bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Analysis of Transient Overvoltage Phenomena for Metal-Oxide Varistor Surge Arrester in LCC-HVDC Transmission System with Special Protection Scheme
Authors: Kang Jaesik
Published: September 2022

This paper proposes a systematic and deterministic method for metal-oxide varistor (MOV) surge arrester selection based on the comprehensive analysis in line-commutated converter (LCC)-based high-voltage direct current (HVDC) transmission systems. For the MOV surge arrester, this paper investigates several significant impacts on the transient overvoltage (TOV) phenomena, which is affected by practical factors such as an operating point of the LCC-HVDC system, synchronous machine operating status of the power system, AC passive filter trip, and communication delay in a special protection system (SPS). In order to determine an appropriate rating of surge arrester, especially for TOV, this paper considers a pattern, magnitude, and duration of TOV based on various fault scenarios in an electrical power system with an LCC-HVDC system. A screening study method with 60 Hz and RMS-based balance system is conducted for examining a wide range of fault scenarios, and then for the specific test cases that need a detailed analysis, electro-magnetic transient (EMT)-based analysis models are developed with an approvable boundary setting method through the equivalent network translation tool. A detailed EMT study is subsequent based on the distinguished cases; as a result, the exact number of metal-oxide resistor stacks could be obtained through the detailed TOV study according to this procedure. The efficacy of the selection method from the proposed procedure based on the comprehensive analysis are verified on a specific power system with a 1.5 GW DC ± 500 kV symmetric monopole LCC-HVDC transmission system.
Boiling Heat Transfer during Flow in Vertical Mini-Channels with a Modified Heated Surface
Authors: Piasecka Magdalena , Strąk Kinga
Published: September 2022

The process with change of phase during flow in mini-channels plays a significant role in many industrial applications, such as microelectronics. Furthermore, methods for heat transfer intensification during flow in channels of small cross-section are still being sought. In this work, studies of the effect of using a modified heated surface on intensification boiling heat transfer in rectangular mini-channels during upward and downward flow are performed. The test section of a group of seven parallel mini-channels 1 mm deep was investigated during the subcooled and saturated flow boiling of FC-72. The temperature of the outer heated wall surface was measured using an infrared camera. During the experiments, two-phase flow structures were captured with a quick camera. Local heat transfer coefficients at the contact surface between the working fluid and the heated surface were determined with the use of a one-dimensional calculation method. To present the results, local temperature measurements and heat transfer coefficients, boiling curves and two-phase flow patterns are shown and analyzed. The results concerning two directions of vertical flow along mini-channels are discussed. Several modified heated surfaces and one smooth were tested for comparison. The main objective was to find out how the modified surface of the heated wall can intensify boiling heat transfer with upward and downward refrigerant flow in mini-channels of rectangular cross-section.
Transferrin Mediated NCC Killing Activity through NCCRP-1 in Nile Tilapia (Oreochromis niloticus)
Authors: Huang Yu , Chen Zhengsi , Xie Ruitao , Wang Pei , Zhang Zhiqiang , Cai Jia , Wang Bei , Jian Jichang
Published: September 2022

Non-specific cytotoxic cell l (NCC) is a kind of important lymphocyte participating in the non-specific immune response in teleost. Non-specific cytotoxic cell receptor protein 1 (NCCRP-1) is a receptor molecule on the surface of NCC and plays an important role in mediating the activity of NCC. However, there are few reports on which signal molecule could transmit signals through NCCRP-1. In this study, yeast two-hybrid library of tilapia liver and head kidney was constructed, and a transferrin from Oreochromis niloticus (On-TF) with interaction protein sequence was obtained by screening the library with bait vector NCCRP-1 of Oreochromis niloticus (On-NCCRP-1). Then, the open reading frame (ORF) of On-TF was cloned, which had 2088 bp in length, encoding polypeptides of 695 amino acids. The deduced amino acid sequence was highly homologous to teleost and similar to mammalian TF, containing two TR_FER domains (25-343th aa and 344-686th aa) for binding iron ions. Furthermore, a point-to-point yeast two-hybrid method was used to further verify whether On-NCCRP-1 could bind to On-TF. The recombinant On-TF (rOn-TF) protein was purified by prokaryotic expression system. In vitro experiments showed that rOn-TF could up-regulate the expression of killing effector molecule of NCC by On-NCCRP-1, and rOn-TF-activated NCCs showed a significantly improved ability to kill FHM cells, indicating that rOn-TF could regulate the NCC signaling pathway through NCC receptor molecule On-NCCRP-1. The results provide a more theoretical basis for understanding the regulation mechanism of NCC activity.
Mapping Decomposition: A Preliminary Study of Non-Destructive Detection of Simulated body Fluids in the Shallow Subsurface
Authors: Barone Pier Matteo , Matsentidi Danielle , Mollard Alex , Kulengowska Nikola , Mistry Mohit
Published: September 2022

