bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Atmospheric Correction and Image Enhancement on Effective Plastic Greenhouse Segments Based on a Semi-Automatic Extraction Method
Authors: Yao Yao , Wang Shixin
Published: November 2022

To improve the multi-resolution segmentation (MRS) quality of plastic greenhouses (PGs) in GaoFen-2 (GF-2) images, the effects of atmospheric correction and image enhancement on effective PG segments (EPGSs) were evaluated. A new semi-automatic method was also proposed to extract EPGSs in an accurate and efficient way. Firstly, GF-2 images were preprocessed via atmospheric correction, orthographical correction, registration, fusion, linear compression, or spatial filtering, and, then, boundary-removed point samples with adjustable density were made based on reference polygons by taking advantage of the characteristics of chessboard segmentation. Subsequently, the point samples were used to quickly and accurately extract segments containing 70% or greater of PG pixels in each MRS result. Finally, the extracted EPGSs were compared and analyzed via intersection over union (IoU), over-segmentation index (OSI), under-segmentation index (USI), error index of total area (ETA), and composite error index (CEI). The experimental results show that, along with the change in control variables, the optimal scale parameter, time of segmentation, IoU, OSI, USI, and CEI all showed strong changing trends, with the values of ETA all close to 0. Furthermore, compared with the control group, all the CEIs of the EPGSs extracted from those corrected and enhanced images resulted in lower values, and an optimal CEI involved linearly compressing the DN value of the atmospheric-corrected fusion image to 0–255, and then using Fast Fourier Transform and a circular low-pass filter with a radius of 800 pixels to filter from the spatial frequency domain; in this case, the CEI had a minimum value of 0.159. The results of this study indicate that the 70% design in the experiment is a reasonable pixel ratio to determine the EPGSs, and the OSI-USI-ETA-CEI pattern can be more effective than IoU when it is needed to evaluate the quality of EPGSs. Moreover, taking into consideration heterogeneity and target characteristics, atmospheric correction and image enhancement prior to MRS can improve the quality of EPGSs.
Regional Small Towns Classification Assessment and Spatial Pattern Integration: A Case Study of the Yunnan Section of the China–Laos Economic Corridor
Authors: Han Jing , Wang Yue , Wang Xingping
Published: November 2022

The role of small towns in regional development is being emphasized, especially in developing countries, where small towns are driving regional spatial integration and optimization from the ‘bottom up’. In the context of further refinement of regional governance, it is important to identify the characteristics of regional small towns and explore the spatial pattern and structure of their development to achieve regional strategic goals. Taking the Yunnan section of the China–Laos Economic Corridor as an example, this study integrated small towns and regional high-quality development needs, constructed a regional small-town classification and evaluation index system, used various quantitative analysis methods to explore the spatial differentiation of regional small towns’ development levels, and constructed a spatial pattern of regional small towns. Our results reveal that: (1) Small towns in the Yunnan section of the China–Laos Economic Corridor showed large variations in the scores of the four indicator types, which were spatially distributed as ‘core-edge’ and ‘peripheral core’. (2) There was spatial autocorrelation in the classification assessment results of small towns, where small towns with similar levels of development were spatially adjacent and dominated by hot spot agglomerations, but with different agglomeration patterns and distribution locations. (3) The spatial pattern of regional small towns was composed of various elements such as points, lines, axes, rings, and clusters, which can meet the diversified development needs of the region. (4) Our study found that the horizontal transportation links of the Yunnan section require strengthening and suggested the construction of a ‘1 + 3’ regional transportation network.
Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells
Authors: Graziosi Agnese , Sita Giulia , Corrieri Camilla , Angelini Sabrina , d’Emmanuele di Villa Bianca Roberta , Mitidieri Emma , Sorrentino Raffaella , Hrelia Patrizia , Morroni Fabiana
Published: November 2022

Endocrine-disrupting chemicals (EDCs) are different natural and synthetic chemicals that may interfere with several mechanisms of the endocrine system producing adverse developmental, metabolic, reproductive, and neurological effects in both human beings and wildlife. Among pesticides, numerous chemicals have been identified as EDCs. MicroRNAs (miRNAs) can regulate gene expression, making fine adjustments in mRNA abundance and regulating proteostasis. We hypothesized that exposure to low doses of atrazine, cypermethrin, and vinclozolin may lead to effects on miRNA expression in SH-SY5Y cells. In particular, the exposure of SH-SY5Y cells to subtoxic concentrations of vinclozolin is able to downregulate miR-29b-3p expression leading to the increase in the related gene expression of ADAM12 and CDK6, which may promote a pro-oncogenic response through the activation of the PI3K/Akt/mTOR pathway and counteracting p53 activity. A better understanding of the molecular mechanisms of EDCs could provide important insight into their role in human disease.
Artificial Dim Light at Night during Pregnancy Can Affect Hormonal and Metabolic Rhythms in Rat Offspring
Authors: Dzirbíková Zuzana , Stebelová Katarína , Kováčová Katarína , Okuliarová Monika , Olexová Lucia , Zeman Michal
Published: November 2022

