bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposed DeepFake Detection Method Using Multiwavelet Transform
Authors: Mohammed Saadi Saadi , Mahmoud Al-Jawher Waleed Ameen
Published: September 2023

Videos made by artificial intelligence (A.I.) seem real, but they are not. When making DeepFake videos, face-swapping methods are frequently employed. The misuse of technology when using fakes, even though it was fun at first, these videos were somewhat recognizable to human eyes. However, as machine learning advanced, it became simpler to produce profound fake videos. It's practically impossible to tell it apart from actual videos now. Using GANs (Generative Adversarial Networks) and other deep learning techniques, DeepFake videos are output technology that may mislead people into thinking something is real when it is not. This study used a MultiWavelet transform to analyze the type of edge and its sharpness to develop a blur inconsistency detecting system. With this capability, it can assess whether or not the facial area is obscured in the video. As a result, it will detect fake videos. This paper reviews DeepFake detection techniques and discusses how they might be combined or altered to get more accurate results. A detection rate of more than 93.5% was obtained, which is quite successful.
The Perceptions of the Use of Translanguaging as a Form of Oral Feedback in Indonesian Tertiary English Language Teaching Context
Authors: Silalahi Ronald Maraden Parlindungan , Widianingtyas Nugraheni , Murniati Murniati , Novia Jessica , Sanjaya Fauzaan Akmal , Karlin Gina
Published: September 2023

As the practice of using different languages to extend the process of knowledge construction, translanguaging is often performed in teachers’ corrective feedback in foreign language classrooms. The research aimed to analyze students’ perception of the implementation of translanguaging as a form of oral corrective feedback in an EFL-speaking context at a private university in Indonesia. This study used a mixed-methods sequential explanatory design through two phases of data collection: a questionnaire (N=60) and semi-structured interviews (N=8). The findings of this study indicate that students perceive translanguaging as a beneficial practice in implementing oral corrective feedback in the EFL-speaking classroom, such as increasing the chances for language acquisition, empowering students to take educational risks, creating a more welcoming and socially inclusive learning environment due to students’ diverse language proficiency, and increasing in-classroom participation and engagement. However, it is also perceived that translanguaging should not be used too excessively to avoid confusion amongst students with lower target language proficiency. It is recommended that teachers give students a fair chance to interact meaningfully with more than one language by including translanguaging oral feedback as a pedagogical strategy, to help students reach their academic goals, notice differences in language, and promote bilingualism and biliteracy. The students' positive opinions of translanguaging highlighted its potential as an effective pedagogical technique. It is also hoped that this research becomes a basis for establishing English language teaching policies that are appropriate to the multilingual pedagogical context in Indonesia.
Compressible Large Eddy Simulation of Thermoacoustic Instabilities in the PRECCINSTA Combustor Using Flamelet Generated Manifolds With Dynamic Thickened Flame Model
Authors: Gövert Simon , Lipkowicz Jonathan Timo , Janus Bertram
Published: September 2023

The fully compressible, density-based CFD-solver TRACE has been extended for simulations of turbulent reacting flows in aero engine gas turbine combustors. The flamelet generated manifolds combustion model is utilized to account for detailed chemical kinetics and combined with the dynamically thickened flame model to resolve the flame front on the large eddy simulation (LES) mesh. The chemistry tabulation is coupled with the LES solver by inversion of the transported energy equation using tabulated mixture averaged NASA polynomial coefficients. LES of the PRECCINSTA test case, a lean, partially premixed swirl combustor are performed and the two distinctive regimes are correctly predicted: a stable regime with a “quite” stable flame and an unstable regime with an oscillating flame driven by self-excited thermoacoustic instabilities. Statistics collected from the simulations, mean, and root-mean-square values are in good agreement with the experimental reference data for both operating conditions. The dominant frequency of the unstable flame deviates from the measurement by about 100 Hz and requires further investigation. The results demonstrate the general suitability of the simulation framework for reacting flow simulations in gas turbine combustion systems and the prediction of self-excited thermoacoustic oscillations.
A Surge/Stall-Capable Dynamic Performance Simulation Methodology for a Turbojet Engine
Authors: Güllü Emrah , Aran Gökhan
Published: September 2023

A lumped-parameter dynamic performance model for a single-spool turbojet engine is presented in this paper. This model can handle pre and poststall transients under forward and reverse-flow conditions. The inter-component volume technique is employed instead of the standard matching technique to be able to handle high-frequency transients and reverse-flow conditions. Inspired by Greitzer's lumped-parameter surge model, momentum (duct) and volume elements are placed within the flow path to handle surge dynamics. Compressor and turbine maps are extended to low-flow and reverse-flow regions using a combination of the guidelines presented by Kurzke, the cubic axisymmetric characteristics of Moore and Greitzer, and a quadratic function guess for in-stall characteristics. Combustor efficiency, stability limits, and delay are taken from the literature. Poststall behavior of the model is validated using the data available in the literature for a Rolls-Royce Viper engine. A good match is observed with a correct prediction of poststall behaviors, which transition from surge after locked stall to multiple surge cycles around 80% speed and multiple surge cycles to surge after flameout around 95% speed. The effects of different modeling choices and modeling parameters on the obtained results are discussed. The produced model can be calibrated for a specific engine with surge tests, and it can be used for hard-to-test scenarios like surge after shaft breakage. Different surge/stall-causing events, such as fuel spiking, in-bleeding, and shaft breakage, are simulated to see the capabilities of the model.
Optimizing Micro Gas Turbine Operation in a Microgrid System With Natural Gas and Hydrogen Fuel: An Artificial Intelligence-Based Approach
Authors: Banihabib Reyhaneh , Skaug Fadnes Fredrik , Assadi Mohsen , Bensmann Boris
Published: September 2023

