bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms and Outcomes of Metabolic Surgery in Type 2 Diabetes
Authors: Fazliana Mansor , Nor Hanipah Zubaidah
Published: November 2022

This review is aimed at synthesizing the mechanisms and outcomes of metabolic surgery on the endocrine system, microbiome, metabolomics, and at the molecular level. We review the hormonal, adipokine, microbiota, microRNA, and metabolomic changes in human and animal models following metabolic surgery for the treatment of obesity and diabetes. The most relevant studies in this area over the past 17 years have been considered for this review. In most cases, metabolic procedures, especially those that include intestinal bypass components, showed the remission of type 2 diabetes. This involves a variety of weight-independent mechanisms to improve glucose homeostasis, improving insulin sensitivity and secretion, gut microbiota, and bile acid cross-talk.
A Heterogeneity-Aware Replacement Policy for the Partitioned Cache on Asymmetric Multi-Core Architectures
Authors: Fang Juan , Kong Han , Yang Huijing , Xu Yixiang , Cai Min
Published: November 2022

In an asymmetric multi-core architecture, multiple heterogeneous cores share the last-level cache (LLC). Due to the different memory access requirements among heterogeneous cores, the LLC competition is more intense. In the current work, we propose a heterogeneity-aware replacement policy for the partitioned cache (HAPC), which reduces the mutual interference between cores through cache partitioning, and tracks the shared reuse state of each cache block within the partition at runtime to guide the replacement policy to keep cache blocks shared by multiple cores in multithreaded programs. In the process of updating the reuse state, considering the difference of memory accesses to LLC by heterogeneous cores, the cache replacement policy tends to keep cache blocks required by big cores, to better improve the LLC access efficiency of big cores. Compared with LRU and the SRCP, which are the state-of-the-art cache replacement algorithms, the performance of big cores can be significantly improved by HAPC when running multithreaded programs, while the impact on little cores is almost negligible, thus improving the overall performance of the system.
Kinetic Model and Experiment for Self-Ignition of Triethylaluminum and Triethylborane Droplets in Air
Authors: Frolov Sergey M. , Basevich Valentin Y. , Belyaev Andrey A. , Shamshin Igor O. , Aksenov Viktor S. , Frolov Fedor S. , Storozhenko Pavel A. , Guseinov Shirin L.
Published: November 2022

Triethylaluminum Al(C2H5)3, TEA, and triethylborane, B(C2H5)3, TEB, are transparent, colorless, pyrophoric liquids with boiling points of approximately 190 °C and 95 °C, respectively. Upon contact with ambient air, TEA, TEB, as well as their mixtures and solutions, in hydrocarbon solvents, ignite. They can also violently react with water. TEA and TEB can be used as hypergolic rocket propellants and incendiary compositions. In this manuscript, a novel scheme of the heterogeneous interaction of gaseous oxygen with liquid TEA/TEB microdroplets accompanied by the release of light hydrocarbon radicals into the gas phase is used for calculating the self-ignition of a spatially homogeneous mixture of fuel microdroplets in ambient air at normal pressure and temperature (NPT) conditions. In the primary initiation step, TEA and TEB react with oxygen, producing an ethyl radical, which can initiate an autoxidation chain. The ignition delay is shown to decrease with the decrease in the droplet size. Preliminary experiments on the self-ignition of pulsed and continuous TEA–TEB sprays in ambient air at NPT conditions are used for estimating the Arrhenius parameters of the rate-limiting reaction. Experiments confirm that the self-ignition delay of TEA–TEB sprays decreases with the injection pressure and provide the data for estimating the activation energy of the rate-limiting reaction, which appears to be close to 2 kcal/mol.
A Methylotrophic Bacterium Growing with the Antidiabetic Drug Metformin as Its Sole Carbon, Nitrogen and Energy Source
Authors: Chaignaud Pauline , Gruffaz Christelle , Borreca Adrien , Fouteau Stéphanie , Kuhn Lauriane , Masbou Jérémy , Rouy Zoé , Hammann Philippe , Imfeld Gwenaël , Roche David , Vuilleumier Stéphane
Published: November 2022

Metformin is one of the most prescribed antidiabetic agents worldwide and is also considered for other therapeutic applications including cancer and endocrine disorders. It is largely unmetabolized by human enzymes and its presence in the environment has raised concern, with reported toxic effects on aquatic life and potentially also on humans. We report on the isolation and characterisation of strain MD1, an aerobic methylotrophic bacterium growing with metformin as its sole carbon, nitrogen and energy source. Strain MD1 degrades metformin into dimethylamine used for growth, and guanylurea as a side-product. Sequence analysis of its fully assembled genome showed its affiliation to Aminobacter niigataensis. Differential proteomics and transcriptomics, as well as mini-transposon mutagenesis of the strain, point to genes and proteins essential for growth with metformin and potentially associated with hydrolytic C-N cleavage of metformin or with cellular transport of metformin and guanylurea. The obtained results suggest the recent evolution of the growth-supporting capacity of strain MD1 to degrade metformin. Our results identify candidate proteins of the enzymatic system for metformin transformation in strain MD1 and will inform future research on the fate of metformin and its degradation products in the environment and in humans.
Developing New Tools to Fight Human Pathogens: A Journey through the Advances in RNA Technologies
Authors: Costa Vanessa G. , Costa Susana M. , Saramago Margarida , Cunha Marta V. , Arraiano Cecília M. , Viegas Sandra C. , Matos Rute G.
Published: November 2022

