bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSPA5 Repressed Ferroptosis to Promote Colorectal Cancer Development by Maintaining GPX4 Stability
Authors: Wang Ronglin , Hua Lei , Ma Peixiang , Song Yang , Min Jie , Zhao Ting , Shi Jingjie , Guo Yongdong , Li Shanshan , Zhang Chao , Yang Cheng , Zhu Liaoliao , Gan Dongxue , Li Junqiang , Su Haichuan 
Published: September 2021

Abstract
Background:Colorectal cancer (CRC) is one of the most malignant cancers and its pathological mechanism is largely unknown.Unfolded protein response and ferroptosis are both critical factors involved in CRC development. However, their relationship in CRC remains to be explored. Methods:In this study, erastin was used to induce ferroptosis in CRC cells. Cell viability and apoptosis were assessed by CCK-8 and colony formation assayand annexin V/propidium iodide staining, respectively. Ferroptosis was confirmed by the detection of glutathione, malondialdehyde, and lipid reactive oxygen species. Unfolded protein response-related proteins and GPX4 protein were analyzed by western blotting. The CRC datasetswere analyzed using the R software, GEPIA2 and TIMER2.0. Results:The results indicated that GPX4 was decreased when treated with the ferroptosis inducer erastin. As an intrinsic protective pathway, the unfolded protein response was activated and HSPA5 was increasedduring ferroptosis. HSPA5 was found to attenuateerastin-induced GPX4 decrease, repress ferroptosis, and promote CRC cell growth both in vitro and in vivo. Mechanistically, HSPA5 bounddirectly to GPX4 andthe interaction between HSPA5 and GPX4increased when treated with erastinfor a short time period. Although the HSPA5-GPX4 interaction failed to completely reverse erastin-induced GPX4 decrease, HSPA5 slowed down GPX4 degradation process and gave CRC cells more time to adjust to erastin toxicity. Additionally, HSPA5 was demonstrated to play a diagnostic role and correlated to immune microenvironment in CRC patients.Conclusion:Our study demonstrates that increased HSPA5 was an intrinsic protective strategy to resist ferroptosis. Specifically, HSPA5 restrained ferroptosis to promote colorectal cancer development by maintaining GPX4 stability. Our study provides potential diagnostic and therapeutic targets for patients with CRC.
Epigenetic Dysregulation of the Expression of PRSS3 Splice Variants Increases the Heterogeneity of Transcripts and Functionality in Human Hepatocellular Carcinoma
Authors: Lin Shuye , Xu Hanli , Pang Mengdi , Zhou Xiaomeng , Pan Yuanming , Zhang Lishu , Guan Xin , Wang Xiaoyue , Lin Bonan , Tian Rongmeng , Chen Keqiang , Zhang Xiaochen , Yang Zijiang , Ji Fengmin , Huang Yingying , Wei Wu , Gong Wanghua , Ren Jianke , Wang Ji Ming , Guo Mingzhou , Huang Jiaqiang 
Published: September 2021

Abstract
Background

Hepatocellular carcinoma (HCC) is one of the most lethal human tumors with extensive heterogeneity. Serine protease 3 (PRSS3) is an indispensable member of the trypsin family and has been implicated in the pathogenesis of several malignancies including HCC. However, paradoxical effects of PPRSS3 on carcinogenesis impede the utilization of its biomarker potential. We hereby systematically dissected the expression of four known splice variants of PRSS3 (PRSS3-SVs) and their functional relevance to HCC.
Methods

The expression and DNA methylation of PRSS3 transcripts and their associated clinical relevance in HCC were analyzed using several publicly available datasets and were validated using qPCR-based assays. Functional assays were performed on gain- and loss-of-function cell models, in which PRSS3 transcript constructs were separately transfected after PRSS3 expression was knocked out by CRISPR-Cas9 editing.
Results

