bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational Design of a Gd(III)–Cu(II) Nanobooster for Chemodynamic Therapy Against Cancer Cells
Authors: Shi Xin-Ya , Shen Ting-Xiao , Zhang Ao-Lin , Tan Li-Tao , Shen Wen-Chang , Zhong Hai-Jiang , Zhang Shun-Lin , Gu Yu-Lan , Shen Lei
Published: April 2022

Copper (II) containing coordination complexes have attracted much attention for chemodynamic therapy (CDT) against cancer cells. In this study, the bimetallic nanobooster [Gd2Cu(L)2(H2O)10]·6H2O was prepared by a solvothermal method based on tetrazole carboxylic acid ligand H4L [H4L = 3,3-di (1H-tetrazol-5-yl) pentanedioic acid]. It showed considerable cytotoxicity toward three kinds of human cancer cells (HeLa, HepG2, and HT29). The MTT assay showed that the IC50 (half-maximal inhibitory concentration) of the complex NPs on HeLa cells (4.9 μg/ml) is superior to that of HepG2 (11.1 μg/ml) and HT29 (5.5 μg/ml). This result showed that [Gd2Cu(L)2(H2O)10]·6H2O NPs can inhibit cell proliferation in vitro and may be potential candidates for chemodynamic therapy. In addition, the cytotoxicity was also confirmed by the trypan blue staining experiment. The results promise the great potential of Gd(III)–Cu(II) for CDT against cancer cells.
Hydroisomerization of n-Hexadecane Over Nickel-Modified SAPO-11 Molecular Sieve-Supported NiWS Catalysts: Effects of Modification Methods
Authors: Dai Xiaojun , Cheng Yan , Si Meng , Wei Qiang , Zhou Yasong
Published: April 2022

The complexation-excessive impregnation modification method, which was original in this study, and the ion-exchange method and the in situ modification method were used to synthesize Ni-modified SAPO-11 molecular sieves. With the Ni-modified SAPO-11 samples as support, the corresponding NiWS-supported catalysts for the hydroisomerization of n-hexadecane were prepared. The effects of Ni-modification on SAPO-11 characteristics and the active phase were studied. The structure, morphology, and acidity of SAPO-11, as well as the interaction between active metals and support, the morphology, dispersibility, and stacking number of the active phase, were all changed by Ni-modification methods. The complexation-excessive impregnation modification method deleted a portion of Al from SAPO-11 molecular sieves while simultaneously integrating Ni into the skeletal structure of the surface layer of SAPO-11 molecular sieves, considerably enhancing the acidity of SAPO-11 molecular sieves. Furthermore, during dealumination, ethylenediaminetetraacetic acid generated more mesoporous structures and increased the mesoporous volume of SAPO-11 molecular sieves. Because the complexation-excessive impregnation modification method increased the amount of Ni in the surface framework of the SAPO-11 molecular sieve, it has weakened the interaction between the active phase and the support, improved the properties of the active phase, and greatly improved the hydroisomerization performance of NiW/NiSAPO-11. The yield of i-hexadecane of NiW/NiSAPO-11 increased by 39.3% when compared to NiW/NiSAPO-11. It presented a realistic approach for increasing the acidity of SAPO-11, reducing the interaction between active metals and support, and improving the active phase stacking problem.
Junin Virus Activates p38 MAPK and HSP27 Upon Entry
Authors: Fitzpatrick Collin J. , Mudhasani Rajini R. , Altamura Louis A. , Campbell Catherine E. , Tran Julie P. , Beitzel Brett F. , Narayanan Aarthi , de la Fuente Cynthia L. , Kehn-Hall Kylene , Smith Jeffrey M. , Schmaljohn Connie S. , Garrison Aura R.
Published: April 2022

Junín virus (JUNV), a New World arenavirus, is a rodent-borne virus and the causative agent of Argentine hemorrhagic fever. Humans become infected through exposure to rodent host secreta and excreta and the resulting infection can lead to an acute inflammatory disease with significant morbidity and mortality. Little is understood about the molecular pathogenesis of arenavirus hemorrhagic fever infections. We utilized Reverse Phase Protein Microarrays (RPPA) to compare global alterations in the host proteome following infection with an attenuated vaccine strain, Candid#1 (CD1), and the most parental virulent strain, XJ13, of JUNV in a human cell culture line. Human small airway epithelial cells were infected with CD1 or XJ13 at an MOI of 10, or mock infected. To determine proteomic changes at early timepoints (T = 1, 3, 8 and 24 h), the JUNV infected or mock infected cells were lysed in compatible buffers for RPPA. Out of 113 proteins that were examined by RPPA, 14 proteins were significantly altered following JUNV infection. Several proteins were commonly phosphorylated between the two strains and these correspond to entry and early replication events, to include p38 mitogen-activated protein kinase (MAPK), heat shock protein 27 (HSP27), and nuclear factor kappa B (NFκB). We qualitatively confirmed the alterations of these three proteins following infection by western blot analysis. We also determined that the inhibition of either p38 MAPK, with the small molecule inhibitor SB 203580 or siRNA knockdown, or HSP27, by siRNA knockdown, significantly decreases JUNV replication. Our data suggests that HSP27 phosphorylation at S82 upon virus infection is dependent on p38 MAPK activity. This work sheds light on the nuances of arenavirus replication.
Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
Authors: O’Flaherty Katherine , Chan Jo-Anne , Cutts Julia C. , Zaloumis Sophie G. , Ashley Elizabeth A. , Phyo Aung Pyae , Drew Damien R. , Dondorp Arjen M. , Day Nicholas P. , Dhorda Mehul , Fairhurst Rick M. , Lim Pharath , Amaratunga Chanaki , Pukrittayakamee Sasithon , Hien Tran Tinh , Htut Ye , Mayxay Mayfong , Faiz M. Abul , Mokuolu Olugbenga A. , Onyamboko Marie A. , Fanello Caterina , Takashima Eizo , Tsuboi Takafumi , Theisen Michael , Nosten Francois , Beeson James G. , Simpson Julie A. , White Nicholas J. , Fowkes Freya J. I.
Published: April 2022

