bluuebunny/crossref_metadata_2025 huggingface dataset:
Excited-State Dynamics Leading Either to Triplet Formation or Coordinative Expansion following Photolysis of Cu(II)-Porphyrins: A DFT, TD-DFT, Luminescence and Femtosecond Time-Resolved Absorbance Study
Authors: McGarry Ross J. , Varvarezos Lazaros , Pryce Mary T. , Long Conor
Published: August 2023

The photophysical properties of Cu(II) complexes with 5,10,15,20-meso-tetrakis(phenyl)porphyrin and 5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin are examined via the luminescence and femtosecond time-resolved absorbance methods, respectively. These studies are supported by DFT and TD-DFT calculations, which highlight the important role played by ligand-to-metal charge-transfer states in directing the system toward either intersystem crossing to the triplet hypersurface or coordinative expansion to a five-coordinate quasi-stable intermediate. The latter processes occur when the porphyrin is photolyzed in the presence of suitably located Lewis bases. Femtosecond time-resolved absorbance measurements of Cu(II)-5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin confirm that the coordinative expansion in water occurs in approximately 700 fs, while crossing to the triplet hypersurface takes approximately 140 fs in the same solvent. These processes are mutually exclusive, although both can occur simultaneously depending on the environment of the porphyrin. The ratio of the two processes depends on the relative orientation of the Lewis base with respect to the copper atom at the time of excitation. As a consequence, copper porphyrins such as these are excellent probes in the environment of the porphyrin and can be used to identify the location of the porphyrin when interacting with DNA fragments.
Measurement of Thermal Stress by X-ray Nano-Diffraction in (111)-Oriented Nanotwinned Cu Bumps for Cu/SiO2 Hybrid Joints
Authors: Hsu Wei-You , Yang Shih-Chi , Lin You-Yi , Hsieh Wan-Zhen , Tu King-Ning , Chiu Wei-Lan , Chang Hsiang-Hung , Chiang Ching-Yu , Chen Chih
Published: August 2023

X-ray nanodiffraction was used to measure the thermal stress of 10 µm nanotwinned Cu bumps in Cu/SiO2 hybrid structures at −55 °C, 27 °C, 100 °C, 150 °C, and 200 °C. Bonding can be achieved without externally applied compression. The X-ray beam size is about 100 nm in diameter. The Cu bump is dominated by (111) oriented nano-twins. Before the hybrid bonding, the thermal stress in Cu bumps is compressive and remains compressive after bonding. The average stress in the bonded Cu joint at 200 °C is as large as −169.1 MPa. In addition, using the strain data measured at various temperatures, one can calculate the effective thermal expansion coefficient (CTE) for the 10 µm Cu bumps confined by the SiO2 dielectrics. This study reports a useful approach on measuring the strain and stress in oriented metal bumps confined by SiO2 dielectrics. The results also provide a deeper understanding on the mechanism of hybrid bonding without externally applied compression.
Measuring the Rheological and Textural Properties of Thick Purees Used to Manage Patients with Swallowing Disorders
Authors: Ismael-Mohammed Kovan , Bolivar-Prados Mireia , Laguna Laura , Clavé Pere
Published: August 2023

Texture-modified diets are the first-line compensatory strategy for older patients with swallowing and mastication disorders. However, the absence of a common protocol to assess textural properties inhibits their standardization and quality control and, thus, patient safety. This study aimed to (a) assess the rheological and textural properties of ten thick purees (Texture C, British Dietetic Association), (b) understand the effect of oral processing, and (c) measure the properties of the ready-to-swallow bolus after oral processing in healthy adults. Shear viscosity at 50 s−1 and 300 s−1 and textural properties (maximum force, cohesiveness, and adhesiveness) of boluses of ten thick purees were analyzed with a rheometer and a texture analyzer before and after oral processing (ready-to-swallow) in five healthy volunteers. Viscosity varied by 81.78% at 50 s−1 (900–4800 mPa·s) among purees before oral processing. Maximum force varied by 60% (0.47–1.2 N); cohesiveness, 18% (0.66–0.82), and adhesiveness, 32% (0.74–1.1 N·s). The high variability of viscosity was also present in ready-to-swallow boluses, 70.32% among purees. Oral processing significantly reduced viscosity in most purees (French omelet, zucchini omelet, turkey stew, red lentils, noodles, and hake fish) and also significantly reduced maximum force (7–36%) and adhesiveness (17–51%) but hardly affected cohesiveness (<5%). All thick purees met the qualitative textural descriptors for Level C texture. However, all ten purees showed significant differences in all parameters measured instrumentally and were affected differently by oral processing. This study demonstrates the need to use instrumental quality control using standardized protocols and SI units to narrow the variability and provide the optimal values for patients with dysphagia who require texture-modified diets.
A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis
Authors: Hill W. Stephen , Dohnalek Margaret H. , Ha Yejin , Kim Seok-Jung , Jung Jae-Chul , Kang Seung-Baik
Published: August 2023

