bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Quality Dry Etching of LiNbO3 Assisted by Proton Substitution through H2-Plasma Surface Treatment
Authors: Aryal Arjun , Stricklin Isaac , Behzadirad Mahmoud , Branch Darren , Siddiqui Aleem , Busani Tito
Published: August 2022

The exceptional material properties of Lithium Niobate (LiNbO3) make it an excellent material platform for a wide range of RF, MEMS, phononic and photonic applications; however, nano-micro scale device concepts require high fidelity processing of LN films. Here, we reported a highly optimized processing methodology that achieves a deep etch with nearly vertical and smooth sidewalls. We demonstrated that Ti/Al/Cr stack works perfectly as a hard mask material during long plasma dry etching, where periodically pausing the etching and chemical cleaning between cycles were leveraged to avoid thermal effects and byproduct redeposition. To improve mask quality on X- and Y-cut substrates, a H2-plasma treatment was implemented to relieve surface tension by modifying the top surface atoms. Structures with etch depths as deep as 3.4 µm were obtained in our process across a range of crystallographic orientations with a smooth sidewall and perfect verticality on several crystallographic facets.
Recent Progress on Graphene-Based Nanocomposites for Electrochemical Sodium-Ion Storage
Authors: Li Mai , Zhu Kailan , Zhao Hanxue , Meng Zheyi
Published: August 2022

In advancing battery technologies, primary attention is paid to developing and optimizing low-cost electrode materials capable of fast reversible ion insertion and extraction with good cycling ability. Sodium-ion batteries stand out due to their inexpensive price and comparable operating principle to lithium-ion batteries. To achieve this target, various graphene-based nanocomposites fabricate strategies have been proposed to help realize the nanostructured electrode for high electrochemical performance sodium-ion batteries. In this review, the graphene-based nanocomposites were introduced according to the following main categories: graphene surface modification and doping, three-dimensional structured graphene, graphene coated on the surface of active materials, and the intercalation layer stacked graphene. Through one or more of the above strategies, graphene is compounded with active substances to prepare the nanocomposite electrode, which is applied as the anode or cathode to sodium-ion batteries. The recent research progress of graphene-based nanocomposites for SIBs is also summarized in this study based on the above categories, especially for nanocomposite fabricate methods, the structural characteristics of electrodes as well as the influence of graphene on the performance of the SIBs. In addition, the relevant mechanism is also within the scope of this discussion, such as synergistic effect of graphene with active substances, the insertion/deintercalation process of sodium ions in different kinds of nanocomposites, and electrochemical reaction mechanism in the energy storage. At the end of this study, a series of strategies are summarized to address the challenges of graphene-based nanocomposites and several critical research prospects of SIBs that provide insights for future investigations.
Preparation of Three-Dimensional MF/Ti3C2Tx/PmPD by Interfacial Polymerization for Efficient Hexavalent Chromium Removal
Authors: Jin Linfeng , Pan Qinglin , Li Xiaorui , Su Changqing , Wang Zhongyu , Wang Haiying , Huang Lei
Published: August 2022

Heavy metal pollution is a serious threat to human health and the ecological environment, but adsorption technology based on nano adsorbents can effectively treat the crisis. However, due to the nanoscale effect, nano adsorbents have some crucial shortcomings, such as recycling difficulty and the loss of nanoparticles, which seriously limit their application. The feasible assembly of nano adsorbents is an accessible technology in urgent need of a breakthrough. In this study, three-dimensional (3D) adsorbent (MF/Ti3C2Tx/PmPD) with excellent performance and favorable recyclability was prepared by interfacial polymerization with melamine foam (MF) as the framework, two-dimensional (2D) titanium carbide (Ti3C2Tx) as the bridge and Poly (m-Phenylenediamine) (PmPD) as the active nano component. The morphology, structure, mechanical property of MF/Ti3C2Tx/PmPD and reference MF/PmPD were investigated through a scanning electron microscope (SEM), Fourier transformed infrared spectra (FT-IR), Raman scattering spectra and a pressure-stress test, respectively. Owning to the regulation of Ti3C2Tx on the morphology and structure of PmPD, MF/Ti3C2Tx/PmPD showed excellent adsorption capacity (352.15 mg/g) and favorable cycling performance. R–P and pseudo-second-order kinetics models could well describe the adsorption phenomenon, indicating that the adsorption process involved a composite process of single-layer and multi-layer adsorption and was dominated by chemical adsorption. In this research, the preparation mechanism of MF/Ti3C2Tx/PmPD and the adsorption process of Cr(VI) were systematically investigated, which provided a feasible approach for the feasible assembly and application of nano adsorbents in the environmental field.
Effects of Rhenium Substitution of Co and Fe in Spinel CoFe2O4 Ferrite Nanomaterials
Authors: Zheng Yuruo , Hussain Ghulam , Li Shuyi , Batool Shanta , Wang Xiawa
Published: August 2022

