bluuebunny/crossref_metadata_2025 huggingface dataset:
Powdery Mildew Resistance Phenotypes of Wheat Gene Bank Accessions
Authors: Dreiseitl Antonín
Published: August 2021

Powdery mildew (Blumeria graminis f. sp. tritici) is a common pathogen of bread wheat (Triticum aestivum L.), and genetic resistance is an effective and environmentally friendly method to reduce its adverse impact. The introgression of novel genes from wheat progenitors and related species can increase the diversity of disease resistance and accumulation of minor genes to improve the crop’s resistance durability. To accomplish these two actions, host genotypes without major resistances should be preferably used. Therefore, the main aim of this study was to carry out seedling tests to detect such resistances in a set of wheat accessions from the Czech gene bank and to group the cultivars according to their phenotype. Ear progenies of 448 selected cultivars originating from 33 countries were inoculated with three isolates of the pathogen. Twenty-eight cultivars were heterogeneous, and 110 cultivars showed resistance to at least one isolate. Fifty-nine cultivars, mostly from Northwest Europe, were resistant to all three isolates were more than three times more frequently recorded in spring than in winter cultivars. Results will facilitate a rational and practical approach preferably using the set of cultivars without major resistances for both mentioned methods of breeding wheat cultivars resistant to powdery mildew.
Design and Synthesis of Novel Peptides to Protect Ferulic Acid against Ultraviolet Radiation Based on Domain Site IIA of Bovine Serum Albumin
Authors: Wu Yinghan , Farrag Hisham N. , Kato Tamaki , Li Hua , Ikeno Shinya
Published: August 2021

Ferulic acid (FA) is known for its excellent antioxidant properties, which can provide many health benefits. One of its drawbacks is its instability under UVA light, which limits its potency. In this study, the new peptides LW2 (QNKRFYFRKNQ) and CW2 (a cyclic form of LW2) were designed based on bovine serum albumin site IIA conformation. A UVA irradiation experiment was performed to investigate the protective ability of these peptides towards FA against UVA damage. The percentages of FA remaining under UV irradiation due to the protection of CW2 and LW2 were 83% and 76%, respectively. The results showed the importance of the cationic residues and hydrophobic residues included in the peptide sequences. Moreover, the cyclic rigid structure showed greater protective ability as compared to its linear counterpart.
Blood-Derived α-Synuclein Aggregated in the Substantia Nigra of Parabiotic Mice
Authors: Ma Xizhen , Chen Leilei , Song Ning , Qu Le , Wang Jun , Xie Junxia
Published: August 2021

As a pathological biomarker of Parkinson’s disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the brains of mice and whether α-synuclein in the brain could be cleared by parabiosis. Heterochronic parabiosis was performed on SNCAA53T transgenic mice (A53T mice) and wildtype mice. The levels of human α-synuclein in the blood and substantia nigra of wildtype mice were significantly increased after 4-month parabiosis with A53T mice. Moreover, the expression of α-synuclein filament, but not of total α-synuclein, was significantly increased in the substantia nigra of wildtype mice that were paired with A53T mice. However, the levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system; however, it appears to be difficult to clear it from the brain in a short period of time.
A Novel Method for the Determination of Vitamin D Metabolites Assessed at the Blood-Cerebrospinal Fluid Barrier
Authors: Zelzer Sieglinde , Meinitzer Andreas , Herrmann Markus , Goessler Walter , Enko Dietmar
Published: August 2021

The brain’s supply with vitamin D is poorly understood. Therefore, the present study aimed to determine 25-hydroxy vitamin D3 (25(OH)D) and 24,25-dihydroxy vitamin D (24,25(OH)2D3) in serum and cerebrospinal fluid (CSF) from individuals with intact and disturbed brain-CSF-barrier (BCB) function. In 292 pairs of serum and CSF samples the vitamin D metabolites were measured with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). CSF/serum ratios (QALB, Q25(OH)D, Q24,25(OH)2D3) were calculated. Median (IQR) serum concentrations of 25(OH)D and 24,25(OH)2D3 were 63.8 (43.4–83.9) nmol/L and 4.2 (2.2–6.2) nmol/L. The CSF concentrations of both metabolites accounted for 3.7 and 3.3% of the respective serum concentrations. Serum 25(OH)D correlated inversely with Q25(OH)D and Q24,25(OH)2D3 implying a more efficient transport of both metabolites across the BCB when the serum concentration of 25(OH)D is low. In patients with BCB dysfunction, the CSF concentrations and the CSF/serum ratios of both vitamin D metabolites were higher than in individuals with intact BCB. The CSF concentrations of 25(OH)D and 24,25(OH)2D3 depend on BCB function and the respective serum concentrations of both metabolites. Higher vitamin D metabolite concentrations in CSF of patients with impaired BCB function may be due to passive diffusion across the BCB.
The Efficacy of Naïve versus Modified Mesenchymal Stem Cells in Improving Muscle Function in Duchenne Muscular Dystrophy: A Systematic Review
Authors: Shen Oscar Yuan-Jie , Chen Yi-Fan , Xu Hong-Tao , Lee Chien-Wei
Published: August 2021