The processes of decomposition that the body will have after the time of death are peculiar and complex. The body swells and expels gases and fluids, and the flesh decays. It also attracts many insects and scavengers. We know that these fluids are nutrients for the vegetation, and if the body is inhumed in the subsurface, they allow a rapid crop growth that remote sensors can mark. During forensic investigations, mapping the fluid migration in the subsurface can help reconstruct the genesis of a clandestine grave. Several studies show how different remote sensors and analyses can be sensitive to human burials. This paper presents a preliminary experiment studying the fluid dispersion in the subsurface using simulated body fluids in a shallow grave and detecting it through the ground penetrating radar (GPR) technique (given its ability to detect dielectric constant changes in the investigated media) and other remote sensing techniques. Although the simulation of the body fluids related to the dielectric constant was accurate and allowed us to better understand how decomposition in the subsurface does not always migrate in the way that was initially expected (toward gravity), other typical characteristics of the body fluids, other soils and external factors were left out and would be studied in future simulations.
Horses, Humans, and Domestic Bodily Knowledge in All’s Well That Ends Well
Authors: Nunn Hillary M.
Published: September 2022

Without visual cues, modern viewers may not discern the ways that All’s Well That Ends Well brings together the bodies of horses and humans, asking viewers to consider the physical dependence and sometimes overlapping medical conditions the two species share. Helena’s success in curing the King’s fistula and conceiving Bertram’s child have not been linked to the skills involved in working with horses, let alone the blurring of boundaries between the human and the equine. This is particularly striking given that the play associates both the King and Bertram—the two men she must win over to gain happiness—with images of veterinary care and riding as represented in the era’s household medical and horsemanship manuals. Early modern recipe books provide a valuable glimpse of how seventeenth century viewers might have pictured the interconnectedness of human and animal bodies, in health and in sickness. These books make clear that some cures for fistulas could be used on humans or on horses. Such medicines take as a given the human body’s embeddedness on its surroundings, revealing an essential dependence between humans and horses, often blurring the boundaries assumed to exist between them. The play positions Helena not only as a practitioner of household medicine skilled in caring for humans and animals alike, but also as a subtle and resourceful horsewoman able to coerce others to do her bidding.
Revealing Personality Triggers for Media Vicarious Traumatization: A Fuzzy-Set Qualitative Comparative Analysis
Authors: Huang Xin , Shi Yibin , Gao Guannan
Published: September 2022

People may experience media vicarious traumatization due to frequent exposure to media coverage of disasters. Currently, the influential relationship between personality traits and media vicarious traumatization still lacks systematic and in-depth research. Based on the MU5735 airplane crash, this study explored the effects of configurations of personality traits on media vicarious traumatization by analyzing data from 331 Chinese university students (Mage = 22.63 years, SD = 2.67, range = 18 to 29, n = 186 male and n = 145 female) using Fuzzy-set Qualitative Comparative Analysis (fsQCA). The results revealed that five combinations of the Big Five personality traits could lead to media vicarious traumatization, the combinations of configurations are: (1) high conscientiousness, high agreeableness, and high neuroticism; (2) high conscientiousness, high extraversion, and high agreeableness; (3) high extraversion, high neuroticism, low conscientiousness, and low agreeableness; (4) high openness, high extraversion, high agreeableness, and high neuroticism; (5) high extraversion, high agreeableness, low openness, and low neuroticism. Furthermore, sociodemographic variables (gender, age, and education) interacted with personality traits and also resulted in different configurations of media vicarious traumatization. This study indicates the asymmetric relationships between personality traits and media vicarious traumatization, identifies the vulnerable groups to facilitate targeted trauma interventions for university students according to different configurations, and provides a reference for public psychological relief efforts in emergencies.
The “Transparency for Safety” Triangle: Developing a Smart Transparency Framework to Achieve a Safety Learning Community
Authors: Lindhout Paul , Reniers Genserik
Published: September 2022

Transparency about health and safety risks is a complex societal, moral, ethical and political concept. Full transparency does not come natural for any of the key stakeholder groups: organizations, authorities and the people. If safety information is not sufficiently shared between them, people and the environment can be harmed. The authors explored the literature on transparency in sharing health and safety information. The findings show that such transparency as a subject is abundant in the literature but the exchange of information is far from complete in practice. Health and safety information is shared both via internal flows within each stakeholder group and via external flows between them. All three main stakeholders in pursuit of true safety for their own reasons, building trust via sharing of health and safety information, require improvement in transparency and a safety information broker between them. This constitutes a smart transparency and information exchange framework. The authors recommend developing a transparency standard, to study cyber-socio-technical systems safety and to include currently underutilized experiential knowledge available from the general public in the societal discourse. The authors propose a societal domain extension to a holistic safety culture model in support of a learning safety community.
Effect of Exercise on Vascular Function and Blood Lipids in Postmenopausal Women: A Systematic Review and Network Meta-Analysis
Authors: Xin Chenxi , Ye Mingyi , Zhang Qianqian , He Hui
Published: September 2022

