Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluoro...Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.展开更多
The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) proj...The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) projects: 1) Strategy;2) Infrastructure;3) Technology;4) Processes & Procedures;5) Governance;6) Culture;7) People;8) Goals & Metrics and selected six critical success factors from these categories: 1) Operational Efficiency;2) Time Savings;3) Timeframe to Realize Value;4) Employee Engagement;5) Participation;6) Number of Sponsored Ideas. End users of the digital transformation efforts through Citizen Development were asked to assess the six critical success measures in terms of performance and importance criteria. The research results identified that focus should be applied to improving “Timeframe to Realize Value”, on “Operational Efficiency”, and on “Time Savings” to deliver success.展开更多
Canine parvovirus 2(CPV-2)is a highly contagious virus in dogs that typically causes hemorrhagic enteritis and a high mortality rate in unvaccinated puppies.The genetic variability and antigenic diversity of CPV-2 hin...Canine parvovirus 2(CPV-2)is a highly contagious virus in dogs that typically causes hemorrhagic enteritis and a high mortality rate in unvaccinated puppies.The genetic variability and antigenic diversity of CPV-2 hinder its efective prevention of infection by vaccination.To investigate the epidemiology and genetic characteristics of CPV-2 in China,rectal swabs from afected dogs were collected from diferent animal clinics in Kunshan from 2022 to 2023.Preliminary detection and capsid gene sequencing of CPV-2 were performed using previously described primers and protocols.The overall detection rate for CPV-2 was 16.5%(33/200).A signifcant association was found between the CPV-2-positivity and clinical signs,age,breed and vaccination status.Sequence analysis revealed the presence of CPV-2c genotypes in all positive samples,which were genetically similar to other Asian CPV-2c strains.Notably,four key mutations(A5G,F267Y,Y324I and Q370R)were detected in all isolates,and one novel mutation(I447M)was detected in three CPV-2 isolates.These mutations in the CPV-2 strains could impact vaccine efcacy and the efectiveness of the virus immune evasion.Surprisingly,no recombination events were observed between the identifed CPV-2c strains and reference strains from China.Our data revealed that amino acid residues 324,426 and 440 of VP2 may under strong selection pressure.This pattern of genetic variation in the CPV-2 lineage warrants continuous laboratory-based surveillance programs in other parts of China to better understand the pattern of seasonal distribution and association between emerging genotypes and the intensity of disease severity.展开更多
Background:In today’s society the ongoing discussion about euthanasia triggers emotionally charged debates surrounding the delicate balance between valuing life and respecting an individual’s autonomy.With the persi...Background:In today’s society the ongoing discussion about euthanasia triggers emotionally charged debates surrounding the delicate balance between valuing life and respecting an individual’s autonomy.With the persistence of this debate,there has been the emergence of the concept of the so-called alternative:palliative care.Positioned as a substitute for euthanasia,palliative care aims to alleviate suffering in terminally ill patients without engaging in the ethical dilemmas associated with euthanasia.Methods:This paper explores the facets of palliative care highlighting its core objectives such as providing adequate pain relief as a compassionate alternative to euthanasia.Results:By examining palliative care as a comprehensive approach to end of life support,this study challenges the perceived necessity of euthanasia and advocates,for compassionate and dignified end of life experiences.Conclusion:In conclusion,palliative care emerges as a viable and ethically sound alternative to euthanasia,emphasizing the importance of compassionate end-of-life care and pain management.展开更多
This paper provides a comprehensive examination of euthanasia from various perspectives,including medical,legal,religious,philosophical,and moral.The study also explores the public perceptions and trends in Malta.The ...This paper provides a comprehensive examination of euthanasia from various perspectives,including medical,legal,religious,philosophical,and moral.The study also explores the public perceptions and trends in Malta.The medical perspective analyses the benefits and risks of euthanasia and its impact on the healthcare system.The legal perspective discusses the legality of euthanasia in Malta and the potential legal implications of legalizing the practice.The religious perspective explores the beliefs of various religious groups in Malta,particularly Catholicism,on euthanasia.The philosophical perspective discusses the ethical and moral considerations of euthanasia.The paper also analyses the results of surveys conducted in Malta,examining the public’s attitudes towards euthanasia.Overall,the study provides a thorough analysis of euthanasia from various angles,shedding light on the complex and controversial nature of the topic.展开更多
基金supported through the Faculty of Medicine and Surgery Award 2021 University of Malta(awarded to K.F).
