Cardiac MRI Sequences With Temporal Consistency for Coronary Artery Disease Diagnosis
Authors: Chen Yutian , Xie Wen , Zhang Jiawei , Qiu Hailong , Zeng Dewen , Shi Yiyu , Yuan Haiyun , Zhuang Jian , Jia Qianjun , Zhang Yanchun , Dong Yuhao , Huang Meiping , Xu Xiaowei
Published: February 2022

Coronary artery disease (CAD) is the most common cause of death globally, and its diagnosis is usually based on manual myocardial (MYO) segmentation of MRI sequences. As manual segmentation is tedious, time-consuming, and with low replicability, automatic MYO segmentation using machine learning techniques has been widely explored recently. However, almost all the existing methods treat the input MRI sequences independently, which fails to capture the temporal information between sequences, e.g., the shape and location information of the myocardium in sequences along time. In this article, we propose a MYO segmentation framework for sequence of cardiac MRI (CMR) scanning images of the left ventricular (LV) cavity, right ventricular (RV) cavity, and myocardium. Specifically, we propose to combine conventional neural networks and recurrent neural networks to incorporate temporal information between sequences to ensure temporal consistency. We evaluated our framework on the automated cardiac diagnosis challenge (ACDC) dataset. The experiment results demonstrate that our framework can improve the segmentation accuracy by up to 2% in the Dice coefficient.
Sedimentology and Geochemistry of the Lower Permian Shanxi Formation Shan 23 Submember Transitional Shale, Eastern Ordos Basin, North China
Authors: Gu Yifan , Li Xingtao , Qi Lin , Li Shuxin , Jiang Yuqiang , Fu Yonghong , Yang Xiaoshuai
Published: February 2022

Shanxi Formation Shan 23 Submember transitional shale in Eastern Ordos Basin is characterized by high TOC value, wide distribution, and large single-layer/cumulative thickness. In this study, based on section division of Shan 23 Submember, petrographic, mineralogical, and high-resolution geochemical analyses were integrated to reveal sedimentary environment, detrital influx, paleoclimate, paleosalinity, and paleoredox conditions. Results indicate that Shan 23 Submember is divided into four sections (Shan 23-1, Shan 23-2, Shan 23-3, and Shan 23-4). The upper part of the Shan 23-1 section is dominated by bay facies, which is characterized by high TOC value (2.75%–10.96%, avg. 6.98%), low detrital influx proxies (Zr, 97–527 ppm, avg. 310 ppm; Ti, 1985–7591 ppm, avg. 3938 ppm), relatively dry paleoclimate condition (CIA*, 41.96–92.58, avg. 75.55; Sr/Cu, 6.23–14.49, avg. 8.87), high paleosalinity proxies (Sr/Ba, 0.39–1.29, avg. 0.62), and relatively anoxic reduction condition (UEF, 0.83–3.00, avg. 1.67; MoEF, 3.95–27.00, avg. 15.56). By comparison, the other three sections are dominated by a combination of transitional facies, including barrier island, lagoon, tidal flat, and swamp. In this interval, shale is deposited in lagoon facies. The paleoclimate gradually tends to be warm and humid, which results in increasing the chemical weathering intensity. Meanwhile, the detrital influx increases, and the paleoredox condition tends to be oxic. The above conditions are not conducive to the preservation of organic matter in lagoon facies shale.
Early Life Interventions Can Shape Aging
Authors: Bartke Andrzej , Sun Liou Y. , Li Xinna , Miller Richard A.
Published: February 2022