A long scientific journey has led to prominent technological advances in the RNA field, and several new types of molecules have been discovered, from non-coding RNAs (ncRNAs) to riboswitches, small interfering RNAs (siRNAs) and CRISPR systems. Such findings, together with the recognition of the advantages of RNA in terms of its functional performance, have attracted the attention of synthetic biologists to create potent RNA-based tools for biotechnological and medical applications. In this review, we have gathered the knowledge on the connection between RNA metabolism and pathogenesis in Gram-positive and Gram-negative bacteria. We further discuss how RNA techniques have contributed to the building of this knowledge and the development of new tools in synthetic biology for the diagnosis and treatment of diseases caused by pathogenic microorganisms. Infectious diseases are still a world-leading cause of death and morbidity, and RNA-based therapeutics have arisen as an alternative way to achieve success. There are still obstacles to overcome in its application, but much progress has been made in a fast and effective manner, paving the way for the solid establishment of RNA-based therapies in the future.
Impact of Recycled Process Water on Electrochemical Reactivity of Sulphide Ore
Authors: Musuku Benjamin , Dahl Olli
Published: November 2022

The Kevitsa Cu–Ni sequential flotation process is characterised by poor nickel recovery during summer periods (May–September). Evidently, the process water matrix in summer is different from that in other seasons; however, the Cu flotation performance is scarcely affected by the changes in the water matrix across the seasons. Increasingly different process water quality was generated through a grinding-and-dissolution protocol and its impact on the electrochemical reactivity of sulphide ore was studied. The main objective of this approach was to mimic the increasingly different quality of plant process water emanating from a closed-process water loop. Dissolved oxygen demand tests were conducted on the Kevitsa ore using water of varying quality from dissolution loops. The effect of the temperature and fine grind on the oxidation rates was also investigated. The study was coupled with EDTA metal ion extraction and xanthate adsorption tests. These showed that the number of dissolution loops, which has an impact on water quality, has a direct impact on the rate of oxidation of the ore. A fine grind and high temperature both increase the oxidation rates of the ore. The Kevitsa ore is most reactive in the first 10–20 min after milling. Furthermore, oxidation rates are also driven by the amount of pyrrhotite in the ore, with chalcopyrite being the least reactive, as indicated by the EDTA data. Xanthate adsorption is impacted by the water quality and fine grind. The combined effect of water quality, temperature and fine grind is expected to influence the flotation behaviour of sulphide minerals. The poor nickel recovery of the Kevitsa ore during the summer period is attributable to the unfavourable process water quality, which accelerates the oxidation of the ore during the summer period.
Reduction in Skeletal Muscle Mass in Progressive Supranuclear Palsy in Comparison with Parkinson’s Disease: A Preliminary Retrospective Longitudinal Study
Authors: Takamatsu Yasuyuki , Aiba Ikuko
Published: November 2022

Progressive supranuclear palsy (PSP) manifests with the loss of skeletal muscle mass, but the longitudinal changes have not been investigated. We studied changes in body composition, including in skeletal muscle mass, in patients with PSP twice, approximately 1 year or more apart, and we compared these measurements with those of patients with Parkinson’s disease (PD). The total number of participants was 42: 10 men had PD, 13 men had PSP, 8 women had PD, and 11 women had PSP. Using a body composition analyzer, we measured such parameters as body mass index (BMI), skeletal muscle mass, basal metabolic rate (BMR), body fat percentage (BFP), and the ratio of extracellular water to total body water. We also calculated the skeletal muscle mass index (SMI). We measured the Barthel index to assess activities of daily living. The Barthel index was lower in patients with PSP than in those with PD at the first evaluation, and it worsened by the time of the second evaluation. In men with PSP, skeletal muscle mass was far more reduced than in those with PD, but no such changes were found among women with either disease. The SMI of men with PSP was correlated significantly with BMI, BMR, BFP, and the Barthel index. Skeletal muscle mass diminished faster in patients with PSP, especially in men, than in patients with PD, probably because of inactivity.
A Novel Strategy to Enhance the Photostability of InP/ZnSe/ZnS Quantum Dots with Zr Doping
Authors: Cheng Xunqiang , Liu Mingming , Zhang Qinggang , He Mengda , Liao Xinrong , Wan Qun , Zhan Wenji , Kong Long , Li Liang
Published: November 2022

Plentiful research of InP semiconductor quantum dots (QDs) has been launched over the past few decades for their excellent photoluminescence properties and environmentally friendly characteristics in various applications. However, InP QDs show inferior photostability because they are extremely sensitive to the ambient environment. In this study, we propose a novel method to enhance the photostability of InP/ZnSe/ZnS QDs by doping zirconium into the ZnS layer. We certify that Zr can be oxidized to Zr oxides, which can prevent the QDs from suffering oxidation during light irradiation. The InP/ZnSe/ZnS:Zr QDs maintained 78% of the original photoluminescence quantum yields without significant photodegradation under the irradiation of LED light (450 nm, 3.0 W power intensity) for 14 h, while conventional InP/ZnSe/ZnS QDs dramatically decreased to 29%.
Recent Advancements in Tin Halide Perovskite-Based Solar Cells and Thermoelectric Devices
Authors: Baranwal Ajay Kumar , Hayase Shuzi
Published: November 2022

