The three core issues in the“digital human rights”debate are whether“digital human rights”are possible,necessary,and feasible.Both sides of the debate focus on discovering the value of“digital human rights”to in...The three core issues in the“digital human rights”debate are whether“digital human rights”are possible,necessary,and feasible.Both sides of the debate focus on discovering the value of“digital human rights”to individuals from a semantic level,but ignore the significance of“digital human rights”to the whole society and its subsystems at the level of social structure.By introducing Niklas Luhmann's System Theory,this observation blind spot can be eliminated.Fundamental rights are devoted to directly shaping not a physiological-psychological“individual”as a social environment but a social“person”that can be included by social systems.It is clear that digital human rights are the right to participate in digital communication of a“human”as a“person”,so they are possible in terms of conceptual definition.Digital human rights can help“people”lower the threshold for participation in digital communication,limit the excessive expansion of social systems,and promote the free and complete expression of body and mind,so they are necessary for social functions.There are limitations in the existing two ideas of“incorporating digital human rights into the constitution”.Based on the new construction idea of System Theory of Law,digital human rights as the right to participate in digital communication can be typified into digital communication in social sub-fields such as politics,economy,science,and art.The right to participate constructs a complete digital human rights system,making it feasible on the basis of the constitution.展开更多
Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 a...Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.展开更多
Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata...Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal...TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.展开更多
Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocyt...Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.展开更多
Space travel since the 1960s has led to a number of physiological alterations to homeostasis in astronauts. Extensive variation in the pattern of responses observed has led a concerted effort to develop countermeasure...Space travel since the 1960s has led to a number of physiological alterations to homeostasis in astronauts. Extensive variation in the pattern of responses observed has led a concerted effort to develop countermeasures to overcome such changes and restore homeostasis, and thus “health” is defined as more “Earth-like”. These adaptations to a space environment by a species which evolved and normally exists in the 1 g environment, the geomagnetic field, and background radiation of Earth are viewed as threats to health as defined by the conditions of Earth. Exposure to space can lead to alterations in genomic stability and epigenetic signatures, alterations which could redefine “health” and responses to risks for loss of health for those who will return to Earth. In contrast, in the future individuals born in non-Earth space environments will likely develop an integrated metabolic set point defined by those conditions. They will thus be shaped by both the local environments, and space-associated genomic/epigenomic alterations to their parents. Therefore, such an altered set point for those born and raised in non-Earth space environments will potentially have physiological and molecular consequences which may lead to either new evolutionary adaptation, or to compromise of long term health due to drastically altered set points for integrated physiologic function which is at odds with the evolutionary history of humans. The implications of the two options will be critical for defining “health” in altered environments encountered during space ventures, as well as providing insights into the regulation of human integrity at the physiological level. Therefore, the definition of “health” is dependent on the boundary conditions surrounding development and maturation, and is a dynamic concept.展开更多
Traditional human rights theory tends to hold that human rights should be aimed at defending public authority and that the legal issue of human rights is a matter of public law.However,the development of human rights ...Traditional human rights theory tends to hold that human rights should be aimed at defending public authority and that the legal issue of human rights is a matter of public law.However,the development of human rights concepts and practices is not just confined to this.A textual search shows that the term“human rights”exists widely in China’s civil judicial documents.Among the 3,412 civil judicial documents we researched,the concept of“human rights”penetrates all kinds of disputes in lawsuits,ranging from property rights,contracts,labor,and torts to marital property,which is embedded in both the claims of the parties concerned and the reasoning of judges.Human rights have become the discourse and yardstick for understanding and evaluating social behavior.The widespread use of the term“human rights”in civil judicial documents reflects at least three concepts related to human rights:first,the rights to subsistence and development are the primary basic human rights;second,the judicial protection of human rights is a bottom-line guarantee;third,the protection of human rights aims to achieve equal rights.Today,judges quote the theory of human rights in judicial judgments from time to time,evidencing that human rights have a practical function in judicial adjudication activities,and in practice this is mainly manifested in declaring righteous values and strengthening arguments with the values and ideas related to human rights,using the provisions concerning human rights in the Constitution to interpret the constitutionality,and using the principles of human rights to interpret blurred rules and rank the importance of different rights.展开更多
