bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerium Oxide Nanorods Synthesized by Dalbergia sissoo Extract for Antioxidant, Cytotoxicity, and Photocatalytic Applications
Authors: Alam Mir Waqas , Naeem Sumaira , Usman Sheikh Muhammad , Kanwal Qudsia , BaQais Amal , Aldughaylibi Fatimah Saeed , Nahvi Insha , Zaidi Noushi
Published: November 2022

In this study, cerium oxide nanorods (CeO2-NRs) were synthesized by using the phytochemicals present in the Dalbergia sissoo extract. The physiochemical characteristics of the as-prepared CeO2-NRs were investigated by using ultraviolet-visible spectroscopy (UV-VIS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction analysis (XRD). The SEM and UV-VIS analyses revealed that the acquired nanomaterials possessed a rod-like morphology while the XRD results further confirmed that the synthesized NRs exhibited a cubic crystal lattice system. The antioxidant capacity of the synthesized CeO2-NRs was investigated by using several in vitro biochemical assays. It was observed that the synthesized NRs exhibited better antioxidant potential in comparison to the industrial antioxidant of the butylated hydroxyanisole (BHA) in 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The biochemical assays, including lipid peroxidation (LPO), total antioxidant capacity (TAC), and catalase activity (CAT), were also performed in the human lymphocytes incubated with the CeO2-NRs to investigate the impact of the NRs on these oxidative biomarkers. Enhanced reductive capabilities were observed in all the assays, revealing that the NRs possess excellent antioxidant properties. Moreover, the cytotoxic potential of the CeO2-NRs was also investigated with the MTT assay. The CeO2-NRs were found to effectively kill off the cancerous cells (MCF-7 human breast cancer cell line), further indicating that the synthesized NRs exhibit anticancer potential as well. One of the major applications studied for the prepared CeO2-NRs was performing the statistical optimization of the photocatalytic degradation reaction of the methyl orange (MO) dye. The reaction was optimized by using the technique of response surface methodology (RSM). This advanced approach facilitates the development of the predictive model on the basis of central composite design (CCD) for this degradation reaction. The maximum degradation of 99.31% was achieved at the experimental optimized conditions, which corresponded rather well with the predicted percentage degradation values of 99.58%. These results indicate that the developed predictive model can effectively explain the performed experimental reaction. To conclude, the CeO2-NRs exhibited excellent results for multiple applications.
Theoretical Study of Hydrogen Production from Ammonia Borane Catalyzed by Metal and Non-Metal Diatom-Doped Cobalt Phosphide
Authors: Li Dong-Heng , Li Qiao-Mei , Qi Shuang-Ling , Qin Hai-Chuan , Liang Xiao-Qin , Li Laicai
Published: November 2022

The decomposition of ammonia borane (NH3BH3) to produce hydrogen has developed a promising technology to alleviate the energy crisis. In this paper, metal and non-metal diatom-doped CoP as catalyst was applied to study hydrogen evolution from NH3BH3 by density functional theory (DFT) calculations. Herein, five catalysts were investigated in detail: pristine CoP, Ni- and N-doped CoP (CoPNi-N), Ga- and N-doped CoP (CoPGa-N), Ni- and S-doped CoP (CoPNi-S), and Zn- and S-doped CoP (CoPZn-S). Firstly, the stable adsorption structure and adsorption energy of NH3BH3 on each catalytic slab were obtained. Additionally, the charge density differences (CDD) between NH3BH3 and the five different catalysts were calculated, which revealed the interaction between the NH3BH3 and the catalytic slab. Then, four different reaction pathways were designed for the five catalysts to discuss the catalytic mechanism of hydrogen evolution. By calculating the activation energies of the control steps of the four reaction pathways, the optimal reaction pathways of each catalyst were found. For the five catalysts, the optimal reaction pathways and activation energies are different from each other. Compared with undoped CoP, it can be seen that CoPGa-N, CoPNi-S, and CoPZn-S can better contribute hydrogen evolution from NH3BH3. Finally, the band structures and density of states of the five catalysts were obtained, which manifests that CoPGa-N, CoPNi-S, and CoPZn-S have high-achieving catalytic activity and further verifies our conclusions. These results can provide theoretical references for the future study of highly active CoP catalytic materials.
Pharmacokinetic Comparison of Eight Major Compounds of Lonicerae japonicae flos after Oral Administration in Normal Rats and Rats with Liver Injury
Authors: Wang Xuejiao , Liu Songtao , Yang Lin , Dong Jiaojiao , Zhang Shihao , Lv Jiahao , Yang Liu , Jiang Hai
Published: November 2022

Traditional Chinese medicine considers Lonicerae japonicae flos to have antibacterial detoxification, liver protection, and gallbladder protection. At present, studies have proven that Lonicerae japonicae flos has a good therapeutic effect on liver injury. Therefore, to confirm the clinical applicability of Lonicerae japonicae flos in the treatment of liver injury, we were the first to compare the pharmacokinetics of an oral ethanol extract of Lonicerae japonicae flos in normal rats and carbon tetrachloride-induced liver injury model rats. A method was developed for the simultaneous determination of 3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, protocatechuic acid, Sweroside, and Secoxyloganin in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry. The results show that the method is reliable and reproducible and can be used for quantitative determination of biological samples. The pharmacokinetic parameters showed that the area under the concentration–time curve of eight compounds in the model group was significantly increased. The results showed that the total absorption of the active components of Lonicerae japonicae flos in the blood increased, the clearance rate slowed down, and the bioavailability of Lonicerae japonicae flos increased in liver injury diseases.
Design of Nanostructured Hybrid Electrodes Based on a Liquid Crystalline Zn(II) Coordination Complex-Carbon Nanotubes Composition for the Specific Electrochemical Sensing of Uric Acid
Authors: Negrea Sorina , Andelescu Adelina A. , Ilies (b. Motoc) Sorina , Cretu Carmen , Cseh Liliana , Rastei Mircea , Donnio Bertrand , Szerb Elisabeta I. , Manea Florica
Published: November 2022

