bluuebunny/crossref_metadata_2025 huggingface dataset:
Recently Approved Drugs for Lowering and Controlling Intraocular Pressure to Reduce Vision Loss in Ocular Hypertensive and Glaucoma Patients
Authors: Sharif Najam A.
Published: May 2023

Serious vision loss occurs in patients affected by chronically raised intraocular pressure (IOP), a characteristic of many forms of glaucoma where damage to the optic nerve components causes progressive degeneration of retinal and brain neurons involved in visual perception. While many risk factors abound and have been validated for this glaucomatous optic neuropathy (GON), the major one is ocular hypertension (OHT), which results from the accumulation of excess aqueous humor (AQH) fluid in the anterior chamber of the eye. Millions around the world suffer from this asymptomatic and progressive degenerative eye disease. Since clinical evidence has revealed a strong correlation between the reduction in elevated IOP/OHT and GON progression, many drugs, devices, and surgical techniques have been developed to lower and control IOP. The constant quest for new pharmaceuticals and other modalities with superior therapeutic indices has recently yielded health authority-approved novel drugs with unique pharmacological signatures and mechanism(s) of action and AQH drainage microdevices for effectively and durably treating OHT. A unique nitric oxide-donating conjugate of latanoprost, an FP-receptor prostaglandin (PG; latanoprostene bunod), new rho kinase inhibitors (ripasudil; netarsudil), a novel non-PG EP2-receptor-selective agonist (omidenepag isopropyl), and a form of FP-receptor PG in a slow-release intracameral implant (Durysta) represent the additions to the pharmaceutical toolchest to mitigate the ravages of OHT. Despite these advances, early diagnosis of OHT and glaucoma still lags behind and would benefit from further concerted effort and attention.
Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin
Authors: Eruçar Fatma Memnune , Kuran Fadıl Kaan , Altıparmak Ülbegi Gülsüm , Özbey Süheyla , Karavuş Şule Nur , Arcan Gülşah Gamze , Yazıcı Tütüniş Seçil , Tan Nur , Aksoy Sağırlı Pınar , Miski Mahmut
Published: May 2023

Ancient physicians frequently used the resin of Ferula species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of Ferula species. The dichloromethane extract of the roots of Ferula huber-morathii exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC50 = 52 µg/mL, 72 µg/mL, and 20 µg/mL, respectively). Fifteen sesquiterpene coumarin ethers with cytotoxic activity were isolated from the dichloromethane extract of the roots of F. huber-morathii using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (1), conferol (2), feselol (3), badrakemone (4), mogoltadone (5), farnesiferol A (6), farnesiferol A acetate (7), gummosin (8), ferukrin (9), ferukrin acetate (10), deacetylkellerin (11), kellerin (12), samarcandone (13), samarcandin (14), and samarcandin acetate (15). The absolute configuration of samarcandin (14) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (R)-MTPA ester of samarcandin (24). Conferol (2) and mogoltadone (5) were found to be the most potent cytotoxic compounds against all three cancer cell lines; furthermore, these compounds exhibit low cytotoxic activity against the non-cancerous human umbilical vein epithelial cells (HUVEC) cell line. Investigation of the biological activity mechanisms of mogoltadone (5) revealed that while suppressing the levels of Bcl-XL and procaspase-3 in the COLO 205 cancer cell line, it did not have a significant effect on the Bcl-XL, caspase-3, and β-catenin protein levels of the HUVEC cell line, which may explain the cytotoxic selectivity of mogoltadone (5) on cancer cell lines.
Metabolomics and Network Analyses Reveal Phenylalanine and Tyrosine as Signatures of Anthracycline-Induced Hepatotoxicity
Authors: Liu Peipei , Wu Jing , Yu Xinyue , Guo Linling , Zhao Ling , Ban Tao , Huang Yin
Published: May 2023

The chemotherapy drug doxorubicin (DOX) is an anthracycline with over 30% incidence of liver injury in breast cancer patients, yet the mechanism of its hepatotoxicity remains unclear. To identify potential biomarkers for anthracycline-induced hepatotoxicity (AIH), we generated clinically-relevant mouse and rat models administered low-dose, long-term DOX. These models exhibited significant liver damage but no decline in cardiac function. Through untargeted metabolic profiling of the liver, we identified 27 differential metabolites in a mouse model and 28 in a rat model. We then constructed a metabolite-metabolite network for each animal model and computationally identified several potential metabolic markers, with particular emphasis on aromatic amino acids, including phenylalanine, tyrosine, and tryptophan. We further performed targeted metabolomics analysis on DOX-treated 4T1 breast cancer mice for external validation. We found significant (p < 0.001) reductions in hepatic levels of phenylalanine and tyrosine (but not tryptophan) following DOX treatment, which were strongly correlated with serum aminotransferases (ALT and AST) levels. In summary, the results of our study present compelling evidence supporting the use of phenylalanine and tyrosine as metabolic signatures of AIH.
Emerging Preclinical Applications of Humanized Mouse Models in the Discovery and Validation of Novel Immunotherapeutics and Their Mechanisms of Action for Improved Cancer Treatment
Authors: Karnik Isha , Her Zhisheng , Neo Shu Hui , Liu Wai Nam , Chen Qingfeng
Published: May 2023

