bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics analysis and vivo experiment of Artemisia argyi essential oil for the treatment of pressure ulcer by modulating Wnt/β-catenin pathway
Authors: Lu shuting , Xie xiangyu , Ou weiwei , Huang ling , Tang lulu 
Published: April 2022

Abstract
Background
Pressure ulcer (PU) is a complex inflammatory disease caused by a variety of factors, which seriously affect the quality of life of patients and are an urgent challenge for clinical medical and nursing care. Artemisia argyi essential oil (AAEO) possesses a wide range of pharmacological properties in antibacterial, antioxidation, and anti-inflammation. To observe the effect of AAEO via modulating Wnt/β-catenin signaling pathway in accelerating the PU wound healing in rats.
Materials and methods
Bioinformatics methods were used for differential analysis of pressure ulcer genes. Differentially expressed genes (DEGs), Gene Ontology (GO) enrichment analysis, and protein-protein interaction networks were established to find the potential mechanism of PU. Sprague-Dawley rats (n = 10) were randomly divided into Control group, Model group, and AAEO group. Rats in the AAEO groups with PU were treated with AAEO topical daily for 10 days. To investigate how AAEO treats pressure ulcers, researchers used HE staining, Masson's staining, quantitative real-time PCR, and Western blotting analysis.
Results
A total of 26 upregulated and 69 downregulated genes were identified through intersected genes of Wnt/β-catenin pathway with GSE137897. GO analysis revealed that main items involved in inflammation response with the differentially expressed genes. Six hub genes with high degrees of connectivity were picked out, namely WNT3A, GSK3B, FZD1, BMP4, AXIN2, and SOX9 in the PPI network. In addition, rats experiment found that AAEO promotes wound healing by inhibiting apoptosis and Wnt/β-catenin signaling pathway. The INOS and IL-16 levels showed that AAEO significantly reduces inflammation in PU tissues. The Bax, Bcl-2, and Caspase-9 levels showed that AAEO inhibits apoptosis. We also observed that AAEO increase the expression of gsk3b, a downstream protein of the pathway, leading to the inhibition of β-catenin expression levels in vivo.
Conclusions
The study indicated that AAEO accelerates PU wound healing via mediating Wnt/β-catenin pathway.
VEGF to CITED2 Ratio Predicts the Collateral Circulation of Acute Ischemic Stroke
Authors: Lu Minyi , Liu Yuben , Xian Zhiqiang , Yu Xiaoyao , Chen Jian , Tan Sheng , Zhang Peidong , Guo Yang 
Published: April 2022

Abstract
Background: Evaluating the collateral circulation of acute ischemic stroke (AIS) mainly depends on the imaging examination. At present, there is no effective and sensitive biomarker for collateral circulation. Thus, the research objective was to evaluate the predicting role of the vascular endothelial growth factor to CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 Ratio (VEGF/CITED2) from peripheral blood mononuclear cells in the collateral circulation of AIS.Methods: A total of 67 patients with AIS were included in the study. We classified patients into two groups (the good collateral group and the poor collateral group) by DWI-ASPECTS score. The western blot was applied to test the protein expression of vascular endothelial growth factor (VEGF) and CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 (CITED2). Then, we calculated the VEGF/CITED2 and collected other clinical data. Binary logistic regression analysis between collateral circulation and clinical data was performed. Finally, Receiver operating characteristic (ROC) curve analysis was used to explore the predictive value of VEGF/CITED2.Results: There was a statistically significant difference in the white blood cell (WBC) count (P=0.036), neutrophil count (P=0.035), fibrinogen (Fib, P=0.038), homocysteine (Hcy, P=0.047), and VEGF/CITED2 (P=0.017) between the good collateral group and the poor collateral group. Moreover, WBC count (OR 0.77, 95%CI 0.63-0.95, P=0.016), neutrophil count (OR 0.78, 95%CI 0.63-0.95, P=0.016), NLR (OR 0.83, 95%CI 0.68-1.02, P=0.075), Hcy (OR 0.87, 95%CI 0.75-1.00, P=0.054), and Fib (OR 0.59, 95%CI 0.34-1.02, P=0.059) were the risk factors, and VEGF/CITED2 (OR 165.79, 95%CI 7.25-3791.54, P=0.001) was an independent protective factor. The ROC analyses showed an area under the ROC curve (AUC) of the VEGF/CITED2 was 0.861 (95%CI 0.761-0.961). The optimal cutoff value of 1.013 for VEGF/CITED2 had a sensitivity of 89.1% and a specificity of 85.7%.Conclusions: In patients with AIS, the VEGF/CITED2 was related to the establishment of collateral circulation. The VEGF/CITED2 is a potentially valuable biomarker for predicting collateral circulation.Trial registration: Clinical Trials. gov, NCT05345366, Registered on April 19, 2022, retrospectively registered.
Advanced simulations and screening to design a 3C protease inhibitor against the drug resistant human norovirus-induced gastroenteritis
Authors: Behmard Esmaeil , Barzegari Ebrahim , Farjadfar Akbar , Kouhpayeh Amin , Najafipour Sohrab 
Published: April 2022

