bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the unfolded protein response transducer IRE1α by SERPINH1 aggravates periodontitis with diabetes mellitus via prolonged ER stress
Authors: Li Mengdi , Huang Shuheng , Zhang Yong , Song Zhi , Fu Haijun , Lin Zhengmei , Huang Xin
Published: September 2021

Background
The hyperglycemic microenvironment induced by diabetes mellitus aggravates the inflammatory response, in which the inositol-requiring enzyme-1α (IRE1α) signal transduction pathway of the unfolded protein response (UPR) participates. This study aimed to investigate the mechanism by which hyperglycemia regulates the IRE1α signaling pathway and affects endoplasmic reticulum (ER) homeostasis in human gingival epithelium in periodontitis with diabetes mellitus (DP).
Methods
Human gingival epithelium samples from healthy subjects, subjects with periodontitis and subjects with DP were collected, in vitro cultures of human gingival epithelial cells were challenged with a hyperglycemic microenvironment to observe the effects of diabetes on periodontal inflammation and to assess UPR-IRE1α signaling in human gingival epithelium in DP. Subsequently, RNA sequencing (RNA-seq) data was analyzed to investigate the expression of ER-related genes in human gingival epithelium. Furthermore, to explore the key role of serpin family H member 1 (SERPINH1) in the regulation of UPR-IRE1α signaling in a hyperglycemic microenvironment, experiments in SERPINH1-knockdown and SERPINH1-overexpression models were established in vitro.
Results
Diabetes causes a hyperinflammatory response in human gingival epithelium, which accelerates periodontal inflammation. A hyperglycemic microenvironment inhibited the inositol-requiring enzyme-1α / X-box binding protein 1 (IRE1α/XBP1) axis, decreased the expression of glucose regulated protein 78 (GRP78), and ultimately impaired the UPR, causing ER stress to be prolonged or more severe in human gingival epithelium. The RNA-seq and experiments revealed that the mechanism by which periodontitis is aggravated in individuals with diabetes mellitus may involve decreased SERPINH1 expression. SERPINH1 might act as an activator of IRE1α, maintaining human gingival epithelium homeostasis, suppressing nuclear factor-κB signaling pathway and reducing NOD-like receptor, pyrin domain containing protein 3 (NLRP3) and interleukin-1 beta (IL-1β) expression by preventing prolonged ER stress induced by high-glucose conditions.
Conclusion
Regulation of the UPR transducer IRE1α by SERPINH1 alleviates DP by mitigating prolonged ER stress.
Early Prone Positioning in Acute Respiratory Distress Syndrome Related to COVID-19: A Propensity Score Analysis from the Multicentric Cohort COVID-ICU network. The ProneCOVID Study.
Authors: TERRIER Christophe LE , Sigaud Florian , Lebbah Said , Desmedt Luc , Hajage David , Guérin Claude , Pugin Jérôme , Primmaz Steve , Terzi Nicolas
Published: September 2021

Background Delaying time to prone positioning (PP) may be associated with higher mortality in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). We evaluated the use and the impact of early PP on clinical outcomes in intubated patients hospitalized in intensive care units (ICUs) for COVID-19.Methods All intubated patients with ARDS due to COVID-19 were involved in a secondary analysis from a prospective multicenter cohort study of COVID-ICU network including 149 ICUs across France, Belgian and Switzerland. Patients were followed-up until Day-90. The primary outcome was survival at Day-60. Analysis used a Cox proportional hazard model including a propensity score. Results Among 2137 intubated patients, 1504 (70.4%) were placed in PP during their ICU stay, and 491 (23%) during the first 24 hrs following ICU admission. One hundred and eighty-one patients (36.9%) of the early PP group had a PaO2/FiO2 ratio > 150 mmHg when prone positioning was initiated. Among non-early PP group patients, 1013 (47.4%) patients had finally been placed in PP within a median delay of 3 days after ICU admission. Day-60 mortality in non-early PP group was 34.2% vs. 39.3% in the early PP group (p = 0.038). Day-28 and Day-90 mortality as well as the need for adjunctive therapies were more important in patients with early PP. After propensity score adjustment, no significant difference in survival at Day-60 was found between the two-study groups (HR 1.34 [0.96-1.68], p=0.09 and HR 1.19 [0.998-1.412], p=0.053 in complete case analysis or in multiple imputation analysis, respectively).Conclusions In a large multicentric international cohort of intubated ICU patients with ARDS due to COVID-19, PP has been used frequently as a main treatment. In this study, early PP started within 24 hrs after ICU admission was not associated with a survival benefit compared to PP after day 1.
Enzymatic Synthesis of Cellulose in Space: Gravity Is a Crucial Factor for Building Cellulose II Gel Structure
Authors: Kuga Tomohiro , Sunagawa Naoki , Igrashi Kiyohiko
Published: September 2021

