bluuebunny/crossref_metadata_2025 huggingface dataset:
miR‐302a‐3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells induced by hypoxia–reoxygenation injury
Authors: Bai Tao , Cui Yanzhi , Yang Xian , Cui Xinyue , Yan Congmin , Tang Ying , Cao Xiaoming , Dong Chunhui
Published: October 2021

New Findings

What is the central question of this study?

How does miR‐302a‐3p play a role in hypoxia–reoxygenation‐induced pyroptosis of renal tubular epithelial cells?

What is the main finding and its importance?

Hypoxia–reoxygenation treatment upregulated the expression of miR‐302a‐3p in HK‐2 cells, and then inhibited the transcription of FMRP translational regulator 1 (FMR1), so as to promote the activation of the NLRP3 inflammasome and aggravate the pyroptosis of HK‐2 cells. miR‐302a‐3p was used as a molecular target in this study, which provides a new theoretical basis for the treatment of renal failure.

Hypoxia–reoxygenation (H/R) induction can affect miRNA expression and then control NLR family pyrin domain containing 3 (NLRP3) inflammasome‐mediated pyroptosis. This study investigated the mechanism of miR‐302a‐3p in H/R‐induced renal tubular epithelial cell (RTEC) pyroptosis. Human HK‐2 RTECs were induced by H/R. Lactate dehydrogenase content, cell activity and pyroptosis, and levels of NLRP3, GSDMD‐N, caspase‐1, interleukin (IL)‐1β, IL‐18, superoxide dismutase, and malondialdehyde were detected to verify the effect of H/R on HK‐2 cells. The NLRP3 inflammasome action was evaluated after H/R‐induced HK‐2 cells were treated with BAY11‐7082, an inflammasome inhibitor. After inhibiting miR‐302a‐3p expression, the changes of pyroptosis were observed. The binding relation between miR‐302a‐3p and FMRP translational regulator 1 (FMR1) was verified. A function‐rescue experiment verified the role of FMR1 in the regulation of pyroptosis. H/R‐induced HK‐2 cells showed significant pyroptosis injury, and the NLRP3 inflammasome was activated. After inhibiting the NLRP3 inflammasome, H/R‐induced apoptosis was inhibited. After H/R treatment, miR‐302a‐3p in HK‐2 cells was increased, and miR‐302a‐3p downregulation limited H/R‐induced NLRP3 inflammasome‐mediated pyroptosis. FMR1 is the target of miR‐302a‐3p. Inhibition of FMR1 alleviated the inhibition of H/R‐induced HK‐2 cell pyroptosis by miR‐302a‐3p inhibitor. Collectively, inhibiting miR‐302a‐3p can weaken its targeted inhibition on FMR1, thereby inhibiting the activation of NLRP3 inflammasomes and reducing caspase‐1‐dependent pyroptosis in HK‐2 cells.
The Study of Genetic Polymorphism of Fungal Pathogens Using iPBS Assays
Authors: Khapilina O.N. , Turzhanova A.S. , Shevtsov V.A. , Tumenbaeva A.R. , Raiser O.B. , Tagimanova D.S. , Kalendar R.N.
Published: October 2021

Species of the genus Alternaria are widely distributed as saprophytes on plant residues, as well as pathogens of various plant species. On wheat seeds, Alternaria fungi are localized in the endosperm and fruit shells, causing symptoms of "black germ" disease, and are a dominant component of the wheat seed microbiome. Recently, due to the high potential danger of these fungi, much attention has been paid to the study of the genetic variability of populations that exist in certain climatic conditions. Using retrotransposon sequences as markers increase knowledge about phylogenetic relationships within populations of phytopathogenic fungi, as well as their biodiversity.

The iPBS (inter-priming binding sites) method used in this work was applied to detect genetic polymorphism of isolates of the genus Alternaria, as the most frequently encountered genus (the frequency of isolation was more than 50%). The isolates were isolated from wheat seeds that were cultivated in various ecological regions. The 4 iPBS primers used in this study amplified 387 fragments, 352 of which were polymorphic. The level of detected polymorphism varied from 66% when using primer 2224 to 100% when using primer 2242. The information content index of the PIC (polymorphism information content) primers varied in the range of 0.894-0.987. Analysis of genetic polymorphism revealed significant genetic variability among fungal isolates. Genetic analysis of amplification profiles of isolates of fungi of the genus Alternaria conducted using the GenAlex 6.5 software differentiated all isolates into 2 large groups. Isolates of A. infectoria were isolated in a separate cluster. Isolates of A. alternata and A. tennuissima were grouped in a different cluster depending on the species. Research results show that the iPBS method is highly effective for the genetic differentiation of phytopathogenic fungi at both intraspecific and interspecific levels.
Molybdoenzyme Participation In Plant Biochemical Processes
Authors: Tokasheva D.S. , Nurbekova Zh.A. , Akbassova A.Zh. , Omarov R.T.
Published: October 2021

