bluuebunny/crossref_metadata_2025 huggingface dataset:
Colloidal Lithography for Photovoltaics: An Attractive Route for Light Management
Authors: Oliveira Rui D. , Mouquinho Ana , Centeno Pedro , Alexandre Miguel , Haque Sirazul , Martins Rodrigo , Fortunato Elvira , Águas Hugo , Mendes Manuel J.
Published: June 2021

The pursuit of ever-more efficient, reliable, and affordable solar cells has pushed the development of nano/micro-technological solutions capable of boosting photovoltaic (PV) performance without significantly increasing costs. One of the most relevant solutions is based on light management via photonic wavelength-sized structures, as these enable pronounced efficiency improvements by reducing reflection and by trapping the light inside the devices. Furthermore, optimized microstructured coatings allow self-cleaning functionality via effective water repulsion, which reduces the accumulation of dust and particles that cause shading. Nevertheless, when it comes to market deployment, nano/micro-patterning strategies can only find application in the PV industry if their integration does not require high additional costs or delays in high-throughput solar cell manufacturing. As such, colloidal lithography (CL) is considered the preferential structuring method for PV, as it is an inexpensive and highly scalable soft-patterning technique allowing nanoscopic precision over indefinitely large areas. Tuning specific parameters, such as the size of colloids, shape, monodispersity, and final arrangement, CL enables the production of various templates/masks for different purposes and applications. This review intends to compile several recent high-profile works on this subject and how they can influence the future of solar electricity.
The Effect of Four Weeks Dietary Intervention with 8-Hour Time-Restricted Eating on Body Composition and Cardiometabolic Risk Factors in Young Adults
Authors: Park Su-Jeong , Yang Jae-Won , Song Yoon-Ju
Published: June 2021

Recently, intermittent fasting, also known as time-restricted eating (TRE), has become a popular diet trend. Compared to animal studies, there have been few studies and inconclusive findings investigating the effects of TRE in humans. In this study, we examined the effects of 8 h TRE on body weight and cardiometabolic risk factors in young adults who were mainly active at night. A total of 33 young adults completed the 8 h TRE for 4 weeks. Body composition was measured by bioelectrical impedance analysis at baseline and every 2 weeks, and blood samples were collected at baseline and week 4. Daily dietary records were logged throughout the intervention period. Participants experienced significant changes in body weight (−1.0 ± 1.4 kg), body mass index (−0.4 ± 0.5 kg/m2), and body fat (−0.4 ± 1.9%) after 4 weeks of TRE. When participants were divided into weight loss/gain groups based on their weight change in week 4, fat mass reduction was significantly higher in the weight loss group than in the weight gain group. Regarding cardiometabolic risk factors, levels of fasting insulin and insulin resistance improved in the weight loss group after intervention, but not in the weight gain group. All subjects showed late-shifted sleeping patterns, but no significant differences in sleep duration, sleep quality, or psychological measures between the two groups. When meal frequency and energy proportion were evaluated, the average meal frequency was 2.8 ± 0.5 and energy proportions of breakfast, lunch, dinner, and snacks were 4.5, 39.2, 37.6, and 18.5%, respectively; there were no significant differences between the two groups. However, the saturated fat intake at dinner was lower in the weight loss group (3.1 ± 3.2%, 6.0 ± 2.5% respectively). In conclusion, 8 h TRE can be applied as a lifestyle strategy to manage body weight and cardiometabolic risk factors among young adults with late chronotypes.
Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice
Authors: Blanco-Gandía María del Carmen , Ródenas-González Francisco , Pascual María , Reguilón Marina Daiana , Guerri Consuelo , Miñarro José , Rodríguez-Arias Marta
Published: June 2021

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.
Usual Protein Intake Amount and Sources of Nursing Home Residents with (Risk of) Malnutrition and Effects of an Individualized Nutritional Intervention: An enable Study
Authors: Seemer Johanna , Volkert Dorothee , Fleckenstein-Sußmann Daniela , Bader-Mittermaier Stephanie , Sieber Cornel Christian , Kiesswetter Eva
Published: June 2021