We previously reported in vitro synthesis of highly ordered crystalline cellulose II by reverse reaction of cellodextrin phosphorylase from the cellulolytic bacterium Clostridium ( Hungateiclostridium ) thermocellum ( Ct CDP), but the formation mechanism of the cellulose crystals and highly ordered structure has long been unclear. Considering the specific density of cellulose versus water, the formation of crystalline and highly ordered structure in an aqueous solution should be affected by gravity. Thus, we synthesized cellulose with Ct CDP at the International Space Station, where sedimentation and convection due to gravity are negligible. Optical microscopic observation suggested that cellulose in space has a gel-like appearance without apparent aggregation, in contrast to cellulose synthesized on the ground. Small-angle Xray scattering (SAXS) and wide-angle X-ray scattering (WAXS) indicated that cellulose synthesized in space has a more uniform particle distribution in the ~100 nm scale region than cellulose synthesized on the ground. Scanning electron microscopy (SEM) showed that both celluloses have a micrometer scale network structure, whereas a fine fiber network was constructed only under microgravity. These results indicate that gravity plays a role in cellulose II crystal sedimentation and the building of network structure, and synthesis in space could play a role in the design of unique materials.
Inhibition of MiR-20a by Pterostilbene Facilitates Prostate Cancer Cells Killed by NK Cells Via up-Regulation of NKG2D Ligands and Down-Regulation of TGF-β1
Authors: Li Zhang , Simin Liang , Jian Kang , Xin Gou , Kuang Youlin
Published: September 2021

Purpose-Natural killer (NK) cells play a potent role in antitumor immunity via spontaneously eliminating tumor directly. However, some tumors such as prostate cancer constantly escape this immune response by down-regulating cell surface molecule recognition and/or secreting immune impressive cytokines. Pterostilbene, a dietary compound primarily found in blueberries, exhibits a potential anti-tumor activities and immunoregulation function. However, whether it could affect NK cells immune response against prostate cancer is not clear.Methods-NK cell cytotoxicity against prostate cancer cells was analyzed using the CytoTox 96 cytotoxicity assay kit. Flow cytometry was used to detected NK cell degranulation, NK cell-surface and intracellular protein expression. The effects of pterostilbene on TGF-β1 secretion were determined by Enzyme-linked immunosorbent assay. The candidate target gene of miR-20a was determined by luciferase reporter assay and the expression of major histocompatibility complex class I chain-related proteins A and B (MICA/B) was detected by quantitative real-time polymerase chain reaction.Results-We found pterostilbene could enhance expression of MICA/B on prostate cancer cells surface, which are ligands of the natural killer group 2 member D (NKG2D) expressed by NK cells, and inhibit TGF-β1 secretion by prostate cancer cells. Further, we discovered that these effects were caused by inhibition of miR-20a in prostate cancer cells by pterostilbene. MiR-20a could target the 3’ untranslated region (UTR) of MICA/B, resulting in their expression down-regulation. Inhibition of TGF-β1 function by its specific antibody attenuated its impairment to NKG2D on NK cells. Finally, we observed that pterostilbene-treated prostate cancer cells were more easily to be killed by NK cells.Conclusions-Our findings demonstrated inhibition of miR-20a by pterostilbene in prostate cancer cells could increase MICA/B expression and decrease TGF-β1 secretion, which enhanced NK cell-mediated cytotoxicity againt prostate cancer cells, suggesting a potential approach for increasing anti-prostate cancer immune.
Extractable quantum work from a two-mode Gaussian state in a noisy channel
Authors: Cuzminschi Marina , Aurelian Isar , Zubarev Alexei
Published: September 2021

We study a Szilard engine based on a Gaussian state of a system consisting of two bosonic modes placed in a noisy channel. As the initial state of the system is taken an entangled squeezed thermal state, and the quantum work is extracted by performing a measurement on one of the two modes. We use the Markovian Kossakowski-Lindblad master equation for describing the time evolution of the open system and the quantum work definition based on the second order R\'{e}nyi entropy to simulate the engine. We show that the extractable quantum work increases with the temperature of the reservoir and the squeezing between the modes, average numbers of thermal photons and frequencies of the modes. The work increases also with the strength of the measurement, attaining the maximal values in the case of a heterodyne detection. As well the extractable work is decreasing by increasing the squeezing parameter of the noisy channel and it oscillates with the phase of the squeezed thermal reservoir.
Comparison of Flexion Relaxation Phenomenon Between Female Yogis and Matched Non- Athlete Group
Authors: Ramezani Marzyeh , Yoosefinejad Amin Kordi , Motealleh Alireza , Ghofrani-Jahromi Mohsen
Published: September 2021

Background: Trunk flexion is a common exercise during daily activities. Flexion relaxation phenomenon (FRP) occurs during forward bending in which there is a sudden silence of erector spinae (ES) muscles. The pattern of forward bending differs in yoga practitioners. This learned pattern probably predisposes yogis to injuries.The hypothesis of this study was that FRP differs in yogis in comparison to non-yogis individuals.Methods: This observational cross-sectional study was performed on 60 women assigned into yogis and non-athlete groups. Each participant was asked to bend forward and then return to the initial position. ES activity was recorded at L3 level, 4 cm from mid line during the trial. Trunk inclination and lumbar flexion angles were calculated at FRP onset and cessation moments. Results: The FRP phenomenon occurred in 80% of yoga practitioners in comparison to 96.7% in the control group. Trunk inclination angle was significantly greater at FRP initiation in yogis compared to control group. Lumbar flexion angle was not different between the groups. Conclusions: It is concluded that the altered pattern of forward bending observed in yogis may change patterns of ES muscles activity if it becomes part of a person's daily lifestyle which might predispose these muscles to fatigue and subsequent injuries.
The Relationship Between Ethical Awareness in Nursing Profession, and Moral Sensitivity in Nurses of Hamadan University of Medical Sciences, Iran.
Authors: Mohammadi Ziba , Darderafshi Sahel , Akhlaghi Mahboubeh , Makvandi Zeinab
Published: September 2021

