bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interplay between Candida albicans, Vaginal Mucosa, Host Immunity and Resident Microbiota in Health and Disease: An Overview and Future Perspectives
Authors: Gaziano Roberta , Sabbatini Samuele , Monari Claudia
Published: May 2023

Vulvovaginal candidiasis (VVC), which is primarily caused by Candida albicans, is an infection that affects up to 75% of all reproductive-age women worldwide. Recurrent VVC (RVVC) is defined as >3 episodes per year and affects nearly 8% of women globally. At mucosal sites of the vagina, a delicate and complex balance exists between Candida spp., host immunity and local microbial communities. In fact, both immune response and microbiota composition play a central role in counteracting overgrowth of the fungus and maintaining homeostasis in the host. If this balance is perturbed, the conditions may favor C. albicans overgrowth and the yeast-to-hyphal transition, predisposing the host to VVC. To date, the factors that affect the equilibrium between Candida spp. and the host and drive the transition from C. albicans commensalism to pathogenicity are not yet fully understood. Understanding the host- and fungus-related factors that drive VVC pathogenesis is of paramount importance for the development of adequate therapeutic interventions to combat this common genital infection. This review focuses on the latest advances in the pathogenic mechanisms implicated in the onset of VVC and also discusses novel potential strategies, with a special focus on the use of probiotics and vaginal microbiota transplantation in the treatment and/or prevention of recurrent VVC.
Parameter Optimization of the Separation Process for Hematite and Quartz Mixture Minerals Based on a Cyclone Centrifugal Separator
Authors: Jin Yanling , Xie Haiyun , Zeng Peng , Chen Jialing , Chen Luzheng , Liu Dianwen , Liu Rongxin
Published: May 2023

The current centrifugal concentrators do not continuously concentrate heavy minerals of large mass weight—for example, in the processing of iron oxides. A cyclone centrifugal separator is a new type of beneficiation equipment that has been developed on the basis of the principles of centrifugal separation and hydrocyclones. In this study, a cyclone centrifugal separator was used for the beneficiation of a hematite–quartz mixture, and the separation effect under different operating conditions was analyzed. The results showed that various factors, such as the feeding concentration, the feeding pressure, and the number of fluidization holes in the separation cone, had a significant influence on the separation performance of the cyclone centrifugal separator. The single-factor separation test results showed that the appropriate operating conditions were a feeding concentration of 10%, a feeding pressure of 120 kPa, a 40-hole separation cone, a settling port pressure of 70 kPa, and an overflow port pressure of 50 kPa. The results of the open circuit separation test that was designed on the basis of the single-factor experiment showed that the concentrate grade of Fe in the hematite–quartz mixture, with 44.12% Fe, was 54.42% after beneficiation, indicating better beneficiation separation effects. This study provides a new approach for the beneficiation of a large number of difficult-to-select hematite ores in China, and can provide a reference for the further expansion and application of the cyclone centrifugal separator in the field of mineral processing.
Recovery of Li2CO3 from Spent LiFePO4 by Using a Novel Impurity Elimination Process
Authors: Chen Wen-Lan , Chen Chi , Xiao Hao , Chen Cheng-Wei , Sun Dan
Published: May 2023

The large-scale implementations of lithium iron phosphate (LFP) batteries for energy storage systems have been gaining attention around the world due to their quality of high technological maturity and flexible configuration. Unfortunately, the exponential production of LFP batteries is accompanied by an annual accumulation of spent batteries and a premature consumption of the lithium resource. Recycling souring critical battery materials such as Li2CO3 is essential to reduce the supply chain risk and achieve net carbon neutrality goals. During the recovery of Li2CO3, impurity removal is the most crucial step in the hydrometallurgy process of spent LiFePO4, which determines the purity of Li2CO3. By investigating and comparing the results of impurity elimination from the purified Li+-containing liquids with strong and weak alkalis under identical pH conditions, respectively, a strategy based on an alkali mixture has been proposed. The purified Li+-containing liquid was, thereafter, concentrated and sodium carbonate was added in order to precipitate Li2CO3. As a result, a high purity Li2CO3 (99.51%) of battery grade was obtained. LiFePO4 prepared with the recovered Li2CO3 and FePO4 as raw materials also displayed a comparative high capacity and stable cycle performance to the commercial product and further verified the electrochemical activity of the recovered materials.
The Role of Stabilizing Copolymer in Determining the Physicochemical Properties of Conjugated Polymer Nanoparticles and Their Nanomedical Applications
Authors: Zhao Miao , Uzunoff Anton , Green Mark , Rakovich Aliaksandra
Published: May 2023