Nursing home (NH) residents with (risk of) malnutrition are at particular risk of low protein intake (PI). The aim of the present analysis was (1) to characterize usual PI (total amount/day (d) and meal, sources/d and meal) of NH residents with (risk of) malnutrition and (2) to evaluate the effects of an individualized nutritional intervention on usual PI. Forty residents (75% female, 85 ± 8 years) with (risk of) malnutrition and inadequate dietary intake received 6 weeks of usual care followed by 6 weeks of intervention. During the intervention phase, an additional 29 ± 11 g/d from a protein-energy drink and/or 2 protein creams were offered to compensate for individual energy and/or protein deficiencies. PI was assessed with two 3-day-weighing records in each phase and assigned to 4 meals and 12 sources. During the usual care phase, mean PI was 41 ± 10 g/d. Lunch and dinner contributed 31 ± 11% and 32 ± 9% to daily intake, respectively. Dairy products (median 9 (interquartile range 6–14) g/d), starchy foods (7 (5–10) g/d) and meat/meat products (6 (3–9) g/d) were the main protein sources in usual PI. During the intervention phase, an additional 18 ± 10 g/d were consumed. Daily PI from usual sources did not differ between usual care and intervention phase (41 ± 10 g/d vs. 42 ± 11 g/d, p = 0.434). In conclusion, daily and per meal PI were very low in NH residents with (risk of) malnutrition, highlighting the importance of adequate intervention strategies. An individualized intervention successfully increased PI without affecting protein intake from usual sources.
Beneficial Effects of a Specially Designed Home Meal Replacement on Cardiometabolic Parameters in Individuals with Obesity: Preliminary Results of a Randomized Controlled Clinical Trial
Authors: Lee Jae-Woo , Kim Yonghwan , Hyun Taisun , Song Seunghye , Yang Woojung , Kim Ye-Seul , You Hyo-Sun , Chang Young-Chang , Shin Seung-Ho , Kang Hee-Taik
Published: June 2021

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride–glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention (p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).
Aerobic Exercise Training Prevents Insulin Resistance and Hepatic Lipid Accumulation in LDL Receptor Knockout Mice Chronically Fed a Low-Sodium Diet
Authors: da Silva Ferreira Guilherme , Bochi Ana Paula Garcia , Pinto Paula Ramos , Del Bianco Vanessa , Rodrigues Letícia Gomes , Morais Mychel Raony Paiva Teixeira , Nakandakare Edna Regina , Machado Ubiratan Fabres , Catanozi Sergio , Passarelli Marisa
Published: June 2021

Background: A low-sodium (LS) diet reduces blood pressure, contributing to the prevention of cardiovascular diseases. However, intense dietary sodium restriction impairs insulin sensitivity and worsens lipid profile. Considering the benefits of aerobic exercise training (AET), the effect of LS diet and AET in hepatic lipid content and gene expression was investigated in LDL receptor knockout (LDLr-KO) mice. Methods: Twelve-week-old male LDLr-KO mice fed a normal sodium (NS) or LS diet were kept sedentary (S) or trained (T) for 90 days. Body mass, plasma lipids, insulin tolerance testing, hepatic triglyceride (TG) content, gene expression, and citrate synthase (CS) activity were determined. Results were compared by 2-way ANOVA and Tukey’s post-test. Results: Compared to NS, LS increased body mass and plasma TG, and impaired insulin sensitivity, which was prevented by AET. The LS-S group, but not the LS-T group, presented greater hepatic TG than the NS-S group. The LS diet increased the expression of genes related to insulin resistance (ApocIII, G6pc, Pck1) and reduced those involved in oxidative capacity (Prkaa1, Prkaa2, Ppara, Lipe) and lipoprotein assembly (Mttp). Conclusion: AET prevented the LS-diet-induced TG accumulation in the liver by improving insulin sensitivity and the expression of insulin-regulated genes and oxidative capacity.
Carbohydrate Considerations for Athletes with a Spinal Cord Injury
Authors: Ruettimann Belinda , Perret Claudio , Parnell Jill A. , Flueck Joelle Leonie
Published: June 2021

The Paralympic movement is growing in popularity, resulting in increased numbers of athletes with a spinal cord injury (SCI) competing in various sport disciplines. Athletes with an SCI require specialized recommendations to promote health and to maximize performance, as evidenced by their metabolic and physiological adaptations. Nutrition is a key factor for optimal performance; however, scientifically supported nutritional recommendations are limited. This review summarizes the current knowledge regarding the importance of carbohydrates (CHO) for health and performance in athletes with an SCI. Factors possibly affecting CHO needs, such as muscle atrophy, reduced energy expenditure, and secondary complications are analyzed comprehensively. Furthermore, a model calculation for CHO requirements during an endurance event is provided. Along with assessing the effectiveness of CHO supplementation in the athletic population with SCI, the evaluation of their CHO intake from the available research supplies background to current practices. Finally, future directions are identified. In conclusion, the direct transfer of CHO guidelines from able-bodied (AB) athletes to athletes with an SCI does not seem to be reasonable. Based on the critical role of CHOs in exercise performance, establishing recommendations for athletes with an SCI should be the overall objective for prospective research.
The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis
Authors: Morandi Fabio , Bensa Veronica , Calarco Enzo , Pastorino Fabio , Perri Patrizia , Corrias Maria Valeria , Ponzoni Mirco , Brignole Chiara
Published: June 2021

