bluuebunny/crossref_metadata_2025 huggingface dataset:
Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models
Authors: Magistrati Martina , Gilea Alexandru Ionut , Ceccatelli Berti Camilla , Baruffini Enrico , Dallabona Cristina
Published: January 2023

In eukaryotes, mitochondrial RNAs (mt-tRNAs and mt-rRNAs) are subject to specific nucleotide modifications, which are critical for distinct functions linked to the synthesis of mitochondrial proteins encoded by mitochondrial genes, and thus for oxidative phosphorylation. In recent years, mutations in genes encoding for mt-RNAs modifying enzymes have been identified as being causative of primary mitochondrial diseases, which have been called modopathies. These latter pathologies can be caused by mutations in genes involved in the modification either of tRNAs or of rRNAs, resulting in the absence of/decrease in a specific nucleotide modification and thus on the impairment of the efficiency or the accuracy of the mitochondrial protein synthesis. Most of these mutations are sporadic or private, thus it is fundamental that their pathogenicity is confirmed through the use of a model system. This review will focus on the activity of genes that, when mutated, are associated with modopathies, on the molecular mechanisms through which the enzymes introduce the nucleotide modifications, on the pathological phenotypes associated with mutations in these genes and on the contribution of the yeast Saccharomyces cerevisiae to confirming the pathogenicity of novel mutations and, in some cases, for defining the molecular defects.
Functional Characterization of the GNAT Family Histone Acetyltransferase Elp3 and GcnE in Aspergillus fumigatus
Authors: Choi Young-Ho , Park Sung-Hun , Kim Sung-Su , Lee Min-Woo , Yu Jae-Hyuk , Shin Kwang-Soo
Published: January 2023

Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a pivotal role in the regulation of gene expression and diverse biological processes. However, the function of GNAT family HATs, especially Elp3, in the opportunistic human pathogenic fungus Aspergillus fumigatus is largely unknown. To investigate the roles of the GNAT family HATs Elp3 and GcnE in the A. fumigatus, we have generated and characterized individual null Δelp3 and ΔgcnE mutants. The radial growth of fungal colonies was significantly decreased by the loss of elp3 or gcnE, and the number of asexual spores (conidia) in the ΔgcnE mutant was significantly reduced. Moreover, the mRNA levels of the key asexual development regulators were also significantly low in the ΔgcnE mutant compared to wild type (WT). Whereas both the Δelp3 and ΔgcnE mutants were markedly impaired in the formation of adherent biofilms, the ΔgcnE mutant showed a complete loss of surface structure and of intercellular matrix. The ΔgcnE mutant responded differently to oxidative stressors and showed significant susceptibility to triazole antifungal agents. Furthermore, Elp3 and GcnE function oppositely in the production of secondary metabolites, and the ΔgcnE mutant showed attenuated virulence. In conclusion, Elp3 and GcnE are associated with diverse biological processes and can be potential targets for controlling the pathogenic fungus.
Promotion of Protein Solubility and Reduction in Stiffness in Human Lenses by Aggrelyte-1: Implications for Reversing Presbyopia
Authors: Panja Sudipta , Gaikwad Hanmant , Rankenberg Johanna , Nam Mi-Hyun , Nagaraj Ram H.
Published: January 2023

With aging, human lenses lose the ability to focus on nearby objects due to decreases in accommodative ability, a condition known as presbyopia. An increase in stiffness or decrease in lens elasticity due to protein aggregation and insolubilization are the primary reasons for presbyopia. In this study, we tested aggrelyte-1 (S,N-diacetyl glutathione diethyl ester) for its ability to promote protein solubility and decrease the stiffness of lenses through its dual property of lysine acetylation and disulfide reduction. Treatment of water-insoluble proteins from aged human lenses (58–75 years) with aggrelyte-1 significantly increased the solubility of those proteins. A control compound that did not contain the S-acetyl group (aggrelyte-1C) was substantially less efficient in solubilizing water-insoluble proteins. Aggrelyte-1-treated solubilized protein had significant amounts of acetyllysine, as measured by Western blotting and LC-MS/MS. Aggrelytes increased the protein-free thiol content in the solubilized protein. Aged mouse (7 months) and human (44–66 years) lenses treated with aggrelyte-1 showed reduced stiffness accompanied by higher free thiol and acetyllysine levels compared with those treated with aggrelyte-1C or untreated controls. Our results suggested that aggrelyte-1 reduced lens stiffness through acetylation followed by disulfide reduction. This proof-of-concept study paves the way for developing aggrelyte-1 and related compounds to reverse presbyopia.
In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III
Authors: Witkowski Jakub , Polak Sebastian , Pawelec Dariusz , Rogulski Zbigniew
Published: January 2023