Cancer therapeutics have undergone immense research over the past decade. While chemotherapies remain the mainstay treatments for many cancers, the advent of new molecular techniques has opened doors for more targeted modalities towards cancer cells. Although immune checkpoint inhibitors (ICIs) have demonstrated therapeutic efficacy in treating cancer, adverse side effects related to excessive inflammation are often reported. There is a lack of clinically relevant animal models to probe the human immune response towards ICI-based interventions. Humanized mouse models have emerged as valuable tools for pre-clinical research to evaluate the efficacy and safety of immunotherapy. This review focuses on the establishment of humanized mouse models, highlighting the challenges and recent advances in these models for targeted drug discovery and the validation of therapeutic strategies in cancer treatment. Furthermore, the potential of these models in the process of uncovering novel disease mechanisms is discussed.
Influence of Polyvinylpyrrolidone Molecular Weight and Concentration on the Precipitation Inhibition of Supersaturated Solutions of Poorly Soluble Drugs
Authors: Odeh Afnan Bany , El-Sayed Boushra , Knopp Matthias Manne , Rades Thomas , Blaabjerg Lasse Ingerslev
Published: May 2023

Supersaturating drug delivery systems such as solid dispersions of a drug in a polymer are frequently used in pharmaceutical development to enable oral delivery of poorly soluble drugs. In this study, the influence of the concentration and molecular weight of polyvinylpyrrolidone (PVP) on the precipitation inhibition of the poorly soluble drugs albendazole, ketoconazole and tadalafil is investigated to expand the understanding of the mechanism of PVP as a polymeric precipitation inhibitor. A three-level full-factorial design was used to delineate the influence of polymer concentration and viscosity of the dissolution medium on precipitation inhibition. Solutions of PVP K15, K30, K60 or K120 at concentrations of 0.1, 0.5 and 1% (w/v), as well as isoviscous solutions of PVP of increasing molecular weight, were prepared. Supersaturation of the three model drugs was induced by the use of a solvent-shift method. Precipitation of the three model drugs from supersaturated solutions in the absence and presence of polymer was investigated by the use of a solvent-shift method. Time–concentration profiles of the respective drugs in the absence and presence of polymer pre-dissolved in the dissolution medium were obtained by the use of a μDISS Profiler™ to determine the onset of nucleation and the precipitation rate. Multiple linear regression was used to evaluate the hypothesis that precipitation inhibition is influenced by the PVP concentration (i.e., the number of repeat units of the polymer) and the medium viscosity of the polymer for the three model drugs. This study showed that an increased concentration of PVP (i.e., an increased concentration of the PVP repeat units, independent of the molecular weight of the polymer) in solution increased the onset of nucleation and decreased the precipitation rate of the respective drugs during supersaturation, which can be explained by an increase in molecular interactions between the drug and polymer with increasing concentrations of polymer. In contrast, the medium viscosity had no significant influence on the onset of the nucleation and precipitation rate of the drugs, which can be explained by solution viscosity having a negligible effect on the rate of drug diffusion from bulk solution to the crystal nuclei. In conclusion, the precipitation inhibition of the respective drugs is influenced by the concentration of PVP, i.e., by molecular interactions between the drug and polymer. In contrast, the molecular mobility of the drug in solution, i.e., the medium viscosity, has no influence on the precipitation inhibition of the drugs.
Increased Bone Marrow Uptake and Accumulation of Very-Late Antigen-4 Targeted Lipid Nanoparticles
Authors: Swart Laura E. , Fens Marcel H. A. M. , van Oort Anita , Waranecki Piotr , Mata Casimiro L. Daniel , Tuk David , Hendriksen Martijn , van den Brink Luca , Schweighart Elizabeth , Seinen Cor , Nelson Ryan , Krippner-Heidenreich Anja , O’Toole Tom , Schiffelers Raymond M. , Kooijmans Sander , Heidenreich Olaf
Published: May 2023

Lipid nanoparticles (LNPs) have evolved rapidly as promising delivery systems for oligonucleotides, including siRNAs. However, current clinical LNP formulations show high liver accumulation after systemic administration, which is unfavorable for the treatment of extrahepatic diseases, such as hematological disorders. Here we describe the specific targeting of LNPs to hematopoietic progenitor cells in the bone marrow. Functionalization of the LNPs with a modified Leu-Asp-Val tripeptide, a specific ligand for the very-late antigen 4 resulted in an improved uptake and functional siRNA delivery in patient-derived leukemia cells when compared to their non-targeted counterparts. Moreover, surface-modified LNPs displayed significantly improved bone-marrow accumulation and retention. These were associated with increased LNP uptake by immature hematopoietic progenitor cells, also suggesting similarly improved uptake by leukemic stem cells. In summary, we describe an LNP formulation that successfully targets the bone marrow including leukemic stem cells. Our results thereby support the further development of LNPs for targeted therapeutic interventions for leukemia and other hematological disorders.
The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies
Authors: Laface Carmelo , Maselli Felicia Maria , Santoro Anna Natalizia , Iaia Maria Laura , Ambrogio Francesca , Laterza Marigia , Guarini Chiara , De Santis Pierluigi , Perrone Martina , Fedele Palma
Published: May 2023

