bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Extracellular Ca2+ and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells
Authors: Kulbacka Julita , Rembiałkowska Nina , Szewczyk Anna , Moreira Helena , Szyjka Anna , Girkontaitė Irutė , Grela Kamil P. , Novickij Vitalij
Published: June 2021

(1) Background: Calcium electroporation (CaEP) is based on the application of electrical pulses to permeabilize cells (electroporation) and allow cytotoxic doses of calcium to enter the cell. (2) Methods: In this work, we have used doxorubicin-resistant (DX) and non-resistant models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVo/DX), and investigated the susceptibility of the cells to extracellular Ca2+ and electric fields in the 20 ns–900 ns pulse duration range. (3) Results: We have observed that colon cancer cells were less susceptible to PEF than breast cancer cells. An extracellular Ca2+ (2 mM) with PEF was more disruptive for DX-resistant cells. The expression of glycoprotein P (MDR1, P-gp) as a drug resistance marker was detected by the immunofluorescent (CLSM) method and rhodamine-123 efflux as an MDR1 activity. MDR1 expression was not significantly modified by nanosecond electroporation in multidrug-resistant cells, but a combination with calcium ions significantly inhibited MDR1 activity and cell viability. (4) Conclusions: We believe that PEF with calcium ions can reduce drug resistance by inhibiting drug efflux activity. This phenomenon of MDR mechanism disruption seems promising in anticancer protocols.
Predicting Postoperative Complications in Cancer Patients: A Survey Bridging Classical and Machine Learning Contributions to Postsurgical Risk Analysis
Authors: Gonçalves Daniel M. , Henriques Rui , Costa Rafael S.
Published: June 2021

Postoperative complications can impose a significant burden, increasing morbidity, mortality, and the in-hospital length of stay. Today, the number of studies available on the prognostication of postsurgical complications in cancer patients is growing and has already created a considerable set of dispersed contributions. This work provides a comprehensive survey on postoperative risk analysis, integrating principles from classic risk scores and machine-learning approaches within a coherent frame. A qualitative comparison is offered, taking into consideration the available cohort data and the targeted postsurgical outcomes of morbidity (such as the occurrence, nature or severity of postsurgical complications and hospitalization needs) and mortality. This work further establishes a taxonomy to assess the adequacy of cohort studies and guide the development and assessment of new learning approaches for the study and prediction of postoperative complications.
Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis
Authors: Krupenko Natalia I. , Sharma Jaspreet , Fogle Halle M. , Pediaditakis Peter , Strickland Kyle C. , Du Xiuxia , Helke Kristi L. , Sumner Susan , Krupenko Sergey A.
Published: June 2021

Cytosolic 10-formyltetrahydrofolate dehydrogenase (ALDH1L1) is commonly downregulated in human cancers through promoter methylation. We proposed that ALDH1L1 loss promotes malignant tumor growth. Here, we investigated the effect of the Aldh1l1 mouse knockout (Aldh1l1−/−) on hepatocellular carcinoma using a chemical carcinogenesis model. Fifteen-day-old male Aldh1l1 knockout mice and their wild-type littermate controls (Aldh1l1+/+) were injected intraperitoneally with 20 μg/g body weight of DEN (diethylnitrosamine). Mice were sacrificed 10, 20, 28, and 36 weeks post-DEN injection, and livers were examined for tumor multiplicity and size. We observed that while tumor multiplicity did not differ between Aldh1l1−/− and Aldh1l1+/+ animals, larger tumors grew in Aldh1l1−/− compared to Aldh1l1+/+ mice at 28 and 36 weeks. Profound differences between Aldh1l1−/− and Aldh1l1+/+ mice in the expression of inflammation-related genes were seen at 10 and 20 weeks. Of note, large tumors from wild-type mice showed a strong decrease of ALDH1L1 protein at 36 weeks. Metabolomic analysis of liver tissues at 20 weeks showed stronger differences in Aldh1l1+/+ versus Aldh1l1−/− metabotypes than at 10 weeks, which underscores metabolic pathways that respond to DEN in an ALDH1L1-dependent manner. Our study indicates that Aldh1l1 knockout promoted liver tumor growth without affecting tumor initiation or multiplicity.
Immune Circuits to Shape Natural Killer Cells in Cancer
Authors: Mattiola Irene
Published: June 2021

Natural killer (NK) cells are innate lymphoid cells playing an important role in anti-cancer immunity. NK cells are efficient in controlling the spreading of metastasis but are not very powerful in fighting against primary tumors. The NK cell capability to infiltrate and persist in the tumor microenvironment and to exert their antitumoral functions is often limited by tumor escape mechanisms. These tumor-mediated strategies not only induce NK cell tolerance but also interfere with the NK cell-dependent immune networking. This review will provide an overview of the tumor escape mechanisms impacting NK cells, identify the immune circuits regulating the NK cell-dependent antitumor immunity and revise the emerging therapeutic approaches to unleash NK cells in cancer.
The Risk Factors for Radiation Pneumonitis after Single-Fraction Carbon-Ion Radiotherapy for Lung Cancer or Metastasis
Authors: Ono Takashi , Yamamoto Naoyoshi , Nomoto Akihiro , Nakajima Mio , Iwai Yuma , Isozaki Yuka , Kasuya Goro , Ishikawa Hitoshi , Nemoto Kenji , Tsuji Hiroshi
Published: June 2021