It is well documented that the environment of the developing fetus, including availability of nutrients and presence of toxins, can have major impact on adult phenotype, age-related traits and risk of chronic disease. There is also accumulating evidence that postnatal environment can impact adult characteristics related to evolutionary fitness, health, and aging. To determine whether early life hormonal interventions can alter trajectory of aging, we have examined the effects of early life growth hormone (GH) replacement therapy in Prop1df (Ames dwarf) mice which are GH deficient and remarkably long lived. Twice-daily GH injections between the ages of two and eight weeks completely normalized (“rescued”) a number of adult metabolic characteristics believed to contribute to extended longevity of these mutants. Importantly, longevity of Ames dwarf mice was reduced by early life GH treatment. This was associated with histone H3 modifications. We conclude that the trajectory of mammalian aging can be modified by early life interventions. Mechanistic links among interventions during postnatal development, adult metabolic characteristics, aging, and longevity, apparently involve epigenetic phenomena.
Assessment of Long-Term Proppant Conductivity
Authors: Wang Jun , Xiong Youming , Jiao Guoying , Lei Dengsheng
Published: February 2022

Long-term conductivity data is essential to predict the production performance of the fractured well. It is necessary to know its long-term conductivity when choosing Tianxiang ceramic to prop hydraulic fractures in Northwest China. Its long-term conductivity was evaluated using DL-2000 equipment. Testing time at each closure stress point is more than 7 h, though the procedure used is similar to the recommended practice for short-term proppant conductivity. This test also investigates how factors such as proppant concentration and proppant size affected long-term conductivity. The results show these factors have a significant effect on long-term conductivity. Conductivity increases as proppant concentration rises, contributing to the increase of proppant volume and fracture height. Large proppants provide higher conductivity because large proppants have higher pore space and higher proppant pack height. High experimental temperature increases proppant conductivity due to dissolution and migration of minor fines and impurities. Besides, due to compaction, conductivity declines with the increase of testing time. Therefore, short-term conductivity is higher than long-term conductivity, while conductivity drops as testing time lasts. The results imply that Tianxiang ceramic performs as well as other ceramic proppants. It can offer proppant conductivity required by stimulation and qualifies to stimulate oil and gas wells in China. The achievements of this experiment will benefit hydraulic fracturing stimulation.
A Semi-Analytical Mathematical Model for Off-Center Fractured Vertical Wells With Asymmetrical Fractures in Columnar Coalbed Methane
Authors: Ji Anzhao , Chen Zhanjun , Wang Yufeng , Zhang Guangsheng , Mao Zhenglin , Chen Fenjun
Published: February 2022

Coalbed methane (CBM) is one of the important unconventional oil and gas resources. Since the permeability of the CBM reservoir is very low, CBM is usually developed by hydraulic fracturing technology to enhance gas productivity. In fact, most of the wells are not at the center of the columnar CBM reservoirs, which leads to different wellbore pressure responses. It is meaningful to analyze the wellbore pressure response of the off-center fractured vertical wells with asymmetrical fracture. The adsorption-desorption, fracture asymmetry are considered and a semi-analytical mathematical model is established. The pressure wellbore solution of the Laplace domain can be obtained by Laplace transformation, model coupling, and Gauss elimination. Then, the Stehfest numerical inversion is employed to obtain the pressure solution and rate distribution in the real-time domain. This semi-analytical solution is verified; the results show that the wellbore pressure includes six flow regimes, which include bilinear flow, linear flow, elliptic flow, radial flow, arc boundary reflection, and boundary dominated flow regime. The influence of fracture angle, dimensionless conductivity, and off-center distance on wellbore pressure and rate distribution are discussed in detail.
Collective Action Towards Risk Management in Informal Urban Areas in Medellín: COVID-19 Lessons for Reducing Vulnerability and Inequality
Authors: Garcia Ferrari Soledad , Crane De Narváez Stephanie , Castro Mera Wilmar Edgardo , Velásquez Carlos , Bain Amelia A.
Published: February 2022