The development of in vitro/in vivo translational methods and a clinical trial framework for synergistically acting drug combinations are needed to identify optimal therapeutic conditions with the most effective therapeutic strategies. We performed physiologically based pharmacokinetic–pharmacodynamic (PBPK/PD) modelling and virtual clinical trial simulations for siremadlin, trametinib, and their combination in a virtual representation of melanoma patients. In this study, we built PBPK/PD models based on data from in vitro absorption, distribution, metabolism, and excretion (ADME), and in vivo animals’ pharmacokinetic–pharmacodynamic (PK/PD) and clinical data determined from the literature or estimated by the Simcyp simulator (version V21). The developed PBPK/PD models account for interactions between siremadlin and trametinib at the PK and PD levels. Interaction at the PK level was predicted at the absorption level based on findings from animal studies, whereas PD interaction was based on the in vitro cytotoxicity results. This approach, combined with virtual clinical trials, allowed for the estimation of PK/PD profiles, as well as melanoma patient characteristics in which this therapy may be noninferior to the dabrafenib and trametinib drug combination. PBPK/PD modelling, combined with virtual clinical trial simulation, can be a powerful tool that allows for proper estimation of the clinical effect of the above-mentioned anticancer drug combination based on the results of in vitro studies. This approach based on in vitro/in vivo extrapolation may help in the design of potential clinical trials using siremadlin and trametinib and provide a rationale for their use in patients with melanoma.
Optimizing Axial and Peripheral Substitutions in Si-Centered Naphthalocyanine Dyes for Enhancing Aqueous Solubility and Photoacoustic Signal Intensity
Authors: Saad Mohammad Ahsan , Pawle Robert , Selfridge Scott , Contreras Leslie , Xavierselvan Marvin , Nguyen Christopher D. , Mallidi Srivalleesha , Hasan Tayyaba
Published: January 2023

Photoacoustic imaging using external contrast agents is emerging as a powerful modality for real-time molecular imaging of deep-seated tumors. There are several chromophores, such as indocyanine green and IRDye800, that can potentially be used for photoacoustic imaging; however, their use is limited due to several drawbacks, particularly photostability. There is, therefore, an urgent need to design agents to enhance contrast in photoacoustic imaging. Naphthalocyanine dyes have been demonstrated for their use as photoacoustic contrast agents; however, their low solubility in aqueous solvents and high aggregation propensity limit their application. In this study, we report the synthesis and characterization of silicon-centered naphthalocyanine dyes with high aqueous solubility and near infra-red (NIR) absorption in the range of 850–920 nm which make them ideal candidates for photoacoustic imaging. A series of Silicon-centered naphthalocyanine dyes were developed with varying axial and peripheral substitutions, all in an attempt to enhance their aqueous solubility and improve photophysical properties. We demonstrate that axial incorporation of charged ammonium mesylate group enhances water solubility. Moreover, the incorporation of peripheral 2-methoxyethoxy groups at the α-position modulates the electronic properties by altering the π-electron delocalization and enhancing photoacoustic signal amplitude. In addition, all the dyes were synthesized to incorporate an N-hydroxysuccinimidyl group to enable further bioconjugation. In summary, we report the synthesis of water-soluble silicon-centered naphthalocyanine dyes with a high photoacoustic signal amplitude that can potentially be used as contrast agents for molecular photoacoustic imaging.
Exploring the Biological Properties of Zn(II) Bisthiosemicarbazone Helicates
Authors: Fernández-Fariña Sandra , Velo-Heleno Isabel , Carballido Rocío , Martínez-Calvo Miguel , Barcia Ramiro , Palacios Òscar , Capdevila Mercè , González-Noya Ana M. , Pedrido Rosa
Published: January 2023

The design of artificial helicoidal molecules derived from metal ions with biological properties is one of the objectives within metallosupramolecular chemistry. Herein, we report three zinc helicates derived from a family of bisthiosemicarbazone ligands with different terminal groups, Zn2(LMe)2∙2H2O 1, Zn2(LPh)2∙2H2O 2 and Zn2(LPhNO2)23, obtained by an electrochemical methodology. These helicates have been fully characterized by different techniques, including X-ray diffraction. Biological studies of the zinc(II) helicates such as toxicity assays with erythrocytes and interaction studies with proteins and oligonucleotides were performed, demonstrating in all cases low toxicity and an absence of covalent interaction with the proteins and oligonucleotides. The in vitro cytotoxicity of the helicates was tested against MCF-7 (human breast carcinoma), A2780 (human ovarian carcinoma cells), NCI-H460 (human lung carcinoma cells) and MRC-5 (normal human lung fibroblasts), comparing the IC50 values with cisplatin. We will try to demonstrate if the terminal substituent of the ligand precursor exerts any effect in toxicity or in the antitumor activity of the zinc helicates.
The Renal Manifestations of SARS-CoV-2: A Guide for Family Physicians
Authors: Morrissey Austin P. , Elzinad Nagla , Hayek Chris El , Lotfollahzadeh Saran , Chitalia Vipul C.
Published: January 2023

COVID-19 is a devastating systemic disease characterized by multisystem involvement driven by exuberant hyperinflammatory and dysregulations in coagulation. In COVID-19 patients, renal failure contributes to morbidity and mortality, and its early detection and timely management are critical to minimize such untoward and irreversible complications. In the healthcare system, family physicians constitute the first node in the management of patients, yet there is a dearth of reports and guidelines focusing on them for specific organ affection. This review provides an overview of recent studies examining the renal manifestations following SARS-CoV-2 infection. We focus on the tell-tale signs and laboratory findings of renal affection in the pediatric and adult populations with COVID-19, specifically for family practitioners to assist in their appropriate triage. Among different manifestations, urinary abnormalities and a modest increase in creatinine are the early indicators of renal affection in COVID-19 patients. Although renal transplant patients are conventionally managed by specialized teams, they may present to family physicians during a pandemic. This review provides a framework for family physicians to promptly detect early indicators of renal involvement in patients infected with SARS-CoV-2, including providing triage guidance for kidney transplant recipients.
Ab Initio Investigation of the Adsorption of CO2 Molecules on Defect Sites of Graphene Surfaces: Role of Local Vacancy Structures
Authors: Wang Cui , Wang Ziming , Zhang Shujie , Zhang Jianliang , Li Kejiang
Published: January 2023