Artificial light at night (ALAN) is considered an environmental risk factor that can interfere with the circadian control of the endocrine system and metabolism. We studied the impact of ALAN during pregnancy on the hormonal and biochemical parameters in rat pups at postnatal (P) days P3, P10, and P20. Control dams (CTRL) were kept in a standard light-dark regime, and ALAN dams were exposed to dim ALAN (<2 lx) during the whole pregnancy. A plasma melatonin rhythm was found in all CTRL groups, whereas in ALAN pups, melatonin was not rhythmic at P3, and its amplitude was lowered at P10; no differences were found between groups at P20. Plasma corticosterone was rhythmic at P20 in both groups, with decreased mesor in ALAN pups. Plasma thyroid hormones exhibited an inconsistent developmental pattern, and vasopressin levels were suppressed at the beginning of the dark phase at P20 in ALAN compared to CTRL. Glucose and cholesterol showed significant daily rhythms in CTRL but not in ALAN offspring at P3. Exposure to ALAN during pregnancy disturbed the development of daily rhythms in measured hormones and metabolites, suggesting that ALAN during pregnancy can act as an endocrine disruptor that can interfere with the normal development of the progeny.
Biocompatibility of a Ti-Rich Medium-Entropy Alloy with Glioblastoma Astrocytoma Cells
Authors: Ho Wen-Fu , Wong Ka-Kin , Lee Mei-Hwa , Thomas James L. , Chang Ya-Chun , Wu Shih-Ching , Hsu Hsueh-Chuan , Lin Hung-Yin
Published: November 2022

Titanium and titanium alloys are widely used in medical devices and implants; thus, the biocompatibility of these metals is of great importance. In this study, glioblastoma astrocytoma cellular responses to Ti65-Zr18-Nb16-Mo1 (Ti65M, metastable medium-entropy alloy), Ti-13Nb-7Sn-4Mo (TNSM, titanium alloy), and commercially pure titanium (CP-Ti) were studied. Several physical parameters (crystal phase structure, surface roughness and hardness) of the titanium alloys were measured, and the correlation with the cellular viability was investigated. Finally, the relative protein expression in cellular proliferation pathways was measured and compared with mRNA expression assessed with quantitative real-time reverse transcription polymerase chain reaction assay (qRT-PCR).
AQP4-MOG Double-Positive Neuromyelitis Optica Spectrum Disorder: Case Report with Central and Peripheral Nervous System Involvement and Review of Literature
Authors: Spiezia Antonio Luca , Carotenuto Antonio , Iovino Aniello , Moccia Marcello , Gastaldi Matteo , Iodice Rosa , Tedeschi Enrico , Petracca Maria , Lavorgna Luigi , d’Ambrosio Alessandro , Brescia Morra Vincenzo , Lanzillo Roberta
Published: November 2022

(1) The co-occurrence of AQP4 and myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with demyelinating disorders is extremely rare. In addition, a concomitant involvement of the peripheral nervous system (PNS) has been described either in association with AQP4 antibodies-positive neuromyelitis optica spectrum disorder (NMOSD), or MOG-associated disease. We report on a case of NMOSD with co-occurrence of AQP4 and MOG antibodies and concomitant central and peripheral nervous system involvement. We also reviewed available cases of AQP4-MOG double-positive patients. (2) Brain and spine MRI, cerebrospinal fluid studies, and electrophysiological test were performed. Serum AQP4 and MOG positivity was assessed with live cell-based assay. (3) A 62-year-old woman presented with recurrent optic neuritis, myelitis, and radiculitis, tested positive for AQP4 and MOG antibodies, and was treated successfully with rituximab. (4) Although few cases of AQP4-MOG double-positive patients were already described mostly affecting females with a concomitant spinal cord and optical nerve involvement, we describe the first case of double-positive NMOSD with the peculiar involvement of both central and peripheral nervous system.
Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”
Authors: Teppert Karin , Wang Xueting , Anders Kathleen , Evaristo César , Lock Dominik , Künkele Annette
Published: November 2022

T cell-based immunotherapy has demonstrated great therapeutic potential in recent decades, on the one hand, by using tumor-infiltrating lymphocytes (TILs) and, on the other hand, by engineering T cells to obtain anti-tumor specificities through the introduction of either engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs). Given the distinct design of both receptors and the type of antigen that is encountered, the requirements for proper antigen engagement and downstream signal transduction by TCRs and CARs differ. Synapse formation and signal transduction of CAR T cells, despite further refinement of CAR T cell designs, still do not fully recapitulate that of TCR T cells and might limit CAR T cell persistence and functionality. Thus, deep knowledge about the molecular differences in CAR and TCR T cell signaling would greatly advance the further optimization of CAR designs and elucidate under which circumstances a combination of both receptors would improve the functionality of T cells for cancer treatment. Herein, we provide a comprehensive review about similarities and differences by directly comparing the architecture, synapse formation and signaling of TCRs and CARs, highlighting the knowns and unknowns. In the second part of the review, we discuss the current status of combining CAR and TCR technologies, encouraging a change in perspective from “TCR versus CAR” to “TCR and CAR”.
Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β
Authors: Jardin Isaac , Berna-Erro Alejandro , Nieto-Felipe Joel , Macias Alvaro , Sanchez-Collado Jose , Lopez Jose J. , Salido Gines M. , Rosado Juan A.
Published: November 2022

Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP3 generation, which results in intracellular Ca2+ store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders. Orai1 is, together with STIM1, the key element of SOCE, conducting the Ca2+ release-activated Ca2+ (CRAC) current and, in association with TRPC1, the store-operated Ca2+ (SOC) current. Additionally, Orai1 is involved in non-capacitative pathways, as the arachidonate-regulated or LTC4-regulated Ca2+ channel (ARC/LRC), store-independent Ca2+ influx activated by the secretory pathway Ca2+-ATPase (SPCA2) and the small conductance Ca2+-activated K+ channel 3 (SK3). Furthermore, Orai1 possesses two variants, Orai1α and Orai1β, the latter lacking 63 amino acids in the N-terminus as compared to the full-length Orai1α form, which confers distinct features to each variant. Here, we review the current knowledge about the differences between Orai1α and Orai1β, the implications of the Ca2+ signals triggered by each variant, and their downstream modulatory effect within the cell.
Extracellular Vesicles from 50,000 Generation Clones of the Escherichia coli Long-Term Evolution Experiment
Authors: Laurin David , Mercier Corinne , Quansah Nyamekye , Robert Julie Suzanne , Usson Yves , Schneider Dominique , Hindré Thomas , Schaack Béatrice
Published: November 2022

Extracellular vesicles (EVs) are critical elements of cell–cell communication. Here, we characterized the outer membrane vesicles (OMVs) released by specific clones of Escherichia coli isolated from the Long-Term Evolution Experiment after 50,000 generations (50K) of adaptation to glucose minimal medium. Compared with their ancestor, the evolved clones produce small OMVs but also larger ones which display variable amounts of both OmpA and LPS. Tracking ancestral, fluorescently labelled OMVs revealed that they fuse with both ancestral- and 50K-evolved cells, albeit in different proportions. We quantified that less than 2% of the cells from one 50K-evolved clone acquired the fluorescence delivered by OMVs from the ancestral strain but that one cell concomitantly fuses with several OMVs. Globally, our results showed that OMV production in E. coli is a phenotype that varies along bacterial evolution and question the contribution of OMVs-mediated interactions in bacterial adaptation.
[68Ga]Ga-DATA5m-LM4, a PET Radiotracer in the Diagnosis of SST2R-Positive Tumors: Preclinical and First Clinical Results
Authors: Kanellopoulos Panagiotis , Nock Berthold A. , Greifenstein Lukas , Baum Richard P. , Roesch Frank , Maina Theodosia
Published: November 2022

Radiolabeled somatostatin subtype 2 receptor (SST2R)-antagonists have shown advantageous profiles for cancer theranostics compared with agonists. On the other hand, the newly introduced hybrid chelator (6-pentanoic acid)-6-(amino)methyl-1,4-diazepinetriacetate (DATA5m) rapidly binds Ga-68 (t1/2: 67.7 min) at much lower temperature, thus allowing for quick access to “ready-for-injection” [68Ga]Ga-tracers in hospitals. We herein introduce [68Ga]Ga-DATA5m-LM4 for PET/CT imaging of SST2R-positive human tumors. LM4 was obtained by 4Pal3/Tyr3-substitution in the known SST2R antagonist LM3 (H-DPhe-c[DCys-Tyr-DAph(Cbm)-Lys-Thr-Cys]-DTyr-NH2) and DATA5m was coupled at the N-terminus for labeling with radiogallium (Ga-67/68). [67Ga]Ga-DATA5m-LM4 was evaluated in HEK293-SST2R cells and mice models in a head-to-head comparison with [67Ga]Ga-DOTA-LM3. Clinical grade [68Ga]Ga-DATA5m-LM4 was prepared and injected in a neuroendocrine tumor (NET) patient for PET/CT imaging. DATA5m-LM4 displayed high SST2R binding affinity. [67Ga]Ga-DATA5m-LM4 showed markedly higher uptake in HEK293-SST2R cells versus [67Ga]Ga-DOTA-LM3 and was stable in vivo. In HEK293-SST2R xenograft-bearing mice, it achieved longer tumor retention and less kidney uptake than [67Ga]Ga-DOTA-LM3. [68Ga]Ga-DATA5m-LM4 accurately visualized tumor lesions with high contrast on PET/CT. In short, [68Ga]Ga-DATA5m-LM4 has shown excellent prospects for the PET/CT diagnosis of SST2R-positive tumors, further highlighting the benefits of Ga-68 labeling in a hospital environment via the DATA5m-chelator route.
Treatment of HFpEF beyond the SGLT2-Is: Does the Addition of GLP-1 RA Improve Cardiometabolic Risk and Outcomes in Diabetic Patients?
Authors: Belli Martina , Barone Lucy , Bellia Alfonso , Sergi Domenico , Lecis Dalgisio , Prandi Francesca Romana , Milite Marialucia , Galluccio Chiara , Muscoli Saverio , Romeo Francesco , Barillà Francesco
Published: November 2022

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.
Non-Conserved Amino Acid Residues Modulate the Thermodynamics of Zn(II) Binding to Classical ββα Zinc Finger Domains
Authors: Kluska Katarzyna , Chorążewska Aleksandra , Peris-Díaz Manuel David , Adamczyk Justyna , Krężel Artur
Published: November 2022

