The freeze-drying of biopolymers presents a fresh option with greater potential for application in soil subgrade stabilization. A freeze-dried combination of β-glucan (BG) and γ-poly-glutamic acid (GPA) biopolymers was used to treat low compressible clay (CL) and low compressible silt (ML) soils in dosages of 0.5%, 1%, 1.5%, and 2%. The California bearing ratio (CBR) test for the treated specimens was performed under three curing conditions: (i) thermal curing at 60 °C, (ii) air-curing for seven days followed by submergence for 4 days, and (iii) no curing, i.e., tested immediately after mixing. To investigate the influence of shear strength on the freeze-dried biopolymer-stabilized soil specimens and their variations with aging, unconfined compressive strength (UCS) tests were conducted after thermal curing at 60 °C for 3 days, 7 days, and 7 days of thermal curing followed by 21 days of air curing. The maximum CBR of 125.3% was observed for thermally cured CL and a minimum CBR of 6.1% was observed under soaked curing conditions for ML soils. Scanning electron microscopy (SEM), infrared spectroscopy, average particle size, permeability, and adsorption tests revealed the pore filling, biopolymer adsorption and coating on the soil surface, and agglomeration of the soil along with the presence of hydrogen bonds, covalent amide bonds, and Van der Waals forces that contributed to the stiffening of the stabilized soil. Using three-dimensional (3D) finite element analysis (FEA) and layered elastic analysis (LEA), a mechanistic–empirical pavement design was carried out for the stabilized soil and a design thickness catalog was prepared for the maximum CBR. The cost reductions for a 1 km section of the pavement were expected to be 12.5%. Full article

High-aspect-ratio micro- and mesoscale metallic components (HAR-MMMCs) can play some unique roles in quite a few application fields, but their cost-efficient fabrication is significantly difficult to accomplish. To address this issue, this study proposes a necked-entrance through-mask (NTM) periodically lifting electroforming technology with an impinging jet electrolyte supply. The effects of the size of the necked entrance of the through-mask and the jet speed of the electrolyte on electrodeposition behaviors, including the thickness distribution of the growing top surface, deposition defect formation, geometrical accuracy, and electrodeposition rate, are investigated numerically and experimentally. Ensuring an appropriate size of the necked entrance can effectively improve the uniformity of deposition thickness, while higher electrolyte flow velocities help enhance the density of the components under higher current densities, reducing the formation of deposition defects. It was shown that several precision HAR-MMMCs with an AR of 3.65 and a surface roughness (Ra) of down to 36 nm can be achieved simultaneously with a relatively high deposition rate of 3.6 μm/min and thickness variation as low as 1.4%. Due to the high current density and excellent mass transfer effects in the electroforming conditions, the successful electroforming of components with a Vickers microhardness of up to 520.5 HV was achieved. Mesoscale precision columns with circular and Y-shaped cross-sections were fabricated by using this modified through-mask movable electroforming process. The proposed NTM periodic lifting electroforming method is promisingly advantageous in fabricating precision HAR-MMMCs cost-efficiently. Full article

Clinical trials with single-agent venetoclax/ABT-199 (anti-apoptotic BCL2 inhibitor) revealed that diffuse large B-cell lymphoma (DLBCL) is not solely dependent on BCL2 for survival. Gaining insight into pathways/proteins that increase venetoclax sensitivity or unique vulnerabilities in venetoclax-resistant DLBCL would provide new potential treatment avenues. Therefore, we generated acquired venetoclax-resistant DLBCL cells and evaluated these together with intrinsically venetoclax-resistant and -sensitive DLBCL lines. We identified resistance mechanisms, including alterations in BCL2 family members that differed between intrinsic and acquired venetoclax resistance and increased dependencies on specific pathways. Although combination treatments with BCL2 family member inhibitors may overcome venetoclax resistance, RNA-sequencing and drug/compound screens revealed that venetoclax-resistant DLBCL cells, including those with TP53 mutation, had a preferential dependency on oxidative phosphorylation. Mitochondrial electron transport chain complex I inhibition induced venetoclax-resistant, but not venetoclax-sensitive, DLBCL cell death. Inhibition of IDH2 (mitochondrial redox regulator) synergistically overcame venetoclax resistance. Additionally, both acquired and intrinsic venetoclax-resistant DLBCL cells were similarly sensitive to inhibitors of transcription, B-cell receptor signaling, and class I histone deacetylases. These approaches were also effective in DLBCL, follicular, and marginal zone lymphoma patient samples. Our results reveal there are multiple ways to circumvent or overcome the diverse venetoclax resistance mechanisms in DLBCL and other B-cell lymphomas and identify critical targetable pathways for future clinical investigations. Full article

