bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Antimicrobial Peptides Fail to Induce Leucocyte Innate Immune Functions but Elicit Opposing Transcriptomic Profiles in European Sea Bass and Gilthead Seabream
Authors: Cervera Laura , Chaves-Pozo Elena , Cuesta Alberto
Published: February 2024

Antimicrobial peptides (AMPs) are promising molecules in diverse fields, including aquaculture. AMPs possess lytic effects on a wide range of pathogens, resulting in a potential replacement for traditional antimicrobials in aquaculture. In addition, they also have modulatory effects on host immune responses. Thus, the objective of this work was to evaluate the immunomodulatory capability of three known synthetic AMPs derived from European sea bass, NK-lysin (Nkl), hepcidin (Hamp), and dicentracin (Dic), in head-kidney cell suspensions from European sea bass and gilthead seabream. The tested peptides were neither cytotoxic for European sea bass nor gilthead seabream cells and failed to modulate the respiratory burst and phagocytosis activities. However, they modified the pattern of transcription of immune-related genes differently in both species. Peptides were able to promote the expression of marker genes for anti-inflammatory (il10), antiviral (mx, irf3), cell-mediated cytotoxicity (nccrp1, gzmb), and antibody responses (ighm) in European sea bass, with the Nkl peptide being the most effective. Contrary to this, the effects of those peptides on gilthead seabream mainly resulted in the suppression of immune responses. To conclude, European sea bass-derived peptides can be postulated as potential tools for immunostimulation in European sea bass fish farms, but more efforts are required for their universal use in other species.
Meirols A–C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42
Authors: Lee Min , Kang Jong , Yang Jeong-Wook , Lee Hwa-Sun , Heo Chang-Su , Park Sun , Shin Hee
Published: February 2024

Three new catecholic compounds, named meirols A–C (2–4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 μM (ascorbic acid, EC50 = 7.81 μM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 μM, respectively (acarbose, IC50 = 301.93 μM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 μM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 μM.
Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells
Authors: Pulat Sultan , Yang Inho , Lee Jihye , Hwang Sunghoon , Zhou Rui , Gamage Chathurika D. B. , Varlı Mücahit , Taş İsa , Yang Yi , Park So-Yeon , Hong Ahreum , Kim Jeong-Hyeon , Oh Dong-Chan , Kim Hangun , Nam Sang-Jip , Kang Heonjoong
Published: February 2024

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 μM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.
Synthesis of Bioactive Nickel Nanoparticles Using Bacterial Strains from an Antarctic Consortium
Authors: Nagoth Joseph Amruthraj , John Maria Sindhura , Ramasamy Kesava Priyan , Mancini Alessio , Zannotti Marco , Piras Sara , Giovannetti Rita , Rathnam Lydia , Miceli Cristina , Biondini Maria Chiara , Pucciarelli Sandra
Published: February 2024

Marine microorganisms have been demonstrated to be an important source for bioactive molecules. In this paper we report the synthesis of Ni nanoparticles (NiSNPs) used as reducing and capping agents for five bacterial strains isolated from an Antarctic marine consortium: Marinomonas sp. ef1, Rhodococcus sp. ef1, Pseudomonas sp. ef1, Brevundimonas sp. ef1, and Bacillus sp. ef1. The NiSNPs were characterized by Ultraviolet–visible (UV–vis) spectroscopy, Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), X-ray diffraction (XRD) and Fourier Transform Infrared (FTIR) spectroscopic analysis. The maximum absorbances in the UV–Vis spectra were in the range of 374 nm to 422 nm, corresponding to the Surface plasmon resonance (SPR) of Nickel. DLS revealed NiSNPs with sizes between 40 and 45 nm. All NiSNPs were polycrystalline with a face-centered cubic lattice, as revealed by XRD analyses. The NiSNPs zeta potential values were highly negative. TEM analysis showed that the NiSNPs were either spherical or rod shaped, well segregated, and with a size between 20 and 50 nm. The FTIR spectra revealed peaks of amino acid and protein binding to the NiSNPs. Finally, all the NiSNPs possess significant antimicrobial activity, which may play an important role in the management of infectious diseases affecting human health.
The Association between the Extent of the Osteoarthritic Meniscus Degeneration and Cigarette Smoking—A Pilot Study
Authors: Zabrzyńska Maria , Pasiński Maciej , Gagat Maciej , Kułakowski Michał , Woźniak Łukasz , Elster Karol , Antosik Paulina , Zabrzyński Jan
Published: February 2024