Recent experiences of socio-environmental disasters in Latin America have demonstrated the ineffectiveness of the state as a social actor in the organisation, coordination and implementation of adequate public policies to face these emergencies. This affects the most vulnerable urban areas, leading to unequal levels of impact from crises and disasters within cities. As a response, local collective actions, led by citizens, have emerged to manage risks. In Medellín, Colombia, in the context of the current COVID-19 crisis, our research identified a diverse repertoire of collective actions within informal, vulnerable communities, including collaboration towards improving food security, sanitation, pedagogy for self-care and prevention, and financial aid. Although these actions have had limited scope within the context of the ongoing COVID-19 pandemic, they demonstrate the need to promote a more proactive interaction between society and the state, based on a series of agreed interventions, promoting the exchange of knowledge and articulation of actions in the production and improvement of informal urban areas. This research explores how these collective actions have developed through a set of semi-structured interviews with community leaders and key actors in Medellín, with a view to identifying lessons for state-community dynamics in relation to disaster risk management and achieving a more integrated approach to improving habitat conditions within vulnerable urban areas. This work demonstrates that vulnerable communities in informal urban settlements can actively address their exposure to risk through locally-oriented, bottom-up collective actions. However, key linkages with institutional frameworks are needed to strengthen state-community dynamics and facilitate sustainable, inclusive and equitable development in cities.
Remote Sensing Image-Based Comprehensive Monitoring Detection Platform for Coastal Tidal Mudflat Ecological Development
Authors: Xiao Shengjun , Yi Lin , Wang Zengjie , Liu Huiyu , Gao Hong , Yu Zhaoyuan
Published: February 2022

Considering the embarrassments related to inadequate safety monitoring detection and chaotic development order during the current ecological development of coastal tidal mudflat, we put forward a remote sensing image-based comprehensive monitoring detection platform integrating image data acquisition, mechanism analysis, comprehensive evaluation, and intelligent monitoring detection for coastal tidal mudflat ecological development. The platform includes imaging and data fusion technology, comprehensive evaluation and spatial layout optimization technology, and dynamic safety monitoring and early warning technology. A case study on Dafeng coastal tidal mudflat was conducted. The results show that our research can provide substantial reference for the coordination, dynamic management, and comprehensive regulation for the ecological development of coastal tidal mudflat.
Evaluation of Water Resources Utilization Efficiency in Guangdong Province Based on the DEA–Malmquist Model
Authors: Cheng Lifen , Song Song , Xie Yufeng
Published: February 2022

In this study, we examined the temporal and spatial trends of water utilization efficiency in the highly developed Guangdong Province based on a data envelopment analysis (DEA) model and Malmquist index, trying to evaluate and predict the water utilization status in prefecture-level cities from the input–output perspective. The results showed that the water utilization efficiency in Guangdong Province in 2012–2018 was on a fluctuating upward trend, although the utilization efficiency had not reached the DEA efficiency; spatially, the water utilization efficiency in Guangdong Province was relatively high in the Pearl River Delta and the surrounding cities, but low in the Western Guangdong region; in the perspective of efficiency decomposition factors, technological change was the most pervasive driving force of the water utilization efficiency. Pearl River Delta and Northern Guangdong made progress in productivity due to the advantages of scale expansion benefit. Eastern Guangdong achieved improvement in all-over parameters and made the largest growth in water utilization efficiency, while Western Guangdong basically profited from organizational management during the study period; the prediction analysis revealed a continuous increase in the water utilization efficiency in Guangdong Province during 2019–2025 with an average annual growth rate of about 0.6%, benefiting mainly from the technological innovation and secondly from management renewal, while scale expansion benefit tended to decline. Furthermore, spatial heterogeneity exhibited a decreasing tendency in the future owing to the rapid water utilization efficiency increase in the Western and Eastern Guangdong. It is suggested that the technological innovation and the integrated management capability in water use should be paid more attention to enhance the water utilization efficiency in Guangdong Province. Achieving a balance between economic growth and water resource protection, and promoting the sustainable development of the nature-economy-society compound system is of the utmost priority in Guangdong.
Design of a Combined System Based on Multi-Objective Optimization for Fine Particulate Matter (PM2.5) Prediction
Authors: Bai Lu , Li Hongmin , Zeng Bo , Huang Xiaojia
Published: February 2022

