bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Modification of Cysteine with 3-Arylpropriolonitrile Improves the In Vivo Stability of Albumin-Conjugated Urate Oxidase Therapeutic Protein
Authors: Yang Byungseop , Kwon Inchan
Published: September 2021

3-arylpropiolonitriles (APN) are promising alternatives to maleimide for chemo-selective thiol conjugation, because the reaction product has a remarkably hydrolytic stability compared with that of thiol-maleimide reactions in vitro. However, whether cysteine modification with APN enhances stability in vivo compared to thiol-maleimide reactions remains unclear, probably due to the too short in vivo serum half-life of a protein to observe significant cleavage of thiol-maleimide/-APN reaction products. The conjugation of human serum albumin (HSA) to a therapeutic protein reportedly prolongs the in vivo serum half-life. To evaluate the in vivo stability of the thiol-APN reaction product, we prepared HSA-conjugated Arthrobacter globiformis urate oxidase (AgUox), a therapeutic protein for gout treatment. Site-specific HSA conjugation to AgUox was achieved by combining site-specific incorporation of tetrazine containing an amino acid (frTet) into AgUox and a crosslinker containing trans-cyclooctene and either thiol-maleimide (AgUox-MAL-HSA) or -APN chemistry (AgUox-APN-HSA). Substantial cleavage of the thioester of AgUox-MAL-HSA was observed in vitro, whereas no cleavage of the thiol-APN product of AgUox-APN-HSA was observed. Furthermore, the in vivo serum half-life of AgUox-APN-HSA in the late phase was significantly longer than that of AgUox-MAL-HSA. Overall, these results demonstrate that the thiol-APN chemistry enhanced the in vivo stability of the HSA-conjugated therapeutic protein.
Highly Sensitive Luminescent Bioassay Using Recombinant Escherichia coli Biosensor for Rapid Detection of Low Cr(VI) Concentration in Environmental Water
Authors: Wang Guey-Horng , Cheng Chiu-Yu , Tsai Teh-Hua , Chiang Pin-Kuan , Chung Ying-Chien
Published: September 2021

In this study, we constructed a recombinant Escherichia coli strain with different promoters inserted between the chromate-sensing regulator chrB and the reporter gene luxAB to sense low hexavalent chromium (Cr(VI)) concentrations (<0.05 mg/L); subsequently, its biosensor characteristics (sensitivity, selectivity, and specificity) for measuring Cr(VI) in various water bodies were evaluated. The luminescence intensity of each biosensor depended on pH, temperature, detection time, coexisting carbon source, coexisting ion, Cr(VI) oxyanion form, Cr(VI) concentration, cell type, and type of medium. Recombinant lux-expressing E. coli with the T7 promoter (T7-lux-E. coli, limit of detection (LOD) = 0.0005 mg/L) had the highest luminescence intensity or was the most sensitive for Cr(VI) detection, followed by E. coli with the T3 promoter (T3-lux-E. coli, LOD = 0.001 mg/L) and that with the SP6 promoter (SP6-lux-E. coli, LOD = 0.005 mg/L). All biosensors could be used to determine whether the Cr(VI) standard was met in terms of water quality, even when using thawing frozen cells as biosensors after 90-day cryogenic storage. The SP6-lux-E. coli biosensor had the shortest detection time (0.5 h) and the highest adaptability to environmental interference. The T7-lux-E. coli biosensor—with the optimal LOD, a wide measurement range (0.0005–0.5 mg/L), and low deviation (−5.0–7.9%) in detecting Cr(VI) from industrial effluents, domestic effluents, and surface water—is an efficient Cr(VI) biosensor. This unprecedented study is to evaluate recombinant lux E. coli with dissimilar promoters for their possible practice in Cr(VI) measurement in water bodies, and the biosensor performance is clearly superior to that of past systems in terms of detection time, LOD, and detection deviation for real water samples.
Understanding the Functional Expression of
Na+-Coupled SLC4 Transporters in the Renal and Nervous Systems: A Review
Authors: Du Le , Zahra Aqeela , Jia Meng , Wang Qun , Wu Jianping
Published: September 2021

Acid-base homeostasis is crucial for numerous physiological processes. Na+/HCO3− cotransporters (NBCs) belong to the solute carrier 4 (SLC4) family, which regulates intracellular pH as well as HCO3− absorption and secretion. However, knowledge of the structural functions of these proteins remains limited. Electrogenic NBC (NBCe-1) is thought to be the primary factor promoting the precise acid–base equilibrium in distinct cell types for filtration and reabsorption, as well as the function of neurons and glia. NBC dysregulation is strongly linked to several diseases. As such, the need for special drugs that interfere with the transmission function of NBC is becoming increasingly urgent. In this review, we focus on the structural and functional characteristics of NBCe1, and discuss the roles of NBCe1 in the kidney, central nervous system (CNS), and related disorders, we also summarize the research on NBC inhibitors. NBCe1 and the related pathways should be further investigated, so that new medications may be developed to address the related conditions.
Cortical Visual Impairment in Childhood: ‘Blindsight’ and the Sprague Effect Revisited
Authors: Leisman Gerry , Machado Calixto , Melillo Robert
Published: September 2021