Abstract: Background: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL. Methods: We initially enrolled 45 consecutive patients during the period September 2019–September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients. Results: The patients’ mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values (p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP (p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned. Conclusion: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns. Full article

Purpose: This study aimed to evaluate the feasibility of using [⁶⁸Ga]-fibroblast-activating protein inhibitor (FAPI) positron emission tomography (PET) imaging for diagnosing pulmonary fibrosis in a mouse model. We also examined its value in monitoring treatment response and compared it with traditional [¹⁸F]-fluorodeoxyglucose (FDG) PET and computed tomography (CT) imaging. Methods: A model of idiopathic pulmonary fibrosis was established using intratracheal injection of bleomycin (BLM, 2 mg/kg) into C57BL/6 male mice. For the treatment of IPF, a daily oral dose of 400 mg/kg/day of pirfenidone was administered from 9 to 28 days after the establishment of the model. Disease progression and treatment efficacy were assessed at different stages of the disease every week for four weeks using CT, [¹⁸F]FDG PET, and [⁶⁸Ga]FAPI PET (baseline imaging performed at week 0). Mice were sacrificed and lung tissues were harvested for hematoxylin-eosin staining, picrosirius red staining, and immunohistochemical staining for glucose transporter 1 (GLUT1) and FAP. Expression levels of GLUT1 and FAP in pathological sections were quantified. Correlations between imaging parameters and pathological quantitative values were analyzed. Results: CT, [¹⁸F]FDG PET and [⁶⁸Ga]FAPI PET revealed anatomical and functional changes in the lung that reflected progression of pulmonary fibrosis. In untreated mice with pulmonary fibrosis, lung uptake of [¹⁸F]FDG peaked on day 14, while [⁶⁸Ga]FAPI uptake and mean lung density peaked on day 21. In mice treated with pirfenidone, mean lung density and lung uptake of both PET tracers decreased. Mean lung density, [¹⁸F]FDG uptake, and [⁶⁸Ga]FAPI uptake correlated well with quantitative values of picrosirius red staining, GLUT1 expression, and FAP expression, respectively. Conclusions: Although traditional CT and [¹⁸F]FDG PET reflect anatomical and metabolic status in fibrotic lung, [⁶⁸Ga]FAPI PET provides a means of evaluating fibrosis progression and monitoring treatment response. Full article

Arthrospira platensis, commonly known as Spirulina, is a photosynthetic filamentous cyanobacterium (blue–green microalga) that has been utilized as a food source since ancient times. More recently, it has gained significant popularity as a dietary supplement due to its rich content of micro- and macro-nutrients. Of particular interest is a water soluble phycobiliprotein derived from Spirulina known as phycocyanin C (C-PC), which stands out as the most abundant protein in this cyanobacterium. C-PC is a fluorescent protein, with its chromophore represented by the tetrapyrrole molecule phycocyanobilin B (PCB-B). While C-PC is commonly employed in food for its coloring properties, it also serves as the molecular basis for numerous nutraceutical features associated with Spirulina. Indeed, the comprehensive C-PC, and to some extent, the isolated PCB-B, has been linked to various health-promoting effects. These benefits encompass conditions triggered by oxidative stress, inflammation, and other pathological conditions. The present review focuses on the bio-pharmacological properties of these molecules, positioning them as promising agents for potential new applications in the expanding nutraceutical market. Full article