This study aimed to compare and rank the effectiveness of aerobic exercise (AE), resistance training (RT), combined training (CT), and water exercise (WE) on vascular function and blood lipids in postmenopausal women using a network meta-analysis (NMA). Methods: We searched the PubMed, Cochrane, Embase, Web of Science, and EBSCO (SPORTDiscus) databases to identify randomized controlled trials investigating the effects of exercise on vascular function and blood lipids in postmenopausal women. The retrieval period was from inception to March 2022. Two reviewers independently screened the retrieved articles, extracted pertinent data, and assessed the risk of bias of the included studies. Results: A total of 38 studies involving 1407 patients were included in this study. The results of the NMA indicated that WE had the greatest effect on systolic blood pressure (SBP) (surface under the cumulative ranking [SUCRA] = 84.9) and total cholesterol (TC) (SUCRA = 93.1); CT had the greatest effect on triglycerides (TG) (SUCRA = 96.2), high-density lipoprotein cholesterol (HDL-C) (SUCRA = 94.8), and diastolic blood pressure (DBP) (SUCRA = 91.1); RT had the greatest effect on low-density lipoprotein cholesterol (LDL-C) (SUCRA = 79.4). Conclusion: The results suggest that exercise can effectively improve the PWV, SBP, and DBP and the levels of TC, TG, and LDL-C in postmenopausal women. WE had the best effect on improving TC and SBP. CT had the best effect on improving TG, HDL-C, and DBP. To improve LDL-C, RT can achieve a good effect. Considering the limitations of NMA, more RCTS need to be performed in the future to provide more direct evidence of the effectiveness of various exercise interventions on vascular health in postmenopausal women.
Pregnancy Complications in Pandemics: Is Pregnancy-Related Anxiety a Possible Physiological Risk Factor?
Authors: Abahussain Eman , Al-Otaibi Manal , Al-Humaidi Khulud , Al-Mutairi Sultanah , Al-Khatir Alexandra , Abualnaja Amani , Al-Mazidi Sarah
Published: September 2022

Background: Birth and pregnancy complications increased by 10.2% during the 2019 coronavirus (COVID-19) pandemic. Pregnant women are at high risk for anxiety, which might trigger physio-logical stress, leading to pregnancy complications. Aim: This study aimed to investigate factors leading to antenatal anxiety during the COVID-19 pandemic. We also aimed to discuss our find-ings with regard to the current literature about pregnancy complications. Methods: This cross-sectional study interviewed 377 pregnant women and assessed anxiety using a validated 7-item general anxiety disorder (GAD-7) scale. Anxiety was related to physiological and demo-graphic parameters. Anxiety was subdivided into pandemic- and pregnancy-related anxiety to minimize results bias. Results: Our results showed that 75.3% of pregnant women were anxious. The mean GAD-7 score was 8.28 ± 5. Linear regression analysis showed that for every increase in the number of previous pregnancies, there was a 1.3 increase in anxiety level (p < 0.001). Women with no previous miscarriages were more anxious (p < 0.001). Surprisingly, pregnant women who were previously infected with COVID-19 were 6% less stressed. Pregnant women with comorbid-ities were more stressed (p < 0.001). Low income (p < 0.001) and age (p < 0.05) were the demo-graphic factors most significantly related to increased anxiety. Conclusions: The prevalence of pregnancy-related anxiety increased threefold in Saudi Arabia due to the COVID-19 pandemic. Healthcare support should be available remotely during pandemics; pregnant women (especially those with comorbidities) should be educated about the risks of infection and complications to prevent anxiety-related complications during pregnancy.
Development of a Novel Primer–TaqMan Probe Set for Diagnosis and Quantification of Meloidogyne enterolobii in Soil Using qPCR and Droplet Digital PCR Assays
Authors: Chen Yuan , Long Haibo , Feng Tuizi , Pei Yueling , Sun Yanfang , Zhang Xinchun
Published: September 2022

Early detection of pathogens before the planting season is valuable to forecast disease occurrence. Therefore, rapid and reliable diagnostic approaches are urgently needed, especially for one of the most aggressive root knot nematodes, Meloidogyne enterolobii. In this study, we developed a novel primer–TaqMan probe set aimed at M. enterolobii. The primer–probe set was successfully applied in the identification and quantification of M. enterolobii via qPCR technology. It was also suitable for improved PCR technology, known as ddPCR analyses, and this work presents the first application of this technology for plant parasitic nematodes. Compared with qPCR, ddPCR exhibited better performance with regard to analytical sensitivity, which can provide a more accurate detection of M. enterolobii concealed in field soil. In addition, we generated standard curves to calculate the number of eggs in soil using the qPCR and ddPCR platforms. Hopefully, the results herein will be helpful for forecasting disease severity of M. enterolobii infection and adopting effective management strategies.
Validation of Appropriate Reference Genes for qRT–PCR Normalization in Oat (Avena sativa L.) under UV-B and High-Light Stresses
Authors: Yin Hang , Yin Danni , Zhang Mingzhi , Gao Zhiqiang , Tuluhong Muzhapaer , Li Xiaoming , Li Jikai , Li Bing , Cui Guowen
Published: September 2022