An in-depth investigation into the adsorption of CO2 on graphene vacancies is essential for the understanding of their applications in various industries. Herein, we report an investigation of the effects of vacancy defects on CO2 gas adsorption behavior on graphene surfaces using the density functional theory. The results show that the formation of vacancies leads to various deformations of local carbon structures, resulting in different adsorption capabilities. Even though most carbon atoms studied can only trigger physisorption, there are also carbon sites that are energetically favored for chemisorption. The general order of the adsorption capabilities of the local carbon atoms is as follows: carbon atoms with dangling bonds > carbon atoms shared by five- and six-membered rings and a vacancy > carbon atoms shared by two six-membered rings and a vacancy. A stronger interaction in the adsorption process generally corresponds to more obvious changes in the partial density of states and a larger amount of transferred charge.
Physical Properties and Antimicrobial Release Ability of Gentamicin-Loaded Apatite Cement/α-TCP Composites: An In Vitro Study
Authors: Sasaki Kazuki , Ninomiya Yoshiaki , Takechi Masaaki , Tsuru Kanji , Ishikawa Kunio , Shigeishi Hideo , Ohta Kouji , Aikawa Tomonao
Published: January 2023

Apatite cement (AC), which has excellent osteoconductive ability, and alpha-tricalcium phosphate (α-TCP), which can be used for bone replacement, are useful bone substitute materials. The objective of this study was to clarify the physical properties and antimicrobial release ability of antibiotic-loaded AC/α-TCP composites in vitro. Gentamicin-loaded, rapid setting AC/α-TCP composites were prepared in 2 mixing ratios (10:3 and 10:6). The cement paste of AC/α-TCP composites was prepared in a plastic mold and dried in a thermostatic chamber at 37 °C and 100% relative humidity for 24 h. A diametral tensile strength test, powder X-ray diffraction analysis, and gentamicin release test were performed. The diametral tensile strengths of the AC/α-TCP composites were significantly less than that of AC alone. Powder X-ray diffraction patterns exhibited the characteristic peaks of hydroxyapatite in the AC/α-TCP composites and gentamicin-loaded AC/α-TCP composites. The concentration of the released gentamicin was maintained above the minimum inhibitory concentration of Staphylococcus aureus until Day 30 in both the gentamicin-loaded AC/α-TCP composites (10:3 and 10:6). Our results suggest that a gentamicin-loaded AC/α-TCP composite has potential as a drug delivery system. Further study is essential to investigate the antimicrobial activity and safety of the gentamicin-loaded AC/α-TCP composites in animal models.
Determination of Particle Size Distributions of Bulk Samples Using Micro-Computed Tomography and Artificial Intelligence
Authors: Höving Stefan , Neuendorf Laura , Betting Timo , Kockmann Norbert
Published: January 2023

The knowledge of product particle size distribution (PSD) in crystallization processes is of high interest for the pharmaceutical and fine chemical industries, as well as in research and development. Not only can the efficiency of crystallization/production processes and product quality be increased but also new equipment can be qualitatively characterized. A large variety of analytical methods for PSDs is available, most of which have underlying assumptions and corresponding errors affecting the measurement of the volume of individual particles. In this work we present a method for the determination of particle volumes in a bulk sample via micro-computed tomography and the application of artificial intelligence. The particle size of bulk samples of sucrose were measured with this method and compared to classical indirect measurement methods. Advantages of the workflow are presented.
Prediction of the Long-Term Performance of an Existing Warm Recycled Motorway Pavement
Authors: Ingrassia Lorenzo Paolo , Spadoni Sara , Ferrotti Gilda , Virgili Amedeo , Canestrari Francesco
Published: January 2023

Warm mix asphalt (WMA) technologies allow the production, lay-down and compaction of asphalt mixtures at reduced temperatures and the use of higher amounts of reclaimed asphalt pavement (RAP) with respect to conventional hot mix asphalt (HMA), leading to significant environmental benefits and energy savings. However, limited data is available on the long-term performance of such pavements. The objective of this study was to predict the long-term performance of an existing warm recycled motorway pavement (made with WMA mixtures containing RAP) constructed in 2016 in central Italy, along with the corresponding hot recycled pavement (made with HMA mixtures containing RAP). For this purpose, cores were taken from the pavements in 2022 to investigate the binder and base courses through dynamic modulus and cyclic fatigue tests, according to the simplified viscoelastic continuum damage (S-VECD) testing approach. The results of the tests were used to predict the service life of the pavements using two pieces of software, KENPAVE and FlexPAVE, based respectively on the elastic design method and the viscoelastic design method in the presence of damage. The FlexPAVE results indicated that the expected service life of the WMA pavement is much longer than that of the HMA pavement, mainly because the WMA mixtures have better damage properties than the HMA mixtures. Conversely, the KENPAVE simulations predicted a similar service life for the two pavements, highlighting the impossibility of the elastic method to catch the actual contribution of high-performance non-standard materials. The promising outcomes of the FlexPAVE simulations further encourage the application of warm recycled pavements.
Evidence of Tribological Adaptation Controlled by Tribosynthesis of FeWO4 on an WC-Reinforced Electron Beam M2 Steel Coating Rubbed against a HSS Disk in a Range of Sliding Speeds
Authors: Savchenko Nickolai , Fedin Evgeny , Sevostyanova Irina , Moskvichev Evgeny , Vorontsov Andrey , Tarasov Sergei
Published: January 2023