Osteoarthritis is a significant global health problem. Many patients seek more effective alternatives to nonsteroidal anti-inflammatory medicines or commercial supplements to manage joint pain and inflammation. FlexPro MD® (FP-MD) combines krill oil, astaxanthin, and lower molecular weight hyaluronic acid to support joint health. A 12-week, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of FP-MD and placebo once daily in participants (n = 100) with mild osteoarthritis of the knee or hip joint. For the primary endpoint of joint pain score, per-protocol participants (n = 75) in the FP-MD group (n = 37) had a statistically significantly greater mean reduction from baseline in the Korean Visual Analog Scale (K-VAS) at week 12 compared with participants in the placebo group (n = 38) (20.8 ± 16.16 mm vs. 10.6 ± 17.58, p = 0.0105). The Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) total score was also significantly improved in the FP-MD group at week 12 compared with placebo (−13.0 ± 13.62 vs. −5.5 ± 18.08, p = 0.0489), especially an improvement in pain score (−2.5 ± 2.92 vs. −1.3 ± 3.94, p = 0.02635). FP-MD group had greater improvement in joint function scoring by investigator assessment (p = 0.0127) and by group participants (p = 0.0070). A statistically significantly greater number of patients reported adverse events in the placebo group compared with the FP-MD group (16% vs. 4%, p = 0.0455), most commonly gastrointestinal disorders in both of the groups. These findings suggest that FP-MD is well tolerated and can be effectively used to address joint pain in patients diagnosed with mild osteoarthritis, the main symptom of this condition.
Impact of Vitamin D Deficiency on Tumor Aggressiveness in Neuroendocrine Neoplasms
Authors: Albertelli Manuela , Petolicchio Cristian , Brasili Sara , Pogna Andrea , Boschetti Mara , Luciano Giorgio , Campana Davide , Gay Stefano , Veresani Alessandro , Ferone Diego , Vera Lara
Published: August 2023

Background: The role of vitamin D (25(OH)D) in the pathogenesis and outcome of several conditions, including autoimmune diseases, diabetes and cancers is largely described in the literature. The aims of this study were to evaluate the prevalence of 25(OH)D deficit in a cohort of patients with neuroendocrine neoplasms (NENs) in comparison to a matched healthy control group and to analyze the possible role of 25(OH)D as a prognostic factor for NENs in terms of biological aggressiveness, tumor progression and survival. Methods: From 2009 to 2023, 172 patients with NENs (99 females; median age, 63 years) were included in the study. Serum 25(OH)D levels were defined as deficient if ≤20 ng/mL. The possible associations between 25(OH)D levels and disease grading, staging, ki67%, overall survival (OS), and progression-free survival (PFS) were considered. Results: NEN patients had significantly lower 25(OH)D levels compared to controls (p < 0.001) regardless of the primary origin. Patients with 25(OH)D < 20 ng/mL had a significantly higher ki67 index (p = 0.02) compared to the ones with 25(OH)D levels above 20 ng/mL. Patients with disease progression were found to have a significantly lower 25(OH)D at baseline (p = 0.02), whereas PFS and OS were not significantly influenced by 25(OH)D. Conclusions: Vitamin D deficiency is highly prevalent among NENs and is associated with higher ki67 and disease progression. Our study highlights the importance of monitoring 25(OH)D levels in patients with NENs, as its deficiency appeared to be linked to the worst biological tumor aggressiveness.
Population Interest in Information on Obesity, Nutrition, and Occupational Health and Its Relationship with the Prevalence of Obesity: An Infodemiological Study
Authors: Melián-Fleitas Liliana , Franco-Pérez Álvaro , Sanz-Valero Javier , Wanden-Berghe Carmina
Published: August 2023

Objective: To identify and analyze population interest in obesity, nutrition, and occupational health and safety and its relationship with the worldwide prevalence of obesity through information search trends. Method: In this ecological study, data were obtained through online access to Google Trends using the topics “obesity”, “nutrition”, and “occupational health and safety”. Obesity data were obtained from the World Health Organization (WHO) website for crude adult prevalence and estimates by region. The variables studied were relative search volume (RSV), temporal evolution, milestone, trend, and seasonality. The temporal evolution of the search trends was examined by regression analysis (R2). To assess the relationship between quantitative variables, the Spearman correlation coefficient (Rho) was used. Seasonality was verified using the augmented Dickey–Fuller (ADF) test. Results: The RSV trends were as follows: obesity (R2 = 0.04, p = 0.004); nutrition (R2 = 0.42, p < 0.001); and occupational health and safety (R2 = 0.45, p < 0.001). The analysis of seasonality showed the absence of a temporal pattern (p < 0.05 for all terms). The associations between world obesity prevalence (WOP) and the different RSVs were as follows: WOP versus RSV obesity, Rho = −0.79, p = 0.003; WOP versus RSV nutrition, Rho = 0.57, p = 0.044; and WOP versus RSV occupational health and safety, Rho = −0.93, p = 0.001. Conclusions: Population interest in obesity continues to be a trend in countries with the highest prevalence, although there are clear signs popularity loss in favor of searches focused on possible solutions and treatments, with a notable increase in searches related to nutrition and diet. Despite the fact that most people spend a large part of their time in the workplace and that interventions including various strategies have been shown to be useful in combating overweight and obesity, there has been a decrease in the population’s interest in information related to obesity in the workplace. This information can be used as a guide for public health approaches to obesity and its relationship to nutrition and a healthy diet, approaches that are of equal utility and applicability in occupational health.
Early Life Nutrition Factors and Risk of Acute Leukemia in Children: Systematic Review and Meta-Analysis
Authors: Kintossou Ambroise Kouame , Blanco-Lopez Jessica , Iguacel Isabel , Pisanu Silvia , Almeida Claudia Choma Bettega , Steliarova-Foucher Eva , Sierens Ciska , Gunter Marc J. , Ladas Elena J. , Barr Ronald D. , Van Herck Koen , Kozlakidis Zisis , Huybrechts Inge
Published: August 2023

