bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender Differences and Postoperative Delirium in Adult Patients Undergoing Cardiac Valve Surgery
Authors: Wang Hongbai , Guo Xiaoxiao , Zhu Xianlin , Li Yinan , Jia Yuan , Zhang Zhe , Yuan Su , Yan Fuxia
Published: November 2021

Background: Postoperative delirium (POD) is common in patients following cardiac surgery. According to studies on non-cardiac surgery, males suffered from higher incidence of POD. However, there is no report about effect of gender differences on POD occurrence in cardiac surgery patients. The aim of this study was to investigate the effect of gender differences on POD occurrence in adult patients after cardiac valve surgery.

Methods: This is a retrospective case-control study. We recorded the clinical data in adult patients who underwent elective cardiac valve surgery from May 2019 to October 2020. POD was assessed by the Confusion Assessment Method for Intensive Care Unit. Univariate analysis was used to screen the potential risk factors. Collinearity analysis was conducted to detect overlapping predictor variables on the outcomes. A multivariate logistic regression with odds ratio (OR) and 95% confidence interval (CI) was used to identify the independent risk factors. The Hosmer-Lemeshow test was performed to show the good calibration of the logistic regression model.

Results: In total, we recorded the perioperative data in 431 adult patients, including 212 males and 219 females. Sixty patients suffered from POD, including 39 males and 21 females. Twenty-one perioperative variables were selected, and 11 were screened by univariate analysis. We did not detect the severe collinearity among the 11 variables. Male gender was identified as a significant risk factor in POD occurrence in patients undergoing cardiac surgery (Adjusted OR: 2.213, 95% CI: 1.049–4.670, P = 0.037). The Hosmer-Lemeshow test demonstrated good calibration of the logistic regression model (χ2 = 7.238, P = 0.511). Besides, compared with females, the relationship of male and delirium subtypes was as follows: (1) hyperactive: adjusted OR: 3.384, 95% CI: 1.335–8.580, P = 0.010; (2) hypoactive: adjusted OR: 0.509, 95% CI: 0.147–1.766, P = 0.287. A Stratification analysis by age demonstrated that the males showed higher POD incidence in patients aged younger than 60 years (adjusted OR: 4.384, 95% CI: 1.318–14.586, P = 0.016).

Conclusions: Male gender is an important risk factor in POD occurrence in patients following cardiac surgery. Furthermore, the incidence of hyperactive delirium is higher in males. Besides, the male patients aged younger than 60 years are at high risk of POD. We should pay more attention to the male patients to prevent their POD occurrence.
Wnt2 Contributes to the Development of Atherosclerosis
Authors: Zhang Jinyu , Rojas Samuel , Singh Sanjay , Musich Phillip R. , Gutierrez Matthew , Yao Zhiqiang , Thewke Douglas , Jiang Yong
Published: November 2021

Atherosclerosis, is a chronic inflammatory disease, characterized by the narrowing of the arteries resulting from the formation of intimal plaques in the wall of arteries. Yet the molecular mechanisms responsible for maintaining the development and progression of atherosclerotic lesions have not been fully defined. In this study, we show that TGF-β activates the endothelial-to-mesenchymal transition (EndMT) in cultured human aortic endothelial cells (HAECs) and this transition is dependent on the key executor of the Wnt signaling pathway in vitro. This study presents the first evidence describing the mechanistic details of the TGF-β-induced EndMT signaling pathway in HAECs by documenting the cellular transition to the mesenchymal phenotype including the expression of mesenchymal markers α-SMA and PDGFRα, and the loss of endothelial markers including VE-cadherin and CD31. Furthermore, a short hairpin RNA (shRNA) screening revealed that Wnt2 signaling is required for TGF-β-mediated EndMT of HAECs. Also, we found that LDLR−/− mice fed on a high-fat western-type diet (21% fat, 0.2% cholesterol) expressed high levels of Wnt2 protein in atherosclerotic lesions, confirming that this signaling pathway is involved in atherosclerosis in vivo. These findings suggest that Wnt2 may contribute to atherosclerotic plaque development and this study will render Wnt2 as a potential target for therapeutic intervention aiming at controlling atherosclerosis.
Case Report: Occurrence of Severe Thoracic Aortic Aneurysms (Involving the Ascending, Arch, and Descending Segments) as a Result of Fibulin-4 Deficiency: A Rare Pathology With Successful Management
Authors: Thomas Paul , Venugopalan Aparna , Narayanan Siddharth , Mathew Thomas , Cherukuwada Lakshmi Parvathi Deepti , Chandran Shilpa , Pradeep Jithu , Fitzgibbons Timothy P. , George Vijo
Published: November 2021