The Chinese concept of human rights serves as the core value of China’s path of human rights development,guiding the comprehensive advancement of China’s human rights cause and providing Chinese wisdom for the devel...The Chinese concept of human rights serves as the core value of China’s path of human rights development,guiding the comprehensive advancement of China’s human rights cause and providing Chinese wisdom for the development of human rights cause worldwide.Throughout the development process of China’s human rights cause in the new era,the international communication of the Chinese concept of human rights has achieved positive results and played an essential role in the international human rights discourse struggle,external exchanges on human rights,and the transformation of international human rights mechanisms.However,it also faces challenges such as the dominance of Western human rights concepts,the marginalization of the Chinese concept of human rights,the incomplete establishment of China’s external discourse system on human rights,and constraints on international communication channels.Therefore,in the new era,it is crucial to address the weaknesses in the international communication of the Chinese concept of human rights,optimize communication channels,and enhance its international influence.展开更多
The construction of a barrier-free environment contains a rich connotation of human rights protection,and is closely related to the study of human rights protection in China.With the evolution of the concept of barrie...The construction of a barrier-free environment contains a rich connotation of human rights protection,and is closely related to the study of human rights protection in China.With the evolution of the concept of barrier-free design and the expansion of its beneficiary groups,constructing a barrier-free environment has become a basic task that benefits all members of society and meets the public needs of all the people,with its core goal expanding from the protection of the rights of the disabled to the protection of the basic rights and interests of all members of society.Building a barrier-free environment from the perspective of the Marxist human rights concept is conducive to safeguarding the people’s right to subsistence and development,and at the same time,it satisfies their demand for the right to pursue a high-quality and better life and reflects the common vision of everyone in society fully enjoying human rights.promoting the construction of a barrier-free environment in terms of legal protection based on China’s institutional advantages can improve and innovate the country’s legislation on the construction of a barrier-free environment,so as to play an exemplary and guiding role in enhancing the international barrier-free level and enable all people to enjoy the good life created through the drive to build a barrier-free environment.展开更多
The concept of"human"is essential in bioethics.Generally speaking,the concept of"human"is related to the identity of personality.This paper systematically discusses the concept of"personality ...The concept of"human"is essential in bioethics.Generally speaking,the concept of"human"is related to the identity of personality.This paper systematically discusses the concept of"personality identity"and"human"by Locke,Parfit and Kant.In comparison,Locke views self-awareness or reason as the key element of any appropriate concepts of"human".On the basis of Locke's viewpoint,Parfit makes explanation of the identity of personality,and points out that personality identity should be connected with physical and psychological continuity.This view has been a progress but still has a utility thought.Therefore,the understanding of the concept of"human"is not entirely out of its species,and should be deeply based on our own as the main body of the concept.展开更多
BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of canc...BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.展开更多
This paper discusses two alternative ways of existence of the human being: participation in the concept of reason and participation in the events of the world. It is argued that the traditional Western philosophy fro...This paper discusses two alternative ways of existence of the human being: participation in the concept of reason and participation in the events of the world. It is argued that the traditional Western philosophy from Parmenides and Plato to R. Descartes, I. Kant, and G. Hegel can be described as the participation in the concept of reason. This tradition is characterized by the goal to assimilate the things of the world by concept of reason and in accordance with a project reason, to change the world. This led to the ecological catastrophe. We can overcome ecological catastrophe successfully only when we change the paradigm and shift to the paradigm of participation in the events of the world. The article is based on A. Badiou's conception of event which is contrasted with Descartes' conception of the event. Argumentation of the article shows the importance of B. Spinoza's monistic philosophy for our epoch, which is struck by the ecological disaster. This philosophy is not characterised by the war between things and thoughts, because both thoughts and things are attributes expressing the same God or Nature and are not in conflict with one another.展开更多
Human Capital Management(HCM)is a management concept that demands theoretical foundations for implementation.It must not be easily equated with human resource management activities.HCM must include initiatives directl...Human Capital Management(HCM)is a management concept that demands theoretical foundations for implementation.It must not be easily equated with human resource management activities.HCM must include initiatives directly focused on the knowledge resources that are at the organization’s disposal.However,using only internal knowledge resources is not enough to raise the level of competitiveness.Organizations must reach outside their environment.It has been adopted that,in instrumental terms,HCM is based on intentionally selected and applied organizational,technical,social,formal,and legal,as well as economic and financial instruments in a manner that enables the organization’s goals to be achieved.At the inter-organizational level,HCM was included in the organization’s business ecosystem as the organization gains new opportunities to use the knowledge and human capital of its stakeholders thanks to its network connections.It is from this perspective that the article proposes the main concepts,goals and practices,methods that HCM can serve.展开更多
Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogene...Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.展开更多
What is summarized as'harmony is of paramount importance' is a most prominent philosophical approach embraced by China's Confucian culture. This is an extension of the approach summarized as 'the peopl...What is summarized as'harmony is of paramount importance' is a most prominent philosophical approach embraced by China's Confucian culture. This is an extension of the approach summarized as 'the people are of paramount importance.' It calls for harmonious human relations, obliging one to respect others' rights and interests while protecting the rights and interests of one's own. Harmony as a philosophical approach manifests itself, in many ways, in the realm of human rights in China today. To name just a few: the country's political system of multi-party cooperation under the leadership of the Chinese Communist Party, harmony that prevails between different religions in the country, and the country's call for international dialogue and cooperation to promote the human rights cause. As a fine Chinese tradition, this philosophical approach is being carried forward.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
The China Society of Human Rights Studies and the Human Rights Research Center at Nankai University jointly hosted a seminar on"The 10th Anniversary of the Blue Book on Human Rights and the Chinese Human Rights C...The China Society of Human Rights Studies and the Human Rights Research Center at Nankai University jointly hosted a seminar on"The 10th Anniversary of the Blue Book on Human Rights and the Chinese Human Rights Concept,Discourse and Theory"on December 19th,2020.Experts at the meeting expressed their views and discussed the organization,style,and system of the Blue Book on Human Rights;the concept,expression,and dissemination of the Chinese human rights discourse;the paradigm,principle,and structure of the Chinese human rights theory;and the objectives,paths,and development of the Chinese human rights enterprise.展开更多
Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alle...Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.展开更多
基金a phased achievement of the research project“Research on the Basic Issues of Digital Rule of Law from the Perspective of System Theory”(Project Approval Number 22AZD149)。
文摘The three core issues in the“digital human rights”debate are whether“digital human rights”are possible,necessary,and feasible.Both sides of the debate focus on discovering the value of“digital human rights”to individuals from a semantic level,but ignore the significance of“digital human rights”to the whole society and its subsystems at the level of social structure.By introducing Niklas Luhmann's System Theory,this observation blind spot can be eliminated.Fundamental rights are devoted to directly shaping not a physiological-psychological“individual”as a social environment but a social“person”that can be included by social systems.It is clear that digital human rights are the right to participate in digital communication of a“human”as a“person”,so they are possible in terms of conceptual definition.Digital human rights can help“people”lower the threshold for participation in digital communication,limit the excessive expansion of social systems,and promote the free and complete expression of body and mind,so they are necessary for social functions.There are limitations in the existing two ideas of“incorporating digital human rights into the constitution”.Based on the new construction idea of System Theory of Law,digital human rights as the right to participate in digital communication can be typified into digital communication in social sub-fields such as politics,economy,science,and art.The right to participate constructs a complete digital human rights system,making it feasible on the basis of the constitution.
文摘Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.
文摘Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金supported by the Koeln Fortune Program/Faculty of Medicine,University of Cologne,the Alzheimer Forschung Initiative e.V.(grant#22039,to HZ)open-access funding from the DFG/GRC issued to the University of CologneAlzheimer Forschung Initiative e.V.for Open Access Publishing(a publication grant#P2401,to MAAK)。
文摘TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.
基金supported by the National Natural Science Foundation of China,No.82301403(to DZ)。
文摘Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.
文摘Space travel since the 1960s has led to a number of physiological alterations to homeostasis in astronauts. Extensive variation in the pattern of responses observed has led a concerted effort to develop countermeasures to overcome such changes and restore homeostasis, and thus “health” is defined as more “Earth-like”. These adaptations to a space environment by a species which evolved and normally exists in the 1 g environment, the geomagnetic field, and background radiation of Earth are viewed as threats to health as defined by the conditions of Earth. Exposure to space can lead to alterations in genomic stability and epigenetic signatures, alterations which could redefine “health” and responses to risks for loss of health for those who will return to Earth. In contrast, in the future individuals born in non-Earth space environments will likely develop an integrated metabolic set point defined by those conditions. They will thus be shaped by both the local environments, and space-associated genomic/epigenomic alterations to their parents. Therefore, such an altered set point for those born and raised in non-Earth space environments will potentially have physiological and molecular consequences which may lead to either new evolutionary adaptation, or to compromise of long term health due to drastically altered set points for integrated physiologic function which is at odds with the evolutionary history of humans. The implications of the two options will be critical for defining “health” in altered environments encountered during space ventures, as well as providing insights into the regulation of human integrity at the physiological level. Therefore, the definition of “health” is dependent on the boundary conditions surrounding development and maturation, and is a dynamic concept.
