bluuebunny/crossref_metadata_2025 huggingface dataset:
Parameter Identification of the Yoshida-Uemori Hardening Model for Remanufacturing
Authors: Xia Xuhui , Gong Mingjian , Wang Tong , Liu Yubo , Zhang Huan , Zhang Zelin
Published: November 2021

The deformation of plastics during production and service means that retired parts often possess different mechanical states, and this can directly affect not only the properties of remanufactured mechanical parts, but also the design of the remanufacturing process itself. In this paper, we describe the stress-strain relationship for remanufacturing, in particular the cyclic deformation of parts, by using the particle swarm optimization (PSO) method to acquire the Yoshida-Uemori (Y-U) hardening model parameters. To achieve this, tension-compression experimental data of AA7075-O, standard PSO, oscillating second-order PSO (OS-PSO) and variable weight PSO (VW-PSO) were acquired separately. The influence of particle numbers on the inverse analysis efficiency was studied based on standard PSO. Comparing the results of PSO variations showed that: (1) standard PSO is able to avoid local solutions and obtain Y-U model parameters to the same degree of precision as the OS-PSO; (2) by adjusting section weight, the VW-PSO could improve local fitting accuracy and adapt to asymmetric deformation; (3) by reducing particle numbers to a certain extent, the efficiency of analysis can be improved while also maintaining accuracy.
A Comparative Investigation of Conventional and Hammering-Assisted Incremental Sheet Forming Processes for AA1050 H14 Sheets
Authors: Shahare Harshal Y. , Dubey Abhay Kumar , Kumar Pavan , Yu Hailiang , Pesin Alexander , Pustovoytov Denis , Tandon Puneet
Published: November 2021

Incremental Sheet Forming (ISF) is emerging as one of the popular dieless forming processes for the small-sized batch production of sheet metal components. However, the parts formed by the ISF process suffer from poor surface finish, geometric inaccuracy, and non-uniform thinning, which leads to poor part characteristics. Hammering, on the other hand, plays an important role in relieving residual stresses, and thus enhances the material properties through a change in grain structure. A few studies based on shot peening, one of the types of hammering operation, revealed that shot peening can produce nanostructure surfaces with different characteristics. This paper introduces a novel process, named the Incremental Sheet Hammering (ISH) process, i.e., integration of incremental sheet forming (ISF) process and hammering to improve the efficacy of the ISF process. Controlled hammering in the ISF process causes an alternating motion at the tool-sheet interface in the local deformation zone. This motion leads to enhanced material flow and subsequent improvement in the surface finish. Typical toolpath strategies are incorporated to impart the tool movement. The mechanics of the process is further explored through explicit-dynamic numerical models and experimental investigations on 1 mm thick AA1050 sheets. The varying wall angle truncated cone (VWATC) and constant wall angle truncated cone (CWATC) test geometries are identified to compare the ISF and ISH processes. The results indicate that the formability is improved in terms of wall angle, forming depth and forming limits. Further, ISF and ISH processes are compared based on the numerical and experimental results. The indicative statistical analysis is performed which shows that the ISH process would lead to an overall 10.99% improvement in the quality of the parts primarily in the surface finish and forming forces.
Binary Simplification as an Effective Tool in Metabolomics Data Analysis
Authors: Traquete Francisco , Luz João , Cordeiro Carlos , Sousa Silva Marta , Ferreira António E. N.
Published: November 2021

Metabolomics aims to perform a comprehensive identification and quantification of the small molecules present in a biological system. Due to metabolite diversity in concentration, structure, and chemical characteristics, the use of high-resolution methodologies, such as mass spectrometry (MS) or nuclear magnetic resonance (NMR), is required. In metabolomics data analysis, suitable data pre-processing, and pre-treatment procedures are fundamental, with subsequent steps aiming at highlighting the significant biological variation between samples over background noise. Traditional data analysis focuses primarily on the comparison of the features’ intensity values. However, intensity data are highly variable between experimental batches, instruments, and pre-processing methods or parameters. The aim of this work was to develop a new pre-treatment method for MS-based metabolomics data, in the context of sample profiling and discrimination, considering only the occurrence of spectral features, encoding feature presence as 1 and absence as 0. This “Binary Simplification” encoding (BinSim) was used to transform several benchmark datasets before the application of clustering and classification methods. The performance of these methods after the BinSim pre-treatment was consistently as good as and often better than after different combinations of traditional, intensity-based, pre-treatments. Binary Simplification is, therefore, a viable pre-treatment procedure that effectively simplifies metabolomics data-analysis pipelines.
Towards High Throughput Structuring of Liquid Foams in Microchannels: Effect of Geometry, Flowrate and Formulation
Authors: Sepulveda Julian , Montillet Agnès , Valle Dominique Della , Loisel Catherine , Riaublanc Alain
Published: November 2021