A metallomesogen based on an Zn(II) coordination complex was employed as precursor to obtain a complex matrix nanoplatform for the fabrication of a high-performance electrochemical hybrid sensor. Three representative paste electrodes, which differ by the weight ratio between Zn(II) metallomesogen and carbon nanotubes (CNT), i.e., PE_01, PE_02 and PE_03, were obtained by mixing the materials in different amounts. The composition with the largest amount of CNT with respect to Zn complex, i.e., PE_03, gives the best electrochemical signal for uric acid detection by cyclic voltammetry in an alkaline medium. The amphiphilic structure of the Zn(II) coordination complex likely induces a regular separation between the metal centers favoring the redox system through their reduction, followed by stripping, and is characterized by enhanced electrocatalytic activity towards uric acid oxidation. The comparative detection of uric acid between the PE_03 paste electrode and the commercial zinc electrode demonstrated the superiority of the former, and its great potential for the development of advanced electrochemical detection of uric acid. Advanced electrochemical techniques, such as differential-pulsed voltammetry (DPV) and square-wave voltammetry (SWV), allowed for the highly sensitive detection of uric acid in aqueous alkaline solutions. In addition, a good and fast amperometric signal for uric acid detection was achieved by multiple-pulsed amperometry, which was validated by urine analysis.
Plasmonic Sensing and Switches Enriched by Tailorable Multiple Fano Resonances in Rotational Misalignment Metasurfaces
Authors: Xu Xiaofeng , Luo Xiao-Qing , Liu Qinke , Li Yan , Zhu Weihua , Chen Zhiyong , Liu Wuming , Wang Xin-Lin
Published: November 2022

Fano resonances that feature strong field enhancement in the narrowband range have motivated extensive studies of light–matter interactions in plasmonic nanomaterials. Optical metasurfaces that are subject to different mirror symmetries have been dedicated to achieving nanoscale light manipulation via plasmonic Fano resonances, thus enabling advantages for high-sensitivity optical sensing and optical switches. Here, we investigate the plasmonic sensing and switches enriched by tailorable multiple Fano resonances that undergo in-plane mirror symmetry or asymmetry in a hybrid rotational misalignment metasurface, which consists of periodic metallic arrays with concentric C-shaped- and circular-ring-aperture unit cells. We found that the plasmonic double Fano resonances can be realized by undergoing mirror symmetry along the X-axis. The plasmonic multiple Fano resonances can be tailored by adjusting the level of the mirror asymmetry along the Z-axis. Moreover, the Fano-resonance-based plasmonic sensing that suffer from mirror symmetry or asymmetry can be implemented by changing the related structural parameters of the unit cells. The passive dual-wavelength plasmonic switches of specific polarization can be achieved within mirror symmetry and asymmetry. These results could entail benefits for metasurface-based devices, which are also used in sensing, beam-splitter, and optical communication systems.
Laser-Induced µ-Rooms for Osteocytes on Implant Surface: An In Vivo Study
Authors: Veiko Vadim , Karlagina Yuliya , Zernitckaia Ekaterina , Egorova Elena , Radaev Maxim , Yaremenko Andrey , Chernenko Gennadiy , Romanov Valery , Shchedrina Nadezhda , Ivanova Elena , Chichkov Boris , Odintsova Galina
Published: November 2022

Laser processing of dental implant surfaces is becoming a more widespread replacement for classical techniques due to its undeniable advantages, including control of oxide formation and structure and surface relief at the microscale. Thus, using a laser, we created several biomimetic topographies of various shapes on the surface of titanium screw-shaped implants to research their success and survival rates. A distinctive feature of the topographies is the presence of “µ-rooms”, which are special spaces created by the depressions and elevations and are analogous to the µ-sized room in which the osteocyte will potentially live. We conducted the comparable in vivo study using dental implants with continuous (G-topography with µ-canals), discrete (S-topography with μ-cavities), and irregular (I-topography) laser-induced topographies. A histological analysis performed with the statistical method (with p-value less than 0.05) was conducted, which showed that G-topography had the highest BIC parameter and contained the highest number of mature osteocytes, indicating the best secondary stability and osseointegration.
Overview of Advanced Micro-Nano Manufacturing Technologies for Triboelectric Nanogenerators
Authors: Huang Xinlong , Qi Youchao , Bu Tianzhao , Li Xinrui , Liu Guoxu , Zeng Jianhua , Fan Beibei , Zhang Chi
Published: November 2022

