bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight on Mercapto-Coumarins: Synthesis and Reactivity
Authors: El-Sawy Eslam Reda , Abdelwahab Ahmed Bakr , Kirsch Gilbert
Published: March 2022

Mercapto (or sulfanyl)-coumarins are heterocycles of great interest in the development of valuable active structures in material and biological domains. They represent a highly exploitable class of compounds that open many possibilities for further chemical transformations. The present review aims to draw focus toward the synthetic applicability of various forms of mercapto-coumarins and their representations in pharmaceuticals and industries. This work covers the literature issued from 1970 to 2021.
Simultaneous Determination of Sulfonamides Antibiotics in Environmental Water and Seafood Samples Using Ultrasonic-Assisted Dispersive Liquid-Liquid Microextraction Coupled with High Performance Liquid Chromatography
Authors: Wang Yixiao , Li Jinhua , Ji Ling , Chen Lingxin
Published: March 2022

The residues and abuse of antibiotics have seriously endangered ecological balance and human health; meanwhile, antibiotics determination is very difficult because of their low levels and multiple categories in complicated matrices. Appropriate sample pretreatment is usually imperative to enrich (ultra)trace antibiotics and eliminate matrix interference prior to chromatographic analysis. Dispersive liquid-liquid microextraction (DLLME) has become an ideal pretreatment technique owing to its simplicity, effectiveness, low-consumption, etc. In this work, an ultrasonic-assisted DLLME (UA-DLLME) was developed for the simultaneous extraction of seven sulfonamides (SAs) antibiotics in environmental water and seafood samples coupled with HPLC-DAD determination. Several parameters affecting UA-DLLME efficiency were systematically optimized, and consequently the SAs were separated and detected within 14.5 min. The obtained limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.7–7.8 μg/L and 2.4–26.0 μg/L for three water samples (seawater, aquaculture wastewater and lake water) and two seafood samples (pomfrets and shrimps). High recoveries (80.0–116.0%) with low relative standard deviations (0.1–8.1%) were achieved for all the tested samples at three spiked levels. Notably, sulfadimethoxine was found at 24.49 μg/L in one seawater sample. The facile, robust and benign DLLME-HPLC method demonstrated promising perspectives for multiresidue analysis of antibiotics.
Synthesis and Anti-Trypanosoma cruzi Biological Evaluation of Novel 2-Nitropyrrole Derivatives
Authors: Mathias Fanny , Kabri Youssef , Brun Damien , Primas Nicolas , Di Giorgio Carole , Vanelle Patrice
Published: March 2022

Human American trypanosomiasis, called Chagas disease, caused by T. cruzi protozoan infection, represents a major public health problem, with about 7000 annual deaths in Latin America. As part of the search for new and safe anti-Trypanosoma cruzi derivatives involving nitroheterocycles, we report herein the synthesis of ten 1-substituted 2-nitropyrrole compounds and their biological evaluation. After an optimization phase, a convergent synthesis methodology was used to obtain these new final compounds in two steps from the 2-nitropyrrole starting product. All the designed derivatives follow Lipinski’s rule of five. The cytotoxicity evaluation on CHO cells showed no significant cytotoxicity, except for compound 3 (CC50 = 24.3 µM). Compound 18 appeared to show activity against T. cruzi intracellular amastigotes form (EC50 = 3.6 ± 1.8 µM) and good selectivity over the vero host cells. Unfortunately, this compound 18 showed an insufficient maximum effect compared to the reference drug (nifurtimox). Whether longer duration treatments may eliminate all parasites remains to be explored.
Recent Advances in Divergent Synthetic Strategies for Indole-Based Natural Product Libraries
Authors: Kim Taegwan , Ha Min Woo , Kim Jonghoon
Published: March 2022

Considering the potential bioactivities of natural product and natural product-like compounds with highly complex and diverse structures, the screening of collections and small-molecule libraries for high-throughput screening (HTS) and high-content screening (HCS) has emerged as a powerful tool in the development of novel therapeutic agents. Herein, we review the recent advances in divergent synthetic approaches such as complexity-to-diversity (Ctd) and biomimetic strategies for the generation of structurally complex and diverse indole-based natural product and natural product-like small-molecule libraries.
The Image Identification Application with HfO2-Based Replaceable 1T1R Neural Networks
Authors: Lin Jinfu , Liu Hongxia , Wang Shulong , Wang Dong , Wu Lei
Published: March 2022

This paper mainly studies the hardware implementation of a fully connected neural network based on the 1T1R (one-transistor-one-resistor) array and its application in handwritten digital image recognition. The 1T1R arrays are prepared by connecting the memristor and nMOSFET in series, and a single-layer and a double-layer fully connected neural network are established. The recognition accuracy of 8 × 8 handwritten digital images reaches 95.19%. By randomly replacing the devices with failed devices, it is found that the stuck-off devices have little effect on the accuracy of the network, but the stuck-on devices will cause a sharp reduction of accuracy. By using the measured conductivity adjustment range and precision data of the memristor, the relationship between the recognition accuracy of the network and the number of hidden neurons is simulated. The simulation results match the experimental results. Compared with the neural network based on the precision of 32-bit floating point, the difference is lower than 1%.
Ionic Liquid@Metal-Organic Framework as a Solid Electrolyte in a Lithium-Ion Battery: Current Performance and Perspective at Molecular Level
Authors: Majid Mohd Faridzuan , Mohd Zaid Hayyiratul Fatimah , Kait Chong Fai , Ahmad Azizan , Jumbri Khairulazhar
Published: March 2022