Neuroblastoma (NB) is the most common extra-cranial solid tumor of pediatric age. The prognosis for high-risk NB patients remains poor, and new treatment strategies are desirable. The olive leaf extract (OLE) is constituted by phenolic compounds, whose health beneficial effects were reported. Here, the anti-tumor effects of OLE were investigated in vitro on a panel of NB cell lines in terms of (i) reduction of cell viability; (ii) inhibition of cell proliferation through cell cycle arrest; (iii) induction of apoptosis; and (iv) inhibition of cell migration. Furthermore, cytotoxicity experiments, by combining OLE with the chemotherapeutic topotecan, were also performed. OLE reduced the cell viability of NB cells in a time- and dose-dependent manner in 2D and 3D models. NB cells exposed to OLE underwent inhibition of cell proliferation, which was characterized by an arrest of the cell cycle progression in G0/G1 phase and by the accumulation of cells in the sub-G0 phase, which is peculiar of apoptotic death. This was confirmed by a dose-dependent increase of Annexin V+ cells (peculiar of apoptosis) and upregulation of caspases 3 and 7 protein levels. Moreover, OLE inhibited the migration of NB cells. Finally, the anti-tumor efficacy of the chemotherapeutic topotecan, in terms of cell viability reduction, was greatly enhanced by its combination with OLE. In conclusion, OLE has anti-tumor activity against NB by inhibiting cell proliferation and migration and by inducing apoptosis.
Effects of the Traditional Mediterranean Diet in Patients with Otitis Media with Effusion
Authors: Calatayud-Sáez Fernando M. , Calatayud Blanca , Calatayud Ana
Published: June 2021

Introduction: Otitis media with effusion (OME) is common in pediatric primary care consultations. Its etiology is multifactorial, although it has been proven that inflammation factors mediate and that immunity is in a phase of relative immaturity. The objective of this study was to assess the effects of the Traditional Mediterranean Diet (TMD) modulating inflammation and immunity in patients diagnosed with OME. Materials and Methods: A analysis as a single-group pre-test/post-test was conducted on 40 girls and 40 boys between 18 months and 5 years old. Tympanometry normalization was the main test to control the benefit of diet. Clinical and therapeutic variables were studied through evaluation questionnaires, a quality test of the diet, as well as various anthropometric parameters. Results: At the end of one year, tympanometry had normalized in 85% of patients. The remaining 15% had normal audiometry and/or associated symptoms had decreased. Likewise, episodes of recurrent colds decreased from 5.96 ± 1.41 to 2.55 ± 0.37; bacterial complications of 3.09 ± 0.75 to 0.61 ± 0.06 and persistent nasal obstruction of 1.92 ± 0.27 to 0.26 ± 0.05. The degree of satisfaction of the families with the program was very high. Conclusions: The application of the Traditional Mediterranean Diet could have promising effects in the prevention and treatment of otitis media with effusion.
Deletion Mutants of Francisella Phagosomal Transporters FptA and FptF Are Highly Attenuated for Virulence and Are Protective Against Lethal Intranasal Francisella LVS Challenge in a Murine Model of Respiratory Tularemia
Authors: Hobbs Brandi E. , Matson Courtney A. , Theofilou Vasileios I. , Webb Tonya J. , Younis Rania H. , Barry Eileen M.
Published: June 2021

Francisella tularensis (Ft) is a Gram-negative, facultative intracellular bacterium that is a Tier 1 Select Agent of concern for biodefense for which there is no licensed vaccine. A subfamily of 9 Francisella phagosomal transporter (fpt) genes belonging to the Major Facilitator Superfamily of transporters was identified as critical to pathogenesis and potential targets for attenuation and vaccine development. We evaluated the attenuation and protective capacity of LVS derivatives with deletions of the fptA and fptF genes in the C57BL/6J mouse model of respiratory tularemia. LVSΔfptA and LVSΔfptF were highly attenuated with LD50 values of >20 times that of LVS when administered intranasally and conferred 100% protection against lethal challenge. Immune responses to the fpt mutant strains in mouse lungs on day 6 post-infection were substantially modified compared to LVS and were associated with reduced organ burdens and reduced pathology. The immune responses to LVSΔfptA and LVSΔfptF were characterized by decreased levels of IL-10 and IL-1β in the BALF versus LVS, and increased numbers of B cells, αβ and γδ T cells, NK cells, and DCs versus LVS. These results support a fundamental requirement for FptA and FptF in the pathogenesis of Ft and the modulation of the host immune response.
Subtyping Cryptosporidium xiaoi, a Common Pathogen in Sheep and Goats
Authors: Fan Yingying , Huang Xitong , Guo Sheng , Yang Fang , Yang Xin , Guo Yaqiong , Feng Yaoyu , Xiao Lihua , Li Na
Published: June 2021