Introduction

Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates.

Methods

In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment.

Results

Microscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071).

Conclusion

Pfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum.
The Comparison of Inflammatory Cytokines (IL-6 and IL-18) and Immune Cells in Japanese Encephalitis Patients With Different Progression
Authors: Zhou Yun , Bian Peiyu , Du Hong , Wang Tao , Li Mengyuan , Hu Haifeng , Ye Chuantao , Zheng Xuyang , Zhang Ying , Lei Yinfeng , Jia Zhansheng , Lian Jianqi
Published: April 2022

Background

Japanese encephalitis virus (JEV) is the main cause of viral encephalitis in Asia. Nowadays, no effective and specific therapy for JE patients is available except supportive treatment. The fatality rate of JE patients is still about 30%, and more than half of survivors suffered from various neuropsychiatric sequelae. Thus, more attention should be paid to JE.

Methods

In this study, a retrospective cohort of JE patients was collected and the general features of JE patients admitted into the Department of Infectious Diseases were analyzed. Meanwhile, the dynamic change of plasma cytokines and immune cells in JE patients with divergent prognosis was detected and analyzed.

Results

We found a mounted proportion of adult/old patients in JE cases. The level of IL-6 and IL-18 increased in JE patients especially in fatal individuals. There was a continuous decreased percentage of CD4+ T and B cells in severe JE patients with fatal outcome compared with the surviving JE patients.

Conclusions

The consistent high level of IL-6 and IL-18 in the plasma and low proportion of CD4+ T and B cells in the PBMCs might be the indicators of poor prognosis.
Uniform Polylogarithmic Space Completeness
Authors: Ferrarotti Flavio , González Senén , Schewe Klaus-Dieter , Turull-Torres José María
Published: April 2022

It is well-known that polylogarithmic space (PolyL for short) does not have complete problems under logarithmic space many-one reductions. Thus, we propose an alternative notion of completeness inspired by the concept of uniformity studied in circuit complexity theory. We then prove the existence of a uniformly complete problem for PolyL under this new notion. Moreover, we provide evidence that uniformly complete problems can help us to understand the still unclear relationship between complexity classes such as PolyL and polynomial time.
The Potential of Metabolism-Related Gene OGDHL as a Biomarker for Myocardial Remodeling in Dilated Cardiomyopathy
Authors: Tang Yaohan , Zhu Yaoxi , Lu Yang , Yang Hongmin , Yang Han , Li Lixia , Liu Changhu , Du Yimei , Yuan Jing
Published: April 2022

The development of dilated cardiomyopathy (DCM) is accompanied by a series of metabolic disorders, resulting in myocardial remodeling or exacerbation, while the mechanism remains not completely clear. This study was to find out the key metabolism-related genes involved in the onset of DCM, providing new insight into the pathogenesis of this disease. The datasets of GSE57338, GSE116250, and GSE5406 associated with hearts of patients with DCM were downloaded from the Gene Expression Omnibus database. GSE57338 was analyzed to screen out metabolism-related differentially expressed genes (DEGs), while GSE116250 and GSE5406 were utilized to verify the optimal genes through R software. Support vector machine recursive feature elimination algorithm and least absolute shrinkage and selection operator algorithm were used to determine key genes. Finally, 6 of 39 metabolism-related DEGs were screened out and identified as the optimal genes. After quantitative reverse-transcription polymerase chain reaction (qRT-PCR) validation performed on the samples drawn from the left ventricles of human hearts, it showed that only the expression of oxoglutarate dehydrogenase-like (OGDHL) increased while PLA2G2 decreased significantly in patients with DCM compared with non-failing donors, respectively. Furthermore, the higher OGDHL protein expression, except the change of PLA2G2, was also found in DCM hearts, and its mRNA expression was negatively correlated with myocardial Masson’s scores (r = –0.84, P = 0.009) and left ventricular end-diastolic diameter (LVEDd; r = –0.82, P = 0.014), which might be regulated by miR-3925-5p through further bioinformatics prediction and qRT-PCR verification. The data then suggested that the metabolism-related gene OGDHL was associated with myocardial fibrosis of DCM and probably a biomarker for myocardial remodeling in patients with DCM.
Mendelian Randomization Study of Heart Failure and Stroke Subtypes
Authors: Li Quan , Yan Shijiao , Li Yan , Kang Hai , Zhu Huadong , Lv Chuanzhu
Published: April 2022

Background

Whether heart failure (HF) is an independent risk factor of ischemic stroke (IS) and hemorrhagic stroke remains controversial. We employed a multivariable Mendelian randomization (MR) to further investigate the causal effects of HF on the risk of stroke and stroke subtypes.

