bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between In Vitro Neutralization Assay and Serological Tests for Protective Antibodies Detection
Authors: Bonifacio Maria Addolorata , Laterza Riccardo , Vinella Angela , Schirinzi Annalisa , Defilippis Mariangela , Di Serio Francesca , Ostuni Angelo , Fasanella Antonio , Mariggiò Maria Addolorata
Published: August 2022

Serological assays are useful in investigating the development of humoral immunity against SARS-CoV-2 in the context of epidemiological studies focusing on the spread of protective immunity. The plaque reduction neutralization test (PRNT) is the gold standard method to assess the titer of protective antibodies in serum samples. However, to provide a result, the PRNT requires several days, skilled operators, and biosafety level 3 laboratories. Therefore, alternative methods are being assessed to establish a relationship between their outcomes and PRNT results. In this work, four different immunoassays (Roche Elecsys® Anti SARS-CoV-2 S, Snibe MAGLUMI® SARS-CoV-2 S-RBD IgG, Snibe MAGLUMI® 2019-nCoV IgG, and EUROIMMUN® SARS-CoV-2 NeutraLISA assays, respectively) have been performed on individuals healed after SARS-CoV-2 infection. The correlation between each assay and the reference method has been explored through linear regression modeling, as well as through the calculation of Pearson’s and Spearman’s coefficients. Furthermore, the ability of serological tests to discriminate samples with high titers of neutralizing antibodies (>160) has been assessed by ROC curve analyses, Cohen’s Kappa coefficient, and positive predictive agreement. The EUROIMMUN® NeutraLISA assay displayed the best correlation with PRNT results (Pearson and Spearman coefficients equal to 0.660 and 0.784, respectively), as well as the ROC curve with the highest accuracy, sensitivity, and specificity (0.857, 0.889, and 0.829, respectively).
Engineering of Leuconostoc citreum for Efficient Bioconversion of Soy Isoflavone Glycosides to Their Aglycone Forms
Authors: Son Jaewoo , Jeong Ki Jun
Published: August 2022

Soy isoflavones are phytochemicals that possess various beneficial physiological properties such as anti-aging, anti-tumor, and antioxidant properties. Since soy isoflavones exist in glycoside forms, their bioavailability requires initial hydrolysis of the sugar moieties bound to them to be efficiently absorbed through the gut epithelium. Instead of conventional chemical hydrolysis using acids or organic solvents, alternative strategies for enhancing the bioavailability of soy isoflavones using biological methods are gaining attention. Here, we engineered Leuconostoc citreum isolated from Korean kimchi for efficient bioconversion of soy isoflavone glycosides into their aglycone forms to enhance their bioavailability. We first constructed an expression module based on the isoflavone hydrolase (IH)-encoding gene of Bifidobacterium lactis, which mediates conversion of isoflavone glycosides to aglycone forms. Using a high copy number plasmid and bicistronic expression design, the IH was successfully synthesized in L. citreum. Additionally, we determined enzymatic activity of the IH using an in vivo β-glucosidase assay and confirmed its highly efficient bioconversion efficiency for various types of isoflavone glycosides. Finally, we successfully demonstrated that the engineered L. citreum could convert isoflavone glycosides present in fermented soymilk into aglycones.
ATP5B Is an Essential Factor for Hepatitis B Virus Entry
Authors: Ueda Keiji , Suwanmanee Yadarat
Published: August 2022

Elucidation of the factors responsible for hepatitis B virus (HBV) is extremely important in order to understand the viral life cycle and pathogenesis, and thereby explore potential anti-HBV drugs. The recent determination that sodium taurocholate co-transporting peptide (NTCP) is an essential molecule for the HBV entry into cells led to the development of an HBV infection system in vitro using a human hepatocellular carcinoma (HCC) cell line expressing NTCP; however, the precise mechanism of HBV entry is still largely unknown, and thus it may be necessary to elucidate all the molecules involved. Here, we identified ATP5B as another essential factor for HBV entry. ATP5B was expressed on the cell surface of the HCC cell lines and bound with myristoylated but not with non-myristoylated preS1 2-47, which supported the notion that ATP5B is involved in the HBV entry process. Knockdown of ATP5B in NTCP-expressing HepG2 cells, which allowed HBV infection, reduced HBV infectivity with less cccDNA formation. Taken together, these results strongly suggested that ATP5B is an essential factor for HBV entry into the cells.
Mitochonic Acid 5 Improves Duchenne Muscular Dystrophy and Parkinson’s Disease Model of Caenorhabditis elegans
Authors: Wu Xintong , Nagasawa Satoi , Muto Kasumi , Ueda Maiko , Suzuki Chitose , Abe Takaaki , Higashitani Atsushi
Published: August 2022

