bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraarticular Injections of Mesenchymal Stem Cells in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Efficacy
Authors: Rodríguez-Merchán Emérito Carlos
Published: November 2022

More than 10% of the world’s population suffers from osteoarthritis (OA) of the knee, with a lifetime risk of 45%. Current treatments for knee OA pain are as follows: weight control; oral pharmacological treatment (non-steroidal anti-inflammatory drugs, paracetamol, opioids); mechanical aids (crutches, walkers, braces, orthotics); therapeutic physical exercise; and intraarticular injections of corticosteroids, hyaluronic acid, and platelet-rich plasma (PRP). The problem is that such treatments usually relieve joint pain for only a short period of time. With respect to intraarticular injections, corticosteroids relieve pain for several weeks, while hyaluronic acid and PRP relieve pain for several months. When the above treatments fail to control knee pain, total knee arthroplasty (TKA) is usually indicated; however, although a very effective surgical technique, it can be associated with medical and postoperative (surgery-related) complications. Therefore, it seems essential to look for safe and effective alternative treatments to TKA. Recently, there has been much research on intraarticular injections of mesenchymal stem cells (MSCs) for the management of OA of the knee joint. This article reviews the latest information on the molecular mechanisms of action of MSCs and their potential therapeutic benefit in clinical practice in patients with painful knee OA. Although most recent publications claim that intraarticular injections of MSCs relieve joint pain in the short term, their efficacy remains controversial given that the existing scientific information on MSCs is indecisive. Before recommending intraarticular MSCs injections routinely in patients with painful knee OA, more studies comparing MSCs with placebo are needed. Furthermore, a standard protocol for intraarticular injections of MSCs in knee OA is needed.
miRNA Pathway Alteration in Response to Non-Coding RNA Delivery in Viral Vector-Based Gene Therapy
Authors: Savenkova Darya A. , Makarova Aelita-Luiza A. , Shalik Igor K. , Yudkin Dmitry V.
Published: November 2022

Gene therapy is widely used to treat incurable disorders and has become a routine procedure in clinical practice. Since viruses can exhibit specific tropisms, effectively penetrate the cell, and are easy to use, most gene therapy approaches are based on viral delivery of genetic material. However, viral vectors have some disadvantages, such as immune response and cytotoxicity induced by a disturbance of cell metabolism, including miRNA pathways that are an important part of transcription regulation. Therefore, any viral-based gene therapy approach involves the evaluation of side effects and safety. It is possible for such effects to be caused either by the viral vectors themselves or by the delivered genetic material. Many gene therapy techniques use non-coding RNA delivery as an effective agent for gene expression regulation, with the risk of cellular miRNA pathways being affected due to the nature of the non-coding RNAs. This review describes the effect of viral vector entry and non-coding RNA delivery by these vectors on miRNA signaling pathways.
Congenital Stationary Night Blindness: Clinical and Genetic Features
Authors: Kim Angela H. , Liu Pei-Kang , Chang Yin-Hsi , Kang Eugene Yu-Chuan , Wang Hung-Hsuan , Chen Nelson , Tseng Yun-Ju , Seo Go Hun , Lee Hane , Liu Laura , Chao An-Ning , Chen Kuan-Jen , Hwang Yih-Shiou , Wu Wei-Chi , Lai Chi-Chun , Tsang Stephen H. , Hsiao Meng-Chang , Wang Nan-Kai
Published: November 2022

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert–Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype–phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype–phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.
Impact of Four Ovine TMEM154 Haplotypes on Ewes during Multiyear Lentivirus Exposure
Authors: Freking Brad A. , Murphy Tom W. , Chitko-McKown Carol G. , Workman Aspen M. , Heaton Michael P.
Published: November 2022

Polypeptide variation encoded by the ovine transmembrane protein 154 gene (TMEM154) is associated with susceptibility to ovine lentivirus, the causative agent of Ovine Progressive Pneumonia (OPP) and Visna/Maedi. Our aim was to compare the four most prevalent TMEM154 haplotypes on the incidence of infection and ewe productivity during natural multiyear virus exposure. Prospective cohort studies were designed to test gene action and estimate effects of TMEM154 haplotypes encoding distinctive variant residues: K35 (“1”), I70 (“2”), ancestral (“3”), and A4del/M44 (“4”). Exposure consisted of co-mingling infected ewes at a rate greater than 30% with serological status evaluated every four months. For ewes with one or two copies of the highly susceptible haplotypes “2” and ”3”, the infection prevalence steadily increased to nearly 100% at 55 months. Haplotypes “2” and “3” were equally susceptible and dominant to haplotype “1”. A difference was not detected (p < 0.53) in the magnitude of effect with haplotype combinations of “1” and ”4”. The ewe infection prevalence with “1,1”; “1,4”; and “4,4” was 10% to 40% at 55 months. The latter suggested that two copies of the K35 amino acid substitution (“1”) were as effective as a homozygous TMEM154 “knockout” with the frame-shift deletion mutation (“4”) in reducing infection susceptibility. When considering ewe reproductive performance, a difference was not detected when comparing haplotypes “2”, and “3” to each other, or “1” and “4” to each other. Our study indicated that ewes with two copies of the severely truncated versions of TMEM154 (“4,4”) had normal lamb productivity. Without complete understanding of the natural function of TMEM154 our recommendations to producers interested in using TMEM154 selection to reduce their flock’s genetic predisposition to OPP are encouraged to increase the frequency of TMEM154 haplotype K35 (“1”) since it encodes a full-length protein with minimal difference to the ancestral polypeptide.
The Patatin–Like Phospholipase Domain Containing Protein 7 Regulates Macrophage Classical Activation through SIRT1/NF-κB and p38 MAPK Pathways
Authors: Zhao Zheng , Heier Christoph , Pang Huimin , Wang Yu , Huang Feifei , Chang Pingan
Published: November 2022