Abstract
Human norovirus (HuNoV) causes acute viral gastroenteritis in all age groups, and dehydration and severe diarrhea in the elderly. The World Health Organization reports ~ 1.45 million deaths from acute gastroenteritis annually in the world. Rupintrivir, an inhibitory medicine against the human rhinovirus C3 protease, has been reported to inhibit HuNoV 3C protease. However, several HuNoV 3C protease mutations have been revealed to reduce the susceptibility of HuNoV to rupintrivir. The structural details behind rupintrivir-resistance of these single-point mutations (A105V and I109V) are not still clear. Hence, in this study, a combination of computational techniques were used to determine the rupintrivir-resistance mechanism and to propose an inhibitor against wild-type and mutant HuNoV 3C protease through structure-based virtual screening. Dynamic structural results indicated the unstable binding of rupintrivir at the cleft binding site of the wild-type and mutant 3C proteases, leading to its detachment. Our findings presented that the domain II of the HuNoV 3C protease had a critical role in binding of inhibitory molecules. Binding energy computations, steered molecular dynamics and umbrella sampling simulations confirmed that amentoflavone, the novel suggested inhibitor, strongly binds to the cleft site of all protease models and has a good structural stability in the complex system along the molecular dynamic simulations. Our in silico study proposed the selected compound as a potential inhibitor against the HuNoV 3C protease. However, additional experimental and clinical studies are required to corroborate the therapeutic efficacy of the compound.
Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies Emergence of Slowly Growing Drug-Tolerant Cancer Cells
Authors: Celeste Frank , Powers Scott 
Published: April 2022

Abstract
Drug resistance continues to be a major obstacle to curing cancer. Resistance can evolve from a subpopulation of cancer cells that initially survive drug treatment and then gradually form a pool of slowly growing drug-tolerant cells. Several studies have pinpointed activation of a specific bypass pathway that appears to provide the critical therapeutic target for preventing drug tolerance. Here we take a systems-biology approach using proteomics and genomics to examine the development of drug tolerance to EGFR inhibitors in EGFR-mutant lung adenocarcinoma cells and BRAF inhibitors in BRAF-mutant melanoma cells. We found that there are numerous alternative mitogenic pathways that become activated in both cases, including YAP, STAT3, IGFR1, and phospholipase C (PLC)/protein kinase C (PKC) pathways. Our results suggest that an effective therapeutic strategy to prevent drug tolerance will need to take multiple alternative mitogenic pathways into account rather than focusing on one specific pathway.
Odor Identification Quantitatively by Odorant Receptor Vectors
Authors: Kawai Kosei , Morishita Shin 
Published: April 2022

Abstract
Background: Odors are perceived by individuals through sensation, memory, experience, etc., and mainly subjective and qualitative evaluation has been performed until now. On the other hand, since Buck et al. succeeded in cloning the odorant receptor in 1991, researchers have shown interest in olfaction system, and molecular biology researches on olfaction system have begun actively. However, no objective evaluation has been made on the identification or similarity of odors. As for the odorant sensors, an odor is identified by using quartz oscillators or semiconductors and measuring a change in characteristics caused by odor molecules adhering to the sensor. In this study, we attempted to quantitatively express the direct association between odorant receptors and odor molecules at each concentration. The degree of similarity evaluated by taking inner product of the odorant receptor vectors was verified by comparing with the results by sensory evaluation tests published in past literatures in the form of correlation coefficient. A multi-layered artificial neural network whose input was the elements of prescribed odorant receptor vector was also introduced to identify odorant molecules in the output layer.Results: The inner product of proposed odorant receptor vector might evaluate the degree of similarity quantitatively among various odorants. Further, it might be possible to identify odorant molecules by the artificial neural network using EC50 of receptors to various odorants.Conclusions: In this paper, we proposed a vector consisting of the EC50 of odorant receptors and compared the inner product of the vector with the results of sensory evaluation tests based on the responses of odorant receptors to odorant substances at various concentrations. It was shown that not only the correlation between each odorant substance but also the correlation between the inner product of the odorant substance receptor vector and the results of the sensory evaluation test can be quantitatively evaluated. It was also shown that the EC50 of each odorant receptor can be placed in the input layer of an artificial neural network, and that an artificial neural network with odor molecules as the output layer can discriminate odors.
Guidance and counselling services in secondary schools in eastern Gojjam Administrative Zone: a mixed design evaluation of priority needs, service barriers and facilitators
Authors: Bitew Tesera , Adam Temesgen 
Published: April 2022