Methods

Genetically predicted HF was selected as an instrumental variable (IV) from published genome-wide association studies (GWAS) meta-analyses. Stroke data with different etiologies were extracted as outcome variables from another two GWAS meta-analyses. The random-effects inverse variance-weighted (IVW) model was applied as the main method, along with sensitivity analysis. Atrial fibrillation (AF), coronary heart disease (CHD), and systolic blood pressure (SBP) were controlled for mediating effects in multivariable MR.

Results

Genetically predicted HF was significantly associated with any IS [odds ratio (OR), 1.39; 95% CI, 1.12–1.74; p = 0.03], large artery stroke (LAS; OR, 1.84; 95% CI, 1.27–2.65; p = 0.001), and cardioembolic stroke (CES; OR, 1.73; 95% CI, 1.21–2.47; p = 0.003), but without small vessel stroke (SVS; OR, 1.1; 95% CI, 0.80–1.52; p = 0.56) and intracerebral hemorrhage (ICH; OR, 0.86; 95% CI, 0.41–1.83; p = 0.699) in univariable MR. However, these significant associations were attenuated to the null after adjusting for confounding factor in multivariable MR.

Conclusion

There was no direct causal association between HF and stroke in our study. The association between HF and IS can be driven by AF, CHD, and SBP.
The Additive Value of Cardiovascular Magnetic Resonance in Convalescent COVID-19 Patients
Authors: Borlotti Alessandra , Thomaides-Brears Helena , Georgiopoulos Georgios , Banerjee Rajarshi , Robson Matthew D. , Fusco Dahlene N. , Masci Pier-Giorgio
Published: April 2022

In COVID-19 the development of severe viral pneumonia that is coupled with systemic inflammatory response triggers multi-organ failure and is of major concern. Cardiac involvement occurs in nearly 60% of patients with pre-existing cardiovascular conditions and heralds worse clinical outcome. Diagnoses carried out in the acute phase of COVID-19 rely upon increased levels of circulating cardiac injury biomarkers and transthoracic echocardiography. These diagnostics, however, were unable to pinpoint the mechanisms of cardiac injury in COVID-19 patients. Identifying the main features of cardiac injury remains an urgent yet unmet need in cardiology, given the potential clinical consequences. Cardiovascular magnetic resonance (CMR) provides an unparalleled opportunity to gain a deeper insight into myocardial injury given its unique ability to interrogate the properties of myocardial tissue. This endeavor is particularly important in convalescent COVID-19 patients as many continue to experience chest pain, palpitations, dyspnea and exertional fatigue, six or more months after the acute illness. This review will provide a critical appraisal of research on cardiovascular damage in convalescent adult COVID-19 patients with an emphasis on the use of CMR and its value to our understanding of organ damage.
Evolution, Recent Progress and Perspectives of the Seismic Monitoring of Building Structures in Romania
Authors: Tiganescu Alexandru , Craifaleanu Iolanda-Gabriela , Aldea Alexandru , Grecu Bogdan , Vacareanu Radu , Toma-Danila Dragos , Balan Stefan-Florin , Dragomir Claudiu-Sorin
Published: April 2022

The seismic instrumentation of structures in order to assess their condition and to track it over long periods or after representative events has proven to be a topic of large interest, under continuous development at international level. The seismic hazard of Romania poses one of the most dangerous threats for the country, in terms of potential physical and socio-economic losses. In recent years, taking advantage of the new scientific and technological advances, among which the exponential growth in computational resources, significant improvements have been made in extending the seismic networks for structural monitoring and using the data as input for products and services addressed not only to the research community but also to stakeholders. The paper covers focused aspects of the topic for Romania, referring to past developments of the most important institutions and seismic networks in the country and the current status, including the research and regulatory gaps. Currently, three main research and academic institutions perform structural health monitoring of twenty-two buildings in Romania. As the number of monitored buildings grows and new actors in the private sector start to get involved in the process, the need for data standardization and a regulatory framework increases. Ongoing national and international projects (PREVENT, SETTING, TURNkey) address these issues and outline the roadmap for future actions of the main institutions responsible for seismic risk reduction, including authorities, research and academia.
Sea Surface Height Changes due to the Tropical Cyclone-Induced Water Mixing in the Yellow Sea, Korea
Authors: Kang KiRyong , Moon Il-Ju
Published: April 2022

Sea surface height changes due to the tropical cyclone (TC)-induced water mixing in the Yellow Sea, Korea, were investigated using temperature and salinity profile data obtained by two Argo floats during the summer and fall of 2018 and 2020. Strong winds and low pressure, which are important characteristics of TCs, caused horizontal and vertical sea surface water movement and induced water mixing. This caused an increase in mixed layer depth, a decrease in water density, and an increase in specific volume. Specific volume changes related to the water steric effect were directly linked to sea surface height changes. During the TC Soulik (1819) period, the thermocline deepened by more than 10 m, and the steric sea level was increased by more than 3 cm. Other TC cases, such as Jebi (1821), Trami (1824), and Kong-Rey (1825), showed sea level increases of 1–2 cm. In 2020, 3 TCs–Bavi (2008), Maysak (2009), and Haishen (2010)—showed minor sea level increases (about 0.5–1 cm) because of weak mixing due to their high moving speeds or weak impacts. As a post-TC impact, the water mixing could cause a rise in sea levels due to the steric effect of seawater.
Evaluation of the Effect on Sexual Performance of a Nutraceutical Combination Containing Alpha Lipoic Acid, Vitis vinifera L. and Ginkgo biloba, Compared to Placebo, Avanafil or a Combination of Nutraceutical Plus Avanafil in Males With Type 2 Diabetes Mellitus With Erectile Dysfunction
Authors: Derosa Giuseppe , D’Angelo Angela , Preti Paola Stefania , Maffioli Pamela
Published: April 2022