Acute leukemia commonly occurs in young children with peak incidence at the age of 2–5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case–control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76–0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937.
Targeting Autophagy, Apoptosis, and SIRT1/Nrf2 Axis with Topiramate Underlies Its Neuroprotective Effect against Cadmium-Evoked Cognitive Deficits in Rats
Authors: Arab Hany H. , Eid Ahmed H. , Yahia Rania , Alsufyani Shuruq E. , Ashour Ahmed M. , El-Sheikh Azza A. K. , Darwish Hany W. , Saad Muhammed A. , Al-Shorbagy Muhammad Y. , Masoud Marwa A.
Published: August 2023

Cadmium is an environmental toxicant that instigates cognitive deficits with excessive glutamate excitatory neuroactivity in the brain. Topiramate, a glutamate receptor antagonist, has displayed favorable neuroprotection against epilepsy, cerebral ischemia, and Huntington’s disease; however, its effect on cadmium neurotoxicity remains to be investigated. In this study, topiramate was tested for its potential to combat the cognitive deficits induced by cadmium in rats with an emphasis on hippocampal oxidative insult, apoptosis, and autophagy. After topiramate intake (50 mg/kg/day; p.o.) for 8 weeks, behavioral disturbances and molecular changes in the hippocampal area were explored. Herein, Morris water maze, Y-maze, and novel object recognition test revealed that topiramate rescued cadmium-induced memory/learning deficits. Moreover, topiramate significantly lowered hippocampal histopathological damage scores. Mechanistically, topiramate significantly replenished hippocampal GLP-1 and dampened Aβ42 and p-tau neurotoxic cues. Notably, it significantly diminished hippocampal glutamate content and enhanced acetylcholine and GABA neurotransmitters. The behavioral recovery was prompted by hippocampal suppression of the pro-oxidant events with notable activation of SIRT1/Nrf2/HO-1 axis. Moreover, topiramate inactivated GSK-3β and dampened the hippocampal apoptotic changes. In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway. Together, the pro-autophagic, antioxidant, and anti-apoptotic features of topiramate contributed to its neuroprotective properties in rats intoxicated with cadmium. Therefore, it may be useful to mitigate cadmium-induced cognitive deficits.
Critical Signaling Transduction Pathways and Intestinal Barrier: Implications for Pathophysiology and Therapeutics
Authors: Gao Jingwang , Cao Bo , Zhao Ruiyang , Li Hanghang , Xu Qixuan , Wei Bo
Published: August 2023

The intestinal barrier is a sum of the functions and structures consisting of the intestinal mucosal epithelium, mucus, intestinal flora, secretory immunoglobulins, and digestive juices. It is the first-line defense mechanism that resists nonspecific infections with powerful functions that include physical, endocrine, and immune defenses. Health and physiological homeostasis are greatly dependent on the sturdiness of the intestinal barrier shield, whose dysfunction can contribute to the progression of numerous types of intestinal diseases. Disorders of internal homeostasis may also induce barrier impairment and form vicious cycles during the response to diseases. Therefore, the identification of the underlying mechanisms involved in intestinal barrier function and the development of effective drugs targeting its damage have become popular research topics. Evidence has shown that multiple signaling pathways and corresponding critical molecules are extensively involved in the regulation of the barrier pathophysiological state. Ectopic expression or activation of signaling pathways plays an essential role in the process of shield destruction. Although some drugs, such as molecular or signaling inhibitors, are currently used for the treatment of intestinal diseases, their efficacy cannot meet current medical requirements. In this review, we summarize the current achievements in research on the relationships between the intestinal barrier and signaling pathways. The limitations and future perspectives are also discussed to provide new horizons for targeted therapies for restoring intestinal barrier function that have translational potential.
Investigation of the Interaction between Mechanosynthesized ZnS Nanoparticles and Albumin Using Fluorescence Spectroscopy
Authors: Lukáčová Bujňáková Zdenka , Dutková Erika , Jakubíková Jana , Cholujová Danka , Varhač Rastislav , Borysenko Larysa , Melnyk Inna
Published: August 2023