In the era of the Internet of Things, various electronics play an important role in information interaction, in which the power supply is an urgent problem to be solved. Triboelectric nanogenerator (TENG) is an emerging mechanical energy harvesting technology that can serve as a power source for electronics, which is developing towards high performance, miniaturization and integration. Herein, the advanced micro-nano manufacturing technologies are systematically reviewed for TENGs. First, film preparation such as physical vapor deposition, chemical vapor deposition, electrochemical deposition, electrospinning and screen printing for triboelectric layers are introduced and discussed. Then, surface processing, such as soft lithography, laser ablation, inductively coupled plasma and nanoimprint for micro-nano structures on the surface of triboelectric layers are also introduced and discussed. In addition, micro-electromechanical system fabrication for TENG devices such as acoustic and vibration sensors, is introduced, and their current challenges are analyzed. Finally, the challenges of the advanced micro-nano manufacturing technologies for the TENGs are systematically summarized, and further development is prospected.
Temporal Trends in Incidence of Nutritional Deficiency among Older Adults in China: A Secondary Analysis of the Global Burden of Disease Study 1990–2019
Authors: Xiao Linqi , Fu Jialin , Lin Likai , Han Yong
Published: November 2022

Nutritional deficiency is prevalent among the elderly, and it is associated with many adverse health consequences. China is rapidly moving toward an aging society with a large population; however, evidence on the epidemiological trends in nutritional deficiency among the Chinese elderly is limited. Data on the incidence of nutritional deficiency among Chinese adults aged 65 years or above from 1990 to 2019 were extracted from the Global Burden of Disease 2019 database. We used the joinpoint regression method to estimate the average annual percentage change (AAPC) and to describe trend patterns. Age, period, and cohort effects were determined using age–period–cohort models. From 1990 to 2019, the incidence of vitamin A deficiency and iodine deficiency among Chinese older adults decreased from 1784.12 and 8.20 to 304.27 and 7.26 per 100,000, with AAPCs of −0.41 (−0.44, −0.38)% and −5.86 (−6.29, −5.43)%, respectively. A continually increasing trend was seen for incidence rates of protein-energy malnutrition, from 1342.02 to 2275.87 per 100,000 person-years, with an AAPC of 1.70 (1.40, 2.01)%. These trends were more pronounced among men than women. A strong age effect and birth cohort effect were present. Specifically, the population that was older or born later had a lower incidence of deficiencies in vitamin A and iodine but a higher incidence of protein-energy malnutrition. The results show a substantial reduction in vitamin A and iodine deficiencies among the Chinese elderly, and health policies and public awareness are needed to address the burden of protein-energy malnutrition in this population.
The Association between Maternal B Vitamins in Early Pregnancy and Gestational Diabetes Mellitus: A Prospective Cohort Study
Authors: Wang Na , Zhou Tianchun , Ma Xiaoxia , Lin Yuping , Ding Yan
Published: November 2022

Background: This study evaluated the association between maternal B vitamins in early pregnancy and gestational diabetes mellitus (GDM) risk. Methods: A cohort of 1265 pregnant women was recruited at 8–15 weeks of gestation in 2021–2022 (Shanghai, China). Pregnancies with both serum B vitamin measurements at recruitment and glucose measurements at 24–28 weeks of gestation were included in the final analysis. Results: Of the 1065 pregnancies, in the final analysis, GDM occurred in 121 women (11.36%). In multivariate logistic models, an increased risk trend across serum vitamin B1 quartiles with GDM was observed (p-Trend = 0.001). Compared with women in the lowest quartile of serum vitamin B6, those in the upper two quartiles had approximately twofold higher odds of GDM. Moreover, compared with women with vitamin B12 levels < 150 pmol/L, those with vitamin B12 levels > 150 pmol/L had lower odds of GDM (p = 0.005). The restricted cubic spline regression models also revealed that serum vitamin B6 and vitamin B12 were associated with an increased risk of GDM in a nonlinear fashion. Conclusions: Our study shows that higher maternal serum vitamin B1 and B6 levels in early pregnancy are associated with increased GDM risk, while sufficient vitamin B12 status is associated with lower GDM risk.
Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
Authors: Chen Ying , Tian Peijun , Wang Zheng , Pan Ruili , Shang Kexin , Wang Gang , Zhao Jianxin , Chen Wei
Published: November 2022

Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic mild stress (UCMS) was used to assess the effects of IAA administration (50 mg/kg). Treatment with IAA for 5 weeks attenuated depression and anxiety-like behaviours, improved hypothalamus–pituitary–adrenal axis dysfunction and increased brain-derived neurotrophic factor expression. IAA supplementation also enhanced the serotonin pathway in the brain and gut. UCMS caused an imbalance of microbial indole metabolites in the colon, whereas IAA treatment reversed this. However, IAA intake did not affect the concentrations of indoles in the brain. Intestinal bacteria in different sections of the gut were altered by IAA treatment, with the colon showing more changes than other segments. The gut microbiome in the colon had increased proportions of Ruminococcaceae UCG013, Ruminiclostridium 6, Prevotella, Alloprevotella and Bacteroides species, which can produce short-chain fatty acids and indole derivatives. Cumulatively, our study highlights the potential of IAA treatment to alleviate mood disorders and offers a theoretical basis for understanding the antidepressant effects of IAA.
Does Timing Matter? A Narrative Review of Intermittent Fasting Variants and Their Effects on Bodyweight and Body Composition
Authors: Aragon Alan A. , Schoenfeld Brad J.
Published: November 2022