The excellent optoelectronic properties of tin halide perovskites (Sn-PVKs) have made them a promising candidate for replacing toxic Pb counterparts. Concurrently, their enormous potential in photon harvesting and thermoelectricity applications has attracted increasing attention. The optoelectronic properties of Sn-PVKs are governed by the flexible nature of SnI6 octahedra, and they exhibit extremely low thermal conductivity. Due to these diverse applications, this review first analyzes the structural properties, optoelectronic properties, defect physics, and thermoelectric properties of Sn-PVKs. Then, recent techniques developed to solve limitations with Sn-PVK-based devices to improve their photoelectric and thermoelectric performance are discussed in detail. Finally, the challenges and prospects for further development of Sn-PVK-based devices are discussed.
Eucalyptus-Mediated Synthesized Silver Nanoparticles-Coated Urinary Catheter Inhibits Microbial Migration and Biofilm Formation
Authors: Lethongkam Sakkarin , Paosen Supakit , Bilhman Siwaporn , Dumjun Krittima , Wunnoo Suttiwan , Choojit Suntree , Siri Ratchaneewan , Daengngam Chalongrat , Voravuthikunchai Supayang P. , Bejrananda Tanan
Published: November 2022

Catheter-associated urinary tract infections (CAUTIs) are significant complications among catheterized patients, resulting in increased morbidity, mortality rates, and healthcare costs. Foley urinary catheters coated with synthesized silver nanoparticles (AgNPs) using Eucalyptus camaldulensis leaf extract were developed using a green chemistry principle. In situ-deposited AgNPs with particle size ranging between 20 and 120 nm on the catheter surface were illustrated by scanning electron microscopy. Atomic force microscopy revealed the changes in surface roughness after coating with nanoparticles. The coated catheter could significantly inhibit microbial adhesion and biofilm formation performed in pooled human urine-supplemented media to mimic a microenvironment during infections (p 0.05). AgNPs-coated catheter exhibited broad-spectrum antimicrobial activity against important pathogens, causing CAUTIs with no cytotoxic effects on HeLa cells. A reduction in microbial viability in biofilms was observed under confocal laser scanning microscopy. A catheter bridge model demonstrated complete prevention of Proteus mirabilis migration by the coated catheter. Significant inhibition of ascending motility of Escherichia coli and P. mirabilis along the AgNPs-coated catheter was demonstrated in an in vitro bladder model (p 0.05). The results suggested that the AgNPs-coated urinary catheter could be applied as an alternative strategy to minimize the risk of CAUTIs by preventing bacterial colonization and biofilm formation.
Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis
Authors: Chan Gordon Chun Kau , Than Win Hlaing , Kwan Bonnie Ching Ha , Lai Ka Bik , Chan Ronald Cheong Kin , Teoh Jeremy Yuen Chun , Ng Jack Kit Chung , Chow Kai Ming , Cheng Phyllis Mei Shan , Law Man Ching , Leung Chi Bon , Li Philip Kam Tao , Szeto Cheuk Chun
Published: November 2022

Background: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. Methods: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. Results: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57–3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08–2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80–13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13–12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006–0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02–0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35–50.5, p = 0.02). Conclusion: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.
Lag Time Determinations in Beer Samples. Influence of Alcohol and PBN Concentration in EPR Spin Trapping Experiments
Authors: Porcu Maria Cristina , Fadda Angela , Sanna Daniele
Published: November 2022

The beers’ lag time measured with the PBN (N-t-Butyl-α-phenylnitrone) spin trapping experiments coupled with EPR spectroscopy is related to their antioxidant capacity and shelf life. The effect on the lag time of the alcohol content of the beer (starting values, 9 and 13%) and PBN concentration (50 or 200 mM) was analyzed on three samples, a pilsner, a strong lager, and a blonde Ale heated at 60 °C to trigger the production of the 1-hydroxyethyl radical. The lag time was determined only for the strong lager beer, with the values depending on the experimental conditions, being higher when PBN had a lower concentration. The antioxidant activity of the three beers gave the following values: 0.9089 mL pilsner beer/mg DPPH, 0.8510 mL strong lager beer/mg DPPH, and 0.7184 mL blonde Ale beer/mg DPPH, indicating that the unsuccessful determination of the lag time was not due to stale beers. The EPR intensity of the PBN adduct after 150 min (I150) and the area under the curve (AUC) were also measured and related to the oxidative stability of beers. Further studies are needed to verify the influence of the heating temperature in samples that do not show a lag time at 60 °C.
Seroprevalence of Equine Influenza and Its Associated Risk Factors in Northwest Nigeria
Authors: Olufemi Olaolu T. , Edeh Emmanuel R. , Isyaku Mustapha S. , Haliru Mustapha , Samaila Shafiu , Mshelia Philip W. , Owolodun Olajide A. , Newton J. Richard , Daly Janet M.
Published: November 2022