The paper discusses and provides support for diverse processes of brain plasticity in visual function after damage in infancy and childhood in comparison with injury that occurs in the adult brain. We provide support and description of neuroplastic mechanisms in childhood that do not seemingly exist in the same way in the adult brain. Examples include the ability to foster the development of thalamocortical connectivities that can circumvent the lesion and reach their cortical destination in the occipital cortex as the developing brain is more efficient in building new connections. Supporting this claim is the fact that in those with central visual field defects we can note that the extrastriatal visual connectivities are greater when a lesion occurs earlier in life as opposed to in the neurologically mature adult. The result is a significantly more optimized system of visual and spatial exploration within the ‘blind’ field of view. The discussion is provided within the context of “blindsight” and the “Sprague Effect”.
A Robust Construction Safety Performance Evaluation Framework for Workers’ Compensation Insurance: A Proposed Alternative to EMR
Authors: Al-Kasasbeh Maha , Abudayyeh Osama , Olimat Hosam , Liu Hexu , Al Mamlook Rabia , Alfoul Bilal Abu
Published: September 2021

The construction work environment remains one of the most hazardous among all industries. Construction injuries directly impact the workers and the work itself, including personal suffering, construction delays, productivity losses, higher insurance premiums, and possible liability suits for all parties involved in the project. The costs resulting from personal injuries, combined with the associated financial impact resulting from schedule disruptions, insurance hikes, and workers’ compensation, can impact a project’s profitability. Many of these impacts can be minimized or avoided through the continuous assessment and improvement of safety policies and practices. This paper aims to propose a new safety assessment methodology that equips insurance companies and construction managers with an optimal mechanism for evaluating the safety performance of construction companies. The proposed model consists of 20 evaluation criteria that are used to establish the efficiency benchmarks and provide comparison feedback for improving the company’s safety plans and procedures. These criteria are determined based on leading and lagging safety performance indicators. The data envelopment analysis (DEA) technique is used as the underlying model to assess the relative efficiency of safety practices objectively. Two illustration case studies are provided to demonstrate the dual effectiveness of the DEA model. The presented research contributes to the body of knowledge by formalizing a robust, effective, and consistent safety performance assessment. The model equips the company with the ability to track both the progression and the retrogression over time and provides feedback on ineffective practices that need more attention. Simultaneously, the model gives them more detailed safety performance information that can replace the current experience modification rating (EMR) approach. It provides insurance companies with an objective and robust evaluation model for selecting optimum rates for their clients. In addition, the data comparison utility offered by the DEA model and its criteria can be helpful for insurance companies to provide effective advice to their clients on which safety aspects to improve in their future strategies.
Degradation Assessment of Natural Stone Claddings over Their Service Life: Comparison between Tehran (Iran) and Lisbon (Portugal)
Authors: Mousavi S. H. , Silva Ana , de Brito Jorge , Ekhlassi A. , Hosseini S. B.
Published: September 2021

Now more than ever, the construction sector is aiming to adopt more sustainable solutions. To achieve this purpose, more durable solutions must be adopted, making rational decisions at the design and maintenance stages regarding the conditions of environmental exposure and use. In this sense, knowledge regarding the service life of building components is crucial. This knowledge should not be a general concept, or a standard value, and adapting practices from one country to another is extremely challenging. In this sense, this study analyses the service life of natural stone claddings. We adopt a methodology initially proposed for Lisbon (Portugal), intending to evaluate its applicability to other geographical contexts, in order to perform a more reliable service life prediction of stone claddings located in Tehran (Iran). An estimated service life of 65 years was obtained for a sample of 162 stone claddings directly adhered to the substrate, located in Tehran, which were analysed by in situ inspections. The impact of different conditions (e.g., type of stone and environmental exposure conditions) on the service life of stone claddings in Tehran was quantified, which revealed that the exposure to environmental agents, such as wind, rain and pollutants, is the main cause of degradation of the natural stone claddings.
Analysis of Photopic and Melanopic Lighting in Teaching Environments
Authors: Ezpeleta Silvia , Orduna-Hospital Elvira , Solana Teresa , Aporta Justiniano , Pinilla Isabel , Sánchez-Cano Ana
Published: September 2021

Daylight and lighting seem to be a key tool for people’s well-being, however, there are no specific and agreed recommendations that address both photopic and melanopic aspects in educational environments. The present work analyzed melanopic light in four teaching environments considering photopic indoor lighting, daylight depending on the window orientation, location of the observer in the room, and their line of view. The façade direction, daylight at 11.00 a.m. for six months from October to March, and the characteristics of each classroom, such as reflectance of the surfaces, location of the luminaires and their spectral and spatial power distributions, or calculation points affecting the melanopic light reaching the corneal vertical plane of a hypothetical control observer were studied. For this evaluation, classrooms were experimentally treated and simulated using DialuxEvo software, and the computer-generated values resembled the experimental values. Once the study was performed, an improvement proposal, based on LED lighting, was made to optimize the classroom lighting considering the melanopic requirements, which we ensured that users who passed through these classrooms had an adequate amount light at any time of the day. Our results simplify to the greatest lighting projects and enable designers to carry out optimized evaluations of specific environments from both the photometric and circadian perspectives.
Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy
Authors: Szudy-Szczyrek Aneta , Ahern Sean , Kozioł Magdalena , Majowicz Daria , Szczyrek Michał , Krawczyk Janusz , Hus Marek
Published: September 2021