Searching for a suitable electrolyte in a lithium-ion battery is a challenging task. The electrolyte must not only be chemically and mechanically stable, but also be able to transport lithium ions efficiently. Ionic liquid incorporated into a metal–organic framework (IL@MOF) has currently emerged as an interesting class of hybrid material that could offer excellent electrochemical properties. However, the understanding of the mechanism and factors that govern its fast ionic conduction is crucial as well. In this review, the characteristics and potential use of IL@MOF as an electrolyte in a lithium-ion battery are highlighted. The importance of computational methods is emphasized as a comprehensive tool to investigate the atomistic behavior of IL@MOF and its interaction in electrochemical environments.
Optimization of Platinum Nanoparticles (PtNPs) Synthesis by Acid Phosphatase Mediated Eco-Benign Combined with Photocatalytic and Bioactivity Assessments
Authors: Rehman Khalil ur , Gouda Mostafa , Zaman Umber , Tahir Kamran , Khan Shahid Ullah , Saeed Sumbul , Khojah Ebtihal , El-Beltagy Alaa , Zaky Ahmed A. , Naeem Mohamed , Khan Muhammad Imran , Khattak Noor Saeed
Published: March 2022

Noble metal nanoparticles (NMNPs) are viable alternative green sources compared to the chemical available methods in several approach like Food, medical, biotechnology, and textile industries. The biological synthesis of platinum nanoparticles (PtNPs), as a strong photocatalytic agent, has proved as more effective and safer method. In this study, PtNPs were synthesized at four different temperatures (25 °C, 50 °C, 70 °C, and 100 °C). PtNPs synthesized at 100 °C were smaller and exhibited spherical morphology with a high degree of dispersion. A series of physicochemical characterizations were applied to investigate the synthesis, particle size, crystalline nature, and surface morphology of PtNPs. The biosynthesized PtNPs were tested for the photodegradation of methylene blue (MB) under visible light irradiations. The results showed that PtNPs exhibited remarkable photocatalytic activity by degrading 98% of MB only in 40 min. The acid phosphatase mediated PtNPs showed strong bacterial inhibition efficiency against S. aureus and E. coli. Furthermore, it showed high antioxidant activity (88%) against 1,1-diphenyl-2-picryl-hydrazil (DPPH). In conclusion, this study provided an overview of the applications of PtNPs in food chemistry, biotechnology, and textile industries for the deterioration of the natural and synthetic dyes and its potential application in the suppression of pathogenic microbes of the biological systems. Thus, it could be used as a novel approach in the food microbiology, biomedical and environmental applications.
Silicon Thermo-Optic Switches with Graphene Heaters Operating at Mid-Infrared Waveband
Authors: Zhong Chuyu , Zhang Zhibin , Ma Hui , Wei Maoliang , Ye Yuting , Wu Jianghong , Tang Bo , Zhang Peng , Liu Ruonan , Li Junying , Li Lan , Hu Xiaoyong , Liu Kaihui , Lin Hongtao
Published: March 2022

The mid-infrared (MIR, 2–20 μm) waveband is of great interest for integrated photonics in many applications such as on-chip spectroscopic chemical sensing, and optical communication. Thermo-optic switches are essential to large-scale integrated photonic circuits at MIR wavebands. However, current technologies require a thick cladding layer, high driving voltages or may introduce high losses in MIR wavelengths, limiting the performance. This paper has demonstrated thermo-optic (TO) switches operating at 2 μm by integrating graphene onto silicon-on-insulator (SOI) structures. The remarkable thermal and optical properties of graphene make it an excellent heater material platform. The lower loss of graphene at MIR wavelength can reduce the required cladding thickness for the thermo-optics phase shifter from micrometers to tens of nanometers, resulting in a lower driving voltage and power consumption. The modulation efficiency of the microring resonator (MRR) switch was 0.11 nm/mW. The power consumption for 8-dB extinction ratio was 5.18 mW (0.8 V modulation voltage), and the rise/fall time was 3.72/3.96 μs. Furthermore, we demonstrated a 2 × 2 Mach-Zehnder interferometer (MZI) TO switch with a high extinction ratio of more than 27 dB and a switching rise/fall time of 4.92/4.97 μs. A comprehensive analysis of the device performance affected by the device structure and the graphene Fermi level was also performed. The theoretical figure of merit (2.644 mW−1μs−1) of graphene heaters is three orders of magnitude higher than that of metal heaters. Such results indicate graphene is an exceptional nanomaterial for future MIR optical interconnects.
NiMnO3 Anchored on Reduced Graphene Oxide Nanosheets: A New High-Performance Microwave Absorbing Material
Authors: Zhang Pin , Yao Yao , Zhou Wenke , Liu Yawen , Cao Xiaowei , Zhang Zhi
Published: March 2022

With the increasing influence of electromagnetic radiation on precision instruments and organisms, there is an urgent need for research on lightweight and high-strength electromagnetic wave absorbing materials. This study has probed into a new composite absorbing material based on reduced graphene oxide (rGO)-NiMnO3, where the like-core-shell NiMnO3 is anchored on the rGO nanosheets to significantly improve the electromagnetic wave dissipation ability of the composite material using the inter-component dipole polarization and interface polarization. At the same time, NiMnO3 can effectively adjust the impedance matching ratio of rGO so that electromagnetic waves can effectively enter the absorbing material. At a thickness of 3.73 mm, the maximum absorption strength of rGO-NiMnO3 reaches −61.4 dB at 6.6 GHz; at a thickness of 2.5 mm, the adequate absorption bandwidth is 10.04–18.00 GHz, achieving a full coverage for the Ku band. As a new option for preparing lightweight and broadband electromagnetic wave absorbing materials, rGO-NiMnO3 is an ideal material for electromagnetic wave protection.
Comparing Thickness and Doping-Induced Effects on the Normal States of Infinite-Layer Electron-Doped Cuprates: Is There Anything to Learn?
Authors: Sacco Chiara , Galdi Alice , Romeo Francesco , Coppola Nunzia , Orgiani Pasquale , Wei Haofei I. , Shen Kyle M. , Schlom Darrell G. , Maritato Luigi
Published: March 2022