The practice of fasting recently has been purported to have clinical benefits, particularly as an intervention against obesity and its related pathologies. Although a number of different temporal dietary restriction strategies have been employed in practice, they are generally classified under the umbrella term “intermittent fasting” (IF). IF can be stratified into two main categories: (1) intra-weekly fasting (alternate-day fasting/ADF, twice-weekly fasting/TWF) and (2) intra-daily fasting (early time-restricted eating/eTRE and delayed time-restricted eating/dTRE). A growing body of evidence indicates that IF is a viable alternative to daily caloric restriction (DCR), showing effectiveness as a weight loss intervention. This paper narratively reviews the literature on the effects of various commonly used IF strategies on body weight and body composition when compared to traditional DCR approaches, and draws conclusions for their practical application. A specific focus is provided as to the use of IF in combination with regimented exercise programs and the associated effects on fat mass and lean mass.
Assessing Consumer Willingness to Pay for Nutritional Information Using a Dietary App
Authors: Sadrmousavigargari Seyyedehsara , Cubero Dudinskaya Emilia , Mandolesi Serena , Naspetti Simona , Mojaverian Seyed Mojtaba , Zanoli Raffaele
Published: November 2022

A healthy society is the foundation of development in every country, and one way to achieve a healthy society is to promote healthy nutrition. An unbalanced diet is one of the leading causes of noncommunicable diseases globally. If food was correctly selected and correctly consumed, both the problems of overeating and lack of nutrition could be largely solved while also decreasing public health costs. Interventions such as presenting necessary information and warning labels would help consumers make better food choices. Hence, providing nutritional information to consumers becomes essential. The present study investigates the importance of nutrition information labels on consumers’ preferences by estimating their willingness to pay for features and information provided by a dietary software program (app). An application can easily display the information to the consumers and help them make informed food choices. A discrete choice experiment investigated consumers’ preferences and willingness to pay to receive nutritional information. Mixed multinomial logit and latent class analysis were applied. The results showed the existence of heterogeneity in consumer preferences for different nutritional information provided by the application. Consumers are willing to pay more for salt and fat alerts. The results of this study allow for the analysis of consumers’ interest in nutritional information. Such results are essential for the industry for future investments in similar applications that potentially could help consumers make better informed choices.
Non-Digestible Oligosaccharides: A Novel Treatment for Respiratory Infections?
Authors: Cai Yang , Folkerts Gert , Braber Saskia
Published: November 2022

Emerging antimicrobial resistance in respiratory infections requires novel intervention strategies. Non-digestible oligosaccharides (NDOs) are a diverse group of carbohydrates with broad protective effects. In addition to promoting the colonization of beneficial gut microbiota and maintaining the intestinal homeostasis, NDOs act as decoy receptors, effectively blocking the attachment of pathogens on host cells. NDOs also function as a bacteriostatic agent, inhibiting the growth of specific pathogenic bacteria. Based on this fact, NDOs potentiate the actions of antimicrobial drugs. Therefore, there is an increasing interest in characterizing the anti-infective properties of NDOs. This focused review provides insights into the mechanisms by which representative NDOs may suppress respiratory infections by targeting pathogens and host cells. We summarized the most interesting mechanisms of NDOs, including maintenance of gut microbiota homeostasis, interference with TLR-mediated signaling, anti-oxidative effects and bacterial toxin neutralization, bacteriostatic and bactericidal effects, and anti-adhesion or anti-invasive properties. A detailed understanding of anti-infective mechanisms of NDOs against respiratory pathogens may contribute to the development of add-on therapy or alternatives to antimicrobials.
Plasma FGF21 Levels Are Not Associated with Weight Loss or Improvements in Metabolic Health Markers upon 12 Weeks of Energy Restriction: Secondary Analysis of an RCT
Authors: Gijbels Anouk , Schutte Sophie , Esser Diederik , Michielsen Charlotte C. J. R. , Siebelink Els , Mars Monica , Mensink Marco , Afman Lydia A.
Published: November 2022

Recent studies suggest that circulating fibroblast growth factor 21 (FGF21) may be a marker of metabolic health status. We performed a secondary analysis of a 12-week randomized controlled trial to investigate the effects of two energy restriction (ER) diets on fasting and postprandial plasma FGF21 levels, as well as to explore correlations of plasma FGF21 with metabolic health markers, (macro)nutrient intake and sweet-taste preference. Abdominally obese subjects aged 40–70 years (n = 110) were randomized to one of two 25% ER diets (high-nutrient-quality diet or low-nutrient-quality diet) or a control group. Plasma FGF21 was measured in the fasting state and 120 min after a mixed meal. Both ER diets did not affect fasting or postprandial plasma FGF21 levels despite weight loss and accompanying health improvements. At baseline, the postprandial FGF21 response was inversely correlated to fasting plasma glucose (ρ = −0.24, p = 0.020) and insulin (ρ = −0.32, p = 0.001), HOMA-IR (ρ = −0.34, p = 0.001), visceral adipose tissue (ρ = −0.24, p = 0.046), and the liver enzyme aspartate aminotransferase (ρ = −0.23, p = 0.021). Diet-induced changes in these markers did not correlate to changes in plasma FGF21 levels upon intervention. Baseline higher habitual polysaccharide intake, but not mono- and disaccharide intake or sweet-taste preference, was related to lower fasting plasma FGF21 (p = 0.022). In conclusion, we found no clear evidence that fasting plasma FGF21 is a marker for metabolic health status. Circulating FGF21 dynamics in response to an acute nutritional challenge may reflect metabolic health status better than fasting levels.
Effects of Ingesting Both Catechins and Chlorogenic Acids on Glucose, Incretin, and Insulin Sensitivity in Healthy Men: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial
Authors: Yanagimoto Aya , Matsui Yuji , Yamaguchi Tohru , Hibi Masanobu , Kobayashi Shigeru , Osaki Noriko
Published: November 2022