Innate lymphoid cells (ILCs) are a recently identified family of lymphocyte-like cells lacking a specific antigen receptor. They are part of the innate immune system. They play a key role in tissue homeostasis and also control inflammatory and neoplastic processes. In response to environmental stimuli, ILCs change their phenotype and functions, and influence the activity of other cells in the microenvironment. ILC dysfunction can lead to a wide variety of diseases, including cancer. ILC can be divided into three subgroups: ILC Group 1, comprising NK cells and ILC1; Group 2, including ILC2 alone; and Group 3, containing Lymphoid Tissue inducers (LTi) and ILC3 cells. While Group 1 ILCs mainly exert antitumour activity, Group 2 and Group 3 ILCs are protumorigenic in nature. A growing body of preclinical and clinical data support the role of ILCs in the pathogenesis of multiple myeloma (MM). Therefore, targeting ILCs may be of clinical benefit. In this manuscript, we review the available data on the role of ILCs in MM immunology and therapy.
Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation
Authors: Nathansen Jacqueline , Meyer Felix , Müller Luise , Schmitz Marc , Borgmann Kerstin , Dubrovska Anna
Published: September 2021

Cancer stem cells (CSCs) are pluripotent and highly tumorigenic cells that can re-populate a tumor and cause relapses even after initially successful therapy. As with tissue stem cells, CSCs possess enhanced DNA repair mechanisms. An active DNA damage response alleviates the increased oxidative and replicative stress and leads to therapy resistance. On the other hand, mutations in DNA repair genes cause genomic instability, therefore driving tumor evolution and developing highly aggressive CSC phenotypes. However, the role of DNA repair proteins in CSCs extends beyond the level of DNA damage. In recent years, more and more studies have reported the unexpected role of DNA repair proteins in the regulation of transcription, CSC signaling pathways, intracellular levels of reactive oxygen species (ROS), and epithelial–mesenchymal transition (EMT). Moreover, DNA damage signaling plays an essential role in the immune response towards tumor cells. Due to its high importance for the CSC phenotype and treatment resistance, the DNA damage response is a promising target for individualized therapies. Furthermore, understanding the dependence of CSC on DNA repair pathways can be therapeutically exploited to induce synthetic lethality and sensitize CSCs to anti-cancer therapies. This review discusses the different roles of DNA repair proteins in CSC maintenance and their potential as therapeutic targets.
Increased Circulating Levels of Galectin Proteins in Patients with Breast, Colon, and Lung Cancer
Authors: Blair Bailey B. , Funkhouser Avery T. , Goodwin Jane L. , Strigenz Alexander M. , Chaballout Basil H. , Martin Julie C. , Arthur Connie M. , Funk Christopher Ronald , Edenfield W. Jeffery , Blenda Anna V.
Published: September 2021

Galectins are proteins with high-affinity β-galactoside-binding sites that function in a variety of signaling pathways through interactions with glycoproteins. The known contributions of galectins-1, -3, -7, -8, and -9 to angiogenesis, metastasis, cell division, and evasion of immune destruction led us to investigate the circulating levels of these galectins in cancer patients. This study compares galectin concentrations by enzyme-linked immunosorbent assay (ELISA) from each stage of breast, lung, and colon cancer. Galectins-1 and -7, which share a prototype structure, were found to have statistically significant increases in breast and lung cancer. Of the tandem-repeat galectins, galectin-8 showed no statistically significant change in these cancer types, but galectin-9 was increased in colon and lung cancer. Galectin-3 is the only chimera-type galectin and was increased in all stages of breast, colon, and lung cancer. In conclusion, there were significant differences in the galectin levels in patients with these cancers compared with healthy controls, and galectin levels did not significantly change from stage to stage. These findings suggest that further research on the roles of galectins early in disease pathogenesis may lead to novel indications for galectin inhibitors.
Comparison between Local Excision and Radical Resection for the Treatment of Rectal Cancer in ypT0-1 Patients: An Analysis of the Clinicopathological Factors and Survival Rates
Authors: Oh Soo Young , Park In Ja , Kim Young IL , Lee Jong-Lyul , Kim Chan Wook , Yoon Yong Sik , Lim Seok-Byung , Yu Chang Sik , Kim Jin Cheon
Published: September 2021

