bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLAC8 facilitates osteosarcoma growth and metastasis by upregulating CXCL5 expression via miR-363-3p
Authors: Huang Xiaoyu , Zhang Yan , Zhang Yanting , Liu Yongheng , Han Xiuxin , Zhang Chao , Wei Xianfu , Xu Yao , Zhang Jin , Feng Jinyan , Wang Guowen 
Published: February 2023

Abstract
Background: Osteosarcoma (OS) is characterized by its highly aggressive nature and metastatic potential. Although dysregulated PLAC8 was reported in various cancers, its function and underlying mechanism in OS metastasis remains largely unknown.
Methods: The expression of PLAC8 was detected by qRT-PCR and Western blot in OS clinical tissues and OS cell lines. CCK-8, colony formation, transwell and wound healing assays were performed to assess its effect on tumor cell proliferation and mobility. The relationship between PLAC8 and CXCL5 expression was analyzed by TIMER 2.0 database, qRT-PCR, Western blot and immunohistochemical staining. The qRT-PCR, Western blot, and luciferase reporter assays were performed to explore molecular mechanisms through which PLAC8 mediates the expression of miR-363-3p, thus modulating the expression of CXCL5.Subcutaneous transplantation, orthotopic tibia implantation, and tail-vein injection mouse model were employed to evaluate the role of PLAC8 on OS tumor growth and lung metastasis.
Results: We found PLAC8 was upregulated in OS tissues and OS cell lines, and its overexpression facilitated the aggressive progression of OS. Besides, we identified CXCL5, as a downstream target gene of PLAC8, could potentiate OS cell proliferation, migration, and invasion. Mechanistically, PLAC8 down-regulated the levels of miR-363-3p which directly targeted CXCL5 3'-UTR, thus enhancing the proliferative and metastatic potency of OS cells. In subcutaneous transplantation and orthotopic tibia implantation mouse model, down-regulation of PLAC8 could markedly attenuate the OS tumorigenesis. In tail-vein injection mouse model, knockdown of PLAC8 could prominently restrain the OS lung metastasis. Moreover, we found that rhCXCL5 and miR-363-3p inhibitors significantly reversed the suppressive effect of PLAC8 silencing on OS growth and lung metastasis in vivo.
Conclusions: PLAC8 is highly expressed in OS, which especially contributes to tumor growth and metastasis by regulating the miR-363-3p/CXCL5 axis. This study suggested that PLAC8 may serve as a promoter in OS and provided new insight into the treatment of OS lung metastasis.
Lobe-specific Analysis of Perioperative Chemotherapy for Non-small Cell Lung Cancer Patients
Authors: Lei Xi , Li Tong , Mao Fuling , Ren Fan , Tang Quanying , Cao Weibo , Zu Lingling , Xu Song 
Published: February 2023

Abstract
Objectives: Perioperative cisplatin-based chemotherapy decreases the risk of death over surgery alone and is a standard-of-care. Here, we examined perioperative chemotherapy indications for stage IB-III non-small cell lung cancer (NSCLC) patients according to lobe-specific analysis.
Methods: Resectable NSCLC patients with stage IB–III who received perioperative chemotherapy with and without radiotherapy after lung resection were identified from the SEER database. Propensity score matching (PSM) analysis was performed to reduce the inherent bias of retrospective studies. The Kaplan–Meier method and log-rank tests were used to assess the differences in overall survival (OS).
Results: The study enrolled 23,844 patients before PSM. The perioperative chemotherapy group had better OS than the non-perioperative chemotherapy group in stage IB–III NSCLC patients before and after PSM. However, subgroup analysis according to stage demonstrated that perioperative chemotherapy did not markedly benefit patients with stage IB. Furthermore, lobar subgroup analysis did not show survival advantages in primary tumors located in either the right middle lobe in stages II and III NSCLC or the right lower lobe in stage III NSCLC.
Conclusions: Lobe-specific perioperative chemotherapy is recommended in NSCLC patients. For stage IB NSCLC, right middle lobe NSCLC from stage IB-III and right lower lobe NSCLC from stage III, perioperative chemotherapy might not confer survival benefits.
Evaluation and Influencing Factors of the Tourism Industry Efficiency under Carbon Emission Constraints in China
Authors: Si Xiaopeng , Tang Zi , Wang Weili , Liang Yan 
Published: February 2023

