bluuebunny/crossref_metadata_2025 huggingface dataset:
Miocene Volcanism in the Slovenský Raj Mountains: Magmatic, Space, and Time Relationships in the Western Carpathians
Authors: Demko Rastislav , Putiš Marián , Li Qiu-Li , Chew David , Ackerman Lukáš , Nemec Ondrej
Published: December 2023

The Miocene volcanic-intrusive complex in the Slovenský Raj Mountains, middle Slovakia, comprises a swarm of subalkaline basalts and basaltic andesites with alkaline basalts, trachybasalts and basaltic trachyandesites. Basaltic to doleritic feeder dykes and sporadic hyaloclastite lavas are exposed in contact with the Triassic Bódvaszilas Formation of the Silica Nappe. The primary clinopyroxene, plagioclase, and Fe-Ti oxide assemblage also contains calcite spheroids inferred to represent carbonatitic melt. These spheroids are associated with subsolidus chlorite, actinolite, magnetite, titanite, calcite, and epidote. Micropoikilitic clinopyroxene, albite, and Ti-magnetite formed due to rapid quenching. There was an incorporation of host rock carbonate during the eruption. The erupted products are the result of magmatic differentiation of the parental basaltic tholeiitic magma with a redox of ∆QFM = +1 to +3, affected by varying degrees of 0%–50% fractionation and the assimilation of carbonate material in a shallow magmatic reservoir. REE geochemistry shows N-MORB-like type patterns with both LaN/YbN and LaN/SmN < 1 at near constant Eu/Eu* (~0.9). This is supported by εNd(t=13 Ma) values of +8.0 to +7.4 determined from the basaltic rocks. The REE values can be modeled by 1% fractional melting of garnet peridotite mixed with 7% melting of spinel peridotite of PM composition (1:9 proportions). SIMS and LA-ICP-MS U/Pb analysis of zircons yields a concordant age of 12.69 ± 0.24 Ma and a 13.3 ± 0.16 Ma intercept (Serravallian) age. The Middle Miocene volcanic activity was related to subduction-collision processes along the boundary of the Cenozoic ALCAPA (Alps–Carpathians–Pannonia) microplate and the southern margin of the European plate.
Transformation of Ginsenosides by Lactiplantibacillus plantarum MB11 Fermentation: Minor Ginsenosides Conversion and Enhancement of Anti-Colorectal Cancer Activity
Authors: Shen Yunjiao , Gao Yansong , Yang Ge , Zhao Zijian , Zhao Yujuan , Gao Lei , Zhao Lei , Li Shengyu
Published: December 2023

The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.
Application of Cyclocarya paliurus–Kiwifruit Composite Fermented to Enhance Antioxidant Capacity, Flavor, and Sensory Characteristics of Kiwi Wine
Authors: Liu Jing , Guan Weiliang , Sun Zhidong , Ni Yunfan , He Long , Tian Fang , Cai Luyun
Published: December 2023

A new fermentation method for kiwi wine was explored by developing the well-known medicinal and edible plant Cyclocarya paliurus (C. paliurus) to create more value with undersized kiwifruits. In this study, the changes in bioactive substances during the C. paliurus–kiwi winemaking process were analyzed on the basis of response surface optimization results, and the antioxidant capacity, aromatic compounds, and sensory quality of the C. paliurus–kiwi composite wine with kiwi wine and two commercial kiwi wines were compared. The results showed that DPPH radical, OH− radical, and ABTS+ scavenging rates remained at over 60.0%, 90.0%, and 70.0% in C. paliurus–kiwi wine, respectively. The total flavonoid content (TFC) and total polyphenol content (TPC) of C. paliurus–kiwi wine were significantly higher than those of the other three kiwi wines. C. paliurus–kiwi wine received the highest score and detected 43 volatile compounds. Ethyl hexanoate, which showed stronger fruity and sweet aromas, was one of the main aroma components of C. paliurus–kiwi wine and different from commercial wines. This wine has a good flavor with a natural and quality feeling of C. paliurus–kiwifruit extract, low-cost processing, and great market potential.
Spider-Venom Peptides: Structure, Bioactivity, Strategy, and Research Applications
Authors: Guo Ruiyin , Guo Gang , Wang Aili , Xu Gaochi , Lai Ren , Jin Hui
Published: December 2023

Spiders (Araneae), having thrived for over 300 million years, exhibit remarkable diversity, with 47,000 described species and an estimated 150,000 species in existence. Evolving with intricate venom, spiders are nature’s skilled predators. While only a small fraction of spiders pose a threat to humans, their venoms contain complex compounds, holding promise as drug leads. Spider venoms primarily serve to immobilize prey, achieved through neurotoxins targeting ion channels. Peptides constitute a major part of these venoms, displaying diverse pharmacological activities, and making them appealing for drug development. Moreover, spider-venom peptides have emerged as valuable tools for exploring human disease mechanisms. This review focuses on the roles of spider-venom peptides in spider survival strategies and their dual significance as pharmaceutical research tools. By integrating recent discoveries, it provides a comprehensive overview of these peptides, their targets, bioactivities, and their relevance in spider survival and medical research.
A Review of Distribution and Profiles of HBCD in Different Environmental Media of China
Authors: Deng Jinglin , Liu Wenbin , Gao Lirong , Jia Tianqi , He Yunchen , Mao Tianao , Hussain Javid
Published: December 2023