Classical zinc fingers domains (ZFs) bind Zn(II) ion by a pair of cysteine and histidine residues to adopt a characteristic and stable ββα fold containing a small hydrophobic core. As a component of transcription factors, they recognize specific DNA sequences to transcript particular genes. The loss of Zn(II) disrupts the unique structure and function of the whole protein. It has been shown that the saturation of ZFs under cellular conditions is strictly related to their affinity for Zn(II). High affinity warrants their constant saturation, while medium affinity results in their transient structurization depending on cellular zinc availability. Therefore, there must be factors hidden in the sequence and structure of ZFs that impact Zn(II)-to-protein affinities to control their function. Using molecular dynamics simulations and experimental spectroscopic and calorimetric approaches, we showed that particular non-conserved residues derived from ZF sequences impact hydrogen bond formation. Our in silico and in vitro studies show that non-conserved residues can alter metal-coupled folding mechanisms and overall ZF stability. Furthermore, we show that Zn(II) binding to ZFs can also be entropically driven. This preference does not correlate either with Zn(II) binding site or with the extent of the secondary structure but is strictly related to a reservoir of interactions within the second coordination shell, which may loosen or tighten up the structure. Our findings shed new light on how the functionality of ZFs is modulated by non-coordinating residues diversity under cellular conditions. Moreover, they can be helpful for systematic backbone alteration of native ZF ββα scaffold to create artificial foldamers and proteins with improved stability.
Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
Authors: Silvestri Beatrice , Mochi Michela , Garone Maria Giovanna , Rosa Alessandro
Published: November 2022

The main goal of this review is to provide an updated overview of the involvement of the RNA-binding protein (RBP) HuD, encoded by the ELAVL4 gene, in nervous system development, maintenance, and function, and its emerging role in nervous system diseases. A particular focus is on recent studies reporting altered HuD levels, or activity, in disease models and patients. Substantial evidence suggests HuD involvement in Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). Interestingly, while possible disease-causing mutations in the ELAVL4 gene remain elusive, a common theme in these diseases seems to be the altered regulation of HuD at multiple steps, including post-transcriptional and post-translational levels. In turn, the changed activity of HuD can have profound implications for its target transcripts, which are overly stabilized in case of HuD gain of function (as proposed in PD and ALS) or reduced in case of decreased HuD binding (as suggested by some studies in AD). Moreover, the recent discovery that HuD is a component of pathological cytoplasmic inclusion in both familial and sporadic ALS patients might help uncover the common molecular mechanisms underlying such complex diseases. We believe that deepening our understanding of the involvement of HuD in neurodegeneration could help developing new diagnostic and therapeutic tools.
Dissection of Functional Domains of Orc1-2, the Archaeal Global DNA Damage-Responsive Regulator
Authors: Liu Xiaotong , Sun Mengmeng , Xu Ruyi , Shen Yulong , Huang Qihong , Feng Xu , She Qunxin
Published: November 2022

Orc1-2 is a non-initiator ortholog of archaeal/eukaryotic Orc1 proteins, which functions as a global regulator in DNA damage-responsive (DDR) expression. As for Orc1 initiators, the DDR regulator harbors an AAA+ ATPase domain, an Initiator-Specific Motif (ISM) and a winged-helix (wH) DNA-binding domain, which are also organized in a similar fashion. To investigate how Orc1-2 mediates the DDR regulation, the orc1-2 mutants inactivating each of these functional domains were constructed with Saccharolobus islandicus and genetically characterized. We found that disruption of each functional domain completely abolished the DDR regulation in these orc1-2 mutants. Strikingly, inactivation of ATP hydrolysis of Orc1-2 rendered an inviable mutant. However, the cell lethality can be suppressed by the deficiency of the DNA binding in the same protein, and it occurs independent of any DNA damage signal. Mutant Orc1-2 proteins were then obtained and investigated for DNA-binding in vitro. This revealed that both the AAA+ ATPase and the wH domains are involved in DNA-binding, where ISM and R381R383 in wH are responsible for specific DNA binding. We further show that Orc1-2 regulation occurs in two distinct steps: (a) eliciting cell division inhibition at a low Orc1-2 content, and this regulation is switched on by ATP binding and turned off by ATP hydrolysis; any failure in turning off the regulation leads to growth inhibition and cell death; (b) activation of the expression of DDR gene encoding DNA repair proteins at an elevated level of Orc1-2.
In Vivo Sustained Release of the Retrograde Transport Inhibitor Retro-2.1 Formulated in a Thermosensitive Hydrogel
Authors: Vinck Robin , Nguyen Laetitia Anvi , Munier Mathilde , Caramelle Lucie , Karpman Diana , Barbier Julien , Pruvost Alain , Cintrat Jean-Christophe , Gillet Daniel
Published: November 2022

A recently developed inhibitor of retrograde transport, namely Retro-2.1, proved to be a potent and broad-spectrum lead in vitro against intracellular pathogens, such as toxins, parasites, intracellular bacteria and viruses. To circumvent its low aqueous solubility, a formulation in poly(ethylene glycol)-block-poly(D,L)lactide micelle nanoparticles was developed. This formulation enabled the study of the pharmacokinetic parameters of Retro-2.1 in mice following intravenous and intraperitoneal injections, revealing a short blood circulation time, with an elimination half-life of 5 and 6.7 h, respectively. To explain the poor pharmacokinetic parameters, the metabolic stability of Retro-2.1 was studied in vitro and in vivo, revealing fast cytochrome-P-450-mediated metabolism into a less potent hydroxylated analogue. Subcutaneous injection of Retro-2.1 formulated in a biocompatible and bioresorbable polymer-based thermosensitive hydrogel allowed for sustained release of the drug, with an elimination half-life of 19 h, and better control of its metabolism. This study provides a guideline on how to administer this promising lead in vivo in order to study its efficacy.
Osteoblast Demineralization Induced by Oxidized High-Density Lipoprotein via the Inflammatory Pathway Is Suppressed by Adiponectin
Authors: Harun Noor Hanisa , Froemming Gabriele Ruth Anisah , Mohd Ismail Aletza , Nawawi Hapizah , Mokhtar Siti Shuhada , Abd Muid Suhaila
Published: November 2022