Molybdenum is a key microelement in plant vital functioning. The microelement can be absorbed by the plants only in the form of molybdate-anion.  The Molybdenum deficiency affects negatively to the most important agricultural growing.  As molybdenum takes part in such vital mechanisms as nitrogen and sulfur metabolism, plant hormone biosynthesis, and purine banding catabolism. Molybdenum is included in enzyme content which is called molybdoenzyms. Having bonded with molybdopterin it creates molybdenum co-factor (Moco) and gets oxidation-reduction properties. Moco is included in active site of molybdoenzymes. They take part in sulfur and nitrogen metabolism, and detrimental compound detoxication. Molybdenum deficiency is characterized by the slow plant growth, low amount of chlorophyll ascorbic acid capacity.It was noticed that plants suffering from the molybdenum deficiency can be saved, sodium molibdate can be used, it can be put directly in the soil or plant leaves can sprayed with the solution. There are five plant molibdoenzymes which are currently known: sulfite oxidase (SO), xanthine dehydrogenase (XD), nitrate reductase (NR), aldehyde oxidase (AO) and mitochondrial amidoxim-regenerative component. Nitrate reductase catalyzes the first stage of nitrate assimilation, eucariotic organisms contain three isoforms of the molybdoezimes: A NADH, A NAD(P)H и NADPH.  Xanthine dehydrogenase regulates purine metabolism. XD increases plant antioxidant ability and slows down leaves aging. Molybdoenzymess are involved in the process of the stress adaptation, defining of the mechanisms and their reaction to environmental stress conditions is important for plant stress resistance.
Evaluation Of The Mutagenic Potential Of The Polyphenol Extract From Blueberries In The Ames Test
Authors: Shulgau Z.T. , Sergazy S.D. , Zhulikeeva A.M. , Dautov A.Y. , Gulyayev A.Y. , Kovalenko L.V. , Belotserkovtseva L.D. , Kavushevskaya N.S. , Logutenko A.V.
Published: October 2021

In this research, mutagenic properties of blueberry polyphenol extract were studied in gene mutation induction test (Ames test) on four strains of Salmonella typhimurium TA98, TA100, TA1535, TA1537. None of the strains of Salmonella typhimurium showed statistically reliable dose-dependent increase in number of revertant colonies in the presence of investigated drug in the studied dose range from 4,0 to 40,0 mg/ml relative to baseline of spontaneous mutations. The blueberry extract does not have any mutagenic activity in the researched dose range in relation to TA98, TA100, TA1535, TA1537 strains of Salmonella typhimurium.
Secretory Expression Of The Glucan Endo-1,3-Beta-D-Glucosidase Gene Of Secale Cereale In Yeast Pichia Pastoris
Authors: Saginova M. , Akishev Zh. , Sarsen A. , Kiribayeva A. , Khassenov B.
Published: October 2021

For survival in cold conditions, many organisms have developed unique adaptive mechanisms based on the synthesis of antifreeze proteins, peptides and glycoproteins that prevent ice formation at negative temperatures. These molecules tend to bind ice crystals and lower the freezing point of the solution without the formation of large crystals. Antifreeze proteins (AFP) were found in almost all types of living organisms, including insects, fungus, yeasts, bacteria and plants. The gene of antifreeze protein - glucan endo-1,3-beta-D-glucosidase (ScGlu-3) from Secale cereale was cloned into shuttle vector pPICZαA. The competent cells of yeast Pichia pastoris GS115 were transformed and the producer strain was obtained, which secreted of ScGlu-3 into the culture medium using 3% methanol as the only carbon source. It was found by western blotting that the maximum accumulation of ScGlu-3 in the culture occurs after 48 hours of fermentation on a medium with methanol. Established that rScGlu-3 precipitates at 50-65% of ammonium sulfate.
Genetic Engineering Materials Bank of The National Center for Biotechnology
Authors: Sarsen A. , Saginova M. , Mukanov B. , Aktayeva S. , Akishev Zh. , Mussakhmetov A. , Kiribayeva A. , Baltin K. , Silayev D. , Khassenov B.
Published: October 2021

For the development of science-intensive technologies in biology, biotechnology and medicine, it is necessary to store valuable DNA samples: genes of enzymes, antigens, proteins for various purposes, and DNA loci in a depository. Storing DNA is inexpensive, and having such a depository will reduce the time spent on research in basic and applied science.

The genetically engineered materials bank has been formed at the National center for biotechnology. Now, the bank has 88 samples of cloned genes of enzymes, antigens, proteins and diagnostically significant loci. Plasmid vectors with cloned genes are stored at a temperature -20°С. Besides competent cells of Escherichia coli strain DH5α were transformed with vectors and recombinant strains were isolated. Recombinant strains carrying the required plasmid vectors are stored for cryopreservation at a temperature -80°С.
Specifications of Nutrition with Healthy and Pathological Conditions of Psoriasis
Authors: Nurgozhina A. , Yermekbayeva B. , Gulyayev A. , Kozhakhmetov S. , Sergazy Sh. , Nurgaziyev M. , Aitenov Y. , Chulenbayeva L. , Tuyakova A. , Kushugulova A.
Published: October 2021

Psoriasis is a long-lasting autoimmune disease characterized by patches of abnormal skin. 183 participants in the experiment were selected for the study, half of which are with psoriasis disease. All participants in the study passed the EPIC-Norfolk Food Frequency Questionnaire, which was completed once and included a diet over the past week. The aim of the study was to identify the intakes of different nutrients in two groups by age. After questionnaire FETA tool was used to analyze all answers (http://www.srl.cam.ac.uk/epic/epicffq/).  The output was the results for all nutrients and macro and microelements that are in the food. Significant differences in patients were in eight nutrients, namely: betacarotene, carotene, fructose, potassium, potatoes, fruits, nuts and seeds, and vegetables. All differences are in favor of healthy patients. Patients with psoriasis had a diet with low income of fruits and vegetables which brought to the deficiency in some nutrients and vitamins. The used tool for converting food frequency questionnaire data into nutrient and food group values can be used widely for different study populations.
Express Method for Species idenTification of Livestock Products Based on Multiplex PCR
Authors: Kalendar R. , Bektayev R.
Published: October 2021

