bluuebunny/crossref_metadata_2025 huggingface dataset:
Allocation of Flood Drainage Rights in Watershed Using a Hybrid FBWM-Grey-TOPSIS Method: A Case Study of the Jiangsu Section of the Sunan Canal, China
Authors: Zhang Xiaoyan , Shen Juqin , Sun Fuhua , Wang Shou , Zhang Shuxuan , Chen Jian
Published: July 2022

In this study, an FDR allocation scheme based on synergetic theory was designed to alleviate the drainage conflicts caused by the grabbing of flood drainage rights (FDR) in each region of the basin. An FDR allocation index system was constructed by employing synergetic theory and following the principles of safety, equity, efficiency, and sustainability. A new multi-criteria decision-making method, called FBWM-Grey-TOPSIS, was developed, which is based on the integration of the fuzzy best–worst method (FBWM) and Grey-TOPSIS. Among them, the FBWM method was used to distinguish the importance of subsystems and order parameters, and the Grey-TOPSIS method is applied to obtain the optimal FDR assignment results. Taking the Jiangsu section of the Sunan Canal as an example, the FDRs of the four regions in the basin were allocated. The results reveal that the proportion of FDRs obtained in descending order is Changzhou (32.69%), Suzhou (24.88%), Wuxi (23.01%), and Zhenjiang (19.42%). In addition, the performance of the proposed method is demonstrated by sensitivity analysis and comparative analysis with the existing methods. The methodology and research results presented in this paper can help governments and agencies achieve a scientific allocation of FDR in watersheds, thus promoting harmonious watershed development.
Analysis of the Urban Land Use Efficiency in the New-Type Urbanization Process of China’s Yangtze River Economic Belt
Authors: Yang Liu , Han Bingyang , Ma Zhili , Wang Ting , Lin Yingchao
Published: July 2022

The accelerated urbanization process in China has caused a shift in the urban land use structure. The Chinese government has issued ‘the National New-type Urbanization Plan’ focusing on the rational use of resources, which is of great significance for the intensification and sustainability of land use. In promoting the construction of the new-type urbanization (N-TU), enhancing the urban land use efficiency (ULUE) is crucial to regional coordinated development. This study uses panel data from 2011 to 2020 for 11 provinces (cities) in the Yangtze River Economic Belt (YREB) and adopts the super efficiency (SE) slacks-based measure (SBM) model with undesirable outputs and the entropy weight method to calculate the ULUE and N-TU levels. The study uses the System generalized method of moment (Sys-GMM) to study the N-TU’s impact on the ULUE empirically. The results indicate: (i) the overall trend of new-type urbanization level is gradually increasing and has the characteristics of uneven spatial distribution between provinces. (ii) The ULUE shows a fluctuating upward trend during the studied period. (iii) The N-TU and its subsystems have significant positive effects on the ULUE. Overall, this study aims to explore the relationship between the N-TU and ULUE enriching the theoretical analysis and empirical research in related fields, thus helping decision makers in the assessment and design of policy recommendations.
Metabolic and Obesity Phenotype Trajectories in Taiwanese Medical Personnel
Authors: Chang Hsin-Yun , Chang Jer-Hao , Chang Yin-Fan , Wu Chih-Hsing , Yang Yi-Ching
Published: July 2022

The distribution of metabolic and obesity phenotypes in Taiwanese medical personnel is unknown. In this study, trajectory analysis with repeated measurements was used to explore the development and associated risk factors of different metabolic and obesity phenotypes in hospital staff from a Taiwanese medical center. The results demonstrated that metabolically unhealthy workers presented with a higher body mass index (BMI) compared with their metabolically healthy counterparts. Male and aged > 40 years hospital workers were more likely to be in a deleterious metabolic/obesity state. Meanwhile, profession and working hours were not significantly associated with the development of certain phenotypes in our study. These results shed light on the necessity of adequate data retrieval regarding working hours, and a nuanced examination of working conditions among different professions. Our findings are helpful for the development of advanced guidance regarding health promotion in hospital workers.
Engaging Public Health Critical Race Praxis in Local Social Determinants of Health Research: The Youth Health Equity and Action Research Training Program in Portland, OR—yHEARTPDX
Authors: Petteway Ryan J. , González Lourdes A.
Published: July 2022