As one of the most common genetic conditions, Duchenne muscular dystrophy (DMD) is a fatal disease caused by a recessive mutation resulting in muscle weakness in both voluntary and involuntary muscles and, eventually, in death because of cardiovascular failure. Currently, there is no pharmacologically curative treatment of DMD, but there is evidence supporting that mesenchymal stem cells (MSCs) are a novel solution for treating DMD. This systematic review focused on elucidating the therapeutic efficacy of MSCs on the DMD in vivo model. A key issue of previous studies was the material-choice, naïve MSCs or modified MSCs; modified MSCs are activated by culture methods or genetic modification. In summary, MSCs seem to improve pulmonary and cardiac functions and thereby improve survival regardless of them being naïve or modified. The improved function of distal skeletal muscles was observed only with primed MSCs treatment but not naïve MSCs. While MSCs can provide significant benefits to DMD mouse models, there is little to no data on the results in human patients. Due to the limited number of human studies, the differences in study design, and the insufficient understanding of mechanisms of action, more rigorous comparative trials are needed to elucidate which types of MSCs and modifications have optimal therapeutic potential.
Lactococcus lactis Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire
Authors: Arukha Ananta Prasad , Freguia Christian Furlan , Mishra Meerambika , Jha Jyoti K. , Kariyawasam Subhashinie , Fanger Neil A. , Zimmermann Ellen M. , Fanger Gary R. , Sahay Bikash
Published: August 2021

Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease management, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of Lactobacillus acidophilus that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade Lactococcus lactis to further investigate and characterize the protective mechanisms of the actions of SlpA. Oral administration of SlpA-expressing L. lactis (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in humans.
Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma
Authors: Pelaia Corrado , Pelaia Giulia , Longhini Federico , Crimi Claudia , Calabrese Cecilia , Gallelli Luca , Sciacqua Angela , Vatrella Alessandro
Published: August 2021

Alarmins are innate cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), which are mainly produced by airway epithelium and exert a prominent role in asthma pathobiology. In particular, several environmental factors such as allergens, cigarette smoking, airborne pollutants, and infectious agents trigger the release of alarmins, which in turn act as upstream activators of pro-inflammatory pathways underlying type 2 (T2-high) asthma. Indeed, alarmins directly activate group 2 innate lymphoid cells (ILC2), eosinophils, basophils, and mast cells and also stimulate dendritic cells to drive the commitment of naïve T helper (Th) cells towards the Th2 immunophenotype. Therefore, TSLP, IL-33, and IL-25 represent suitable targets for add-on therapies of severe asthma. Within this context, the fully human anti-TSLP monoclonal antibody tezepelumab has been evaluated in very promising randomized clinical trials. Tezepelumab and other anti-alarmins are thus likely to become, in the near future, valuable therapeutic options for the biological treatment of uncontrolled severe asthma.
Heteronemin Suppresses Lymphangiogenesis Through ARF-1 and MMP-9/VE-Cadherin/Vimentin
Authors: Chen Hsien-Lin , Su Yu-Chieh , Chen Huang-Chi , Su Jui-Hsin , Wu Chang-Yi , Wang Shih-Wei , Lin In-Pin , Chen Chung-Yi , Lee Chien-Hsing
Published: August 2021

Lymphatic metastasis is a biological procedure associated with the pathogenesis of several diseases, especially in tumor metastasis. Therefore, regulation of lymphangiogenesis has become a promising strategy for cancer therapy. In this study, we aimed to investigate the anti-lymphangiogenic effect of heteronemin (SP-1) isolated from the sponge Hyrtios sp. in vitro and in vivo. Human lymphatic endothelial cells (LECs) were utilized to evaluate the anti-lymphangiogenic effect of SP-1 in vitro. Molecular docking, western blotting, flow-cytometry, MTT and ELISA were performed to investigate the mechanism of action. For in vivo approaches, the transgenic (fli1:EGFP; gata1:DsRed) zebrafish and mouse ear sponges were used. Molecular docking studies showed that SP-1 is a potent vascular endothelial growth factor receptor 3 (VEGFR-3)-binding compound. Treatment of LEC with SP-1 reduced the phosphorylation of VEGFR-3. SP-1 suppressed the development of the thoracic duct in zebrafish and mouse lymphangiogenesis ear sponges in vivo. Mechanistically, SP-1 induced the cell cycle arrest of LECs in the G0/G1 phase and reduced the downstream of VEGFR-3, such as phosphorylated MEK/ERK and NF-κB. In addition, SP-1 inhibited LECs’ tubulogenesis and migration through the ARF-1 and MMP-9/VE-cadherin/vimentin. Overall, anti-lymphangiogenic properties of SP-1 occur by downregulating the VEGFR-3 cascade, ARF-1 and MMP-9/VE-cadherin/vimentin. Collectively, these results proposed that SP-1 might be a potential candidate for the treatment of lymphangiogenesis-associated diseases.
Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis
Authors: Xiao Jerry , Pohlmann Paula R. , Isaacs Claudine , Weinberg Benjamin A. , He Aiwu R. , Schlegel Richard , Agarwal Seema
Published: August 2021