Food falsification has direct impact on public health, fair-trades and wildlife. A test system for simultaneous detecting DNA of Bos taurus/Ovis aries, Equus cabalus, Sus scrofa, Canis lupus, Mus musculus/Rattus rattus species, and Homo sapiens in livestock products was developed. Species-specific primers sets were designed targeting SINE repeat elements. Screening of target species in commercial sausages reflected its application to detect target species in process foods. The assay was tested to detect at least 0.01 pg DNA under suspected meats in sausages. The high sensitivity and specificity of species identification proposed method was shown. The possibility of using the developed test system for assessing the qualitative composition of various food products was demonstrated.
Isolation and Identification of New Strains of Lactic Bacteria from The Microbiom of Young Carp Fish
Authors: Tekebayeva Zh.B. , Bissenova G.N. , Dossova A.D. , Urazova M.S. , Shevtsov А.В. , Temirkhanov A.Zh. , Rakisheva А.K. , Abzhalelov A.B. , Sarmurzina Z.S.
Published: October 2021

Isolation and screening of new strains of lactic acid bacteria from the gut microbiome of carp and carp fingerlings were carried out. Morphological and cultural properties of isolates were studied. All isolates revealed high antagonistic activity against such opportunistic bacteria as Shewanella ximenensis AU 2R-1 B-RKM 0724, Pseudomonas taiwanensis CB 2R-1 B-RKM 0726, Pseudomonas aeruginosa G13 B-RKM 0427, Aeromonas punctata G30 B-RKM 0287, Staphylococcus aureus В-RKM 0470, Escherichia coli В-RKM 0447. Based on the analysis of the nucleotide sequences of the 16S rRNA gene fragment, 6 most active LAB cultures were identified, which belong to representatives of the genera Pediococcus, Lactobacillus and Leuconostoc. The procedure of depositing all strains in the Central Museum of Microorganisms of the Republican Collection of Microorganisms was carried out.
Efficacy of Nanoencapsulated Daptomycin in an Experimental Methicillin-Resistant Staphylococcus aureus Bone and Joint Infection Model
Authors: Jacqueline Cedric , Caillon Jocelyne , Meyer Olivier , Dailly Eric , Simonsson Carl , Lenaerts Vincent , Asehnoune Karim , Reghal Amokrane , Potel Gilles
Published: October 2021

Staphylococcus aureus
bone infections remain a therapeutic challenge, leading to long and expensive hospitalizations. Systemic antibiotic treatments are inconsistently effective, due to insufficient penetration into the infectious site.
Thorough QT Study To Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults
Authors: Newman Lori M. , Kankam Martin , Nakamura Aya , Conrad Tom , Mueller John , O’Donnell John , Osborn Blaire L. , Gu Kenan , Saviolakis George A.
Published: October 2021

Zoliflodacin is a novel spiropyrimidinetrione antibiotic being developed as single oral dose treatment to address the growing global threat of
Neisseria gonorrhoeae
. To evaluate the cardiac safety of zoliflodacin, a thorough QT/QTc (TQT) study was performed in healthy subjects.
Comparative Efficacy of Rifapentine Alone and in Combination with Isoniazid for Latent Tuberculosis Infection: a Translational Pharmacokinetic-Pharmacodynamic Modeling Study
Authors: Radtke Kendra K. , Ernest Jacqueline P. , Zhang Nan , Ammerman Nicole C. , Nuermberger Eric , Belknap Robert , Boyd Rosanna , Sterling Timothy R. , Savic Rada M.
Published: October 2021

Rifapentine has facilitated treatment shortening for latent tuberculosis infection (LTBI) in combination with isoniazid once weekly for 3 months (3HP) or daily for 1 month (1HP). Our objective was to determine the optimal rifapentine dose for a 6-week monotherapy regimen (6wP) and predict clinical efficacy.
Secretory Proteases of the Human Skin Microbiome
Authors: Chua Wisely , Poh Si En , Li Hao
Published: October 2021

The human skin is our outermost layer and serves as a protective barrier against external insults. Advances in next-generation sequencing have enabled the discoveries of a rich and diverse community of microbes—bacteria, fungi, and viruses that are residents of this surface.
Sensory Perception in Bacterial Cyclic Diguanylate Signal Transduction
Authors: Randall Trevor E. , Eckartt Kelly , Kakumanu Sravya , Price-Whelan Alexa , Dietrich Lars E. P. , Harrison Joe J.
Published: October 2021

Cyclic diguanylate (c-di-GMP) signal transduction systems provide bacteria with the ability to sense changing cell status or environmental conditions and then execute suitable physiological and social behaviors in response. In this review, we provide a comprehensive census of the stimuli and receptors that are linked to the modulation of intracellular c-di-GMP.
Supplemental Material: Volcanic origin of the mercury anomalies at the Cretaceous-Paleogene transition of Bidart, France
Authors: Font Eric , al. et
Published: October 2021

Detailed analytical methods, Table S1 (Hg concentration, total organic carbon, and Ir concentration of the Bidart samples), Table S2 (Hg isotope composition of the Bidart samples), and methods.
Supplemental Material: No plate tectonics necessary to explain Eoarchean rocks at Isua (Greenland)
Authors: Rollinson Hugh
Published: October 2021

Data sources and geochemical modeling.
Supplemental Material: A fragile record of fleeting water on Mars
Authors: Koeppel Ari H.D. , al. et
Published: October 2021