Background: knowledge about moral principles and having moral sensitivity lead to the right decision in nurses when facing moral problems. This study aimed to investigate the relationship between ethical awareness in the nursing profession and moral sensitivity in nurses of Hamadan University of Medical Sciences in 2018.Methods: In this cross-sectional study, 333 nurses working in teaching hospitals of Hamadan University of Medical Sciences participated; selected by stratified sampling method with proportional allocation. Data collection tools included demographic information form, and questionnaires of ethics awareness in the nursing profession, and moral sensitivity. Data normality was assessed by Kolmogorov-Smirnov test and according to which, parametric t-test and ANOVA or non-parametric Mann-Whitney and Kruskal-Wallis tests were done in SPSS 24.Results: The results showed that the overall mean score of nurses' awareness and moral sensitivity was moderate. Also, the majority of nurses had a moderate level of awareness (65.3%) and moral sensitivity (80.4%). The level of ethics awareness by gender and the level of moral sensitivity in according to gender, marital status, shift work and employment status were significantly different (p <0.05). The findings showed that there was no statistically significant correlation between ethical awareness and moral sensitivity in nurses.Conclusion: given to the moderate level of awareness and moral sensitivity of nurses, efforts should be made to improve and promote ethical issues in nursing. It is also recommended to conduct more tailoring studies to teaching the principles of ethical awareness and moral sensitivity and to recognizing the factors affecting them.
An Integrated Analysis of Prognostic and Immune Infiltrates for Hub Genes as Potential Survival Indicators in Patients with Lung Adenocarcinoma
Authors: Xu Zhiyun , Wang Shi , Ren Zhijian , Gao Xiang , Xu Lin , Ren Binhui
Published: September 2021

Objective: Lung adenocarcinoma is one of the major subtypes of lung cancer. However, the prognosis of individuals with LUAD is still not promising. Therefore, this research aims to discover useful biomarkers to enhance the treatment and diagnosis of LUAD.Methods: GEO2R was used to identify common up-regulated DEGs in the GSE32863, GSE40791 and GSE75037. The DEGs were submitted to Metascape for gene ontology and pathway enrichment analysis. Metascape was also utilized to construct the PPI network, and the MCODE plug-in was employed to filter important subnetworks. The prognosis and expression levels of the hub genes were evaluated using the UALCAN, GEPIA2, and Kaplan-Meier plotter databases. The Timer database was utilized to confirm the correlation between immune cells infiltration and the expression levels of hub genes in LUAD tissues.Results: This research discovered 307 common up-regulated DEGs, and gene ontology and pathway enrichment analysis indicated that they were mostly enriched in mitotic cell cycle process and cell cycle pathway. DEGs in the subnetwork with the largest number of genes were AURKB, CCNB2, CDC20, CDCA5, CDCA8, CENPF and KNTC1. The seven hub genes were highly expressed in LUAD tissues and had a poor prognosis. AURKB, CCNB2, and CDC20 were inversely associated with B and CD4+ T cells. CDCA5, CDCA8, and CENPF have a substantially negative correlation with B Cell, but positive correlation with Neutrophil. Conclusions: This research demonstrates that increased expression of seven hub genes is associated with worse prognosis for LUAD patients. Additionally, immune cells infiltrating LUAD tissues may serve as a regulating mechanism.
Decreased CSF clearance and increased brain amyloid in Alzheimer’s disease
Authors: li yi , Rusinek Henry , Butler Tracy , Glodzik Lidia , Pirraglia Elizabeth , Babich John , Mozley P. David , Nehmeh Sadek , Pahlajani Silky , Wang Xiuyuan , Tanzi Emily B. , Zhou Liangdong , Strauss Sara , Carare Roxana , Theise Neil , Okamura Nobuyuki , de Leon Mony J.
Published: September 2021

In sporadic Alzheimer’s disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living human subjects. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. Prior MRI phase contrast studies have reported reduced aqueductal CSF flow in AD. Using PET and tau tracer 18F-THK5117, we previously reported that the ventricular CSF clearance of the PET tracer was reduced in AD and associated with elevated brain Aβ levels. In the present study, using two PET tracers, 18F-THK5351 and 11C-PiB to estimate CSF clearance, we observe that the ventricular CSF clearance measures were correlated (r = .66, p < .01), with reductions in AD of 18 and 27%, respectively. We also replicated a significant relationship between ventricular CSF clearance (18F-THK5331) and brain Aβ load (r = −.64, p < .01). With a larger sample size, we extended our observations to show that reduced CSF clearance is associated with reductions in cortical thickness and cognitive performance. Overall, the findings support the hypothesis that failed CSF clearance is a feature of AD that is related to Aβ deposition and to the pathology of AD. Longitudinal studies are needed to determine whether failed CSF clearance is a predictor of progressive amyloidosis or its consequence.
The road beyond licensing: The impact of a driver licensing support program on employment outcomes for Aboriginal and Torres Strait Islander Australians
Authors: Porykali Bobby , Cullen Patricia , Hunter Kate , Rogers Kris , Kang Melissa , Young Nareen , Senserrick Teresa , Clapham Kathleen , Ivers Rebecca
Published: September 2021

