bluuebunny/crossref_metadata_2025 huggingface dataset:
The Receptor Tyrosine Kinase c-Met Promotes Lipid Accumulation in 3T3-L1 Adipocytes
Authors: Park Yu-Kyoung , Jang Byeong-Churl
Published: May 2023

The receptor tyrosine kinase c-Met is elaborated in embryogenesis, morphogenesis, metabolism, cell growth, and differentiation. JNJ38877605 (JNJ) is an inhibitor of c-Met with anti-tumor activity. The c-Met expression and its role in adipocyte differentiation are unknown. Here, we investigated the c-Met expression and phosphorylation, knockdown (KD) effects, and pharmacological inhibition of c-Met by JNJ on fat accumulation in murine preadipocyte 3T3-L1 cells. During 3T3-L1 preadipocyte differentiation, strikingly, c-Met expression at the protein and mRNA levels and the protein phosphorylation on Y1234/1235 and Y1349 is crucial for inducing its kinase catalytic activity and activating a docking site for signal transducers were increased in a time-dependent manner. Of note, JNJ treatment at 20 μM that strongly inhibits c-Met phosphorylation without altering its total expression resulted in less lipid accumulation and triglyceride (TG) content with no cytotoxicity. JNJ further reduced the expression of adipogenic regulators, including CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), and perilipin A. Moreover, JNJ treatment increased cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) phosphorylation but decreased ATP levels. Significantly, KD of c-Met suppressed fat accumulation and triglyceride (TG) quantity and reduced the expression of C/EBP-α, PPAR-γ, FAS, ACC, and perilipin A. Collectively, the present results demonstrate that c-Met is a novel, highly conserved mediator of adipogenesis regulating lipid accumulation in murine adipocytes.
Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer
Authors: Szymański Łukasz , Lieto Krystyna , Zdanowski Robert , Lewicki Sławomir , Tassan Jean-Pierre , Kubiak Jacek Z.
Published: May 2023

Maternal embryonic leucine-zipper kinase (MELK) plays a significant role in cell cycle progression, mitosis, cell migration, cell renewal, gene expression, embryogenesis, proliferation, apoptosis, and spliceosome assembly. In addition, MELK is known to be overexpressed in multiple types of cancer and is associated with cancer proliferation. Tumorigenesis shares many similarities with wound healing, in which the rate of cell proliferation is a critical factor. Therefore, this study aimed to determine the involvement of MELK in the regulation of cell division in two cell types involved in this process, namely fibroblasts and keratinocytes. We examined how temporal overexpression of wild-type and kinase-dead MELK kinase variants affect the rate of proliferation, viability, cell cycle, and phosphorylation state of other kinases involved in these processes, such as ERK1/2, AKT1, MAPK9, p38, and p53. We explored if MELK could be used as a therapeutic stimulator of accelerated wound healing via increased proliferation. We observed that aberrant expression of MELK results in abnormal proliferation, altered cell cycle distribution, and decreased viability of the cells, which challenge the utility of MELK in accelerated wound healing. Our results indicate that, at least in healthy cells, any deviation from precisely controlled MELK expression is harmful to fibroblasts and keratinocytes.
Phafins Are More Than Phosphoinositide-Binding Proteins
Authors: Tang Tuoxian , Hasan Mahmudul , Capelluto Daniel G. S.
Published: May 2023

Phafins are PH (Pleckstrin Homology) and FYVE (Fab1, YOTB, Vac1, and EEA1) domain-containing proteins. The Phafin protein family is classified into two groups based on their sequence homology and functional similarity: Phafin1 and Phafin2. This protein family is unique because both the PH and FYVE domains bind to phosphatidylinositol 3-phosphate [PtdIns(3)P], a phosphoinositide primarily found in endosomal and lysosomal membranes. Phafin proteins act as PtdIns(3)P effectors in apoptosis, endocytic cargo trafficking, and autophagy. Additionally, Phafin2 is recruited to macropinocytic compartments through coincidence detection of PtdIns(3)P and PtdIns(4)P. Membrane-associated Phafins serve as adaptor proteins that recruit other binding partners. In addition to the phosphoinositide-binding domains, Phafin proteins present a poly aspartic acid motif that regulates membrane binding specificity. In this review, we summarize the involvement of Phafins in several cellular pathways and their potential physiological functions while highlighting the similarities and differences between Phafin1 and Phafin2. Besides, we discuss research perspectives for Phafins.
Potential Biomarkers to Distinguish Type 1 Myocardial Infarction in Troponin-Elevated Diseases
Authors: Kwon Sohyen , Park Sang-Hyun , Mun Sora , Lee Jiyeong , Kang Hee-Gyoo
Published: May 2023

Classifying myocardial infarction by subtype is crucial for appropriate patient management. Although troponin is currently the most commonly used biomarker, it is not a specific marker for myocardial infarction and cannot distinguish subtypes. Furthermore, previous studies have confirmed that proteins known as myocardial infarction markers could function to distinguish the type of myocardial infarction. Therefore, we identify a marker that can distinguish type 1 myocardial infarction from other diseases with elevated troponin. We used mass spectrometry to compare type 1 myocardial infarction with other conditions characterized by troponin elevation and identified new candidate markers for disease classification. We then verified these markers, along with those already known to be associated with cardiovascular disease and plaque rupture. We identified α-1 acid glycoprotein 2, corticosteroid-binding globulin, and serotransferrin as potential distinguishing markers. The presence of these markers and other parameters, such as chest pain, electrocardiogram, and troponin levels from the complementary diagnostic processes, could provide valuable information to specifically diagnose type 1 myocardial infarction.
Anomalous Oligomerization Behavior of E. coli Aquaporin Z in Detergent and in Nanodiscs
Authors: Surya Wahyu , Yong Clare Pei Yii , Tyagi Anu , Bhushan Shashi , Torres Jaume
Published: May 2023

