bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a novel nannochloropsis strain with enhanced violaxanthin yield for large‐scale production
Authors: Park Su-Bin , Yun Jin-Ho , Ryu Ae Jin , Yun Joohyun , Kim Ji Won , Lee Sujin , Choi Saehae , Cho Dae-Hyun , Choi Dong-Yun , Lee Yong Jae , Kim Hee-Sik 
Published: February 2021

Abstract
Background
Nannochloropsis is a marine microalga that has been extensively studied. The major carotenoid produced by this group of microalgae is violaxanthin, which exhibits anti-inflammatory, anti-photoaging, and antiproliferative activities. Therefore, it has a wide range of potential applications. However, large-scale production of this pigment has not been much studied, thereby limiting its industrial application.

Results
To develop a novel strain producing high amount of violaxanthin, various Nannochloropsis species were isolated from seawater samples and their violaxanthin production potential were compared. Of the strains tested, N. oceanica WS-1 exhibited the highest violaxanthin productivity; to further enhance the violaxanthin yield of WS-1, we performed gamma-ray-mediated random mutagenesis followed by colorimetric screening. As a result, Mutant M1 was selected because of its significant higher violaxanthin content and biomass productivity than WS-1 (5.21 ± 0.33 mg g− 1 and 0.2101 g L− 1 d− 1, respectively). Subsequently, we employed a 10 L-scale bioreactor to confirm the large-scale production potential of M1, and the results indicated a 43.54 % increase in violaxanthin production compared with WS-1. In addition, comparative transcriptomic analysis performed under normal light condition identified possible mechanisms associated with remediating photo-inhibitory damage and other key responses in M1, which seemed to at least partially explain enhanced violaxanthin content and delayed growth.

Conclusions
Nannochloropsis oceanica mutant (M1) with enhanced violaxanthin content was developed and its physiological characteristics were investigated. In addition, enhanced production of violaxanthin was demonstrated in the large-scale cultivation. Key transcriptomic responses that are seemingly associated with different physiological responses of M1 were elucidated under normal light condition, the details of which would guide ongoing efforts to further maximize the industrial potential of violaxanthin producing strains.
Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma
Authors: Zhao JiangSheng , Chen GuoFeng , Li Jingqi , Liu Shiqi , Jin Quan , Zhang ZhengWei , Qi Fuzhen , Zhang JianHuai , Xu JianBo 
Published: February 2021

Abstract
Background
PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC.

Methods

PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing.

Results
PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2.

Conclusions
This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.
Malaria in migrant agricultural workers in western Ethiopia: entomological assessment of malaria transmission risk
Authors: Dugassa Sisay , Murphy Mathew , Chibsa Sheleme , Tadesse Yehualashet , Yohannes Gedeon , Lorenz Lena M. , Solomon Hiwot , Yewhalaw Delenasaw , Irish Seth R. 
Published: February 2021

Abstract
Background
Ethiopia has made great strides in malaria control over the last two decades. However, this progress has not been uniform and one concern has been reported high rates of malaria transmission in large agricultural development areas in western Ethiopia. Improved vector control is one way this transmission might be addressed, but little is known about malaria vectors in this part of the country.

Methods
To better understand the vector species involved in malaria transmission and their behaviour, human landing collections were conducted in Dangur woreda, Benishangul-Gumuz, between July and December 2017. This period encompasses the months with the highest rain and the peak mosquito population. Mosquitoes were identified to species and tested for the presence of Plasmodium sporozoites.

Results
The predominant species of the Anopheles collected was Anopheles arabiensis (1,733; i.e. 61.3 % of the entire Anopheles), which was also the only species identified with sporozoites (Plasmodium falciparum and Plasmodium vivax). Anopheles arabiensis was collected as early in the evening as 18:00 h-19:00 h, and host-seeking continued until 5:00 h-6:00 h. Nearly equal numbers were collected indoors and outdoors. The calculated entomological inoculation rate for An. arabiensis for the study period was 1.41 infectious bites per month. More An. arabiensis were collected inside and outside worker’s shelters than in fields where workers were working at night.

Conclusions
Anopheles arabiensis is likely to be the primary vector of malaria in the agricultural development areas studied. High rates of human biting took place inside and outdoor near workers’ residential housing. Improved and targeted vector control in this area might considerably reduce malaria transmission.
Parasite genetic diversity reflects continued residual malaria transmission in Vhembe District, a hotspot in the Limpopo Province of South Africa
Authors: Gwarinda Hazel B. , Tessema Sofonias K. , Raman Jaishree , Greenhouse Bryan , Birkholtz Lyn-Marié 
Published: February 2021

Abstract
Background
South Africa aims to eliminate malaria transmission by 2023. However, despite sustained vector control efforts and case management interventions, the Vhembe District remains a malaria transmission hotspot. To better understand Plasmodium falciparum transmission dynamics in the area, this study characterized the genetic diversity of parasites circulating within the Vhembe District.

