bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Bis(amino acids) Containing the Styryl-cyclobutane Core by Photosensitized [2+2]-Cross-cycloaddition of Allylidene-5(4H)-oxazolones
Authors: Sierra Sonia , Dalmau David , Alegre-Requena Juan V. , Pop Alexandra , Silvestru Cristian , Marín Maria Luisa , Boscá Francisco , Urriolabeitia Esteban P.
Published: April 2023

The irradiation of 2-aryl-4-(E-3′-aryl-allylidene)-5(4H)-oxazolones 1 with blue light (456 nm) in the presence of [Ru(bpy)3](BF4)2 (bpy = 2,2′-bipyridine, 5% mol) gives the unstable cyclobutane-bis(oxazolones) 2 by [2+2]-photocycloaddition of two oxazolones 1. Each oxazolone contributes to the formation of 2 with a different C=C bond, one of them reacting through the exocyclic C=C bond, while the other does so through the styryl group. Treatment of unstable cyclobutanes 2 with NaOMe/MeOH produces the oxazolone ring opening reaction, affording stable styryl-cyclobutane bis(amino acids) 3. The reaction starts with formation of the T1 excited state of the photosensitizer 3[Ru*(bpy)3]2+, which reacts with S0 of oxazolones 1 through energy transfer to give the oxazolone T1 state 3(oxa*)-1, which is the reactive species and was characterized by transient absorption spectroscopy. Measurement of the half-life of 3(oxa*)-1 for 1a, 1b and 1d shows large values for 1a and 1b (10–12 μs), while that of 1d is shorter (726 ns). Density functional theory (DFT) modeling displays strong structural differences in the T1 states of the three oxazolones. Moreover, study of the spin density of T1 state 3(oxa*)-1 provides clues to understanding the different reactivity of 4-allylidene-oxazolones described here with respect to the previously reported 4-arylidene-oxazolones.
Difference in Levels of Vitamin D between Indoor and Outdoor Athletes: A Systematic Review and Meta-Analysis
Authors: Bârsan Maria , Chelaru Vlad-Florin , Râjnoveanu Armand-Gabriel , Popa Ștefan Lucian , Socaciu Andreea-Iulia , Bădulescu Andrei-Vlad
Published: April 2023

Vitamin D, its importance in different processes taking place in the human body, the effects of abnormal levels of this hormone, either too low or too high, and the need for supplementation have been extensively researched thus far. Variances in exposure to sunlight can cause vitamin D levels to fluctuate. Indoor activity can be a factor for these fluctuations and can lead to a decrease in vitamin D levels. We conducted a systematic review and meta-analysis aiming to identify whether indoor compared to outdoor training has a significant influence on vitamin D levels; we also performed subgroup analyses and multivariate meta-regression. The type of training has an impact on vitamin D levels that is influenced by multiple cofounders. In a subgroup analysis not considering cofounders, the mean serum vitamin D was 3.73 ng/mL higher in outdoor athletes, a difference which barely fails to achieve significance (p = 0.052, a total sample size of 5150). The indoor–outdoor difference is only significant (clinically and statistically) when considering studies performed exclusively on Asian athletes (a mean difference of 9.85 ng/mL, p < 0.01, and a total sample size of 303). When performing the analyses within each season, no significant differences are observed between indoor and outdoor athletes. To control for multiple cofounders (the season, latitude, and Asian/Caucasian race) simultaneously, we constructed a multivariate meta-regression model, which estimated a serum vitamin D concentration lower by 4.446 ng/mL in indoor athletes. While a multivariate model suggests that outdoor training is associated with slightly higher vitamin D concentrations when controlling for the season, latitude, and Asian/Caucasian race, the type of training has a numerically and clinically small impact. This suggests that vitamin D levels and the need for supplementation should not be decided based on training type alone.
Mitoregulin Contributes to Creatine Shuttling and Cardiolipin Protection in Mice Muscle
Authors: Averina Olga A. , Permyakov Oleg A. , Emelianova Mariia A. , Grigoryeva Olga O. , Lovat Maxim L. , Egorova Anna E. , Grinchenko Andrei V. , Kumeiko Vadim V. , Marey Maria V. , Manskikh Vasily N. , Dontsova Olga A. , Vysokikh Mikhail Yu. , Sergiev Petr V.
Published: April 2023

Small peptides compose a large share of the mitochondrial proteome. Mitoregulin (Mtln) is a mitochondrial peptide known to contribute to the respiratory complex I functioning and other processes in mitochondria. In our previous studies, we demonstrated that Mtln knockout mice develop obesity and accumulate triglycerides and other oxidation substrates in serum, concomitant with an exhaustion of tricarboxylic acids cycle intermediates. Here we examined the functional role of Mtln in skeletal muscles, one of the major energy consuming tissues. We observed reduced muscle strength for Mtln knockout mice. Decrease of the mitochondrial cardiolipin and concomitant increase in monolysocardiolipin concentration upon Mtln inactivation is likely to be a consequence of imbalance between oxidative damage and remodeling of cardiolipin. It is accompanied by the mitochondrial creatine kinase octamer dissociation and suboptimal respiratory chain performance in Mtln knockout mice.
A Decellularized Uterine Endometrial Scaffold Enhances Regeneration of the Endometrium in Rats
Authors: Yoshimasa Yushi , Takao Tomoka , Katakura Satomi , Tomisato Shoko , Masuda Hirotaka , Tanaka Mamoru , Maruyama Tetsuo
Published: April 2023