Cryptosporidiosis is a significant cause of diarrhea in sheep and goats. Among the over 40 established species of Cryptosporidium, Cryptosporidium xiaoi is one of the dominant species infecting ovine and caprine animals. The lack of subtyping tools makes it impossible to examine the transmission of this pathogen. In the present study, we identified and characterized the 60-kDa glycoprotein (gp60) gene by sequencing the genome of C. xiaoi. The GP60 protein of C. xiaoi had a signal peptide, a furin cleavage site of RSRR, a glycosylphosphatidylinositol anchor, and over 100 O-glycosylation sites. Based on the gp60 sequence, a subtyping tool was developed and used in characterizing C. xiaoi in 355 positive samples from sheep and goats in China. A high sequence heterogeneity was observed in the gp60 gene, with 94 sequence types in 12 subtype families, namely XXIIIa to XXIIIl. Co-infections with multiple subtypes were common in these animals, suggesting that genetic recombination might be responsible for the high diversity within C. xiaoi. This was supported by the mosaic sequence patterns among the subtype families. In addition, a potential host adaptation was identified within this species, reflected by the exclusive occurrence of XXIIIa, XXIIIc, XXIIIg, and XXIIIj in goats. This subtyping tool should be useful in studies of the genetic diversity and transmission dynamics of C. xiaoi.
Whole Genome Sequence Analysis of Mycobacterium bovis Cattle Isolates, Algeria
Authors: Tazerart Fatah , Saad Jamal , Sahraoui Naima , Yala Djamel , Niar Abdellatif , Drancourt Michel
Published: June 2021

Mycobacterium bovis (M. bovis), a Mycobacterium tuberculosis complex species responsible for tuberculosis in cattle and zoonotic tuberculosis in humans, is present in Algeria. In Algeria however, the M. bovis population structure is unknown, limiting understanding of the sources and transmission of bovine tuberculosis. In this study, we identified the whole genome sequence (WGS) of 13 M. bovis strains isolated from animals exhibiting lesions compatible with tuberculosis, which were slaughtered and inspected in five slaughterhouses in Algeria. We found that six isolates were grouped together with reference clinical strains of M. bovis genotype-Unknown2. One isolate was related to M. bovis genotype-Unknown7, one isolate was related to M. bovis genotype-Unknown4, three isolates belonged to M. bovis genotype-Europe 2 and there was one new clone for two M. bovis isolates. Two isolates from Blida exhibited no pairwise differences in single nucleotide polymorphisms. None of these 13 isolates were closely related to four zoonotic M. bovis isolates previously characterized in Algeria. In Algeria, the epidemiology of bovine tuberculosis in cattle is partly driven by cross border movements of animals and animal products.
A Proteinase 3 Contribution to Juvenile Idiopathic Arthritis-Associated Cartilage Damage
Authors: Patterson Eric K. , Vanin Moreno Nicolas , Fraser Douglas D. , Cepinskas Gediminas , Iida Takaya , Berard Roberta A.
Published: June 2021

A full understanding of the molecular mechanisms implicated in the etiopathogenesis of juvenile idiopathic arthritis (JIA) is lacking. A critical role for leukocyte proteolytic activity (e.g., elastase and cathepsin G) has been proposed. While leukocyte elastase’s (HLE) role has been documented, the potential contribution of proteinase 3 (PR3), a serine protease present in abundance in neutrophils, has not been evaluated. In this study we investigated: (1) PR3 concentrations in the synovial fluid of JIA patients using ELISA and (2) the cartilage degradation potential of PR3 by measuring the hydrolysis of fluorescently labeled collagen II in vitro. In parallel, concentrations and collagen II hydrolysis by HLE were assessed. Additionally, the levels of the co-secreted primary granule protein myeloperoxidase (MPO) were assessed in synovial fluid of patients diagnosed with JIA. We report the following levels of analytes in JIA synovial fluid: PR3—114 ± 100 ng/mL (mean ± SD), HLE—1272 ± 1219 ng/mL, and MPO—1129 ± 1659 ng/mL, with a very strong correlation between the PR3 and HLE concentrations (rs = 0.898, p < 1 × 10–6). Importantly, PR3 hydrolyzed fluorescently labeled collagen II as efficiently as HLE. Taken together, these novel findings suggest that PR3 (in addition to HLE) contributes to JIA-associated joint damage.
Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy
Authors: El-Kady Mohamed M. , Naggar Reham A. , Guimei Maha , Talaat Iman M. , Shaker Olfat G. , Saber-Ayad Maha
Published: June 2021

Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg−1) compared to that of enalapril at a dose of 10 mg·kg−1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease.
Erratum: Zahn et al. Manipulation of Medicinal Products for Oral Administration to Paediatric Patients at a German University Hospital: An Observational Study. Pharmaceutics 2020, 12, 583
Authors: Zahn Julia , Hoerning André , Trollmann Regina , Rascher Wolfgang , Neubert Antje
Published: June 2021

The authors wish to make the following corrections to the affiliation and acknowledgments part [...]
Recent Advances of Nanotechnology-Facilitated Bacteria-Based Drug and Gene Delivery Systems for Cancer Treatment
Authors: Zhu Chaojie , Ji Zhiheng , Ma Junkai , Ding Zhijie , Shen Jie , Wang Qiwen
Published: June 2021