Circulating tumor cells (CTCs) are single cells or clusters of cells within the circulatory system of a cancer patient. While most CTCs will perish, a small proportion will proceed to colonize the metastatic niche. The clinical importance of CTCs was reaffirmed by the 2008 FDA approval of CellSearch®, a platform that could extract EpCAM-positive, CD45-negative cells from whole blood samples. Many further studies have demonstrated the presence of CTCs to stratify patients based on overall and progression-free survival, among other clinical indices. Given their unique role in metastasis, CTCs could also offer a glimpse into the genetic drivers of metastasis. Investigation of CTCs has already led to groundbreaking discoveries such as receptor switching between primary tumors and metastatic nodules in breast cancer, which could greatly affect disease management, as well as CTC-immune cell interactions that enhance colonization. In this review, we will highlight the growing variety of isolation techniques for investigating CTCs. Next, we will provide clinically relevant context for CTCs, discussing key clinical trials involving CTCs. Finally, we will provide insight into the future of CTC studies and some questions that CTCs are primed to answer.
Activated Alpha 2-Macroglobulin Is a Novel Mediator of Mesangial Cell Profibrotic Signaling in Diabetic Kidney Disease
Authors: Trink Jackie , Li Renzhong , Palarasah Yaseelan , Troyanov Stéphan , Andersen Thomas E. , Sidelmann Johannes J. , Inman Mark D. , Pizzo Salvatore V. , Gao Bo , Krepinsky Joan C.
Published: August 2021

Diabetic kidney disease (DKD) is caused by the overproduction of extracellular matrix proteins (ECM) by glomerular mesangial cells (MCs). We previously showed that high glucose (HG) induces cell surface translocation of GRP78 (csGRP78), mediating PI3K/Akt activation and downstream ECM production. Activated alpha 2-macroglobulin (α2M*) is a ligand known to initiate this signaling cascade. Importantly, increased α2M was observed in diabetic patients’ serum, saliva, and glomeruli. Primary MCs were used to assess HG responses. The role of α2M* was assessed using siRNA, a neutralizing antibody and inhibitory peptide. Kidneys from type 1 diabetic Akita and CD1 mice and human DKD patients were stained for α2M/α2M*. α2M transcript and protein were significantly increased with HG in vitro and in vivo in diabetic kidneys. A similar increase in α2M* was seen in media and kidneys, where it localized to the mesangium. No appreciable α2M* was seen in normal kidneys. Knockdown or neutralization of α2M/α2M* inhibited HG-induced profibrotic signaling (Akt activation) and matrix/cytokine upregulation (collagen IV, fibronectin, CTGF, and TGFβ1). In patients with established DKD, urinary α2M* and TGFβ1 levels were correlated. These data reveal an important role for α2M* in the pathogenesis of DKD and support further investigation as a potential novel therapeutic target.
Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats
Authors: Chen Chung-Hwan , Cheng Tsung-Lin , Chang Chi-Fen , Huang Hsuan-Ti , Lin Sung-Yen , Wu Meng-Hsing , Kang Lin
Published: August 2021

Osteoarthritis (OA) and osteoporosis (OP) are common among older women, especially postmenopausal women. Glucosamine (GlcN) is a common medication for OA, but it may induce insulin resistance and β-cell dysfunction, especially if ovarian hormones are lacking. Raloxifene (RLX) is a selective estrogen receptor modulator and also an OP drug. Previously, we found that estrogen could improve GlcN-induced insulin resistance in ovariectomized (OVX) rats. Here, we further hypothesized that RLX, similarly to estrogen, can ameliorate GlcN-induced insulin resistance in OVX rats. We used GlcN to induce insulin resistance in OVX rats as a model for evaluating the protective effects of RLX in vivo. We used a pancreatic β-cell line, MIN-6, to study the mechanisms underlying the effect of RLX in GlcN-induced β-cell dysfunction in vitro. Increases in fasting plasma glucose, insulin, and homeostasis model assessments of insulin resistance in OVX Sprague Dawley rats treated with GlcN were reversed by RLX treatment (n = 8 in each group). Skeletal muscle GLUT-4 increased, liver PEPCK decreased, pancreatic islet hypertrophy, and β-cell apoptosis in OVX rats treated with GlcN was ameliorated by RLX. The negative effects of GlcN on insulin secretion and cell viability in MIN-6 cells were related to the upregulation of reticulum (ER) stress-associated proteins (C/EBP homologous protein, phospho-extracellular signal-regulated kinase, phospho-c-JunN-terminal kinase), the expression of which was reduced by RLX. Pretreatment with estrogen receptor antagonists reversed the protective effects of RLX. GlcN can induce insulin resistance, β-cell dysfunction, and apoptosis in OVX rats and increase ER stress-related proteins in β-cells, whereas RLX can reverse these adverse effects. The effects of RLX act mainly through estrogen receptor α; therefore, RLX may be a candidate drug for postmenopausal women with OA and OP.
Cytokine (IL-10, IL-6, TNF-α and TGF-β1) Gene Polymorphisms in Chronic Hepatitis C Virus Infection among Malay Male Drug Abusers
Authors: Noh Ismail Che , Ahmad Imran , Suraiya Siti , Musa Nur Fadhlina , Nurul Asma Abdullah , Ruzilawati Abu Bakar
Published: August 2021