Aim

To evaluate if therapy with a nutraceutical combination of alpha lipoic acid, Vitis vinifera L. and Ginkgo biloba (Blunorm forte®) can be helpful and be synergic with Avanafil.

Methods

The trial included 123 males with type 2 diabetic mellitus and with erectile dysfunction (ED), aged ≥18 years. Patients were divided in four different arms: 1st arm: placebo during the three months of treatment and before sexual act; 2nd arm: placebo for three months and Avanafil: 1 tablet, 200 mg, 15-30 minutes before sexual act; 3rd arm: Blunorm forte: 1 tablet, 40 minutes before the meal (breakfast) during the three months and Avanafil: 1 tablet, 200 mg, 15-30 minutes before sexual act; 4th arm: Blunorm forte: 1 tablet, 40 minutes before the meal (breakfast and dinner) during the three months and placebo 15-30 minutes before sexual act.

Results

A significant reduction of fasting plasma glucose, and homeostasis model assessment-insulin resistance index were recorded both in Avanafil + Blunorm forte and with Blunorm forte. Metalloproteinases-2, and -9 were reduced in the Avanafil + Blunorm forte group. High sensitivity-C-reactive protein was decreased by both Avanafil, and Avanafil + Blunorm forte group. No variations were recorded with the other treatments.

The group treated with Blunorm forte and Avanafil reached a higher International Index of Erectile Function (IIEF) score after 3 months of therapy compared to baseline and placebo and compared to Avanafil and Blunorm forte taken alone.

Conclusion

Blunorm forte® can be helpful and synergic with Avanafil in increasing sexual performance compared to placebo.
Expressions of Serum lncRNAs in Diabetic Retinopathy – A Potential Diagnostic Tool
Authors: Biswas Saumik , Coyle Ali , Chen Shali , Gostimir Miso , Gonder John , Chakrabarti Subrata
Published: April 2022

With increasing incidence of diabetes worldwide, there is an ever-expanding number of patients with chronic diabetic complications such as diabetic retinopathy (DR), one of the leading causes of blindness in the working age population. Early screening for the onset and severity of DR is essential for timely intervention. With recent advancements in genomic technologies, epigenetic alterations in DR are beginning to unravel. Long non-coding RNAs (lncRNAs), which are key epigenetic mediators, have demonstrated implications in several (DR) related processes. Based on the previous research, we have developed a serum-based, multi-panel PCR test using 9 lncRNAs (ANRIL, MALAT1, WISPER, ZFAS1, H19, HOTAIR, HULC, MEG3, and MIAT) to identify and validate whether this panel could be used as a diagnostic and prognostic tool for DR. We initially used a cell culture model (human retinal endothelial cells) and confirmed that 25 mM glucose induces upregulations of ANRIL, HOTAIR, HULC, MALAT1, and ZFAS1, and downregulation of H19 compared to 5 mM glucose controls. Then as an initial proof-of-concept, we tested vitreous humor and serum samples from a small cohort of non-diabetic (N=10) and diabetic patients with proliferative retinopathy (PDR, N=11) and measured the levels of the 9 lncRNAs. Differential expressions of lncRNAs were found in the vitreous and serum of patients and showed significant correlations. We expanded our approach and assessed the same lncRNAs using samples from a larger cohort of diabetic (n= 59; M/F:44/15) and non-diabetic patients (n= 11; M/F:4/7). Significant increased lncRNA expressions of ANRIL, H19, HOTAIR, HULC, MIAT, WISPER and ZFAS1 were observed in the serum of diabetic patients (with varying stages of DR) compared to non-diabetics. No significant correlations were demonstrated between lncRNA expressions and creatinine or glycated hemoglobin (HbA1C) levels. Using ROC and further analyses, we identified distinct lncRNA phenotype combinations, which may be used to identify patients with DR. Data from this study indicate that a panel of serum lncRNAs may be used for a potential screening test for DR. Further large-scale studies are needed to validate this notion.
Dynamic Modeling and Flexibility Analysis of an Integrated Electrical and Thermal Energy System With the Heat Pump–Thermal Storage
Authors: Hao Junhong , Gou Xing , Wang Shunjiang , Chen Qun , Gao Kai
Published: April 2022