This work is part of a study aiming to design a high-throughput foaming microsystem. The main focused field of application is the food industry. With the objective of improving the design of the microdevice, the effects of the geometry and the nature of the liquid base are presently investigated through visualizations of the flow typology of bubbles trains, aiming to expand the knowledge on key parameters that lead to an improved gas breakup. The tested set of conditions is not encountered in traditional microfluidics systems: i.e., throughputs up to 19 L·h−1 for the liquid phase, process velocities around 20 m·s−1 and flow of complex fluids. The behavior of solutions based on xanthan gum (XG) and whey proteins (WPI) is compared to that of solutions containing one of these ingredients or other ones (caseinates, glycerol). The structural and end-used properties of the final foams, namely the bubble diameter and rheological behavior, are evaluated. The incorporation of XG induces bubble shape stabilization even at the highest shear rates (~105 s−1) encountered in the mixing channel. “Controlled” interfacial breakup by tip-streaming or binary breakup are only observed with the WPI/XG biopolymers. This study indubitably highlights the essential role of the process/formulation interaction in the development of structural and functional properties of food foams when using microfluidics at high throughput.
Design of Planar Array Transducers Based on Connected 1–3 Piezoelectric Composites
Authors: Wang Jiacheng , Zhong Chao , Hao Shaohua , Lv Ning , Wang Likun
Published: November 2021

To improve the transmission performance and preparation of a transducer array, two planar array transducers based on connected 1–3 piezoelectric composites as a matrix were designed. Each transducer contained 25 array elements with a gap of 1 mm between them. The length, width and height of each array element were 1 mm, 26 mm and 5 mm, respectively. Two kinds of array transducers were tested through finite element simulation and experiments. The array transducer prototype was fabricated based on two kinds of composite materials, and the fabrication cycle was short. Our results show that the maximum transmission voltage response of the two-phase 1–3 full array driver is up to 179 dB at 200–400 kHz and the acoustic radiation intensity can be increased by up to 22% compared with the traditional splicing transducer array. It is suitable for short-range target positioning and measurement. Moreover, in the single element mode, the beam of the three-phase 1–3 transducer has no sidelobe and a single element −3 dB beam width of up to 91°. Furthermore, the beam width of the two-phase 1–3 type is 54°, and the acoustic radiation breadth is improved by 40.6%. The three-phase 1–3 type array transducer has the characteristics of concentrated acoustic transmission energy of the whole array, and its −3 dB beam width is 3.5°. The beam width decreased by 12.5%, indicating that the three-phase 1–3 type transducer is suitable for short-range target detection and perception. The two array transducers have their own advantages in transmitting the voltage response and beam width, which must be selected on the basis of the requirements of practical applications.
Leaky Gut Syndrome Is Associated with Endotoxemia and Serum (1→3)-β-D-Glucan in Severe Dengue Infection
Authors: Chancharoenthana Wiwat , Leelahavanichkul Asada , Ariyanon Wassawon , Vadcharavivad Somratai , Phatcharophaswattanakul Suphasit , Kamolratanakul Supitcha , Leaungwutiwong Pornsawan , Phumratanaprapin Weerapong , Wilairatana Polrat
Published: November 2021

The hallmark of severe dengue infection is the increased vascular permeability and hemodynamic alteration that might be associated with an intestinal permeability defect. However, the mechanisms underlying the gastrointestinal-related symptoms of dengue are not well characterized. A prospective observational study was conducted on patients with dengue who were categorized according to: (i) febrile versus critical phase and (ii) hospitalized patients with versus without the warning signs to evaluate the gut barrier using lactulose-to-mannitol excretion ratio (LEMR). Serum endotoxins, (1→3)-β-D-glucan (BG), and inflammatory parameters were measured. A total of 48 and 38 patients were enrolled in febrile illness and critical phase, respectively, while 22 and 64 patients presented with or without the warning signs, respectively. At enrollment, a positive LEMR test was found in 20 patients (91%) with warning signs, regardless of phase of infection. Likewise, serum endotoxins and BG, the indirect biomarkers for leaky gut, prominently increased in patients who developed severe dengue when compared with the non-severe dengue (endotoxins, 399.1 versus 143.4 pg/mL (p < 0.0001); BG, 123 versus 73.8 pg/mL (p = 0.016)). Modest impaired intestinal permeability occurred in dengue patients, particularly those with warning signs, and were associated with endotoxemia and elevated BG. Thus, leaky gut syndrome might be associated with severity of dengue infection.
A Review of the Milestones Reached by the Attainable Region Optimisation Technique in Particle Size Reduction
Authors: Chimwani Ngonidzashe
Published: November 2021

