bluuebunny/crossref_metadata_2025 huggingface dataset:
Ketone Bodies and SIRT1, Synergic Epigenetic Regulators for Metabolic Health: A Narrative Review
Authors: Tozzi Rossella , Cipriani Fiammetta , Masi Davide , Basciani Sabrina , Watanabe Mikiko , Lubrano Carla , Gnessi Lucio , Mariani Stefania
Published: August 2022

Ketone bodies (KBs) and Sirtuin-1 (SIRT1) have received increasing attention over the past two decades given their pivotal function in a variety of biological contexts, including transcriptional regulation, cell cycle progression, inflammation, metabolism, neurological and cardiovascular physiology, and cancer. As a consequence, the modulation of KBs and SIRT1 is considered a promising therapeutic option for many diseases. The direct regulation of gene expression can occur in vivo through histone modifications mediated by both SIRT1 and KBs during fasting or low-carbohydrate diets, and dietary metabolites may contribute to epigenetic regulation, leading to greater genomic plasticity. In this review, we provide an updated overview of the epigenetic interactions between KBs and SIRT1, with a particular glance at their central, synergistic roles for metabolic health.
Associations between Body Composition and Vitamin D Status in Children with Overweight and Obesity Participating in a 1-Year Lifestyle Intervention
Authors: Kasvis Popi , Cohen Tamara R. , Loiselle Sarah-Ève , Hazell Tom J. , Vanstone Catherine A. , Weiler Hope A.
Published: August 2022

Background: To examine associations between body composition and vitamin D status in children participating in a lifestyle intervention. Methods: Children (6–12 y, n = 101) with a body mass index (BMI)-for-age >85th percentile were randomized to six dietitian-led behavior counselling sessions or no intervention. Plasma 25-hydroxyvitamin D (25(OH)D), anthropometry, and body composition using dual-energy X-ray absorptiometry were assessed every 3 months for 1 year. For each anthropometry variable (z-scores), tertiles were created to test for differences in 25(OH)D over time (tertile-by-time), and for changes in the z-score (loss, maintain, gain)-by-time, and according to fat patterning (android vs. gynoid) using mixed effects models. Results: The baseline plasma 25(OH)D was 62.2 nmol/L (95%CI: 58.7–65.7), and none < 30 nmol/L. At 6 mo, children with gynoid fat patterning had higher 25(OH)D concentrations than in those with android fat patterning (64.5 ± 1.1 nmol/L vs. 50.4 ± 1.0 nmol/L, p < 0.003, Cohen’s f = 0.20). Children with the lowest lean mass index z-score at 9 mo had higher plasma 25(OH)D concentrations than children with the highest z-score at baseline, 3 mo, and 6 mo (p < 0.05, Cohen’s f = 0.20). No other significant differences were observed. Conclusion: In this longitudinal study, vitamin D deficiency was not present in children 6–12 y of age with obesity. Reductions in adiposity did not alter the vitamin D status.
SARC-F Is a Predictor of Longer LOS and Hospital Readmission in Hospitalized Patients after a Cardiovascular Event
Authors: Fayh Ana Paula Trussardi , Guedes Francisco Felipe de Oliveira , Calado Guilherme Carlos Filgueira , Queiroz Sandra Azevedo , Anselmo Marina Gabriely Gomes Barbosa , Sousa Iasmin Matias de
Published: August 2022

It is already established that sarcopenia is associated with adverse outcomes; however, few studies have focused on patients who have suffered an acute cardiovascular event. The use of SARC-F, a 5-item sarcopenia screening questionnaire, in these patients remains to be investigated. We aimed to investigate whether SARC-F can predict adverse outcomes in patients admitted to a hospital with a suspected infarction. This is a 1-year prospective cohort study. During hospitalization, patients completed the SARC-F questionnaire (scores ≥ 4 considered positive for the risk of sarcopenia). Length of hospital stay (LOS), new hospital admission, myocardial infarction, and cardiovascular mortality were collected via medical records and phone interviews. In total, 180 patients were evaluated. The median age was 60.6 years; 72.3% of the participants were men, and half of the sample had comorbidities. The median SARC-F score was 1.0 (interquartile range, 0–3.0), and 21.1% of the participants screened positive. Risk of sarcopenia was independently associated with longer LOS (odds ratio, 2.34; 95% CI, 1.09–5.04; p = 0.030) and hospital readmission (odds ratio, 3.73; 95% CI, 1.60–8.69; p = 0.002). One-fifth of post-acute cardiovascular event patients in this cohort screened positive for sarcopenia using the SARC-F screening questionnaire. Positive scores were associated with a longer LOS and hospital readmission.
Association of Vitamin D Supplementation with Cardiovascular Events: A Systematic Review and Meta-Analysis
Authors: Pei Yi-Yan , Zhang Yu , Peng Xing-Chen , Liu Zhe-Ran , Xu Ping , Fang Fang
Published: August 2022