Conjugated polymer nanoparticles (CPNs) are a promising class of nanomaterials for biomedical applications, such as bioimaging, gene and drug delivery/release, photodynamic therapy (PDT), photothermal therapy (PTT), and environmental sensing. Over the past decade, many reports have been published detailing their synthesis and their various potential applications, including some very comprehensive reviews of these topics. In contrast, there is a distinct lack of overview of the role the stabilizing copolymer shells have on the properties of CPNs. This review attempts to correct this oversight by scrutinizing reports detailing the synthesis and application of CPNs stabilized with some commonly-used copolymers, namely F127 (Pluronic poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) diacrylate), PSMA (poly(styrene-co-maleic anhydride)), PLGA (poly(D, L-lactide-co-glycolide)) and PEG (polyethylene glycol) derivatives. The analysis of the reported physicochemical properties and biological applications of these CPNs provides insights into the advantages of each group of copolymers for specific applications and offers a set of guidance criteria for the selection of an appropriate copolymer when designing CPNs-based probes. Finally, the challenges and outlooks in the field are highlighted.
Reply to Kaminski, N.E.; Cohen, S.M. Comment on “Bischoff et al. The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer. Nanomaterials 2022, 12, 1256”
Authors: Bischoff Nicolaj S. , Proquin Héloïse , Jetten Marlon J. , Schrooders Yannick , Jonkhout Marloes C. M. , Briedé Jacco J. , van Breda Simone G. , Jennen Danyel G. J. , Medina-Reyes Estefany I. , Delgado-Buenrostro Norma L. , Chirino Yolanda I. , van Loveren Henk , de Kok Theo M.
Published: May 2023

We appreciate the interest in our article describing transcriptome changes in a transgenic mouse model carrying an APC gene mutation and would like to reply to the reader [...]
Current Applications of Liposomes for the Delivery of Vitamins: A Systematic Review
Authors: Chaves Matheus A. , Ferreira Letícia S. , Baldino Lucia , Pinho Samantha C. , Reverchon Ernesto
Published: May 2023

Liposomes have been used for several decades for the encapsulation of drugs and bioactives in cosmetics and cosmeceuticals. On the other hand, the use of these phospholipid vesicles in food applications is more recent and is increasing significantly in the last ten years. Although in different stages of technological maturity—in the case of cosmetics, many products are on the market—processes to obtain liposomes suitable for the encapsulation and delivery of bioactives are highly expensive, especially those aiming at scaling up. Among the bioactives proposed for cosmetics and food applications, vitamins are the most frequently used. Despite the differences between the administration routes (oral for food and mainly dermal for cosmetics), some challenges are very similar (e.g., stability, bioactive load, average size, increase in drug bioaccessibility and bioavailability). In the present work, a systematic review of the technological advancements in the nanoencapsulation of vitamins using liposomes and related processes was performed; challenges and future perspectives were also discussed in order to underline the advantages of these drug-loaded biocompatible nanocarriers for cosmetics and food applications.
Efficient and Broadband Emission in Dy3+-Doped Glass-Ceramic Fibers for Tunable Yellow Fiber Laser
Authors: Chen Qianyi , Wu Minbo , Xiong Puxian , Zhao Yajing , Tian Shuhang , Xiao Yao , Sun Yongsheng , Chen Dongdan , Xu Shanhui , Yang Zhongmin
Published: May 2023

Yellow lasers are of great interest in biology, medicine and display technology. However, nonlinear emission of near-infrared lasers at yellow still presents particularly complex optical alignment to date. Here, to the best of our knowledge, we demonstrate the fabrication of a NaLa(WO4)2: Dy3+ glass-ceramic fiber (GCF) for the first time. More importantly, the emission band of the GCF, which is around 575 nm, has a wide full-width half maximum (FWHM) of 18~22 nm, which is remarkably larger than that of the Dy3+-doped YAG crystal (<7 nm). The precursor fiber (PF) was drawn using the molten core drawing (MCD) method. In particular, benefiting from the in situ nanocrystals fabricated in the amorphous fiber core after thermal treatment, the resultant glass-ceramic fiber exhibits a five-times enhancement of luminescence intensity around 575 nm, compared with the precursor fiber, while retaining its broadband emission. Overall, this work is anticipated to offer a high potential GCF with prominent bandwidth for the direct access of a tunable yellow laser.
Students’ Perceptions of Their Student-Operated Restaurant Experience: A Qualitative Study
Authors: Clark Allison Ells , Woodbury Brittany , Patten Emily Vaterlaus , Stokes Nathan
Published: May 2023

As there is a rapid increase in the consumption of food outside the home, it is essential that future foodservice managers are well prepared for their critical role in menu creation and nutrition care planning in a variety of foodservice establishments. Student-operated restaurants (SORs) are one method of experiential learning used to educate future foodservice managers. This study aimed to explore the students’ perceptions of their SOR experience and the extent to which nutrition concepts were incorporated in their program. This is a research area that has not been explored previously. For this study, a total of eighteen students from four universities were recruited via email to participate in interviews. Results from the qualitative thematic analysis of interview data revealed the following three overarching themes related to students’ SOR experience: (1) Interpersonal Relationships and Mentoring, (2) Assessment of Immediate Experience, and (3) Moving Forward, Added Value, and Growth. Regarding nutrition, while some students felt that nutrition principles were effectively addressed during their SOR experience, other students acknowledged a lack of nutritional emphasis in their SOR and expressed a desire for a greater application of the nutritional principles learned in other classes. The SOR experience described by students was rich as they developed a variety of relationships and skills.
The Impact of Linoleic Acid on Infant Health in the Absence or Presence of DHA in Infant Formulas
Authors: Einerhand Alexandra W. C. , Mi Wiola , Haandrikman Alfred , Sheng Xiao-Yang , Calder Philip C.
Published: May 2023