Aquaporins are tetrameric integral membrane proteins that act as water channels, and can also permeabilize membranes to other solutes. The monomer appears to be the functional form despite all aquaporins being organized as tetramers, which therefore must provide a clear functional advantage. In addition to this quaternary organization, some aquaporins can act as adhesion molecules in membrane junctions, when tetramers located in opposing membranes interact via their extracellular domains. These stacked forms have been observed in a range of aquaporins, whether using lipidic membrane environments, in electron crystallography, or using detergent micelles, in single-particle cryo-electron microscopy (cryo-EM). In the latter technique, structural studies can be performed when the aquaporin is reconstituted into nanodiscs of lipids that are surrounded by a protein scaffold. During attempts to study E. coli Aquaporin Z (AqpZ), we have found that in some conditions these nanodiscs tend to form filaments that appear to be either thicker head-to-tail or thinner side-to-side stacks of nanodiscs. Nanodisc oligomerization was observed using orthogonal analytical techniques analytical ultra-centrifugation and mass photometry, although the nature of the oligomers (head-to-tail or side-to-side) could not be determined. Using the latter technique, the AqpZ tetramer itself formed oligomers of increasing size when solubilized only in detergent, which is consistent with multiple stacking of AqpZ tetramers. We observed images consistent with both of these filaments in negative staining EM conditions, but only thicker filaments in cryo-EM conditions. We hypothesize that the apparent nanodisc side-to-side arrangement that can only be visualized in negative staining conditions is related to artifacts due to the sample preparation. Filaments of any kind were not observed in EM when nanodiscs did not contain AqpZ, or after addition of detergent into the nanodisc cryo-EM preparation, at concentrations that did not disrupt nanodisc formation. To our knowledge, these filaments have not been observed in nanodiscs preparations of other membrane proteins. AqpZ, like other aquaporins has a charge asymmetry between the cytoplasmic (more positive) and the extracellular sides, which may explain the likely head-to-tail stacking observed, both in nanodisc preparations and also in detergent micelles.
Sodium–Glucose Cotransporter 2 Inhibitors in Patients with Diabetes and Coronary Artery Disease: Translating the Benefits of the Molecular Mechanisms of Gliflozins into Clinical Practice
Authors: Cesaro Arturo , Acerbo Vincenzo , Vetrano Erica , Signore Giovanni , Scherillo Gianmaria , Rotolo Francesco Paolo , De Michele Gianantonio , Scialla Francesco , Raucci Giuseppe , Panico Domenico , Gragnano Felice , Moscarella Elisabetta , Galiero Raffaele , Caturano Alfredo , Ruggiero Roberto , Sasso Ferdinando Carlo , Calabrò Paolo
Published: May 2023

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially developed for the treatment of diabetes due to their antihyperglycemic activity. However, in the light of the most recent clinical studies, they are revolutionizing the approach to cardiovascular disease in patients with and without diabetes. We aimed to generate real-world data about the use of SGLT2i in patients with T2DM and coronary artery disease (CAD), focusing on their effectiveness in glycemic control, adherence, long-term efficacy, and safety outcomes. On the basis of the inclusion and exclusion criteria, 143 patients were enrolled. Patients were treated with canagliflozin (n = 33 patients; 23%), dapagliflozin (n = 52 patients, 36.4%), empagliflozin (n = 48 patients; 33.6%), or ertugliflozin (n = 10 patients; 7%) as monotherapy or in combination with other antidiabetic drugs. All patients performed a clinical visit, and their medical history, blood sampling, and anthropometric parameters were measured at discharge and at 1-year follow-up. The reduction in HbA1c % value at 12 months was significant (8.2 vs. 7.4; p < 0.001). Trends in body weight and body mass index also confirmed the positive effect of the treatment (p < 0.0001), as did the reduction in abdominal adiposity (expressed via waist circumference). At 1-year follow-up, 74.1% of patients were adherent to the treatment, and 81.1% were persistent to the treatment. A total of 27 patients (18.8%) had to discontinue treatment early due to drug intolerance caused by genitourinary infections (11.9%), the drub being permanently ineffective (HbA1c not at target or decreasing: 4.9%), or because of expressing. a desire not to continue (2%). No major drug-related adverse events (diabetic ketoacidosis, Fournier’s gangrene, lower-limb amputations) occurred at follow-up, while MACE events occurred in 14 patients (9.8%). In real-world patients with T2DM and CAD, SGLT2i have been effective in long-term glycemic control and the improvement in anthropometric indices with good tolerance, high adherence, persistence to treatment, and no major adverse events at 1-year follow-up.
The Small-Molecule Enhancers of Autophagy AUTEN-67 and -99 Delay Ageing in Drosophila Striated Muscle Cells
Authors: Komlós Marcell , Szinyákovics Janka , Falcsik Gergő , Sigmond Tímea , Jezsó Bálint , Vellai Tibor , Kovács Tibor
Published: May 2023