Equine influenza (EI) is a fast-spreading respiratory disease of equids caused by equine influenza A virus (EIV), often resulting in high morbidity and a huge economic impact on the equine industry globally. In this cross-sectional study to determine the seroprevalence of EI and its associated risk factors, sera from 830 horses bled on a single occasion in Northwest Nigeria between October 2019 and January 2020 were screened for antibodies to A/equine/Richmond/1/2007 (H3N8) using the single radial haemolysis (SRH) assay. Antibodies were detected in 71.3% (592/830, 95% CI: 68–74%) of horses (SRH area ≥ 0.5 mm2). Although there were statistically significant univariable associations between seropositivity and age, sex, breed, purpose and coat colour, only age remained significant when included with each of the other variables in bivariable analyses. There was a clear trend for increasing odds of seropositivity with increasing age: OR 1.6, 95% CI: 1.05–2.40 (p = 0.03) for 5–14-year-olds and OR 8.13, 95% CI: 2.75–24.1 (p < 0.001) for ≥15-year-olds compared to horses <5 years old. The mean SRH value was 78.2 mm2 (median = 88 mm2, interquartile range = 0–121 mm2) with only 9% of the horses having an SRH value > 150 mm2, considered sufficient to protect against clinical disease and virus shedding. Comparative screening of a subset of the horses (n = 118) with a 2019 H3N8 virus (A/equine/Worcestershire/2019) revealed a significantly greater seropositivity (p = 0.0001) than A/equine/Richmond/1/2007 consistent with exposure of the population during a widespread outbreak of EI in the region in 2019. In conclusion, there was an insufficient level of protection against EI in the region and introduction of a vaccination programme with vaccines containing recently circulating virus is recommended to mitigate against further outbreaks of EI in Nigeria.
Extracellular Vesicles Derived from Allergen Immunotherapy-Treated Mice Suppressed IL-5 Production from Group 2 Innate Lymphoid Cells
Authors: Matsuda Masaya , Shimizu Seito , Kitatani Kazuyuki , Nabe Takeshi
Published: November 2022

Allergen immunotherapy (AIT), such as subcutaneous immunotherapy (SCIT), is a treatment targeting the causes of allergic diseases. The roles of extracellular vesicles (EVs), bilayer lipid membrane blebs released from all types of cells, in AIT have not been clarified. To examine the roles of EVs in SCIT, it was analyzed whether (1) EVs are phenotypically changed by treatment with SCIT, and (2) EVs derived from SCIT treatment suppress the function of group 2 innate lymphoid cells (ILC2s), which are major cells contributing to type 2 allergic inflammation. As a result, (1) expression of CD9, a canonical EV marker, was highly up-regulated by SCIT in a murine model of asthma; and (2) IL-5 production from ILC2s in vitro was significantly decreased by the addition of serum EVs derived from SCIT-treated but not non-SCIT-treated mice. In conclusion, it was indicated that EVs were transformed by SCIT, changing to a suppressive phenotype of type 2 allergic inflammation.
In Vivo Inhibitory Assessment of Potential Antifungal Agents on Nosema ceranae Proliferation in Honey Bees
Authors: Bahreini Rassol , Nasr Medhat , Docherty Cassandra , de Herdt Olivia , Feindel David , Muirhead Samantha
Published: November 2022

Nosema ceranae Fries, 1996, causes contagious fungal nosemosis disease in managed honey bees, Apis mellifera L. It is associated around the world with winter losses and colony collapse disorder. We used a laboratory in vivo screening assay to test curcumin, fenbendazole, nitrofurazone and ornidazole against N. ceranae in honey bees to identify novel compounds with anti-nosemosis activity compared to the commercially available medication Fumagilin-B®. Over a 20-day period, Nosema-inoculated bees in Plexiglas cages were orally treated with subsequent dilutions of candidate compounds, or Fumagilin-B® at the recommended dose, with three replicates per treatment. Outcomes indicated that fenbendazole suppressed Nosema spore proliferation, resulting in lower spore abundance in live bees (0.36 ± 1.18 million spores per bee) and dead bees (0.03 ± 0.25 million spores per bee), in comparison to Fumagilin-B®-treated live bees (3.21 ± 2.19 million spores per bee) and dead bees (3.5 ± 0.6 million spores per bee). Our findings suggest that Fumagilin-B® at the recommended dose suppressed Nosema. However, it was also likely responsible for killing Nosema-infected bees (24% mortality). Bees treated with fenbendazole experienced a greater survival probability (71%), followed by ornidazole (69%), compared to Nosema-infected non-treated control bees (20%). This research revealed that among screened compounds, fenbendazole, along with ornidazole, has potential effective antifungal activities against N. ceranae in a controlled laboratory environment.
Diagnosis of SARS-CoV-2 during the Pandemic by Multiplex RT-rPCR hCoV Test: Future Perspectives
Authors: Inchingolo Alessio Danilo , Gargiulo Ciro Isacco , Malcangi Giuseppina , Ciocia Anna Maria , Patano Assunta , Azzollini Daniela , Piras Fabio , Barile Giuseppe , Settanni Vito , Mancini Antonio , Garofoli Grazia , Palmieri Giulia , Di Pede Chiara , Rapone Biagio , Inchingolo Angelo Michele , Jones Megan , Corriero Alberto , Brienza Nicola , Parisi Antonio , Bianco Angelica , Capozzi Loredana , Del Sambro Laura , Simone Domenico , Bordea Ioana Roxana , Tartaglia Gianluca Martino , Scarano Antonio , Lorusso Felice , Macchia Luigi , Migliore Giovanni , Pham Van Hung , Dipalma Gianna , Inchingolo Francesco
Published: November 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a significant threat to public health. However, among the Coronaviridae family members, there are other viruses that can also cause infections in humans. Among these, severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) have posed significant threats to human health in the past. Other human pathogenic coronaviruses have been identified, and they are known to cause respiratory diseases with manifestations ranging from mild to severe. In this study, we evaluated the performance of a multiplex RT-rPCR specific to seven human pathogenic coronaviruses in mainly detecting SARS-CoV-2 directly from nasopharyngeal swabs obtained from suspected COVID-19 infected patients, while simultaneously detecting different human pathogenic coronaviruses in case these were also present. We tested 1195 clinical samples suspected of COVID-19 infection. The assay identified that 69% of the samples tested positive for SARS-CoV-2 (1195), which was confirmed using another SARS-CoV-2 RT-PCR kit available in our laboratory. None of these clinical samples were positive for SARS-CoV, MERS-CoV or HCoV. This means that during the endemic phase of COVID-19, infection with other human pathogenic coronaviruses, even the common cold coronavirus (HCoV), is very uncommon. Our study also confirmed that the multiplex RT-rPCR is a sensitive assay for detecting SARS-CoV-2 regardless of differences among the variants. This multiplex RT-rPCR is also time- and cost-saving and very easy to apply in the diagnostic laboratory due to its simple procedure and its stability in storage after preparation. These features make the assay a valuable approach in screening procedures for the rapid detection of SARS-CoV-2 and other human pathogenic coronaviruses that could affect public health.
Human Papillomaviruses-Related Cancers: An Update on the Presence and Prevention Strategies in the Middle East and North African Regions
Authors: Fernandes Queenie , Allouch Soumaya , Gupta Ishita , Elmakaty Ibrahim , Elzawawi Khaled E. , Amarah Ahmed , Al-Thawadi Hamda , Al-Farsi Halema , Vranic Semir , Al Moustafa Ala-Eddin
Published: November 2022