Methods
A total of 1153 falciparum-positive rapid diagnostic tests (RDTs) were randomly collected from seven clinics within the district, over three consecutive years (2016, 2017 and 2018) during the wet and dry malaria transmission seasons. Using 26 neutral microsatellite markers, differences in genetic diversity were described using a multiparameter scale of multiplicity of infection (MOI), inbreeding metric (Fws), number of unique alleles (A), expected heterozygosity (He), multilocus linkage disequilibrium (LD) and genetic differentiation, and were associated with temporal and geospatial variances.

Results
A total of 747 (65%) samples were successfully genotyped. Moderate to high genetic diversity (mean He = 0.74 ± 0.03) was observed in the parasite population. This was ascribed to high allelic richness (mean A = 12.2 ± 1.2). The majority of samples (99%) had unique multi-locus genotypes, indicating high genetic diversity in the sample set. Complex infections were observed in 66% of samples (mean MOI = 2.13 ± 0.04), with 33% of infections showing high within-host diversity as described by the Fws metric. Low, but significant LD (standardised index of association, ISA = 0.08, P < 0.001) was observed that indicates recombination of distinct clones. Limited impact of temporal (FST range − 0.00005 to 0.0003) and spatial (FST = − 0.028 to 0.023) variation on genetic diversity existed during the sampling timeframe and study sites respectively.

Conclusions
Consistent with the Vhembe District’s classification as a ‘high’ transmission setting within South Africa, P. falciparum diversity in the area was moderate to high and complex. This study showed that genetic diversity within the parasite population reflects the continued residual transmission observed in the Vhembe District. This data can be used as a reference point for the assessment of the effectiveness of on-going interventions over time, the identification of imported cases and/or outbreaks, as well as monitoring for the potential spread of anti-malarial drug resistance.
Correlation between antimicrobial resistance and biofilm formation capability among Klebsiella pneumoniae strains isolated from hospitalized patients in Iran
Authors: Shadkam Shadi , Goli Hamid Reza , Mirzaei Bahman , Gholami Mehrdad , Ahanjan Mohammad 
Published: February 2021

Abstract
Background
Klebsiella pneumoniae is a common cause of nosocomial infections. Antibiotic resistance and ability to form biofilm, as two key virulence factors of K. pneumoniae, are involved in the persistence of infections. The purpose of this study was to investigate the correlation between antimicrobial resistance and biofilm formation capability among K. pneumoniae strains isolated from hospitalized patients in Iran.

Methods
Over a 10-month period, a total of 100 non-duplicate K. pneumoniae strains were collected. Antibiotic susceptibility was determined by Kirby–Bauer disk diffusion method according to CLSI. Biofilm production was assessed by tissue culture plate method. Finally, polymerase chain reaction was conducted to detect four families of carbapenemase: blaIMP, blaVIM, blaNDM, blaOXA−48; biofilm formation associated genes: treC, wza, luxS; and K. pneumoniae confirming gene: rpoB.

Results
Most of the isolates were resistant to trimethoprim-sulfamethoxazole (52 %), cefotaxime (51 %), cefepime (43 %), and ceftriaxone (43 %). Among all the 100 isolates, 67 were multidrug-resistant (MDR), and 11 were extensively drug-resistant (XDR). The prevalence of the blaVIM, blaIMP, blaNDM, and blaOXA−48 genes were 7 , 11 , 5 , and 28 %, respectively. The results of biofilm formation in the tissue culture plate assay indicated that 75 (75 %) strains could produce biofilm and only 25 (25 %) isolates were not able to form biofilm. Among these isolates, 25 % formed fully established biofilms, 19 % were categorized as moderately biofilm-producing, 31 % formed weak biofilms, and 25 % were non-biofilm-producers. The antimicrobial resistance among biofilm former strains was found to be significantly higher than that of non-biofilm former strains (p < 0.05). Molecular distribution of biofilm formation genes revealed that 98 , 96 , and 34 % of the isolates carried luxS, treC, and wza genes, respectively.