Autophagy (cellular self-degradation) plays a major role in maintaining the functional integrity (homeostasis) of essentially all eukaryotic cells. During the process, superfluous and damaged cellular constituents are delivered into the lysosomal compartment for enzymatic degradation. In humans, age-related defects in autophagy have been linked to the incidence of various age-associated degenerative pathologies (e.g., cancer, neurodegenerative diseases, diabetes, tissue atrophy and fibrosis, and immune deficiency) and accelerated ageing. Muscle mass decreases at detectable levels already in middle-aged patients, and this change can increase up to 30–50% at age 80. AUTEN-67 and -99, two small-molecule enhancers of autophagy with cytoprotective and anti-ageing effects have been previously identified and initially characterized. These compounds can increase the life span in wild-type and neurodegenerative model strains of the fruit fly Drosophila melanogaster. Adult flies were treated with these AUTEN molecules via feeding. Fluorescence and electron microscopy and Western blotting were used to assess the level of autophagy and cellular senescence. Flying tests were used to measure the locomotor ability of the treated animals at different ages. In the current study, the effects of AUTEN-67 and -99 were observed on striated muscle cells using the Drosophila indirect flight muscle (IFM) as a model. The two molecules were capable of inducing autophagy in IFM cells, thereby lowering the accumulation of protein aggregates and damaged mitochondria, both characterizing muscle ageing. Furthermore, the two molecules significantly improved the flying ability of treated animals. AUTEN-67 and -99 decrease the rate at which striated muscle cells age. These results may have a significant medical relevance that could be further examined in mammalian models.
Inhibition of ITK Signaling Causes Amelioration in Sepsis-Associated Neuroinflammation and Depression-like State in Mice
Authors: Algahtani Mohammad M. , Alshehri Samiyah , Alqarni Sana S. , Ahmad Sheikh F. , Al-Harbi Naif O. , Alqarni Saleh A. , Alfardan Ali S. , Ibrahim Khalid E. , Attia Sabry M. , Nadeem Ahmed
Published: May 2023

Sepsis affects millions of people worldwide and is associated with multiorgan dysfunction that is a major cause of increased morbidity and mortality. Sepsis is associated with several morbidities, such as lung, liver, and central nervous system (CNS) dysfunction. Sepsis-associated CNS dysfunction usually leads to several mental problems including depression. IL-17A is one of the crucial cytokines that is expressed and secreted by Th17 cells. Th17 cells are reported to be involved in the pathogenesis of depression and anxiety in humans and animals. One of the protein tyrosine kinases that plays a key role in controlling the development/differentiation of Th17 cells is ITK. However, the role of ITK in sepsis-associated neuroinflammation and depression-like symptoms in mice has not been investigated earlier. Therefore, this study investigated the efficacy of the ITK inhibitor, BMS 509744, in sepsis-linked neuroinflammation (ITK, IL-17A, NFkB, iNOS, MPO, lipid peroxides, IL-6, MCP-1, IL-17A) and a battery of depression-like behavioral tests, such as sucrose preference, tail suspension, and the marble burying test. Further, the effect of the ITK inhibitor on anti-inflammatory signaling (Foxp3, IL-10, Nrf2, HO-1, SOD-2) was assessed in the CNS. Our data show that sepsis causes increased ITK protein expression, IL-17A signaling, and neuroinflammatory mediators in the CNS that are associated with a depression-like state in mice. ITK inhibitor-treated mice with sepsis show attenuated IL-17A signaling, which is associated with the upregulation of IL-10/Nrf2 signaling and the amelioration of depression-like symptoms in mice. Our data show, for the first time, that the ITK inhibition strategy may counteract sepsis-mediated depression through a reduction in IL-17A signaling in the CNS.
ELMO1 Deficiency Reduces Neutrophil Chemotaxis in Murine Peritonitis
Authors: Yu Shuxiang , Geng Xiaoke , Liu Huibing , Zhang Yunyun , Cao Xiumei , Li Baojie , Yan Jianshe
Published: May 2023

Peritoneal inflammation remains a major cause of treatment failure in patients with kidney failure who receive peritoneal dialysis. Peritoneal inflammation is characterized by an increase in neutrophil infiltration. However, the molecular mechanisms that control neutrophil recruitment in peritonitis are not fully understood. ELMO and DOCK proteins form complexes which function as guanine nucleotide exchange factors to activate the small GTPase Rac to regulate F-actin dynamics during chemotaxis. In the current study, we found that deletion of the Elmo1 gene causes defects in chemotaxis and the adhesion of neutrophils. ELMO1 plays a role in the fMLP-induced activation of Rac1 in parallel with the PI3K and mTORC2 signaling pathways. Importantly, we also reveal that peritoneal inflammation is alleviated in Elmo1 knockout mice in the mouse model of thioglycollate-induced peritonitis. Our results suggest that ELMO1 functions as an evolutionarily conserved regulator for the activation of Rac to control the chemotaxis of neutrophils both in vitro and in vivo. Our results suggest that the targeted inhibition of ELMO1 may pave the way for the design of novel anti-inflammatory therapies for peritonitis.
Melatonin and Kidney Health: From Fetal Stage to Later Life
Authors: Tang Kuo-Shu , Ho Chun-Yi , Hsu Chien-Ning , Tain You-Lin
Published: May 2023

Melatonin, an endogenous hormone mainly released at night by the pineal gland, has multifaceted biofunctions. Emerging evidence points to melatonin having a crucial role in kidney health and disease. As the prevalence of chronic kidney disease (CKD) is still rising, a superior strategy to advance global kidney health is needed to not just treat CKD, but prevent it early on. Adult kidney disease can have its origins in early life. This review aims to evaluate the recent literature regarding melatonin’s effect on kidney development, its clinical uses in the early stage of life, animal models documenting preventive applications of melatonin on offspring’s kidney-related disease, and a thorough summary of therapeutic considerations concerning melatonin supplementation.
Interleukin-1ß Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4α Independent of c-Jun
Authors: Nimphy Jonas , Ibrahim Sara , Dayoub Rania , Kubitza Marion , Melter Michael , Weiss Thomas S.
Published: May 2023

