bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-Stage Robust Liner Container Booking with Uncertain Customer Demand
Authors: Zhu Hanghang , Pei Zhi
Published: April 2023

Since third-party logistics (3PL) offers discounted prices for booking containers in advance, the container booking decisions are preferably made prior to the realization of customer demand by the companies with international trade business. When facing uncertain customer demand influenced by various factors, it is significant for companies to make proper container booking decisions and order fulfillment plans to minimize the total cost, including the container booking cost and the penalty cost of an unfulfilled order. In this paper, a two-stage robust liner container booking problem (2-RLCBP) was investigated, and an exact algorithm with high efficiency was designed to solve the problem based on the column-and-constraint generation (C&CG) framework. Compared to other methods with gaps of more than 70% existing after 3600 s, the proposed algorithm can get the optimal solution of the real case instance in 700 s. Furthermore, compared to the deterministic model, the two-stage robust optimization model can reduce more than 10% of the worst-case total cost when the budget level and demand deviation level are greater than 0.6, which verifies the effectiveness of the proposed robust approach. Furthermore, our work is the first to adopt a two-stage robust optimization approach for the problem of booking a liner container.
Correction: Hussaine, S.M.; Mu, L. Intelligent Prediction of Maximum Ground Settlement Induced by EPB Shield Tunneling Using Automated Machine Learning Techniques. Mathematics 2022, 10, 4637
Authors: Hussaine Syed Mujtaba , Mu Linlong
Published: April 2023

The authors wish to make the following corrections to this paper [...]
Multiple Myeloma Cell Simulation Using an Agent-Based Framework Coupled with a Continuous Fluid Model
Authors: Urdeitx Pau , Clara-Trujillo Sandra , Gomez Ribelles Jose Luis , Doweidar Mohamed H.
Published: April 2023

Bone marrow mechanical conditions play a key role in multiple myeloma cancer. The complex mechanical and chemical conditions, as well as the interactions with other resident cells, hinder the development of effective treatments. Agent-based computational models, capable of defining the specific conditions for every single cell, can be a useful tool to identify the specific tumor microenvironment. In this sense, we have developed a novel hybrid 3D agent-based model with coupled fluid and particle dynamics to study multiple myeloma cells’ growth. The model, which considers cell–cell interactions, cell maturation, and cell proliferation, has been implemented by employing user-defined functions in the commercial software Fluent. To validate and calibrate the model, cell sedimentation velocity and cell proliferation rates have been compared with in vitro results, as well as with another previously in-house developed model. The results show that cell proliferation increased as cell–cell, and cell–extracellular matrix interactions increased, as a result of the reduction n maturation time. Cells in contact form cell aggregates, increasing cell–cell interactions and thus cell proliferation. Saturation in cell proliferation was observed when cell aggregates increased in size and the lack of space inhibited internal cells’ proliferation. Compared with the previous model, a huge reduction in computational costs was obtained, allowing for an increase in the number of simulated cells.
Alginate Core-Shell Capsules Production through Coextrusion Methods: Principles and Technologies
Authors: Bennacef Chanez , Desobry-Banon Sylvie , Probst Laurent , Desobry Stéphane
Published: April 2023

This paper provides an overview of coextrusion methods for encapsulation. Encapsulation involves the coating or entrapment of a core material such as food ingredients, enzymes, cells, or bioactives. Encapsulation can help compounds add to other matrices, stabilize compounds during storage, or enable controlled delivery. This review explores the principal l coextrusion methods available that can be used to produce core-shell capsules through the use of coaxial nozzles. Four methods for encapsulation by coextrusion are examined in detail, including dripping, jet cutting, centrifugal, and electrohydrodynamic systems. The targeted capsule size determines the appropriate parameters for each method. Coextrusion technology is a promising encapsulation technique able to generate core-shell capsules in a controlled manner, which can be applied to cosmetic, food, pharmaceutical, agriculture, and textile industries. Coextrusion is an excellent way to preserve active molecules and present a significant economic interest.
The Use of PuraStat® in the Management of Walled-Off Pancreatic Necrosis Drained Using Lumen-Apposing Metal Stents: A Case Series
Authors: Binda Cecilia , Fugazza Alessandro , Fabbri Stefano , Coluccio Chiara , Repici Alessandro , Tarantino Ilaria , Anderloni Andrea , Fabbri Carlo
Published: April 2023

Background and Objectives: Bleeding is one of the most feared and frequent adverse events in the case of EUS-guided drainage of WOPN using lumen-apposing metal stents (LAMSs) and of direct endoscopic necrosectomy (DEN). When it occurs, its management is still controversial. In the last few years, PuraStat, a novel hemostatic peptide gel has been introduced, expanding the toolbox of the endoscopic hemostatic agents. The aim of this case series was to evaluate the safety and efficacy of PuraStat in preventing and controlling bleeding of WOPN drainage using LAMSs. Materials and Methods: This is a multicenter, retrospective pilot study from three high-volume centers in Italy, including all consecutive patients treated with the novel hemostatic peptide gel after LAMSs placement for the drainage of symptomatic WOPN between 2019 and 2022. Results: A total of 10 patients were included. All patients underwent at least one session of DEN. Technical success of PuraStat was achieved in 100% of patients. In seven cases PuraStat was placed for post-DEN bleeding prevention, with one patient experiencing bleeding after DEN. In three cases, on the other hand, PuraStat was placed to manage active bleeding: two cases of oozing were successfully controlled with gel application, and a massive spurting from a retroperitoneal vessel required subsequent angiography. No re-bleeding occurred. No PuraStat-related adverse events were reported. Conclusions: This novel peptide gel could represent a promising hemostatic device, both in preventing and managing active bleeding after EUS-guided drainage of WON. Further prospective studies are needed to confirm its efficacy.
Effect of Silicon Wafer Surface Stains on Copper-Assisted Chemical Etching
Authors: Ma Liang , Chen Xiuhua , Tang Chenggui , Li Shaoyuan , Xi Fengshuo , Lan Huayan , Ma Wenhui , Chang Yuanchih
Published: April 2023