Hexabromocyclododecane (HBCD) is the most important flame retardant that has been used in Expanded Polystyrene foam and Extruded Polystyrene foam in the past forty years across the world. China was the major producer and user of HBCD, and the total HBCD production was about 0.3 million tons. Although HBCD was completely banned in China in 2021 because of its long-range transport, bioaccumulation and toxicity, there is still a lot of residue in the environment. Therefore, we reviewed multiple studies concerning the distribution of HBCD in diverse environmental matrices, such as in the air, dust, soil, water, sediment, and biota. Results revealed that HBCD levels in different environments in China present geographical variation and were at a high level compared with other countries. In all environmental media, relatively high HBCD concentrations have been found in industrial and urban areas. Industrialization and urbanization are two important factors that influence the concentration and distribution of HBCD in the environment. In terms of isomer, γ-HBCD was the dominant isomer in soil, water, and sediment, while in the biota α-HBCD was the predominant isomer.
Pinus koraiensis Essential Oil Attenuates the Pathogenicity of Superbacteria by Suppressing Virulence Gene Expression
Authors: Kim Ji-Hee , Kim Young-Hoi , Park Bog-Im , Choi Na-Young , Kim Kang-Ju
Published: December 2023

In the quest to combat infections attributable to antibiotic-resistant superbacteria, an essential oil derived from the needles of Pinus koraiensis Sieb. et Zucc. (PKEO) has emerged as a promising solution. In this study, we demonstrate that PKEO can be used to inhibit the growth, glucose metabolite acidogenicity, and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA). Quantitative PCR analysis provided direct evidence that PKEO reduces the mRNA expression of the accessory gene regulator A (agrA) and staphylococcal accessory regulator A (sarA), thereby indicating its inhibitory effect on pathogenic regulatory genes. Chromatographic analyses of PKEO identified terpene hydrocarbons as prominent essential oil constituents. These compounds, notably α-pinene, limonene, and β-caryophyllene, have been established to have antimicrobial properties. Our findings indicate that an oil derived from P. koraiensis can effectively combat antibiotic-resistant strains by disrupting the pathogenicity regulatory system, thereby establishing PKEO as a promising candidate for the treatment of MRSA infections.
Bioactivities of Steroids and Sesquiterpenes from the Branches and Leaves of Aglaia lawii
Authors: Dong Jingjing , Liu Hanfei , Wang Huan , Lou Huayong , Pan Weidong , Li Jinyu
Published: December 2023

Five undescribed steroids and one sesquiterpene, named Aglaians A–F, along with sixteen known analogs, have been isolated from the branches and leaves of Aglaia lawii. Its structure was elucidated by IR, HRESIMS, 1D and 2D NMR, quantum-chemical calculations, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. The cytotoxic and antibacterial activities of six human tumor cell lines were evaluated (MDA-MB-231, MCF-7, Ln-cap, A549, HeLa, and HepG-2), and four strains of bacteria (Bacterium subtilis, Phytophthora cinnamomic, Acrogenic bacterium, and Ralstonia solanacearum). The bioassay results indicated that compounds 3 and 5 exhibited moderate antitumor activity with IC50 values ranging from 16.72 to 36.14 μM. Furthermore, compounds 3–5 possess antibacterial activities against four bacteria with MIC values of 25–100 μM.
Enhanced Catalytic Soot Oxidation over Co-Based Metal Oxides: Effects of Transition Metal Doping
Authors: Luo Jianbin , Zhu Xinbo , Zhong Zhiwei , Chen Geng , Hong Yu , Zhou Zijian
Published: December 2023

A series of Co-M (M = Fe, Cr, and Mn) catalysts were synthesized by the sol-gel method for soot oxidation in a loose contact mode. The Co-Fe catalyst exhibited the best catalytic activity among the tested samples, with the characteristic temperatures (T10, T50, and T90) of 470 °C, 557 °C, and 602 °C, respectively, which were 57 °C, 51 °C, and 51 °C lower than those of the CoOx catalyst. Catalyst characterizations of N2 adsorption–desorption, X-ray diffraction (XRD), X-ray photo-electron spectrometry (XPS), and the temperature programmed desorption of O2 (O2-TPD) were performed to gain insights into the relationships between the activity of catalytic soot oxidation and the catalyst properties. The content of Co2+ (68.6%) increased due to the interactions between Co and Fe, while the redox properties and the relative concentration of surface oxygen adsorption (51.7%) were all improved, which could significantly boost the activity of catalytic soot oxidation. The effects of NO and contact mode on soot oxidation were investigated over the Co-Fe catalyst. The addition of 1000 ppm of NO led to significant reductions in T10, T50, and T90 by 92 °C, 106 °C, and 104 °C, respectively, compared to the case without the NO addition. In the tight contact mode, the soot oxidation was accelerated over the Co-Fe catalyst, resulting in 46 °C, 50 °C, and 50 °C reductions in T10, T50, and T90 compared to the loose contact mode. The comparison between real soot and model Printex-U showed that the T50 value of real soot (455 °C) was 102 °C lower than the model Printex-U soot.
Complexation of Boronic Acid with Chiral α-Hydroxycarboxylic Acids and the Ability of the Complexes to Catalyze α-Hydroxycarboxylic Acid Esterification
Authors: Meng Zhonglei , Qin Rongxiu , Wen Rusi , Xie Junkang , Chen Haiyan , Li Guiqing
Published: December 2023