Partial or whole regeneration of the uterine endometrium using extracellular matrix (ECM)-based scaffolds is a therapeutic strategy for uterine infertility due to functional and/or structural endometrial defects. Here, we examined whether the entire endometrium can be regenerated circumferentially using an acellular ECM scaffold (decellularized endometrial scaffold, DES) prepared from rat endometrium. We placed a silicone tube alone to prevent adhesions or a DES loaded with a silicone tube into a recipient uterus in which the endometrium had been surgically removed circumferentially. Histological and immunofluorescent analyses of the uteri one month after tube placement revealed more abundant regenerated endometrial stroma in the uterine horns treated with tube-loaded DES compared to those treated with a tube alone. Luminal and glandular epithelia, however, were not fully recapitulated. These results suggest that DES can enhance the regeneration of endometrial stroma but additional intervention(s) are needed to induce epithelization. Furthermore, the prevention of adhesions alone allowed the endometrial stroma to regenerate circumferentially even without a DES, but to a lesser degree than that with a DES. The use of a DES together with the prevention of adhesions may be beneficial for efficient endometrial regeneration in the uterus that is largely deficient of endometrium.
Exploiting Enzyme in the Polymer Synthesis for a Remarkable Increase in Thermal Conductivity
Authors: Petran Anca , Radu Teodora , Dan Monica , Nan Alexandrina
Published: April 2023

The interest in polymers with high thermal conductivity increased much because of their inherent properties such as low density, low cost, flexibility, and good chemical resistance. However, it is challenging to engineer plastics with good heat transfer characteristics, processability, and required strength. Improving the degree of the chain alignment and forming a continuous thermal conduction network is expected to enhance thermal conductivity. This research aimed to develop polymers with a high thermal conductivity that can be interesting for several applications. Two polymers, namely poly(benzofuran-co-arylacetic acid) and poly(tartronic-co-glycolic acid), with high thermal conductivity containing microscopically ordered structures were prepared by performing enzyme-catalyzed (Novozyme-435) polymerization of the corresponding α-hydroxy acids 4-hydroxymandelic acid and tartronic acid, respectively. A comparison between the polymer’s structure and heat transfer obtained by mere thermal polymerization before and enzyme-catalyzed polymerization will now be discussed, revealing a dramatic increase in thermal conductivity in the latter case. The polymer structures were investigated by FTIR spectroscopy, nuclear magnetic resonance (NMR) spectroscopy in liquid- and solid-state (ss-NMR), and powder X-ray diffraction. The thermal conductivity and diffusivity were measured using the transient plane source technique.
MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer
Authors: Hu Bing , Chen Ru , Jiang Ming , Xiong Situ , Xie An , Liu Xiaoqiang , Fu Bin
Published: April 2023

Globally, bladder cancer (BLCA) is still the leading cause of death in patients with tumors. The function and underlying mechanism of MTX-211, an EFGR and PI3K kinase inhibitor, have not been elucidated. This study examined the function of MTX-211 in BLCA cells using in vitro and in vivo assays. RNA sequencing, quantitative real-time polymerase chain reaction, Western blotting, co-immunoprecipitation, and immunofluorescence were performed to elucidate the underlying mechanism. Our observations revealed that MTX-211 has a time- and concentration-dependent inhibitory effect on bladder cancer cell proliferation. Flow cytometry analysis showed that cell apoptosis and G0/G1 cell cycle arrest were significantly induced by MTX-211. MTX-211 inhibited intracellular glutathione (GSH) metabolism, leading to a decrease in GSH levels and an increase in reactive oxygen species. GSH supplementation partly reversed the inhibitory effects of MTX-211. Further experiments verified that MTX-211 promoted NFR2 protein ubiquitinated degradation via facilitating the binding of Keap1 and NRF2, subsequently resulting in the downregulated expression of GCLM, which plays a vital role in GSH synthesis. This study provided evidence that MTX-211 effectively inhibited BLCA cell proliferation via depleting GSH levels through Keap1/NRF2/GCLM signaling pathway. Thus, MTX-211 could be a promising therapeutic agent for cancer.
A Functional Yeast-Based Screen Identifies the Host Microtubule Cytoskeleton as a Target of Numerous Chlamydia pneumoniae Proteins
Authors: Wevers Carolin , Höhler Mona , Alcázar-Román Abel R. , Hegemann Johannes H. , Fleig Ursula
Published: April 2023

Bacterial pathogens have evolved intricate ways to manipulate the host to support infection. Here, we systematically assessed the importance of the microtubule cytoskeleton for infection by Chlamydiae, which are obligate intracellular bacteria that are of great importance for human health. The elimination of microtubules in human HEp-2 cells prior to C. pneumoniae infection profoundly attenuated the infection efficiency, demonstrating the need for microtubules for the early infection processes. To identify microtubule-modulating C. pneumoniae proteins, a screen in the model yeast Schizosaccharomyces pombe was performed. Unexpectedly, among 116 selected chlamydial proteins, more than 10%, namely, 13 proteins, massively altered the yeast interphase microtubule cytoskeleton. With two exceptions, these proteins were predicted to be inclusion membrane proteins. As proof of principle, we selected the conserved CPn0443 protein, which caused massive microtubule instability in yeast, for further analysis. CPn0443 bound and bundled microtubules in vitro and co-localized partially with microtubules in vivo in yeast and human cells. Furthermore, CPn0443-transfected U2OS cells had a significantly reduced infection rate by C. pneumoniae EBs. Thus, our yeast screen identified numerous proteins encoded using the highly reduced C. pneumoniae genome that modulated microtubule dynamics. Hijacking of the host microtubule cytoskeleton must be a vital part of chlamydial infection.
Inhibition of BET Proteins Regulates Fcγ Receptor Function and Reduces Inflammation in Rheumatoid Arthritis
Authors: Shankar Divya , Merchand-Reyes Giovanna , Buteyn Nathaniel J. , Santhanam Ramasamy , Fang Huiqing , Kumar Krishan , Mo Xiaokui , Ganesan Latha P. , Jarjour Wael , Butchar Jonathan P. , Tridandapani Susheela
Published: April 2023