Detailed descriptions of the methods and datasets used in this study.
Supplemental Material: Early Pennsylvanian sediment routing to the Ouachita Basin (southeastern United States) and barriers to transcontinental sediment transport sourced from the Appalachian orogen based on detrital zircon U-Pb and Hf analysis
Authors: Allred I.J. , Blum M.D.
Published: October 2021

Table S1: Detrital zircon (DZ) U-Pb isotopic data. Table S2: DZ U-Pb isotopic data from a higher-n approach. Table S3: DZ Hf isotopic data. Table S4: Multi-dimensional scaling (MDS) sample key.
Supplemental Material: Quantitative analysis of hillshed geomorphology and critical zone function: Raising the hillshed to watershed status
Authors: Brecheisen Zachary , al. et
Published: October 2021

Comparison of inverted terrain processing implemented in this study to TopoToolbox results for interfluve (ridge-line) extraction and hierarchical ordering. Different topographic curvature metrics are also explored at varying raster resolutions across hillshed orders.
Illness and injury among Norwegian Para athletes over five consecutive Paralympic Summer and Winter Games cycles: prevailing high illness burden on the road from 2012 to 2020
Authors: Steffen Kathrin , Clarsen Benjamin , Gjelsvik Hilde , Haugvad Lars , Koivisto-Mørk Anu , Bahr Roald , Berge Hilde Moseby
Published: October 2021

Objective

To describe the illness and injury pattern of Norwegian Para athletes over five consecutive Paralympic Summer and Winter Games cycles and to identify which health problems should be targeted in risk management plans with respect to impairment types.

Methods

We monitored athletes from 12 to 18 months prior to each Game using a weekly online questionnaire (Oslo Sports Trauma Research Center-H2 (OSTRC-H2)). We asked them to report all health problems they had experienced in the preceding 7 days, irrespective of their consequences on their sports participation or performance and whether they had sought medical attention.

Results

Between 2011 and 2020, 94 candidate athletes were included in this monitoring programme and prepared to represent Norway; of these, 66 (71%) were finally selected for multiple Paralympic Games. The overall response rate to the weekly questionnaires was 87%. At any given time during the five observation cycles, 37% of the athletes (95% CI 36% to 38%) reported having at least one health problem. Athletes with neurological impairments (n=51) lost 10 days per year due to respiratory problems (95% CI 9 to 11) compared with 9 days (8-10) among those with musculoskeletal impairments (n=37). Gastrointestinal problems caused a time loss of on average 4 days per year in athletes with neurological impairments versus 1 day in athletes with musculoskeletal impairments (mean difference 2.7 days, 2.1–3.3). Musculoskeletal injuries generated a high burden for both athlete groups, in particular, to the elbow, shoulder and lumbosacral regions.

Conclusion

At any given time, nearly two out of five elite Norwegian Para athletes reported at least one health problem. Respiratory tract and other infections; gastrointestinal problems, injuries to the shoulder, elbow and lumbosacral regions represented the greatest health burden. Our findings can help guide the allocation of clinical resources, which should include a broad network of medical specialists, together with dieticians and physiotherapists, to meet the health challenges in Para athletes.
Whole blood versus component therapy for haemostatic resuscitation of major bleeding: a protocol for a systematic review and meta-analysis
Authors: Ssentongo Anna E , Ssentongo Paddy , Heilbrunn Emily , Laufenberg Puopolo Lacee , Chinchilli Vernon M , Oh John , Hazelton Joshua
Published: October 2021

Introduction

There is a renewed interest in the use of whole blood (WB) to manage patients with life-threatening bleeding. We aimed to estimate mortality and complications risk between WB and blood component therapy for haemostatic resuscitation of major bleeding.

Methods

We will conduct a systematic review and meta-analysis of studies published between 1 January 1980 and 1 January 2020, identified from PubMed and Scopus databases. Population will be patients who require blood transfusion (traumatic operative, obstetric and gastrointestinal bleeding). Intervention is WB transfusion such as fresh WB (WB unit stored for less than 48 hours), leukoreduced modified WB (with platelets removed during filtration), warm fresh WB (stored warm at 22°C for up to 8 hours and then for a maximum of an additional 24 hours at 4°C). The primary outcomes will be the 24-hour and 30-day survival rates (in-hospital mortality). Comparator is blood component therapy (red blood cells, fresh-frozen plasma and platelets given together in a 1:1:1 unit ratio). The Cochrane risk of bias tool for randomised controlled trials and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) for observation studies will be used to assess the risk of bias of included studies. We will use random-effects models for the pooling of studies. Interstudy heterogeneity will be assessed by the Cochran Q statistic, where p<0.10 will be considered statistically significant and quantified by I2statistic, where I2≥50% will indicate substantial heterogeneity. We will perform subgroup and meta-regression analyses to assess geographical differences and other study-level factors explaining variations in the reported mortality risk. Results will be reported as risk ratios and their 95% CIs.

Ethics and dissemination

No ethics clearance is required as no primary data will be collected. The results will be presented at scientific conferences and published in a peer-reviewed journal.
Spatiotemporal analysis of the first wave of COVID-19 hospitalisations in Birmingham, UK
Authors: Watson Samuel I , Diggle Peter J , Chipeta Michael G , Lilford Richard J
Published: October 2021

Objectives

To evaluate the spatiotemporal distribution of the incidence of COVID-19 hospitalisations in Birmingham, UK during the first wave of the pandemic to support the design of public health disease control policies.