There are no studies on the risk factors of radiation pneumonitis (RP) after carbon-ion radiotherapy at a dose of 50 Gy (relative biological effectiveness (RBE)) in a single fraction. The objective of this study was to identify factors associated with RP after radiotherapy, including dose–volume parameters. Ninety-eight patients without a history of thoracic radiotherapy who underwent treatment for solitary lung tumors between July 2013 and April 2016 were retrospectively analyzed. Treatment was planned using Xio-N. The median follow-up duration was 53 months, and the median clinical target volume was 32.3 mL. Three patients developed grade 2 RP, and one patient developed grade 3 interstitial pneumonitis. None of the patients developed grade 4 or 5 RP. The dose-volume parameters of the normal lung irradiated at least with 5–30 Gy (RBE), and the mean lung dose was significantly lower in patients with grade 0–1 RP than in those with grade 2–3 RP. Pretreatment with higher SP-D and interstitial pneumonitis were significant factors for the occurrence of symptomatic RP. The present study showed a certain standard for single-fraction carbon-ion radiotherapy that does not increase the risk of RP; however, further validation studies are needed.
Tumor Microenvironment-Derived Metabolites: A Guide to Find New Metabolic Therapeutic Targets and Biomarkers
Authors: García-Cañaveras Juan C. , Lahoz Agustín
Published: June 2021

Metabolic reprogramming is a hallmark of cancer that enables cancer cells to grow, proliferate and survive. This metabolic rewiring is intrinsically regulated by mutations in oncogenes and tumor suppressors, but also extrinsically by tumor microenvironment factors (nutrient and oxygen availability, cell-to-cell interactions, cytokines, hormones, etc.). Intriguingly, only a few cancers are driven by mutations in metabolic genes, which lead metabolites with oncogenic properties (i.e., oncometabolites) to accumulate. In the last decade, there has been rekindled interest in understanding how dysregulated metabolism and its crosstalk with various cell types in the tumor microenvironment not only sustains biosynthesis and energy production for cancer cells, but also contributes to immune escape. An assessment of dysregulated intratumor metabolism has long since been exploited for cancer diagnosis, monitoring and therapy, as exemplified by 18F-2-deoxyglucose positron emission tomography imaging. However, the efficient delivery of precision medicine demands less invasive, cheaper and faster technologies to precisely predict and monitor therapy response. The metabolomic analysis of tumor and/or microenvironment-derived metabolites in readily accessible biological samples is likely to play an important role in this sense. Here, we review altered cancer metabolism and its crosstalk with the tumor microenvironment to focus on energy and biomass sources, oncometabolites and the production of immunosuppressive metabolites. We provide an overview of current pharmacological approaches targeting such dysregulated metabolic landscapes and noninvasive approaches to characterize cancer metabolism for diagnosis, therapy and efficacy assessment.
Inhibition of miR-222 by Oncolytic Adenovirus-Encoded miRNA Sponges Promotes Viral Oncolysis and Elicits Antitumor Effects in Pancreatic Cancer Models
Authors: Raimondi Giulia , Gea-Sorlí Sabrina , Otero-Mateo Marc , Fillat Cristina
Published: June 2021

Oncolytic adenoviruses (OA) are envisioned as a therapeutic option for patients with cancer, designed to preferentially replicate in cancer cells. However, the high number of genetic alterations in tumors can generate a context in which adenoviruses have difficulties replicating. Abnormal miRNAs expression is a trademark of pancreatic cancer, with several oncogenic miRNAs playing essential roles in cancer-associated pathways. The perturbed miRNome induces reprogramming of gene expression in host cells that can impact the complex interplay between cellular processes and viral replication. We have studied the effects of overexpressed miRNAs on oncolytic adenoviral activity and identified miRNAs modulators of adenoviral oncolysis in pancreatic cancer cells. Inhibition of the highly upregulated miR-222 sensitized cancer cells to oncolysis. To provide a therapeutic application to this insight, we engineered the oncolytic adenovirus AdNuPARmE1A with miR-222 binding sites, working as sponges to withdraw the miRNA from the cellular environment. AdNuPAR-E-miR222-S mediated-decrease of miR-222 expression in pancreatic cancer cells strongly improved the viral yield and enhanced the adenoviral cytotoxic effects. Antitumoral studies confirmed a high activity for AdNuPARmE1A-miR222-S in vivo, controlling tumor progression more effectively than the scrambled control virus in xenografts. We demonstrated that the increased antitumor potency of the novel oncolytic virus resulted from the combinatory effects of miR-222 oncomiR inhibition and the restoration of miR-222 target genes activity enhancing viral fitness.
Synthesis Design of Electronegativity Dependent WO3 and WO3∙0.33H2O Materials for a Better Understanding of TiO2/WO3 Composites’ Photocatalytic Activity
Authors: Székely István , Kedves Endre-Zsolt , Pap Zsolt , Baia Monica
Published: June 2021