Background: low vitamin D status has been associated with an increased incidence of cardiovascular events. However, whether vitamin D supplementation would reduce the incidence of cardiovascular events remains unclear. Purpose: To perform a systematic review and meta-analysis of the effect of vitamin D supplementation on the mortality and incidence of cardiovascular events. Data Sources: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from their inception until 3 May 2022. Study Selection: Two authors searched for randomized clinical trials that reported vitamin D supplementation’s effect on cardiovascular events outcomes. Data Extraction: Two authors conducted independent data extraction. Data Synthesis: We identified 41,809 reports; after exclusions, 18 trials with a total of 70,278 participants were eligible for analysis. Vitamin D supplementation was not associated with the mortality of cardiovascular events (RR 0.96, 95% CI 0.88–1.06, I2 = 0%), the incidence of stroke (RR 1.05, 95% CI 0.92–1.20, I2 = 0%), myocardial infarction (RR 0.97, 95% CI 0.87–1.09, I2 = 0%), total cardiovascular events (RR 0.97, 95% CI 0.91–1.04, I2 = 27%), or cerebrovascular events (RR 1.01, 95% CI 0.87–1.18, I2 = 0%). Limitation: Cardiovascular events were the secondary outcome in most trials and thus, might be selectively reported. Conclusion: In this meta-analysis of randomized clinical trials, vitamin D supplementation was not associated with a lower risk of cardiovascular events than no supplementation. These findings do not support the routine use of vitamin D supplementation in general.
Efficacy and Safety of Omija (Schisandra chinensis) Extract Mixture on the Improvement of Hyperglycemia: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial
Authors: Kim Da-Som , Baek Hyang-Im , Ha Ki-Chan , Cha Youn-Soo , Park Soo-Jung
Published: August 2022

A previous animal study demonstrated that the administration of Omija extract and soybean mixture (OSM) improved glycemic control in the type 2 diabetes model. In this study, we conducted a 12-week, randomized, double-blinded, and placebo-controlled clinical trial to determine the effects of OSM in humans with hyperglycemia. Participants with fasting plasma concentrations of 100–140 mg/dL were enrolled (n = 80) and administered either OSM or placebo products for 12 weeks. The outcomes included measurements of efficacy (fasting plasma glucose (FPG), postprandial glucose (PPG), fasting plasma insulin (FPI), postprandial insulin (PPI), hemoglobin A1c (HbA1c), C-peptide, fructosamine, and lipid parameters) and safety at baseline and at 12 weeks. After the intervention, the OSM group showed significantly decreased levels of FPG, PPG (30, 60 min), PPI (60 min), insulin area under the curve (AUC), fructosamine, and low-density-lipoprotein (LDL) cholesterol compared to the placebo group. No clinically significant changes in any safety parameter were observed. Therefore, it is hypothesized that OSM supplementation is an effective and safe functional food supplement for humans with hyperglycemia.
High-Protein, Low-Glycaemic Meal Replacement Improves Physical Health-Related Quality of Life in High-Risk Persons for Metabolic Syndrome—A Subanalysis of the Randomised-Controlled ACOORH Trial
Authors: Kempf Kerstin , Röhling Martin , Banzer Winfried , Braumann Klaus Michael , Halle Martin , Schaller Nina , McCarthy David , Predel Hans Georg , Schenkenberger Isabelle , Tan Susanne , Toplak Hermann , Martin Stephan , Berg Aloys ,   on behalf of the ACOORH Study Group
Published: August 2022

While obesity impairs health-related quality of life (HRQOL), lifestyle interventions targeting weight reduction have been effective in improving HRQOL. Therefore, we hypothesised that a meal replacement-based lifestyle intervention, which has been shown to successfully reduce weight, would also improve HRQOL more effectively than a lifestyle intervention alone. In the international, multicenter, randomised-controlled ACOORH-trial (Almased-Concept-against- Overweight-and-Obesity-and-Related-Health-Risk), overweight or obese participants with elevated risk for metabolic syndrome (n = 463) were randomised into two groups. Both groups received telemonitoring devices and nutritional advice. The intervention group additionally used a protein-rich, low-glycaemic meal replacement for 6 months. HRQOL was estimated at baseline, after 3 and 12 months, using the SF-36 questionnaire, and all datasets providing HRQOL data (n = 263) were included in this predefined subanalysis. Stronger improvements in the physical component summary (PCS) were observed in the intervention compared to the control group, peaking after 3 months (estimated treatment difference 2.7 [1.2; 4.2]; p < 0.0001), but also in the long-term. Multiple regression analysis demonstrated that insulin levels and the achieved weight loss were associated with the mental component summary (MCS) after 12 months (p < 0.05). Thus, meal replacement-based lifestyle intervention is not only effective in weight reduction but, concomitantly, in enhancing HRQOL.
Perspectives of Nursing Students on Promoting Reflection in the Clinical Setting: A Qualitative Study
Authors: Alsalamah Yasir , Albagawi Bander , Babkair Lisa , Alsalamah Fahed , Itani Mohammad S. , Tassi Ahmad , Fawaz Mirna
Published: August 2022

Background: Reflection increases meta-cognitive capacities, promotes student-instructor relationships, overcomes the theory-practice gap, and enriches learning. This study aims at exploring nursing students’ perspectives on the facilitators of reflective practices in the clinical setting. Methods: Semi-structured interviews were conducted among 21 Saudi nursing students at one major university in Saudi Arabia. Results: Two major themes were prevalent upon thematic analysis, namely, “Personal Drivers of Reflection” which consisted of “Motivation to Learn”, “Desire to develop”, “Ethical Regard”, and “Responsibility towards patients” and “External Drivers of Reflection” which consisted of “Patient characteristics”, “Case complexity”, and “Competent Instructors”. Conclusion: As per the results of the study, nursing students perceived that they underwent reflection as a response to personal motivational and external educational aspects. According to the findings, instructors should assist students through clinical reflection, with a special focus on their interactions and motivation.
First Human Case of Tick-Borne Encephalitis in Non-Endemic Region in Italy: A Case Report
Authors: Barp Nicole , Cappi Cinzia , Meschiari Marianna , Battistel Marzia , Libbra Maria Vittoria , Ferri Maria Alice , Ballestri Stefano , Gallerani Altea , Ferrari Filippo , Meacci Marisa , Sarti Mario , Capitelli Mariano , Mussini Cristina , Franceschini Erica
Published: August 2022

