bluuebunny/crossref_metadata_2025 huggingface dataset:
Upscaled Production of Satellite-Free Droplets: Step Emulsification with Deterministic Lateral Displacement
Authors: Ji Guangchong , Masui Shuzo , Kanno Yusuke , Nisisako Takasi
Published: July 2024

Step emulsification is a key technique for achieving scalable production of monodisperse emulsion droplets owing to its resilience to flow fluctuations. However, the persistent issue of satellite droplets, an inherent byproduct of main droplets, poses challenges for achieving truly uniform product sizes. In a previous study, we introduced a module with step-emulsifier nozzles upstream and deterministic lateral displacement (DLD) micropillar arrays downstream to generate satellite-free droplets at a low throughput. In this study, we demonstrate an upscaled parallelized setup with ten modules that were designed to produce satellite-free droplets. Each module integrated 100 step-emulsification nozzles in the upstream region with DLD micropillar arrays downstream. We conducted 3D flow simulations to ensure homogeneous distribution of the input fluids. Uniformly supplying an aqueous polyvinyl alcohol solution and an acrylate monomer as continuous and dispersed phases into the ten modules, the nozzles in each module exhibited a production rate of 539.5 ± 28.6 drop/s (n = 10). We successfully isolated the main droplets with a mean diameter of 66 μm and a coefficient of variation of 3.1% from satellite droplets with a mean diameter of 3 μm. The total throughput was 3.0 mL/h. The high yield and contamination-free features of our approach are promising for diverse industrial applications.
Accurate Detection and Analysis of Pore Defects in Laser Powder Bed Fusion WE43 Magnesium Alloys
Authors: Men Zhengxing , Wang Liang , Gao Xi , Chen Wen , Ji Chen , Li Ziche , Li Kun
Published: July 2024

To explore the size, morphology, and distribution patterns of internal pore defects in WE43 magnesium alloy formed by laser powder bed fusion (LPBF), as well as their impact on its mechanical properties, computer tomography (CT), metallographic microscopy, and scanning electron microscopy were used to observe the material’s microstructure and the morphology of tensile test fractures. The study revealed that a large number of randomly distributed non-circular pore defects exist internally in the LPBF-formed WE43 magnesium alloy, with a defect volume fraction of 0.16%. Approximately 80% of the defects had equivalent diameters concentrated in the range of 10∼40 μm, and 56.2% of the defects had sphericity values between 0.65∼0.7 μm, with the maximum defect equivalent diameter being 122 μm. There were a few spherical pores around 20 μm in diameter in the specimens, and unfused powder particles were found in pore defects near the edges of the parts. Under the test conditions, the fusion pool structure of LPBF-formed WE43 magnesium alloy resembled a semi-elliptical shape with a height of around 66 μm, capable of fusion three layers of powder material in a single pass. Columnar grains formed at the edge of individual fusion pools, while the central area exhibited equiaxed grains. The “scale-like pattern” formed by overlapping fusion pool structures resulted in the microstructure of LPBF-formed WE43 magnesium alloy mainly consisting of fine equiaxed grains with a size of 2.5 μm and columnar grains distributed in a band-like manner.
Rapid Classification and Differentiation of Sepsis-Related Pathogens Using FT-IR Spectroscopy
Authors: Ahmed Shwan , Albahri Jawaher , Shams Sahand , Sosa-Portugal Silvana , Lima Cassio , Xu Yun , McGalliard Rachel , Jones Trevor , Parry Christopher M. , Timofte Dorina , Carrol Enitan D. , Muhamadali Howbeer , Goodacre Royston
Published: July 2024

Sepsis is a life-threatening condition arising from a dysregulated host immune response to infection, leading to a substantial global health burden. The accurate identification of bacterial pathogens in sepsis is essential for guiding effective antimicrobial therapy and optimising patient outcomes. Traditional culture-based bacterial typing methods present inherent limitations, necessitating the exploration of alternative diagnostic approaches. This study reports the successful application of Fourier-transform infrared (FT-IR) spectroscopy in combination with chemometrics as a potent tool for the classification and discrimination of microbial species and strains, primarily sourced from individuals with invasive infections. These samples were obtained from various children with suspected sepsis infections with bacteria and fungi originating at different sites. We conducted a comprehensive analysis utilising 212 isolates from 14 distinct genera, comprising 202 bacterial and 10 fungal isolates. With the spectral analysis taking several weeks, we present the incorporation of quality control samples to mitigate potential variations that may arise between different sample plates, especially when dealing with a large sample size. The results demonstrated a remarkable consistency in clustering patterns among 14 genera when subjected to principal component analysis (PCA). Particularly, Candida, a fungal genus, was distinctly recovered away from bacterial samples. Principal component discriminant function analysis (PC-DFA) allowed for distinct discrimination between different bacterial groups, particularly Gram-negative and Gram-positive bacteria. Clear differentiation was also observed between coagulase-negative staphylococci (CNS) and Staphylococcus aureus isolates, while methicillin-resistant S. aureus (MRSA) was also separated from methicillin-susceptible S. aureus (MSSA) isolates. Furthermore, highly accurate discrimination was achieved between Enterococcus and vancomycin-resistant enterococci isolates with 98.4% accuracy using partial least squares-discriminant analysis. The study also demonstrates the specificity of FT-IR, as it effectively discriminates between individual isolates of Streptococcus and Candida at their respective species levels. The findings of this study establish a strong groundwork for the broader implementation of FT-IR and chemometrics in clinical and microbiological applications. The potential of these techniques for enhanced microbial classification holds significant promise in the diagnosis and management of invasive bacterial infections, thereby contributing to improved patient outcomes.
Liver Stiffness Evaluation in Chronic Hepatitis C Patients with Cirrhosis before and after Direct-Acting Antivirals
Authors: Stasi Cristina , Brillanti Stefano
Published: July 2024