In the coming years, decentralized power generation systems with renewables are expected to take a leading role, and micro gas turbines will serve as backup sources to compensate for times of low inputs from other sources. In order to deal with the unpredictable energy inputs from renewables, the micro gas turbine must be capable of running under varying load conditions and making fast transitions between them. The operation of a micro gas turbine in an integrated microgrid (MG) has the potential to reduce operational costs and ensure the delivery of demanded heat and power to consumers. This paper investigates the operation of a micro gas turbine in a MG, serving as a supplementary power source for a municipal building. The building's required energy is initially provided by wind turbine power, and the micro gas turbine serves as a backup source during times of wind power deficiency. The micro gas turbine can operate using a natural gas/hydrogen fuel blend ranging from zero to 100% hydrogen. Furthermore, a water electrolyzer with a hydrogen tank is available to operate as a storage system within the MG. The study's results demonstrate the economic and environmental benefits of using hydrogen storage and optimizing operational planning in the MG. The primary objective of the paper is to highlight the feasibility and benefits of employing micro gas turbines and hydrogen storage systems within a MG as a renewable energy backup power source.
Development of Boron-Containing Electrolyte Additive for Lithium-Ion Batteries
Authors: Sarıgöl Zahid , Özkan Gülay , Özkan Göksel
Published: September 2023

In this study, triphenylphosphine boron trifluoride (BF3 · PPh3) was synthesized to be used as an electrolyte additive in Li/LiCoO2 half-cells. Fourier-transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance, and X-ray photoelectron spectroscopy analysis techniques were used to determine the structure and composition of the synthesized substance. The battery performance was investigated by adding certain amounts of BF3 · PPh3 in 1 M LiPF6-ethylene carbonate/dimethyl carbonate/diethyl carbonate (1:1:1 by volume) electrolyte. CR2032 coin cells were assembled with the electrodes and electrolytes prepared in the laboratory. The electrochemical behaviors of the battery were investigated via cyclic voltammetry and charge–discharge tests. The addition of 0.5 wt% and 1 wt% BF3 · PPh3 in the electrolyte improved the lithium-ion battery’s ionic conductivity and capacity retention. The results show that BF3 · PPh3 has potential applications in lithium-ion batteries.
Full-angle high-reflection ultrathin composite film realizing high spatial resolution of scintillation crystal array
Authors: Yang Jing , Wang Linwei , Chen Zhang , Xue Zhongjun , Zhao Shuwen , Ding Dongzhou
Published: September 2023

The performance of current nuclear medicine imaging systems is largely limited by the performance of detectors, and high spatial resolution detectors require high optical yield scintillator arrays. In this work, we simulated and designed for the first time a distributed Bragg reflector (multilayer dielectric film) that covers the entire lutetium yttrium oxyorthosilicate emission spectral band and consists of three 1/4 wavelength (λ/4) primary film systems centered at 420, 500, and 575 nm. In order to achieve ultrahigh reflectivity at the full incidence angle of the scintillator emitting surface, we propose a master optical configuration combining the dielectric film with a metal film/diffuse reflection adhesive. To explain this mechanism, we also simulated the change in reflectivity of the actual inner surface light collection. Experimental results show that a combination of a highly reflective reflector can achieve full-angle high reflectance at the total angle of incidence. We find that the dielectric film does not change the total reflection structure inside the crystal, while the light-blocking layer changes and increases the angular reflection of the dielectric film about the angle. These findings provide important insights into surface treatment as well as the design of scintillation crystal arrays, with far-reaching implications for high spatial resolution optical imaging systems.
Role of dislocations on Sn diffusion during low temperature annealing of GeSn layers
Authors: Stanchu Hryhorii , Said Abdulla , Olorunsola Oluwatobi , Acharya Sudip , Amoah Sylvester , Zamani-Alavijeh Mohammad , de Oliveira Fernando M. , Chhetri Santosh Karki , Hu Jin , Mazur Yuriy I. , Yu Shui-Qing , Salamo Gregory
Published: September 2023

A study of the mechanism of Sn out-diffusion was performed by annealing Ge0.905Sn0.095 layers at 300 °C. The changes in Sn composition and strain state were confirmed by x-ray diffraction and photoluminescence spectroscopy. Surface defects, appearing as Sn particles, with the highest density of 3.5 × 108 cm−2 were detected by atomic force microscopy after annealing for 2 h. The strain in the GeSn layer stabilized for more prolonged annealing, while the density of particles decreased and their size increased. Annealing results are discussed in terms of Sn segregation and subsequent diffusion along dislocation lines, enhanced out-diffusion by dislocations migration, and surface particle coalescence.
Localization and classification of scattered nonlinear ultrasonic signatures in bio-mechanical media using time reversal approach
Authors: Dvořáková Zuzana , Dos Santos Serge , Kůs Václav , Převorovský Zdeněk
Published: September 2023