In the present work, the tribological experiments on sliding the electron beam composite M2+WC coating have been carried out with characterization of the sample microstructures and phases both before and after the testing using metallography, SEM, EDS, and XRD. The sliding in the speed range 0.8–3.6 m/s resulted in simultaneous reduction in both wear rate and coefficient of friction with the sliding speed. Investigations showed that such a tribological adaptation was due to the tribochemical generation of lubricative FeWO4 and Fe2WO6 mixed oxides and the generation of a mechanically mixed composite layer on the worn surfaces that consisted of carbide fragments, an oxidized metal matrix, and was lubricated by in-situ formed mixed iron-tungsten oxides.
Structural and Functional Picosecond Laser Modification of the Nimonic 263 Superalloy in Different Environmental Conditions and Optimization of the Irradiation Process
Authors: Rajčić Boris , Šibalija Tatjana , Nikolić Vladimir , Čekada Miha , Savović Jelena , Petronić Sanja , Milovanović Dubravka
Published: January 2023

In this experimental study, picosecond laser treatment was performed on a nickel-based superalloy Nimonic 263, aiming to investigate the surface effects induced by irradiation in different atmospheric conditions and, concerning changes in surface composition, regarding the possibility for improvement of its functionality. Besides the varying laser parameters, such as a number of pulses and pulse energy, environmental conditions are also varied. All surface modifications were carried out in standard laboratory conditions and a nitrogen- and argon-rich atmosphere. The resulting topography effects depend on the specific laser treatment and could be categorized as increased roughness, crater formation, and formation of the laser-induced periodic surface structures (LIPSS). Changes in the chemical surface composition are distinguished as the potential formation of the protective oxides/nitrides on the sample surface. Numerous characterization techniques analyse the resulting effects on the topography and surface parameters. The multi-response parametric optimization of the picosecond laser process was performed using an advanced statistical method based on Taguchi’s robust parameter design. Finally, the optimal parameter conditions for Nimonic 263 modification are suggested.
Structurally Diverse Diterpenes from the South China Sea Soft Coral Sarcophyton trocheliophorum
Authors: Song Yu-Ting , Yu Dan-Dan , Su Ming-Zhi , Luo Hui , Cao Jian-Guo , Liang Lin-Fu , Yang Fan , Guo Yue-Wei
Published: January 2023

The present investigation of the South China Sea soft coral Sarcophyton trocheliophorum resulted in the discovery of six new polyoxygenated diterpenes, namely sartrocheliols A–E (1, 3, 5–8) along with four known ones, 2, 4, 9, and 10. Based on extensive spectroscopic data analysis, sartrocheliol A (1) was identified as an uncommon capnosane diterpene, while sartrocheliols B–E (3, 5–8) were established as cembrane diterpenes. They displayed diverse structural features not only at the distinctly different carbon frameworks but also at the various types of heterocycles, including the epoxide, γ-lactone, furan, and pyran rings. Moreover, their absolute configurations were determined by a combination of quantum mechanical-nuclear magnetic resonance (QM-NMR) approach, modified Mosher’s method, and X-ray diffraction analysis. In the anti-tumor bioassay, compound 4 exhibited moderate cytotoxic activities against A549, H1975, MDA-MB-231, and H1299 cells with the IC50 values ranging from 26.3 to 47.9 μM.
Dinoflagellate Amphiesmal Dynamics: Cell Wall Deposition with Ecdysis and Cellular Growth
Authors: Kwok Alvin Chun Man , Chan Wai Sun , Wong Joseph Tin Yum
Published: January 2023

Dinoflagellates are a major aquatic protist group with amphiesma, multiple cortical membranous “cell wall” layers that contain large circum-cortical alveolar sacs (AVs). AVs undergo extensive remodeling during cell- and life-cycle transitions, including ecdysal cysts (ECs) and resting cysts that are important in some harmful algal bloom initiation–termination. AVs are large cortical vesicular compartments, within which are elaborate cellulosic thecal plates (CTPs), in thecate species, and the pellicular layer (PL). AV-CTPs provide cellular mechanical protection and are targets of vesicular transport that are replaced during EC-swarmer cell transition, or with increased deposition during the cellular growth cycle. AV-PL exhibits dynamical-replacement with vesicular trafficking that are orchestrated with amphiesmal chlortetracycline-labeled Ca2+ stores signaling, integrating cellular growth with different modes of cell division cycle/progression. We reviewed the dynamics of amphiesma during different cell division cycle modes and life cycle stages, and its multifaceted regulations, focusing on the regulatory and functional readouts, including the coral–zooxanthellae interactions.
Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy/DAPK2/Apoptosis Signaling Cascade
Authors: Chang Chun-Han , Lin Bo-Jyun , Chen Chun-Han , Nguyen Nham-Linh , Hsieh Tsung-Han , Su Jui-Hsin , Chen Mei-Chuan
Published: January 2023

