bluuebunny/crossref_metadata_2025 huggingface dataset:
Forecasting Iranian Government Responses to Cyberattacks
Authors: Givens Austen , Sanders Nikki , Douglas Corye J.
Published: June 2022

Extant scholarship on Iranian cyber warfare emphasizes the ways in which Tehran’s cyber capabilities might be employed offensively to achieve its foreign policy objectives. Comparatively little attention, however, has been given to the ways in which Iran might leverage these same cyber assets in retaliatory strikes. This article argues that because of the unique combination of endogenous and exogenous variables affecting contemporary Iran, including diplomatic isolation and economic sanctions, as well as Iran’s historical track record of carrying out its foreign policy through proxies, Iranian cyber retaliation is likely to be executed through third parties, mostly symbolic in nature, and proportionate in scale.
Bidirectional DC-DC Converter Circuits and Smart Control Algorithms: A Review
Authors: V Viswanatha , A.C Ramachandra , R Venkata Siva Reddy
Published: June 2022

The entire article has been dedicated to cover the current state-of-the-art in Bidirectional DC-DC converter topologies and its smart control algorithms, identified the research gaps and concluded with the motivation for taking up the work. It covers the literature survey of Bidirectional buck-boost DC-DC converters and control schemes are carried out on two aspects, one is on topology perspective and another one is on control schemes. Different topologies with and without transformers of bidirectional DC - DC converters are discussed. Non-isolated converters establish the DC path between input and output sides while transformer based converters cancels the DC path in between input and output sides since it introduces AC line between two DC lines just like in flyback converter. Transformer less converter is preferred when there is no much protection needed for load from high voltage levels also these converters are used in high power applications. The Bidirectional DC-DC converter can switch the power between two DC sources and the load. To do so, it has to use proper control schemes and control algorithms. It can store the excess energy in batteries or in super capacitors. In contrast, isolated topologies contain transformers in their circuits. Due to this, it offers advantages like safeguarding sensitive loads from high power which is at input side. In addition to it, multiple input and output ports can be established. With the isolation in DC-DC converters, input and output sections are separated from electrical stand point of view. With isolation, both input and output sections will not be having common ground point .The DC path is removed with isolation due to usage of transformer in DC-DC converters. In contrast to its features, it is capable to be used in low power applications since transformer is switching at high frequency, the size of the coil reduces and hence it can handle limited rate of current. The bidirectional DC-DC converters are categorized based on isolation property so called isolated bidirectional converters. Features and applications of each topology is presented. Comparative analysis w.r.t research gaps between all the topologies is presented. Also the scope of control schemes with artificial intelligence is discussed. Pros and cons of each control scheme i.e. research gaps in control schemes and impact of control scheme for bidirectional DC-DC converters are also presented.
Problems and Countermeasures for Surgical Resection of Primary Pulmonary Artery Sarcoma
Authors: Ichinokawa Hideomi , Takamochi Kazuya , Fukui Mariko , Hattori Aritoshi , Matsunaga Takeshi , Suzuki Kenji
Published: June 2022

Background
This study clarified the problems and countermeasures of surgical treatment by examining surgical cases of pulmonary artery sarcoma.
Methods
The records of 10 patients with pulmonary artery sarcoma who underwent surgery at our hospital between January 2007 and October 2020 were retrospectively examined.
Results
The positive rate of vascular stumps was 7/10. Chest computed tomography scan showed positive margins of ≤ 20 mm between the tumor and surgical dissection in all cases (6/6). Additionally, the distance between the tumor location on computed tomography and the dissection line during surgery needed to be at least 20 mm (2/3). However, even at a distance of 25 mm, one case with a positive margin was observed. Postoperative recurrence was 6/9 cases, and the median recurrence period was as short as 9 months (range, 3-19 months). Postoperative treatment was required in 4/9 cases (chemotherapy/radiotherapy/chemoradiotherapy = 1/2/1). The median survival was 11 months (range, 0.5-24 months).
Conclusions
Extended surgery should be performed as much as possible, with a distance of at least 20 mm between the location of the tumor on computed tomography scan and the incision line during surgery. Intensive care for intrathoracic recurrence follow-up is required for 1 year after surgery.
Induction of iPSC-derived Prg4-positive cells with characteristics of superficial zone chondrocytes and fibroblast-like synovial cells
Authors: Satake Takashi , Komura Shingo , Aoki Hitomi , Hirakawa Akihiro , Imai Yuuki , Akiyama Haruhiko
Published: June 2022