Tick-borne encephalitis (TBE), a human viral infectious disease caused by the tick-borne encephalitis virus (TBEV), is emerging in Italy, especially in the north-eastern area. No human cases of autochthonous TBE have been reported in Italy’s central regions (such as Emilia-Romagna, Italy). However, here we describe the first human case of TBEV infection in this region, pointing to endemic transmission of TBEV, supporting the concept of circulation of TBEV and of the presence of a possible hot spot in the Serramazzoni region in the Emilian Apennines.
Independent Circulation of Leishmania major and Leishmania tropica in Their Respective Sandfly Vectors for Transmission of Zoonotic and Chronic Cutaneous Leishmaniasis Co-Existing in a Mixed Focus of Central Tunisia
Authors: Abbas Mohammed Abdo Saghir , Lachheb Jihene , Chelbi Ifhem , Louati Dorra , Dachraoui Khalil , Ben Miled Slimene , Zhioua Elyes
Published: August 2022

Zoonotic cutaneous leishmaniasis (ZCL) and chronic cutaneous leishmaniasis (CCL) are known to overlap in Central Tunisia. Sandflies were collected using sticky traps and CDC light-traps set in rodent burrows at the ecotones surrounding the village, in houses, and in animal shelters during July–October 2017, 2018, and 2019. A total of 17,175 sandflies were collected during the three sandfly seasons and identified morphologically to species level. Of a total of 18 sandfly species reported in Tunisia, 16 were identified in this mixed focus of ZCL and CCL. Except for the rocky mountainous areas, Phlebotomus papatasi was the most abundant sandfly species in all biotopes. In the mountainous areas, Phlebotomus sergenti is the most abundant sandfly species belonging to the genus Phlebotomus. Female sandflies were tested for the presence of Leishmania species by PCR. The overall infection prevalence of sandflies with Leishmania major and Leishmania tropica was 0.42% and 0.065%, respectively. The sequencing of PCR-amplified ITS1 products showed that L. major is the predominant species in all biotopes and transmitted mostly by P. papaptasi followed by Phlebotomus longicuspis and Sergentomyia species. Leishmania tropica was detected in Phlebotomus sergenti and in Phlebotomus longicuspis collected in bedrooms and in the ecotone of rocky mountainous areas. Our results provided strong evidence that the proximity of human settlements to biotopes of rodent reservoir hosts of L. major and of L. tropica resulted into the cocirculation of both Leishmania species leading to a mixed focus of ZCL and CCL. The epidemiology of leishmaniases in North Africa is highly complex by the high diversity of sandfly vectors and their associated Leishmania species, leading to a mixed form of cutaneous leishmaniasis. It is of major epidemiological importance to point to the risk of spillover from rural to urban areas leading to the anthroponization of cutaneous leishmaniasis. Therefore, efficient control to reduce the indoor abundance of sandfly vectors in order to reduce the incidence of leishmaniases is urgently needed.
Occurrence and Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Strains Isolated from Hospitalized Patients in Poland—A Single Centre Study
Authors: Sarowska Jolanta , Choroszy-Krol Irena , Jama-Kmiecik Agnieszka , Mączyńska Beata , Cholewa Sylwia , Frej-Madrzak Magdalena
Published: August 2022

The global emergence and spread of genes responsible for the production of ESBL (extended-spectrum beta-lactamases) and carbapenemases in Klebsiella pneumoniae isolates poses a serious threat to public health. The aim of this study was to retrospectively analyze the frequency of occurrence and drug resistance of selected alarm agents isolated from patients of the specialist hospital in Wrocław. A total of 13,528 clinical materials collected from patients of a specialist hospital in Wrocław were analyzed in the period from 1 January 2020 to 31 December 2020. Overall, 3894 bacterial strains were isolated from clinical materials, including 416 K. pneumoniae isolates. K. pneumoniae that showed resistance to ETP (ertapenem) and/or MEM (meropenem) were tested using phenotypic tests for the detection of KPC (carbapenemase-producing Klebsiella), MBL (metallo-β-lactamase) and OXA-48 (oxacilinase-48) carbapenemases. In the case of a positive or doubtful result of the phenotypic test, immunochromatographic tests and the CarbaNP test were performed. In total, 58 K. pneumoniae isolates resistant to 1 or more carbapenem antibiotics were isolated. Of the 58 strains, 16 (27.6%) were isolated from rectal swabs conducted on CPE (carbapenemase-producing Enterobacteriaceae) carriers. In the case of CRE (carbapenem-resistant Enterobacteriaceae) K. pneumoniae, carbapenemases were detected in 28/58 (48.3%) isolates. Notably, 23/28 K. pneumoniae isolates produced MBL/NDM (New Delhi metallo-β-lactamase) (82.1%), 5/28 produced VIM (Verona-intergon-encoded metallo-β-lactamase) (14.3%), and one produced MBL/NDM + OXA-48. Carbapenemases were detected in 13 of 16 (81.3%) carbapenem-resistant K. pneumoniae isolates derived from rectal swabs. The significant participation of CRE and CPE isolates in the infections proves the need to test patients admitted to hospital wards for their status as a CPE carrier in order to limit the emergence of new epidemic outbreaks.
Complete Genomic RNA Sequence of Tuberose Mild Mosaic Virus and Tuberose Mild Mottle Virus Acquired by High-Throughput Sequencing
Authors: Prajapati Malyaj R. , Manav Aakansha , Singhal Pankhuri , Sidharthan Venkidusamy K. , Sirohi Ujjwal , Kumar Mukesh , Bharti Mahesh Kumar , Singh Jitender , Kumar Pankaj , Kumar Ravindra , Prakash Satya , Baranwal Virendra Kumar
Published: August 2022