Background and Objectives: The negative effects of smoking on the musculoskeletal system were presented by many authors, although the relationship between smoking and osteoarthritis remains unclear. The aim of this paper was to investigate the negative effects of smoking on meniscal tissue in osteoarthritic knees by microscopic examination, by adapting the Bonar scoring system and its modifications. Materials and Methods: The study involved 34 patients with varus knees, from whom 65 samples of knee menisci were obtained. The mean age in the studied group was 65.385 years. The smoking status of the patients concluded that there were 13 smokers and 21 nonsmokers. Results: Among smokers, the mean classical Bonar score was 8.42 and the mean modified Bonar score was 6.65, while nonsmokers were characterized by scores of 8.51 and 7.35, respectively. There was a statistically significant negative correlation between the number of cigarettes and the collagen in the medial meniscus (p = 0.0197). Moreover, in the medial meniscus, the modified Bonar score correlated negatively with the number of cigarettes (p = 0.0180). Similarly, such a correlation was observed between the number of cigarettes and the modified Bonar score in the lateral meniscus (p = 0.04571). Furthermore, no correlation was identified between the number of cigarettes and the classical Bonar score in the lateral meniscus. There was a statistically significant difference in the collagen variable value between the smokers and nonsmokers groups (p = 0.04525). Conclusions: The microscopic investigation showed no differences in the menisci of smokers and nonsmokers, except for the collagen, which was more organized in smokers. Moreover, the modified Bonar score was correlated negatively with the number of cigarettes, which supports the role of neovascularization in meniscus pathology under the influence of tobacco smoking.
Comparative Analysis of Vascular Structures in OLIF51 and the Lateral Corridor Approach under Supine MRI and Intraoperative Enhanced CT in the Lateral Decubitus Position
Authors: Kotani Yoshihisa , Tachi Hiroyuki , Ikeura Atsushi , Tanaka Takahiro , Saito Takanori
Published: February 2024

Background and Objectives: As the oblique lateral interbody fusion at L5/S1 (OLIF51) and the lateral corridor approach (LCA) have gained popularity, an understanding of the precise vascular structure at the L5/S1 level is indispensable. The objectives of this study were to investigate the vascular anatomy at the L5/S1 level, and to compare the movement of vascular tissue between the supine and lateral decubitus positions using intraoperative enhanced CT and MRI. Materials and Methods: A total of 43 patients who underwent either OLIF51 or LCA were investigated with an average age at surgery of 60.4 (37–80) years old. The preoperative MRI was taken to observe the axial and sagittal anatomy of the vascular position under the supine position. The intraoperative vein-enhanced CT was taken just before incision in the right decubitus position, and compared to supine MRI anatomy. Iliolumbar vein appearance and its types were also classified. Results: The average vascular window allowed for OLIF51 was 22.8 mm and 34.1 mm at either the L5 caudal endplate level or the S1 cephalad endplate level, respectively. The LCA was 14.2 mm and 12.6 mm at either level, respectively. The left common iliac vein moved 3.8 mm and 6.9 mm to the right direction at either level from supine to the right decubitus position, respectively. The bifurcation moved 6.3 mm to the caudal direction from supine to right decubitus. The iliolumbar vein was located at 31 mm laterally from the midline, and the MRI detection rate was 52%. Conclusions: The precise measurement of vascular anatomy indicated that the OLIF51 approach was the standard minimally invasive anterior approach for the L5/S1 disc level compared to LCA; however, there were many variations in quantitative anatomy as well as significant vascular movements between the supine and right decubitus positions. In the clinical setting of OLIF51 and LCA surgeries, careful preoperative evaluation and intraoperative 3D imaging are recommended for safe and accurate surgery.
Explainable Model Using Shapley Additive Explanations Approach on Wound Infection after Wide Soft Tissue Sarcoma Resection: “Big Data” Analysis Based on Health Insurance Review and Assessment Service Hub
Authors: Choi Ji-Hye , Choi Yumin , Lee Kwang-Sig , Ahn Ki-Hoon , Jang Woo Young
Published: February 2024

Background and Objectives: Soft tissue sarcomas represent a heterogeneous group of malignant mesenchymal tissues. Despite their low prevalence, soft tissue sarcomas present clinical challenges for orthopedic surgeons owing to their aggressive nature, and perioperative wound infections. However, the low prevalence of soft tissue sarcomas has hindered the availability of large-scale studies. This study aimed to analyze wound infections after wide resection in patients with soft tissue sarcomas by employing big data analytics from the Hub of the Health Insurance Review and Assessment Service (HIRA). Materials and Methods: Patients who underwent wide excision of soft tissue sarcomas between 2010 and 2021 were included. Data were collected from the HIRA database of approximately 50 million individuals’ information in the Republic of Korea. The data collected included demographic information, diagnoses, prescribed medications, and surgical procedures. Random forest has been used to analyze the major associated determinants. A total of 10,906 observations with complete data were divided into training and validation sets in an 80:20 ratio (8773 vs. 2193 cases). Random forest permutation importance was employed to identify the major predictors of infection and Shapley Additive Explanations (SHAP) values were derived to analyze the directions of associations with predictors. Results: A total of 10,969 patients who underwent wide excision of soft tissue sarcomas were included. Among the study population, 886 (8.08%) patients had post-operative infections requiring surgery. The overall transfusion rate for wide excision was 20.67% (2267 patients). Risk factors among the comorbidities of each patient with wound infection were analyzed and dependence plots of individual features were visualized. The transfusion dependence plot reveals a distinctive pattern, with SHAP values displaying a negative trend for individuals without blood transfusions and a positive trend for those who received blood transfusions, emphasizing the substantial impact of blood transfusions on the likelihood of wound infection. Conclusions: Using the machine learning random forest model and the SHAP values, the perioperative transfusion, male sex, old age, and low SES were important features of wound infection in soft-tissue sarcoma patients.
Experimental Investigation on the Energy and Exergy Efficiency of the Vacuum Membrane Distillation System with Its Various Configurations
Authors: Najib Abdullah , Mana Turki , Ali Emad , Al-Ansary Hany , Almehmadi Fahad Awjah , Alhoshan Mansour
Published: February 2024