The attainable region (AR) is an optimization method adopted for use in comminution to achieve different objective functions, which all converge to optimising the production of the desired particle size distributions for downstream processes. The technique has so far mostly been used to optimise the breakage of particles in tumbling mills. It achieved the desired purpose by unveiling all possible outcomes derived from a combination of operational parameters that are bound by trajectories showing the limitations of a system. The technique has given the scientific community lenses to see the behaviour of different parameters in ball mills otherwise known as the black boxes due to their concealing nature. Since its inception, the AR technique has been applied to data obtained from the laboratory tests and simulated industrial mills and the results sometimes contradict or confirm the conventional milling practices in the industry. This makes the already conservative mining industry sceptical about its adoption. This review thus assesses the milestone covered as far as the AR development in comminution is concerned. It also helps to clarify the sources of the discrepancies between the AR results and the conventional knowledge concerning the optimisation of ball mill operational parameters.
Assessment of the Impact of Modification of Calcium Sorbents and the Possibility of Their Use in Desulfurization for Oxy-Fuel Combustion Process
Authors: Wichliński Michał , Włodarczyk Renata
Published: November 2021

The paper describes the possibilities of simple and effective modification of calcium sorbents used for flue gas desulfurization with a size between of 125–250 µm. The additives to the sorbents in the amount of 0.5% and 1.0% were inorganic sodium and lithium compounds. The research on the reactivity of sorbents was analyzed in the process of simultaneous calcination and sulfation at the temperature of 850 °C. The type of Na+ or Li+ cations and the inorganic salt anions have an influence on the modification of calcium sorbents in order to improve the efficiency of the calcination and sulfation process. Modification of calcium sorbents by adding inorganic sodium and lithium compounds, regardless of the amount, changes the reactivity coefficient RI [mol/mol] and the absolute sorption coefficient CI [g S/kg sorbent]. In the case of inorganic sodium salt (Additive 1), regardless of the amount of modifier added, there was a visible improvement in the reactivity of the sorbent: 1.0% of the additive caused an increase in the RI coefficient in relation to the raw sorbent by over 14%, and in the case of the CI coefficient by over 24%. Additional research was the analysis of the limestone behavior mechanism during the simultaneous calcination and sulfation (SCS) process under conditions of elevated temperature and with variable CO2 and O2 contents in the flue gas. The behavior of sorbents with a size distribution of 125–250 µm was assessed on the basis of the change in mass of the samples by determining the reactivity coefficient RI, [mol/mol] and the absolute sorption coefficient CI, [g S/kg sorbent]. Using the mercury porosimetry technique, the change in sorbent porosity in the subsequent stages of the simultaneous calcination and sulfation process was investigated. The process was carried out in the temperature range corresponding to the oxy-combustion (i.e., from 850 °C to 1000 °C).
Regioisomers Salviprolin A and B, Unprecedented Rosmarinic Acid Conjugated Dinorditerpenoids from Salvia przewalskii Maxim
Authors: Su Xiangdong , Wu Yichuang , Wu Meifang , Lu Jielang , Jia Shujie , He Xin , Liu Shuna , Zhou Yuyang , Xing Hui , Xue Yongbo
Published: November 2021

Salvia przewalskii Maxim is a perennial plant from the genus Salvia (family Lamiaceae). The roots of S. przewalskii were long used as a traditional herb to treat blood circulation related illnesses in China. As part of our continuing interest in polycyclic natural products from medicinal plants, two unprecedented adducts comprised of a dinor-diterpenoid and a 9′-nor-rosmarinic acid derivative, linked by a 1,4-benzodioxane motif (1 and 2), were isolated from the roots of S. przewalskii. Their structures were established by extensive spectroscopic approaches including 1D, 2D NMR, and HRFABMS. Their cytotoxic activities against five human tumor cell lines were evaluated.
Rational Design of Simple Organocatalysts for the HSiCl3 Enantioselective Reduction of (E)-N-(1-Phenylethylidene)aniline
Authors: Maciá María , Porcar Raúl , Martí-Centelles Vicente , García-Verdugo Eduardo , Burguete Maria Isabel , Luis Santiago V.
Published: November 2021

Prolinamides are well-known organocatalysts for the HSiCl3 reduction of imines; however, custom design of catalysts is based on trial-and-error experiments. In this work, we have used a combination of computational calculations and experimental work, including kinetic analyses, to properly understand this process and to design optimized catalysts for the benchmark (E)-N-(1-phenylethylidene)aniline. The best results have been obtained with the amide derived from 4-methoxyaniline and the N-pivaloyl protected proline, for which the catalyzed process is almost 600 times faster than the uncatalyzed one. Mechanistic studies reveal that the formation of the component supramolecular complex catalyst-HSiCl3-substrate, involving hydrogen bonding breaking and costly conformational changes in the prolinamide, is an important step in the overall process.
Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads
Authors: Hengphasatporn Kowit , Kaewmalai Benyapa , Jansongsaeng Somruedee , Badavath Vishnu Nayak , Saelee Thanaphon , Chokmahasarn Thamonwan , Khotavivattana Tanatorn , Shigeta Yasuteru , Rungrotmongkol Thanyada , Boonyasuppayakorn Siwaporn
Published: November 2021