The social determinants of health (SDH) have long been considered a core mechanism through which racial health inequities are (re)produced and incubated in the U.S. Moreover, scholars have expressly—and appropriately—named structural racism as a precursor to inequities associated with SDH. However, while research on racial health inequities—SDH-related or otherwise—continues to grow, communities of color remain grossly underrepresented as public health researchers and practitioners. Additionally, although SDH are experienced in a very local sense, much research and practice fails to more deeply and thoroughly engage and center local community knowledges. Thus, much work around SDH and racial health inequities presents, ironically, as structurally racist itself—being done/led mostly by White scholars and in ways that do not “center the margins”. Moreover, in the context of public health practice, youth perspective is seldom centered within local health department (LHD) community SDH assessment efforts. With these challenges in mind, this paper introduces and discusses the development of the youth health equity and action research training (yHEART) program as a model for public health researchers/practitioners to engage public health critical race praxis (PHCRP) to better understand and respond to local SDH in communities of color. Specifically, we highlight the significance of PHCRP principles of “voice” and “social construction of knowledge” in advancing antiracism in research and LHD practice related to local SDH. First, we articulate core conceptual and theoretical groundings that informed the yHEART program’s development and animate its ongoing training and research activities. Second, we outline the program’s core training components and overall process, and provide some brief illustrative examples of work completed during the program’s first iteration—yHEART PDX, Vol.I: Youth Participatory Research on Local Social Determinants of Health. We then close with a discussion that reflects on program strengths, challenges, and implications for SDH and racial health equity research/practice in light of growing calls for an antiracist public health.
Thirty Years of sRNA-Mediated Regulation in Staphylococcus aureus: From Initial Discoveries to In Vivo Biological Implications
Authors: Menard Guillaume , Silard Chloé , Suriray Marie , Rouillon Astrid , Augagneur Yoann
Published: July 2022

Staphylococcus aureus is a widespread livestock and human pathogen that colonizes diverse microenvironments within its host. Its adaptation to the environmental conditions encountered within humans relies on coordinated gene expression. This requires a sophisticated regulatory network, among which regulatory RNAs (usually called sRNAs) have emerged as key players over the last 30 years. In S. aureus, sRNAs regulate target genes at the post-transcriptional level through base–pair interactions. The functional characterization of a subset revealed that they participate in all biological processes, including virulence, metabolic adaptation, and antibiotic resistance. In this review, we report 30 years of S. aureus sRNA studies, from their discovery to the in-depth characterizations of some of them. We also discuss their actual in vivo contribution, which is still lagging behind, and their place within the complex regulatory network. These shall be key aspects to consider in order to clearly uncover their in vivo biological functions.
Age-Related Hearing Loss: The Link between Inflammaging, Immunosenescence, and Gut Dysbiosis
Authors: Kociszewska Dagmara , Vlajkovic Srdjan
Published: July 2022

This article provides a theoretical overview of the association between age-related hearing loss (ARHL), immune system ageing (immunosenescence), and chronic inflammation. ARHL, or presbyacusis, is the most common sensory disability that significantly reduces the quality of life and has a high economic impact. This disorder is linked to genetic risk factors but is also influenced by a lifelong cumulative effect of environmental stressors, such as noise, otological diseases, or ototoxic drugs. Age-related hearing loss and other age-related disorders share common mechanisms which often converge on low-grade chronic inflammation known as “inflammaging”. Various stimuli can sustain inflammaging, including pathogens, cell debris, nutrients, and gut microbiota. As a result of ageing, the immune system can become defective, leading to the accumulation of unresolved inflammatory processes in the body. Gut microbiota plays a central role in inflammaging because it can release inflammatory mediators and crosstalk with other organ systems. A proinflammatory gut environment associated with ageing could result in a leaky gut and the translocation of bacterial metabolites and inflammatory mediators to distant organs via the systemic circulation. Here, we postulate that inflammaging, as a result of immunosenescence and gut dysbiosis, accelerates age-related cochlear degeneration, contributing to the development of ARHL. Age-dependent gut dysbiosis was included as a hypothetical link that should receive more attention in future studies.
Alternative Splicing and Its Roles in Plant Metabolism
Authors: Lam Pui Ying , Wang Lanxiang , Lo Clive , Zhu Fu-Yuan
Published: July 2022

Plant metabolism, including primary metabolism such as tricarboxylic acid cycle, glycolysis, shikimate and amino acid pathways as well as specialized metabolism such as biosynthesis of phenolics, alkaloids and saponins, contributes to plant survival, growth, development and interactions with the environment. To this end, these metabolic processes are tightly and finely regulated transcriptionally, post-transcriptionally, translationally and post-translationally in response to different growth and developmental stages as well as the constantly changing environment. In this review, we summarize and describe the current knowledge of the regulation of plant metabolism by alternative splicing, a post-transcriptional regulatory mechanism that generates multiple protein isoforms from a single gene by using alternative splice sites during splicing. Numerous genes in plant metabolism have been shown to be alternatively spliced under different developmental stages and stress conditions. In particular, alternative splicing serves as a regulatory mechanism to fine-tune plant metabolism by altering biochemical activities, interaction and subcellular localization of proteins encoded by splice isoforms of various genes.
Neuropathic Pain Induces Interleukin-1β Sensitive Bimodal Glycinergic Activity in the Central Amygdala
Authors: Oliva Carolina A. , Stehberg Jimmy , Barra Rafael , Mariqueo Trinidad
Published: July 2022

