bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Dynamics Simulations for the Co‐Adsorption of Binary Electrolytes at the Interface of Montmorillonite and Aqueous Solutions
Authors: Yang Sen , Li Xiong , Jia Zengqiang , Li Qinyi , Yang Gang 
Published: October 2018

Core Ideas
Adsorption behaviors for different binary electrolytes at clay surfaces are presented.
Major rather than minor adsorption modes are always more affected by co‐ions.
Degrees of altering the adsorption numbers and strengths rely strongly on co‐ions.
When alone and co‐existent, adsorption modes of metal ions remain consistent.
Each binary system has peculiarities during adsorption as discussed in the text.
Multiple electrolytes exist in almost all soil systems, and in this work, molecular dynamics was employed to tackle the adsorption of different binary electrolytes (PbCl2/CdCl2, PbCl2/NaCl, PbCl2/CsCl and KCl/CsCl) at montmorillonite–water interfaces, providing insights to the mechanisms of co‐adsorption and the impacts of co‐ions. In all cases, the adsorption modes of metal ions are not altered by co‐ions, while co‐ions exhibit the pronounced impacts on the adsorption numbers and strengths, and the main rather than minor adsorption modes are always more affected. In addition to these general principles, each type of binary systems has the peculiarities: Coexistence promotes Pb2+ adsorption while inhibits Cd2+ adsorption; Coexistence inhibits Pb2+ adsorption while promotes Cs+ adsorption; Coexistence promotes each other's adsorption of Pb2+ and Na+; Coexistence promotes Cs+ adsorption while inhibits K+ adsorption; All co‐ions improve Pb2+ stabilities, while coexistence of Pb2+ reduces Cd2+ stabilities and improves Cs+ and Na+ stabilities; Competition for inner‐sphere binding sites is not beneficial for the stabilities of both K+ and Cs+. Heavy and radioactive metal ions are a focus of this study and results are also helpful to manage their pollutions.
From Levinthal’s Paradox to the Effects of Cell Environmental Perturbation on Protein Folding
Authors: Zeng Juan , Huang Zunnan 
Published: October 2018

Background:The rapidly increasing number of known protein sequences calls for more efficient methods to predict the Three-Dimensional (3D) structures of proteins, thus providing basic knowledge for rational drug design. Understanding the folding mechanism of proteins is valuable for predicting their 3D structures and for designing proteins with new functions and medicinal applications. Levinthal’s paradox is that although the astronomical number of conformations possible even for proteins as small as 100 residues cannot be fully sampled, proteins in nature normally fold into the native state within timescales ranging from microseconds to hours. These conflicting results reveal that there are factors in organisms that can assist in protein folding.Methods:In this paper, we selected a crowded cell-like environment and temperature, and the top three Posttranslational Modifications (PTMs) as examples to show that Levinthal’s paradox does not reflect the folding mechanism of proteins. We then revealed the effects of these factors on protein folding.Results:The results summarized in this review indicate that a crowded cell-like environment, temperature, and the top three PTMs reshape the Free Energy Landscapes (FELs) of proteins, thereby regulating the folding process. The balance between entropy and enthalpy is the key to understanding the effect of the crowded cell-like environment and PTMs on protein folding. In addition, the stability/flexibility of proteins is regulated by temperature.Conclusion:This paper concludes that the cellular environment could directly intervene in protein folding. The long-term interactions of the cellular environment and sequence evolution may enable proteins to fold efficiently. Therefore, to correctly understand the folding mechanism of proteins, the effect of the cellular environment on protein folding should be considered.
Benzimidazole Derivatives as Potential Antimicrobial and Antiulcer Agents: A Mini Review
Authors: Ganie Ali Mohd , Dar Ayaz Mahmood , Khan Fairooz Ahmad , Dar Bashir Ahmad 
Published: October 2018

:Here in we report the number of strategies for the synthesis of differently substituted benzimidazole derivatives. The protocols involved in the syntheses of these derivatives were one-pot or multi-component. The characterization studies of these derivatives were carried by using different spectroscopic techniques (1H NMR, 13C NMR and MS) and elemental analyses. The biological screening studies revealed that these benzimidazole derivatives show potential antibacterial as well as antifungal behavior. These benzimidazole derivatives not only depicted potential antiulcer properties but also showed moderate to good anticancer/cytotoxic behavior against different cancer cell lines.
Development of New Potential Anticancer Metal Complexes Derived from 2-Hydrazinobenzothiazole
Authors: Elsayed Shadia A. , Saad Entsar A. , Mostafa Sahar I. 
Published: October 2018