Oat is a food and forage crop species widely cultivated worldwide, and it is also an important forage grass in plateau regions of China, where there is a high level of ultraviolet radiation and sunlight. Screening suitable reference genes for oat under UV-B and high-light stresses is a prerequisite for ensuring the accuracy of real-time quantitative PCR (qRT–PCR) data used in plant adaptation research. In this study, eight candidate reference genes (sulfite oxidase, SUOX; victorin binding protein, VBP; actin-encoding, Actin1; protein PSK SIMULATOR 1-like, PSKS1; TATA-binding protein 2-like, TBP2; ubiquitin-conjugating enzyme E2, UBC2; elongation factor 1-alpha, EF1-α; glyceraldehyde-3-phosphate dehydrogenase 1, GAPDH1;) were selected based on previous studies and our oat transcriptome data. The expression stability of these reference genes in oat roots, stems, and leaves under UV-B and high-light stresses was first calculated using three frequently used statistical software (geNorm, NormFinder, and BestKeeper), and then the comprehensive stability of these genes was evaluated using RefFinder. The results showed that the most stably expressed reference genes in the roots, stems, and leaves of oat under UV-B stress were EF1-α, TBP2, and PSKS1, respectively; the most stably expressed reference genes in the roots, stems, and leaves under high-light stress were PSKS1, UBC2, and PSKS1, respectively. PSKS1 was the most stably expressed reference gene in all the samples. The reliability of the selected reference genes was further validated by analysis of the expression of the phenylalanine ammonia-lyase (PAL) gene. This study highlights reference genes for accurate quantitative analysis of gene expression in different tissues of oat under UV-B and high-light stresses.
The Extracts of Dendrobium Alleviate Dry Eye Disease in Rat Model by Regulating Aquaporin Expression and MAPKs/NF-κB Signalling
Authors: Ling Jiawei , Chan Chung-Lap , Ho Chi-Yan , Gao Xun , Tsang Sin-Man , Leung Ping-Chung , Hu Jiang-Miao , Wong Chun-Kwok
Published: September 2022

Dry eye is one of the most common ocular surface diseases caused by tear film instability and ocular surface damage due to an abnormal quality or quantity of tears. Inflammatory factors can initiate relevant transduction signalling pathways and trigger the inflammatory cascade response, resulting in ocular surface inflammation. It has been shown that the active ingredients in Dendrobium, such as polysaccharides, alkaloids and phenols, have anti-inflammatory, anti-tumour and immunity-boosting effects, and Dendrobium officinale extract can improve glandular secretion function, increase salivary secretion and increase the expression level of water channel protein in salivary glands in patients with dry eye syndromes. We investigated the in vitro cytoprotective effect of Dendrobium extracts in sodium chloride induced hyperosmotic conditions in human cornea keratocytes (HKs). Results showed that Dendrobium officinale Kimura et Migo water extract (DOW) and Dendrobium loddigesii Rolfe water extract (DLW) could upregulate the expression of aquaporins (AQP)5 protein, thus exerting a repairing effect by promoting cell migration. Furthermore, oral administration of DOW and DLW enhanced tear production in rats and exerted a protective effect on ocular surface damage. DOW and DLW could upregulate the expression of AQP5 and mucin (muc)5ac proteins in the lacrimal gland and reduce the inflammatory response. DOW and DLW inhibited the activation of the corresponding mitogen-activated protein kinases (MAPK) and NF-KB pathway, thereby playing a role in improving dry eye symptoms. This study provides a new perspective on dry eye treatment, and DOW and DLW may be potential therapeutic agents for dry eye.
Metal Cluster Triggered-Assembling Heterogeneous Au-Ag Nanoclusters with Highly Loading Performance and Biocompatible Capability
Authors: He Xiaoxiao , Ma Xiaohong , Yang Yujun , Hu Xi , Wang Teng , Chen Shiyue , Mao Xiang
Published: September 2022

In this work, we firstly report the preparation of heterogeneously assembled structures Au-Ag nanoclusters (NCs) as good drug carriers with high loading performance and biocompatible capability. As glutathione-protected Au and Ag clusters self-assembled into porous Au-Ag NCs, the size value is about 1.358 (±0.05) nm. The morphology characterization revealed that the diameter of Au-Ag NCs is approximately 120 nm, as well as the corresponding potential ability in loading performance of the metal cluster triggered-assembling process. Compared with individual components, the stability and loading performance of heterogeneous Au-Ag NCs were improved and exhibit that the relative biocompatibility was enhanced. The exact information about this is that cell viability was approximately to 98% when cells were incubated with 100 µg mL−1 particle solution for 3 days. The drug release of Adriamycin from Au-Ag NCs was carried out in PBS at pH = 7.4 and 5.8, respectively. By simulating in vivo and tumor microenvironment, the release efficiency could reach over 65% at pH = 5.8 but less than 30% at pH = 7.2. Using an ultrasound field as external environment can accelerate the assembling process while metal clusters triggered assembling Au-Ag NCs. The size and morphology of the assembled Au-Ag NCs can be controlled by using different power parameters (8 W, 13 W, 18 W) under ambient atmosphere. Overall, a novel approach is exhibited, which conveys assembling work for metal clusters triggers into heterogeneous structures with porous characteristic. Its existing properties such as water-solubility, stability, low toxicity and capsulation can be considered as dependable agents in various biomedical applications and drug carriers in immunotherapies.
Removal of Copper(II) from Aqueous Environment Using Silk Sericin-Derived Carbon
Authors: Xiao Yuting , Luo Ruixiao , Ji Yansong , Li Shiwei , Hu Hongmei , Zhang Xiaoning
Published: September 2022