Overactivation of immune responses is a hallmark of autoimmune disease pathogenesis. This includes the heightened production of inflammatory cytokines such as Tumor Necrosis Factor α (TNFα), and the secretion of autoantibodies such as isotypes of rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA). Fcγ receptors (FcγR) expressed on the surface of myeloid cells bind Immunoglobulin G (IgG) immune complexes. Recognition of autoantigen-antibody complexes by FcγR induces an inflammatory phenotype that results in tissue damage and further escalation of the inflammatory response. Bromodomain and extra-terminal protein (BET) inhibition is associated with reduced immune responses, making the BET family a potential therapeutic target for autoimmune diseases such as rheumatoid arthritis (RA). In this paper, we examined the BET inhibitor PLX51107 and its effect on regulating FcγR expression and function in RA. PLX51107 significantly downregulated expression of FcγRIIa, FcγRIIb, FcγRIIIa, and the common γ-chain, FcϵR1-γ, in both healthy donor and RA patient monocytes. Consistent with this, PLX51107 treatment attenuated signaling events downstream of FcγR activation. This was accompanied by a significant decrease in phagocytosis and TNFα production. Finally, in a collagen-induced arthritis model, PLX51107-treatment reduced FcγR expression in vivo accompanied by a significant reduction in footpad swelling. These results suggest that BET inhibition is a novel therapeutic approach that requires further exploration as a treatment for patients with RA.
Identification and Functional Analysis of foxo Genes in Chinese Tongue Sole (Cynoglossus semilaevis)
Authors: Zhang Tingting , Zhang Mengqian , Sun Yuxuan , Li Lu , Cheng Peng , Li Xihong , Wang Na , Chen Songlin , Xu Wenteng
Published: April 2023

The Chinese tongue sole (Cynoglossus semilaevis) is a traditional, precious fish in China. Due to the large growth difference between males and females, the investigation of their sex determination and differentiation mechanisms receives a great deal of attention. Forkhead Box O (FoxO) plays versatile roles in the regulation of sex differentiation and reproduction. Our recent transcriptomic analysis has shown that foxo genes may participate in the male differentiation and spermatogenesis of Chinese tongue sole. In this study, six Csfoxo members (Csfoxo1a, Csfoxo3a, Csfoxo3b, Csfoxo4, Csfoxo6-like, and Csfoxo1a-like) were identified. Phylogenetic analysis indicated that these six members were clustered into four groups corresponding to their denomination. The expression patterns of the gonads at different developmental stages were further analyzed. All members showed high levels of expression in the early stages (before 6 months post-hatching), and this expression was male-biased. In addition, promoter analysis found that the addition of C/EBPα and c-Jun transcription factors enhanced the transcriptional activities of Csfoxo1a, Csfoxo3a, Csfoxo3b, and Csfoxo4. The siRNA-mediated knockdown of the Csfoxo1a, Csfoxo3a, and Csfoxo3b genes in the testicular cell line of Chinese tongue sole affected the expression of genes related to sex differentiation and spermatogenesis. These results have broadened the understanding of foxo’s function and provide valuable data for studying the male differentiation of tongue sole.
Can Neutrophils Prevent Nosocomial Pneumonia after Serious Injury?
Authors: Macáková Kristína , Kaczmarek Elzbieta , Itagaki Kiyoshi
Published: April 2023

Nosocomial pneumonia is a leading cause of critical illness and mortality among seriously injured trauma patients. However, the link between injury and the development of nosocomial pneumonia is still not well recognized. Our work strongly suggests that mitochondrial damage-associated molecular patterns (mtDAMPs), especially mitochondrial formyl peptides (mtFPs) released by tissue injury, play a significant role in developing nosocomial pneumonia after a serious injury. Polymorphonuclear leukocytes (neutrophils, PMN) migrate toward the injury site by detecting mtFPs through formyl peptide receptor 1 (FPR1) to fight/contain bacterial infection and clean up debris. Activation of FPR1 by mtFPs enables PMN to reach the injury site; however, at the same time it leads to homo- and heterologous desensitization/internalization of chemokine receptors. Thus, PMN are not responsive to secondary infections, including those from bacteria-infected lungs. This may enable a progression of bacterial growth in the lungs and nosocomial pneumonia. We propose that the intratracheal application of exogenously isolated PMN may prevent pneumonia coupled with a serious injury.
Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1H,3H)-diones via Annulation of Anthranilic Esters with N-pyridyl Ureas
Authors: Baykova Svetlana O. , Geyl Kirill K. , Baykov Sergey V. , Boyarskiy Vadim P.
Published: April 2023

A new route for the synthesis of quinazolin-2,4(1H,3H)-diones and thieno [2,3-d]pyrimidine-2,4(1H,3H)-diones substituted by pyridyl/quinolinyl moiety in position 3 has been developed. The proposed method concluded in an annulation of substituted anthranilic esters or 2-aminothiophene-3-carboxylates with 1,1-dimethyl-3-(pyridin-2-yl) ureas. The process consists of the formation of N-aryl-N′-pyridyl ureas followed by their cyclocondensation into the corresponding fused heterocycles. The reaction does not require the use of metal catalysts and proceeds with moderate to good yields (up to 89%). The scope of the method is more than 30 examples, including compounds with both electron-withdrawing and electron-donating groups, as well as diverse functionalities. At the same time, strong electron-acceptor substituents in the pyridine ring of the starting ureas reduce the product yield or even prevent the cyclocondensation step. The reaction can be easily scaled to gram quantities.
Predictive Biomarkers for Immune-Checkpoint Inhibitor Treatment Response in Patients with Hepatocellular Carcinoma
Authors: Ji Jun Ho , Ha Sang Yun , Lee Danbi , Sankar Kamya , Koltsova Ekaterina K. , Abou-Alfa Ghassan K. , Yang Ju Dong
Published: April 2023