This paper deals with the time reversal approach along with signal classification using ϕ-divergences in biomedical applications for localization and statistical classification of ultrasonic nonlinearities. The time reversal (TR) approach in combination with nonlinear elastic wave spectroscopy (NEWS) is used to obtain the nonlinear signature of air bubbles with different sizes and ultrasound contrast agents in a liquid. An optimized chirp-coded signal in the range of 0.6–3 MHz is used as a compression coding. The signal classification is performed using the fuzzy classification method and the divergence decision tree algorithm using specific ϕ-divergence spectral measures extracted from the received ultrasonic response containing acoustic nonlinearities. The classification results prove that different types of nonlinearities extracted with classical “pulse inversion” based coding methods can be identified. Simultaneously, the different positions of scattered sources are distinguished by ϕ-divergence methods. The potential of time reversal nonlinear elastic wave spectroscopy methods for understanding of ultrasonic wave propagation in complex media is clearly exhibited.
IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus
Authors: Ingle Harshad , Makimaa Heyde , Aggarwal Somya , Deng Hongju , Foster Lynne , Li Yuhao , Kennedy Elizabeth A. , Peterson Stefan T. , Wilen Craig B. , Lee Sanghyun , Suthar Mehul S. , Baldridge Megan T.
Published: September 2023

Norovirus is a leading cause of epidemic viral gastroenteritis, with no currently approved vaccines or antivirals. Murine norovirus (MNoV) is a well-characterized model of norovirus pathogenesis in vivo, and persistent strains exhibit lifelong intestinal infection. Interferon-λ (IFN-λ) is a potent antiviral that rapidly cures MNoV. We previously demonstrated that IFN-λ signaling in intestinal epithelial cells (IECs) controls persistent MNoV, and here demonstrate that IFN-λ acts on tuft cells, the exclusive site of MNoV persistence, to limit infection. While interrogating the source of IFN-λ to regulate MNoV, we confirmed that MDA5-MAVS signaling, required for IFN-λ induction to MNoV in vitro, controls persistent MNoV in vivo. We demonstrate that MAVS in IECs and not immune cells controls MNoV. MAVS in nonsusceptible enterocytes, but not in tuft cells, restricts MNoV, implicating noninfected cells as the IFN-λ source. Our findings indicate that host sensing of MNoV is distinct from cellular tropism, suggesting intercellular communication between IECs for antiviral signaling induction in uninfected bystander cells.
Subtropical Mode Water south of Japan impacts typhoon intensity
Authors: Oka Eitarou , Sugimoto Shusaku , Kobashi Fumiaki , Nishikawa Hatsumi , Kanada Sachie , Nasuno Tomoe , Kawamura Ryuichi , Nonaka Masami
Published: September 2023

Subtropical Mode Water (STMW), characterized by vertically uniform temperature of ~17°C, is distributed horizontally over 5000 kilometers at the 100- to 500-meter depths in the subtropical North Pacific Ocean. Its formation and spreading fluctuate in relation to the Pacific Decadal Oscillation and the Kuroshio path variation, but the feedback from STMW on the sea surface temperature (SST) and the overlying atmosphere remains unclear. Using Argo profiling float data, we show that STMW south of Japan, whose thickness varies decadally, modulates the overlying thermal structure throughout the year by increasing isotherm uplift with increasing thickness. The STMW-induced decadal temperature change has a magnitude of up to ~1°C and is large in the warm season in the presence of the seasonal thermocline. Furthermore, 50-year observations, together with numerical simulation, show that SST, upper ocean heat content, and typhoon intensification rate have been significantly lower in years with thicker STMW and higher in years with thinner STMW.
Valence electron concentration as key parameter to control the fracture resistance of refractory high-entropy carbides
Authors: Sangiovanni Davide G. , Kaufmann Kevin , Vecchio Kenneth
Published: September 2023

Although high-entropy carbides (HECs) have hardness often superior to that of parent compounds, their brittleness—a problem shared with most ceramics—has severely limited their reliability. Refractory HECs in particular are attracting considerable interest due to their unique combination of mechanical and physical properties, tunable over a vast compositional space. Here, combining statistics of crack formation in bulk specimens subject to mild, moderate, and severe nanoindentation loading with ab initio molecular dynamics simulations of alloys under tension, we show that the resistance to fracture of cubic-B1 HECs correlates with their valence electron concentration (VEC). Electronic structure analyses show that VEC ≳ 9.4 electrons per formula unit enhances alloy fracture resistance due to a facile rehybridization of electronic metallic states, which activates transformation plasticity at the yield point. Our work demonstrates a reliable strategy for computationally guided and rule-based (i.e., VEC) engineering of deformation mechanisms in high entropy, solid solution, and doped ceramics.
Glutaredoxin attenuates glutathione levels via deglutathionylation of Otub1 and subsequent destabilization of system xC−
Authors: Aboushousha Reem , van der Velden Jos , Hamilton Nicholas , Peng Zhihua , MacPherson Maximilian , Erickson Cuixia , White Sheryl , Wouters Emiel F. M. , Reynaert Niki L. , Seward David J. , Li Jianing , Janssen-Heininger Yvonne M. W.
Published: September 2023