Almost 17% of Western patients affected by non-small cell lung cancer (NSCLC) have an activating epidermal growth factor receptor (EGFR) gene mutation. Del19 and L858R are the most-common ones; they are positive predictive factors for EGFR tyrosine kinase inhibitors (TKIs). Currently, osimertinib, a third-generation TKI, is the standard first-line therapy for advanced NSCLC patients with common EGFR mutations. This drug is also administered as a second-line treatment for those patients with the T790M EGFR mutation and previously treated with first- (erlotinib, gefitinib) or second- (afatinib) generation TKIs. However, despite the high clinical efficacy, the prognosis remains severe due to intrinsic or acquired resistance to EGRF-TKIs. Various mechanisms of resistance have been reported including the activation of other signalling pathways, the development of secondary mutations, the alteration of the downstream pathways, and phenotypic transformation. However, further data are needed to achieve the goal of overcoming resistance to EGFR-TKIs, hence the necessity of discovering novel genetic targets and developing new-generation drugs. This review aimed to deepen the knowledge of intrinsic and acquired molecular mechanisms of resistance to EGFR-TKIs and the development of new therapeutic strategies to overcome TKIs’ resistance.
Rapid Adaptation of Chimonobambusa opienensis Leaves to Crown–Thinning in Giant Panda Ecological Corridor, Niba Mountain
Authors: Fang Di , Xian Junren , Chen Guopeng , Zhang Yuanbin , Qin Hantang , Fu Xin , Lin Liyang , Ai Yuxuan , Yang Zhanbiao , Xu Xiaoxun , Yang Yuanxiang , Cheng Zhang
Published: May 2023

Leaf traits reflect the ecological strategy in heterogeneous contexts and are widely used to explore the adaption of plant species to environmental change. However, the knowledge of short-term effect of canopy management on understorey plant leaf traits is still limited. Here, we studied the short-term effect of crown–thinning on the leaf morphological traits of bamboo (Chimonobambusa opienensis), an important understorey plant and staple food for the giant panda (Ailuropoda melanoleuca) of Niba Mountain. Our treatments were two crown–thinnings (spruce plantation, CS, and deciduous broad-leaved forest, CB) and two controls (broad-leaved forest canopy, FC, and the bamboo grove of clearcutting, BC). The results showed that: the CS enhanced the annual leaf length, width, area, and thickness, CB decreased almost all annual leaf traits, and perennial leaf traits in CS and CB were the opposite. The log-transformed allometric relationships of length vs. width, biomass vs. area were significantly positive while those of specific leaf area vs. thickness were significantly negative, which varied largely in treatments and age. The leaf traits and allometric relationships suggested that the CS created a more suitable habitat for bamboo growth. This study highlighted that the understorey bamboo leaf traits could adapt the improved light environment induced by crown–thinning rapidly.
Metal-Resistant PGPR Strain Azospirillum brasilense EMCC1454 Enhances Growth and Chromium Stress Tolerance of Chickpea (Cicer arietinum L.) by Modulating Redox Potential, Osmolytes, Antioxidants, and Stress-Related Gene Expression
Authors: El-Ballat Enas M. , Elsilk Sobhy E. , Ali Hayssam M. , Ali Hamada E. , Hano Christophe , El-Esawi Mohamed A.
Published: May 2023

Heavy metal stress, including from chromium, has detrimental effects on crop growth and yields worldwide. Plant growth-promoting rhizobacteria (PGPR) have demonstrated great efficiency in mitigating these adverse effects. The present study investigated the potential of the PGPR strain Azospirillum brasilense EMCC1454 as a useful bio-inoculant for boosting the growth, performance and chromium stress tolerance of chickpea (Cicer arietinum L.) plants exposed to varying levels of chromium stress (0, 130 and 260 µM K2Cr2O7). The results revealed that A. brasilense EMCC1454 could tolerate chromium stress up to 260 µM and exhibited various plant growth-promoting (PGP) activities, including nitrogen fixation, phosphate solubilization, and generation of siderophore, trehalose, exopolysaccharide, ACC deaminase, indole acetic acid, and hydrolytic enzymes. Chromium stress doses induced the formation of PGP substances and antioxidants in A. brasilense EMCC1454. In addition, plant growth experiments showed that chromium stress significantly inhibited the growth, minerals acquisition, leaf relative water content, biosynthesis of photosynthetic pigments, gas exchange traits, and levels of phenolics and flavonoids of chickpea plants. Contrarily, it increased the concentrations of proline, glycine betaine, soluble sugars, proteins, oxidative stress markers, and enzymatic (CAT, APX, SOD, and POD) and non-enzymatic (ascorbic acid and glutathione) antioxidants in plants. On the other hand, A. brasilense EMCC1454 application alleviated oxidative stress markers and significantly boosted the growth traits, gas exchange characteristics, nutrient acquisition, osmolyte formation, and enzymatic and non-enzymatic antioxidants in chromium-stressed plants. Moreover, this bacterial inoculation upregulated the expression of genes related to stress tolerance (CAT, SOD, APX, CHS, DREB2A, CHI, and PAL). Overall, the current study demonstrated the effectiveness of A. brasilense EMCC1454 in enhancing plant growth and mitigating chromium toxicity impacts on chickpea plants grown under chromium stress circumstances by modulating the antioxidant machinery, photosynthesis, osmolyte production, and stress-related gene expression.
Characterization of Carotenoid Cleavage Oxygenase Genes in Cerasus humilis and Functional Analysis of ChCCD1
Authors: Cheng Chunzhen , Yang Rui , Yin Lu , Zhang Jianying , Gao Limin , Lu Rong , Yang Yan , Wang Pengfei , Mu Xiaopeng , Zhang Shuai , Zhang Bin , Zhang Jiancheng
Published: May 2023