A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC50 of 2.36 ± 0.22, and 10.55 ± 3.37 µM, respectively, while the cytotoxicities were similar to the original apigenin at the CC50 of 70.34 ± 11.79, and 82.82 ± 11.68 µM, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.
A UPLC-DAD-Based Bio-Screening Assay for the Evaluation of the Angiotensin Converting Enzyme Inhibitory Potential of Plant Extracts and Compounds: Pyrroquinazoline Alkaloids from Adhatoda vasica as a Case Study
Authors: Tehreem Syeda , Rahman Saeedur , Bhatti Muhammad Salman , Uddin Reaz , Khan Muhammad Noman , Tauseef Saba , El-Seedi Hesham R. , Bin Muhsinah Abdullatif , Uddin Jalal , Musharraf Syed Ghulam
Published: November 2021

Angiotensin converting enzyme (ACE) plays a crucial role in regulating blood pressure in the human body. Identification of potential ACE inhibitors from medicinal plants supported the idea of repurposing these medicinal plants against hypertension. A method based on ultra-performance liquid chromatography (UPLC) coupled with a diode array detector (DAD) was used for the rapid screening of plant extracts and purified compounds to determine their ACE inhibitory activity. Hippuryl-histidiyl-leucine (HHL) was used as a substrate, which is converted into hippuric acid (HA) by the action of ACE. A calibration curve of the substrate HHL was developed with the linear regression 0.999. The limits of detection and quantification of this method were found to be 0.134 and 0.4061 mM, respectively. Different parameters of ACE inhibitory assay were optimized, including concentration, incubation time and temperature. The ACE inhibition potential of Adhatoda vasica (methanolic-aqueous extract) and its isolated pyrroquinazoline alkaloids, vasicinol (1), vasicine (2) and vasicinone (3) was evaluated. Compounds 1–3 were characterized by various spectroscopic techniques. The IC50 values of vasicinol (1), vasicine (2) and vasicinone (3) were found to be 6.45, 2.60 and 13.49 mM, respectively. Molecular docking studies of compounds 1–3 were also performed. Among these compounds, vasicinol (1) binds as effectively as captopril, a standard drug of ACE inhibition.
In Silico Structure-Guided Optimization and Molecular Simulation Studies of 3-Phenoxy-4-(3-trifluoromethylphenyl)pyridazines as Potent Phytoene Desaturase Inhibitors
Authors: Yang Lijun , Wang Dawei , Ma Dejun , Zhang Di , Zhou Nuo , Wang Jing , Xu Han , Xi Zhen
Published: November 2021

A series of novel 3-phenoxy-4-(3-trifluoromethylphenyl)pyridazines 2–5 were designed, based on the structure of our previous lead compound 1 through the in silico structure-guided optimization approach. The results showed that some of these new compounds showed a good herbicidal activity at the rate of 750 g ai/ha by both pre- and post-emergence applications, especially compound 2a, which displayed a comparable pre-emergence herbicidal activity to diflufenican at 300–750 g ai/ha, and a higher post-emergence herbicidal activity than diflufenican at the rates of 300–750 g ai/ha. Additionally, 2a was safe to wheat by both pre- and post-emergence applications at 300 g ai/ha, showing the compound’s potential for weed control in wheat fields. Our molecular simulation studies revealed the important factors involved in the interaction between 2a and Synechococcus PDS. This work provided a lead compound for weed control in wheat fields.
Simultaneous Determination of Vitamins D3 (Calcitriol, Cholecalciferol) and K2 (Menaquinone-4 and Menaquinone-7) in Dietary Supplements by UHPLC
Authors: Becze Anca , Babalau Fuss Vanda Liliana , Scurtu Daniela Alexandra , Tomoaia-Cotisel Maria , Mocanu Aurora , Cadar Oana
Published: November 2021

The content and composition of dietary supplements is of great interest due to their increasing consumption and variety of available brand offered in the market. Accurate determination of vitamins is important for the improvement of dietary supplement quality and nutrition assessments. In this regard, the simultaneous determination of vitamin D3 (calcitriol—CT and cholecalciferol—CHL) and K2 (menaquinone-4—MK-4 and menaquinone-7—MK-7) in dietary supplements was developed by using ultra-high-pressure liquid chromatography (UHPLC). The overall runtime per sample was above 35 min, with the retention times of 2.40, 6.59, 7.06, and 32.6 min for vitamin D3 (CT and CHL) and vitamin K2 (MK-4 and MK-7), respectively. The limits of detection and limits of quantification for the target nutritional compounds ranged between 0.04–0.05 µg/mL, respectively. The validation results indicated that the method had reasonable linearity (R2 ≥ 0.9990), good recovery (>82%), satisfactory intra-day precision (≤1.9%) and inter-day precision (≤3.5%), and high selectivity and specificity. The validated UHPLC method was demonstrated to be precise, accurate, and robust for the simultaneous determination of vitamins D3 (CT and CHL) and K2 (MK-4 and MK-7) in dietary supplements.
Continuous Flow Synthesis of Anticancer Drugs
Authors: Di Filippo Mara , Baumann Marcus
Published: November 2021