The complexation of boric acid (BA) with various α-hydroxycarboxylic acids (HCAs) was examined by analyzing the change in the optical rotation after the addition of BA to aqueous HCA solutions, and the catalytic properties of the complexes were examined by catalyzing the esterification of the HCAs. The absolute values of the optical rotation of the HCAs increased with increasing BA-to-HCA molar ratio, and the rate of change of the optical rotation gradually decreased as the BA-to-HCA molar ratio increased, reaching a minimum value at a molar ratio of approximately three. As a catalyst, BA could catalyze the acetylation of hydroxyl groups in addition to the esterification of HCAs. Compared to the conventional synthesis routes of ATBC and ATOC, a synthesis route with BA as the catalyst allowed for a lower frequency of catalyst separation and replacement while providing light-colored products. BA could catalyze the formation of triethyl citrate, and the yield of triethyl citrate reached 93.8%. BA could also catalyze the reaction between malic acid and pinene to produce borneol malate. After saponification of borneol malate, borneol was obtained with a yield of 39%.
Synthesis of Trifluoromethylated Pyrimido[1,2-b]indazole Derivatives through the Cyclocondensation of 3-Aminoindazoles with Ketoester and Their Functionalization via Suzuki-Miyaura Cross-Coupling and SNAr Reactions
Authors: Tellal Sakina , Jismy Badr , Hikem-Oukacha Djamila , Abarbri Mohamed
Published: December 2023

A new series of trifluoromethylated pyrimido[1,2-b]indazol-4(1H)-one derivatives was synthesized with good to excellent yields through a simple condensation of 3-aminoindazole derivatives with ethyl 4,4,4-trifluoro 3-oxobutanoate. The functionalization of the corresponding chlorinated fused tricyclic scaffolds via Suzuki-Miyaura and aromatic nucleophilic substitution reactions led to the synthesis of highly diverse trifluoromethylated pyrimido[1,2-b]indazole derivatives with good yields.
Naphtho[1,8-de][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-d]isoxazole 2-Oxide: A Novel Isomerization of the N-Oxide to Nitrile Oxide en Route to Isoxazol(in)es
Authors: Gerontitis Ioannis E. , Tsoungas Petros G. , Varvounis George
Published: December 2023

Naphtho[1,8-de][1,2]oxazin-4-ol and its acyl or benzyl derivatives ring open to various 2,8-dihydroxy-1-naphthonitriles, which, through (de)protection protocols and reduction, afford the target (E)-2-hydroxy-8-methoxy-1-naphthaldehyde. This was converted to its corresponding oxime, which was oxidatively o-cyclized with phenyliodine(III) diacetate (PIDA) to 9-methoxynaphtho[1,2-d]isoxazole 2-oxide. The latter, in deuterated DMSO at room temperature, was rearranged to its isomer 2-hydroxy-8-methoxy(naphthalen-1-yl)nitrile oxide. The isomerization was detected by time-course plot 1H NMR spectroscopy and further identified from its 13C NMR and HRMS spectra. The nitrile oxide was stable in (non)deuterated DMSO for at least 18 h. A 3,4-bis(2-hydroxy-8-methoxynaphthalen-1-yl)-1,2,5-oxadiazole 2-oxide, as a dimerization product or an isocyanate as a rearrangement isomer, was ruled out, the former by its HRMS spectrum and the latter by its 1,3-dipolar cycloaddition reactions to substituted isoxazoles.
Exploring the Role of Lycium barbarum Polysaccharide in Corneal Injury Repair and Investigating the Relevant Mechanisms through In Vivo and In Vitro Experiments
Authors: Liu Qian , Nan Yi , Yang Yifan , Li Xiangyang , Jiang Wenjie , Jiao Taiqiang , Li Jiaqing , Jia Xusheng , Ye Mengyi , Niu Yang , Yuan Ling
Published: December 2023

Lycium barbarum polysaccharide (LBP) is the main active component of Fructus Lycii, exhibiting various biological activities. This study aims to explore the protective effects of LBP on human corneal epithelial cells (HCEC) and a rat corneal injury model. Potential target points for LBP improving corneal injury repair were screened from public databases, and functional and pathway enrichment analyses of core targets were conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rat corneal alkali burns and HCEC oxidative stress injury models were established, and the results were validated through slit lamp examination, HE staining, TUNEL assay, immunofluorescence, CCK-8 assay, flow cytometry, scratch assay, and qRT-PCR methods. In the context of database retrieval, identification of 10 LBP monosaccharide components and 50 corneal injury repair-related targets was achieved. KEGG pathway analysis suggested that LBP might regulate the IL-17 and TNF signaling pathways through targets such as JUN, CASP3, and MMP9, thereby improving corneal damage. In vivo and in vitro experimental results indicated that LBP could reduce the increase of inflammation index scores (p < 0.05), inflammatory cell density (p < 0.01), TUNEL-positive cells (p < 0.01), corneal opacity scores (p < 0.01), and expression of corneal stromal fibrosis-related proteins α-SMA, FN, and COL (p < 0.01) caused by chemical damage to rat corneas. LBP inhibited oxidative stress-induced decreases in cell viability (p < 0.001) and migration healing ability (p < 0.01) in HCECs, reducing apoptosis rates (p < 0.001), ROS levels (p < 0.001), and the expression of inflammatory factors TNF-α and IL-6 (p < 0.01). qRT-PCR results demonstrated that LBP intervention decreased the mRNA levels of JUN, CASP3, and MMP9 in H2O2-induced alkaline-burned corneas and HCECs (p < 0.01).The integrated results from network pharmacology and validation experiments suggest that the inhibitory effects of LBP on apoptosis, inflammation, and fibrosis after corneal injury may be achieved through the suppression of the TNF and IL-17 signaling pathways mediated by JUN, CASP3, and MMP9.
Immunomodulatory Activity and Its Mechanisms of Two Polysaccharides from Poria cocos
Authors: Zhang Wuxia , He Jiaqi , Zheng Danping , Zhao Panpan , Wang Yingdong , Zhao Jinzhong , Li Peng
Published: December 2023