Hymedesmiidae is one of the largest families of marine sponges and stands out as an exceptional source of variable metabolites with diverse biological activities. In this study, the ethyl acetate fraction (HE) of a Hymedesmia sp. marine sponge from the Red Sea, Egypt, was analyzed for the first time using Ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) analysis. The analysis tentatively identified 29 compounds in this fraction, including the isolation and identification of six compounds (two pyrimidine nucleosides, one purine, and two pyrimidine bases in addition to one cerebroside) for the first time. The structures of the isolated compounds were established by 1D and 2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared) spectroscopy. Furthermore, the cytotoxic, antioxidant, and antimicrobial activities of the ethyl acetate fraction were evaluated in vitro. The fraction exhibited strong DPPH scavenging activity with an IC₅₀ of 78.7 µg/mL, compared to ascorbic acid as a positive control with an IC₅₀ of 10.6 µg/mL. It also demonstrated significant cytotoxic activity with IC₅₀ values of 13.5 µg/mL and 25.3 µg/mL against HCT-116 and HEP-2 cell lines, respectively, compared to vinblastine as a positive control with IC₅₀ values of 2.34 µg/mL and 6.61 µg/mL against HCT-116 and HEP-2, respectively. Additionally, the ethyl acetate fraction displayed promising antibacterial activity against S. aureus with a MIC value of 62.5 µg/mL, compared to ciprofloxacin as a positive control with MIC values of 1.56 µg/mL for Gram-positive bacteria and 3.125 µg/mL for Gram-negative bacteria. It also exhibited activity against E. coli and P. aeruginosa with MIC values of 250 µg/mL and 500 µg/mL, respectively. Briefly, this is the first report on the biological activities and secondary metabolite content of the ethyl acetate fraction of Hymedesmia sp. marine sponge, emphasizing the potential for further research against resistant bacterial and fungal strains, as well as different cancer cell lines. The ethyl acetate fraction of Hymedesmia sp. is a promising source of safe and unique natural drugs with potential therapeutic and pharmaceutical benefits. Full article

Lipophilicity is one of the principal parameters that describe the pharmacokinetic behavior of a drug, including its absorption, distribution, metabolism, elimination, and toxicity. In this study, the lipophilicity and other physicochemical, pharmacokinetic, and toxicity properties that affect the bioavailability of newly synthesized dialkylaminoalkyldiquinothiazine hybrids as potential drug candidates are presented. The lipophilicity, as R_M0, was determined experimentally by the RP-TLC method using RP18 plates and acetone–TRIS buffer (pH 7.4) as the mobile phase. The chromatographic parameters of lipophilicity were compared to computationally calculated partition coefficients obtained by various types of programs such as iLOGP, XLOGP3, WLOGP, MLOGP, SILCOS-IT, LogP, logP, and milogP. In addition, the selected ADMET parameters were determined in silico using the SwissADME and pkCSM platforms and correlated with the experimental lipophilicity descriptors. The results of the lipophilicity study confirm that the applied algorithms can be useful for the rapid prediction of logP values during the first stage of study of the examined drug candidates. Of all the algorithms used, the biggest similarity to the chromatographic value (R_M0) for certain compounds was seen with iLogP. It was found that both the SwissADME and pkCSM web tools are good sources of a wide range of ADMET parameters that describe the pharmacokinetic profiles of the studied compounds and can be fast and low-cost tools in the evaluation of examined drug candidates during the early stages of the development process. Full article