This paper addresses a retrofitting vacuum membrane distillation (VMD) setup to reduce the accumulated pressure inside the permeated side. This modification is necessary to extend the operation of the VMD to extreme operation conditions of higher hot water temperatures. This modification, denoted as a hybrid configuration, proposes the injection of a cold water stream into the VMD cell without mixing it with the permeate. Energy and exergy efficiency analyses were performed to assess the effectiveness of the hybrid configuration. The performance of the modified system indicated an improvement in terms of permeate flux (J), the gain output ratio (GOR), and the utilitarian exergetic efficiency (ηex,u), which reach up to two and three times that of the base configuration of the VMD system. However, the exergetic efficiency (ηex) of the hybrid system showed marginal improvement compared to the base case over the tested range of hot water temperatures. This is because the enhanced vapor production is penalized by excess energy consumption. Moreover, the highest exergy destruction percentages occurred in the operational components (e.g., heater and chillers) which fall in the range of 19.0–68.9%. The exergy destruction percentage in the original components (e.g., the VMD cell and condenser) did not exceed 8.3%. Furthermore, this study indicated that the hybrid configuration requires additional tuning and optimization to perform efficiently over wide operating conditions.
Cold Rolling Technology Optimization for EN AW 4343/3003/4343 Cladded Aluminum Alloys and Influence of Parameters on Microstructure, Mechanical Properties and Sustainable Recyclability
Authors: Kropf Bojan , Cvahte Peter , Arzenšek Matija , Kraner Jakob
Published: February 2024

The present study investigates the accumulative roll bonding process applied to the EN AW 3003 aluminum alloy, serving as a composite material on both sides and consisting of the EN AW 4343 aluminum alloy. For the characterization of the optical microscopy, corrosion tests with saltwater acetic acid and mechanical properties before and after the braze test were employed. The numerical simulations accurately predicted the industrial cold rolling values for the rolling force and surface temperature. The most comprehensive understanding of the cold rolling parameters for both side-cladded materials was achieved by combining predictions for cladded and uncladded materials. The thickness of the cladded layer presented as a percentage after roll bonding was 18.7%. During the cold rolling and annealing, the cladded thickness was increased to 24.7% of the final 0.3 mm of the total cold-rolled product thickness. According to the performed braze test for final thickness, the ultimate tensile strength and yield strength were decreased, and the elongation increased to 18.1%. In addition to the described changes in mechanical properties, the material’s anisotropy improved from 5.4% in the cold-rolled condition to 2.0% after the braze test. After multiple re-meltings of the cladded material, the analyzed chemical compositions allow for recycling and reuse as different 4xxx, 5xxx, and 6xxx alloys.
Passively Q-Switched Er-Doped Fiber Laser Based on Bentonite Clay (Al2H2O6Si) Saturable Absorber
Authors: Asghar Haroon , Khalid Umer Sayyab , Sohail Muhammad , Alrebdi Tahani A. , Umar Zeshan A. , Alshehri A. M. , Ahmed Rizwan , Baig M. Aslam
Published: February 2024

This paper presents the investigations toward the direct use of bentonite clay (Al2H2O6Si) nanoparticles to act like a saturable absorber (SA) for the Q-switched pulse operation of an erbium-doped fiber laser (EDFL). The measured results reveal that with the incorporation of bentonite clay nanopowder as a SA, an EDFL is realized with a Q-switching mechanism starting at a pump power of 30.8 mW, and a Q-switched emission wavelength was noticed at 1562.94 nm at 142 mW pump power. With an increased pump from 30.8 mW to 278.96 mW, the temporal pulse parameters including minimum pulse duration and maximum pulse repetition rates were reported as 2.6 µs and 103.6 kHz, respectively. The highest peak power, signal-to-noise ratio, output power and pulse energy were noticed to be 16.56 mW, 51 dB, 4.6 mW, and 47 nJ, respectively, at a highest pump power of 278.96 mW. This study highlights the significance of bentonite clay (Al2H2O6Si) nanoparticles as a potential candidate for a saturable absorber for achieving nonlinear photonics applications.
Three-Dimensional-Printed Instrument for Isothermal Nucleic Acid Amplification with Real-Time Colorimetric Imaging
Authors: Layne Tiffany R. , Scott Anchi , Cunha Larissa L. , Turiello Rachelle , Landers James P.
Published: February 2024