Tumors with good response to preoperative chemoradiotherapy have a favorable prognosis, and these findings raise interest in rectum-sparing strategies. This study aimed to compare the oncologic outcome between local excision and radical resection in ypT0-1 patients and to analyze prognostic factors. Patients with primary rectal cancer diagnosed with ypT0-1 after PCRT followed by either radical resection (RR) or local excision (LE) between 2005 and 2014 were included in this study (LE = 78, RR = 442). Clinicopathologic features, recurrence-free survival (RFS), and OS were analyzed. There was no statistically significant difference in the RFS and OS between the LE and RR groups. Clinical T stage (cT3-4) before PCRT was related to RFS and in the LE group (p = 0.022). Lymph node metastasis (HR: 4.884, 95% confidence interval: 2.451–9.732, p < 0.001) in the final pathology was the only factor associated with RFS, showing a statistically significant difference in the RR group. Lymph node metastasis and age were associated with OS in the RR group. This study confirms the oncologic feasibility of LE in ypT0-1 rectal cancer after PCRT. Additionally, careful patient selection with higher accuracy modalities should be updated to improve treatment outcomes of LE.
The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?
Authors: Oh Byeongsang , Boyle Frances , Pavlakis Nick , Clarke Stephen , Eade Thomas , Hruby George , Lamoury Gillian , Carroll Susan , Morgia Marita , Kneebone Andrew , Stevens Mark , Liu Wen , Corless Brian , Molloy Mark , Kong Benjamin , Libermann Towia , Rosenthal David , Back Michael
Published: September 2021

Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for “cancer” and “immunotherapy/immune checkpoint inhibitor” and “microbiome/microbiota” and/or “fecal microbiome transplant FMT”. The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.
Correction: Pardo-Sánchez et al. Increased Tumor Growth Rate and Mesenchymal Properties of NSCLC-Patient-Derived Xenograft Models during Serial Transplantation. Cancers 2021, 13, 2980
Authors: Pardo-Sánchez José Miguel , Mancheño Nuria , Cerón José , Jordá Carlos , Ansotegui Emilio , Juan Óscar , Palanca Sarai , Cremades Antonio , Gandía Carolina , Farràs Rosa
Published: September 2021

The authors would like to make a correction to their published paper [...]
Catalytic Hydrocracking of Fresh and Waste Frying Oil over Ni- and Mo-Based Catalysts Supported on Sulfated Silica for Biogasoline Production
Authors: Wijaya Karna , Nadia Asma , Dinana Arina , Pratiwi Amalia Febia , Tikoalu Alfrets Daniel , Wibowo Arief Cahyo
Published: September 2021

The synthesis of a sulfated silica catalyst and its modification with Ni and/or Mo metal, along with its application for the hydrocracking of fresh and waste frying oil into biogasoline, were conducted. Synthesis of the catalysts was initiated with the sulfation of silica (SiO2) material by H2SO4 using the sol-gel method. Ni and/or Mo metal were impregnated into the SO4/SiO2 matrix with concentration variations of 1, 2, and 3 wt%. The sulfation process and promotion by Molybdenum (Mo) metal in the modified catalyst successfully increased the catalytic activity and selectivity. Among the catalysts investigated, Ni-SS2 exhibited the best performance for the hydrocracking reaction with waste frying oil. This catalyst was able to achieve a conversion of the liquid product of 71.47% and a selectivity of 58.73% for the gasoline fraction (C5-C12). NiMo-SS3 showed the highest percentage of activity and selectivity in the hydrocracking of fresh frying oil at 51.50 and 43.22 wt%, respectively.
Comment on Weber et al. Mayenite-Based Electride C12A7e−: A Reactivity and Stability Study. Catalysts 2021, 11, 334
Authors: Inoue Yasunori , Kitano Masaaki , Hosono Hideo
Published: September 2021

In 2012, we reported that C12A7 electride (C12A7: e−) significantly promotes the catalytic activity of Ru nanoparticles for ammonia synthesis through the electron donation from the C12A7: e− with a low work function (2.4 eV) to Ru [...]
Effect of Pyrolysis Conditions on the Performance of Co–Doped MOF–Derived Carbon Catalysts for Oxygen Reduction Reaction
Authors: Cui Ning , Bi Kexiao , Sun Wei , Wu Qianqian , Li Yinan , Xu Tiewei , Lv Binjiang , Zhang Shuling
Published: September 2021

MOF–derived porous carbon is a type of promising catalyst to replace expensive Pt–based catalysts for oxygen reduction reaction (ORR). The catalytic activity for ORR depends closely on pyrolysis conditions. In this work, a Co–doped ZIF–8 material was chosen as a research object. The effect of pyrolysis conditions (temperature, heating rate, two–step heating) on the ORR performance of ZIF–derived carbon catalysts was systematically studied. The Co–ZIF–8 catalyst carbonized at 900 °C exhibits better ORR catalytic activity than that carbonized at 800 °C and 1000 °C. Moreover, a low heating rate can enhance catalytic activity. Two–step pyrolysis is proven to be an effective way to improve the performance of catalysts. Reducing the heating rate in the low–temperature stage is more beneficial to the ORR performance, compared to the heating rate in the high–temperature stage. The results show that the Co–ZIF–8 catalyst exhibits the best performance when the precursor was heated to 350 °C at 2 °C/min, and then heated to 900 °C at 5 °C/min. The optimum Co–ZIF–8 catalyst shows a half–wave potential of 0.82 V and a current density of 5.2 mA·cm−2 in 0.1 M KOH solution. It also exhibits high content of defects and good graphitization. TEM mapping shows that Co and N atoms are highly dispersed in the polyhedral carbon skeleton. However, two–step pyrolysis has no significant effect on the stability of the catalyst.
Catalyst Replacement Policy on Multienzymatic Systems: Theoretical Study in the One-Pot Sequential Batch Production of Lactofructose Syrup
Authors: Silva Pablo , Arancibia Vanessa , Cid Daniela , Romero Oscar , Illanes Andrés , Wilson Lorena
Published: September 2021