Mitochonic Acid 5 (MA-5) enhances mitochondrial ATP production, restores fibroblasts from mitochondrial disease patients and extends the lifespan of the disease model “Mitomouse”. Additionally, MA-5 interacts with mitofilin and modulates the mitochondrial inner membrane organizing system (MINOS) in mammalian cultured cells. Here, we used the nematode Caenorhabditis elegans to investigate whether MA-5 improves the Duchenne muscular dystrophy (DMD) model. Firstly, we confirmed the efficient penetration of MA-5 in the mitochondria of C. elegans. MA-5 also alleviated symptoms such as movement decline, muscular tone, mitochondrial fragmentation and Ca2+ accumulation of the DMD model. To assess the effect of MA-5 on mitochondria perturbation, we employed a low concentration of rotenone with or without MA-5. MA-5 significantly suppressed rotenone-induced mitochondria reactive oxygen species (ROS) increase, mitochondrial network fragmentation and nuclear destruction in body wall muscles as well as endogenous ATP levels decline. In addition, MA-5 suppressed rotenone-induced degeneration of dopaminergic cephalic (CEP) neurons seen in the Parkinson’s disease (PD) model. Furthermore, the application of MA-5 reduced mitochondrial swelling due to the immt-1 null mutation. These results indicate that MA-5 has broad mitochondrial homing and MINOS stabilizing activity in metazoans and may be a therapeutic agent for these by ameliorating mitochondrial dysfunction in DMD and PD.
A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective
Authors: Trinh Xuan-Tung , Long Nguyen-Van , Van Anh Le Thi , Nga Pham Thi , Giang Nguyen Ngan , Chien Pham Ngoc , Nam Sun-Young , Heo Chan-Yeong
Published: August 2022

Wound healing is a recovering process of damaged tissues by replacing dysfunctional injured cellular structures. Natural compounds for wound treatment have been widely used for centuries. Numerous published works provided reviews of natural compounds for wound healing applications, which separated the approaches based on different categories such as characteristics, bioactivities, and modes of action. However, current studies provide reviews of natural compounds that originated from only plants or animals. In this work, we provide a comprehensive review of natural compounds sourced from both plants and animals that target the different bioactivities of healing to promote wound resolution. The compounds were classified into four main groups (i.e., anti-inflammation, anti-oxidant, anti-bacterial, and collagen promotion), mostly studied in current literature from 1992 to 2022. Those compounds are listed in tables for readers to search for their origin, bioactivity, and targeting phases in wound healing. We also reviewed the trend in using natural compounds for wound healing.
Palmoplantar Keratoderma: A Molecular Genetic Analysis of Family Cases
Authors: Shchagina Olga , Fedotov Valeriy , Markova Tatiana , Shatokhina Olga , Ryzhkova Oksana , Fedotova Tatiana , Polyakov Aleksander
Published: August 2022

Palmoplantar keratoderma is a clinically polymorphic disorder with a heterogeneous etiology characterized by marked hyperkeratotic lesions on the surface of palms and soles. Hereditary forms of palmoplantar keratoderma usually have autosomal dominant inheritance and are caused by mutations in dozens of genes, most of which belong to the keratin family. We carried out clinical and molecular genetic analysis of the affected and healthy members of four families with autosomal dominant palmoplantar keratoderma. In three out of four family cases of autosomal dominant palmoplantar keratoderma, the following molecular genetic causes were established: in two families—previously non-described missense mutations in the AQP5 gene (NM_001651.4): c.369C>G (p.(Asn123Lys)) and c.103T>G (p.(Trp35Gly)); in one family—a described splice site mutation in the KRT9 gene (NM_000226.4): c.31T>G. In one family, the possible cause of palmoplantar keratoderma was detected—a variant in the KRT1 gene (NM_006121.4): c.931G>A (p.(Glu311Lys)).
Impact of Growth Conditions on Pseudomonas fluorescens Morphology Characterized by Atomic Force Microscopy
Authors: Kahli Houssem , Béven Laure , Grauby-Heywang Christine , Debez Nesrine , Gammoudi Ibtissem , Moroté Fabien , Sbartai Hana , Cohen-Bouhacina Touria
Published: August 2022

This work is dedicated to the characterization by Atomic Force Microscopy (AFM) of Pseudomonas fluorescens, bacteria having high potential in biotechnology. They were first studied first in optimal conditions in terms of culture medium and temperature. AFM revealed a more-or-less elongated morphology with typical dimensions in the micrometer range, and an organization of the outer membrane characterized by the presence of long and randomly distributed ripples, which are likely related to the organization of lipopolysaccharides (LPS). The outer membrane also presents invaginations, some of them showing a reorganization of ripples, which could be the first sign of a bacterial stress response. In a second step, bacteria grown under unfavorable conditions were characterized. The choice of the medium appeared to be more critical in the case of the second generation of cells, the less adapted medium inducing not only changes in the membrane organization but also larger damages in bacteria. An increased growth temperature affected both the usual “swollen” morphology and the organization of the outer membrane. Here also, LPS likely contribute to membrane remodelling, which makes them potential markers to track cell state changes.
Cysteine Regulates Oxidative Stress and Glutathione-Related Antioxidative Capacity before and after Colorectal Tumor Resection
Authors: Chiang Feng-Fan , Chao Te-Hsin , Huang Shih-Chien , Cheng Chien-Hsiang , Tseng Yu-Yao , Huang Yi-Chia
Published: August 2022