After the introduction of direct-acting antivirals, parallel significant clinical progress has been achieved in the assessment of liver fibrosis progression/regression before treatment and during the follow-up of the cirrhotic patients with chronic hepatitis C virus (HCV) infection. The evolution of chronic hepatitis C into liver cirrhosis is correlated with an extensive accumulation of the extracellular matrix, leading to the formation of large amounts of fibrotic tissues that, initially, are concentrated in periportal areas and, in the later stages, surround the nodules of regenerating hepatocytes. The progressive increase in the fibrotic matrix contributes to vascular disturbances (favoring the development of portal hypertension) and to microenvironmental changes. The four clinical stages of liver cirrhosis are predictors for different clinical scenarios. The wide-ranging functions of the liver require different methods for their assessment. The non-invasive evaluation using transient elastography is useful in determining the longitudinal modifications of fibrosis during and after treatment with direct-acting antivirals. The liver stiffness evaluation, known to have a wide range of values in cirrhotic patients, can offer different prognostic implications after sustained virological response. This review discusses the different time points of liver stiffness evaluation that appear to show a more well-defined propensity to identify adequate monitoring schedules for these patients.
The Devonian Kalarskoe Epithermal Occurrence of the Kaburchak Au-Ag Cluster in the Altai-Sayan Folded Area, Russia: Geological Setting; Mineralogical, Geochemical, and Geochronological Features
Authors: Chernykh Alexander I. , Leibham Polina N. , Sokolova Lidia A. , Yakubovich Olga V. , Anosova Maria O. , Naumov Evgeny A.
Published: July 2024

Prospecting efforts to located Au mineralization within the Altai-Sayan fold area (ASFA) over previous decades have revealed that Devonian epithermal Au-Ag mineralization is more widespread than previously recognized. The preservation of this type of mineralization in Paleozoic rocks offers new prospects for the exploration of Au-Ag deposits in the underexplored region of Gornaya Shoria. The Kalarskoe epithermal Au-Ag occurrence represents Devonian epithermal mineralization within the Kaburchak cluster, Gornaya Shoria, Russia. This occurrence is confined to zones of argillic alteration that were superimposed on previously formed propylites. The argillic-altered rocks host quartz-sulfide veinlet zones. The mineralization of the Kalarskoe site is characterized by a high abundance of sulfide minerals: commonly, 5%–10%; often, up to 20%; and in some cases, up to 60%–70%. The ore minerals are represented by pyrite, arsenopyrite, sphalerite, galena, chalcopyrite, fahlores, native Au, and electrum, as well as by the sulfosalts Pb, Bi, Ag, Cu, and the tellurides of Au, Ag, and Pb. Based on mineralogical observations, at least four generations of sulfide mineral formations are distinguished within the ore occurrence. The mineralization of the Kalarskoe ore occurrence may be assigned to the intermediate sulfidation (IS) type. The results of the (U,Th)-He dating of pyrite from the pyrite-arsenopyrite massive body (pyr-3 and 4) revealed the protracted history of the mineralization in the intervals from ~399 to ~371 Ma. The obtained results substantially enhance the prospecting models for the exploration of epithermal Au-Ag deposits in the western part of the Altai-Sayan fold area (ASFA).
Petrogenesis and Tectonic Implications of the Granite Porphyry in the Sinongduo Ag-Pb-Zn Deposit, Central Tibet: Constraints from Geochronology, Geochemistry, and Sr-Nd Isotopes
Authors: Zhang Peng , Li Zhuang , Zhao Feng , Liu Xinkai
Published: July 2024

The Paleocene ore deposits related to the India–Asia continental collision are widely distributed in the Gangdese metallogenic belt. Among these, Sinongduo is the first discovered epithermal Ag-Pb-Zn deposit in the Lhasa terrane. However, there is still controversy over the ore-forming magma in this deposit. This study mainly reports new zircon U-Pb isotopic ages, whole-rock geochemistry, and Sr-Nd isotopic data for the granite porphyry from the Sinongduo deposit, aiming to discuss the petrogenesis and tectonic setting of the granite porphyry and its genetic link between the Ag-Pb-Zn mineralization. The results show that zircon U-Pb analyses yield ages of 62.9 ± 0.5 Ma and 59.0 ± 0.7 Ma for the granite porphyry, indicating that it formed during the Paleocene period. The timing of the granite porphyry intrusion is contemporaneous with the mineralization, suggesting that it is most likely the ore-forming magma in the Sinongduo deposit. The granite porphyry has high SiO2 and K2O, moderate Al2O3, and low Na2O, CaO, and FeOT contents, and it displays significant enrichments in LREEs and LILEs and depletions in HREEs and HFSEs, with negative Eu anomaly. The granite porphyry is a peraluminous series and can be classified as S-type granite. Moreover, the granite porphyry shows relatively high ratios of (87Sr/86Sr)i and low values of εNd(t). The geochemical and isotopic compositions of the granite porphyry from the Sinongduo area are similar to those of the upper continental crust, which suggests that the granite porphyry was most likely derived from the melting of the upper continental crust in the Lhasa terrane during the India–Asia collisional tectonic setting.
New Derivatives of Modified Starch for Food Technology
Authors: Konował Emilia , Sulej-Chojnacka Joanna , Prochaska Krystyna
Published: July 2024