The design of a semiconductor or a composite semiconductor system—with applications in materials science—is complex because its morphology and structure depend on several parameters. These parameters are the precursor type, solvent, pH of the solution, synthesis approach, or shaping agents. This study gives meaningful insight regarding the synthesis design of such WO3 materials. By systematically alternating the precursor (sodium tungstate dihydrate—NWH, or ammonium tungstate hydrate—AMT), subsequently shaping the agents (halide salts—NaX, KX, or hydrohalic acids—HX; X = F−, Cl−, Br−, I−), we have obtained WO3 semiconductors by hydrothermal treatment, which in composite systems can enhance the commercial TiO2 photocatalytic activity. We investigated three sample series: WO3-NWH-NaX/WO3-NWH-KX and, subsequently, WO3-AMT-HX. The presence of W+5 centers was evidenced by Raman and X-ray photoelectron spectroscopy. W+5 and W+6 species affected the band gap values of the NaX and KX series; a higher percentage of W+5 and, subsequently, W+6 caused a redshift, while, regarding the HX series, it led to a blue shift. Increased electronegativity of the halide anions has an unfavorable effect on the composites’ photoactivity. In contrast, in the case of hydrohalic acids, it had a positive impact.
Editorial—Special Issue “Catalysis for Energy Production”
Authors: Goula Maria A. , Polychronopoulou Kyriaki
Published: June 2021

The rapid increase in anthropogenic greenhouse gas concentrations in the last several decades means that the effects of climate change are fast becoming the familiar horsemen of a planetary apocalypse. Catalysis, one of the pillars of the chemical and petrochemical industries, will play a critical role in the effort to reduce the flow of greenhouse gases into the atmosphere. This Special Issue is timely, as it provides a collection of high-quality manuscripts in a diverse range of topics, which include the production of green hydrogen via water electrolysis, the steam reforming of ethanol, propane or glycerol, the dry reforming of methane, and the autothermal reforming of diesel surrogate fuel. The topic of the transformation of biomass waste to chemicals is also well represented as is the tackling of CO2 emissions via novel utilization technologies. The Editors are grateful to all authors for their valuable contributions and confident that this Special Issue will prove valuable to scholars, university professors and students alike.
In Vitro Digestibility and Antioxidant Activity of Plant Protein Isolate and Milk Protein Concentrate Blends
Authors: Khalesi Mohammadreza , FitzGerald Richard J.
Published: June 2021

The replacement of animal with plant proteins in human diets has been increasing in recent years. The impact of blending milk protein concentrate (MPC) with protein isolates from soy (SPI), rice (RPI) and pea (PPI) on the in vitro digestibility and antioxidant activity of the resultant blends was investigated. Different plant protein–MPC blends (i.e., SPI–MPC (25:75), RPI–MPC (50:50) and PPI–MPC (25:75)) were analyzed. The lowest protein digestibility corrected amino acid score (PDCAAS) was associated with RPI (0.70), while the blends had PDCAAS values above 1.00 demonstrating the high digestibility of the proteins in the blends studied. An in vitro simulated gastrointestinal digestion was carried out on the samples. The degree of hydrolysis and gel permeation high performance liquid chromatography profiles showed that the SPI–MPC blend was more extensively digested in the gastric phase compared with the two other blends, while the PPI–MPC and RPI–MPC blends were mainly digested during the intestinal phase. The SPI–MPC digested blend had the highest 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity having a half maximal effective concentration (EC50) of 0.10 ± 0.01 mg/mL. The findings show that blends of plant protein with MPC had higher in vitro digestibility and antioxidant activity compared to the individual plant protein isolates.
Ionic Liquid-Assisted Synthesis of Ag3PO4 Spheres for Boosting Photodegradation Activity under Visible Light
Authors: Zhang Beibei , Zhang Lu , Zhang Yulong , Liu Chao , Xia Jiexiang , Li Huaming
Published: June 2021

In this work, a simple chemical precipitation method was employed to prepare spherical-like Ag3PO4 material (IL-Ag3PO4) with exposed {111} facet in the presence of reactive ionic liquid 1-butyl-3-methylimidazole dihydrogen phosphate ([Omim]H2PO4). The crystal structure, microstructure, optical properties, and visible-light photocatalytic performance of as-prepared materials were studied in detail. The addition of ionic liquids played a crucial role in forming spherical-like morphology of IL-Ag3PO4 sample. Compared with traditional Ag3PO4 material, the intensity ratio of {222}/{200} facets in XRD pattern of IL-Ag3PO4 was significantly enhanced, indicating the main {111} facets exposed on the surface of IL-Ag3PO4 sample. The presence of exposed {111} facet was advantageous for facilitating the charge carrier transfer and separation. The light-harvesting capacity of IL-Ag3PO4 was larger than that of Ag3PO4. The photocatalytic activity of samples was evaluated by degrading rhodamine B (RhB) and p-chlorophenol (4-CP) under visible light. The photodegradation efficiencies of IL-Ag3PO4 were 1.94 and 2.45 times higher than that of Ag3PO4 for RhB and 4-CP removal, respectively, attributing to a synergy from the exposed {111} facet and enhanced photoabsorption. Based on active species capturing experiments, holes (h+), and superoxide radical (•O2−) were the main active species for visible-light-driven RhB photodegradation. This study will provide a promising prospect for designing and synthesizing ionic liquid-assisted photocatalysts with a high efficiency.
Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting
Authors: Puccetti Matteo , Pariano Marilena , Renga Giorgia , Santarelli Ilaria , D’Onofrio Fiorella , Bellet Marina M. , Stincardini Claudia , Bartoli Andrea , Costantini Claudio , Romani Luigina , Ricci Maurizio , Giovagnoli Stefano
Published: June 2021