Continuous flow chemistry is by now an established and valued synthesis technology regularly exploited in academic and industrial laboratories to bring about the improved preparation of a variety of molecular structures. Benefits such as better heat and mass transfer, improved process control and safety, a small equipment footprint, as well as the ability to integrate in-line analysis and purification tools into telescoped sequences are often cited when comparing flow to analogous batch processes. In this short review, the latest developments regarding the exploitation of continuous flow protocols towards the synthesis of anticancer drugs are evaluated. Our efforts focus predominately on the period of 2016–2021 and highlight key case studies where either the final active pharmaceutical ingredient (API) or its building blocks were produced continuously. It is hoped that this manuscript will serve as a useful synopsis showcasing the impact of continuous flow chemistry towards the generation of important anticancer drugs.
Functionalized Magnetic Nanomaterials in Agricultural Applications
Authors: Spanos Alexandros , Athanasiou Kyriakos , Ioannou Andreas , Fotopoulos Vasileios , Krasia-Christoforou Theodora
Published: November 2021

The development of functional nanomaterials exhibiting cost-effectiveness, biocompatibility and biodegradability in the form of nanoadditives, nanofertilizers, nanosensors, nanopesticides and herbicides, etc., has attracted considerable attention in the field of agriculture. Such nanomaterials have demonstrated the ability to increase crop production, enable the efficient and targeted delivery of agrochemicals and nutrients, enhance plant resistance to various stress factors and act as nanosensors for the detection of various pollutants, plant diseases and insufficient plant nutrition. Among others, functional magnetic nanomaterials based on iron, iron oxide, cobalt, cobalt and nickel ferrite nanoparticles, etc., are currently being investigated in agricultural applications due to their unique and tunable magnetic properties, the existing versatility with regard to their (bio)functionalization, and in some cases, their inherent ability to increase crop yield. This review article provides an up-to-date appraisal of functionalized magnetic nanomaterials being explored in the agricultural sector.
Contribution to Improvement of Fatigue Properties of Zr-4 Alloy: Gradient Nanostructured Surface Layer versus Compressive Residual Stress
Authors: Geng Donghui , Sun Qiaoyan , Xin Chao , Xiao Lin
Published: November 2021

The gradient nanostructured (GNS) layer forms beneath the surface of Zr-4 samples by the surface mechanical grinding treatment (SMGT) process, which increases the fatigue strength apparently due to the synergistic effect of the gradient nanostructured layer and compressive residual stress. The SMGTed Zr-4 samples are subjected to annealing to remove residual stress (A-SMGT) and the individual effect of the GNS layer and compressive residual stress can be clarified. The results show that the gradient nanostructure in the surface is stable after annealing at 400 °C for 2 h but residual stress is apparently removed. Both SMGTed and A-SMGTed Zr-4 samples exhibit higher fatigue strength than that of coarse-grained (CG) Zr-4 alloy. The fatigue fracture of Zr-4 alloy indicates that the hard GNS surface layer hinders fatigue cracks from approaching the surface and leads to a lower fatigue striation space than that of CG Zr-4 samples. The offset fatigue strength of 106 cycles is taken for SMRT-ed, A-SMRT-ed, and CG Zr-4 samples and the results indicate clearly that the GNS surface layer is a key factor for the improvement of fatigue strength of the Zr-4 alloy with surface mechanical grinding treatment.
Dietary Supplementation with Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial
Authors: Elsaid Ahmed F. , Agrawal Sudhanshu , Agrawal Anshu , Ghoneum Mamdooh
Published: November 2021

Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.
Relationship between Serum 25OH-Vitamin D2 Level and Vitamin D Status of Children Aged 3–5 Years in China
Authors: Pang Xuehong , Yang Zhenyu , Wang Jie , Duan Yifan , Zhao Liyun , Yu Dongmei , Lai Jianqiang
Published: November 2021

Background: Vitamin D deficiency is prevalent globally and there is lack of evidence as to how 25(OH)D2 contributes to vitamin D status. The aim of this study was to describe vitamin D status and to assess the role of vitamin D2, a dietary vitamin D source, against the vitamin D status of children aged 3–5 years in China. Methods: Data were extracted from the Chinese National Nutrition and Health Surveillance (CNNHS) in 2013. The concentration of serum 25(OH)D2 and 25(OH)D3 was measured by using LC-MS/MS. Results: A total of 1435 subjects were enrolled and serum 25(OH)D were analyzed. The prevalence of total serum 25(OH)D < 30 nmol/L was 8.9%. Serum 25(OH)D2 was detected in 10.9% of the studied children. After adjusting for confounding factors, total 25(OH)D concentration was 8.48 nmol/L lower and odds ratio of vitamin D deficiency was 4.20 times (OR (95%CI): 4.20 (1.64, 10.77)) in children without 25(OH)D2 than those with 25(OH)D2 detected. Conclusions: Vitamin D deficiency was common among children aged 3–5 years in China. Vitamin D2 may play a role in preventing vitamin D deficiency in Chinese children aged 3–5 years.
Cost and Cost Effectiveness of a Pilot m-Health Intervention Targeting Parents of School-Aged Children to Improve the Nutritional Quality of Foods Packed in the Lunchbox
Authors: Brown Alison , Sutherland Rachel , Reeves Penny , Nathan Nicole , Wolfenden Luke
Published: November 2021