Aortic diseases requiring surgery in childhood are distinctive and rare. Very few reports in the literature account for the occurrence of multiple thoracic aortic aneurysms in the same pediatric patient because of a genetic cause. We report a rare occurrence of severe thoracic aortic aneurysms (involving the ascending, arch and descending aortic segments) with severe aortic insufficiency in a 7-year-old female child secondary to the extremely rare and often lethal genetic disorder, cutis laxa. She was eventually identified as a carrier of a homozygousEFEMP2(aliasFBLN4) mutation. This gene encodes the extracellular matrix protein fibulin-4, and its mutation is associated with autosomal recessive cutis laxa type 1B that leads to severe aortopathy with aneurysm formation and vascular tortuosity. Parents of the child were not known to be consanguineous. Significant symptomatic improvement in the patient could be discerned after timely intervention with the valve-sparing aortic root replacement (David V procedure) and a concomitant aortic arch replacement. This is a unique report with a successful outcome that highlights the occurrence of a rare hereditary aortopathy associated with a high morbidity and mortality, and the importance of an early diagnosis and timely management. It also offers insight to physicians in having a very broad differential and multimodal approach in handling rare pediatric cardio-pathologies with a genetic predisposition.
Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Sant'Anna Lucas Bonacossa , Couceiro Sérgio Lívio Menezes , Ferreira Eduardo Amar , Sant'Anna Mariana Bonacossa , Cardoso Pedro Rey , Mesquita Evandro Tinoco , Sant'Anna Guilherme Mendes , Sant'Anna Fernando Mendes
Published: November 2021

Objectives: The aim of this study was to evaluate the effects of invasive vagal nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF).

Background: Heart failure is characterized by autonomic nervous system imbalance and electrical events that can lead to sudden death. The effects of parasympathetic (vagal) stimulation in patients with HF are not well-established.

Methods: From May 1994 to July 2020, a systematic review was performed using PubMed, Embase, and Cochrane Library for clinical trials, comparing VNS with medical therapy for the management of chronic HFrEF (EF ≤ 40%). A meta-analysis of several outcomes and adverse effects was completed, and GRADE was used to assess the level of evidence.

Results: Four randomized controlled trials (RCT) and three prospective studies, totalizing 1,263 patients were identified; 756 treated with VNS and 507 with medical therapy. RCT data were included in the meta-analysis (fixed-effect distribution). Adverse effects related to VNS were observed in only 11% of patients. VNS was associated with significant improvement (GRADE = High) in the New York Heart Association (NYHA) functional class (OR, 2.72, 95% CI: 2.07–3.57, p < 0.0001), quality of life (MD −14.18, 95% CI: −18.09 to −10.28, p < 0.0001), a 6-min walk test (MD, 55.46, 95% CI: 39.11–71.81, p < 0.0001) and NT-proBNP levels (MD −144.25, 95% CI: −238.31 to −50.18, p = 0.003). There was no difference in mortality (OR, 1.24; 95% CI: 0.82–1.89, p = 0.43).

Conclusions: A high grade of evidence demonstrated that vagal nerve stimulation improves NYHA functional class, a 6-min walk test, quality of life, and NT-proBNP levels in patients with chronic HFrEF, with no differences in mortality.
A Scoping Review on Access and Use of Technology in Youth Experiencing Homelessness: Implications for Healthcare
Authors: Lal Shalini , Halicki-Asakawa Amané , Fauvelle Amélie
Published: November 2021

Introduction:Youth are among the fastest growing subset of the homeless population. Youth experiencing homelessness (YEH) face multiple barriers in accessing health information and health care services. As such, they may best be reached through information and communication technologies (ICTs); however, limited efforts have been made to synthesize literature on this topic. In this paper, we review studies on access and use of ICTs among YEH. We also discuss the implications of the review for healthcare.

Methods:Using scoping review methodology, we searched four databases (Medline, Embase, PsycInfo, and CINAHL) for studies published between 2005 and 2019, screening 1,927 titles and abstracts.

Results:We identified 19 articles reporting on studies with YEH between the ages of 12-30, the majority of which were published in the USA. On average, more than half of the samples owned smartphones, used social media, and accessed the internet weekly to search for housing, employment, health information, and to communicate with family, peers, and health workers; however, many youths faced barriers to sustaining their access to technology. Benefits of using ICTs were connecting with home-based peers, family, and case workers, which was associated with a reduction in substance use, risky sexual health behaviors, and severity of mental health symptoms. Connecting with negative, street-based social ties was identified as the most common risk factor to using ICTs due to its association with engaging in risky sex behaviors and substance abuse.