Air pollution forecasting plays a pivotal role in environmental governance, so a large number of scholars have devoted themselves to the study of air pollution forecasting models. Although numerous studies have focused on this field, they failed to consider fully the linear feature, non-linear feature, and fuzzy features contained in the original series. To fill this gap, a new combined system is built to consider features in the original series and accurately forecast PM2.5 concentration, which incorporates an efficient data decomposition strategy to extract the primary features of the PM2.5 concentration series and remove the noise component, and five forecasting models selected from three types of models to obtain the preliminary forecasting results, and a multi-objective optimization algorithm to combine the prediction results to produce the final prediction values. Empirical studies results indicated that in terms of RMSE the developed combined system achieves 0.652 6%, 0.810 1%, and 0.775 0% in three study cities, respectively. Compared to other prediction models, the RMSE improved by 60% on average in the study cities.
A Community-Based Conservation Initiative for Wolves in the Ladakh Trans-Himalaya, India
Authors: Sonam Karma , Dorjay Rigzen , Khanyari Munib , Bijoor Ajay , Lobzang Sherab , Sharma Manvi , Suresh Shruti , Mishra Charudutt , Suryawanshi Kulbhushansingh R.
Published: February 2022

We describe a pilot community-based conservation initiative for wolves Canis lupus that involves (i) voluntary deactivation of traditional trapping pits called Shandong, (ii) commitment to wildlife conservation by the local community, and (iii) collaborative construction and consecration of a Stupa (Buddhist shrine) in the vicinity of the Shandong as a symbol of conservation and repentance for past hunting. People and wolves have a complex relationship, in part shaped by predation on livestock, which can have severe impacts on livelihoods in pastoral societies. Consequently, wolf conservation often evokes strong and polarizing reactions. To control wolf populations, livestock herders across the Trans- Himalayan and Tibetan regions use different types of traps. Shandong is a relatively large, widely used traditional trapping pit with inverted funnel-shaped stone walls, usually built near villages or herder camps. Typically, a live domestic animal is placed in the pit to attract the wolves. Once the wolves jump into the pit, the funnel shaped walls prevent them from escaping, and trapped wolves are usually stoned to death. In an extensive survey covering over 25,000 sq. km, we enumerated 94 Shandong in 58 of the 64 surveyed villages in Ladakh between June 2019 and March 2020. Thirty of these had been used to kill wolves within the past 10 years, while 7 had been destroyed. Shandong that were not in use were of poorer condition. Since 2017, we have worked with community members, local monks, and the region’s religious leaders to support the neutralization of the Shandong while preserving their structure, and assisted the communities to build Stupas and to consecrate them. Our pilot efforts with three communities appear to generate pride locally, and hold promise for promoting wolf conservation in Ladakh and in large parts of Trans-Himalayan and Tibetan regions that share similar cultural settings.
Current Models to Study the Sporothrix-Host Interaction
Authors: Vargas-Macías Ana P. , Gómez-Gaviria Manuela , García-Carnero Laura C. , Mora-Montes Héctor M.
Published: February 2022

Sporotrichosis is a worldwide distributed subcutaneous mycosis that affects mammals, including human beings. The infection is caused by members of the Sporothrix pathogenic clade, which includes Sporothrix schenckii, Sporothrix brasiliensis, and Sporothrix globosa. The fungus can be acquired through traumatic inoculation of conidia growing in vegetal debris or by zoonotic transmission from sick animals. Although is not considered a life-threatening disease, it is an emergent health problem that affects mostly immunocompromised patients. The sporotrichosis causative agents differ in their virulence, host range, and sensitivity to antifungal drugs; therefore, it is relevant to understand the molecular bases of their pathogenesis, interaction with immune effectors, and mechanisms to acquired resistance to antifungal compounds. Murine models are considered the gold standard to address these questions; however, some alternative hosts offer numerous advantages over mammalian models, such as invertebrates like Galleria mellonella and Tenebrio molitor, or ex vivo models, which are useful tools to approach questions beyond virulence, without the ethical or budgetary features associated with the use of animal models. In this review, we analyze the different models currently used to study the host-Sporothrix interaction.
Identification and Validation of a Pyroptosis-Related Prognostic Model for Gastric Cancer
Authors: Liang Chaowei , Fan Jiaxin , Liang Chaojie , Guo Jiansheng
Published: February 2022