Background: Lubricin, a proteoglycan encoded by the PRG4 gene, is synthesised by superficial zone (SFZ) chondrocytes and synovial cells. It reduces friction between joints and allows the smooth sliding of tendons. Although lubricin has been shown to be effective against osteoarthritis and synovitis in animals, its clinical application remains untested. In this study, we aimed to induce lubricin-expressing cells from pluripotent stem cells (iPSCs) and applied them locally via cell transplantation.Methods: To generate iPSCs, OCT3/4, SOX2, KLF4, and L-MYC were transduced into fibroblasts derived from Prg4-mRFP1 transgenic mice. We established a protocol for the differentiation of iPSC-derived Prg4-mRFP1-positive cells and characterised their mRNA expression profile. Finally, we injected Prg4-mRFP1-positive cells into the paratenon surrounding the Achilles tendons and knee joints of severe combined immunodeficiency mice and assessed lubricin expression.Results: Wnt3a, activin A, TGF-β1, and bFGF were applied to induce the differentiation of iPSC-derived Prg4-mRFP1-positive cells. Markers related to SFZ chondrocytes and fibroblast-like synovial cells (FLSs) were expressed during differentiation. RNA-sequencing indicated that iPSC-derived Prg4-mRFP1-positive cells manifested expression profiles typical of SFZ chondrocytes and FLSs. Transplanted iPSC-derived Prg4-mRFP1-positive cells survived around the Achilles tendons and in knee joints. Conclusions: The present study describes a protocol for the differentiation of iPSC-derived Prg4-positive cells with characteristics of SFZ chondrocytes and FLSs. Transplantation of lubricin-expressing cells offers promise as a therapy against arthritis and synovitis.
Seroprevalence of Hepatitis C Virus in Jinan, China, 2008–2020
Authors: Xu Mingjie , Liu Fang , Zhao Qianqian , Zhou Yunying , Zhuang Yuanmei , Ji Mingyu
Published: June 2022

Background:
Updated estimate of anti-HCV prevalence is critical for developing strategies to manage or eliminate HCV infection. To achieve this, a comprehensive study was conducted for the seroprevalence of HCV among patients in Jinan Central Hospital, China.
Methods:
From 2008 to 2020, 365,210 patients were tested for anti-HCV, core antigen of Hepatitis C Virus (HCV cAg), hepatitis B surface antigen (HBsAg), syphilis antibody (anti-TP), HIV antigen + antibody (Ag + Ab) assays, antiHAV IgM and antiHEV IgM.
Results:
The HCV seroprevalence was 0.79%. HCV seroprevalence is related to age distribution, the children (< 18 years) had a lower HCV seropositivity 0.15%, and among adults (≥ 18 years) was 0.81%. A increasing prevalence of HCV was found in adults aged greater than or equal to 41 years, the HCV seropositivity for those aged between 41 to 80 accounted for 74.56% of all seropositiveindividuals. Surprisingly, rate of HCV-HIV co-infection was 0. The HCV seroprevalence of patients in Kidney Disease Unit & Dialysis Department was much higher than patients in other departments, whether in inpatients or outpatients.
Conclusions
A lower HCV seroprevalence in Jinan, but a higher HCV seroprevalence in Kidney Disease Unit & Dialysis Department, especially in patients on hemodialysis.
Gorham-Stout syndrome: a chylothorax disease with massive bony destruction
Authors: Hong Ping-Yang , Zhang Xiao-Bin , Zhao Yi-Lin , Huang Mao-Hong , Zeng Hui-Qing
Published: June 2022

Gorham–Stout syndrome is a sporadic condition characterized by a tumor-like lesion with extensive osteolysis, severe symptoms, and a poor prognosis. Poor prognostic indicators include osteolytic lesions of the spine and pleura effusion. We presented a case in which the condition first manifested itself at the age of 67, with exacerbated shortness of breath. The patient's imaging studies (CT scan, MRI, and PET/CT) revealed osteolytic lesions (the skull, several spines, several ribs, both shoulder blades, and the pelvis). After a tissue biopsy of the spine, postoperative pathology revealed that a portion of the bone had been replaced by lymphatic-derived endothelial cells that stained positive for D2-40. The tests permitted parasitosis, thyroid or parathyroid disease, parasitosis, lymphoma, neoplasia, or an autoimmune problem to be ruled out. On the patient, we performed a superior vena cava angiography. There was an abnormal expansion of the azygos vein into the superior vena cava, as well as local contrast agent retention. The injection of zoledronic acid was used to prevent bone loss. After the therapy, his shortness of breath was greatly reduced. He experienced ongoing shortness of breath alleviation during the 2-month follow-up visit.
Theoritical Study of Channel Coded Secured Nano Communication Network in QCA Platform.
Authors: TAPNA SUPARBA , Chakrabarti Kisalaya , Mukhopadhyay Debarka
Published: June 2022

QCA “Quantum Dot-Cellular Automata” is another nano-technology model, that fills in an elective answer for CMOS that have numerous actual cutoff points and heaps of hardware limits. QCA is a semiconductor less innovation as well as data is passed dependent on electron charge and by common electrostatic repugnance among them. QCA has exceptionally higher gadget thickness, quicker exchanging speed timing and very low force utilization. QCA circuits in cryptographic application may assume a significant part. Both unscrambling as well as encryption measure is executed utilizing rationale circuit based on QCA. The research paper depicts fundamental method for creating cipher text in QCA, which may be useful in secure nanocommunication based on QCA.In secured encryption it is finding the realistic way in a secured authentication. The results’ execution along with testing is carried out by utilizing QCA Designer-2.0.3 tool.
Quality of Work Life of Magnetic Resonance Imaging Technologists: A Cross-Sectional Study
Authors: AlMugren Ghadah , Zedan Haya
Published: June 2022