Background: With increasingly tough graduated driver licensing laws in all Australian States and Territories, driver licensing support programs are recognised as being important to support Aboriginal and Torres Strait Islander peoples to obtain a driver licence. Such programs appear to improve licensing attainment rates, but few studies have examined the broader impact that these programs can have. This research aims to examine the impact of a NSW based driver licensing support program (Driving Change) on client employment outcomes. Methods: Driving Change was delivered from February 2013 to August 2016 in 4 urban and 7 regional Aboriginal communities of New South Wales. Clients were followed-up at 6 months or more following contact with the program as part of routine program operations. Descriptive statistics and regression models were used to analyse data.Results: From 933 clients contacted 254 agreed to provide feedback, a response rate of 27%. Those that responded were mostly female (57%), aged 24 years and under (72%), unemployed (85%) with secondary education or less (71%) and from a regional area (74%). Adjusted logistic regression indicated that clients who achieved an independent licence were more likely (OR: 2.5, 95% CI: 1.22 – 5.24, p=0.001) of reporting a new job or change in job than those who did not attain a licence. Clients from regional areas were more likely (OR: 1.72, 95% CI: 1.27 – 2.33, p=0.001) to gain an independent licence than those from urban areas. Clients from regional areas were also more likely to report an improvement in employment outcomes (OR: 1.2, 95% CI: 0.52 – 2.52, p=0.72,) compared to those from urban areas, though results were not statistically significant. Discussion: This licensing support program increased licensing attainment particularly in regional areas and also had a beneficial effect on employment for those who gained a licence through the program. Clients were predominantly young and unemployed, which are often a hard to reach cohort. There is a need for future licensing programs to collect client employment data and explore approaches for sustainable collaboration between employment agencies and Governments.Conclusion: Licensing programs appear to be effective in improving employment outcomes. Future licensing programs being delivered in regional areas need integrated pathways into employment opportunities to provide holistic services that address the social and economic challenges faced by Aboriginal and Torres Strait Islander Australians.
Multi-shuttle AS/RS Dimensions Optimization Using a Genetic Algorithm – Case of the Multi-aisle Configuration
Authors: FANDI wahiba , KOULOUGHLI Sihem , GHOMRI Latefa
Published: September 2021

Over the past few years, automated storage and retrieval systems (AS/RSs) have been increasingly improving. It is worth mentioning that multi-shuttle storage/retrieval (S/R) machines were gradually introduced to the market some years ago. These machines, which possess a high speed of execution, are able to transport several pallets at a time during the same trip, as opposed to single-shuttle S/R machines which can carry only one pallet at a time. It should be noted that the installation of this type of system requires a significant financial investment, and therefore it is highly recommended that this system be well studied and designed prior to its installation. It is widely acknowledged that one of the most important objectives while designing an AS/RS is to achieve the shortest time for one single cycle. The present work aims at designing an AS/RS with optimal dimensions for the purpose of minimizing the time in a multi-cycle implementation. To do this, it was decided to consider a multi-aisle automated storage/ retrieval system (AS/RS) with a multi-shuttle S/R machine. In addition, a genetic algorithm (GA) was used for the optimization of the system.
Research on the Optimal Allocation of Tolerances of CNC Machine Tools Based on Small Deformation of Grinding Wheel
Authors: Fan Jinwei , Xie Bentian , Zhao Qinzhi , Wang Junjian
Published: September 2021

In order to solve the problem of precision optimization design of CNC machine tools, this paper proposes an optimized allocation method of machine tool tolerance parameters that takes into account the slight deformation of the machine tool. First, establish a tolerance-based geometric error prediction model, and establish a spatial motion error model based on the theory of multi-body systems(MBS); Homogeneously, perform finite element analysis(FEA) on the CNC internal cylindrical compound grinding machine to obtain the slight deformation of the machine tool, and apply the result to the optimal tolerance allocation In the constraint conditions, the final optimal allocation plan is obtained; Finally, the genetic algorithm is used to simulate and analyze the plan, and the optimal tolerance allocation result is obtained. The result shows that most of the tolerance parameters have been relaxed, which means that the machine tool’s manufacturing cost. Through experiments, it is verified that the optimized machine tool machining accuracy pass rates are 98.5%, 98.25%, and 97.85%, respectively. Therefore, the optimal allocation method of tolerances that considers small deformations proposed in this paper is effective.
Effect of Density on Mediterranean Pine Seedlings Using the Nelder Wheel Design: Analysis of Survival and Early Growth
Authors: Ruano Irene , Pando Valentín , Bravo Felipe
Published: September 2021

Background: There is growing interest in mixed-species forests but a lack of studies that analyse them for regeneration phases or any stage other than mature stands. Information is scarce about relatively unproductive species such as Pinus pinaster and Pinus halepensis in Mediterranean ecosystems. The objective of this study was to investigate inter- and intra-specific interactions of both species in different tree densities during the first years of establishment. Five Nelder wheel plots were planted to test densities ranging from 1000 to 80000 seedlings/ha and simulate establishment sub-processes at high densities. Pinus pinaster and Pinus halepensis were mixed along the spokes, to obtain three mixture levels in which 100%, 80% or 60% of the seedlings were of the same species. Cox proportional-hazards models and binomial logistic regressions were fitted to analyse seedling survival. Early growth (basal diameter and height at one and four years after plantation) was analysed by fitting linear mixed-effects models. Results: Pinus halepensis showed higher survival rates and basal diameter increments but more time is needed to know how Pinus pinaster responds to density and mixture. Conclusions: Both competitive and facilitating seedling interactions were observed at higher densities, which facilitate seedling survival but decrease early growth. Pinus halepensis showed higher survival rates and basal diameter increments but more time is necessary to determine Pinus pinaster response to density and mixture.
Axial-Ligand-Cleavable Silicon Phthalocyanines Triggered by Near-Infrared Light toward Design of Photosensitizers for Photoimmunotherapy
Authors: Takakura Hideo , Matsuhiro Shino , Kobayashi Masato , Goto Yuto , Harada Mei , Taketsugu Tetsuya , Ogawa Mikako
Published: September 2021