Sericin is a by-product of the silk industry. Its recycling contributes to environmental protection and the sustainable development of the cocoon silk industry. In this paper, on the basis of realizing sericin enrichment in solution, the Cu(II) adsorption capacities of sericin-derived carbon (SC), prepared at different pyrolysis temperatures, were studied. SC was characterized using scanning electron microscopy (SEM) and the zeta potential. The effects of the initial concentration of Cu(II), pH, adsorption temperature, and contact time on the adsorption process were evaluated, followed by an investigation of the mechanism of Cu(II) adsorption by SC. The results showed that SC has a porous structure that provides sites for Cu(II) adsorption. The maximum adsorption capacity of Cu(II) onto SC1050, 17.97 mg/g, was obtained at an adsorption temperature of 35 °C and a pH of 5.5. In addition, the pseudo-second-order kinetic model and Langmuir isotherm model correctly described the adsorption process of Cu(II) onto SC1050. Therefore, SC can act as a potential adsorbent for removing Cu(II) from water. This study helps promote the effective use of cocoon silk resources.
An Amidase Contributes to Full Virulence of Sclerotinia sclerotiorum
Authors: Li Wei , Lu Junxing , Yang Chenghuizi , Arildsen Kate , Li Xin , Xia Shitou
Published: September 2022

Sclerotinia sclerotiorum is one of the most notorious and ubiquitous soilborne plant pathogens, causing serious economic losses to a large number of hosts worldwide. Although virulence factors have been identified in this filamentous fungus, including various cell-wall-degrading enzymes, toxins, oxalic acids and effectors, our understanding of its virulence strategies is far from complete. To explore novel factors contributing to disease, a new pipeline combining forward genetic screening and next-generation sequencing was utilized in this study. Analysis of a hypovirulent mutant revealed that a mutation in an amidase-encoding gene, Sscle_10g079050, resulted in reduced virulence. This is a first report on the contribution of an amidase to fungal virulence, likely through affecting oxalic acid homeostasis.
Inhibition of GABAAR or Application of Lactobacillus casei Zhang Alleviates Ulcerative Colitis in Mice: GABAAR as a Potential Target for Intestinal Epithelial Renewal and Repair
Authors: Wang Qiuzhen , Deng Ziteng , Lan Jing , Li Dan , Fan Kai , Chang Jianyu , Ma Yunfei
Published: September 2022

Emerging evidence indicates that the gamma−aminobutyric acid type A receptor (GABAAR) and Lactobacillus casei Zhang regulate colitis in a variety of ways, such as by participating in host immune and inflammatory responses, altering the gut microbiota, and influencing intestinal barrier function. However, not much is known about the mechanisms by which GABAAR and L. casei affect colon epithelial cell renewal and the interaction between GABAAR and L. casei during this process. To elucidate this, we established a dextran sulfate sodium (DSS)−induced model and measured the mouse body weights, colon length, the disease activity index (DAI), and histological scores. Our results indicated that inhibition of GABAAR alleviated the DSS−induced colitis symptoms, resulting in less weight loss and more intact colon tissue. Moreover, treatment with bicuculline (Bic, a GABAAR inhibitor) increased the levels of PCNA, β−catenin, and TCF4 in mice with colitis. Interestingly, open field test performances showed that inhibition of GABAAR also attenuated colitis−related anxiety−like behavior. By 16S RNA gene sequencing analysis, we showed that inhibition of GABAAR partially reversed the gut dysbacteriosis of DSS−induced mice and increased the abundance of beneficial bacteria. Additionally, L. casei Zhang supplementation inhibited the expression of GABAAR in mice with colitis, promoted the proliferation and renewal of colon epithelial cells, and alleviated anxiety−like behavior and intestinal microflora disorder in mice. Thus, GABAAR plays a key role in the beneficial effects of L. casei on DSS−induced colitis in mice.
Mesenchymal Stem Cell-Derived Extracellular Vesicles as Proposed Therapy in a Rat Model of Cerebral Small Vessel Disease
Authors: Guy Reut , Herman Shay , Benyamini Hadar , Ben-Zur Tali , Kobo Hila , Pasmanik-Chor Metsada , Yaacobi Dafna , Barel Eric , Yagil Chana , Yagil Yoram , Offen Daniel
Published: September 2022

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been employed in the past decade as therapeutic agents in various diseases, including central nervous system (CNS) disorders. We currently aimed to use MSC-EVs as potential treatment for cerebral small vessel disease (CSVD), a complex disorder with a variety of manifestations. MSC-EVs were intranasally administrated to salt-sensitive hypertension prone SBH/y rats that were DOCA-salt loaded (SBH/y-DS), which we have previously shown is a model of CSVD. MSC-EVs accumulated within brain lesion sites of SBH/y-DS. An in vitro model of an inflammatory environment in the brain demonstrated anti-inflammatory properties of MSC-EVs. Following in vivo MSC-EV treatment, gene set enrichment analysis (GSEA) of SBH/y-DS cortices revealed downregulation of immune system response-related gene sets. In addition, MSC-EVs downregulated gene sets related to apoptosis, wound healing and coagulation, and upregulated gene sets associated with synaptic signaling and cognition. While no specific gene was markedly altered upon treatment, the synergistic effect of all gene alternations was sufficient to increase animal survival and improve the neurological state of affected SBH/y-DS rats. Our data suggest MSC-EVs act as microenvironment modulators, through various molecular pathways. We conclude that MSC-EVs may serve as beneficial therapeutic measure for multifactorial disorders, such as CSVD.
The Microbiota–Gut–Brain Axis in Psychiatric Disorders
Authors: Góralczyk-Bińkowska Aleksandra , Szmajda-Krygier Dagmara , Kozłowska Elżbieta
Published: September 2022