The food industry extensively uses chemically modified starches and their hydrolysates, which is mainly due to their emulsification ability. Therefore, it becomes inevitable to develop new starch derivatives, including modified starch hydrolysates, and effective preparation methods to meet the increasing demands of producers, consumers, and technology. This study comprehensively researches the physical, chemical, and functional properties (such as the water-binding capacity, swelling power, solubility, and fat absorption capacity) of chemically modified biopolymers and their enzymatic hydrolysis products. We utilized oxidized and acetylated potato and waxy-corn starches with varying degrees of substitution by carboxyl and acetyl groups in our research. The process of enzymatic hydrolysis was performed in a recirculated membrane reactor (CRMR). Our findings indicated that the physicochemical properties of starch derivatives and their hydrolysates depended on the biological origin of the biopolymer and the type and degree of modification. However, the presence of carboxyl groups in the modified starch molecules is critical and affects the rheological properties and water-binding capacity of the starch preparations. For example, in the case of waxy-corn starch preparations with a lower content of carboxyl groups (i.e., derivatives with a low degree of oxidation), the water-binding capacity (WBC) increases when compared to native starch. The highest WBC value of 206.3% was noted for the doubly modified waxy-corn starch with an oxidation degree of 0.2% and an acetylation degree of 2.5%, while native waxy-corn starch shows a WBC of 161.4%. In contrast, it was observed that preparations with a higher content of carboxyl groups, i.e., derivatives with an oxidation degree of 2.5%, show a lower swelling power compared to native waxy starch.
A Comparative Study of Surfactant Solutions Used for Enhanced Oil Recovery in Shale and Tight Formations: Experimental Evaluation and Numerical Analysis
Authors: Chen Weidong , Geng Xiangfei , Ding Bin , Liu Weidong , Jiang Ke , Xu Qinglong , Guan Baoshan , Peng Lin , Peng Huan
Published: July 2024

Applying chemical enhanced oil recovery (EOR) to shale and tight formations is expected to accelerate China’s Shale Revolution as it did in conventional reservoirs. However, its screening and modeling are more complex. EOR operations are faced with choices of chemicals including traditional surfactant solutions, surfactant solutions in the form of micro-emulsions (nano-emulsions), and nano-fluids, which have similar effects to surfactant solutions. This study presents a systematic comparative analysis composed of laboratory screening and numerical modeling. It was conducted on three scales: tests of chemical morphology and properties, analysis of micro-oil-displacing performance, and simulation of macro-oil-increasing effect. The results showed that although all surfactant solutions had the effects of reducing interfacial tension, altering wettability, and enhancing imbibition, the nano-emulsion with the lowest hydrodynamic radius is the optimal selection. This is attributed to the fact that the properties of the nano-emulsion match well with the characteristics of these shale and tight reservoirs. The nano-emulsion is capable of integrating into the tight matrix, interacting with the oil and rock, and supplying the energy for oil to flow out. This study provides a comprehensive understanding of the role that surfactant solutions could play in the EOR of unconventional reservoirs.
Expression Profiles of ITGA8 and VANGL2 Are Altered in Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Authors: Pavlović Nikola , Kelam Nela , Racetin Anita , Filipović Natalija , Pogorelić Zenon , Prusac Ivana Kuzmić , Vukojević Katarina
Published: July 2024

Kidney failures in infants are mostly caused by congenital anomalies of the kidney and urinary tract (CAKUT), which are among the most common congenital birth disorders worldwide when paired with cardiac abnormalities. People with CAKUT often have severe kidney failure as a result of a wide range of abnormalities that can occur alone or in conjunction with other syndromic disorders. In this study, we aimed to investigate the expression pattern of CAKUT candidate genes alpha-8 integrin (ITGA8) and Van Gogh-like 2 (VANGL2) in fetal tissues of healthy and CAKUT-affected kidneys using immunohistochemistry and immunofluorescence. We found that under CAKUT circumstances, the expressions of ITGA8 and VANGL2 are changed. Additionally, we showed that VANGL2 expression is constant during fetal aging, but ITGA8 expression varies. Moreover, compared to normal healthy kidneys (CTRL), ITGA8 is poorly expressed in duplex kidneys (DKs) and dysplastic kidneys (DYS), whereas VANGL2 is substantially expressed in dysplastic kidneys (DYS) and poorly expressed in hypoplastic kidneys (HYP). These results point to VANGL2 and ITGA8 as potential prognostic indicators for CAKUT malformations. Further research is necessary to explore the molecular mechanisms underlying this differential expression of ITGA8 and VANGL2.
Analysis of the Behavior of Deep Eutectic Solvents upon Addition of Water: Its Effects over a Catalytic Reaction
Authors: Campodónico Paola R. , Alarcón-Espósito Jazmín , Alcázar Jackson J. , Olivares Belén , Suárez-Rozas Cristian
Published: July 2024