Neuropathic pain reduces GABA and glycine receptor (GlyR)-mediated activity in spinal and supraspinal regions associated with pain processing. Interleukin-1β (IL-1β) alters Central Amygdala (CeA) excitability by reducing glycinergic inhibition in a mechanism that involves the auxiliary β-subunit of GlyR (βGlyR), which is highly expressed in this region. However, GlyR activity and its modulation by IL-1β in supraspinal brain regions under neuropathic pain have not been studied. We performed chronic constriction injury (CCI) of the sciatic nerve in male Sprague Dawley rats, a procedure that induces hind paw plantar hyperalgesia and neuropathic pain. Ten days later, the rats were euthanized, and their brains were sliced. Glycinergic spontaneous inhibitory currents (sIPSCs) were recorded in the CeA slices. The sIPSCs from CeA neurons of CCI animals show a bimodal amplitude distribution, different from the normal distribution in Sham animals, with small and large amplitudes of similar decay constants. The perfusion of IL-1β (10 ng/mL) in these slices reduced the amplitudes within the first five minutes, with a pronounced effect on the largest amplitudes. Our data support a possible role for CeA GlyRs in pain processing and in the neuroimmune modulation of pain perception.
Phosphate in the Context of Cognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease
Authors: Rroji Merita , Figurek Andreja , Viggiano Davide , Capasso Giovambattista , Spasovski Goce
Published: July 2022

The nervous system and the kidneys are linked under physiological states to maintain normal body homeostasis. In chronic kidney disease (CKD), damaged kidneys can impair the central nervous system, including cerebrovascular disease and cognitive impairment (CI). Recently, kidney disease has been proposed as a new modifiable risk factor for dementia. It is reported that uremic toxins may have direct neurotoxic (astrocyte activation and neuronal death) and/or indirect action through vascular effects (cerebral endothelial dysfunction, calcification, and inflammation). This review summarizes the evidence from research investigating the pathophysiological effects of phosphate toxicity in the nervous system, raising the question of whether the control of hyperphosphatemia in CKD would lower patients’ risk of developing cognitive impairment and dementia.
H2+CO2 Synergistic Plasma Positioning Carboxyl Defects in g-C3N4 with Engineered Electronic Structure and Active Sites for Efficient Photocatalytic H2 Evolution
Authors: Wang Daqian , Zhang Zhihao , Xu Shuchuan , Guo Ying , Kang Shifei , Chang Xijiang
Published: July 2022

Defective functional-group-endowed polymer semiconductors, which have unique photoelectric properties and rapid carrier separation properties, are an emerging type of high-performance photocatalyst for various energy and environmental applications. However, traditional oxidation etching chemical methods struggle to introduce defects or produce special functional group structures gently and controllably, which limits the implementation and application of the defective functional group modification strategy. Here, with the surface carboxyl modification of graphitic carbon nitride (g-C3N4) photocatalyst as an example, we show for the first time the feasibility and precise modification potential of the non-thermal plasma method. In this method, the microwave plasma technique is employed to generate highly active plasma in a combined H2+CO2 gas environment. The plasma treatment allows for scalable production of high-quality defective carboxyl group-endowed g-C3N4 nanosheets with mesopores. The rapid H2+CO2 plasma immersion treatment can precisely tune the electronic and band structures of g-C3N4 nanosheets within 10 min. This conjoint approach also promotes charge-carrier separation and accelerates the photocatalyst-catalyzed H2 evolution rate from 1.68 mmol h−1g−1 (raw g-C3N4) to 8.53 mmol h−1g−1 (H2+CO2-pCN) under Xenon lamp irradiation. The apparent quantum yield (AQY) of the H2+CO2-pCN with the presence of 5 wt.% Pt cocatalyst is 4.14% at 450 nm. Combined with density functional theory calculations, we illustrate that the synergistic N vacancy generation and carboxyl species grafting modifies raw g-C3N4 materials by introducing ideal defective carboxyl groups into the framework of heptazine ring g-C3N4, leading to significantly optimized electronic structure and active sites for efficient photocatalytic H2 evolution. The 5.08-times enhancement in the photocatalytic H2 evolution over the as-developed catalysts reveal the potential and maneuverability of the non-thermal plasma method in positioning carboxyl defects and mesoporous morphology. This work presents new understanding about the defect engineering mechanism in g-C3N4 semiconductors, and thus paves the way for rational design of effective polymeric photocatalysts through advanced defective functional group engineering techniques evolving CO2 as the industrial carrier gas.
Homozygosity for a Novel DOCK7 Variant Due to Segmental Uniparental Isodisomy of Chromosome 1 Associated with Early Infantile Epileptic Encephalopathy (EIEE) and Cortical Visual Impairment
Authors: Kivrak Pfiffner Fatma , Koller Samuel , Ménétrey Anika , Graf Urs , Bähr Luzy , Maspoli Alessandro , Hackenberg Annette , Kottke Raimund , Gerth-Kahlert Christina , Berger Wolfgang
Published: July 2022