In this work, nanoparticles of Co1−xRexFe2O4 and CoFe2−xRexO4 (0 ≤ x ≤ 0.05) were synthesized by the sol-gel method. The Rietveld refinement analysis of XRD and Raman data revealed that all of the prepared samples were single phase with a cubic spinel-type structure. With the substitution of Re, the lattice parameters were slightly increased, and Raman spectra peak positions corresponding to the movement of the tetrahedral sublattice shifted to a higher energy position. Furthermore, Raman spectra showed the splitting of T2g mode into branches, indicating the presence of different cations at crystallographic A- and B-sites. The SEM micrograph confirms that surface Re exchange changes the coordination environment of metals and induces Fe-site structure distortion, thereby revealing more active sites for reactions and indicating the bulk sample’s porous and agglomerated morphology. The vibrating sample magnetometer (VSM) results demonstrated that the synthesized nanoparticles of all samples were ferromagnetic across the entire temperature range of 300–4 K. The estimated magnetic parameters, such as the saturation magnetization, remanent magnetization, coercivity, blocking temperature (TB), and magnetic anisotropy, were found to reduce for the Co-site doping with the increasing doping ratio of Re, while in the Fe site, they enhanced with the increasing doping ratio. The ZFC-FC magnetization curve revealed the presence of spin-glass-like behavior due to the strong dipole–dipole interactions in these ferrite nanoparticles over the whole temperature range. Finally, the dielectric constant (εr′) and dielectric loss (tanδ) were sharply enhanced at low frequencies, while the AC conductivity increased at high frequencies. The sharp increases at high temperatures are explained by enhancing the barrier for charge mobility at grain boundaries, suggesting that samples were highly resistive. Interestingly, these parameters (εr′, tanδ) were found to be higher for the Fe-site doping with the increasing Re doping ratio compared with the Co site.
Device Modeling of Organic Photovoltaic Cells with Traditional and Inverted Cells Using s-SWCNT:C60 as Active Layer
Authors: Moorthy Vijai M. , Srivastava Viranjay M.
Published: August 2022

This research work presents a thorough analysis of Traditional Organic Solar Cell (TOSC) and novel designed Inverted OSC (IOSC) using Bulk Hetero-Junction (BHJ) structure. Herein, 2D photovoltaic device models were used to observe the results of the semiconducting Single Wall Carbon Nanotube (s-SWCNT):C60-based organic photovoltaic. This work has improved the BHJ photodiodes by varying the active layer thickness. The analysis has been performed at various active layer thicknesses from 50 to 300 nm using the active material s-SWCNT:C60. An analysis with various parameters to determine the most effective parameters for organic photovoltaic performance has been conducted. As a result, it has been established that IOSC has the maximum efficiency of 10.4%, which is higher than the efficiency of TOSC (9.5%). In addition, the active layer with the highest efficacy has been recorded using this material for both TOSC and IOSC Nano Photodiodes (NPDs). Furthermore, the diode structure and geometrical parameters have been optimized and compared to maximize the performance of photodiodes.
Charge Transport in UV-Oxidized Graphene and Its Dependence on the Extent of Oxidation
Authors: Lee Hwa Yong , Haidari Mohd Musaib , Kee Eun Hee , Choi Jin Sik , Park Bae Ho , Campbell Eleanor E. B. , Jhang Sung Ho
Published: August 2022

Graphene oxides with different degrees of oxidation are prepared by controlling UV irradiation on graphene, and the charge transport and the evolution of the transport gap are investigated according to the extent of oxidation. With increasing oxygenous defect density nD, a transition from ballistic to diffusive conduction occurs at nD≃1012 cm−2 and the transport gap grows in proportion to nD. Considering the potential fluctuation related to the e−h puddle, the bandgap of graphene oxide is deduced to be Eg≃30nD(1012cm−2) meV. The temperature dependence of conductivity showed metal–insulator transitions at nD≃0.3×1012 cm−2, consistent with Ioffe–Regel criterion. For graphene oxides at nD≥4.9×1012 cm−2, analysis indicated charge transport occurred via 2D variable range hopping conduction between localized sp2 domain. Our work elucidates the transport mechanism at different extents of oxidation and supports the possibility of adjusting the bandgap with oxygen content.
Associations of the Mediterranean-Style Dietary Pattern Score with Coronary Artery Calcification and Pericardial Adiposity in a Sample of US Adults
Authors: Richardson Leigh Ann , Basu Arpita , Chien Lung-Chang , Alman Amy C. , Snell-Bergeon Janet K.
Published: August 2022

Several studies have identified improvements in the risks of cardiovascular disease in adults following a Mediterranean dietary pattern. However, data are scarce on its association with coronary artery calcification (CAC) and pericardial adiposity (PAT) in US adults with and without diabetes. To address this gap, we conducted a case-control study using baseline data from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study [n = 1255; Type 1 Diabetes (T1D): n = 563; non-Diabetes Mellitus (non-DM): n = 692]. Participants completed a validated food frequency questionnaire, fasting (12 h overnight fast) biochemical analyses, and a physical examination including anthropometric measures. CAC and PAT were measured using electron beam-computed tomography. Logistic regression models were used to examine the associations of the Mediterranean-Style Dietary Pattern Score (MSDPS) with CAC (presence or absence), and linear regression models were applied to PAT analyses. In all of the adjusted models, no significant associations with CAC were found. For PAT, an increasing MSDPS was consistently associated with its lower volume in models adjusted for age, sex, diabetes status, total calories, and body mass index (all p < 0.05). The association between MSDPS and PAT was attenuated after adjusting for serum lipids and physical activity. In conclusion, the baseline data from the CACTI study show that a greater adherence to MSDPS is associated with a lower PAT volume and provide evidence that the Mediterranean dietary pattern is associated with lower cardiovascular risk markers.
Perirenal Fat Thickness Significantly Associated with Prognosis of Metastatic Renal Cell Cancer Patients Receiving Anti-VEGF Therapy
Authors: Ning Kang , Li Zhen , Liu Huiming , Tian Xi , Wang Jun , Wu Yi , Xiong Longbin , Zou Xiangpeng , Peng Yulu , Zhou Zhaohui , Zhou Fangjian , Yu Chunping , Luo Junhang , Zhang Hailiang , Dong Pei , Zhang Zhiling
Published: August 2022