Abstract
Background: Problem areas that need urgent guidance and counselling intervention were not prioritized and barriers to fulfil these priority needs were not investigated in secondary schools of Ethiopia. Objective: This study aims to investigate students’ priority guidance and counselling needs and barriers and opportunities of meeting such guidance and counselling needs. Methods: A mixed methods design was used. A cross-sectional quantitative survey was used to investigate: (1) priority areas of guidance and counselling needs of the students and, (2) associates of these priority areas of counselling needs using linear regression. We conducted in-depth interview and FGD with school counsellors and school principals to investigate: (1) barriers and opportunities of providing guidance and counselling services. Thematic analysis was used to analyse the qualitative data. Results: Student participants were most worried about their education and vocation than their emotional, behavioural and social problems. Increment in depressive symptoms (β=0.266, p<001) and anxiety (β=0.154, p<001) scores were positively associated with increased score in guidance and counselling needs. Themes were identified as challenges related to meet prioritized student guidance and counselling needs were: (1) administrative challenges (2) counsellor competencies and motivation (3) resource constraints (4) beliefs (staff perceptions, cultural beliefs). Conclusion : Priority areas of guidance and counselling have been identified and barriers to meet such needs have been explored.
Collective Adaptability in a Replication Network of Minimal Nucleobase Sequences
Authors: Vela-Gallego Sonia , Pardo-Botero Zulay , Moya Cristian , Escosura Andrés de la 
Published: April 2022

Abstract
A major challenge for understanding the origins of life is to explore how replication networks can engage in an evolutionary process. Herein, we shed light on this problem by implementing a network constituted by two different types of extremely simple biological components: the amino acid cysteine and the canonical nucleobases adenine and thymine, connected through amide bonds to the cysteine amino group and oxidation of its thiol into three possible disulfides. Supramolecular and kinetic analyses revealed that both self- and mutual interactions between such dinucleobase compounds drive their assembly and replication pathways. Those pathways involving sequence complementarity led to enhanced replication rates, suggesting a potential bias for selection. The interplay of synergistic dynamics and competition between replicators was then simulated, under conditions that are not easily accessible with experiments, in an open reactor parametrized and constrained with the unprecedentedly complete experimental kinetic data obtained for our replicative network. Interestingly, the simulations show bistability, as a selective amplification of different species depending on the initial mixture composition. Overall, this network configuration can favor a collective adaptability to changes in the availability of feedstock molecules, with disulfide exchange reactions serving as 'wires' that connect the different individual auto- and cross-catalytic pathways.
Hydrogen occupation and hydrogen-induced volume expansion in Fe0.9Ni0.1Dxat highP-Tconditions
Authors: Shito Chikara , Kagi Hiroyuki , Kakizawa Sho , Aoki Katsutoshi , Komatsu Kazuki , Iizuka-Oku Riko , Abe Jun , Saitoh Hirioyuki , Sano-Furukawa Asami , Hattori Takanori 
Published: April 2022