Inflammasomes and innate immune cells have been shown to contribute to liver injury, thereby activating Kupffer cells, which release several cytokines, including IL-6, IL-1ß, and TNFα. Augmenter of liver regeneration (ALR) is a hepatotropic co-mitogen that was found to have anti-oxidative and anti-apoptotic properties and to attenuate experimental non-alcoholic fatty liver disease (NAFLD) and cholestasis. Additionally, hepatic ALR expression is diminished in patients with NAFLD or cholestasis, but less is known about the mechanisms of its regulation under these conditions. Therefore, we aimed to investigate the role of IL-1ß in ALR expression and to elucidate the molecular mechanism of this regulation in vitro. We found that ALR promoter activity and mRNA and protein expression were reduced upon treatment with IL-1ß. Early growth response protein-1 (Egr-1), an ALR inducer, was induced by IL-1ß but could not activate ALR expression, which may be attributed to reduced Egr-1 binding to the ALR promoter. The expression and nuclear localization of hepatocyte nuclear factor 4 α (HNF4α), another ALR-inducing transcription factor, was reduced by IL-1ß. Interestingly, c-Jun, a potential regulator of ALR and HNF4α, showed increased nuclear phosphorylation levels upon IL-1ß treatment but did not change the expression of ALR or HNF4α. In conclusion, this study offers evidence regarding the regulation of anti-apoptotic and anti-oxidative ALR by IL-1ß through reduced Egr-1 promoter binding and diminished HNF4α expression independent of c-Jun activation. Low ALR tissue levels in NAFLD and cholestatic liver injury may be caused by IL-1ß and contribute to disease progression.
Why Does Rehabilitation Not (Always) Work in Osteoarthritis? Does Rehabilitation Need Molecular Biology?
Authors: Zdziechowski Adam , Gluba-Sagr Anna , Rysz Jacek , Woldańska-Okońska Marta
Published: May 2023

Osteoarthritis (OA) is a common disease among the human population worldwide. OA causes functional impairment, leads to disability and poses serious socioeconomic burden. The rehabilitation offers a function-oriented method to reduce the disability using diverse interventions (kinesiotherapy, physical therapy, occupational therapy, education, and pharmacotherapy). OA as a widespread disease among elderly patients is often treated by rehabilitation specialists and physiotherapists, however the results of rehabilitation are sometimes unsatisfactory. The understanding of molecular mechanisms activated by rehabilitation may enable the development of more effective rehabilitation procedures. Molecular biology methods may prove crucial in rehabilitation as the majority of rehabilitation procedures cannot be estimated in double-blinded placebo-controlled trials commonly used in pharmacotherapy. This article attempts to present and estimate the role of molecular biology in the development of modern rehabilitation. The role of clinicians in adequate molecular biology experimental design is also described.
OsLPR5 Encoding Ferroxidase Positively Regulates the Tolerance to Salt Stress in Rice
Authors: Zhao Juan , Meng Xin , Zhang Zhaonian , Wang Mei , Nie Fanhao , Liu Qingpo
Published: May 2023

Salinity is a major abiotic stress that harms rice growth and productivity. Low phosphate roots (LPRs) play a central role in Pi deficiency-mediated inhibition of primary root growth and have ferroxidase activity. However, the function of LPRs in salt stress response and tolerance in plants remains largely unknown. Here, we reported that the OsLPR5 was induced by NaCl stress and positively regulates the tolerance to salt stress in rice. Under NaCl stress, overexpression of OsLPR5 led to increased ferroxidase activity, more green leaves, higher levels of chlorophyll and lower MDA contents compared with the WT. In addition, OsLPR5 could promote the accumulation of cell osmotic adjustment substances and promote ROS-scavenging enzyme activities. Conversely, the mutant lpr5 had a lower ferroxidase activity and suffered severe damage under salt stress. Moreover, knock out of OsLPR5 caused excessive Na+ levels and Na+/K+ ratios. Taken together, our results exemplify a new molecular link between ferroxidase and salt stress tolerance in rice.
Combined Transcriptome and Metabolome Analysis of Smooth Muscle of Myostatin Knockout Cattle
Authors: Gu Mingjuan , Wang Song , Di Anqi , Wu Di , Hai Chao , Liu Xuefei , Bai Chunling , Su Guanghua , Yang Lei , Li Guangpeng
Published: May 2023