Tuberose (Polianthes tuberosa) is an ornamental flowering crop of the Amaryllidaceae family. Tuberose mild mosaic virus (TuMMV) and tuberose mild mottle virus (TuMMoV), members of the genus Potyvirus, are ubiquitously distributed in most tuberose growing countries worldwide with low biological incidence. Here, we report the first coding-complete genomic RNA of TuMMV and TuMMoV obtained through high-throughput sequencing (HTS) and further, the presence of both the viruses were confirmed using virus-specific primers in RT-PCR assays. Excluding the poly (A) tail, the coding-complete genomic RNA of TuMMV and TuMMoV was 9485 and 9462 nucleotides (nts) in length, respectively, and contained a single large open reading frame (ORF). Polyprotein encoded by both the viral genomes contained nine putative cleavage sites. BLASTn analysis of TuMMV and TuMMoV genomes showed 72.40–76.80% and 67.95–77% nucleotide sequence similarities, respectively, with the existing potyviral sequences. Phylogenetic analysis based on genome sequences showed that TuMMV and TuMMoV clustered in a distinct clade to other potyviruses. Further studies are required to understand the mechanism of symptom development, distribution, genetic variability, and their possible threat to tuberose production in India.
Progress in Prophylactic and Therapeutic EBV Vaccine Development Based on Molecular Characteristics of EBV Target Antigens
Authors: Rozman Marija , Korać Petra , Jambrosic Karlo , Židovec Lepej Snjezana
Published: August 2022

Epstein–Barr virus (EBV) was discovered in 1964 in the cell line of Burkitt lymphoma and became first known human oncogenic virus. EBV belongs to the Herpesviridae family, and is present worldwide as it infects 95% of people. Infection with EBV usually happens during childhood when it remains asymptomatic; however, in adults, it can cause an acute infection known as infectious mononucleosis. In addition, EBV can cause wide range of tumors with origins in B lymphocytes, T lymphocytes, and NK cells. Its oncogenicity and wide distribution indicated the need for vaccine development. Research on mice and cultured cells as well as human clinical trials have been in progress for a few decades for both prophylactic and therapeutic EBV vaccines. The main targets of the vaccines are EBV envelope glycoproteins such as gp350 and EBV latent genes. The long wait for the EBV vaccine is due to the complexity of the EBV replication cycle and the wide range of its host cells. Although some strategies such as the use of dendritic cells and recombinant Vaccinia viral vectors have shown success, ongoing clinical trials using mRNA-based vaccines as well as new delivery systems as nanoparticles are yet to show the best choice of vaccine target and its production strategy.
Impact of MnTBAP and Baricitinib Treatment on Hutchinson–Gilford Progeria Fibroblasts
Authors: Vehns Elena , Arnold Rouven , Djabali Karima
Published: August 2022

Hutchinson–Gilford progeria syndrome (HGPS) is a rare premature aging disease. It is caused by a mutation in the LMNA gene, which results in a 50-amino-acid truncation of prelamin A. The resultant truncated prelamin A (progerin) lacks the cleavage site for the zinc-metallopeptidase ZMPSTE24. Progerin is permanently farnesylated, carboxymethylated, and strongly anchored to the nuclear envelope. This leads to abnormalities, such as altered nuclear shape, mitochondrial dysfunction, and inflammation. HGPS patients display symptoms of physiological aging, including atherosclerosis, alopecia, lipodystrophy, and arthritis. Currently, no cure for HGPS exists. Here we focus on a drug combination consisting of the superoxide dismutase mimetic MnTBAP and JAK1/2 inhibitor baricitinib (Bar) to restore phenotypic alterations in HGPS fibroblasts. Treating HGPS fibroblasts with the MnTBAP/Bar combination improved mitochondrial functions and sustained Bar’s positive effects on reducing progerin and pro-inflammatory factor levels. Collectively, MnTBAP/Bar combination treatment ameliorates the aberrant phenotype of HGPS fibroblasts and is a potential treatment strategy for patients with HGPS.
Design, Synthesis, and Antitumor Evaluation of Novel Mono-Carbonyl Curcumin Analogs in Hepatocellular Carcinoma Cell
Authors: Yu Pan , Cao Weiya , Zhao Linguo , Han Qing , Yang Shilong , Yang Kepeng , Pan Xiaolei , Wang Qianyun , Wang Yuan
Published: August 2022