Both linoleic acid (LA) and α-linolenic acid (ALA) are essential dietary fatty acids, and a balanced dietary supply of these is of the utmost importance for health. In many countries across the globe, the LA level and LA/ALA ratio in breast milk (BM) are high. For infant formula (IF), the maximum LA level set by authorities (e.g., Codex or China) is 1400 mg LA/100 kcal ≈ 28% of total fatty acid (FA) ≈ 12.6% of energy. The aims of this study are: (1) to provide an overview of polyunsaturated fatty acid (PUFA) levels in BM across the world, and (2) to determine the health impact of different LA levels and LA/ALA ratios in IF by reviewing the published literature in the context of the current regulatory framework. The lipid composition of BM from mothers living in 31 different countries was determined based on a literature review. This review also includes data from infant studies (intervention/cohort) on nutritional needs regarding LA and ALA, safety, and biological effects. The impact of various LA/ALA ratios in IF on DHA status was assessed within the context of the current worldwide regulatory framework including China and the EU. Country averages of LA and ALA in BM range from 8.5–26.9% FA and 0.3–2.65% FA, respectively. The average BM LA level across the world, including mainland China, is below the maximum 28% FA, and no toxicological or long-term safety data are available on LA levels > 28% FA. Although recommended IF LA/ALA ratios range from 5:1 to 15:1, ratios closer to 5:1 seem to promote a higher endogenous synthesis of DHA. However, even those infants fed IF with more optimal LA/ALA ratios do not reach the DHA levels observed in breastfed infants, and the levels of DHA present are not sufficient to have positive effects on vision. Current evidence suggests that there is no benefit to going beyond the maximum LA level of 28% FA in IF. To achieve the DHA levels found in BM, the addition of DHA to IF is necessary, which is in line with regulations in China and the EU. Virtually all intervention studies investigating LA levels and safety were conducted in Western countries in the absence of added DHA. Therefore, well-designed intervention trials in infants across the globe are required to obtain clarity about optimal and safe levels of LA and LA/ALA ratios in IF.
The Role of Nutrition in Osteosarcopenic Obesity: Lessons Learned during the Last 10 Years and Future Horizons
Authors: Perna Simone , Rondanelli Mariangela
Published: May 2023

The term Osteosarcopenic Obesity (OSO) was introduced for the first time in 2014 by Ilic et al [...]
Docosahexaenoic Acid Alleviates Trimethylamine-N-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells
Authors: Syu Jia-Ning , Lin Hung-Yu , Huang Tun Yu , Lee Der-Yen , Chiang En-Pei Isabel , Tang Feng-Yao
Published: May 2023

Background: Human endothelial progenitor cells (hEPCs), originating from hemangioblasts in bone marrow (BM), migrate into the blood circulation, differentiate into endothelial cells, and could act as an alternative tool for tissue regeneration. In addition, trimethylamine-N-oxide (TMAO), one of the gut microbiota metabolites, has been identified as an atherosclerosis risk factor. However, the deleterious effects of TMAO on the neovascularization of hEPCs have not been studied yet. Results: Our results demonstrated that TMAO dose-dependently impaired human stem cell factor (SCF)-mediated neovascularization in hEPCs. The action of TMAO was through the inactivation of Akt/endothelial nitric oxide synthase (eNOS), MAPK/ERK signaling pathways, and an upregulation of microRNA (miR)-221. Docosahexaenoic acid (DHA) could effectively inhibit the cellular miR-221 level and induce the phosphorylation level of Akt/eNOS, MAPK/ERK signaling molecules, and neovascularization in hEPCs. DHA enhanced cellular amounts of reduced form glutathione (GSH) through an increased expression of the gamma-glutamylcysteine synthetase (γ-GCS) protein. Conclusions: TMAO could significantly inhibit SCF-mediated neovascularization, in part in association with an upregulation of miR-221 level, inactivation of Akt/eNOS and MAPK/ERK cascades, suppression of γ-GCS protein, and decreased levels of GSH and GSH/GSSG ratio. Furthermore, the DHA could alleviate the detrimental effects of TMAO and induce neovasculogenesis through suppression of miR-221 level, activation of Akt/eNOS and MAPK/ERK signaling cascades, increased expression of γ-GCS protein, and increment of cellular GSH level and GSH/GSSG ratio in hEPCs.
Nutrient Inadequacy in Korean Young Adults with Depression: A Case Control Study
Authors: Yoon Su-In , Moon Hye-Ri , Lee So Rok , Zhang Jingnan , Lee Soojin , Cho Jin Ah
Published: May 2023

The role of diet is gaining attention among the modifiable factors associated with depression; thus, this case–control study examined the association between nutrition and depression in young Korean adults. Dietary surveys in individuals with depression (n = 39) and age- and gender-matched controls (n = 76) were conducted using food records and food frequency questionnaires. Men with depression consumed less mushrooms and meat, while women consumed significantly less grains (p < 0.05). Overall, the depression group consumed less energy and nutrients, and the difference was more pronounced in men. The male depression group had lower nutrient adequacy ratio (NAR) for energy, protein, vitamin A, thiamine, niacin, folate, and phosphorus, whereas the female depression group had lower NARs for energy, protein, niacin, and vitamin B12. The depression group had a significantly lower mean adequacy ratio in both genders. Furthermore, the proportion of inappropriate nutrient intake was higher in both genders of the depression group, exhibiting significant differences in energy, protein, niacin, folate, and zinc in men and energy, riboflavin, folate, and vitamin C in women. Hence, both men and women in the depression group had poor nutrient intake and high rates of nutrient inadequacy and improper consumption. This suggests that the quantity and quality of meals should be improved for individuals with depressive symptoms.
Breakfast Practices in Malaysia, Nutrient Intake and Diet Quality: A Study Based on the Malaysian Food Barometer
Authors: Mognard Elise , Sanubari Theresia Pratiwi Elingsetyo , Alem Yasmine , Yuen Jan Li , Ragavan Neethianhantan Ari , Ismail Mohd Noor , Poulain Jean-Pierre
Published: May 2023