In this paper, ZnS nanoparticles were bioconjugated with bovine serum albumin and prepared in a form of nanosuspension using a wet circulation grinding. The stable nanosuspension with monomodal particle size distribution (d50 = 137 nm) and negative zeta potential (−18.3 mV) was obtained. The sorption kinetics and isotherm were determined. Interactions between ZnS and albumin were studied using the fluorescence techniques. The quenching mechanism, describing both static and dynamic interactions, was investigated. Various parameters were calculated, including the quenching rate constant, binding constant, stoichiometry of the binding process, and accessibility of fluorophore to the quencher. It has been found that tryptophan, in comparison to tyrosine, can be closer to the binding site established by analyzing the synchronous fluorescence spectra. The cellular mechanism in multiple myeloma cells treated with nanosuspension was evaluated by fluorescence assays for quantification of apoptosis, assessment of mitochondrial membrane potential and evaluation of cell cycle changes. The preliminary results confirm that the nontoxic nature of ZnS nanoparticles is potentially applicable in drug delivery systems. Additionally, slight changes in the secondary structure of albumin, accompanied by a decrease in α-helix content, were investigated using the FTIR method after analyzing the deconvoluted Amide I band spectra of ZnS nanoparticles conjugated with albumin. Thermogravimetric analysis and long-term stability studies were also performed to obtain a complete picture about the studied system.
Hyperbranched Polymers: Recent Advances in Photodynamic Therapy against Cancer
Authors: Chen Jie , Zhang Yichuan
Published: August 2023

Hyperbranched polymers are a class of three-dimensional dendritic polymers with highly branched architectures. Their unique structural features endow them with promising physical and chemical properties, such as abundant surface functional groups, intramolecular cavities, and low viscosity. Therefore, hyperbranched-polymer-constructed cargo delivery carriers have drawn increasing interest and are being utilized in many biomedical applications. When applied for photodynamic therapy, photosensitizers are encapsulated in or covalently incorporated into hyperbranched polymers to improve their solubility, stability, and targeting efficiency and promote the therapeutic efficacy. This review will focus on the state-of-the-art studies concerning recent progress in hyperbranched-polymer-fabricated phototherapeutic nanomaterials with emphases on the building-block structures, synthetic strategies, and their combination with the codelivered diagnostics and synergistic therapeutics. We expect to bring our demonstration to the field to increase the understanding of the structure–property relationships and promote the further development of advanced photodynamic-therapy nanosystems.
Effect of Compaction Pressure on the Enzymatic Activity of Pancreatin in Directly Compressible Formulations
Authors: Zakowiecki Daniel , Edinger Peter , Hess Tobias , Paszkowska Jadwiga , Staniszewska Marcela , Romanova Svitlana , Garbacz Grzegorz
Published: August 2023

Tableting of biomolecules is a challenging formulation phase due to their sensitivity to various process parameters, such as compression pressure, process dynamics, or the temperature generated. In the present study, pancreatin was employed as a model enzyme mixture, which was formulated in tablet form utilizing the synergistic effects of brittle and plastic excipients (dibasic calcium phosphate and microcrystalline cellulose, respectively). The effect of varying compaction pressure and lubricant concentration on the generated temperature and enzymatic activity was evaluated. The tablets were analyzed for pancreatin content and the activity of two enzymes (protease and amylase) using pharmacopoeial tests. This study indicated that the formulations proposed here allow tableting over a wide range of compaction pressures without adversely affecting pancreatin content and its enzymatic activity.
Spheroid Formation and Recovery Using Superhydrophobic Coating for Regenerative Purposes
Authors: Morán María , Cirisano Francesca , Ferrari Michele
Published: August 2023

Cell therapies commonly pursue tissue stimulation for regenerative purposes by replacing cell numbers or supplying for functional deficiencies. To this aim, monodispersed cells are usually transplanted for incorporation by local injection. The limitations of this strategy include poor success associated with cell death, insufficient retention, or cell damage due to shear forces associated with the injection. Spheroids have recently emerged as a model that mimics an in vivo environment with more representative cell-to-cell interactions and better intercellular communication. Nevertheless, cost-effective and lab friendly fabrication and effectively performed recovery are challenges that restrict the broad application of spheroids. In this work, glass surfaces were modified with an environmentally friendly superhydrophobic coating. The superhydrophobic surfaces were used for the 3D spheroid preparation of fibroblasts (3T3 cell line) and keratinocytes (HaCaT cell line). The effectiveness of the spheroids to be recovered and grown under 2D culture conditions was evaluated. The morphology of the migrated cells from the 3D spheroids was characterized at the nano-microscale through 3D profilometry. The results demonstrated improved adhesion and proliferation in the migrated cells, both advanced properties for regenerative applications.
Spray-Dried Inhalable Microparticles Combining Remdesivir and Ebselen against SARS-CoV-2 Infection
Authors: Saha Tushar , Sinha Shubhra , Harfoot Rhodri , Quiñones-Mateu Miguel E. , Das Shyamal C.
Published: August 2023