A series of hybrid compounds with triazole and thiazolidine nuclei connected by a linker has been synthesized and extensively studied. Various synthetic methods for the target compounds have been tested. A microbiological assessment of the obtained compounds was carried out on strains of pathogenic fungi C. albicans, C. non-albicans, multidrug-resistant C. auris, Rhizopus arrhizus, Aspergillus spp. and some dermatophytes and other yeasts. The lowest obtained MIC values for target compounds lie between 0.003 µg/mL and 0.5 µg/mL and therefore the compounds are not inferior or several times better than commercial azole drugs. The length of the acylpiperazine linker has a limited effect on antifungal activity. Some bioisosteric analogues were tested in microbiological analysis, but turned out to be weaker than the leader in activity. The highest activity was demonstrated by a compound with para-chlorobenzylidene substituent in the thiazolidine fragment. Molecular modelling was used to predict binding modes of synthesized molecules and rationalize experimentally observed SAR. The leader compound is twice more effective in inhibiting the formation of germ tubes by Candida albicans yeast cells compared to voriconazole. An increased level of Pdr5, an azoles drug efflux pump was observed, but the increase is lower than that caused by azoles. The results can be useful for further development of more powerful and safe antifungal agents. Full article

The function of the sense of taste is usually confined to the ability to perceive the flavor of food to assess and use the nutrients necessary for healthy survival and to discard those that may be harmful, toxic, or unpleasant. It is almost unanimously agreed that the perception of bitter taste prevents the consumption of toxins from plants, decaying foods, and drugs. Forty years ago, while practicing medicine in a rural area of the Colombian Amazon, I had an unexpected encounter with the Inga Indians. I faced the challenge of accepting that their traditional medicine was effective and that the medicinal plants they used had a real therapeutic effect. Wanting to follow a process of learning about medicinal plants on their terms, I found that, for them, the taste of plants is a primary and fundamental key to understanding their functioning. One of the most exciting results was discovering the therapeutic value of bitter plants. The present review aims to understand whether there is any scientific support for this hypothesis from the traditional world. Can the taste of plants explain their possible therapeutic benefit? In the last 20 years, we have made novel advances in the knowledge of the physiology of taste. Our purpose will be to explore these scientific advances to determine if the bitter taste of medicinal plants benefits human health. Full article

Self-driving car research can effectively reduce the occurrence of traffic accidents, but when encountering sudden people or obstacles cutting into the lane, how to reduce the damage hazard to traffic participants and make ethical decisions is the key point that the development of self-driving technology must break through. When faced with sudden traffic participants, self-driving vehicles need to make ethical decisions between ramming into the traffic participants or other obstacles. Therefore, in this paper, we propose a model decision planning method based on multi-objective evaluation function path evaluation of local path planning. This method addresses the ethical model disagreement problem of self-driving vehicles encountering traffic participants and other obstacles. The aim is to ensure the safety of the lives of the traffic participants and achieve the vehicle’s reasonable ethical decision planning. Firstly, when anticipating traffic participants and other obstacles, the vehicle’s planning intention decisions are obtained through fuzzy algorithms. Different sets of curves for various positions are generated based on dynamic programming algorithms. These curves are then fitted using B-spline curves, incorporating obstacle collision costs, and classifying obstacles into different types with varying cost weights. Secondly, factors such as path length and average path curvature are considered for path total cost calculations. Finally, a local path that avoids traffic participants is obtained. This path is then tracked using a pure pursuit algorithm. The proposed algorithm’s effectiveness is verified through simulation experiments and comparative analyses conducted on the MATLAB platform. In conclusion, this research promotes a safer and more sustainable transport system in line with the principles of sustainable development by addressing the challenges associated with safety and ethical decision making in self-driving cars. Full article