We grew Sr1-xLaxCuO2 thin films and SrCuO2/Sr0.9La0.1CuO2/SrCuO2 trilayers by reflection high-energy diffraction-calibrated layer-by-layer molecular beam epitaxy, to study their electrical transport properties as a function of the doping and thickness of the central Sr0.9La0.1CuO2 layer. For the trilayer samples, as already observed in underdoped SLCO films, the electrical resistivity versus temperature curves as a function of the central layer thickness show, for thicknesses thinner than 20 unit cells, sudden upturns in the low temperature range with the possibility for identifying, in the normal state, the T* and a T** temperatures, respectively, separating high-temperature linear behavior and low-temperature quadratic dependence. By plotting the T* and T** values as a function of TConset for both the thin films and the trilayers, the data fall on the same curves. This result suggests that, for the investigated trilayers, the superconducting critical temperature is the important parameter able to describe the normal state properties and that, in the limit of very thin central layers, such properties are mainly influenced by the modification of the energy band structure and not by interface-related disorder.
Suspended Multifunctional Nanocellulose as Additive for Mortars
Authors: Diamanti Maria Vittoria , Tedeschi Cristina , Taccia Mariagiovanna , Torri Giangiacomo , Massironi Nicolò , Tognoli Chiara , Vismara Elena
Published: March 2022

Cellulose derivatives have found significant applications in composite materials, mainly because of the increased mechanical performance they ensure. When added to cement-based materials, either in the form of nanocrystals, nanofibrils or micro/nanofibers, cellulose acts on the mixture with fresh and hardened properties, affecting rheology, shrinkage, hydration, and the resulting mechanical properties, microstructure, and durability. Commercial cotton wool was selected as starting material to produce multifunctional nanocelluloses to test as additives for mortars. Cotton wool was oxidized to oxidized nanocellulose (ONC), a charged nanocellulose capable of electrostatic interaction, merging cellulose and nanoparticles properties. Oxidized nanocellulose (ONC) was further functionalized by a radical-based mechanism with glycidyl methacrylate (GMA) and with a mixture of GMA and the crosslinking agent ethylene glycol dimethacrylate (EGDMA) affording ONC-GMA and ONC-GMA-EGDMA, both multifunctional-charged nanocellulose merging cellulose and bound acrylates properties. In this work, only ONC was found to be properly suitable for suspension and addition to a commercial mortar to assess the variation in mechanical properties and water-mortar interactions as a consequence of the modified microstructure obtained. The addition of oxidized nanocellulose caused an alteration of mortar porosity, with a decreased percentage of porosity and pore size distribution shifted towards smaller pores, with a consequent increase in compressive resistance, decrease in water absorption coefficient, and increased percentage of micropores present in the material, indicating a potential improvement in mortar durability.
Formulation and In Vitro Efficacy Assessment of Teucrium marum Extract Loading Hyalurosomes Enriched with Tween 80 and Glycerol
Authors: Firoznezhad Mohammad , Castangia Ines , Tuberoso Carlo Ignazio Giovanni , Cottiglia Filippo , Marongiu Francesca , Porceddu Marco , Usach Iris , Escribano-Ferrer Elvira , Manca Maria Letizia , Manconi Maria
Published: March 2022

The extract of Teucrium marum L. (Lamiaceae) was obtained using the aerial parts of the plant, by means of a maceration process. Verbascoside, caffeic acids derivatives and flavonols were the main components contained in the extract as detected using high-performance liquid chromatography coupled with diode array detector (HPLC–DAD) as an analytical method. The extract was successfully incorporated into hyalurosomes, which were further enriched by adding a water cosolvent (glycerol) and a surfactant (Tween 80), thus obtaining glycerohyalurosomes. Liposomes, transfersomes and glycerosomes were prepared as well and used as comparisons. All vesicles were small, as the mean diameter was never higher than ~115 nm, thus ideal for topical application and stable on storage, probably thanks to the highly negative surface charge of the vesicles (~−33 mV). The cryo-TEM images confirmed the formation of close-packed, oligolamellar and multicompartment hyalurosomes and glycerohyalurosomes in which around 95% of the used extract was retained, confirming their ability to simultaneously load a wide range of molecules having different chemical natures. Moreover, the extract, when loaded in hyalurosomes and glycerohyalurosomes was able to counteract the damages induced in the fibroblasts by hydrogen peroxide to a better extent (viability~110%) than that loaded in the other vesicles (viability~100%), and effectively promoted their proliferation and migration ensuring the healing of the wound performed in a cell monolayer (scratch assay) during 48 h of experiment. Overall in vitro results confirmed the potential of glycerohyalurosomes as delivery systems for T. marum extract for the treatment of skin lesions connected with oxidative stress.
Plasma Retinoid Concentrations Are Altered in Pregnant Women
Authors: Czuba Lindsay C. , Fay Emily E. , LaFrance Jeffrey , Smith Chase K. , Shum Sara , Moreni Sue L. , Mao Jennie , Isoherranen Nina , Hebert Mary F.
Published: March 2022