Design

A geospatial statistical model was estimated as part of a real-time disease surveillance system to predict local daily incidence of COVID-19.

Participants

All hospitalisations for COVID-19 to University Hospitals Birmingham NHS Foundation Trust between 1 February 2020 and 30 September 2020.

Outcome measures

Predictions of the incidence and cumulative incidence of COVID-19 hospitalisations in local areas, its weekly change and identification of predictive covariates.

Results

Peak hospitalisations occurred in the first and second weeks of April 2020 with significant variation in incidence and incidence rate ratios across the city. Population age, ethnicity and socioeconomic deprivation were strong predictors of local incidence. Hospitalisations demonstrated strong day of the week effects with fewer hospitalisations (10%–20% less) at the weekend. There was low temporal correlation in unexplained variance. By day 50 at the end of the first lockdown period, the top 2.5% of small areas had experienced five times as many cases per 10 000 population as the bottom 2.5%.

Conclusions

Local demographic factors were strong predictors of relative levels of incidence and can be used to target local areas for disease control measures. The real-time disease surveillance system provides a useful complement to other surveillance approaches by producing real-time, quantitative and probabilistic summaries of key outcomes at fine spatial resolution to inform disease control programmes.
Invasive alien species in protected areas: the dynamics of Pinus taeda at Rio Canoas State Park – Brazil
Authors: Ricardo Bruna Hellen , Siminski Alexandre , dos Reis Maurício Sedrez
Published: October 2021

Biological invasion is a growing problem, and species of the genus Pinus are known to be a problem in the forests of southern Brazil, including in conservation units. Here, we studied the ecology of Pinus taeda L. invasion in Rio Canoas State Park (PAERC) in regards to forest inventory, soil seed bank analysis, and seed rain assessment, in three distinct successional stages inside the park referred to as “Pinus invasion”, “Old Growth Vegetation”, and “Initial Vegetation”. The forest inventory of 33 (20 m × 20 m) plots found Pinus in two of the three evaluated environments. Seed rain was collected bimonthly using 33 (1 m × 1 m) seed traps for a period of 1 year. The major seed distribution periods were in April and June, confirming data found in the literature. The seed bank was analyzed in February (summer) and June (winter) of 2018. Samples were kept in a greenhouse for a period of 120 days each. Summer evaluation showed no emergence of Pinus taeda seedlings, but the winter evaluation (June) did show the emergence of seedlings. The results showed that the soil seed bank is not persistent. Accordingly, the Pinus invasion reported at PAERC requires a restoration program, as well as one that controls reinfestation.
Functional analysis of co-expression networks of zebrafish ace2 reveals enrichment of pathways associated with development and disease
Authors: Keskus Ayse Gokce , Tombaz Melike , Arici Burcin Irem , Dincaslan Fatma Betul , Nabi Afshan , Shehwana Huma , Konu Ozlen
Published: October 2021

Human Angiotensin I Converting Enzyme 2 (ACE2) plays an essential role in blood pressure regulation and SARS-CoV-2 entry. ACE2 has a highly conserved, one-to-one ortholog (ace2) in zebrafish, which is an important model for human diseases. However, the zebrafish ace2 expression profile has not yet been studied during early development, between genders, across different genotypes, or in disease. Moreover, a network-based meta-analysis for the extraction of functionally enriched pathways associated with differential ace2 expression is lacking in the literature. Herein, we first identified significant development-, tissue-, genotype-, and gender-specific modulations in ace2 expression via meta-analysis of zebrafish Affymetrix transcriptomics datasets (ndatasets = 107); and the correlation analysis of ace2 meta-differential expression profile revealed distinct positively and negatively correlated local functionally enriched gene networks. Moreover, we demonstrated that ace2 expression was significantly modulated under different physiological and pathological conditions related to development, tissue, gender, diet, infection, and inflammation using additional RNA-seq datasets. Our findings implicate a novel translational role for zebrafish ace2 in organ differentiation and pathologies observed in the intestines and liver.
Impact of Stand and Landscape Management on Forest Pest Damage
Authors: Marini Lorenzo , Ayres Matthew P. , Jactel Hervé
Published: October 2021

One promising approach to mitigate the negative impacts of insect pests in forests is to adapt forestry practices to create ecosystems that are more resistant and resilient to biotic disturbances. At the stand scale, local stand management practices often cause idiosyncratic effects on forest pests depending on the environmental context and the focal pest species. However, increasing tree diversity appears to be a general strategy for reducing pest damage across several forest types. At the landscape scale, increasing forest heterogeneity (e.g., intermixing different forest types and/or age classes) represents a promising frontier for improving forest resistance and resilience and for avoiding large-scale outbreaks. In addition to their greater resilience, heterogeneous forest landscapes frequently support a wide range of ecosystem functions and services. A challenge will be to develop cooperation and coordination among multiple actors at spatial scales that transcend historical practices in forest management.
Perspective Shift Across Modalities
Authors: Maier Emar , Steinbach Markus
Published: October 2021

Languages offer various ways to present what someone said, thought, imagined, felt, and so on from their perspective. The prototypical example of a perspective-shifting device is direct quotation. In this review we define perspective shift in terms of indexical shift: A direct quotation like “Selena said, ‘Oh, I don't know.’” involves perspective shift because the first-person indexical ‘I’ refers to Selena, not to the actual speaker. We then discuss a variety of noncanonical modality-specific perspective-shifting devices: role shift in sign language, quotatives in spoken language, free indirect discourse in written language, and point-of-view shift in visual language. We show that these devices permit complex mixed forms of perspective shift which may involve nonlinguistic gestural as well as visual components.
Introduction to the Theme “New Insights, Strategies, and Therapeutics for Common Diseases”
Authors: Insel Paul A. , Blaschke Terrence F. , Amara Susan G. , Meyer Urs A.
Published: October 2021

The reviews in Volume 62 of the Annual Review of Pharmacology and Toxicology ( ARPT) cover a diverse range of topics. A theme that encompasses many of these reviews is their relevance to common diseases and disorders, including type 2 diabetes, heart failure, cancer, tuberculosis, Alzheimer's disease, neurodegenerative disorders, and Down syndrome. Other reviews highlight important aspects of therapeutics, including placebos and patient-centric approaches to drug formulation. The reviews with this thematic focus, as well as other reviews in this volume, emphasize new mechanistic insights, experimental and therapeutic strategies, and novel insights regarding topics in the disciplines of pharmacology and toxicology. As the editors of ARPT, we believe that these reviews help advance those disciplines and, even more importantly, have the potential to improve the health care of the world's population.
Transorgan short-chain fatty acid fluxes in the fasted and postprandial state in the pig
Authors: Kirschner Sarah K. , ten Have Gabriëlla A. M. , Engelen Mariëlle P. K. J. , Deutz Nicolaas E. P.
Published: October 2021

Using a multicatheterized pig model, we identified the portal-drained viscera as the main releasing compartment of the short-chain fatty acids acetate, propionate, butyrate, isovalerate, and valerate in the fasted and postprandial states. Low hepatic acetate metabolism resulted in a high splanchnic release, whereas all other SCFAs were extensively cleared resulting in low but significant splanchnic releases. Muscle and kidneys are the main peripheral SCFA metabolizing organs during fasting and in the postprandial state.
Picture Fuzzy Maclaurin Symmetric Mean Operators and Their Applications in Solving Multiattribute Decision-Making Problems
Authors: Ullah Kifayat
Published: October 2021

To evaluate objects under uncertainty, many fuzzy frameworks have been designed and investigated so far. Among them, the frame of picture fuzzy set (PFS) is of considerable significance which can describe the four possible aspects of expert’s opinion using a degree of membership (DM), degree of nonmembership (DNM), degree of abstinence (DA), and degree of refusal (DR) in a certain range. Aggregation of information is always challenging especially when the input arguments are interrelated. To deal with such cases, the goal of this study is to develop the notion of the Maclaurin symmetric mean (MSM) operator as it aggregates information under uncertain environments and considers the relationship of the input arguments, which make it unique. In this paper, we studied the theory of MSM operators in the layout of PFSs and discussed their applications in the selection of the most suitable enterprise resource management (ERP) scheme for engineering purposes. We developed picture fuzzy MSM (PFMSM) operators and investigated their validity. We developed the multiattribute decision-making (MADM) algorithm based on the PFMSM operators to examine the performance of the ERP systems using picture fuzzy information. A numerical example to evaluate the performance of ERP systems is studied, and the effects of the associated parameters are discussed. The proposed aggregated results using PFMSM operators are found to be reliable as it takes into account the interrelationship of the input information, unlike traditional aggregation operators. A comparative study of the proposed PFMSM operators is also studied.
Notch1 Signaling Contributes to Mechanical Allodynia Associated with Cyclophosphamide-Induced Cystitis by Promoting Microglia Activation and Neuroinflammation
Authors: Chen Jialiang , Ding Honglu , Liu Bolong , Zhou Xiangfu , Zhou Xin , Lin Zhijun , Yang Fei , Zhan Hailun , Xiao Hengjun
Published: October 2021

Aims. Notch1 signaling regulates microglia activation, which promotes neuroinflammation. Neuroinflammation plays an essential role in various kinds of pain sensation, including bladder-related pain in bladder pain syndrome/interstitial cystitis (BPS/IC). However, the impact of Notch1 signaling on mechanical allodynia in cyclophosphamide- (CYP-) induced cystitis is unclear. This study is aimed at determining whether and how Notch1 signaling modulates mechanical allodynia of CYP-induced cystitis. Methods. CYP was peritoneally injected to establish a bladder pain syndrome/interstitial cystitis (BPS/IC) rat model. A γ-secretase inhibitor, DAPT, was intrathecally injected to modulate Notch1 signaling indirectly. Mechanical withdrawal threshold in the lower abdomen was measured with von Frey filaments using the up-down method. The expression of Notch1 signaling, Iba-1, OX-42, TNF-α, and IL-1β in the L6-S1 spinal dorsal horn (SDH) was measured with Western blotting analysis and immunofluorescence staining. Results. Notch1 and Notch intracellular domain (NICD) were both upregulated in the SDH of the cystitis group. Moreover, the expression of Notch1 and NICD was negatively correlated with the mechanical withdrawal threshold of the cystitis rats. Furthermore, treatment with DAPT attenuated mechanical allodynia in CYP-induced cystitis and inhibited microglia activation, leading to decreased production of TNF-α and IL-1β. Conclusion. Notch1 signaling contributes to mechanical allodynia associated with CYP-induced cystitis by promoting microglia activation and neuroinflammation. Our study showed that inhibition of Notch1 signaling might have therapeutic value for treating pain symptoms in BPS/IC.
Forgotten Coindex for the Derived Sum Graphs under Cartesian Product
Authors: Ibraheem Muhammad , Aljohani Meshari M. , Javaid Muhammad , Alanazi Abdulaziz Mohammed
Published: October 2021