Inflammation plays a major role in the pathophysiology of cystic fibrosis (CF), a multisystem disease. Anti-inflammatory therapies are, therefore, of interest in CF, provided that the inhibition of inflammation does not compromise the ability to fight pathogens. Here, we assess whether indole-3-aldehyde (3-IAld), a ligand of the aryl hydrocarbon receptor (AhR), may encompass such an activity. We resorted to biopharmaceutical technologies in order to deliver 3-IAld directly into the lung, via dry powder inhalation, or into the gut, via enteric microparticles, in murine models of CF infection and inflammation. We found the site-specific delivery of 3-IAld to be an efficient strategy to restore immune and microbial homeostasis in CF organs, and mitigate lung and gut inflammatory pathology in response to fungal infections, in the relative absence of local and systemic inflammatory toxicity. Thus, enhanced delivery to target organs of AhR agonists, such as 3-IAld, may pave the way for the development of safe and effective anti-inflammatory agents in CF.
Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders
Authors: Mor Adrian , Tankiewicz-Kwedlo Anna , Krupa Anna , Pawlak Dariusz
Published: June 2021

Neurodegenerative disorders are chronic and life-threatening conditions negatively affecting the quality of patients’ lives. They often have a genetic background, but oxidative stress and mitochondrial damage seem to be at least partly responsible for their development. Recent reports indicate that the activation of the kynurenine pathway (KP), caused by an activation of proinflammatory factors accompanying neurodegenerative processes, leads to the accumulation of its neuroactive and pro-oxidative metabolites. This leads to an increase in the oxidative stress level, which increases mitochondrial damage, and disrupts the cellular energy metabolism. This significantly reduces viability and impairs the proper functioning of central nervous system cells and may aggravate symptoms of many psychiatric and neurodegenerative disorders. This suggests that the modulation of KP activity could be effective in alleviating these symptoms. Numerous reports indicate that tryptophan supplementation, inhibition of KP enzymes, and administration or analogs of KP metabolites show promising results in the management of neurodegenerative disorders in animal models. This review gathers and systematizes the knowledge concerning the role of metabolites and enzymes of the KP in the development of oxidative damage within brain cells during neurodegenerative disorders and potential strategies that could reduce the severity of this process.
UNC-45A Is Highly Expressed in the Proliferative Cells of the Mouse Genital Tract and in the Microtubule-Rich Areas of the Mouse Nervous System
Authors: Clemente Valentino , Hoshino Asumi , Meints Joyce , Shetty Mihir , Starr Tim , Lee Michael , Bazzaro Martina
Published: June 2021

UNC-45A (Protein unc-45 homolog A) is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the actomyosin system and a Microtubule (MT)-destabilizing protein, which is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment not only in highly proliferating and prone to remodeling cells, but also in microtubule-rich areas, of the ovaries and the nervous system, respectively. In both apparatuses, UNC-45A is also abundantly expressed in the ciliated epithelium. As regulators of actomyosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development, our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development as well as in neurodegeneration.
Keratinocytes Regulate the Threshold of Inflammation by Inhibiting T Cell Effector Functions
Authors: Seiringer Peter , Eyerich Stefanie , Eyerich Kilian , Dittlein Daniela , Pilz Anna Caroline , Scala Emanuele , Ring Johannes , Behrendt Heidrun , Cavani Andrea , Traidl-Hoffmann Claudia
Published: June 2021

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.
Cancer Stem-Like Phenotype of Mitochondria Dysfunctional Hep3B Hepatocellular Carcinoma Cell Line
Authors: Han Yu-Seon , Yi Eui-Yeun , Jegal Myeong-Eun , Kim Yung-Jin
Published: June 2021

Mitochondria are major organelles that play various roles in cells, and mitochondrial dysfunction is the main cause of numerous diseases. Mitochondrial dysfunction also occurs in many cancer cells, and these changes are known to affect malignancy. The mitochondria of normal embryonic stem cells (ESCs) exist in an undifferentiated state and do not function properly. We hypothesized that mitochondrial dysfunction in cancer cells caused by the depletion of mitochondrial DNA might be similar to the mitochondrial state of ESCs. We generated mitochondria dysfunctional (ρ0) cells from the Hep3B hepatocellular carcinoma cell line and tested whether these ρ0 cells show cancer stem-like properties, such as self-renewal, chemotherapy resistance, and angiogenesis. Compared with Hep3B cells, the characteristics of each cancer stem-like cell were increased in Hep3B/ρ0 cells. The Hep3B/ρ0 cells formed a continuous and large sphere from a single cell. Additionally, the Hep3B/ρ0 cells showed resistance to the anticancer drug doxorubicin because of the increased expression of ATP-binding cassette Subfamily B Member 1. The Hep3B/ρ0 conditioned medium induced more and thicker blood vessels and increased the mobility and invasiveness of the blood vessel cells. Therefore, our data suggest that mitochondrial dysfunction can transform cancer cells into cancer stem-like cells.
Targeting Canonical and Non-Canonical STAT Signaling Pathways in Renal Diseases
Authors: Gai Lili , Zhu Yuting , Zhang Chun , Meng Xianfang
Published: June 2021