Silicon wafer slicing is a crucial process during solar cell fabrication, but it often stains the silicon wafer surface. Thus, this work systematically investigated the composition, source, and cleaning method of typical white spot stains on silicon wafer surfaces. The EDS and XPS results showed that the white spot stains contained CaCO3 and SiO2 that were consistent with the filler components in sticky silicon ingot glue. The effects of stains on copper deposition and copper-assisted chemical etching were studied. White spot stains remained attached to the silicon surface after deposition and etching. These stains affected the uniform deposition of copper particles on the surface of the silicon wafer and also impeded the catalytic etching of copper particles. Finally, KOH solution was combined with an ultrasonic field to remove surface stains from the silicon wafer. This study provides important guidance for the removal of silicon wafer contaminants to fabricate high-efficiency solar cells.
Physically-Based Methodology for the Characterization of Wrinkling Limit Curve Validated by Yoshida Tests
Authors: Santos João A.O. , Magrinho João P.G. , Silva Maria Beatriz
Published: April 2023

This paper presents a new experimental methodology for determining the formability limits by wrinkling in sheet metal forming using Yoshida buckling tests (YBTs). The YBT has been the most used formability test by the scientific community to determine the occurrence of wrinkling, on the one hand, due to its simple clamping configuration directly related to the kinematics of tensile tests. On the other hand, the formability test replicates the occurrence of wrinkling in deformation regions under tension, similar to the side wall wrinkling of a deep drawn part. The new physically-based methodology is built upon the direct analysis of the in-plane minor strain and its strain rate for a point located at the center of the YBT specimen. Application of the methodology in AA1050–O aluminium alloy sheets enabled the experimental determination of the onset of wrinkling. Results also showed that in contrast to conventional techniques, where the wrinkling prediction is based in a specified percentage of the initial thickness of the blank (5–10%), considering a physical wrinkle-triggering factor enables one to identify the precise moment at which wrinkling occurs. The proposed physically-based methodology provides a new level of understanding of the YBT behavior and the onset of wrinkling determination for sheet metal forming with a higher degree of accuracy.
Metabolomic Profiling in Mouse Model of Menopause-Associated Asthma
Authors: Pederson William P. , Ellerman Laurie M. , Jin Yan , Gu Haiwei , Ledford Julie G.
Published: April 2023

Menopause-associated asthma impacts a subset of women, tends to be more severe, and is less responsive to current treatments. We recently developed a model of menopause-associated asthma using 4-Vinylcyclohexene Diepoxide (VCD) and house dust mites (HDM). The goal of this study was to uncover potential biomarkers and drivers of menopause-onset asthma by assessing serum and bronchoalveolar lavage fluid (BALF) samples from mice with and without menopause and HDM challenge by large-scale targeted metabolomics. Female mice were treated with VCD/HDM to model menopause-associated asthma, and serum and BALF samples were processed for large-scale targeted metabolomic assessment. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) was used to examine metabolites of potential biological significance. We identified over 50 individual metabolites, impacting 46 metabolic pathways, in the serum and BALF that were significantly different across the four study groups. In particular, glutamate, GABA, phosphocreatine, and pyroglutamic acid, which are involved in glutamate/glutamine, glutathione, and arginine and proline metabolisms, were significantly impacted in the menopausal HDM-challenged mice. Additionally, several metabolites had significant correlations with total airway resistance including glutamic acid, histamine, uridine, cytosine, cytidine, and acetamide. Using metabolic profiling, we identified metabolites and metabolic pathways that may aid in discriminating potential biomarkers for and drivers of menopause-associated asthma.
Bee Pollen and Probiotics’ Potential to Protect and Treat Intestinal Permeability in Propionic Acid-Induced Rodent Model of Autism
Authors: Alonazi Mona , Ben Bacha Abir , Alharbi Mona G. , Khayyat Arwa Ishaq A. , AL-Ayadhi Laila , El-Ansary Afaf
Published: April 2023