Polyporaceae is an important fungal family that has been a source of natural products with a range of pharmaceutical activities in China. In our previous study, two polysaccharides, PCWPW and PCWPS, with significant antioxidant and antidepressant activity were obtained from Poria cocos. In this study, we evaluated their potential molecular mechanisms in the immunomodulation of macrophages. PCWPW and PCWPS were characterized by GC–MS analysis to contain 1,3-linked Glcp. ELISA assays results demonstrated that the secretion of TNF-α was significantly enhanced by PCWPW/PCWPS. RNA-seq data demonstrated that PCWPS treatment modulated the expression of immune-related genes in macrophages, which was further confirmed by RT-qPCR assays. The activation of TNF-α secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-α cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-κB or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-α expression through the NF-κB/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from Poria cocos have potential as drug candidates for immune-related disease treatment.
Co-Removal of Fe/V Impurity in H2TiO3 Synthesized from Ti-Bearing Blast Furnace Slag
Authors: Yang Fan , Peng Qiugui , Wang Jing , Xiang Lan
Published: December 2023

Ti-bearing blast furnace slag (TBFS) can be converted to impurity bearing TiOSO4 solution for TiO2 pigment production. However, the H2TiO3 (MTA) hydrolyzed from the solution has too high Fe/V impurity to meet the standard for TiO2 pigment. In this study, we found that Fe3+ and V3+ were easily hydrolyzed and entered the MTA lattice, and hence could not be removed by washing. Furthermore, Fe/V was hard to co-remove by the traditional reduction method. Therefore, the Fe/V non-hydrolysis condition (Ti3+ = 0.01 M, F = 3.0, T = 130 °C; Ti3+ = 0.01 M, F = 3.5, T = 150 °C) was determined by thermodynamic calculations. However, at these conditions, the Ti hydrolysis ratio was low or the reaction time was long. Therefore, a new two-step hydrothermal hydrolysis process was proposed. Step 1 (130 °C, 2 h) ensured the non-hydrolysis of V3+, and Ti was partially hydrolyzed to increase the H2SO4 concentration. Step 2 (150 °C, 2 h) ensured a high Ti hydrolysis ratio (>0.95) and short total reaction time (4–6 h). Finally, a high-purity MTA was obtained (Fe = 21 ppm, V = 145 ppm). These results provide new insights into the control of the hydrolysis of impurity ions in solutions and help to optimize the process of TiO2 pigment preparation from TBFS.
Graphene Architecture-Supported Porous Cobalt–Iron Fluoride Nanosheets for Promoting the Oxygen Evolution Reaction
Authors: Lu Yanhui , Han Xu , Zhang Yiting , Yu Xu
Published: December 2023

The design of efficient oxygen evolution reaction (OER) electrocatalysts is of great significance for improving the energy efficiency of water electrolysis for hydrogen production. In this work, low-temperature fluorination and the introduction of a conductive substrate strategy greatly improve the OER performance in alkaline solutions. Cobalt–iron fluoride nanosheets supported on reduced graphene architectures are constructed by a one-step solvothermal method and further low-temperature fluorination treatment. The conductive graphene architectures can increase the conductivity of catalysts, and the transition metal ions act as electron acceptors to reduce the Fermi level of graphene, resulting in a low OER overpotential. The surface of the catalyst becomes porous and rough after fluorination, which can expose more active sites and improve the OER performance. Finally, the catalyst exhibits excellent catalytic performance in 1 M KOH, and the overpotential is 245 mV with a Tafel slope of 90 mV dec−1, which is better than the commercially available IrO2 catalyst. The good stability of the catalyst is confirmed with a chronoamperometry (CA) test and the change in surface chemistry is elucidated by comparing the XPS before and after the CA test. This work provides a new strategy to construct transition metal fluoride-based materials for boosted OER catalysts.
Effects of Synthesis Conditions of Na0.44MnO2 Precursor on the Electrochemical Performance of Reduced Li2MnO3 Cathode Materials for Lithium-Ion Batteries
Authors: Sun Ya , Cheng Jialuo , Tu Zhiqi , Chen Meihe , Huang Qiaoyang , Wang Chunlei , Yan Juntao
Published: December 2023