Breakfast is often referred to as the “most important meal of the day” in shaping diet quality. This study established the patterns of breakfast consumption in Malaysia and assessed its contribution to the overall quality of the diet based on the 24 h recall data from the nationally representative and cross-sectional Malaysian Food Barometer (MFB, second data collection, 2018) to assess breakfast intake among adults (n = 1604). Diet quality was measured using the Nutrient Rich Food index (NRF) 9.3. The nutritional profile of breakfast was compared across tertiles of NRF 9.3. Overall, 89% of Malaysians consume breakfast. Breakfast was found to provide 474 kcal on average. The Malaysian daily diet was found to be rich in fats, saturated fats, total sugars, and sodium, with breakfast making a significant contribution to the daily intakes of these nutrients. Intakes of fiber, potassium, calcium, vitamins C and D, folate, iron, zinc, and magnesium were low. Breakfast was related to the overall diet quality measured by the NRF index. This study revealed that the breakfasts consumed by Malaysian adults were found to be nutritionally unbalanced. This analysis could serve as a basis for nutrient recommendations grounded in existing social and cultural breakfast patterns.
Dysfunction of Inflammatory Pathways and Their Relationship with Anti-Hypothalamic Autoantibodies in Patients with Anorexia Nervosa
Authors: Amerio Andrea , Escelsior Andrea , Martino Eleonora , Strangio Antonella , Giacomini Costanza , Montagna Elisa , Aguglia Andrea , Bellomo Marina , Sukkar Samir Giuseppe , Saverino Daniele
Published: May 2023

Background: Despite several attempts, the etiopathogenesis of anorexia nervosa (AN) is still unknown. However, the activation of the immune response in neuropsychiatric diseases, including AN, is increasingly evident. We aimed to explore immune response parameters in patients with AN and identify the link between the presence of specific autoantibodies for hypothalamic antigens and the inflammatory response. The relationship between inflammatory markers and the duration of the disease has been also investigated. Methods: Twenty-two patients with AN were included, and none were under psychopharmacological treatment or suffering from autoimmune conditions. Serum concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and IL-21 were determined by ELISA kits. In addition, autoantibodies against hypothalamic antigens are quantitatively evaluated. Results: IL-6, IL-1 β, TNF-α, and TGF-β are significantly increased in patients with AN. A positive correlation with body mass index and with the amount of autoantibody specific for hypothalamic antigens exists. Notably, a progressive reduction of cytokines correlates with the progression of AN. In addition, IL-21 is increased in the blood of patients with AN and negatively correlates with autoantibody concentrations. Conclusions: This study shows that the increased pro-inflammatory phenotype in patients affected by AN correlates with the concentration of autoantibody specific for hypothalamic antigens. Of interest, the pro-inflammatory state seems to be reduced with duration of AN. In addition, IL-21 could work as a stimulant of the immune response, thus possibly increasing the autoreactivity.
Association of Sociodemographic, Socioeconomic and Lifestyle Characteristics with Low Protein and Energy Intake in the Healthy Swiss Population
Authors: Wimmer Roxana , Audétat Andrea , Binggeli Julia , Schuetz Philipp , Kaegi-Braun Nina
Published: May 2023

A balanced diet has the goal of providing adequate amounts of different nutrients to promote and maintain physical and psychological health. Our aim was to study the association between different sociodemographic, socioeconomic and lifestyle factors and low energy or protein intake among the Swiss population. This is a cross-sectional cohort study based on the national nutritional survey “MenuCH”, which is the first representative, detailed assessment of dietary habits in the adult Swiss population conducted in 2014/2015. We compared the mean protein and caloric intake based on two 24 h recall nutritional assessments with current recommendations based on resting metabolic rate calculation and DACH guidelines. A total of 1919 participants with a median age of 46 years and 53% females were included. Overall, 10.9% and 20.2% of participants had an energy and protein intake, respectively, below the dietary reference values. However, a high income (>9000 CHF per month) reduced the risk of low energy intake (OR 0.49 [0.26–0.94], p = 0.032), obesity (OR 6.55 [3.77–11.38], p < 0.01), and living in a household with children (OR 2.1 [1.15–3.85], p = 0.016) was associated with higher risk. Regarding low protein intake, the most important risk factors were an age group of 65–75 years (OR 2.94 [1.57–5.52], p = 0.001) and female gender (OR 1.73 [1.15–2.6], p = 0.008). Regular meat consumption reduced the risk of low protein intake (OR of 0.23 (0.1–0.53), p = 0.001). Within this survey, several socio-economic and lifestyle factors were associated with low energy and protein intake in the healthy Swiss population. A bunderstanding of these factors may help to reduce the risk of malnutrition.
Hepatitis C and Thalassemia: A Story with (Almost) a Happy Ending
Authors: Origa Raffaella
Published: May 2023