Epidemiologic studies have revealed that consuming green tea or coffee reduces diabetes risk. We evaluated the effects of the combined consumption of green tea catechins and coffee chlorogenic acids (GTC+CCA) on postprandial glucose, the insulin incretin response, and insulin sensitivity. Eleven healthy men were recruited for this randomized, double-blinded, placebo-controlled crossover trial. The participants consumed a GTC+CCA-enriched beverage (620 mg GTC, 373 mg CCA, and 119 mg caffeine/day) for three weeks; the placebo beverages (PLA) contained no GTC or CCA (PLA: 0 mg GTC, 0 mg CCA, and 119 mg caffeine/day). Postprandial glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) responses were measured at baseline and after treatments. GTC+CCA consumption for three weeks showed a significant treatment-by-time interaction on glucose changes after the ingestion of high-fat and high-carbohydrate meals, however, it did not affect fasting glucose levels. Insulin sensitivity was enhanced by GCT+CCA compared with PLA. GTC+CCA consumption resulted in a significant increase in postprandial GLP-1 and a decrease in GIP compared to PLA. Consuming a combination of GTC and CCA for three weeks significantly improved postprandial glycemic control, GLP-1 response, and postprandial insulin sensitivity in healthy individuals and may be effective in preventing diabetes.
Recovering the Conformal Limit of Color Superconducting Quark Matter within a Confining Density Functional Approach
Authors: Ivanytskyi Oleksii , Blaschke David B.
Published: November 2022

We generalize a recently proposed confining relativistic density-functional approach to the case of density-dependent vector and diquark couplings. The particular behavior of these couplings is motivated by the non-perturbative gluon exchange in dense quark matter and provides the conformal limit at asymptotically high densities. We demonstrate that this feature of the quark matter EoS is consistent with a significant stiffness in the density range typical for the interiors of neutron stars. In order to model these astrophysical objects, we construct a family of hybrid quark-hadron EoSs of cold stellar matter. We also confront our approach with the observational constraints on the mass–radius relation of neutron stars and their tidal deformabilities and argue in favor of a quark matter onset at masses below 1.0M⊙.
Biliary Sepsis Due to Recurrent Acute Calculus Cholecystitis (ACC) in a High Surgical-Risk Elderly Patient: An Unexpected Complication
Authors: Sermonesi Giacomo , Rampini Alessia , Convertini Girolamo , Bova Raffaele , Zanini Nicola , Bertelli Riccardo , Vallicelli Carlo , Favi Francesco , Stacchini Giacomo , Faccani Enrico , Fabbri Nicola , Catena Fausto
Published: November 2022

Acute calculus cholecystitis (ACC) is increasing in frequency within an ageing population, in which biliary tract infection, including cholecystitis and cholangitis, is the second most common cause of sepsis, with higher morbidity and mortality rates. Patient’s critical conditions, such as septic shock or anaesthesiology contraindication, may be reasons to avoid laparoscopic cholecystectomy—the first-line treatment of ACC—preferring gallbladder drainage. It can aid in patient’s stabilization with also the benefit of identifying the causative organism to establish a targeted antibiotic therapy, especially in patients at high risk for antimicrobial resistance such as healthcare-associated infection. Nevertheless, a recent randomized clinical trial showed that laparoscopic cholecystectomy can reduce the rate of major complications compared with percutaneous catheter drainage in critically ill patients too. On the other hand, among the possibilities to control biliary sepsis in non-operative management of ACC, according to recent meta-analysis, endoscopic gallbladder drainage showed better clinical success rate, and it is gaining popularity because of the potential advantage of allowing gallstones clearance to reduce recurrences of ACC. However, complications that may arise, although rare, can worsen an already weak clinical condition, as happened to the high surgical-risk elderly patient taken into account in our case report.
Norbornene and Related Structures as Scaffolds in the Search for New Cancer Treatments
Authors: Calvo-Martín Gorka , Plano Daniel , Martínez-Sáez Nuria , Aydillo Carlos , Moreno Esther , Espuelas Socorro , Sanmartín Carmen
Published: November 2022

The norbornene scaffold has arisen as a promising structure in medicinal chemistry due to its possible therapeutic application in cancer treatment. The development of norbornene-based derivatives as potential chemotherapeutic agents is attracting significant attention. Here, we report an unprecedented review on the recent advances of investigations into the antitumoral efficacy of different compounds, including the abovementioned bicyclic scaffold in their structure, in combination with chemotherapeutic agents or forming metal complexes. The impact that structural modifications to these bicyclic compounds have on the antitumoral properties and the mechanisms by which these norbornene derivatives act are discussed in this review. In addition, the use of norbornene, and its related compounds, encapsulation in nanosystems for its use in cancer therapies is here detailed.
Introduction of a SiFA Moiety into the D-Glutamate Chain of DOTA-PP-F11N Results in Radiohybrid-Based CCK-2R-Targeted Compounds with Improved Pharmacokinetics In Vivo
Authors: Holzleitner Nadine , Günther Thomas , Beck Roswitha , Lapa Constantin , Wester Hans-Jürgen
Published: November 2022