Discussion:This review supports the advancement of research and practice on using ICTs to deliver public health information and health services to YEH, while also considering the health-related risks, benefits, and barriers that YEH face when accessing ICTs.
Wnt Signaling in Periodontal Disease
Authors: González-Quintanilla David , Abásolo Nicolás , Astudillo Pablo
Published: November 2021

Periodontitis is a multifactorial and chronic condition associated with the formation of a dysbiotic biofilm, leading to a pro-inflammatory environment that can modulate cell signaling. The Wnt pathway plays fundamental roles during homeostasis and disease, and emerging evidence suggests its involvement in the maintenance of the periodontium and the development of periodontitis. Here, we summarize the role of the Wnt/β-catenin and non-canonical Wnt signaling pathways in periodontitis. The accumulated data suggests specific roles for each branch of the Wnt pathway. Wnt5a emerges as a critical player promoting periodontal ligament remodeling and impairing regenerative responses modulated by the Wnt/β-catenin pathway, such as alveolar bone formation. Collectively, the evidence suggests that achieving a proper balance between the Wnt/β-catenin and non-canonical pathways, rather than their independent modulation, might contribute to controlling the progression and severity of the periodontal disease.
The Rasch Model Cannot Reveal Systematic Differential Item Functioning in Single Tests: Subset DIF Analysis as an Alternative Methodology
Authors: Humphry Stephen , Montuoro Paul
Published: November 2021

This article demonstrates that the Rasch model cannot reveal systematic differential item functioning (DIF) in single tests. The person total score is the sufficient statistic for the person parameter estimate, eliminating the possibility for residuals at the test level. An alternative approach is to use subset DIF analysis to search for DIF in item subsets that form the components of the broader latent trait. In this methodology, person parameter estimates are initially calculated using all test items. Then, in separate analyses, these person estimates are compared to the observed means in each subset, and the residuals assessed. As such, this methodology tests the assumption that the person locations in each factor group are invariant across subsets. The first objective is to demonstrate that in single tests differences in factor groups will appear as differences in the mean person estimates and the distributions of these estimates. The second objective is to demonstrate how subset DIF analysis reveals differences between person estimates and the observed means in subsets. Implications for practitioners are discussed.
The Leptin System and Diet: A Mini Review of the Current Evidence
Authors: Mendoza-Herrera Kenny , Florio Andrea A. , Moore Maggie , Marrero Abrania , Tamez Martha , Bhupathiraju Shilpa N. , Mattei Josiemer
Published: November 2021

Leptin promotes satiety and modulates energy balance and weight. Diet-induced obesity leads to leptin resistance, exacerbating overeating. We reviewed the literature on the relationship between diet and leptin, which suggests that addressing leptin resistance through dietary interventions can contribute counteracting obesity. Albeit some limitations (e.g., limited rigor, small samples sizes), studies in animals and humans show that diets high in fat, carbohydrates, fructose, and sucrose, and low in protein are drivers of leptin resistance. Despite methodological heterogeneity pertaining to this body of literature, experimental studies show that energy-restricted diets can reduce leptinemia both in the short and long term and potentially reverse leptin resistance in humans. We also discuss limitations of this evidence, future lines of research, and implications for clinical and public health translations. Main limitations include the lack of a single universally-accepted definition of leptin resistance, and of adequate ways to accurately measure it in humans. The use of leptin sensitizers (drugs) and genetically individualized diets are alternatives against leptin resistance that should be further researched in humans. The tested very-low-energy intervention diets are challenging to translate into wide clinical or population recommendations. In conclusion, the link between nutritional components and leptin resistance, as well as research indicating that this condition is reversible, emphasizes the potential of diet to recover sensitivity to this hormone. A harmonized definition of leptin resistance, reliable methods to measure it, and large-scale, translational, clinical, and precision nutrition research involving rigorous methods are needed to benefit populations through these approaches.
Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial
Authors: Sun Chengjun , Lu Biao , Liu Yu , Zhang Yaqin , Wei Haiyan , Hu Xu , Hu Pei , Zhao Qian , Liu Yanling , Ye Kan , Wang Kan , Gu Zaiyan , Liu Zheng , Ye Jin , Zhang Hongxiao , Zhu Hong , Jiang Zhihong , Liu Yanjie , Wan Naijun , Yan Chengming , Yin Jianying , Ying Lirong , Huang Feng , Yin Qingjin , Xi Li , Luo Feihong , Cheng Ruoqian
Published: November 2021

Context

Long-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending.

Objective

We studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children.

Design, Setting, and Patients

This multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children.

Intervention

Subjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks.

Main Outcome Measure

The primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes.

Results

At week 26, the median HtSDSCA changed from −2.75, −2.82, and −2.78 to −2.31, −2.43, and −2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%–90.34% and 76.08%–90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups.