Analyzing the change trend of urban green space (UGS) and exploring related driving forces can provide scientific reference for sustainable development in rapidly urbanizing areas. However, the spatial and temporal driving mechanisms of the drivers on UGS patterns at different scales are still not deeply understood. Based on the GlobeLand30 land cover data, nighttime lighting data and spatial statistics from 2000 to 2020, this study analyzed the size, shape and diversity of UGS in Guangzhou at the urban level, gradient level and township level with multiple landscape indices. Diversity means the richness of UGS patch types. The selected indices include percent of landscape (PLAND), largest path index (LPI), landscape shape index (LSI), aggregation index (AI) and Shannon’s diversity index (SHDI). The spatiotemporal heterogeneity of the drivers was then explored using the spatiotemporal weighted regression (GTWR) method. Results showed the following: (1) During 2000−2020, the total amount of UGS in Guangzhou increased slightly and then decreased gradually. UGS was mainly transferred into artificial surfaces (lands modified by human activities). (2) The UGS landscape showed a non-linear trend along the urban–rural gradient and fluctuated more in the interval of 20–60% urbanization level. PLAND, LPI and AI decreased significantly in areas with higher levels of urbanization. LSI increased and SHDI decreased significantly in areas with lower levels of urbanization. At township level, the landscape indices showed significant spatial autocorrelation. They transformed from discrete changes at the edge and at the junction of the administrative district to large-scale aggregated change, especially in northern areas. (3) The size of UGSs was mainly influenced by natural factors and population density, but their shape and diversity were mainly influenced by socio-economic factors. More regular shapes of green patches were expected in higher urbanization areas. Population agglomeration positively influenced green space patterns in the northeastern and southern regions (Zengcheng, Conghua and Nansha). Meanwhile the negative influence of urban expansion on the green space pattern in the central and southern regions decreased over time. This study contributes to an in-depth understanding of how the key factors affect the different changes of UGS with time and space and provides methodological support for the long-term zoning planning and management of UGS. Full article

The issue of sustainability has once again received attention and promotion in the post-COVID-19 pandemic era. Countries worldwide have launched returnable cup services for beverages, such as Taiwan, which is a highly developed market for hand-shaken drinks, and various beverage and convenience stores have been gradually launching this service. However, reasonable usage rates have yet to be achieved. This study aimed to explore the psychological cognition of using a returnable cups service by understanding the motivation affecting the behavior intention through external and internal influencing and categorizing realistic cognition, which observes the motivating factors from three perspectives: passively acquired awareness, autonomous consciousness, and perception in real life for further achieving environmental sustainability. Research found that when consumers’ environmental awareness is insufficient to sacrifice convenience, it is necessary to employ a service strategy design for passive influence. The focal point for influencing consumer attitudes lies in the backend of services, particularly in cup return, which is the chain-closing juncture. The result can provide the beverage industry and governments with a reference to promote returnable cups and contribute to plastic reduction in sustainable development. Full article

A new hydrothermal hot isostatic pressing (HHIP) approach, involving hydrothermal water conditions and no usage of inert gas, was hypothesized and tested on 3D-printed Al-10%Si-0.3%Mg (%Wt) parts. The aluminum-based metal was practically inert at the applied HHIPing conditions of 300–350 MPa and 250–350 °C, which enabled the employment of a long (6–24 h) HHIP treatment with hardly any loss of material (the overall loss due to corrosion was mostly <0.5% w/w). Applying the new approach on the above-mentioned samples resulted in an 85.7% reduction in the AM micro-pores, along with a 90.8% reduction in the pores’ surface area at a temperature of 350 °C, which is much lower than the 500–520 °C applied in common argon-based aluminum HIPing treatments, while practically maintaining the as-recieved microstructure. These results show that better mechanical properties can be expected when using the suggested treatment without affecting the material fatigue resistance due to grain growth. The proof of concept presented in this work can pave the way to applying the new HHIPing approach to other AM metal parts. Full article

Tropical dry forests (TDFs) are ecosystems of high biocultural value, in which agroforestry systems (AFSs) have been essential in their management and conservation. We aimed to characterize agroforestry practices and analyze their capacity to conserve perennial plant diversity. In addition, we sought to evaluate how the management of TDFs as AFSs, together with their regeneration, influences species diversity and vegetation structure in a landscape with AFSs and TDFs in different conservation states. We compared the species diversity and basal area (BA) of plants in active and fallow AFSs at different regeneration stages in Zacualpan, Colima, Mexico. We found that AFSs harbored 71% of species richness (⁰D), forming a mosaic that contributed to the gamma diversity (124 species) of TDFs in the area. AFSs supported 23 endemic and 12 protected species. TDFs, active and advanced regeneration AFSs, had the highest number of useful species and diversity. Species richness (⁰D) in management categories increased as succession progressed, but not the BA, possibly due to frequent browsing and wood and firewood extraction. However, BA may be related to the management of useful trees maintained through agroforestry practices. We suggest increasing the matrix quality through a mosaic of active and fallow AFSs to promote ecological connectivity and biodiversity conservation. Full article