Hepatocellular carcinoma (HCC) has one of the highest mortality rates among solid cancers. Late diagnosis and a lack of efficacious treatment options contribute to the dismal prognosis of HCC. Immune checkpoint inhibitor (ICI)-based immunotherapy has presented a new milestone in the treatment of cancer. Immunotherapy has yielded remarkable treatment responses in a range of cancer types including HCC. Based on the therapeutic effect of ICI alone (programmed cell death (PD)-1/programmed death-ligand1 (PD-L)1 antibody), investigators have developed combined ICI therapies including ICI + ICI, ICI + tyrosine kinase inhibitor (TKI), and ICI + locoregional treatment or novel immunotherapy. Although these regimens have demonstrated increasing treatment efficacy with the addition of novel drugs, the development of biomarkers to predict toxicity and treatment response in patients receiving ICI is in urgent need. PD-L1 expression in tumor cells received the most attention in early studies among various predictive biomarkers. However, PD-L1 expression alone has limited utility as a predictive biomarker in HCC. Accordingly, subsequent studies have evaluated the utility of tumor mutational burden (TMB), gene signatures, and multiplex immunohistochemistry (IHC) as predictive biomarkers. In this review, we aim to discuss the current state of immunotherapy for HCC, the results of the predictive biomarker studies, and future direction.
Nifedipine Ameliorates Cellular Differentiation Defects of Smn-Deficient Motor Neurons and Enhances Neuromuscular Transmission in SMA Mice
Authors: Tejero Rocio , Alsakkal Mohammad , Hennlein Luisa , Lopez-Cabello Ana M. , Jablonka Sibylle , Tabares Lucia
Published: April 2023

In spinal muscular atrophy (SMA), mutations in or loss of the Survival Motor Neuron 1 (SMN1) gene reduce full-length SMN protein levels, which leads to the degeneration of a percentage of motor neurons. In mouse models of SMA, the development and maintenance of spinal motor neurons and the neuromuscular junction (NMJ) function are altered. Since nifedipine is known to be neuroprotective and increases neurotransmission in nerve terminals, we investigated its effects on cultured spinal cord motor neurons and motor nerve terminals of control and SMA mice. We found that application of nifedipine increased the frequency of spontaneous Ca2+ transients, growth cone size, cluster-like formations of Cav2.2 channels, and it normalized axon extension in SMA neurons in culture. At the NMJ, nifedipine significantly increased evoked and spontaneous release at low-frequency stimulation in both genotypes. High-strength stimulation revealed that nifedipine increased the size of the readily releasable pool (RRP) of vesicles in control but not SMA mice. These findings provide experimental evidence about the ability of nifedipine to prevent the appearance of developmental defects in SMA embryonic motor neurons in culture and reveal to which extent nifedipine could still increase neurotransmission at the NMJ in SMA mice under different functional demands.
Integrative Proteomics and Metabolomics Analysis Reveals the Role of Small Signaling Peptide Rapid Alkalinization Factor 34 (RALF34) in Cucumber Roots
Authors: Shumilina Julia , Kiryushkin Alexey S. , Frolova Nadezhda , Mashkina Valeria , Ilina Elena L. , Puchkova Vera A. , Danko Katerina , Silinskaya Svetlana , Serebryakov Evgeny B. , Soboleva Alena , Bilova Tatiana , Orlova Anastasia , Guseva Elizaveta D. , Repkin Egor , Pawlowski Katharina , Frolov Andrej , Demchenko Kirill N.
Published: April 2023

The main role of RALF small signaling peptides was reported to be the alkalization control of the apoplast for improvement of nutrient absorption; however, the exact function of individual RALF peptides such as RALF34 remains unknown. The Arabidopsis RALF34 (AtRALF34) peptide was proposed to be part of the gene regulatory network of lateral root initiation. Cucumber is an excellent model for studying a special form of lateral root initiation taking place in the meristem of the parental root. We attempted to elucidate the role of the regulatory pathway in which RALF34 is a participant using cucumber transgenic hairy roots overexpressing CsRALF34 for comprehensive, integrated metabolomics and proteomics studies, focusing on the analysis of stress response markers. CsRALF34 overexpression resulted in the inhibition of root growth and regulation of cell proliferation, specifically in blocking the G2/M transition in cucumber roots. Based on these results, we propose that CsRALF34 is not part of the gene regulatory networks involved in the early steps of lateral root initiation. Instead, we suggest that CsRALF34 modulates ROS homeostasis and triggers the controlled production of hydroxyl radicals in root cells, possibly associated with intracellular signal transduction. Altogether, our results support the role of RALF peptides as ROS regulators.
Carrageenans and Their Oligosaccharides from Red Seaweeds Ahnfeltiopsis flabelliformis and Mastocarpus pacificus (Phyllophoraceae) and Their Antiproliferative Activity
Authors: Kravchenko Anna O. , Menchinskaya Ekaterina S. , Isakov Vladimir V. , Glazunov Valery P. , Yermak Irina M.
Published: April 2023