Early infantile epileptic encephalopathy (EIEE) is a severe neurologic and neurodevelopmental disease that manifests in the first year of life. It shows a high degree of genetic heterogeneity, but the genetic origin is only identified in half of the cases. We report the case of a female child initially diagnosed with Leber congenital amaurosis (LCA), an early-onset retinal dystrophy due to photoreceptor cell degeneration in the retina. The first examination at 9 months of age revealed no reaction to light or objects and showed wandering eye movements. Ophthalmological examination did not show any ocular abnormalities. The patient displayed mildly dysmorphic features and a global developmental delay. Brain MRI demonstrated pontine hypo-/dysplasia. The patient developed myoclonic epileptic seizures and epileptic spasms with focal and generalized epileptiform discharges on electroencephalogram (EEG) at the age of 16 months. Genetic screening for a potentially pathogenic DNA sequence variant by whole-exome sequencing (WES) revealed a novel, conserved, homozygous frameshift variant (c.5391delA, p.(Ala1798LeufsTer59)) in exon 42 of the DOCK7 gene (NM_001271999.1). Further analysis by SNP array (Karyomapping) showed loss of heterozygosity (LOH) in four segments of chromosome 1. WES data of the parents and the index patient (trio analysis) demonstrated that chromosome 1 was exclusively inherited from the mother. Four LOH segments of chromosome 1 alternately showed isodisomy (UPiD) and heterodisomy (UPhD). In WES data, the father was a noncarrier, and the mother was heterozygous for this DOCK7 variant. The DOCK7 gene is located in 1p31.3, a region situated in one of the four isodisomic segments of chromosome 1, explaining the homozygosity seen in the affected child. Finally, Sanger sequencing confirmed maternal UPiD for the DOCK7 variant. Homozygous or compound heterozygous pathogenic variants in the DOCK7 (dedicator of cytokinesis 7) gene are associated with autosomal recessive, early infantile epileptic encephalopathy 23 (EIEE23; OMIM #615,859), a rare and heterogeneous group of neurodevelopmental disorders diagnosed during early childhood. To our knowledge, this is the first report of segmental uniparental iso- and heterodisomy of chromosome 1, leading to homozygosity of the DOCK7 frameshift variant in the affected patient.
Multipotential Role of Growth Factor Mimetic Peptides for Osteochondral Tissue Engineering
Authors: Rizzo Maria Giovanna , Palermo Nicoletta , D’Amora Ugo , Oddo Salvatore , Guglielmino Salvatore Pietro Paolo , Conoci Sabrina , Szychlinska Marta Anna , Calabrese Giovanna
Published: July 2022

Articular cartilage is characterized by a poor self-healing capacity due to its aneural and avascular nature. Once injured, it undergoes a series of catabolic processes which lead to its progressive degeneration and the onset of a severe chronic disease called osteoarthritis (OA). In OA, important alterations of the morpho-functional organization occur in the cartilage extracellular matrix, involving all the nearby tissues, including the subchondral bone. Osteochondral engineering, based on a perfect combination of cells, biomaterials and biomolecules, is becoming increasingly successful for the regeneration of injured cartilage and underlying subchondral bone tissue. To this end, recently, several peptides have been explored as active molecules and enrichment motifs for the functionalization of biomaterials due to their ability to be easily chemically synthesized, as well as their tunable physico-chemical features, low immunogenicity issues and functional group modeling properties. In addition, they have shown a good aptitude to penetrate into the tissue due to their small size and stability at room temperature. In particular, growth-factor-derived peptides can play multiple functions in bone and cartilage repair, exhibiting chondrogenic/osteogenic differentiation properties. Among the most studied peptides, great attention has been paid to transforming growth factor-β and bone morphogenetic protein mimetic peptides, cell-penetrating peptides, cell-binding peptides, self-assembling peptides and extracellular matrix-derived peptides. Moreover, recently, phage display technology is emerging as a powerful selection technique for obtaining functional peptides on a large scale and at a low cost. In particular, these peptides have demonstrated advantages such as high biocompatibility; the ability to be immobilized directly on chondro- and osteoinductive nanomaterials; and improving the cell attachment, differentiation, development and regeneration of osteochondral tissue. In this context, the aim of the present review was to go through the recent literature underlining the importance of studying novel functional motifs related to growth factor mimetic peptides that could be a useful tool in osteochondral repair strategies. Moreover, the review summarizes the current knowledge of the use of phage display peptides in osteochondral tissue regeneration.
The Clinical Spectrum and Disease Course of DRAM2 Retinopathy
Authors: Krašovec Tjaša , Volk Marija , Šuštar Habjan Maja , Hawlina Marko , Vidović Valentinčič Nataša , Fakin Ana
Published: July 2022

Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone–rod or rod–cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease.
Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
Authors: Liu Qinrui , Wang Hu , Wang Hualin , Li Na , He Ruyi , Liu Zhiguo
Published: July 2022

Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of Per1/Per2 Double knockout (DKO) reduced the reproductive capacity of elderly male mice. The sperm motility and spermatogenic capacity of male DKO mice were weak. Hormone-targeted metabolomics showed reduced plasma levels of free testosterone in DKO male mice compared with WT male mice. Transcriptomic analysis of testicular tissue showed the down-regulation of testosterone synthesis-related enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, and Star) in the steroid hormone synthesis pathway. Spermatogenesis genes, Tubd1 and Pafah1b were down-regulated, influencing tubulin dynamics and leading to impaired motility. Seleno-compound metabolic loci, Scly and Sephs2, were up-regulated and Slc7a11 and Selenop were down-regulated. Western-blotting showed that steroid acute regulatory protein (StAR) and p-CREB, PKA and AC1 were reduced in testicular tissue of DKO mice compared to WT. Therefore, Per1/Per2 disruption reduced testosterone synthesis and sperm motility by affecting the PKA-StAR pathway, leading to decreased fertility.
Silver@quercetin Nanoparticles with Aggregation-Induced Emission for Bioimaging In Vitro and In Vivo
Authors: Li Yuanyuan , Xiao Daming , Li Shujun , Chen Zhijun , Liu Shouxin , Li Jian
Published: July 2022