AbstractThe density of the Earth’s core is several percent lower than that of iron-nickel alloy under conditions of pressure and temperature equivalent to the Earth’s core. Hydrogen is one of the most promising constituents accounting for the density deficit, but hydrogen occupation sites and density decrease of iron-nickel alloy caused by hydrogenation have never been investigated. In this study, the phase relation and crystal structure of Fe0.9Ni0.1Hx(Dx) at high pressures and temperatures up to 12 GPa and 1000 K were clarified by in situ X-ray diffraction and neutron diffraction measurements. Under the P-T conditions of the present study, no deuterium atoms occupied tetragonal (T) sites of face-centered cubic (fcc) Fe0.9Ni0.1Dx, although the T-site occupation was previously reported for fcc FeHx(Dx). The deuterium-induced volume expansion per deuterium vD was determined to be 2.45(4) and 3.31(6) Å3 for fcc and hcp Fe0.9Ni0.1Dx, respectively. These vD values are significantly larger than the corresponding values for FeDx. The vD value for fcc Fe0.9Ni0.1Dx slightly increases with increasing temperature. This study suggests that only 10% of nickel in iron drastically changes the behaviors of hydrogen in metal. Assuming that vD is constant regardless of pressure, the maximum hydrogen content in the Earth’s inner core is estimated to be one to two times the amount of hydrogen in the oceans.
Solanum pubescens Wild Fruits Essential Oil - A Golden Casket for its
Antimicrobial and Anti-inflammatory Mediated Wound Healing Efficacy
in Vertebrate Model Mus musculus
Authors: Rahman Haseebur , Rahman Nazneen , Haris Mir , Pradhoshini Kumara Perumal , Shareef Mohamed Ahadu , Musthafa Mohamed Saiyad , Rajagopal Rajakrishnan , Alfarhan Ahmed , Thirupathi Anand , Chang Soon Woong , Balasubramani Ravindran 
Published: April 2022

Background:
Solanum pubescens Willd, growing wild in the hills of Rayadurg jurisdiction of Southwestern Andhra Pradesh, has gained significant attention among researchers for its diverse folkloric applications, existence of novel phytochemicals and leaf extracts which hold great medicinal promises. To date, the S. pubescens fruit’s essential oil (SPO) has never been investigated.

Methods:
The current research has been focused to evaluate the chemical composition of S. pubescens fruit essential oil through Gas Chromatography–Mass Spectrometry (GC-MS), followed by the investigation of antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities in appropriate models to uncover its biological potentials. Extraction of (Solanopuboil/SPO) from the fresh unripe fruits of Solanum pubescens was carried out in Buchner funnel and Whatman no.10 filter paper and concentrated at 40oC using a rotary evaporator. The metabolic proﬁling of SPO was analysed by GC–MS technique. The MIC, MBC, activity index, and total antimicrobial activity of SPO were evaluated using standard procedures. Anti-inflammatory activity of SPO was screened using Carrageenan induced paw oedema and Cotton pellet-induced granuloma. Tail immersion test, Acetic acid writhing response and Formalin paw lick test was performed in rats in order to examine the analgesic activity of SPO. Wound healing activity of SPO was investigated by performing the incision wound model, Excision wound model and Dead space wound model in rats.

Results:
The SPO displayed a constant degree of antimicrobial activity against B. cereus, B. subtilis, E. coli, A. niger, A. fumigatus and C. albicans with significant anti-inﬂammatory and analgesic activities. Also, a prominent wound healing potential of it was observed in
excision, incision and dead space wound models with considerable elevation in granulation tissue hydroxyproline, hexuronic acid and hexosamine content in association with remarkable regulation of anti-inflammatory and antioxidant markers i.e., Lipid peroxidase (LPO), Nitric Oxide (NO), Superoxide dismutase (SOD), Glutathione (GSH), Catalase (CAT), Glutathione Peroxidase (GPx).

Conclusion:
These findings strongly validate the therapeutic potential of S. pubescens fruit essential oil in antimicrobial and anti-inflammatory mediated wound healing
and suggests its promising application as valuable and novel indigenous leads in the food and pharmaceutical industries. To the best of our knowledge, this is the first-ever investigatory report on the systematic phytochemical and therapeutic examination of S. pubescens fruit essential oil.
Binding Sites of Anticancer Drugs on Human Serum Albumin (HSA): A
Review
Authors: Molaei Pejman , Mahaki Hanie , Manoochehri Hamed , Tanzadehpanah Hamid 
Published: April 2022

Background:
To recognize the action of pharmacologically approved anticancer drugs in
biological systems, information regarding its pharmacokinetics, such as its transport within the
plasma and delivery to its target site, is essential. In this study, we have tried to collect and present
complete information about how these drugs bind to human serum albumin (HSA) protein. HSA
functions as the main transport protein for an enormous variety of ligands in circulation and plays a
vital role in the efficacy, metabolism, distribution, and elimination of these agents.

Method:
Therefore, this study includes information about the quenching constant, the binding
constant obtained from Stern-Volmer and Hill equations, and molecular docking.