Cysteine might scavenge free radicals and is a limiting substrate for the cellular synthesis of glutathione (GSH). We investigated the association of cysteine with oxidative stress and GSH-related antioxidant capacity in colorectal cancer (CRC) patients. Plasma samples were drawn from 66 patients 1 day before (pre-resection) and 4 weeks after resection (post-resection). Tumor and adjacent normal tissues were collected. We measured levels of plasma and tissue cysteine, homocysteine, oxidative stress indicators (malondialdehyde, MDA; advanced oxidation protein products, AOPP), GSH, and antioxidant enzyme activities. After tumor resection, patients had significantly higher levels of plasma cysteine, homocysteine, MDA, AOPP, and GSH-related antioxidant enzyme activities when compared with pre-resection. Levels of cysteine, homocysteine, AOPP and all antioxidant capacity indicators in tumor tissue were significantly higher than those levels in the adjacent normal tissue. Plasma cysteine levels measured at pre-resection were positively associated with MDA levels in the tumor and in the adjacent normal tissues. Cysteine levels in tumor and adjacent normal tissues were significantly associated with tissue levels of homocysteine, almost as indicators of oxidative stress and antioxidant capacities. Cysteine in the circulation was likely utilized to mediate GSH-related antioxidant capacity and further cope with increased oxidative stress in tumor and adjacent normal tissues.
Molecular Immunology in Hematological Disorders
Authors: Takami Akiyoshi
Published: August 2022

This Special Issue aims to highlight the molecular mechanisms involved in the development and progression of hematologic malignancies such as leukemia, lymphoma, and myeloma [...]
Behavior and Functional Roles of CD34+ Mesenchymal Cells in Mammalian Testes
Authors: Abe Shin-ichi
Published: August 2022

Mammalian testes consist of seminiferous tubules within which Sertoli cells line up at the periphery and nurse germ cells, and of interstitia that harbor various cells such as peritubular myoid cells (PMCs), Leydig cells (LCs), vascular endothelial cells, immune cells such as macrophages, and mesenchymal (stromal) cells. Morphological studies have recently reported the presence of telocytes with telopodes in the interstitium of adult mouse, rat, and human testes. CD34+PDGFRα+ telocytes with long and moniliform telopodes form reticular networks with various cell types such as LCs, PMCs, and vessels, indicating their potential functions in cell–cell communications and tissue homeostasis. Functional studies have recently been performed on testicular interstitial cells and CD34+ cells, using 3D re-aggregate cultures of dissociated testicular cells, and cell cultures. Direct observation of CD34+ cells and adult LCs (ALCs) revealed that CD34+ cells extend thin cytoplasmic processes (telopodes), move toward the LC–CD34+ cell-re-aggregates, and finally enter into the re-aggregates, indicating the chemotactic behavior of CD34+ telocytes toward ALCs. In mammalian testes, important roles of mesenchymal interstitial cells as stem/progenitors in the differentiation and regeneration of LCs have been reported. Here, reports on testicular telocytes so far obtained are reviewed, and future perspectives on the studies of testicular telocytes are noted.
In Vitro and In Vivo Activities of Tilmicosin and Acetylisovaleryltylosin Tartrate against Toxoplasma gondii
Authors: Ma Yazhen , Cao Xinru , Wang Hui , Song Xingju , Hu Dandan
Published: August 2022

Toxoplasma gondii is a widespread intracellular pathogen that infects humans and a variety of animals. The current therapeutic strategy for human toxoplasmosis is a combination of sulphadiazine and pyrimethamine. However, this combination still has a high failure rate and is ineffective against chronic infections. Therefore, it is important to discover a new anti-T. gondii drug that is safer and more effective in both humans and animals. In this study, we describe the anti-T. gondii activities of the 16-membered macrolide tilmicosin and acetylisovaleryltylosin tartrate (ATLL). Both tilmicosin and ATLL potently inhibited T. gondii with a half-maximal effective concentration (EC50) of 17.96 μM and 10.67 μM, respectively. Interestingly, tilmicosin and ATLL had different effects on the parasites. ATLL exhibited a potent inhibitory effect on intracellular parasite growth, while tilmicosin suppressed parasites extracellularly. By studying the lytic cycle of T. gondii after treatment, we found that ATLL potently inhibited the intracellular proliferation of tachyzoites, while tilmicosin affected the invasion of tachyzoites. Immunofluorescence analysis using ATLL-treated T. gondii showed morphologically abnormal parasites, which may be due to the inhibition of tachyzoite proliferation and division. In addition, tilmicosin and ATLL significantly delayed the death of mice caused by acute toxoplasmosis. Our results suggest that ATLL has potent anti-Toxoplasma activity both in vitro and in vivo and may be an alternative to toxoplasmosis in the future.
Topographical Distribution and Phenotype of Resident Meibomian Gland Orifice Immune Cells (MOICs) in Mice and the Effects of Topical Benzalkonium Chloride (BAK)
Authors: Wu Ching Yi , Wu Mengliang , Huang Xin , Gu Ben J. , Maldonado-Codina Carole , Morgan Philip B. , Downie Laura E. , Chinnery Holly R.
Published: August 2022

Meibomian gland orifices (MGOs) are located along the eyelid margin and secrete meibum into the tear film. The profile of resident innate immune cells (ICs) at this site is not well understood. The distribution and phenotype of resident ICs around MGOs in mice was investigated and herein defined as MGO-associated immune cells (MOICs). The effect of topical 0.1% benzalkonium chloride (BAK) on MOICs was also assessed. Eyelids from healthy CD11ceYFP and Cx3cr1gfp/gfp mice aged three or seven months were compared. ICs were identified as CD11c+, Cx3cr1+, and MHC-II+ using four-colour immunostaining and confocal microscopy. MOIC density was variable but clustered around MGOs. There were more CD11c+ MOICs in three-month-old compared with seven-month-old mice (three-month-old: 893 ± 449 cells/mm2 vs. seven-month-old: 593 ± 493 cells/mm2, p = 0.004). Along the eyelid margin, there was a decreasing gradient of CD11c+ MOIC density in three-month-old mice (nasal: 1003 ± 369 cells/mm2, vs. central: 946 ± 574 cells/mm2, vs. temporal: 731 ± 353 cells/mm2, p = 0.044). Cx3cr1-deficient mice had two-fold fewer MHC-II+ MOICs, suggesting a role for Cx3cr1 receptor signaling in meibomian gland surveillance. CD11c+ MOIC density was lower in BAK-exposed eyes compared to saline-treated controls, suggesting a change in homeostasis. This study provides novel insight into resident ICs located at MGOs, and their contribution to MG homeostasis.
Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance
Authors: Jo Hyein , Shim Kyeonghee , Jeoung Dooil
Published: August 2022