Carotenoid cleavage oxygenases (CCOs) are key enzymes that function in degrading carotenoids into a variety of apocarotenoids and some other compounds. In this study, we performed genome-wide identification and characterization analysis of CCO genes in Cerasus humilis. Totally, nine CCO genes could be classified into six subfamilies, including carotenoid cleavage dioxygenase 1 (CCD1), CCD4, CCD7, CCD8, CCD-like and nine-cis-epoxycarotenoid dioxygenase (NCED), were identified. Results of gene expression analysis showed that ChCCOs exhibited diverse expression patterns in different organs and in fruits at different ripening stages. To investigate the roles of ChCCOs in carotenoids degradation, enzyme assays of the ChCCD1 and ChCCD4 were performed in Escerichia coli BL21(DE3) that can accumulate lycopene, β-carotene and zeaxanthin. The prokaryotic expressed ChCCD1 resulted in obvious degradation of lycopene, β-carotene and zeaxanthin, but ChCCD4 did not show similar functions. To further determine the cleaved volatile apocarotenoids of these two proteins, headspace gas chromatography/mass spectrometer analysis was performed. Results showed that ChCCD1 could cleave lycopene at 5, 6 and 5′, 6′ positions to produce 6-methy-5-hepten-2-one and could catalyze β-carotene at 9, 10 and 9′, 10′ positions to generate β-ionone. Our study will be helpful for clarifying the roles of CCO genes especially ChCCD1 in regulating carotenoid degradation and apocarotenoid production in C. humilis.
Soybean Root Transcriptomics: Insights into Sucrose Signaling at the Crossroads of Nutrient Deficiency and Biotic Stress Responses
Authors: Nidumolu Leela Chandra Manozna , Lorilla Kristina Mae , Chakravarty Indrani , Uhde-Stone Claudia
Published: May 2023

Soybean (Glycine max) is an important agricultural crop, but nutrient deficiencies frequently limit soybean production. While research has advanced our understanding of plant responses to long-term nutrient deficiencies, less is known about the signaling pathways and immediate responses to certain nutrient deficiencies, such as Pi and Fe deficiencies. Recent studies have shown that sucrose acts as a long-distance signal that is sent in increased concentrations from the shoot to the root in response to various nutrient deficiencies. Here, we mimicked nutrient deficiency-induced sucrose signaling by adding sucrose directly to the roots. To unravel transcriptomic responses to sucrose acting as a signal, we performed Illumina RNA-sequencing of soybean roots treated with sucrose for 20 min and 40 min, compared to non-sucrose-treated controls. We obtained a total of 260 million paired-end reads, mapping to 61,675 soybean genes, some of which are novel (not yet annotated) transcripts. Of these, 358 genes were upregulated after 20 min, and 2416 were upregulated after 40 min of sucrose exposure. GO (gene ontology) analysis revealed a high proportion of sucrose-induced genes involved in signal transduction, particularly hormone, ROS (reactive oxygen species), and calcium signaling, in addition to regulation of transcription. In addition, GO enrichment analysis indicates that sucrose triggers crosstalk between biotic and abiotic stress responses.
The Accumulation of Health-Promoting Nutrients from Representative Organs across Multiple Developmental Stages in Orange Chinese Cabbage
Authors: Zhang Ruixing , Zhang Jiahao , Li Chao , Pan Qiming , Haq Saeed ul , Mosa Walid F. A. , Fang Fang , Zhang Lugang , Li Baohua
Published: May 2023

Orange Chinese cabbage (Brassica rapa L. ssp. pekinensis) is an excellent source of health-promoting nutrients that could reduce the risk of chronic diseases. This study mainly investigated the accumulation patterns of eight lines of orange Chinese cabbage for indolic glucosinolates (GLSs) and pigment content from representative plant organs across multiple developmental stages. The indolic GLSs were highly accumulated at the rosette stage (S2), especially in inner and middle leaves, and the order of indolic GLSs accumulation in non-edible organs was flower > seed > stem > silique. The expression levels of biosynthetic genes in light signaling, MEP, carotenoids, and GLS pathways were consistent with the metabolic accumulation patterns. The results of a principal component analysis show a clear separation of high indolic GLS lines (15S1094 and 18BC6) from low indolic GLS lines (20S530). A negative correlation between the accumulation of indolic GLS and carotenoids was identified in our study. Our work contributes to providing valuable knowledge required to breed, grow, and select orange Chinese cabbage varieties and their eatable organs with higher nutritional value.
In Vitro Multiplication and Rooting of Plum Rootstock ‘Saint Julien’ (Prunus domestica subsp. insititia) under Fluorescent Light and Different LED Spectra
Authors: Nacheva Lilyana , Dimitrova Nataliya , Koleva-Valkova Lyubka , Stefanova Miroslava , Ganeva Tsveta , Nesheva Marieta , Tarakanov Ivan , Vassilev Andon
Published: May 2023