Signal transducer and activator of transcription (STAT) plays an essential role in the inflammatory reaction and immune response of numerous renal diseases. STATs can transmit the signals of cytokines, chemokines, and growth factors from the cell membrane to the nucleus. In the canonical STAT signaling pathways, upon binding with their cognate receptors, cytokines lead to a caspase of Janus kinases (JAKs) and STATs tyrosine phosphorylation and activation. Besides receptor-associated tyrosine kinases JAKs, receptors with intrinsic tyrosine kinase activities, G-protein coupled receptors, and non-receptor tyrosine kinases can also activate STATs through tyrosine phosphorylation or, alternatively, other post-translational modifications. Activated STATs translocate into the nucleus and mediate the transcription of specific genes, thus mediating the progression of various renal diseases. Non-canonical STAT pathways consist of preassembled receptor complexes, preformed STAT dimers, unphosphorylated STATs (U-STATs), and non-canonical functions including mitochondria modulation, microtubule regulation and heterochromatin stabilization. Most studies targeting STAT signaling pathways have focused on canonical pathways, but research extending into non-canonical STAT pathways would provide novel strategies for treating renal diseases. In this review, we will introduce both canonical and non-canonical STAT pathways and their roles in a variety of renal diseases.
Gene Expression Profile in Different Age Groups and Its Association with Cognitive Function in Healthy Malay Adults in Malaysia
Authors: Abdul Sani Nur Fathiah , Amir Hamzah Ahmad Imran Zaydi , Abu Bakar Zulzikry Hafiz , Mohd Yusof Yasmin Anum , Makpol Suzana , Wan Ngah Wan Zurinah , Damanhuri Hanafi Ahmad
Published: June 2021

The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult’s susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.
Application of Stem Cell Therapy for Infertility
Authors: Saha Sarama , Roy Partha , Corbitt Cynthia , Kakar Sham S.
Published: June 2021

Infertility creates an immense impact on the psychosocial wellbeing of affected couples, leading to poor quality of life. Infertility is now considered to be a global health issue affecting approximately 15% of couples worldwide. It may arise from factors related to the male (30%), including varicocele, undescended testes, testicular cancer, and azoospermia; the female (30%), including premature ovarian failure and uterine disorders; or both partners (30%). With the recent advancement in assisted reproduction technology (ART), many affected couples (80%) could find a solution. However, a substantial number of couples cannot conceive even after ART. Stem cells are now increasingly being investigated as promising alternative therapeutics in translational research of regenerative medicine. Tremendous headway has been made to understand the biology and function of stem cells. Considering the minimum ethical concern and easily available abundant resources, extensive research is being conducted on induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSC) for their potential application in reproductive medicine, especially in cases of infertility resulting from azoospermia and premature ovarian insufficiency. However, most of these investigations have been carried out in animal models. Evolutionary divergence observed in pluripotency among animals and humans requires caution when extrapolating the data obtained from murine models to safely apply them to clinical applications in humans. Hence, more clinical trials based on larger populations need to be carried out to investigate the relevance of stem cell therapy, including its safety and efficacy, in translational infertility medicine.
Long-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion
Authors: Zilundu Prince Last Mudenda , Xu Xiaoying , Liaquat Zaara , Wang Yaqiong , Zhong Ke , Fu Rao , Zhou Lihua
Published: June 2021

Brachial plexus root avulsions cause debilitating upper limb paralysis. Short-term neuroprotective treatments have reported preservation of motor neurons and function in model animals while reports of long-term benefits of such treatments are scarce, especially the morphological sequelae. This morphological study investigated the long-term suppression of c-Jun- and neuronal nitric oxide synthase (nNOS) (neuroprotective treatments for one month) on the motor neuron survival, ultrastructural features of lower motor neurons, and forelimb function at six months after brachial plexus roots avulsion. Neuroprotective treatments reduced oxidative stress and preserved ventral horn motor neurons at the end of the 28-day treatment period relative to vehicle treated ones. Motor neuron sparing was associated with suppression of c-Jun, nNOS, and pro-apoptotic proteins Bim and caspases at this time point. Following 6 months of survival, neutral red staining revealed a significant loss of most of the motor neurons and ventral horn atrophy in the avulsed C6, 7, and 8 cervical segments among the vehicle-treated rats (n = 4). However, rats that received neuroprotective treatments c-Jun JNK inhibitor, SP600125 (n = 4) and a selective inhibitor of nNOS, 7-nitroindazole (n = 4), retained over half of their motor neurons in the ipsilateral avulsed side compared. Myelinated axons in the avulsed ventral horns of vehicle-treated rats were smaller but numerous compared to the intact contralateral ventral horns or neuroprotective-treated groups. In the neuroprotective treatment groups, there was the preservation of myelin thickness around large-caliber axons. Ultrastructural evaluation also confirmed the preservation of organelles including mitochondria and synapses in the two groups that received neuroprotective treatments compared with vehicle controls. Also, forelimb functional evaluation demonstrated that neuroprotective treatments improved functional abilities in the rats. In conclusion, neuroprotective treatments aimed at suppressing degenerative c-Jun and nNOS attenuated apoptosis, provided long-term preservation of motor neurons, their organelles, ventral horn size, and forelimb function.
Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation
Authors: Zhang Zhongwei , Kurashima Yosuke
Published: June 2021