Background: Quality of Work Life (QWL) is a multi-dimensional discipline that is concerned with the quality of life (QoL) at the workplace. This study aimed to assess the QWL level and identify the correlation between QWL dimensions and Job and Career Satisfaction (JCS). Methods: We used the 32-item WRQoL-2 tool, a questionnaire consisting of 6 subscales: Job and Career Satisfaction (JCS), Control at Work (CAW), Home-Work Interface (HWI), General Well-Being (GWB), Stress at Work (SAW), and Work Conditions (WCS), to collect data between October 2019 and December 2019. Results: 57 MRITs (100%) responded to the questionnaire. We found a high level of QWL among MRITs (66.2%, 3.31/5). The level of the JCS was high (71.6%, 3.59/5), with a significant correlation between the JCS and WCS, CAW, HWI, and GWB. An inverse relationship was noted between SAW and JCS. Conclusion: Further research on QWL is advised to diagnose and provide recommendation to resolve issues that may adversely affect the quality of healthcare service provision.
Validation of Low-Density Lipoprotein Cholesterol Equations in Pediatric Population
Authors: ZARARSIZ GÖZDE ERTÜRK , BOLAT SERKAN , CEPHE AHU , KOCHAN NECLA , YERLİTAŞ SERRA İLAYDA , DOĞAN HALEF OKAN , ZARARSIZ GÖKMEN
Published: June 2022

Purpose
This study aimed to validate different low-density lipoprotein cholesterol (LDL-C) estimating equations in the Turkish population, composed of children and adolescents.
Methods
In this study at Sivas Cumhuriyet University Hospital in Sivas (Turkey), a total of 3,908 children under the age of 18 were included. LDL-C was directly measured by direct homogeneous assays such as Roche, Beckman, and Siemens and was predicted by Friedewald’s, Martin-Hopkins’, extended Martin-Hopkins’ and Sampson’s formulas. Firstly, the concordances between the predictions obtained by the direct measurements and formulas were calculated, and then, these results were evaluated both overall and separately for the LDL-C, triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C) sublevels. Linear regression analysis was performed, and residual error plots were generated between each prediction and direct measurement method. Coefficient of determination (R2) and mean absolute deviations were also evaluated.
Results
The overall concordance of the Friedewald, Sampson, Martin-Hopkins and the extended Martin-Hopkins formula were 64.6%, 69.9%, 69.4%, and 84.3% for the Roche direct assay, 69.8%, 71.6%, 73.6% and 80.4% for the Siemens direct assay, 66.5%, 68.8%, 68.9% and 82.1% for the Beckman direct assay, respectively. The extended Martin-Hopkins formula had the highest concordance coefficient in both overall and all sublevels of LDL-C, non-HDL-C, and TG. When estimating the LDL-C categories, the highest underestimation degrees were obtained with the Friedewald formula.
Conclusions
Our analysis, conducted in a large pediatric population, showed that the extended Martin-Hopkins equation gives more reliable results in predicting LDL-C compared to other equations.
Internal benchmarking and investigation to formulate practical innovations in the Moroccan construction industry
Authors: Gartoumi Khalil Idrissi , Aboussaleh Mohamed , Zaki Smail
Published: June 2022

The renovation of the Architecture, Engineering, Construction and Owner Operators (AECOO) industry is at the forefront of countries' concerns. Despite its important place in national economies, it suffers from several challenges. Faced with this paradox, rethinking inspiration has not attracted many countries like Morocco. Any improvement must be based on a thorough analysis for efficient solutions. In this context, the main objective of this paper is to trigger, investigate, and analyse the state and paradoxical aspects of the Moroccan construction industry (MCI). A triangular approach was conducted, consisting of a literature review, official documents, and a survey of 25 professionals and 15 academics in the sector. The results reveal two main failures, one is managerial and the other technological, and the enumeration of ambitions which are also conditioned by the emergence of technology and new managerial approaches. These findings provide a platform for understanding future interventions, support the literature and suggest avenues of research for neighbouring construction industries, developing countries, and Africa due to similarities with Morocco. Furthermore, it provides recommendations for future studies, especially a new research framework for MCI and other similar countries based on the implementation of Building Information Modelling and Lean Construction.
Exosomes released from macrophages infected with Talaromyces marneffei activate the innate immune responses and reduce intracellular multiplication
Authors: Ji Guangquan , Ren Hong , Feng Shan , Wang Hua , Chen Renqiong
Published: June 2022

Recent studies have shown that exosomes are involved in pathogenesis and in the treatment of various tumors and inflammatory diseases. We examined the impacts of exosomes released from Talaromyces marneffei (T. marneffei)-infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection. Exosomes derived from macrophages were extracted using commercial kits and characterized by transmission electron microscopy and western blot. Further, we examine exosomes that regulate IL-10 and TNF-α production and activation of p42 and p44 extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activation of autophagy. We found that exosomes induced activation of ERK1/2 and autophagy, IL-10 and TNF-α production in human macrophages. Furthermore, exosomes decreased the replication of T. marneffei in T. marneffei-infected human macrophages. Interestingly, exosomes isolated from T. marneffei-infected but not from uninfected macrophages can stimulate a proinflammtory response in resting macrophages. Our studies are the first to demonstrate that exosomes isolated from T. marneffei-infected macrophages can induce a proinflammatory response, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine release during T. marneffei infection.
Hyperlactatemia is a predictor of mortality in patients undergoing continuous renal replacement therapy for acute kidney injury
Authors: Kim Seong Geun , Lee Jinwoo , Yun Donghwan , Kang Min Woo , Kim Yong Chul , Kim Dong Ki , Oh Kook-Hwan , Joo Kwon Wook , Kim Yon Su , Han Seung Seok
Published: June 2022

Background
Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury.
Methods
A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1–7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models.
Results
A total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22–2.20) and 4.18 (2.99–5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score).
Conclusions
Hyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset.
Tryptophanylation of Insulin Receptor by WARS Attenuates Insulin Signaling
Authors: Sun Wen-Xing , Zhang Kai-Hui , Zhou Qian , Hu Song-Hua , Lin Yan , Xu Wei , Zhao Shi-Min , Yuan Yi-yuan
Published: June 2022