Curcumin is a polyphenolic natural product that has promising anticancer properties. However, its clinical utility is limited by its chemical instability and poor metabolic properties. In this paper, a series of new curcumin analogs were synthesized and found to be potent antiproliferative agents against the HepG2 cell line by MTT assay. In general, Group B with single ketone and group C with chalcone were markedly more cytotoxic than group A with diketone. Compound B5 was found as the most potent analog (IC50 = 11.33 μM) compared to curcumin (IC50 = 32.83 μM) and the mechanism of its cytotoxicity was investigated. The result of the wound healing assay indicated B5 strong potential to suppress HepG2 cell migration in a dose- and time-dependent manner. Subsequent assays (including JC-1 staining, Bcl-2, and caspase 3 protein levels by Western blotting) confirmed that B5 exposure induced apoptosis in HepG2 cells. Curcumin-induced comprehensive transcriptomes profile, Western blotting, molecular docking, and molecular dynamics analysis showed that the mechanism may relate to the regulation of cellular metabolic process and the expression of AKT protein. Taken together, we could conclude that curcumin and its analogs induced HepG2 cell proliferation, migration, and apoptosis via AKT signaling pathway and the mitochondrial death pathway. This study could lay the foundation for optimizing curcumin and provide valuable information for finding novel anti-HCC drugs.
Metabolic Pathways of Leishmania Parasite: Source of Pertinent Drug Targets and Potent Drug Candidates
Authors: Jain Surbhi , Sahu Utkarsha , Kumar Awanish , Khare Prashant
Published: August 2022

Leishmaniasis is a tropical disease caused by a protozoan parasite Leishmania that is transmitted via infected female sandflies. At present, leishmaniasis treatment mainly counts on chemotherapy. The currently available drugs against leishmaniasis are costly, toxic, with multiple side effects, and limitations in the administration route. The rapid emergence of drug resistance has severely reduced the potency of anti-leishmanial drugs. As a result, there is a pressing need for the development of novel anti-leishmanial drugs with high potency, low cost, acceptable toxicity, and good pharmacokinetics features. Due to the availability of preclinical data, drug repurposing is a valuable approach for speeding up the development of effective anti-leishmanial through pointing to new drug targets in less time, having low costs and risk. Metabolic pathways of this parasite play a crucial role in the growth and proliferation of Leishmania species during the various stages of their life cycle. Based on available genomics/proteomics information, known pathways-based (sterol biosynthetic pathway, purine salvage pathway, glycolysis, GPI biosynthesis, hypusine, polyamine biosynthesis) Leishmania-specific proteins could be targeted with known drugs that were used in other diseases, resulting in finding new promising anti-leishmanial therapeutics. The present review discusses various metabolic pathways of the Leishmania parasite and some drug candidates targeting these pathways effectively that could be potent drugs against leishmaniasis in the future.
Preparation and Study of Solid Lipid Nanoparticles Based on Curcumin, Resveratrol and Capsaicin Containing Linolenic Acid
Authors: Cassano Roberta , Serini Simona , Curcio Federica , Trombino Sonia , Calviello Gabriella
Published: August 2022

Linolenic acid (LNA) is the most highly consumed polyunsaturated fatty acid found in the human diet. It possesses anti-inflammatory effects and the ability to reverse skin-related disorders related to its deficiency. The purpose of this work was to encapsulate LNA in solid lipid nanoparticles (SLNs) based on curcumin, resveratrol and capsaicin for the treatment of atopic dermatitis. These compounds were first esterified with oleic acid to obtain two moonoleate and one oleate ester, then they were used for SLN matrix realization through the emulsification method. The intermediates of the esterification reaction were characterized by FT-IR and 1N-MR analysis. SLNs were characterized by dimensional analysis and encapsulation efficiency. Skin permeation studies, antioxidant and anti-inflammatory activities were evaluated. LNA was released over 24 h from nanoparticles, and resveratrol monooleate-filled SLNs exhibited a good antioxidant activity. The curcumin-based SLNs loaded or not with LNA did not induce significant cytotoxicity in NCTC 2544 and THP-1 cells. Moreover, these SLNs loaded with LNA inhibited the production of IL-6 in NCTC 2544 cells. Overall, our data demonstrate that the synthesized SLNs could represent an efficacious way to deliver LNA to skin cells and to preserve the anti-inflammatory properties of LNA for the topical adjuvant treatment of atopic dermatitis.
Methylphenidate Analogues as a New Class of Potential Disease-Modifying Agents for Parkinson’s Disease: Evidence from Cell Models and Alpha-Synuclein Transgenic Mice
Authors: Casiraghi Andrea , Longhena Francesca , Faustini Gaia , Ribaudo Giovanni , Suigo Lorenzo , Camacho-Hernandez Gisela Andrea , Bono Federica , Brembati Viviana , Newman Amy Hauck , Gianoncelli Alessandra , Straniero Valentina , Bellucci Arianna , Valoti Ermanno
Published: August 2022

Parkinson’s disease (PD) is characterized by dopaminergic nigrostriatal neurons degeneration and Lewy body pathology, mainly composed of α-synuclein (αSyn) fibrillary aggregates. We recently described that the neuronal phosphoprotein Synapsin III (Syn III) participates in αSyn pathology in PD brains and is a permissive factor for αSyn aggregation. Moreover, we reported that the gene silencing of Syn III in a human αSyn transgenic (tg) mouse model of PD at a pathological stage, manifesting marked insoluble αSyn deposits and dopaminergic striatal synaptic dysfunction, could reduce αSyn aggregates, restore synaptic functions and motor activities and exert neuroprotective effects. Interestingly, we also described that the monoamine reuptake inhibitor methylphenidate (MPH) can recover the motor activity of human αSyn tg mice through a dopamine (DA) transporter-independent mechanism, which relies on the re-establishment of the functional interaction between Syn III and α-helical αSyn. These findings support that the pathological αSyn/Syn III interaction may constitute a therapeutic target for PD. Here, we studied MPH and some of its analogues as modulators of the pathological αSyn/Syn III interaction. We identified 4-methyl derivative I-threo as a lead candidate modulating αSyn/Syn III interaction and having the ability to reduce αSyn aggregation in vitro and to restore the motility of αSyn tg mice in vivo more efficiently than MPH. Our results support that MPH derivatives may represent a novel class of αSyn clearing agents for PD therapy.
A Pseudovirus Nanoparticle-Based Trivalent Rotavirus Vaccine Candidate Elicits High and Cross P Type Immune Response
Authors: Xia Ming , Huang Pengwei , Tan Ming
Published: August 2022