Comparative structural analysis of gelling polysaccharides from A. flabelliformis and M. pacificus belonging to Phyllophoraceae and the effect of their structural features and molecular weight on human colon cancer cell lines (HT-29, DLD-1, HCT-116) was carried out. According to chemical analysis, IR and NMR spectroscopies, M. pacificus produces kappa/iota-carrageenan with a predominance of kappa units and minor amounts of mu and/or nu units, while the polysaccharide from A. flabelliformis is iota/kappa-carrageenan (predominance of iota units) and contains negligible amounts of beta- and nu-carrageenans. Iota/kappa- (Afg-OS) and kappa/iota-oligosaccharides (Mp-OS) were obtained from the original polysaccharides through mild acid hydrolysis. The content of more sulfated iota units in Afg-OS (iota/kappa 7:1) was higher than in Mp-OS (1.0:1.8). The poly- and oligosaccharides up to 1 mg/mL did not show a cytotoxic effect on all tested cell lines. Polysaccharides showed an antiproliferative effect only at 1 mg/mL. Oligosaccharides had a more pronounced effect on HT-29 and HCT-116 cells than the original polymers, while HCT-116 cells were slightly more sensitive to their action. Kappa/iota-oligosaccharides exhibit a greater antiproliferative effect and more strongly decrease the number of colonies forming in HCT-116 cells. At the same time, iota/kappa-oligosaccharides inhibit cell migration more strongly. Kappa/iota-oligosaccharides induce apoptosis in the SubG0 and G2/M phases, while iota/kappa-oligosaccharides in the SubG0 phase.
TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness
Authors: Cabrera-Rodríguez Romina , Pérez-Yanes Silvia , Lorenzo-Sánchez Iria , Estévez-Herrera Judith , García-Luis Jonay , Trujillo-González Rodrigo , Valenzuela-Fernández Agustín
Published: April 2023

The transactive response DNA-binding protein (TARDBP/TDP-43) is known to stabilize the anti-HIV-1 factor, histone deacetylase 6 (HDAC6). TDP-43 has been reported to determine cell permissivity to HIV-1 fusion and infection acting on tubulin-deacetylase HDAC6. Here, we studied the functional involvement of TDP-43 in the late stages of the HIV-1 viral cycle. The overexpression of TDP-43, in virus-producing cells, stabilized HDAC6 (i.e., mRNA and protein) and triggered the autophagic clearance of HIV-1 Pr55Gag and Vif proteins. These events inhibited viral particle production and impaired virion infectiveness, observing a reduction in the amount of Pr55Gag and Vif proteins incorporated into virions. A nuclear localization signal (NLS)-TDP-43 mutant was not able to control HIV-1 viral production and infection. Likewise, specific TDP-43-knockdown reduced HDAC6 expression (i.e., mRNA and protein) and increased the expression level of HIV-1 Vif and Pr55Gag proteins and α-tubulin acetylation. Thus, TDP-43 silencing favored virion production and enhanced virus infectious capacity, thereby increasing the amount of Vif and Pr55Gag proteins incorporated into virions. Noteworthy, there was a direct relationship between the content of Vif and Pr55Gag proteins in virions and their infection capacity. Therefore, for TDP-43, the TDP-43/HDAC6 axis could be considered a key factor to control HIV-1 viral production and virus infectiveness.
Cardiovascular Disease, Atherosclerosis and Familial Hypercholesterolemia: From Molecular Mechanisms Causing Pathogenicity to New Therapeutic Approaches
Authors: Jebari-Benslaiman Shifa , Larrea-Sebal Asier , Benito-Vicente Asier , Martín César
Published: April 2023

This Special Issue, “Cardiovascular Disease, Atherosclerosis and Familial Hypercholesterolemia: From Molecular Mechanisms Causing Pathogenicity to New Therapeutic Approaches”, contributes to advancing our knowledge of the molecular mechanisms that drive cardiovascular disease, atherosclerosis and familial hypercholesterolemia and the development of state-of-the-art research in the field [...]
Sow-Offspring Diets Supplemented with Probiotics and Synbiotics Are Associated with Offspring’s Growth Performance and Meat Quality
Authors: Zhu Qian , Azad Md. Abul Kalam , Dong Haibo , Li Chenjian , Li Ruixuan , Cheng Yating , Liu Yang , Yin Yulong , Kong Xiangfeng
Published: April 2023

Probiotics and synbiotics supplementation have been shown to play potential roles in animal production. The present study aimed to evaluate the effects of dietary probiotics and synbiotics supplementation to sows during gestation and lactation and to offspring pigs (sow-offspring) on offspring pigs’ growth performance and meat quality. Sixty-four healthy Bama mini-pigs were selected and randomly allocated into four groups after mating: the control, antibiotics, probiotics, and synbiotics groups. After weaning, two offspring pigs per litter were selected, and four offspring pigs from two litters were merged into one pen. The offspring pigs were fed a basal diet and the same feed additive according to their corresponding sows, representing the control group (Con group), sow-offspring antibiotics group (S-OA group), sow-offspring probiotics group (S-OP group), and sow-offspring synbiotics group (S-OS group). Eight pigs per group were euthanized and sampled at 65, 95, and 125 d old for further analyses. Our findings showed that probiotics supplementation in sow-offspring diets promoted growth and feed intake of offspring pigs during 95–125 d old. Moreover, sow-offspring diets supplemented with probiotics and synbiotics altered meat quality (meat color, pH45min, pH24h, drip loss, cooking yield, and shear force), plasma UN and AMM levels, and gene expressions associated with muscle-fiber types (MyHCI, MyHCIIa, MyHCIIx, and MyHCIIb) and muscle growth and development (Myf5, Myf6, MyoD, and MyoG). This study provides a theoretical basis for the maternal-offspring integration regulation of meat quality by dietary probiotics and synbiotics supplementation.
Kinetic and Regulatory Properties of Yarrowia lipolytica Aconitate Hydratase as a Model-Indicator of Cell Redox State under pH Stress
Authors: Rakhmanova Tatyana I. , Sekova Varvara Yu. , Gessler Natalya N. , Isakova Elena P. , Deryabina Yulia I. , Popova Tatyana N. , Shurubor Yevgeniya I. , Krasnikov Boris F.
Published: April 2023