Background: Increased circulating tryptophan has been linked to insulin resistance and development of type 2 diabetes (T2D). Although the indispensable roles of tryptophan in behavioral health and immunity, which are mediated by its catabolized metabolites, are well documented, whether and how tryptophan directly affects insulin sensitivity remains largely unknown.Methods: The correlation of excessive tryptophan and insulin resistance was verified in tryptophan-rich chow fed mice. The effects of tryptophan and WARS to insulin signaling and glucose uptake were demonstrated in the HPA-v cells, HepG2 cells and HeLa cells. The tryptophanylation site was screened by single-site directed mutagenesis of all lysine residues in the b subunit of IR, and verified using an in vitro tryptophanylation assay. Finally, the detryptophanylation enzyme was identified and its role in insulin sensitivity was addressed by immunoblotting analysis. Results: Mice fed with tryptophan-rich chow developed insulin resistance. Tryptophan can tryptophanylate insulin receptor (IR) and attenuate insulin signaling. Excessive tryptophan promotes tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induces insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT and AS160. SIRT1, but not other sirtuins, detryptophanylates IRW-K1209 to increase the insulin sensitivity.Conclusions: Our results unveiled a novel mechanism of how tryptophan was sensed and tryptophanylated to IR by WARS, thus impaired insulin signaling. Meanwhile, our data indicated that WARS might be a target for insulin sensitivity control.
Subnanometeric optical modulation of a single-molecule electron source
Authors: Yanagisawa Hirofumi , Bohn Markus , Kitoh-Nishioka Hirotaka , Goschin Florian , Kling Matthias F.
Published: June 2022

The irradiation of femtosecond light pulses onto nano-objects creates localised optical fields on the nanostructure surfaces. Plasmonic effects spatially modulate the local-field distribution, achieving optical control of an ultrafast electron source on a scale of approximately 10 nm. Further miniaturisation of such an electron source down to an atomistically small scale is technically difficult by modulating the local-field distribution via plasmonic effects. Here, by illuminating recently identified single-molecule electron sources with femtosecond light pulses, we discovered that largely modulated emission patterns appeared from single C60 molecules, approximately one nanometre in size. Our simulations revealed that the emission patterns represented the single-molecule molecular orbitals (MOs), and the observed modulations originated from the variations of the single-molecule MOs, practically achieving subnanometric optical modulation of an electron source. Our work has thus demonstrated a simple way to continue miniaturising the spatially-controlled electron source down to an atomistic scale using quantum effects.
Optical absorption of conduction electrons in semiconductor nanowires in the presence of the electron-phonon interaction
Authors: Zorik Anas , Farhoud Maher , Sakr Mohammed R.
Published: June 2022

We calculate the energy states and the optical absorption coefficient for electrons in a nanowire in the presence of the Rashba and the longitudinal-optical phonon interactions. The interplay of those interactions results in a splitting in the electron dispersion relation at zero wavevector that grows linearly for the ground state as the strength of the lateral quantum confinement increases. For higher states, the energy splitting increases more rapidly till the state of resonant polaron is reached, then it increases slowly due to the pinning effect. The frequency separation between the well-resolved absorption peaks and their number are greatly influenced by the state of the polarons.
Growth and carcass characteristics of two broiler strains fed diets with varying levels of inclusion of palm kernel oil residue (PKOR)
Authors: Ofori Samuel Ayeh , Hagan J.K , Etim N.N
Published: June 2022

An experiment was carried out to evaluate the effect of strain of broilers and different levels of inclusion of palm kernel oil residue (PKOR) diets on the growth and carcass characteristics of two commercial broiler strains. A total of 450 birds were evaluated in a 2 X 3 factorial experiment involving two broiler strains (Cobb and Ross) and three dietary treatments with 0%, 10% and 20% levels of inclusion of PKOR. For each of the broiler strains, a total of 225 birds were randomly assigned to each of the three diets with each dietary treatment having 75 birds with three replications with 25 birds in each replicate group. The experiment was done using 3-week old broiler chicks and fed over a period of 5 weeks in 18 partitioned deep litter pens (2.5m X 2.1m; floor space of 0.21m2/bird). Both feed and water were supplied ad libitum, under a 24-hour lighting regime. Growth parameters were taken from week three to week eight. At the end of the experimental period, 4 birds from each replicate group were randomly selected and slaughtered for carcass evaluation. Data obtained were subjected to a two-way Analysis of Variance (ANOVA) with strain of broilers and dietary treatments as fixed factors using the general analysis of variance procedure of GenStat. Where differences in means occurred, the means were separated using the least significant difference (lsd) test at 5% level of significance. Data obtained showed no significant genotype effects on the growth performance. There were however significant difference in growth performance with the different levels of inclusion of the PKOR, with the birds on the control diets (0% PKOR) being superior in terms of final live weights as compared to the birds fed 10 and 20% levels of inclusion of the PKOR diets. Interestingly, birds fed 10% levels of inclusion were able to significantly convert feed to meat better (better FCR) than their counterparts on the control and 20% levels of inclusion diets. There were no significant genotype × ration interaction effects on all performance parameters assessed. Data obtained showed no significant (p > 0.05) genotype effects on carcass characteristics. Birds on 0% PKOR recorded significantly (p < 0.05) higher warm carcass weight and warm dressing percentage than birds fed 10% and 20% PKOR; chilled carcass traits assessed were however similar (p > 0.05) for all dietary treatments. The effects of genotype × ration interactions on all carcass traits assessed were not significant (p > 0.05).
Basin-scale factors in emergence of midchannel islands: A process-based morphometric analysis
Authors: Heidari Naghmeh , Yagci Oral , Aksel Murat
Published: June 2022