Near-infrared photoimmunotherapy (NIR-PIT) is a novel phototherapy for the treatment of cancer that uses NIR light and conjugates of antibody-IR700, a silicon phthalocyanine photosensitizer. A key feature of NIR-PIT is light-induced axial ligand cleavage of IR700, which finally causes cytotoxicity. Here, we focused on protonation of the axial ligand on the IR700 anion radical during the photochemical process. The Gibbs energy in the protonation reaction of IR700 derivatives with different axial ligands was calculated. These calculations suggested the order of the cleavage efficiency corresponds to the basicity of the axial ligand (i.e. alkoxy > siloxy (IR700) > phenoxy ≈ oxycarbonyl), which was confirmed by the photoirradiation experiments with synthesized compounds. Thus, axial ligand cleavage is significantly dependent on the basicity of the axial ligand. Our findings suggest that PIT reagent with an IR700 derivative bearing alkoxy group would show better efficacy than IR700.
Isolation of Nannocystis species from Iran and exploring their natural products
Authors: Moradi Azam , Yaghoubi-Avini Mohammad , Wink Joachim
Published: September 2021

Several different techniques were employed for the isolation of Nannocystis from various sources. A polyphasic approach was used for identification. Twelve strains of N. pusilla, N. exedens, and N. konarekensis with distinctive distribution between climates were identified. The bioactivity was examined against a panel of eight bacteria, two yeasts, and one fungus; cytotoxicity was tested on the L929 fibroblast cell line. Eleven strains mainly inhibit Gram-positive bacteria, and only one isolate was cytotoxic. The extracts analysis by HPLC and LC-MS were compared to Myxobase, and eight different compounds were detected; a correlation was observed between compounds and producing species. 70% of strains had the potential to produce structurally diverse compounds. Nannochelins and althiomycin were the most abundant metabolites. The discovery of a new species of Nannocystis and the high potentiality of strains to produce secondary metabolites encourage further sampling and in-depth analysis of extracts to find new active metabolites.
Integrated metabolomic and transcriptomic analysis of the anthocyanin regulatory networks in red walnut
Authors: Wang Lei , Li Lin , Zhao Wei , Meng Haijun , Zhang Ganggang , Wu Wenjiang , Shi Jiangli , Wu Guoliang
Published: September 2021

Background

Walnut is one of the most important dry fruit crops worldwide, typically green leaves and yellow-brown or gray-yellow seed coats. A specific walnut type, red walnut ‘RW-1’ with red leaves and seed coats was selected as plant material because of higher anthocyanins contents. Anthocyanins are important colorants with strong antioxidant activity, especially, benefic for human health. However, few studies focused on the molecular mechanism of anthocyanin biosynthesis in walnut.
Results

From the results of Widely Targeted Metabolome and anthocyanidin detection analysis, 395 substances, including 4 procyanidins and 26 anthocyanins, were identified from the red-leaf walnuts of RW-1 natural hybrid progenies (SR) and the green-leaf walnuts of RW-1 natural hybrid progenies (SG). Among these, all the anthocyanins in SR were significantly up-accumulated comparing with SG. Also, delphinidin 3-O-galactoside, cyanidin 3-O-galactoside, delphinidin 3-O-glucoside and cyanidin 3-O-glucoside were identified to the primary components of anthocyanidins because of the higher contents. It was noted that 9 anthocyanins including malvidin 3-O-galactoside, malvidin 3-O-arabinoside, cyanidin 3-O-(6-O-malonyl-beta-D-glucoside), delphinidin 3-O-glucoside, delphinidin 3,5-O-diglucoside (Delphin), peonidin 3-O-(6-O-malonyl-beta-D-glucoside), petunidin 3-O-(6-O-malonyl-beta-D-glucoside), petunidin 3-O-arabinoside and pelargonidin 3-O-(6-O-malonyl-beta-D-glucoside) were detected only in SR walnut. Furthermore, transcriptome analysis demonstrated that the expression of structural genes (C4H, F3H, F3’5’H and UFGTs), and four MYBs in anthocyanin biosynthetic pathway were significantly higher in SR walnut.
Conclusions

We identified the color formation of SR leaves is due to the accumulation of anthocyanins. And our results obtained the valuable information on the anthocyanin metabolites and candidate genes in anthocyanin biosynthesis, which provided new insights into the anthocyanin biosynthesis in walnuts.
Research designs and instruments to detect physiotherapy overuse of low-value care services in low back pain management: A scoping review protocol
Authors: Kühn Lukas , Lindert Lara , Choi Kyung-Eun (Anna)
Published: September 2021