In recent years, light emitting diodes (LEDs), due to their low energy consumption, low heat emission and specific wavelength irradiation, have become an alternative to fluorescent lamps (FLs) in plant tissue culture. The aim of this study was to investigate the effects of various LED light sources on the in vitro growth and rooting of plum rootstock Saint Julien (Prunus domestica subsp. insititia). The test plantlets were cultivated under a Philips GreenPower LEDs research module illumination system with four spectral regions: white (W), red (R), blue (B) and mixed (W:R:B:far-red = 1:1:1:1). The control plantlets were cultivated under fluorescent lamps (FL) and the photosynthetic photon flux density (PPFD) of all treatments was set at 87 ± 7.5 μmol m−2 s−1. The effect of light source on the selected physiological, biochemical and growth parameters of plantlets was monitored. Additionally, microscopic observations of leaf anatomy, leaf morphometric parameters and stomata characteristics were carried out. The results showed that the multiplication index (MI) varied from 8.3 (B) to 16.3 (R). The MI of plantlets grown under mixed light (WBR) was 9, lower compared to the control (FL) and white light (W), being 12.7 and 10.7, respectively. In addition, a mixed light (WBR) favored plantlets’ stem growth and biomass accumulation at the multiplication stage. Considering these three indicators, we could conclude that under the mixed light, the microplants were of better quality and therefore mixed light (WBR) was more suitable during the multiplication phase. A reduction in both net photosynthesis rate and stomatal conductance in the leaves of plants grown under B were observed. The quantum yield (Yield = FV/FM), which represents the potential photochemical activity of PS II, ranged from 0.805 to 0.831 and corresponded to the typical photochemical activity (0.750–0.830) in the leaves of unstressed healthy plants. The red light had a beneficial effect on the rooting of plum plants; the rooting was over 98%, significantly higher than for the control (FL, 68%) and the mixed light (WBR, 19%). In conclusion, the mixed light (WBR) turned out to be the best choice during the multiplication phase and the red LED light was more suitable during the rooting stage.
A Mousepad Triboelectric-Piezoelectric Hybrid Nanogenerator (TPHNG) for Self-Powered Computer User Behavior Monitoring Sensors and Biomechanical Energy Harvesting
Authors: Jian Gang , Yang Ning , Zhu Shangtao , Meng Qingzhen , Ouyang Chun
Published: May 2023

Hybrid nanogenerators based on the principle of surface charging of functional films are significant in self-powering sensing and energy conversion devices due to their multiple functions and high conversion efficiency, although applications remain limited due to a lack of suitable materials and structures. Here, we investigate a triboelectric-piezoelectric hybrid nanogenerator (TPHNG) in the form of a mousepad for computer user behavior monitoring and energy harvesting. Triboelectric and piezoelectric nanogenerators with different functional films and structures work independently to detect sliding and pressing movements, and the profitable coupling between the two nanogenerators leads to enhanced device outputs/sensitivity. Different mouse operations such as clicking, scrolling, taking-up/putting-down, sliding, moving rate, and pathing can be detected by the device via distinguishable patterns of voltage ranging from 0.6 to 36 V. Based on operation recognition, human behavior monitoring is realized, with monitoring of tasks such as browsing a document and playing a computer game being successfully demonstrated. Energy harvesting from mouse sliding, patting, and bending of the device is realized with output voltages up to 37 V and power up to 48 μW while exhibiting good durability up to 20,000 cycles. This work presents a TPHNG utilizing surface charging for self-powered human behavior sensing and biomechanical energy harvesting.
In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-b-Poly(N-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery
Authors: Huang Yi-Cheng , Zeng Yang-Jie , Lin Yu-Wei , Tai Hung-Chih , Don Trong-Ming
Published: May 2023

Camptothecin (CPT) has been shown to exhibit anticancer activity against several cancers. Nevertheless, CPT is very hydrophobic with poor stability, and thus its medical application is limited. Therefore, various drug carriers have been exploited for effectively delivering CPT to the targeted cancer site. In this study, a dual pH/thermo-responsive block copolymer of poly(acrylic acid-b-N-isopropylacrylamide) (PAA-b-PNP) was synthesized and applied to encapsulate CPT. At temperatures above its cloud point, the block copolymer self-assembled to form nanoparticles (NPs) and in situ encapsulate CPT, owing to their hydrophobic interaction as evidenced by fluorescence spectrometry. Chitosan (CS) was further applied on the surface through the formation of a polyelectrolyte complex with PAA for improving biocompatibility. The average particle size and zeta potential of the developed PAA-b-PNP/CPT/CS NPs in a buffer solution were 168 nm and −30.6 mV, respectively. These NPs were still stable at least for 1 month. The PAA-b-PNP/CS NPs exhibited good biocompatibility toward NIH 3T3 cells. Moreover, they could protect the CPT at pH 2.0 with a very slow-release rate. At pH 6.0, these NPs could be internalized by Caco-2 cells, followed by intracellular release of the CPT. They became highly swollen at pH 7.4, and the released CPT was able to diffuse into the cells at higher intensity. Among several cancer cell lines, the highest cytotoxicity was observed for H460 cells. As a result, these environmentally-responsive NPs have the potential to be applied in oral administration.
Synthesis and Properties of Fully Biobased Crosslinked Starch Oleate Films
Authors: Boetje Laura , Lan Xiaohong , van Dijken Jur , Polhuis Michael , Loos Katja
Published: May 2023