Rodent models may help investigations on the possible link between autism spectrum disorder (ASD) and gut microbiota since autistic patients frequently manifested gastrointestinal troubles as co-morbidities. Thirty young male rats were divided into five groups: Group 1 serves as control; Group 2, bee pollen and probiotic-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism; Group 4 and Group 5, the protective and therapeutic groups were given bee pollen and probiotic combination treatment either before or after the neurotoxic dose of PPA, respectively. Serum occludin, zonulin, lipid peroxides (MDA), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPX), catalase, and gut microbial composition were assessed in all investigated groups. Recorded data clearly indicated the marked elevation in serum occludin (1.23 ± 0.15 ng/mL) and zonulin (1.91 ± 0.13 ng/mL) levels as potent biomarkers of leaky gut in the PPA- treated rats while both were normalized to bee pollen/probiotic-treated rats. Similarly, the high significant decrease in catalase (3.55 ± 0.34 U/dL), GSH (39.68 ± 3.72 µg/mL), GST (29.85 ± 2.18 U/mL), and GPX (13.39 ± 1.54 U/mL) concomitant with a highly significant increase in MDA (3.41 ± 0.12 µmoles/mL) as a marker of oxidative stress was also observed in PPA-treated animals. Interestingly, combined bee pollen/probiotic treatments demonstrated remarkable amelioration of the five studied oxidative stress variables as well as the fecal microbial composition. Overall, our findings demonstrated a new approach to the beneficial use of bee pollen and probiotic combination as a therapeutic intervention strategy to relieve neurotoxic effects of PPA, a short-chain fatty acid linked to the pathoetiology of autism.
Diagnostic Testing Accuracy for Helicobacter pylori Infection among Adult Patients with Dyspepsia in Cuba’s Primary Care Setting
Authors: Duquesne Amílcar , Falcón Rosabel , Galindo Belkys , Feliciano Onelkis , Gutiérrez Oderay , Baldoquín Waldemar , Fonseca Magile C. , Llanes Rafael , Sarmiento Luis
Published: April 2023

Evidence of the effectiveness of the tests used to diagnose Helicobacter pylori (H. pylori) in primary healthcare is limited. This cross-sectional study aims to assess the accuracy of tests used for to diagnose H. pylori infection in primary care patients and its relationship with gastroduodenal pathologies. Over 12 months, 173 primary care patients with dyspeptic symptoms were referred for upper gastrointestinal endoscopy to obtain gastric biopsies, and venous blood was extracted from them. H. pylori infection was detected using a rapid urease test (RUT), real-time polymerase chain reaction (RT-PCR), H. pylori-IgG ELISA, and Western blot (WB). The culture and histological findings were used as the reference standard for H. pylori infection. H. pylori prevalence was 50%. There were no significant differences between men and women overall or by age group. The presence of H. pylori was associated with chronic moderate gastritis and its absence with chronic inactive gastritis, as well as the combination of gastritis and gastric lesions (p < 0.05). RUT and ELISA H. pylori -IgG tests showed the highest overall performance (accuracy 98.9% and 84.4%), followed by WB and RT-PCR (accuracy 79.3% and 73.9%). These findings support the notion that combined invasive and noninvasive methods, such as RUT and H. pylori-IgG ELISA, can be a primary diagnostic screening tool for detecting H. pylori among adult dyspeptic patients in Cuba’s primary care setting.
Updates in Laboratory Identification of Invasive Fungal Infection in Neonates
Authors: He Binghong , Yang Qiong
Published: April 2023

Invasive fungal infection (IFI) in immunocompromised neonates is significantly associated with high morbidity and mortality and has become the third most common infection in Neonatal Intensive Care Units. The early diagnosis of IFI for neonatal patients is difficult because of the lack of specific symptoms. The traditional blood culture remains the gold standard in clinical diagnosis for neonatal patients but it requires a long duration, which delays treatment initiation. Detections of fungal cell-wall components are developed for early diagnosis but the diagnostic accuracy in neonates needs to be improved. PCR-based laboratory methods, such as real-time PCR, droplet digital PCR, and the cationic conjugated polymer fluorescence resonance energy transfer (CCP-FRET) system, distinguish the infected fungal species by their specific nucleic acids and show a high sensitivity and specificity. Particularly, the CCP-FRET system, which contains a cationic conjugated polymer (CCP) fluorescent probe and pathogen-specific DNA labeled with fluorescent dyes, could identify multiple infections simultaneously. In the CCP-FRET system, the CCP and fungal DNA fragments can self-assemble into a complex with an electrostatic interaction and the CCP triggers the FRET effect under ultraviolet light to make the infection visible. Here, we summarize the recent laboratory methods for neonatal IFI identification and provide a new perspective for early clinical fungal diagnosis.
Infrared Spectra of Small Radicals for Exoplanetary Spectroscopy: OH, NH, CN and CH: The State of Current Knowledge
Authors: Civiš Svatopluk , Pastorek Adam , Ferus Martin , Yurchenko Sergei N. , Boudjema Noor-Ines
Published: April 2023

In this study, we present a current state-of-the-art review of middle-to-near IR emission spectra of four simple astrophysically relevant molecular radicals—OH, NH, CN and CH. The spectra of these radicals were measured by means of time-resolved Fourier transform infrared spectroscopy in the 700–7500 cm−1 spectral range and with 0.07–0.02 cm−1 spectral resolution. The radicals were generated in a glow discharge of gaseous mixtures in a specially designed discharge cell. The spectra of short-lived radicals published here are of great importance, especially for the detailed knowledge and study of the composition of exoplanetary atmospheres in selected new planets. Today, with the help of the James Webb telescope and upcoming studies with the help of Plato and Ariel satellites, when the investigated spectral area is extended into the infrared spectral range, it means that detailed knowledge of the infrared spectra of not only stable molecules but also the spectra of short-lived radicals or ions, is indispensable. This paper follows a simple structure. Each radical is described in a separate chapter, starting with historical and actual theoretical background, continued by our experimental results and concluded by spectral line lists with assigned notation.
Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators
Authors: Zhang Zongying , Wang Anqi , Wang Yunhan , Sun Weichen , Zhou Xiaorong , Xu Qiuyun , Mao Liming , Zhang Jie
Published: April 2023