Conclusions

Although notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT02976675.
The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder
Authors: Zhao Shuai , Xia Yi , Huang Yinghong , Zou Haowen , Wang Xumiao , Chen Zhilu , Zhou Hongliang , Han Yinglin , Tang Hao , Yan Rui , Yao Zhijian , Lu Qing
Published: November 2021

The present study was aimed to investigate the relationships between serum thyroid hormones (THs), frontal gray matter volume, and executive function in selected patients with major depressive disorder (MDD). One hundred and four MDD patients and seventy-five healthy controls (HCs) were subjected to thyroid-stimulating hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), and executive function tests and underwent structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis was performed to compare group differences in the gray matter for the frontal lobe. Furthermore, mediation analysis was used to investigate whether gray matter volumes of the frontal gyrus mediated the relationship between serum THs and executive function in MDD patients. MDD patients exhibited significant gray matter volume reduction in several brain regions, including the left rectus, right middle frontal cortex, and left middle frontal cortex. Serum TSH levels are positively associated with altered regional gray matter volume patterns within MFG and executive function. Importantly, gray matter in the right MFG was a significant mediator between serum TSH levels and executive function. These findings expand our understanding of how thyroid function affects brain structure changes and executive function in MDD patients.
The Evolution of Factors Influencing Green Technological Progress in Terms of Carbon Reduction: A Spatial-Temporal Tactic Within Agriculture Industries of China
Authors: Yue Deng , Sarkar Apurbo , Yu Cui , Qian Lu , Minjuan Zhao
Published: November 2021

The impacts of widespread carbon emission trends possessed tremendous pressure for global food security, sustainable development, and ecosystems. Several temporal and spatial patterns of green technology have been adopted to reduce carbon emissions in different regions of China. In China, agriculture industries may have colossal importance for reducing carbon emissions. On the basis of the data from 1998 to 2018, the study uses the heterogeneous stochastic frontier model to quantify the carbon emission reduction potential of agricultural green technology progress in eastern, central, and western regions of China by using the heterogeneous stochastic frontier model. We also analyze the coefficient of variation and its spatial and temporal evolution pattern of carbon intensity decline potential index and explore the potential factors related to the agriculture green technology progress of China. The finding of the study revealed that the carbon emission rate in the agriculture industry of China is very high, whereas adopting green technology is slower because of economic and policy-related factors—the carbon emission of green technological progress. In terms of spatial variations, the changes in various regions were consistent with the overall fluctuating rate compared with the state of another country, but an increasing trend has been traced within the “east-central-west” regions. The overall regional differences are gradually trending, but differences between regions mainly cause them. The increase in the structure of the agricultural agriculture industry, the level of labor, and the increase in administrative environmental regulations will weaken the obstacles to the carbon emission reduction potential of green technological progress. The increase in urbanization, the level of the agricultural economy, and economic and environmental regulations will increase the carbon emission reduction potential of green technological progress. It is necessary to actively promote exchanges and cooperation in green agricultural technology and advanced management concepts, accelerate the optimization and upgrading of the industrial structure, and achieve the goal of peaking carbon emissions through regional coordinated development. Regionally, the overall external environment and the level of green technology progress in the western region need to be improved in all respects. The central and eastern regions need to focus on combining different policy tools to transform them from hindrance to promotion.
Mathematical Model of the Deaeration of Finely Dispersed Solid Media in a Spherical Matrix of a Roller-Type Apparatus
Authors: Kapranova Anna , Tarshis Mikhail , Badaeva Natalya , Sheronina Irina
Published: November 2021

The additional operation of deaeration (compaction) of powders affects the quality of many products of chemical industries, the conditions for their delivery. Otherwise, energy consumption increases significantly. The aim of this work is the modeling of the deaeration of solid finely dispersed media in a gap with perforated hemispherical shapes on the surfaces of the shaft and conveyor belt within the framework of the mechanics of heterogeneous systems. A plane-deformation model is described, neglecting the forces of interphase interaction and taking into account the compressibility of a solid-particle-gas mixture without elastoplastic deformations. The model assumes consideration of the movement of (1) the components of the solid skeleton together with the carrying phase as a whole; (2) gas in an isothermal state through the pores of a finely dispersed material. This work is devoted to the study of part (a), i.e., behavior of the solid particle-gas system as a whole. The efficiency of the seal-deaerator is estimated using the obtained analytical dependencies for the main strength and speed indicators. The change in the degree of compaction of a spherical granule made of kaolin with given strength characteristics is investigated. It is shown that for the initial time interval up to 3.7⨯10−2 s, the growth of the porosity value relative to the horizontal coordinate along the conveyor belt is exponential and increases by a factor of 1.1. After eight such time intervals, the porosity values stabilize along the indicated coordinate with an increase of more than 1.4 times from the initial value.
Durable Biopolymer Films From Lignin-Carbohydrate Complex Derived From a Pulp Mill Side Stream
Authors: Asikanius Brita , Jääskeläinen Anna-Stiina , Koivula Hanna , Oinonen Petri , Österberg Monika
Published: November 2021