Vitamin A is vital to maternal–fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25–28 weeks gestation and 28–32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25–28 weeks gestation, plasma retinol (−27%), 4-oxo-13-cis-retinoic acid (−34%), and albumin (−22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28–32 weeks gestation, plasma retinol (−41%), retinol binding protein 4 (RBP4; −17%), transthyretin (TTR; −21%), albumin (−26%), 13-cis-retinoic acid (−23%) and 4-oxo-13-cis-retinoic acid (−48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum.
Vitamin D Deficiency and Its Association with Iron Deficiency in African Children
Authors: Mogire Reagan M. , Muriuki John Muthii , Morovat Alireza , Mentzer Alexander J. , Webb Emily L. , Kimita Wandia , Ndungu Francis M. , Macharia Alex W. , Cutland Clare L. , Sirima Sodiomon B. , Diarra Amidou , Tiono Alfred B. , Lule Swaib A. , Madhi Shabir A. , Prentice Andrew M. , Bejon Philip , Pettifor John M. , Elliott Alison M. , Adeyemo Adebowale , Williams Thomas N. , Atkinson Sarah H.
Published: March 2022

Vitamin D regulates the master iron hormone hepcidin, and iron in turn alters vitamin D metabolism. Although vitamin D and iron deficiency are highly prevalent globally, little is known about their interactions in Africa. To evaluate associations between vitamin D and iron status we measured markers of iron status, inflammation, malaria parasitemia, and 25-hydroxyvitamin D (25(OH)D) concentrations in 4509 children aged 0.3 months to 8 years living in Kenya, Uganda, Burkina Faso, The Gambia, and South Africa. Prevalence of iron deficiency was 35.1%, and prevalence of vitamin D deficiency was 0.6% and 7.8% as defined by 25(OH)D concentrations of <30 nmol/L and <50 nmol/L, respectively. Children with 25(OH)D concentrations of <50 nmol/L had a 98% increased risk of iron deficiency (OR 1.98 [95% CI 1.52, 2.58]) compared to those with 25(OH)D concentrations >75 nmol/L. 25(OH)D concentrations variably influenced individual markers of iron status. Inflammation interacted with 25(OH)D concentrations to predict ferritin levels. The link between vitamin D and iron status should be considered in strategies to manage these nutrient deficiencies in African children.
In Vitro Gut Fermentation of Whey Protein Hydrolysate: An Evaluation of Its Potential Modulation on Infant Gut Microbiome
Authors: Feng Chunsong , Tian Li , Hong Hui , Wang Quanyu , Zhan Xin , Luo Yongkang , Tan Yuqing
Published: March 2022

Whey protein and its hydrolysate are ubiquitously consumed as nutritional supplements. This study aimed to evaluate the potential effect of whey protein hydrolysate (WPH) on the infant gut microbiome, which is more variable than that of adults. Colonic fermentation was simulated through a static digestion model and fecal culture fermentation, using feces from normal infants aged from 1–3 years old. During in vitro gut fermentation, measurements of short-chain fatty acids (SCFA) concentrations and 16S rRNA amplicon sequencing were performed. Additionally, the growth curves of cultivated probiotics were analyzed to evaluate the prebiotic potential of WPH. Besides the decline of pH in fermentation, the addition of WPH induced a significant increase in the SCFA production and also the relative abundance of Proteobacteria, Bacteroides, and Streptococcus (p < 0.05). The lower ratio of Firmicutes/Bacteroidetes in WPH-supplemented samples indicated the positive modulation of WPH on the gut microbiota, which could benefit the energy balance and metabolism of infants. The stimulation effect of WPH on the probiotics (particularly Lactobacillus acidophilus NCFM) during cultivation implied the prebiotic potential as well. Our findings shed light on WPH as a valuable dietary supplement with not only enriched resources of essential amino acids but also the potential to restore the infant gut microbiome.
Zinc Deficiency Interacts with Intestinal/Urogenital Parasites in the Pathway to Anemia in Preschool Children, Bengo–Angola
Authors: Fançony Cláudia , Soares Ânia , Lavinha João , Brito Miguel
Published: March 2022

In host organisms with normal micronutrient status, nutritional immunity is a strongly regulated response aiming at decreasing the progression and severity of infections. Zinc deficiency may disturb this balance, impairing immune responses to infections, which may indirectly increase infection-related anemia. Since zinc deficiency may associate directly with anemia, the role of infections is often overlooked. Herein, we investigated the participation of infections (or inflammation) in the causal pathway between zinc deficiency and anemia. This transversal study, conducted in 2015 in Bengo-Angola, enrolled 852 under-3-year-old children. Logistic regression models were used to investigate interaction and mediation effects, and significance was confirmed by the Sobel test. In sum, 6.8% of children had zinc deficiency, 45.9% had anemia, and 15.6% had at least one intestinal/urogenital parasite. Furthermore, we found (1) no evidence that inflammation mediates or interacts with zinc deficiency to cause anemia, and (2) zinc deficiency interacts with infections, significantly increasing the odds of anemia (OR: 13.26, p = 0.022). This interaction was stronger among children with iron deficiency anemia (OR: 46.66, p = 0.003). Our results suggest that zinc deficiency may impair the immune response to infections and/or that intestinal parasites could have developed mechanisms to avoid zinc-limited environments. Further studies are needed to corroborate these suggestions.
The Impact of Inpatient Multimodal Treatment or Family-Based Treatment on Six-Month Weight Outcomes in Youth with Anorexia Nervosa: A Naturalistic, Cross-Continental Comparison
Authors: Nadler Janine , Correll Christoph U. , Le Grange Daniel , Accurso Erin C. , Haas Verena
Published: March 2022