Lysophosphatidylcholine (LPC) is a bioactive lipid that modulates macrophage polarization during immune responses, inflammation, and tissue remodeling. Patatin-like phospholipase domain containing protein 7 (PNPLA7) is a lysophospholipase with a preference for LPC. However, the role of PNPLA7 in macrophage polarization as an LPC hydrolase has not been explored. In the current study, we found that PNPLA7 is highly expressed in naïve macrophages and downregulated upon lipopolysaccharide (LPS)-induced polarization towards the classically activated (M1) phenotype. Consistently, overexpression of PNPLA7 suppressed the expression of proinflammatory M1 marker genes, including interleukin 1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor α (TNF-α), whereas knockdown of PNPLA7 augmented the inflammatory gene expression in LPS-challenged macrophages. PNPLA7 overexpression and knockdown increased and decreased Sirtuin1 (SIRT1) mRNA and protein levels, respectively, and affected the acetylation of the nuclear factor-kappa B (NF-κB) p65 subunit, a key transcription factor in M1 polarization. In addition, the levels of phosphorylated p38 mitogen-activated protein kinase (MAPK) were suppressed and enhanced by PNPLA7 overexpression and knockdown, respectively. Taken together, these findings suggest that PNPLA7 suppresses M1 polarization of LPS-challenged macrophages by modulating SIRT1/NF-κB- and p38 MAPK-dependent pathways.
Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus
Authors: Qiu Hong , Li Haobo , Fan Ruiwen , Song Yang , Pan Xuan , Zhang Chunhui , Li Jing
Published: November 2022

We analyzed whole-genome bisulfite sequencing (WGBS) and RNA sequencing data of two young (1 year old) and two adult (9 years old) rhesus macaques (Macaca mulatta) to characterize the genomic DNA methylation profile of the thymus and explore the molecular mechanism of age-related changes in the thymus. Combining the two-omics data, we identified correlations between DNA methylation and gene expression and found that DNA methylation played an essential role in the functional changes of the aging thymus, especially in immunity and coagulation. The hypomethylation levels of C3 and C5AR2 and the hypermethylation level of C7 may lead to the high expressions of these genes in adult rhesus macaque thymuses, thus activating the classical complement pathway and the alternative pathway and enhancing their innate immune function. Adult thymuses had an enhanced coagulation pathway, which may have resulted from the hypomethylation and upregulated expressions of seven coagulation-promoting factor genes (F13A1, CLEC4D, CLEC4E, FCN3, PDGFRA, FGF2 and FGF7) and the hypomethylation and low expression of CPB2 to inhibit the degradation of blood clots. Furthermore, the functional decline in differentiation, activation and maturation of T cells in adult thymuses was also closely related to the changes in methylation levels and gene expression levels of T cell development genes (CD3G, GAD2, ADAMDEC1 and LCK) and the thymogenic hormone gene TMPO. A comparison of the age-related methylated genes among four mammal species revealed that most of the epigenetic clocks were species-specific. Furthermore, based on the genomic landscape of allele-specific DNA methylation, we identified several age-related clustered sequence-dependent allele-specific DNA methylated (cS-ASM) genes. Overall, these DNA methylation patterns may also help to assist with understanding the mechanisms of the aging thymus with the epigenome.
Xylanase Inhibitors: Defense Players in Plant Immunity with Implications in Agro-Industrial Processing
Authors: Tundo Silvio , Mandalà Giulia , Sella Luca , Favaron Francesco , Bedre Renesh , Kalunke Raviraj M.
Published: November 2022