Valorization of side streams offers novel types of raw materials to complement or replace synthetic and food-based alternatives in materials science, increasing profitability and decreasing the environmental impacts of biorefineries. Lignocellulose biomass contains lignin and carbohydrates that are covalently linked into lignin-carbohydrate complexes (LCCs). In biomass fractionation processes, these complexes are conventionally considered as waste, which hinders the biomass fractionation process, and they may solubilize into aqueous effluents. This study presents how LCCs, derived from pulp mill effluent, can be turned into valuable biopolymers for industrial polymer film applications. Free-standing composite films containing hydroxyethyl cellulose (HEC) and LCCs with varying molar mass, charge density and lignin/hemicellulose ratio were prepared to study the effect of LCC amount on mechanical properties and oxygen permeability. Increasing the LCC content increased the yield point and Young’s modulus of the films. Breaking strain measurements revealed a non-linear correlation with the LCC concentration for the samples with higher lignin than hemicellulose content. The addition of LCC enhanced oxygen barrier properties of HEC films significantly even at high relative humidity. The present research demonstrates how a currently underutilized fraction of the biorefinery side stream has the potential to be valorized as a biopolymer in industrial applications, for example as a barrier film for paper and board packaging.
Interval Reliability Evaluation of a Hybrid Energy Generation System With Energy Storage
Authors: Ji Shiyu , Sun Yi , Gao Lin , Yang Huaizhi , Jia Wanqing , Luo Yufeng , Chen Wanrong
Published: November 2021

To deal with the uncertainties of wind power and load residing in the power supply reliability model, an interval reliability evaluation method is proposed by combining the wind power generation and energy storage system (ESS). Firstly, the interval power supply reliability evaluation model, which belongs to an interval mixed integer program (IMIP), is established based on the interval variables. Secondly, the IMIP model is transformed into the deterministic optimization model under two extreme circumstances by utilizing the possibility degree theory of interval numbers. The maximum power supply probability, considering the wind power interval to meet the load demand interval, is sought by optimizing outputs of the ESS and generators, i.e., the upper boundary of the load shedding is the smallest. Finally, the states of wind turbines and generators are generated based on sequential Monte Carlo simulation, and the reliability of the hybrid energy generation system is evaluated by calculating the loss of load expectation, expected energy not supplied, and maximum power supply probability, which provides a basis for establishing interval optimal allocation model of energy storage. IEEE RTS-24 test system is utilized to verify the performance of the proposed method, and the model is solved by the CPLEX 12.7 solver. The simulation results demonstrate the effectiveness and applicability of the proposed method.
Assessing the Environmental Efficiency of Grain Production and Their Spatial Effects: Case Study of Major Grain Production Areas in China
Authors: Xu Hanxiao , Ma Bei , Gao Qiang
Published: November 2021

Environmental factors have a profound impact on the evaluation of grain production efficiency. Taking environmental factors into account can more accurately measure grain production efficiency and identify the development stage of grain production. Based on the global super-efficiency SBM model, environmental factors are included in the grain production efficiency measurement system, while the temporal and spatial evolution characteristics of grain production environmental efficiency and the sources of inefficiency are analyzed. In addition, the Spatial Durbin Model is used to investigate the influencing factors and spatial spillover effects of China’s grain production environmental efficiency. The results show that: environmental factors have a significant impact on the efficiency of grain production in China; the environmental efficiency of grain production in China fluctuates with a downward trend; the environmental efficiency of grain production in different provinces show obvious spatial differentiation and geographical agglomeration; the main influencing factors of the environmental efficiency loss of grain production in major grain production areas are carbon emissions, non-point source pollution of grain production and labor input; the level of education, the level of technological development, and labor transfer have a significant positive spillover effect on the environmental efficiency of China’s grain production, yet disaster rate has a significantly negative one. Thus, it is important to pay attention to resource conservation and pollution control, strengthen cooperation and exchanges between provinces, and take the path of coordinated development between the environment and grain production.
Synthetic Biology-Based Approaches for Microalgal Bio-Removal of Heavy Metals From Wastewater Effluents
Authors: Sattayawat Pachara , Yunus Ian S. , Noirungsee Nuttapol , Mukjang Nilita , Pathom-Aree Wasu , Pekkoh Jeeraporn , Pumas Chayakorn
Published: November 2021

Heavy metal polluted wastewater from industries is currently one of the major environmental concerns leading to insufficient supply of clean water. Several strategies have been implemented to overcome this challenge including the use of microalgae as heavy metal bio-removers. However, there are still limitations that prevent microalgae to function optimally. Synthetic biology is a new biological discipline developed to solve challenging problems via bioengineering approaches. To date, synthetic biology has no universally affirmed definitions; however, it is uncontroversial that synthetic biology utilizes a constructive library of genetic standardized parts to create new biological systems or to redesign existing ones with improved characteristics. In this mini-review, we present state-of-the-art synthetic biology-based approaches that can be used to enhance heavy metal bio-removal from wastewater effluents by microalgae with a narrative synthetic biology workflow (Design-Build-Test-Learn cycle) to guide future developments of more advanced systems. We also provide insights into potent genes and proteins responsible for the bio-removal processes for stepwise developments of more advanced systems. A total of 49 unique genes and proteins are listed based on their eight heavy metals (Mn, Fe, Cu, Zn, As, Cd, Hg, and Pb) bio-removal functions in transport system, cellular tolerance, synthesis of key players in heavy metal bio-removal, biotransformation of heavy metals, and gene expression regulation. Thus, with our library, genetic parts are ready to be recruited for any synthetic biology-based designs. Thereby, this mini-review identifies potential avenues of future research and maps opportunities to unleash more potential of microalgae as heavy metal bio-removers with synthetic biology.
Embryonic Development of Grasshopper Populations Along Latitudinal Gradients Reveal Differential Thermoaccumulation for Adaptation to Climate Warming
Authors: Hao Shuguang , Liu Chunxiang , Ma Chuan , Guo Wei , Kang Le
Published: November 2021