Chronic inflammatory disease (CID) is a category of medical conditions that causes recurrent inflammatory attacks in multiple tissues. The occurrence of CID is related to inappropriate immune responses to normal tissue substances and invading microbes due to many factors, such as defects in the immune system and imbalanced regulation of commensal microbes. Thus, effectively keeping the immune-associated cells and their products in check and inhibiting aberrant activation of the immune system is a key strategy for the management of CID. Canthin-6-ones are a subclass of β-carboline alkaloids isolated from a wide range of species. Several emerging studies based on in vitro and in vivo experiments reveal that canthin-6-ones may have potential therapeutic effects on many inflammatory diseases. However, no study has yet summarized the anti-inflammatory functions and the underlying mechanisms of this class of compounds. This review provides an overview of these studies, focusing on the disease entities and the inflammatory mediators that have been shown to be affected by canthin-6-ones. In particular, the major signaling pathways affected by canthin-6-ones, such as the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the NF-κB signaling pathway, and their roles in several CIDs are discussed. Moreover, we discuss the limitations in studies of canthin-6-ones and provide possible solutions. In addition, a perspective that may suggest possible future research directions is provided. This work may be helpful for further mechanistic studies and possible therapeutic applications of canthin-6-ones in the treatment of CID.
Chiral Binaphthalene Building Blocks for Self-Assembled Nanoscale CPL Emitters
Authors: Hsieh Yu-Yu , Shyue Jing-Jong , Chao Yu-Chiang , Wong Ken-Tsung , Bassani Dario M.
Published: April 2023

The introduction of biuret hydrogen-bonding sites onto chiral binaphthalene-based chromophores was investigated as a route to sub-micron-sized, vesicle-like aggregates endowed with chiroptical properties. The synthesis was conducted from the corresponding chiral 4,4′-dibromo-1,1′-bis(2-naphthol) via Suzuki–Miyaura coupling to afford luminescent chromophores whose emission spectrum could be tuned from blue to yellow-green through extension of the conjugation. For all compounds, the spontaneous formation of hollow spheres with a diameter of ca. 200–800 nm was evidenced by scanning electron microscopy, along with strong asymmetry in the circularly polarized absorption spectra. For some compounds, the emission also displayed circular polarization with values of glum = ca. 10–3 which could be increased upon aggregation.
Graphene Modification by Curcuminoids as an Effective Method to Improve the Dispersion and Stability of PVC/Graphene Nanocomposites
Authors: Wilczewski Sławomir , Skórczewska Katarzyna , Tomaszewska Jolanta , Osial Magdalena , Dąbrowska Agnieszka , Nikiforow Kostiantyn , Jenczyk Piotr , Grzywacz Hubert
Published: April 2023

A large amount of graphene-related research is its use as a filler for polymer composites, including thin nanocomposite films. However, its use is limited by the need for large-scale methods to obtain high–quality filler, as well as its poor dispersion in the polymer matrix. This work presents polymer thin-film composites based on poly(vinyl chloride) (PVC) and graphene, whose surfaces were modified by curcuminoids. TGA, UV–vis, Raman spectroscopy, XPS, TEM, and SEM methods have confirmed the effectiveness of the graphene modification due to π–π interactions. The dispersion of graphene in the PVC solution was investigated by the turbidimetric method. SEM, AFM, and Raman spectroscopy methods evaluated the thin-film composite’s structure. The research showed significant improvements in terms of graphene’s dispersion (in solutions and PVC composites) following the application of curcuminoids. The best results were obtained for materials modified with compounds obtained from the extraction of the rhizome of Curcuma longa L. Modification of the graphene’s surface with these compounds also increased the thermal and chemical stability of PVC/graphene nanocomposites.
Mechanical Force-Induced Color-Variable Luminescence of Carbon Dots in Boric Acid Matrix
Authors: Meng Shuai , Cheng Dengke , Gu Hailing , Li Yuchen , Qin Yukun , Tan Jing , Li Qijun
Published: April 2023

Mechano-luminescent materials that exhibit distinct luminescence responses to force stimuli are urgently anticipated in view of application needs in the fields of sensing, anti-counterfeiting, optoelectronic devices, etc. However, most of the reported materials normally exhibit force-induced changes in luminescent intensity, whereas materials that possess force-induced color-variable luminescence remain rarely reported. Herein, for the first time, a novel mechanical force-induced color-variable luminescence material from carbon dots (CDs) in boric acid (CD@BA) is reported. At low CDs concentration, the luminescence of CD@BA exhibits a grinding-induced color variable from white to blue. This grinding-induced color variable can be switched to yellow-to-white changing by increasing the CDs concentration in BA. The grinding-induced color-variable luminescence originates from dynamic variation in emission ratio of fluorescence and room temperature phosphorescence, due to the influence of oxygen and water vapor in the air. At high CDs concentration, short-wavelength fluorescence undergoes more severe reabsorption compared to room temperature phosphorescence, leading to grinding-induced color-variable switching from white-to-blue to yellow-to-white. Based on the unique properties of CD@BA powder, the applications of recognizing and visualizing fingerprints on the surfaces of various of materials are demonstrated.
Improvement of the In Vitro Cytotoxic Effect on HT-29 Colon Cancer Cells by Combining 5-Fluorouacil and Fluphenazine with Green, Red or Brown Propolis
Authors: Falcão Soraia I. , Duarte Diana , Diallo Moustapha , Santos Joana , Ribeiro Eduarda , Vale Nuno , Vilas-Boas Miguel
Published: April 2023