Li2MnO3 nanobelts have been synthesized via the molten salt method that used the Na0.44MnO2 nanobelts as both the manganese source and precursor template in LiNO3-LiCl eutectic molten salt. The electrochemical properties of Li2MnO3 reduced via a low-temperature reduction process as cathode materials for lithium-ion batteries have been measured and compared. Particularly investigated in this work are the effects of the synthesis conditions, such as reaction temperature, molten salt contents, and reaction time on the morphology and particle size of the synthesized Na0.44MnO2 precursor. Through repeated synthesis characterizations of the Na0.44MnO2 precursor, and comparing the electrochemical properties of the reduced Li2MnO3 nanobelts, the optimum conditions for the best electrochemical performance of the reduced Li2MnO3 are determined to be a molten salt reaction temperature of 850 °C and a molten salt amount of 25 g. When charge–discharged at 0.1 C (1 C = 200 mAh g−1) with a voltage window between 2.0 and 4.8 V, the reduced Li2MnO3 synthesized with reaction temperature of Na0.44MnO2 precursor at 850 °C and molten salt amounts of 25 g exhibits the best rate performance and cycling performance. This work develops a new strategy to prepare manganese-based cathode materials with special morphology.
Enhancing the Stability and Initial Coulombic Efficiency of Silicon Anodes through Coating with Glassy ZIF-4
Authors: Lee In-Hwan , Jin Yongsheng , Jang Hyeon-Sik , Whang Dongmok
Published: December 2023

The high capacity of electrodes allows for a lower mass of electrodes, which is essential for increasing the energy density of the batteries. According to this, silicon is a promising anode candidate for Li-ion batteries due to its high theoretical capacity. However, its practical application is hampered by the significant volume expansion of silicon during battery operation, resulting in pulverization and contact loss. In this study, we developed a stable Li-ion anode that not only solves the problem of the short lifetime of silicon but also preserves the initial efficiency by using silicon nanoparticles covered with glassy ZIF-4 (SZ-4). SZ-4 suppresses silicon pulverization, contact loss, etc. because the glassy ZIF-4 wrapped around the silicon nanoparticles prevents additional SEI formation outside the silicon surface due to the electrically insulating characteristics of glassy ZIF-4. The SZ-4 realized by a simple heat treatment method showed 74% capacity retention after 100 cycles and a high initial efficiency of 78.7%.
Electron Spin–Lattice Relaxation of Substitutional Nitrogen in Silicon: The Role of Disorder and Motional Effects
Authors: Belli Matteo , Fanciulli Marco
Published: December 2023

In a previous investigation, the authors proposed nitrogen as a possible candidate for exploiting the donor spin in silicon quantum devices. This system is characterized by a ground state deeper than the other group V impurities in silicon, offering less stringent requirements on the device temperature necessary to access the unionized state. The nitrogen donor is slightly displaced from the substitutional site, and upon heating, the system undergoes a motional transition. In the present article, we show the results from our investigation on the spin–relaxation times in natSi and 28Si substrates and discuss the motional effects on relaxation. The stretched exponential relaxation observed is interpreted as a distribution of spin–lattice relaxation times, whose origin is also discussed. This information greatly contributes to the assessment of a nitrogen-doped silicon system as a potential candidate for quantum devices working at temperatures higher than those required for other group V donors in silicon.
Berberine Mediates the Production of Butyrate to Ameliorate Cerebral Ischemia via the Gut Microbiota in Mice
Authors: Duan Huijie , Hu Junya , Deng Yang , Zou Junqing , Ding Wangli , Peng Qiang , Duan Rui , Sun Jianguo , Zhu Junrong
Published: December 2023

Ischemic stroke (IS) is a vascular disease group concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has been known to improve stroke, but its mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, the mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes in intestinal flora in model mice after BBR administration using 16SrRNA sequencing. Chromatography–mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes in the microglia and astroglia in the mice brains. Our findings suggest that berberine improves stroke outcomes by modulating the gut microbiota. Specifically, after MCAO/R mice were given berberine, the beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. The administration of butyric acid and an inhibitor of butyric acid synthesis, heptanoyl-CoA, showed that butyric acid improved the stroke outcomes in the model mice. In addition, butyric acid could inhibit the activation of the microglia and astrocytes in the brains of model mice, thereby inhibiting the generation of pro-inflammatory factors IL-6, IL-1β and TNF-α as well as improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment.
Malnutrition, Functional Decline, and Institutionalization in Older Adults after Hospital Discharge Following Community-Acquired Pneumonia
Authors: Clotet-Vidal Sandra , Saez Prieto M. Encarna , Duch Llorach Pol , Gutiérrez Álvaro Santos , Casademont Pou Jordi , Torres Bonafonte Olga H.
Published: December 2023