This study presents the potential role of deep eutectic solvents (DESs) in a lipase-catalyzed hydrolysis reaction as a co-solvent in an aqueous solution given by a phosphate buffer. Ammonium salts, such as choline chloride, were paired with hydrogen bond donors, such as urea, 1,2,3-propanetriol, and 1,2 propanediol. The hydrolysis of p-nitrophenyl laureate was carried out with the lipase Candida antarctica Lipase B (CALB) as a reaction model to evaluate the solvent effect and tested in different DES/buffer phosphate mixtures at different % w/w. The results showed that two mixtures of different DES at 25 % w/w were the most promising solvents, as this percentage enhanced the activities of CALB, as evidenced by its higher catalytic efficiency (kcatKM). The solvent analysis shows that the enzymatic reaction requires a reaction media rich in water molecules to enable hydrogen-bond formation from the reaction media toward the enzymatic reaction, suggesting a better interaction between the substrate and the enzyme-active site. This interaction could be attributed to high degrees of freedom influencing the enzyme conformation given by the reaction media, suggesting that CALB acquires a more restrictive structure in the presence of DES or the stabilized network given by the hydrogen bond from water molecules in the mixture improves the enzymatic activity, conferring conformational stability by solvent effects. This study offers a promising approach for applications and further perspectives on genuinely green industrial solvents.
33S NMR: Recent Advances and Applications
Authors: Gerothanassis Ioannis P. , Kridvin Leonid B.
Published: July 2024

The purpose of this review is to present advances and applications of 33S NMR, which is an underutilized NMR spectroscopy. Experimental NMR aspects in solution, chemical shift tendencies, and quadrupolar relaxation parameters will be briefly summarized. Emphasis will be given to advances and applications in the emerging fields of solid-state and DFT computations of 33S NMR parameters. The majority of the examples were taken from the last twenty years and were selected on the basis of their importance to provide structural, electronic, and dynamic information that is difficult to obtain by other techniques.
Chiral Star-Shaped [CoIII3LnIII] Clusters with Enantiopure Schiff Bases: Synthesis, Structure, and Magnetism
Authors: Ji Liudi , Wang Juntao , Li Zeyu , Zhu Xiaoming , Hu Peng
Published: July 2024

Two enantiomeric pairs of new 3d–4f heterometallic clusters have been synthesized from two enantiomer Schiff base derivatives: (R/S)-2-[(2-hydroxy-1-phenylethylimino)methyl] phenol (R-/S-H2L). The formulae of the series clusters are Co3Ln(R-L)6 (Ln = Dy (1R), Gd (2R)), Co3Ln (S-L)6 (Ln = Dy (1S), Gd (2S)), whose crystal structures and magnetic properties have been characterized. Structural analysis indicated that the above clusters crystallize in the chiral P213 group space. The central lanthanide ion has a coordination geometry of D3 surrounded by three [CoIII(L)2]– anions using six aliphatic oxygen atoms of L2− featuring a star-shaped [CoIII3LnIII] configuration. Magnetic measurements showed the presence of slow magnetic relaxation with an effective energy barrier of 22.33 K in the DyIII derivatives under a zero-dc field. Furthermore, the circular dichroism (CD) spectra of 1R and 1S confirmed their enantiomeric nature.
A Review of Plant-Mediated ZnO Nanoparticles for Photodegradation and Antibacterial Applications
Authors: Mutukwa Dorcas , Taziwa Raymond Tichaona , Khotseng Lindiwe
Published: July 2024

This review focuses on the synthesis of plant-mediated zinc oxide nanoparticles (ZnO NPs) and their applications for antibacterial and photocatalytic degradation of dyes, thereby addressing the need for sustainable and eco-friendly methods for the preparation of NPs. Driven by the significant rise in antibiotic resistance and environmental pollution from dye pollution, there is a need for more effective antibacterial agents and photocatalysts. Therefore, this review explores the synthesis of plant-mediated ZnO NPs, and the influence of reaction parameters such as pH, annealing temperature, plant extract concentration, etc. Additionally, it also looks at the application of plant-mediated ZnO NPs for antibacterial and photodegradation of dyes, focusing on the influence of the properties of the plant-mediated ZnO NPs such as size, shape, and bandgap on the antibacterial and photocatalytic activity. The findings suggest that properties such as shape and size are influenced by reaction parameters and these properties also influence the antibacterial and photocatalytic activity of plant-mediated ZnO NPs. This review concludes that plant-mediated ZnO NPs have the potential to advance green and sustainable materials in antibacterial and photocatalysis applications.
Toxicity of Silver–Chitosan Nanocomposites to Aquatic Microcrustaceans Daphnia magna and Thamnocephalus platyurus and Naturally Luminescent Bacteria Vibrio fischeri
Authors: Sihtmäe Mariliis , Laanoja Jüri , Blinova Irina , Kahru Anne , Kasemets Kaja
Published: July 2024