The human papillomavirus (HPV) is a non-enveloped double-stranded DNA virus capable of infecting skin and mucosa epithelial cells. Commonly, HPV infection is associated with sexually transmitted diseases and is considered the leading cause of cervical cancer and other carcinomas of the anogenital tract. However, several studies reported their involvement in cancers of non-sexual regions, including colorectal, head and neck, and breast cancers. There are several studies from the Middle East and North Africa (MENA) regions on the potential association between high-risk HPVs and cancer; nevertheless, there are limited studies that address the significance of HPV vaccination as a potential guard against these cancers. In the current review, we present a comprehensive description of the current HPV-associated cancers prevalence rates in the MENA region, demonstrating their steady increase with time, especially in African regions. Moreover, we discuss the potential impact of vaccination against HPV infections and its outcome on human health in this region.
Selective Induction of Intrinsic Apoptosis in Retinoblastoma Cells by Novel Cationic Antimicrobial Dodecapeptides
Authors: Suresh Babu Vishnu , Kizhakeyil Atish , Dudeja Gagan , Chaurasia Shyam S. , Barathi Veluchami Amutha , Heymans Stephane , Verma Navin Kumar , Lakshminarayanan Rajamani , Ghosh Arkasubhra
Published: November 2022

Host defense peptides represent an important component of innate immunity. In this work, we report the anticancer properties of a panel of hyper-charged wholly cationic antimicrobial dodecapeptides (CAPs) containing multiple canonical forms of lysine and arginine residues. These CAPs displayed excellent bactericidal activities against a broad range of pathogenic bacteria by dissipating the cytoplasmic membrane potential. Specifically, we identified two CAPs, named HC3 and HC5, that effectively killed a significant number of retinoblastoma (WERI-Rb1) cells (p ≤ 0.01). These two CAPs caused the shrinkage of WERI-Rb1 tumor spheroids (p ≤ 0.01), induced intrinsic apoptosis in WERI-Rb1 cells via activation of caspase 9 and caspase 3, cleaved the PARP protein, and triggered off the phosphorylation of p53 and γH2A.X. Combining HC3 or HC5 with the standard chemotherapeutic drug topotecan showed synergistic anti-cancer activities. Overall, these results suggest that HC3 and HC5 can be exploited as potential therapeutic agents in retinoblastoma as monotherapy or as adjunctive therapy to enhance the effectiveness of currently used treatment modalities.
Selection of an Aptamer against the Enzyme 1-deoxy-D-xylulose-5-phosphate Reductoisomerase from Plasmodium falciparum
Authors: Roca Carlota , Avalos-Padilla Yunuen , Prieto-Simón Beatriz , Iglesias Valentín , Ramírez Miriam , Imperial Santiago , Fernàndez-Busquets Xavier
Published: November 2022