In order to enable 18F- and 177Lu-labelling within the same molecule, we introduced a silicon-based fluoride acceptor (SiFA) into the hexa-D-glutamate chain of DOTA-PP-F11N. In addition, minigastrin analogues with a prolonged as well as γ-linked D-glutamate chain were synthesised and evaluated. CCK-2R affinity (IC50, AR42J cells) and lipophilicity (logD7.4) were determined. Biodistribution studies at 24 h post-injection (p.i.) and µSPECT/CT imaging at 1, 4 and 24 h p.i. were carried out in AR42J tumour-bearing CB17-SCID mice. CCK-2R affinity of (R)-DOTAGA-rhCCK-1 to 18 was enhanced with increasing distance between the SiFA building block and the binding motif. Lipophilicity of [177Lu]Lu-(R)-DOTAGA-rhCCK-1 to 18 was higher compared to that of [177Lu]Lu-DOTA-PP-F11N and [177Lu]Lu-CP04. The respective α- and γ-linked rhCCK derivatives revealing the highest CCK-2R affinity were further evaluated in vivo. In comparison with [177Lu]Lu-DOTA-PP-F11N, [177Lu-]Lu-(R)-DOTAGA-rhCCK-9 and -16 exhibited three- to eight-fold increased activity levels in the tumour at 24 h p.i. However, activity levels in the kidneys were elevated as well. We could show that the introduction of a lipophilic SiFA moiety into the hydrophilic backbone of [177Lu]Lu-DOTA-PP-F11N led to a decelerated blood clearance and thus improved tumour retention. However, elevated kidney retention has to be addressed in future studies.
Effect of Structural Differences in Naringenin, Prenylated Naringenin, and Their Derivatives on the Anti-Influenza Virus Activity and Cellular Uptake of Their Flavanones
Authors: Morimoto Ryosuke , Matsubara Chiaki , Hanada Akari , Omoe Yuta , Ogata Tokutaro , Isegawa Yuji
Published: November 2022

Vaccines and antiviral drugs are widely used to treat influenza infection. However, they cannot rapidly respond to drug-resistant viruses. Therefore, new anti-influenza virus strategies are required. Naringenin is a flavonoid with potential for new antiviral strategies. In this study, we evaluated the antiviral effects of naringenin derivatives and examined the relationship between their cellular uptake and antiviral effects. Madin–Darby canine kidney (MDCK) cells were infected with the A/PR/8/34 strain and exposed to the compound-containing medium for 24 h. The amount of virus in the supernatant was calculated using focus-forming reduction assay. Antiviral activity was evaluated using IC50 and CC50 values. Cells were exposed to a constant concentration of naringenin or prenylated naringenin, and intracellular uptake and distribution were evaluated using a fluorescence microscope. Prenylated naringenin showed strong anti-influenza virus effects, and the amount of intracellular uptake was revealed by the strong intracellular fluorescence. In addition, intracellular distribution differed depending on the position of the prenyl group. The steric factor of naringenin is deeply involved in influenza A virus activity, and prenyl groups are desirable. Furthermore, the prenyl group affects cellular affinity, and the uptake mechanism differs depending on its position. These results provide important information on antiviral strategies.
A Simple Preparation Method of Gelatin Hydrogels Incorporating Cisplatin for Sustained Release
Authors: Suzuki Takahisa , Tsunoda Shigeru , Yamashita Kota , Kuwahara Toshie , Ando Mitsuru , Tabata Yasuhiko , Obama Kazutaka
Published: November 2022

The objective of this study was to develop a new preparation method for cisplatin (CDDP)-incorporated gelatin hydrogels without using chemical crosslinking nor a vacuum heating instrument for dehydrothermal crosslinking. By simply mixing CDDP and gelatin, CDDP-crosslinked gelatin hydrogels (CCGH) were prepared. CDDP functions as a crosslinking agent of gelatin to form the gelatin hydrogel. Simultaneously, CDDP is incorporated into the gelatin hydrogel as a controlled release carrier. CDDP’s in vitro and in vivo anticancer efficacy after incorporation into CCGH was evaluated. In the in vitro system, the CDDP was released gradually due to CCGH degradation with an initial burst release of approximately 16%. CDDP metal-coordinated with the degraded fragment of gelatin was released from CCGH with maintaining the anticancer activity. After intraperitoneal administration of CCGH, CDDP was detected in the blood circulation while its toxicity was low. Following intraperitoneal administration of CCGH in a murine peritoneal dissemination model of human gastric cancer MKN45-Luc cell line, the survival time was significantly prolonged compared with free CDDP solution. It is concluded that CCGH prepared by the CDDP-based crosslinking of gelatin is an excellent sustained release system of CDDP to achieve superior anticancer effects with minimal side effects compared with free CDDP solution.
Evading Doxorubicin-Induced Systemic Immunosuppression Using Ultrasound-Responsive Liposomes Combined with Focused Ultrasound
Authors: Lee Jeongjin , Um Wooram , Moon Hyungwon , Joo Hyeyeon , Song Yeari , Park Minsung , Yoon Been , Kim Hyun-Ryoung , Park Jae Hyung
Published: November 2022

Doxorubicin (DOX) is a representative anticancer drug with a unique ability to induce immunogenic cell death of cancer cells. However, undesired toxicity on immune cells has remained a significant challenge, hindering the usage of DOX in cancer immunotherapy. Here, we report a combined therapy to avoid the off-target toxicity of DOX by adapting ultrasound-responsive liposomal doxorubicin and focused ultrasound exposure. Histological analysis demonstrated that the combined therapy induced less hemosiderosis of splenocytes and improved tumor infiltration of cytotoxic T lymphocytes. Additionally, in vivo therapeutic evaluation results indicate that the combined therapy achieved higher efficacy when combined with PD-1 immune-checkpoint blockade therapy by improving immunogenicity.
Prediction of Drug–Drug–Gene Interaction Scenarios of (E)-Clomiphene and Its Metabolites Using Physiologically Based Pharmacokinetic Modeling
Authors: Kovar Christina , Kovar Lukas , Rüdesheim Simeon , Selzer Dominik , Ganchev Boian , Kröner Patrick , Igel Svitlana , Kerb Reinhold , Schaeffeler Elke , Mürdter Thomas E. , Schwab Matthias , Lehr Thorsten
Published: November 2022