Although high body mass index (BMI) was reported to associate with a better prognosis for metastatic renal cell cancer (mRCC) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, it is an imperfect proxy for the body composition, especially in Asian patients with a lower BMI. The role of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and perirenal fat thickness (PRFT) in mRCC patients was still unknown. Therefore, a multicenter retrospective study of 358 Chinese mRCC patients receiving anti-VEGF therapy was conducted and their body composition was measured via computed tomography. We parameterized VAT, SAT and PRFT according to their median value and BMI according to Chinese criteria (overweight: BMI ≥ 24). We found VAT, SAT, and PRFT (all p < 0.05) but not BMI, significantly associated with overall survival (OS) and progression-free survival (PFS). Multivariate Cox analysis identified PRFT was the independent predictor of OS and PFS, and IMDC expanded with PRFT showed the highest C-index in predicting OS (OS:0.71) compared with VAT, SAT, and BMI. PRFT could increase the area under the curve of the traditional International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in OS (70.54% increase to 74.71%) and PFS (72.22% increase to 75.03%). PRFT was introduced to improve the IMDC model and PRFT-modified IMDC demonstrated higher AIC in predicting OS and PFS compared with the traditional IMDC model. Gene sequencing analysis (n = 6) revealed that patients with high PRFT had increased angiogenesis gene signatures (NES = 1.46, p = 0.04) which might explain why better drug response to anti-VEGF therapy in mRCC patients with high PRFT. The main limitation is retrospective design. This study suggests body composition, especially PRFT, is significantly associated with prognosis in Chinese mRCC patients receiving anti-VEGF therapy. PRFT-modified IMDC model proposed in this study has better clinical predictive value.
Effects of Gestational Sleep Patterns and Their Changes on Maternal Glycemia and Offspring Physical Growth in Early Life
Authors: Zou Jiaojiao , Wei Qian , Ye Peiqi , Shi Yuyang , Zhang Yunhui , Shi Huijing
Published: August 2022

Maternal sleep patterns during pregnancy are drawing increased attention to examine its role in the regulation of maternal glycemia and physical growth of offspring within 24 months. Among 3329 eligible mother–child pairs included in the Shanghai Maternal–Child Pairs Cohort, sleep patterns of pregnant women were assessed by Pittsburgh Sleep Quality Index and objective measurement in early and late pregnancy. Offspring physical growth within 24 months was primarily indicated by the body mass index Z-score (BAZ), catch-up growth, and overweight/obesity. In total, 3329 and 382 pregnant women were included with subjectively assessed and objectively measured sleep pattern, respectively. The increased risk of GDM was associated with maternal night-time sleep duration ≥8.5 h in early pregnancy, or sleep quality change from poor to good during pregnancy (OR = 1.48; 95% CI, 1.06 to 2.07). In the GDM group, the effect of sleep duration in early pregnancy on overweight/obesity in offspring within 24 months showed a U-shaped curve, with a 1.73-fold and 1.43-fold increased risk of overweight/obesity of offspring in pregnant women with <7.5 or ≥8.5 h of sleep duration, respectively. A good gestational sleep pattern was required to reduce the risk of GDM and offspring overweight/obesity within 24 months.
The Modulation of Ubiquinone, a Lipid Antioxidant, on Neuronal Voltage-Gated Sodium Current
Authors: Hung Te-Yu , Wu Sheng-Nan , Huang Chin-Wei
Published: August 2022

Ubiquinone, composed of a 1,4-benzoquinone and naturally produced in the body, actively participates in the mitochondrial redox reaction and functions as an endogenous lipid antioxidant, protecting against peroxidation in the pituitary-dependent hormonal system. However, the questions of if and how ubiquinone directly affects neuronal ionic currents remain largely unsettled. We investigated its effects on ionic currents in pituitary neurons (GH3 and MMQ cells) with the aid of patch-clamp technology. Ubiquinone decreased the peak amplitude of the voltage-gated Na+ current (INa) with a slowing of the inactivation rate. Neither menadione nor superoxide dismutase modified the ubiquinone-induced INa inhibition. In response to an isosceles-triangular ramp pulse, the persistent INa (INa(P)) at high- and low- threshold potentials occurred concurrently with a figure-eight hysteresis loop. With ubiquinone, the INa(P) increased with no change in the intersection voltage, and the magnitude of the voltage-dependent hysteresis of the current was enhanced. Ubiquinone was ineffective in modifying the gating of hyperpolarization-activated cation currents. In MMQ lactotrophs, ubiquinone effectively decreased the amplitude of the INa and the current inactivation rate. In sum, the effects of ubiquinone demonstrated herein occur upstream of its effects on mitochondrial redox processes, involved in its modulation of sodium channels and neuronal excitability.
Diet Quality and Changes in Food Intake during the University Studies in Polish Female Young Adults: Linkages with Food Experiences from Childhood and Perceived Nutrition Concerns
Authors: Pokorski Patryk , Nicewicz Robert , Jeżewska-Zychowicz Marzena
Published: August 2022