One-pot systems are an interesting proposal to carry out multi-enzymatic reactions, though this strategy implies establishing an optimal balance between the activity and operability of the involved enzymes. This is crucial for enzymes with marked differences in their operational stability, such as one-pot production of lactofructose syrup from cheese whey permeate, which involves two enzymes—β-galactosidase (β-gal) and glucose isomerase (GI). The aim of this work was to study the behavior of one-pot sequential batch production of lactofructose syrup considering both enzymes immobilized individually, in order to evaluate and design a strategy of replacement of the catalysts according to their stabilities. To this end, the modelling and simulation of the process was carried out, considering simultaneously the kinetics of both reactions and the kinetics of inactivation of both enzymes. For the latter, it was also considered the modulating effect that sugars present in the medium may have on the stability of β-gal, which is the less stable enzyme. At the simulated reaction conditions of 40 °C, pH 7, and 0.46 (IUGI/IUβ-gal), the results showed that considering the stability of β-gal under non-reactive conditions, meaning in absence of the effect of modulation, it is necessary to carry out four replacements of β-gal for each cycle of use of GI. On the other hand, when considering the modulation caused by the sugars on the β-gal stability, the productivity increases up to 23% in the case of the highest modulation factor studied (η = 0.8). This work shows the feasibility of conducting a one-pot operation with immobilized enzymes of quite different operational stability, and that a proper strategy of biocatalyst replacement increases the productivity of the process.
The Effect of Mass Transfer Rate-Time in Bubbles on Removal of Azoxystrobin in Water by Micro-Sized Jet Array Discharge
Authors: Chen Feng , Yang Dezheng , Yu Feng , Kun Yang , Song Ying
Published: September 2021

In this work, the azoxystrobin removal in water by using a micro-size discharge array was investigated, and the removal efficiency can reach as high as 98.1% after 9 min plasma treatment as well as the energy utilization being only 0.73 g/(kW·h). Based on the relationship between the generation of gas bubbles and parameters of gas-liquid discharge, it was found that the variation of applied voltage, gas flow rate and initial solution temperature could cause particle number change, mass transfer rate change and the mass transfer time change, which significantly affected the practical applications at last. The experimental results indicated that when gas flow rate was 0.7 SLM (Standard Liter per Minute) and the initial solution temperature was 297 K with the applied voltage of 8 kV and discharge frequency of 6 kHz, the removal efficiency of azoxystrobin achieved maximum. Based on the analysis results of liquid mass spectrometry, the removal pathways of azoxystrobin were supposed by the decomposed by-products. Toxicity tests indicated that the decomposed products were safe and non-toxic. So, this study may reveal an azoxystrobin degradation mechanism and provide a safe, reliable and effective way for azoxystrobin degradation.
Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine
Authors: Greco Rosaria , Demartini Chiara , Francavilla Miriam , Zanaboni Anna Maria , Tassorelli Cristina
Published: September 2021

The endocannabinoid system exerts an important role in pain processing and modulation. Modulation of the system with hydrolase inhibitors of anandamide (AEA) or 2-arachidonyl glycerol (2-AG) has proved effective in reducing migraine-like features in animal models of migraine. Here, we investigated the effect of dual inhibition of the AEA and 2-AG catabolic pathways in the nitroglycerin-based animal model of migraine. The dual inhibitor JZL195 was administered to rats 2 h after nitroglycerin or vehicle injection. Rats were then exposed to the open field test and the orofacial formalin test. At the end of the tests, they were sacrificed to evaluate calcitonin gene-related peptide (CGRP) serum levels and gene expression of CGRP and cytokines in the cervical spinal cord and the trigeminal ganglion. The dual inhibitor significantly reduced the nitroglycerin-induced trigeminal hyperalgesia and pain-associated behavior, possibly via cannabinoid 1 receptors-mediated action, but it did not change the hypomotility and the anxiety behaviors induced by nitroglycerin. The decreased hyperalgesia was associated with a reduction in CGRP and cytokine gene expression levels in central and peripheral structures and reduced CGRP serum levels. These data suggest an antinociceptive synergy of the endocannabinoid action in peripheral and central sites, confirming that this system participates in reduction of cephalic pain signals.
Caspase-Dependent HMGB1 Release from Macrophages Participates in Peripheral Neuropathy Caused by Bortezomib, a Proteasome-Inhibiting Chemotherapeutic Agent, in Mice
Authors: Tsubota Maho , Miyazaki Takaya , Ikeda Yuya , Hayashi Yusuke , Aokiba Yui , Tomita Shiori , Sekiguchi Fumiko , Wang Dengli , Nishibori Masahiro , Kawabata Atsufumi
Published: September 2021