There is a continuous effort to develop efficient treatments for coronavirus disease 2019 (COVID-19) and other viral respiratory diseases. Among the different strategies, inhaled treatment is considered one of the most logical and efficient approaches to treating COVID-19, as the causative “SARS-CoV-2 virus RNA” predominantly infects the respiratory tract. COVID-19 treatments initially relied on repurposed drugs, with a few additional strategies developed during the last two years, and all of them are based on monotherapy. However, drug combinations have been found to be more effective than monotherapy in other viral diseases such as HIV, influenza, and hepatitis C virus. In the case of SARS-CoV-2 infection, in vitro studies have shown synergistic antiviral activity combining remdesivir with ebselen, an organoselenium compound. Therefore, these drug combinations could ensure better therapeutic outcomes than the individual agents. In this study, we developed a dry powder formulation containing remdesivir and ebselen using a spray-drying technique and used L-leucine as an aerosolization enhancer. The prepared dry powders were spherical and crystalline, with a mean particle size between 1 and 3 µm, indicating their suitability for inhalation. The emitted dose (ED) and fine particle fraction (FPF) of remdesivir- and ebselen-containing dry powders were ~80% and ~57% when prepared without L-leucine. The ED as well as the FPF significantly increased with values of >86% and >67%, respectively, when L-leucine was incorporated. More importantly, the single and combinational dry powder of remdesivir and ebselen showed minimal cytotoxicity (CC50 > 100 μM) in Calu-3 cells, retaining their anti-SARS-CoV-2 properties (EC50 2.77 to 18.64 μM). In summary, we developed an inhalable dry powder combination of remdesivir and ebselen using a spray-drying technique. The spray-dried inhalable microparticles retained their limited cytotoxicity and specific antiviral properties. Future in vivo studies are needed to verify the potential use of these remdesivir/ebselen combinational spray-dried inhalable microparticles to block the SARS-CoV-2 replication in the respiratory tract.
Investigating Tacrolimus Disposition in Paediatric Patients with a Physiologically Based Pharmacokinetic Model Incorporating CYP3A4 Ontogeny, Mechanistic Absorption and Red Blood Cell Binding
Authors: Van der Veken Matthias , Brouwers Joachim , Ozbey Agustos Cetin , Umehara Kenichi , Stillhart Cordula , Knops Noël , Augustijns Patrick , Parrott Neil John
Published: August 2023

Tacrolimus is a crucial immunosuppressant for organ transplant patients, requiring therapeutic drug monitoring due to its variable exposure after oral intake. Physiologically based pharmacokinetic (PBPK) modelling has provided insights into tacrolimus disposition in adults but has limited application in paediatrics. This study investigated age dependency in tacrolimus exposure at the levels of absorption, metabolism, and distribution. Based on the literature data, a PBPK model was developed to predict tacrolimus exposure in adults after intravenous and oral administration. This model was then extrapolated to the paediatric population, using a unique reference dataset of kidney transplant patients. Selecting adequate ontogeny profiles for hepatic and intestinal CYP3A4 appeared critical to using the model in children. The best model performance was achieved by using the Upreti ontogeny in both the liver and intestines. To mechanistically evaluate the impact of absorption on tacrolimus exposure, biorelevant in vitro solubility and dissolution data were obtained. A relatively fast and complete release of tacrolimus from its amorphous formulation was observed when mimicking adult or paediatric dissolution conditions (dose, fluid volume). In both the adult and paediatric PBPK models, the in vitro dissolution profiles could be adequately substituted by diffusion-layer-based dissolution modelling. At the level of distribution, sensitivity analysis suggested that differences in blood plasma partitioning of tacrolimus may contribute to the variability in exposure in paediatric patients.
Recent Advances in Targeted Drug Delivery Strategy for Enhancing Oncotherapy
Authors: Li Jianmin , Wang Qingluo , Xia Guoyu , Adilijiang Nigela , Li Ying , Hou Zhenqing , Fan Zhongxiong , Li Jinyao
Published: August 2023

Targeted drug delivery is a precise and effective strategy in oncotherapy that can accurately deliver drugs to tumor cells or tissues to enhance their therapeutic effect and, meanwhile, weaken their undesirable side effects on normal cells or tissues. In this research field, a large number of researchers have achieved significant breakthroughs and advances in oncotherapy. Typically, nanocarriers as a promising drug delivery strategy can effectively deliver drugs to the tumor site through enhanced permeability and retention (EPR) effect-mediated passive targeting and various types of receptor-mediated active targeting, respectively. Herein, we review recent targeted drug delivery strategies and technologies for enhancing oncotherapy. In addition, we also review two mainstream drug delivery strategies, passive and active targeting, based on various nanocarriers for enhancing tumor therapy. Meanwhile, a comparison and combination of passive and active targeting are also carried out. Furthermore, we discuss the associated challenges of passive and active targeted drug delivery strategies and the prospects for further study.
Topology Optimization for Digital Light Projector Additive Manufacturing Addressing the In-Situ Structural Strength Issue
Authors: Wang Jun , Liu Jikai , Li Lei
Published: August 2023