This paper presents an analysis of the regulation activity of the partially purified preparations of cellular aconitate hydratase (AH) on the yeast Yarrowia lipolytica cultivated at extreme pH. As a result of purification, enzyme preparations were obtained from cells grown on media at pH 4.0, 5.5, and 9.0, purified by 48-, 46-, and 51-fold and having a specific activity of 0.43, 0.55 and 0.36 E/mg protein, respectively. The kinetic parameters of preparations from cells cultured at extreme pH demonstrated: (1) an increase in the affinity for citrate and isocitrate; and (2) a shift in the pH optima to the acidic and alkaline side in accordance with the modulation of the medium pH. The regulatory properties of the enzyme from cells subjected to alkaline stress showed increased sensitivity to Fe2+ ions and high peroxide resistance. Reduced glutathione (GSH) stimulated AH, while oxidized glutathione (GSSG) inhibited AH. A more pronounced effect of both GSH and GSSG was noted for the enzyme obtained from cells grown at pH 5.5. The data obtained provide new approaches to the use of Y. lipolytica as a model of eukaryotic cells demonstrating the development of a stress-induced pathology and to conducting a detailed analysis of enzymatic activity for its correction.
Evaluation of Automatic Legal Text Summarization Techniques for Greek Case Law
Authors: Koniaris Marios , Galanis Dimitris , Giannini Eugenia , Tsanakas Panayiotis
Published: April 2023

The increasing amount of legal information available online is overwhelming for both citizens and legal professionals, making it difficult and time-consuming to find relevant information and keep up with the latest legal developments. Automatic text summarization techniques can be highly beneficial as they save time, reduce costs, and lessen the cognitive load of legal professionals. However, applying these techniques to legal documents poses several challenges due to the complexity of legal documents and the lack of needed resources, especially in linguistically under-resourced languages, such as the Greek language. In this paper, we address automatic summarization of Greek legal documents. A major challenge in this area is the lack of suitable datasets in the Greek language. In response, we developed a new metadata-rich dataset consisting of selected judgments from the Supreme Civil and Criminal Court of Greece, alongside their reference summaries and category tags, tailored for the purpose of automated legal document summarization. We also adopted several state-of-the-art methods for abstractive and extractive summarization and conducted a comprehensive evaluation of the methods using both human and automatic metrics. Our results: (i) revealed that, while extractive methods exhibit average performance, abstractive methods generate moderately fluent and coherent text, but they tend to receive low scores in relevance and consistency metrics; (ii) indicated the need for metrics that capture better a legal document summary’s coherence, relevance, and consistency; (iii) demonstrated that fine-tuning BERT models on a specific upstream task can significantly improve the model’s performance.
Novel Sophoridine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, Acetylcholinesterase Inhibition, and Morphological Study
Authors: Ang Song , Cao Nana , Zheng Wende , Zhang Zhen , Li Jinxuan , Yan Zhenping , Su Kaize , Wong Wing-Leung , Zhang Kun , Hong Weiqian David , Wu Panpan
Published: April 2023

Two series of novel sophoridine derivatives were designed, synthesized, and evaluated for their anti-mosquito activity. SOP-2g, SOP-2q, and SOP-2r exhibited potential larvicidal activity against Aedes albopictus larva with LC50 values of 330.98, 430.53, and 411.09 ppm, respectively. Analysis of structure–activity relationships indicated that the oxime ester group was beneficial for improving the larvicidal biological activity, whereas the long-chain aliphatic group and fused-ring group were introduced. Furthermore, the larvicidal mechanism was also investigated based on the inhibition assay of acetylcholinesterase (AChE) and the morphological observation of dead larva treated with derivatives. Results indicated that the AChE inhibitory activity of the preferred three derivatives were 63.16%, 46.67%, and 35.11%, respectively, at 250 ppm concentration. Additionally, morphological evidence demonstrated that SOP-2q and SOP-2r induced changes in the larva’s intestinal cavity, caudal gill, and tail, thereby displaying larvicidal action against Ae. albopictus together with AChE inhibition. Therefore, this study implied that sophoridine and its novel derivatives could be used to control the population of mosquito larva, which may also be effective alkaloids to reduce the mosquito population density.
Impact of COVID-19 Infection on Cardiorespiratory Fitness, Sleep, and Psychology of Endurance Athletes—CAESAR Study
Authors: Śliż Daniel , Wiecha Szczepan , Gąsior Jakub S. , Kasiak Przemysław Seweryn , Ulaszewska Katarzyna , Lewandowski Marcin , Barylski Marcin , Mamcarz Artur
Published: April 2023