The transition from adolescence to young adulthood may be associated with unfavorable changes in food intake due to some substantial transformations in social life and environment. Factors that affect food choices and diet quality during early adulthood are still not well-recognized. This paper aims to explore the relationship between females’ childhood food experiences related to parents’ monitoring practices and healthy eating guidance, perceived nutrition concerns, changes in food intake during university studies, and diet quality. A cross-sectional study with the use of CAWI (Computer-Assisted Web Interview) was carried out on 657 female students aged 19–30 years. Beliefs and Eating Habits Questionnaire (KomPAN) was used to assess the frequency of eating various kinds of food and then to calculate the diet-quality index (DQI). Adults’ Memories of Feeding in Childhood (AMoFiC) questionnaire was used to assess food experiences from childhood, and Health Concern Scale (HCS) was used to assess nutrition concerns. Associations between changes in food intake, diet quality, and selected factors describing the study sample were verified using logistic regression analysis. The DQI of the majority of students indicated a low intensity of nonhealthy and pro-healthy dietary characteristics. The intensity was higher among nutrition and health students, those with low nutrition concerns, and those with childhood experiences of monitoring. The chances of a negative change in food intake were increased by a higher score for childhood food experiences associated with parents’ monitoring practices. The chances of a negative DQI were increased by bigger concerns about nutrition and by technical and agricultural majors; however, they were reduced by positive changes in food intake. Both childhood food experiences and perceived nutrition concerns should be factored into strategies aimed at improving youth diet and educating parents about effective parental feeding practices.
Dietary Supplement Use among Older Cancer Survivors: Socio-Demographic Associations, Supplement Types, Reasons for Use, and Cost
Authors: Kaur Harleen , Hoenemeyer Teri , Parrish Kelsey B. , Demark-Wahnefried Wendy
Published: August 2022

Most Americans take dietary supplements (DSs) and use is even higher among cancer survivors. This secondary analysis seeks to identify types, reasons, and costs of supplements used by 367 older cancer survivors enrolled in the Harvest for Health vegetable gardening trial and evaluate associations between supplement intake and medical/socio-demographic factors. Descriptive statistics were used to identify supplement type and reasons for use. Average market price was used to estimate cost. Fifty-nine percent of the sample reported supplement use. Female (OR 2.11, 95% CI 1.35–3.30), non-Hispanic White (OR 1.77, 95% CI 1.05–3.0), and breast and gynecological survivors (OR 1.57, 1.03–2.38) were significantly more likely to report DS use compared to males, minorities, and survivors of other cancers. Use of vitamins (39%), multivitamins (23%), and minerals (12%) were the most prevalent. Commonly reported reasons for supplement use were to improve general health (47%) or treat medical conditions (39%) and cancer-related symptoms (12%). DSs daily costs ranged from USD 0.02 to 19.81, with a mean of USD 1.28 ± 1.74, a median of USD 0.78, and a mode of USD 0.34. DS use is prevalent among older cancer survivors, with overall health reported as the leading reason for use. Out-of-pocket recurrent costs can be substantial and underscore the need to promote a nutrient-rich diet whenever possible in this vulnerable population.
Perception and Understanding of Guideline Daily Amount and Warning Labeling among Mexican Adults during the Law Modification Period
Authors: Campos-Nonato Ismael , Cervantes-Armenta Manuel A. , Pacheco-Miranda Selene , Quezada-Sánchez Amado D. , Contreras-Manzano Alejandra , Barquera Simón , Vargas-Meza Jorge
Published: August 2022

Front-of-pack labeling (FOPL) is a tool that enables consumers to compare foods and select healthier options. Due to low understanding of the Guideline Daily Amount (GDA) labeling among Mexicans, a law was implemented in October 2020 that modified the FOPL to a warning labeling (WL) system. The purpose of this study was to compare the perception and understanding of GDA and WL during the law modification period. We conducted a panel design with two measurements: (1) using GDA label (September 2020) and (2) using WL (October–November). We estimated differences in GDA vs. WL through multinomial logistic regression models and changes were measured through predictive margin contrasts and Wald tests. When comparing the same products with different labels, the participants reported that it would be unlikely/very unlikely that they would consume products packaged with the WL (81.5%; 95%CI: 79.2, 83.8) compared to those with GDA (24.2%; 95%CI: 21.7, 26.7). Consumers’ perception was that the quantities of packaged products they should consume was small or very small when they used the WL (93.8%; 95%CI: 92.4, 95.5) compared to GDA (41.6%; 95%CI: 39.7, 44.6). When comparing food groups, participants were more confident about choosing healthy products when using the WL compared to the GDA. During the implementation of WL in Mexico, the studied population had a better perception and understanding of less healthy packaged foods when using WL, compared to the GDA label.
Effects of Diets Enriched with Conventional or High-Oleic Canola Oils on Vascular Endothelial Function: A Sub-Study of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a Randomized Crossover Controlled Feeding Study
Authors: Davis Kristin M. , Petersen Kristina S. , Bowen Kate J. , Jones Peter J. H. , Taylor Carla G. , Zahradka Peter , Letourneau Karen , Perera Danielle , Wilson Angela , Wagner Paul R. , Kris-Etherton Penny M. , West Sheila G.
Published: August 2022