BackgroundThe provision of low value care services in low back pain management is a problem of global scope. Inappropriate imaging, overmedication and overused invasive therapies are prevalent in physician services. Yet, little is known about overused low-value physiotherapy services. Most studies addressing physiotherapy overuse in low back pain management arose from countries in which physiotherapy is established in primary care. However, measures and instruments addressing physiotherapy overuse limitedly fit legislative conditions of health systems in which physiotherapy is a service of secondary care. Thus, this scoping review’s purpose is to map existing research designs and instruments aiming to detect overused low-value physiotherapy services taking specific healthcare settings and aspects of the medical overuse into account.MethodsThe development of this scoping review is guided by the Arksey and O’Malley framework. A three-step, peer reviewed search strategy in accordance to the PRESS checklist will be conducted on Medline (PubMed), Web of Science and CINHAL. Additionally, grey literature will be searched on googlescholar. Preprints of empirical studies will be included. Initially, two reviewers will independently screen articles for eligibility by title and abstract. A third reviewer will mediate discrepancies. Uncertainties will be eliminated by full text analysis or by contacting the corresponding authors. A four-step analytical process will guide result reporting focusing on major research questions outlined in this protocol. Numerical and narrative tables, graphics and narrative summaries will be methods to summarize and collate results. In the final step, the German health system will serve as an exemplary setting and frame to practically apply results.DiscussionResults of this scoping review will help researchers to systematically select overuse measures referring to aspects of the overuse typology, specific healthcare settings and physiotherapy services. It will further provide information on limitations of present studies and will give advice how to address them. Moreover, this review will illustrate to what degree existing studies succeed to comprehensively cover the concept of the overuse typology.RegistrationThis protocol has been registered on open science framework. (https://osf.io/vzq7k DOI: 10.17605/OSF.IO/PMF2G)
Balanced modulation of neuromuscular synaptic transmission via M1 and M2 muscarinic receptors during inhibition of cholinesterases
Authors: Lenina Oksana A. , Petrov Konstantin A.
Published: September 2021

Organophosphorus (OP) compounds that inhibit acetylcholinesterase are a common cause of poisoning worldwide, resulting in several hundred thousand deaths each year. The pathways activated during OP compound poisoning via overstimulation of muscarinic acetylcholine receptors (mAChRs) play a decisive role in toxidrome. The antidotal therapy includes atropine, which is a nonspecific blocker of all mAChR subtypes. Atropine is efficient for mitigating depression in respiratory control centers but does not benefit patients with OP-induced skeletal muscle weakness. By using an ex vivo model of OP-induced muscle weakness, we studied the effects of the M1/M4 mAChR antagonist pirenzepine and the M2/M4 mAChR antagonist methoctramine on the force of mouse diaphragm muscle contraction. It was shown that weakness caused by the application of paraoxon can be significantly prevented by methoctramine (1 µM). However, neither pirenzepine (0.1 µM) nor atropine (1 µM) was able to prevent muscle weakness. Moreover, the application of pirenzepine significantly reduced the positive effect of methoctramine. Thus, balanced modulation of neuromuscular synaptic transmission via M1 and M2 mAChRs contributes to paraoxon-induced muscle weakness. It was shown that methoctramine (10 µM/kg, i.p.) and atropine (50 µM/kg, i.p.) were equieffective toward increasing the survival of mice poisoned with a 2xLD50 dose of paraoxon.
Superconductivity in In-doped AgSnBiTe3 with possible band inversion
Authors: Mitobe Tsubasa , Hoshi Kazuhisa , Kasem Md. Riad , Kiyama Ryosuke , Usui Hidetomo , Yamashita Aichi , Higashinaka Ryuji , Matsuda Tatsuma D. , Aoki Yuji , Goto Yosuke , Mizuguchi Yoshikazu
Published: September 2021

We investigated the chemical pressure effects on structural and electronic properties of SnTe-based material using partial substitution of Sn by Ag0.5Bi0.5, which results in lattice shrinkage. For Sn1-2x(AgBi)xTe, single-phase polycrystalline samples were obtained with a wide range of x. On the basis of band calculations, we confirmed that the Sn1-2x(AgBi)xTe system is basically possessing band inversion and topologically preserved electronic states. To explore new superconducting phases related to the topological electronic states, we investigated the In-doping effects on structural and superconducting properties for x = 0.33 (AgSnBiTe3). For (AgSnBi)(1-y)/3InyTe, single-phase polycrystalline samples were obtained for y = 0–0.5 by high-pressure synthesis. Superconductivity was observed for y = 0.2–0.5. For y = 0.4, specific heat investigation confirmed the emergence of bulk superconductivity. Because the parameters obtained from specific heat analyses were comparable to In-doped SnTe, we expect that the (AgSnBi)(1-y)/3InyTe and other (Ag,In,Sn,Bi)Te phases are a candidate system for studying topological superconductivity.
Further delineation of the phenotypic spectrum of pathogenic variants in MED13
Authors: Povolotskaya Inna S. , Vetrova Natalya V. , Zhikrivetskaya Svetlana O. , Musatova Elizaveta V. , Klestova Valeriia S. , Shirokova Natalya A. , Tveleneva Aleksandra A. , Kotov Ilya N. , Isaev Artur A. , Pomerantseva Ekaterina A.
Published: September 2021