In the USA, family-based treatment (FBT) with inpatient medical stabilization as needed is the leading evidence-based treatment for youth with anorexia nervosa (AN). In continental Europe, typically inpatient multimodal treatment targeting weight recovery followed by outpatient care (IMT) is standard care, if prior outpatient treatment was not sufficient. Our aim was to compare weekly weight gain and hospital days over six months for adolescents receiving FBT (USA) versus IMT (Germany) using naturalistic treatment data. To yield similar subgroups of youth aged 12–18 years, inclusion criteria were a percent median BMI (%mBMI) between 70–85 and the restrictive AN subtype. Weight gain and hospital days were compared, adjusted further in a multiple linear regression analysis (MLRA) for baseline group differences. Samples differed on baseline %mBMI (FBT [n = 71], 90.5 ± 12.8; IMT [n = 29], 78.3 ± 9.1, p < 0.05). In subgroups with comparable baseline %mBMI, the weekly weight gain over 6 months was similar (FBT [n = 21]: 0.35 ± 0.18 kg/week; IMT [n = 20]: 0.30 ± 0.18, p = 0.390, p = 0.166 after MLRA), but achieved fewer hospital days in FBT (FBT [n = 7]: 4 ± 6 days, IMT [n = 20]: 121 ± 42 days, p < 0.0001 before and after MLRA). FBT may be effective for a subgroup of adolescents with AN currently receiving IMT, but head-to-head studies in the same healthcare system are needed.
Welder’s Anthrax: A Review of an Occupational Disease
Authors: de Perio Marie A. , Hendricks Katherine A. , Dowell Chad H. , Bower William A. , Burton Nancy C. , Dawson Patrick , Schrodt Caroline A. , Salzer Johanna S. , Marston Chung K. , Feldmann Karl , Hoffmaster Alex R. , Antonini James M.
Published: March 2022

Since 1997, nine cases of severe pneumonia, caused by species within the B. cereus group and with a presentation similar to that of inhalation anthrax, were reported in seemingly immunocompetent metalworkers, with most being welders. In seven of the cases, isolates were found to harbor a plasmid similar to the B. anthracis pXO1 that encodes anthrax toxins. In this paper, we review the literature on the B. cereus group spp. pneumonia among welders and other metalworkers, which we term welder’s anthrax. We describe the epidemiology, including more information on two cases of welder’s anthrax in 2020. We also describe the health risks associated with welding, potential mechanisms of infection and pathological damage, prevention measures according to the hierarchy of controls, and clinical and public health considerations. Considering occupational risk factors and controlling exposure to welding fumes and gases among workers, according to the hierarchy of controls, should help prevent disease transmission in the workplace.
Integrated Analysis of the miRNA-mRNA Regulatory Network Involved in HIV-Associated Neurocognitive Disorder
Authors: Liu Chang , Ding Qian , Kong Xiaohong
Published: March 2022

HIV-associated neurocognitive disorder (HAND) is an array of neurocognitive changes associated with HIV infection, and the roles of microRNAs in HAND have not yet been completely revealed. Based on published data and publicly available databases, we constructed an integrated miRNA-mRNA network involved in HAND. Bioinformatics analyses, including gene ontology, network analysis, and KEGG pathway analysis, were applied for further study of the network and the genes of the network. The axon guidance KEGG pathway, three genes NTNG1, EFNB2, CXCL12, and 17 miRNAs which regulate these genes are spotlighted in our study. This study provides new perspectives to the knowledge of miRNAs’ roles in the progression of HAND, and our findings provide potential therapeutic targets and clues of HAND.
Virological and Immunological Outcomes of an Intensified Four-Drug versus a Standard Three-Drug Antiretroviral Regimen, Both Integrase Strand Transfer Inhibitor-Based, in Primary HIV Infection
Authors: Mondi Annalisa , Pinnetti Carmela , Lorenzini Patrizia , Plazzi Maria Maddalena , Abbate Isabella , Camici Marta , Agrati Chiara , Grilli Elisabetta , Gili Francesca , Esvan Rozenn , Orchi Nicoletta , Rozera Gabriella , Amendola Alessandra , Forbici Federica , Gori Caterina , Gagliardini Roberta , Bellagamba Rita , Ammassari Adriana , Cicalini Stefania , Capobianchi Maria Rosaria , Antinori Andrea
Published: March 2022

The optimal therapeutic approach for primary HIV infection (PHI) is still debated. We aimed to compare the viroimmunological response to a four- versus a three-drug regimen, both INSTI-based, in patients with PHI. This was a monocentric, prospective, observational study including all patients diagnosed with PHI from December 2014 to April 2018. Antiretroviral therapy (ART) was started, before genotype resistance test results, with tenofovir/emtricitabine and either raltegravir plus boosted darunavir or dolutegravir. Cumulative probability of virological suppression [VS] (HIV-1 RNA< 40 cp/mL), low-level HIV-1 DNA [LL-HIVDNA] (HIV-1 DNA < 200 copies/106PBMC), and CD4/CD8 ratio ≥1 were estimated using Kaplan–Meier curves. Factors associated with the achievement of VS, LL-HIVDNA, and CD4/CD8 ≥ 1 were assessed by a Cox regression model. We enrolled 144 patients (95.8% male, median age 34 years): 110 (76%) started a four-drug-based therapy, and 34 (24%) a three-drug regimen. Both treatment groups showed a comparable high probability of achieving VS and a similar probability of reaching LL-HIVDNA and a CD4/CD8 ratio ≥1 after 48 weeks from ART initiation. Higher baseline HIV-1 RNA and HIV-1 DNA levels lowered the chance of VS, whereas a better preserved immunocompetence increased that chance. Not statistically significant factors associated with LL-HIVDNA achievement were found, whereas a higher baseline CD4/CD8 ratio predicted the achievement of immune recovery. In PHI patients, the rapid initiation of either an intensified four-drug or a standard three-drug INSTI-based regimen showed comparable responses in terms of VS, viral reservoir size, and immunological recovery.
In Vitro Effects of Cannabidiol on Activated Immune–Inflammatory Pathways in Major Depressive Patients and Healthy Controls
Authors: Rachayon Muanpetch , Jirakran Ketsupar , Sodsai Pimpayao , Klinchanhom Siriwan , Sughondhabirom Atapol , Plaimas Kitiporn , Suratanee Apichat , Maes Michael
Published: March 2022