Cancer is regard as one of the key factors of mortality and morbidity in the world. Treatment is mainly based on chemotherapeutic drugs that, when used in targeted therapies, have serious side effects. 5-fluorouracil (5-FU) is a drug commonly used against colorectal cancer (CRC), despite its side effects. Combination of this compound with natural products is a promising source in cancer treatment research. In recent years, propolis has become the subject of intense pharmacological and chemical studies linked to its diverse biological properties. With a complex composition rich in phenolic compounds, propolis is described as showing positive or synergistic interactions with several chemotherapeutic drugs. The present work evaluated the in vitro cytotoxic activity of the most representative propolis types, such as green, red and brown propolis, in combination with chemotherapeutic or CNS drugs on HT-29 colon cancer cell lines. The phenolic composition of the propolis samples was evaluated by LC-DAD-ESI/MSn analysis. According to the type of propolis, the composition varied; green propolis was rich in terpenic phenolic acids and red propolis in polyprenylated benzophenones and isoflavonoids, while brown propolis was composed mainly of flavonoids and phenylpropanoids. Generally, for all propolis types, the results demonstrated that combing propolis with 5-FU and fluphenazine successfully enhances the in vitro cytotoxic activity. For green propolis, the combination demonstrated an enhancement of the in vitro cytotoxic effect compared to green propolis alone, at all concentrations, while for brown propolis, the combination in the concentration of 100 μg/mL gave a lower number of viable cells, even when compared with 5-FU or fluphenazine alone. The same was observed for the red propolis combination, but with a higher reduction in cell viability. The combination index, calculated based on the Chou–Talalay method, suggested that the combination of 5-FU and propolis extracts had a synergic growth inhibitory effect in HT-29 cells, while with fluphenazine, only green and red propolis, at a concentration of 100 μg/mL, presented synergism.
Competing Magnetic Interactions and Field-Induced Metamagnetic Transition in Highly Crystalline Phase-Tunable Iron Oxide Nanorods
Authors: Attanayake Supun B. , Chanda Amit , Hulse Thomas , Das Raja , Phan Manh-Huong , Srikanth Hariharan
Published: April 2023

The inherent existence of multi phases in iron oxide nanostructures highlights the significance of them being investigated deliberately to understand and possibly control the phases. Here, the effects of annealing at 250 °C with a variable duration on the bulk magnetic and structural properties of high aspect ratio biphase iron oxide nanorods with ferrimagnetic Fe3O4 and antiferromagnetic α-Fe2O3 are explored. Increasing annealing time under a free flow of oxygen enhanced the α-Fe2O3 volume fraction and improved the crystallinity of the Fe3O4 phase, identified in changes in the magnetization as a function of annealing time. A critical annealing time of approximately 3 h maximized the presence of both phases, as observed via an enhancement in the magnetization and an interfacial pinning effect. This is attributed to disordered spins separating the magnetically distinct phases which tend to align with the application of a magnetic field at high temperatures. The increased antiferromagnetic phase can be distinguished due to the field-induced metamagnetic transitions observed in structures annealed for more than 3 h and was especially prominent in the 9 h annealed sample. Our controlled study in determining the changes in volume fractions with annealing time will enable precise control over phase tunability in iron oxide nanorods, allowing custom-made phase volume fractions in different applications ranging from spintronics to biomedical applications.
Nutritional Programming of the Lifespan of Male Drosophila by Activating FOXO on Larval Low-Nutrient Diet
Authors: Gao Yue , Cheng Xingyi , Tian Yao , Yuan Zhixiao , Fan Xiaolan , Yang Deying , Yang Mingyao
Published: April 2023

Nutrition during the developmental stages has long-term effects on adult physiology, disease and lifespan, and is termed nutritional programming. However, the underlying molecular mechanisms of nutritional programming are not yet well understood. In this study, we showed that developmental diets could regulate the lifespan of adult Drosophila in a way that interacts with various adult diets during development and adulthood. Importantly, we demonstrated that a developmental low-yeast diet (0.2SY) extended both the health span and lifespan of male flies under nutrient-replete conditions in adulthood through nutritional programming. Males with a low-yeast diets during developmental stages had a better resistance to starvation and lessened decline of climbing ability with age in adulthood. Critically, we revealed that the activity of the Drosophila transcription factor FOXO (dFOXO) was upregulated in adult males under developmental low-nutrient conditions. The knockdown of dFOXO, with both ubiquitous and fat-body-specific patterns, can completely abolish the lifespan-extending effect from the larval low-yeast diet. Ultimately, we identify that the developmental diet achieved the nutritional programming of the lifespan of adult males by modulating the activity of dFOXO in Drosophila. Together, these results provide molecular evidence that the nutrition in the early life of animals could program the health of their later life and their longevity.
Adherence to Mediterranean Diet: A Population-Based Longitudinal Cohort Study
Authors: Mattavelli Elisa , Olmastroni Elena , Casula Manuela , Grigore Liliana , Pellegatta Fabio , Baragetti Andrea , Magni Paolo , Catapano Alberico L.
Published: April 2023