All novel materials should be analyzed for their potential environmental hazard. In this study, the toxicity of different silver–chitosan nanocomposites—potential candidates for wound dressings or antimicrobial surface coatings—was evaluated using environmentally relevant aquatic microcrustaceans Daphnia magna and Thamnocephalus platyurus and naturally luminescent bacteria Vibrio fischeri. Three silver-chitosan nanocomposites (nAgCSs) with different weight ratios of Ag to CS were studied. Citrate-coated silver nanoparticles (nAg-Cit), AgNO3 (ionic control) and low molecular weight chitosan (LMW CS) were evaluated in parallel. The primary size of nAgCSs was ~50 nm. The average hydrodynamic sizes in deionized water were ≤100 nm, and the zeta potential values were positive (16–26 mV). The nAgCSs proved very toxic to aquatic crustaceans: the 48-h EC50 value for D. magna was 0.065–0.232 mg/L, and the 24-h LC50 value for T. platyurus was 0.25–1.04 mg/L. The toxic effect correlated with the shedding of Ag ions (about 1%) from nAgCSs. Upon exposure of V. fischeri to nAgCSs for 30 min, bacterial luminescence was inhibited by 50% at 13–33 mg/L. However, the inhibitory effect (minimum bactericidal concentration, MBC) on bacterial growth upon 1 h exposure was observed at higher concentrations of nAgCSs, 40–65 mg/L. LMW CS inhibited bacterial luminescence upon 30-min exposure at 5.6 mg/L, but bacterial growth was inhibited at a much higher concentration (1 h MBC > 100 mg/L). The multi-trophic test battery, where D. magna was the most sensitive test organism, ranked the silver-chitosan nanocomposites from ‘extremely toxic’ [L(E)C50 ≤ 0.1 mg/L] to ‘very toxic’ [L(E)C50 > 0.1–1 mg/L]. Chitosan was toxic (EC(L)50) to crustaceans at ~12 mg/L, and ranked accordingly as ‘harmful’ [L(E)C50 > 10–100 mg/L]. Thus, silver-chitosan nanocomposites may pose a hazard to aquatic organisms and must be handled accordingly.
The INFN-LNF Astrophysics and Cosmology Integrated Test Facility Startup
Authors: Porcelli Luca , Dabagov Sultan , Delle Monache Giovanni , Hampai Dariush , Modestino Giuseppina , Savaglio Sandra
Published: July 2024

Starting from January 2023, Permanent Staff Personnel and Associated Personnel of INFN-LNF (Istituto Nazionale di Fisica Nucleare—Laboratori Nazionali di Frascati) have founded, and are setting up, the local Astrophysics and Cosmology Team (ACT). The INFN-LNF ACT joined the initial development phases of one of the forthcoming (early 2030) next-generation cosmology space-borne probes, with particular emphasis on (1) thermal balance tests (and correlation to models) of the electronics of interest; (2) (non)destructive irradiation tests of the electronics of interest and X-ray circuitry diagnostics on a specifically dedicated and instrumented optical bench; and (3) joining the simulation-related, and data analysis-related, activities, at both the cosmological and instrumental levels. The INFN-LNF ACT has constituted an Integrated Test Facility (ITF), which is being instrumented in a dedicated space and will also make use of the pre-existing INFN-LNF infrastructures. In the following, as a first contribution, mainly related to what was completed in late 2023 and early 2024, the activities of the commissioning and setup of the so-called ‘pocket’ cryostat are described, linking them to the envisaged thermal balance tests (and correlation to the models) of the electronics of interest. While mainly devoted to cosmology-oriented tasks, the INFN-LNF ACT ‘pocket’ cryostat will, in principle, be available to the wider community for other dedicated activities.
In Vivo Regulation of Small Molecule Natural Products, Antioxidants, and Nutrients by OAT1 and OAT3
Authors: Falah Kian , Zhang Patrick , Nigam Anisha K. , Maity Koustav , Chang Geoffrey , Granados Jeffry C. , Momper Jeremiah D. , Nigam Sanjay K.
Published: July 2024

The organic anion transporters OAT1 (SLC22A6) and OAT3 (SLC22A8) are drug transporters that are expressed in the kidney, with well-established roles in the in vivo transport of drugs and endogenous metabolites. A comparatively unexplored potential function of these drug transporters is their contribution to the in vivo regulation of natural products (NPs) and their effects on endogenous metabolism. This is important for the evaluation of potential NP interactions with other compounds at the transporter site. Here, we have analyzed the NPs present in several well-established databases from Asian (Chinese, Indian Ayurvedic) and other traditions. Loss of OAT1 and OAT3 in murine knockouts caused serum alterations of many NPs, including flavonoids, vitamins, and indoles. OAT1- and OAT3-dependent NPs were largely separable based on a multivariate analysis of chemical properties. Direct binding to the transporter was confirmed using in vitro transport assays and protein binding assays. Our in vivo and in vitro results, considered in the context of previous data, demonstrate that OAT1 and OAT3 play a pivotal role in the handling of non-synthetic small molecule natural products, NP-derived antioxidants, phytochemicals, and nutrients (e.g., pantothenic acid, thiamine). As described by remote sensing and signaling theory, drug transporters help regulate redox states by meditating the movement of endogenous antioxidants and nutrients between organs and organisms. Our results demonstrate how dietary antioxidants and other NPs might feed into these inter-organ and inter-organismal pathways.
Postbiotics as Molecules Targeting Cellular Events of Aging Brain—The Role in Pathogenesis, Prophylaxis and Treatment of Neurodegenerative Diseases
Authors: Głowacka Pola , Oszajca Katarzyna , Pudlarz Agnieszka , Szemraj Janusz , Witusik-Perkowska Monika
Published: July 2024