Major depressive disorder and major depressive episodes (MDD/MDE) are characterized by the activation of the immune–inflammatory response system (IRS) and the compensatory immune–regulatory system (CIRS). Cannabidiol (CBD) is a phytocannabinoid isolated from the cannabis plant, which is reported to have antidepressant-like and anti-inflammatory effects. The aim of the present study is to examine the effects of CBD on IRS, CIRS, M1, T helper (Th)-1, Th-2, Th-17, T regulatory (Treg) profiles, and growth factors in depression and healthy controls. Culture supernatant of stimulated (5 μg/mL of PHA and 25 μg/mL of LPS) whole blood of 30 depressed patients and 20 controls was assayed for cytokines using the LUMINEX assay. The effects of three CBD concentrations (0.1 µg/mL, 1 µg/mL, and 10 µg/mL) were examined. Depression was characterized by significantly increased PHA + LPS-stimulated Th-1, Th-2, Th-17, Treg, IRS, CIRS, and neurotoxicity profiles. CBD 0.1 µg/mL did not have any immune effects. CBD 1.0 µg/mL decreased CIRS activities but increased growth factor production, while CBD 10.0 µg/mL suppressed Th-1, Th-17, IRS, CIRS, and a neurotoxicity profile and enhanced T cell growth and growth factor production. CBD 1.0 to 10.0 µg/mL dose-dependently decreased sIL-1RA, IL-8, IL-9, IL-10, IL-13, CCL11, G-CSF, IFN-γ, CCL2, CCL4, and CCL5, and increased IL-1β, IL-4, IL-15, IL-17, GM-CSF, TNF-α, FGF, and VEGF. In summary, in this experiment, there was no beneficial effect of CBD on the activated immune profile of depression and higher CBD concentrations can worsen inflammatory processes.
Development of Dibenzothiazepine Derivatives as Multifunctional Compounds for Neuropathic Pain
Authors: Jung Young-Hwan , Kim Yeo Ok , Kang Koon Mook , Lee Hyung Gon , Son Borum , Han Xuehao , Oh Eunseok , Kim Siwon , Seo Seon Hee , Park Jong-Hyun , Park Ki Duk , Kim Woong Mo , Yoon Myung Ha , Kim Yong-Chul
Published: March 2022

Neuropathic pain is a chronic and sometimes intractable condition caused by lesions or diseases of the somatosensory nervous system. Many drugs are available but unfortunately do not provide satisfactory effects in patients, producing limited analgesia and undesirable side effects. Thus, there is an urgent need to develop new pharmaceutical agents to treat neuropathic pain. To date, highly specific agents that modulate a single target, such as receptors or ion channels, never progress to the clinic, which may reflect the diverse etiologies of neuropathic pain seen in the human patient population. Therefore, the development of multifunctional compounds exhibiting two or more pharmacological activities is an attractive strategy for addressing unmet medical needs for the treatment of neuropathic pain. To develop novel multifunctional compounds, key pharmacophores of currently used clinical pain drugs, including pregabalin, fluoxetine and serotonin analogs, were hybridized to the side chain of tianeptine, which has been used as an antidepressant. The biological activities of the hybrid analogs were evaluated at the human transporters of neurotransmitters, including serotonin (hSERT), norepinephrine (hNET) and dopamine (hDAT), as well as mu (μ) and kappa (κ) opioid receptors. The most advanced hybrid of these multifunctional compounds, 17, exhibited multiple transporter inhibitory activities for the uptake of neurotransmitters with IC50 values of 70 nM, 154 nM and 2.01 μM at hSERT, hNET and hDAT, respectively. Additionally, compound 17 showed partial agonism (EC50 = 384 nM) at the μ-opioid receptor with no influence at the κ-opioid receptor. In in vivo pain animal experiments, the multifunctional compound 17 showed significantly reduced allodynia in a spinal nerve ligation (SNL) model by intrathecal administration, indicating that multitargeted strategies in single therapy could considerably benefit patients with multifactorial diseases, such as pain.
Pharmacokinetics of DA-6886, A New 5-HT4 Receptor Agonist, in Rats
Authors: Lee Dae Young , Kang Hee Eun
Published: March 2022

DA-6886 is a novel serotonin (5-hydroxytrypamine [5-HT]) receptor 4 agonist for the potential treatment of constipation-predominant irritable bowel syndrome. The purpose of this study was to validate the quantitative assay of DA-6886 in rat plasma and to evaluate the pharmacokinetics and tissue distribution of DA-6886 in rats. The liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the robust quantification of DA-6886 in rat plasma was successfully validated and applied to the pharmacokinetic studies in rats. The pharmacokinetic parameters of DA-6886 in rats were evaluated following single intravenous or oral administration at three dose levels (2, 10, and 20 mg/kg). DA-6886 exhibited a smaller dose-normalized area under the plasma concentration–time curve (AUC) values and faster clearances in the low-dose group than in the high-dose group following both intravenous and oral administration. The steady-state volume of distribution (Vss) of DA-6886 was relatively large (4.91–7.84 L/kg), which was consistent with its high distribution to the liver, kidney, lung, and digestive tract, and was dose-independent. After oral administration, the extent of absolute bioavailability (F) tended to increase (18.9–55.0%) with an increasing dose. The slope of the log-transformed AUC and/or Cmax values versus log dose was greater than unity and greater for oral administration (~1.9) than for intravenous administration (~1.1). Because the nonlinear pharmacokinetics of DA-6886 was more obviously observed after oral administration, it appears that the saturation of pre-systemic intestinal and/or hepatic first-pass extraction of DA-6886 at high doses occurred.
Development of Stable Nano-Sized Transfersomes as a Rectal Colloid for Enhanced Delivery of Cannabidiol
Authors: Moqejwa Thope , Marimuthu Thashree , Kondiah Pierre P. D. , Choonara Yahya E.
Published: March 2022