Given the role of macrophage-derived high mobility group box 1 (HMGB1) in chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel, we analyzed the role of HMGB1 and macrophages in the CIPN caused by bortezomib, a proteasome-inhibiting chemotherapeutic agent used for the treatment of multiple myeloma. Repeated administration of bortezomib caused CIPN accompanied by early-stage macrophage accumulation in the dorsal root ganglion. This CIPN was prevented by an anti-HMGB1-neutralizing antibody, thrombomodulin alfa capable of accelerating thrombin-dependent degradation of HMGB1, antagonists of the receptor for advanced glycation end-products (RAGE) and C-X-C motif chemokine receptor 4 (CXCR4), known as HMGB1-targeted membrane receptors, or macrophage depletion with liposomal clodronate, as reported in a CIPN model caused by paclitaxel. In macrophage-like RAW264.7 cells, bortezomib as well as MG132, a well-known proteasome inhibitor, caused HMGB1 release, an effect inhibited by caspase inhibitors but not inhibitors of NF-κB and p38 MAP kinase, known to mediate paclitaxel-induced HMGB1 release from macrophages. Bortezomib increased cleaved products of caspase-8 and caused nuclear fragmentation or condensation in macrophages. Repeated treatment with the caspase inhibitor prevented CIPN caused by bortezomib in mice. Our findings suggest that bortezomib causes caspase-dependent release of HMGB1 from macrophages, leading to the development of CIPN via activation of RAGE and CXCR4.
Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair—A Systematic Review of In Vivo Studies
Authors: Lu Victor , Tennyson Maria , Zhang James , Khan Wasim
Published: September 2021

Tendon and ligament injury poses an increasingly large burden to society. This systematic review explores whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon/ligament repair in vivo. On 26 May 2021, a systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase, to identify all studies that utilised MSC-EVs for tendon/ligament healing. Studies administering EVs isolated from human or animal-derived MSCs into in vivo models of tendon/ligament injury were included. In vitro, ex vivo, and in silico studies were excluded, and studies without a control group were excluded. Out of 383 studies identified, 11 met the inclusion criteria. Data on isolation, the characterisation of MSCs and EVs, and the in vivo findings in in vivo models were extracted. All included studies reported better tendon/ligament repair following MSC-EV treatment, but not all found improvements in every parameter measured. Biomechanics, an important index for tendon/ligament repair, was reported by only eight studies, from which evidence linking biomechanical alterations to functional improvement was weak. Nevertheless, the studies in this review showcased the safety and efficacy of MSC-EV therapy for tendon/ligament healing, by attenuating the initial inflammatory response and accelerating tendon matrix regeneration, providing a basis for potential clinical use in tendon/ligament repair.
Nano-Infrared Imaging of Primary Neurons
Authors: Freitas Raul O. , Cernescu Adrian , Engdahl Anders , Paulus Agnes , Levandoski João E. , Martinsson Isak , Hebisch Elke , Sandt Christophe , Gouras Gunnar Keppler , Prinz Christelle N. , Deierborg Tomas , Borondics Ferenc , Klementieva Oxana
Published: September 2021

Alzheimer’s disease (AD) accounts for about 70% of neurodegenerative diseases and is a cause of cognitive decline and death for one-third of seniors. AD is currently underdiagnosed, and it cannot be effectively prevented. Aggregation of amyloid-β (Aβ) proteins has been linked to the development of AD, and it has been established that, under pathological conditions, Aβ proteins undergo structural changes to form β-sheet structures that are considered neurotoxic. Numerous intensive in vitro studies have provided detailed information about amyloid polymorphs; however, little is known on how amyloid β-sheet-enriched aggregates can cause neurotoxicity in relevant settings. We used scattering-type scanning near-field optical microscopy (s-SNOM) to study amyloid structures at the nanoscale, in individual neurons. Specifically, we show that in well-validated systems, s-SNOM can detect amyloid β-sheet structures with nanometer spatial resolution in individual neurons. This is a proof-of-concept study to demonstrate that s-SNOM can be used to detect Aβ-sheet structures on cell surfaces at the nanoscale. Furthermore, this study is intended to raise neurobiologists’ awareness of the potential of s-SNOM as a tool for analyzing amyloid β-sheet structures at the nanoscale in neurons without the need for immunolabeling.
Atopic Manifestations in Children Born Preterm: A Long-Term Observational Study
Authors: Pagano Federica , Conti Maria Giulia , Boscarino Giovanni , Pannucci Chiara , Dito Lucia , Regoli Daniela , Di Chiara Maria , Battaglia Giuseppe , Prota Rita , Cinicola Bianca , Zicari Anna Maria , Aloi Marina , Oliva Salvatore , Terrin Gianluca
Published: September 2021