Adherence to the Mediterranean diet (MedDiet) is recommended for cardiovascular disease prevention. However, recent epidemiological studies report a shift toward lower adherence to MedDiet. We have conducted a prospective cohort study to evaluate changes in individual determinants of MedDiet adherence over time. Clinical information and MedDiet adherence score (MEDAS) were collected in 711 subjects (mean age 68 ± 10 years; 42% males), enrolled in the PLIC study (Progression of Intimal Atherosclerotic Lesions in Carotid arteries), during two visits conducted, on average, 4.5 years apart. MEDAS score worsening and improvements (absolute change, ΔMEDAS) and the variation in the proportion of subjects reporting to meet each MEDAS criteria were assessed. Overall, 34% of the subjects improved their MedDiet adherence (ΔMEDAS: +1.87 ± 1.13), by consuming more olive oil, legumes and fish and use of dishes seasoned with sofrito and 48% subjects worsened their MedDiet adherence (ΔMEDAS: −2.02 ± 1.14) by consuming less fruit, legumes, fish and nuts, with higher rates of worsening in women and subjects aged 50–65 years. Subjects who improved the score were more obese, had higher plasma glucose levels, and metabolic syndrome at the basal visit. In summary, we report an overall decrease in MedDiet adherence, evaluated during a timeframe heavily affected by the COVID-19 pandemic, underlining the need for better dietary interventions.
Association of Body Mass Index with Insulin-like Growth Factor-1 Levels among 3227 Chinese Children Aged 2–18 Years
Authors: Li Yang , Zong Xinnan , Zhang Yaqin , Guo Jiayun , Li Hui
Published: April 2023

Objectives: Insulin-like growth factor-1 (IGF-1) levels are affected by nutritional status, yet there is limited research exploring the association between body mass index (BMI) and IGF-1 levels among children. Methods: This cross-sectional study included 3227 children aged 2–18 years without specific diseases, whose height, weight, and pubertal stages were measured and assessed by pediatricians. BMI standard deviation scores (BMISDS) were used to categorize children as underweight (BMISDS < −2); normal-weight (−2 ≤ BMISDS ≤ 1); overweight (1 < BMISDS ≤ 2); and obese (BMISDS > 2). Children were divided into low-level (<−0.67 SD) and nonlow-level (≥−0.67 SD) groups based on IGF-1 standard deviation scores (IGF-1SDS). The association between IGF-1 and BMI as categorical and continuous variables was explored by Binary logistic regression, the restrictive cubic spline model, and the generalized additive model. Models were adjusted by height and pubertal development. Recursive algorithm and multivariate piecewise linear regression were further utilized to assess the threshold of the smooth curve. Results: IGF-1 levels varied by BMI categories, with the highest levels observed in the overweight group. The proportion of low IGF-1 levels in underweight, normal-weight, overweight, and obese groups was 32.1%, 14.2%, 8.4%, and 6.5%, respectively. The risk odds of low IGF-1 levels in underweight children were 2.86-, 2.20-, and 2.25-fold higher than in children with normal weight before adjustment, after adjustment for height, and after adjustment for height and puberty, respectively. When analyzing the association between BMI and low IGF-1 levels, dose-response analysis demonstrated an inverted J-shaped relationship between BMISDS and low IGF-1 levels. Lower or higher BMISDS increased the odds of low IGF-1 levels, and significance was retained in underweight children but not in obese children. When BMI and IGF-1 levels were used as continuous variables, the relationship between the BMISDS and IGF-1SDS followed a nonlinear inverted U shape. IGF-1SDS increased with the increase of BMISDS (β = 0.174, 95% CI: 0.141 to 0.208, p < 0.01) when BMISDS was less than 1.71 standard deviation (SD) and decreased with the increase of BMISDS (β = −0.358, 95% CI: −0.474 to −0.241, p < 0.01) when BMISDS was greater than 1.71 SD. Conclusions: The relationship between BMI and IGF-1 levels was found to depend on the type of variable, and extremely low or high BMI values could result in a tendency toward low IGF-1 levels, emphasizing the importance of maintaining a normal BMI range for normal IGF-1 levels.
Enhanced Vulnerability of Diabetic Mice to Hypervirulent Streptococcus agalactiae ST-17 Infection
Authors: da Conceição Mendonça Jéssica , Sobral Pena João Matheus , dos Santos Macêdo Noemi , de Souza Rodrigues Dayane , de Oliveira Dayane Alvarinho , Spencer Brady L. , Lopes-Torres Eduardo José , Burcham Lindsey R. , Doran Kelly S. , Nagao Prescilla Emy
Published: April 2023

Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of neonatal sepsis and meningitis but has been recently isolated from non-pregnant adults with underlying medical conditions like diabetes. Despite diabetes being a key risk factor for invasive disease, the pathological consequences during GBS infection remain poorly characterized. Here, we demonstrate the pathogenicity of the GBS90356-ST17 and COH1-ST17 strains in streptozotocin-induced diabetic mice. We show that GBS can spread through the bloodstream and colonize several tissues, presenting a higher bacterial count in diabetic-infected mice when compared to non-diabetic-infected mice. Histological sections of the lungs showed inflammatory cell infiltration, collapsed septa, and red blood cell extravasation in the diabetic-infected group. A significant increase in collagen deposition and elastic fibers were also observed in the lungs. Moreover, the diabetic group presented red blood cells that adhered to the valve wall and disorganized cardiac muscle fibers. An increased expression of KC protein, IL-1β, genes encoding immune cell markers, and ROS (reactive oxygen species) production was observed in diabetic-infected mice, suggesting GBS promotes high levels of inflammation when compared to non-diabetic animals. Our data indicate that efforts to reverse the epidemic of diabetes could considerably reduce the incidence of invasive infection, morbidity and mortality due to GBS.
BCG Vaccination and the Risk of Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Jamshidi Parnian , Danaei Bardia , Mohammadzadeh Benyamin , Arbabi Mahta , Nayebzade Amirhossein , Sechi Leonardo A. , Nasiri Mohammad Javad
Published: April 2023