COVID-19 has a deteriorating impact on health which is especially important for endurance athletes (EAs) who need to maintain continuity of training. The illness affects sleep and psychology, which influence sport performance. The aims of this study were: (1) to assess the consequences of mild COVID-19 on sleep and psychology and (2) to assess the consequences of mild COVID-19 on cardiopulmonary exercise test (CPET) results. A total of 49 EAs (males = 43, 87.76%; females = 6, 12.24%; age = 39.9 ± 7.8 years; height = 178.4 ± 6.8 cm; weight = 76.3 ± 10.4 kg; BMI = 24.0 ± 2.6 kg·m−2) underwent a maximal cycling or running CPET pre- and post-COVID-19 and completed an original survey. Exercise performance deteriorated after COVID-19 (maximal oxygen uptake, VO2max = 47.81 ± 7.81 vs. 44.97 ± 7.00 mL·kg·min−1 pre- and post-infection, respectively; p < 0.001). Waking up at night affected the heart rate (HR) at the respiratory compensation point (RCP) (p = 0.028). Sleep time influenced pulmonary ventilation (p = 0.013), breathing frequency (p = 0.010), and blood lactate concentration (Lac) (p = 0.013) at the RCP. The maximal power/speed (p = 0.046) and HR (p = 0.070) were linked to the quality of sleep. Stress management and relaxation techniques were linked with VO2max (p = 0.046), maximal power/speed (p = 0.033), and maximal Lac (p = 0.045). Cardiorespiratory fitness deteriorated after mild COVID-19 and was correlated with sleep and psychological indices. Medical professionals should encourage EAs to maintain proper mental health and sleep after COVID-19 infection to facilitate recovery.
Long-Term Outcomes of Nasopharyngeal Carcinoma by Epstein–Barr Virus Status in the Chinese Population: A Multicenter Investigation
Authors: Xiong Yudi , Yuan Mengting , Liu Zhigang , Huang Jing , Bi Jianping , Pi Guoliang , Li Ying , Li Yanping , He Hanping , Verma Vivek , Tian Suqing , Han Guang
Published: April 2023

Background: Because the vast majority of nasopharyngeal carcinoma (NPC) in Chinese patients is a direct result of Epstein–Barr virus (EBV) infection, there is a dearth of data for EBV-negative patients in this population. This multicenter study sought to examine the clinical characteristics of EBV-negative patients and compare long-term outcomes with a propensity-matched (1:1.5) EBV-positive cohort. Methods: NPC patients with known EBV status from four hospitals were collated (2013–2021). A logistic regression model was conducted to evaluate the relationship between patient characteristics and EBV status. The Kaplan–Meier method and Cox regression analysis were used to analyze survival data. Results: This study analyzed 48 (40%) EBV-negative and 72 (60%) EBV-positive patients. The median follow-up time was 63.5 months. Most EBV-negative NPC patients (77.1%) were diagnosed in advanced stages with a higher rate (87.5%) of positive lymph node disease, and no significant prognostic factors were discerned in this subpopulation. The EBV-negative disease was more associated with the keratinizing subtype (18.8% vs. 1.4%, p < 0.05). Compared to EBV-negative NPC patients, EBV-positive NPC patients were more likely to develop a local recurrence (9.7% vs. 0%, p = 0.026). There was no statistical difference in mortality (EBV-negative vs. EBV- positive, 8.3% vs. 4.2%, p = 0.34) during the follow-up period. Although the median PFS and median OS were not reached, the 3-year PFS rate was 68.8% vs. 70.8% (EBV-negative vs. EBV-positive, p = 0.06), the 3-year OS rate was 70.8% vs. 76.4% (EBV-negative vs. EBV-positive, p = 0.464), the 5-year PFS rate was 56.3% vs. 50% (EBV-negative vs. EBV-positive, p = 0.451), and the 5-year OS rate was 56.3% vs. 58.3% (EBV-negative vs. EBV-positive, p = 0.051), respectively. These data show that EBV-positive NPC patients seem to have a tendency to gain better survival compared with EBV-negative NPC patients. Conclusions: Most of the EBV-negative patients were in the middle and late stages at the time of diagnosis and were more associated with the keratinizing subtype. EBV status may be associated with prognosis in NPC. EBV positivity seems to be associated with better survival in NPC patients. Still, due to the small cohort of patients and the short observation period for a number of patients, further work is required to corroborate these conclusions.
Sex-Related Differences among Adults with Hypertrophic Obstructive Cardiomyopathy Undergoing Transcoronary Ablation of Septal Hypertrophy
Authors: Alyaydin Emyal , Vogel Julia Kirsten , Luedike Peter , Rassaf Tienush , Jánosi Rolf Alexander , Papathanasiou Maria
Published: April 2023

(1) Background: The transcoronary ablation of septal hypertrophy (TASH) is an established therapy for hypertrophic obstructive cardiomyopathy (HOCM). Previous studies on this topic are characterised by a consistent male predominance and show a worse prognosis in females. (2) Methods: This study is a retrospective analysis of all TASH procedures conducted between 2006 and 2021 at a tertiary academic centre. A solution of 75 µm microspheres (Embozene®, Boston Scientific, Marlborough, MA, USA) was used as an embolising agent. The outcomes of interest were left ventricular outflow tract (LVOT) gradient reduction and symptom improvement among males vs. that among females. Secondarily, we analysed the sex-related differences in procedural safety outcomes and mortality. (3) Results: The study population consisted of 76 patients, with a median age of 61 years. Females comprised 57% of the cohort. We observed no sex-related differences in the baseline LVOT gradients at rest or under provocation (p = 0.560 and p = 0.208, respectively). Females were significantly older at the time of the procedure (p < 0.001), had lower tricuspid annular systolic excursion (TAPSE) (p = 0.009), presented a worse clinical status according to the NYHA functional classification (for NYHA ≥ 3, p < 0.001), and were more often on diuretics (p < 0.001). We did not observe sex-related differences in absolute gradient reduction at rest (p = 0.147) and under provocation (p = 0.709). There was a reduction in the NYHA class by a median value of 1 (p = 0.636) at follow-up for both sexes. Postprocedural access site complications were documented in four cases (two of which concerned females), and complete atrioventricular block was noted in five patients (three of which concerned females). The 10-year survival rates were comparable between the sexes (85% in females and 88% in males). The female sex was not associated with enhanced mortality according to multivariate analysis after adjusting for the confounding variables (HR 0.94; 95% CI 0.376–2.350; p = 0.895), but we observed age-related differences in long-term mortality (HR 1.035; 95% CI 1.007–1.063; p = 0.015). (4) Conclusions: TASH is safe and effective in both sexes, irrespective of their clinical differences. Women present at an advanced age and with more severe symptoms. An advanced age at the time of the intervention is an independent predictor of mortality.
A Prospective Study of Renal Blood Flow during Retrograde Intrarenal Surgery
Authors: Balawender Krzysztof
Published: April 2023