Histone deacetylases (HDACs) regulate gene expression through the epigenetic modification of chromatin structure. HDAC6, unlike many other HDACs, is present in the cytoplasm. Its deacetylates non-histone proteins and plays diverse roles in cancer cell initiation, proliferation, autophagy, and anti-cancer drug resistance. The development of HDAC6-specific inhibitors has been relatively successful. Mechanisms of HDAC6-promoted anti-cancer drug resistance, cancer cell proliferation, and autophagy are discussed. The relationship between autophagy and anti-cancer drug resistance is discussed. The effects of combination therapy, which includes HDAC6 inhibitors, on the sensitivity of cancer cells to chemotherapeutics and immune checkpoint blockade are presented. A summary of clinical trials involving HDAC6-specific inhibitors is also presented. This review presents HDAC6 as a valuable target for developing anti-cancer drugs.
Polymorphisms in the Genes Coding for TLRs, NLRs and RLRs Are Associated with Clinical Parameters of Patients with Acute Myeloid Leukemia
Authors: Wicherska-Pawłowska Katarzyna , Bogunia-Kubik Katarzyna , Kuszczak Bartłomiej , Łacina Piotr , Dratwa Marta , Jaźwiec Bożena , Wróbel Tomasz , Rybka Justyna
Published: August 2022

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.
The Effect of Intensity-Modulated Radiotherapy to the Head and Neck Region on the Oral Innate Immune Response and Oral Microbiome: A Prospective Cohort Study of Head and Neck Tumour Patients
Authors: Mojdami Zahra Dorna , Barbour Abdelahhad , Oveisi Morvarid , Sun Chunxiang , Fine Noah , Saha Sourav , Marks Cara , Elebyary Omnia , Watson Erin , Tenenbaum Howard , Azarpazhooh Amir , Glogauer Michael
Published: August 2022

Neutrophils, also known as polymorphonuclear leukocytes (PMNs), form a significant component of the innate host response, and the consequence of the interaction between the oral microbiota and PMNs is a crucial determinant of oral health status. The impact of radiation therapy (RT) for head and neck tumour (HNT) treatment on the oral innate immune system, neutrophils in particular, and the oral microbiome has not been thoroughly investigated. Therefore, the objective of this study was to characterize RT-mediated changes in oral neutrophils (oPMNs) and the oral microbiome in patients undergoing RT to treat HNTs. Oral rinse samples were collected prior to, during and post-RT from HNT patients receiving RT at Dental Oncology at Princess Margaret Cancer Centre. The oPMNs counts and activation states were analysed using flow cytometry, and the oral microbiome was analysed using 16S rRNA gene sequencing. Statistically significant (p < 0.05) drops in oPMN counts and the activation states of the CD11b, CD16, CD18, CD64 and H3Cit markers from pre-RT to post-RT were observed. Moreover, exposure to RT caused a significant reduction in the relative abundance of commensal Gram-negative bacteria and increased the commensal Gram-positive microbes. Ionizing radiation for the treatment of HNTs simultaneously decreased the recruitment of oPMNs into the oral cavity and suppressed their activation state. The oral microbiome composition post-RT was altered significantly due to RT which may favour the colonization of specific microbial communities unfavourable for the long-term development of a balanced oral microbiome.
Differential Performance and Lung Deposition of Levofloxacin with Different Nebulisers Used in Cystic Fibrosis
Authors: Schwarz Carsten , Procaccianti Claudio , Costa Laura , Brini Riccardo , Friend Richard , Caivano Grazia , Sadafi Hosein , Mussche Charles , Schwenck Nicolas , Hahn Michael , Murgia Xabier , Bianco Federico
Published: August 2022

We compared the performance and levofloxacin (Quinsair) lung deposition of three nebulisers commonly used in CF (I-Neb Advance, eFlow rapid, and LC Plus) with the approved nebuliser Zirela. The delivered dose, delivery rate, and aerosol particle size distribution (APSD) for each device were determined using the methods described in the Pharmacopeia. High-resolution computed tomography scans obtained from seven adult patients with mild CF were used to generate computer-aided, three-dimensional models of their airway tree to assess lung deposition using functional respiratory imaging (FRI). The eFlow rapid and the LC Plus showed poor delivery efficiencies due to their high residual volumes. The I-Neb, which only delivers aerosols during the inspiratory phase, achieved the highest aerosol delivery efficiency. However, the I-Neb showed the largest particle size and lowest delivery rate (2.9 mg/min), which were respectively associated with a high extrathoracic deposition and extremely long nebulisation times (>20 min). Zirela showed the best performance considering delivery efficiency (159.6 mg out of a nominal dose of 240 mg), delivery rate (43.5 mg/min), and lung deposition (20% of the nominal dose), requiring less than 5 min to deliver a full dose of levofloxacin. The present study supports the use of drug-specific nebulisers and discourages the off-label use of general-purpose devices with the present levofloxacin formulation since subtherapeutic lung doses and long nebulisation times may compromise treatment efficacy and adherence.
Sphingosine-1-Phosphate (S1P) Lyase Inhibition Aggravates Atherosclerosis and Induces Plaque Rupture in ApoE−/− Mice
Authors: Keul Petra , Peters Susann , von Wnuck Lipinski Karin , Schröder Nathalie H. , Nowak Melissa K. , Duse Dragos A. , Polzin Amin , Weske Sarah , Gräler Markus H. , Levkau Bodo
Published: August 2022