Rotavirus infection continues to cause significant morbidity and mortality globally. In this study, we further developed the S60-VP8* pseudovirus nanoparticles (PVNPs) displaying the glycan receptor binding VP8* domains of rotavirus spike proteins as a parenteral vaccine candidate. First, we established a scalable method for the large production of tag-free S60-VP8* PVNPs representing four rotavirus P types, P[8], P[4], P[6], and P[11]. The approach consists of two major steps: selective precipitation of the S-VP8* proteins from bacterial lysates using ammonium sulfate, followed by anion exchange chromatography to further purify the target proteins to a high purity. The purified soluble proteins self-assembled into S60-VP8* PVNPs. Importantly, after intramuscular injections, the trivalent vaccine consisting of three PVNPs covering VP8* antigens of P[8], P[4], and P[6] rotaviruses elicited high and broad immunogenicity in mice toward the three predominant P-type rotaviruses. Specifically, the trivalent vaccine-immunized mouse sera showed (1) high and balanced IgG and IgA antibody titers toward all three VP8* types, (2) high blocking titer against the VP8*-glycan receptor interaction, and (3) high and broad neutralizing titers against replications of all P[8], P[4], and P[6] rotaviruses. Therefore, trivalent S60-VP8* PVNPs are a promising non-replicating, parenteral vaccine candidate against the most prevalent rotaviruses worldwide.
Lentiviral Vectors for Ocular Gene Therapy
Authors: Arsenijevic Yvan , Berger Adeline , Udry Florian , Kostic Corinne
Published: August 2022

This review offers the basics of lentiviral vector technologies, their advantages and pitfalls, and an overview of their use in the field of ophthalmology. First, the description of the global challenges encountered to develop safe and efficient lentiviral recombinant vectors for clinical application is provided. The risks and the measures taken to minimize secondary effects as well as new strategies using these vectors are also discussed. This review then focuses on lentiviral vectors specifically designed for ocular therapy and goes over preclinical and clinical studies describing their safety and efficacy. A therapeutic approach using lentiviral vector-mediated gene therapy is currently being developed for many ocular diseases, e.g., aged-related macular degeneration, retinopathy of prematurity, inherited retinal dystrophies (Leber congenital amaurosis type 2, Stargardt disease, Usher syndrome), glaucoma, and corneal fibrosis or engraftment rejection. In summary, this review shows how lentiviral vectors offer an interesting alternative for gene therapy in all ocular compartments.
A Systematic Approach to Providing COVID-19 Vaccinations in the Community by Student Pharmacists
Authors: Luli Alex J. , Morello Candis M. , Lorentz Sarah M. , Bounthavong Mark , Brandl Katharina , Hart Laura A.
Published: August 2022

Doctor of Pharmacy (PharmD) students and faculty at University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) were highly motivated to support local and regional COVID-19 vaccination efforts, which began in January 2021. A system was created to streamline requests for SSPPS volunteers, maximize opportunities for student learning and engagement, and ensure adherence to pharmacy practice standards and laws in the process of assisting with vaccination efforts in the community. An existing model for approving student organized events was modified to fit additional needs for COVID-19 vaccination efforts by SSPPS students and faculty. For each event, students completed a standardized form containing event details including location, date, time, pharmacist preceptors, and duties. All requests were screened by designated SSPPS faculty to ensure student safety, availability, and feasibility. After each event, students and faculty completed a unique online form designed to track volunteer hours. Students received course credit for volunteering and completing a standardized self-reflection. Comments from students’ reflections (n = 74) were analyzed to identify common challenges. Between 11 January 2021 and 31 May 2021, SSPPS faculty and students volunteered for 245 shifts, totaling 1346 h. Students encountered several logistical challenges, such as availability of vaccines. The system utilized allowed for SSPPS students and faculty to play an integral role in COVID-19 vaccination efforts throughout the region.
AI-Enabled Intelligent Visible Light Communications: Challenges, Progress, and Future
Authors: Shi Jianyang , Niu Wenqing , Ha Yinaer , Xu Zengyi , Li Ziwei , Yu Shaohua , Chi Nan
Published: August 2022

Visible light communication (VLC) is a highly promising complement to conventional wireless communication for local-area networking in future 6G. However, the extra electro-optical and photoelectric conversions in VLC systems usually introduce exceeding complexity to communication channels, in particular severe nonlinearities. Artificial intelligence (AI) techniques are investigated to overcome the unique challenges in VLC, whereas considerable obstacles are found in practical VLC systems applied with intelligent learning approaches. In this paper, we present a comprehensive study of the intelligent physical and network layer technologies for AI-empowered intelligent VLC (IVLC). We first depict a full model of the visible light channel and discuss its main challenges. The advantages and disadvantages of machine learning in VLC are discussed and analyzed by simulation. We then present a detailed overview of advances in intelligent physical layers, including optimal coding, channel emulator, MIMO, channel equalization, and optimal decision. Finally, we envision the prospects of IVLC in both the intelligent physical and network layers. This article lays out a roadmap for developing machine learning-based intelligent visible light communication in 6G.
Orbital Angular Momentum of Superpositions of Optical Vortices Perturbed by a Sector Aperture
Authors: Kovalev Alexey A. , Kotlyar Victor V.
Published: August 2022