(1) Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by progressive and irreversible autoimmune destruction of pancreatic beta cell islets, resulting in absolute insulin deficiency. To date, several epidemiologic and observational studies have evaluated the possible impact of BCG vaccination on T1D development, but the results are controversial. To elucidate this issue, we aimed to conduct a systematic review and meta-analysis of published cohort studies in this field. (2) Methods: A systematic search was performed for relevant studies published up to 20 September 2022 using Pubmed/Medline, Embase, and Scopus. Cohort studies, containing original information about the association between T1D and BCG vaccination, were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the risk ratio of T1D in BCG-vaccinated individuals compared to unvaccinated ones were assessed using the fixed effect model. (3) Results: Out of 630 potentially relevant articles, five cohort studies met the inclusion criteria. The total population of all included studies was 864,582. The overall pooled risk ratio of T1D development in BCG vaccinated and unvaccinated individuals was found to be 1.018 (95% CI 0.908–1.141, I2: 0%). (4) Conclusions: Our study revealed no protective or facilitative effect of prior BCG vaccination in T1D development.
Association between Mastitis Occurrence in Dairy Cows and Bedding Characteristics of Compost-Bedded Pack Barns
Authors: Freu Gustavo , Garcia Breno Luis Nery , Tomazi Tiago , Di Leo Gabriela Siqueira , Gheller Larissa Schneider , Bronzo Valerio , Moroni Paolo , Dos Santos Marcos Veiga
Published: April 2023

Compost-bedded pack barns (CB) are receiving increasing attention as a housing system that can potentially improve the welfare of dairy cows. This study characterized the frequency and profile of pathogens isolated from clinical (CM) and subclinical (SCM) mastitis in dairy cows housed in CB. It evaluated the association between mastitis occurrence and bedding characteristics in CB systems. Over six months, seven dairy herds were visited monthly for milk and bedding sample collections. Milk samples from mastitis cases were submitted to microbiological identification by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF MS). Bedding samples were submitted to physical-chemical (pH, organic matter, moisture, and carbon to nitrogen ratio) and microbiological counting (total bacterial counts, coliforms, streptococci, and staphylococci) analyses. Regression analysis was used to determine the association between mastitis occurrence and CB characteristics. Our results showed that Escherichia coli and environmental streptococci were the most frequently isolated pathogens from CM cases, while Staphylococcus chromogenes and contagious pathogens (Staphylococcus aureus and Streptococcus agalactiae) were the most commonly isolated from SCM cases. Bedding moisture content was positively associated with the incidence of CM. The bedding carbon to nitrogen ratio was negatively associated with the incidence of SCM, and the bedding total bacteria counts tended to be associated with the incidence of SCM. Bedding counts of coliforms positively associated with the prevalence of SCM. Our results can support decision-makers in the dairy industry seeking strategies for bedding management and mastitis control.
Inclisiran, Low-Density Lipoprotein Cholesterol and Lipoprotein (a)
Authors: Katsiki Niki , Vrablik Michal , Banach Maciej , Gouni-Berthold Ioanna
Published: April 2023

Dyslipidemia treatment is of major importance in reducing the risk of atherosclerotic cardiovascular disease (ASCVD), which is still the most common cause of death worldwide. During the last decade, a novel lipid-lowering drug category has emerged, i.e., proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Apart from the two available anti-PCSK9 monoclonal antibodies (alirocumab and evolocumab), other nucleic acid-based therapies that inhibit or “silence” the expression of PCSK9 are being developed. Among them, inclisiran is the first-in-class small interfering RNA (siRNA) against PCSK9 that has been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. Importantly, inclisiran therapy may improve low-density lipoprotein cholesterol (LDL-C) target achievement by offering a prolonged and significant LDL-C-lowering effect with the administration of only two doses per year. The present narrative review discusses the ORION/VICTORION clinical trial program that has been designed to investigate the impact of inclisiran on atherogenic lipoproteins and major adverse cardiac events in different patient populations. The results of the completed clinical trials are presented, focusing on the effects of inclisiran on LDL-C and lipoprotein (a) (Lp(a)) levels as well as on other lipid parameters such as apolipoprotein B and non-high-density lipoprotein cholesterol (non-HDL-C). Ongoing clinical trials with inclisiran are also discussed.
Polymer-Based Nanostructures for Pancreatic Beta-Cell Imaging and Non-Invasive Treatment of Diabetes
Authors: Behzadifar Shakila , Barras Alexandre , Plaisance Valérie , Pawlowski Valérie , Szunerits Sabine , Abderrahmani Amar , Boukherroub Rabah
Published: April 2023