It is well known that mast cells (MCs) initiate type I allergic reactions and inflammation in a quick response to the various stimulants, including—but not limited to—allergens, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). MCs highly express receptors of these ligands and proteases (e.g., tryptase, chymase) and cytokines (TNF), and other granular components (e.g., histamine and serotonin) and aggravate the allergic reaction and inflammation. On the other hand, accumulated evidence has revealed that MCs also possess immune-regulatory functions, suppressing chronic inflammation and allergic reactions on some occasions. IL-2 and IL-10 released from MCs inhibit excessive immune responses. Recently, it has been revealed that allergen immunotherapy modulates the function of MCs from their allergic function to their regulatory function to suppress allergic reactions. This evidence suggests the possibility that manipulation of MCs functions will result in a novel approach to the treatment of various MCs-mediated diseases.
Tackling Rural Health, Energy, … and Technological Issues All at Once: A Call for a Global Interdisciplinary Platform for Strengthening Rural Setting Amid the COVID-19 Pandemic
Authors: Amiraslani Farshad
Published: June 2021

The recent COVID-19 pandemic has revealed flaws in rural settings where most people live without the necessary tools, income, and knowledge to tackle such unprecedented global challenges. Here, I argue that despite the research studies conducted on rural areas, these have not solved rising rural issues, notably poverty and illiteracy. I propound a global institute to be formed by governments that provides a platform for empowering rural communities through better training, skills, and competencies. Such global endeavour will ensure the remaining rural communities withstand future pandemics if they occur.
Addressing the Theoretical and Experimental Aspects of Low-Dimensional-Materials-Based FET Immunosensors: A Review
Authors: de Freitas Martins Ernane , Pinotti Luis Francisco , de Carvalho Castro Silva Cecilia , Rocha Alexandre Reily
Published: June 2021

Electrochemical immunosensors (EI) have been widely investigated in the last several years. Among them, immunosensors based on low-dimensional materials (LDM) stand out, as they could provide a substantial gain in fabricating point-of-care devices, paving the way for fast, precise, and sensitive diagnosis of numerous severe illnesses. The high surface area available in LDMs makes it possible to immobilize a high density of bioreceptors, improving the sensitivity in biorecognition events between antibodies and antigens. If on the one hand, many works present promising results in using LDMs as a sensing material in EIs, on the other hand, very few of them discuss the fundamental interactions involved at the interfaces. Understanding the fundamental Chemistry and Physics of the interactions between the surface of LDMs and the bioreceptors, and how the operating conditions and biorecognition events affect those interactions, is vital when proposing new devices. Here, we present a review of recent works on EIs, focusing on devices that use LDMs (1D and 2D) as the sensing substrate. To do so, we highlight both experimental and theoretical aspects, bringing to light the fundamental aspects of the main interactions occurring at the interfaces and the operating mechanisms in which the detections are based.
Optical Sensing of Molecular Oxygen (O2) via Metal Oxide Photoluminescence: A Comparative Study of TiO2, SnO2 and ZnO
Authors: Fioravanti Ambra , Marani Pietro , Morandi Sara , Giordano Laura , Maddalena Pasqualino , Carotta Maria Cristina , Lettieri Stefano
Published: June 2021

A comparative study is presented on the photoluminescence (PL) response toward molecular oxygen (O2) in tin dioxide (SnO2), zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles. The findings show that both PL enhancement and PL quenching can be observed on different materials, arguably depending on the spatial localization of the defects responsible for the PL emission in each different oxide. No significant results are evidenced for SnO2 nanoparticles. ZnO with red/orange emission shown an O2-induced PL enhancement, suggesting that the radiative emission involves holes trapped in surface vacancy oxygen centers. While the ZnO results are scientifically interesting, its performances are inferior to the ones shown by TiO2, which exhibits the most interesting response in terms of sensitivity and versatility of the response. In particular, O2 concentrations in the range of few percent and in the range of a few tenths of a part per million are both detectable through the same mixed-phase TiO2 sample, whose rutile phase gives a reversible and fast response to larger (0.4–2%) O2 concentration while its anatase phase is usable for detection in the 25–75 ppm range. The data for rutile TiO2 suggest that its surfaces host deeply trapped electrons at large densities, allowing good sensitivities and, more notably, a relatively unsaturated response at large concentrations. Future work is expected to improve the understanding and modeling of the photophysical framework that lies behind the observations.
Comparison of Antimicrobial Activity of Chitosan Nanoparticles against Bacteria and Fungi
Authors: Xing Yage , Wang Xiaomin , Guo Xunlian , Yang Ping , Yu Jinze , Shui Yuru , Chen Cunkun , Li Xuanlin , Xu Qinglian , Xu Lin , Bi Xiufang , Liu Xiaocui
Published: June 2021