The SWAP IT program aims to improve the nutritional quality of school lunchboxes via a multicomponent m-health intervention, involving: weekly support messages to parents; physical resources; school nutrition guidelines and lunchbox lessons. SWAP IT has been reported to be effective. This study aims to determine the cost and cost effectiveness of the SWAP IT m-health intervention. The retrospective trial-based economic evaluation was conducted in 12 Catholic primary schools in New South Wales, Australia. Schools were randomised to intervention or usual care. The costs (AUD, 2019) were evaluated from societal perspectives. The direct cost to uptake the intervention and the incremental cost-effectiveness ratios (ICER) were calculated. ICERS were calculated for two outcomes: reduction in total kJ and reduction in discretionary kJ from the lunchbox. The total cost was calculated to be AUD 55, 467. The mean incremental cost per student to receive the intervention was calculated to be AUD 31/student. The cost per reduction in total lunchbox energy was AUD 0.54. The ICER for the reduction in energy from discretionary foods in the lunchbox was AUD 0.24. These findings suggest that this m-health intervention has potential to be cost effective in reducing the kilojoules from discretionary foods packed in school lunchboxes.
Which Microbes Like My Diet and What Does It Mean for My Heart?
Authors: Sawicka-Śmiarowska Emilia , Moniuszko-Malinowska Anna , Kamiński Karol Adam
Published: November 2021

Cardiovascular diseases are the most common causes of hospitalization, death and disability in Europe. Despite our knowledge of nonmodifiable and modifiable cardiovascular classical risk factors, the morbidity and mortality in this group of diseases remains high, leading to high social and economic costs. Therefore, it is necessary to explore new factors, such as the gut microbiome, that may play a role in many crucial pathological processes related to cardiovascular diseases. Diet is a potentially modifiable cardiovascular risk factor. Fats, proteins, carbohydrates, vitamins and minerals are nutrients that are essential to the proper function of the human body. The style and composition of the human diet has changed over time, evolving from a hunter–gatherer diet to an industrialized and Westernized modern diet that includes processed products. The relationship between the gut microbiome, diet and cardiovascular diseases is complex and still not fully understood. In this review, we discuss, in the context of diet, why particular microbes occur in individuals and how they can influence the host’s cardiovascular system in health and disease. We investigate the role of particular microorganisms and changes in the Firmicutes/Bacteroidetes ratio.
Relationship between Dietary Patterns with Benign Prostatic Hyperplasia and Erectile Dysfunction: A Collaborative Review
Authors: Russo Giorgio , Broggi Giuseppe , Cocci Andrea , Capogrosso Paolo , Falcone Marco , Sokolakis Ioannis , Gül Murat , Caltabiano Rosario , Di Mauro Marina
Published: November 2021

Interest in the role of dietary patterns has been consistently emerging in recent years due to much research that has documented the impact of metabolism on erectile dysfunction (ED) and/or benign prostatic hyperplasia (BPH). We conducted a non-systematic review of English articles published from 1964 to September 2021. The search terms were: (“dietary patterns” OR “diet”) AND/OR (“erectile dysfunction”) AND/OR (“benign prostatic hyperplasia”). In the present review, we have highlighted how the association between dietary patterns and two of the most frequent pathologies in urology, namely erectile dysfunction and benign prostatic hyperplasia, is present in the literature. The data suggested that a diet that is more adherent to the Mediterranean diet or that emphasizes the presence of vegetables, fruits, nuts, legumes, and fish or other sources of long-chain (n-3) fats, in addition to reduced content of red meat, may have a beneficial role on erectile function. At the same time, the same beneficial effects can be transferred to BPH as a result of the indirect regulatory effects on prostatic growth and smooth muscle tone, thus determining an improvement in symptoms. Certainly, in-depth studies and translational medicine are needed to confirm these encouraging data.
Hitching a Ride: Examining the Ability of a Specialist Baculovirus to Translocate through Its Insect Host’s Food Plant
Authors: Issa Peter P. , Garvey Michael , Grimmell Scott , Pantha Pramod , Dassanayake Maheshi , Elderd Bret D.
Published: November 2021