Modulating the gut microbiome and its influence on human health is the subject of intense research. The gut microbiota could be associated not only with gastroenterological diseases but also with psychiatric disorders. The importance of factors such as stress, mode of delivery, the role of probiotics, circadian clock system, diet, and occupational and environmental exposure in the relationship between the gut microbiota and brain function through bidirectional communication, described as “the microbiome–gut–brain axis”, is especially underlined. In this review, we discuss the link between the intestinal microbiome and the brain and host response involving different pathways between the intestinal microbiota and the nervous system (e.g., neurotransmitters, endocrine system, immunological mechanisms, or bacterial metabolites). We review the microbiota alterations and their results in the development of psychiatric disorders, including major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD).
Genomic Landscape of Mixed-Phenotype Acute Leukemia
Authors: Hennawi Marah , Pakasticali Nagehan , Tashkandi Hammad , Hussaini Mohammad
Published: September 2022

Mixed-phenotype leukemia (MPAL) is a type of acute leukemia in which the blast population shows mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. MPALs are rare and carry a poor prognosis, thus, often pose both a diagnostic and therapeutic challenge. Conventionally, the diagnosis of MPAL requires either a single blast population with a lineage-defining phenotypic expression of multiple lineages (myeloid, B-cell and/or T-cell) (biphenotypic) or two distinct blast populations that each independently satisfy criteria for designation as AML, B-ALL, and/or T-ALL (bilineage). Given the rarity of MPAL, minimal studies have been performed to describe the genomic landscape of these neoplasms. IRB approval was obtained. Central MCC database was searched for any patient with a diagnosis of acute undifferentiated leukemia (AUL), acute leukemia of ambiguous lineage (ALAL), and MPAL. All patient diagnoses were manually reviewed by a hematopathologist to confirm the diagnosis of MPAL. Genomic and molecular data were collated from the EMR and bioinformatically from MCC genomics repositories. Twenty-eight patients with MPAL were identified. Thirteen were female and 15 were male. Average age was 56 years old (range = 28–81). Ten cases were biclonal and 18 were biphenotypic. Diagnoses were as follows: B/myeloid (n = 18), T/myeloid (n = 9), and T/B (n = 1). Cytogenetic analysis (Karyotype +/− FISH) was available for 27 patients. The most frequent recurrent abnormalities were complex karyotype (n = 8), BCR/ABL1 translocation (n = 6), Del 5q/−5 (n = 4), Polysomy 21 (n = 4). Mutational analysis was available for 18 patients wherein mutations were detected in 45 unique genes. The most frequently mutated genes were TP53 (7), RUNX1 (6), WT1 (4), MLL2 (3), FLT3 (3), CBL (2), ASXL1 (2), TET2 (2), MAP3K6 (2), MLL (2), and MAP3K1 (2). Targetable or potentially targetable biomarkers were found in 56% of cases. Overall survival was 19.5 months (range = 0–70 m). Ten patients were treated with an allogeneic stem cell transplant and had superior outcome (p = 0.0013). In one the largest series of MPAL cases to date, we corroborate previous findings with enriched detection of RUNX1 and FLT3–ITD mutations along with discovery of unreported mutations (MAP3K) that may be amenable to therapeutic manipulation. We also report the frequent occurrence of AML with MDS-related changes (AML-MRC)-defining cytogenetic abnormalities (26%). Finally, we show that those patients that received stem cell transplant had a better overall survival. Our findings support the need to genomically profile MPAL cases to exploit opportunities for targeted therapies in this orphan disease with dismal prognosis.
Interpretable Machine Learning Models for Molecular Design of Tyrosine Kinase Inhibitors Using Variational Autoencoders and Perturbation-Based Approach of Chemical Space Exploration
Authors: Krishnan Keerthi , Kassab Ryan , Agajanian Steve , Verkhivker Gennady
Published: September 2022

In the current study, we introduce an integrative machine learning strategy for the autonomous molecular design of protein kinase inhibitors using variational autoencoders and a novel cluster-based perturbation approach for exploration of the chemical latent space. The proposed strategy combines autoencoder-based embedding of small molecules with a cluster-based perturbation approach for efficient navigation of the latent space and a feature-based kinase inhibition likelihood classifier that guides optimization of the molecular properties and targeted molecular design. In the proposed generative approach, molecules sharing similar structures tend to cluster in the latent space, and interpolating between two molecules in the latent space enables smooth changes in the molecular structures and properties. The results demonstrated that the proposed strategy can efficiently explore the latent space of small molecules and kinase inhibitors along interpretable directions to guide the generation of novel family-specific kinase molecules that display a significant scaffold diversity and optimal biochemical properties. Through assessment of the latent-based and chemical feature-based binary and multiclass classifiers, we developed a robust probabilistic evaluator of kinase inhibition likelihood that is specifically tailored to guide the molecular design of novel SRC kinase molecules. The generated molecules originating from LCK and ABL1 kinase inhibitors yielded ~40% of novel and valid SRC kinase compounds with high kinase inhibition likelihood probability values (p > 0.75) and high similarity (Tanimoto coefficient > 0.6) to the known SRC inhibitors. By combining the molecular perturbation design with the kinase inhibition likelihood analysis and similarity assessments, we showed that the proposed molecular design strategy can produce novel valid molecules and transform known inhibitors of different kinase families into potential chemical probes of the SRC kinase with excellent physicochemical profiles and high similarity to the known SRC kinase drugs. The results of our study suggest that task-specific manipulation of a biased latent space may be an important direction for more effective task-oriented and target-specific autonomous chemical design models.
Brassinosteroid Signaling Downstream Suppressor BIN2 Interacts with SLFRIGIDA-LIKE to Induce Early Flowering in Tomato
Authors: Khan Maqsood , Luo Bote , Hu Miaomiao , Fu Shangtan , Liu Jianwei , Jiang Meng , Zhao Yan , Huang Shuhua , Wang Shufen , Wang Xiaofeng
Published: September 2022