Chitosan nanoparticles (CSNPs) have attracted wide interest; however, there has been no substantial information about a direct comparison of the antimicrobial activity of CSNPs on bacteria and fungi. Thus, in this study, simple, economically feasible CSNPs were synthesized and assessed for their antimicrobial activity. This investigation indicated that the coordination inducing effect of CSNPs could dissociate the tryptophan (Trp) and tyrosine (Tyr) residue groups on the peptide chain of the bovine serum albumin (BSA) molecule, thereby increasing the absorption intensity. The growth of E. coli and S. aureus could be completely inhibited when the concentration of CSNPs in the solution was higher than 0.6 mg/mL. The CSNPs showed more potent antibacterial activity against Gram-negative bacteria (E. coli) than against Gram-positive bacteria (S. aureus). In addition, the CSNPs were effective at initiating cellular leakage of fungal mycelia and damping off fungal pathogens, and their antifungal effects were stronger on P. steckii than on A. oryzae. Furthermore, the antimicrobial activity of the CSNPs was found to be more effective against bacteria than against fungi. This study thus ascertained the antimicrobial activity of synthesized CSNPs against different microorganisms, as well as their different degrees of inhibition.
Preparation and Application of Efficient Biobased Carbon Adsorbents Prepared from Spruce Bark Residues for Efficient Removal of Reactive Dyes and Colors from Synthetic Effluents
Authors: dos Reis Glaydson Simões , Larsson Sylvia H. , Thyrel Mikael , Pham Tung Ngoc , Claudio Lima Eder , de Oliveira Helinando Pequeno , Dotto Guilherme L.
Published: June 2021

Biobased carbon materials (BBC) obtained from Norway spruce (Picea abies Karst.) bark was produced by single-step chemical activation with ZnCl2 or KOH, and pyrolysis at 800 °C for one hour. The chemical activation reagent had a significant impact on the properties of the BBCs. KOH-biobased carbon material (KOH-BBC) had a higher specific surface area (SBET), equal to 1067 m2 g−1, larger pore volume (0.558 cm3 g−1), more mesopores, and a more hydrophilic surface than ZnCl2-BBC. However, the carbon yield for KOH-BBC was 63% lower than for ZnCl2-BBC. Batch adsorption experiments were performed to evaluate the ability of the two BBCs to remove two dyes, reactive orange 16 (RO-16) and reactive blue 4 (RB-4), and treat synthetic effluents. The general order model was most suitable for modeling the adsorption kinetics of both dyes and BBCs. The equilibrium parameters at 22 °C were calculated using the Liu model. Upon adsorption of RO-16, Qmax was 90.1 mg g−1 for ZnCl2-BBC and 354.8 mg g−1 for KOH-BBC. With RB-4, Qmax was 332.9 mg g−1 for ZnCl2-BBC and 582.5 mg g−1 for KOH-BBC. Based on characterization and experimental data, it was suggested that electrostatic interactions and hydrogen bonds between BBCs and RO-16 and RB-4 dyes played the most crucial role in the adsorption process. The biobased carbon materials showed high efficiency for removing RO-16 and RB-4, comparable to the best examples from the literature. Additionally, both the KOH- and ZnCl2-BBC showed a high ability to purify two synthetic effluents, but the KOH-BBC was superior.
The Ambiguous Functions of the Precursors That Enable Nonclassical Modes of Olanzapine Nucleation and Growth
Authors: Warzecha Monika , Florence Alastair J. , Vekilov Peter G.
Published: June 2021

One of the most consequential assumptions of the classical theories of crystal nucleation and growth is the Szilard postulate, which states that molecules from a supersaturated phase join a nucleus or a growing crystal individually. In the last 20 years, observations in complex biological, geological, and engineered environments have brought to light violations of the Szilard rule, whereby molecules assemble into ordered or disordered precursors that then host and promote nucleation or contribute to fast crystal growth. Nonclassical crystallization has risen to a default mode presumed to operate in the majority of the inspected crystallizing systems. In some cases, the existence of precursors in the growth media is admitted as proof for their role in nucleation and growth. With the example of olanzapine, a marketed drug for schizophrenia and bipolar disorder, we demonstrate that molecular assemblies in the solution selectively participate in crystal nucleation and growth. In aqueous and organic solutions, olanzapine assembles into both mesoscopic solute-rich clusters and dimers. The clusters facilitate nucleation of crystals and crystal form transformations. During growth, however, the clusters land on the crystal surface and transform into defects, but do not support step growth. The dimers are present at low concentrations in the supersaturated solution, yet the crystals grow by the association of dimers, and not of the majority monomers. The observations with olanzapine emphasize that detailed studies of the crystal and solution structures and the dynamics of molecular association may empower classical and nonclassical models that advance the understanding of natural crystallization, and support the design and manufacture of promising functional materials.
New Perspective on Thermally Stimulated Luminescence and Crystallization of Barium Borate Oxyfluoride Glasses
Authors: Rodríguez Chialanza Mauricio , Azcune Germán , Bentos Pereira Heinkel , Faccio Ricardo
Published: June 2021