A topology optimization approach is proposed for the design of self-supporting structures for digital light projector (DLP) 3D printing. This method accounts for the adhesion forces between the print part and the resin base during DLP printing to avoid failure of the part due to stress concentration and weak connections. Specifically, the effect of the process-related adhesion forces is first simulated by developing a design variable-interpolated finite element model to capture the intricate mechanical behavior during DLP 3D printing. Guided by the process model, a stress-constrained topology optimization algorithm is formulated with both the SIMP and RAMP interpolation schemes. The interpolations on the stress term and the design-dependent adhesion load are carefully investigated. A sensitivity result on the P-norm stress constraint is fully developed. Finally, the approach is applied to several 2D benchmark examples to validate its efficacy in controlling the process-caused peak P-norm stresses. The effects of alternating between the SIMP and RAMP interpolations and changing the stress upper limits are carefully explored during the numerical trials. Moreover, 3D printing tests are performed to validate the improvement in printability when involving the process-related P-norm stress constraint.
Study on Deterioration Characteristics of a Composite Crossarm Mandrel in a 10 kV Distribution Network Based on Multi-Factor Aging
Authors: Ma Long , Fu Xiaotao , Chen Lincong , Chen Xiaolin , Zhang Cong , Li Xinran , Li Wei , Fu Fangda , Fu Chuanfu , Lin Taobei , Mao Wensheng , Liu Hechen
Published: August 2023

This paper presents a study that conducted 5000 h of multi-factor aging tests on 10 kV composite crossarms, considering the natural environment in coastal areas and actual power line operations. Various aging conditions, such as voltage, rain, temperature, humidity, salt fog, ultraviolet light, and mechanical stress, were applied during the tests. The research initially analyzed the influence of multi-factor aging on the bending and tensile properties of the full-size composite crossarm. Subsequently, a detailed investigation was carried out to assess the impact of aging on the mechanical properties, electrical insulation properties, and microscopic characteristics of the composite crossarm core bar. Results indicated that the tensile strength and bending strength of the full-size composite crossarm mandrel experienced minimal changes after aging, remaining well within operational requirements. However, the silicone rubber outer sheath’s hydrophobicity decreased, leading to the appearance of cracks and holes on the surface, which provided pathways for moisture and salt infiltration into the mandrel. As a consequence, the bending strength and shear strength of the mandrel material were reduced by 16.5% and 37.7%, respectively. Moreover, the electrical performance test demonstrated a slight change in the mandrel’s leakage current, while the electrical breakdown strength decreased by 22.8%. Microscopic analysis using SEM, three-dimensional CT, and TGA revealed that a small amount of resin matrix decomposed and microcracks appeared on the surface. Additionally, the fiber-matrix interface experienced debonding and cracking, leading to an increased moisture absorption rate of the mandrel material.
Formation of Hydrophobic–Hydrophilic Associates in the N-Vinylpyrrolidone and Vinyl Propyl Ether Copolymer Aqueous Solutions
Authors: Kabdushev Sherniyaz , Mun Grigoriy , Suleimenov Ibragim , Alikulov Adilet , Shaikhutdinov Ramazan , Kopishev Eldar
Published: August 2023

Utilizing turbidimetry data, an examination is conducted on the behavior of solutions containing N-vinylpyrrolidone and vinyl propyl ether copolymer within a temperature range coinciding with the occurrence of a phase transition. The investigation reveals that within specific conditions prevailing in this domain, the emergence of entities denoted as hydrophobic–hydrophilic associates is conceivable. These entities are characterized by the presence of a relatively dense core, upheld by hydrophobic interplays, and they are proficient in effectively dispersing irradiation within the optical spectrum. Encircling this core is a hydrophilic periphery that impedes the formation of insoluble precipitates. The development of such associates transpires when hydrophobic interactions have attained a discernible prominence, although they remain inadequate to counteract the forces that drive the expansion of macromolecular coils. Under these circumstances, the energetically favored course of action entails the constitution of a core for the aforementioned associates, involving discrete segments from diverse macromolecules. Notably, the introduction of an additional constituent (ethanol) to the solution, which selectively mitigates hydrophobic interactions, serves to stabilize the hydrophobic–hydrophilic associations.
Aggregation of Thermoresponsive Polymethacrylates in a Dulbecco’s Modified Eagle Medium and Its Salts
Authors: Otulakowski Łukasz , Trzebicka Barbara
Published: August 2023

The thermal behavior and aggregation process of the poly(N-isopropyl acrylamide), poly[oligo(ethylene glycol) methyl ether methacrylate], and poly[(2-hydroxyethyl methacrylate)-co-oligo(ethylene glycol) methyl ether methacrylate] thermoresponsive polymers were studied in a commonly used Dulbecco’s Modified Eagle Medium (DMEM) cell culture medium and solutions of its individual components in the same concentration as found in DMEM. All studied copolymers exhibited an unexpected transmittance profile in the DMEM. During heating above the cloud point temperature (TCP), the polymers additionally aggregated, which led to the formation of their precipitates. The behavior of the polymers was further studied to evaluate how individual salts affected the transition temperature, size (Dh), and stability of the polymer particles. Organic additives, such as amino acids and glucose, had a significantly lesser impact on the thermoresponsive aggregation of the polymers than inorganic ones. Changes to the TCP were small and the formation of precipitates was not observed. The presence of small amounts of amino acids caused a decrease in the polymer aggregate sizes. Obtained results are of utmost importance in thermoresponsive drug nanocarrier studies.
Enhanced Activity and Stability of Heteroatom-Doped Carbon/Bimetal Oxide for Efficient Water-Splitting Reaction
Authors: Periyasamy Thirukumaran , Asrafali Shakila Parveen , Jang Ayoung , Kim Seong-Cheol , Lee Jaewoong
Published: August 2023