Isothermal amplification methods have become popular in research due to the simplicity of the technology needed to run the reactions. Specifically, loop-mediated isothermal amplification (LAMP) has been widely used for various applications since first reported in 2000. LAMP reactions are commonly monitored with the use of colorimetry. Although color changes associated with positive amplification are apparent to the naked eye, this detection method is subjective due to inherent differences in visual perception from person to person. The objectivity of the colorimetric detection method may be improved by programmed image capture over time with simultaneous heating. As such, the development of a novel, one-step, automated, and integrated analysis system capable of performing these tasks in parallel is detailed herein. The device is adaptable to multiple colorimetric dyes, cost-effective, 3D-printed for single-temperature convective heating, and features an easy-to-use LabVIEW software program developed for automated image analysis. The device was optimized and subsequently validated using four messenger-RNA targets and mock forensic samples. The performance of our device was determined to be comparable to that of a conventional thermal cycler and smartphone image analysis, respectively. Moreover, the outlined system is capable of objective colorimetric analysis, with exceptional throughput of up to 96 samples at once.
An Overview of Tick-Borne Encephalitis Epidemiology in Endemic Regions of Continental Croatia, 2017–2023
Authors: Vilibic-Cavlek Tatjana , Krcmar Stjepan , Bogdanic Maja , Tomljenovic Morana , Barbic Ljubo , Roncevic Dobrica , Sabadi Dario , Vucelja Marko , Santini Marija , Hunjak Blazenka , Stevanovic Vladimir , Boljfetic Marko , Bjedov Linda , Masovic Viktor , Potocnik-Hunjadi Tanja , Lakoseljac Danijela , Al-Mufleh Mahmoud , Savic Vladimir
Published: February 2024

Tick-borne encephalitis (TBE) represents an important public health problem in Europe. We analyzed the epidemiology of TBE based on data from humans, animals, and Ixodes ricinus ticks in endemic regions of continental Croatia. In the period from 2017 to 2023, cerebrospinal fluid (CSF) and serum samples of 684 patients with neuroinvasive diseases, 2240 horse serum samples, and 300 sheep serum samples were tested for TBEV. In addition, 8751 I. ricinus ticks were collected. CSF samples were tested using RT-PCR. Serological tests (serum, CSF) were performed using commercial ELISA, with confirmation of cross-reactive samples by a virus neutralization test. Eighty-four autochthonous human TBEV cases were confirmed. The majority of patients were in the age group of 40–69 years (58.3%) with a male predominance (70.2%). TBE showed a bimodal seasonality with a large peak in April–August and a small one in October–November. In addition to humans, TBEV IgG antibodies were found in 12.2% of horses and 9.7% of sheep. Seasonal tick abundance corresponds to the reported number of human infections. Continental Croatia is still an active natural focus of TBE. Continuous monitoring of infections in humans, sentinel animals, and ticks is needed for the implementation of preventive measures.
Iron-Bearing Minerals in the Boda Claystone Formation: Correspondences with Stages of Evolution Revealed by Mössbauer Spectroscopy
Authors: Lázár Károly , Máthé Zoltán , Németh Tibor , Kovács-Kis Viktória , Stichleutner Sándor , Kovács Ivett
Published: February 2024

The Boda Claystone Formation (BCF) is an extended sedimentary sequence formed in a shallow-water salt lake under semi-arid to arid climatic conditions during the middle Permian period. The rock was formed predominantly from denuded and altered products of three primary felsic sources, the Mórágy Metagranite Complex, the Baksa Metamorphic Complex and the rhyolitic Gyűrűfű Formation, resulting in the recent dominant sheet silicate components, illite and chlorite. BCF has been considered a potential host rock for high-level nuclear waste, too. Thus, it has been characterized by several powerful methods so far (X-ray diffraction (XRD), transmission electron microscopy (TEM), etc.). 57Fe Mössbauer spectroscopy may provide a unique additional tool to study iron-bearing minerals. Iron is dominantly present in a ferrous form in minerals of the fresh parent rocks (in the biotite group and amphibole), and in a ferric oxide, hematite, in altered Gyűrűfű Formation. During transformations of biotite group minerals and amphibole, the partial release of ferrous iron or its conversion to ferric form takes place with the stabilization of recent illite and chlorite, while the original layered structure is still preserved. Mössbauer spectroscopy revealed the dominant presence of ferrous iron located in cis-M2 octahedral sites both in parent biotite group minerals and in the final illite, as well as chlorite in both stages. The proportion of ferrous iron in biotite group minerals was halved during the stages of evolution by conversion to ferric iron still in sheet silicate illite or by segregation into separate hematite inclusions. The transformation process of biotite group minerals and amphibole of the source rocks is connected only to the iron-bearing smaller fraction of sheet silicates in the BCF clay mineral assemblage. Determination of Fe2+/Fe3+ ratios in sheet silicates was also pertinent in two sections of BCF. Namely, in samples from the Gorica region, Fe3+ was dominant, siting in illite, whereas Fe2+ was also present in significant portions in chlorite in samples from the Western Mecsek Anticline. The interpretation is deduced in correspondence with results of extended XRD, and high-resolution TEM studies.
Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives
Authors: Liu Zijun , Liu Jiancheng , Gao En , Mao Longfei , Hu Shu , Li Sanqiang
Published: February 2024

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 μM (NCI-H1299), 3.94 ± 0.01 μM (A549) and 1.56 ± 0.06 μM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 μM (A549) and 3.51 ± 0.05 μM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment.
Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact
Authors: Dymova Maya A. , Malysheva Daria O. , Popova Victoria K. , Dmitrienko Elena V. , Endutkin Anton V. , Drokov Danil V. , Mukhanov Vladimir S. , Byvakina Arina A. , Kochneva Galina V. , Artyushenko Polina V. , Shchugoreva Irina A. , Rogova Anastasia V. , Tomilin Felix N. , Kichkailo Anna S. , Richter Vladimir A. , Kuligina Elena V.
Published: February 2024