Glutathione (GSH) is a critical component of the cellular redox system that combats oxidative stress. The glutamate-cystine antiporter, system xC−, is a key player in GSH synthesis that allows for the uptake of cystine, the rate-limiting building block of GSH. It is unclear whether GSH or GSH-dependent protein oxidation [proteinS-glutathionylation (PSSG)] regulates the activity of system xC−. We demonstrate that an environment of enhanced PSSG promotes GSH increases via a system xC−–dependent mechanism. Absence of the deglutathionylase, glutaredoxin (GLRX), augmented SLC7A11 protein and led to significant increases of GSH content.S-glutathionylation of C23 or C204 of the deubiquitinase OTUB1 promoted interaction with the E2-conjugating enzyme UBCH5A, leading to diminished ubiquitination and proteasomal degradation of SLC7A11 and augmentation of GSH, effects that were reversed by GLRX. These findings demonstrate an intricate link between GLRX and GSH viaS-glutathionylation of OTUB1 and system xC−and illuminate a previously unknown feed-forward regulatory mechanism whereby enhanced GSH protein oxidation augments cellular GSH.
A family of carboxypeptidases catalyzing α- and β-tubulin tail processing and deglutamylation
Authors: Nicot Simon , Gillard Ghislain , Impheng Hathaichanok , Joachimiak Ewa , Urbach Serge , Mochizuki Kazufumi , Wloga Dorota , Juge François , Rogowski Krzysztof
Published: September 2023

Tubulin posttranslational modifications represent an important mechanism involved in the regulation of microtubule functions. The most widespread among them are detyrosination, α∆2-tubulin, and polyglutamylation. Here, we describe a family of tubulin-modifying enzymes composed of two closely related proteins, KIAA0895L and KIAA0895, which have tubulin metallocarboxypeptidase activity and thus were termed TMCP1 and TMCP2, respectively. We show that TMCP1 (also known as MATCAP) acts as α-tubulin detyrosinase that also catalyzes α∆2-tubulin. In contrast, TMCP2 preferentially modifies βI-tubulin by removing three amino acids from its C terminus, generating previously unknown βI∆3 modification. We show that βI∆3-tubulin is mostly found on centrioles and mitotic spindles and in cilia. Moreover, we demonstrate that TMCPs also remove posttranslational polyglutamylation and thus act as tubulin deglutamylases. Together, our study describes the identification and comprehensive biochemical analysis of a previously unknown type of tubulin-modifying enzymes involved in the processing of α- and β-tubulin C-terminal tails and deglutamylation.
Copper catalyzed Shono-type oxidation of proline residues in peptide
Authors: Chang Zhe , Wang Si , Huang Jialin , Chen Geshuyi , Tang Zhanyong , Wang Rui , Zhao Depeng
Published: September 2023

Since the initial report in 1975, the Shono oxidation has become a powerful tool to functionalize the α position of amines, including proline derivatives, by electrochemical oxidation. However, the application of electrochemical Shono oxidations is restricted to the preparation of simple building blocks and homogeneous Shono-type oxidation of proline derivatives remains challenging. The late-stage functionalization at proline residues embedded within peptides is highly important as substitutions about the proline ring are known to affect biological and pharmacological activities. Here, we show that homogenous copper-catalyzed oxidation conditions complement the Shono oxidation and this general protocol can be applied to a series of formal C-C coupling reactions with a variety of nucleophiles using a one-pot procedure. This protocol shows good tolerance toward 19 proteinogenic amino acids and was used to functionalize several representative bioactive peptides, including captopril, enalapril, Smac, and endomorphin-2. Last, peptide cyclization can also be achieved by using an appropriately positioned side-chain hydroxyl moiety.
Solar-powered shape-changing origami microfliers
Authors: Johnson Kyle , Arroyos Vicente , Ferran Amélie , Villanueva Raul , Yin Dennis , Elberier Tilboon , Aliseda Alberto , Fuller Sawyer , Iyer Vikram , Gollakota Shyamnath
Published: September 2023

Using wind to disperse microfliers that fall like seeds and leaves can help automate large-scale sensor deployments. Here, we present battery-free microfliers that can change shape in mid-air to vary their dispersal distance. We designed origami microfliers using bistable leaf-out structures and uncovered an important property: A simple change in the shape of these origami structures causes two dramatically different falling behaviors. When unfolded and flat, the microfliers exhibit a tumbling behavior that increases lateral displacement in the wind. When folded inward, their orientation is stabilized, resulting in a downward descent that is less influenced by wind. To electronically transition between these two shapes, we designed a low-power electromagnetic actuator that produces peak forces of up to 200 millinewtons within 25 milliseconds while powered by solar cells. We fabricated a circuit directly on the folded origami structure that includes a programmable microcontroller, a Bluetooth radio, a solar power–harvesting circuit, a pressure sensor to estimate altitude, and a temperature sensor. Outdoor evaluations show that our 414-milligram origami microfliers were able to electronically change their shape mid-air, travel up to 98 meters in a light breeze, and wirelessly transmit data via Bluetooth up to 60 meters away, using only power collected from the sun.
SHP2 promotes sarcoidosis severity by inhibiting SKP2-targeted ubiquitination of TBET in CD8
+
T cells
Authors: Celada Sherly I. , Lim Clarice X. , Carisey Alexandre F. , Ochsner Scott A. , Arce Deza Carlos F. , Rexie Praveen , Poli De Frias Fernando , Cardenas-Castillo Rafael , Polverino Francesca , Hengstschläger Markus , Tsoyi Konstantin , McKenna Neil J. , Kheradmand Farrah , Weichhart Thomas , Rosas Ivan O. , Van Kaer Luc , Celada Lindsay J.
Published: September 2023