Climate warming has a remarkable effect on the distribution, phenology, and development of insects. Although the embryonic development and phenology of non-diapause grasshopper species are more susceptible to warming than those of diapause species, the responses of developmental traits in conspecifically different populations to climate warming remain unknown. Here, we compared the mtDNA sequences and embryonic development of eight populations of grasshopper species (Chorthippus dubius) in field-based manipulated warming and laboratory experiments. The mtDNA sequences showed a significant genetic differentiation of the southernmost population from the other seven populations on the Mongolian Plateau. The embryonic development of the southernmost population was significantly slower than those of the northern populations at the same incubation temperatures. Interestingly, laboratory experiments showed that a significant difference exists in the effective accumulated degree days (EADD) but not in the lower development threshold temperatures (LDTT) among the different populations. The high-latitude populations required less EADD than the low-latitude populations. The warming treatments significantly accelerated the embryonic development in the field and decreased duration from embryos to hatchlings of all eight populations in the incubation. In addition, warming treatments in field significantly increased EADD requirement per stage in the incubation. Linear regression model confirmed that the embryonic development characteristics of eight populations were correlated with the annual mean temperature and total precipitation of embryonic development duration. The results indicated that grasshopper species have evolved a strategy of adjusting their EADD but not their LDTT to adapt to temperature changes. The variations in the EADD among the different populations enabled the grasshopper eggs to buffer the influences of higher temperatures on development and preserve their univoltine nature in temperate regions while encountering warmer climatic conditions. Thus, the findings of this study is valuable for our understanding species variation and evolution, and as such has direct implication for modeling biological response to climate warming.
Structuring Interaction Networks Between Epiphytic Bryophytes and Their Hosts in Yunnan, SW China
Authors: Hu Hai-Xia , Shen Ting , Quan Dong-Li , Nakamura Akihiro , Song Liang
Published: November 2021

Ecological networks are commonly applied to depict general patterns of biotic interactions, which provide tools to understand the mechanism of community assembly. Commensal interactions between epiphytes and their hosts are a major component of species interactions in forest canopies; however, few studies have investigated species assemblage patterns and network structures of epiphyte–host interactions, particularly non-vascular epiphytes in different types of forest. To analyze the characteristics of network structures between epiphytes and their hosts, composition and distribution of epiphytic bryophytes were investigated from 138 host individuals using canopy cranes in a tropical lowland seasonal rain forest (TRF) and a subtropical montane moist evergreen broad-leaved forest (STF), in Southwest China. We structured binary networks between epiphytic bryophytes and their hosts in these two forests, which presented 329 interactions in the TRF and 545 interactions in the STF. Compared to TRF, the bryophyte–host plant networks were more nested but less modular in the STF. However, both forests generally exhibited a significantly nested structure with low levels of specialization and modularity. The relatively high nestedness may stabilize the ecological networks between epiphytic bryophytes and their hosts. Nevertheless, the low modularity in epiphyte–host networks could be attributed to the lack of co-evolutionary processes, and the low degree of specialization suggests that epiphytes are less likely to colonize specific host species. Vertical distribution of the bryophyte species showed structured modules in the tree basal and crown zones, probably attributing to the adaptation to microclimates within a host individual. This study highlights the nested structure of commensal interaction between epiphytic bryophytes and host trees, and provides a scientific basis to identify key host tree species for conservation and management of biodiversity in forest ecosystems.
The Construction of a Prognostic Model Based on a Peptidyl Prolyl Cis–Trans Isomerase Gene Signature in Hepatocellular Carcinoma
Authors: Shi Huadi , Zhong Fulan , Yi Xiaoqiong , Shi Zhenyi , Ou Feiyan , Zuo Yufang , Xu Zumin
Published: November 2021

Objective: The aim of the present study was to construct a prognostic model based on the peptidyl prolyl cis–trans isomerase gene signature and explore the prognostic value of this model in patients with hepatocellular carcinoma.

Methods: The transcriptome and clinical data of hepatocellular carcinoma patients were downloaded from The Cancer Genome Atlas and the International Cancer Genome Consortium database as the training set and validation set, respectively. Peptidyl prolyl cis–trans isomerase gene sets were obtained from the Molecular Signatures Database. The differential expression of peptidyl prolyl cis–trans isomerase genes was analyzed by R software. A prognostic model based on the peptidyl prolyl cis–trans isomerase signature was established by Cox, Lasso, and stepwise regression methods. Kaplan–Meier survival analysis was used to evaluate the prognostic value of the model and validate it with an independent external data. Finally, nomogram and calibration curves were developed in combination with clinical staging and risk score.