Altered plasma sphingosine-1-phosphate (S1P) concentrations are associated with clinical manifestations of atherosclerosis. However, whether long-term elevation of endogenous S1P is pro- or anti-atherogenic remains unclear. Here, we addressed the impact of permanently high S1P levels on atherosclerosis in cholesterol-fed apolipoprotein E-deficient (ApoE−/−) mice over 12 weeks. This was achieved by pharmacological inhibition of the S1P-degrading enzyme S1P lyase with 4-deoxypyridoxine (DOP). DOP treatment dramatically accelerated atherosclerosis development, propagated predominantly unstable plaque phenotypes, and resulted in frequent plaque rupture with atherothrombosis. Macrophages from S1P lyase-inhibited or genetically deficient mice had a defect in cholesterol efflux to apolipoprotein A-I that was accompanied by profoundly downregulated cholesterol transporters ATP-binding cassette transporters ABCA1 and ABCG1. This was dependent on S1P signaling through S1PR3 and resulted in dramatically enhanced atherosclerosis in ApoE−/−/S1PR3−/− mice, where DOP treatment had no additional effect. Thus, high endogenous S1P levels promote atherosclerosis, compromise cholesterol efflux, and cause genuine plaque rupture.
Comments about the IJMS Special Issue: Molecular Interactions and Mechanisms of COVID-19 Inhibition
Authors: Caruso Francesco , Rossi Miriam
Published: August 2022

The unprecedented COVID-19 pandemic showed up during the latter part of 2019 in Wuhan, China [...]
A Multifunctional Light-Driven Swimming Soft Robot for Various Application Scenarios
Authors: Wang Zhen , Shi Dongni , Wang Xiaowen , Chen Yibao , Yuan Zheng , Li Yan , Ge Zhixing , Yang Wenguang
Published: August 2022

The locomotor behavior of creatures in nature can bring a lot of inspiration for the fabrication of soft actuators. In this paper, we fabricated a bionic light-driven swimming soft robot that can perform grasping of tiny objects and achieve the task of object transfer. By adding carbon nanotubes (CNTs), the temperature-sensitive hydrogels can be endowed with light-responsive properties. The fabricated composite hydrogel structure can control the contraction and expansion of volume by light, which is similar to the contraction and diastole behavior of muscles. The oscillation of the fish tail and the grasping action of the normally closed micromanipulator can be achieved by the control of the irradiation of the xenon light source. The bending of the bionic arm can be controlled by the irradiation of a near-infrared (NIR) laser, which transforms the spatial position and posture of the micromanipulator. The proposed scheme is feasible for miniaturized fabrication and application of flexible actuators. This work provides some important insights for the study of light-driven microrobots and light-driven flexible actuators.
Genome-Wide Identification of P450 Genes in Chironomid Propsilocerus akamusi Reveals Candidate Genes Involved in Gut Microbiota-Mediated Detoxification of Chlorpyrifos
Authors: Sun Zeyang , Liu Yue , Xu Haixuan , Yan Chuncai
Published: August 2022

Chironomids commonly dominate macroinvertebrate assemblages in aquatic habitats and these non-biting midges are known for their ability to tolerate contaminants. Studies regarding the interplay between gut microbiota and host detoxification ability is currently a point of interest. Cytochrome P450s (P450s) are critical metabolic enzymes in which a subset is involved in xenobiotic detoxification. In this study, we first conducted an integrated global investigation of P450s based on the whole genomic sequence of Propsilocerus akamusi and retrieved a series of 64 P450 genes which were further classified into 4 clans and 25 families on the basis of phylogenetic relationships. With assistance of RNA-Seq and RT-qPCR validation, the expression profile of screened PaP450s in guts was compared between chlorpyrifos-challenged larvae with deficient gut microbiota (GD) and those with a conventional gut community (CV). An increasing prevalence of chlorpyrifos from sublethal to lethal dosages induced a greater mortality rate of individuals coupled with remarkable downregulation of 14 P450s in GD larval guts when compared to CV ones. Moreover, it turned out that the decreased level of PaCYP3998B1 and PaCYP3987D1 might imply impaired host endogenous detoxification capability potentiated by gut dysbiosis, reflected by a remarkably severe mortality in GD larvae treated with lethal chlorpyrifos. Collectively, our study unveiled candidate P450 genes that might be mediated by gut symbionts in chlorpyrifos-challenged P. akamusi larvae, possibly facilitating further understanding of the detoxified mechanism that chironomids might employ to alleviate poisonousness.
Healthcare-Associated Infective Endocarditis—Surgical Perspectives
Authors: Musci Tatjana , Grubitzsch Herko
Published: August 2022