Xylanase inhibitors (XIs) are plant cell wall proteins largely distributed in monocots that inhibit the hemicellulose degrading activity of microbial xylanases. XIs have been classified into three classes with different structures and inhibition specificities, namely Triticum aestivum xylanase inhibitors (TAXI), xylanase inhibitor proteins (XIP), and thaumatin-like xylanase inhibitors (TLXI). Their involvement in plant defense has been established by several reports. Additionally, these inhibitors have considerable economic relevance because they interfere with the activity of xylanases applied in several agro-industrial processes. Previous reviews highlighted the structural and biochemical properties of XIs and hypothesized their role in plant defense. Here, we aimed to update the information on the genomic organization of XI encoding genes, the inhibition properties of XIs against microbial xylanases, and the structural properties of xylanase-XI interaction. We also deepened the knowledge of XI regulation mechanisms in planta and their involvement in plant defense. Finally, we reported the recently studied strategies to reduce the negative impact of XIs in agro-industrial processes and mentioned their allergenicity potential.
Acute Stress Induces Different Changes on the Expression of BDNF and trkB in the Mesocorticolimbic System of Two Lines of Rats Differing in Their Response to Stressors
Authors: Serra Maria Pina , Sanna Francesco , Boi Marianna , Poddighe Laura , Secci Lorenzo , Trucas Marcello , Fernández-Teruel Alberto , Corda Maria Giuseppa , Giorgi Osvaldo , Quartu Marina
Published: November 2022

The present work was undertaken to investigate the effects of acute forced swimming (FS) on the levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (trkB) proteins in: the ventral tegmental area (VTA); the nucleus accumbens (Acb) shell and core compartments; and the anterior cingulate (ACg), prelimbic (PL) and infralimbic (IL) territories of the prefrontal cortex of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression. We report for the first time that FS induced very rapid and distinct changes in the levels of BDNF and trkB proteins in different areas of the mesocorticolimbic system of RHA and RLA rats. Thus, (1) in the VTA and Acb core, FS elicited a significant increase of both BDNF- and trkB-LI in RHA but not RLA rats, whereas in the Acb shell no significant changes in BDNF- and trkB-LI across the line and treatment were observed; (2) in RLA rats, the basal levels of BDNF-LI in the IL/PL cortex and of trkB-LI in the ACg cortex were markedly lower than those of RHA rats; moreover, BDNF- and trkB-LI in the IL/PL and ACg cortex were increased by FS in RLA rats but decreased in their RHA counterparts. These results provide compelling evidence that the genetic background influences the effects of stress on BDNF/trkB signaling and support the view that the same stressor may impact differently on the expression of BDNF in discrete brain areas.
Estimating Metastatic Risk of Pancreatic Ductal Adenocarcinoma at Single-Cell Resolution
Authors: Chen Sina , Zhou Shunheng , Huang Yu-e , Yuan Mengqin , Lei Wanyue , Chen Jiahao , Lin Kongxuan , Jiang Wei
Published: November 2022

Pancreatic ductal adenocarcinoma (PDAC) is characterized by intra-tumoral heterogeneity, and patients are always diagnosed after metastasis. Thus, finding out how to effectively estimate metastatic risk underlying PDAC is necessary. In this study, we proposed scMetR to evaluate the metastatic risk of tumor cells based on single-cell RNA sequencing (scRNA-seq) data. First, we identified diverse cell types, including tumor cells and other cell types. Next, we grouped tumor cells into three sub-populations according to scMetR score, including metastasis-featuring tumor cells (MFTC), transitional metastatic tumor cells (TransMTC), and conventional tumor cells (ConvTC). We identified metastatic signature genes (MSGs) through comparing MFTC and ConvTC. Functional enrichment analysis showed that up-regulated MSGs were enriched in multiple metastasis-associated pathways. We also found that patients with high expression of up-regulated MSGs had worse prognosis. Spatial mapping of MFTC showed that they are preferentially located in the cancer and duct epithelium region, which was enriched with the ductal cells’ associated inflammation. Further, we inferred cell–cell interactions, and observed that interactions of the ADGRE5 signaling pathway, which is associated with metastasis, were increased in MFTC compared to other tumor sub-populations. Finally, we predicted 12 candidate drugs that had the potential to reverse expression of MSGs. Taken together, we have proposed scMetR to estimate metastatic risk in PDAC patients at single-cell resolution which might facilitate the dissection of tumor heterogeneity.
Scientific Discoveries Supporting Theories in Science: From Thinking to Practice
Authors: Fais Stefano
Published: November 2022

The idea to propose this ambitious title for a Special Issue in the International Journal of Molecular Science came, on one hand, from my personal experience in research in medicine, lasting 41 years, which has often been inspired by chance [...]
Synthesis of Co3O4 Nanoparticles-Decorated Bi12O17Cl2 Hierarchical Microspheres for Enhanced Photocatalytic Degradation of RhB and BPA
Authors: Din Syed Taj Ud , Xie Wan-Feng , Yang Woochul
Published: November 2022