Results: Differential gene expression analysis of hepatocellular carcinoma and adjacent tissues showed that there were 16 upregulated genes. A prognostic model of hepatocellular carcinoma was constructed based on three gene signatures by Cox, Lasso, and stepwise regression analysis. The Kaplan–Meier curve showed that hepatocellular carcinoma patients in high-risk score group had a worse prognosis (p < 0.05). The receiver operating characteristic curve revealed that the area under curve values of predicting the survival rate at 1, 2, 3, 4, and 5 years were 0.725, 0.680, 0.644, 0.630, and 0.639, respectively. In addition, the evaluation results of the model by the validation set were basically consistent with those of the training set. A nomogram incorporating clinical stage and risk score was established, and the calibration curve matched well with the diagonal.

Conclusion: A prognostic model based on 3 peptidyl prolyl cis–trans isomerase gene signatures is expected to provide reference for prognostic risk stratification in patients with hepatocellular carcinoma.
A Web Tool for Consensus Gene Regulatory Network Construction
Authors: Sarkar Chiranjib , Parsad Rajender , Mishra Dwijesh C. , Rai Anil
Published: November 2021

Gene regulatory network (GRN) construction involves various steps of complex computational steps. This step-by-step procedure requires prior knowledge of programming languages such as R. Development of a web tool may reduce this complexity in the analysis steps which can be easy accessible for the user. In this study, a web tool for constructing consensus GRN by combining the outcomes obtained from four methods, namely, correlation, principal component regression, partial least square, and ridge regression, has been developed. We have designed the web tool with an interactive and user-friendly web page using the php programming language. We have used R script for the analysis steps which run in the background of the user interface. Users can upload gene expression data for constructing consensus GRN. The output obtained from analysis will be available in downloadable form in the result window of the web tool.
RAD52: Paradigm of Synthetic Lethality and New Developments
Authors: Rossi Matthew J. , DiDomenico Sarah F. , Patel Mikir , Mazin Alexander V.
Published: November 2021

DNA double-strand breaks and inter-strand cross-links are the most harmful types of DNA damage that cause genomic instability that lead to cancer development. The highest fidelity pathway for repairing damaged double-stranded DNA is termed Homologous recombination (HR). Rad52 is one of the key HR proteins in eukaryotes. Although it is critical for most DNA repair and recombination events in yeast, knockouts of mammalian RAD52 lack any discernable phenotypes. As a consequence, mammalian RAD52 has been long overlooked. That is changing now, as recent work has shown RAD52 to be critical for backup DNA repair pathways in HR-deficient cancer cells. Novel findings have shed light on RAD52’s biochemical activities. RAD52 promotes DNA pairing (D-loop formation), single-strand DNA and DNA:RNA annealing, and inverse strand exchange. These activities contribute to its multiple roles in DNA damage repair including HR, single-strand annealing, break-induced replication, and RNA-mediated repair of DNA. The contributions of RAD52 that are essential to the viability of HR-deficient cancer cells are currently under investigation. These new findings make RAD52 an attractive target for the development of anti-cancer therapies against BRCA-deficient cancers.
Prediction of Protein–Protein Interaction Sites Based on Stratified Attentional Mechanisms
Authors: Tang Minli , Wu Longxin , Yu Xinyu , Chu Zhaoqi , Jin Shuting , Liu Juan
Published: November 2021

Proteins are the basic substances that undertake human life activities, and they often perform their biological functions through interactions with other biological macromolecules, such as cell transmission and signal transduction. Predicting the interaction sites between proteins can deepen the understanding of the principle of protein interactions, but traditional experimental methods are time-consuming and labor-intensive. In this study, a new hierarchical attention network structure, named HANPPIS, by adding six effective features of protein sequence, position-specific scoring matrix (PSSM), secondary structure, pre-training vector, hydrophilic, and amino acid position, is proposed to predict protein–protein interaction (PPI) sites. The experiment proved that our model has obtained very effective results, which was better than the existing advanced calculation methods. More importantly, we used the double-layer attention mechanism to improve the interpretability of the model and to a certain extent solved the problem of the “black box” of deep neural networks, which can be used as a reference for location positioning on the biological level.
Analysis of Common Pathways and Markers From Non-Alcoholic Fatty Liver Disease to Immune-Mediated Diseases
Authors: Gallego-Durán Rocío , Montero-Vallejo Rocío , Maya-Miles Douglas , Lucena Ana , Martin Franz , Ampuero Javier , Romero-Gómez Manuel
Published: November 2021