Pyroptosis is an inflammatory form of programmed cell death triggered by caspase-1/4/5/11 that plays an important role in the occurrence and development of gastric cancer (GC). We investigated the prognostic value of pyroptosis-related genes in GC. The “LIMMA” R package and univariate Cox analysis were used to find pyroptosis-related genes with differential expression and prognostic value in the TCGA cohort and the identified genes were analyzed for GO enrichment and KEGG pathways. The selected genes were then included in a multivariate Cox proportional hazard regression analysis, and a ten genes prognostic model (BIRC2, CD274, IRGM, ANXA2, GBP5, TXNIP, POP1, GBP1, DHX9, and TLR2) was established. To evaluate the predictive value of the risk score on prognosis, patients were divided into high-risk and low-risk groups according to the median risk score, and survival analysis was carried out. Compared with the low-risk group, the OS of GC patients in the high-risk group was significantly worse. Additionally, these results were verified in the GSE84437 and GSE66229 datasets. Finally, through the combination of prognostic gene characteristics and clinicopathological features, a nomogram was established to predict individual survival probability. The results show that the genetic risk characteristics related to clinical features can be used as independent prognostic indicators for patients with GC. In summary, the pyroptosis-related risk signals proposed in this study can potentially predict the prognosis of patients with GC. In addition, we also found significant infiltration of dendritic cells, macrophages, and neutrophils in tissues of high-risk patients.
ARZIMM: A Novel Analytic Platform for the Inference of Microbial Interactions and Community Stability from Longitudinal Microbiome Study
Authors: He Linchen , Wang Chan , Hu Jiyuan , Gao Zhan , Falcone Emilia , Holland Steven M. , Blaser Martin J. , Li Huilin
Published: February 2022

Dynamic changes of microbiome communities may play important roles in human health and diseases. The recent rise in longitudinal microbiome studies calls for statistical methods that can model the temporal dynamic patterns and simultaneously quantify the microbial interactions and community stability. Here, we propose a novel autoregressive zero-inflated mixed-effects model (ARZIMM) to capture the sparse microbial interactions and estimate the community stability. ARZIMM employs a zero-inflated Poisson autoregressive model to model the excessive zero abundances and the non-zero abundances separately, a random effect to investigate the underlining dynamic pattern shared within the group, and a Lasso-type penalty to capture and estimate the sparse microbial interactions. Based on the estimated microbial interaction matrix, we further derive the estimate of community stability, and identify the core dynamic patterns through network inference. Through extensive simulation studies and real data analyses we evaluate ARZIMM in comparison with the other methods.
m6A mRNA Methylation Was Associated With Gene Expression and Lipid Metabolism in Liver of Broilers Under Lipopolysaccharide Stimulation
Authors: Guo Feng , Zhang Yanhong , Ma Jinyou , Yu Yan , Wang Qiuxia , Gao Pei , Wang Li , Xu Zhiyong , Wei Xiaobing , Jing Mengna
Published: February 2022