Myostatin (MSTN), a growth and differentiation factor, plays an important role in regulating skeletal muscle growth and development. MSTN knockout (MSTN-KO) leads to skeletal muscle hypertrophy and regulates metabolic homeostasis. Moreover, MSTN is also detected in smooth muscle. However, the effect of MSTN-KO on smooth muscle has not yet been reported. In this study, combined metabolome and transcriptome analyses were performed to investigate the metabolic and transcriptional profiling in esophageal smooth muscles of MSTN-KO Chinese Luxi Yellow cattle (n = 5, 24 months, average body weight 608.5 ± 17.62 kg) and wild-type (WT) Chinese Luxi Yellow cattle (n = 5, 24 months, average body weight 528.25 ± 11.03 kg). The transcriptome was sequenced using the Illumina Novaseq™ 6000 sequence platform. In total, 337 significantly up- and 129 significantly down-regulated genes were detected in the MSTN-KO cattle compared with the WT Chinese Luxi Yellow cattle. Functional enrichment analysis indicated that the DEGs were mainly enriched in 67 signaling pathways, including cell adhesion molecules, tight junction, and the cGMP-PKG signaling pathway. Metabolomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 130 differential metabolites between the groups, with 56 up-regulated and 74 down-regulated in MSTN knockout cattle compared with WT cattle. Differential metabolites were significantly enriched in 31 pathways, including glycerophospholipid metabolism, histidine metabolism, glutathione metabolism, and purine metabolism. Transcriptome and metabolome were combined to analyze the significant enrichment pathways, and there were three metabolically related pathways, including histidine metabolism, purine metabolism, and arginine and proline metabolism. These results provide important references for in-depth research on the effect of MSTN knockout on smooth muscle.
Generation and Characterization of CYP2E1-Overexpressing HepG2 Cells to Study the Role of CYP2E1 in Hepatic Hypoxia-Reoxygenation Injury
Authors: Alwadei Nouf , Rashid Mamunur , Chandrashekar Devaraj Venkatapura , Rahighi Simin , Totonchy Jennifer , Sharma Ajay , Mehvar Reza
Published: May 2023

The mechanisms of hepatic ischemia/reperfusion (I/R) injury, which occurs during liver transplantation or surgery, are poorly understood. The purpose of the current study was to generate and characterize a HepG2 cell line with a stable overexpression of CYP2E1 to investigate the role of the enzyme in hypoxia/reperfusion (H/R) injury in an ex vivo setting. GFP-tagged CYP2E1 and control clones were developed, and their gene expression and protein levels of GFP and CYP2E1 were determined using RT-PCR and ELISA/Western blot analysis, respectively. Additionally, the CYP2E1 catalytic activity was determined by UPLC-MS/MS analysis of 6-hydroxychlorzoxazone formed from the chlorzoxazone substrate. The CYP2E1 and control clones were subjected to hypoxia (10 h) and reoxygenation (0.5 h), and cell death and reactive oxygen species (ROS) generation were quantitated using LDH and flow cytometry, respectively. Compared with the control clone, the selected CYP2E1 clone showed a 720-fold increase in CYP2E1 expression and a prominent band in the western blot analysis, which was associated with a 150-fold increase in CYP2E1 catalytic activity. The CYP2E1 clone produced 2.3-fold more ROS and 1.9-fold more cell death in the H/R model. It is concluded that the constitutive CYP2E1 in the liver may play a detrimental role in hepatic I/R injury.
Complete Genomic Sequence of Xanthomonas oryzae pv. oryzae Strain, LA20, for Studying Resurgence of Rice Bacterial Blight in the Yangtze River Region, China
Authors: Hou Yuxuan , Liang Yan , Yang Changdeng , Ji Zhijuan , Zeng Yuxiang , Li Guanghao , E Zhiguo
Published: May 2023

Xanthomonas oryzae pv. oryzae (Xoo) is a causative agent of rice bacterial blight (BB). In 2020–2022, BB re-emerged, and there was a break out in the Yangtze River area, China. The pandemic Xoo strain, LA20, was isolated and identified from cultivar Quanyou1606 and demonstrated to be the Chinese R9 Xoo strain, which is able to override the widely adopted xa5-, Xa7- and xa13-mediated resistance in rice varieties in Yangtze River. Here, we report the complete genome of LA20 by PacBio and Illumina sequencing. The assembled genome consists of one circular chromosome of 4,960,087 bp, sharing 99.65% sequence identity with the traditional representative strain, YC11 (R5), in the Yangtze River. Comparative genome analysis of LA20 and YC11 revealed the obvious variability in Tal genes (the uppermost virulence determinants) in numbers and sequences. Particularly, six Tal genes were only found in LA20, but not in YC11, among which Tal1b (pthXo1)/Tal4 (pthXo6), along with the lost one, pthXo3 (avrXa7), might be the major factors for LA20 to overcome xa5-, Xa7- and xa13-mediated resistance, thus, leading to the resurgence of BB. This complete genome of the new pandemic Xoo strain will provide novel insights into pathogen evolution, the traits of pathogenicity on genomic level and the epidemic disease status in China.
AQP3-Dependent PI3K/Akt Modulation in Breast Cancer Cells
Authors: Mlinarić Monika , Lučić Ivan , Milković Lidija , da Silva Inês V. , Tartaro Bujak Ivana , Musani Vesna , Soveral Graça , Čipak Gašparović Ana
Published: May 2023

Aquaporin 3 (AQP3) is a peroxiporin, a membrane protein that channels hydrogen peroxide in addition to water and glycerol. AQP3 expression also correlates with tumor progression and malignancy and is, therefore, a potential target in breast cancer therapy. In addition, epithelial growth factor receptor (EGFR) plays an important role in breast cancer. Therefore, we investigated whether disruption of the lipid raft harboring EGFR could affect AQP3 expression, and conversely, whether AQP3 silencing would affect the EGFR/phosphoinositide-3-kinase (PI3K)/Protein kinase B (PKB or Akt) signaling pathway in breast cancer cell lines with different malignant capacities. We evaluated H2O2 uptake, cell migratory capacity, and expression of PI3K, pAkt/Akt in three breast cancer cell lines, MCF7, SkBr3, and SUM159PT, and in the nontumorigenic breast epithelial cell line MCF10A. Our results show different responses between the tested cell lines, especially when compared to the nontumorigenic cell line. Neither lipid raft disruption nor EGF stimuli had an effect on PI3K/Akt pathway in MCF10A cell line. AQP3-silencing in SkBr3 and SUM159PT showed that AQP3 can modulate PI3K/Akt activation in these cells. Interestingly, SUM159PT cells increase nuclear factor-E2–related factor 2 (NRF2) in response to lipid raft disruption and EGF stimuli, suggesting an oxidative-dependent response to these treatments. These results suggest that in breast cancer cell lines, AQP3 is not directly related to PI3K/Akt pathway but rather in a cell-line-dependent manner.
First-Principles Calculations to Investigate Structural, Electronic, Optical and Magnetic Properties of Pyrochlore Oxides Eu2Tm2O7 (Tm = Hf, Sn, Zr) for Energy Applications
Authors: Abbas Zeesham , Naz Adeela , Hussain Sajjad , Muhammad Shabbir , Algarni H. , Ali Ahsan , Jung Jongwan
Published: May 2023