(I) Introduction: The use of Doppler ultrasound allows us to indirectly assess the effect of increased intrarenal pressure on renal blood flow during retrograde intrarenal surgery (RIRS). On the basis of vascular flow spectra from selected blood vessels in the kidney, it is possible to determine Doppler parameters that reflect the renal perfusion status, which indirectly shows the degree of vasoconstriction and reflects the resistance of kidney tissue. (II) Materials and methods: A total of 56 patients were included in the study. The study assessed the changes of three Doppler parameters of intrarenal blood flow: resistive index-RI, pulsatility index-PI, and acceleration time-AT in the ipsilateral and contralateral kidneys during RIRS. The effects of mean stone volume, energy used, and pre-stenting were examined as predictors and calculated at two time intervals. (III) Results: The mean value of RI and PI was significantly higher in the ipsilateral kidney than in the contralateral kidney just after RIRS. The mean value of the acceleration time was not significantly different before and after RIRS. The values of all three parameters 24 h after the procedure were comparable to their values immediately after the RIRS. The size of the stone exposed to laser lithotripsy, the value of the energy used, and pre-stenting are not factors that significantly influence Doppler parameters during RIRS. (IV) Conclusions: The significant increase in RI and PI after RIRS in the ipsilateral kidney suggests a vasoconstriction of the interlobar arteries generated by increased intrarenal pressure during the procedure.
Risk Factors for Perineal Wound Breakdown in Early Postpartum: A Retrospective Case–Control Study
Authors: Puissegur Amandine , Accoceberry Marie , Rouzaire Marion , Pereira Bruno , Herault Marie , Bruhat Clément , Delabaere Amélie , Gallot Denis
Published: April 2023

We conducted a retrospective case–control study in patients presenting a perineal tear (second degree or higher) or episiotomy complicated by wound breakdown during maternity stay to identify risk factors associated with wound breakdown in early postpartum with a view to improving the quality of care. We collected ante- and intrapartum characteristics and outcomes at the postpartum visit. In all, 84 cases and 249 control subjects were included. In univariate analysis, primiparity, absence of history of vaginal delivery, a longer second phase of labour, instrumental delivery, and a higher degree of laceration emerged as risk factors for early perineal suture breakdown postpartum. Gestational diabetes, peripartum fever, streptococcus B, and suture technique did not emerge as risk factors for perineal breakdown. Multivariate analysis confirmed that instrumental delivery (OR = 2.18 [1.07; 4.41], p = 0.03) and a longer second phase of labour (OR = 1.72 [1.23; 2.42], p = 0.001) were risk factors for early perineal suture breakdown.
Influence of Firefighting Intervention on Fire Spread Characteristics in Ship Engine Room
Authors: Li Chenfeng , Mao Jiayin , Kang Zixiong , Zhao Shengzhu , Ren Huilong
Published: April 2023

The purpose of this paper is to investigate and evaluate the ship engine room fire spreading characteristics based on the effect of firefighting interventions. The large eddy simulation (LES) and theoretical models are employed to simulate a fire scene in the engine room. The fire spreading characteristics and the mechanism of the use of a fine water mist are obtained by varying the ventilation conditions and parameters of the water sprinkler. The results show that the reason why a pool fire can be more easily extinguished as the spray speed increases is because the water mist with a higher spray speed has a larger spray area. Meanwhile, the temperature in the engine room would drop more rapidly with the increasing spray area due to the higher evaporation rate. Furthermore, the arrangement of the ventilation conditions had an obvious effect on the fire spreading characteristics, as the depletion of the combustion medium affects the combustion situation.
Numerical and Experimental Investigations on Non-Linear Wave Action on Offshore Wind Turbine Monopile Foundation
Authors: Deng Sijia , Qin Ming , Ning Dezhi , Lin Lin , Wu Songxiong , Zhang Chongwei
Published: April 2023

Monopiles are commonly utilized in offshore wind farms but are prone to non-linear wave loads and run-ups, significantly affecting their engineering design. Therefore, it is crucial to pursue a complete understanding of the non-linear wave action on monopile foundations. Both numerical and experimental investigations on the non-linear wave loads and run-ups on an offshore wind turbine monopile foundation are performed in this paper. The experiment is carried out at a scale of 1/30 in a wave flume at the State Key Laboratory of Coastal and Offshore Engineering, Dalian University of Technology, in which the wave loads and run-ups along the monopile are measured. Based on the second-order potential flow model and time-domain higher-order boundary element method (HOBEM), the related numerical tests are conducted to study the non-linear effects further. It is found that the present non-linear potential theory is sufficient for the simulation of wave force and run-ups on the monopile in the range of wave slope kA < 0.15 before wave breaking. “W” type distribution of wave run-up along the monopile is found, in which the peak value occurs at the frontward side (i.e., θ =180°) and is the maximum due to full reflection; the two symmetrical minimum amplitudes lie in the zones of (45° ≤ θ ≤ 90°) and (270° ≤ θ ≤ 315°), whose positions shift downward with the increase of wave non-linearity. Energy transfer among the fundamental wave component and higher-order components is also found, which is most apparent on the backward side. Besides, the transverse resonance occurs in the wave flume due to the wavelength being near the flume width, which induces the wave run-up at the backward position larger than that at the frontward position.