Cancer is one of the most devastating and ubiquitous human diseases. Conventional therapies like chemotherapy and radiotherapy are the most widely used cancer treatments. Despite the notable therapeutic improvements that these measures achieve, disappointing therapeutic outcome and cancer reoccurrence commonly following these therapies demonstrate the need for better alternatives. Among them, bacterial therapy has proven to be effective in its intrinsic cancer targeting ability and various therapeutic mechanisms that can be further bolstered by nanotechnology. In this review, we will discuss recent advances of nanotechnology-facilitated bacteria-based drug and gene delivery systems in cancer treatment. Therapeutic mechanisms of these hybrid nanoformulations are highlighted to provide an up-to-date understanding of this emerging field.
Enhancement of Rotator Cuff Healing with Farnesol-Impregnated Gellan Gum/Hyaluronic Acid Hydrogel Membranes in a Rabbit Model
Authors: Lin Yen-Hung , Lee Sheng-I , Lin Feng-Huei , Wu Guan-Xuan , Wu Chun-Shien , Kuo Shyh-Ming
Published: June 2021

Most rotator cuff (RC) tears occur at the bone–tendon interface and cause disability and pain. Farnesol, a sesquiterpene compound, can exert antioxidative and anti-inflammatory effects and promote collagen synthesis. In this rabbit model, either commercial SurgiWrap membrane or hydrogel membranes containing various compositions of gellan gum, hyaluronic acid, and farnesol (hereafter GHF membranes) were applied to the tear site, and the repair of the cuff was examined 2 and 3 weeks afterward. The designed membranes swelled rapidly and adsorbed onto the tear site more readily and closely than the SurgiWrap membrane. The membranes degraded slowly and functioned as both a barrier and a vehicle of slow farnesol release during the repair period. Farnesol enhanced collagen production in myoblasts and tenocytes, and interleukin 6 and tumor necrosis factor α levels were modulated. Gross observations and histological examinations indicated that the GHF membranes impregnated with 4 mM farnesol resulted in superior RC repair. In sum, the slow release of farnesol from hydrogel membranes can be beneficial in the repair of RC injuries.
Intracellular Routing and Recognition of Lipid-Based mRNA Nanoparticles
Authors: Delehedde Christophe , Even Luc , Midoux Patrick , Pichon Chantal , Perche Federico
Published: June 2021

Messenger RNA (mRNA) is being extensively used in gene therapy and vaccination due to its safety over DNA, in the following ways: its lack of integration risk, cytoplasmic expression, and transient expression compatible with fine regulations. However, clinical applications of mRNA are limited by its fast degradation by nucleases, and the activation of detrimental immune responses. Advances in mRNA applications, with the recent approval of COVID-19 vaccines, were fueled by optimization of the mRNA sequence and the development of mRNA delivery systems. Although delivery systems and mRNA sequence optimization have been abundantly reviewed, understanding of the intracellular processing of mRNA is mandatory to improve its applications. We will focus on lipid nanoparticles (LNPs) as they are the most advanced nanocarriers for the delivery of mRNA. Here, we will review how mRNA therapeutic potency can be affected by its interactions with cellular proteins and intracellular distribution.
The Neuropeptide Cortistatin Alleviates Neuropathic Pain in Experimental Models of Peripheral Nerve Injury
Authors: Falo Clara , Benitez Raquel , Caro Marta , Morell Maria , Forte-Lago Irene , Hernandez-Cortes Pedro , Sanchez-Gonzalez Clara , O’Valle Francisco , Delgado Mario , Gonzalez-Rey Elena
Published: June 2021

Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.
Analysis of the Static Behavior of a Single Tree on a Finite Element Model
Authors: Moravčík Ľuboš , Vincúr Radko , Rózová Zdenka
Published: June 2021

This work deals with the innovated complex process of tree risk assessment, from precise geometrical tree shape acquisition to building and analyzing a finite element model under specified load. The acquisition of the 3D geometry of the tree was performed by means of terrestrial laser scanning. Obtained point cloud was optimized and additionally converted to a 3D CAD model, representing the bearing skeleton compound of trunk and main branches. For structural analysis purposes, a finite element model (FEM) was built in the form of beam structure fixed to the ground. Particular beams were defined by geometry, material properties of wood, and cross sections. An acoustic tomography was applied for determination of the precise cross section on investigated locations of an analysis model. Finite element analysis performed on the computational model shows the bearing capacity and deformations of the whole tree structure caused by combinations of load cases like self-weight and static equivalent of wind load. The results of the structural analysis called attention to potentially dangerous places within the tree structure with extreme node displacements or tensile stresses on beams. Thus, we observed a maximal horizontal displacement of 280.4 mm in node N34 and dangerous tensile stress in node N26, where it reaches +23.6 MPa. After filtering some beams with an abnormal cross section geometry, the finite element analysis of the whole tree structure showed the highest tensile stress of +8.8 MPa and highest compressive stress of −8.9 MPa. The suggested method can be applied generally for the prediction of potentially risky tree suspected of breakage and especially for monumental trees, where the presented method can be mostly applicable.
Effect of Drought Stress on Capsaicin and Antioxidant Contents in Pepper Genotypes at Reproductive Stage
Authors: Mahmood Tahir , Rana Rashid Mehmood , Ahmar Sunny , Saeed Saima , Gulzar Asma , Khan Muhammad Azam , Wattoo Fahad Masoud , Wang Xiukang , Branca Ferdinando , Mora-Poblete Freddy , Mafra Gabrielle Sousa , Du Xionming
Published: June 2021