Three newly designed pyrochlore oxides, Eu2Tm2O7 (Tm = Hf, Sn, Zr), are analyzed for their magnetic, optical and electronic properties using ab-initio calculations within the context of density functional theory (DFT). We can refer these compounds as direct bandgap materials because there is a very slight difference between the height of bands at the Γ- and M-point. It is observed that bandgap engineering can be performed by replacing Hf with Sn and Zr. It is observed from total density of states (TDOS) plots that shape and height of curves is not the same in spin up and spin down channels, showing significant magnetic moment in these compounds. It is evident from magnetic properties that a major portion of total magnetic moment (mtot) comes from Eu-atoms. In all compounds, the magnetic moment of O, Hf, Sn and Zr atoms is negative, whereas the magnetic moment of Eu-atoms is positive, showing their antiparallel arrangement. In both spin channels, significant absorption of the incoming photons is also shown by these compounds in the ultraviolet (UV) region. We can conclude on the basis of Rω that these compounds can be utilized in applications such as anti-reflecting coatings. These compounds are potential candidates for photovoltaic applications, such as solar cells, due to efficient absorption of incoming photons in visible and UV regions.
Resistance Monitoring of Nilaparvata lugens to Pymetrozine Based on Reproductive Behavior
Authors: Song Xin-Yu , Peng Yu-Xuan , Gao Yang , Zhang Yan-Chao , Ye Wen-Nan , Lin Pin-Xuan , Gao Cong-Fen , Wu Shun-Fan
Published: May 2023

On the basis of the inhibition effects of pymetrozine on the reproductive behavior of N. lugens, we established a bioassay method to accurately evaluate the toxicity of pymetrozine in N. lugens and clarified the level of pymetrozine resistance of N. lugens in the field. In this study, pymetrozine’s effects on the fecundity of N. lugens were evaluated using the topical application method and rice-seedling-dipping method. Moreover, the resistance of N. lugens to pymetrozine in a pymetrozine-resistant strain (Pym-R) and two field populations (YZ21 and QS21) was determined using the rice-seedling-dipping method and fecundity assay methods. The results showed that treatment of N. lugens third-instar nymphs with LC15, LC50, and LC85 doses of pymetrozine resulted in a significantly reduced fecundity of N. lugens. In addition, N. lugens adults treated with pymetrozine, using the rice-seedling-dipping and topical application method, also exhibited a significantly inhibited fecundity. Using the rice-stem-dipping method, pymetrozine resistance levels were shown to be high in Pym-R (194.6-fold), YZ21 (205.9-fold), and QS21 (212.8-fold), with LC50 values of 522.520 mg/L (Pym-R), 552.962 mg/L (YZ21), and 571.315 (QS21) mg/L. However, when using the rice-seedling-dipping or topical application fecundity assay method, Pym-R (EC50: 14.370 mg/L, RR = 12.4-fold; ED50: 0.560 ng/adult, RR = 10.8-fold), YZ21 (EC50: 12.890 mg/L, RR = 11.2-fold; ED50: 0.280 ng/adult; RR = 5.4-fold), and QS21 (EC50: 13.700 mg/L, RR = 11.9-fold) exhibited moderate or low levels of resistance to pymetrozine. Our studies show that pymetrozine can significantly inhibit the fecundity of N. lugens. The fecundity assay results showed that N. lugens only developed low to moderate levels of resistance to pymetrozine, indicating that pymetrozine can still achieve effective control on the next generation of N. lugens populations.
Radiation Exposure Reduction by Digital Variance Angiography in Lower Limb Angiography: A Randomized Controlled Trial
Authors: Sótonyi Péter , Berczeli Márton , Gyánó Marcell , Legeza Péter , Mihály Zsuzsanna , Csobay-Novák Csaba , Pataki Ákos , Juhász Viktória , Góg István , Szigeti Krisztián , Osváth Szabolcs , Kiss János P. , Nemes Balázs
Published: May 2023

Background: digital variance angiography (DVA) provides higher image quality than digital subtraction angiography (DSA). This study investigates whether the quality reserve of DVA allows for radiation dose reduction during lower limb angiography (LLA), and compares the performance of two DVA algorithms. Methods: this prospective block-randomized controlled study enrolled 114 peripheral arterial disease patients undergoing LLA into normal dose (ND, 1.2 µGy/frame, n = 57) or low-dose (LD, 0.36 µGy/frame, n = 57) groups. DSA images were generated in both groups, DVA1 and DVA2 images were generated in the LD group. Total and DSA-related radiation dose area product (DAP) were analyzed. Image quality was assessed on a 5-grade Likert scale by six readers. Results: the total and DSA-related DAP were reduced by 38% and 61% in the LD group. The overall visual evaluation scores (median (IQR)) of LD-DSA (3.50 (1.17)) were significantly lower than the ND-DSA scores (3.83 (1.00), p < 0.001). There was no difference between ND-DSA and LD-DVA1 (3.83 (1.17)), but the LD-DVA2 scores were significantly higher (4.00 (0.83), p < 0.01). The difference between LD-DVA2 and LD-DVA1 was also significant (p < 0.001). Conclusions: DVA significantly reduced the total and DSA-related radiation dose in LLA, without affecting the image quality. LD-DVA2 images outperformed LD-DVA1, therefore DVA2 might be especially beneficial in lower limb interventions.
Carbon Dioxide Adsorption by a High-Surface-Area Activated Charcoal
Authors: Ahmed Ahmed S. , Alsultan Mohammed , Sabah Assim A. , Swiegers Gerhard F.
Published: May 2023