Midchannel islands were conventionally considered undesirable additional hydraulic resistance to flow for many years and tended to be removed from the main channel as a measure against the flood. Today, it is known that these geomorphic units provide key eco-geomorphological services in the active corridor of natural waterways. This study examined the dynamics behind the occurrence mechanism of midchannel islands considering basin-scale (i.e., land use, elevation, main channel slope, form factor, relief) and fluvial (i.e., sediment yield) variables. Nine drainage basins were selected as samples from the different ecoregions on Earth. Morphometric and hydrological characteristics were determined using hydrological datasets and satellite-based images by means of ArcGIS. Sediment delivery magnitudes for each examined basin were calculated based on an empirical expression. In addition, the development process of isolated midchannel islands was investigated by quantifying their planform morphometric features. The basin-scale analysis showed that the main channel slope, i.e., gravity-induced factors, controls the emergence location of MCIs to a great extent, and the basin sediment yield impacts the density (i.e., number of islands) of MCIs in a unit length of the river. Furthermore, at the individual scale, the morphometric analysis of MCIs revealed that during the MCI growth, the streamlining process diminishes the skin friction. This effect becomes more prominent, particularly at the mature stage of MCIs, and the form drag prevails over the skin friction.
Efficient side-chain deacylation of polymyxin B1 in recombinant Streptomyces strains
Authors: Wang Xiaojing , Wu Kai , Zhang Hanzhi , Liu Jing , Yang Zhijun , Bai Jing , Liu Hao , Shao Lei
Published: June 2022

Objectives: Polymyxins are antibacterial polypeptides used as “last resort” therapy option for multidrug-resistant Gram-negative bacteria. The expansion of polymyxin-resistant infections has inspired development of novel polymyxin derivatives, and deacylation is one of the critical steps in generating those antibiotics. Deacylase from Actinoplanes utahensis hydrolyze the acyl moieties of echinocandins, and also efficiently deacylates daptomycin, ramoplanin and other important antibiotics. Here, deacylase was studied considering its potential usefulness in deacylating polymyxin B1.Results: All the six recombinant strains containing the deacylase gene catalysed hydrolysis of polymyxin B1, yielding cyclic heptapeptide. The efficiency of recombinant S. albus (SAL701) was higher than others, whereby deacylation was the most efficient at 40 °C in 0.2 M Tris buffer (pH 8.0) with 0.2 M Mg2+. The optimal substrate concentration of SAL701 was increased from 2.0 to 6.0 g/L. SAL701 was highly thermostable, showing no loss of activity at 50°C for 12 h, and the mycelia could be recycled at least three times without loss of catalytic activity. SAL701 could not deacylate β-lactam substrate such as penicillin G and cephalosporin C. Deacylase catalyzes the amide bond 1 closest to the nucleus of polymyxin B1 rather than the other bond, suggesting that it has high catalytic site specificity. Homology modeling and the docking results implied Thr190 in deacylase can facilitate hydrolysis with high regioselectivity.Conclusions: These results show that SAL701 is effective in increasing cyclic heptapeptide moiety of polymyxin B1. These properties of the biocatalyst may enable its development in the industrial production of polymyxins antibiotics.
Two Fe mining sub-products and three thiol compounds alleviate Fe deficiency in soybean (Glycine max L.) grown in a calcareous soil in greenhouse conditions
Authors: Gheshlaghi Zahra , Khorassani Reza , ‎ Javier Abadia
Published: June 2022

Purpose
The aim of this work was to test the hypothesis that Fe mining sub-products and thiols can alleviate a moderate Fe-deficiency in the Strategy I species soybean (Glycine max) grown in a calcareous soil in greenhouse conditions.
Methods
Combinations of three Fe sources [Fe(III)-EDDHA and two Fe mining sub-products, both of them containing Fe oxides and one FeS2], and three thiols (glutathione, dithiothreitol and thiophenol) were applied in solution to the soil, three times in a 55 day period, and different parameters related to Fe deficiency were measured. The thiol-mediated solubilization of Fe from the Fe mining sub-products was assessed by measuring in the solution total Fe and the reducible Fe pool using an Fe(II) chelator.
Results
Application of Fe-EDDHA, the two Fe mining sub-products and the three thiols relieved the Fe deficiency symptoms to different extents, increased the Fe concentrations and contents throughout the plant and changed the redox state of leaves and roots, as judged from the changes in reduced and oxidized glutathione, ascorbate and antioxidant enzymes. When using Fe(III)-EDDHA, the addition of thiols led to a better leaf regreening. However, the addition of thiols did not cause further regreening in the case of the Fe mining sub-products, in spite of being able to solubilize Fe from them.
Conclusion
Application of Fe-mining sub-products, thiols and the combination of Fe(III)-EDDHA and thiols could be used to alleviate moderate Fe deficiency in G. max grown in a calcareous soil.
Morphine Exposure and Flash Visual Evoked Potentials in Preterm Infants
Authors: Coviello Caterina , Lori Silvia , Bertini Giovanna , Montano Simona , Gabbanini Simonetta , Bastianelli Maria , Cossu Cesarina , Cavaliere Sara , Frosini Saverio , Dani Carlo
Published: June 2022