Pepper is one of the most important vegetables and spices in the world. Principal pungency is contributed by secondary metabolites called capsaicinoids, mainly synthesized in the placenta of pepper fruit. Various factors, including drought, limit pepper production. Flowering is one of the most sensitive stages affected by drought stress. The current study was conducted to determine the effect of drought on different pepper genotypes at the flowering and pod formation stages. Hot pepper (Pusajuala and Ghotki) and Bell pepper (Green Wonder and PPE-311) genotypes were subjected to drought (35% field capacity) at two different stages (flowering (DF) and pod formation (DP) stage). In comparison, control plants were maintained at 65% field capacity. The data regarding flowering survival rates, antioxidant protein activity, and proline content, were collected. Results indicated that parameters like flower survival percentage, number of fruits per plant, and fruit weight had significant differences among the genotypes in both treatments. A high proline level was observed in Green Wonder at the pod formation stage compared to other genotypes. Capsaicin contents of hot pepper genotypes were affected at the pod formation stage. Antioxidants like GPX were highly active (190 units) in Ghotki at pod formation. Bell pepper genotypes had a high APX activity, highly observed (100 units) in PPE-311 at pod formation, and significantly differ from hot pepper genotypes. In the catalase case, all the genotypes had the highest values in DP compared to control and DF, but Pusajuala (91 units) and Green Wonder (83 units) performed best compared to other genotypes. Overall, the results indicate that drought stress decreased reproductive growth parameters and pungency of pepper fruit as most of the plant energy was consumed in defense molecules (antioxidants). Therefore, water availability at the flowering and pod formation stage is critical to ensure good yield and pepper quality.
The Effect of Plant Growth Compensation by Adding Silicon-Containing Fertilizer under Light Stress Conditions
Authors: Semenova Natalya A. , Smirnov Alexandr A. , Grishin Andrey A. , Pishchalnikov Roman Y. , Chesalin Denis D. , Gudkov Sergey V. , Chilingaryan Narek O. , Skorokhodova Anastasia N. , Dorokhov Alexey S. , Izmailov Andrey Y.
Published: June 2021

The effects of different spectral compositions of light-emitting diode (LED) sources and fertilizer containing biologically active silicon (Si) in the nutrient solution on morphological and physiological plant response were studied. Qualitative indicators and the productivity of plants of a red-leaved and a green-leaved lettuce were estimated. Lettuce was grown applying low-volume hydroponics in closed artificial agroecosystems. The positive effect of Si fertilizer used as a microadditive in the nutrient solution on the freshly harvested biomass was established on the thirtieth day of vegetation under LEDs. Increase in productivity of the red-leaved lettuce for freshly harvested biomass was 26.6%, while for the green-leaved lettuce no loss of dry matter was observed. However, being grown under sodium lamps, a negative impact of Si fertilizer on productivity of both types of plants was observed: the amount of harvested biomass decreased by 22.6% and 30.3% for the green- and red-leaved lettuces, respectively. The effect of using Si fertilizer dramatically changed during the total growing period: up to the fifteenth day of cultivation, a sharp inhibition of the growth of both types of lettuce was observed; then, by the thirtieth day of LED lighting, Si fertilizer showed a stress-protective effect and had a positive influence on the plants. However, by the period of ripening there was no effect of using the fertilizer. Therefore, we can conclude that the use of Si fertilizers is preferable only when LED irradiation is applied throughout the active plant growth period.
Transcriptome and Metabolome Integrated Analysis of Two Ecotypes of Tetrastigma hemsleyanum Reveals Candidate Genes Involved in Chlorogenic Acid Accumulation
Authors: Yin Shuya , Cui Hairui , Zhang Le , Yan Jianli , Qian Lihua , Ruan Songlin
Published: June 2021

T. hemsleyanum plants with different geographical origins contain enormous genetic variability, which causes different composition and content of flavonoids. In this research, integrated analysis of transcriptome and metabolome were performed in two ecotypes of T. hemsleyanum. There were 5428 different expressed transcripts and 236 differentially accumulated metabolites, phenylpropane and flavonoid biosynthesis were most predominantly enriched. A regulatory network of 9 transcripts and 11 compounds up-regulated in RG was formed, and chlorogenic acid was a core component.
Tetraselmis jejuensis sp. nov. (Chlorodendrophyceae), a Euryhaline Microalga Found in Supralittoral Tide Pools at Jeju Island, Korea
Authors: Hyung Jun-Ho , Kim Eun-Joo , Moon Seung-Joo , Kang Nam Seon , Park Jaeyeon
Published: June 2021