In optical communications, it is desirable to know some quantities describing a light field, which are conserved on propagation or resistant to some distortions. Typically, optical vortex beams are characterized by their orbital angular momentum (OAM) and/or topological charge (TC). Here, we show analytically that the OAM of a single rotationally symmetric optical vortex is not affected by an arbitrary-shape aperture or by other amplitude perturbations. For a superposition of two or several optical vortices (with different TCs), we studied what happens to its OAM when it is distorted by a hard-edge sector aperture. We discovered several cases when such perturbation does not violate the OAM of the whole superposition. The first case is when the incident beam consists of two vortices of the same power. The second case is when the aperture half-angle equals π multiplied by an integer number and divided by the difference between the topological charges. For more than two incident beams, this angle equals π multiplied by an integer number and divided by the greatest common divisor of all possible differences between the topological charges. We also show that such a sector aperture also conserves the orthogonality between the complex amplitudes of the constituent vortex beams. For two incident vortex beams with real-valued radial envelopes of the complex amplitudes, the OAM is also conserved, when there is a ±π/2 phase delay between the beams. When two beams with the same power pass through a binary radial grating, their total OAM is also conserved. We hope that these findings could be useful for optical communications since they allow for the identification of incoming optical signals by their OAM by registering only part of the light field within a sector aperture, thus reducing the cost of the receiving devices.
A Theoretical Design of Chiral Molecules through Conformational Lock towards Circularly Polarized Luminescence
Authors: Wang Lewen , He Tengfei , Liao Hailiang , Luo Yige , Ou Wen , Yu Yinye , Yue Wan , Long Guankui , Wei Xingzhan , Zhou Yecheng
Published: August 2022

Circularly polarized (CP) light has shown great potential in quantum computing, optical communications, and three-dimensional displays. It is still a challenge to produce high-efficiency and high-purity CP light. Herein, we proposed a strategy to design chiral organic small molecules for CP light generation. These kinds of chiral molecules are formed by achiral light-emitting groups and achiral alkyl chains through conformational lock, which indicates that chirality can also be introduced into achiral light-emitting groups through rational molecular design. The chirality of these molecules can be further tuned by changing the length of the alkyl chains connecting the diketopyrrolopyrrole unit. The chiroptical properties of these molecules are confirmed by calculated electronic circular dichroism and chiral emission spectra, and further confirmed in experiments. The strategy developed in this work will greatly enlarge the candidate library of chiral luminescent materials.
Existence of Purely Alvén Waves in Magnetic Flux Tubes with Arbitrary Cross-Sections
Authors: Ruderman Michael S. , Petrukhin Nikolai S.
Published: August 2022

We study linear torsional Alfvén waves in a magnetic flux tube with an arbitrary cross-section. We assume that the equilibrium magnetic field is propagating in the z-direction in Cartesian coordinates x,y, and z. The tube cross-section is bounded by a smooth closed curve. Both plasma and magnetic field are homogeneous outside this curve. The magnetic field magnitude is a function of x and y, while the density is a product of two functions: one dependent on z and the other dependent on x and y. As a result, the Alfvén speed is also equal to V0(x,y) times a function of z. We define Alfvén waves as waves that do not disturb plasma density. We show that these waves can exist only when the magnetic field magnitude is a function of V0. When the condition of existence of Alfvén waves is satisfied, the waves are polarised in the directions tangent to the level lines of V0(x,y) and orthogonal to the equilibrium magnetic field. We found that the Alfvén wave amplitude has a specific form that depends on a particular coordinate system.
Responses of Diversity and Productivity to Organo-Mineral Fertilizer Inputs in a High-Natural-Value Grassland, Transylvanian Plain, Romania
Authors: Gaga Ioan , Pacurar Florin , Vaida Ioana , Plesa Anca , Rotar Ioan
Published: August 2022

Ecosystems with high natural value (HNV) have generally been maintained by agricultural practices and are increasingly important for the ecosystem services that they provide and for their socio-economic impact in the ever-changing context. Biodiversity conservation is one of the main objectives of the European Green Deal, which aims to address biodiversity loss, including the potential extinction of one million species. The aim of this research was to trace the effects of organic and mineral fertilizers on the floristic composition, but also on the number of species, of the grasslands with high biodiversity (HNV) from the Transylvanian Plain, Romania. The experiments were established in 2018 on the nemoral area and analyzed the effect of a gradient of five organic and mineral treatments. Fertilization with 10 t ha−1 manure or N50 P25K25 ensures an increase in yield and has a small influence on diversity, and it could be a potential strategy for the maintenance and sustainable use of HNV grasslands. Each fertilization treatment determined species with indicator value that are very useful in the identification and management of HNV grasslands. The dry matter biomass increases proportionally as the amounts of fertilizer applied increase and the number of species decreases.
Effects of Different Microbial Fertilizers on Growth and Rhizosphere Soil Properties of Corn in Newly Reclaimed Land
Authors: Li Xuqing , Lu Qiujun , Li Dingyi , Wang Daoze , Ren Xiaoxu , Yan Jianli , Ahmed Temoor , Li Bin
Published: August 2022