Aging is the most prominent risk factor for neurodegeneration occurrence. The most common neurodegenerative diseases (NDs), Alzheimer’s (AD) and Parkinson’s (PD) diseases, are characterized by the incidence of proteinopathy, abnormal activation of glial cells, oxidative stress, neuroinflammation, impaired autophagy and cellular senescence excessive for the patient’s age. Moreover, mitochondrial disfunction, epigenetic alterations and neurogenesis inhibition, together with increased blood–brain barrier permeability and gut dysbiosis, have been linked to ND pathogenesis. Since NDs still lack curative treatment, recent research has sought therapeutic options in restoring gut microbiota and supplementing probiotic bacteria-derived metabolites with beneficial action to the host—so called postbiotics. The current review focuses on literature explaining cellular mechanisms involved in ND pathogenesis and research addressing the impact that postbiotics as a whole mixture and particular metabolites, such as short-chain fatty acids (SCFAs), lactate, polyamines, polyphenols, tryptophan metabolites, exopolysaccharides and bacterial extracellular vesicles, have on the ageing-associated processes underlying ND occurrence. The review also discusses the issue of implementing postbiotics into ND prophylaxis and therapy, depicting them as compounds addressing senescence-triggered dysfunctions that are worth translating from bench to pharmaceutical market in response to “silver consumers” demands.
Phase Angle as Surrogate Marker of Muscle Weakness in Kidney Transplant Candidates Referred to Prehabilitation
Authors: Marco Ester , Pérez-Sáez María José , Muñoz-Redondo Elena , Curbelo Yulibeth G. , Ramírez-Fuentes Cindry , Meza-Valderrama Delky , Acuña-Pardo Carolina , Muns Mª Dolors , Vázquez-Ibar Olga , Chamoun Betty Odette , Faura-Vendrell Anna , Bach Anna , Crespo Marta , Pascual Julio
Published: July 2024

Phase angle (PhA), a marker of nutritional status obtained by bioelectrical impedance analysis (BIA), is associated with the integrity of cell membranes. Damage to muscle fiber membranes can impact muscle strength, which is related to adverse outcomes in adults with advanced chronic kidney disease (CKD). The main objective of this study was to determine the usefulness of the PhA in identifying muscle weakness in candidates for kidney transplants (KTs). Secondly, it aimed to examine the associations of PhA with other parameters of body composition, exercise performance, and muscle structure. Sensitivity, specificity, and area under the receiver operating characteristics curve were used to evaluate the PhA (index test) as a biomarker of muscle weakness. Muscle strength was estimated with maximal voluntary isometric contraction of the quadriceps (MVCI-Q) of the dominant side. Muscle weakness was defined as MVIC-Q < 40% of body weight. A total of 119 patients were evaluated (mean age 63.7 years, 75.6% men). A phase angle cut-off of 5.1° was identified to classify men with a higher likelihood of having low muscle strength in upper limbs (MVIC-Q 40% of their body weight). Male KT candidates with PhA < 5.1° had poorer exercise capacity, lower muscle strength, less muscle mass, and smaller muscle size. A PhA < 5.1° was significantly associated with an eight-fold higher muscle weakness risk (OR = 8.2, 95%CI 2.3–29.2) in a binary regression model adjusted by age, frailty, and hydration status. Remarkably, PhA is an easily obtainable objective parameter in CKD patients, requiring no volitional effort from the individual. The associations of PhA with aerobic capacity, physical activity, muscle mass, and muscle size underscore its clinical relevance and potential utility in the comprehensive evaluation of these patients.
A Diet Lacking Selenium, but Not Zinc, Copper or Manganese, Induces Anticancer Activity in Mice with Metastatic Cancers
Authors: Díaz-Ortega Patricia , Calderón-Montaño José Manuel , Jiménez-Alonso Julio José , Guillén-Mancina Emilio , Jiménez-González Víctor , Burgos-Morón Estefanía , López-Lázaro Miguel
Published: July 2024

Selenium, zinc, copper, and manganese are essential components of antioxidant enzymes involved in the elimination of reactive oxygen species (ROS). Given that cancer cells produce high levels of ROS and the accumulation of ROS can lead to cell death, cancer cells may be susceptible to strategies that reduce ROS elimination. In this work, we prepared several artificial diets that contained normal carbohydrate, protein, and lipid levels but lacked selenium, zinc, copper, or manganese. The anticancer activity of these diets was examined in a metastatic ovarian cancer model, established by injecting ID8 Trp53−/− murine ovarian cancer cells into the peritoneal cavity of C57BL/6JRj mice. Treatments started 15 days later and consisted of replacing a normal diet with one of the artificial diets for several weeks. A significant improvement in mice survival was observed when the normal diet was replaced with the selenium-free diet. Diets lacking zinc, copper, or manganese showed no significant impact on mice survival. All diets were very well tolerated. The anticancer efficacy of a diet lacking selenium was confirmed in mice with metastatic colon cancer and in mice with metastatic triple-negative breast cancer. These results suggest that diets lacking selenium hold potential for the treatment of metastatic cancers.
Dietary LPC-Bound n-3 LCPUFA Protects against Neonatal Brain Injury in Mice but Does Not Enhance Stem Cell Therapy
Authors: Hermans Eva C. , van Gerven Carlon C. E. , Johnsen Line , Tungen Jørn E. , Nijboer Cora H. , de Theije Caroline G. M.
Published: July 2024

Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21–28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy.
Unveiling the Mechanisms Underlying the Immunotherapeutic Potential of Gene–miRNA and Drugs in Head and Neck Cancer
Authors: Danishuddin  , Haque Md Azizul , Malik Md. Zubbair , Arya Rakesh , Singh Pooja , Lee Jeong-Sang , Kim Jong-Joo , Lee Keun-Woo , Jung Tae-Sung
Published: July 2024

Head and neck cancer ranks as the sixth-most common malignancy worldwide, characterized by high mortality and recurrence rates. Research studies indicate that molecular diagnostics play a crucial role in the early detection and prognostic evaluation of these diseases. This study aimed to identify potential biomarkers for head and neck cancer and elucidate their interactions with miRNAs and possible therapeutic drugs. Four drivers, namely, FN1, IL1A, COL1A1, and MMP9, were identified using network biology and machine learning approaches. Gene set variation analysis (GSVA) showed that these genes were significantly involved in different biological processes and pathways, including coagulation, UV-response-down, apoptosis, NOTCH signaling, Wnt-beta catenin, and other signal pathways. The diagnostic value of these hub genes was validated using receiver operating characteristic (ROC) curves. The top interactive miRNAs, including miR-128-3p, miR-218-5p, miR-214-3p, miR-124-3p, miR-129-2-3p, and miR-1-3p, targeted the key genes. Furthermore, the interaction between the key genes and drugs was also identified. In summary, the key genes and miRNAs or drugs reported in this study might provide valuable information for potential biomarkers to increase the prognosis and diagnosis of head and neck cancer.
Indole Compounds in Oncology: Therapeutic Potential and Mechanistic Insights
Authors: Hassan Sara M. , Farid Alyaa , Panda Siva S. , Bekheit Mohamed S. , Dinkins Holden , Fayad Walid , Girgis Adel S.
Published: July 2024

Cancer remains a formidable global health challenge, with current treatment modalities such as chemotherapy, radiotherapy, surgery, and targeted therapy often hindered by low efficacy and adverse side effects. The indole scaffold, a prominent heterocyclic structure, has emerged as a promising candidate in the fight against cancer. This review consolidates recent advancements in developing natural and synthetic indolyl analogs, highlighting their antiproliferative activities against various cancer types over the past five years. These analogs are categorized based on their efficacy against common cancer types, supported by biochemical assays demonstrating their antiproliferative properties. In this review, emphasis is placed on elucidating the mechanisms of action of these compounds. Given the limitations of conventional cancer therapies, developing targeted therapeutics with enhanced selectivity and reduced side effects remains a critical focus in oncological research.
Hydrogel Loaded with Extracellular Vesicles: An Emerging Strategy for Wound Healing
Authors: Yang Yucan , Chen Huizhi , Li Yunjie , Liang Junting , Huang Feng , Wang Liyan , Miao Huilai , Nanda Himansu Sekhar , Wu Jin , Peng Xinsheng , Zhou Yubin
Published: July 2024

An increasing number of novel biomaterials have been applied in wound healing therapy. Creating beneficial environments and containing various bioactive molecules, hydrogel- and extracellular vesicle (EV)-based therapies have respectively emerged as effective approaches for wound healing. Moreover, the synergistic combination of these two components demonstrates more favorable outcomes in both chronic and acute wound healing. This review provides a comprehensive discussion and summary of the combined application of EVs and hydrogels to address the intricate scenario of wounds. The wound healing process and related biological mechanisms are outlined in the first section. Subsequently, the utilization of EV-loaded hydrogels during the wound healing process is evaluated and discussed. The moist environment created by hydrogels is conducive to wound tissue regeneration. Additionally, the continuous and controlled release of EVs from various origins could be achieved by hydrogel encapsulation. Finally, recent in vitro and in vivo studies reported on hydrogel dressings loaded with EVs are summarized and challenges and opportunities for the future clinical application of this therapeutic approach are outlined.
A Comprehensive Physiologically Based Pharmacokinetic Model for Predicting Vildagliptin Pharmacokinetics: Insights into Dosing in Renal Impairment
Authors: Pasha Mahnoor , Zamir Ammara , Rasool Muhammad Fawad , Saeed Hamid , Ahmad Tanveer , Alqahtani Nawaf Shalih , Alqahtani Lamya Saif , Alqahtani Faleh
Published: July 2024

Physiologically based pharmacokinetic (PBPK) modeling is of great importance in the field of medicine. This study aims to construct a PBPK model, which can provide reliable drug pharmacokinetic (PK) predictions in both healthy and chronic kidney disease (CKD) subjects. To do so, firstly a review of the literature was thoroughly conducted and the PK information of vildagliptin was collected. PBPK modeling software, PK-Sim®, was then used to build and assess the IV, oral, and drug-specific models. Next, the average fold error, visual predictive checks, and predicted/observed ratios were used for the assessment of the robustness of the model for all the essential PK parameters. This evaluation demonstrated that all PK parameters were within an acceptable limit of error, i.e., 2 fold. Also to display the influence of CKD on the total and unbound AUC (the area under the plasma concentration–time curve) and to make modifications in dose, the analysis results of the model on this aspect were further examined. This PBPK model has successfully depicted the variations of PK of vildagliptin in healthy subjects and patients with CKD, which can be useful for medical practitioners in dosage optimization in renal disease patients.
Prunus yedoensis Bark Downregulates the Expression of Cell Adhesion Molecules in Human Endothelial Cell Lines and Relaxes Blood Vessels in Rat Aortic Rings
Authors: Choi Ye Eun , Yang Jung Mo , Jeong Chae Won , Shin Sujin , Park Junkyu , Lee Kyungjin , Cho Ju Hyun
Published: July 2024