Health-care-associated infective endocarditis (HCA-IE), a disease with a poor prognosis, has become increasingly important. As surgical treatment is frequently required, this review aims to outline surgical perspectives on HCA-IE. We searched PubMed to identify publications from January 1980 to March 2022. Reports were evaluated by the authors against a priori inclusion/exclusion criteria. Studies reporting on surgical treatment of HCA-IE including outcome were selected. Currently, HCA-IE accounts for up to 47% of IE cases. Advanced age, cardiac implants, and comorbidity are important predispositions, and intravascular catheters or frequent vascular access are significant sources of infection. Staphylococci and enterococci are the leading causative microorganisms. Surgery, although frequently indicated, is rejected in 24–69% because of prohibitive risk. In-hospital mortality is significant after surgery (29–50%) but highest in patients rejected for operation (52–83%). Furthermore, the length of hospital stay is prolonged. With aging populations, age-dependent morbidity, increasing use of cardiac implants, and growing healthcare utilization, HCA-IE is anticipated to gain further importance. A better understanding of pathogenesis, clinical profile, and outcomes is paramount. Further research on surgical treatment is needed to provide more comprehensive information for defining the most suitable treatment option, finding the optimal time for surgery, and reducing morbidity and mortality.
Arthroscopic Reduction and Fixation of Coronoid Fractures with Bending K-Wire: A New Technique
Authors: Choi Chang Hyun , Seok Hyun-Gyu , Park Sam-Guk
Published: August 2022

The ulnar coronoid process plays a key role in maintaining elbow stability; however, there is no gold standard treatment for ulnar coronoid process fractures. We present a novel surgical technique, arthroscopic reduction and bent K-wire fixation, for type II and III coronoid process fractures according to the O’Driscoll classification. Five patients were treated and retrospectively reviewed between January 2016 and December 2019. All the surgeries were performed by a single surgeon. We evaluated clinical outcomes by evaluating a range of motion, disability of arm, shoulder, and hand (DASH) score, Mayo Elbow Performance score (MEPS), and radiographic images. Intraoperative and postoperative radiographs showed that the fractures healed well and were satisfactorily fixed. The average elbow extension/flexion was −3/130, with an average DASH score of 2.42 and MEPS of 97. Coronoid process fractures can be treated successfully with arthroscopic reduction and fixation of bent K-wire, which allows more rigid fixation and early functional exercise, resulting in good outcomes without special tools.
Post-Operative Infections in Head and Neck Cancer Surgery: Risk Factors for Different Infection Sites
Authors: Pecorari Giancarlo , Riva Giuseppe , Albera Andrea , Cravero Ester , Fassone Elisabetta , Canale Andrea , Albera Roberto
Published: August 2022

Background: Post-operative infections in head and neck cancer (HNC) surgery represent a major problem and are associated with an important increase in mortality, morbidity, and burden on the healthcare system. The aim of this retrospective observational study was to evaluate post-operative infections in HNC surgery and to analyze risk factors, with a specific focus on different sites of infection. Methods: Clinical data about 488 HNC patients who underwent surgery were recorded. Univariate and multivariate analyses were performed to identify risk factors for post-operative infections. Results: Post-operative infections were observed in 22.7% of cases. Respiratory and surgical site infections were the most common. Multiple site infections were observed in 3.9% of cases. Considering all infection sites, advanced stage, tracheotomy, and higher duration of surgery were risk factors at multivariate analysis. Median hospital stay was significantly longer in patients who had post-operative infection (38 vs. 9 days). Conclusions: Post-operative infections may negatively affect surgical outcomes. A correct identification of risk factors may help the physicians to prevent post-operative infections in HNC surgery.
Neuroprotective Effects of Intermittent Theta Burst Stimulation in Parkinson’s Disease (NET-PD): A Study Protocol for a Delayed-Start Randomized Double-Blind Sham-Controlled Trial
Authors: Li Puyu , Luo Ningdi , Sun Sainan , Li Yuanyuan , Shen Dingding , Zhu Xue , Zhou Liche , Zhou Haiyan , Liu Jun
Published: August 2022

Background: As a typical high-disability neurodegenerative disease, Parkinson’s disease (PD) progresses variably, and patients who are clinically insensitive to dopaminergic therapy and whose symptoms fail to improve are commonly observed. As a result, achieving early neuron protection is critical. Methods/Design: The NET-PD study is a 2-year prospective single-center, double-blind, multi-arm, delayed-start, sham-controlled clinical trial assessing the long-term neuroprotective effect of intermittent theta burst stimulation (iTBS) in PD patients. Patients diagnosed with PD, aged 50–80, Hoehn–Yahr stage ≤4, and who maintain medication stability during the study will be enrolled. Clinical assessment and multi-modal markers are used to clarify the clinical improvement and dynamic neuronal changes in PD patients. With a standard deviation of 2, a test level of 0.05, a dropout rate of 10%, and a degree of certainty of 0.9, 60 PD patients are required for this study. Results: The NET-PD project was funded in March 2022, data collection began in July 2022, and is currently in the recruitment phase with two PD patients already enrolled. Data collection is expected to be completed in June 2024. The results are expected for publication in December 2024. Discussion: Previous research has demonstrated a rudimentary method for assessing and delaying PD progression in clinical medication trials. The NET-PD study adopts a rigorous methodology and specific disease-modifying designs to demonstrate the neuroprotective effect of iTBS on PD and investigate the potential mechanism of iTBS in regulating brain and motor functions. We hope to provide supposition for the subsequent exploration of diverse neuroprotection methods.
Interleukin 17 and Its Involvement in Renal Cell Carcinoma
Authors: Jarocki Michał , Karska Julia , Kowalski Szymon , Kiełb Paweł , Nowak Łukasz , Krajewski Wojciech , Saczko Jolanta , Kulbacka Julita , Szydełko Tomasz , Małkiewicz Bartosz
Published: August 2022