Sarcoidosis is an interstitial lung disease (ILD) characterized by interferon-γ (IFN-γ) and T-box expressed in T cells (TBET) dysregulation. Although one-third of patients progress from granulomatous inflammation to severe lung damage, the molecular mechanisms underlying this process remain unclear. Here, we found that pharmacological inhibition of phosphorylated SH2-containing protein tyrosine phosphatase-2 (pSHP2), a facilitator of aberrant IFN-γ abundance, decreased large granuloma formation and macrophage infiltration in the lungs of mice with sarcoidosis-like disease. Positive treatment outcomes were dependent on the effective enhancement of TBET ubiquitination within CD8
+
T cells. Mechanistically, we identified a posttranslational modification pathway in which the E3 F-box protein S-phase kinase–associated protein 2 (SKP2) targets TBET for ubiquitination in T cells under normal conditions. However, this pathway was disrupted by aberrant pSHP2 signaling in CD8
+
T cells from patients with progressive pulmonary sarcoidosis and end-stage disease. Ex vivo inhibition of pSHP2 in CD8
+
T cells from patients with end-stage sarcoidosis enhanced TBET ubiquitination and suppressed IFN-γ and collagen synthesis. Therefore, these studies provided new mechanistic insights into the SHP2-dependent posttranslational regulation of TBET and identified SHP2 inhibition as a potential therapeutic intervention against severe sarcoidosis. Furthermore, these studies also suggest that the small-molecule SHP2 inhibitor SHP099 might be used as a therapeutic measure against human diseases linked to TBET or ubiquitination.
Increased brain microvascular hemoglobin concentrations in children with cerebral malaria
Authors: Smith Rachel L. , Ikeda Allison K. , Rowley Carol A. , Khandhadia Amit , Gorbach Alexander M. , Chimalizeni Yamikani , Taylor Terrie E. , Seydel Karl , Ackerman Hans C.
Published: September 2023

Brain swelling is associated with death from cerebral malaria, but it is unclear whether brain swelling is caused by cerebral edema or vascular congestion—two pathological conditions with distinct effects on tissue hemoglobin concentrations. We used near-infrared spectroscopy (NIRS) to noninvasively study cerebral microvascular hemoglobin concentrations in 46 Malawian children with cerebral malaria. Cerebral malaria was defined by the presence of the malaria parasite
Plasmodium falciparum
on a blood smear, a Blantyre coma score of 2 or less, and retinopathy. Children with uncomplicated malaria (
n
= 33) and healthy children (
n
= 29) were enrolled as comparators. Cerebral microvascular hemoglobin concentrations were higher among children with cerebral malaria compared with those with uncomplicated malaria [median (25th, 75th): 145.2 (95.2, 190.0) μM versus 82.9 (65.7, 105.4) μM,
P
= 0.008]. Cerebral microvascular hemoglobin concentrations correlated with brain swelling score determined by MRI (
r
= 0.37,
P
= 0.03). Fluctuations in cerebral microvascular hemoglobin concentrations over a 30-min time period were characterized using detrended fluctuation analysis (DFA). DFA determined self-similarity of the cerebral microvascular hemoglobin concentration signal to be lower among children with cerebral malaria compared with those with uncomplicated malaria [0.63 (0.54, 0.70) versus 0.91 (0.82, 0.94),
P
< 0.0001]. The lower self-similarity of the hemoglobin concentration signal in children with cerebral malaria suggested impaired regulation of cerebral blood flow. The elevated cerebral tissue hemoglobin concentration and its correlation with brain swelling suggested that excess blood volume, potentially due to vascular congestion, may contribute to brain swelling in cerebral malaria.
Stronger regulation of AI in biomedicine
Authors: Trotsyuk Artem A. , Federico Carole A. , Cho Mildred K. , Altman Russ B. , Magnus David
Published: September 2023

Regulatory agencies need to ensure the safety and equity of AI in biomedicine, and the time to do so is now.
Anti-inflammatory effect of
Lactiplantibacillus plantarum
T1 cell-free supernatants through suppression of oxidative stress and NF-κB- and MAPK-signaling pathways
Authors: Hao Rui , Liu Qianqian , Wang Lu , Jian Wenwen , Cheng Yu , Zhang Qiuyue , Hayer Kim , Kamarudin Raja Idris Raja , Zhang Yi , Lu He , Tu Zeng
Published: September 2023

Lactiplantibacillus plantarum
T1 is an isolated probiotic lactic acid bacterium (LAB) from pickled vegetables in Chongqing, China. In this study, we evaluated the anti-inflammatory activity and the underlying mechanisms of
L. plantarum
T1 cell-free supernatant (CFS) on lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages
in vitro
. Reverse transcription quantitative PCR (RT-qPCR), immunofluorescence, Griess methods, and western blotting were utilized to assess the anti-inflammatory cytokines and antioxidative effect of
L. plantarum
T1 CFS. Our results showed that
L. plantarum
T1 CFS pretreatment significantly reduced pro-inflammatory cytokine levels, including nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor, interleukin (IL)−1β, and IL-6, as well as reactive oxygen species. Interestingly,
L. plantarum
T1 CFS unregulated the antioxidant indicators, including superoxide dismutase, catalase, and glutathione in RAW264.7 cells. Furthermore,
L. plantarum
T1 CFS activated the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway. This study showed the excellent antioxidant and anti-inflammatory properties of
L. plantarum
T1 through multiple pathways, highlighting its potential for further research and application as a probiotic strain.