PRSS3 expression was differentially decreased in HCC cell lines and tissues attributable to aberrant expression of PRSS3-SVs towards bipolarity, in which PRSS3-V2 and then -V1 were dominantly expressed whereas PRSS3-V3 and -V4 were rarely or minimally expressed. The expression of PRSS3-V2 or -V1 was reversely associated with site-specific CpG methylation and was distinct between lowly-expressed PRSS3-SVs with hypermethylation (mPRSS3Low) and highly-expressed PRSS3-SVs with hypomethylation (umPRSS3High). Function analysis revealed that PRSS3-V2 exhibited oncogenic functions distinct from a tumor-suppressive role of ectopic PRSS3-V1 or -V3, or PRSS3-V4 with inhibitory effects in PRSS3 knockout HCC cells. Clinically, aberrant expression of PRSS3-SVs was translated into divergent relevance in patients with HCC, in which significant epigenetic downregulation of PRSS3-V2 was seen in early HCC and was associated with favorable patient outcome.
Conclusions

Aberrant expression of divergent PRSS3-SVs disrupted by CpG methylation may integrate the effects of oncogenic PRSS3-V2 and tumor-suppressive PRSS3-V1, resulting in the molecular diversity and functional plasticity of HCC. Dysregulated expression of PRSS3-V2 by site-specific CpG methylation may have potential diagnostic value for patients with early HCC.
miR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy
Authors: Zhou Yang , Wang Chunyan , Ding Jinye , Sun Yaoqi , Cheng Zhongping 
Published: September 2021

Abstract
Background
Accumulating evidences reveal that aberrant microRNAs (miRNAs) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. Emerging evidences have demonstrated that miR-133a participates in tumorigenesis of various cancers. However, whether miR-133a is associated with cisplatin resistance in ovarian cancer remains unclear.
Objective
To investigate the role of miR-133a in the development of cisplatin resistance in ovarian cancer.
Methods
MiR-133a expression in cisplatin-resistant ovarian cancer cell lines was assessed by reverse-transcription quantitative PCR (RT-qPCR). Cell counting kit-8 (CCK-8) assay was used to evaluate cell viability of tumor cells treated with cisplatin in the presence or absence of miR-133a. Luciferase reporter assay was used to analyze binding of miR-133a with 3’ untranslated regions (3’UTR) of YES proto-oncogene 1 (YES1). The YES1 expression level was analyzed using the dataset from the international cancer genome consortiu (ICGC) and assessed by RT-qPCR and western blotting in vitro. The roles and mechanisms of YES1 on cell functions were further probed via gain- and loss-of-function analysis.
Results
The expression of miR-133a was significantly decreased in cisplatin resistant ovarian cancer cell lines (A2780-DDP and SKOV3-DDP), and the overexpression of miR-133a mimic reduced cisplatin resistance in A2780-DDP and SKOV3-DDP cells and the treatment of miR-133a inhibitor increased cisplatin sensitive in normal A2780 and SKOV3 cells. MiR-133a binds 3’UTR of YES1 and down-regulates its expression. Bioinformatics analysis revealed that YES1 expression was upregulated in recurrent cisplatin resistance ovarian cancer tissue and in vitro experiments also verified its upregulating in cisplatin resistance cell lines. Furthermore, we discovered that miR-133a down-regulated the expression of YES1 and thus inhibited the cell autophagy to reduce cisplatin resistance. Yes1 knockdown significantly suppressed the cisplatin resistance of ovarian cancer cells through inhibiting autophagy in vitro. Xenograft tumor implantation further demonstrated that Yes1 overexpression promoted ovarian tumor development and cisplatin resistance.
Conclusion
Our results suggest that miR-133a/YES1 axis plays a critical role in cisplatin resistance in human ovarian cancer by regulating cell autophagy, which might serve as a promising therapeutic target for ovarian cancer chemotherapy treatment in the future.
Diversity of cultivable bacteria from deep-Sea sediments of the Colombian Caribbean and their Potential in Bioremediation
Authors: Blandon Lina , Marín Mario Alejandro , Quintero Marynes , Jutinico-Shubach Laura Marcela , Montoya-Giraldo Manuela , Santos Marisol , Gómez-León Javier 
Published: September 2021