Background: Morphine is one of the most common analgesic drug, used to minimizing pain and stress in the hospitalized infants, however, concerns on its role on brain development have been expressed. Aim of the present study was to evaluate the effect of morphine exposure during NICU stay on flash visual evoked potentials (VEP) at term equivalent age (TEA), and on visual outcomes at 9 months corrected age (CA) in preterm infants.Methods: Infants with a gestational age (GA) at birth <30 weeks were prospectively enrolled. Latencies of N1, N2, P2 were measured, as P2 amplitude. N3 was categorized present/absent. Morphine cumulative dose (mg/kg) was calculated as average daily dose adjusted for patient’s weight during the NICU stay. Multivariate regression analyses were performed to assess the association between morphine exposure and VEP components, and visual outcomes. Results: Sixty infants were enrolled. Thirteen infants received morphine (22.8.%). N1, P2 and N2 latency had a positive association with morphine, even after correcting for GA, postmenstrual age at VEP registration, days of ventilation (DOV), retinopathy of prematurity and painful procedures (R=0.42, R=0.47, R=0.43 respectively, and p=0.048, p=0.001, p=0.006 respectively). Presence of N3 component was associated with higher number of DOV (R=0.38, p=0.004). No association was found between morphine and P2 amplitude, and with ophthalmic evaluation.Conclusion: Higher morphine dose predicted longer N1, N2 and P2 latency at TEA. However morphine was not correlated with altered ophthalmic evaluation at 9 months.
Apoptotic-like PCD inducing HRC gene when silenced enhances multiple disease resistance in plants
Authors: Kushalappa Ajjamada , NG Hegde , Gunnaiah Raghavendra , Sathe Atul , Yogendra Kalenahalli , Ajjamada Lissa
Published: June 2022

Programed cell death (PCD) plays an important role in plant environmental stress and has the potential to be manipulated to enhance disease resistance. Plants have innate immunity and, following pathogen perception, the host induces a Hypersensitive Response PCD (HR-PCD), leading to pattern (PTI) or effector triggered immunity (ETI). Here we report a non-HR type or apoptotic-like PCD (AL-PCD) in pathogen infected wheat and potato. The pathogen induced Ca2+ in the apoplast is transported to the cytosol where it binds to calmodulin (CAM). The Ca2+-CAM binds to histidine-rich-calcium-binding-protein (HRC) increasing Ca2+ concentration in the cytosol. The HRC moves to the nucleus and increases Ca2+ concentration that triggers endonucleases which induce AL-PCD, but not when HRC is silenced. The absence of AL-PCD reduced food for pathogen which results in reduced biomass and mycotoxin accumulation. The reduced gene function inhibition, promotes expression of the R-gene repertoire of the host, leading to enhanced multiple pathogen resistance. The functional HRC in commercial varieties of different crops can be silenced by CRISPR-Cas9 genome editing to enhance resistance to multiple pathogens.
Protective effect of N-acetyl cysteine on mitochondrial dynamic imbalance in Temporal lobe Epilepsy: possible role of mTOR
Authors: Mohammadi Ekram , Nikbakht Farnaz , Barati Mahmoud , Roghani Mehrdad , Vazifekhah Somayeh , Mohammadkhanizadeh Ali , Babaei Javad Fahanik
Published: June 2022

Epilepsy is a neurological disorder, and understanding the underlying molecular mechanisms is critical for the development of more effective therapies. It is believed that mTOR (Mechanistic Target of Rapamycin kinases) activity and the mitochondrial dynamic balance change during epilepsy. mTOR affects mitochondrial fission by stimulating the translation of mitochondrial fission process 1 (MTFP1). In this study, the protective role of N-acetylcysteine was studied in temporal lobe epilepsy (TLE) through the regulation of mTOR and mitochondrial dynamic proteins. Rats received N-acetylcysteine (oral administration) seven days before induction of epilepsy, followed by one day after epilepsy. TLE was induced by microinjection of kainite into left lateral ventricle. The total mTOR and Drp1 levels were detected in the hippocampus by western blotting. MFN1 was assessed using immunohistochemistry, and the expression of Fis.1 and MTFP1 (fission-related proteins) and OPA (fusion-related protein) was detected by real time PCR. The mitochondrial membrane potential was measured by Rhodamin 123. The results showed that 72 h after induction of epilepsy, the mTOR protein level increased, and the balance of the mitochondrial dynamic was disturbed; however, oral administration of NAC decreased the mTOR protein level and improved the mitochondrial dynamic. We concluded that NAC plays a neuroprotective role in temporal lobe epilepsy, probably through decreasing the mTOR protein level, which can improve the imbalance in the mitochondrial dynamic.
Regeneration of Cochlear Hair Cells in Adult Mice by Chemical Mediated Reprogramming
Authors: Quan Yi-Zhou , Wei Wei , Ergin Volkan , Rameshbabu Arun Prabhu , Huang Mingqian , Tian Chunjie , Saladi SV , Indzhykulian Artur , Chen Zheng-Yi
Published: June 2022