Clomiphene, a selective estrogen receptor modulator (SERM), has been used for the treatment of anovulation for more than 50 years. However, since (E)-clomiphene ((E)-Clom) and its metabolites are eliminated primarily via Cytochrome P450 (CYP) 2D6 and CYP3A4, exposure can be affected by CYP2D6 polymorphisms and concomitant use with CYP inhibitors. Thus, clomiphene therapy may be susceptible to drug–gene interactions (DGIs), drug–drug interactions (DDIs) and drug–drug–gene interactions (DDGIs). Physiologically based pharmacokinetic (PBPK) modeling is a tool to quantify such DGI and DD(G)I scenarios. This study aimed to develop a whole-body PBPK model of (E)-Clom including three important metabolites to describe and predict DGI and DD(G)I effects. Model performance was evaluated both graphically and by calculating quantitative measures. Here, 90% of predicted Cmax and 80% of AUClast values were within two-fold of the corresponding observed value for DGIs and DD(G)Is with clarithromycin and paroxetine. The model also revealed quantitative contributions of different CYP enzymes to the involved metabolic pathways of (E)-Clom and its metabolites. The developed PBPK model can be employed to assess the exposure of (E)-Clom and its active metabolites in as-yet unexplored DD(G)I scenarios in future studies.
Cavitation Feedback Control of Focused Ultrasound Blood-Brain Barrier Opening for Drug Delivery in Patients with Parkinson’s Disease
Authors: Huang Yuexi , Meng Ying , Pople Christopher B. , Bethune Allison , Jones Ryan M. , Abrahao Agessandro , Hamani Clement , Kalia Suneil K. , Kalia Lorraine V. , Lipsman Nir , Hynynen Kullervo
Published: November 2022

Magnetic resonance-guided focused ultrasound (MRgFUS), in conjunction with circulating microbubbles, is an emerging technology that can transiently enhance the permeability of the blood-brain barrier (BBB) locally and non-invasively to facilitate targeted drug delivery to the brain. In this clinical trial, the feasibility and safety of BBB modulation in the putamen were evaluated for biweekly therapeutic agent delivery in patients with Parkinson’s disease. The performance of the clinical MRgFUS system’s cavitation feedback controller for active power modulation throughout the exposures was examined. The putamen was targeted unilaterally by an ExAblate Neuro MRgFUS system operating at 220 kHz. Definity microbubbles were infused via a saline bag gravity drip at a rate of 4 µL/kg per 5 min. A cavitation emissions-based feedback controller was employed to modulate the acoustic power automatically according to prescribed target cavitation dose levels. BBB opening was measured by Gadolinium (Gd)-enhanced T1-weighted MR imaging, and the presence of potential micro-hemorrhages induced by the exposures was assessed via T2*-weighted MR imaging. A total of 12 treatment sessions were carried out across four patients, with target cavitation dose levels ranging from 0.20–0.40. BBB permeability in the targeted putamen was elevated successfully in all treatments, with a 14% ± 6% mean increase in Gd-enhanced T1-weighted MRI signal intensity relative to the untreated contralateral side. No indications of red blood cell extravasations were observed on MR imaging scans acquired one day following each treatment session. The cavitation emissions-based feedback controller was effective in modulating acoustic power levels to ensure BBB permeability enhancement while avoiding micro-hemorrhages, however, further technical advancements are warranted to improve its performance for use across a wide variety of brain diseases.
Folate-Functionalization Enhances Cytotoxicity of Multivalent DNA Nanocages on Triple-Negative Breast Cancer Cells
Authors: Unida Valeria , Vindigni Giulia , Raniolo Sofia , Stolfi Carmine , Desideri Alessandro , Biocca Silvia
Published: November 2022

DNA is an excellent programmable polymer for the generation of self-assembled multivalent nanostructures useful for biomedical applications. Herein, we developed (i) folate-functionalized nanocages (Fol-NC), very efficiently internalized by tumor cells overexpressing the α isoform of the folate receptor; (ii) AS1411-linked nanocages (Apt-NC), internalized through nucleolin, a protein overexpressed in the cell surface of many types of cancers; and (iii) nanostructures that harbor both folate and AS1411 aptamer functionalization (Fol-Apt-NC). We analyzed the specific miRNA silencing activity of all types of nanostructures harboring miRNA sequestering sequences complementary to miR-21 and the cytotoxic effect when loaded with doxorubicin in a drug-resistant triple-negative breast cancer cell line. We demonstrate that the presence of folate as a targeting ligand increases the efficiency in miR-21 silencing compared to nanocages functionalized with AS1411. Double-functionalized nanocages (Fol-Apt-NC), loaded with doxorubicin, resulted in an increase of over 51% of the cytotoxic effect on MDA-MB-231 cells compared to free doxorubicin, demonstrating, besides selectivity, the ability of nanocages to overcome Dox chemoresistance. The higher efficiency of the folate-functionalized nanocages is due to the way of entrance, which induces more than four times higher intracellular stability and indicates that the folate-mediated route of cell entry is more efficient than the nucleolin-mediated one when both folate and AS1411 modifications are present.
Electrospinning of n-hemin/PAN Nanocomposite Membranes and Its Photo-Enhanced Enzyme-like Catalysis
Authors: Han Xu , Tao Yun , Xu Chao , Deng Yicong , Meng Zisen , Dou Zhenhao , Wang Peng , Feng Quan
Published: November 2022