Background and aims: Community-acquired pneumonia (CAP) is a major threat to older adults, but mid-term implications are poorly described. The aim was to analyze functional decline, institutionalization, malnutrition, and risk factors after hospital admission for CAP. Methods: This prospective observational study included patients over 65 years discharged after CAP between May 2019 and July 2021. We performed a comprehensive geriatric assessment and a general nutritional assessment 30–60 days after CAP. This included the MNA and blood test with trace elements and vitamins. The main outcomes were functional decline, institutionalization, and malnutrition. Multivariate logistic regression was used for the analyses. Results: In total, 144 patients of 77.15 ± 7.91 years, 55.6% male, and 9% previously institutionalized were analyzed. At hospital admission, the Charlson Comorbidity Index (CCI) was 1.5 ± 1.6, the Pneumonia Severity Index was 98.1 ± 25.9, and the previous Barthel Index (BI) was 93.06 ± 17.13. Hospital stay was 9.72 ± 7.88 days. After 44.6 ± 14.4 days, 48.6% patients showed functional decline and 19.4% were institutionalized. Age (OR 1.17; CI 95% 1.09–1.26), previous institutionalization (29.1; 3.7–224.7), BI (1.09; 1.05–1.14), CCI (1.5; 1.1–2.1), and length of stay (1.1, 1.02–1.18) were independently associated with functional decline. The only predictors of new institutionalization were previous BI (0.96; 0.93–0.99) and length of stay (1.06; 1.00–1.13). The MNA indicated malnutrition in 28% of the community-dwelling patients and 67.9% of those institutionalized, with risk of malnutrition being 45.7% and 9.5%, respectively, after an average of 44.6 days of CAP diagnosis. The predictors of malnutrition were previous institutionalization (10.62; 2.20–51.21), BI (0.95; 0.92–0.98), and length of stay (1.12; 1.04–1.20). Micronutrient deficiencies were mainly zinc (61.8%), vitamin D (54.5%), and vitamin C (45.1%). An MNA score < 17 points or hypoalbuminemia showed good specificity to identify these deficiencies. Conclusions: After CAP admission, functional decline, institutionalization, and malnutrition rates were high. Longer hospital stay was a common risk factor for all outcomes. The presence of hypoalbuminemia or an MNA < 17 in older patients should prompt suspicion of deficiencies in micronutrients, such as vitamin D, C, and zinc.
Mediterranean Diet and Cardiovascular Disease: The Moderating Role of Adequate Sleep—Results from the ATTICA Cohort Study (2002–2022)
Authors: Damigou Evangelia , Chrysohoou Christina , Vafia Christina , Barkas Fotios , Kravvariti Evrydiki , Vlachopoulou Elpiniki , Kyrili Konstantina , Tsioufis Costas , Pitsavos Christos , Liberopoulos Evangelos , Sfikakis Petros P. , Panagiotakos Demosthenes
Published: December 2023

The relationship between diet, sleep duration and cardiovascular disease (CVD) has not been well understood. The aim of the present study was to test the potential modifying role of sleep duration in the association between adherence to the Mediterranean-type diet (MD) and CVD risk. The study consisted of n = 313 initially free-of-CVD adults, from the ATTICA cohort study (2002–2022), with available information on sleep habits. Sleep habits were categorized as inadequate and adequate sleep duration (< or ≥7 h/day, respectively). In multi-adjusted analysis, MD adherence was inversely associated with CVD risk [Hazard Ratio-HR per 1/55 in MedDietScore: 0.80, 95% Confidence Interval-CI: 0.65, 0.98]. A significant interaction between sleep duration and MedDietScore was observed (p < 0.001). In subgroup analysis, the protective association between MD adherence and CVD risk was found only in participants who slept adequately, i.e., >7 h/day [HR:0.80, 95%CI: 0.65, 0.98]. Those who had a high adherence to the MD along with adequate sleep habits, had a 70% reduced 20-year CVD risk [HR:0.30, 95%CI: 0.11, 0.80], compared to those who had a low MD adherence and inadequate sleep habits. Sleep duration should be a part of an individual’s lifestyle, together with dietary and other habits, to effectively evaluate CVD risk for future events.
Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice
Authors: Toivio Lotta , Launonen Hanna , Lindén Jere , Lehto Markku , Vapaatalo Heikki , Salmenkari Hanne , Korpela Riitta
Published: December 2023

Ketogenic diets (KDs) have been studied in preclinical models of intestinal diseases. However, little is known of how the fat source of these diets influences the intestinal barrier. Herein, we studied the impact of four-week feeding with KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) on paracellular permeability of the intestine to iohexol in healthy male C57BL/6J mice. We investigated jejunal and colonic tight junction protein expression, histological changes, and inflammatory markers (Il1b, Il6, Tnf, and Lcn2), as well as the activity and expression of intestinal alkaline phosphatase (IAP) in feces and jejunal tissue, respectively, and plasma lipopolysaccharide. KDs did not change intestinal permeability to iohexol after two or twenty-six days of feeding regardless of fat quality. SFA-KD, but not LA-KD, upregulated the colonic expression of tight junction proteins claudin-1 and -4, as well as the activity of IAP. Both KDs resulted in increased epithelial vacuolation in jejunum, and this was pronounced in SFA-KD. Jejunal Il1β expression was lower and colonic Il6 expression higher in LA-KD compared to SFA-KD. In colon, Tnf mRNA was increased in LA-KD when compared to controls. Overall, the results suggest that KDs do not influence intestinal permeability to iohexol but elicit changes in colonic tight junction proteins and inflammatory markers in both jejunum and colon. Future research will show whether these changes become of importance upon proinflammatory insults.
Nurturing Infants to Prevent Atopic Dermatitis and Food Allergies: A Longitudinal Study
Authors: Vassilopoulou Emilia , Rallis Dimitrios , Milani Gregorio Paolo , Agostoni Carlo , Feketea Gavriela , Lithoxopoulou Maria , Stefanaki Evangelia , Ladomenou Fani , Douladiris Nikolaos , Cronin Caoimhe , Popescu Codruta Alina , Pop Raluca Maria , Bocsan Ioana Corina , Tsabouri Sophia
Published: December 2023