The Laasraoui segmented and Arrhenius flow stress model, dynamic recrystallization (DRX) model, grain size prediction model, and hot processing map (HPM) of Fe-Cr-Mo-Mn steels were established through isothermal compression tests. The models and HPM were proven by experiment to be highly accurate. As the deformation temperature decreased or the strain rate increased, the flow stress increased and the grain size of the Fe-Cr-Mo-Mn steel decreased, while the volume fraction of DRX (X_drx) decreased. The optimal range of the hot processing was determined to be 1050–1200 °C/0.369–1 s⁻¹. Zigzag-like grain boundaries (GBs) and intergranular cracks were found in the unstable region, in which the disordered martensitic structure was observed. The orderly packet martensite was formed in the general processing region, and the mixed structure with incomplete DRX grains was composed of coarse and fine grains. The microstructure in the optimum processing region was composed of DRX grains and the multistage martensite. The validity of the Laasraoui segmented flow stress model, DRX model, grain size prediction model, and HPM was verified by upsetting tests. Full article

Rett syndrome (RTT) is a rare neurodevelopmental disorder caused by mutation in the X-linked gene methyl-CpG-binding protein 2 (Mecp2), a ubiquitously expressed transcriptional regulator. RTT results in mental retardation and developmental regression that affects approximately 1 in 10,000 females. Currently, there is no curative treatment for RTT. Thus, it is crucial to develop new therapeutic approaches for children suffering from RTT. Several studies suggested that RTT is linked with defects in cholesterol homeostasis, but for the first time, therapeutic evaluation is carried out by modulating this pathway. Moreover, AAV-based CYP46A1 overexpression, the enzyme involved in cholesterol pathway, has been demonstrated to be efficient in several neurodegenerative diseases. Based on these data, we strongly believe that CYP46A1 could be a relevant therapeutic target for RTT. Herein, we evaluated the effects of intravenous AAVPHP.eB-hCYP46A1-HA delivery in male and female Mecp2-deficient mice. The applied AAVPHP.eB-hCYP46A1 transduced essential neurons of the central nervous system (CNS). CYP46A1 overexpression alleviates behavioral alterations in both male and female Mecp2 knockout mice and extends the lifespan in Mecp2-deficient males. Several parameters related to cholesterol pathway are improved and correction of mitochondrial activity is demonstrated in treated mice, which highlighted the clear therapeutic benefit of CYP46A1 through the neuroprotection effect. IV delivery of AAVPHP.eB-CYP46A1 is perfectly well tolerated with no inflammation observed in the CNS of the treated mice. Altogether, our results strongly suggest that CYP46A1 is a relevant target and overexpression could alleviate the phenotype of Rett patients. Full article

Short glass fibers are generally used in posterior dental restorations to enhance the mechanical properties and improve the material microstructure. Two resin-based composites (S0 and SF) were formulated and characterized to investigate the influence of zirconium in their characteristics and properties. The organic part of the investigated materials was the same (BisGMA, TEGDMA, and a photochemical polymerization system), and in the inorganic part, besides quart, glassA, and hydroxylapatite with Zn, sample S0 contained strontium glass with zirconium and sample SF contained fiber powder of chopped zirconium. The samples were characterized by the degree of conversion (DC), mechanical properties, water sorption (WS), scanning electron microscopy (SEM), atomic force microscopy (AFM) before and after the WS test, and antimicrobial properties. The results obtained were subjected to one-way ANOVA and Tukey’s statistical tests. Both samples had a high DC. Regarding the mechanical properties, both samples were very similar, except DTS, which was higher for the composite without fibers. After 14 days, the WS value of the SF sample was lower than that of the S0 sample. Water caused significant changes in the topography of the SF sample, but thanks to its antimicrobial properties and the diffusion phenomenon, SF had a more pronounced antimicrobial effect. This study shows that the addition of appropriate amounts of Sr-Zr-glass powder gives the material in which it is added similar properties to material containing chopped zirconium glass fiber powder. According to the antimicrobial test results, resin composites containing experimental zirconia fillings can be considered in future in vitro clinical studies for posterior reconstructions with significantly improved mechanical properties. Full article