IMPORTANCE

L. plantarum
T1 stood out in a series of acid and bile salt tolerance and bacterial inhibition tests as a probiotic isolated from paocai, which provides many health benefits to the host by inhibiting the growth of harmful pathogenic microorganisms and suppressing excessive levels of oxidative stress and inflammation. Not all LAB have good probiotic functions and are used in various applications. The anti-inflammatory antioxidant potential and mechanisms of
L. plantarum
T1 CFS have not been described and reported. By using RT-qPCR, Griess method, and western blotting, we showed that
L. plantarum
T1 CFS had anti-inflammatory and antioxidant effects. Griess assay, TBA assay, WST-8 assay, immunofluorescence assay, RT-qPCR, and western blotting data revealed that its anti-inflammatory and antioxidant mechanisms were associated with oxidative stress and NF-κB and MAPK signaling pathways. The anti-inflammatory and antioxidant effects of
L. plantarum
T1 CFS in paocai generates opportunities for probiotic product development.
Epstein-Barr virus LMP1 enhances levels of large extracellular vesicle-associated PD-L1
Authors: Abou Harb Monica , Meckes David G. , Sun Li
Published: September 2023

The circulating nature of extracellular vesicles (EVs) allows for the transfer of cargo to proximal or distant cells, making them vital mediators of cellular communication. Epstein-Barr virus (EBV)–infected cells have been found to release EVs containing viral proteins, such as the major viral oncogene latent membrane protein 1 (LMP1). LMP1 has been observed to regulate the cellular gene expression of the programmed cell death protein 1 ligand (PD-L1), a protein known to suppress the immune system through binding to a receptor found on cytotoxic T cells. Recent studies have established that PD-L1 is packaged into small EVs (sEVs), potentially contributing to the evasion of lung cancer cells from the immune system. Furthermore, it has been observed that large EVs (lEVs) are shed in significant quantities by tumor cells, with elevated levels of lEVs being associated with disease metastasis and cancer aggressiveness. The present study demonstrated that lEVs from nasopharyngeal carcinoma cells exhibit a significant enrichment of PD-L1. Furthermore, the EBV protein LMP1 was found to play a key role in regulating PD-L1 levels within these lEVs. These PD-L1+ lEVs containing LMP1 are likely to contribute to the immunosuppressive microenvironment found in EBV-associated cancers.

IMPORTANCE

A growing body of evidence has supported the notion that viruses utilize EVs and associated pathways to incorporate viral products. This allows for the evasion of an immune response while enabling viral spread within the host. Given that viral proteins often elicit strong antigenic peptides that are recognized by T cells, the regulation of the PD-L1 pathway through the overexpression of lEV-associated PD-L1 may serve as a strategy for immune evasion by viruses. The discovery that EBV LMP1 increases the secretion of PD-L1 in larger EVs identifies a new potential target for immune blockade therapy in EBV-associated cancers. Our findings may help to clarify the mechanism of LMP1-mediated enhancement of PD-L1 packaging into lEVs and may lead to the identification of more specific targets for treatment. Additionally, the identification of lEV biomarkers that predict a viral origin of disease could allow for more targeted therapies to be developed.
Dengue virus NS1 secretion is regulated via importin-subunit β1 controlling expression of the chaperone GRp78 and targeted by the clinical drug ivermectin
Authors: Denolly Solène , Guo Hongbo , Martens Miriam , Płaszczyca Anna , Scaturro Pietro , Prasad Vibhu , Kongmanas Kessiri , Punyadee Nuntaya , Songjaeng Adisak , Mairiang Dumrong , Pichlmair Andreas , Avirutnan Panisadee , Bartenschlager Ralf
Published: September 2023

Dengue virus (DENV) is a major human pathogen. An important pathogenicity factor is non-structural protein 1 (NS1) required for viral replication and secreted from infected cells. A clinical study indicated that the anti-parasitic drug ivermectin lowers NS1 blood levels without affecting viremia. Ivermectin targets nuclear transport by binding to importin-α, but how NS1 secretion in patients is suppressed by this drug is unknown. We show that ivermectin impairs folding and secretion of endoplasmic reticulum-luminal glycoproteins, including NS1. Proteomic analysis identified chaperones interacting with NS1, including GRp78 (78-kDa glucose-regulated protein, also known as HSPA5 or BIP). This chaperone increased in abundance on DENV infection via activation of the unfolded protein response (UPR). Ivermectin blocked the nuclear transport of transcription factors required for UPR, thus impairing GRp78 upregulation and NS1 secretion. Reduction of GRp78 and NS1 secretion was also observed in patients treated with ivermectin. These results link nuclear transport and its inhibition by ivermectin to folding and secretion of luminal glycoproteins, including DENV NS1.