Donor screening has nearly eliminated the risk of hepatitis C virus post-transfusion transmission in resource-rich settings. Moreover, the use of direct antiviral agents made it possible to treat the majority of patients with thalassemia and hepatitis C. However, this achievement, while extremely significant, does not erase the effects of the virus in terms of fibrogenesis and mutagenic risk, and adult patients with thalassemia are facing the long-term consequences of the chronic infection both on the liver and extrahepatically. As in the general population, it is in mainly patients with cirrhosis who are increasing in age, even though they are now HCV RNA-negative, who are at risk of hepatocellular carcinoma, which continues to be statistically much more frequent in individuals with than without thalassemia. In certain resource-limited settings, the World Health Organization has estimated that up to 25 percent of blood donations do not undergo screening. It is therefore not surprising that hepatitis virus infection is still the most prevalent in patients with thalassemia worldwide.
Influence of Bifidobacterium breve on the Glycaemic Control, Lipid Profile and Microbiome of Type 2 Diabetic Subjects: A Preliminary Randomized Clinical Trial
Authors: Chaiyasut Chaiyavat , Sivamaruthi Bhagavathi Sundaram , Lailerd Narissara , Sirilun Sasithorn , Thangaleela Subramanian , Khongtan Suchanat , Bharathi Muruganantham , Kesika Periyanaina , Saelee Manee , Choeisoongnern Thiwanya , Fukngoen Pranom , Peerajan Sartjin , Sittiprapaporn Phakkharawat
Published: May 2023

Type 2 diabetes mellitus (T2DM) is one of the most highly prevalent metabolic disorders worldwide. Uncontrolled T2DM can lead to other health threats such as cardiac arrest, lower-limb amputation, blindness, stroke, impaired kidney function, and microvascular and macrovascular complications. Many studies have demonstrated the association between gut microbiota and diabetes development and probiotic supplementation in improving glycemic properties in T2DM. The study aimed to evaluate the influence of Bifidobacterium breve supplementation on glycemic control, lipid profile, and microbiome of T2DM subjects. Forty participants were randomly divided into two groups, and they received probiotics (50 × 109 CFU/day) or placebo interventions (corn starch; 10 mg/day) for 12 weeks. The changes in the blood-urea nitrogen (BUN), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), fasting blood sugar (FBS), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine levels, and other factors such as body-mass index, visceral fat, body fat, and body weight were assessed at baseline and after 12 weeks. B. breve supplementation significantly reduced BUN, creatinine, LDL, TG, and HbA1c levels compared to the placebo group. Significant changes were observed in the microbiome of the probiotic-treated group compared to the placebo group. Firmicutes and proteobacteria were predominant in the placebo and probiotic-treated groups. Genera Streptococcus, Butyricicoccus, and species Eubacterium hallii were significantly reduced in the probiotic-treated group compared to the placebo. Overall results suggested that B. breve supplementation could prevent worsening of representative clinical parameters in T2DM subjects. The current study has limitations, including fewer subjects, a single probiotic strain, and fewer metagenomic samples for microbiome analysis. Therefore, the results of the current study require further validation using more experimental subjects.
Validation of Freshly Isolated Rat Renal Cells as a Tool for Preclinical Assessment of Radiolabeled Receptor-Specific Peptide Uptake in the Kidney
Authors: Barta Pavel , Nachtigal Petr , Maixnerova Jana , Zemankova Lenka , Trejtnar Frantisek
Published: May 2023

The synthetic analogs of regulatory peptides radiolabeled with adequate radionuclides are perspective tools in nuclear medicine. However, undesirable uptake and retention in the kidney limit their application. Specific in vitro methods are used to evaluate undesirable renal accumulation. Therefore, we investigated the usefulness of freshly isolated rat renal cells for evaluating renal cellular uptake of receptor-specific peptide analogs. Special attention was given to megalin as this transport system is an important contributor to the active renal uptake of the peptides. Freshly isolated renal cells were obtained from native rat kidneys by the collagenase method. Compounds with known accumulation in renal cells were used to verify the viability of cellular transport systems. Megalin expressions in isolated rat renal cells were compared to two other potential renal cell models by Western blotting. Specific tubular cell markers were used to confirm the presence of proximal tubular cells expressing megalin in isolated rat renal cell preparations by immunohistochemistry. Colocalization experiments on isolated rat kidney cells confirmed the presence of proximal tubular cells bearing megalin in preparations. The applicability of the method was tested by an accumulation study with several analogs of somatostatin and gastrin labeled with indium-111 or lutetium-177. Therefore, isolated rat renal cells may be an effective screening tool for in vitro analyses of renal uptake and comparative renal accumulation studies of radiolabeled peptides or other radiolabeled compounds with potential nephrotoxicity.
Combination of Niclosamide and Pirfenidone Alleviates Pulmonary Fibrosis by Inhibiting Oxidative Stress and MAPK/Nf-κB and STATs Regulated Genes
Authors: Wanas Hanaa , Elbadawy Hossein M. , Almikhlafi Mohannad A. , Hamoud Amany E. , Ali Eid N. , Galal Amr M.
Published: May 2023