An activated carbon (AC) with a high surface area of 4320.7 m2/g was synthesized via the chemical and thermal processing of walnut residues. The resulting activated charcoal was characterized by various techniques, including Brunauer–Emmett–Teller (BET) surface area analysis, scanning electron microscopy (SEM), and IR spectroscopy. The prepared activated carbon was studied for its capacity to adsorb CO2 gas. When exposed to CO2 for 60 min in a closed chamber at atmospheric pressure at 25 °C, the adsorption of a notable 301.1 mmol CO2 (13.25 g CO2) per gram of activated carbon was observed.
Structure and Property of Diamond-like Carbon Coating with Si and O Co-Doping Deposited by Reactive Magnetron Sputtering
Authors: Dai Wei , Wu Liang , Wang Qimin
Published: May 2023

In this paper, diamond-like carbon (DLC) coatings with Si and O co-doping (Si/O-DLC) were deposited by reactive magnetron sputtering using a gas mixture of C2H2, O2 and Ar to sputter a silicon/graphite splicing target. The O content in the Si/O-DLC coatings was controlled by tuning the O2 flux in the gas mixture. The composition, chemical bond structure, mechanical properties and tribological behavior of the coatings were investigated by X-ray photoelectron spectroscopy, Fourier infrared spectrometer, Raman spectroscopy, nanoindentation, a scratch tester and a ball-on-disk tribometer. The electrical resistivity of the Si/O-DLC coatings was also studied using the four-point probe method. The results show that the doping O tends to bond with Si to form a silicon–oxygen compound, causing a decrease in the sp3 content as well as the hardness of the coatings. The tribological performance of the coatings can be improved due to the formation of the silicon–oxygen compound, which can effectively reduce the friction coefficient. In addition, the insulating silicon–oxygen compound is doped into the C-C network structure, significantly improving the surface resistivity of the DLC coating with a low sp3 content. The Si/O-DLC coatings with good mechanical properties, tribological performance and electrical insulation properties might be used as protection and insulation layers for microelectronics.
Use of Dregs as a Replacement for Hydrated Lime in Cement Coating Mortar
Authors: de Oliveira Alencar Ibeiro , Subhani Mahbube , Aramburu Arthur Behenck , Rossetto Hebert Luis , Trindade Guilherme Höehr , dos Santos White José , de Avila Delucis Rafael
Published: May 2023

The pulp and paper industry generates a significant volume of solid waste during its operations. In order to mitigate the environmental impact caused by this industry, one of its residues was applied in eco-friendly composites. Therefore, this research aims to use green liquor dregs as a partial replacement for lime in coating mortars. Hydrated lime was replaced by dregs in percentages of 10%, 15%, 20%, and 30%, and the manufactured mortar specimens were tested in terms of their flowability, air content, and specific gravity in the fresh state. In the hardened state, physical and chemical characterization was carried out to determine the influence of the introduction of the dregs on the properties of the different types of mortar. Mechanical testing of the mortar specimens’ compressive, flexural, and adhesive strengths was carried out, and scanning electron microscopy was performed to evaluate the microstructural features of the cement composites. In general, the types of mortar with dregs showed a high degree of similarity to conventional mortar in all studied aspects, including the 30% replacement group. The obtained SEM images indicated that the presence of dregs in the mortar did not change the formational mechanism of C-S-H crystals, maintaining the mechanical properties of the material even after the accelerated aging procedure was performed, reaching similar levels of flexural, compressive, and tensile bond strengths when compared to the neat mortar. Furthermore, tensile bond levels reached approximately 0.9 MPa for all the studied types of mortar, allowing the material to be used in external applications.
Influence of Calcined Clay Pozzolan and Aggregate Size on the Mechanical and Durability Properties of Pervious Concrete
Authors: Boakye Kwabena , Khorami Morteza
Published: May 2023

Pervious concrete has been reported as a viable solution to reduce stormwater run-off, the heat-island effect, road noise, and pavement flooding. Previous researchers have focused on analysing the structural properties and functionality of pervious concrete. However, relatively few studies have been conducted into the addition of supplementary cementitious materials (SCMs), such as calcined clay, in pervious concrete and its effect on long-term durability. This paper has studied the effect of calcined clay pozzolan as a partial substitute for Portland cement in pervious concrete, together with the influence of coarse aggregate size. A water–binder ratio of 0.4 and aggregate–binder ratio of 4.0, as well as a superplasticiser content of 0.95%, were maintained for all mixes. Two sizes of coarse aggregates were used for this study: 9.5 mm and 20 mm. CEM-I cement was partly substituted with calcined clay in dosages of 0 to 30% in replacement intervals of 5%. The mechanical tests conducted included the split tensile test, compressive strength test, and flexural strength test. Durability measurements such as the rapid chloride permeability test (RCPT), thermal conductivity and sulphate resistance tests were also carried out. The mechanical properties of the pervious concrete followed a similar trend. The results showed that at 20% replacement with calcined clay, the compressive strength increased by 12.7% and 16% for 9.5 mm and 20 mm aggregates, respectively. The flexural strength improved by 13.5% and 11.5%, whereas the splitting tensile strength increased by 35.4% and 35.7%, respectively, as compared to the reference concrete. Beyond 20% replacement, the tested strengths declined. The optimum calcined clay replacement was found to be 20% by weight. Generally, pervious concrete prepared with 9.5 mm obtained improved mechanical and durability properties, as compared to those of 20 mm aggregates.
On the Generalization of Deep Learning Models in Video Deepfake Detection
Authors: Coccomini Davide Alessandro , Caldelli Roberto , Falchi Fabrizio , Gennaro Claudio
Published: May 2023