The integration of high-efficiency heat pump and thermal storage devices is of great significance to realize the synergy between efficient and flexible operation of the integrated electric and thermal energy systems. This article proposed an integrated electric–thermal energy system with heat pump and thermal storage devices and introduced the heat current method for constructing its overall dynamic power flow model by considering energy transfer, conversion, and storage processes. On this basis, we derived the overall system constraint and component constraint equations. Under the objective of wind power curtailment minimization, the comprehensive effects of the dynamic characteristics of the heat pump, thermal storage capacity, new wind power installation, and new heat load on the electric and thermal output are analyzed. The results show that the dispatching accuracy of wind power output can be improved by up to 8% by taking into account the dynamic characteristics of the heat pump. The combination of heat pump and thermal storage device results in a leverage factor of 3.06 and 0.17 for the storage and release processes, respectively, effectively increasing the flexibility of system scheduling. The coordination between the newly added wind power installation and the added new heat load, with the higher operating temperature of the heat pump, is more conducive to promote wind power accommodation and improve the system’s overall flexibility. These results provide the necessary basis for the development of an integrated dispatch plan for the integrated electric and thermal energy systems containing the heat pump–thermal storage.
New Insight Into Visual Adaptation in the Mudskipper Cornea: From Morphology to the Cornea-Related COL8A2 Gene
Authors: Hu Wenxian , Mu Yuan , Lin Feng , Li Xu , Zhang Jie
Published: April 2022

Much research has focused on visual system evolution in bony fishes. The capacity of visual systems to perceive and respond to external signals is integral to evolutionary success. However, integrated research on the mechanisms of adaptive evolution based on corneal structure and related genes remains limited. In this study, scanning electron microscopy (SEM) was used to assess the microstructure and adaptation of corneal epithelial cells. Then, the evolution of the cornea-related COL8A2 gene was investigated. We found various projections (microridges, microplicae, microholes, and microvilli) on the corneal epithelial cells of amphibious mudskippers. Compared with those of fully aquatic fishes, these microstructures were considered adaptations to the variable environments experienced by amphibious mudskippers, as they can resist dryness in terrestrial environments and infection in aquatic environments. Moreover, strong purifying selection was detected for COL8A2. In addition, some specific amino acid substitution sites were also identified in the COL8A2 sequence in mudskippers. Interestingly, the evolutionary rate of the COL8A2 gene was significantly and positively correlated with maximum diving depth in our dataset. Specifically, with increasing diving depth, the evolutionary rate of the COL8A2 gene seemed to gradually accelerate. The results indicated that the cornea of bony fishes has evolved through adaptation to cope with the different diving depths encountered during the evolutionary process, with the corneal evolution of the amphibious mudskipper group showing a unique pattern.
Integrative Analysis of Long- and Short-Read Transcriptomes Identify the Regulation of Terpenoids Biosynthesis Under Shading Cultivation in Oenanthe javanica
Authors: Feng Kai , Kan Xia-Yue , Li Rui , Yan Ya-Jie , Zhao Shu-Ping , Wu Peng , Li Liang-Jun
Published: April 2022

Water dropwort (Oenanthe javanica) is a popular vegetable with high nutritional value and distinctive flavor. The flavor is mainly correlate with the biosynthesis of terpenoids. Shading cultivation was used to improve the flavor in the production of water dropwort. However, the changes of terpenoids and the genes involved in terpenoids biosynthesis under shading treatment remains unclear. In this study, the long- and short-reads transcriptomes of water dropwort were constructed. In total, 57,743 non-redundant high-quality transcripts were obtained from the transcriptome. 28,514 SSRs were identified from non-redundant transcripts and the mono-nucleotide repeats were the most abundant SSRs. The lncRNAs of water dropwort were recognized and their target genes were predicted. The volatile compound contents in petioles and leaf blades of water dropwort were decreased after the shading treatment. The DEGs analysis was performed to identify the terpenoids biosynthesis genes. The results indicated that 5,288 DEGs were differentially expressed in petiole, of which 22 DEGs were enriched in the terpenoids backbone biosynthesis pathway. A total of 12 DEGs in terpenoids biosynthesis pathway were selected and further verified by qRT-PCR assay, demonstrating that the terpenoids biosynthesis genes were down-regulated under shading treatment. Here, the full-length transcriptome was constructed and the regulatory genes related to terpenoids biosynthesis in water dropwort were also investigated. These results will provide useful information for future researches on functional genomics and terpenoids biosynthesis mechanism in water dropwort.
Desire for Birth Companionship Among Pregnant Women Attending Antenatal Care in Debremarkos City, Northwest Ethiopia: Magnitude and Associated Factors
Authors: Assfaw Hussien Mohammed , Abuhay Mulunesh , Asratie Melaku Hunie
Published: April 2022

Background

Birth companionship is one of the components of the respectful maternity continuum of care recommended by the World Health Organization (WHO). Women's desire for birth companionship needs to be given attention during the antenatal care period to make them ready during labor and delivery. There is a dearth of study about the status of women's desire for birth companionship and associated factors.

Objective

This study aimed to assess the prevalence of desire for birth companionship and associated factors among pregnant women in Debremarkos city, northwest Ethiopia.

Methods

Institution-based cross-sectional study was conducted from February 1, 2021 to March 30, 2021 in Debremarkos city, northwest Ethiopia. A total of 423 participants were accessed by systematic random sampling. A face-to-face interviewer-administered questionnaire was employed. The data were entered into Epi data version 4.6 and transformed to SPSS version 25. Binary logistic regression analysis was done, and variables with a p-value ≤ 0.2 on bivariable analysis were taken for multivariable analysis. Adjusted odds ratio with a 95% confidence interval was used to detect the association, and a p-value of <0.05 in the multivariable analysis was used to declare statistical significance.