Cytokines play an important role in modulating inflammation during viral infection, including hepatitis C virus (HCV) infection. Genetic polymorphisms of cytokines can alter the immune response against this infection. The objective of this study was to investigate the possible association between chronic hepatitis C virus infection susceptibility and cytokine gene polymorphism for interleukin-10 (IL-10) rs1800896 and rs1800871, interleukin 6 (IL-6) rs1800795, TNF-α rs1800629, and TGF-β1 rs1800471 in Malay male drug abusers. The study was conducted on 76 HCV-positive (HP) male drug abusers and 40 controls (HCV-negative male drug abusers). We found that there were significant differences in the frequencies of genotype for IL-10 rs1800871 (p = 0.0386) and at the allelic level for IL-10 rs1800896 A versus G allele (p = 0.0142) between the HP group and the control group. However, there were no significant differences in gene polymorphism in interleukin 6 rs1800795, TNF-α rs1800629 and TGF-β1 rs1800471. These findings suggest significant associations between gene polymorphism for IL-10 rs1800871, IL-10 rs1800896 (at the allelic level) and susceptibility to HCV infection among Malay male drug abusers.
Glomerular Mesangial Cell pH Homeostasis Mediates Mineralocorticoid Receptor-Induced Cell Proliferation
Authors: Gekle Michael , Mildenberger Sigrid
Published: August 2021

Mineralocorticoids (e.g., aldosterone) support chronic inflammatory tissue damage, including glomerular mesangial injury leading to glomerulosclerosis. Furthermore, aldosterone leads to activation of the extracellular signal-regulated kinases (ERK1/2) in rat glomerular mesangial cells (GMC). Because ERK1/2 can affect cellular pH homeostasis via activation of Na+/H+-exchange (NHE) and the resulting cellular alkalinization may support proliferation, we tested the hypothesis that aldosterone affects pH homeostasis and thereby cell proliferation as well as collagen secretion also in primary rat GMC. Cytoplasmic pH and calcium were assessed by single-cell fluorescence ratio imaging, using the dyes BCECF or FURA2, respectively. Proliferation was determined by cell counting, thymidine incorporation and collagen secretion by collagenase-sensitive proline incorporation and ERK1/2-phosphorylation by Western blot. Nanomolar aldosterone induces a rapid cytosolic alkalinization which is prevented by NHE inhibition (10 µmol/L EIPA) and by blockade of the mineralocorticoid receptor (100 nmol/L spironolactone). pH changes were not affected by inhibition of HCO3− transporters and were not dependent on HCO3−. Aldosterone enhanced ERK1/2 phosphorylation and inhibition of ERK1/2-phosphorylation (10 µmol/L U0126) prevented aldosterone-induced alkalinization. Furthermore, aldosterone induced proliferation of GMC and collagen secretion, both of which were prevented by U0126 and EIPA. Cytosolic calcium was not involved in this aldosterone action. In conclusion, our data show that aldosterone can induce GMC proliferation via a MR and ERK1/2-mediated activation of NHE with subsequent cytosolic alkalinization. GMC proliferation leads to glomerular hypercellularity and dysfunction. This effect presents a possible mechanism contributing to mineralocorticoid receptor-induced pathogenesis of glomerular mesangial injury during chronic kidney disease.
Detection of Infectious Viruses Using CRISPR-Cas12-Based Assay
Authors: Talwar Chandana S. , Park Kwang-Hyun , Ahn Woo-Chan , Kim Yong-Sam , Kwon Oh Seok , Yong Dongeun , Kang Taejoon , Woo Euijeon
Published: August 2021

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has severely influenced public health and economics. For the detection of SARS-CoV-2, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein (Cas)-based assays have been emerged because of their simplicity, sensitivity, specificity, and wide applicability. Herein, we have developed a CRISPR-Cas12-based assay for the detection of SARS-CoV-2. In the assay, the target amplicons are produced by isothermal reverse transcription recombinase polymerase amplification (RT-RPA) and recognized by a CRISPR-Cas12a/guide RNA (gRNA) complex that is coupled with the collateral cleavage activity of fluorophore-tagged probes, allowing either a fluorescent measurement or naked-eye detection on a lateral flow paper strip. This assay enables the sensitive detection of SARS-CoV-2 at a low concentration of 10 copies per sample. Moreover, the reliability of the method is verified by using nasal swabs and sputum of COVID-19 patients. We also proved that the current assay can be applied to other viruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV), with no major changes to the basic scheme of testing. It is anticipated that the CRISPR-Cas12-based assay has the potential to serve as a point-of-care testing (POCT) tool for a wide range of infectious viruses.
A Smart Core-Crosslinked Supramolecular Drug Delivery System (SDDS) Enabled by Pendant Cyclodextrins Encapsulation of Drug Dimers via Host-Guest Interaction
Authors: Xing Xin , Guo Zhijun , Su Yue , Yang Zhen , Qian Jiwen , Tu Chunlai , Zhu Lijuan , Xu Feng
Published: August 2021

Owing to poor aqueous solubility and low delivery efficiency, most of anti-cancer chemodrugs depend on various smart drug delivery platforms to enhance the treatment efficacy. Herein, a stimuli-responsive supramolecular drug delivery system (SDDS) is developed based on polymeric cyclodextrins (PCD) which crosslinked by stimuli-cleavable drug dimers via host-guest interaction. PEGylated PCD was precisely controlled synthesized by ring-opening polymerization and azide-alkyne click chemistry, and two doxorubicins (DOX) were linked with a disulfide bond to form a drug dimer (ss-DOX). They then co-assembled into supramolecular micelles. Drug dimers were utilized as cross-linkers to stabilize the micelles. The drug loading efficiency was very high that could be up to 98%. The size and morphology were measured by DLS and TEM. Owing to the disulfide bonds of drug dimers, these supramolecular micelles were dissociated by treating with dithiothreitol (DTT). In the meanwhile, the free DOXs were recovered and released from cavities of cyclodextrins because of dynamic equilibrium and hydrophilicity changes. The release profile was studied under mimic physiological conditions. Furthermore, in vitro cytotoxicity study showed excellent anti-cancer efficacy of reduced-responsive supramolecular polymeric micelles. Therefore, it can be served as a safe and stimuli-responsive SDDS for cancer therapy.
Effects of Father and Mother Attachment on Depressive Symptoms in Middle Childhood and Adolescence: The Mediating Role of Emotion Regulation
Authors: Iwanski Alexandra , Lichtenstein Lucie , Mühling Laura E. , Zimmermann Peter
Published: August 2021