IMPORTANCE

Dengue virus (DENV) is a major human pathogen that can cause hemorrhagic fever and shock syndrome. One important factor of DENV pathogenicity is non-structural protein 1 (NS1), a glycoprotein that is secreted from infected cells. Here we study the mode of action of the widely used drug ivermectin, used to treat parasitic infections and recently shown to lower NS1 blood levels in DENV-infected patients. We found that ivermectin blocks the nuclear transport of transcription factors required for the expression of chaperones that support the folding and secretion of glycoproteins, including NS1. Impairing nuclear transport of these transcription factors by ivermectin or depleting them from infected cells dampens NS1 folding and thus its secretion. These results reveal a novel mode of action of ivermectin that might apply to other flaviviruses as well.
Two-sided effects of the organic phosphorus phytate on a globally important marine coccolithophorid phytoplankton
Authors: Li Jiashun , Zhang Kaidian , Li Ling , Wang Yujie , Wang Cong , Lin Senjie
Published: September 2023

Dissolved organic phosphorus (DOP) is a potential source of aquatic eutrophication and pollution because it can potentially stimulate growth in some species and inhibit growth in other species of algae, the foundation of the marine ecosystem. Inositol hexaphosphate (also named phytic acid or PA), an abundant organophosphate, is presumably ubiquitous in the marine environment, but how it affects marine primary producers is poorly understood. Here, we investigated the bioavailability of this DOP to the cosmopolitan coccolithophore
Emiliania huxleyi
. Our results showed that
E
.
huxleyi
cells can take up PA and dissolved inorganic phosphorus (DIP) simultaneously. Absorbed PA can efficiently support algal growth, producing cell yield between DIP and phosphorus (P)-depleted conditions. Accordingly, PA supply as the sole P source highly influences cellular metabolism and nutrient stoichiometry. Particularly, PA-grown cultures exhibited enhanced carbon fixation, increased lipid content, activated energy metabolism, and induced nitrogen assimilation. However, our data suggest that PA may also exert some levels of toxic effects on
E. huxleyi
. This study provides novel insights into the variable effects of a DOP on marine phytoplankton, which will inform new inquiries about how the complex DOP constituencies in the ocean will shape phytoplankton community structure and function.

IMPORTANCE

The dissolved organic phosphorus (DOP) utilization in phytoplankton plays vital roles in cellular P homeostasis, P-nutrient niche, and the dynamics of community structure in marine ecosystems, but its mechanisms, potentially varying with species, are far from clear. In this study, we investigated the utilization of a widespread DOP species, which is commonly produced by plants (land plants and marine macrophytes) and released into coastal areas, in a globally distributed bloom-forming coccolithophore species in various phosphorus environments. Using a combination of physiological and transcriptomic measurements and analyses, our experimental results revealed the complex mechanism and two-sided effects of DOP (major algal growth-supporting and minor toxic effects) in this species, providing a novel perspective on phytoplankton nutrient regulation.
Detailed descriptions of physical activity patterns among individuals with diabetes and prediabetes: the Lolland-Falster Health Study
Authors: Mortensen Sofie Rath , Skou Søren T , Brønd Jan Christian , Ried-Larsen Mathias , Petersen Therese Lockenwitz , Jørgensen Lars Bo , Jepsen Randi , Tang Lars Hermann , Bruun-Rasmussen Neda Esmailzadeh , Grøntved Anders
Published: September 2023

Introduction

This study aimed to describe objectively measured physical activity patterns, including daily activity according to day type (weekdays and weekend days) and the four seasons, frequency, distribution, and timing of engagement in activity during the day in individuals with diabetes and prediabetes and compared with individuals with no diabetes.

Research design and methods

This cross-sectional study included data from the Danish household-based, mixed rural-provincial population study, The Lolland-Falster Health Study from 2016 to 2020. Participants were categorized into diabetes, prediabetes, and no diabetes based on their glycated hemoglobin level and self-reported use of diabetes medication. Outcome was physical activity in terms of intensity (time spent in sedentary, light, moderate, vigorous, and moderate to vigorous physical activity (MVPA) intensities), adherence to recommendations, frequency and distribution of highly inactive days (<5 min MVPA/day), and timing of engagement in activity assessed with a lower-back worn accelerometer.

Results

Among 3157 participants, 181 (5.7 %) had diabetes and 568 (18.0 %) had prediabetes. Of participants with diabetes, 63.2% did not adhere to the WHO recommendations of weekly MVPA, while numbers of participants with prediabetes and participants with no diabetes were 59.5% and 49.6%, respectively. Around a third of participants with diabetes were highly inactive daily (<5 min MVPA/day) and had >2 consecutive days of inactivity during a 7-days period. Mean time spent physically active at any intensity (light, moderate, and vigorous) during a day was lower among participants with diabetes compared with participants with no diabetes and particularly from 12:00 to 15:00 (mean difference of −6.3 min MVPA (95% CI −10.2 to −2.4)). Following adjustments, significant differences in physical activity persisted between diabetes versus no diabetes, but between participants with prediabetes versus no diabetes, results were non-significant after adjusting for body mass index.

Conclusions

Inactivity was highly prevalent among individuals with diabetes and prediabetes, and distinct daily activity patterns surfaced when comparing these groups with those having no diabetes. This highlights a need to optimize current diabetes treatment and prevention to accommodate the large differences in activity engagement.
Parental diabetes distress is a stronger predictor of child HbA1c than diabetes device use in school-age children with type 1 diabetes
Authors: Patton Susana R , Kahhan Nicole , Pierce Jessica S , Benson Matthew , Fox Larry A , Clements Mark A
Published: September 2023

Introduction

Diabetes distress (DD) describes the unrelenting emotional and behavioral challenges of living with, and caring for someone living with, type 1 diabetes (T1D). We investigated associations between parent-reported and child-reported DD, T1D device use, and child glycated hemoglobin (HbA1c) in 157 families of school-age children.