Partial replacement of saturated fatty acids (SFA) with unsaturated fatty acids is recommended to reduce cardiovascular disease (CVD) risk. Monounsaturated fatty acids (MUFA), including oleic acid, are associated with lower CVD risk. Measurement of flow-mediated dilation of the brachial artery (FMD) is the gold standard for measuring endothelial function and predicts CVD risk. This study examined the effect of partially replacing SFA with MUFA from conventional canola oil and high-oleic acid canola oil on FMD. Participants (n = 31) with an elevated waist circumference plus ≥1 additional metabolic syndrome criterion completed FMD measures as part of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a multi-center, double-blind, three-period crossover, controlled feeding randomized trial. Diet periods were 6 weeks, separated by ≥4-week washouts. Experimental diets were provided during all feeding periods. Diets only differed by the fatty acid profile of the oils: canola oil (CO; 17.5% energy from MUFA, 9.2% polyunsaturated fatty acids (PUFA), 6.6% SFA), high-oleic acid canola oil (HOCO; 19.1% MUFA, 7.0% PUFA, 6.4% SFA), and a control oil blend (CON; 11% MUFA, 10% PUFA, 12% SFA). Multilevel models were used to examine the effect of the diets on FMD. No significant between-diet differences were observed for average brachial artery diameter (CO: 6.70 ± 0.15 mm, HOCO: 6.57 ± 0.15 mm, CON: 6.73 ± 0.14 mm; p = 0.72), peak brachial artery diameter (CO: 7.11 ± 0.15 mm, HOCO: 7.02 ± 0.15 mm, CON: 6.41 ± 0.48 mm; p = 0.80), or FMD (CO: 6.32 ± 0.51%, HOCO: 6.96 ± 0.49%, CON: 6.41 ± 0.48%; p = 0.81). Partial replacement of SFA with MUFA from CO and HOCO had no effect on FMD in participants with or at risk of metabolic syndrome.
An Investigation of the Effect of Water Additives on Broiler Growth and the Caecal Microbiota at Harvest
Authors: Greene Genevieve , Koolman Leonard , Whyte Paul , Burgess Catherine M. , Lynch Helen , Coffey Aidan , Lucey Brigid , O’Connor Lisa , Bolton Declan
Published: August 2022

Campylobacter is the most common foodborne pathogen in developed countries and most cases are associated with poultry. This study investigated the effect of three anti-Campylobacter water additives on broiler growth and on the caecal microbiota at harvest using 16S rRNA amplicon sequencing. Mixtures of organic acids (OA) and essential oils (EO) were administered to broilers for the entirety of the production cycle (35 d) and medium-chain fatty acids (MCFA) for 5 d immediately before harvest, under commercial conditions. Bird weight gain was significantly (p < 0.001) reduced in broilers receiving the OA and EO treatments. While this was most likely due to reduced water intake and corresponding lower feed consumption, changes to the caecal microbiota may also have contributed. Firmicutes made up over 75% of the bacteria regardless of sample type, while the minor phyla included Bacteroidetes, Actinobacteria, Melainabacteria, and Proteobacteria. There were no significant (p > 0.05) differences in the alpha diversity as measured using ACE, Chao1, and Shannon indices, except for control (water) versus MCFA and OA versus MCFA, using the Wilcox test. In contrast, there was a significant (p < 0.05) difference in beta diversity when the treated were compared to the untreated control and main flock samples, while linear discriminant analysis effect size (LeFSe) identified three OTUs that were present in the control but absent in the treated birds. It was concluded that the water additives tested adversely affected broiler performance, which may, at least in part, be due to changes in the caecal microbiota, assuming that the altered microbiota at day 35 is indicative of a change throughout the production cycle.
The Skin Microbiome in Cutaneous T-Cell Lymphomas (CTCL)—A Narrative Review
Authors: Łyko Magdalena , Jankowska-Konsur Alina
Published: August 2022

In recent years, numerous studies have shown a significant role of the skin microbiome in the development and exacerbation of skin diseases. Cutaneous T-cell lymphomas (CTCL) are a group of malignancies primary involving skin, with unclear pathogenesis and etiology. As external triggers appear to contribute to chronic skin inflammation and the malignant transformation of T-cells, some microorganisms or dysbiosis may be involved in these processes. Recently, studies analyzing the skin microbiome composition and diversity have been willingly conducted in CTCL patients. In this review, we summarize currently available data on the skin microbiome in CTLC. We refer to a healthy skin microbiome and the contribution of microorganisms in the pathogenesis and progression of other skin diseases, focusing on atopic dermatitis and its similarities to CTCL. Moreover, we present information about the possible role of identified microorganisms in CTCL development and progression. Additionally, we summarize information about the involvement of Staphylococcus aureus in CTCL pathogenesis. This article also presents therapeutic options used in CTCL and discusses how they may influence the microbiome.
Zika Virus Infection Alters Gene Expression and Poly-Adenylation Patterns in Placental Cells
Authors: Sotcheff Stephanea L. , Chen John Yun-Chung , Elrod Nathan , Cao Jun , Jaworski Elizabeth , Kuyumcu-Martinez Mugé N. , Shi Pei-Yong , Routh Andrew L.
Published: August 2022