Strategies to overcome irreversible cochlear hair cell (HC) damage and loss are of vital importance to develop treatment for hearing loss. In mature mammalian cochlea, Myc and Notch1 co-activation reprograms supporting cells (SC) for HC regeneration. To understand the mechanisms underlying reprogramming, we performed single cell RNAseq and uncovered the pathways including Wnt and cAMP, whose blockade attenuate HC regeneration. We screened and identified a combination (the cocktail) of drug-like compounds of small molecules and siRNAs to activate the pathways of Myc, Notch1, Wnt and cAMP. We show that the cocktail effectively replaces Myc and Notch1 transgenes to reprogram adult wildtype supporting cells for HC regeneration in vitro. Finally, we demonstrate the cocktail is capable of reprogramming adult cochlea for HC regeneration in wild-type mice with hair cell loss in vivo. Our study identified a strategy by a clinically-relevant approach to reprogram mature inner ear for HC regeneration, laying the foundation for hearing restoration by HC regeneration.
Epigenetic Malleability at Core Promoter Initiates Tobacco PR-1a Expression post Salicylic Acid Treatment
Authors: Lodhi Niraj , Singh Mala , Srivast Rakesh , Sawant Samir V. , Tuli Rakesh
Published: June 2022

Tobacco’s PR-1a gene is induced by pathogen attack or exogenous application of Salicylic Acid (SA). However, the epigenetic modifications of the inducible promoter of the PR-1a gene are not fully understood yet. Nucleosome mapping and chromatin immunoprecipitation assay were used to delineate the histone modifications on the PR-1a promoter. Here, we report correlated consequences of the epigenetic modifications correspond to disassembly of the nucleosome (spans from − 102 to + 55 bp, masks TATA and transcription initiation) and repressor complex from core promoter, eventually initiates the transcription of PR-1a gene post SA treatment. ChIP assays suggest repressive chromatin of di- methylation at H3K9 and H4K20 of nucleosome over core promoter in uninduced state. While active chromatin marks di and trimethylation of H3K4, acetylation of H3K9 and H4K16 are increased which are associated to the transcription initiation of PR-1a following SA treatment. Class I and II mammalian histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) enhances the expression of PR-1a by facilitating the histone acetylation post SA treatment. However, increased expression of a negative regulator (SNI1) of AtPR1, suppresses AtPR1 expression in Arabidopsis thaliana. Further, we report increased expression of AtPR1 in uninduced LSD1 mutant plants, suppressed AtPR1 in uninduced histone acetyl transferases (HATs) mutant plants, SNI1 dependent negative regulation of AtPR1 suggest that its inactive state is indeed maintained by a repressive complex.
Multi-task Learning and Ensemble Approach to Predict Cognitive Scores for Patients with Alzheimer's Disease
Authors: Ma Daren , Pabalan Christabelle , Rajagopal Abhejit , Akanksha Akanksha , Interian Yannet , Raj Ashish
Published: June 2022

During its chronic degenerative course, Alzheimer's Disease takes a huge toll on the cognitive abilities of patients. Assessment of current and future cognition is an integral component of a diagnosis of dementia, and therefore an important clinical and scientific goal. Unfortunately, subjective, time-consuming and operator-sensitive clinical surveys or neuropyschiatric batteries remain the only viable method of assessing cognition. Given that MRI is the most prevalent, cost-effective, and clinically important imaging modality, it may be considered a suitable predictor of cognition. Yet, it has hitherto proved very challenging to predict one from the other. Here we propose that an image-based Deep Learning model can be custom-built to achieve this goal. We designed a novel multi-task UNet model to predict the subjects’ current and future cognition (via ADAS-Cog scores), taking as input baseline T1-weighted MRI and demographic risk factors. The key innovation in the model is that it seeks to solve two adjacent but relevant tasks: image segmentation into tissue types; and prediction of cognition. The first task gives a high-accuracy segmentation of the brain, comparable to other cutting edge segmentation methods. The features trained from the segmentation task are used in the cognition task. This combination is shown to be far superior to stand-alone single-shot models of cognition. We achieved excellent accuracy in both baseline and time-series forecast of ADAS-Cog scores. Through further feature map analysis made on the receptive fields, we were able to impart much-needed interpretability to the model, critical for real-world clinical practice. This study constitutes the best-reported performance of any comparable approach, and opens the door towards machine-based tracking of AD progression.
Effects of high pressure treatments (ultra-high hydrostatic pressure and high pressure homogenization) on bighead carp (Aristichthys nobilis) myofibrillar protein native state and its hydrolysate
Authors: Chen Mengting , Wang Lan , Wu Wenjin
Published: June 2022

The impacts of four treatments ultra-high hydrostatic pressure (UHP), high pressure homogenization (HPH), combined UHP + HPH (U-H), and HPH +UHP (H-U) on bighead carp (Aristichthys nobilis) myofibrillar protein (BMP) structure, functional hydrolysis property to pepsin, and antioxidant activity of hydrolysates were investigated. All treatments led to increase in low-molecular-weight BMP, the BMP stability, and hydrophobic group exposure, but decrease in total sulfhydryl content and BMP particle size, thus resulting in increased hydrolysis and antioxidant capacity of enzymatic hydrolysates. U-H treated BMP exhibited the highest surface hydrophobicity (924.5±1.0), zeta potential absolute value (18.88±0.11 mV), hydrolysis degree (54.5±1.6%), and antioxidant activity, but the lowest α-helix (21.84±2.61%), intrinsic fluorescence spectrum intensity, total sulfhydryl (7.24±0.07 μmol/g), and mean particle size (182.57±2.23 nm). Therefore, U-H might be a promising pretreatment to prepare bioactive peptide.
Differences in gene mutation profiles of colon cancer patients with or without a KRAS mutation
Authors: Chang Shujian , Zhou Yudan , Wu Ruirong , Ge Xiaosong , Pu Yong
Published: June 2022