Fluorescent materials based on aggregation-induced emission luminogens (AIEgens) have unique advantages for in situ and real-time monitoring of biomolecules and biological processes because of their high luminescence intensity and resistance to photobleaching. Unfortunately, many AIEgens require time-consuming and expensive syntheses, and the presence of residual toxic reagents reduces their biocompatibility. Herein, silver@quercetin nanoparticles (Ag@QCNPs), which have a clear core–shell structure, were prepared by redox reaction of quercetin (QC), a polyphenolic compound widely obtained from plants, including those used as foods, and silver ions. Ag@QCNPs show both aggregation-induced luminescence and the distinct plasma scattering of silver nanoparticles, as well as good resistance to photobleaching and biocompatibility. The Ag@QCNPs were successfully used for cytoplasmic labeling of living cells and for computerized tomography imaging in tumor-bearing mice, demonstrating their potential for clinical applications.
Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways
Authors: Bonetti Gabriele , Paolacci Stefano , Samaja Michele , Maltese Paolo Enrico , Michelini Sandro , Michelini Serena , Michelini Silvia , Ricci Maurizio , Cestari Marina , Dautaj Astrit , Medori Maria Chiara , Bertelli Matteo
Published: July 2022

Lymphedema is a chronic inflammatory disorder caused by ineffective fluid uptake by the lymphatic system, with effects mainly on the lower limbs. Lymphedema is either primary, when caused by genetic mutations, or secondary, when it follows injury, infection, or surgery. In this study, we aim to assess to what extent the current genetic tests detect genetic variants of lymphedema, and to identify the major molecular pathways that underlie this rather unknown disease. We recruited 147 individuals with a clinical diagnosis of primary lymphedema and used established genetic tests on their blood or saliva specimens. Only 11 of these were positive, while other probands were either negative (63) or inconclusive (73). The low efficacy of such tests calls for greater insight into the underlying mechanisms to increase accuracy. For this purpose, we built a molecular pathways diagram based on a literature analysis (OMIM, Kegg, PubMed, Scopus) of candidate and diagnostic genes. The PI3K/AKT and the RAS/MAPK pathways emerged as primary candidates responsible for lymphedema diagnosis, while the Rho/ROCK pathway appeared less critical. The results of this study suggest the most important pathways involved in the pathogenesis of lymphedema, and outline the most promising diagnostic and candidate genes to diagnose this disease.
Morphological and Proteomic Analyses of Soybean Seedling Interaction Mechanism Affected by Fiber Crosslinked with Zinc-Oxide Nanoparticles
Authors: Komatsu Setsuko , Murata Kazuki , Yakeishi Sayuri , Shimada Kazuyuki , Yamaguchi Hisateru , Hitachi Keisuke , Tsuchida Kunihiro , Obi Rumina , Akita Shoichi , Fukuda Ryo
Published: July 2022

Nanoparticles (NPs) enhance soybean growth; however, their precise mechanism is not clearly understood. To develop a more effective method using NPs for the enhancement of soybean growth, fiber crosslinked with zinc oxide (ZnO) NPs was prepared. The solution of ZnO NPs with 200 nm promoted soybean growth at the concentration of 10 ppm, while fibers crosslinked with ZnO NPs promoted growth at a 1 ppm concentration. Soybeans grown on fiber cross-linked with ZnO NPs had higher Zn content in their roots than those grown in ZnO NPs solution. To study the positive mechanism of fiber crosslinked with ZnO NPs on soybean growth, a proteomic technique was used. Proteins categorized in photosynthesis and secondary metabolism accumulated more in soybeans grown on fiber crosslinked with ZnO NPs than in those grown in ZnO NPs solution. Furthermore, significantly accumulated proteins, which were NADPH oxidoreductase and tubulins, were confirmed using immunoblot analysis. The abundance of NADPH oxidoreductase increased in soybean by ZnO NPs application. These results suggest that fiber crosslinked with ZnO NPs enhances soybean growth through the increase of photosynthesis and secondary metabolism. Additionally, the accumulation of NADPH oxidoreductase might relate to the effect of auxin with fiber crosslinked with ZnO NPs on soybean growth.
Indirect Enantioseparations: Recent Advances in Chiral Metabolomics for Biomedical Research
Authors: Bogos Luisa-Gabriela , Pralea Ioana-Ecaterina , Moldovan Radu-Cristian , Iuga Cristina-Adela
Published: July 2022