Aptamers are currently being investigated for their potential to improve virotherapy. They offer several advantages, including the ability to prevent the aggregation of viral particles, enhance target specificity, and protect against the neutralizing effects of antibodies. The purpose of this study was to comprehensively investigate an aptamer capable of enhancing virotherapy. This involved characterizing the previously selected aptamer for vaccinia virus (VACV), evaluating the aggregation and molecular interaction of the optimized aptamers with the recombinant oncolytic virus VV-GMCSF-Lact, and estimating their immunoshielding properties in the presence of human blood serum. We chose one optimized aptamer, NV14t_56, with the highest affinity to the virus from the pool of several truncated aptamers and built its 3D model. The NV14t_56 remained stable in human blood serum for 1 h and bound to VV-GMCSF-Lact in the micromolar range (Kd ≈ 0.35 μM). Based on dynamic light scattering data, it has been demonstrated that aptamers surround viral particles and inhibit aggregate formation. In the presence of serum, the hydrodynamic diameter (by intensity) of the aptamer–virus complex did not change. Microscale thermophoresis (MST) experiments showed that NV14t_56 binds with virus (EC50 = 1.487 × 109 PFU/mL). The analysis of the amplitudes of MST curves reveals that the components of the serum bind to the aptamer–virus complex without disrupting it. In vitro experiments demonstrated the efficacy of VV-GMCSF-Lact in conjunction with the aptamer when exposed to human blood serum in the absence of neutralizing antibodies (Nabs). Thus, NV14t_56 has the ability to inhibit virus aggregation, allowing VV-GMCSF-Lact to maintain its effectiveness throughout the storage period and subsequent use. When employing aptamers as protective agents for oncolytic viruses, the presence of neutralizing antibodies should be taken into account.
A Novel Antimicrobial Mechanism of Azalomycin F Acting on Lipoteichoic Acid Synthase and Cell Envelope
Authors: Luo Zilong , Li Pingyi , Zhang Duoduo , Zhu Jianping , Wang Wan , Zhao Wenjia , Li Peibo , Yuan Ganjun
Published: February 2024

Lipoteichoic acid (LTA) plays an essential role in bacterial growth and resistance to antibiotics, and LTA synthetase (LtaS) was considered as an attractive target for combating Gram-positive infections. Azalomycin F, a natural guanidyl-containing polyhydroxy macrolide, can target the LTA of Staphylococcus aureus. Using various technologies including enzyme-linked immunosorbent assay, transmission electron microscope, proteomics, and parallel reaction monitoring, here, the experimental results indicated that azalomycin F can accelerate the LTA release and disrupt the cell envelope, which would also lead to the feedback upregulation on the expressions of LtaS and other related enzymes. Simultaneously, the reconstituted enzyme activity evaluations showed that azalomycin F can significantly inhibit the extracellular catalytic domain of LtaS (eLtaS), while this was vague for LtaS embedded in the liposomes. Subsequently, the fluorescence analyses for five incubation systems containing azalomycin F and eLtaS or the LtaS-embedded liposome indicated that azalomcyin F can spontaneously bind to the active center of LtaS. Combining the mass spectroscopy analyses and the molecular dockings, the results further indicated that this interaction involves the binding sites of substrates and the LTA prolongation, especially the residues Lys299, Phe353, Trp354 and His416. All these suggested that azalomycin F has multiple antibacterial mechanisms against S. aureus. It can not only inhibit LTA biosynthesis through the interactions of its guanidyl side chain with the active center of LtaS but also disrupt the cell envelope through the synergistic effect of accelerating the LTA release, damaging the cell membrane, and electrostatically interacting with LTA. Simultaneously, these antibacterial mechanisms exhibit a synergistic inhibition effect on S. aureus cells, which would eventually cause the cellular autolysis.
HoberUI: An Exploration of Kinematic Structures as Interactive Input Devices
Authors: Razevicius Gvidas , Roudaut Anne , Karnik Abhijit
Published: February 2024

Deployable kinematic structures can transform themselves from a small closed configuration to a large deployed one. These structures are widely used in many engineering fields including aerospace, architecture, robotics and to some extent within HCI. In this paper, we investigate the use of a symmetric spherical deployable structure and its application to interface control. We present HoberUI, a bimanual symmetric tangible interface with 7 degrees of freedom and explore its use for manipulating 3D environments. We base this on the toy version of the deployable structure called the Hoberman sphere, which consists of pantographic scissor mechanisms and is capable of homogeneous shrinkage and expansion. We first explore the space for designing and implementing interactions through such kinematic structures and apply this to 3D object manipulation. We then explore HoberUI’s usability through a user evaluation that shows the intuitiveness and potential of using instrumented kinematic structures as input devices for bespoke applications.
A Cohort Study of the Influence of the 12-Component Modified Japanese Diet Index on Oral and Gut Microbiota in the Japanese General Population
Authors: Sato Satoshi , Chinda Daisuke , Iino Chikara , Sawada Kaori , Mikami Tatsuya , Nakaji Shigeyuki , Sakuraba Hirotake , Fukuda Shinsaku
Published: February 2024