Current cannabidiol (CBD) formulations are challenged with unpredictable release and absorption. Rational design of a rectal colloid delivery system can provide a practical alternative. In this study the inherent physiochemical properties of transferosomes were harnessed for the development of a nano-sized transfersomes to yield more stable release, absorption, and bioavailability of CBD as a rectal colloid. Transfersomes composed of soya lecithin, cholesterol, and polysorbate 80 were synthesized via thin film evaporation and characterized for size, entrapment efficiency (%), morphology, CBD release, ex vivo permeation, and physicochemical stability. The optimized formulation for rectal delivery entrapped up to 80.0 ± 0.077% of CBD with a hydrodynamic particle size of 130 nm, a PDI value of 0.285, and zeta potential of −15.97 mV. The morphological investigation via SEM and TEM revealed that the transfersomes were spherical and unilamellar vesicles coinciding with the enhanced ex vivo permeation across the excised rat colorectal membrane. Furthermore, transfersomes improved the stability of the encapsulated CBD for up to 6 months at room temperature and showed significant promise that the transfersomes promoted rectal tissue permeation with superior stability and afforded tunable release kinetics of CBD as a botanical therapeutic with inherent poor bioavailability.
Macrolide Treatment Failure due to Drug–Drug Interactions: Real-World Evidence to Evaluate a Pharmacological Hypothesis
Authors: Cicali Brian , Schmidt Stephan , Zeitlinger Markus , Brown Joshua D.
Published: March 2022

Macrolide antibiotics have received criticism concerning their use and risk of treatment failure. Nevertheless, they are an important class of antibiotics and are frequently used in clinical practice for treating a variety of infections. This study sought to utilize pharmacoepidemiology methods and pharmacology principles to estimate the risk of macrolide treatment failure and quantify the influence of their pharmacokinetics on the risk of treatment failure, using clinically reported drug–drug interaction data. Using a large, commercial claims database (2006–2015), inclusion and exclusion criteria were applied to create a cohort of patients who received a macrolide for three common acute infections. Furthermore, an additional analysis examining only bacterial pneumonia events treated with macrolides was conducted. These criteria were formulated specifically to ensure treatment failure would not be expected nor influenced by intrinsic or extrinsic factors. Treatment failure rates were 6% within the common acute infections and 8% in the bacterial pneumonia populations. Regression results indicated that macrolide AUC changes greater than 50% had a significant effect on treatment failure risk, particularly for azithromycin. In fact, our results show that decreased or increased exposure change can influence failure risk, by 35% or 12%, respectively, for the acute infection scenarios. The bacterial pneumonia results were less significant with respect to the regression analyses. This integration of pharmacoepidemiology and clinical pharmacology provides a framework for utilizing real-world data to provide insight into pharmacokinetic mechanisms and support future study development related to antibiotic treatments.
Injectable Hydrogel Based on Protein-Polyester Microporous Network as an Implantable Niche for Active Cell Recruitment
Authors: Phan V.H. Giang , Murugesan Mohanapriya , Manivasagan Panchanathan , Nguyen Thanh Loc , Phan Thuy-Hien , Luu Cuong Hung , Ho Duy-Khiet , Li Yi , Kim Jaeyun , Lee Doo Sung , Thambi Thavasyappan
Published: March 2022

Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed an injectable protein-polymer-based porous hydrogel network composed of lysozyme and poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) (Lys-PCLA) bioconjugate for the active recruitment dendritic cells (DCs). The Lys-PCLA bioconjugates are prepared using thiol-ene reaction between thiolated lysozyme (Lys-SH) and acrylated PCLA (PCLA-Ac). The free-flowing Lys-PCLA bioconjugate sols at low temperature transformed to immovable gel at the physiological condition and exhibited stability upon dilution with buffers. According to the in vitro toxicity test, the Lys-PCLA bioconjugate and PCLA copolymer were non-toxic to RAW 263.7 cells at higher concentrations (1000 µg/mL). In addition, subcutaneous administration of Lys-PCLA bioconjugate sols formed stable hydrogel depot instantly, which suggested the in situ gel forming ability of the bioconjugate. Moreover, the Lys-PCLA bioconjugate hydrogel depot formed at the interface between subcutaneous tissue and dermis layers allowed the active migration and recruitment of DCs. As suggested by these results, the in-situ forming injectable Lys-PCLA bioconjugate hydrogel depot may serve as an implantable immune niche for the recruitment and modification of DCs.
Comparative Pharmacokinetics of Sulfadiazine and Its Metabolite N4-Acetyl Sulfadiazine in Grass Carp (Ctenopharyngodon idella) at Different Temperatures after Oral Administration
Authors: Xu Ning , Li Miao , Lin Zhoumeng , Ai Xiaohui
Published: March 2022