The methyl erythritol phosphate (MEP) pathway of isoprenoid biosynthesis is essential for malaria parasites and also for several human pathogenic bacteria, thus representing an interesting target for future antimalarials and antibiotics and for diagnostic strategies. We have developed a DNA aptamer (D10) against Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme of this metabolic route. D10 binds in vitro to recombinant DXR from P. falciparum and Escherichia coli, showing at 10 µM a ca. 50% inhibition of the bacterial enzyme. In silico docking analysis indicates that D10 associates with DXR in solvent-exposed regions outside the active center pocket. According to fluorescence confocal microscopy data, this aptamer specifically targets in P. falciparum in vitro cultures the apicoplast organelle where the MEP pathway is localized and is, therefore, a highly specific marker of red blood cells parasitized by Plasmodium vs. naïve erythrocytes. D10 is also selective for the detection of MEP+ bacteria (e.g., E. coli and Pseudomonas aeruginosa) vs. those lacking DXR (e.g., Enterococcus faecalis). Based on these results, we discuss the potential of DNA aptamers in the development of ligands that can outcompete the performance of the well-established antibody technology for future therapeutic and diagnostic approaches.
Biologic Evaluation of a Heterodimeric HER2-Albumin Targeted Affibody Molecule Produced by Chemo-Enzymatic Peptide Synthesis
Authors: Liu Yongsheng , Güler Rezan , Liao Yunqi , Vorobyeva Anzhelika , Widmark Olof , Meuleman Theodorus J. , Koijen Anna , van den Bos Leendert J. , Naasz Robert , Bodenko Vitalina , Orlova Anna , Ekblad Caroline , Tolmachev Vladimir , Frejd Fredrik Y.
Published: November 2022

Targeted molecular radiation therapy is a promising emerging treatment modality in oncology, and peptide synthesis may shorten the time to reach the clinical stage. In this study, we have explored Chemo-Enzymatic Peptide Synthesis, or CEPS, as a new means of producing a therapeutic HER2 targeted Affibody® molecule, comprising a C-terminal albumin binding domain (ABD) for half-life extension and a total length of 108 amino acids. In addition, a DOTA moiety could be incorporated at N-terminus directly during the synthesis step and subsequently utilized for site-specific radiolabeling with the therapeutic radionuclide 177Lu. Retained thermodynamic stability as well as retained binding to both HER2 and albumin was verified. Furthermore, HER2 binding specificity of the radiolabeled Affibody molecule was confirmed by an in vitro saturation assay showing a significantly higher cell-bound activity of SKOV-3 (high HER2 expression) compared with BxPC3 (low HER2 expression), both in the presence and absence of HSA. In vivo evaluation in mice bearing HER2 expressing xenografts also showed specific tumor targeting as well as extended time in circulation and reduced kidney uptake compared with a HER2 targeted Affibody molecule without the ABD moiety. To conclude, we have demonstrated that CEPS can be used for production of Affibody-fusion molecules with retained in vitro and in vivo functionality.
siRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases
Authors: Kalita Tutu , Dezfouli Saba Abbasi , Pandey Lalit M. , Uludag Hasan
Published: November 2022

RNAi (RNA interference)-based technology is emerging as a versatile tool which has been widely utilized in the treatment of various diseases. siRNA can alter gene expression by binding to the target mRNA and thereby inhibiting its translation. This remarkable potential of siRNA makes it a useful candidate, and it has been successively used in the treatment of diseases, including cancer. However, certain properties of siRNA such as its large size and susceptibility to degradation by RNases are major drawbacks of using this technology at the broader scale. To overcome these challenges, there is a requirement for versatile tools for safe and efficient delivery of siRNA to its target site. Lipid nanoparticles (LNPs) have been extensively explored to this end, and this paper reviews different types of LNPs, namely liposomes, solid lipid NPs, nanostructured lipid carriers, and nanoemulsions, to highlight this delivery mode. The materials and methods of preparation of the LNPs have been described here, and pertinent physicochemical properties such as particle size, surface charge, surface modifications, and PEGylation in enhancing the delivery performance (stability and specificity) have been summarized. We have discussed in detail various challenges facing LNPs and various strategies to overcome biological barriers to undertake the safe delivery of siRNA to a target site. We additionally highlighted representative therapeutic applications of LNP formulations with siRNA that may offer unique therapeutic benefits in such wide areas as acute myeloid leukaemia, breast cancer, liver disease, hepatitis B and COVID-19 as recent examples.
Label-Free Assessment of Mannitol Accumulation Following Osmotic Blood–Brain Barrier Opening Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging
Authors: Liu Jing , Chu Chengyan , Zhang Jia , Bie Chongxue , Chen Lin , Aafreen Safiya , Xu Jiadi , Kamson David O. , van Zijl Peter C. M. , Walczak Piotr , Janowski Miroslaw , Liu Guanshu
Published: November 2022

Purpose: Mannitol is a hyperosmolar agent for reducing intracranial pressure and inducing osmotic blood–brain barrier opening (OBBBO). There is a great clinical need for a non-invasive method to optimize the safety of mannitol dosing. The aim of this study was to develop a label-free Chemical Exchange Saturation Transfer (CEST)-based MRI approach for detecting intracranial accumulation of mannitol following OBBBO. Methods: In vitro MRI was conducted to measure the CEST properties of D-mannitol of different concentrations and pH. In vivo MRI and MRS measurements were conducted on Sprague-Dawley rats using a Biospec 11.7T horizontal MRI scanner. Rats were catheterized at the internal carotid artery (ICA) and randomly grouped to receive either 1 mL or 3 mL D-mannitol. CEST MR images were acquired before and at 20 min after the infusion. Results: In vitro MRI showed that mannitol has a strong, broad CEST contrast at around 0.8 ppm with a mM CEST MRI detectability. In vivo studies showed that CEST MRI could effectively detect mannitol in the brain. The low dose mannitol treatment led to OBBBO but no significant mannitol accumulation, whereas the high dose regimen resulted in both OBBBO and mannitol accumulation. The CEST MRI findings were consistent with 1H-MRS and Gd-enhanced MRI assessments. Conclusion: We demonstrated that CEST MRI can be used for non-invasive, label-free detection of mannitol accumulation in the brain following BBBO treatment. This method may be useful as a rapid imaging tool to optimize the dosing of mannitol-based OBBBO and improve its safety and efficacy.
Instability Challenges and Stabilization Strategies of Pharmaceutical Proteins
Authors: Akbarian Mohsen , Chen Shu-Hui
Published: November 2022