We found the euryhaline microalga, Tetraselmis jejuensis sp. nov., which was adapted to supralittoral tide pools with salinities varying from 0.3–3.1%. Fifteen strains of T. jejuensis were isolated from Daejeong (DJ) and Yongduam (YO), and clonal cultures were established in the laboratory. Morphological characterization revealed that the cells have a compressed shape, four flagella emerging from a depression near the apex in two opposite pairs, a cup-shaped chloroplast containing one pyrenoid surrounded by starch, and eyespot regions not located near the flagellar base. T. jejuensis cells showed distinct characteristics compared to other Tetraselmis species. First, a regular subunit pattern with honeycomb-like structures was predominantly displayed on the surface in the middle of the cell body. Second, the pyrenoid was invaded by both cytoplasmic channels comprising electron-dense material separated from the cytoplasm, and two branches of small cytoplasmic channels (canaliculi) in various directions, which characterize the subgenus Tetrathele. Eyespot regions containing a large number of osmiophilic globules, packed closely together and arranged in subcircular close packing of diverse sizes, were dispersed throughout the chloroplast. In the phylogenetic analysis of small subunit (SSU) rDNA sequences, the 15 strains isolated from DJ and YO separated a newly branched clade in the Chlorodendrophyceae at the base of a clade comprising the T. carteriiformi/subcordiformis clade, T. chuii/suecica clade, and T. striata/convolutae clade. The strains in the diverging clade were considered to belong to the same species. The SSU rDNA sequences of the DJ and YO strains showed a maximum difference of 1.53% and 1.19% compared to Tetraselmis suecica (MK541745), the closest species of the family based on the phylogenetic analysis, respectively. Based on morphological, molecular, and physiological features, we suggest a new species in the genus Tetraselmis named Tetraselmis jejuensis, with the species name “jejuensis” referring to the collection site, Jeju Island, Korea.
A Transcriptional Analysis of the Genes Involved in the Ascorbic Acid Pathways Based on a Comparison of the Juice and Leaves of Navel and Anthocyanin-Rich Sweet Orange Varieties
Authors: Caruso Paola , Russo Maria Patrizia , Caruso Marco , Guardo Mario Di , Russo Giuseppe , Fabroni Simona , Timpanaro Nicolina , Licciardello Concetta
Published: June 2021

Sweet oranges are an important source of ascorbic acid (AsA). In this study, the content of AsA in the juice and leaves of four orange clonal selections, different in terms of maturity time and the presence/absence of anthocyanins, was correlated with the transcription levels of the main genes involved in the biosynthesis, recycling, and degradation pathways. Within each variety, differences in the above pathways and the AsA amount were found between the analysed tissues. Variations were also observed at different stages of fruit development and maturation. At the beginning of fruit development, AsA accumulation was attributable to the synergic action of l-galactose and Myo-inositol, while the l-gulose pathway was predominant between the end of fruit development and the beginning of ripening. In leaves, the l-galactose pathway appeared to play a major role in AsA accumulation, even though higher GalUr isoform expression suggests a synergistic contribution of both pathways in this tissue. In juice, the trend of the AsA content may be related to the decrease in the transcription levels of the GME, GDH, MyoOx, and GalUr12 genes. Newhall was the genotype that accumulated the most AsA. The difference between Newhall and the other varieties seems to be attributable to the GLDH, GalUr12, APX2, and DHAR3 genes.
Nanocelluloses: Sources, Pretreatment, Isolations, Modification, and Its Application as the Drug Carriers
Authors: Lunardi Valentino Bervia , Soetaredjo Felycia Edi , Putro Jindrayani Nyoo , Santoso Shella Permatasari , Yuliana Maria , Sunarso Jaka , Ju Yi-Hsu , Ismadji Suryadi
Published: June 2021

The ‘Back-to-nature’ concept has currently been adopted intensively in various industries, especially the pharmaceutical industry. In the past few decades, the overuse of synthetic chemicals has caused severe damage to the environment and ecosystem. One class of natural materials developed to substitute artificial chemicals in the pharmaceutical industries is the natural polymers, including cellulose and its derivatives. The development of nanocelluloses as nanocarriers in drug delivery systems has reached an advanced stage. Cellulose nanofiber (CNF), nanocrystal cellulose (NCC), and bacterial nanocellulose (BC) are the most common nanocellulose used as nanocarriers in drug delivery systems. Modification and functionalization using various processes and chemicals have been carried out to increase the adsorption and drug delivery performance of nanocellulose. Nanocellulose may be attached to the drug by physical interaction or chemical functionalization for covalent drug binding. Current development of nanocarrier formulations such as surfactant nanocellulose, ultra-lightweight porous materials, hydrogel, polyelectrolytes, and inorganic hybridizations has advanced to enable the construction of stimuli-responsive and specific recognition characteristics. Thus, an opportunity has emerged to develop a new generation of nanocellulose-based carriers that can modulate the drug conveyance for diverse drug characteristics. This review provides insights into selecting appropriate nanocellulose-based hybrid materials and the available modification routes to achieve satisfactory carrier performance and briefly discusses the essential criteria to achieve high-quality nanocellulose.
Feasibility Assessment of Parathyroid Hormone Adsorption by Using Polysaccharide-Based Multilayer Film Systems
Authors: Juang Ruey-Shin , Su Xing , Lee I-Chi
Published: June 2021