Conclusions
The rise of antibiotic resistance among biofilm-producer strains demonstrates a serious concern about limited treatment options in the hospital settings. All of the data suggest that fundamental actions and introduction of novel strategies for controlling of K. pneumoniae biofilm-related infections is essential.
mRNA vaccine: a potential therapeutic strategy
Authors: Wang Yang , Zhang Ziqi , Luo Jingwen , Han Xuejiao , Wei Yuquan , Wei Xiawei 
Published: February 2021

AbstractmRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.
Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia
Authors: Cruz-Bautista Ivette , Huerta-Chagoya Alicia , Moreno-Macías Hortensia , Rodríguez-Guillén Rosario , Ordóñez-Sánchez María Luisa , Segura-Kato Yayoi , Mehta Roopa , Almeda-Valdés Paloma , Gómez-Munguía Lizeth , Ruiz-De Chávez Ximena , Rosas-Flota Ximena , Andrade-Amado Arali , Bernal-Barroeta Bárbara , López-Carrasco María Guadalupe , Guillén-Pineda Luz Elizabeth , López-Estrada Angelina , Elías-López Daniel , Martagón-Rosado Alexandro J. , Gómez-Velasco Donají , Lam-Chung Cesar Ernesto , Bello-Chavolla Omar Yaxmehen , Del Razo-Olvera Fabiola , Cetina-Pérez Lucely D. , Acosta-Rodríguez José Luis , Tusié-Luna María Teresa , Aguilar-Salinas Carlos A. 
Published: February 2021

Abstract
Background
Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease.

Methods
This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups.

Results
Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901–0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG.

Conclusions
The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.
Tailored liposomal nanotraps for the treatment of Streptococcal infections
Authors: Besançon Hervé , Babiychuk Viktoriia , Larpin Yu , Köffel René , Schittny Dominik , Brockhus Lara , Hathaway Lucy J. , Sendi Parham , Draeger Annette , Babiychuk Eduard 
Published: February 2021

Abstract
Background
Streptococcal infections are associated with life-threatening pneumonia and sepsis. The rise in antibiotic resistance calls for novel approaches to treat bacterial diseases. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. In contrast to antibiotics, anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins (hemolysins) that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are specifically targeted by bacterial toxins are being developed in order to neutralize-by competitive sequestration-numerous exotoxins.

Results
In this study, the liposomal nanotrap technology is further developed to simultaneously neutralize the whole palette of cytolysins produced by Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis-pathogens that can cause life-threatening streptococcal toxic shock syndrome. We show that the mixture of liposomes containing high amounts of cholesterol and liposomes composed exclusively of choline-containing phospholipids is fully protective against the combined action of exotoxins secreted by these pathogens.

Conclusions
Unravelling the universal mechanisms that define targeting of host cells by streptococcal cytolysins paves the way for a broad-spectrum anti-toxin therapy that can be applied without a diagnostic delay for the treatment of bacterial infections including those caused by antibiotic-resistant pathogens.
Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice
Authors: Liao Chia-Chih , Yu Huang-Ping , Yang Shih-Chun , Alalaiwe Ahmed , Dai You-Shan , Liu Fu-Chao , Fang Jia-You 
Published: February 2021

Abstract
Background
Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury.

Results
The mean nanoparticle size and zeta potential of the NLCs were 171 nm and − 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%.

Conclusions
The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.
Quantitative proteomic profiling of Cervicovaginal fluid from pregnant women with term and preterm birth
Authors: Kim Young Eun , Kim Kwonseong , Oh Han Bin , Lee Sung Ki , Kang Dukjin 
Published: February 2021

Abstract
Background
Preterm birth (PTB) is one of major causes of perinatal mortality and neonatal morbidity, but knowledge of its complex etiology is still limited. Here we present cervicovaginal fluid (CVF) protein profiles of pregnant women who subsequently delivered at spontaneous preterm or term, aiming to identify differentially expressed CVF proteins in PTB and term birth.

Methods
The CVF proteome of women who sequentially delivered at preterm and term was analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS). We compared the CVF proteome of PTB (n = 5) and control subjects (term birth, n = 7) using pooled control CVF (term birth, n = 20) as spike-in standard.

Results
We identified 1294 CVF proteins, of which 605 were newly identified proteins. Of 990 proteins quantified in both PTB and term birth, 52 proteins were significantly up/down-regulated in PTB compared to term birth. The differentially expressed proteins were functionally associated to immune response, endopeptidase inhibitors and structural constituent of cytoskeleton. Finally, we confirm the down-regulation of SERPINB7 (a serine-type protease inhibitor) in PTB compared to control by Western blot.

Conclusions
Taken together, our study provide quantitative CVF proteome profiles of pregnant women who ultimately delivered at preterm and term. These promising results could help to improve the understanding of PTB etiology and to discover biomarkers for asymptomatic PTB.