Bladder cancer (BC) is one of the most prevalent cancers worldwide. However, the recurrence rate and five-year survival rate have not been significantly improved in advanced BC, and new therapeutic strategies are urgently needed. The anticancer activity of stellettin B (SP-2), a triterpene isolated from the marine sponge Rhabdastrella sp., was evaluated with the MTT assay as well as PI and Annexin V/7-AAD staining. Detailed mechanisms were elucidated through an NGS analysis, protein arrays, and Western blotting. SP-2 suppressed the viability of BC cells without severe toxicity towards normal uroepithelial cells, and it increased apoptosis with the activation of caspase 3/8/9, PARP, and γH2AX. The phosphorylation of FGFR3 and its downstream targets were downregulated by SP-2. Meanwhile, it induced autophagy in BC cells as evidenced by LC3-II formation and p62 downregulation. The inhibition of autophagy using pharmacological inhibitors or through an ATG5-knockout protected RT-112 cells from SP-2-induced cell viability suppression and apoptosis. In addition, the upregulation of DAPK2 mRNA and protein expression also contributed to SP-2-induced cytotoxicity and apoptosis. In RT-112 cells, an FGFR3-TACC3-knockout caused the downregulation of DAPK2, autophagy, and apoptosis. In conclusion, this is the first study demonstrating that SP-2 exhibits potent anti-BC activity by suppressing the FGFR3-TACC3/Akt/mTOR pathway, which further activates a novel autophagy/DAPK2/apoptosis signaling cascade.
Tunability of the Superconductivity of NbSe2 Films Grown by Two-Step Vapor Deposition
Authors: Lin Huihui , Chang Meijuan , Fu Xingjie , Li Pengfei , Chen Maoxin , Wu Luyan , Yang Fangqi , Zhang Quan
Published: January 2023

Layered metallic transition-metal dichalcogenides (TMDCs) are ideal platforms for exploring their fascinating electronic properties at two-dimensional limits, such as their charge density wave (CDW) and superconductivity. Therefore, developing ways to improve the crystallization quality of TMDCs is urgently needed. Here we report superconductively tunable NbSe2 grown by a two-step vapor deposition method. By optimizing the sputtering conditions, superconducting NbSe2 films were prepared from highly crystalline Nb films. The bilayer NbSe2 films showed a superconducting transition temperature that was up to 3.1 K. Similar to the salt-assisted chemical vapor deposition (CVD) method, superconducting monolayer NbSe2 crystals were also grown from a selenide precursor, and the growth strategy is suitable for many other TMDCs. Our growth method not only provides a way to improve the crystalline quality of TMDC films, but also gives new insight into the growth of monolayer TMDCs. It holds promise for exploring two-dimensional TMDCs in fundamental research and device applications.
Physicochemical Characterizations, Digestibility, and Lipolysis Inhibitory Effects of Highland Barley Resistant Starches Prepared by Physical and Enzymatic Methods
Authors: Wang Cong , Tian Xinyi , Zhang Xiayin , Zhang Zhiming , Zhang Xiaoyu , Zeng Xiaoxiong
Published: January 2023

This study aimed to investigate the differences in the physicochemical and structural characteristics, digestibility, and lipolysis inhibitory potential in vitro of highland barley resistant starches (HBRSs) prepared by autoclaving (HBSA), microwave-assisted autoclaving (HBSM), isoamylase (HBSI) and pullulanase (HBSP) debranching modifications. Results revealed that the resistant starch content of native starch was significantly elevated after modifications. HBSA and HBSM showed distinctly higher swelling power and water-binding capacities along with lower amylose amounts and solubilities than those of HBSI and HBSP (p < 0.05). Fourier transform infrared spectroscopy and X-ray diffraction exhibited that HBSP displayed the highest degree of the ordered crystalline region and crystallinity with a mixture of CB- and V-type polymorphs. Meanwhile, HBSA and HBSM were characterized by their high degree of the amorphous region with a mixture of B- and V-type polymorphs. Physical and enzymatic modifications resulted in different functionalities of HBRSs, among which HBSP showed the lowest digestibility and HBSM exhibited the highest inhibitory activity on lipolysis due to their structure and structure-based morphology and particle size. This study provided significant insights into the development of native starch from highland barley as an alternative functional food.
Efficient Optosensing of Hippuric Acid in the Undiluted Human Urine with Hydrophilic “Turn-On”-Type Fluorescent Hollow Molecularly Imprinted Polymer Microparticles
Authors: Zhang Wanlan , Li Qun , Zhang Huiqi
Published: January 2023