Background: Attachment and emotion regulation play a decisive role in the developmental pathways of adaptation or maladaptation. This study tested concurrent and longitudinal associations between the attachment to mother and father, sadness regulation, and depressive symptoms. Methods: A total of 1110 participants from middle childhood to adolescence completed measures of attachment, emotion regulation, and depressive symptomatology. In total, 307 of them participated in the longitudinal assessment. Results: Results revealed attachment affects emotion regulation strategies and depressive symptoms. Furthermore, we found linear effects of the cumulative number of secure attachment relationships on adaptive and maladaptive deactivating sadness regulation, as well as on depressive symptoms. Longitudinal analysis showed the significant mediating role of sadness regulation in the relationship between attachment and depressive symptoms. Conclusions: Adaptive and maladaptive deactivating sadness regulation explain the longitudinal effects of attachment on depressive symptoms. Insecurely attached children and adolescents use maladaptive and adaptive sadness regulation strategies, but differ in their hierarchy of strategy use.
A Review on Metal Ions Modified TiO2 for Photocatalytic Degradation of Organic Pollutants
Authors: Jiang Dafu , Otitoju Tunmise Ayode , Ouyang Yuanyuan , Shoparwe Noor Fazliani , Wang Song , Zhang Ailing , Li Sanxi
Published: August 2021

TiO2 is a semiconductor material with high chemical stability and low toxicity. It is widely used in the fields of catalysis, sensing, hydrogen production, optics and optoelectronics. However, TiO2 photocatalyst is sensitive to ultraviolet (UV) light; this is why its photocatalytic activity and quantum efficiency are reduced. To enhance the photocatalytic efficiency in the visible light range as well as to increase the number of the active sites on the crystal surface or inhibit the recombination rate of photogenerated electron–hole pairs electrons, various metal ions were used to modify TiO2. This review paper comprehensively summarizes the latest progress on the modification of TiO2 photocatalyst by a variety of metal ions. Lastly, the future prospects of the modification of TiO2 as a photocatalyst are proposed.
A Titania-Supported Polyoxometalate and Au Cocatalyst for Efficient Photocatalytic Environmental Remediation
Authors: Lin Feng , Yang Yun , Zhang Zhen , Tang Nanfang , Zhu Guangqi
Published: August 2021

Photocatalysis has been considered an effective method for environmental purification and pollutant removal, with many experiments having being performed. The sustainable development of environmentally friendly materials that can photocatalytically oxidize and degrade contaminants is widely studied. Here, we report the results of the photocatalytic oxidation of contaminants (over 99% conversion of the contaminants was achieved) on a tri-component photocatalyst by the simultaneous decoration of Au nanoparticles and a new type of Sn-substituted Keggin structure polyoxometalate (POM) on a TiO2 semiconductor (denoted as AuPT). The light absorption and the electron–hole pair separation capacity of TiO2 was significantly ameliorated on AuPT. The synergistic effect of the Au resonance energy transfer (RET) course and the POM redox transformation can be advantageous to the efficient transmission of photogenerated electrons and holes in a way that achieves efficient photocatalytic oxidation of contaminants.
Oleate Hydratase from Lactobacillus rhamnosus ATCC 53103: A FADH2-Dependent Enzyme with Remarkable Industrial Potential
Authors: Serra Stefano , De Simeis Davide , Marzorati Stefano , Valentino Mattia
Published: August 2021

Recently, we described the preparation of the recombinant oleate hydratase from Lactobacillus rhamnosus ATCC 53103. We observed that the purified C-terminal His-tagged enzyme was completely inactive and the catalytic activity was partially restored only in presence of a large amount of flavin adenine dinucleotide (FAD). In the present work, we assess that this hydratase in the presence of the reduced form of flavin adenine dinucleotide (FADH2) is at least one hundred times as active as in the presence of the same concentration of FAD. By means of two different biochemical processes, we demonstrated unambiguously that oleate hydratase from Lactobacillus rhamnosus ATCC 53103 is a FADH2-dependent enzyme. As a first relevant application of this discovery, we devised a preparative procedure for the stereoselective synthesis of (R)-10-hydroxystearic acid. Accordingly, the hydration of oleic acid (up to 50 g/L) is performed on a multigram scale using the recombinant hydratase and FADH2 generated in situ as cofactor. The produced (R)-10-hydroxystearic acid (ee > 97%) precipitates from the reaction solvent (water/glycerol/ethanol) and is conveniently recovered by simple filtration (>90% yield).
Ultrafiltration of Saithe (Pollachius virens) Protein Hydrolysates and Its Effect on Antioxidative Activity
Authors: Hjellnes Veronica , Rustad Turid , Jensen Ida-Johanne , Eiken Elin , Pettersen Stine Marie , Falch Eva
Published: August 2021