The incidence of cardiovascular diseases, such as high blood pressure, is increasing worldwide, owing to population aging and irregular lifestyle habits. Previous studies have reported the vasorelaxant effects of Prunus yedoensis bark methanol extract. However, various solvent extracts of P. yedoensis bark and their vascular relaxation mechanisms have not been sufficiently studied. We prepared extracts of P. yedoensis bark using various solvents (water, 30% ethanol, and 70% ethanol). P. yedoensis bark 30% ethanol extract (PYB-30E) decreased the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in human umbilical vein endothelial cells (HUVECs) activated with 200 ng/mL TNF-α. Additionally, PYB-30E showed vasodilatory effects on isolated rat aortic rings. This was confirmed to be the result of the activation of the NO/cGMP pathway, regulation of non-selective calcium-activated K+ channels, and calcium channel blockade. Additionally, PYB-30E significantly reduced systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR). Taken together, our results indicated that PYB-30E is a candidate functional material with preventive and therapeutic effects against hypertension.
Locoregional Radiotherapy in Patients with Advanced Breast Cancer Treated with Cyclin-Dependent Kinase 4/6 Inhibitors Based on Real-World Data
Authors: Kubeczko Marcin , Gabryś Dorota , Polakiewicz-Gilowska Anna , Bobek-Billewicz Barbara , Jarząb Michał
Published: July 2024

Background. The use of locoregional radiotherapy (RT) in patients with advanced ER-positive, HER2-negative breast cancer remains a topic of ongoing debate. In this study, we aimed to evaluate the efficacy of locoregional RT in advanced breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in a first-line setting. Methods. We conducted a retrospective analysis of patients diagnosed with advanced breast cancer between 2018 and 2023 who received treatment with CDK4/6i and underwent locoregional radiotherapy. Results. Among the 371 patients treated with CDK4/6i as part of their first-line therapy, 23 received locoregional RT either concurrently or sequentially with CDK4/6 inhibitors. Disease progression within the breast occurred in 19 patients (5.1%). Among these cases, five patients had previously undergone breast RT (5/23, 21.7%), while 14 did not (14/348, 4.0%, p = 0.004). All cases of local progression after RT followed palliative doses and were accompanied by early systemic progression. The 2-year PFS in the entire cohort of patients treated with locoregional RT was 65.7% (95% CI: 40.5–82.3%). Notably, patients who received higher RT doses had longer 2-year PFS (83.3%, 95% CI: 27.3–97.5%) than those with palliative RT doses (59.3%, 95% CI: 30.7–79.3%); however, the results were not statistically significant (p = 0.58). Furthermore, the 2-year local control in the entire cohort with locoregional RT was 73.0% (95% CI: 46.5–87.9%). Importantly, no local progression was observed after RT when using high doses. Conclusions. The addition of locoregional radiotherapy to first-line CDK4/6 inhibitors warrants further investigation across various clinical scenarios in advanced breast cancer. Palliative radiation regimens delivered early in breast oligoprogression may not always suffice, emphasizing the need for comprehensive studies in this context.
Phytochemical Profile, Antioxidant, Anti-Atopic, and Anti-Inflammatory Activities of Filipendula glaberrima Nakai at Different Growth Stages
Authors: Lee Hak-Dong , Tonog Genevieve , Uy Neil Patrick , Lee Yunji , Kim Ki-Young , Kim Hangeun , Lee Sanghyun
Published: July 2024

Since atopic dermatitis is an inflammatory skin disease, natural remedies, such as Filipendula glaberrima Nakai (FG), with anti-inflammatory properties are possible promising therapeutic options. This study aimed to investigate the therapeutic potential of FG extracts at different growth stages. Seven compounds were isolated from the FG leaf extracts using open-column chromatography, and they were analyzed using HPLC. The extracts were further evaluated for their total polyphenol and flavonoid content (TPC and TFC). The in vitro antioxidant properties of the FG extracts were evaluated using radical scavenging assays, whereas their anti-inflammatory activities were assessed by evaluating their ability to inhibit the production of inflammation-associated biomarkers using the Griess assay and ELISA, respectively. The MTT assay was used to evaluate the viability and cytotoxicity of the FG extracts in keratinocyte cell lines. The results showed that the full-flowering stage exhibited the highest TPC, TFC, and antioxidant activities, thus suggesting a positive correlation between these properties. All FG extracts showed significant anti-inflammatory activity by inhibiting the production of pro-inflammatory biomarkers in lipopolysaccharide-stimulated macrophages. Additionally, the FG extracts suppressed the production of cytokines and chemokines in keratinocytes, indicating their anti-atopic potential. HPLC analysis revealed that the full-flowering stage had the highest content of all the analyzed phytochemicals (gallic acid, (+)-catechin, hyperin, miquelianin, astragalin, afzelin, and quercetin). These results suggest that the full-flowering stage of FG is the most promising source for therapeutic applications owing to its superior phytochemical profile and biological activities. This study highlights the potential of FG extracts, particularly in its full-flowering stage, as a natural therapeutic agent for the management of inflammation-related diseases, and it can also serve as a reference for further research on FG.