The Japanese diet is a healthy dietary pattern, and the oral or gut microbiota have been identified as the main factors underlying the beneficial effects of the Japanese diet. However, epidemiological studies on Japanese dietary patterns calculated from daily eating habits in the general population yielded inconsistent findings. This study aimed to determine the association between the 12-component modified Japanese Diet Index (mJDI12) and the oral and gut microbiota in the general population of a rural area in Japan. After propensity-score matching, 396 participants (198 each in the low and high mJDI12 groups) were picked out. One year after the follow up survey, we reclassified the subjects and compared the low and high mJDI12 groups again. Participants with a high mJDI12 had a higher relative abundance of butyric acid-producing bacteria in their gut microbiota. Moreover, the significantly higher dietary fiber intake in the high mJDI12 group suggested that the high intake of dietary fiber contributed to an increase in butyric acid-producing bacteria in the gut. In contrast, in individuals with a high mJDI12, only Allpprevotella was decreased in the oral microbiota. Thus, the Japanese dietary pattern can have beneficial effects by improving the oral and gut microbiota.
Indirect Calorimetry-Based Novel Approach for Evaluating Metabolic Flexibility and Its Association with Circulating Metabolic Markers in Middle-Aged Subjects
Authors: Murru Elisabetta , Manca Claudia , Carta Gianfranca , Ruggiu Michele , Solinas Roberto , Montisci Roberta , Hodson Leanne , Dearlove David , Mollica Maria Pina , Tocco Filippo , Banni Sebastiano
Published: February 2024

We propose a novel method for assessing metabolic flexibility (MF) through indirect calorimetry. A total of twenty healthy volunteers (10 females; 10 males) aged 45–65 were categorized into a Low-Intensity activity group (LI, 0–1 session of 1 h per week) and a High-Intensity activity group (HI, 5–6 sessions of 2 h per week). Volunteers underwent a stepwise exercise test on a cycle ergometer, connected to a calorimeter, to examine respiratory gas exchange to evaluate peak fatty acid Oxidation (PFO) and peak carbohydrate oxidation (PCO). Circulating peroxisome proliferator-activated receptor α (PPARα) biomarkers, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio and N-oleoylethanolamine (OEA), and the endocannabinoid- 2-arachidonoylglycerol (2-AG), were evaluated. We developed two MF parameters: the MF index (MFI), calculated by the product of PFO normalized per kg of fat-free mass (FFM) and the percentage of VO2max at PFO, and the peak energy substrates’ oxidation (PESO), computed by summing the kilocalories from the PFO and PCO, normalized per kg FFM. The MFI and PESO were significantly different between the HI and LI groups, showing strong correlations with the circulating bioactive substances. Higher DHA/EPA ratio (p ≤ 0.05) and OEA (p ≤ 0.01), but lower 2-AG levels (p ≤ 0.01) were found in the HI group. These new parameters successfully established a functional link between MF and the balance of PPARα/endocannabinoid systems.
Correlation between Selenium and Zinc Levels and Survival among Prostate Cancer Patients
Authors: Pietrzak Sandra , Marciniak Wojciech , Derkacz Róża , Matuszczak Milena , Kiljańczyk Adam , Baszuk Piotr , Bryśkiewicz Marta , Sikorski Andrzej , Gronwald Jacek , Słojewski Marcin , Cybulski Cezary , Gołąb Adam , Huzarski Tomasz , Dębniak Tadeusz , Lener Marcin R. , Jakubowska Anna , Kluz Tomasz , Scott Rodney J. , Lubiński Jan
Published: February 2024

The most prevalent type of cancer among males is prostate cancer. Survival is considered quite good, but it can be further improved when risk factors are optimized. One of these factors is micronutrients, including Se and Zn. To our knowledge, the interaction between Se and Zn and prostate cancer remains undescribed. This study aimed to investigate the optimal levels of selenium (Se) and zinc (Zn) and their impact on the survival of individuals diagnosed with prostate cancer. A total of 338 prostate cancer patients were enrolled in this study, which was conducted in Poland between 2009 and 2015. Mass spectrometry, which uses inductively coupled plasma mass, was used to assess serum element levels before treatment. The study participants were categorized into quartiles (QI-QIV) based on the distributions of Se and Zn levels observed among surviving participants. Cox regression was used to assess the association between serum Se and Zn levels and the survival of prostate cancer patients. Our results reveal the effect of combined Se and Zn levels on survival in prostate cancer patients (SeQI-ZnQI vs. SeQIV-ZnQIV; HR = 20.9). These results need further research to establish Se/Zn norms for different populations.
A Myeloid-Specific Lack of IL-4Rα Prevents the Development of Alternatively Activated Macrophages and Enhances Immunity to Experimental Cysticercosis
Authors: Olguín Jonadab E. , Corano-Arredondo Edmundo , Hernández-Gómez Victoria , Rivera-Montoya Irma , Rodríguez Mario A. , Medina-Andrade Itzel , Arendse Berenice , Brombacher Frank , Terrazas Luis I.
Published: February 2024