The pathogenesis of pulmonary fibrosis (PF) is extremely complex and involves numerous intersecting pathways. The successful management of PF may require combining multiple agents. There is a growing body of evidence that suggests the potential benefits of niclosamide (NCL), an FDA-approved anthelminthic drug, in targeting different fibrogenesis molecules. This study aimed at investigating the anti-fibrotic potential of NCL alone and in combination with pirfenidone (PRF), an approved drug for PF, in a bleomycin (BLM) induced PF experimental model. PF was induced in rats by intratracheal BLM administration. The effect of NCL and PRF individually and in combination on different histological and biochemical parameters of fibrosis was investigated. Results revealed that NCL and PRF individually and in combination alleviated the histopathological changes, extracellular matrix deposition and myofibroblastic activation induced by BLM. NCL and PRF either individually or in combination inhibited the oxidative stress and subsequent pathways. They modulated the process of fibrogenesis by inhibiting MAPK/NF-κB and downstream cytokines. They inhibited STATs and downstream survival-related genes including BCL-2, VEGF, HIF-α and IL-6. Combining both drugs showed significant improvement in the tested markers in comparison to the monotherapy. NCL, therefore, has a potential synergistic effect with PRF in reducing the severity of PF.
Aggregation, Cytotoxicity and DNA Binding in a Series of Calix[4]arene Amphiphile Containing Aminotriazole Groups
Authors: Mironova Diana , Makarov Egor , Bilyukova Islamiya , Akyol Kevser , Sultanova Elsa , Evtugyn Vladimir , Davletshin Damir , Gilyazova Elvina , Bulatov Emil , Burilov Vladimir , Solovieva Svetlana , Antipin Igor
Published: May 2023

The present work focuses on the study of the aggregation and complexing properties of calixarenes as potential DNA condensation agents for gene delivery. In the current study, 1,4-triazole derivatives of calix[4]arenes 7 and 8 containing monoammonium fragments were synthesized. The synthesized compound’s structure was characterized by using various spectroscopic techniques (FTIR, HRESI MS, ¹H NMR and ¹³C NMR). The interactions between a series of calix[4]arene-containing aminotriazole groups (triazole-containing macrocycles with diethylenetriammonium fragments (3 and 4) and triazole-containing macrocycles with monoammonium fragments (7 and 8)) and calf thymus DNA were carried out via UV absorption, fluorescence spectroscopy, dynamic light scattering and zeta potential measurements. The role of the binding forces of calixarene–DNA complexes was analyzed. Photophysical and morphological studies revealed the interaction of the calixarenes 3, 4 and 8 with ct-DNA, which transformed the fibrous structure of ct-DNA to completely condensed compact structures that are 50 nm in diameter. The cytotoxic properties of calixarenes 3, 4, 7 and 8 against cancerous cells (MCF7, PC-3) as well as a healthy cell line (HSF) were investigated. Compound 4 was found to have the highest toxic effect on MCF7 breast adenocarcinoma (IC50 3.3 μM).
Feasibility of Using Oncology-Specific Electronic Health Record (EHR) Data to Emulate Clinical Trial Eligibility Criteria
Authors: Wilson Thomas W. , Dye Joseph T. , Spark Sarah , Robert Nicholas J. , Espirito Janet L. , Amirian E. Susan
Published: May 2023

We examined eligibility criteria from recent oncology clinical trials to see whether real-world data (RWD) from electronic health records (EHRs) could be used to create external control groups for clinical trials. Trials were identified from the Aggregate Analysis of ClinicalTrials.gov database; the selected trials were for oncology drugs approved by the FDA in 2020. Verbatim text from trial inclusion and exclusion criteria was qualitatively assessed by an expert panel to determine if criteria could be ascertained from structured and unstructured EHR data. Identified criteria were categorized (cancer-related, comorbidity-related, demographic, functional status, and trial operations) and subcategorized. Among 53 identified trials, 20 met the requirements for study inclusion, which included 463 eligibility criteria. Percentages of criteria by category were as follows: cancer-related factors (46%), comorbidities (20%), functional status (18%), trial operations (14%), and demographics (2%). For 18 of the 20 trials, 80% of the eligibility criteria could be ascertained with RWD; for 4 of the 20, it was 100%. When trial operation-specific criteria were excluded, all 20 met the 100% threshold. Our study indicates that both structured and unstructured data from community-based oncology-specific EHRs can be used for determining patient eligibility for external control arms for clinical trials.
Cistracurium Besylate 10 mg/mL Solution Compounded in a Hospital Pharmacy to Prevent Drug Shortages: A Stability Study Involving Four Degradation Products
Authors: Roche Marine , Danel Cécile , Simon Nicolas , Kouach Mostafa , Bouchfaa Myriam , Berneron Christophe , Odou Pascal , Lannoy Damien
Published: May 2023

Background: Stability study of a 10 mg/mL injectable cisatracurium solution stored refrigerated in amber glass ampoules for 18 months (M18). Methods: 4000 ampoules were aseptically compounded using European Pharmacopoeia (EP)-grade cisatracurium besylate, sterile water for injection, and benzenesulfonic acid. We developed and validated a stability-indicating HPLC-UV method for cisatracurium and laudanosine. At each stability study time point, we recorded the visual aspect, cisatracurium and laudanosine levels, pH, and osmolality. Sterility, bacterial endotoxin content, and non-visible particles in solution were checked after compounding (T0) and after M12 and M18 of storage. We used HPLC-MS/MS to identify the degradation products (DPs). Results: During the study, osmolality remained stable, pH decreased slightly, and the organoleptic properties did not change. The number of non-visible particles remained below the EP’s threshold. Sterility was preserved, and bacterial endotoxin level remained below the calculated threshold. Cisatracurium concentration remained within the ±10% acceptance interval for 15 months and then decreased to 88.7% of C0 after M18. The laudanosine generated accounted for less than a fifth of the cisatracurium degradation, and three DPs were generated—identified as EP impurity A, impurities E/F, and impurities N/O. Conclusion: Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months.
APJ as Promising Therapeutic Target of Peptide Analogues in Myocardial Infarction- and Hypertension-Induced Heart Failure
Authors: Rossin Daniela , Vanni Roberto , Lo Iacono Marco , Cristallini Caterina , Giachino Claudia , Rastaldo Raffaella
Published: May 2023