The development of complex biological sample-compatible fluorescent molecularly imprinted polymers (MIPs) with improved performances is highly important for their real-world bioanalytical and biomedical applications. Herein, we report on the first hydrophilic “turn-on”-type fluorescent hollow MIP microparticles capable of directly, highly selectively, and rapidly optosensing hippuric acid (HA) in the undiluted human urine samples. These fluorescent hollow MIP microparticles were readily obtained through first the synthesis of core-shell-corona-structured nitrobenzoxadiazole (NBD)-labeled hydrophilic fluorescent MIP microspheres by performing one-pot surface-initiated atom transfer radical polymerization on the preformed “living” silica particles and subsequent removal of their silica core via hydrofluoric acid etching. They showed “turn-on” fluorescence and high optosensing selectivity and sensitivity toward HA in the artificial urine (the limit of detection = 0.097 μM) as well as outstanding photostability and reusability. Particularly, they exhibited much more stable aqueous dispersion ability, significantly faster optosensing kinetics, and higher optosensing sensitivity than their solid counterparts. They were also directly used for quantifying HA in the undiluted human urine with good recoveries (96.0%–102.0%) and high accuracy (RSD ≤ 4.0%), even in the presence of several analogues of HA. Such fluorescent hollow MIP microparticles hold much promise for rapid and accurate HA detection in the clinical diagnostic field.
Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells
Authors: Tu Erh-Chuang , Hsu Wei-Li , Tzen Jason T. C.
Published: January 2023

Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety of wild Pu’er tea plants were two major ingredients responsible for the anti-influenza activity. As the COVID-19 outbreak is still lurking, developing safe and cost-effective therapeutics is an urgent need. This study aimed to evaluate the effects of these tea compounds on the infection of mouse hepatitis virus (MHV), a β-coronavirus serving as a surrogate for SARS-CoV. Treatment with strictinin (100 μM), but not theacrine, completely eliminated MHV infection, as indicated by a pronounced reduction in plaque formation, nucleocapsid protein expression, and progeny production of MHV. Subsequently, a time-of-drug addition protocol, including pre-, co-, or post-treatment, was exploited to further evaluate the possible mechanism of antiviral activity mediated by strictinin, and remdesivir, a potential drug for the treatment of SARS-CoV-2, was used as a positive control against MHV infection. The results showed that all three treatments of remdesivir (20 μM) completely blocked MHV infection. In contrast, no significant effect on MHV infection was observed when cells were pre-treated with strictinin (100 μM) prior to infection, while significant inhibition of MHV infection was observed when strictinin was introduced upon viral adsorption (co-treatment) and after viral entry (post-treatment). Of note, as compared with the co-treatment group, the inhibitory effect of strictinin was more striking in the post-treatment group. These results indicate that strictinin suppresses MHV infection by multiple mechanisms; it possibly interferes with viral entry and also critical step(s) of viral infection. Evidently, strictinin significantly inhibited MHV infection and might be a suitable ingredient for protection against coronavirus infection.
A Review on Recent Approaches on Molecular Docking Studies of Novel Compounds Targeting Acetylcholinesterase in Alzheimer Disease
Authors: Peitzika Stergiani-Chrysovalanti , Pontiki Eleni
Published: January 2023

Alzheimer’s disease (AD), a neurodegenerative brain disorder that affects millions of people worldwide, is characterized by memory loss and cognitive decline. Low levels of acetylcholine and abnormal levels of beta-amyloid, T protein aggregation, inflammation, and oxidative stress, have been associated with AD, and therefore, research has been oriented towards the cholinergic system and primarily on acetylcholinesterase (AChE) inhibitors. In this review, we are focusing on the discovery of AChE inhibitors using computer-based modeling and simulation techniques, covering the recent literature from 2018–2022. More specifically, the review discusses the structures of novel, potent acetylcholinesterase inhibitors and their binding mode to AChE, as well as the physicochemical requirements for the design of potential AChE inhibitors.
An Aluminum-Based Microfluidic Chip for Polymerase Chain Reaction Diagnosis
Authors: Yang Siyu , Zhang Ziyi , Xian Qingyue , Song Qi , Liu Yiteng , Gao Yibo , Wen Weijia
Published: January 2023

Real-time polymerase chain reaction (real-time PCR) tests were successfully conducted in an aluminum-based microfluidic chip developed in this work. The reaction chamber was coated with silicone-modified epoxy resin to isolate the reaction system from metal surfaces, preventing the metal ions from interfering with the reaction process. The patterned aluminum substrate was bonded with a hydroxylated glass mask using silicone sealant at room temperature. The effect of thermal expansion was counteracted by the elasticity of cured silicone. With the heating process closely monitored, real-time PCR testing in reaction chambers proceeded smoothly, and the results show similar quantification cycle values to those of traditional test sets. Scanning electron microscope (SEM) and atomic force microscopy (AFM) images showed that the surface of the reaction chamber was smoothly coated, illustrating the promising coating and isolating properties. Energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma-optical emission spectrometer (ICP-OES) showed that no metal ions escaped from the metal to the chip surface. Fourier-transform infrared spectroscopy (FTIR) was used to check the surface chemical state before and after tests, and the unchanged infrared absorption peaks indicated the unreacted, antifouling surface. The limit of detection (LOD) of at least two copies can be obtained in this chip.
Dextran Formulations as Effective Delivery Systems of Therapeutic Agents
Authors: Petrovici Anca Roxana , Pinteala Mariana , Simionescu Natalia
Published: January 2023