The research community is actively exploring ways to create cost-efficient and high-performing electrocatalysts for the oxygen evolution reaction. In this investigation, an innovative technique was employed to produce heteroatom-doped carbon containing NiCo oxides, i.e., HC/NiCo oxide@800, in the form of a three-dimensional hierarchical flower. This method involved the reduction of a bimetallic (Ni, Co) metal–organic framework, followed by carefully controlled oxidative calcination. The resulting porous flower-like structure possess numerous advantages, such as expansive specific surface areas, excellent conductivity, and multiple electrocatalytic active sites for both hydrogen and oxygen evolution reactions. Moreover, the presence of oxygen vacancies within HC/NiCo oxide@800 significantly enhances the conductivity of the NiCo substance, thus expediting the kinetics of both the processes. These benefits work together synergistically to enhance the electrocatalytic performance of HC/NiCo oxide@800. Empirical findings reveal that HC/NiCo oxide@800 electrocatalysts demonstrate exceptional catalytic activity, minimal overpotential, and remarkable stability when deployed for both hydrogen evolution and oxygen evolution reactions in alkaline environments. This investigation introduces a fresh avenue for creating porous composite electrocatalysts by transforming metal–organic frameworks with controllable structures. This approach holds promise for advancing electrochemical energy conversion devices by facilitating the development of efficient and customizable electrocatalytic materials.
Bacitracin Supplementation as a Growth Promoter Down-Regulates Innate and Adaptive Cytokines in Broilers’ Intestines
Authors: Dal Pont Gabriela C. , Lee Annah , Bortoluzzi Cristiano , Farnell Yuhua Z. , Gougoulias Christos , Kogut Michael H.
Published: August 2023

In the past decade, the withdrawal of antibiotics used as growth promoters (AGP) has increased some poultry industry challenges, such as the rise of intestinal diseases. Experts advocate that AGPs improve performance due to the modulation of the intestinal microbiota, with resulting anti-inflammatory effects. However, the impact and interactions of AGPs with the host intestinal immune system are still unknown, which represents issues in developing effective alternatives for AGPs. Therefore, this study was aimed at better understanding the potential mechanism of action of bacitracin used as AGP and its impacts on the intestinal immune system. Ninety day-of-hatch chickens were randomly assigned to two treatments with three repetitions of fifteen birds, a control (CNT) group with a corn/soybean meal standard diet, and a control diet supplemented with 50 g/ton of feed of bacitracin (BMD). The cytokines’ and chemokines’ production (IFN-α, IFN-γ, IL-16, IL-10, IL-21, IL-6, M-CSF, MIP-3α, MIP-1β, VEGF and CCL-5) were assessed in the jejunum and ileum at 14, 21, 28 and 36 days of age by using a chicken-specific cytokine/chemokine peptide ELISA array. Broilers with BMD supplementation were found to have a lower production of IL-16, IFN-γ, M-CSF, IL-21, MIP-1β and VEGF in the jejunum at 14 d. However, from 21 through 36 days, the effect of BMD on cytokine production in the jejunum was negligible except for CCL-5, which was reduced at D36. In the ileum, BMD effects on the cytokine profile started at 28 d, when BMD-supplemented broilers showed a reduced IL-6 production level. At day 36, BMD reduced IL-16 and MIP-3α production but increased VEGF concentration in the ileum tissue. The present study demonstrated that the use of bacitracin as an AGP modulates the small intestine immune system, especially in the first phase of the broiler’s life (up to 14 days). Moreover, BMD anti-inflammatory effects include not only innate immunity but also seemed to influence the development of the adaptive immune response as seen by the decreased production of IL-21 and IL-16. These results demonstrate that a commonly used AGP in broiler feed had a local anti-inflammatory effect.
The Holy See and Disability Sport: From Attention to Commitment
Authors: Vanysacker Dries
Published: August 2023

Research overviews of and historiography on the attitude of the Catholic Church and theologians towards athletes with intellectual and physical disabilities assume that the Church and theologians have only very recently begun to interest themselves in this subject. Starting from John Paul II’s contribution to this field, and above all from his integral anthropological vision, this article assesses his position by comparing it with that of his two successors Benedict XVI and Francis. Especially the latter’s addresses and interviews and the official documents on sport issued by the Holy See during his pontificate are testimony to his special commitment to athletes with disabilities. The article also examines the history of the Holy See and studies its attention to athletes with a disability. The results of this inquiry are that papal interest in this field is not limited to, nor did it start with the pontificate of John Paul II. Instead, it dates from the very beginning of the modern phenomenon of sport, with Pope Pius X at the beginning of the 20th century, continued by Pius XII and John XXIII. The latter’s speech to the participants of the first Paralympic Games in 1960 is the strongest indication of a pre-John Paul II affirmation of disabled sport. This points to the importance of taking a more nuanced position in the current debate, although it is clear that Pope Francis must be considered the champion of the Holy See’s commitment to the inclusion of athletes with a disability.
Lidar-Derived Rockfall Inventory—An Analysis of the Geomorphic Evolution of Rock Slopes and Modifying the Rockfall Activity Index (RAI)
Authors: Markus Shane J. , Wartman Joseph , Olsen Michael , Darrow Margaret M.
Published: August 2023