Low mineralization activity by human osteoblast cells (HOBs) indicates abnormal bone remodeling that potentially leads to osteoporosis. Oxidation, the most prominent form of high-density lipoprotein (HDL) modification, is suggested to affect bone mineralization through the inflammatory pathway. Adiponectin, which possesses anti-inflammatory activity, is postulated to have the ability to suppress the detrimental effects of oxidized HDL (oxHDL). This study aimed to investigate the effects of HDL before and after oxidation on markers of mineralization and inflammation. The protective effects of adiponectin on demineralization and inflammation induced by oxHDL were also investigated. OxHDL at 100 µg/mL protein had the highest inhibitory effect on mineralization, followed by lower calcium incorporation. OxHDL also had significantly lower expression of a mineralization marker (COL1A2) and higher expression of inflammatory markers (IL-6, TNF-α, and RELA proto-oncogene, NF-κβ (p65)) compared to the unstimulated control group. These findings suggest that oxHDL reduces the mineralization activity of HOBs by increasing the expression of inflammatory markers. Interestingly, co-incubation of adiponectin and oxHDL in HOBs resulted in higher expression of mineralization markers (ALPL, COL1A2, BGLAP, and RUNX2) and significantly reduced all targeted inflammatory markers compared to the oxHDL groups. On the contrary, HDL increased the expression of mineralization markers (COL1A2 and STAT-3) and exhibited lower expression of inflammatory cytokines (IL-6 and TNF-α), proving the protective effect of HDL beyond the reverse cholesterol transport activity.
Fermented Taiwanofungus camphoratus Extract Ameliorates Psoriasis-Associated Response in HaCaT Cells via Modulating NF-𝜅B and mTOR Pathways
Authors: Shen Jia-Wei , Wu Po-Yuan , Kuo Yueh-Hsiung , Chang Qiao-Xin , Wen Kuo-Ching , Chiang Hsiu-Mei
Published: November 2022

Psoriasis is a chronic autoimmune disease, and until now, it remains an incurable disease. Therefore, the development of new drugs or agents that ameliorate the disease will have marketing potential. Taiwanofungus camphoratus (TC) is a specific fungus in Taiwan. It is demonstrated to have anticancer, anti-inflammation, and hepatoprotective effects. However, the effects of TC fermented extract on psoriasis are under investigation. In this research, we studied the ability of TC on antioxidative activity and the efficacy of TC on interleukin-17 (IL-17A)-induced intracellular oxidative stress, inflammation-relative, and proliferation-relative protein expression in human keratinocytes. The results of a DPPH radical scavenging assay, reducing power assay, and hydroxyl peroxide inhibition assay indicated that TC has a potent antioxidant ability. Furthermore, TC could reduce IL-17A-induced intracellular ROS generation and restore the NADPH level. In the investigation of pathogenesis, we discovered TC could regulate inflammatory and cell proliferation pathways via p-IKKα/p-p65 and p-mTOR/p-p70S6k signaling pathways in human keratinocytes. In conclusion, TC showed characteristics such as antioxidant, anti-inflammatory, and anti-psoriatic-associated responses. It is expected to be developed as a candidate for oxidative-stress-induced skin disorders or psoriasis treatment.
Spermidine and 1,3-Diaminopropane Have Opposite Effects on the Final Stage of Cephalosporin C Biosynthesis in High-Yielding Acremonium chrysogenum Strain
Authors: Zhgun Alexander A. , Eldarov Mikhail A.
Published: November 2022

The addition of exogenous polyamines increases the production of antibiotic cephalosporin C (CPC) in Acremonium chrysogenum high-yielding (HY) strain during fermentation on a complex medium. However, the molecular basis of this phenomenon is still unknown. In the current study, we developed a special synthetic medium on which we revealed the opposite effect of polyamines. The addition of 1,3-diaminopropane resulted in an increase in the yield of CPC by 12–15%. However, the addition of spermidine resulted in a decrease in the yield of CPC by 14–15% and accumulation of its metabolic pathway precursor, deacetylcephalosporin C (DAC); the total amount of cephems (DAC and CPC) was the same as after the addition of DAP. This indicates that spermidine, but not 1,3-diaminopropane, affects the final stage of CPC biosynthesis, associated with the acetylation of its precursor. In both cases, upregulation of biosynthetic genes from beta-lactam BGCs occurred at the same level as compared to the control; expression of transport genes was at the control level. The opposite effect may be due to the fact that N1-acetylation is much more efficient during spermidine catabolism than for 1,3-diaminopropane. The addition of spermidine, but not 1,3-diaminopropane, depleted the pool of acetyl coenzyme A by more than two-fold compared to control, which could lead to the accumulation of DAC.
Extracellular Vesicles and Their Roles in the Tumor Immune Microenvironment
Authors: Reale Antonia , Khong Tiffany , Spencer Andrew
Published: November 2022