Hemin possesses great potential in eliminating organic pollutants due to its mild reaction condition, light-harvesting efficiency, and environmental friendliness. However, it has drawbacks such as being easy to aggregate and hard to recycle, and poor stability should be improved in practical application. Herein, the subject developed an electrospinning approach to enable the hemin particulates to be immobilized onto polyacrylonitrile (PAN) nanofibers stably. Hydrogen peroxide (H2O2) was adopted as an oxidant in the system to simulate the enzymatic catalysis of hemin in an organism. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), UV-Vis diffuse reflection spectroscopy (DRS), and electron spin resonance spectroscopy (ESR) analysis was employed to discuss the morphology, structure, and mechanism of the prepared n-hemin/PAN nanocomposite membranes, and 0.02 mmol L−1 of the rhodamine B (RhB) removal activity in different conditions was also verified with these membranes. The kinetic studies showed that n-hemin/PAN nanocomposite membranes maintained excellent properties both in adsorption and degradation. Around 42% RhB could be adsorbed in the dark, while 91% RhB decolorized under xenon lamp irradiation in 110 min, suggesting the catalytic performance of n-hemin/PAN was greatly driven by light irradiation. Differing from the axial coordinated hemin complexes, n-hemin/PAN would catalyze hydrogen peroxide into •OH radicals rather than •OOH and high-valent metal-oxo species. This work provides an effective way to support hemin as nanocomposite membranes, in which the molecular interaction between polymer and hemin made their light adsorption an obvious red shift.
Analysis of Erosion Characteristics and Erosion Mechanism of Polypropylene Fiber Tailings Recycled Concrete in Salt Spray Environment
Authors: Chen Xiuyun , Li Tao , Zhan Meng , Ding Yijie , Leng Faguang , Sun Jia
Published: November 2022

Economic development and infrastructure improvement will inevitably lead to the accumulation of construction waste and tailings, which has not only a huge impact on the environment but is also a waste of resources. Recycling these resources and making green concrete is an effective way to solve these problems. In this study, the salt spray erosion characteristics and erosion mechanism of tailings recycled concrete (TRC) with polypropylene fibers were studied through macro and micro methods. The results showed that its compressive strength and splitting tensile strength increased at first and then decreased, with the optimum content of 0.6–0.9%, and the strength increase coefficient reached its maximum value at the erosion period being 14 d to 28 d. Under the same erosion cycle, when the fiber content was low (≤0.6–0.9%), the erosion depth hardly fluctuated. While the fiber content changed from 0.6% to 1.2%, the erosion depth and curing ability (erosion for 90 days) increased by 16.29% and 11.20%, which implied that its erosion resistance decreased sharply. Through SEM microscopic analysis, it could be observed that when the fiber content was low, the matrix structure and porosity had little change; while the fiber content was excessive, the porosity increased greatly. The longer the erosion period was, the greater the cumulative expansion of salt crystals was, and the larger the porosity was, whose results were in good agreement with the experimental results. This research provides a significant theoretical basis for the application of TRC in engineering.
Behavior of Hybrid Reinforced Concrete Bridge Decks under Static and Fatigue Loading
Authors: McRory Jared W. , Pozo-Lora Fray F. , Benson Zachary , Tawadrous Raed , Maguire Marc
Published: November 2022

This paper presents a new bridge deck reinforcement alternative using hybrid reinforced concrete (Hybrid) consisting of Glass Fiber Reinforced Polymer (GFRP) rebar and alkali-resistant fiberglass composite macrofibers added to the concrete mixture. Fiberglass composite macrofibers are a miniaturized GFRP reinforcing bar that is a composite of resin and glass fibers. An experimental testing program and analytical modeling were conducted to evaluate the structural performance at the service and ultimate limit states. Thirteen full-scale bridge deck specimens were constructed and tested under static and fatigue loading. The fatigue loading was applied up to two million cycles at a frequency of 4 Hz. Post-fatigue, the specimens were tested to failure to compare pre-and post-fatigue behavior. Simplified and moment-curvature analytical models were used to predict the specimens’ flexural strength at the ultimate level, and both were found to be accurate for predicting pre- and post-fatigue strength. Deflection and crack width were monitored throughout the fatigue loading, and these values were compared to the recommended AASHTO LRFD serviceability limits. Testing and analytical results showed that the Hybrid deck is a viable alternative to steel-reinforced and GFRP-reinforced bridge decks for flexural behavior. The service and ultimate level behavior of each bridge deck type was adequate as compared to the AASHTO LRFD service limits. The exceptional post-peak energy absorption demonstrated by the Hybrid adds ductility to previously elastic GFRP reinforced sections.
Chemical Recycling of High-Molecular-Weight Organosilicon Compounds in Supercritical Fluids
Authors: Elmanovich Igor V. , Sizov Victor E. , Zefirov Vadim V. , Kalinina Alexandra A. , Gallyamov Marat O. , Papkov Vladimir S. , Muzafarov Aziz M.
Published: November 2022

The main known patterns of thermal and/or catalytic destruction of high-molecular-weight organosilicon compounds are considered from the viewpoint of the prospects for processing their wastes. The advantages of using supercritical fluids in plastic recycling are outlined. They are related to a high diffusion rate, efficient extraction of degradation products, the dependence of solvent properties on pressure and temperature, etc. A promising area for further research is described concerning the application of supercritical fluids for processing the wastes of organosilicon macromolecular compounds.