The widely expressed G protein-coupled apelin receptor (APJ) is activated by two bioactive endogenous peptides, apelin and ELABELA (ELA). The apelin/ELA-APJ-related pathway has been found involved in the regulation of many physiological and pathological cardiovascular processes. Increasing studies are deepening the role of the APJ pathway in limiting hypertension and myocardial ischaemia, thus reducing cardiac fibrosis and adverse tissue remodelling, outlining APJ regulation as a potential therapeutic target for heart failure prevention. However, the low plasma half-life of native apelin and ELABELA isoforms lowered their potential for pharmacological applications. In recent years, many research groups focused their attention on studying how APJ ligand modifications could affect receptor structure and dynamics as well as its downstream signalling. This review summarises the novel insights regarding the role of APJ-related pathways in myocardial infarction and hypertension. Furthermore, recent progress in designing synthetic compounds or analogues of APJ ligands able to fully activate the apelinergic pathway is reported. Determining how to exogenously regulate the APJ activation could help to outline a promising therapy for cardiac diseases.
Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice
Authors: Kaikousidis Christos , Papakyriakopoulou Paraskevi , Dokoumetzidis Aristides , Valsami Georgia
Published: May 2023

Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism. Due to these physiological peculiarities of the nasal cavity, compartmental modeling for nasal formulation is considered a demanding process. For this purpose, intravenous models have been proposed, based on the fast absorption from the olfactory nerve. However, most of the sophisticated approaches are required to describe the different absorption events occurring in the nasal cavity. Donepezil was recently formulated in the form of nasal film ensuring drug delivery in both bloodstream and the brain. In this work, a three-compartment model was first developed to describe donepezil oral brain and blood pharmacokinetics. Subsequently, using parameters estimated by this model, an intranasal model was developed dividing the administered dose into three fractions, corresponding to absorption directly to the bloodstream and brain, as well as indirectly to the brain expressed through transit compartments. Hence, the models of this study aim to describe the drug flow on both occasions and quantify the direct nose-to-brain and systemic distribution.
The Screening of Broadly Neutralizing Antibodies Targeting the SARS-CoV-2 Spike Protein by mRNA Immunization in Mice
Authors: An Zhiyin , Zhang Yu , Yu Xiang , Xia Jia , Yin Yanan , Li Guoming , Lu Jing , Fan Xuemei , Xu Yingjie
Published: May 2023

Neutralizing antibodies (nAbs), the popular antiviral drugs used for the treatment of COVID-19, are effective in reducing viral load and hospitalization. Currently, most nAbs are screened from convalescent or vaccinated individuals through single B-cell sequencing which requires cutting-edge facilities. Moreover, owing to the rapid mutation of SARS-CoV-2, some approved nAbs are no longer effective. In the present study, we designed a new approach to acquiring broadly neutralizing antibodies (bnAbs) from mRNA-vaccinated mice. Using the flexibility and speed of mRNA vaccine preparation, we designed a chimeric mRNA vaccine and sequential immunization strategies to acquire bnAbs in mice within a short period. By comparing different vaccination orders, we found that the initially administered vaccine had a greater effect on the neutralizing potency of mouse sera. Ultimately, we screened a strain of bnAb that neutralized wild-type, Beta, and Delta SARS-CoV-2 pseudoviruses. We synthesized the mRNAs of the heavy and light chains of this antibody and verified its neutralizing potency. This study developed a new strategy to screen for bnAbs in mRNA-vaccinated mice and identified a more effective immunization strategy for inducing bnAbs, providing valuable insights for future antibody drug development.
Periodic Artifacts Generation and Suppression in X-ray Ptychography
Authors: Liu Shilei , Xu Zijian , Xing Zhenjiang , Zhang Xiangzhi , Li Ruoru , Qin Zeping , Wang Yong , Tai Renzhong
Published: May 2023

As a unique coherent diffraction imaging method, X-ray ptychography has an ultrahigh resolution of several nanometers for extended samples. However, ptychography is often degraded by various noises that are mixed with diffracted signals on the detector. Some of the noises can transform into periodic artifacts (PAs) in reconstructed images, which is a basic problem in raster-scan ptychography. Herein, we propose a novel periodic-artifact suppressing algorithm (PASA) and present a new understanding of PAs or raster-grid pathology generation mechanisms, which include static intensity (SI) as an important cause of PAs. The PASA employs a gradient descent scheme to iteratively separate the SI pattern from original datasets and a probe support constraint applied in the object update. Both simulative and experimental data reconstructions demonstrated the effectiveness of the new algorithm in suppressing PAs and improving ptychography resolution and indicated a better performance of the PASA method in PA removal compared to other mainstream algorithms. In the meantime, we provided a complete description of SI conception and its key role in PA generation. The present work enhances the feasibility of raster-scan ptychography and could inspire new thoughts for dealing with various noises in ptychography.
Effect of Deep Placement Fertilization on the Distribution of Biomass, Nutrients, and Root System Development in Potato Plants
Authors: Niedziński Tomasz , Rutkowska Beata , Łabętowicz Jan , Szulc Wiesław
Published: May 2023