Background:Due to the side effects of clinically approved anticancer drugs there is a great need to explore and develop new metal-based anticancer drug molecules of high efficiency with less or no side effects.Objective:To synthesize new metal complexes of 2-hydrazinobenzothiazole (hbt) and to investigate their potential anticancer characteristics.Methods:New five complexes; [VO(hbt)2SO4].4H2O (1), [Ru(hbt)2Cl3(H2O)] (2), [M(hbt)2Cl2] [M(II) = Pd (3), Pt (4)] and [Ag(hbt)2].NO3 (5) were prepared and their structure was investigated by means of FTIR, 1H NMR, ESI-MS and UV-Vis spectra, elemental and thermal analysis, magnetic and molar conductance measurements. The ligand and its complexes were examined as anticancer agents against Ehrlich ascites carcinoma (EAC) and human cancer cells (hepatocellular carcinoma Hep-G2, mammary gland breast cancer MCF-7 and colorectal carcinoma HCT-116). This feature is further supported by the DNAmetal complexes binding ability. In addition, anti-oxidation activity of the complexes was investigated.Results:Complex (5) shows the highest anticancer activity with IC50 of 5.15, 9.9, 13.1 and 17.7 µg/mL for EAC, HePG-2, MCF-7 and HCT-116, respectively. Complexes (2) and (3) show promising cytotoxicity against EAC and HePG-2 cells with IC50 5.49 and 16.2 µg/mL, respectively. While, complexes (1) and (4) show optimistic cytotoxicity against EAC with IC50 of 9.63 and 11.25 µg/mL, respectively. The order of DNA binding ability of the complexes is (5) > (3) > (2) > (1) > (4). Among the five complexes, complex (5) shows the best anti-oxidation activity.Conclusion:Complex (5) showed the highest DNA binding ability, anti-oxidation and anticancer activities.
The Superior Antitumor Effect of Self-Assembled Paclitaxel Nanofilaments for Lung Cancer Cells
Authors: He Mengyu , Zhu Jiali , Yu Na , Kong Hui , Zeng Xiaoning , Xie Weiping , Xu Huae 
Published: October 2018

Objectives: Paclitaxel (Ptx) has been regarded as one of the most effective chemotherapeutic
drugs for lung cancers. Increasing studies focused on the nano-delivery system of Ptx due to its poor
solubility and hypersensitivity. The aim of the recent study was to investigate the antitumor effects of
self-assembled Ptx nano-filaments for lung cancer cells.
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Methods: In the present study, we designed and synthesized novel Ptx-loaded nano-filaments through
conjugation of Ptx and succinic acid (SA) (Ptx-SA, P-NFs). Non-small cell lung cancer (NSCLC) A549
and H460 cells were used for detecting the antitumor effects of P-NFs, including cytotoxicity, apoptosis,
and migration. Western blotting was performed for analyzing mechanism.

Results:
P-NFs nano-filaments exerted superior antitumor effects against NSCLC cells compared with
free Ptx using cytotoxicity tests. Furthermore, P-NFs nano-filaments were much more effective in inducing
NSCLC cells apoptosis and inhibiting A549 cells migration than free Ptx. To elucidate the underlying
mechanisms, the expression of apoptotic and endoplasmic reticulum (ER) stress proteins was
detected. The results indicated that P-NFs nano-filaments enhanced the expression of bax/bcl-2, protein
kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1&#945; (IRE1&#945;), phospho-
c-Jun N-terminal kinase (p-JNK), and C/EPB homologous protein (CHOP), which suggested that
the strong antitumor effect of P-NFs nano-filaments may be partially attributed to the activation ER
stress.