(1) Background: Preterm birth exposes the infant to the known risk factors for atopic diseases. We aimed to study the neonatal risk factors and to describe the clinical manifestations of atopy, including the march of symptoms, in a cohort of preschool children born preterm. (2) Methods: We enrolled neonates with gestational age < 32 weeks or birth weight < 1500 g. We classified patients in cases and controls according to the presence of at least one atopic manifestation. (3) Results: We observed 72 cases and 93 controls. Multivariate models showed that the administration of more than one cycle of antibiotics (B 0.902, p = 0.026) and gestational diabetes (B 1.207, p = 0.035) influence the risk of atopy in babies born preterm. In addition, risk of atopic dermatitis was influenced by gestational age < 29 weeks (B −1.710, p = 0.025) and gestational diabetes (B 1.275, p = 0.027). The risk of wheeze was associated with familiarity for asthma (B 1.392, p = 0.022) and the administration of more than one cycle of antibiotics (B 0.969, p = 0.025). We observed a significant reduction in the rate of atopic manifestation after 2 years of life (33.9% vs. 23.8%, p < 0.05). (4) Conclusions: Modifiable (gestational diabetes, antibiotics use) and unmodifiable (familiarity for asthma) conditions influence the risk of atopy in babies born preterm. Extreme prematurity reduces the risk of atopic dermatitis. Preterm babies showed a peculiar atopic march.
Iatrogenic Blood Loss in Very Low Birth Weight Infants and Transfusion of Packed Red Blood Cells in a Tertiary Care Neonatal Intensive Care Unit
Authors: Aboalqez Ahmed , Deindl Philipp , Ebenebe Chinedu Ulrich , Singer Dominique , Blohm Martin Ernst
Published: September 2021

An adequate blood volume is important for neonatal adaptation. The study objective was to quantify the cumulative iatrogenic blood loss in very low birth weight (VLBW) infants by blood sampling and the necessity of packed red cell transfusions from birth to discharge from the hospital. In total, 132 consecutive VLBW infants were treated in 2019 and 2020 with a median birth weight of 1180 g (range 370–1495 g) and a median length of stay of 54 days (range 0–154 days) were included. During the initial four weeks of life, the median absolute amount of blood sampling was 16.5 mL (IQR 12.3–21.1 mL), sampling volume was different with 14.0 mL (IQR 12.1–16.2 mL) for non-transfused infants and 21.6 mL (IQR 17.5–29.4 mL) for transfused infants. During the entire length of stay, 31.8% of the patients had at least one transfusion. In a generalized logistic regression model, the cumulative amount of blood sampling (p < 0.01) and lower hematocrit at birth (p = 0.02) were independent predictors for the necessity of blood transfusion. Therefore, optimized patient blood management in VLBW neonates should include sparse blood sampling to avoid iatrogenic blood loss.
Factors Associating with the Segmental Postural Control during Sitting in Moderate-to-Late Preterm Infants via Longitudinal Study
Authors: Sangkarit Noppharath , Siritaratiwat Wantana , Bennett Surussawadi , Tapanya Weerasak
Published: September 2021

(1) Background: biological variables and particular child rearing practices could be linked to postural control and rates of sitting onset. The segmental Assessment of Trunk Control (SATCo) is currently used as an assessment of postural control with a specific segment on premature infants. However, the association between related factors and segmental trunk control during sitting development in preterm infants via longitudinal assessments is still limited. Objective: to investigate the associations between biological and child rearing factors and segmental trunk control during sitting in moderate to late premature birth from the age of 4 months to age of independent sitting attainment. (2) Methods: forty-two infants born between 32 and 36 weeks of gestation were recruited. Their segmental trunk control was assessed using the SATCo. Their related factors were recorded from the age of 4 months to early onset of independent sitting attainment. The generalised estimating equation (GEE) model was used to identify the association between related factors and the SATCo with a linear distribution. (3) Results: cause of prematurity, baby rocking recliner and baby walker usage were negative factors, while play in a sitting position, opportunity to move on a traditional mat and sleep mattress were positive factors contributing to the segmental control of the trunk. (4) Conclusions: the experience of sitting on different surfaces and an opportunity to sit without support during the child rearing period from age of 4 months corrected could be positive factors associating with the segmental trunk control in moderate-to-late premature infants.
Cementless Ceramic-on-Ceramic Total Hip Replacement in Children and Adolescents
Authors: Trisolino Giovanni , Stallone Stefano , Castagnini Francesco , Bordini Barbara , Cosentino Monica , Lucchini Stefano , Zarantonello Paola , Ferrari Daniele , Dallari Dante , Traina Francesco
Published: September 2021