A topological index (TI) is a molecular descriptor that is applied on a chemical structure to compute the associated numerical value which measures volume, density, boiling point, melting point, surface tension, or solubility of this structure. It is an efficient mathematical method in avoiding laboratory experiments and time-consuming. The forgotten coindex of a structure or (molecular) graph

H

is defined as the sum of the degrees of all the possible pairs of nonadjacent vertices in

H

. For

D
∈

S
,
R
,
Q
,
T

and the connected graph

H

, the derived graphs

D

H

are obtained by applying the operations

S

(subdivided),

R

(triangle parallel),

Q

(line superposition), and

T

(total graph), respectively. Moreover, a derived sum graph (

D

-sum graph) is obtained by the Cartesian product of the graph

H

2

with the graph

D

H

1

. In this study, we compute forgotten coindex of the

D

-sum graphs

H

1
+
S

H

2

(

S

-sum),

H

1
+
R

H

2

(

R

-sum),

H

1
+
Q

H

2

(

Q

-sum), and

H

1
+
T

H

2

(

T

-sum) in the form of various indices and coindices of the factor graphs

H

1

and

H

2

. At the end, we have analyzed our results using numerical tables and graphical behaviour for some particular

D

-sum graphs.
Segmentation of Overlapping Cervical Cells with Mask Region Convolutional Neural Network
Authors: Chen Jiajia , Zhang Baocan
Published: October 2021

The task of segmenting cytoplasm in cytology images is one of the most challenging tasks in cervix cytological analysis due to the presence of fuzzy and highly overlapping cells. Deep learning-based diagnostic technology has proven to be effective in segmenting complex medical images. We present a two-stage framework based on Mask RCNN to automatically segment overlapping cells. In stage one, candidate cytoplasm bounding boxes are proposed. In stage two, pixel-to-pixel alignment is used to refine the boundary and category classification is also presented. The performance of the proposed method is evaluated on publicly available datasets from ISBI 2014 and 2015. The experimental results demonstrate that our method outperforms other state-of-the-art approaches with DSC 0.92 and FPRp 0.0008 at the DSC threshold of 0.8. Those results indicate that our Mask RCNN-based segmentation method could be effective in cytological analysis.
Complications after Dynamic Hip Screw Osteosynthesis of Proximal Femoral Fractures at Army Instructional Hospital-Libreville
Authors: Bombah F. M. , Diawara M. , Ekani B. Y. , Nana T. , Mikiela A.
Published: October 2021

The DHS system is an effective means of open reduction and internal fixation of proximal femur fractures. Postoperative complications are little described and deserve to be studied for better preventive and curative treatment. We report the observations of five (5) patients who presented postoperative complications specific to the DHS system at army instructional Hospital-Libreville. These described complications are related to deterioration of internal fixation leading to callus, nonunion, or infection. Those found are the cut out phenomenon, avascular necrosis of the femoral head, and the fracture of the DHS system. All these complications required surgical revision without functional repercussions at the last follow-up. Complications of internal fixation by the DHS system can be avoided by rigorous asepsis, adequate indications for surgery, and rigorous surgical techniques. Good management can restore hip function.
Classification of Alzheimer’s Disease Using Gaussian-Based Bayesian Parameter Optimization for Deep Convolutional LSTM Network
Authors: Sethi Monika , Ahuja Sachin , Rani Shalli , Bawa Puneet , Zaguia Atef
Published: October 2021

Alzheimer’s disease (AD) is one of the most important causes of mortality in elderly people, and it is often challenging to use traditional manual procedures when diagnosing a disease in the early stages. The successful implementation of machine learning (ML) techniques has also shown their effectiveness and its reliability as one of the better options for an early diagnosis of AD. But the heterogeneous dimensions and composition of the disease data have undoubtedly made diagnostics more difficult, needing a sufficient model choice to overcome the difficulty. Therefore, in this paper, four different 2D and 3D convolutional neural network (CNN) frameworks based on Bayesian search optimization are proposed to develop an optimized deep learning model to predict the early onset of AD binary and ternary classification on magnetic resonance imaging (MRI) scans. Moreover, certain hyperparameters such as learning rate, optimizers, and hidden units are to be set and adjusted for the performance boosting of the deep learning model. Bayesian optimization enables to leverage advantage throughout the experiments: A persistent hyperparameter space testing provides not only the output but also about the nearest conclusions. In this way, the series of experiments needed to explore space can be substantially reduced. Finally, alongside the use of Bayesian approaches, long short-term memory (LSTM) through the process of augmentation has resulted in finding the better settings of the model that too in less iterations with an relative improvement (RI) of 7.03%, 12.19%, 10.80%, and 11.99% over the four systems optimized with manual hyperparameters tuning such that hyperparameters that look more appealing from past data as well as the conventional techniques of manual selection.
Design of Painting Art Style Rendering System Based on Convolutional Neural Network
Authors: Xie Xingyu , Lv Bin
Published: October 2021