Chiral metabolomics is starting to become a well-defined research field, powered by the recent advances in separation techniques. This review aimed to cover the most relevant advances in indirect enantioseparations of endogenous metabolites that were published over the last 10 years, including improvements and development of new chiral derivatizing agents, along with advances in separation methodologies. Moreover, special emphasis is put on exciting advances in separation techniques combined with mass spectrometry, such as chiral discrimination by ion-mobility mass spectrometry together with untargeted strategies for profiling of chiral metabolites in complex matrices. These advances signify a leap in chiral metabolomics technologies that will surely offer a solid base to better understand the specific roles of enantiomeric metabolites in systems biology.
Impaired Bestrophin Channel Activity in an iPSC-RPE Model of Best Vitelliform Macular Dystrophy (BVMD) from an Early Onset Patient Carrying the P77S Dominant Mutation
Authors: Navinés-Ferrer Arnau , Ruiz-Nogales Sheila , Navarro Rafael , Pomares Esther
Published: July 2022

Best Vitelliform Macular dystrophy (BVMD) is the most prevalent of the distinctive retinal dystrophies caused by mutations in the BEST1 gene. This gene, which encodes for a homopentameric calcium-activated ion channel, is crucial for the homeostasis and function of the retinal pigment epithelia (RPE), the cell type responsible for recycling the visual pigments generated by photoreceptor cells. In BVMD patients, mutations in this gene induce functional problems in the RPE cell layer with an accumulation of lipofucsin that evolves into cell death and loss of sight. In this work, we employ iPSC-RPE cells derived from a patient with the p.Pro77Ser dominant mutation to determine the correlation between this variant and the ocular phenotype. To this purpose, gene and protein expression and localization are evaluated in iPSC-RPE cells along with functional assays like phagocytosis and anion channel activity. Our cell model shows no differences in gene expression, protein expression/localization, or phagocytosis capacity, but presents an increased chloride entrance, indicating that the p.Pro77Ser variant might be a gain-of-function mutation. We hypothesize that this variant disturbs the neck region of the BEST1 channel, affecting channel function but maintaining cell homeostasis in the short term. This data shed new light on the different phenotypes of dominant mutations in BEST1, and emphasize the importance of understanding its molecular mechanisms. Furthermore, the data widen the knowledge of this pathology and open the door for a better diagnosis and prognosis of the disease.
Bioengineered Silkworm for Producing Cocoons with High Fibroin Content for Regenerated Fibroin Biomaterial-Based Applications
Authors: Yamano Mana , Hirose Ryoko , Lye Ping Ying , Takaki Keiko , Maruta Rina , On Liew Mervyn Wing , Sakurai Shinichi , Mori Hajime , Kotani Eiji
Published: July 2022

Silk fibroin exhibits high biocompatibility and biodegradability, making it a versatile biomaterial for medical applications. However, contaminated silkworm-derived substances in remnant sericin from the filature and degumming process can result in undesired immune reactions and silk allergy, limiting the widespread use of fibroin. Here, we established transgenic silkworms with modified middle silk glands, in which sericin expression was repressed by the ectopic expression of cabbage butterfly-derived cytotoxin pierisin-1A, to produce cocoons composed solely of fibroin. Intact, nondegraded fibroin can be prepared from the transgenic cocoons without the need for sericin removal by the filature and degumming steps that cause fibroin degradation. A wide-angle X-ray diffraction analysis revealed low crystallinity in the transgenic cocoons. However, nondegraded fibroin obtained from transgenic cocoons enabled the formation of fibroin sponges with varying densities by using 1–5% (v/v) alcohol. The effective chondrogenic differentiation of ATDC5 cells was induced following their cultivation on substrates coated with intact fibroin. Our results showed that intact, allergen-free fibroin can be obtained from transgenic cocoons without the need for sericin removal, providing a method to produce fibroin-based materials with high biocompatibility for biomedical uses.
Bortezomib Eliminates Persistent Chlamydia trachomatis Infection through Rapid and Specific Host Cell Apoptosis
Authors: Itoh Ryota , Kurihara Yusuke , Yoshimura Michinobu , Hiromatsu Kenji
Published: July 2022

Chlamydia trachomatis, a parasitic intracellular bacterium, is a major human pathogen that causes millions of trachoma, sexually transmitted infections, and pneumonia cases worldwide. Previously, peptidomimetic inhibitors consisting of a hydrophobic dipeptide derivative exhibited significant inhibitory effects against chlamydial growth. Based on this finding, this study showed that both bortezomib (BTZ) and ixazomib (IXA), anticancer drugs characterized by proteasome inhibitors, have intensive inhibitory activity against Chlamydia. Both BTZ and IXA consisted of hydrophobic dipeptide derivatives and strongly restricted the growth of Chlamydia (BTZ, IC50 = 24 nM). In contrast, no growth inhibitory effect was observed for other nonintracellular parasitic bacteria, such as Escherichia coli. BTZ and IXA appeared to inhibit chlamydial growth bacteriostatically via electron microscopy. Surprisingly, Chlamydia-infected cells that induced a persistent infection state were selectively eliminated by BTZ treatment, whereas uninfected cells survived. These results strongly suggested the potential of boron compounds based on hydrophobic dipeptides for treating chlamydial infections, including persistent infections, which may be useful for future therapeutic use in chlamydial infectious diseases.
The Role of Beta Cell Recovery in Type 2 Diabetes Remission
Authors: Suleiman Mara , Marselli Lorella , Cnop Miriam , Eizirik Decio L. , De Luca Carmela , Femia Francesca R. , Tesi Marta , Del Guerra Silvia , Marchetti Piero
Published: July 2022