The whitefish industry generates a huge amount of rest raw material, which is currently wasted or underutilized in the production of low-value products such as animal feed. While fish muscle is the primary product of use for human consumption, rest raw material has great potential as a source of protein and bioactive peptides for the production of food ingredients and nutraceuticals. Enzymatic hydrolysis is a biotechnological processing method that can be used to extract protein from fish rest raw material into a protein hydrolysate. This study aimed at investigating the functionality of ultrafiltration as an industrial processing method and its effect on the bioactivity of protein hydrolysates. Protein hydrolysates were produced by enzymatic hydrolysis of saithe (Pollachius virens) head and backbone caught at two separate occasions to investigate the effect of seasonal variations. Ultrafiltration effectively concentrated larger peptides (>4 kDa) and smaller peptides (<4 kDa) in separate fractions, with a protein yield of 31% in the fraction <4 kDa. The unfiltered hydrolysate was found to have a higher antioxidative activity compared to the <4 kDa fraction in ABTS, FRAP, and ORAC assays. These results indicate that ultrafiltration does not effectively increase bioactivity by concentrating small peptides and that bioactivity is dependent on several properties, including interaction with larger peptides.
Phosphorylation-Mediated Molecular Pathway Changes in Human Pituitary Neuroendocrine Tumors Identified by Quantitative Phosphoproteomics
Authors: Li Jiajia , Wen Siqi , Li Biao , Li Na , Zhan Xianquan
Published: August 2021

To investigate the biological role of protein phosphorylation in human nonfunctional pituitary neuroendocrine tumors (NF-PitNETs), proteins extracted from NF-PitNET and control tissues were analyzed with tandem mass tag (TMT)-based quantitative proteomics coupled with TiO2 enrichment of phosphopeptides. A total of 595 differentially phosphorylated proteins (DPPs) with 1412 phosphosites were identified in NF-PitNETs compared to controls (p < 0.05). KEGG pathway network analysis of 595 DPPs identified nine statistically significant signaling pathways, including the spliceosome pathway, the RNA transport pathway, proteoglycans in cancer, SNARE interactions in vesicular transport, platelet activation, bacterial invasion of epithelial cells, tight junctions, vascular smooth muscle contraction, and protein processing in the endoplasmic reticulum. GO analysis revealed that these DPPs were involved in multiple cellular components (CCs), biological processes (BPs), and molecule functions (MFs). The kinase analysis of 595 DPPs identified seven kinases, including GRP78, WSTF, PKN2, PRP4, LOK, NEK1, and AMPKA1, and the substrate of these kinases could provide new ideas for seeking drug targets for NF-PitNETs. The randomly selected DPP calnexin was further confirmed with immunoprecipitation (IP) and Western blot (WB). These findings provide the first DPP profiling, phosphorylation-mediated molecular network alterations, and the key kinase profiling in NF-PitNET pathogenesis, which are a precious resource for understanding the biological roles of protein phosphorylation in NF-PitNET pathogenesis and discovering effective phosphoprotein biomarkers and therapeutic targets and drugs for the management of NF-PitNETs.
Brain Sparing Effect on Neurodevelopment in Children with Intrauterine Growth Restriction: A Systematic Review
Authors: Benítez-Marín María José , Marín-Clavijo Jesús , Blanco-Elena Juan Antonio , Jiménez-López Jesús , González-Mesa Ernesto
Published: August 2021

Background: Fetal growth restriction (FGR) is a pregnancy complication. Multiple studies have connected FGR to poor cognitive development, behavior disorders, and academic difficulties during childhood. Brain sparing has traditionally been defined as an adaptive phenomenon in which the brain obtains the blood flow that it needs. However, this adaptive phenomenon might not have a complete protective effect. This publication aims to systematically review the consequences of brain redistribution on neurodevelopment in children who presented with placental intrauterine growth restriction. Methods: We performed a systematic review according to PRISMA guidelines. It included studies on intrauterine growth restriction or small-for-gestational-age (SGA) fetuses, which middle cerebral artery was measured, and neurodevelopment assessed during childhood. PUBMED and EMBASE databases were searched for relevant published studies. Results: Of the 526 studies reviewed, only 12 were included. Brain sparing was associated with poor cognitive function and lower scores in IQ. Cerebral redistribution was related to better executive function and better behavior at 4 years old but not at 12 years old. Conclusions: We can assume that fetal brain sparing could not be a fully protective phenomenon. We could not find clinical differences in behavioral and executive functions because the results were heterogeneous. Some cognitive abilities could be affected in FGR brain sparing fetuses.
Early Intervention in Unilateral Cerebral Palsy: Let’s Listen to the Families! What Are Their Desires and Perspectives? A Preliminary Family-Researcher Co-Design Study
Authors: Palomo-Carrión Rocío , Romay-Barrero Helena , Pinero-Pinto Elena , Romero-Galisteo Rita-Pilar , López-Muñoz Purificación , Martínez-Galán Inés
Published: August 2021