Results

The prevalence of desire for birth companionship was 57.45% (52.6–62.2%). Women who were the primary decision-maker for maternal health care services [adjusted odds ratio (AOR) =3.0; 95% CI 1.7–5.6], women with planned pregnancy (AOR = 2.0; 95% CI 1.0–3.9), women who have no bad obstetric history (AOR = 2.3; 95% CI 1.2–4.4), and women whose 1st antenatal care visit starts within the second trimester (AOR = 2.6; 1.6–4.4) were statistically significant with desire on birth companionship.

Conclusions

Desire of pregnant women for birth companionship was high in this study. Improving women's decision-making power, emphasis on the type of pregnancy, obstetrical history, and early initiation of antenatal care visit were the suggested areas to increase the desire of women for birth companionship.
Sialylation as an Important Regulator of Antibody Function
Authors: Vattepu Ravi , Sneed Sunny Lyn , Anthony Robert M.
Published: April 2022

Antibodies play a critical role in linking the adaptive immune response to the innate immune system. In humans, antibodies are categorized into five classes, IgG, IgM, IgA, IgE, and IgD, based on constant region sequence, structure, and tropism. In serum, IgG is the most abundant antibody, comprising 75% of antibodies in circulation, followed by IgA at 15%, IgM at 10%, and IgD and IgE are the least abundant. All human antibody classes are post-translationally modified by sugars. The resulting glycans take on many divergent structures and can be attached in an N-linked or O-linked manner, and are distinct by antibody class, and by position on each antibody. Many of these glycan structures on antibodies are capped by sialic acid. It is well established that the composition of the N-linked glycans on IgG exert a profound influence on its effector functions. However, recent studies have described the influence of glycans, particularly sialic acid for other antibody classes. Here, we discuss the role of glycosylation, with a focus on terminal sialylation, in the biology and function across all antibody classes. Sialylation has been shown to influence not only IgG, but IgE, IgM, and IgA biology, making it an important and unappreciated regulator of antibody function.
Non-Invasive Measurement Using Deep Learning Algorithm Based on Multi-Source Features Fusion to Predict PD-L1 Expression and Survival in NSCLC
Authors: Wang Chengdi , Ma Jiechao , Shao Jun , Zhang Shu , Li Jingwei , Yan Junpeng , Zhao Zhehao , Bai Congchen , Yu Yizhou , Li Weimin
Published: April 2022

Background

Programmed death-ligand 1 (PD-L1) assessment of lung cancer in immunohistochemical assays was only approved diagnostic biomarker for immunotherapy. But the tumor proportion score (TPS) of PD-L1 was challenging owing to invasive sampling and intertumoral heterogeneity. There was a strong demand for the development of an artificial intelligence (AI) system to measure PD-L1 expression signature (ES) non-invasively.

Methods

We developed an AI system using deep learning (DL), radiomics and combination models based on computed tomography (CT) images of 1,135 non-small cell lung cancer (NSCLC) patients with PD-L1 status. The deep learning feature was obtained through a 3D ResNet as the feature map extractor and the specialized classifier was constructed for the prediction and evaluation tasks. Then, a Cox proportional-hazards model combined with clinical factors and PD-L1 ES was utilized to evaluate prognosis in survival cohort.

Results

The combination model achieved a robust high-performance with area under the receiver operating characteristic curves (AUCs) of 0.950 (95% CI, 0.938–0.960), 0.934 (95% CI, 0.906–0.964), and 0.946 (95% CI, 0.933–0.958), for predicting PD-L1ES <1%, 1–49%, and ≥50% in validation cohort, respectively. Additionally, when combination model was trained on multi-source features the performance of overall survival evaluation (C-index: 0.89) could be superior compared to these of the clinical model alone (C-index: 0.86).

Conclusion

A non-invasive measurement using deep learning was proposed to access PD-L1 expression and survival outcomes of NSCLC. This study also indicated that deep learning model combined with clinical characteristics improved prediction capabilities, which would assist physicians in making rapid decision on clinical treatment options.
Neuro-Inflammatory Response and Brain-Peripheral Crosstalk in Sepsis and Stroke
Authors: Bourhy Lena , Mazeraud Aurélien , Bozza Fernando A. , Turc Guillaume , Lledo Pierre-Marie , Sharshar Tarek
Published: April 2022

Despite recent therapeutic advances, ischemic stroke is still a leading cause of death and disability. There is renewed attention on peripheral inflammatory signaling as a way of modulating the post-ischemic neuro-inflammatory process. The immune-brain crosstalk has long been the focus for understanding the mechanisms of sickness behavior, which is an adaptive autonomic, neuroendocrine, and behavioral response to a peripheral inflammation. It is mediated by humoral and neural pathways that mainly involve the circumventricular organs and vagal nerve, respectively. In this review we address the question of how sepsis and stroke can dysregulate this adaptive response, notably by impairing the central integration of peripheral signaling, but also by efferent control of the immune response. We highlight the potential role of gut–brain and brain–spleen signaling in stroke.
Deconvolution of Adult T-Cell Leukemia/Lymphoma With Single-Cell RNA-Seq Using Frozen Archived Skin Tissue Reveals New Subset of Cancer-Associated Fibroblast
Authors: Joo Eun-Hye , Bae Jai Hee , Park Jihye , Bang Yoon Ji , Han Joseph , Gulati Nicholas , Kim Jong-Il , Park Chung-Gyu , Park Woong-Yang , Kim Hyun Je
Published: April 2022