Maintaining the structure of protein and peptide drugs has become one of the most important goals of scientists in recent decades. Cold and thermal denaturation conditions, lyophilization and freeze drying, different pH conditions, concentrations, ionic strength, environmental agitation, the interaction between the surface of liquid and air as well as liquid and solid, and even the architectural structure of storage containers are among the factors that affect the stability of these therapeutic biomacromolecules. The use of genetic engineering, side-directed mutagenesis, fusion strategies, solvent engineering, the addition of various preservatives, surfactants, and additives are some of the solutions to overcome these problems. This article will discuss the types of stress that lead to instabilities of different proteins used in pharmaceutics including regulatory proteins, antibodies, and antibody-drug conjugates, and then all the methods for fighting these stresses will be reviewed. New and existing analytical methods that are used to detect the instabilities, mainly changes in their primary and higher order structures, are briefly summarized.
The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control
Authors: Di Marzo Maurizio , Babolin Nicola , Viana Vívian Ebeling , de Oliveira Antonio Costa , Gugi Bruno , Caporali Elisabetta , Herrera-Ubaldo Humberto , Martínez-Estrada Eduardo , Driouich Azeddine , de Folter Stefan , Colombo Lucia , Ezquer Ignacio
Published: November 2022

Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. We have linked these studies to cell wall composition and structure. Interestingly, we have found that disruption of genes involved in pectin maturation and hemicellulose deposition strongly influence germination dynamics. Finally, we focused on two transcriptional regulators, SEEDSTICK (STK) and LEUNIG-HOMOLOG (LUH), which positively regulate seed growth. Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development.
Exploring the Chemical Composition of Bulgarian Lavender Absolute (Lavandula Angustifolia Mill.) by GC/MS and GC-FID
Authors: Nedeltcheva-Antonova Daniela , Gechovska Kamelia , Bozhanov Stanislav , Antonov Liudmil
Published: November 2022

Lavender (L. angustifolia Mill.) is an important essential oil-bearing and medicinal plant with high commercial value. Lavender scent components can be derived not only as an essential oil but also as lavender concrete or absolute. The development of reliable analytical methods for origin assessment and quality assurance is of significant fundamental importance and high practical interest. Therefore, a comprehensive chemical profiling of seven industrial samples of Bulgarian lavender absolute (L. angustifolia Mill.) was performed by means of gas chromatography–mass spectrometry (GC/MS) and gas chromatography with flame ionization detection (GC-FID). As a result, 111 individual compounds were identified by GC/MS, and their quantitative content was simultaneously determined by GC-FID, representing 94.28–97.43% of the total contents of the lavender absolute. According to our results, the main constituents of lavender absolute (LA) are representatives of the terpene compounds (with the dominating presence of oxygenated monoterpenes, 52.83–80.55%), followed by sesquiterpenes (7.80–15.21%) and triterpenoids (as minor components). Coumarins in various amounts (1.79–14.73%) and aliphatic compounds (hydrocarbons, ketones, esters, etc.) are found, as well. The acyclic monoterpene linalool is the main terpene alcohol and, together with its ester linalyl acetate, are the two main constituents in the LAs. Linalool was found in concentrations of 27.33–38.24% in the LA1-LA6 samples and 20.74% in the LA7 samples. The amount of linalyl acetate was in the range of 26.58 to 37.39% in the LA1–LA6 samples, while, surprisingly, it was not observed in LA7. This study shows that the chemical profile of the studied LAs is close to the lavender essential oil (LO), fulfilling most of the requirements of the International Standard ISO 3515:2002.
New Proposal of Epiphytic Bromeliaceae Functional Groups to Include Nebulophytes and Shallow Tanks
Authors: Reyes-García Casandra , Pereira-Zaldívar Narcy Anai , Espadas-Manrique Celene , Tamayo-Chim Manuela , Chilpa-Galván Nahlleli , Cach-Pérez Manuel Jesús , Ramírez-Medina Marypaz , Benavides Ana Maria , Hietz Peter , Zotz Gerhard , Andrade José Luis , Cardelús Catherine , de Paula Oliveira Rodolfo , Einzmann Helena J. R. , Guzmán Jacob Valeria , Krömer Thorsten , Pinzón Juan P. , Sarmento Cabral Juliano , Wanek Wolfgang , Woods Carrie
Published: November 2022