Brassinosteroid (BR) signaling is very important in plant developmental processes. Its various components interact to form a signaling cascade. These components are widely studied in Arabidopsis; however, very little information is available on tomatoes. Brassinosteroid Insensitive 2 (BIN2), the downstream suppressor of BR signaling, plays a critical role in BR signal pathway, while FRIGIDA as a key suppressor of Flowering Locus C with overexpression could cause early flowering; however, how the BR signaling regulates FRIGIDA homologous protein to adjust flowering time is still unknown. This study identified 12 FRIGIDA-LIKE proteins with a conserved FRIGIDA domain in tomatoes. Yeast two-hybrid and BiFC confirmed that SlBIN2 interacts with 4 SlFRLs, which are sub-cellularly localized in the nucleus. Tissue-specific expression of SlFRLs was observed highly in young roots and flowers. Biological results revealed that SlFRLs interact with SlBIN2 to regulate early flowering. Further, the mRNA level of SlBIN2 also increased in SlFRL-overexpressed lines. The relative expression of SlCPD increased upon SlFRL silencing, while SlDWF and SlBIN2 were decreased, both of which are important for BR signaling. Our research firstly provides molecular evidence that BRs regulate tomato flowering through the interaction between SlFRLs and SlBIN2. This study will promote the understanding of the specific pathway essential for floral regulation.
Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D
Authors: Koszegi Balazs , Balogh Gabor , Berente Zoltan , Vranesics Anett , Pollak Edit , Molnar Laszlo , Takatsy Aniko , Poor Viktoria , Wahr Matyas , Antus Csenge , Eros Krisztian , Vigh Laszlo , Gallyas Ferenc , Peter Maria , Veres Balazs
Published: September 2022

In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases.
Characterizing Antimicrobial Resistance in Clinically Relevant Bacteria Isolated at the Human/Animal/Environment Interface Using Whole-Genome Sequencing in Austria
Authors: Cabal Adriana , Rab Gerhard , Daza-Prieto Beatriz , Stöger Anna , Peischl Nadine , Chakeri Ali , Mo Solveig Sølverød , Bock Harald , Fuchs Klemens , Sucher Jasmin , Rathammer Krista , Hasenberger Petra , Stadtbauer Silke , Caniça Manuela , Strauß Peter , Allerberger Franz , Wögerbauer Markus , Ruppitsch Werner
Published: September 2022

Antimicrobial resistance (AMR) is a public health issue attributed to the misuse of antibiotics in human and veterinary medicine. Since AMR surveillance requires a One Health approach, we sampled nine interconnected compartments at a hydrological open-air lab (HOAL) in Austria to obtain six bacterial species included in the WHO priority list of antibiotic-resistant bacteria (ARB). Whole genome sequencing-based typing included core genome multilocus sequence typing (cgMLST). Genetic and phenotypic characterization of AMR was performed for all isolates. Eighty-nine clinically-relevant bacteria were obtained from eight compartments including 49 E. coli, 27 E. faecalis, 7 K. pneumoniae and 6 E. faecium. Clusters of isolates from the same species obtained in different sample collection dates were detected. Of the isolates, 29.2% were resistant to at least one antimicrobial. E. coli and E. faecalis isolates from different compartments had acquired antimicrobial resistance genes (ARGs) associated with veterinary drugs such as aminoglycosides and tetracyclines, some of which were carried in conjugative and mobilizable plasmids. Three multidrug resistant (MDR) E. coli isolates were found in samples from field drainage and wastewater. Early detection of ARGs and ARB in natural and farm-related environments can identify hotspots of AMR and help prevent its emergence and dissemination along the food/feed chain.
A Combined Cell-Worm Approach to Search for Compounds Counteracting the Toxicity of Tau Oligomers In Vivo
Authors: Natale Carmina , Barzago Maria Monica , Colnaghi Luca , De Luigi Ada , Orsini Franca , Fioriti Luana , Diomede Luisa
Published: September 2022