The increasing use of deep learning techniques to manipulate images and videos, commonly referred to as “deepfakes”, is making it more challenging to differentiate between real and fake content, while various deepfake detection systems have been developed, they often struggle to detect deepfakes in real-world situations. In particular, these methods are often unable to effectively distinguish images or videos when these are modified using novel techniques which have not been used in the training set. In this study, we carry out an analysis of different deep learning architectures in an attempt to understand which is more capable of better generalizing the concept of deepfake. According to our results, it appears that Convolutional Neural Networks (CNNs) seem to be more capable of storing specific anomalies and thus excel in cases of datasets with a limited number of elements and manipulation methodologies. The Vision Transformer, conversely, is more effective when trained with more varied datasets, achieving more outstanding generalization capabilities than the other methods analysed. Finally, the Swin Transformer appears to be a good alternative for using an attention-based method in a more limited data regime and performs very well in cross-dataset scenarios. All the analysed architectures seem to have a different way to look at deepfakes, but since in a real-world environment the generalization capability is essential, based on the experiments carried out, the attention-based architectures seem to provide superior performances.
Aspergillus Galactomannan Titer as a Diagnostic Marker of Invasive Pulmonary Aspergillosis in Lung Transplant Recipients: A Single-Center Retrospective Cohort Study
Authors: Kim Eun-Young , Yong Seung-Hyun , Sung Min-Dong , Woo A-La , Park Young-Mok , Kim Ha-Eun , Jung Su-Jin , Kim Song-Yee , Lee Jin-Gu , Kim Young-Sam , Paik Hyo-Chae , Park Moo-Suk
Published: May 2023

Invasive pulmonary aspergillosis (IPA) can occur in immunocompromised patients, and an early detection and intensive treatment are crucial. We sought to determine the potential of Aspergillus galactomannan antigen titer (AGT) in serum and bronchoalveolar lavage fluid (BALF) and serum titers of beta-D-glucan (BDG) to predict IPA in lung transplantation recipients, as opposed to pneumonia unrelated to IPA. We retrospectively reviewed the medical records of 192 lung transplant recipients. Overall, 26 recipients had been diagnosed with proven IPA, 40 recipients with probable IPA, and 75 recipients with pneumonia unrelated to IPA. We analyzed AGT levels in IPA and non-IPA pneumonia patients and used ROC curves to determine the diagnostic cutoff value. The Serum AGT cutoff value was 0.560 (index level), with a sensitivity of 50%, specificity of 91%, and AUC of 0.724, and the BALF AGT cutoff value was 0.600, with a sensitivity of 85%, specificity of 85%, and AUC of 0.895. Revised EORTC suggests a diagnostic cutoff value of 1.0 in both serum and BALF AGT when IPA is highly suspicious. In our group, serum AGT of 1.0 showed a sensitivity of 27% and a specificity of 97%, and BALF AGT of 1.0 showed a sensitivity of 60% and a specificity of 95%. The result suggested that a lower cutoff could be beneficial in the lung transplant group. In multivariable analysis, serum and BALF AGT, with a minimal correlation between the two, showed a correlation with a history of diabetes mellitus.
Exploration of the Strategy for Improving the Expression of Heterologous Sweet Protein Monellin in Aspergillus niger
Authors: Li Ke , Zheng Junwei , Yu Leyi , Wang Bin , Pan Li
Published: May 2023

Aspergillus niger is a primary cell factory for food-grade protein (enzyme) production due to its strong protein secretion capacity and unique safety characteristics. The bottleneck issue for the current A. niger expression system is the difference in expression yield of heterologous proteins of non-fungal origin compared to those of fungal origin, which is about three orders of magnitude. The sweet protein monellin, derived from West African plants, has the potential to become a food-grade sweetener due to its high sweetness and the benefit of not containing sugar itself, but it is extremely difficult to establish a research model for heterologous expression in A. niger, owing to extremely low expression, a small molecular weight, and being undetectable with conventional protein electrophoresis. HiBiT-Tag was fused with low-expressing monellin in this work to create a research model for heterologous protein expression in A. niger at ultra-low levels. We increased monellin expression by increasing the monellin copy number, fusing monellin with the endogenous highly expressed glycosylase glaA, and eliminating extracellular protease degradation, among other strategies. In addition, we investigated the effects of overexpression of molecular chaperones, inhibiting the ERAD pathway, and enhancing the synthesis of phosphatidylinositol, phosphatidylcholine, and diglycerides in the biomembrane system. Using medium optimization, we finally obtained 0.284 mg/L of monellin in the supernatant of the shake flask. This is the first time recombinant monellin has been expressed in A. niger, with the goal of investigating ways to improve the secretory expression of heterologous proteins at ultra-low levels, which can serve as a model for the expression of other heterologous proteins in A. niger.