In this study, the plasma pharmacokinetics and tissue disposition of sulfadiazine (SDZ) and its main metabolite, N4-acetyl sulfadiazine (ACT-SDZ), were compared between 18 and 24 °C following a single oral administration of SDZ at 50 mg/kg in grass carp (Ctenopharyngodon idella). The plasma and tissues were sampled from 0.167 h up to 96 h and analyzed by ultra-performance liquid chromatography with an ultraviolet detector. The pharmacokinetic parameters were estimated using a one-compartmental approach. Results showed that pharmacokinetics of SDZ and ACT-SDZ in plasma and tissues were notably influenced by the increase of temperature. The increased temperature shortened the absorption half-life (K01_HL) of SDZ and ACT-SDZ in gill, kidney, and plasma, but increased in liver and muscle + skin. The elimination half-life (K10_HF) and the area under concentration-time curve (AUC0–∞) of SDZ and ACT-SDZ all presented a declined trend. The apparent volume of distribution (V_F) of SDZ in plasma was increased from 0.93 to 1.64 L/kg, and the apparent systemic total body clearance (Cl_F) was also increased from 0.01 to 0.05 L/h/kg. Overall, the rise of temperature decreased K10_HF, AUC0–∞ of SDZ, and ACT-SDZ in plasma and tissues, but increased V_F and Cl_F in the plasma for SDZ.
Microfluidics Formulated Liposomes of Hypoxia Activated Prodrug for Treatment of Pancreatic Cancer
Authors: Shah Vidhi M. , Dorrell Craig , Al-Fatease Adel , Allen-Petersen Brittany L. , Woo Yeonhee , Bortnyak Yuliya , Gheewala Rohi , Sheppard Brett C. , Sears Rosalie C. , Alani Adam WG.
Published: March 2022

Pancreatic ductal adenocarcinoma (PDAC) presents as an unmet clinical challenge for drug delivery due to its unique hypoxic biology. Vinblastine-N-Oxide (CPD100) is a hypoxia-activated prodrug (HAP) that selectively converts to its parent compound, vinblastine, a potent cytotoxic agent, under oxygen gradient. The study evaluates the efficacy of microfluidics formulated liposomal CPD100 (CPD100Li) in PDAC. CPD100Li were formulated with a size of 95 nm and a polydispersity index of 0.2. CPD100Li was stable for a period of 18 months when freeze-dried at a concentration of 3.55 mg/mL. CPD100 and CPD100Li confirmed selective activation at low oxygen levels in pancreatic cancer cell lines. Moreover, in 3D spheroids, CPD100Li displayed higher penetration and disruption compared to CPD100. In patient-derived 3D organoids, CPD100Li exhibited higher cell inhibition in the organoids that displayed higher expression of hypoxia-inducible factor 1 alpha (HIF1A) compared to CPD100. In the orthotopic model, the combination of CPD100Li with gemcitabine (GEM) (standard of care for PDAC) showed higher efficacy than CPD100Li alone for a period of 90 days. In summary, the evaluation of CPD100Li in multiple cellular models provides a strong foundation for its clinical application in PDAC.
Diphlorethohydroxycarmalol Derived from Ishige okamurae Improves Behavioral and Physiological Responses of Muscle Atrophy Induced by Dexamethasone in an In-Vivo Model
Authors: Ryu Bomi , Oh Seyeon , Yang Hye-Won , Sosorburam Batsukh , Chung Dong-Min , Seo Minyoung , Park Shin-Jae , Byun Kyunghee , Jeon You-Jin
Published: March 2022

Muscle atrophy refers to the loss of skeletal muscle mass, myofiber size, and related physical functions such as walking speed or grip strength caused by aging or a lack of physical activity due to injury or illness and can also be attributed to excessive exposure to corticosteroids. Ishige okamurae (IO) and its active component, diphlorethohydroxycarmalol (DPHC), have been known to improve glucose homeostasis by controlling the contraction of skeletal muscles. Based on this idea, we hypothesized that the effects of DPHC and IO extract on muscle metabolism are associated with their role in improving muscle physical function. This study assessed the effects of DPHC or IO extract on muscle behavioral responses with their metabolic properties in muscle atrophy induced by glucocorticoids and dexamethasone (DEX) in vivo. In addition to the improvement in muscle behavioral response by DPHC or IO extract, the loss of muscle fiber and the related metabolic properties by DEX exposure in the gastrocnemius and soleus of calf muscle was prevented. These findings suggest that IO extract and its active component DPHC can potentially prevent muscle atrophy caused by exposure to corticosteroids and could be used to treat reverse skeletal atrophy.
Calibration Method for Line-Structured Light Three-Dimensional Measurement Based on a Simple Target
Authors: Li Xuexing , Zhang Wenhui , Song Guanglei
Published: March 2022

Line-structured light three-dimensional (3D) measurement is apt for measuring the 3D profile of objects in complex industrial environments. The light-plane calibration, which is a crucial link, greatly affects the accuracy of measurement results. This paper proposes a novel calibration method for line-structured light 3D measurement based on a simple target, i.e., a single cylindrical target (SCT). First, the line-structured light intersects with the target to generate a light stripe. Meanwhile, the camera captures the calibration images, extracts the refined subpixel center points of the light stripe (RSCP) and detects the elliptic profiles of the two ends of the cylindrical target (EPCT). Second, two elliptical cones defined by the EPCT and the camera optical center are determined. Combining the two defined elliptical cones and the known radius of the SCT, we can uniquely solve the axis equation of the SCT. Finally, because the coordinates of RSCP in the camera coordinate system fulfill both the camera model and the cylindrical equation, these coordinates can be solved and used to obtain the optimal solution of the light-plane equation. The results of simulations and experiments verify that our proposed method has higher accuracy and effectiveness.