A clear relationship between the tau assemblies and toxicity has still to be established. To correlate the tau conformation with its proteotoxic effect in vivo, we developed an innovative cell-worm-based approach. HEK293 cells expressing tau P301L under a tetracycline-inducible system (HEK T-Rex) were employed to produce different tau assemblies whose proteotoxic potential was evaluated using C. elegans. Lysates from cells induced for five days significantly reduced the worm’s locomotor activity. This toxic effect was not related to the total amount of tau produced by cells or to its phosphorylation state but was related to the formation of multimeric tau assemblies, particularly tetrameric ones. We investigated the applicability of this approach for testing compounds acting against oligomeric tau toxicity, using doxycycline (Doxy) as a prototype drug. Doxy affected tau solubility and promoted the disassembly of already formed toxic aggregates in lysates of cells induced for five days. These effects translated into a dose-dependent protective action in C. elegans. These findings confirm the validity of the combined HEK T-Rex cells and the C. elegans-based approach as a platform for pharmacological screening.
Proteomic, Transcriptomic, Mutational, and Functional Assays Reveal the Involvement of Both THF and PLP Sites at the GmSHMT08 in Resistance to Soybean Cyst Nematode
Authors: Lakhssassi Naoufal , Knizia Dounya , El Baze Abdelhalim , Lakhssassi Aicha , Meksem Jonas , Meksem Khalid
Published: September 2022

The serine hydroxymethyltransferase (SHMT; E.C. 2.1.2.1) is involved in the interconversion of serine/glycine and tetrahydrofolate (THF)/5,10-methylene THF, playing a key role in one-carbon metabolism, the de novo purine pathway, cellular methylation reactions, redox homeostasis maintenance, and methionine and thymidylate synthesis. GmSHMT08 is the soybean gene underlying soybean cyst nematode (SCN) resistance at the Rhg4 locus. GmSHMT08 protein contains four tetrahydrofolate (THF) cofactor binding sites (L129, L135, F284, N374) and six pyridoxal phosphate (PLP) cofactor binding/catalysis sites (Y59, G106, G107, H134, S190A, H218). In the current study, proteomic analysis of a data set of protein complex immunoprecipitated using GmSHMT08 antibodies under SCN infected soybean roots reveals the presence of enriched pathways that mainly use glycine/serine as a substrate (glyoxylate cycle, redox homeostasis, glycolysis, and heme biosynthesis). Root and leaf transcriptomic analysis of differentially expressed genes under SCN infection supported the proteomic data, pointing directly to the involvement of the interconversion reaction carried out by the serine hydroxymethyltransferase enzyme. Direct site mutagenesis revealed that all mutated THF and PLP sites at the GmSHMT08 resulted in increased SCN resistance. We have shown the involvement of PLP sites in SCN resistance. Specially, the effect of the two Y59 and S190 PLP sites was more drastic than the tested THF sites. This unprecedented finding will help us to identify the biological outcomes of THF and PLP residues at the GmSHMT08 and to understand SCN resistance mechanisms.
Enhancing Effects of the Cyano Group on the C-X∙∙∙N Hydrogen or Halogen Bond in Complexes of X-Cyanomethanes with Trimethyl Amine: CH3−n(CN)nX∙∙∙NMe3, (n = 0–3; X = H, Cl, Br, I)
Authors: Parra Rubén D. , Grabowski Sławomir J.
Published: September 2022

In this paper, density functional theory and wave function theory calculations are carried out to investigate the strength and nature of the intermolecular C-X∙∙∙N bond interaction as a function of the number of cyano groups, CN, in the X-bond donor while maintaining the X-bond acceptor as fixed. Specifically, complexes of X-cyanomethanes with trimethyl amine CH3−n(CN)nX∙∙∙NMe3 (n = 0–3; X = H, Cl, Br, I) are used as model systems. Geometrical parameters and vibrational C-X-stretching frequencies as well as interaction energies are used as relevant indicators to gauge hydrogen or halogen bond strength in the complexes. Additional characteristics of interactions that link these complexes, i.e., hydrogen or halogen bonds, are calculated with the use of the following theoretical tools: the atoms in molecules (AIM) approach, the natural bond orbital (NBO) method, and energy decomposition analysis (EDA). The results show that, for the specified X-center, the strength of C-X∙∙∙N interaction increases significantly and in a non-additive fashion with the number of CN groups. Moreover, the nature (noncovalent or partly covalent) of the interactions is revealed via the AIM approach.
Nutrient-Mediated Perception and Signalling in Human Metabolism: A Perspective of Nutrigenomics
Authors: Lal Milan Kumar , Sharma Eshita , Tiwari Rahul Kumar , Devi Rajni , Mishra Udit Nandan , Thakur Richa , Gupta Rucku , Dey Abhijit , Lal Priyanka , Kumar Awadhesh , Altaf Muhammad Ahsan , Sahu Durgesh Nandini , Kumar Ravinder , Singh Brajesh , Sahu Sunil Kumar
Published: September 2022

The interaction between selective nutrients and linked genes involving a specific organ reveals the genetic make-up of an individual in response to a particular nutrient. The interaction of genes with food opens opportunities for the addition of bioactive compounds for specific populations comprising identical genotypes. The slight difference in the genetic blueprints of humans is advantageous in determining the effect of nutrients and their metabolism in the body. The basic knowledge of emerging nutrigenomics and nutrigenetics can be applied to optimize health, prevention, and treatment of diseases. In addition, nutrient-mediated pathways detecting the cellular concentration of nutrients such as sugars, amino acids, lipids, and metabolites are integrated and coordinated at the organismal level via hormone signals. This review deals with the interaction of nutrients with various aspects of nutrigenetics and nutrigenomics along with pathways involved in nutrient sensing and regulation, which can provide a detailed understanding of this new leading edge in nutrition research and its potential application to dietetic practice.