Abstract
The diversity of deep-sea cultivable bacteria was studied in seven sediment samples of the Colombian Caribbean. Three hundred and fifty two marine bacteria were isolated according to its distinct morphological character on the solid media, then DNA sequences of the 16S rRNA were amplified to identify the isolated strains. The identified bacterial were arranged in three phylogenetic groups, Firmicutes, Proteobacteria, and Actinobacteria, with 34 different OTUs defined at ≥97% of similarity and 70 OTUs at ≥98.65%, being the 51% Firmicutes, 34% Proteobacteria and 15% Actinobacteria. Bacillus and Fictibacillus were the dominant genera in Firmicutes, Halomonas and Pseudomonas in Proteobacteria and Streptomyces and Micromonospora in Actinobacteria. In addition, the strains were tested for biosurfactants and lipases production, with 120 biosurfactant producing strains (mainly Firmicutes) and, 56 lipases producing strains (Proteobacteria). This report contributes to the understanding of the detailed physiology and the complex environmental processes associated with the marine deep-sea cultivable bacteria from the Colombian Caribbean.
Genetic Relationship and Structural Analysis of Resident Pacific Salmon Oncorhynchus Masou in Mijiang River, China
Authors: Liang Shan , Song Bizeng , Chong Xiangyu , Zheng Wei , Yin Xuwang , Nie Hongtao 
Published: September 2021

Abstract
Masu salmon Oncorhynchus masou has been listed as national second-class protected species in China, and many of its local populations have been under threats of decline because of environmental deterioration by human activity, such as habitat loss, water pollution, or dams. Genetic characteristics should be clarified in wild masu salmon population for an effective protection and recovery. In the present study, we explained genetic relationship and structure of masu salmon population in Mijaing River by sequencing the COI gene and analyzing microsatellite makers. Results of COI sequences analysis revealed 15 gene variable sites in approximately 696 bp, which defined 12 haplotypes, including some haplotypes related to geographic regions. The NJ tree indicated genetic relationship that we preliminarily inferred, that is, the masu salmon from Mijiang River belonged to the cherry salmon family (O. masoumasou). Results based on 14 microsatellite loci showed high haplotype diversity and low nucleotide diversity, indicating low genetic diversity of wild masu population in Mijaing River. The observed genetic structure was influenced primarily by bottlenecks due to overfishing and habitat loss. Since masu salmon has become highly vulnerable in China, we recommend to strengthen the protection of resident masu salmon population.
Understanding the Abrupt Effect of Spousal Bereavement on Mortality: an Application of Complex Dynamic Systems Theory
Authors: Katsiferis Alexandros , Nielsen Pernille Yde , Jensen Majken K. , Westendorp Rudi G.J 
Published: September 2021

Abstract
BackgroundThe process of aging renders older people susceptible for adverse outcomes upon stress. Various indicators derived from complex systems theory have been proposed for quantifying resilience in living organisms, including humans. We investigated the ability of system-based indicators in capturing the dynamics of resilience in humans who suffer the adversity of spousal bereavement and tested their predictive power in mortality as a finite health transition.MethodsUsing longitudinal register data on weekly healthcare consumption of all Danish citizens over the age of 65 from January 1st, 2011, throughout December 31st, 2016, we performed statistical comparisons of the indicators ‘average’, ‘slope’, ‘mean squared error’, and ‘lag-1 autocorrelation’ one year before and after spousal bereavement, stratified for age and sex. The relation between levels of these indicators before bereavement and mortality hazards thereafter was determined by time to event analysis and the added value for mortality prediction was estimated by the time dependent area under the receiver operating characteristic curve.ResultsThe study included 934,003 citizens of whom 51,890 experienced spousal bereavement and 2862 died in the first year thereafter. Values of all dynamic indicators were significantly higher with increasing age, in men compared to women, and except lag-1 autocorrelation, higher in the year after bereavement (all p-values < 0.001). All dynamic indicators before bereavement were positively related with mortality hazards thereafter (all p-values < 0.001). The area under the curve of the final model to predict mortality, including all relevant indicators, was 77.7% for males and it was 81.8% for females.ConclusionsIt is concluded that healthcare consumption is increased, more volatile and accelerating with aging and in men compared to women. High values of these dynamic indicators before bereavement indicate loss of resilience as manifested by their predictive value to predict mortality when mourning after spousal loss.
Nascent alt-protein chemoproteomics reveals a repressor of ribosome biogenesis
Authors: Slavoff Sarah , Cao Xiongwen , Khitun Alexandra , Harold Cecelia , Bryant Carson , Zheng Shu-Jian , Baserga Susan 
Published: September 2021