Cerebral palsy (CP) is a clinical diagnosis based on a combination of clinical and neurological signs, which occurs between the ages of 12 and 24 months. Cerebral palsy or a high risk of cerebral palsy can be accurately predicted before 5–6 months, which is the corrected age. This would allow the initiation of intervention at an early stage. Parents must be more involved in the development and implementation of the early therapy, increasing opportunities for parent–child interaction. The aim of this study was to learn from the perspectives of families with children under 12 months with unilateral cerebral palsy (UCP), what ingredients (barriers and facilitators) should be involved in early intervention so that we could co-design (researchers and families) a multidisciplinary guideline for a global intervention addressed to the needs of the child and the family. Semi-structured interviews were conducted at a time and venue convenient for the families. A total of ten families with experience in early intervention were invited to attend the interview with open questions: (1) What components should early intervention have for a baby diagnosed with UCP? (2) What components should early intervention have for the family? (3) What should the involvement of the family be in early intervention? (4) What barriers included in early intervention should be removed? From the data analysis, three key topics emerged and were subsequently named by focus group participants: (1) UCP early intervention components, (2) family involvement in early intervention of UCP, and (3) removing barriers and creating facilitators within early intervention. The participation of the families (mothers) in the co-design of the necessary ingredients within the scope of a multidisciplinary early intervention guide aimed at children with UCP under 12 months allows learning about their reality and not that of the therapist. The following list highlights the present barriers as perceived by the parents: intervention as spectators, therapeutic goals, clinic environment, and lack of empathy, and the possible facilitators determined by the parents during the implementation comprised teamwork, the family’s goals, motivation during the intervention, and learning at home. Thus, an early intervention program to improve global functionality should address family involvement through multidisciplinary coaching and the modification of the environment, encouraging family goals and family support through the family–therapist team.
Wolf-Hirschhorn Syndrome: Clinical and Genetic Study of 7 New Cases, and Mini Review
Authors: Gavril Eva-Cristiana , Luca Alina Costina , Curpan Alexandrina-Stefania , Popescu Roxana , Resmerita Irina , Panzaru Monica Cristina , Butnariu Lacramioara Ionela , Gorduza Eusebiu Vlad , Gramescu Mihaela , Rusu Cristina
Published: August 2021

Wolf–Hirschhorn syndrome (WHS), a rare disorder determined by distal 4p deletion, is characterized by a pre and postnatal growth retardation, hypotonia, intellectual disability, epilepsy, craniofacial dysmorphism, and congenital fusion anomalies. The clinical aspects are dependent on the deletion’ size. Our aim was to identify rare specific characteristics in a cohort of seven cases with 4p deletion and to assess the utility of Multiplex ligation-dependent probe amplification (MLPA) (cheap and sensitive test)—combined kits—as a diagnostic test and selection tool for cases that require other investigations (chromosomal microarray analysis—CMA, karyotype). For all cases we conducted a clinical examination with the main features identified: facial dysmorphism, intellectual disability, postnatal development delay, cardiac defects and hypotonia. In some cases, we observed seizures, structural brain abnormalities, immunodeficiencies, and renal anomalies. Prenatal growth retardation was detected in a relatively small number of cases, but postnatal growth failure was a constant feature. In all cases, the clinical diagnosis was confirmed by genetic analyses: karyotype and/or MLPA. In conclusion, renal and brain defects, as well as immunodeficiency are rare manifestations and should be looked for. Although CMA is the standard test, in our experience, MLPA is also a reliable screening method as the identified cases were either confirmed by MLPA or selected for further investigations.
Performance of Seven SARS-CoV-2 Self-Tests Based on Saliva, Anterior Nasal and Nasopharyngeal Swabs Corrected for Infectiousness in Real-Life Conditions: A Cross-Sectional Test Accuracy Study
Authors: Homza Miroslav , Zelena Hana , Janosek Jaroslav , Tomaskova Hana , Jezo Eduard , Kloudova Alena , Mrazek Jakub , Murinova Vera , Madar Rastislav
Published: August 2021

Many studies reported good performance of nasopharyngeal swab-based antigen tests for detecting SARS-CoV-2-positive individuals; however, studies independently evaluating the quality of antigen tests utilizing anterior nasal swabs or saliva swabs are still rare, although such tests are widely used for mass testing. In our study, sensitivities, specificities and predictive values of seven antigen tests for detection of SARS-CoV-2 (one using nasopharyngeal swabs, two using anterior nasal swabs and four using saliva) were evaluated. In a setting of a high-capacity testing center, nasopharyngeal swabs for quantitative PCR (qPCR) were taken and, at the same time, antigen testing was performed in accordance with manufacturers’ instructions for the respective tests. In samples where qPCR and antigen tests yielded different results, virus culture was performed to evaluate the presence of the viable virus. Sensitivities and specificities of individual tests were calculated using both qPCR and qPCR corrected for viability as the reference. In addition, calculations were also performed for data categorized according to the cycle threshold and symptomatic status. The test using nasopharyngeal swabs yielded the best results (sensitivity of 80.6% relative to PCR and 91.2% when corrected for viability) while none of the remaining tests (anterior nasal swab or saliva-based tests) came even close to the WHO criteria for overall sensitivity. Hence, we advise caution when using antigen tests with alternative sampling methods without independent validation.
Classification of Sleep Apnea Based on Sub-Band Decomposition of EEG Signals
Authors: Jayaraj Rajeswari , Mohan Jagannath
Published: August 2021