Dextran is by far one of the most interesting non-toxic, bio-compatible macromolecules, an exopolysaccharide biosynthesized by lactic acid bacteria. It has been extensively used as a major component in many types of drug-delivery systems (DDS), which can be submitted to the next in-vivo testing stages, and may be proposed for clinical trials or pharmaceutical use approval. An important aspect to consider in order to maintain high DDS’ biocompatibility is the use of dextran obtained by fermentation processes and with a minimum chemical modification degree. By performing chemical modifications, artefacts can appear in the dextran spatial structure that can lead to decreased biocompatibility or even cytotoxicity. The present review aims to systematize DDS depending on the dextran type used and the biologically active compounds transported, in order to obtain desired therapeutic effects. So far, pure dextran and modified dextran such as acetalated, oxidised, carboxymethyl, diethylaminoethyl-dextran and dextran sulphate sodium, were used to develop several DDSs: microspheres, microparticles, nanoparticles, nanodroplets, liposomes, micelles and nanomicelles, hydrogels, films, nanowires, bio-conjugates, medical adhesives and others. The DDS are critically presented by structures, biocompatibility, drugs loaded and therapeutic points of view in order to highlight future therapeutic perspectives.
Synthesis and Preclinical Evaluation of Three Novel 68Ga-Labeled Bispecific PSMA/FAP-Targeting Tracers for Prostate Cancer Imaging
Authors: Verena Arsyangela , Zhang Zhengxing , Kuo Hsiou-Ting , Merkens Helen , Zeisler Jutta , Wilson Ryan , Bendre Shreya , Wong Antonio A. W. L. , Bénard François , Lin Kuo-Shyan
Published: January 2023

Tumor heterogeneity limits the efficacy and reliability of monospecific radiopharmaceuticals in prostate cancer diagnosis and therapy. To overcome this limitation and improve lesion detection sensitivity, we developed and evaluated three bispecific radiotracers that can target both prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are the two key proteins overexpressed in prostate cancer. Three FAP-targeting ligands with various linker lengths were synthesized through multistep organic synthesis, and then connected to the PSMA-targeting motif. IC50(PSMA) and IC50(FAP) values of Ga-complexed bispecific ligands, Ga-AV01017, Ga-AV01030, and Ga-AV01038 were 25.2–71.6 and 1.25–2.74 nM, respectively. The uptake values in PSMA-expressing LNCaP tumor xenografts were 4.38 ± 0.55, 5.17 ± 0.51, and 4.25 ± 0.86 %ID/g for [68Ga]Ga-AV01017, [68Ga]Ga-AV01030, and [68Ga]Ga-AV01038, respectively, which were lower than the monospecific PSMA-targeting tracer [68Ga]Ga-HTK03041 (23.1 ± 6.11 %ID/g). The uptake values in FAP-expressing HEK293T:hFAP tumor xenografts were 2.99 ± 0.37, 3.69 ± 0.81, 3.64 ± 0.83 %ID/g for [68Ga]Ga-AV01017, [68Ga]Ga-AV01030, and [68Ga]Ga-AV01038, respectively, which were also lower than the monospecific FAP-targeting tracer, [68Ga]Ga-FAPI-04 (12.5 ± 2.00 %ID/g). We observed that the bispecific tracers had prolonged blood retention, in which tracers with a longer linker tend to have a higher blood uptake and lower tumor uptake. Further investigations are needed to optimize the linker selection to generate promising bispecific PSMA/FAP-targeting tracers for prostate cancer imaging.
The Use of Anhydrous Barium Hydroxide for Selective Alkylation of Dialkyloxy-tert-butyl-calix[4]arenes
Authors: Yesypenko Oleksandr A. , Trybrat Oleksandr O. , Kalchenko Vitaly I.
Published: January 2023

A practical method of selective alkylation of the third hydroxyl group of disubstituted tert-butyl-calix[4]arenes using anhydrous barium hydroxide as a base was developed in this study. The use of this method in the synthesis of inherently chiral derivatives is shown herein.
Mechanisms of Phototoxic Effects of Cationic Porphyrins on Human Cells In Vitro
Authors: Yegorov Yegor E. , Vishnyakova Khava S. , Pan Xiaowen , Egorov Anton E. , Popov Konstantin V. , Tevonyan Liana L. , Chashchina Galina V. , Kaluzhny Dmitry N.
Published: January 2023

The toxic effects of four cationic porphyrins on various human cells were studied in vitro. It was found that, under dark conditions, porphyrins are almost nontoxic, while, under the action of light, the toxic effect was observed starting from nanomolar concentrations. At a concentration of 100 nM, porphyrins caused inhibition of metabolism in the MTT test in normal and cancer cells. Furthermore, low concentrations of porphyrins inhibited colony formation. The toxic effect was nonlinear; with increasing concentrations of various porphyrins, up to about 1 μM, the effect reached a plateau. In addition to the MTT test, this was repeated in experiments examining cell permeability to trypan blue, as well as survival after 24 h. The first visible manifestation of the toxic action of porphyrins is blebbing and swelling of cells. Against the background of this process, permeability to porphyrins and trypan blue appears. Subsequently, most cells (even mitotic cells) freeze in this swollen state for a long time (24 and even 48 h), remaining attached. Cellular morphology is mostly preserved. Thus, it is clear that the cells undergo mainly necrotic death. The hypothesis proposed is that the concentration dependence of membrane damage indicates a limited number of porphyrin targets on the membrane. These targets may be any ion channels, which should be considered in photodynamic therapy.
One-Pot Synthesis of NiSe2 with Layered Structure for Nickel-Zinc Battery
Authors: Chen Shi , Huang Yifeng , Li Haoran , Wang Fuxin , Xu Wei , Zheng Dezhou , Lu Xihong
Published: January 2023