Three-dimensional (3D) hierarchical microspheres of Bi12O17Cl2 (BOC) were prepared via a facile solvothermal method using a binary solvent for the photocatalytic degradation of Rhodamine-B (RhB) and Bisphenol-A (BPA). Co3O4 nanoparticles (NPs)-decorated BOC (Co3O4/BOC) heterostructures were synthesized to further enhance their photocatalytic performance. The microstructural, morphological, and compositional characterization showed that the BOC microspheres are composed of thin (~20 nm thick) nanosheets with a 3D hierarchical morphology and a high surface area. Compared to the pure BOC photocatalyst, the 20-Co3O4/BOC heterostructure showed enhanced degradation efficiency of RhB (97.4%) and BPA (88.4%). The radical trapping experiments confirmed that superoxide (•O2−) radicals played a primary role in the photocatalytic degradation of RhB and BPA. The enhanced photocatalytic performances of the hierarchical Co3O4/BOC heterostructure are attributable to the synergetic effects of the highly specific surface area, the extension of light absorption to the more visible light region, and the suppression of photoexcited electron-hole recombination. Our developed nanocomposites are beneficial for the construction of other bismuth-based compounds and their heterostructure for use in high-performance photocatalytic applications.
Characterizing the Status of Energetic Metabolism of Dinoflagellate Resting Cysts under Mock Conditions of Marine Sediments via Physiological and Transcriptional Measurements
Authors: Li Fengting , Yue Caixia , Deng Yunyan , Tang Ying Zhong
Published: November 2022

Similar to the seeds of higher plants, resting cysts, a non-motile, benthic, and dormant stage in the life history of many dinoflagellate species, play vital roles via germination in the seasonal dynamics and particularly the initiation of harmful algal blooms (HABs) of dinoflagellates. It is thus crucial for resting cysts to balance between the energetic catabolism for viability maintenance and the energy preservation for germination during their dormancy. Despite this importance, studies on how resting cysts of dinoflagellates accomplish energetic metabolism in marine sediment have been virtually absent. In this study, using the cosmopolitan HABs-causing species Scrippsiella acuminata as a representative, we measured the transcriptional activity of the most efficient pathway of the energy catabolism tricarboxylic acid (TCA) cycle, cell viability (via neutral red staining), and the cellular ATP content of resting cysts under a set of mock conditions in marine sediments (e.g., 4 °C, darkness, and anoxia) for a maximum period of one year. Based on the correlation analyses among the expression levels of genes, cyst viability, and ATP content, we revealed that the TCA cycle was still a crucial pathway of energetic catabolism for resting cysts under aerobic conditions, and its expression was elevated at higher temperatures, light irradiation, and the early stage of dormancy. Under anaerobic conditions, however, the TCA cycle pathway ceased expression in resting cysts, as also supported by ATP measurements. Our results have laid a cornerstone for the comprehensive revelation of the energetic metabolism and biochemical processes of dormancy of resting cysts in marine sediments.
COP1 Mediates Dark-Induced Stomatal Closure by Suppressing FT, TSF and SOC1 Expression to Promote NO Accumulation in Arabidopsis Guard Cells
Authors: An Yu-Yan , Li Jing , Feng Yu-Xin , Sun Zhi-Mao , Li Zhong-Qi , Wang Xiao-Ting , Zhang Mei-Xiang , He Jun-Min
Published: November 2022

RING-finger-type ubiquitin E3 ligase Constitutively Photomorphogenic 1 (COP1) and floral integrators such as FLOWERING LOCUS T (FT), TWIN SISTER OF FT (TSF) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) have been identified as regulators of stomatal movement. However, little is known about their roles and relationship in dark-induced stomatal closure. Here, we demonstrated that COP1 is required for dark-induced stomatal closure using cop1 mutant. The cop1 mutant closed stomata in response to exogenous nitric oxide (NO) but not hydrogen peroxide (H2O2), and H2O2 but not NO accumulated in cop1 in darkness, further indicating that COP1 acts downstream of H2O2 and upstream of NO in dark-induced stomatal closure. Expression of FT, TSF and SOC1 in wild-type (WT) plants decreased significantly with dark duration time, but this process was blocked in cop1. Furthermore, ft, tsf, and soc1 mutants accumulated NO and closed stomata faster than WT plants in response to darkness. Altogether, our results indicate that COP1 transduces H2O2 signaling, promotes NO accumulation in guard cells by suppressing FT, TSF and SOC1 expression, and consequently leads to stomatal closure in darkness. These findings add new insights into the mechanisms of dark-induced stomatal closure.
Functional Analyses of a Small Secreted Cysteine-Rich Protein ThSCSP_14 in Tilletia horrida
Authors: Shu Xinyue , Xu Deze , Jiang Yuqi , Liang Juan , Xiang Ting , Wang Yuxuan , Zhang Weike , Han Xue , Jiao Chunhai , Zheng Aiping , Li Ping , Yin Desuo , Wang Aijun
Published: November 2022

Tilletia horrida is a biotrophic basidiomycete fungus that causes rice kernel smut, one of the most significant diseases in hybrid rice-growing areas worldwide. Little is known about the pathogenic mechanisms and functions of effectors in T. horrida. Here, we performed functional studies of the effectors in T. horrida and found that, of six putative effectors tested, only ThSCSP_14 caused the cell death phenotype in epidermal cells of Nicotiana benthamiana leaves. ThSCSP_14 was upregulated early on during the infection process, and the encoded protein was secreted. The predicted signal peptide (SP) of ThSCSP_14 was required for its ability to induce the necrosis phenotype. Furthermore, the ability of ThSCSP_14 to trigger cell death in N. benthamiana depended on suppressing the G2 allele of Skp1 (SGT1), required for Mla12 resistance (RAR1), heat-shock protein 90 (HSP90), and somatic embryogenesis receptor-like kinase (SERK3). It is important to note that ThSCSP_14 induced a plant defense response in N. benthamiana leaves. Hence, these results demonstrate that ThSCSP_14 is a possible effector that plays an essential role in T. horrida–host interactions.
A Context-Aware Android Malware Detection Approach Using Machine Learning
Authors: AlJarrah Mohammed , Yaseen Qussai , Mustafa Ahmad
Published: November 2022