Hepatic inflammation is always accompanied with abnormal lipid metabolism. Whether N6-methyladenosine (m6A) mRNA methylation affects irregular inflammatory lipid level is unclear. Here, the m6A modification patterns in chicken liver at the acute stage of LPS-stimulated inflammation and at the normal state were explored via m6A and RNA sequencing and bioinformatics analysis. A total of 7,815 m6A peaks distributed in 5,066 genes were identified in the normal chicken liver and were mostly located in the CDS, 3′UTR region, and around the stop codon. At 2 h after the LPS intraperitoneal injection, the m6A modification pattern changed and showed 1,200 different m6A peaks. The hyper- and hypo-m6A peaks were differentially located, with the former mostly located in the CDS region and the latter in the 3′UTR and in the region near the stop codon. The hyper- or hypo-methylated genes were enriched in different GO ontology and pathways. Co-analysis revealed a significantly positive relationship between the fold change of m6A methylation level and the relative fold change of mRNA expression. Moreover, computational prediction of protein–protein interaction (PPI) showed that genes with altered m6A methylation and mRNA expression levels were clustered in processes involved in lipid metabolism, immune response, DNA replication, and protein ubiquitination. CD18 and SREBP-1 were the two hub genes clustered in the immune process and lipid metabolism, respectively. Hub gene AGPAT2 was suggested to link the immune response and lipid metabolism clusters in the PPI network. This study presented the first m6A map of broiler chicken liver at the acute stage of LPS induced inflammation. The findings may shed lights on the possible mechanisms of m6A-mediated lipid metabolism disorder in inflammation.
PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma
Authors: Meng Zhishang , Chen Yanzhu , Wu Wenyi , Yan Bin , Zhang Lusi , Chen Huihui , Meng Yongan , Liang Youling , Yao Xiaoxi , Luo Jing
Published: February 2022

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM develops and is sustained by inflammation and immunosuppression from the tumor microenvironment (TME). This study sought to identify a reliable TME-related biomarker that could provide survival prediction and new insight into therapy for UM patients. Based on clinical characteristics and the RNA-seq transcriptome data of 80 samples from The Cancer Genome Atlas (TCGA) database, PRRX1 as a TME- and prognosis-related gene was identified using the ESTIMATE algorithm and the LASSO–Cox regression model. A prognostic model based on PRRX1 was constructed and validated with a Gene Expression Omnibus (GEO) dataset of 63 samples. High PRRX1 expression was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Comprehensive results of the prognostic analysis showed that PRRX1 was an independent and reliable predictor of UM. Then the results of immunological characteristics demonstrated that higher expression of PRRX1 was accompanied by higher expression of immune checkpoint genes, lower tumor mutation burden (TMB), and greater tumor cell infiltration into the TME. Gene set enrichment analysis (GSEA) showed that high PRRX1 expression correlated with angiogenesis, epithelial–mesenchymal transition (EMT), and inflammation. Furthermore, downregulation of PRRX1 weakened the process of EMT, reduced cell invasion and migration of human UM cell line MuM-2B in vitro. Taken together, these findings indicated that increased PRRX1 expression is independently a prognostic factor of poorer OS and MFS in patients with UM, and that PRRX1 promotes malignant progression of UM by facilitating EMT, suggesting that PRRX1 may be a potential target for UM therapy.
Efficient DNA Repair Mitigates Replication Stress Resulting in Less Immunogenic Cytosolic DNA in Radioresistant Breast Cancer Stem Cells
Authors: Meyer Felix , Engel Anna Maria , Krause Ann Kristin , Wagner Tim , Poole Lena , Dubrovska Anna , Peitzsch Claudia , Rothkamm Kai , Petersen Cordula , Borgmann Kerstin
Published: February 2022

Cancer stem cells (CSCs) are a major cause of tumor therapy failure. This is mainly attributed to increased DNA repair capacity and immune escape. Recent studies have shown that functional DNA repair via homologous recombination (HR) prevents radiation-induced accumulation of DNA in the cytoplasm, thereby inhibiting the intracellular immune response. However, it is unclear whether CSCs can suppress radiation-induced cytoplasmic dsDNA formation. Here, we show that the increased radioresistance of ALDH1-positive breast cancer stem cells (BCSCs) in S phase is mediated by both enhanced DNA double-strand break repair and improved replication fork protection due to HR. Both HR-mediated processes lead to suppression of radiation-induced replication stress and consequently reduction of cytoplasmic dsDNA. The amount of cytoplasmic dsDNA correlated significantly with BCSC content (p=0.0002). This clearly indicates that HR-dependent avoidance of radiation-induced replication stress mediates radioresistance and contributes to its immune evasion. Consistent with this, enhancement of replication stress by inhibition of ataxia telangiectasia and RAD3 related (ATR) resulted in significant radiosensitization (SER37 increase 1.7-2.8 Gy, p<0.0001). Therefore, disruption of HR-mediated processes, particularly in replication, opens a CSC-specific radiosensitization option by enhancing their intracellular immune response.
Emerging Roles of lncRNAs Regulating RNA-Mediated Type-I Interferon Signaling Pathway
Authors: Ji Xiaoxin , Meng Wei , Liu Zichuan , Mu Xin
Published: February 2022