The bioactive surface modification of implantable devices paves the way towards the personalized healthcare practice by providing a versatile and tunable approach that increase the patient outcome, facilitate the medical procedure, and reduce the indirect or secondary effects. The purpose of our study was to assess the performance of composite coatings based on biopolymeric spheres of poly(lactide-co-glycolide) embedded with hydroxyapatite (HA) and methotrexate (MTX). Bio-simulated tests performed for up to one week evidenced the gradual release of the antitumor drug and the biomineralization potential of PLGA/HA-MTX sphere coatings. The composite materials proved superior biocompatibility and promoted enhanced cell adhesion and proliferation with respect to human preosteoblast and osteosarcoma cell lines when compared to pristine titanium. Full article

Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds. Poly(octamethylene suberate) (POS) nanoparticles (POS-NPs) were used as a matrix to encapsulate four therapeutic molecules used to treat skin disorders: caffeine (CF), quercetin (QR), hydrocortisone (HC), and adapalene (AD). Hydrophobicity and chemical structure of bioactive compounds (BCs) influenced the physicochemical stability of drug-loaded nanoparticles. The particle size of drug-loaded nanoparticles was between 254.9 nm for the CF-POS-NP and 1291.3 for QR-POS-NP. Particles had a negative charge from −27.6 mV (QR) to −49.2 mV (HC). Drug loading content for all BC-POS-NPs varies between 36.11 ± 1.48% (CF-POS-NP) and 66.66 ± 4.87% (AD-POS-NP), and their entrapment efficiency is relatively high (28.30 ± 1.81% and 99.95 ± 0.04%, respectively). Calorimetric analysis showed the appearance of polymorphism for AD- and HC-loaded systems and the drug’s complete solubilisation into all nanoparticle formulations. FTIR and NMR spectra showed apparent drug incorporation into the polymer matrix of NPs. The encapsulation of BCs enhanced the antioxidative effect. The prepared POS nanoparticles’ cytotoxicity was studied using two dermal cell lines, keratinocyte (HaCaT) cells and fibroblasts (HDFn). The nanoparticle cytotoxic effect was more substantial on HaCaT cell lines. A reconstructed human epidermis (RHE) was successfully used to investigate the penetration of polymeric NPs. Based on permeation and histology studies, HC-POS-NPs and CF-POS-NPs were shown not to be suitable for dermal applications with the explored drug concentrations. AD presents a high permeation rate and no toxic impact on RHE. Full article

The global deployment of renewable energies has taken off and calls for a continuous increase in foreign investments and cooperation, particularly because many states cannot cover the costs and technological requirements of the energy transition on their own. Therefore, there should be policies and legal frameworks in place to protect and thereby promote foreign investments. International Investment Agreements (IIAs) can, ceteris paribus, contribute to this goal. These agreements contain a set of obligations that protect foreign investments against possible discriminatory or arbitrary conduct of the host states. This includes transparency obligations that can help to create a level playing field for national and foreign renewable energy investors. Unfortunately, the concept of transparency, and its inherent implications, has not been clearly defined to date, and its relationship with renewable energy investments is still under investigation. Therefore, it is important to realise the prevailing transparency obligations under IIAs, and the best practices that can better meet the particular requirements of renewable energy investments. Using a qualitative approach, this article intends to pursue this goal by providing an overview of the concept of transparency, exploring its status in the context of fair and equitable treatment (FET), and analysing favourable transparency clauses in the light of renewable energy investment considerations. Full article