The demand for modern materials, especially glasses, used in different applications, such as radiation sensors and spectral converters, requires a detailed study of their properties. The incorporation of fluoride compounds in borate glasses and their crystallization at the nanometric scale allows the properties of these materials to be further enhanced. Although many works showed improvements in some of these properties, some critical aspects, such as the crystallization mechanism and the role of the fluorine phase, need more investigation. We worked with xNaF (100 − x)BaO·2B2O3 glasses with x = 0, 5, 10, 15, 20, 25, 30, and 35% (in mol) to increase the knowledge in this field. The structural modifications and the thermally stimulated luminescence of the glasses were studied, and their crystallization was analyzed by thermal analysis and X-ray diffraction. A continuous trap distribution was found, which was responsible for its very good luminescent signal, especially in glasses with 20% NaF. By selecting a suitable amount of NaF, it is possible to obtain nanocrystals of BaF2. These promising results we reached show the applicability of these materials.
Pressure-Induced Structural Phase Transition and Metallization in Ga2Se3 Up to 40.2 GPa under Non-Hydrostatic and Hydrostatic Environments
Authors: Hong Meiling , Dai Lidong , Hu Haiying , Zhang Xinyu
Published: June 2021

A series of investigations on the structural, vibrational, and electrical transport characterizations for Ga2Se3 were conducted up to 40.2 GPa under different hydrostatic environments by virtue of Raman scattering, electrical conductivity, high-resolution transmission electron microscopy, and atomic force microscopy. Upon compression, Ga2Se3 underwent a phase transformation from the zinc-blende to NaCl-type structure at 10.6 GPa under non-hydrostatic conditions, which was manifested by the disappearance of an A mode and the noticeable discontinuities in the pressure-dependent Raman full width at half maximum (FWHMs) and electrical conductivity. Further increasing the pressure to 18.8 GPa, the semiconductor-to-metal phase transition occurred in Ga2Se3, which was evidenced by the high-pressure variable-temperature electrical conductivity measurements. However, the higher structural transition pressure point of 13.2 GPa was detected for Ga2Se3 under hydrostatic conditions, which was possibly related to the protective influence of the pressure medium. Upon decompression, the phase transformation and metallization were found to be reversible but existed in the large pressure hysteresis effect under different hydrostatic environments. Systematic research on the high-pressure structural and electrical transport properties for Ga2Se3 would be helpful to further explore the crystal structure evolution and electrical transport properties for other A2B3-type compounds.
A Theoretical Model of Quasicrystal Resonators: A Guided Optimization Approach
Authors: Cui Libin , Hayat Anwer , Lv Linzheng , Xu Zhiyang , Zhai Tianrui
Published: June 2021

Fibonacci-spaced defect resonators were analytically investigated by cavity coupling, which exhibited a series of well-defined optical modes in fractals. The analytic model can be used to predict the output performance of microcavity lasers based on Fibonacci-spaced defect resonators, such as the mode number, resonant frequency, and Q factor. All results obtained by the analytical solution are in good consistency with that obtained by the finite-difference time-domain method. The simulation result shows that the Q factor of the resonant modes would increase dramatically with the appearance of narrower optical modes. The proposed theoretical model can be used to inversely design high performance polymer lasers based on the Fibonacci-spaced defect resonators.
Computational Chemistry-Guided Syntheses and Crystal Structures of the Heavier Lanthanide Hydride Oxides DyHO, ErHO, and LuHO
Authors: Zapp Nicolas , Sheptyakov Denis , Kohlmann Holger
Published: June 2021

Heteroanionic hydrides offer great possibilities in the design of functional materials. For ternary rare earth hydride oxide REHO, several modifications were reported with indications for a significant phase width with respect to H and O of the cubic representatives. We obtained DyHO and ErHO as well as the thus far elusive LuHO from solid-state reactions of RE2O3 and REH3 or LuH3 with CaO and investigated their crystal structures by neutron and X-ray powder diffraction. While DyHO, ErHO, and LuHO adopted the cubic anion-ordered half-Heusler LiAlSi structure type (F4¯3m, a(DyHO) = 5.30945(10) Å, a(ErHO) = 5.24615(7) Å, a(LuHO) = 5.171591(13) Å), LuHO additionally formed the orthorhombic anti-LiMgN structure type (Pnma; LuHO: a = 7.3493(7) Å, b = 3.6747(4) Å, c = 5.1985(3) Å; LuDO: a = 7.3116(16) Å, b = 3.6492(8) Å, c = 5.2021(7) Å). A comparison of the cubic compounds’ lattice parameters enabled a significant distinction between REHO and REH1+2xO1−x (x < 0 or x > 0). Furthermore, a computational chemistry study revealed the formation of REHO compounds of the smallest rare earth elements to be disfavored in comparison to the sesquioxides, which is why they may only be obtained by mild synthesis conditions.