Abstract

In response to carbon peak and carbon neutrality targets, a broad industrial transformation is underway in China's tourism industry. This paper applies the Data Envelopment Analysis (DEA) model to calculate the efficiency of the tourism industry under carbon emission constraints and further investigates its influencing factors through the Tobit regression. The results are as follows: (1) The tourism efficiency under carbon emission constraints of China from 2000 to 2019 showed a trend of first rising and then declining, and there were obvious regional differences; (2) The total factor productivity of tourism in China increased significantly from 2000 to 2019, the contribution of technical progress, pure technical efficiency, and scale efficiency to it decrease in succession; (3) The factors of industrial structure, transportation convenience, economic development level, degree of opening to the outside world, the level of scientific and technological development have varying degrees of influence on tourism efficiency. Based on the analysis results, this paper puts forward several policy recommendations on tourism efficiency and low-carbon development. The conclusions of this paper are of certain significance for developing countries to improve tourism efficiency and achieve high-quality development of tourism industry in the context of sustainable development.
Twin Prime Conjecture Proof
Authors: Thompson Daniel 
Published: February 2023

Abstract
The Twin Prime conjecture first proposed by French mathematician Alphonse de Polignac in the year 1846 remains unproven until now. This paper sets out to prove the Twin Prime conjecture by creating a system of equations and finding both a y element of ℕ, (y ϵ ℕ) and a y element of k, (y ϵ k) to find the twin prime values and then two further values where each will differ by an exact amount. From this proof the method demonstrates that the elements of these phenomena prove that there will be an infinite number of twin primes that differ by two.
MSC: 11-xx
Roles of Nuclear Receptors in Esophageal Cancer
Authors: Deng Lihao , Liu Jiaxuan , Chen Wei-Dong , Wang Yan-Dong 
Published: February 2023

Background:
Esophageal cancer (EC), including esophageal squamous cell carcinoma
(ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs
predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear
receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a
large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs),
Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X
receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes
or tumor suppressors in EC progression.

Objectives:
NRs are associated with the progression of many cancers, including EC. Some NRs,
such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs
in EC is helpful for further understanding the development of EC. Preclinical research and development
of small molecule compound drugs targeting NRs have provided new ideas for the potential
targeted therapy of EC.

Methods:
This review summarizes the studies on NRs in EC in recent years, mainly including in
vitro cell experiments and in vivo animal experiments.

Results:
NRs influence EC progress in a variety of ways. They mainly affect the proliferation,
migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation
or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor
stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting
NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of
NRs will become a potential therapeutic regimen for EC.

Conclusion:
The studies on the roles of NRs in EC have provided a theoretical basis for us to further
understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for
the treatment of different diseases.
Fructo-oligosaccharides Ameliorate Intestinal Mechanical Barrier Injury
in Piglets Induced by Soybean Antigen in vitro and in vivo
Authors: Mi Mengmeng , Chang Meinan , Huang Yihong , Zhao Jinpeng , Pan Li , Bao Nan , Qin Guixin , Zhao Yuan 
Published: February 2023

Background:
Fructose oligosaccharides (FOS) have been shown to reduce soybean antigen-induced hypersensitivity in piglets, but their effects on intestinal epithelial barrier function have not been characterized. Therefore, this study aimed to determine the effects of FOS on intestinal barrier injury induced by soybean antigen in piglets in vitro and in vivo.

Methods:
We studied the protective effects of FOS against mechanical barrier dysfunction induced using β-conglycinin or glycinin in porcine intestinal epithelial cells (IPEC-J2), and measured the serum concentrations of diamine oxidase (DAO), D-lactic acid, and endotoxin, and the expression of tight junction (TJ) proteins, in piglets.

Results:
We found that FOS concentration dependently increases cell activity, trans-epithelial electrical resistance, and TJ protein expression (P<0.05) and reduces alkaline phosphatase (AP) activity (P<0.05) in vitro. In addition, the serum DAO, D-lactic acid, and endotoxin concentrations were reduced by FOS administration in piglets (P<0.05). Both in vitro and in vivo, the expression levels of TJ proteins (zona occludens 1 and occludin) were increased significantly by FOS (P<0.05).

Conclusion:
Therefore, FOS protect against intestinal injury induced by soybean antigen in piglets, which may provide a basis for the prevention of allergy.
Parasite Metalo-aminopeptidases as Targets in Human Infectious Diseases
Authors: Aguado Mirtha E. , Izquierdo Maikel , González-Matos Maikel , Varela Ana C. , Méndez Yanira , del Rivero Maday A. , Rivera Daniel G. , González-Bacerio Jorge 
Published: February 2023

Background:
Parasitic human infectious diseases are a worldwide health problem due to
the increased resistance to conventional drugs. For this reason, the identification of novel molecular
targets and the discovery of new chemotherapeutic agents are urgently required. Metalo-
aminopeptidases are promising targets in parasitic infections. They participate in crucial processes
for parasite growth and pathogenesis.

Objective:
In this review, we describe the structural, functional and kinetic properties, and inhibitors,
of several parasite metalo-aminopeptidases, for their use as targets in parasitic diseases.

Conclusion:
Plasmodium falciparum M1 and M17 aminopeptidases are essential enzymes for parasite
development, and M18 aminopeptidase could be involved in hemoglobin digestion and erythrocyte
invasion and egression. Trypanosoma cruzi, T. brucei and Leishmania major acidic M17
aminopeptidases can play a nutritional role. T. brucei basic M17 aminopeptidase down-regulation
delays the cytokinesis. The inhibition of Leishmania basic M17 aminopeptidase could affect parasite
viability. L. donovani methionyl aminopeptidase inhibition prevents apoptosis but not the parasite
death. Decrease in Acanthamoeba castellanii M17 aminopeptidase activity produces cell wall
structural modifications and encystation inhibition. Inhibition of Babesia bovis growth is probably
related to the inhibition of the parasite M17 aminopeptidase, probably involved in host hemoglobin
degradation. Schistosoma mansoni M17 aminopeptidases inhibition may affect parasite development,
since they could participate in hemoglobin degradation, surface membrane remodeling and
eggs hatching. Toxoplasma gondii M17 aminopeptidase inhibition could attenuate parasite virulence,
since it is apparently involved in the hydrolysis of cathepsin Cs- or proteasome-produced
dipeptides and/or cell attachment/invasion processes. These data are relevant to validate these enzymes
as targets.
Electrospun Scaffold-based Antibiotic Therapeutics for Chronic Wound
Recovery
Authors: Tamilarasi Ganesan Padmini , Sabarees Govindaraj , Krishnan Manikandan , Gouthaman Siddan , Alagarsamy Veerachamy , Solomon Viswas Raja 
Published: February 2023

Abstract:
Treatment of a wound infection caused by a multidrug-resistant (MDR) bacterium is challenging
since traditional medicine is incapable of curing such infections. As a result, there is a critical
need to develop wound dressings resistant to MDR bacteria. Over half of diabetic and burn wounds
showed clinical symptoms of infection. Diabetes is a metabolic disorder that may have various consequences,
including chronic sores, vascular damage, and neuropathy. Microbial infection and oxidative
stress to the fibroblast are common causes of slow and ineffective wound healing. Since wound healing
and tissue repair are complex cascades of cellular activities, prompt and ordered healing is critical
throughout this process. Despite advances in medication development and sophisticated formulations,
treating persistent wound infections remains difficult. The drawbacks of administering antibiotics
through the digestive system have motivated the development of enhanced therapeutic dressings with
antibacterial activity and the application of antibiotics by localized administration. Antimicrobial
wound dressings have great promise for reducing infection risk and improving the healing rate of
chronic lesions. Most current research in skin tissue engineering focuses on developing threedimensional
scaffolds that mimic natural skin's extracellular matrix (ECM). Electrospinning is a wellestablished
method for producing nanoscale fibers. It is a simple, cost-effective, reproducible, and
efficient process for encapsulating hydrophobic and hydrophilic antimicrobial compounds in synthetic
and natural polymeric carriers. This review discusses various nanofibers as novel delivery systems for
antimicrobial compounds in chronic wound healing. We will discuss the significant polymers used to
make nanofibers, their manufacturing processes, and, most importantly, their antibacterial effectiveness
against microorganisms that typically cause chronic wound infections.
Synthesis and Biological Evaluation of 2-Amino-1-phenyl-benzimidazole
Derivatives as BACE1 Inhibitors
Authors: Dai Xiao-Bin , Wu Shi-Han , Ding Ning , Ma Yi-Yuan , Tong Zhen-Jiang , Wu Jia-Zhen , Wang Yi-Bo , Yu Yan-Cheng , Leng Xue-Jiao , Xue Xin , Xu Jin-Guo , Dai Wei-Chen , Xie Ke , Zhao Jing-Han , Hong Yu-Qi , Lan Tian-Xi , Mu Tian-Yu , Wang Xiao-Long , Sun Shan-Liang , Li Nian-Guang , Liang Qiao-Li , Chang Liang 
Published: February 2023

Background:
Alzheimer’s disease (AD), a chronic neurodegenerative disorder predominantly
occurs among the elderly, is the leading cause of dementia. The accumulation of β-amyloid (Aβ) is considered
the main pathogenies of AD, and β-site APP-cleaving enzyme 1 (BACE1) plays an important role
in the formulation of Aβ.

Objective:
In order to find a new scaffold as BACE1 inhibitors, a series of novel 2-amino-1-phenylbenzimidazole
derivatives were designed and synthesized in this work.

Methods:
Using our previous L-5 as a lead compound, we applied a scaffold hopping method and merged
2-amino-1-methyl-4-phenyl-1H-imidazol-5 (4H)-one into benzimidazole, so a novel class of BACE1
inhibitors T1~T20 with the structure of 2-amino-1-phenyl-benzimidazole were designed and synthesized.

Results:
The biological activity evaluation indicated that the target compounds showed inhibitory activities
against BACE1, with T14 being the most potent (IC50 = 0.45 μM), it also exhibited good logP value
and tPSA. The docking studies indicated that compound T14 could form important hydrogen bonds with
Asp289 and Asp93.

Conclusion:
Compound T14 could be used as a potential BACE1 inhibitor for further modification to
treat AD.
Discharge Planning for People with Inpatient Hyperglycaemia: A Review on Pharmacological Management
Authors: Gangopadhyay Kalyan Kumar , Sahay Rakesh Kumar , Gupta Sunil , Ayyar Vageesh , Das Sambit , Bhattacharya Saptarshi , Bhandari Sudhir , Bhattacharyya Arpandev 
Published: February 2023

Abstract:Inadequate glycaemic control post-discharge is the root cause of readmission in people with diabetes mellitus (DM) and is often linked to improper discharge planning (DP). A structured DP plays a crucial role in ensuring continuing home care and avoiding readmissions. DP should help patients in self-care and provide appropriate guidance to maintain optimal glycaemic control. There is a scarcity of reports and recommendations on the proper DP for people with DM on insulin therapy. The present review provides important consideration based on experts’ opinions from the National Insulin and Incretin summit (NIIS), focusing on the effective treatment strategies at the time of discharge, especially for insulin therapy. A review of literature from PubMed and Embase was conducted. The consensus was derived, and recommendations were made on effective DP for patients with DM. Recommendations were drawn at the NIIS for post-discharge treatment for medical and surgical cases, stress-induced hyperglycaemia, elderly, pregnant women, and coronavirus disease 2019 (COVID-19) cases. The committee also recommended a comprehensive checklist to assist the physicians during discharge.
PMPTCE-HNEA: Predicting Metabolic Pathway Types of Chemicals and
Enzymes with a Heterogeneous Network Embedding Algorithm
Authors: Wang Hao , Chen Lei 
Published: February 2023

Background:
Metabolic chemical reaction is one of the main types of fundamental processes
to maintain life. Generally, each reaction needs an enzyme. The metabolic pathway collects a series of
chemical reactions at the system level. As compounds and enzymes are two important components in
each metabolic pathway, identification of metabolic pathways that a given compound or enzyme can
participate is the first important step for understanding the mechanism of metabolic pathways.

Objective:
The purpose of this study was to build efficient computational methods to predict the metabolic
pathways of compounds and enzymes.

Methods:
Novel multi-label classifiers were proposed to identify metabolic pathway types, reported in
KEGG, of compounds and enzymes. Three heterogeneous networks defining compounds and enzymes
as nodes were constructed. To extract more informative features of compounds and enzymes, we generalized
the powerful network embedding algorithm, Mashup, to its heterogeneous network version,
named MashupH. RAndom k-labELsets (RAKEL) was employed to build the classifiers and support
vector machine or random forest was selected as the base classification algorithm.

Results:
The 10-fold cross-validation results indicated the good performance of the proposed classifiers
and such performance was superior to the previous classifier that adopted features yielded by Mashup.
Furthermore, some key parameters of MashupH that might contribute to or influence the classifiers
were analyzed.

Conclusion:
The features yielded by MashupH were more informative than those produced by Mashup
on heterogeneous networks. This was the main reason the new classifiers were superior to those using
features yielded by Mashup.
Recent Progresses in Chalcone Derivatives as Potential Anticancer Agents
Authors: Yang Jiahui , Lv Jianmei , Cheng Shuxian , Jing Tingyu , Meng Tenghao , Huo Dezhen , Ma Xin , Wen Ran 
Published: February 2023

Abstract:
Chalcones are members of the flavonoid family and act as intermediates in the biosynthesis of flavonoids,
which are widespread in plants. Meanwhile, chalcones are important precursors for synthetic manipulations and act as
mediators in the synthesis of useful therapeutic compounds, which have demonstrated a wide range of biological activities.
Numerous studies have reported the synthesis and medicinal significance of chalcone derivatives. Cancer is
one of the major causes of death worldwide. Although various therapies have been proposed for diverse types of cancer,
their associated limitations and side effects urged researchers to develop more safe, potent and selective anticancer
agents. Based on the literature review, the presence of chalcone derivatives as the main component, a substituent,
or a side-chain in different biologically active compounds could serve as a reliable platform for synthetic organic
chemists to synthesize new compounds bearing this moiety, owing to their similar or superior activities compared to
those of the standards. The diversity of the chalcone family also lends itself to broad-spectrum biological applications
in oncology. This review, therefore, sheds light on the latest structure and the anticancer potency of different synthetics
(bearing other anticancer pharmacophores based on simple, functional groups, and dimer chalcone derivatives) and
natural chalcone hybrids. It is confirmed that the information compiled in this review article, many chalcone hybrids
have been found with promising anticancer activities. Therefore, this review may be convenient for designing novel
chalcone molecules with enhanced medicinal properties according to the structure of the compounds.
Gambogic Acid Lysinate-induced Cervical Cancer SiHa Cells Apoptosis in vitro and
in vivo
Authors: Niu Jie , Sun Jingyu , Liu Yahua , Guo Jun , Zhang Xin , Lin Yajun 
Published: February 2023

Background:
Surgical resection and chemotherapy are the primary treatment options for cervical cancer;
however, efficacy of chemotherapy drugs is limited by drug resistance. There is an urgent need to find new compounds.
Gambogic acid lysinate (GAL), a new compound made from gambogic acid and lysine, has good anti-tumor
activity, however, the effect of GAL on cervical cancer remains undetermined.

Objective:
The present study sought to explore the anti-tumor activity of GAL in SiHa cells.

Methods:
Cell viability was detected by means of an MTT assay, a cell growth curve was drawn with Microsoft Excel
2010, the cell cycle and cell apoptosis were evaluated by flow cytometry, and Western blotting was employed to explore
the mechanism of GAL. Additionally, the in vivo anti-tumor activity of GAL was studied through a xenograft
tumor model in nude mice.

Results:
GAL inhibited the proliferation of both SiHa cells (IC50 was 0.83 μmol/l and 0.77 μmol/l respectively for 48 h
and 72 h) and HeLa cells (IC50 did not reach). In SiHa cells, GAL (1 and 2 μmol/l) inhibited cell proliferation and 2
μmol/l GAL could also induce cell apoptosis and decrease the number of S phase. Both 1 and 2 μmol/l GAL inhibited
SiHa cells invasion and increased the number of G0/G1 phase. The results of Western blot assay demonstrated that P53
and P21 were involved in SiHa cells S phase arrest and BCL-2 and BAX were involved in SiHa cells apoptosis. In vivo
study showed that the growth of SiHa cell xenograft tumors was inhibited via cell apoptosis induced by GAL (2.5
mg/kg body weight), however, GAL (2.5 mg/kg body weight) had no significant effect on weight gain of mice.

Conclusion:
GAL induced SiHa cells apoptosis by BCL-2 and BAX pathway and SiHa cells S phase arrest by P53 and
P21 pathway in vitro and inhibited the growth of SiHa cell xenograft tumors.