The type-I interferon (IFN-I) signaling pathway plays pivot roles in defending against pathogen invasion. Exogenous ssRNA and dsRNA could be immunogenic. RNA-mediated IFN signaling is extensively studied in the field. The incorrect functioning of this pathway leads to either autoimmune diseases or suffering from microorganism invasion. From the discrimination of “self” and “non-self” molecules by receptors to the fine-tune modulations in downstream cascades, all steps are under the surveillance featured by complex feedbacks and regulators. Studies in recent years highlighted the emerging roles of long noncoding RNAs (lncRNAs) as a reservoir for signaling regulation. LncRNAs bind to targets through the structure and sequence, and thus the mechanisms of action can be complex and specific. Here, we summarized lncRNAs modulating the RNA-activated IFN-I signaling pathway according to the event order during the signaling. We hope this review help understand how lncRNAs are participating in the regulation of IFN-I signaling.
HLA-G and the MHC Cusp Theory
Authors: Scavuzzi Bruna Miglioranza , van Drongelen Vincent , Holoshitz Joseph
Published: February 2022

Human leukocyte antigens (HLA) are significant genetic risk factors in a long list of diseases. However, the mechanisms underlying these associations remain elusive in many cases. The best-characterized function of classical major histocompatibility complex (MHC) antigens is to allow safe presentation of antigenic peptides via a self/non-self-discrimination process. Therefore, most hypotheses to date have posited that the observed associations between certain HLA molecules and human diseases involve antigen presentation (AP). However, these hypotheses often represent inconsistencies with current knowledge. To offer answers to the inconsistencies, a decade ago we have invoked the MHC Cusp theory, postulating that in addition to its main role in AP, the MHC codes for allele-specific molecules that act as ligands in a conformationally-conserved cusp-like fold, which upon interaction with cognate receptors can trigger MHC-associated diseases. In the ensuing years, we have provided empirical evidence that substantiates the theory in several HLA-Class II-associated autoimmune diseases. Notably, in a recent study we have demonstrated that HLA-DRB1 alleles known to protect against several autoimmune diseases encode a protective epitope at the cusp region, which activates anti-inflammatory signaling leading to transcriptional and functional modulatory effects. Relevant to the topic of this session, cusp ligands demonstrate several similarities to the functional effects of HLA-G. The overall goal of this opinion article is to delineate the parallels and distinctive features of the MHC Cusp theory with structural and functional aspects of HLA-G molecules.
Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis
Authors: Elst Jessy , De Puysseleyr Leander P. , Ebo Didier G. , Faber Margaretha A. , Van Gasse Athina L. , van der Poorten Marie-Line M. , Decuyper Ine I. , Bridts Chris H. , Mertens Christel , Van Houdt Michel , Hagendorens Margo M. , De Clerck Luc S. , Verlinden Anke , Vermeulen Katrien , Maes Marie-Berthe , Berneman Zwi N. , Valent Peter , Sabato Vito
Published: February 2022

Background

Uncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis.

Objective

This study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA+), CMCD patients without anaphylaxis (CMCD/ANA-), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA+) and patients with a non-mast cell haematological pathology (NMHP).

Methods

This study included 20 patients with CMCD/WVA+, 24 with CMCD/ANA-, 19 with WVA+, 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included.

Results

Higher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations.

Conclusion

Patients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis.