bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of road damage prediction due to overload using HDM-4 method
Authors: Arifin Muhammad Zainul , Prabowo Prabowo , Wicaksono Agus Dwi 
Published: February 2024

The road use load should essentially conform to the plan load as stated in the design guidelines. But in reality, the load received by the road is more than standard, so it has the potential to accelerate road damage. This study aims to predict the increase in the value of the International Roughness Index (IRI) and model the increase in value (IRI) due to overload. The approach method used in the analysis is the prediction of an increase in the IRI value due to excess load. The data collection method is carried out on road sections which include IRI values, vehicle load testing, CBR values and environmental conditions. The location of data collection is carried out on BTS Provincial Road. Surabaya City – Legundi. The analysis method for the prediction of the IRI value is the HDM-4 method, while to model the prediction of the increase in the IRI value is used exponential method with various parameters related to the results. The prediction results show that overload affects the increase in the IRI value. From the initial IRI value of 2.37, if the road is traversed by vehicles with standard loads for 20 years, the IRI value increases to 10.42. While the road traveled by overloaded vehicles within 20 years from an IRI value of 2.37 will increase to 16.88. With overload, the IRI value increases very sharply with the exponential model y=2.3583e0.0982x. While the standard load by generating an exponential model y=2.3825e0.0739x. From the results of the exponential model, load overload resulted in a significant increase in the IRI value with a growth rate of 0.0982. When compared to normal expenses which only experienced a growth rate of 0.0739. The modeling results show that overload will increase the growth of very high IRI values with the exponential model increase graph
Study of the influence of the technical level of railway vehicles on braking characteristics
Authors: Abdullaev Ayaz , Huseynov Ilham , Elyazov Israil , Abdullaev Ramin 
Published: February 2024

In the article, the traction transmission of modern STADLER KISS trains is studied. The study of the effect of the technical level of the traction transmission on the braking characteristics of the train is discussed. The application of an innovative traction reducer is proposed, which allows to increase the result indicator according to the unit consumption of the traction transmission. Taking the reduction of the mass of the proposed thrust reducer as one of the main factors shaping the effect on the braking system, the possibility of reducing the inertia coefficient of the rotating parts and the technical parameters considered in the equation of motion of the train is shown. Taking into account the method of calculating the braking distance, the braking distance in different speed ranges is calculated in a practical example, by evaluating the braking efficiency, the possibility of reducing the braking distance by 5 % and reducing the braking time in proportion is shown. As a result of the experiments carried out by the researchers, it became clear that the technical level of traction transmission, consisting of multi-stage innovative reducers, directly affects the movement of trains. Thus, increasing the value of the coefficient of inertia of the rotating parts should allow accelerating the acceleration and braking times of the trains, passing the flats quickly, reducing the braking distance and saving some fuel resources. By conducting emergency braking tests, experimental values of the train's braking distance and braking time were determined and their compliance with the reported values was confirmed. Taking into account the advantages of the proposed reducer, a comparative description of the graphs of the dependence of braking distance and braking time on speed is given
Nepetin Attenuates Atopic Dermatitis in HaCaT Cells and BALB/c Mice Through MyD88-MKK3/6-Akt Signaling
Authors: Gong Guowei , Ganesan Kumar , Zheng Yuzhong , Xiao Jian , Dong Tina , Tsim Karl 
Published: February 2024

Abstract:
Nepetin is a type of O-methylated flavone (6-hydroxy luteolin) and has been
found in many herbal medicines that exhibit various pharmacological properties, including
anti-inflammatory responses. Here, we aimed to investigate the efficacy of nepetin
in attenuating inflammatory responses in cultured keratinocytes and 2,4-dinitrochlorobenzene
(DNCB)-induced atopic dermatitis (AD) in BALB/c mice. Various assay
methods including cell viability, flow cytometry, fluorometry, confocal microscopy,
western blot, ELISA techniques, staining methods, score and scratch frequency assessment,
etc. were employed to explore the mechanisms. LPS-treated keratinocytes showed
a significant increase in inflammatory mediators (iNOS, COX-2, PGES2, and NO) and
cytokines (IL-1β, IL-6, and TNF-α) in a dose-dependent manner. Treatment with
nepetin prevented LPS-induced cell death and inhibited inflammatory mediators and the
production of cytokines in cultured keratinocytes. This inhibition was achieved by
nepetin, which inhibited LPS-induced ROS production and the translocation of NF-κB
in the cultures, thereby inhibiting the generation of inflammatory mediators and/or cytokines.
In a mouse model of AD, treatment with nepetin reduced skin inflammation
symptoms in a dose-dependent manner, as evidenced by the significant reduction of inflammation-
related cytokines, skin lesions, and behavior scores. Based on the present in
vitro and in vivo study, nepetin is the safest bioactive compound with potential therapeutic
applications for AD-related skin lesions and adverse skin reactions.
Treatment of MRSA Infection: Where are We?
Authors: Nazli Adila , Tao Wenlan , You Hengyao , He Xiaoli , He Yun 
Published: February 2024

Abstract:
Staphylococcus aureus is a leading cause of septicemia, endocarditis, pneumonia, skin and soft tissue infections, bone and joint infections, and hospital-acquired infections. In particular, methicillin-resistant Staphylococcus aureus (MRSA) is associated
with high morbidity and mortality, and continues to be a major public health problem.
The emergence of multidrug-resistant MRSA strains along with the wide consumption
of antibiotics has made anti-MRSA treatment a huge challenge. Novel treatment strategies (e.g., novel antimicrobials and new administrations) against MRSA are urgently
needed. In the past decade, pharmaceutical companies have invested more in the research and development (R&D) of new antimicrobials and strategies, spurred by favorable policies. All research articles were collected from authentic online databases, including Google Scholar, PubMed, Scopus, and Web of Science, by using different combinations of keywords, including ‘anti-MRSA’, ‘antibiotic’, ‘antimicrobial’, ‘clinical trial’,
‘clinical phase’, clinical studies’, and ‘pipeline’. The information extracted from articles
was compared to information provided on the drug manufacturer’s website and ClinicalTrials.gov (https://clinicaltrials.gov/) to confirm the latest development phase of anti-MRSA agents. The present review focuses on the current development status of new
anti-MRSA strategies concerning chemistry, pharmacological target(s), indications,
route of administration, efficacy and safety, pharmacokinetics, and pharmacodynamics,
and aims to discuss the challenges and opportunities in developing drugs for anti-MRSA
infections.
Pharmacokinetics of Anti-rheumatic Drugs Methotrexate and
Tofacitinib with its Metabolite M9 in Rats by UPLC-MS/MS
Authors: Gu Er-min , Xue Lingjie , Zhou Chenjian , Xia Yang , Dai Ge-xin 
Published: February 2024

Background:
Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid
arthritis (RA). The clinical efficacy and safety of an administered tofacitinib, either
monotherapy or in combination with conventional synthetic disease-modifying anti-rheumatic
drugs, mainly methotrexate (MTX), have been evaluated. The high plasma concentration
with delayed medicine clearance may affect the liver and/or kidney functions. In
this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-
MS/MS) method for the quantitative analysis of methotrexate, tofacitinib, and
metabolite M9 in plasma of Sprague Dawley (SD) rats was developed, and its effectiveness
was validated as well.

Methods:
Methotrexate, tofacitinib, M9 and fedratinib (internal standard, IS) were separated
by gradient elution. The chromatography was performed on an Acquity BEH
C18 (2.1 mm × 50 mm, 1.7 μm) column with the mobile phases of acetonitrile and 0.1%
formic acid aqueous solution with different proportions at the flow rate of 0.30 mL/min.
In the positive ionization mode, the analyzes were detected using a Xevo TQ-S triple
quadrupole tandem mass spectrometer, with the following mass transition pairs: m/z
313.12 → 148.97 for tofacitinib, m/z 329.10 → 165.00 for M9 and m/z 455.12 →
308.05 for methotrexate.

Results:
The obtained results manifested good calibration linearity over the ranges of tofacitinib
at 0.1-100 ng/mL, M9 at 0.05-100 ng/mL, and methotrexate at 0.05-100
ng/mL. The lower limit of quantifications (LLOQs) of methotrexate, tofacitinib and M9
were 0.05 ng/mL, 0.1 ng/mL and 0.05 ng/mL, respectively. Intra-day and inter-day accuracy
values were confirmed with a range of -6.3% to 12.7%, while intra-day and inter--
day precision values were ≤14.4%. Additionally, recoveries were greater than 86.5% for
each compound without significant matrix effects.

Conclusion:
The currently established analytical method exhibited great potential for
the evaluation of plasma concentrations of methotrexate, tofacitinib and M9 simultaneously,
greatly reducing the detection time, which would serve as a supplementary role in
formulating dose decisions to achieve personalized treatment, identify drugs that cause
adverse reactions and finally, to assess drug-drug interactions on clinical studies.
MNK: A Novel Promising Target for Cancer Immunotherapy
Authors: Shu Pei , Lei Yanna , Gao Ge , Li Xiaoyu , Qin Diyuan , Zhang Benxia , Chen Yue , Ma Qizhi , Wang Yongsheng 
Published: February 2024

Abstract:
Cancer immunotherapy has demonstrated remarkable success in the treatment
of multiple advanced malignancies, especially approaches to target the immune checkpoint.
Nonetheless, the limited response rate remains a barrier to broader application.
Identifying other ways to extend the beneficiaries to a large extent is needed. Emerging
evidence has shown that mitogen-activated protein kinase-interacting kinases (MNKs)
could be regarded as a novel, attractive target for cancer immunotherapy that is closely
correlated with cancer biology and therapies. A comprehensive understanding of the
role and mechanism of MNKs in cancer will shed light on the discovery of novel therapeutic
strategies for cancer treatment. In this review, we outlined the structure of MNKs,
their function and expression, and how MNKs affect tumor progression and elucidated
the evidence supporting MNKs as a new promising treatment modality in human cancers.
N,N'-disubstituted Ureas as Novel Antiplatelet Agents: Synthesis, Pharmacological Evaluation and In Silico Studies
Authors: de Souza Furtado Priscila , Viana Gil Mendes , de Oliveira Alana Agnes Silva Camargo , Rabelo Vitor Won-Held , Cerqueira Ingryd Wenderroschy , Paschoal Caroline Reis Santiago , da Silva Honorio Thiago , Simon Alice , Rodrigues Carlos Rangel , Abreu Paula Alvarez , Cabral Lucio Mendes , Sathler Plínio Cunha 
Published: February 2024

Introduction:
Thrombotic disorders are among the leading causes of morbidity and
mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic
limitations and adverse effects such as hemorrhagic conditions, highlighting the importance
of developing more effective antiplatelet agents.

Methods:
In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet
profiles through in vitro, ex vivo, and in silico studies.

Results:
The synthesized derivatives exhibited a selective inhibitory profile against platelet aggregation
induced by arachidonic acid (AA) in vitro, without significantly affecting other aspects of
primary hemostasis and blood coagulation. The compounds that showed inhibition greater than
85% were submitted to the analysis of their potency by calculating the concentration required to inhibit
50% of platelet aggregation induced by AA (IC50). Urea derivative 3a was the most potent
with IC50 of 1.45 μM. Interestingly, this derivative inhibited more than 90% of platelet aggregation
induced by AA ex vivo, with a similar effect to acetylsalicylic acid. In the hemolysis assay,
most of the urea derivatives presented values below 10% suggesting good hemocompatibility. Additionally,
the compounds tested at 100 μM also showed no cytotoxic effects in HepG2 and Vero
cells. The in silico results suggested that compound 3a may bind to the key residue of COX-1 similar
to AA and known COX-1 inhibitors, and the results are also in agreement with our SAR,
which suggests that the inhibition of this enzyme is the most likely mechanism of antiplatelet activity.

Conclusion:
Therefore, these results demonstrated that N,N'-disubstituted ureas are promising candidates
for the development of novel antiplatelet agents.
Human Umbilical Cord Mesenchymal Stem Cell Exosome-derived
miR-335-5p Alleviated Lipopolysaccharide-induced Acute Lung
Injury by Regulating the m6A Level of ITGβ4 Gene
Authors: Li Linrui , Zhang Xi , Chen Yanping 
Published: February 2024

Background:
Acute lung injury (ALI) is a serious complication that may accompany
severe pneumonia in children. Derived from exosomes of human umbilical
cord mesenchymal stem cell exosome (HucMSC-Exo) can contribute to the regeneration
of damaged lung tissue. This study aims to investigate the impact of HucMSC-Exo on
ALI and its potential mechanisms.

Methods:
Firstly, RT-qPCR was performed to assess the expression of miR-335-5p. Subsequently,
Pearson correlation analysis was performed to examine the correlation between
METTL14 and miR-335-5p, as well as the correlation between METTL14 and ITGB4.,
while RNA immunoprecipitation (RIP) was used to determine the m6A modification
level of ITGβ4. Additionally, molecular biology techniques were employed to evaluate
the expression of glycolysis-related factors. Definitively, an LPS-induced ALI model
was established to investigate the effect of miR-335-5p on mice lung tissue.

Results:
miR-335-5p was found to be highly expressed in HucMSC-Exo. Transfection
with miR-335-5p mimics resulted in increased glucose uptake. Pearson correlation analysis
revealed a negative correlation between METTL14 and miR-335-5p, as well as between
METTL14 and ITGβ4. The m6A level of ITGβ4 was elevated in ALI. Overexpression
of METTL14 was found to reduce the expression and glucose uptake of ITGβ4,
while overexpression of ITGβ4 reversed the effects of METTL14 overexpression. in
vivo, results demonstrated that miR-335-5p can improve the extent of lung tissue lesions
and reduce glycolytic levels.

method:
HucMSC-Exos were successfully cultured and identified. The LPS-induced ALI model was established using A549 cells and BALB/c mice. Pearson correlation coefficient analyzed the association between METTL14 and miR-335-5p or ITGβ4 in clinical specimens. The modification level of m6A was detected using RNA m6A colorimetry and RNA immunoprecipitation. The cell damage, apoptosis, expression of inflammatory factors, and glycolytic-related factors were determined molecularly and immunohistochemically in various groups.

Conclusion:
This study reveals the mechanism by which miR-335-5p derived from
HucMSC-Exo could alleviate LPS-induced ALI by regulating the m6A modification of
ITGβ4, providing a new direction for the treatment of ALI.
Rhodotorulic Acid and its Derivatives: Synthesis, Properties, and Applications
Authors: Stefaniak Joanna , Nowak Michał Grzegorz , Skwarecki Andrzej Stanisław 
Published: February 2024

:
Siderophores are low molecular weight compounds produced by microorganisms
to scavenge iron in iron-deficient environments. Rhodotorulic acid, a natural hydroxamate
siderophore, plays a vital role in iron acquisition for fungi and bacteria. As
the simplest natural hydroxamate siderophore, it exhibits a high affinity for ferric ions,
enabling it to form stable complexes that facilitate iron uptake and transport within microorganisms.
This article provides a comprehensive analysis of this hydroxamate
siderophore, rhodotorulic acid, its synthesis, physicochemical properties, and biological
significance. It also explores its applications in antifungal and plant protection strategies.
Insights into RA derivatives reveal distinct biological effects and applications with
potential in various fields, from antioxidants to antifungals. Rhodotorulic acid and its
derivatives show promise for novel therapies, plant protection strategies, and iron supplementation
in agriculture. Understanding their properties could advance science and
medicine with sustainable practices.
Role of Ferroptosis in the Progression of COVID-19 and the Development
of Long COVID
Authors: Zhao Wen , Wang Siyuan , Han Yuxin , Zhang Hongkun , Cao Jiacen , Dong Shasha , Li Dongdong , Lei Miao , Liu Chuanmiao , Gao Yu 
Published: February 2024

Objective::
This study aimed to examine the role of ferroptosis on the pathogenesis
and progression of COVID-19.

background:
-

Materials and Methods:
A total of 127 patients who were hospitalized for COVID-19
were categorized into two groups according to the intensity of oxygen therapy (highflow
or low-flow). Clinical characteristics, laboratory parameters, plasma markers, and
peripheral blood mononuclear cell (PBMC) markers were measured at baseline and one
or two weeks after treatment. Telephone follow-up was performed 3 months after
discharge to assess long COVID.

Results::
Patients receiving high-flow oxygen therapy had greater levels of neutrophils,
D-dimer, C reactive protein, procalcitonin, plasma protein levels of tumor necrosis factor-
alpha (TNF-α), interleukin 6 (IL-6), IL-17, acyl-CoA synthetase long-chain family
member 4 (ACSL4), and PBMC mRNA level of TNF-α but had lower levels of lymphocytes
and plasma glutathione peroxidase 4 (GPX4). There were negative correlations of
plasma GPX4 and cystine/glutamate transporter-11 (SLC7A11) with TNF-α, IL-6, and
IL-17 and positive correlations of ACSL4 with inflammatory markers in plasma and
PBMCs. The plasma levels of TNF-α, IL-6, IL-17, and ACSL4 were significantly lower
after treatment than at baseline, but there were higher post-treatment levels of lymphocytes,
GPX4, and SLC7A11. Patients with long COVID had a lower baseline level of
plasma SLC7A11.

Conclusion::
Ferroptosis is activated during the progression of COVID-19, and a low
baseline level of a ferroptosis marker (SLC7A11) may indicate an increased risk for
long COVID-19. Ferroptosis has potential as a clinical indicator of long COVID and as
a therapeutic target.
Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration
Authors: Li Xiao-Long , Yu Xiao-Yu , Tao Yu-Ao , Xu Yu-Zhu , Li Xi , Wang Jia-Dong , Zhang Le-Le , Wang Yun-Tao , Fan Pan 
Published: February 2024

Abstract:
Intervertebral disc degeneration (IDD) is a common musculoskeletal system
disease, which is one of the most important causes of low back pain. Despite the high
prevalence of IDD, current treatments are limited to relieving symptoms, and there are
no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative
stress, the result of an imbalance between the production of reactive oxygen species
(ROS) and clearance by the antioxidant defense system, plays an important role in the
progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production,
which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit
lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review,
we discussed the antioxidant effects of polyphenols and their regulatory role in different
molecular pathways associated with the pathogenesis of IDD, as well as the limitations
and future prospects of polyphenols as a potential treatment of IDD.
Targeting NLRP3 Inflammasome: Structure, Function, and Inhibitors
Authors: Lou Shengying , Wu Miaolian , Cui Sunliang 
Published: February 2024

Abstract:
Inflammasomes are multimeric protein complexes that can detect various physiological
stimuli and danger signals. As a result, they perform a crucial function in the innate
immune response. The NLRP3 inflammasome, as a vital constituent of the inflammasome
family, is significant in defending against pathogen invasion and preserving cellhomeostasis.
NLRP3 inflammasome dysregulation is connected to various pathological
conditions, including inflammatory diseases, cancer, and cardiovascular and neurodegenerative
diseases. This profile makes NLRP3 an applicable target for treating related diseases,
and therefore, there are rising NLRP3 inhibitors disclosed for therapy. Herein, we
summarized the updated advances in the structure, function, and inhibitors of NLRP3 inflammasome.
Moreover, we aimed to provide an overview of the existing products and future
directions for drug research and development.
Network Pharmacology and In vitro Experimental Verification to Explore the
Mechanism of Chaiqin Qingning Capsule in the Treatment of Pain
Authors: Gao Hongjin , Chen Zhengwei , Halihaman Buliduhong , Huang Lianzhan , Wang Zhen , Ding Xuansheng 
Published: February 2024

Background:
Chaiqin Qingning capsule (CQQNC) has been used to relieve pain in practice.
However, the active components, pain targets, and molecular mechanisms for pain control are unclear.

Objective:
To explore the active components and potential mechanisms of the analgesic effect of CQQNC
through network pharmacology and in vitro experiments.

Methods:
The main active components and the corresponding targets of CQQNC were screened from the
TCMSP and the SwissTargetPrediction databases. Pain-related targets were selected in the OMIM, Gene-
Cards, and DrugBank databases. These targets were intersected to obtain potential analgesic targets. The analgesic
targets were imported into the STRING and DAVID databases for protein-protein interaction (PPI),
gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
enrichment analyses. Cytoscape software (V3.7.1) was used to construct an active component-intersection
network. Finally, the key components were docked with the core targets. The analgesic mechanism of
CQQNC was verified by RAW264.7 cell experiment.

Results:
30 active CQQNC components, 617 corresponding targets, and 3,214 pain-related target genes were
found. The main active components were quercetin, kaempferol, and chenodeoxycholic acid etc. The key targets
were ALB, AKT1, TNF, IL6, TP53, IL1B, and SRC. CQQNC can exert an analgesic effect through
PI3K-Akt, MAPK signaling pathways, etc. Molecular docking showed that these active components had good
binding activities with key targets. The results of in vitro experiments showed that CQQNC could exert antiinflammatory
and analgesic effects through MAPK/AKT/NF-kB signaling pathways.

Conclusion:
CQQNC exerts pain control through inhibiting MAPK/AKT/NF-kB signaling pathways.