RAS plays an important role in the carcinogenesis of colorectal epithelial cells, but RAS mutations are only present, at most, in approximately 50% of patients. In order to compare the gene mutation profiles of patients with or without a KRAS mutation, the clinicopathological data of 858 patients and NGS test results of 1697 patients with colorectal cancer were used in this analysis. In 858 patients, the mutation rate of KRAS was 50.8% (i.e., 436/858). Only 2 out of 349 (0.5%) KRAS mutant patients had a BRAF mutation, while 25 out of 422 (5.9%) KRAS wild-type patients had a BRAF mutation (p < 0.0001). The median OS of patients with a mutant or wild-type KRAS were 83.47 months and not reached, respectively (HR: 0.8147; 95% CI: 0.6271–1.051; p = 0.1153). The NGS results showed that in RAS mutant patients, genes with a high mutation rate mainly included APC, TP53, PIK3CA, Smad4, and Fbxw7, and in RAS wild-type patients, genes with a high mutation rate mainly included TP53, APC, LRP1B, MYC, and BRAF. The mutation rates of BRAF and EGFR in the RAS wild-type group were 15% and 9%, respectively, while they were only 3% in the RAS mutant group. The mutation rate of PIK3CA in the RAS mutant group was 31%, while that in the RAS wild-type group was 14%. The mutation rate of APC was 72.2% (i.e., 687/952). The mutation rate of the gene, RNF43, in the APC wild-type group was 5.23 times higher than that in the APC mutant group, and the gene, NSD1, in the APC wild-type group was 0.07 times higher than that in the APC mutant group. The mutation rate of TP53 was 78.2% (i.e., 744/952). The mutation rate of MLH1 in the TP53 wild-type group was 8.42 times higher than that in the TP53 mutant group, which was significantly higher than that in the TP53 mutant group. Generally, the gene mutation profiles were significantly different between KRAS mutation and wild-type colorectal cancer patients. A single gene mutation may be sufficient to cause the dysfunction of a signal transduction pathway, and APC, TP53, or RAS are not necessary for the carcinogenesis of sporadic colorectal cancer.
Tim-3/Galectin-9 pathway and expression of CD8 + Treg cells and related factors in patients with alveolar echinococcosis
Authors: Zhao Hui , Ma Yuyu , Tian Fengming , Li Bin , Xiao Ning , Mo Xiaojin , Min Hongyue , Cai Xuanlin , Zhang Ting , Ma Xiumin , aibibula madinaimu
Published: June 2022

Objective: Host immune status plays a crucial role in the parasitism, lesion activity and disease progression of Echinococcus multilocularis (EM). Therefore, by demonstrating that the Tim-3/galactose lectin-9 signaling pathway has an immunosuppressive function and the expression of CD8 + Treg cells and related factors in patients with alveolar encephalopathy (AE), this study can determine the relationship and function of the Tim-3/galactose lectin-9 understanding signaling pathway with CD8 + Treg cells in AE. Methods: The proportions of CD8 + Treg cells, CD8 + CD28 + IL-10 + T cells, CD8 + CD28 + TGF-β + T cells and Tim-3 + CD8 + Treg cells in peripheral blood were first determined in control subjects (n=30), and AE patients (n=33) were examined by flow cytometry. Foxp3 and Tim-3 / Galectin-9 mRNA levels in peripheral blood PBMC from control and AE patients were then measured by QRT-PCR. Finally, the expression of IL-10, TGF-β and Tim-3 / Galectin-9 in the infected livers of AE patients was verified by immunohistochemistry.Results: 1. The proportions of peripheral blood CD8 + Treg cells (P<0.001), CD8 + CD28 + IL-10 + T cells (P<0.001) and CD8 + CD28 + TGF-β + T cells (P<0.001) were significantly higher in AE patients than in controls. 2. The expression of Tim-3 was significantly upregulated in peripheral blood CD8 + Treg cells in AE patients (P <0.001). 3. Foxp3 (P<0.001) and Tim-3/galactose lectin-9 (P<0.001, P<0.001)) mRNA levels were significantly elevated in peripheral blood PBMC from AE patients, and Foxp3 and Tim-3 (r 2 =0.489, P<0.001) with galactose lectin-9 (r 2 =0.366, P=0.047) mRNA levels were positively correlated. 4. Infected individuals showed higher expression of IL-10 (P<0.001), TGF-β (P<0.001) and Tim-3/galactose lectin-9 (P<0.001, P<0.001) in the livers of AE patients than in the distal part of the infection, with IL-10 expression (r 2 =0.852, P<0.001; r2=0.803 P<0.001) 、TGF-β (r 2 =0.770 P<0.001 ;r 2 =0.806, P<0.001) was positively correlated with Tim-3/galactose lectin-9. Conclusion: This study hypothesized that high expression of Tim-3 on the surface of CD8 + Treg cells in AE patients increases the number and function of CD8 + Treg cells and that expression of the Tim-3/galactose lectin-9 pathway promotes the expression of the transcription factor Foxp3 and the inhibitory cytokines IL-10 and TGF-β. This phenomenon is not conducive to the elimination of multifocal echinococcosis in patients, which ultimately leads to persistent exacerbation of the infection.