Background: Atopic dermatitis (AD) at a young age often precedes the development of food allergies. Although AD affects millions of infants worldwide, prenatal and postnatal risk factors, and their association with the development of food allergies later on, are not fully elucidated. This study seeks to investigate AD epidemiology in infancy and its risk factors, examining early-life factors (both prenatal and postnatal) that could contribute to the later development of food allergies. Methods: Between January 2019 and December 2019, 501 infants were included in this prospective cohort study. Longitudinal data collection was performed through maternal interviews, the first one conducted within three days after the delivery and the second within 24 to 36 months after the delivery, encompassing variables such as demographics, family history of atopy, maternal smoking, antibiotic use during pregnancy, the mode of delivery, breastfeeding history, food practices, and greenness exposure within 3 days from delivery, while they were still in the hospital. Results: Maternal smoking during pregnancy (p = 0.001) and an older sibling atopy history (p = 0.03) was significantly linked to AD incidence. Cesarean section delivery (p = 0.04) was associated with a higher risk of food allergies in infants with AD. Having a garden at home correlated with a higher likelihood of AD (p = 0.01), and food elimination without medical guidance (p = 0.02) due to AD correlated with an elevated risk of food allergies. Conclusions: Encouraging timely allergenic food introduction while promoting dietary diversity, rich in plant-based foods, maternal smoking cessation, and professional dietary guidance may help minimize AD and food allergy risk. Future studies should address the role of greenness in the development of AD and food allergies.
What Differentiates Rural and Urban Patients with Type 1 Diabetes—A Pilot Study
Authors: Sińska Beata I. , Kucharska Alicja , Rzońca Ewa , Wronka Leszek , Bączek Grażyna , Gałązkowski Robert , Olejniczak Dominik , Rzońca Patryk
Published: December 2023

The effective management of diabetes is a complex issue and may be determined according to numerous patient-dependent and patient-independent factors. This study aimed to analyze the relationship between the place of residence and selected sociodemographic, psychological and diabetes-related parameters in people with type 1 diabetes (T1D). This study was conducted on 419 adults with T1D using nonprobability sampling. The following questionnaires were used: the Diabetes Dietary Guidelines Adherence Index, the Acceptance of Illness Scale, the Sense of Responsibility for Health Scale, the Diabetes Eating Problem Survey-Revised scale, the Eating Attitudes Test and questions on sociodemographic and diabetes-related parameters. People living in rural areas were characterized by a significantly lower age and level of education, a higher incidence of being overweight, a higher glycated hemoglobin concentration, a lower number of glucose measurements during the day and a higher level of acceptance of the disease compared to urban residents. The degree of adherence to dietary recommendations and the sense of responsibility for one’s own health were significantly higher among urban residents. It is necessary to assess barriers to a proper diet and to increase the effectiveness in managing the disease in rural communities. Targeted actions promoting the health of type 1 diabetics need to be developed with particular emphasis on patients from rural areas.
Effect of Punicalagin and Ellagic Acid on Human Fibroblasts In Vitro: A Preliminary Evaluation of Their Therapeutic Potential
Authors: Illescas-Montes Rebeca , Rueda-Fernández Manuel , González-Acedo Anabel , Melguizo-Rodríguez Lucía , García-Recio Enrique , Ramos-Torrecillas Javier , García-Martínez Olga
Published: December 2023

Background: Pomegranate is a fruit that contains various phenolic compounds, including punicalagin and ellagic acid, which have been attributed to anti-inflammatory, antioxidant, and anticarcinogenic properties, among others. Objective: To evaluate the effect of punicalagin and ellagic acid on the viability, migration, cell cycle, and antigenic profile of cultured human fibroblasts (CCD-1064Sk). MTT spectrophotometry was carried out to determine cell viability, cell culture inserts were used for migration trials, and flow cytometry was performed for antigenic profile and cell cycle analyses. Cells were treated with each phenolic compound for 24 h at doses of 10−5 to 10−9 M. Results: Cell viability was always significantly higher in treated versus control cells except for punicalagin at 10−9 M. Doses of punicalagin and ellagic acid in subsequent assays were 10−6 M or 10−7 M, which increased the cell migration capacity and upregulated fibronectin and α-actin expression without altering the cell cycle. Conclusions: These in vitro findings indicate that punicalagin and ellagic acid promote fibroblast functions that are involved in epithelial tissue healing.
Emerging Pharmaceutical Therapies to Address the Inadequacy of a Gluten-Free Diet for Celiac Disease
Authors: Crepaldi Martina , Palo Michela , Maniero Daria , Bertin Luisa , Savarino Edoardo Vincenzo , Anderson Robert P. , Zingone Fabiana
Published: December 2023

Celiac disease (CeD) is a chronic autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environmental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist despite apparent compliance with a GFD. This could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on a GFD who experience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This review will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.
A Mechanistic Review on How Berberine Use Combats Diabetes and Related Complications: Molecular, Cellular, and Metabolic Effects
Authors: Askari Vahid Reza , Khosravi Kimia , Baradaran Rahimi Vafa , Garzoli Stefania
Published: December 2023