Background: total hip replacement (THR) is a rare surgical option in children and adolescents with disabling hip diseases. The aim of this study is to report results from a retrospective cohort of patients aged 18 years or less who underwent cementless Ceramic-on-Ceramic (CoC) THR at a single institution, investigating clinical and radiographic outcomes, survival rates, and reasons for revision of the implants. Materials and methods: we queried the Registry of Prosthetic Orthopedic Implants (RIPO) to identify all children and adolescents undergoing THR between 2000 and 2019 at a single Institution. Inclusion criteria were patients undergoing cementless CoC THR, aged less than 18 years at surgery, followed for at least 2 years. Sixty-eight patients (74 hips) matched all the inclusion criteria and were enrolled in the study. We assessed the clinical and radiographic outcomes, the rate of complications, the survival rate, and reasons for revision of the implants. Results: The mean follow-up was 6.6 ± 4.4 years (range 2–20). The most frequent reason for THR was post-traumatic or chemotherapy-induced avascular necrosis (38%). The overall survival rate of the cohort was 97.6% (95% CI: 84.9–99.7%) at 5 years of follow-up, 94.4% (95% CI: 79.8–98.6%) at 10 years and 15 years of follow-up. Two THR in two patients (2.7%) required revision. With the numbers available, Cox regression analysis could not detect any significant interaction between preoperative or intraoperative variables and implant survivorship (p-value 0.242 to 0.989).” The average HOOS was 85 ± 14.3 (range 30.6–100). Overall, 23 patients (48%) reported excellent HOOS scores (>90 points), 21 patients (44%) reported acceptable HOOS scores (60–90 points) while 4 patients (8%) reported poor outcomes (<60 points). Twenty-one patients (43%) were regularly involved into moderate- to high-intensity sport activities (UCLA ≥ 6). Conclusions: Cementless CoC THR is a successful procedure in children and teenagers, having demonstrated high implant survivorship and low rates of complications and failure. A meticulous preoperative planning and implant selection is mandatory, to avoid implant malposition, which is the main reason of failure and revision in these cases. Further studies are needed to assess the impact of the THR on the psychosocial wellbeing of teenagers, as well as risks and benefits and cost-effectiveness in comparison to the hip preserving surgical procedures.
The Effect of Climate Variability on Maize Production in the Ejura-Sekyedumase Municipality, Ghana
Authors: Cudjoe Godwin P. , Antwi-Agyei Phillip , Gyampoh Benjamin A.
Published: September 2021

Agriculture is one of the sectors most susceptible to changes in climatic conditions. The impact is even stronger in Africa, where rain-fed agriculture is vital for daily subsistence, but where adaptive capacity is low. It is therefore crucial to increase the understanding of the actual climate change dynamics on agricultural productivity. This study examined the effects of changes in climatic variables such as rainfall and temperature on maize production in the Ejura-Sekyedumase Municipality, Ghana. Regression, chi-square and trend analyses were used to establish the relationship between climate variables (rainfall and temperature) and maize yield in the study area. This was supplemented with participatory household interviews with 120 farmers to understand the perception of farmers on rainfall and temperature patterns. The results from the study respondents and trend analysis show that rainfall is shorter in terms of duration and less predictable, whilst temperature has increased. The findings suggest that the general relationship between rainfall, temperature and maize yield is such that maize yield increased with increasing rainfall of the right amount and distribution pattern and decreased with increasing temperature. The study concludes that climate variability and/or change is evident in the study area and its effect on maize yield is severe.
Microstructure Characterization of Ni-Based Alloys for Packaging Application upon Long-Term Heat Treatment
Authors: Ren Jianbing , Ma Yilong , Li Kejian
Published: September 2021

In this study, an investigation was conducted to examine two types of Ni-based alloys upon long-term heat treatment and compare their grains, surface corrosion layers and microhardness values. The working environment of the tested samples was a temperature of 1000 °C for 5000 h. Two samples, respectively, contained low (~8 wt.%) and high (~16 wt.%) contents of Mo, and the low-Mo-content sample contained Nb (~4 wt.%) and other elements. The grains, precipitates, corrosion layers and microhardness values of the samples before and after heat treatment were determined by scanning electron microscopy, electron back-scattered diffraction, transmission electron microscopy, X-ray diffraction analysis and Vickers hardness tests. The results revealed that the grain was surprisingly stable in the sample with the higher Mo content; after heat treatment, the grain size was ~35 μm, which was similar to the grain size before heat treatment. Moreover, for the sample with the higher Mo content, the microhardness was found to be higher, especially after long-term high-temperature treatment, which is of great significance for the long service life of materials.
Nanomaterial-Based Drug Targeted Therapy for Cardiovascular Diseases: Ischemic Heart Failure and Atherosclerosis
Authors: Haba Mihai Ștefan Cristian , Șerban Dragomir N. , Șerban Lăcrămioara , Tudorancea Ivona Maria , Haba Raluca Maria , Mitu Ovidiu , Iliescu Radu , Tudorancea Ionuț
Published: September 2021

Cardiovascular diseases (CVDs) represent the most important epidemic of our century, with more than 37 million patients globally. Furthermore, CVDs are associated with high morbidity and mortality, and also increased hospitalization rates and poor quality of life. Out of the plethora of conditions that can lead to CVDs, atherosclerosis and ischemic heart disease are responsible for more than 2/3 of the cases that end in severe heart failure and finally death. Current therapy strategies for CVDs focus mostly on symptomatic benefits and have a moderate impact on the underlying physiopathological mechanisms. Modern therapies try to approach different physiopathological pathways such as reduction of inflammation, macrophage regulation, inhibition of apoptosis, stem-cell differentiation and cellular regeneration. Recent technological advances make possible the development of several nanoparticles used not only for the diagnosis of cardiovascular diseases, but also for targeted drug delivery. Due to their high specificity, nanocarriers can deliver molecules with poor pharmacokinetics and dynamics such as: peptides, proteins, polynucleotides, genes and even stem cells. In this review we focused on the applications of nanoparticles in the diagnosis and treatment of ischemic heart failure and atherosclerosis.