The study was carried out in designed pots—rhizoboxes. Root systems were evaluated using computer scanning to determine total length, root area, and root diameter. The study showed a favorable effect of deep placement of fertilizers on total yield, increasing biomass yield by 7–17% relative to surface fertilization. The largest biomass increase under the influence of deep fertilization was obtained in the case of tuber yield, in which a yield increase of 18–34% was obtained. Higher yields of potato tubers were obtained under depth fertilization compared to surface application of fertilizers. Under the influence of deep fertilization at a depth of 20 cm, the uptake of nitrogen and phosphorus by potato biomass increased by 20–21%. Increased depth of fertilization increased the proportion of nitrogen accumulated in the tubers, while in the case of phosphorus, no effect of depth on P distribution was shown. An analysis of root system parameters showed a positive effect on increases in length and total root area under deep fertilization of potato plants. Based on the study, it was found that the distribution of dry matter, nutrients, and potato root development parameters were most optimal when fertilizer granules were applied at a depth of 20 cm.
ChIP-Based Nuclear DNA Isolation for Genome Sequencing in Pyropia to Remove Cytosol and Bacterial DNA Contamination
Authors: Zhang Zehao , Wang Junhao , Zhang Xiaoqian , Guan Xiaowei , Gao Tian , Mao Yunxiang , Poetsch Ansgar , Wang Dongmei
Published: May 2023

Contamination from cytosolic DNA (plastid and mitochondrion) and epiphytic bacteria is challenging the efficiency and accuracy of genome-wide analysis of nori-producing marine seaweed Pyropia yezoensis. Unlike bacteria and organellar DNA, Pyropia nuclear DNA is closely associated with histone proteins. In this study, we applied Chromatin Immunoprecipitation (ChIP) of histone H3 to isolate nuclear DNA, followed by high-throughput sequencing. More than 99.41% of ChIP-sequencing data were successfully aligned to the reference nuclear genome; this was remarkably higher than those from direct extraction and direct extraction data, in which 40.96% to 42.95% are from plastids. The proportion of data that were mapped to the bacterial database when using ChIP extraction was very low. Additionally, ChIP data can cover up to 89.00% of the nuclear genome, higher than direct extraction data at equal data size and comparable to the latter at equal sequencing depth. The uncovered regions from the three methods are mostly overlapping, suggesting that incomplete sequencing accounts for the missing data, rather than failed chromatin-antibody binding in the ChIP extraction method. This ChIP extraction method can successfully separate nuclear DNA from cytosolic DNA and bacterial DNA, thus overwhelmingly reducing the sequencing cost in a genome resequencing project and providing strictly purified reference data for genome assembly. The method’s applicability to other macroalgae makes it a valuable contribution to the algal research community.
Morpho-Physiological Evaluation of Solanum betaceum Cav. In Vitro Cloned Plants: A Comparison of Different Micropropagation Methods
Authors: Correia Mariana , Lopes Tércia , Puga Ana Patrícia , Pinto Glória , Canhoto Jorge , Correia Sandra
Published: May 2023

Tamarillo (Solanum betaceum Cav.) is a subtropical solanaceous tree with increasing agronomic interest due to its nutritious edible fruits. Growing demand for tamarillo plants and fruits requires optimization of existing propagation methods and scaled-up systems for large-scale cloning of selected germplasm. Three in vitro protocols have been used to micropropagate tamarillo: (1) axillary shoot proliferation in a semisolid medium, (2) organogenesis, and (3) somatic embryogenesis procedures. Variables such as the age of the established shoot cultures and rooting treatments were also analyzed. The morphological and physiological quality of acclimatized plants derived from all the methodologies were compared, with seed-derived plants used as a control group. Overall, the results show that in vitro-derived plants have a similar development to seed-derived plants. Micropropagation by axillary shoot proliferation was highly efficient, with rooting rates above 80% in most treatments. Organogenesis induction was more effective from lamina explants using MS media with 2.0 mg·L−1 6-benzylaminopurine. Both organogenesis and somatic embryogenesis-derived plants were also morphologically and physiologically equivalent to seed and axillary shoot-derived plants. The specificities of each micropropagation method are discussed.
Theoretical Analyses of Turgor Pressure during Stress Relaxation and Water Uptake, and after Changes in Expansive Growth Rate When Water Uptake Is Normal and Reduced
Authors: Ortega Joseph K. E.
Published: May 2023

Turgor pressure provides the force needed to stress and deform the cell walls of plants, algae, and fungi during expansive growth. However, turgor pressure plays another subtle but equally important role in expansive growth of walled cells: it connects the two biophysical processes of water uptake and wall deformation to ensure that the volumetric rates of water uptake and enlargement of the cell wall chamber are equal. In this study, the role of turgor pressure as a ‘connector’ is investigated analytically by employing validated and established biophysical equations. The objective is to determine the effect of ‘wall loosening’ on the magnitude of turgor pressure. It is known that an increase or decrease in turgor pressure and/or wall loosening rate increases or decreases the expansive growth rate, respectively. Interestingly, it is shown that an increase in the wall loosening rate decreases the turgor pressure slightly, thus reducing the effect of wall loosening on increasing the expansive growth rate. Other analyses reveal that reducing the rate of water uptake results in a larger decrease in turgor pressure with the same increase in wall loosening rate, which further reduces the effect of wall loosening on increasing the expansive growth rate.