Abstract
Many unannotated microproteins and alternative proteins (alt-proteins) have recently been found to be co-encoded with canonical proteins, but few of their functions are known. Motivated by the hypothesis that alt-proteins undergoing active or stress-induced synthesis could play important cellular roles, here, we developed a chemoproteomic pipeline to identify nascent alt-proteins in human cells. We identified 22 actively translated unannotated alt-proteins, one of which is upregulated after DNA damage stress. We further defined MINAS-60 (MIcroprotein that Negatively regulates ASsembly of the pre-60S ribosomal subunit), a nucleolar localized alt-protein co-encoded with human RBM10. Depletion of MINAS-60 increases the amount of the mature 60S ribosomal subunit, consequently upregulating global protein synthesis and cell proliferation by repressing late-stage pre-60S assembly and export of the 60S ribosome subunit to the cytoplasm. Together, these results implicate MINAS-60 as a repressor of ribosome biogenesis, and demonstrate that chemoproteomics can enable generation of functional hypotheses for uncharacterized alt-proteins.
Analysis of nuclear fusion exists inside earth
Authors: Dong Shupeng 
Published: September 2021

Abstract
Using the falsification method, it is proved that "There are three main sources of heat in the deep earth: (1) heat from when the planet formed and accreted, which has not yet been lost; (2) frictional heating, caused by denser core material sinking to the center of the planet; and (3) heat from the decay of radioactive elements" is a false proposition, it is inferred that the source of heat in the deep earth must have an unknown exothermic factor, and this exothermic factor is the heat from intermolecular nuclear fusion. Then, using the quantum tunneling effect of proton and the observed continental plate drift facts, it is determined that there must be nuclear fusion inside the earth. Through the diagram of temperature of planet Earth, it can be determined that the endothermic nuclear fusion reaction occurs in the core of the earth, and because the water becomes solid and cannot ionize hydrogen ions, nuclear fusion cannot occur, so as to determine that the temperature at Earth's center is the freezing point of the saline solution at the center of the earth's core.
Complexity Measure based on Sensitivity Analysis Applied to an Intensive Care Unit system
Authors: Paiva Joao R. B. , Gomes Viviane M. , Barbosa Poliana S. , Almeida Fabiana R. , Wainer Gabriel A. , Gomes Flavio A. , Calixto Wesley P. 
Published: September 2021

Abstract
This work proposes a system complexity metric and its application to Intensive Care Unit (ICU) system. The methodology for applying said complexity metric comprises: (i) parameters sensitivity indices calculation, (ii) mapping connections dynamics between system components, and (iii) system’s complexity calculation. After simulating the ICU computer model and using the proposed methodology, we obtained results regarding: number of admissions, number of patients in queue, length of stay, beds in use, ICU performance, and system complexity values (in regular or overloaded operation). As the number of patients in queue increased, the ICU system complexity also increased, indicating a need for policies to promote system robustness.
Pharmacological Modulation of TRPM2 Channels via TRPM2 Pathway Leads to Neuroprotection in MPTP-induced Parkinson’s Disease in Sprague Dawley Rats
Authors: Vaidya Bhupesh , Kaur Harpinder , Thapak Pavan , Sharma Shyam Sunder , Singh Jitendra N 
Published: September 2021

Abstract
Transient receptor potential melastatin-2 (TRPM2) channels are cation channels activated by oxidative stress and adenosine di-phosphate ribose (ADPR). Role of TRPM2 channels has been postulated in several neurological disorders, but, it has not been explored in animal models of Parkinson’s disease (PD). Thus, the role of TRPM2 and its associated poly (ADP-ribose) polymerase (PARP) signalling pathways were investigated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model using TRPM2 inhibitor, 2-aminoethyl diphenyl borinate (2-APB) and PARP inhibitor, N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino) acetamide hydrochloride (PJ-34). PD was induced by using a bilateral intranigral administration of MPTP in Sprague-Dawley rats, and different parameters were evaluated. An increase in the oxidative stress was observed, leading to the locomotor and cognitive deficits in the PD rats. PD rats also showed an increased TRPM2 expression in striatum and mid brain accompanied by reduced expression of tyrosine-hydroxylase (TH) in comparison to sham animals. Intraperitoneal administration of 2-aminoethyl diphenyl borinate (2-APB) and N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino) acetamide hydrochloride (PJ-34) led to an improvement in the locomotor and cognitive deficits in comparison to MPTP-induced PD rats. These improvements were accompanied by a reduction in the levels of oxidative stress and an increase in TH levels in striatum and mid brain. In addition, these pharmacological interventions also led to a decrease in the expression of TRPM2 in PD in striatum and mid brain. Our results provide a rationale for the development of potent pharmacological agents targeting TRPM2-PARP pathway to provide therapeutic benefits for the treatment of neurological disease like PD.
Quantitative Proteomics Reveals Protein Dysregulation During T Cell Activation in Multiple Sclerosis Patients Compared to Healthy Controls
Authors: Cappelletti Chiara , Eriksson Anna Maria , Brorson Ina Skaara , Leikfoss Ingvild S. , Kråbøl Oda Glomstad , Høgestøl Einar August , Vitelli Valeria , Mjaavatten Olav , Harbo Hanne F. , Berven Frode Steingrimsen , Bos Steffan D. , Berge Tone 
Published: September 2021