Berberine (BBR) is an isoquinoline alkaloid that can be extracted from herbs such as Coptis, Phellodendron, and Berberis. BBR has been widely used as a folk medicine to treat various disorders. It is a multi-target drug with multiple mechanisms. Studies have shown that it has antioxidant and anti-inflammatory properties and can also adjust intestinal microbial flora. This review focused on the promising antidiabetic effects of BBR in several cellular, animal, and clinical studies. Based on previous research, BBR significantly reduced levels of fasting blood glucose, hemoglobin A1C, inflammatory cytokines, and oxidative stress markers. Furthermore, BBR stimulated insulin secretion and improved insulin resistance through different pathways, including up-regulation of protein expression of proliferator-activated receptor (PPAR)-γ, glucose transporter (GLUT) 4, PI3K/AKT, and AMP-activated protein kinase (AMPK) activation. Interestingly, it was demonstrated that BBR has protective effects against diabetes complications, such as diabetic-induced hepatic damage, cardiovascular disorders, nephropathy, and neuropathy. Furthermore, multiple clinical trial studies have emphasized the ameliorative effects of BBR in type 2 diabetic patients.
CP-673451, a Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces Apoptosis in Opisthorchis viverrini-Associated Cholangiocarcinoma via Nrf2 Suppression and Enhanced ROS
Authors: Duangdara Jinchutha , Boonsri Boonyakorn , Sayinta Apinya , Supradit Kittiya , Thintharua Pakpoom , Kumkate Supeecha , Suriyonplengsaeng Chinnawut , Larbcharoensub Noppadol , Mingphruedhi Somkit , Rungsakulkij Narongsak , Muangkaew Paramin , Tangtawee Pongsatorn , Vassanasiri Watoo , Suragul Wikran , Janvilisri Tavan , Tohtong Rutaiwan , Bates David O. , Wongprasert Kanokpan
Published: December 2023

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) play essential roles in promoting cholangiocarcinoma (CCA) cell survival by mediating paracrine crosstalk between tumor and cancer-associated fibroblasts (CAFs), indicating the potential of PDGFR as a target for CCA treatment. Clinical trials evaluating PDGFR inhibitors for CCA treatment have shown limited efficacy. Furthermore, little is known about the role of PDGF/PDGFR expression and the mechanism underlying PDGFR inhibitors in CCA related to Opisthorchis viverrini (OV). Therefore, we examined the effect of PDGFR inhibitors in OV-related CCA cells and investigated the molecular mechanism involved. We found that the PDGF and PDGFR mRNAs were overexpressed in CCA tissues compared to resection margins. Notably, PDGFR-α showed high expression in CCA cells, while PDGFR-β was predominantly expressed in CAFs. The selective inhibitor CP-673451 induced CCA cell death by suppressing the PI3K/Akt/Nrf2 pathway, leading to a decreased expression of Nrf2-targeted antioxidant genes. Consequently, this led to an increase in ROS levels and the promotion of CCA apoptosis. CP-673451 is a promising PDGFR-targeted drug for CCA and supports the further clinical investigation of CP-673451 for CCA treatment, particularly in the context of OV-related cases.
Targeted PLGA–Chitosan Nanoparticles for NIR-Triggered Phototherapy and Imaging of HER2-Positive Tumors
Authors: Kotelnikova Polina A. , Shipunova Victoria O. , Deyev Sergey M.
Published: December 2023

Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGA–chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light. Nile Blue (NB) is a biocompatible solvatochromic NIR dye that serves as an imaging agent. Laser irradiation of IR-780 dye leads to a temperature rise and the generation of reactive oxygen species (ROS). Resonance energy transfer between two dyes allows visualization of tumors in a wide range of visible and IR wavelengths. The combination of two NIR dyes enables the use of nanoparticles for diagnostics only or theranostics. Modification of poly(lactic-co-glycolic acid) (PLGA)–chitosan nanoparticles with trastuzumab provides an efficient nanoparticle uptake by tumor cells and promotes more than sixfold specificity towards HER2-positive cells, leading to a synergistic anticancer effect. We demonstrate optical imaging of the HER2-positive mouse mammary tumor and tumor-specific accumulation of PLGA–IR-780–NB nanoparticles in vivo after intravenous administration. We managed to achieve almost complete suppression of the proliferative activity of cells in vitro by irradiation with an 808 nm laser with a power of 0.27 W for 1 min at a concentration at which nanoparticles are nontoxic to cells in the dark.
Comparative Analysis of Nucleic Acid-Binding Polymers as Potential Anti-Inflammatory Nanocarriers
Authors: Bhansali Divya , Akinade Tolulope , Li Tianyu , Zhong Yiling , Liu Feng , Huang Hanyao , Tu Zhaoxu , Devey Elsie A. , Zhu Yuefei , Jensen Dane D. , Leong Kam W.
Published: December 2023

Conventionally, nanocarriers are used to regulate the controlled release of therapeutic payloads. Increasingly, they can also be designed to have an intrinsic therapeutic effect. For example, a positively charged nanocarrier can bind damage-associated molecular patterns, inhibiting toll-like receptor (TLR) pathway activation and thus modulating inflammation. These nucleic acid-binding nanomaterials (NABNs), which scavenge pro-inflammatory stimuli, exist in diverse forms, ranging from soluble polymers to nanoparticles and 2D nanosheets. Unlike conventional drugs that primarily address inflammation symptoms, these NABPs target the upstream inflammation initiation pathway by removing the agonists responsible for inflammation. Many NABNs have demonstrated effectiveness in murine models of inflammatory diseases. However, these scavengers have not been systematically studied and compared within a single setting. Herein, we screen a subset of the most potent NABNs to define their relative efficiency in scavenging cell-free nucleic acids and inhibiting various TLR pathways. This study helps interpret existing in vivo results and provides insights into the future design of anti-inflammatory nanocarriers.