Plant vascular systems can translocate the entomopathogen Bacillus thuringiensis from the soil into plant tissues. However, whether other soil dwelling entomopathogens utilize plant vascular tissue for movement has not yet been fully explored. We used Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) to evaluate whether baculoviruses, a common entomopathogen and bioinsecticide, can be transported through the plant vascular pathways of Zea mays. We found that our treatments did not allow a sufficient virus translocation into the plant to induce a lethal infection in insects, which was confirmed by a molecular analysis. While other entomopathogens translocate, baculoviruses may not be one of them.
Emergence of Methicillin-Resistant Staphylococcus aureus ST239/241 SCCmec-III Mercury in Eastern Algeria
Authors: Aouati Hanane , Hadjadj Linda , Aouati Farida , Agabou Amir , Ben Khedher Mariem , Bousseboua Hacène , Bentchouala Chafia , Rolain Jean-Marc , Diene Seydina M.
Published: November 2021

In this paper, we investigate the epidemiology of infections-associated Staphylococcusaureus (S. aureus) from the Medical Intensive Care Unit (MICU) at University Hospital Center of Constantine (UHCC) in Algeria, with a special emphasis on methicillin-resistant strains (MRSA) revealed by cefoxitin disks (30 μg), then confirmed by penicillin-binding protein (PBP2a) agglutination and real-time polymerase chain reaction (RT-PCR) targeting mecA and mecC genes. Staphylococcal Cassette Chromosome mec (SCCmec type), staphylococcal protein A (spa-type), multilocus sequence type (MLST), Panton–Valentine Leucocidin (PVL), and toxic shock syndrome toxin-1 (TSST-1) were further investigated in all isolates, and whole genome sequencing was performed for a selected subset of three hospital-acquired MRSA (HA-MRSA) isolates. A measurement of 80% out of the 50 S. aureus isolates were identified as HA-MRSA harbouring the mecA gene, and 72.5% of them were multidrug resistant (MDR). Twelve STs, four different SCCmec cassettes, fourteen spa types, ten isolates Panton–Valentine Leukocidin (PVL)-positive, and three isolates TSST-1 were identified. Interestingly, there was a high prevalence (n = 29; 72.5%) of a worrisome emerging clone: the HA-MRSA ST239/241 SCCmec-III mercury with PVL negative, resistant to β-lactams, aminoglycosides, quinolones, and tetracyclines. Other clones of HA-MRSA isolates were also identified, including PVL-positive ST80 SCCmec-IV/SCCmec-unknown (22.5%), ST34 SCCmec-V with TSST-1 positive (2.5%), and PVL-negative ST72 SCCmec-II (2.5%). Genome analysis enables us to describe the first detection of both PVL-negative HA-MRSA ST239/241 SCCmec-III mercury carrying ccrC, as well as SCCmec-V cassette, which dramatically changes the epidemiology of S. aureus infections in one of the hospitals in eastern Algeria.
Host Protease Activity on Bacterial Pathogens Promotes Complement and Antibiotic-Directed Killing
Authors: Chen Shaorong , Zhang Dongmei , Roberts Alexandria-Jade , Lu Hsueh-Chung , Cannon Carolyn L. , Qin Qing-Ming , de Figueiredo Paul
Published: November 2021

Our understanding of how the host immune system thwarts bacterial evasive mechanisms remains incomplete. Here, we show that host protease neutrophil elastase acts on Acinetobacter baumannii and Pseudomonas aeruginosa to destroy factors that prevent serum-associated, complement-directed killing. The protease activity also enhances bacterial susceptibility to antibiotics in sera. These findings implicate a new paradigm where host protease activity on bacteria acts combinatorially with the host complement system and antibiotics to defeat bacterial pathogens.
The Role of Lactic Acid on Wound Healing, Cell Growth, Cell Cycle Kinetics, and Gene Expression of Cultured Junctional Epithelium Cells in the Pathophysiology of Periodontal Disease
Authors: Ishikawa Taichi , Sasaki Daisuke , Aizawa Ryo , Yamamoto Matsuo , Yaegashi Takashi , Irié Tarou , Sasaki Minoru
Published: November 2021

Lactic acid (LA) is short-chain fatty acid, such as butyric acid and propionic acid, that is produced as a metabolite of lactic acid bacteria, including periodontopathic bacteria. These short-chain fatty acids have positive effects on human health but can also have negative effects, such as the promotion of periodontal disease (PD), which is caused by periodontal pathogens present in the gingival sulcus. PD is characterized by apical migration of junctional epithelium, deepening of pockets, and alveolar bone loss. Thus, the junctional epithelial cells that form the bottom of the gingival sulcus are extremely important in investigating the pathophysiology of PD. The aim of this study was to investigate the effect of LA on wound healing, cell growth, cell cycle kinetics, and gene expression of cultured junctional epithelium cells. The results showed that stimulation with 10 mM LA slowed wound healing of the junctional epithelial cell layer and arrested the cell cycle in the G0/G1 (early cell cycle) phase, thereby inhibiting cell growth. However, cell destruction was not observed. LA also enhanced mRNA expression of integrin α5, interleukin (IL)-6, IL-8, intercellular adhesion molecule-1, and receptor activator of nuclear factor kappa-B ligand. The results of this study suggest that stimulation of junctional epithelial cells with high concentrations of LA could exacerbate PD, similarly to butyric acid and propionic acid.
A Review of the Impact of the COVID-19 Pandemic on Colorectal Cancer Screening: Implications and Solutions
Authors: Sundaram Suneha , Olson Sean , Sharma Paranjay , Rajendra Shanmugarajah
Published: November 2021