Diabetes poses major economic, social, and public health challenges in all countries worldwide. Besides cardiovascular disease and microangiopathy, diabetes is a leading cause of foot ulcers and lower limb amputations. With the continued rise of diabetes prevalence, it is expected that the future burden of diabetes complications, early mortality, and disabilities will increase. The diabetes epidemic is partly caused by the current lack of clinical imaging diagnostic tools, the timely monitoring of insulin secretion and insulin-expressing cell mass (beta (β)-cells), and the lack of patients’ adherence to treatment, because some drugs are not tolerated or invasively administrated. In addition to this, there is a lack of efficient topical treatment capable of stopping the progression of disabilities, in particular for treating foot ulcers. In this context, polymer-based nanostructures garnered significant interest due to their tunable physicochemical characteristics, rich diversity, and biocompatibility. This review article emphasizes the last advances and discusses the prospects in the use of polymeric materials as nanocarriers for β-cell imaging and non-invasive drug delivery of insulin and antidiabetic drugs in the management of blood glucose and foot ulcers.
Small Extracellular Vesicles’ miRNAs: Biomarkers and Therapeutics for Neurodegenerative Diseases
Authors: Lim Wei Qing , Michelle Luk Kie Hoon , Lee Kah Yee , Nurul Nasuha , Loh Sin Jade , Yeow Zhen Xiong , Wong Qi Xuan , Daniel Looi Qi Hao , Chong Pan Pan , How Chee Wun , Hamzah Sharina , Foo Jhi Biau
Published: April 2023

Neurodegenerative diseases are critical in the healthcare system as patients suffer from progressive diseases despite currently available drug management. Indeed, the growing ageing population will burden the country’s healthcare system and the caretakers. Thus, there is a need for new management that could stop or reverse the progression of neurodegenerative diseases. Stem cells possess a remarkable regenerative potential that has long been investigated to resolve these issues. Some breakthroughs have been achieved thus far to replace the damaged brain cells; however, the procedure’s invasiveness has prompted scientists to investigate using stem-cell small extracellular vesicles (sEVs) as a non-invasive cell-free therapy to address the limitations of cell therapy. With the advancement of technology to understand the molecular changes of neurodegenerative diseases, efforts have been made to enrich stem cells’ sEVs with miRNAs to increase the therapeutic efficacy of the sEVs. In this article, the pathophysiology of various neurodegenerative diseases is highlighted. The role of miRNAs from sEVs as biomarkers and treatments is also discussed. Lastly, the applications and delivery of stem cells and their miRNA-enriched sEVs for treating neurodegenerative diseases are emphasised and reviewed.
Establishment of an Antiplasmodial Vaccine Based on PfRH5-Encoding RNA Replicons Stabilized by Cationic Liposomes
Authors: Fotoran Wesley L. , Silva Jamile Ramos da , Glitz Christiane , Ferreira Luís Carlos de Souza , Wunderlich Gerhard
Published: April 2023

Background: Nucleic acid-based vaccines have been studied for the past four decades, but the approval of the first messenger RNA (mRNA) vaccines during the COVID-19 pandemic opened renewed perspectives for the development of similar vaccines against different infectious diseases. Presently available mRNA vaccines are based on non-replicative mRNA, which contains modified nucleosides encased in lipid vesicles, allowing for entry into the host cell cytoplasm, and reducing inflammatory reactions. An alternative immunization strategy employs self-amplifying mRNA (samRNA) derived from alphaviruses, but lacks viral structural genes. Once incorporated into ionizable lipid shells, these vaccines lead to enhanced gene expression, and lower mRNA doses are required to induce protective immune responses. In the present study, we tested a samRNA vaccine formulation based on the SP6 Venezuelan equine encephalitis (VEE) vector incorporated into cationic liposomes (dimethyldioctadecyl ammonium bromide and a cholesterol derivative). Three vaccines were generated that encoded two reporter genes (GFP and nanoLuc) and the Plasmodium falciparum reticulocyte binding protein homologue 5 (PfRH5). Methods: Transfection assays were performed using Vero and HEK293T cells, and the mice were immunized via the intradermal route using a tattooing device. Results: The liposome–replicon complexes showed high transfection efficiencies with in vitro cultured cells, whereas tattooing immunization with GFP-encoding replicons demonstrated gene expression in mouse skin up to 48 h after immunization. Mice immunized with liposomal PfRH5-encoding RNA replicons elicited antibodies that recognized the native protein expressed in P. falciparum schizont extracts, and inhibited the growth of the parasite in vitro. Conclusion: Intradermal delivery of cationic lipid-encapsulated samRNA constructs is a feasible approach for developing future malaria vaccines.
Quantitative Endogenous Fluorescence Analysis Discriminates Glioblastoma Tumor through Visible and NIR Excitation
Authors: Mehidine Hussein , Kaadou Mouawad Emile , Varlet Pascale , Devaux Bertrand , Abi Haidar Darine
Published: April 2023

Nowadays, the ability to diagnose brain tumors intraoperatively and delineate their margins, as accurately as possible, is of primordial importance during surgery. However, the exact tumor boundaries and targets are difficult to find due to the similar visual appearances especially at the margins, leading in many cases to poor surgical outcomes and a high risk of recurrences. To solve this dogma, our group tried to determine different tissue optical signatures such as optical parameters and endogenous fluorescence. For that, we conducted a comparative study to differentiate between healthy and tumorous tissues under one- and two-photon excitations on optical properties to explore several optical parameters. In addition, the study of endogenous fluorescence can successfully help with the discrimination between tissue types using one- and two-photon excitations. This works suggests that the multimodal analysis of optical signatures of tissues could be a reliable technique that can be used to differentiate between healthy and tumorous tissues. This can help in the future with the implementation of such techniques in vivo during surgery to help the surgeon with the decision that needs to be taken as for tissue resection.