Adult T-cell Leukemia/Lymphoma (ATLL) is a rare aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection. However, little is known about the underlying activated molecular pathways at the single cell level. Moreover, the intercellular communications between the tumor microenvironment (TME) and tumor cells in this malignancy are currently unknown. Difficulties in harvesting fresh tissue in a clinical setting have hampered our deeper understanding of this malignancy. Herein, we examined ATLL using archived fresh frozen tissue after biopsy using single-cell RNA sequencing (scRNA-seq) with T-cell receptor (TCR) clonal analysis. Highly clonal tumor cells showed multiple activating pathways, suggesting dynamic evolution of the malignancy. By dissecting diverse cell types comprising the TME, we identified a novel subset of cancer-associated fibroblast, which showed enriched epidermal growth factor receptor (EGFR)-related transcripts including early growth response 1 and 2 (EGR1 and EGR2). Cancer associated fibroblasts (CAFs) of ATLL play an important role for CD4 T-cell proliferation via FGF7-FGF1 and PDGFA-PDGFRA/B signaling, and CAFs, particularly EGR-enriched, are also associated with CD8 and NKT expansion by EGFR. These findings suggest a potential targeted therapeutic pathway to better treat this neoplasm.
The Long Non-Coding RNA Nostrill Regulates Transcription of Irf7 Through Interaction With NF-κB p65 to Enhance Intestinal Epithelial Defense Against Cryptosporidium parvum
Authors: Mathy Nicholas W. , Deng Silu , Gong Ai-Yu , Li Min , Wang Yang , Burleigh Olivia , Kochvar Andrew , Whiteford Erin R. , Shibata Annemarie , Chen Xian-Ming
Published: April 2022

The cells of the intestinal epithelium establish the frontline for host defense against pathogens in the gastrointestinal tract and play a vital role in the initiation of the immune response. Increasing evidence supports the role of long non-coding RNAs (lncRNAs) as critical regulators of diverse cellular processes, however, their role in antimicrobial host defense is incompletely understood. In this study, we provide evidence that the lncRNA Nostrill is upregulated in the intestinal epithelium following infection byCryptosporidium parvum, a globally prevalent apicomplexan parasite that causes significant diarrheal disease and an important opportunistic pathogen in the immunocompromised and AIDS patients. Induction of Nostrill in infected intestinal epithelial cells was triggered by NF-κB signaling and was observed to enhance epithelial defense by decreasing parasitic infection burden. Nostrill participates in the transcriptional regulation ofC. parvum-induced Irf7 expression through interactions with NF-κB p65, and induction of Nostrill promotes epigenetic histone modifications and occupancy of RNA polymerase II at theIrf7promoter. Our data suggest that the induction of Nostrill promotes antiparasitic defense againstC. parvumand enhances intestinal epithelial antimicrobial defense through contributions to transcriptional regulation of immune-related genes, such asIrf7.
D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K/Akt/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver Disease
Authors: Hu Mengyao , Chen Yu , Deng Fan , Chang Bo , Luo Jialiang , Dong Lijun , Lu Xiao , Zhang Yi , Chen Zhengliang , Zhou Jia
Published: April 2022

This study investigated the protective properties and mechanisms of D-mannose against hepatic steatosis in experimental alcoholic liver disease (ALD). Drinking-water supplementation of D-mannose significantly attenuated hepatic steatosis in a standard mouse ALD model established by chronic-binge ethanol feeding, especially hepatocyte lipid deposition. This function of D-mannose on lipid accumulation in hepatocytes was also confirmed using ethanol-treated primary mouse hepatocytes (PMHs) with a D-mannose supplement. Meanwhile, D-mannose regulated lipid metabolism by rescuing ethanol-mediated reduction of fatty acid oxidation genes (PPARα, ACOX1, CPT1) and elevation of lipogenic genes (SREBP1c, ACC1, FASN). PI3K/Akt/mTOR signaling pathway was involved in this effect of D-mannose on lipid metabolism since PI3K/Akt/mTOR pathway inhibitors or agonists could abolish this effect in PMHs. Overall, our findings suggest that D-mannose exhibits its anti-steatosis effect in ALD by regulating hepatocyte lipid metabolism via PI3K/Akt/mTOR signaling pathway.
Genetic Modifiers of Thymic Selection and Central Tolerance in Type 1 Diabetes
Authors: Kissler Stephan
Published: April 2022

Type 1 diabetes (T1D) is caused by the T cell-driven autoimmune destruction of insulin-producing cells in the pancreas. T1D served as the prototypical autoimmune disease for genome wide association studies (GWAS) after having already been the subject of many linkage and association studies prior to the development of GWAS technology. Of the many T1D-associated gene variants, a minority appear disease-specific, while most are shared with one or more other autoimmune condition. Shared disease variants suggest defects in fundamental aspects of immune tolerance. The first layer of protective tolerance induction is known as central tolerance and takes place during the thymic selection of T cells. In this article, we will review candidate genes for type 1 diabetes whose function implicates them in central tolerance. We will describe examples of gene variants that modify the function of T cells intrinsically and others that indirectly affect thymic selection. Overall, these insights will show that a significant component of the genetic risk for T1D – and autoimmunity in general – pertains to the earliest stages of tolerance induction, at a time when protective intervention may not be feasible.
No Population Structure of Bigeye Tunas (Thunnus obesus) in the Western and Central Pacific Ocean Indicated by Single Nucleotide Polymorphisms
Authors: Natasha Janice , Stockwell Brian L. , Marie Amandine D. , Hampton John , Smith Neville , Nicol Simon , Rico Ciro
Published: April 2022