Type 2 diabetes (T2D) has been considered a relentlessly worsening disease, due to the progressive deterioration of the pancreatic beta cell functional mass. Recent evidence indicates, however, that remission of T2D may occur in variable proportions of patients after specific treatments that are associated with recovery of beta cell function. Here we review the available information on the recovery of beta cells in (a) non-diabetic individuals previously exposed to metabolic stress; (b) T2D patients following low-calorie diets, pharmacological therapies or bariatric surgery; (c) human islets isolated from non-diabetic organ donors that recover from “lipo-glucotoxic” conditions; and (d) human islets isolated from T2D organ donors and exposed to specific treatments. The improvement of insulin secretion reported by these studies and the associated molecular traits unveil the possibility to promote T2D remission by directly targeting pancreatic beta cells.
Overexpression of OsGF14f Enhances Quantitative Leaf Blast and Bacterial Blight Resistance in Rice
Authors: Ma Yamei , Yang Jianyuan , Dong Jingfang , Zhang Shaohong , Yang Wu , Zhao Junliang , Yang Tifeng , Chen Luo , Zhou Lian , Wang Jian , Chen Jiansong , Li Wenhui , Wu Wei , Liu Qing , Liu Bin
Published: July 2022

Although it is known that rice 14-3-3 family genes are involved in various defense responses, the functions of OsGF14f in response to diseases have not been reported. Here, we showed that the transcription of OsGF14f was significantly induced by leaf blast infection, and the overexpression of OsGF14f quantitatively enhanced resistance to leaf blast and bacterial blight in rice. Further analysis showed that the expression levels of salicylic acid (SA) pathway-associated genes (PAL1, NH1, PR1a and PR10) in the OsGF14f-overexpressing plants, were higher than those in wild-type plants after inoculation with the blast isolate (Magnaporthe oryzae Barr). In addition, the expression level of OsGF14f was significantly induced after SA treatment, and higher endogenous SA levels were observed in the OsGF14f-overexpressing plants compared with that in wild-type plants, especially after blast challenge. Taken together, these results suggest that OsGF14f positively regulates leaf blast and bacterial blight resistance in rice via the SA-dependent signaling pathway.
New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease
Authors: Bertran Laia , Jorba-Martin Rosa , Barrientos-Riosalido Andrea , Portillo-Carrasquer Marta , Aguilar Carmen , Riesco David , Martínez Salomé , Vives Margarita , Sabench Fàtima , Castillo Daniel Del , Richart Cristóbal , Auguet Teresa
Published: July 2022

Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic development and in some pathological processes. Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, and negative associations with weight and jejunal Toll-like receptors (TLR4) and TLR5 expression. Regarding jejunal OLFM4, we observed positive correlations with circulating interleukin (IL)-8, IL-10, IL-17 and jejunal TLR9. In conclusion, OLFM2 in the liver seems to play a relevant role in NAFLD progression, while OLFM4 in the jejunum could be involved in gut dysbiosis-related inflammatory events.
Sphingosine-1-Phosphate-Triggered Expression of Cathelicidin LL-37 Promotes the Growth of Human Bladder Cancer Cells
Authors: Wollny Tomasz , Wnorowska Urszula , Piktel Ewelina , Suprewicz Łukasz , Król Grzegorz , Głuszek Katarzyna , Góźdź Stanisław , Kopczyński Janusz , Bucki Robert
Published: July 2022

It has been proven that tumour growth and progression are regulated by a variety of mediators released during the inflammatory process preceding the tumour appearance, but the role of inflammation in the development of bladder cancer is ambiguous. This study was designed around the hypothesis that sphingosine-1-phosphate (S1P), as a regulator of several cellular processes important in both inflammation and cancer development, may exert some of the pro-tumorigenic effects indirectly due to its ability to regulate the expression of human cathelicidin (hCAP-18). LL-37 peptide released from hCAP-18 is involved in the development of various types of cancer in humans, especially those associated with infections. Using immunohistological staining, we showed high expression of hCAP-18/LL-37 and sphingosine kinase 1 (the enzyme that forms S1P from sphingosine) in human bladder cancer cells. In a cell culture model, S1P was able to stimulate the expression and release of hCAP-18/LL-37 from human bladder cells, and the addition of LL-37 peptide dose-dependently increased their proliferation. Additionally, the effect of S1P on LL-37 release was inhibited in the presence of FTY720P, a synthetic immunosuppressant that blocks S1P receptors. Together, this study presents the possibility of paracrine relation in which LL-37 production following cell stimulation by S1P promotes the development and growth of bladder cancer.
Innate Immunity in Calcinosis Cutis
Authors: Jiang Simon W. , Petty Amy J. , Nicholas Matilda W.
Published: July 2022

Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue, manifesting as variably shaped papules, nodules, and plaques that can substantially impair quality of life. The pathophysiology of calcinosis cutis involves dysregulation of proinflammatory cytokines, leukocytes, and other components of the innate immune system. In some conditions associated with calcinosis cutis, elevated serum calcium, phosphate, and vitamin D may also perturb innate immunity. The mechanisms by which these lead to cutaneous and subcutaneous calcification likely parallel those seen in vascular calcification. The role of aberrant innate immunity is further supported by the association between various autoantibodies with calcinosis cutis, such as anti-MDA5, anti-NXP2, anti-centromere, and anti-topoisomerase I. Treatments for calcinosis cutis remain limited and largely experimental, although mechanistically many therapies appear to focus on dampening innate immune responses. Further research is needed to better understand the innate immune pathophysiology and establish treatment options based on randomized-controlled trials.
Combined Effects of Soil Silicon and Host Plant Resistance on Planthoppers, Blast and Bacterial Blight in Tropical Rice
Authors: Vu Quynh , Dossa Gerbert Sylvestre , Mundaca Enrique A. , Settele Josef , Crisol-Martínez Eduardo , Horgan Finbarr G.
Published: July 2022

Soil silicon enhances rice defenses against a range of biotic stresses. However, the magnitude of these effects can depend on the nature of the rice variety. We conducted a series of greenhouse experiments to examine the effects of silicon on planthoppers (Nilaparvata lugens [BPH] and Sogatella furcifera [WBPH]), a leafhopper (Nephotettix virescens [GLH]), blast disease (Magnaporthe grisea) and bacterial blight (Xanthomonas oryzae) in susceptible and resistant rice. We added powdered silica gel (SiO2) to paddy soil at equivalent to 0.25, 1.0, and 4.0 t ha−1. Added silicon reduced BPH nymph settling, but the effect was negligible under high nitrogen. In a choice experiment, BPH egg-laying was lower than untreated controls under all silicon treatments regardless of nitrogen or variety, whereas, in a no-choice experiment, silicon reduced egg-laying on the susceptible but not the resistant (BPH32 gene) variety. Stronger effects in choice experiments suggest that silicon mainly enhanced antixenosis defenses. We found no effects of silicon on WBPH or GLH. Silicon reduced blast damage to susceptible and resistant (Piz, Piz-5 and Pi9 genes) rice. Silicon reduced damage from a virulent strain of bacterial blight but had little effect on a less virulent strain in susceptible and resistant (Xa4, Xa7 and Xa4 + Xa7 genes) varieties. When combined with resistance, silicon had an additive effect in reducing biomass losses to plants infested with bacterial blight (resistance up to 50%; silicon 20%). We discuss how silicon-containing soil amendments can be combined with host resistance to reduce biotic stresses in rice.
Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function
Authors: Kalisnik Jurij Matija , Steblovnik Klemen , Hrovat Eva , Jerin Ales , Skitek Milan , Dinges Christian , Fischlein Theodor , Zibert Janez
Published: July 2022

We have recently shown that minor subclinical creatinine dynamic changes enable the excellent detection of acute kidney injury (AKI) within 6–12 h after cardiac surgery. The aim of the present study was to examine a combination of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine for enhanced AKI detection early after cardiac surgery. Elective patients with normal renal function undergoing cardiac surgery using cardiopulmonary bypass were enrolled. Concentrations of plasma NGAL, serum CysC and serum creatinine were determined after the induction of general anesthesia, at the termination of the cardiopulmonary bypass and 2 h thereafter. Out of 119 enrolled patients, 51 (43%) developed AKI. A model utilizing an NGAL, CysC and creatinine triple biomarker panel including sequential relative changes provides a better prediction of cardiac surgery-associated acute kidney injury than any biomarker alone already 2 h after the termination of the cardiopulmonary bypass. The area under the receiver-operator curve was 0.77, sensitivity 77% and specificity 68%.
A Comparative Study on Surgical Treatment of Valvular Heart Disease between High-Volume Cardiac Centers in China and STS Data
Authors: Lin Hongyuan , Gong Jiamiao , Wu Yongjian , Zheng Zhe , Hou Jianfeng
Published: July 2022

The goal of this study is to summarize valvular surgery data from the Chinese Cardiac Surgery Registry (CCSR) and compare it to the most recent data from the Society of Thoracic Surgeons (STS). From 2016 to 2018, a total of 34,386 cases of the seven most common valvular surgical procedures was obtained from the CCSR. We calculated the proportions of different procedures in the CCSR cohort (n = 34,386) as well as the change in operation volume for each procedure. We also compiled rates of postoperative in-hospital mortality and five major complications across all procedures. All of the results were compared to the STS data. The CCSR and STS data showed divergent trends in valvular heart disease features and operation volume. Although the proportion of MV repair in the CCSR (13.7%) data was lower than in the STS data (23.2%), it demonstrated a substantial upward trend. In terms of operation volume, the CCSR data showed an upward trend, but the STS data showed a downward trend. CCSR procedures showed lower mortality (2% vs. 2.6%), reoperation (2.8% vs. 4.3%), and permanent stroke (0.5% vs. 1.6%) rates than STS procedures but higher rates of prolonged ventilation (22.4% vs. 10.4%) and renal failure (5.6% vs. 3.2%). Valvular surgery quality in China’s leading cardiac hospitals is roughly comparable to that in the United States. China, on the other hand, has some shortcomings that need improvement.