Abstract
Background: Multiple sclerosis (MS) is an autoimmune, neurodegenerative disorder with a strong genetic component that acts in a complex interaction with environmental factors for disease development. CD4 + T cells are pivotal players in MS pathogenesis, where peripherally activated T cells migrate to the central nervous system leading to demyelination and axonal degeneration. Through a proteomic approach, we aim at identifying dysregulated pathways in activated T cells from MS patients as compared to healthy controls. Methods: CD4 + T cells were purified from peripheral blood from MS patients and healthy controls by magnetic separation. Cells were left unstimulated or stimulated in vitro through the TCR and costimulatory CD28 receptor for 24 hours prior to sampling. Electrospray liquid chromatographytandem mass spectrometry was used to measure protein abundances. Results: Upon T cell activation the abundance of 1,801 proteins was changed. Among these proteins, we observed an enrichment of proteins expressed by MS-susceptibility genes. When comparing protein abundances in T cell samples from healthy controls and MS patients, 18 and 33 proteins were differentially expressed in unstimulated and stimulated CD4 + T cells, respectively. Moreover, 353 and 304 proteins were identified as proteins exclusively induced upon T cell activation in healthy controls and MS patients, respectively and dysregulation of the Nur77 pathway was observed only in samples from MS patients. Conclusions: Our study highlights the importance of CD4 + T cell activation for MS, as proteins that change in abundance upon T cell activation are enriched for proteins encoded by MS susceptibility genes. The results provide evidence for proteomic disturbances in T cell activation in MS, and pinpoint to dysregulation of the Nur77 pathway, a biological pathway known to limit aberrant effector T cell responses.
Shortening of Leucocyte Telomerase Length Is Independently Correlated With High Body Mass Index and Subcutaneous Obesity (Predominantly Truncal), in Asian Indian Women With Prediabetes
Authors: Bhatt Surya Prakash , Misra Anoop , Pandey Ravindra Mohan , Upadhyay Ashish Datt 
Published: September 2021

Abstract
Introduction: Leucocyte telomerase length (LTL) are inked to accelerate aging and premature mortality. In this research, we aimed to explore the relations between biochemical and anthropometry markers and LTL in Asian Indian women with prediabetes.Methods: In this study, 797 prediabetic women (aged 20-60 years, obese, 492; non obese, 305) were recruited. Demographic and clinical profiles, medical history, skin exposure and duration of sunlight exposure were determined. Anthropometry, fasting blood glucose and serum 25-hydroxyvitamin D [25(OH) D] were evaluated. LTL was quantified by a quantitative polymerase chain reaction (qPCR). The study subjects were separated into quartiles groups according to the LTL.Results: The average telomerase length (T/S) ratio was significantly decreased with increasing age. The average telomerase length (T/S) ratio was significantly shorter in obese women with prediabetes (p<0.05). Univariate and multivariable linear regression analysis after adjustment for age, family income, education and hypertension showed that LTL was inversely correlated with body mass index (BMI), waist and hip circumference, waist-hip and waist-to-height ratio, and truncal skinfolds (subscapular, lateral thoracic, and subscapular/triceps ratio, central and total). Multivariable linear regression analysis identified BMI (93%, p<0.0001), central (92%, p<0.0001) and total skinfolds (90%, p<0.0001) as independent predictors of LTL. Conclusions: Besides age, obesity, and subcutaneous adiposity (predominantly truncal) are major contributors to telomerase shortening in Asian Indian women with prediabetes.