Land reclamation may expand the supply of usable land for food security. Soil microorganisms have been considered as an amendment in immature soil to improve its quality. However, different microbial fertilizers’ effects on plant growth in immature soil have largely been unexplored. In order to evaluate the effects of different microbial fertilizers on immature soil, the soil quality and microbial community structure of corn rhizosphere soil samples under different microbial fertilizers were investigated. The results revealed a significant difference between microbial fertilizers (especially seaweed microbial fertilizer, SMF) and commercial chemical compound fertilizers in the soil properties and microbial community structure. Indeed, SMF caused a 486.21%, 23.17%, 21.08%, 38.33%, and 482.39% increase in Flavobacteriaceae, Planctomycetaceae, Chitinophagaceae, Acidobacteria_Gp3, and Mortierellaceae but a 23.82%, 18.66%, 42.36%, 29.12%, 81.97%, 42.19%, and 99.33% reduction in Cytophagales, Comamonadaceae, Rhodospirillaceae, Sinobacteaceae, Aspergillaceae, Myrmecridiaceae, and Typhulaceae, respectively; while CCF caused an 85.68% and 183.22% increase in Xanthomonadaceae and Mortierellaceae but a 31.29%, 36.02%, and 65.74% reduction in Cytophagales, Spartobacteria, and Cyphellophoraceae compared with the control based on 16S and ITS amplicon sequencing of soil microflora. Furthermore, redundancy discriminant analysis of the microbial communities and soil properties indicated that the main variables of the bacterial and fungal communities included exchangeable Ca, organic matter content, total N, and available P. Overall, the results of this study revealed significant changes under different fertilizer conditions in the microbiota and chemical properties of corn soil. Microbial fertilizers, particularly SMF and SM, can be used as a good amendment for newly reclaimed land.
Nitrapyrin Mitigates Nitrous Oxide Emissions, and Improves Maize Yield and Nitrogen Efficiency under Waterlogged Field
Authors: Ren Baizhao , Ma Zhentao , Zhao Bin , Liu Peng , Zhang Jiwang
Published: August 2022

In order to explore the effects of nitrapyrin (N-Serve) application on greenhouse gas emission and nitrogen (N) leaching of a waterlogged maize (Zea mays L.) field, we investigated the effects of applying nitrapyrin on soil ammonium (NH4+-N) and nitrate nitrogen (NO3−-N) content, nitrous oxide (N2O) fluxes, and the warming potential (GWPN2O) in a waterlogged maize field. The design included three treatments: waterlogging treatment with only urea application (V-3WL), waterlogging treatment with urea and nitrapyrin application (V-3WL+N), and no waterlogging treatment applying only urea (CK). Our results revealed that waterlogging led to the increase of nitrate concentrations across the soil profile, thus potentially increasing N leaching and decreasing N use efficiency. The accumulated N2O emissions increased significantly in waterlogged plots compared to control plots, and maximum N2O emission fluxes occurred during the process of soil drying after waterlogging; this resulted in an increase in GWPN2O and N2O greenhouse gas intensity (GHGIN2O) by 299% and 504%, respectively, compared to those of CK. However, nitrapyrin application was able to reduce N2O emissions. Nitrapyrin application was also good for decreasing GWPN2O and GHGIN2O by 34% and 50%, respectively, compared to V-3WL. In addition, nitrapyrin application was conducive to reduce N leaching and improve N use efficiency, resulting in a yield increase by 34%, compared to that of V-3WL. The application of nitrapyrin helped to mitigate agriculture-source greenhouse effects and N leaching induced by waterlogging, and was a high N-efficient fertilizer method for a waterlogged field.
Valorization of Traditional Italian Walnut (Juglans regia L.) Production: Genetic, Nutritional and Sensory Characterization of Locally Grown Varieties in the Trentino Region
Authors: Di Pierro Erica A. , Franceschi Pietro , Endrizzi Isabella , Farneti Brian , Poles Lara , Masuero Domenico , Khomenko Iuliia , Trenti Francesco , Marrano Annarita , Vrhovsek Urska , Gasperi Flavia , Biasioli Franco , Guella Graziano , Bianco Luca , Troggio Michela
Published: August 2022

Juglans regia (L.) is cultivated worldwide for its nutrient-rich nuts. In Italy, despite the growing demand, walnut cultivation has gone through a strong decline in recent decades, which led to Italy being among the top five net importing countries. To promote the development of local high-quality Italian walnut production, we devised a multidisciplinary project to highlight the distinctive traits of three varieties grown in the mountainous region Trentino (northeast of Italy): the heirloom ‘Bleggiana’, a second local accession called local Franquette and the French cultivar ‘Lara’, recently introduced in the local production to increase yield. The genetic characterization confirmed the uniqueness of ‘Bleggiana’ and revealed local Franquette as a newly described autochthonous variety, thus named ‘Blegette’. The metabolic profiles highlighted a valuable nutritional composition of the local varieties, richer in polyphenols and with a lower ω-6/ω-3 ratio than the commercial ‘Lara’. ‘Blegette’ obtained the highest preference scores from consumers for both the visual aspect and tasting; however, the volatile organic compound profiles did not discriminate among the characterized cultivars. The described local varieties represent an interesting reservoir of walnut genetic diversity and quality properties, which deserve future investigation on agronomically useful traits (e.g., local adaptation and water usage) for a high-quality and sustainable production.