文摘Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.
文摘The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) projects: 1) Strategy;2) Infrastructure;3) Technology;4) Processes & Procedures;5) Governance;6) Culture;7) People;8) Goals & Metrics and selected six critical success factors from these categories: 1) Operational Efficiency;2) Time Savings;3) Timeframe to Realize Value;4) Employee Engagement;5) Participation;6) Number of Sponsored Ideas. End users of the digital transformation efforts through Citizen Development were asked to assess the six critical success measures in terms of performance and importance criteria. The research results identified that focus should be applied to improving “Timeframe to Realize Value”, on “Operational Efficiency”, and on “Time Savings” to deliver success.
基金Kunshan Municipal Government research funding(Grant Number:22KKSGR075).
文摘Canine parvovirus 2(CPV-2)is a highly contagious virus in dogs that typically causes hemorrhagic enteritis and a high mortality rate in unvaccinated puppies.The genetic variability and antigenic diversity of CPV-2 hinder its efective prevention of infection by vaccination.To investigate the epidemiology and genetic characteristics of CPV-2 in China,rectal swabs from afected dogs were collected from diferent animal clinics in Kunshan from 2022 to 2023.Preliminary detection and capsid gene sequencing of CPV-2 were performed using previously described primers and protocols.The overall detection rate for CPV-2 was 16.5%(33/200).A signifcant association was found between the CPV-2-positivity and clinical signs,age,breed and vaccination status.Sequence analysis revealed the presence of CPV-2c genotypes in all positive samples,which were genetically similar to other Asian CPV-2c strains.Notably,four key mutations(A5G,F267Y,Y324I and Q370R)were detected in all isolates,and one novel mutation(I447M)was detected in three CPV-2 isolates.These mutations in the CPV-2 strains could impact vaccine efcacy and the efectiveness of the virus immune evasion.Surprisingly,no recombination events were observed between the identifed CPV-2c strains and reference strains from China.Our data revealed that amino acid residues 324,426 and 440 of VP2 may under strong selection pressure.This pattern of genetic variation in the CPV-2 lineage warrants continuous laboratory-based surveillance programs in other parts of China to better understand the pattern of seasonal distribution and association between emerging genotypes and the intensity of disease severity.
文摘Background:In today’s society the ongoing discussion about euthanasia triggers emotionally charged debates surrounding the delicate balance between valuing life and respecting an individual’s autonomy.With the persistence of this debate,there has been the emergence of the concept of the so-called alternative:palliative care.Positioned as a substitute for euthanasia,palliative care aims to alleviate suffering in terminally ill patients without engaging in the ethical dilemmas associated with euthanasia.Methods:This paper explores the facets of palliative care highlighting its core objectives such as providing adequate pain relief as a compassionate alternative to euthanasia.Results:By examining palliative care as a comprehensive approach to end of life support,this study challenges the perceived necessity of euthanasia and advocates,for compassionate and dignified end of life experiences.Conclusion:In conclusion,palliative care emerges as a viable and ethically sound alternative to euthanasia,emphasizing the importance of compassionate end-of-life care and pain management.
文摘This paper provides a comprehensive examination of euthanasia from various perspectives,including medical,legal,religious,philosophical,and moral.The study also explores the public perceptions and trends in Malta.The medical perspective analyses the benefits and risks of euthanasia and its impact on the healthcare system.The legal perspective discusses the legality of euthanasia in Malta and the potential legal implications of legalizing the practice.The religious perspective explores the beliefs of various religious groups in Malta,particularly Catholicism,on euthanasia.The philosophical perspective discusses the ethical and moral considerations of euthanasia.The paper also analyses the results of surveys conducted in Malta,examining the public’s attitudes towards euthanasia.Overall,the study provides a thorough analysis of euthanasia from various angles,shedding light on the complex and controversial nature of the topic.