The COVID-19 pandemic has impacted all aspects of medical care, including cancer screening and preventative measures. Colorectal cancer screening declined significantly at the onset of the pandemic as the result of an intentional effort to conserve resources, prioritize emergencies and reduce risk of transmission. There has already been an increase in diagnosis at more advanced stages and symptomatic emergencies due to suspended screenings. As endoscopy units find their way back to pre-pandemic practices, a backlog of cases remains. The missed CRC diagnoses amongst the missed screenings carry a risk of increased morbidity and mortality which will only increase as time-to-diagnosis grows. This review discusses the impact of COVID-19 on colonoscopy screening rates, trends in stages/symptoms/circumstances at diagnosis, and economic and social impact of delayed diagnosis. Triaging and use of FITs are proposed solutions to the challenge of catching up with the large number of pandemic-driven missed CRC screenings.
Tick Immunobiology and Extracellular Traps: An Integrative Vision to Control of Vectors
Authors: Aguilar-Díaz Hugo , Quiroz-Castañeda Rosa Estela , Salazar-Morales Karina , Cossío-Bayúgar Raquel , Miranda-Miranda Estefan
Published: November 2021

Ticks are hematophagous ectoparasites that infest a diverse number of vertebrate hosts. The tick immunobiology plays a significant role in establishing and transmitting many pathogens to their hosts. To control tick infestations, the acaricide application is a commonly used method with severe environmental consequences and the selection of tick-resistant populations. With these drawbacks, new tick control methods need to be developed, and the immune system of ticks contains a plethora of potential candidates for vaccine design. Additionally, tick immunity is based on an orchestrated action of humoral and cellular immune responses. Therefore, the actors of these responses are the object of our study in this review since they are new targets in anti-tick vaccine design. We present their role in the immune response that positions them as feasible targets that can be blocked, inhibited, interfered with, and overexpressed, and then elucidate a new method to control tick infestations through the development of vaccines. We also propose Extracellular Traps Formation (ETosis) in ticks as a process to eliminate their natural enemies and those pathogens they transmit (vectorial capacity), which results attractive since they are a source of acting molecules with potential use as vaccines.
Positron Emission Tomography in Animal Models of Alzheimer’s Disease Amyloidosis: Translational Implications
Authors: Ni Ruiqing
Published: November 2021

Animal models of Alzheimer’s disease amyloidosis that recapitulate cerebral amyloid-beta pathology have been widely used in preclinical research and have greatly enabled the mechanistic understanding of Alzheimer’s disease and the development of therapeutics. Comprehensive deep phenotyping of the pathophysiological and biochemical features in these animal models is essential. Recent advances in positron emission tomography have allowed the non-invasive visualization of the alterations in the brain of animal models and in patients with Alzheimer’s disease. These tools have facilitated our understanding of disease mechanisms and provided longitudinal monitoring of treatment effects in animal models of Alzheimer’s disease amyloidosis. In this review, we focus on recent positron emission tomography studies of cerebral amyloid-beta accumulation, hypoglucose metabolism, synaptic and neurotransmitter receptor deficits (cholinergic and glutamatergic system), blood–brain barrier impairment, and neuroinflammation (microgliosis and astrocytosis) in animal models of Alzheimer’s disease amyloidosis. We further propose the emerging targets and tracers for reflecting the pathophysiological changes and discuss outstanding challenges in disease animal models and future outlook in the on-chip characterization of imaging biomarkers towards clinical translation.
The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management
Authors: Bernard Amandine , Danigo Aurore , Bourthoumieu Sylvie , Mroué Mohamad , Desmoulière Alexis , Sturtz Franck , Rovini Amandine , Demiot Claire
Published: November 2021

Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our knowledge about the molecular basis of the pharmacology and functioning of CCK2R. This review focuses on the cellular localization of CCK2R specifically in the sensory nervous system and discusses in further detail the molecular mechanisms and signal transduction pathways involved in controlling pain perception. We then provide a comprehensive overview of the most successful compounds targeting CCK2R and report recent advances in pharmacological strategies used to achieve CCK2R modulation. We purposely distinguish between CCK2R benefits obtained in preclinical models and outcomes in clinical trials with different pain etiologies. Lastly, we emphasize the biological and clinical relevance of CCK2R as a promising target for the development of new treatments for pain management.