The current work demonstrated that P-NFs nano-filaments showed superior cytotoxicity of
lung cancer cells, highlighting a novel profile of nano-filaments delivery systems as potential strategies
for facilitating the therapeutic efficacy of Ptx in lung cancer treatment.
Ursolic Acid in Cancer Treatment and Metastatic Chemoprevention: From Synthesized Derivatives to Nanoformulations in Preclinical Studies
Authors: Zou Junjie , Lin Juanfang , Li Chao , Zhao Ruirui , Fan Lulu , Yu Jesse , Shao Jingwei 
Published: October 2018

Background:Cancer metastasis has emerged as a major public health threat that causes majority of cancer fatalities. Traditional chemotherapeutics have been effective in the past but suffer from low therapeutic efficiency and harmful side-effects. Recently, it has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anti-cancer properties. More importantly, UA has the features of low toxicity, liver protection and the potential of anti-cancer metastasis.Objective:This article aimed at reviewing the great potential of UA used as a candidate drug in the field of cancer therapy relating to suppression of tumor initiation, progression and metastasis.Methods:Selective searches were conducted in Pubmed, Google Scholar and Web of Science using the keywords and subheadings from database inception to December 2017. Systemic reviews are summarized here.Results:UA has exhibited chemopreventive and therapeutic effects of cancer mainly through inducing apoptosis, inhibiting cell proliferation, preventing tumor angiogenesis and metastatic. UA nanoformulations could enhance the solubility and bioavailability of UA as well as exhibit better inhibitory effect on tumor growth and metastasis.Conclusion:The information presented in this article can provide useful references for further studies on making UA a promising anti-cancer drug, especially as a prophylactic metastatic agent for clinical applications.
Targeting Upstream Kinases of STAT3 in Human Medulloblastoma Cells
Authors: Wei Jia , Ma Ling , Li Chenglong , Pierson Christopher R. , Finlay Jonathan L. , Lin Jiayuh 
Published: October 2018

Background:Medulloblastoma is the most common malignant brain tumor in children. Despite improvement in overall survival rate, it still lacks an effective targeted treatment strategy. The Janus family of cytoplasmic tyrosine kinases (JAKs) and Src kinases, upstream protein kinases of signal transducer and activator of transcription 3 (STAT3), play important roles in medulloblastoma pathogenesis and therefore represent potential therapeutic targets.Methods:In this report, we examined the inhibitory efficacy of the JAK1/2 inhibitor, ruxolitinib, the JAK3 inhibitor, tofacitinib and two Src inhibitors, KX2-391 and dasatinib.Results:These small molecule drugs significantly reduce cell viability and inhibit cell migration and colony formation in human medulloblastoma cells in vitro. Src inhibitors have more potent efficacy than JAK inhibitors in inhibiting medulloblastoma cell migration ability. The Src inhibitors can inhibit both phosphorylation of STAT3 and Src while JAK inhibitors reduce JAK/STAT3 phosphorylation. We also investigated the combined effect of the Src inhibitor, dasatinib with cisplatin. The results show that dasatinib exerts synergistic effects with cisplatin in human medulloblastoma cells through the inhibition of STAT3 and Src.Conclusion:Our results suggest that the small molecule inhibitors of STAT3 upstream kinases, ruxolitinib, tofacitinib, KX2-391, and dasatinib could be novel and attractive candidate drugs for the treatment of human medulloblastoma.
Osimertinib Quantitative and Gene Variation Analyses in Cerebrospinal Fluid and Plasma of a Non-small Cell Lung Cancer Patient with Leptomeningeal Metastases
Authors: Song Yuanyuan , Liu Peng , Huang Yu , Guan Yanfang , Han Xiaohong , Shi Yuankai 
Published: October 2018

Background:
Leptomeningeal metastases (LM) are much more frequent in patients of
non-small lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.
Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI)
shows promising efficacy for LM.

Objective:
The aim of this study was to analyze the concentration of osimertinib and gene variation
of circulating tumor DNA (ctDNA) in human plasma and cerebrospinal fluid (CSF). Furthermore,
we explored whether ctDNA in CSF might be used as a biomarker to predict and monitor therapeutic
responses.

Methods:
The dynamic paired CSF and blood samples were collected from the NSCLC patient with
LM acquired EGFR-TKI resistance. A method based on ultra-high performance liquid chromatography-
tandem mass spectrometry (UPLC-MS/MS) was developed and validated for detecting
osimertinib in CSF and plasma samples. Gene variations of ctDNA were tested by next-generation
sequencing with a panel of 1021 genes.