The Android platform has become the most popular smartphone operating system, which makes it a target for malicious mobile apps. This paper proposes a machine learning-based approach for Android malware detection based on application features. Unlike many prior research that focused exclusively on API Calls and permissions features to improve detection efficiency and accuracy, this paper incorporates applications’ contextual features with API Calls and permissions features. Moreover, the proposed approach extracted a new dataset of static API Calls and permission features using a large dataset of malicious and benign Android APK samples. Furthermore, the proposed approach used the Information Gain algorithm to reduce the API and permission feature space from 527 to the most relevant 50 features only. Several combinations of API Calls, permissions, and contextual features were used. These combinations were fed into different machine-learning algorithms to show the significance of using the selected contextual features in detecting Android malware. The experiments show that the proposed model achieved a very high accuracy of about 99.4% when using contextual features in comparison to 97.2% without using contextual features. Moreover, the paper shows that the proposed approach outperformed the state-of-the-art models considered in this work.
Leaf Nutritional Content, Tree Richness, and Season Shape the Caterpillar Functional Trait Composition Hosted by Trees
Authors: Anttonen Perttu , Li Yi , Chesters Douglas , Davrinche Andréa , Haider Sylvia , Bruelheide Helge , Chen Jing-Ting , Wang Ming-Qiang , Ma Ke-Ping , Zhu Chao-Dong , Schuldt Andreas
Published: November 2022

Nutritional content of host plants is expected to drive caterpillar species assemblages and their trait composition. These relationships are altered by tree richness-induced neighborhood variation and a seasonal decline in leaf quality. We tested how key functional traits related to the growth and defenses of the average caterpillar hosted by a tree species are shaped by nutritional host quality. We measured morphological traits and estimated plant community-level diet breadth based on occurrences from 1020 caterpillars representing 146 species in a subtropical tree diversity experiment from spring to autumn in one year. We focused on interspecific caterpillar trait variation by analyzing presence-only patterns of caterpillar species for each tree species. Our results show that tree richness positively affected caterpillar species-sharing among tree species, which resulted in lowered trait variation and led to higher caterpillar richness for each tree species. However, community-level diet breadth depended more on the nutritional content of host trees. Higher nutritional quality also supported species-poorer but more abundant communities of smaller and less well-defended caterpillars. This study demonstrates that the leaf nutritional quality of trees shapes caterpillar trait composition across diverse species assemblages at fine spatial scales in a way that can be predicted by ecological theory.
Environmental Effects on Taxonomic Turnover in Soil Fauna across Multiple Forest Ecosystems in East Asia
Authors: Li Peikun , Zhang Jian , Ding Shunping , Yan Peisen , Zhang Panpan , Ding Shengyan
Published: November 2022

The large-scale spatial variation in and causes of biotic turnover of soil fauna remain poorly understood. Analyses were conducted based on published data from 14 independent sampling sites across five forest ecosystems in East Asia. Jaccard and Sørensen’s indices were used to measure turnover rates in soil fauna orders. A redundancy analysis was used to investigate multiple environmental controls of the composition of soil fauna communities. The results showed that both Jaccard’s and Sørensen’s index increased significantly with increasing latitude difference. The environment explained 54.1%, 50.6%, 57.3% and 50.9% of the total variance, and spatial factors explained 13.8%, 15.9%, 21.0% and 12.6% of the total variance in the orders’ composition regarding overall, phytophagous, predatory and saprophagous fauna, respectively. In addition, climate factors in environmental processes were observed to have a stronger effect than soil factors on the orders’ turnover rates. Our results support the hypothesis that the effect of environment factors on soil animal taxa turnover is more important than the effect of spatial factors. Climatic factors explained more variation in the turnover of phytophagic fauna, but soil and environment factors equally explained the variation in the turnover of predatory fauna. This study provides evidence to support both environmental filtering and dispersal limitation hypotheses at the regional and population scales.
A New Genus and Species of Gall-Forming Fordini (Hemiptera: Aphididae) on Rhus wilsonii Hemsl. from Yunnan, China
Authors: Hébert Catherine , Xu Xin , Yang Zixiang , Favret Colin
Published: November 2022

A new species of gall-forming aphid from China, Qiao jinshaensis gen. et sp. nov., is described from Rhus wilsonii Hemsl. Morphological identification and molecular analyses both support the establishment of a new genus. A diagnosis combining morphological and molecular characters from alate viviparae is provided and specimen metadata are published in an open-access and machine-readable format.
Reproduction Evaluation and Transcription Analysis of Aphis gossypii under Various Photoperiods
Authors: Liu Zhe , Zhang Shuai , Zhu Ying , Jing Tianxing , Su Honghua , Hu Jin , Jiang Xin , Yang Yizhong
Published: November 2022