Transition metal organic framework materials and their selenides are considered to be one of the most promising cathode materials for nickel-zinc (denoted as Ni-Zn) batteries due to their low cost, environmental friendliness, and controllable microstructure. Yet, their low capacity and poor cycling performance severely restricts their further development. Herein, we developed a simple one-pot hydrothermal process to directly synthesize NiSe2 (denotes as NiSe2-X based on the molar amount of SeO2 added) stacked layered sheets. Benefiting from the peculiar architectures, the fabricated NiSe2−1//Zn battery based on NiSe2 and the Zn plate exhibits a high specific capacity of 231.6 mAh g−1 at 1 A g−1, and excellent rate performance (162.8 mAh g−1 at 10 A g−1). In addition, the NiSe2//Zn battery also presents a satisfactory cycle life at the high current density of 8 A g−1 (almost no decay compared to the initial specific capacity after 1000 cycles). Additionally, the battery device also exhibits a satisfactory energy density of 343.2 Wh kg−1 and a peak power density of 11.7 kW kg−1. This work provides a simple attempt to design a high-performance layered cathode material for aqueous Ni-Zn batteries.
Ta3N5 Nanobelt-Loaded Ru Nanoparticle Hybrids’ Electrocatalysis for Hydrogen Evolution in Alkaline Media
Authors: Zhang Xinyu , Xu Lulu , Wu Xingcai , Tao Yourong , Xiong Weiwei
Published: January 2023

Electrochemical hydrogen evolution is a highly efficient way to produce hydrogen, but since it is limited by high-cost electrocatalysts, the preparation of high-efficiency electrocatalysts with fewer or free noble metals is important. Here, Ta3N5 nanobelt (NB)-loaded Ru nanoparticle (NP) hybrids with various ratios, including 1~10 wt% Ru/Ta3N5, are constructed to electrocatalyze water splitting for a hydrogen evolution reaction (HER) in alkaline media. The results show that 5 wt% Ru/Ta3N5 NBs have good HER properties with an overpotential of 64.6 mV, a Tafel slope of 84.92 mV/dec at 10 mA/cm2 in 1 M of KOH solution, and good stability. The overpotential of the HER is lower than that of Pt/C (20 wt%) at current densities of 26.3 mA/cm2 or more. The morphologies and structures of the materials are characterized by scanning electron microscopy and high-resolution transmission electron microscopy, respectively. X-ray photoelectron energy spectroscopy (XPS) demonstrates that a good HER performance is generated by the synergistic effect and electronic transfer of Ru to Ta3N5. Our electrochemical analyses and theoretical calculations indicate that Ru/Ta3N5 interfaces play an important role as real active sites.
Evaluating the Antimicrobial and Anti-Hemolytic Activity of Synthesized Pseudopeptide against Leptospiral Species: In Silico and In Vitro Approach
Authors: Dharmashekar Chandan , Shreevatsa Bhargav , Jain Anisha S. , Harendra Bhavana , Pradeep Sushma , Vishwanath Prashanth M. , Singh Pranav , V Balamurugan , KK Vinod , Patil Sharanagouda S. , Shati Ali A. , Alfaifi Mohammad Y. , Elbehairi Serag Eldin I. , Amachawadi Raghavendra G. , Kollur Shiva Prasad , Shivamallu Chandan
Published: January 2023

Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase—capable of moving inside mitochondria—which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 μg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira, and therefore, this can be used as an alternative drug for the treatment of leptospirosis.
Future Antimicrobials: Natural and Functionalized Phenolics
Authors: Lobiuc Andrei , Pavăl Naomi-Eunicia , Mangalagiu Ionel I. , Gheorghiță Roxana , Teliban Gabriel-Ciprian , Amăriucăi-Mantu Dorina , Stoleru Vasile
Published: January 2023

With incidence of antimicrobial resistance rising globally, there is a continuous need for development of new antimicrobial molecules. Phenolic compounds having a versatile scaffold that allows for a broad range of chemical additions; they also exhibit potent antimicrobial activities which can be enhanced significantly through functionalization. Synthetic routes such as esterification, phosphorylation, hydroxylation or enzymatic conjugation may increase the antimicrobial activity of compounds and reduce minimal concentrations needed. With potent action mechanisms interfering with bacterial cell wall synthesis, DNA replication or enzyme production, phenolics can target multiple sites in bacteria, leading to a much higher sensitivity of cells towards these natural compounds. The current review summarizes some of the most important knowledge on functionalization of natural phenolic compounds and the effects on their antimicrobial activity.