Metabolic associated fatty liver disease (MAFLD) is the most prevalent form of liver disease worldwide, accounting for a high liver-related mortality and morbidity with extensive multi-organ involvement. This entity has displaced viral hepatitis as the main cause of severe forms of hepatic diseases, although the onset and transition of MAFLD stages still remains unclear. Nevertheless, innate and adaptive immune responses seem to play an essential role in the establishment and further progression of this disease. The immune system is responsible of safeguard and preserves organs and systems function, and might be altered under different stimuli. Thus, the liver suffers from metabolic and immune changes leading to different injuries and loss of function. It has been stablished that cell-cell crosstalk is a key process in the hepatic homeostasis maintenance. There is mounting evidence suggesting that MAFLD pathogenesis is determined by a complex interaction of environmental, genetic and host factors that leads to a full plethora of outcomes. Therefore, herein we will revisit and discuss the interplay between immune mechanisms and MAFLD, highlighting the potential role of immunological markers in an attempt to clarify its relationship.
Gain-of-Function Mutations R249C and S250C in Complement C2 Protein Increase C3 Deposition in the Presence of C-Reactive Protein
Authors: Urban Aleksandra , Kowalska Daria , Stasiłojć Grzegorz , Kuźniewska Alicja , Skrobińska Anna , Arjona Emilia , Alonso Eugenia Castellote , Fenollosa Segarra María Ángeles , Jongerius Ilse , Spaapen Robbert , Satchell Simon , Thiel Marcel , Ołdziej Stanisław , Rodriguez de Córdoba Santiago , Okrój Marcin
Published: November 2021

The impairment of the alternative complement pathway contributes to rare kidney diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). We recently described an aHUS patient carrying an exceptional gain-of-function (GoF) mutation (S250C) in the classical complement pathway component C2 leading to the formation of hyperactive classical convertases. We now report the identification of the same mutation and another C2 GoF mutation R249C in two other patients with a glomerulopathy of uncertain etiology. Both mutations stabilize the classical C3 convertases by a similar mechanism. The presence of R249C and S250C variants in serum increases complement-dependent cytotoxicity (CDC) in antibody-sensitized human cells and elevates deposition of C3 on ELISA plates coated with C-reactive protein (CRP), as well as on the surface of glomerular endothelial cells. Our data justify the inclusion of classical pathway genes in the genetic analysis of patients suspected of complement-driven renal disorders. Also, we point out CRP as a potential antibody-independent trigger capable of driving excessive complement activation in carriers of the GoF mutations in complement C2.
Dual Targeting by Inhibition of Phosphoinositide-3-Kinase and Mammalian Target of Rapamycin Attenuates the Neuroinflammatory Responses in Murine Hippocampal Cells and Seizures in C57BL/6 Mice
Authors: Vyas Preeti , Tulsawani Rajkumar , Vohora Divya
Published: November 2021

Emerging evidence suggests the association of seizures and inflammation; however, underlying cell signaling mechanisms are still not fully understood. Overactivation of phosphoinositide-3-kinases is associated with both neuroinflammation and seizures. Herein, we speculate the PI3K/Akt/mTOR pathway as a promising therapeutic target for neuroinflammation-mediated seizures and associated neurodegeneration. Firstly, we cultured HT22 cells for detection of the downstream cell signaling events activated in a lipopolysaccharide (LPS)-primed pilocarpine (PILO) model. We then evaluated the effects of 7-day treatment of buparlisib (PI3K inhibitor, 25 mg/kg p.o.), dactolisib (PI3K/mTOR inhibitor, 25 mg/kg p.o.), and rapamycin (mTORC1 inhibitor, 10 mg/kg p.o.) in an LPS-primed PILO model of seizures in C57BL/6 mice. LPS priming resulted in enhanced seizure severity and reduced latency. Buparlisib and dactolisib, but not rapamycin, prolonged latency to seizures and reduced neuronal loss, while all drugs attenuated seizure severity. Buparlisib and dactolisib further reduced cellular redox, mitochondrial membrane potential, cleaved caspase-3 and p53, nuclear integrity, and attenuated NF-κB, IL-1β, IL-6, TNF-α, and TGF-β1 and TGF-β2 signaling both in vitro and in vivo post-PILO and LPS+PILO inductions; however, rapamycin mitigated the same only in the PILO model. Both drugs protected against neuronal cell death demonstrating the contribution of this pathway in the seizure-induced neuronal pyknosis; however, rapamycin showed resistance in a combination model. Furthermore, LPS and PILO exposure enhanced pAkt/Akt and phospho-p70S6/total-p70S6 kinase activity, while buparlisib and dactolisib, but not rapamycin, could reduce it in a combination model. Partial rapamycin resistance was observed possibly due to the reactivation of the pathway by a functionally different complex of mTOR, i.e., mTORC2. Our study substantiated the plausible involvement of PI3K-mediated apoptotic and inflammatory pathways in LPS-primed PILO-induced seizures and provides evidence that its modulation constitutes an anti-inflammatory mechanism by which seizure inhibitory effects are observed. We showed dual inhibition by dactolisib as a promising approach. Targeting this pathway at two nodes at a time may provide new avenues for antiseizure therapies.