To determine the role that the IL-4/IL13 receptor plays in the development of alternatively activated macrophages (AAM or M2) and their role in the regulation of immunity to the extraintestinal phase of the helminth parasite Taenia crassiceps, we followed the infection in a mouse strain lacking the IL-4Rα gene (IL-4Rα−/−) and in the macrophage/neutrophil-specific IL-4Rα-deficient mouse strain (LysMcreIL-4Rα−/lox or cre/LoxP). While 100% of T. crassiceps-infected IL-4Rα+/+ (WT) mice harbored large parasite loads, more than 50% of th eIL-4Rα−/− mice resolved the infection. Approximately 88% of the LysMcreIL-4Rα−/lox mice displayed a sterilizing immunity to the infection. The remaining few infected cre/LoxP mice displayed the lowest number of larvae in their peritoneal cavity. The inability of the WT mice to control the infection was associated with antigen-specific Th2-type responses with higher levels of IgG1, IL-4, IL-13, and total IgE, reduced NO production, and increased arginase activity. In contrast, IL-4Rα−/− semi-resistant mice showed a Th1/Th2 combined response. Furthermore, macrophages from the WT mice displayed higher transcripts for Arginase-1 and RELM-α, as well as increased expression of PD-L2 with robust suppressive activity over anti-CD3/CD28 stimulated T cells; all of these features are associated with the AAM or M2 macrophage phenotype. In contrast, both the IL-4Rα−/− and LysMcreIL-4Rα−/lox mice did not fully develop AAM or display suppressive activity over CD3/CD28 stimulated T cells, reducing PDL2 expression. Additionally, T-CD8+ but no T-CD4+ cells showed a suppressive phenotype with increased Tim-3 and PD1 expression in WT and IL-4Rα−/−, which were absent in T. crassiceps-infected LysMcreIL-4Rα−/lox mice. These findings demonstrate a critical role for the IL-4 signaling pathway in sustaining AAM and its suppressive activity during cysticercosis, suggesting a pivotal role for AAM in favoring susceptibility to T. crassiceps infection. Thus, the absence of these suppressor cells is one of the leading mechanisms to control experimental cysticercosis successfully.
A Comparative Study of Genetic Diversity and Multiplicity of Infection in Uncomplicated Plasmodium falciparum Infections in Selected Regions of Pre-Elimination and High Transmission Settings Using MSP1 and MSP2 Genes
Authors: Akoniyon Olusegun Philip , Akiibinu Moses , Adeleke Matthew A. , Maharaj Rajendra , Okpeku Moses
Published: February 2024

Background: Understanding the genetic structure of P. falciparum population in different regions is pivotal to malaria elimination. Genetic diversity and the multiplicity of infection are indicators used for measuring malaria endemicity across different transmission settings. Therefore, this study characterized P. falciparum infections from selected areas constituting pre-elimination and high transmission settings in South Africa and Nigeria, respectively. Methods: Parasite genomic DNA was extracted from 129 participants with uncomplicated P. falciparum infections. Isolates were collected from 78 participants in South Africa (southern Africa) and 51 in Nigeria (western Africa). Allelic typing of the msp1 and msp2 genes was carried out using nested PCR. Results: In msp1, the K1 allele (39.7%) was the most common allele among the South African isolates, while the RO33 allele (90.2%) was the most common allele among the Nigerian isolates. In the msp2 gene, FC27 and IC3D7 showed almost the same percentage distribution (44.9% and 43.6%) in the South African isolates, whereas FC27 had the highest percentage distribution (60.8%) in the Nigerian isolates. The msp2 gene showed highly distinctive genotypes, indicating high genetic diversity in the South African isolates, whereas msp1 showed high genetic diversity in the Nigerian isolates. The RO33 allelic family displayed an inverse relationship with participants’ age in the Nigerian isolates. The overall multiplicity of infection (MOI) was significantly higher in Nigeria (2.87) than in South Africa (2.44) (p < 0.000 *). In addition, heterozygosity was moderately higher in South Africa (1.46) than in Nigeria (1.13). Conclusions: The high genetic diversity and MOI in P. falciparum that were observed in this study could provide surveillance data, on the basis of which appropriate control strategies should be adopted.
Inflammatory Patterns Associated with Legionella in HIV and Pneumonia Coinfections
Authors: Head Breanne M. , Trajtman Adriana , Mao Ruochen , Bernard Kathryn , Vélez Lázaro , Marin Diana , López Lucelly , Rueda Zulma Vanessa , Keynan Yoav
Published: February 2024

Legionella infections have a propensity for occurring in HIV-infected individuals, with immunosuppressed individuals tending to present with more severe disease. However, understanding regarding the Legionella host response in immune compromised individuals is lacking. This study investigated the inflammatory profiles associated with Legionella infection in patients hospitalized with HIV and pneumonia in Medellín, Colombia from February 2007 to April 2014, and correlated these profiles with clinical outcomes. Sample aliquots from the Colombian cohort were shipped to Canada where Legionella infections and systemic cytokine profiles were determined using real-time PCR and bead-based technology, respectively. To determine the effect of Legionella coinfection on clinical outcome, a patient database was consulted, comparing laboratory results and outcomes between Legionella-positive and -negative individuals. Principal component analysis revealed higher plasma concentrations of eotaxin, IP-10 and MCP-1 (p = 0.0046) during Legionella infection. Individuals with this immune profile also had higher rates of intensive care unit admissions (adjusted relative risk 1.047 [95% confidence interval 1.027–1.066]). Results demonstrate that systemic markers of monocyte/macrophage activation and differentiation (eotaxin, MCP-1, and IP-10) are associated with Legionella infection and worse patient outcomes. Further investigations are warranted to determine how this cytokine profile may play a role in Legionella pneumonia pathogenesis or immunity.
Strategies to Improve Cannabidiol Bioavailability and Drug Delivery
Authors: O’Sullivan Saoirse Elizabeth , Jensen Sanne Skov , Kolli Aditya Reddy , Nikolajsen Gitte Nykjær , Bruun Heidi Ziegler , Hoeng Julia
Published: February 2024