Results:
The concentrations of osimertinib in CSF were significantly lower than that in plasma
(penetration rate was 1.47%). Mutations included mTOR, EGFR, CHECK1, ABCC11, and TP53
were explored in ctDNA from plasma and CSF samples. The detected mutation rate of CSF samples
was higher than that of plasma samples (50% vs. 25%). Our data further revealed that the variations
allele frequency (VAF) and molecular tumor burden index (mTBI) of ctDNA derived from CSF exhibited
the negative correlation with efficacy of treatment.

Conclusion:
ctDNA from CSF might be a useful biomarker for monitoring the efficacy of treatment
and an effective complement to nuclear magnetic resonance imaging (MRI) for LM.
Synthesis of New Thiosemicarbazones and Semicarbazones Containing the 1,2,3-1H-triazole-isatin Scaffold: Trypanocidal, Cytotoxicity, Electrochemical Assays, and Molecular Docking
Authors: Silva Bianca N.M. , Sales Junior Policarpo A. , Romanha Alvaro J. , Murta Silvane M.F. , Lima Camilo H.S. , Albuquerque Magaly G. , D'Elia Eliane , Rodrigues José G.A. , Ferreira Vitor F. , Silva Fernando C. , Pinto Angelo C. , Silva Bárbara V. 
Published: October 2018

Background:
Chagas disease, also known as American trypanosomiasis, is classified as
one of the 17 most important neglected diseases by the World Health Organization. The only drugs
with proven efficacy against Chagas disease are benznidazole and nifurtimox, however both show
adverse effects, poor clinical efficacy, and development of resistance. For these reasons, the search
for new effective chemical entities is a challenge to research groups and the pharmaceutical industry.

Objective:
Synthesis and evaluation of antitrypanosomal activities of a series of thiosemicarbazones
and semicarbazones containing 1,2,3-1H triazole isatin scaffold.

Method:
5&'-(4-alkyl/aryl)-1H-1,2,3-triazole-isatins were prepared by Huisgen 1,3-dipolar
cycloaddition and the thiosemicarbazones and semicarbazones were obtained by the 1:1 reactions
of the carbonylated derivatives with thiosemicarbazide and semicarbazide hydrochloride,
respectively, in methanol, using conventional reflux or microwave heating. The compounds were
assayed for in vitro trypanocidal activity against Trypanosoma cruzi, the aetiological agent of
Chagas disease. Beyond the thio/semicarbazone derivatives, isatin and triazole synthetic
intermediates were also evaluated for comparison.

Results:
A series of compounds were prepared in good yields. Among the 37 compounds evaluated,
18 were found to be active, in particular thiosemicarbazones containing a non-polar saturated
alkyl chain (IC50 = 24.1, 38.6, and 83.2 &µM; SI = 11.6, 11.8, and 14.0, respectively). To further
elucidate the mechanism of action of these new compounds, the redox behaviour of some active
and inactive derivatives was studied by cyclic voltammetry. Molecular docking studies were also
performed in two validated protein targets of Trypanosoma cruzi, i.e., cruzipain (CRZ) and phosphodiesterase
C (TcrPDEC).

Conclusion:
A class of thio/semicarbazones structurally simple and easily accessible was synthesized.
Compounds containing thiosemicarbazone moieties showed the best results in the series, being
more active than the corresponding semicarbazones. Our results indicated that the activity of
these compounds does not originate from an oxidation-reduction pathway but probably from the
interactions with trypanosomal enzymes.
Methamphetamine Abusers’ Personality Traits and its Relational with Spiritual Well-being and Perceived Social Support
Authors: Jalali Amir , Shabrandi Bistoun , Jalali Rostam , Salari Nader 
Published: October 2018

Background:
Psychoactive substance abuse is a psychosocial disorder that its, emergence,
continuation, and treatment are associated with personality factors, spiritual well-being, and
social support.

Objective:
This study was conducted to investigate the relationship between personality traits with
spiritual well-being and perceived social support in methamphetamine users undergoing treatment in
2016 in the clinics of Kermanshah City, Iran.

Methods:
This cross-sectional study was conducted on a sample of 117 methamphetamine users undergoing
treatment in addiction clinics of Kermanshah City, Iran. The formed study population was
prepared by convenience sampling according to the inclusion-exclusion criteria. Data were collected
using a demographic form, NEO Five-Factor Inventory, Paloutzian and Ellison’s spiritual wellbeing
scale, and perceived social support inventory of Fleming et al. The collected data were analyzed
by parametric and nonparametric tests in SPSS v.23.