To classify between normal and sleep apnea subjects based on sub-band decomposition of electroencephalogram (EEG) signals. This study comprised 159 subjects obtained from the ISRUC (Institute of System and Robotics—University of Coimbra), Sleep-EDF (European Data Format), and CAP (Cyclic Alternating Pattern) Sleep database, which consists of normal and sleep apnea subjects. The wavelet packet decomposition method was incorporated to categorize the EEG signals into five frequency bands, namely, alpha, beta, delta, gamma, and theta. Entropy and energy (non-linear) for all bands was calculated and as a result, 10 features were obtained for each EEG signal. The ratio of EEG bands included four parameters, including heart rate, brain perfusion, neural activity, and synchronization. In this study, a support vector machine with kernels and random forest classifiers was used for classification. The performance measures demonstrated that the improved results were obtained from the support vector machine classifier with a kernel polynomial order 2. The accuracy (90%), sensitivity (100%), and specificity (83%) with 14 features were estimated using the data obtained from ISRUC database. The proposed study is feasible and seems to be accurate in classifying the subjects with sleep apnea based on the extracted features from EEG signals using a support vector machine classifier.
CD5-Positive B Lymphocytes after Kidney Transplantation
Authors: Zieliński Maciej , Tarasewicz Agnieszka , Zielińska Hanna , Jankowska Magdalena , Sakowska Justyna , Dukat-Mazurek Anna , Moszkowska Grażyna , Rutkowski Bolesław , Dębska-Ślizień Alicja , Trzonkowski Piotr
Published: August 2021

Kidney transplantation is the treatment of choice for end-stage kidney diseases. Unfortunately, kidney allograft recipients rarely develop tolerance or accommodation and require life-long immunosuppression. Among many other regulatory mechanisms, CD5+ B lymphocytes (mainly B-1a) seem to be involved in the process of allograft acceptance. These cells are the major source of natural, low-affinity antibodies, which are polyreactive. Thus, we hypothesized that CD5+ B cells could be referred to as a biomarker in those patients who developed accommodation towards kidney allotransplant. In this study, 52 low-immunized kidney transplant recipients were evaluated for transplant outcome up to 8 y post-transplant. The follow up included anti-HLA antibodies, B cells phenotype and cytokines. We have identified a cohort of recipients who produced alloantibodies (Abs+), which was associated with increased levels of CD5+ B cells, mainly during the first year after transplantation but also later on. Importantly, creatinine levels were comparable between Abs+ and Abs− allorecipients at 2 years after the transplantation and graft survival rate was comparable between these groups even eight years post-transplant. So, it seems that despite the presence of alloantibodies the graft function was sustained when the level of CD5+ B cells was increased. Targeting CD5+ B cells may be a valuable therapeutic option to increase transplant success. The phenotype can be also tried as a biomarker to increase the effectiveness of individualized post-transplant treatments.
Applications of Artificial Intelligence for the Diagnosis of Gastrointestinal Diseases
Authors: Pecere Silvia , Milluzzo Sebastian Manuel , Esposito Gianluca , Dilaghi Emanuele , Telese Andrea , Eusebi Leonardo Henry
Published: August 2021

The development of convolutional neural networks has achieved impressive advances of machine learning in recent years, leading to an increasing use of artificial intelligence (AI) in the field of gastrointestinal (GI) diseases. AI networks have been trained to differentiate benign from malignant lesions, analyze endoscopic and radiological GI images, and assess histological diagnoses, obtaining excellent results and high overall diagnostic accuracy. Nevertheless, there data are lacking on side effects of AI in the gastroenterology field, and high-quality studies comparing the performance of AI networks to health care professionals are still limited. Thus, large, controlled trials in real-time clinical settings are warranted to assess the role of AI in daily clinical practice. This narrative review gives an overview of some of the most relevant potential applications of AI for gastrointestinal diseases, highlighting advantages and main limitations and providing considerations for future development.
Diagnostic Performance of Serum Biomarkers Fibroblast Growth Factor 21, Galectin-3 and Copeptin for Heart Failure with Preserved Ejection Fraction in a Sample of Patients with Type 2 Diabetes Mellitus
Authors: Ianoș Raluca D. , Pop Călin , Iancu Mihaela , Rahaian Rodica , Cozma Angela , Procopciuc Lucia M.
Published: August 2021

More than half of the patients with heart failure have preserved ejection fraction (HFpEF), however evidence shows a mortality rate comparable to those with reduced ejection fraction. The aim of this study was to evaluate whether FGF21, galectin-3 and copeptin can be used as biomarkers to identify HFpEF in patients with confirmed type 2 diabetes mellitus (DM). Sixty-nine diabetic patients were enrolled and divided into two groups: patients with HFpEF (n = 40) and those without HFpEF (n = 29). The ability of the studied biomarkers to discriminate HFpEF cases from non-HFpEF subjects were evaluated by the area under the Receiver Operating Characteristics (ROC) curve and the 95% confidence interval (CI). Compared to patients without heart failure, those with HFpEF had significantly higher levels of FGF21 (mean 146.79 pg/mL vs. 298.98 pg/mL). The AUC value of FGF21 was 0.88, 95% CI: [0.80, 0.96], Se = 85% [70.2, 94.3], Sp = 79.3% [60.3, 92.0], at an optimal cut-off value of 217.40 pg/mL. There was no statistical significance associated with galectin-3 and copeptin between patient cohorts. In conclusion, galectin-3 and copeptin levels were not effective for detecting HFpEF, while FGF21 is a promising biomarker for diagnosing HFpEF in DM patients.