Tumor cells actively incorporate molecules (e.g., proteins, lipids, RNA) into particles named extracellular vesicles (EVs). Several groups have demonstrated that EVs can be transferred to target (recipient) cells, making EVs an important means of intercellular communication. Indeed, EVs are able to modulate the functions of target cells by reprogramming signaling pathways. In a cancer context, EVs promote the formation of a supportive tumor microenvironment (TME) and (pre)metastatic niches. Recent studies have revealed that immune cells, tumor cells and their secretome, including EVs, promote changes in the TME and immunosuppressive functions of immune cells (e.g., natural killer, dendritic cells, T and B cells, monocytes, macrophages) that allow tumor cells to establish and propagate. Despite the growing knowledge on EVs and on their roles in cancer and as modulators of the immune response/escape, the translation into clinical practice remains in its early stages, hence requiring improved translational research in the EVs field. Here, we comprehensively review the current knowledge and most recent research on the roles of EVs in tumor immune evasion and immunosuppression in both solid tumors and hematological malignancies. We also highlight the clinical utility of EV-mediated immunosuppression targeting and EV-engineering. Importantly, we discuss the controversial role of EVs in cancer biology, current limitations and future perspectives to further the EV knowledge into clinical practice.
The Effect of Upadacitinib on Lipid Profile and Cardiovascular Events: A Meta-Analysis of Randomized Controlled Trials
Authors: Makris Anastasios , Barkas Fotios , Sfikakis Petros P. , Liberopoulos Evangelos , Agouridis Aris P.
Published: November 2022

Background: Our aim was to systematically investigate the effect of upadacitinib, an oral JAK-1 selective inhibitor, on lipid profile and cardiovascular disease risk. Methods: PubMed, PubMed Central and ClinicalTrials.gov databases were searched for relevant randomized controlled trials (RCTs) up to 31 July 2022. We performed a qualitative synthesis of published RCTs to investigate the associations of upadacitinib with lipoprotein changes, along with a quantitative synthesis of MACE and mean lipoprotein changes where there were available data. Results: Nineteen RCTs were eligible for the present systematic review, which included 10,656 patients with a mean age of 51 years and a follow-up period of 12–52 weeks. Increases in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were noted upon upadacitinib administration (3–48 mg/day) in 15 studies, while the LDL-C:HDL-C ratio remained unchanged. The pooled analyses of three placebo-controlled RCTs (n = 2577) demonstrated that upadacitinib at 15 mg increased the LDL-C by 15.18 mg/dL (95% CI: 7.77–22.59) and HDL-C by 7.89 mg/dL (95% CI: 7.08–8.69). According to the pooled analysis of 15 placebo-controlled RCTs (n = 7695), upadacitinib had no effect on MACE (risk ratio, RR: 0.62; 95% CI: 0.24–1.60). A sub-analysis focusing on upadacitinib at 15 mg (12 studies, n = 5395) demonstrated similar results (RR: 0.67; 95% CI: 0.19–2.36). Conclusions: Treatment with upadacitinib increases both LDL-C and HDL-C levels. Nevertheless, upadacitinib had no significant effect on the cardiovascular disease risk during a ≤52-week follow-up.
Free Light Chains, High Mobility Group Box 1, and Mortality in Hemodialysis Patients
Authors: Lacquaniti Antonio , Campo Susanna , Falliti Giuseppe , Caruso Daniele , Gargano Romana , Giunta Elena , Monardo Paolo
Published: November 2022

Background: Uremic toxins are associated with immune dysfunction and inflammation. The inadequate removal by hemodialysis (HD) of serum free light chains (FLCs) determines their accumulation. This study evaluated FLCs in HD patients, analyzing their relations with other biomarkers, such as serum high mobility group box 1 (HMGB1). Methods: FLC and HMGB1 were evaluated in a cohort of 119 HD patients. κFLC and λFLC were summated to give a combined (c) FLC concentration. Patients were followed prospectively until the end of the observation period of four years, or until the endpoint: the patient’s death. Results: cFLC values in HD patients were 244.4 (197.9–273.5) mg/L. We detected a significant reduction in CD8+ cells and a decreased CD4+/CD8+ ratio. HMGB1 levels were 94.5 (55–302) pg/mL. After multivariate analysis, cFLCs correlated with β2-microglobulin and the CD4+/CD8+ ratio. Subjects with cFLC values above 263 mg/L and with sHMGB1 values < 80 pg/mL experienced a significantly faster evolution to the endpoint (mean follow-up time to progression of 27.5 and 28.5 months, respectively; p < 0.001). After an adjusted multivariate Cox analysis, cFLCs were associated with 11% increased risk of death, whereas low sHMGB1 increased this risk by 5%. Conclusions: cFLCs and HMGB1 reflect the inflammation and immune dysfunction in HD patients representing two strong and independent risk markers of mortality.
Improving the Anchorage in Textile Reinforced Cement Composites by 3D Spacer Connections: Experimental Study of Flexural and Cracking Behaviors
Authors: El Kadi Michael , Van Hemelrijck Danny , Tysmans Tine
Published: November 2022