Aphis gossypii Glover (Hemiptera, Aphidoidae) is a polyphagous pest, whose complex phenotypic form, combined with its high fecundity and short reproductive cycle, has caused serious economic losses to agriculture worldwide. Photoperiod plays an important role in the reproduction of aphids. However, the molecular mechanisms underlying its response to seasonal photoperiodic changes are not known. In this study, the effects of different photoperiod treatments (8 L:16 D, 10 L:14 D, 12 L:12 D and 14 L:10 D) on A. gossypii reproduction in the first, third, and fifth generations at low temperatures were investigated. Then, transcriptome sequencing analysis was performed after the fifth generation of A. gossypii, exposed to different photoperiods (8 L:16 D and 12 L:12 D), using high-throughput sequencing technology. The results showed that (I) the effect of photoperiod on aphids was gradually evident with increasing exposure generations. In general, daylight extension help the A. gossypii to reproduce with the optimum photoperiod of L:D 12:12. (II) The transcriptome analysis results showed that 170 differentially expressed genes (DEGs) (123 downregulated and 47 upregulated genes) were identified between aphids under 8 h daylight and 12 h daylight. (III) Gene Ontology (GO) enrichment analysis showed that the DEGs involved in “proteolysis”, “metabolic process”, “peptidase activity” and “structural molecule activity” were significantly enriched; Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that there were more DEGs in “Longevity regulating pathway-multiple species”, “Lysosome”, “Endocytosis”, “Spliceosome” and “Protein processing in endoplasmic reticulum”. (IV) Ten related genes were chosen for validation of statistical analysis based on RNA-Seq by the reverse transcription quantitative (RT-qPCR). The comparison was consistent with the expression pattern and supported the accuracy and reliability of RNA-Seq. In summary, the genes involved in these pathways play an important role in the reproduction of A. gossypii under photoperiodical changes. These will contribute to the sustainable management of cotton aphids through the disruption of their reproduction by the method of RNA interference in the future.
Performance of PEO/Polymer Coatings on the Biodegradability, Antibacterial Effect and Biocompatibility of Mg-Based Materials
Authors: Fattah-alhosseini Arash , Chaharmahali Razieh , Rajabi Armin , Babaei Kazem , Kaseem Mosab
Published: November 2022

Magnesium (Mg) alloys have recently attracted attention in biomedicine as biodegradable materials with non-toxic degradable products. Such compounds have become a frontier in the study of biodegradable materials because of their remarkable biomechanical compatibility and superior biocompatibility. The use of Mg-based implants reduces the negative consequences of permanent biological implants by eliminating the necessity for biomaterial surgery following the healing process. However, the quick deterioration, formation of considerable gas of hydrogen volumes and a rise in the body environment pH are obstacles in the application of Mg as an implant material. Hence, compelling advances for erosion resistance and biocompatibility of magnesium and its alloys are noteworthy. Surface modification may be a practical approach because it improves the erosion resistance compared with extensive preparation of a treated surface for progressed bone recovery and cell attachment. Coating produced by plasma electrolytic oxidation (PEO) seems a compelling method in order to enhance magnesium and the properties of its alloys. PEO-formed coatings cannot provide long-term protection in the physiological environment due to their porous nature. Thus, a polymer coating is applied on the porous PEO-formed coating, which is steadily applied on the surface. Polymer coatings improve the biocompatibility properties of Mg and its alloys and increase corrosion resistance. In this article, the most recent advancements in PEO/polymer composite coatings are reviewed, and the biocompatibility of such coatings is examined.
Speed Optimization of Container Ship Considering Route Segmentation and Weather Data Loading: Turning Point-Time Segmentation Method
Authors: Li Xiaohe , Sun Baozhi , Jin Jianhai , Ding Jun
Published: November 2022

As one of the ship energy efficiency optimization measures with the most energy saving and emission reduction potential, ship speed optimization has been recommended by the International Maritime Organization. In ship speed optimization, considering the influence of weather conditions, route segmentation and weather data loading methods significantly affect the reliability of speed optimization results. Therefore, taking the ocean-going container ship as the research object, on the basis of constructing the main engine fuel consumption prediction model and shaft speed prediction model based on machine learning methods, a route segmentation and weather loading-speed optimization iterative algorithm is proposed in this study. Single-objective speed optimization research is then conducted based on the algorithm. The research results show that the proposed algorithm effectively reduces the difference between optimized fuel consumption and actual fuel consumption, and can achieve a fuel-saving rate between 2.1% and 5.2%. This study achieves an accurate and reliable prediction of ship fuel consumption and shaft speed, and solves the strong coupling problem between route segmentation, weather loading, and speed optimization by iterative optimization of ship speed. The proposed algorithm provides strong technical support for ships to achieve the goal of energy saving and emission reduction.
Towards a Consensus on an ICF-Based Classification System for Horizontal Sound-Source Localization
Authors: Mertens Griet , Andries Ellen , Kurz Anja , Tȧvora-Vieira Dayse , Calvino Miryam , Amann Edda , Anderson Ilona , Lorens Artur
Published: November 2022