Flaviviruses are small RNA viruses that are mainly transmitted via arthropod vectors and are found in tropic and sub-tropical regions. Most infections are asymptomatic (90–95%), but symptoms can be as severe as hemorrhagic fever and encephalitis. One recently emerged flavivirus is Zika virus (ZIKV), which was originally isolated from rhesus monkeys in Uganda roughly 70 years ago but has recently spread east, reaching S. America in 2015–2016. This outbreak was associated with the development of Guillain–Barré syndrome in adults and microcephaly in infants born to expectant mothers infected early in pregnancy. ZIKV must traverse the placenta to impact the development of the fetus, but the mechanisms responsible are unknown. While flaviviruses are known to disrupt splicing patterns in host cells, little is known about how flaviviruses such as ZIKV impact the alternative polyadenylation (APA) of host transcripts. This is important as APA is well-established as a mechanism in the regulation of mRNA metabolism and translation. Thus, we sought to characterize transcriptomic changes including APA in human placental (JEG3) cells in response to ZIKV infection using Poly(A)-ClickSeq (PAC-Seq). We used our differential Poly(A)-cluster (DPAC) analysis pipeline to characterize changes in differential gene expression, alternative poly-adenylation (APA) and the use of alternative terminal exons. We identified 98 upregulated genes and 28 downregulated genes. Pathway enrichment analysis indicated that many RNA processing and immune pathways were upregulated in ZIKV-infected JEG3 cells. We also updated DPAC to provide additional metrics of APA including the percentage-distal usage index (PDUI), which revealed that APA was extensive and the 3′ UTRs of 229 genes were lengthened while 269 were shortened. We further found that there were 214 upregulated and 59 downregulated poly(A)-clusters (PACs). We extracted the nucleotide sequences surrounding these PACs and found that the canonical signals for poly-adenylation (binding site for poly-A binding protein (PABP) upstream and a GU-rich region down-stream of the PAC) were only enriched in the downregulated PACs. These results indicate that ZIKV infection makes JEG3 cells more permissive to non-canonical poly-adenylation signals.
mRNA-Loaded Lipid Nanoparticles Targeting Immune Cells in the Spleen for Use as Cancer Vaccines
Authors: Shimosakai Ryoya , Khalil Ikramy A. , Kimura Seigo , Harashima Hideyoshi
Published: August 2022

mRNA delivery has recently gained substantial interest for possible use in vaccines. Recently approved mRNA vaccines are administered intramuscularly where they transfect antigen-presenting cells (APCs) near the site of administration, resulting in an immune response. The spleen contains high numbers of APCs, which are located near B and T lymphocytes. Therefore, transfecting APCs in the spleen would be expected to produce a more efficient immune response, but this is a challenging task due to the different biological barriers. Success requires the development of an efficient system that can transfect different immune cells in the spleen. In this study, we report on the development of mRNA-loaded lipid nanoparticles (LNPs) targeting immune cells in the spleen with the goal of eliciting an efficient immune response against the antigen encoded in the mRNA. The developed system is composed of mRNA loaded in LNPs whose lipid composition was optimized for maximum transfection into spleen cells. Dendritic cells, macrophages and B cells in the spleen were efficiently transfected. The optimized LNPs produced efficient dose-dependent cytotoxic T lymphocyte activities that were significantly higher than that produced after local administration. The optimized LNPs encapsulating tumor-antigen encoding mRNA showed both prophylactic and therapeutic antitumor effects in mice.
Neuroprotective Effects of an Edible Pigment Brilliant Blue FCF against Behavioral Abnormity in MCAO Rats
Authors: Le Jingyang , Xiao Xiao , Zhang Difan , Feng Yi , Wu Zhuoying , Mao Yuechun , Mou Chenye , Xie Yanfei , Chen Xiaowei , Liu Hao , Cui Wei
Published: August 2022

Ischemic stroke leads to hypoxia-induced neuronal death and behavioral abnormity, and is a major cause of death in the modern society. However, the treatments of this disease are limited. Brilliant Blue FCF (BBF) is an edible pigment used in the food industry that with multiple aromatic rings and sulfonic acid groups in its structure. BBF and its derivatives were proved to cross the blood-brain barrier and have advantages on the therapy of neuropsychiatric diseases. In this study, BBF, but not its derivatives, significantly ameliorated chemical hypoxia-induced cell death in HT22 hippocampal neuronal cell line. Moreover, protective effects of BBF were attributed to the inhibition of the extracellular regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK3β) pathways as evidenced by Western blotting analysis and specific inhibitors. Furthermore, BBF significantly reduced neurological and behavioral abnormity, and decreased brain infarct volume and cerebral edema induced by middle cerebral artery occlusion/reperfusion (MCAO) in rats. MCAO-induced increase of p-ERK in ischemic penumbra was reduced by BBF in rats. These results suggested that BBF prevented chemical hypoxia-induced otoxicity and MCAO-induced behavioral abnormity via the inhibition of the ERK and GSK3β pathways, indicating the potential use of BBF for treating ischemic stroke
Therapeutic Effect of Benidipine on Medication-Related Osteonecrosis of the Jaw
Authors: Matsunaka Ken , Imai Mikio , Sanda Koma , Yasunami Noriyuki , Furuhashi Akihiro , Atsuta Ikiru , Wada Hiroko , Ayukawa Yasunori
Published: August 2022

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable disease that is typically observed in patients with osteoporosis or tumors that have been treated with either bisphosphonate (BP) or antiangiogenic medicine. The mechanism of MRONJ pathogenesis remains unclear, and no effective definitive treatment modalities have been reported to date. Previous reports have indicated that a single injection of benidipine, an antihypertensive calcium channel blocker, in the vicinity of a tooth extraction socket promotes wound healing in healthy rats. The present study was conducted to elucidate the possibility of using benidipine to promote the healing of MRONJ-like lesions. In this study, benidipine was administered near the site of MRONJ symptom onset in a model rat, which was then sacrificed two weeks after benidipine injection, and analyzed using histological sections and CT images. The analysis showed that in the benidipine groups, necrotic bone was reduced, and soft tissue continuity was recovered. Furthermore, the distance between epithelial edges, length of necrotic bone exposed in the oral cavity, necrotic bone area, and necrotic bone ratio were significantly smaller in the benidipine group. These results suggest that a single injection of benidipine in the vicinity of MRONJ-like lesions can promote osteonecrotic extraction socket healing.
Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model
Authors: Peng Zheng-Hong , Jogdeo Chinmay M. , Li Jing , Xie Ying , Wang Yazhe , Sheinin Yuri M. , Kopeček Jindřich , Oupický David
Published: August 2022

Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. Here, we introduce a polymeric conjugate P-DOX-iRGD that not only significantly suppressed primary tumor growth but also substantially inhibited pulmonary metastasis in an orthotopic mouse model of breast cancer. In addition, treatment with P-DOX-iRGD markedly reduced breast cancer-induced splenomegaly and liver hematopoiesis. Interestingly, contrasting results were seen for the free form and polymeric form of DOX in vitro and in vivo, which may be attributed to the enhanced permeability and retention (EPR) effect.
Combination-Based Strategies for the Treatment of Actinic Keratoses with Photodynamic Therapy: An Evidence-Based Review
Authors: Piaserico Stefano , Mazzetto Roberto , Sartor Emma , Bortoletti Carlotta
Published: August 2022

Photodynamic therapy (PDT) is a highly effective and widely adopted treatment strategy for many skin diseases, particularly for multiple actinic keratoses (AKs). However, PDT is ineffective in some cases, especially if AKs occur in the acral part of the body. Several methods to improve the efficacy of PDT without significantly increasing the risks of side effects have been proposed. In this study, we reviewed the combination-based PDT treatments described in the literature for treating AKs; both post-treatment and pretreatment were considered including topical (i.e., diclofenac, imiquimod, adapalene, 5-fluorouracil, and calcitriol), systemic (i.e., acitretin, methotrexate, and polypodium leucotomos), and mechanical–physical (i.e., radiofrequency, thermomechanical fractional injury, microneedling, microdermabrasion, and laser) treatment strategies. Topical pretreatments with imiquimod, adapalene, 5-fluorouracil, and calcipotriol were more successful than PDT alone in treating AKs, while the effect of diclofenac gel was less clear. Both mechanical laser treatment with CO2 and Er:YAG (Erbium:Yttrium–Aluminum–Garnet) as well as systemic treatment with Polypodium leucotomos were also effective. Different approaches were relatively more effective in particular situations such as in immunosuppressed patients, AKs in the extremities, or thicker AKs. Conclusions: Several studies showed that a combination-based approach enhanced the effectiveness of PDT. However, more studies are needed to further understand the effectiveness of combination therapy in clinical practice and to investigate the role of acitretin, methotrexate, vitamin D, thermomechanical fractional injury, and microdermabrasion in humans.
Combinatorial Therapy of Letrozole- and Quercetin-Loaded Spanlastics for Enhanced Cytotoxicity against MCF-7 Breast Cancer Cells
Authors: Mekkawy Aml I. , Eleraky Nermin E. , Soliman Ghareb M. , Elnaggar Mohamed G. , Elnaggar Marwa G.
Published: August 2022

Breast cancer is the most widespread cancer in women with rising incidence, prevalence, and mortality in developed regions. Most breast cancers (80%) are estrogen receptor–positive, indicating that disease progression could be controlled by estrogen inhibition in the breast tissue. However, drug resistance limits the benefits of this approach. Combinatorial treatment could overcome the resistance and improve the outcome of breast cancer treatment. In the current study, we prepared letrozole-(LTZSPs) and quercetin-loaded spanlastics (QuSPs) using different edge activators—Tween 80, Brij 35, and Cremophor RH40—with different concentrations. The spanlastics were evaluated for their average particles size, surface charge, and percent encapsulation efficiency. The optimized formulations were further examined using transmission electron microscopy, Fourier transform infrared spectroscopy, in vitro drug release and ex vivo skin permeation studies. The prepared spherical LTZSPs and QuSPs had average particle sizes ranged between 129–310 nm and 240–560 nm, respectively, with negative surface charge and high LTZ and Qu encapsulation (94.3–97.2% and 97.9–99.6%, respectively). The in vitro release study of LTZ and Qu from the selected formulations showed a sustained drug release for 24 h with reasonable flux and permeation through the rat skin. Further, we evaluated the in vitro cytotoxicity, cell cycle analysis, and intracellular reactive oxygen species (ROS) of the combination therapy of letrozole and quercetin either in soluble form or loaded in spanlastics against MCF-7 breast cancer cells. The LTZSPs and QuSPs combination was superior to the individual treatments and the soluble free drugs in terms of in vitro cytotoxicity, cell cycle analysis, and ROS studies. These results confirm the potential of LTZSPs and QuSPs combination for transdermal delivery of drugs for enhanced breast cancer management.
Host Response Modulation Therapy in the Diabetes Mellitus—Periodontitis Conjuncture: A Narrative Review
Authors: Sufaru Irina-Georgeta , Teslaru Silvia , Pasarin Liliana , Iovan Gianina , Stoleriu Simona , Solomon Sorina Mihaela
Published: August 2022

The inflammatory response of the host in periodontitis is the phenomenon that underlies the onset and evolution of periodontal destructive phenomena. A number of systemic factors, such as diabetes mellitus (DM), can negatively affect the patient with periodontitis, just as the periodontal disease can aggravate the status of the DM patient. Host response modulation therapy involves the use of anti-inflammatory and anti-oxidant products aimed at resolving inflammation, stopping destructive processes, and promoting periodontal healing, all important aspects in patients with high tissue loss rates, such as diabetic patients. This paper reviews the data available in the literature on the relationship between DM and periodontitis, the main substances modulating the inflammatory response (nonsteroidal anti-inflammatory drugs, sub-antimicrobial doses of doxycycline, or omega-3 fatty acids and their products, specialized pro-resolving mediators), as well as their application in diabetic patients.
An Overview of the Supramolecular Systems for Gene and Drug Delivery in Tissue Regeneration
Authors: Ranamalla Saketh Reddy , Porfire Alina Silvia , Tomuță Ioan , Banciu Manuela
Published: August 2022