Starch oleate (degree of substitution = 2.2) films were cast and crosslinked in the presence of air using UV curing (UVC) or heat curing (HC). A commercial photoinitiator (CPI, Irgacure 184) and a natural photoinitiator (NPI, a mixture of biobased 3-hydroxyflavone and n-phenylglycine) were used for UVC. No initiator was used during HC. Isothermal gravimetric analyses, Fourier Transform Infrared (FTIR) measurements, and gel content measurements revealed that all three methods were effective in crosslinking, with HC being the most efficient. All methods increased the maximum strengths of film, with HC causing the largest increase (from 4.14 to 7.37 MPa). This is consistent with a higher degree of crosslinking occurring with HC. DSC analyses showed that the Tg signal flattened as film crosslink densities increased, even disappearing in the case of HC and UVC with CPI. Thermal gravimetric analyses (TGA) indicated that films cured with NPI were least affected by degradation during curing. These results suggest that cured starch oleate films could be suitable for replacing the fossil-fuel-derived plastics currently used in mulch films or packaging applications.
Biomimetic Hydroxyapatite Crystals Growth on Phosphorylated Chitosan Films by In Vitro Mineralization Used as Dental Substitute Materials
Authors: Rahmani Fathia , Larbi Bouamrane Omar , Ben Bouabdallah Amina , Atanase Leonard I. , Hellal Abdelkader , Apintiliesei Aurelian Nichita
Published: May 2023

Chitosan (CS) films exhibit great potential as a substrate for the in vitro mineralization process. In this study, to mimic the formation of nanohydroxyapatite (HAP) as natural tissue, CS films coated with a porous calcium phosphate were investigated using scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), Fourier transforms infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). Calcium phosphate coating deposited on phosphorylated derivatives of CS was obtained by a process based on phosphorylation, Ca(OH)2 treatment and artificial saliva solution (ASS) immersion. The phosphorylated CS films (PCS) were obtained by partial hydrolysis of the PO4 functionalities. It was demonstrated that this precursor phase could induce the growth and the nucleation of the porous calcium phosphate coating when immersed in ASS. Moreover, oriented crystals and qualitative control of calcium phosphate phases on CS matrices are obtained in a biomimetic mode. Furthermore, in vitro antimicrobial activity of PCS was evaluated against three species of oral bacteria and fungi. It revealed an increase in antimicrobial activity with minimum inhibition concentration (MIC) values of 0.10% (Candida albicans), 0.05% (Staphylococcus aureus) and 0.025% (Escherichia coli) which proves their possible use as dental substitute materials.
Preparation and Properties of a Lightweight, High-Strength, and Heat-Resistant Rigid Cross-Linked PVC Foam
Authors: Jiang Kun , Li Yingchun , Wang Heyun , Jia Hao , Jiang Haoji , Li Hao , Sheng Ao
Published: May 2023

A rigid poly(vinyl chloride) foam with a cross-linked network structure was prepared by adding 3-glycidoxypropyltriethoxysilane (KH-561) into the universal formulation. The resulting foam had excellent heat resistance because of the increasing degree of cross-linking and number of Si–O bonds with a high heat resistance. The as-prepared foam was verified using Fourier-transform infrared spectroscopy (FTIR), energy-dispersive spectrometry (EDS) and foam residue (gel) analysis, which demonstrated that KH-561 was successfully grafted and cross-linked on the PVC chains. Finally, the effects of different KH-561 and NaHSO3 additions on the mechanical properties and heat resistance of the foams were studied. The results showed that the mechanical properties of the rigid cross-linked PVC foam were raised after adding a certain amount of KH-561 and NaHSO3. The residue (gel), decomposition temperature, and chemical stability of the foam significantly improved compared to the universal rigid cross-linked PVC foam (Tg = 72.2 °C). The Tg of the foam could reach 78.1 °C without any mechanical degradation. The results have important engineering application value regarding the preparation of lightweight, high-strength, heat-resistant, and rigid cross-linked PVC foam materials.
Additive Manufacturing of Polymer/Bioactive Glass Scaffolds for Regenerative Medicine: A Review
Authors: Martelli Andrea , Bellucci Devis , Cannillo Valeria
Published: May 2023

Tissue engineering (TE) is a branch of regenerative medicine with enormous potential to regenerate damaged tissues using synthetic grafts such as scaffolds. Polymers and bioactive glasses (BGs) are popular materials for scaffold production because of their tunable properties and ability to interact with the body for effective tissue regeneration. Due to their composition and amorphous structure, BGs possess a significant affinity with the recipient’s tissue. Additive manufacturing (AM), a method that allows the creation of complex shapes and internal structures, is a promising approach for scaffold production. However, despite the promising results obtained so far, several challenges remain in the field of TE. One critical area for improvement is tailoring the mechanical properties of scaffolds to meet specific tissue requirements. In addition, achieving improved cell viability and controlled degradation of scaffolds is necessary to ensure successful tissue regeneration. This review provides a critical summary of the potential and limitations of polymer/BG scaffold production via AM covering extrusion-, lithography-, and laser-based 3D-printing techniques. The review highlights the importance of addressing the current challenges in TE to develop effective and reliable strategies for tissue regeneration.
Investigation into the Rheological Properties and Microstructure of Silt/Crumb Rubber Compound-Modified Asphalt
Authors: Huang Lu , Geng Jiuguang , Chen Mingyuan , Niu Yanhui , Wang Wenhao , Gao Zichen
Published: May 2023