The study aimed to develop a consensus classification system for the reporting of sound localization testing results, especially in the field of cochlear implantation. Against the background of an overview of the wide variations present in localization testing procedures and reporting metrics, a novel classification system was proposed to report localization errors according to the widely accepted International Classification of Functioning, Disability and Health (ICF) framework. The obtained HEARRING_LOC_ICF scale includes the ICF graded scale: 0 (no impairment), 1 (mild impairment), 2 (moderate impairment), 3 (severe impairment), and 4 (complete impairment). Improvement of comparability of localization results across institutes, localization testing setups, and listeners was demonstrated by applying the classification system retrospectively to data obtained from cohorts of normal-hearing and cochlear implant listeners at our institutes. The application of our classification system will help to facilitate multi-center studies, as well as allowing better meta-analyses of data, resulting in improved evidence-based practice in the field.
Clinical EEG of Rett Syndrome: Group Analysis Supplemented with Longitudinal Case Report
Authors: Portnova Galina , Neklyudova Anastasia , Voinova Victoria , Sysoeva Olga
Published: November 2022

Rett syndrome (RTT), a severe neurodevelopmental disorder caused by MECP2 gene abnormalities, is characterized by atypical EEG activity, and its detailed examination is lacking. We combined the comparison of one-time eyes open EEG resting state activity from 32 girls with RTT and their 41 typically developing peers (age 2–16 years old) with longitudinal following of one girl with RTT to reveal EEG parameters which correspond to the RTT progression. Traditional measures, such as epileptiform abnormalities, generalized background activity, beta activity and the sensorimotor rhythm, were supplemented by a new frequency rate index measured as the ratio between high- and low-frequency power of sensorimotor rhythm. Almost all studied EEG parameters differentiated the groups; however, only the elevated generalized background slowing and decrease in our newly introduced frequency rate index which reflects attenuation in the proportion of the upper band of sensorimotor rhythm in RTT showed significant relation with RTT progression both in longitudinal case and group analysis. Moreover, only this novel index was linked to the breathing irregularities RTT symptom. The percentage of epileptiform activity was unrelated to RTT severity, confirming previous studies. Thus, resting EEG can provide information about the pathophysiological changes caused by MECP2 abnormalities and disease progression.
DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy
Authors: Robinson Karyn G. , Marsh Adam G. , Lee Stephanie K. , Hicks Jonathan , Romero Brigette , Batish Mona , Crowgey Erin L. , Shrader M. Wade , Akins Robert E.
Published: November 2022

Spastic type cerebral palsy (CP) is a complex neuromuscular disorder that involves altered skeletal muscle microanatomy and growth, but little is known about the mechanisms contributing to muscle pathophysiology and dysfunction. Traditional genomic approaches have provided limited insight regarding disease onset and severity, but recent epigenomic studies indicate that DNA methylation patterns can be altered in CP. Here, we examined whether a diagnosis of spastic CP is associated with intrinsic DNA methylation differences in myoblasts and myotubes derived from muscle resident stem cell populations (satellite cells; SCs). Twelve subjects were enrolled (6 CP; 6 control) with informed consent/assent. Skeletal muscle biopsies were obtained during orthopedic surgeries, and SCs were isolated and cultured to establish patient–specific myoblast cell lines capable of proliferation and differentiation in culture. DNA methylation analyses indicated significant differences at 525 individual CpG sites in proliferating SC–derived myoblasts (MB) and 1774 CpG sites in differentiating SC–derived myotubes (MT). Of these, 79 CpG sites were common in both culture types. The distribution of differentially methylated 1 Mbp chromosomal segments indicated distinct regional hypo– and hyper–methylation patterns, and significant enrichment of differentially methylated sites on chromosomes 12, 13, 14, 15, 18, and 20. Average methylation load across 2000 bp regions flanking transcriptional start sites was significantly different in 3 genes in MBs, and 10 genes in MTs. SC derived MBs isolated from study participants with spastic CP exhibited fundamental differences in DNA methylation compared to controls at multiple levels of organization that may reveal new targets for studies of mechanisms contributing to muscle dysregulation in spastic CP.
Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders
Authors: Gomez Limia Cintia , Baird Megan , Schwartz Maura , Saxena Smita , Meyer Kathrin , Wein Nicolas
Published: November 2022