Textile-reinforced cement (TRC) composites can lead to significant material (and dimensional) savings compared to steel-reinforced concrete, particularly when applied in thin-walled structures such as façade panels, shells, etc. In conditions where the geometrical restrictions do not allow for sufficient anchorage, however, the exploitation of this reinforcement may be suboptimal and the TRC’s mechanical properties may decrease. As shown in the literature, the use of 3D textile reinforcement can lead to an improved anchorage in the reinforcement points and superior post-cracking behavior in terms of bending. The question remains as to whether similar improvements can be achieved using 3D spacer connections, inserted post-manufacturing of the textiles. Therefore, this research experimentally investigated the effect of discretely inserted spacer connections on the flexural properties and cracking behavior of TRCs. Six different TRC beam configurations—varying in the placement of the spacer connections over the span—were investigated. Moreover, a comparison was made with two additional configurations: one equivalent 2D TRC system (using the same in-plane textiles but without through-thickness connections) and one 3D TRC system using knitted 3D textiles (with spacer yarns uniformly distributed). The four-point bending tests were monitored via digital image correlation (DIC) to visualize the full-field cracking pattern. The experimental results showed that the spacer connections could strongly improve the post-cracking bending stiffness and the modulus of rupture (MOR) when placed close to the free end of the sample and could also lead to reduced crack widths when placed around the midspan.
Application of Probabilistic Approach to Investigate Influence of Details in Time History of Temperature Changes on the HCF Life of Integrated Bridge Steel Piles Installed on Water
Authors: Abdollahnia Hamid , Alizadeh Elizei Mohammad Hadi , Reza Kashyzadeh Kazem
Published: November 2022

This research estimates the high-cycle fatigue (HCF) life of integrated concrete bridge installed on water due to temperature changes. To this end, CATIA software was used to geometrically model of a real-scale bridge. Next, thermal–structural coupling analysis was performed by finite element (FE) simulation in ANSYS WORKBENCH software. The comparison technique with experimental data was used to validate the simulation. Afterward, thermal analysis was performed due to air temperature changes in different modes, including the average monthly temperature changes (large variations) as well as the maximum and minimum monthly temperature changes (small variations). The results showed that the most changes in deck length and subsequent maximum deviation in the upper part of steel piles were related to the three warm seasons in the presence of the water. Eventually, a probabilistic approach was employed to find variable amplitude fatigue lifetime of the component based on the number of annual loading blocks. To achieve the high-accuracy response, the effective parameters of the proposed probabilistic approach, including order of Fourier series and the stress range, were optimized automatically. In addition, to obtain HCF behavior of raw material, axial tension–compression fatigue tests were performed on the standard specimens fabricated from steel piles. The results revealed that considering small variations in the calculation of structural fatigue life led to a 550% reduction in life compared to structural analysis due to large variations. In addition, the obtained results were compared with the finite element results.
An Overview of Knowledge Graph Reasoning: Key Technologies and Applications
Authors: Chen Yonghong , Li Hao , Li Han , Liu Wenhao , Wu Yirui , Huang Qian , Wan Shaohua
Published: November 2022

In recent years, with the rapid development of Internet technology and applications, the scale of Internet data has exploded, which contains a significant amount of valuable knowledge. The best methods for the organization, expression, calculation, and deep analysis of this knowledge have attracted a great deal of attention. The knowledge graph has emerged as a rich and intuitive way to express knowledge. Knowledge reasoning based on knowledge graphs is one of the current research hot spots in knowledge graphs and has played an important role in wireless communication networks, intelligent question answering, and other applications. Knowledge graph-oriented knowledge reasoning aims to deduce new knowledge or identify wrong knowledge from existing knowledge. Different from traditional knowledge reasoning, knowledge reasoning methods oriented to knowledge graphs are more diversified due to the concise, intuitive, flexible, and rich knowledge expression forms in knowledge graphs. Based on the basic concepts of knowledge graphs and knowledge graph reasoning, this paper introduces the latest research progress in knowledge graph-oriented knowledge reasoning methods in recent years. Specifically, according to different reasoning methods, knowledge graph reasoning includes rule-based reasoning, distributed representation-based reasoning, neural network-based reasoning, and mixed reasoning. These methods are summarized in detail, and the future research directions and prospects of knowledge reasoning based on knowledge graphs are discussed and prospected.
Socioeconomic and Environmental Benefits of Expanding Urban Green Areas: A Joint Application of i-Tree and LCA Approaches
Authors: Oliveira Mariana , Santagata Remo , Kaiser Serena , Liu Yanxin , Vassillo Chiara , Ghisellini Patrizia , Liu Gengyuan , Ulgiati Sergio
Published: November 2022

Green infrastructures deliver countless functions for counteracting climate change, air pollution, floods, and heat islands, contributing at the same time to water and carbon recycling as well as to renewable energies and feedstock provisioning. Properly addressing such environmental problems would require huge investments that could be decreased thanks to the further implementation of urban forests. Local administrations are designing participative projects to improve territories and their living conditions. The i-Tree Canopy modelling tool and the life cycle assessment method are jointly applied to evaluate the potential benefits of increasing tree coverage within the boundaries of the Metropolitan City of Naples, Southern Italy. Results highlighted that tree coverage could increase by about 2.4 million trees, thus generating 51% more benefits in pollutants removal, carbon sequestration and stormwater management. The benefits are also explored and confirmed by means of the life cycle assessment method. The potential tree cover is expected to provide a total annual economic benefit of USD 55 million, purchasing power parity value adjusted, representing USD 18 per citizen and USD 99,117 per square kilometre of implemented urban forest. These results can support a potential replication elsewhere and provide a reference for the sustainable improvement of cities by expanding urban green areas.
Historical Water Management Strategies—Case Study of Traditional Villages in Southern China, Hunan Province
Authors: DongGe Ning , Yan Jinbiao , Liu Peilin , van den Toorn Martin , Fekete Albert
Published: November 2022