Nowadays, molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms has been taken under ‘the molecular magnifying glass’ and, therefore, it is possible to discover complex relationships between the cytophysiology and immune system action. An example could be renal cell carcinoma (RCC) which has deep interactions with immune mediators such as Interleukin 17 (IL-17)—an inflammatory cytokine reacting to tissue damage and external pathogens. RCC is one of the most fatal urological cancers because of its often late diagnosis and poor susceptibility to therapies. IL-17 and its relationship with tumors is extremely complex and constitutes a recent topic for numerous studies. What is worth highlighting is IL-17’s dual character in cancer development—it could be pro- as well as anti-tumorigenic. The aim of this review is to summarize the newest data considering multiple connections between IL-17 and RCC.
Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases
Authors: Montegiove Nicolò , Calzoni Eleonora , Emiliani Carla , Cesaretti Alessio
Published: August 2022

Diseases affecting the central nervous system (CNS) are among the most disabling and the most difficult to cure due to the presence of the blood–brain barrier (BBB) which represents an impediment from a therapeutic and diagnostic point of view as it limits the entry of most drugs. The use of biocompatible polymer nanoparticles (NPs) as vehicles for targeted drug delivery to the brain arouses increasing interest. However, the route of administration of these vectors remains critical as the drug must be delivered without being degraded to achieve a therapeutic effect. An innovative approach for the administration of drugs to the brain using polymeric carriers is represented by the nose-to-brain (NtB) route which involves the administration of the therapeutic molecule through the neuro-olfactory epithelium of the nasal mucosa. Nasal administration is a non-invasive approach that allows the rapid transport of the drug directly to the brain and minimizes its systemic exposure. To date, many studies involve the use of polymer NPs for the NtB transport of drugs to the brain for the treatment of a whole series of disabling neurological diseases for which, as of today, there is no cure. In this review, various types of biodegradable polymer NPs for drug delivery to the brain through the NtB route are discussed and particular attention is devoted to the treatment of neurological diseases such as Glioblastoma and neurodegenerative diseases.
Optimization of the Hydrodynamic Performance of a Double-Vane Otter Board Based on Orthogonal Experiments
Authors: Wang Lei , Zhang Xun , Wan Rong , Xu Qingchang , Qi Guangrui
Published: August 2022

An orthogonal experiment was conducted to study the effects of the aspect ratio, camber of the fore wing, and gap ratio of front and rear wing panels on the hydrodynamic performance of double-vane otter boards. The design of the orthogonal experiment comprised three factors (each having three levels), namely the aspect ratio (1.0, 1.5, and 2.0), camber (0.12, 0.14, and 0.16), and gap ratio (0.25, 0.30, and 0.35), the drag coefficient Cx and the lift coefficient Cy of nine otter board models obtained in a wind tunnel experiment, and the lift–drag ratio K obtained by calculation. The lift–drag ratio for a working angle of attack of 30° was selected as the inspection index, and the experimental data were analyzed in an orthogonal design-direct analysis. Analysis of each factor revealed that the optimal level combination of factors was A3B3C3 and that the decreasing order of the effects of the factors was A (aspect ratio) > B (gap ratio) > C (camber). The orthogonal experiment thus obtained an optimal otter board in terms of the aspect ratio (2.0), fore wing camber (0.16), and gap ratio (0.35), with the aspect ratio having the greatest effect on performance. The hydrodynamic performances of the otter board with the optimized structure and another otter board model were compared in numerical simulation, which verified the correctness of the analysis results. The experimental results provide a reference for the optimal design of the double-vane otter board.
Racial/Ethnic Differences in the Pharmacokinetics of Antipsychotics: Focusing on East Asians
Authors: Lin Shih-Ku
Published: August 2022

Empirical clinical studies have suggested that East Asian patients may require lower dosages of psychotropic drugs, such as antipsychotics, lithium, and antidepressants, than non-Asians. Both the pharmacokinetic and pharmacodynamic properties of a drug can affect the clinical response of an illness. The levels of antipsychotics used for the treatment of schizophrenia may affect patient clinical responses; several factors can affect these levels, including patient medication adherence, body weight (BW) or body mass index, smoking habits, and sex. The cytochrome P450 (CYP) system is a major factor affecting the blood levels of antipsychotics because many antipsychotics are metabolized by this system. There were notable genetic differences between people of different races. In this study, we determined the racial or ethnic differences in the metabolic patterns of some selected antipsychotics by reviewing therapeutic drug monitoring studies in East Asian populations. The plasma concentrations of haloperidol, clozapine, quetiapine, aripiprazole, and lurasidone, which are metabolized by specific CYP enzymes, were determined to be higher, under the same daily dose, in East Asian populations than in Western populations.
Constructed Wetland for Sustainable and Low-Cost Wastewater Treatment: Review Article
Authors: Waly Marwa M. , Ahmed Taha , Abunada Ziyad , Mickovski Slobodan B. , Thomson Craig
Published: August 2022