Neurodegenerative disorders (NDDs), such as Alzheimer’s disease (AD) and Parkinson’s Disease (PD), are a group of heterogeneous diseases that mainly affect central nervous system (CNS) functions. A subset of NDDs exhibit CNS dysfunction and muscle degeneration, as observed in Gangliosidosis 1 (GM1) and late stages of PD. Neuromuscular disorders (NMDs) are a group of diseases in which patients show primary progressive muscle weaknesses, including Duchenne Muscular Dystrophy (DMD), Pompe disease, and Spinal Muscular Atrophy (SMA). NDDs and NMDs typically have a genetic component, which affects the physiological functioning of critical cellular processes, leading to pathogenesis. Currently, there is no cure or efficient treatment for most of these diseases. More than 200 clinical trials have been completed or are currently underway in order to establish safety, tolerability, and efficacy of promising gene therapy approaches. Thus, gene therapy-based therapeutics, including viral or non-viral delivery, are very appealing for the treatment of NDDs and NMDs. In particular, adeno-associated viral vectors (AAV) are an attractive option for gene therapy for NDDs and NMDs. However, limitations have been identified after systemic delivery, including the suboptimal capacity of these therapies to traverse the blood–brain barrier (BBB), degradation of the particles during the delivery, high reactivity of the patient’s immune system during the treatment, and the potential need for redosing. To circumvent these limitations, several preclinical and clinical studies have suggested intrathecal (IT) delivery to target the CNS and peripheral organs via cerebrospinal fluid (CSF). CSF administration can vastly improve the delivery of small molecules and drugs to the brain and spinal cord as compared to systemic delivery. Here, we review AAV biology and vector design elements, different therapeutic routes of administration, and highlight CSF delivery as an attractive route of administration. We discuss the different aspects of neuromuscular and neurodegenerative diseases, such as pathogenesis, the landscape of mutations, and the biological processes associated with the disease. We also describe the hallmarks of NDDs and NMDs as well as discuss current therapeutic approaches and clinical progress in viral and non-viral gene therapy and enzyme replacement strategies for those diseases.
1.5T MR-Guided Daily-Adaptive SBRT for Prostate Cancer: Preliminary Report of Toxicity and Quality of Life of the First 100 Patients
Authors: Alongi Filippo , Rigo Michele , Figlia Vanessa , Nicosia Luca , Mazzola Rosario , Giaj Levra Niccolò , Ricchetti Francesco , Trapani Giovanna , Attinà Giorgio , Vitale Claudio , Pastorello Edoardo , De Simone Antonio , Gurrera Davide , Naccarato Stefania , Sicignano Gianluisa , Ruggieri Ruggero , Cuccia Francesco
Published: November 2022

Purpose: The present study reports the preliminary outcomes in terms of adverse events and quality of life in the first 100 patients treated with 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. Methods: From October 2019 to December 2020, 100 patients, enrolled in a prospective study, received MR-guided SBRT for prostate cancer. Rectal spacer insertion was optional and administered in 37 patients. In total, 32 patients received androgen deprivation therapy in accordance with international guidelines. A prospective collection of data regarding toxicity and quality of life was performed. Results: The median age was 71 years (range, 52–84). The median total dose delivered was 35 Gy (35–36.25 Gy) in five sessions, either on alternate days (n = 25) or consecutive days (n = 75). For acute toxicity, we recorded: seven cases of acute G2 urinary pain and four cases of G2 gastrointestinal events. The median follow-up was 12 months (3–20), recording three late G2 urinary events and one G3 case, consisting of a patient who required a TURP 8 months after the treatment. For gastrointestinal toxicity, we observed 3 G ≥ 2 GI events, including one patient who received argon laser therapy for radiation-induced proctitis. Up to the last follow-up, all patients are alive and with no evidence of biochemical relapse, except for an M1 low-volume patient in distant progression two months after radiotherapy. QoL evaluation reported a substantial resolution of any discomfort within the second follow-up after radiotherapy, with the only exception being sexual items. Notably, after one year, global health items were improved compared to the baseline assessment. Conclusions: This study reports very promising outcomes in terms of adverse events and QoL, supporting the role of 1.5T MR-guided SBRT for prostate cancer. To date, this series is one of the first and largest available in the literature. Long-term results are warranted.
Non-Invasive Archaeological Methodologies for the Analysis of the Port Structures of Portus Ilicitanus (Santa Pola, Alicante)
Authors: Álvarez Tortosa Juan Francisco , Catalán González Francisco Javier , Mateo Corredor Daniel , Ruiz Barroso Manuel , Molina Vidal Jaime
Published: November 2022

The traditional identification of the ancient port of Ilici with the current town of Santa Pola in Alicante (Spain) has been based on a small number of punctual, unconnected, and too partial archaeological interventions. Since 2017, a program of geophysical surveys has been performed with a Stream X model multi-channel georadar IDS. This program has been focused mainly on the so-called Mercado de Viguetes, an area in which archaeological excavations have hardly been carried out. The geophysical surveys have allowed us to draw part of the urban fabric of the central core of the Portus Ilicitanus, revealing a set of structures that can be assimilated into a port area: warehouses, houses, open spaces, and decantation basins to produce salted fish, and the probable eastern boundary of the complex identified with the port dock. Altogether, two predominant alignments can be assimilated into the Early Imperial and Late Imperial construction phases. Non-invasive archaeological methodologies have become the main resource for archaeological analysis and heritage protection in view of the current impossibility of carrying out archaeological excavations in this area of Santa Pola.