The poor physicochemical properties of cannabidiol (CBD) hamper its clinical development. The aim of this review was to examine the literature to identify novel oral products and delivery strategies for CBD, while assessing their clinical implications and translatability. Evaluation of the published literature revealed that oral CBD strategies are primarily focused on lipid-based and emulsion solutions or encapsulations, which improve the overall pharmacokinetics (PK) of CBD. Some emulsion formulations demonstrate more rapid systemic delivery. Variability in the PK effects of different oral CBD products is apparent across species. Several novel administration routes exist for CBD delivery that may offer promise for specific indications. For example, intranasal administration and inhalation allow quick delivery of CBD to the plasma and the brain, whereas transdermal and transmucosal administration routes deliver CBD systemically more slowly. There are limited but promising data on novel delivery routes such as intramuscular and subcutaneous. Very limited data show that CBD is generally well distributed across tissues and that some CBD products enable increased delivery of CBD to different brain regions. However, evidence is limited regarding whether changes in CBD PK profiles and tissue distribution equate to superior therapeutic efficacy across indications and whether specific CBD products might be suited to particular indications.
Cutaneous Alternariosis in Immunosuppressed Patients Treated with Photodynamic Therapy and Oral Antifungals, a Synergistic Strategy
Authors: Gil-Pallares Pedro , Gracia-Cazaña Tamara , Álvarez-Salafranca Marcial , Gorgojo Marcos Antonio , García-García Mar , Beltrán-Rosel Antonio , Almenara-Blasco Manuel , Navarro-Bielsa Alba , Gilaberte Yolanda
Published: February 2024

Cutaneous alternariosis is a rare condition, more frequently presented in immunocompromised patients, which usually requires long courses of systemic antifungals that may interact with other medications. The presented series shows three cases of cutaneous alternariosis in immunocompromised patients and organ transplant recipients that were successfully treated with photodynamic therapy and oral antifungals, allowing a reduction in the systemic treatment duration and therefore decreasing the risk of side effects and drug interactions.
Advances in Non-Small Cell Lung Cancer (NSCLC) Treatment—A Paradigm Shift in Oncology
Authors: Ali Azhar
Published: February 2024

Non-Small Cell Lung Cancer (NSCLC) management remains a formidable challenge in the field of oncology, representing a significant global health burden [...]
Seleno-Warfare against Cancer: Decoding Antitumor Activity of Novel Acylselenoureas and Se-Acylisoselenoureas
Authors: Angulo-Elizari Eduardo , Raza Asif , Encío Ignacio , Sharma Arun K. , Sanmartín Carmen , Plano Daniel
Published: February 2024

Currently, cancer remains a global health problem. Despite the existence of several treatments, including chemotherapy, immunotherapy, and radiation therapy, the survival rate for most cancer patients, particularly those with metastasis, remains unsatisfactory. Thus, there is a continuous need to develop novel, effective therapies. In this work, 22 novel molecules containing selenium are reported, including seven Se-acylisoselenoureas synthesized from aliphatic carbodiimides as well as acylselenoureas with the same carbo- and heterocycles and aliphatic amines. After an initial screening at two doses (50 and 10 µM) in MDA-MB-231 (breast), HTB-54 (lung), DU-145 (prostate), and HCT-116 (colon) tumor cell lines, the ten most active compounds were identified. Additionally, these ten hits were also submitted to the DTP program of the NCI to study their cytotoxicity in a panel of 60 cancer cell lines. Compound 4 was identified as the most potent antiproliferative compound. The results obtained showed that compound 4 presented IC50 values lower than 10 µM in the cancer cell lines, although it was not the most selective one. Furthermore, compound 4 was found to inhibit cell growth and cause cell death by inducing apoptosis partially via ROS production. Overall, our results suggest that compound 4 could be a potential chemotherapeutic drug for different types of cancer.
Spatial Relation Awareness Module for Phase Unwrapping
Authors: Azuma Chiori , Ito Tomoyoshi , Shimobaba Tomoyoshi
Published: February 2024

Phase unwrapping is a technique used to recover the original phase from the wrapped phase in the range (−π,π]. Various methods have been proposed for phase unwrapping. In particular, methods using convolutional neural networks (CNNs) have been extensively researched because of their high robustness against noise and fast inference speed. However, conventional CNN-based methods discard the local position information and relationships between pixels in the convolution process, resulting in poor phase-unwrapping performance. To obtain better phase unwrapping results, we propose a module that combines a global convolution network, which applies convolutional layers with a kernel size equivalent to that of the feature maps, and CoordConv, which acquires the positional relationships between pixels. We validated the performance of the proposed method by comparing it with a quality-guided path algorithm and deep learning-based phase unwrapping methods and found that the proposed method is highly robust against noise.