Results:
The results showed that 82.2% of participants had a moderate level of agreeableness,
88.1% had moderate neuroticism, 93.2% had moderate extraversion, 87.2% had moderate conscientiousness,
and 92.2% had a moderate level of openness to experience. In addition, 76.9% of participants
had a low level of spiritual well-being and the remaining 23.1% had a moderate spiritual wellness.
The mean spiritual well-being and perceived social support scores of participants were
69.94±10.86 and 33.94±7.55, respectively. The findings showed a significant relationship between
personality traits and spiritual well-being and social support in methamphetamine users (p = 0.05).

Conclusion:
The results indicate that personality traits, perceived social support, and spiritual wellbeing
can be considered as risk factors for methamphetamine abuse.
Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection
Authors: Zamani Sara , Sohrabi Amir , Hosseini Seyed Masoud , Rahnamaye-Farzami Marjan , Akbari Abolfazl 
Published: October 2018

Background:Early diagnosis is an important factor to improve the survival of Invasive Cervical Cancer (ICC) patients. Molecular biomarkers such as micro RNA (miRNA) can be used in the early detection of ICC. The expression of miR-21 and miR-29a are deregulated in many types of human cancers.Objective:The aim of this study was to investigate the differences in miR-21 and miR-29a expression patterns in the Human Papilloma Virus (HPV) infection and various grades of cervical cancer among Iranian women.Methods:Small RNAs were extracted from positive for HPV, cervical cancer and healthy samples from 43, 50 and 46 individuals, respectively. Expression levels of miR-21 and miR-29a were analyzed by SYBR Green real-time RT-PCR using specific primers, and 5s rRNA as the internal reference gene.Results:Results have shown a significant increase in miR-21 and decrease in miR-29 in cancerous samples in comparison with the control groups (P < 0.0001).Conclusion:This study illustrated that miR-21 and miR-29a could be operated as an oncogene and tumor-suppressor in cervical cancer progression. More studies are needed to demonstrate the role of miR-21 and miR-29a as potential biomarkers for the diagnosis of cervical cancer in future investigations.
The Mediating Role of Perceived Social Support Between Physical Activity Habit Strength and Depressive Symptoms in People Seeking to Decrease Their Cardiovascular Risk: Cross-Sectional Study
Authors: Storm Vera , Reinwand Dominique Alexandra , Wienert Julian , Tan Shu-Ling , Lippke Sonia 
Published: October 2018

Background
Regular physical activity treatment has been advocated for the prevention and rehabilitation of patients at risk of cardiovascular diseases and depressive symptoms. How physical activity is related to depressive symptoms is widely discussed.

Objective
The aim of this internet-based study was to investigate the role of perceived social support in the relationship between physical activity habit strength and depressive symptoms.

Methods
In total, 790 participants (mean 50.9 years, SD 12.2, range 20-84 years) who were interested in reducing their cardiovascular risk were recruited in Germany and the Netherlands. Data collection was conducted via an internet-based questionnaire addressing physical activity habit strength, depressive symptoms, and perceived social support. Cross-sectional data analysis was done with SPSS version 24 using the Macro PROCESS version 2 16.3 by Hayes with bootstrapping (10,000 samples), providing 95% CIs.

Results
Physical activity habit strength was negatively related to depressive symptoms (r=–.13, P=.006), but this interrelation disappeared when controlling for perceived social support (beta=–.14, SE 0.09, P=.11). However, there was an indirect relationship between physical activity habit strength and depressive symptoms, which was mediated via perceived social support (beta=–.13; SE 0.04, 95% CI –0.21 to 0.06). The negative relationship between physical activity habit strength and depressive symptoms was fully mediated by perceived social support.

Conclusions
We suggest that physical activity treatment in people interested in reducing their cardiovascular risk should also embed social support to target depressive symptoms. Internet-based interventions and electronic health may provide a good option for doing so.

Trial Registration
ClinicalTrials.gov NCT01909349; https://clinicaltrials.gov/ct2/show/NCT01909349 (Archived by WebCite at http://www.webcitation.org/73Y9RfdiY)