Chronic kidney disease (CKD) is a systemic disorder that combines complex bone and mineral abnormalities. The high level of parathyroid hormone (PTH) in the blood causes irreversible renal dysfunction and cardiovascular disease. Therefore, it is necessary to reduce level of PTH in the blood of patients with uremic state. In this study, chitosan and heparin were chosen to form polysaccharide-based multilayer films based on their antibacterial ability, good biocompatibility and hemocompatibility. In addition, a previous study has revealed that PTH is a heparin/polyanion binding protein because of the similarity of heparin to the cell surface proteoglycans. Subsequently, the surface properties including thickness, surface hydrophobicity and surface charge of a series of multilayer films were analyzed. The PTH adsorption rate of a series of multilayer films was also assessed. The results revealed that the optimizing condition is (CHI/HEP)2.5 and 60 min in both PBS only and PBS with the addition of bovine serum albumin, which demonstrated the specific adsorption of PTH on the materials. Furthermore, the hemolysis test also revealed that (CHI/HEP)2.5 shows good blood compatibility. It is considered that polysaccharide-based multilayer films may provide an alternative for the surface modification of hemodialysis membranes and equipment.
Research on the Anticorrosion Properties of CeO2-GO/EP Nanocomposite Coating in Simulated Sea Water
Authors: Liu Xiaoyan , Liu Ruidan , Li Tianyu , Liu Yanqi , Liu Li , Lyu Kai , Shah Surendra P.
Published: June 2021

Graphene is a two-dimensional sheet of regular hexagonal honeycomb lattice formed by sp2 hybrid orbital bonding, with only one layer thickness of a single atom, which is known as the “super king” of the 21st century. Previous studies have shown that cerium oxide-graphene oxide (CeO2-GO(4:1)) nanocomposites eliminated the agglomeration of graphene to some extent and the CeO2-GO(4:1) epoxy coating could be prepared with good anti-corrosion performance. In this paper, CeO2-GO(4:1) nanocomposites were prepared by the hydrothermal synthesis method, and the three-electrode method was used for electrochemical tests. The state evolution of CeO2-GO(4:1)/EP coating and the synergy between CeO2-GO(4:1)/EP and corrosion inhibitor in simulated seawater solution with different concentrations (20%, 40%, 60%) were analyzed and illustrated by Optical Microscope (OM) characterization, Open Circuit Potential (OCP), Electrochemical alternating current Impedance Spectroscopy (EIS), Mott–Schottky curve and Tafel curve. The results indicated that CeO2-GO(4:1) nanocomposites showed good corrosion resistance in a marine environment. This research lays a solid theoretical foundation for the application of cerium oxide-modified graphene oxide anticorrosive coating in marine engineering.
Deciphering the Role of π-Interactions in Polyelectrolyte Complexes Using Rationally Designed Peptides
Authors: Tabandeh Sara , Lemus Cristina Elisabeth , Leon Lorraine
Published: June 2021

Electrostatic interactions, and specifically π-interactions play a significant role in the liquid-liquid phase separation of proteins and formation of membraneless organelles/or biological condensates. Sequence patterning of peptides allows creating protein-like structures and controlling the chemistry and interactions of the mimetic molecules. A library of oppositely charged polypeptides was designed and synthesized to investigate the role of π-interactions on phase separation and secondary structures of polyelectrolyte complexes. Phenylalanine was chosen as the π-containing residue and was used together with lysine or glutamic acid in the design of positively or negatively charged sequences. The effect of charge density and also the substitution of fluorine on the phenylalanine ring, known to disrupt π-interactions, were investigated. Characterization analysis using MALDI-TOF mass spectroscopy, H NMR, and circular dichroism (CD) confirmed the molecular structure and chiral pattern of peptide sequences. Despite an alternating sequence of chirality previously shown to promote liquid-liquid phase separation, complexes appeared as solid precipitates, suggesting strong interactions between the sequence pairs. The secondary structures of sequence pairs showed the formation of hydrogen-bonded structures with a β-sheet signal in FTIR spectroscopy. The presence of fluorine decreased hydrogen bonding due to its inhibitory effect on π-interactions. π-interactions resulted in enhanced stability of complexes against salt, and higher critical salt concentrations for complexes with more π-containing amino acids. Furthermore, UV-vis spectroscopy showed that sequences containing π-interactions and increased charge density encapsulated a small charged molecule with π-bonds with high efficiency. These findings highlight the interplay between ionic, hydrophobic, hydrogen bonding, and π-interactions in polyelectrolyte complex formation and enhance our understanding of phase separation phenomena in protein-like structures.