Near the coast of China, a large amount of sediment is produced during construction work. In order to mitigate the environmental damage caused by sediment and enhance the performance of rubber-modified asphalt effectively, solidified silt material and waste rubber were prepared to modify asphalt, and its macroscopic properties, such as viscosity and chemical composition, were determined via a routine physical test, DSR, Fourier Transform Infrared Spectroscopy (FTIR), and Fluorescence Microscopy (FM). The results show that, with the increase in powder particles and the addition of a certain amount of hardened mud, the mixing and compaction temperature of modified asphalt can be significantly increased—still reaching the design standard. In addition, the high thermal stability and fatigue resistance of the modified asphalt were clearly better than those of the ordinary asphalt. From the FTIR analysis, rubber particles and hardened silt only exhibited mechanical agitation with the asphalt. Considering that excessive silt might result in the aggregation of matrix asphalt, the addition of an appropriate amount of hardened solidified silt material can eliminate the aggregation. Therefore, the performance of modified asphalt was optimum when solidified silt was added. Our research can provide an effective theoretical basis and reference values for the practical application of compound-modified asphalt. Therefore, 6%HCS(6:4)-CRMA have better performance. Compared to ordinary rubber-modified asphalt, the composite-modified asphalt binder has better physical properties and a more suitable construction temperature. The composite-modified asphalt uses discarded rubber and silt as raw materials, which can effectively protect the environment. Meanwhile, the modified asphalt has excellent rheological properties and fatigue resistance.
Experimental Investigation of Fatigue Capacity of Bending-Anchored CFRP Cables
Authors: Wu Jingyu , Zhu Yongquan , Li Chenggao
Published: May 2023

In this study, the variation of fatigue stiffness, fatigue life, and residual strength, as well as the macroscopic damage initiation, expansion, and fracture of CFRP (carbon fiber reinforced polymer) rods in bending-anchored CFRP cable, were investigated experimentally to verify the anchoring performance of the bending anchoring system and evaluate the additional shear effect caused by bending anchoring. Additionally, the acoustic emission technique was used to monitor the progression of critical microscopic damage to CFRP rods in a bending anchoring system, which is closely related to the compression-shear fracture of CFRP rods within the anchor. The experimental results indicate that after the fatigue cycles of two million, the residual strength retention rate of CFRP rod was as high as 95.1% and 76.7% under the stress amplitudes of 500 MPa and 600 MPa, indicating good fatigue resistance. Moreover, the bending-anchored CFRP cable could withstand 2 million cycles of fatigue loading with a maximum stress of 0.4 σult and an amplitude of 500 MPa without obvious fatigue damage. Moreover, under more severe fatigue-loading conditions, it can be found that fiber splitting in CFRP rods in the free section of cable and compression-shear fracture of CFRP rods are the predominant macroscopic damage modes, and the spatial distribution of macroscopic fatigue damage of CFRP rods reveals that the additional shear effect has become the determining factor in the fatigue resistance of the cable. This study demonstrates the good fatigue-bearing capacity of CFRP cable with a bending anchoring system, and the findings can be used for the optimization of the bending anchoring system to further enhance its fatigue resistance, which further promotes the application and development of CFRP cable and bending anchoring system in bridge structures.
Kinetic Monte Carlo Convergence Demands for Thermochemical Recycling Kinetics of Vinyl Polymers with Dominant Depropagation
Authors: Moens Eli K. C. , Marien Yoshi W. , Trigilio Alessandro D. , Van Geem Kevin M. , Van Steenberge Paul H. M. , D’hooge Dagmar R.
Published: May 2023

As societal interest in recycling of plastics increases, modeling thermochemical recycling of vinyl polymers, e.g., via pyrolysis or reactive extrusion, becomes increasingly important. A key aspect remains the reliability of the simulation results with fewer evaluation studies regarding convergence as in the polymerization or polymer reaction engineering field. Using the coupled matrix-based Monte Carlo (CMMC) framework, tracking the unzipping of individual chains according to a general intrinsic reaction scheme consisting of fission, β-scission, and termination, it is however illustrated that similar convergence demands as in polymerization benchmark studies can be employed, i.e., threshold values for the average relative error predictions on conversion and chain length averages can be maintained. For this illustration, three theoretical feedstocks are considered as generated from CMMC polymer synthesis simulations, allowing to study the effect of the initial chain length range and the number of defects on the convergence demands. It is shown that feedstocks with a broader chain length distribution and a long tail require a larger Monte Carlo simulation volume, and that the head–head effects play a key role in the type of degradation mechanism and overall degradation rate. A minimal number of chains around 5 × 105 is needed to properly reflect the degradation kinetics. A certain degree of noise can be allowed at the higher carbon-based conversions due to the inevitable decrease in number of chains.
Migration Behavior of NH4+ and Na+ in a Bentonite-Clay Mixed Soil Column and Numerical Simulation
Authors: Sun Wenjing , Tang Qiantong , Xu Gang , Tan Yunzhi
Published: May 2023

The landfill barriers effectively prevented the migration of high-concentration pollutants, such as NH4+ and Na+, from the landfills to the surrounding environment. However, due to the high hydraulic head inside the landfill compared to the surrounding environment, NH4+ and Na+ can migrate towards the outside of the landfill barrier with the infiltrating solution, potentially causing harm to the surrounding environment. To address this, saturated mixed soil column samples made of bentonite and Shanghai clay, with bentonite contents of 3% and 10%, were used in this study. Permeability coefficients of the column samples in solutions are obtained by using permeation tests, and using NaCl and NH4Cl solutions with concentrations of 37.4 mmol/L and 74.8 mmol/L, respectively. The concentration-depth result of the column samples after permeation tests was determined using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) and Ion Chromatography (ICS-1100). Numerical simulations are used to investigate the effect of downstream solute concentration of the barriers on upstream solute concentration, dry density, and bentonite content of the barriers. The results indicate that the permeability coefficient of the soil column samples exposed to NH4Cl solution is greater than that of samples exposed to NaCl solution. This can be attributed to the stronger cation exchange of montmorillonite for NH4+, resulting in less swelling of the bentonite and more micro-pores, leading to an increase in the permeability coefficient. The concentration of Na+ is higher than that of NH4+ at the same depth of the column samples, indicating that Na+ has a higher migration rate in the column sample. This could be attributed to the relatively fast diffusion of Na+ on the surface of the bentonite and larger hydration radius of Na+. According to the simulation results, the recommended values for the bentonite clay mixed-soil barrier wall are as follows in this study: a thickness of 43 cm, a dry density of 1.5 g/cm3, and a bentonite content of 5%.
Mathematical and Physical Modelling of Transient Multi-Phase Flows in a Ladle Shroud during Start-Up
Authors: Gonzalez-Morales Daniel R. , Girard Bruno , Labrecque Chantal , Isac Mihaiela M. , Guthrie Roderick I. L.
Published: May 2023