Convolutional Neural Network- (CNN-) based GAN models mainly suffer from problems such as data set limitation and rendering efficiency in the segmentation and rendering of painting art. In order to solve these problems, this paper uses the improved cycle generative adversarial network (CycleGAN) to render the current image style. This method replaces the deep residual network (ResNet) of the original network generator with a dense connected convolutional network (DenseNet) and uses the perceptual loss function for adversarial training. The painting art style rendering system built in this paper is based on perceptual adversarial network (PAN) for the improved CycleGAN that suppresses the limitation of the network model on paired samples. The proposed method also improves the quality of the image generated by the artistic style of painting and further improves the stability and speeds up the network convergence speed. Experiments were conducted on the painting art style rendering system based on the proposed model. Experimental results have shown that the image style rendering method based on the perceptual adversarial error to improve the CycleGAN + PAN model can achieve better results. The PSNR value of the generated image is increased by 6.27% on average, and the SSIM values are all increased by about 10%. Therefore, the improved CycleGAN + PAN image painting art style rendering method produces better painting art style images, which has strong application value.
Chinese Herbal Formula Huoxiang Zhengqi for Dampness Pattern in Atopic Dermatitis and Diarrhea-Predominant Irritable Bowel Syndrome: Rationale and Design of a Master Protocol
Authors: Huang Qian , Guo Xiaohui , Xuan Meiling , Ouyang Wenwei , Wen Zehuai
Published: October 2021

Introduction. Atopic dermatitis (AD) and diarrhea-predominant irritable bowel syndrome (IBS-D) are two recurrent diseases with limited effective treatments. In Chinese Medicine (CM) theory, they may share dampness pattern as the same dominant pathogenesis at a certain stage and, thus, can be treated with the same method. While Chinese herbal formula Huoxiang Zhengqi (HXZQ) has been reported as an effective dampness-resolving therapy for both AD and IBS-D, further high-quality clinical studies are still needed. In addition, HXZQ lacks accurate clinical positioning based on CM patterns. Therefore, we utilize a master protocol design to evaluate HXZQ for dampness pattern simultaneously in AD and IBS-D, with the aim of identifying the pattern-defined population of HXZQ. Methods and Analysis. This master protocol design includes two randomized controlled trials (RCTs) and a real-world observational study. Based on two registry cohorts of AD and IBS-D, patients with dampness pattern will be enrolled in the RCTs to receive either HXZQ oral liquid or a placebo for 4 weeks and then will be followed up for another 4 weeks, while patients with nondampness pattern will constitute the observational study and experience a 12-week follow-up. A total of 678 AD patients and 322 IBS-D patients will be recruited from 14 hospitals in China over a 3-year period. The eczema area and severity index (EASI) and the proportion of responders for adequate relief (AR) are the primary outcomes in AD and IBS-D, respectively. Analysis will be undertaken separately in each substudy, and then an overall analysis combining multiple subgroups will be performed to comprehensively investigate the effect of HXZQ. Discussion. This study will provide high-quality efficacy evidence of HXZQ for AD and IBS-D patients and give an example of postmarketing evaluation for CM products under the pattern dominating different disease research model. The study is registered with ChiCTR1900026700 and ChiCTR1900026837.
Corneal Allografts: Factors for and against Acceptance
Authors: Sakowska Justyna , Glasner Paulina , Zieliński Maciej , Trzonkowski Piotr , Glasner Leopold
Published: October 2021

Cornea is one of the most commonly transplanted tissues worldwide. However, it is usually omitted in the field of transplantology. Transplantation of the cornea is performed to treat many ocular diseases. It restores eyesight significantly improving the quality of life. Advancements in banking of explanted corneas and progressive surgical techniques increased availability and outcomes of transplantation. Despite the vast growth in the field of transplantation laboratory testing, standards for corneal transplantation still do not include HLA typing or alloantibody detection. This standard practice is based on immune privilege dogma that accounts for high success rates of corneal transplantation. However, the increasing need for retransplantation in high-risk patients with markedly higher risk of rejection causes ophthalmology transplantation centers to reevaluate their standard algorithms. In this review we discuss immune privilege mechanisms influencing the allograft acceptance and factors disrupting the natural immunosuppressive environment of the eye. Current developments in testing and immunosuppressive treatments (including cell therapies), when applied in corneal transplantation, may give very good results, decrease the possibility of rejection, and reduce the need for retransplantation, which is fairly frequent nowadays.
Analysis of Mental State of Patients after Drug Addiction and Withdrawal Guided by PETCT Image Based on Optimized Image Fusion Algorithm
Authors: Pang Yaowen , Peng Xiang
Published: October 2021

Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) studies have shown that drug-dependent patients are activated in different addictive brain areas under the stimulation of relevant environmental cues, which in turn leads to craving and relapse. This study uses magnetic resonance spectroscopy to measure brain temperature to explore the brain temperature changes in different addictive brain regions of heroin and methamphetamine addicts in a short-term withdrawal state and to explore whether the quantitative index of brain temperature change can be used as a diagnostic drug Methods. The subjects were scanned by resting-state MRI spectroscopy first and then subjected to MRI spectroscopy scanning under visual stimulation. The subjects were required to watch the heroin/meth-related clue pictures carefully during visual stimulation. The measured chemical shift value of N-acetyl-aspartic acid (NAA) is substituted into the brain temperature calculation formula T = 37 + 100 to obtain the brain temperature before and after visual stimulation. In addition, the anxiety and depression states of heroin and methamphetamine-dependent patients were evaluated. Results. There was no statistically significant change in the brain temperature of the prefrontal cortex before and after visual stimulation in heroin and methamphetamine-dependent subjects; compared with the normal group, there was no change in prefrontal cortex brain temperature before and after visual stimulation in heroin and methamphetamine-dependent subjects. Statistical Significance. The changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients were not statistically significant; compared with the normal group, there was no statistically significant difference in the changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients. Conclusion. This study initially found that the visual cues related to heroin and methamphetamine were not enough to cause significant changes in the brain temperature of the prefrontal cortex.