Introduction:Diagnostic yield of the genetic testing in search for the molecular basis of neurodevelopmental diseases remains low due to incomplete knowledge of the phenotypic spectrum of pathogenic variants in a specific gene. Recently the MED13 gene was linked to neurodevelopmental disease. Methods:Four families with children affected by autism spectrum disorder (ASD) were recruited to the study. Extensive genetic testing was performed for each proband: CGG repeat expansion analysis in FMR1 gene; whole exome sequencing (WES); array comparative genomic hybridization (aCGH); maternity and paternity confirmation. Genetic variants which were revealed by WES were verified with Sanger sequencing or aCGH in probands and their relatives. Results:Four rare heterozygous genetic variants in MED13 gene were identified in four unrelated patients with clinical features matching MED13-associated phenotype: intellectual disability (ID) of various degrees, speech delay, ASD and mild facial dysmorphisms. Three of the variants occurred de novo, while one was inherited maternally, in accordance with previous findings, suggesting incomplete penetrance. A patient with a de novo missense mutation in the intrinsic disordered region of MED13 developed seizures similarly to the only other reported patient with a pathogenic missense variant in this region. Limitations:Additional functional studies are needed to elucidate molecular mechanisms of the disease and distinguish between pathogenic and non-pathogenic variation.Conclusion:Our data strongly support the role of MED13 in neurodevelopmental disease by eliminating other common genetic defects. We expand the phenotypic spectrum of the disease causing variants: pathogenic missense variants in the intrinsic disordered region of MED13 may lead to a phenotype with seizures and incomplete penetrance of the maternally inherited variants may occur.
Metagenomics-informed soil biogeochemical models projected less carbon loss in tropical soils in response to climate warming
Authors: song Yang , Yao Qiuming , Yang Xiaojuan , Wright Stuart , Wang Gangsheng , Hazen Terry , Turner Benjamin , Tfaily Malak , Pasa-Tolic Ljiljana , Jonston Eric , Kim Minjae , Konstantinidis Konstantinos , Pan Chongle , Mayes Melanie
Published: September 2021

A major challenge of quantifying feedback between microbial communities and climate is the vast diversity of microbial communities and the intricacy of soil biogeochemical processes they mediate. We overcome this challenge by simplifying the representation of diverse enzyme functions from metagenomics data. We developed a dynamic allocation scheme for enzyme functional classes (EFCs) based on the premise that microbial communities act to maximize acquisition of limiting resources while minimizing energy expenditure for acquiring unlimited resources. We incorporated this scheme into a biogeochemical model to explicitly represent microbial functional diversity and simulate responses of microbially-mediated soil biogeochemical processes to varying environmental and nutrient conditions. Representing microbial functional diversity and environmental acclimation improved predictions of the stoichiometry of microbial biomass and mitigated the sensitivity of soil organic carbon to warming in nutrient-deficient regions. Our results indicate the importance of microbial functional diversity and environmental acclimation for projecting climate feedbacks of nutrient-limited soils.
Ultraviolett – die unsichtbare Seite der Blumen
Authors: Lunau Klaus
Published: September 2021

Blumen sind Kommunikationsstrukturen zwischen Blütenpflanzen und ihren Bestäubern. Dabei spielen visuelle Farbsignale eine herausragende Rolle. Da kein Bestäuber über ein dem Menschen ähnliches Farbsehsystem verfügt, beruht das Verstehen von Blumenfarben auf einer Analyse mit den Augen des betrachtenden Blütenbesuchers. Ultraviolettes Licht hat dabei eine Sonderstellung, da es für Menschen unsichtbar, für die meisten Blütenbesucher aber wahrnehmbar und eine von vielen Blüten ausgebildete Farbkomponente bildet. UV kann zu Kommunikation zwischen Blüte und Bestäuber entscheidend beitragen. UV- Muster auf Blüten schützen Pollen vor UV-Strahlung und sind gleichzeitig wegweisende Strukturen, mit deren Hilfe Blütenbesucher einen Landeplatz und eine Belohnung finden und gleichzeitig so manipuliert werden, dass die Übertragung von Pollen auf den Bestäuber oder von diesem auf die Narbe anderer Blüten wahrscheinlicher wird. Blütenfarbmuster, die durch Glanz erzeugt werden, können auf sichtbar glänzenden Nektar hinweisen oder diesen vortäuschen. Mit UV-Aufnahmen und Falschfarbenfotos in Bienensicht wird die Bedeutung ultravioletter Farbkomponenten auf Blüten deutlich gemacht.
„No bees, no Bembel!“ – oder: Was das „Stöffche“ mit Bestäubung zu tun hat
Authors: Heubach Katja , Collet Torsten
Published: September 2021

Apfelwein, das „Stöffche“, gilt als Frankfurter Nationalgetränk. Nach Zerstörung der lokalen Weinstöcke durch die Reblaus am Ende des 19. Jahrhunderts wurden vermehrt Streuobstwiesen für die Apfel(wein)produktion angelegt. Früchte können nur geerntet werden, wenn Insekten zuvor die Apfelblüten bestäubt haben. Honig- und Wildbienen sowie andere Insekten erbringen für uns deshalb eine wichtige Ökosystemleistung. Ohne die Bestäuber gäbe es keine Äpfel, keinen Apfelwein und bliebe der Frankfurter Apfelweinkrug (Bembel) leer: „No bees, no Bembel!“. Der auch für uns Menschen so wichtige Aspekt der Bestäubung wird im Palmengarten und Botanischen Garten Frankfurt im Rahmen des Leitthemas „Blüten- und Bestäuberbiologie“ vielseitig beleuchtet. Herzstück des Leitthemas ist das im Jahr 2021 eröffnete neue Blüten- und Schmetterlingshaus mit frei fliegenden tropischen Schmetterlingen sowie die zugehörige Ausstellung „Abgestaubt! - Von Blüten und ihren Bestäubern“. Im Freiland von Palmengarten und Botanischen Garten können die Besucher*innen eine Vielzahl wildlebender Insektenarten beobachten und so theoretisches Wissen mit praktischem Erleben festigen.
Andreas Roloff (Hrsg.) Trockenstress bei Bäumen. Ursachen. Strategien. Praxis.
Authors: Steinecke Hilke
Published: September 2021