The Bromeliaceae family has been used as a model to study adaptive radiation due to its terrestrial, epilithic, and epiphytic habits with wide morpho-physiological variation. Functional groups described by Pittendrigh in 1948 have been an integral part of ecophysiological studies. In the current study, we revisited the functional groups of epiphytic bromeliads using a 204 species trait database sampled throughout the Americas. Our objective was to define epiphytic functional groups within bromeliads based on unsupervised classification, including species from the dry to the wet end of the Neotropics. We performed a hierarchical cluster analysis with 16 functional traits and a discriminant analysis, to test for the separation between these groups. Herbarium records were used to map species distributions and to analyze the climate and ecosystems inhabited. The clustering supported five groups, C3 tank and CAM tank bromeliads with deep tanks, while the atmospheric group (according to Pittendrigh) was divided into nebulophytes, bromeliads with shallow tanks, and bromeliads with pseudobulbs. The two former groups showed distinct traits related to resource (water) acquisition, such as fog (nebulophytes) and dew (shallow tanks). We discuss how the functional traits relate to the ecosystems inhabited and the relevance of acknowledging the new functional groups.
Asymmetric Reciprocal Crossing Behavior of an Andean Blueberry (V. meridionale) × Lingonberry (V. vitis-idaea) Hybrid
Authors: Ehlenfeldt Mark K. , Ogden Elizabeth , Rowland Lisa J.
Published: November 2022

The fertility and crossing behavior of a tetraploid hybrid of 4x Andean blueberry (V. meridionale) and lingonberry (V. vitis-idaea) was evaluated through a series of crosses. Crosses of the hybrid with highbush blueberry produced divergent results. When used as a female with V. corymbosum males, virtually all offspring were hexaploid, most likely arising from 2n = 4x = 48 female gametes, and 1n = 2x = 24 male gametes. However, when used as a male, tetraploid hybrids were produced, resulting from 1n = 2x = 24 gametes from each parent. To further examine this crossing behavior, the 4x V. meridionale—V. vitis-idaea interspecific hybrid was pollinated with 6x V. virgatum (rabbiteye blueberry). Analogous to the previous crosses, 7x hybrids were produced from the joining of 2n = 4x = 48 female gametes with 1n = 3x = 36 male gametes. Such reciprocal crossing asymmetry is unprecedented. The ability to produce both 6x and 4x offspring from the same V. corymbosum parents allows the potential of bridging a V. meridionale hybrid genotype to both the tetraploid (V. corymbosum) and hexaploid (V. virgatum) commercial crop levels.
Essential Oil Variability of Superior Myrtle (Myrtus communis L.) Accessions Grown under the Same Conditions
Authors: Shahbazian Donya , Karami Akbar , Raouf Fard Fatemeh , Eshghi Saeid , Maggi Filippo
Published: November 2022

Myrtle (Myrtus communis L., Myrtaceae) has numerous applications in pharmacology, food technology, and cosmetic industry. The current research aimed at measuring variations in the leaf essential oil (EO) compositions of 14 superior myrtle accessions originating in natural habitats of south Iran. The plants were grown under greenhouse conditions. Fresh leaf samples were harvested in June 2021. Based on dry matter, the extractable amount of EO in the accessions ranged from 0.42% (BN2) to 2.6% (BN5). According to GC/MS analysis, the major compounds in the EO were α-pinene (2.35–53.09%), linalyl acetate (0–45.3%), caryophyllene oxide (0.97–21.8%), germacrene D (0–19.19%), α-humulene (0–18.97%), 1,8-cineole (0–18.0%), limonene (0–17.4%), and p-cymene (0–13.2%). These myrtle accessions were classified into four groups, including I: caryophyllene oxide/germacrene D/α-humulene/methyl eugenol chemotype; II: α-pinene/p-cymene/α-humulene and (E)-β-caryophyllene; III: α-pinene/1,8-cineole, and linalool; IV: linalyl acetate/γ-terpinene/1,8, cineole/limonene. These classifications were established by considering the main EO components using hierarchical cluster analysis (HCA) and principal component analysis (PCA). In summary, this study provided new insights into available opportunities of selecting suitable genotypes for commercial cultivation purposes and planning breeding programs in the future.
Correlation between Vegetation Structure and Species Diversity in Traditional Villages in Karst Topographic Regions of the Zunyi City, China
Authors: Deng Caijie , Huang Zongsheng , Zhang Xiaojing , Zhao Hua , Jiang Siyu , Ren Yuxin
Published: November 2022

Studying the relationship between vegetation structure and diversity is important in an area having karst topography and unique traditional customs. We selected a total of six traditional villages in Zunyi City, China, to collect vegetation data. Additionally, using one-way ANOVA and the Pearson correlation coefficient analytic method to analyze, the results showed that, overall, plant communities were mostly regularly distributed. The overall differentiation degree was low aggregation, intensity, and the extreme intensity mixed state. Overall, competitive pressure, growth vigor and stability were better than the natural forest. The community stability index at lower altitude was significantly higher than that at higher altitude. The recorded plant communities in the living space were typically aggregated, the plant communities were randomly distributed in the production space, and the plant communities were uniformly distributed in the ecological space. In general, the diversity indexes, except the Jh index, were the highest in the herb layer; the second was in the shrub layer and the lowest was in the tree layer. Species diversity at the middle altitude was higher than that at low and high altitudes (except for the shrub at a high altitude of 1100–1160 m). The overall plant species diversity was highest in the living space, second highest in the ecological space and lowest in the production space. On the whole, there was a significant correlation between the spatial structure of plant communities and the species diversity of plant communities at different altitudes, and in PLE spaces. The main objective of this study was to reveal the plant community structure, species diversity, and their relationship under the dual effects of national traditional culture and karst landform. Additionally, we sought to provide theoretical guidance for the construction of plant community protection and biodiversity conservation in traditional villages in karst areas.