Research design and methods

Parents completed the Parent Problem Areas in Diabetes-Child (PPAID-C) and children completed the Problem Areas in Diabetes-Child (PAID-C) to assess for DD levels. Parents also completed a demographic form where they reported current insulin pump or continuous glucose monitor (CGM) use (ie, user/non-user). We measured child HbA1c using a valid home kit and central laboratory. We used correlations and linear regression for our analyses.

Results

Children were 49% boys and 77.1% non-Hispanic white (child age (mean±SD)=10.2±1.5 years, T1D duration=3.8±2.4 years, HbA1c=7.96±1.62%). Most parents self-identified as mothers (89%) and as married (78%). Parents’ mean PPAID-C score was 51.83±16.79 (range: 16–96) and children’s mean PAID-C score was 31.59±12.39 (range: 11–66). Higher child HbA1c correlated with non-pump users (r=−0.16, p<0.05), higher PPAID-C scores (r=0.36, p<0.001) and higher PAID-C scores (r=0.24, p<0.001), but there was no association between child HbA1c and CGM use. A regression model predicting child HbA1c based on demographic variables, pump use, and parent-reported and child-reported DD suggested parents’ PPAID-C score was the strongest predictor of child HbA1c.

Conclusions

Our analyses suggest parent DD is a strong predictor of child HbA1c and is another modifiable treatment target for lowering child HbA1c.
Prevention and promotion effects of Self Help Plus: secondary analysis of cluster randomised controlled trial data among South Sudanese refugee women in Uganda
Authors: Augustinavicius Jura , Purgato Marianna , Tedeschi Federico , Musci Rashelle , Leku Marx Ronald , Carswell Kenneth , Lakin Daniel , van Ommeren Mark , Cuijpers Pim , Sijbrandij Marit , Karyotaki Eirini , Tol Wietse A , Barbui Corrado
Published: September 2023

Introduction

Evidence-based and scalable prevention and promotion focused mental health and psychosocial support interventions are needed for conflict-affected populations in humanitarian settings. This study retrospectively assessed whether participation in Self Help Plus (SH+) versus enhanced usual care (EUC) resulted in reduced incidence of probable mental disorder and increased positive mental health and well-being post-intervention among South Sudanese refugee women in Uganda.

Methods

This study used secondary data from treatment-oriented pilot (n=50) and fully-powered cluster randomised controlled trials (cRCT)s (n=694) of SH+ versus EUC. Data from baseline and post-intervention assessments were combined. A composite latent indicator for mental health problems was generated using mental health and well-being measures included in both cRCTs. In order to assess incidence, a binary variable approximating probable mental disorder was created to exclude those with probable mental disorder from the analysis sample and as the primary prevention outcome. The promotive effects of SH+ relative to EUC were examined in the same sample by assessing subjective well-being and psychological flexibility scale scores.

Results

A single factor for mental health problems was identified with all factor loadings >0.30 and acceptable internal consistency (α=0.70). We excluded 161 women who met criteria for probable mental disorder at baseline. Among those with at least moderate psychological distress but without probable mental disorder at baseline and with follow-up data (n=538), the incidence of probable mental disorder at post-intervention was lower among those who participated in SH+ relative to EUC (Risk ratio =0.16, 95% CI: 0.05 to 0.53). Participation in SH+ versus EUC was also associated with increased subjective well-being (β=2.62, 95% CI: 1.63 to 3.60) and psychological flexibility (β=4.55, 95% CI: 2.92 to 6.18) at post-intervention assessment.

Conclusions

These results support the use and further testing of SH+ as a selective and indicated prevention and promotion focused psychosocial intervention in humanitarian settings.

Trial registration number

ISRCTN50148022.
Screening for renal cell carcinoma in renal transplant recipients: a single-centre retrospective study
Authors: Yohannan Binoy , Sridhar Arthi , Kaur Harmanpreet , DeGolovine Aleksandra , Maithel Neha
Published: September 2023

Objectives

The primary objective of our study was to evaluate the effectiveness of renal cell carcinoma (RCC) screening in renal transplant (RT) recipients.

Design

Single-centre retrospective study.

Setting and participants

1998 RT recipients who underwent RT at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC) between 1 January 1999 and 31 December 2019 were included and we identified 16 patients (0.8%) with RCC. An additional four patients with RCC who underwent RT elsewhere but received follow-up at MHH TMC were also included. Subject races included white (20%), black (50%), Hispanic (20%) and Asian (10%).

Outcome measures

The RCC stage at diagnosis and outcomes were compared between patients who were screening versus those who were not.

Results

We identified a total of 20 patients with post-RT RCC, 75% of whom were men. The median age at diagnosis was 56 years. RCC histologies included clear cell (75%), papillary (20%) and chromophobe (5%). Patients with post-RT RCC who had screening (n=12) underwent ultrasound or CT annually or every 2 years, whereas eight patients had no screening. All 12 patients who had screening had early-stage disease at diagnosis (stage I (n=11) or stage II (n=1)) and were cured by nephrectomy (n=10) or cryotherapy (n=2). In patients who had no screening, three (37.5%) had stage IV RCC at diagnosis and all of whom died of metastatic disease. There was a statistically significant difference in RCC-specific survival in patients who were screened (p=0.01) compared with those who were not screened.

Conclusion

All RT recipients who had RCC diagnosed based on screening had early-stage disease and there were no RCC-related deaths. Screening is an effective intervention in RT recipients to reduce RCC-related mortality.