-
A somewhat random walk through nuclear and particle physics
Authors: Cohen Thomas , Poniatowski Nicholas
Published: September 2021

These notes are an outgrowth of an advanced undergraduate course taught at the University of Maryland, College Park. They are intended as an introduction to various aspects of particle and nuclear physics with an emphasis on the role of symmetry. The basic philosophy is to introduce many of the fundamental ideas in nuclear and particle physics using relatively sophisticated mathematical tools -- but to do so in as a simplified a context to explain the underlying ideas. Thus, for example, the Higgs mechanism is discussed in terms of an Abelian Higgs model. The emphasis is largely, but not entirely theoretical in orientation. The goal is for readers to develop an understanding of many of the underlying issues in a relatively sophisticated way.
Mometasone furoate in the treatment of allergic rhinitis: a complex therapeutic effect
Authors: Fassakhov R. S. , Marapov D. I.
Published: September 2021

The review examines the role of mometasone furoate (NSMF) intranasal spray (Nasonex) in the treatment of allergic rhinitis (AR). There is a wide prevalence of AR both among children and adults, its adverse effect on the quality of life of patients. It is emphasized that the main means of therapy for moderate and severe course in accordance with international and Russian recommendations for the diagnosis and treatment of AR are intranasal glucocorticosteroids (INGKS). The pharmacological features of the MF molecule that underlie its efficacy and safety, including the affinity, lipophilicity and viscosity of the drug, as well as low systemic bioavailability, are discussed in detail. The therapeutic effects of NSMF in the treatment of seasonal and perennial AR, its effect on nasal symptoms are discussed in detail. The beneficial effect of NSMF therapy on nasal congestion is emphasized separately. The beneficial effect of NSMF treatment on other clinical manifestations of AR, including ocular symptoms, effects on sleep, and olfactory function, has been noted. The safety issues of NSMF use are discussed in detail, including systemic effects, such as effects on adrenal function, eye, and growth retardation in children, and local adverse effects on the nasal mucosa; there is a high profile of local and systemic safety of long-term use of NSMF in the treatment of AR in both adults and children.
Secondary exocrine pancreatic insufficiency. Features of the choice of the enzyme
Authors: Pakhomova I. G.
Published: September 2021

Exocrine pancreatic insufficiency is quite common in clinical practice of doctors of many specialties. Decrease in intraduodenal lipase levels below 5–10% of normal leads to pancreatic steatorrhea, weight loss and a potential decrease in quality of life. These clinical manifestations are more often presented in patients with a primary genesis of exocrine pancreatic insufficiency, while secondary exocrine insufficiency is more often subclinical, which predetermines its early diagnosis. However, many methods for diagnosing exocrine pancreatic insufficiency, which have been developed and used in clinical practice in recent years, have low sensitivity or specificity, or are time-consuming and poorly tolerated by patients. The method for determining the level of coprological elastase is not always reliable, especially in patients with chronic diarrhea, which predetermines its implementation in formalized stool, for example, during therapy. It is important to take into account the fact that with moderate exocrine pancreatic insufficiency, the sensitivity and specificity of assessing the level of fecal elastase can weaken by 30%. However, regardless of the receipt of diagnostic data and the cause of the development of exocrine pancreatic insufficiency, the goal of therapy is to eliminate the processes of maldigestion and malabsorption, reduce the severity of symptoms of indigestion and prevent their negative consequences. At the  same time, it is necessary to include an enzyme preparation in the complex therapy, the choice of which, its dosage and duration of therapy are determined taking into account the individual characteristics of the patient and the severity of exocrine pancreatic insufficiency. In addition, in patients with suspected exocrine pancreatic insufficiency due to clinical manifestations, it is possible to use empirical enzyme replacement therapy. An example of such an approach for patients with secondary exocrine insufficiency is the appointment of the enzyme preparation containing pancreatin.
Diagnostics of functional disorders of the gastrointestinal tract in patients with constipation
Authors: Kazyulin A. N. , Samsonov A. A. , Kucheryavyy Yu. A. , Cheremushkin S. V. , Gilyuk A. V.
Published: September 2021

The purpose of the review is to acquaint general practitioners, therapists, gastroenterologists with the possibilities of diagnosing functional disorders of the gastrointestinal tract associated with constipation, as well as to draw attention to the need for additional examination methods for a comprehensive assessment of functional disorders of the gastrointestinal tract in patients with constipation on pathogenesis.

Functional constipation is an urgent problem today due to its prevalence among different age groups, a negative impact on the quality of life, as well as the variability of the clinical forms of diseases associated with this symptom. The modern diagnostic algorithm for chronic constipation consists of several stages, including the identification of signs of the disease, according to the Rome criteria of the IV revision (2016), the identification of symptoms of “red flags” and laboratory and instrumental research. It should be borne in mind that functional constipation is often based on the pathology of the anorectal zone, which is an important factor in the diagnosis and development of further therapeutic strategies. The article provides an overview of modern and promising methods for diagnosing functional disorders of defecation, taking into account functional disorders of the anorectal zone associated with constipation.

Functional methods such as anorectal manometry, rectal sensory test and balloon expulsion test are the  most studied and obligatory tests for an objective assessment of the sensorimotor function of the anorectal zone. In Russia, these methods are used very little, which requires extensive familiarization of practitioners with the advantages of these techniques. Knowledge and application of the presented examination algorithms will help the clinician to increase the overall diagnostic efficiency and apply the most justified tactics of managing patients with functional pathology of the digestive system associated with constipation.