The current management of the bigeye tuna (Thunnus obesus) fishery in the Western and Central Pacific Ocean (WCPO) is based on a “single-stock” paradigm. We investigated the spatial and temporal distribution of the neutral and potentially adaptive genetic diversity in samples collected from waters near Micronesia, Marshall, Phoenix and Gilbert Islands and French Polynesia using genotyping by sequence and single nucleotide polymorphisms (SNP). Analysis of 144 individuals and 2,682 SNP did not provide any substantial evidence to challenge the current assumption of panmixia in the WCPO using putatively neutral loci. However, there was a signal of potentially adaptive divergence (FST range 0.11–0.24) of samples collected in 2013 in the exclusive economic zone of the Phoenix Islands, possibly because of exposure to differing selective constraints. The geographic origin of these tuna remains to be determined, as the samples originate from tagging cruises that sample large schools of tuna, and some of those tuna have subsequently showed substantial movement. We highly recommend further studies involving large sample sizes of larvae and young-of-the-year across the region and over multiple years to uncover the underlying processes that are potentially driving adaptive divergence and to infer any biological significance it may have on conservation and management of tropical bigeye tuna fishery stock.
Sex and Size Influence the Spatiotemporal Distribution of White Sharks, With Implications for Interactions With Fisheries and Spatial Management in the Southwest Indian Ocean
Authors: Kock Alison A. , Lombard Amanda T. , Daly Ryan , Goodall Victoria , Meÿer Michael , Johnson Ryan , Fischer Chris , Koen Pieter , Irion Dylan , Gennari Enrico , Towner Alison , Jewell Oliver J. D. , da Silva Charlene , Dicken Matthew L. , Smale Malcolm J. , Photopoulou Theoni
Published: April 2022

Human activities in the oceans increase the extinction risk of marine megafauna. Interventions require an understanding of movement patterns and the spatiotemporal overlap with threats. We analysed the movement patterns of 33 white sharks (Carcharodon carcharias) satellite-tagged in South Africa between 2012 and 2014 to investigate the influence of size, sex and season on movement patterns and the spatial and temporal overlap with longline and gillnet fisheries and marine protected areas (MPAs). We used a hidden Markov model to identify ‘resident’ and ‘transient’ movement states and investigate the effect of covariates on the transition probabilities between states. A model with sex, total length and season had the most support. Tagged sharks were more likely to be in a resident state near the coast and a transient state away from the coast, while the probability of finding a shark in the transient state increased with size. White sharks moved across vast areas of the southwest Indian Ocean, emphasising the need for a regional management plan. White sharks overlapped with longline and gillnet fisheries within 25% of South Africa’s Exclusive Economic Zone and spent 15% of their time exposed to these fisheries during the study period. The demersal shark longline fishery had the highest relative spatial and temporal overlap, followed by the pelagic longline fishery and the KwaZulu-Natal (KZN) shark nets and drumlines. However, the KZN shark nets and drumlines reported the highest white shark catches, emphasising the need to combine shark movement and fishing effort with reliable catch records to assess risks to shark populations accurately. White shark exposure to shark nets and drumlines, by movement state, sex and maturity status, corresponded with the catch composition of the fishery, providing support for a meaningful exposure risk estimate. White sharks spent significantly more time in MPAs than expected by chance, likely due to increased prey abundance or less disturbance, suggesting that MPAs can benefit large, mobile marine megafauna. Conservation of white sharks in Southern Africa can be improved by implementing non-lethal solutions to beach safety, increasing the observer coverage in fisheries, and continued monitoring of movement patterns and existing and emerging threats.
Diffraction-based Residual Stress Mapping of a Stress Frame of Gray Iron via Vibratory Stress Relief Method
Authors: Chen Shi-Wei , Huang E-Wen , Chiu Sung-Mao , Reid Mark , Wu Cheng-Yen , Paradowska Anna M. , Lam Tu-Ngoc , Wu Yu-Hao , Lee Soo Yeol , Lu Shao-Chien , Chen Shin-An , Lin Yan-Gu , Weng Shih-Chang
Published: April 2022

The role of residual stress is critical, particularly for machine tools demanding accuracy below 1 µm. Although minor stresses are subjected to a tiny area, the applied force can cause devastating distortions on the precision components at this length scale. In this research, we systematically investigated the residual stress in a stress frame of the gray iron used in machine tools using synchrotron X-ray and neutron sources. Through the combination of these techniques, the residual stresses on the surface, inside the bulk, and in average were presented. Comprehensive analysis results shed light on the vibratory stress relief technique, which reduced the residual stresses and stabilized them, even materials undergoing cycling heating. Although compressive stresses are not effectively reduced, this technique is useful in improving the mechanical stability of the materials in machine tools.