Results:
Molecular docking was carried out to detect the binding models of HSA–anticancer drugs
and the binding site of the drugs in HSA, which further revealed the contribution of amino acid
residues of HSA in the drug complex binding.

Conclusion:
This review study showed that site I of the protein located in domain II can be
considered the most critical binding site for anticancer drugs.
Antioxidation Abilities of Sesquiterpenoids from Curcuma aromatica
in vitro
Authors: Zhang Mi , Dai Weifeng , Wang Dong , Chen Chonglian 
Published: April 2022

Aim and Objectives:
In our previous study, 21 sesquiterpenoids with different skeleton
types were isolated from the radix of Curcuma aromatica Salisb., a traditional Chinese medicine
used for treating depression and qi and blood stasis. C. aromatica enhanced PC12 cell viability upon
damage by H2O2. The aim of this study was to elucidate the antioxidation capability of these
sesquiterpenoids using a model of H2O2-induced PC12 cells and analyze the correlation between
their structure and bio-activity.

Materials and Methods:
PC12 cells were simultaneously treated with 400 μM H2O2 and sesquiterpenoid
compounds or vitamin E (used as a positive control) for 24 h. The activities of GSH-Px,
LDH, CAT, and SOD were detected by ELISA kits. The reactive oxygen species (ROS) level in
the cells was determined by the fluorescence probe DCFH-DA. [Ca2+]i was detected based on the
Fluo 2-AM fluorescence labeling assay. The structures of sesquiterpenoids were featured with 41
selected molecular descriptors, and the relationship between active parameters and structural features
was determined by the partial least squares (PLS) analysis.

Results:
All twenty-one sesquiterpenoids from the radix of C. aromatica increased the activities of
GSH-Px, CAT, and SOD, and decreased the LDH leakage, and levels of ROS level and [Ca2+]i to
different degrees. Some relationships were observed between the molecular descriptors featured by
the sesquiterpenoids and GSH-Px, CAT, SOD, LDH, ROS, and [Ca2+]i by PLS analysis.

Conclusions:
Twenty-one sesquiterpenoids showed different antioxidation abilities as measured by
a model of H2O2-induced PC12 cells. Five molecular descriptors were positively correlated with
GSH-Px, CAT, SOD, and were negatively correlated with LDH and [Ca2+].
Silk Derived Fe/N-Doping Porous Carbon Nanosheets for Chloramphenicol Electrochemical Detection
Authors: Chang Wenzhuo , Zhu Yongxi , Ma Yongjun , Zheng Zhixiang , Wang Chunming 
Published: April 2022

Background:
The use of modified electrochemical sensors is essential for the detection of antibiotic
drug abuse. The main objective of this article is to develop a silk-derived carbon material for the modification
of pyrolytic graphite electrodes (PGE) for the sensitive detection of chloramphenicol (CAP).

Methods:
We proposed a pyrolysis synthesis of porous carbon nanosheets (Fe-Silk PNC) using silk as a
precursor. Properties of carbon nanosheets had been improved by the Fe-Nx atoms doping, which was
attributed to the β-sheet structures and amino-group-rich chemical structures of silk fibroin, and this material
has been used to modify the pyrolytic graphite electrode (PGE) for the electrochemical determination
of CAP. Scanning electron microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR)
were used to determine the morphology and properties of Fe-Silk PNC surface. In the electrochemical
determination, cyclic voltammetry (CV) showed a superior current response while bare electrode performed
an inferior result. In addition, different scan rate, pH, accumulation time and accumulation potential
were carefully optimized, which proved that this material is appropriate for CAP detection. Finally,
differential pulse voltammetry (DPV) method was used for quantitative measurements.

Result:
In this study, DPV determination of CAP showed the linear relationship with increasing concentration
ranged from 1 to 200 μM, and the low detection limit was 0.57 μM (S/N = 3). SEM and FT-IR
results further demonstrated the N-doped carbon nanomaterials were successfully synthesized. With excellent
sensing performance achieved, the practicability of the sensor has been evaluated to detect CAP in
chicken, shrimps and fish.

Conclusion:
In summary, a silk derived biomass porous carbon nanomaterial Fe-Silk PNC was simply
fabricated and used as a novel electrode material. This kind of novel Fe-Silk PNC modified electrode
exhibited excellent sensitivity, anti-interference ability, repeatability, wide linear rang, and was successfully
used for determination of CAP in real samples. Therefore, the biomass derived nanomaterial is expected
to be used in new sensing materials.