Based on the landscape architecture of traditional settlements in southern China, this study takes water as a vital element through field investigation and model analysis to explore the water management strategies of two traditional villages in Xiangjiang River Basin, Hunan Province. We have found that traditional settlements are located between rivers and mountains. The community of the settlement has a strong interaction with the water environment. The water management system consists of two parts: the rainwater collection and storage system of a single building and the settlement’ s water collection and drainage system. Through calculation, we found that the amounts of water collected (per year) between the two villages are different: ZhangGuYing (Z village) = 5.73 million L, ShangGanTang (S village) = 1.784 million L, in spite of the fact that water management strategies of the two settlements are similar. Further analysis shows that the difference is related to the adaption of the precipitation and topography of the surrounding areas. The above-mentioned systematic management strategy of water resources has been used until currently, with adaptability, low cost, and sustainability. It has outstanding significance for the current demand for sustainable development from both resource management and cultural aspects.
Efficacy and Failure Patterns of Early SBRT to the Primary Tumor in Advanced EGFR-Mutation-Positive Lung Cancer with EFGR-TKI Treatment: A Prospective, Single Arm, Phase II Study
Authors: Shi Yangyang , Xu Hailing , Raynor William Y. , Ding Jiapei , Lin Ling , Zhou Chao , Wang Wei , Meng Yinnan , Wu Xiaomai , Chen Xiaofeng , Lv Dongqing , Yang Haihua
Published: November 2022

Early stereotactic body radiation therapy (SBRT) to the primary tumor combined with epidermal growth factor receptor tyrosine kinase inhibitor (EFGR-TKI) treatment may increase progression-free survival (PFS) by delaying resistance in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). In this prospective, single arm, phase II study, patients with advanced NSCLC were treated with EGFR-TKI (icotinib 125 mg tid or gefitinib 250 mg qd) for one month followed by SBRT (40–60 Gy/5–8 F/5–10 d) to the primary tumor with concurrent EGFR-TKI until disease progression. The primary endpoint was PFS and the patterns of failure. Overall survival (OS) and adverse effects (AEs) were secondary endpoints. Overall, 41 advanced NSCLC patients with EGFR mutations received treatment with 24.42 months of median follow-up time. On average, SBRT was initiated 1.49 months after EGFR-TKI administration. Tumors were found to have an average shrinkage rate of 42.50%. Median PFS was 15.23 months (95% CI 13.10–17.36), while median OS was 27.57 months (95% CI 23.05–32.09). Thirty-three patients were found to have disease progression, of which new site failure (NF) (22 patients, 66.66%) was the most common pattern, followed by original site failure (OF) (7 patients, 21.21%) and simultaneous OF/NF (ONF) (4 patients, 12.12%). There were no Aes equal to or greater than grade 3, with the most frequent AE being radiation pneumonitis. Therefore, administering therapy targeted at the primary tumor using early SBRT after EGFR-TKI initiation is a new potentially safe and effective approach to treat EGFR-mutant advanced NSCLC.
Effectiveness of CPR in Hypogravity Conditions—A Systematic Review
Authors: Overbeek Remco , Schmitz Jan , Rehnberg Lucas , Benyoucef Yacine , Dusse Fabian , Russomano Thais , Hinkelbein Jochen
Published: November 2022

(1) Background: Cardiopulmonary resuscitation (CPR), as a form of basic life support, is critical for maintaining cardiac and cerebral perfusion during cardiac arrest, a medical condition with high expected mortality. Current guidelines emphasize the importance of rapid recognition and prompt initiation of high-quality CPR, including appropriate cardiac compression depth and rate. As space agencies plan missions to the Moon or even to explore Mars, the duration of missions will increase and with it the chance of life-threatening conditions requiring CPR. The objective of this review was to examine the effectiveness and feasibility of chest compressions as part of CPR following current terrestrial guidelines under hypogravity conditions such as those encountered on planetary or lunar surfaces; (2) Methods: A systematic literature search was conducted by two independent reviewers (PubMed, Cochrane Register of Controlled Trials, ResearchGate, National Aeronautics and Space Administration (NASA)). Only controlled trials conducting CPR following guidelines from 2010 and after with advised compression depths of 50 mm and above were included; (3) Results: Four different publications were identified. All studies examined CPR feasibility in 0.38 G simulating the gravitational force on Mars. Two studies also simulated hypogravity on the Moon with a force of 0.17 G/0,16 G. All CPR protocols consisted of chest compressions only without ventilation. A compression rate above 100/s could be maintained in all studies and hypogravity conditions. Two studies showed a significant reduction of compression depth in 0.38 G (−7.2 mm/−8.71 mm) and 0.17 G (−12.6 mm/−9.85 mm), respectively, with nearly similar heart rates, compared to 1 G conditions. In the other two studies, participants with higher body weight could maintain a nearly adequate mean depth while effort measured by heart rate (+23/+13.85 bpm) and VO2max (+5.4 mL·kg−1·min−1) increased significantly; (4) Conclusions: Adequate CPR quality in hypogravity can only be achieved under increased physical stress to compensate for functional weight loss. Without this extra effort, the depth of compression quickly falls below the guideline level, especially for light-weight rescuers. This means faster fatigue during resuscitation and the need for more frequent changes of the resuscitator than advised in terrestrial guidelines. Alternative techniques in the straddling position should be further investigated in hypogravity.