Rockfall presents a significant risk to the safety and economy of communities and infrastructure in mountainous regions. The recently-developed Rockfall Activity Index (RAI) utilizes high-resolution terrestrial lidar-derived digital elevation models (DEMs) of rock slopes to categorize a slope face into seven distinct morphological units, or “RAI classes”. This paper focuses on a comprehensive study conducted at four sites in Alaska, USA, where a robust lidar-based five-year inventory of 4381 rockfall events was analyzed. The primary objective was to investigate variations in failure characteristics, such as cumulative magnitude–frequency distributions, non-cumulative power–law parameters, average annual failure rates, and average failure depths, among the different RAI classes. The findings demonstrate that the seven RAI classes effectively differentiate the rock slope based on unique mass-wasting characteristics. Furthermore, the research explores spatial and temporal variations in these failure characteristics. Based on the study’s outcomes, recommendations are provided for modifying the RAI parameters for each RAI class, specifically the annual failure rate and average failure depth. These modifications aim to enhance the accuracy and effectiveness of rockfall hazard assessments.
Time Reversal Detection for Moving Targets in Clutter Environments
Authors: Lian Hao , Yang Minglei , Xu Saiqin , Zhou Dingsen , Liu Meng
Published: August 2023

Moving target detection plays a pivotal role in many applications, especially in radar systems. In addition, time-reversal (TR) technology can improve radar detection probability by effectively solving the problem of multipath signals. However, detection performance can be affected when clutter exists and target Doppler shifts are unknown. For this reason, we propose a novel moving target detection algorithm that leverages TR technology and a novel waveform optimization method in clutter and multipath signal environments. In this paper, we establish a TR signal model for a moving target in such environments and derive the TR average likelihood ratio test (TR-ALRT) detector. Additionally, we introduce a waveform optimization method that adapts to clutter and unknown Doppler information further to enhance the performance of the TR-ALRT detector. Consequently, a TR-ALRT waveform optimization (TR-ALRT-WO) detector is derived to adapt to the unknown Doppler and environment information, thereby improving the detection probability. Comparative analysis with other detectors under the same conditions validates the effectiveness of our proposed TR-ALRT-WO detector. Furthermore, numerical experiments demonstrate the superior performance of the proposed detection algorithm.
The CNES Solutions for Improving the Positioning Accuracy with Post-Processed Phase Biases, a Snapshot Mode, and High-Frequency Doppler Measurements Embedded in Recent Advances of the PPP-WIZARD Demonstrator
Authors: Gazzino Clément , Blot Alexis , Bernadotte Elodie , Jayle Théo , Laymand Marion , Lelarge Nicolas , Lacabanne Aude , Laurichesse Denis
Published: August 2023

For many years, the navigation team at the French Space Agency (CNES) has been developing its Precise Point Positioning project. The goal was initially to promote a technique called undifferenced ambiguity resolution. One of the main characteristics of this technique is the capability for a user receiver to perform centimeter-level accuracy in real time. To do so, a demonstrator has been built. Its architecture is composed of three main elements: a correction processing software called the server part, a means to transmit the corrections using standardized messages, and a user software capable of handling the corrections to compute an accurate positioning at the user level. In this paper, we present the recent advances in the CNES precise point positioning demonstrator. They are composed of some evolution of the network of stations and server software, the implementation of the new state space representation standard, a new method for instantaneous ambiguity resolution using uncombined four-frequency signals, its implementation in real-time at the server and the user level, and the use of high-rate Doppler measurements to improve the accuracy of the solution in harsh urban environments. On top of that, the computation of high-accuracy post-processed phase biases with the majority of current GNSS signals supported, compatible with the uncombined method and a new online positioning service to demonstrate the capacity of the user software, is demonstrated.
Student’s t-Based Robust Poisson Multi-Bernoulli Mixture Filter under Heavy-Tailed Process and Measurement Noises
Authors: Zhu Jiangbo , Xie Weixin , Liu Zongxiang
Published: August 2023

A novel Student’s t-based robust Poisson multi-Bernoulli mixture (PMBM) filter is proposed to effectively perform multi-target tracking under heavy-tailed process and measurement noises. To cope with the common scenario where the process and measurement noises possess different heavy-tailed degrees, the proposed filter models this noise as two Student’s t-distributions with different degrees of freedom. Furthermore, this method considers that the scale matrix of the one-step predictive probability density function is unknown and models it as an inverse-Wishart distribution to mitigate the influence of heavy-tailed process noise. A closed-form recursion of the PMBM filter for propagating the approximated Gaussian-based PMBM posterior density is derived by introducing the variational Bayesian approach and a hierarchical Gaussian state-space model. The overall performance improvement is demonstrated through three simulations.
Editorial for the Special Issue “Review of Application Areas of GPR”
Authors: Lombardi Federico , Podd Frank , Solla Mercedes
Published: August 2023

Ground-penetrating radar (GPR) started as a radio echo sounding technology during the second half of the last century, but it is now a well-established and widely adopted technology for producing high-resolution images of subsurface [...]