Tissue regeneration is a prominent area of research, developing biomaterials aimed to be tunable, mechanistic scaffolds that mimic the physiological environment of the tissue. These biomaterials are projected to effectively possess similar chemical and biological properties, while at the same time are required to be safely and quickly degradable in the body once the desired restoration is achieved. Supramolecular systems composed of reversible, non-covalently connected, self-assembly units that respond to biological stimuli and signal cells have efficiently been developed as preferred biomaterials. Their biocompatibility and the ability to engineer the functionality have led to promising results in regenerative therapy. This review was intended to illuminate those who wish to envisage the niche translational research in regenerative therapy by summarizing the various explored types, chemistry, mechanisms, stimuli receptivity, and other advancements of supramolecular systems.
Physiologically Based Pharmacokinetic Modeling to Describe the CYP2D6 Activity Score-Dependent Metabolism of Paroxetine, Atomoxetine and Risperidone
Authors: Rüdesheim Simeon , Selzer Dominik , Mürdter Thomas , Igel Svitlana , Kerb Reinhold , Schwab Matthias , Lehr Thorsten
Published: August 2022

The cytochrome P450 2D6 (CYP2D6) genotype is the single most important determinant of CYP2D6 activity as well as interindividual and interpopulation variability in CYP2D6 activity. Here, the CYP2D6 activity score provides an established tool to categorize the large number of CYP2D6 alleles by activity and facilitates the process of genotype-to-phenotype translation. Compared to the broad traditional phenotype categories, the CYP2D6 activity score additionally serves as a superior scale of CYP2D6 activity due to its finer graduation. Physiologically based pharmacokinetic (PBPK) models have been successfully used to describe and predict the activity score-dependent metabolism of CYP2D6 substrates. This study aimed to describe CYP2D6 drug–gene interactions (DGIs) of important CYP2D6 substrates paroxetine, atomoxetine and risperidone by developing a substrate-independent approach to model their activity score-dependent metabolism. The models were developed in PK-Sim®, using a total of 57 plasma concentration–time profiles, and showed good performance, especially in DGI scenarios where 10/12, 5/5 and 7/7 of DGI AUClast ratios and 9/12, 5/5 and 7/7 of DGI Cmax ratios were within the prediction success limits. Finally, the models were used to predict their compound’s exposure for different CYP2D6 activity scores during steady state. Here, predicted DGI AUCss ratios were 3.4, 13.6 and 2.0 (poor metabolizers; activity score = 0) and 0.2, 0.5 and 0.95 (ultrarapid metabolizers; activity score = 3) for paroxetine, atomoxetine and risperidone active moiety (risperidone + 9-hydroxyrisperidone), respectively.
Genetics of the Inverse Relationship between Grain Yield and Grain Protein Content in Common Wheat
Authors: Geyer Manuel , Mohler Volker , Hartl Lorenz
Published: August 2022

Grain protein content (GPC) is one of the most important criteria to determine the quality of common wheat (Triticum aestivum). One of the major obstacles for bread wheat production is the negative correlation between GPC and grain yield (GY). Previous studies demonstrated that the deviation from this inverse relationship is highly heritable. However, little is known about the genetics controlling these deviations in common wheat. To fill this gap, we performed quantitative trait locus (QTL) analysis for GY, GPC, and four derived GY-GPC indices using an eight-way multiparent advanced generation intercross population comprising 394 lines. Interval mapping was conducted using phenotypic data from up to nine environments and genotypic data from a 20k single-nucleotide polymorphism array. The four indices were highly heritable (0.76–0.88) and showed distinct correlations to GY and GPC. Interval mapping revealed that GY, GPC, and GY-GPC indices were controlled by 6, 12, and 12 unique QTL, of which each explained only a small amount of phenotypic variance (R2 ≤ 10%). Ten of the 12 index QTL were independent of loci affecting GY and GPC. QTL regions harboured several candidate genes, including Rht-1, WAPO-A1, TaTEF-7A, and NRT2.6-7A. The study confirmed the usefulness of indices to mitigate the inverse GY-GPC relationship in breeding, though the selection method should reflect their polygenic inheritance.
Synthesis of Polycarboxylate Viscosity Reducer and the Effect of Different Chain Lengths of Polyether on Viscosity Reduction of Heavy Oil
Authors: Wang Junqi , Liu Ruiqing , Tang Yiwen , Zhu Junfeng , Sun Yonghui , Zhang Guanghua
Published: August 2022

Since there are not many studies on the application of polymeric surfactants in viscosity reduction emulsification of heavy oil, a series of polyether carboxylic acid–sulfonate polymeric surfactants were synthesized. The viscosity reduction performance and the effect of different chain lengths on the viscosity reduction effect were also investigated. The viscosity reduction, emulsification, wetting, and foaming performance tests showed that the viscosity reduction performance of this series of polymeric surfactants was excellent, with the viscosity reduction rate exceeding 95%, and the viscosity was reduced to 97 mPa·s by the polymeric surfactant with a molecular weight of 600 polyethers. It was also concluded that among the three surfactants with different side chains, the polymeric surfactant with a polyether molecular weight of 600, which is the medium side-chain length, had the best viscosity reduction performance. The study showed that the polyether carboxylic acid–sulfonate polymer surfactant had a promising application in the viscosity reduction of heavy oil.