There is a growing need for more sustainable wastewater treatment technologies to provide non-conventional water sources. Constructed Wetland systems (CW) are viewed as a low-cost treatment technology with proven treatment efficiency. CWS can treat a variety of contaminants using low energy and natural systems by altering various design parameters. There are two configuration types of constructed wetlands: vertical (VF) and horizontal flow CW (HF). Both configurations have been widely adopted in both large and pilot scale studies with proven records of reasonable wastewater treatment efficiency. The current article reviews the recent development of CW technology and highlights the main achievements and successful applications for wastewater treatment at various locations. The review has indicated that a considerable removal efficiency is attained while using engineered CW systems with variable treatment rates for various pollutants. The treatment efficiency is a function of various parameters including wastewater type, scale dimensions, applied plant and the retention time. The review compared the treatment efficiency for both VF and HF and has revealed that various removal rates of BOD, COD, TSS, TN, TP and NH₄ was attained using both configurations. Yet, the removal efficiency in the case of VF was slightly higher compared with the HF with an average treatment level of 77% and 68% was achieved in both systems, respectively. The review revealed that the CW is an effective and sustainable technology for wastewater treatment with the initial influent level, microbial biofilm, detention time, plant species and configuration among the most dominating parameters that are directly controlling the removal rates.
Mismatched Relationship between Urban Industrial Land Consumption and Growth of Manufacturing: Evidence from the Yangtze River Delta
Authors: Zhang Congguo , Yao Di , Zhen Yanlin , Li Weiwei , Li Kerun
Published: August 2022

Background: The precise allocation and efficient use of industrial land are necessary for the development and optimization of urban production space; however, the mismatches between urban industrial land consumption and the growth of manufacturing are becoming more serious and has become the primary obstacle to sustainable urban development. Methods: Based on a combination of the Boston Consulting Group matrix, spatial mismatch model, decoupling index, GIS, and Geodetector tools, this paper conducts an empirical study on the Yangtze River Delta region in an attempt to reveal the spatio-temporal evolution of the mismatch between urban industrial land changes and the growth of manufacturing and provide a basis for spatial planning and land management in the new era. Results: The distribution of urban industrial land is characterized by high heterogeneity and agglomeration, the coexistence of expansion and contraction, and increasingly complex and diversified changes. Gross domestic product, government revenue, the added value of tertiary industry, and government investment in science and technology indicate that the goal orientation and scale effect of economic growth play a decisive role in the allocation of urban industrial land and that the influence of industrial structures and technological innovation is rapidly increasing. The interaction between the different factors is a bifactor enhancement, for example, land used for logistics and storage, utilities, commercial and other services, and the import and export trade, which have a strong synergistic enhancement effect. The mismatches between urban industrial land changes and the growth of manufacturing are still within a reasonable degree but there is an increasing number of cities with negative mismatches, making it necessary to implement a differentiated spatial adjustment and management policy. Conclusions: Compared with the mismatches of mobile resources such as labor, finance, and capital, the mismatches of immovable land resources have an increasing impact with more serious consequences and it is harder to make optimizations and corrections. However, the academic community has limited knowledge about land resource mismatches. By quantitatively assessing the mismatches between industrial land consumption and the growth of manufacturing in YRD cities, this paper argues that the mismatches can be rectified through spatial and land use planning and suggests the establishment of a zoning management and governance system to achieve the optimal allocation of urban industrial land resources through the implementation of a “standard land + commitment system” and industrial land protection lines.
Initial Testing of an Approximated, Fast Calculation Procedure for Personalized Dosimetry in Radionuclide Therapy Based on Planar Whole-Body Scan and Monte-Carlo Specific Dose Rates from the OpenDose Project
Authors: Bianco Davide , Nappi Carmela , Piscopo Leandra , Volpe Fabio , Manganelli Mariarosaria , Volpicelli Federica , Loffredo Filomena , Totaro Pasquale , Quarto Maria , Cuocolo Alberto , Klain Michele
Published: August 2022

Individualized dosimetry in nuclear medicine is currently at least advisable in order to obtain the best risk–benefit balance in terms of the maximal dose to lesions and under-threshold doses to radiosensitive organs. This article aims to propose a procedure for fast dosimetric calculations based on planar whole-body scintigraphy (WBS) images and developed to be employed in everyday clinical practice. Methods: For simplicity and legacy reasons, the method is based on planar imaging dosimetry, complemented with some assumptions on the radiopharmaceutical kinetics empirically derived from single-photon emission tomography/computed tomography (SPECT/CT) image analysis. The idea is to exploit a rough estimate of the time-integrated activity as has been suggested for SPECT/CT dosimetry but using planar images. The resulting further reduction in dose estimation accuracy is moderated by the use of a high-precision Monte-Carlo S-factor, such as those available within the OpenDose project. Results: We moved the problem of individualized dosimetry to a transformed space where comparing doses was imparted to the ICRP Average Male/Female computational phantom, resulting from an activity distribution related to patient’s pharmaceutical uptake. This is a fast method for the personalized dosimetric evaluation of radionuclide therapy, bearing in mind that the resulting doses are meaningful in comparison with thresholds calculated in the same framework. Conclusion: The simplified scheme proposed here can help the community, or even the single physician, establish a quantitative guide-for-the-eye approach to individualized dosimetry.