The Ladle Shroud has become an important part of secondary steelmaking, with its role in reducing liquid steel contamination and process improvements. Due to the inherent negative pressure at the lower nozzle–Ladle Shroud joint, it is well known that Ladle Shrouds, protecting steel flows between a Ladle and a tundish below, can suffer from inadvertent ingress of air. Therefore, there is a need to apply inert gas injection at the joint. In the present paper, 3D transient multi-phase simulations of flows occurring for a Reverse Tapered Ladle Shroud during start-up were studied using CFD software ANSYS Fluent 19.1. This allowed us to study the initial multi-phase flow developed during the start-up and potential steel reoxidation, based on a first principles approach. Time-dependent phase fields as well as attendant velocity and turbulence fields were obtained, resulting in the prediction of a turbulent multi-phase flow during start-up and filling. Additionally, some transient phenomena like steel splashing and air suction were observed mathematically. A full-scale water model of the Ladle Shroud was used to qualitatively validate the initial multi-phase turbulent flow inside the Ladle Shroud, in the absence of inert gas injection.
Control Strategy Based on Artificial Intelligence for a Double-Stage Absorption Heat Transformer
Authors: Vázquez-Aveledo Suset , Romero Rosenberg J. , Montiel-González Moisés , Cerezo Jesús
Published: May 2023

Thermal energy recovery systems have different candidates to mitigate CO2 emissions as recommended by the UN in its list of SDGs. One of these promising systems is thermal absorption transformers, which generally use lithium-water bromide as the working fluid. A Double Stage Heat Transformer (DSHT) is a thermal machine that allows the recovery of thermal energy at a higher temperature than it is supplied through the effect of steam absorption in a concentrated solution of lithium bromide. There are very precise thermodynamic models which allow us to calculate all the possible operating conditions of the DSHT. To perform the control of these systems, the use of Artificial Intelligence (AI) is proposed with two computational techniques—Fuzzy Logic (FL) and Artificial Neural Network (ANN)—to calculate in real-time the set of variables that maximize the product’s Gross Temperature Lift (GTL) and Coefficient of Performance (COP) in a DSHT. The values for Coefficient of Determination (R2), Mean Square Error Root (MRSE), and Mean Error Bias (MBE) for the two types of computational techniques were analyzed and compared with the purpose of identifying which of them may be more accurate to calculate the operating conditions (temperatures, pressures, concentration and flows) with the highest COP for an interval of the value of the temperature absorption entered by the user. The result of the analysis of the evaluated techniques concluded that the control strategy of a DSHT in real-time will be based on the precise calculation of the refrigerant flow in the second evaporator with a Neural Network of 30 neurons, 300 weights and 40 bias, as it is more accurate than the Fuzzy Logic technique. The goodness-of-fit for two computational techniques was evaluated as having an R2 higher than 0.98 for the provided data. Future AI controllers must be based on evaporator flow values with evaporator power at 3.9−04 kg/KJ.
Industrial Drying of Fruit and Vegetable Products: Customized Smart Monitoring and Analytical Characterization of Process Variables in the OTTORTO Project
Authors: Spagnuolo Antonio , Vetromile Carmela , Masiello Antonio , De Santo Giuseppe , Suriano Mattia , Mercuri Giorgio , Pellegrino Michele , Piccolo Giancarlo , Lubritto Carmine , Di Cicco Maria Rosa
Published: May 2023

In the era of digitalization, the process industry is one of the sectors most affected by the need for change. The adoption of IoT-based intelligent monitoring systems for the collection of real-time measurements of energy and other essential operational variables, on one hand, makes it possible to accumulate big data useful for the company management to monitor the stability of the production process over time, and on the other hand, helps to develop predictive models that enable more efficient work and production. The OTTORTO project stems from the need of the FARRIS company to adapt its production line to agriculture 4.0 policies, responding to the higher goals of digitization and technological transition imposed at the national and EU level. The objectives of the current study are (i) to present an “ad hoc” customized intelligent and multi-parameter monitoring system to derive real-time temperature and humidity measurements inside the company’s industrial drying kilns; and (ii) to show how it is possible to extract information from operational data and convert it into a decision support too and an effective knowledge medium to better understand the production process. Studying the correlations between temperature and humidity measurements showed that for most of the observation period, the system was thermodynamically quite stable in terms of major operational risks, such as humidity saturation inside the kilns causing condensation on the products to be dried. However, to remedy the occasional occurrence of such inefficiencies, implementing kilns with the introduction of forced air extraction systems could bring significant benefits in terms of improved energy-environmental performance.