文摘Traditional human rights theory tends to hold that human rights should be aimed at defending public authority and that the legal issue of human rights is a matter of public law.However,the development of human rights concepts and practices is not just confined to this.A textual search shows that the term“human rights”exists widely in China’s civil judicial documents.Among the 3,412 civil judicial documents we researched,the concept of“human rights”penetrates all kinds of disputes in lawsuits,ranging from property rights,contracts,labor,and torts to marital property,which is embedded in both the claims of the parties concerned and the reasoning of judges.Human rights have become the discourse and yardstick for understanding and evaluating social behavior.The widespread use of the term“human rights”in civil judicial documents reflects at least three concepts related to human rights:first,the rights to subsistence and development are the primary basic human rights;second,the judicial protection of human rights is a bottom-line guarantee;third,the protection of human rights aims to achieve equal rights.Today,judges quote the theory of human rights in judicial judgments from time to time,evidencing that human rights have a practical function in judicial adjudication activities,and in practice this is mainly manifested in declaring righteous values and strengthening arguments with the values and ideas related to human rights,using the provisions concerning human rights in the Constitution to interpret the constitutionality,and using the principles of human rights to interpret blurred rules and rank the importance of different rights.
文摘The Chinese concept of human rights serves as the core value of China’s path of human rights development,guiding the comprehensive advancement of China’s human rights cause and providing Chinese wisdom for the development of human rights cause worldwide.Throughout the development process of China’s human rights cause in the new era,the international communication of the Chinese concept of human rights has achieved positive results and played an essential role in the international human rights discourse struggle,external exchanges on human rights,and the transformation of international human rights mechanisms.However,it also faces challenges such as the dominance of Western human rights concepts,the marginalization of the Chinese concept of human rights,the incomplete establishment of China’s external discourse system on human rights,and constraints on international communication channels.Therefore,in the new era,it is crucial to address the weaknesses in the international communication of the Chinese concept of human rights,optimize communication channels,and enhance its international influence.
基金the National Social Science Fund major project“Study on the Construction of a Barrier-Free Environment”(Project Approval Number 22&ZD186).
文摘The construction of a barrier-free environment contains a rich connotation of human rights protection,and is closely related to the study of human rights protection in China.With the evolution of the concept of barrier-free design and the expansion of its beneficiary groups,constructing a barrier-free environment has become a basic task that benefits all members of society and meets the public needs of all the people,with its core goal expanding from the protection of the rights of the disabled to the protection of the basic rights and interests of all members of society.Building a barrier-free environment from the perspective of the Marxist human rights concept is conducive to safeguarding the people’s right to subsistence and development,and at the same time,it satisfies their demand for the right to pursue a high-quality and better life and reflects the common vision of everyone in society fully enjoying human rights.promoting the construction of a barrier-free environment in terms of legal protection based on China’s institutional advantages can improve and innovate the country’s legislation on the construction of a barrier-free environment,so as to play an exemplary and guiding role in enhancing the international barrier-free level and enable all people to enjoy the good life created through the drive to build a barrier-free environment.
基金supported by the Fundamental Research Funds for the Central University entitled“Research on Thompson’s Theory of Prima Facie Right”(SWU1009038)
文摘The concept of"human"is essential in bioethics.Generally speaking,the concept of"human"is related to the identity of personality.This paper systematically discusses the concept of"personality identity"and"human"by Locke,Parfit and Kant.In comparison,Locke views self-awareness or reason as the key element of any appropriate concepts of"human".On the basis of Locke's viewpoint,Parfit makes explanation of the identity of personality,and points out that personality identity should be connected with physical and psychological continuity.This view has been a progress but still has a utility thought.Therefore,the understanding of the concept of"human"is not entirely out of its species,and should be deeply based on our own as the main body of the concept.
基金Supported by National Natural Science Foundation of China,No.82360329Inner Mongolia Medical University General Project,No.YKD2023MS047Inner Mongolia Health Commission Science and Technology Plan Project,No.202201275.
文摘BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.
文摘This paper discusses two alternative ways of existence of the human being: participation in the concept of reason and participation in the events of the world. It is argued that the traditional Western philosophy from Parmenides and Plato to R. Descartes, I. Kant, and G. Hegel can be described as the participation in the concept of reason. This tradition is characterized by the goal to assimilate the things of the world by concept of reason and in accordance with a project reason, to change the world. This led to the ecological catastrophe. We can overcome ecological catastrophe successfully only when we change the paradigm and shift to the paradigm of participation in the events of the world. The article is based on A. Badiou's conception of event which is contrasted with Descartes' conception of the event. Argumentation of the article shows the importance of B. Spinoza's monistic philosophy for our epoch, which is struck by the ecological disaster. This philosophy is not characterised by the war between things and thoughts, because both thoughts and things are attributes expressing the same God or Nature and are not in conflict with one another.
文摘Human Capital Management(HCM)is a management concept that demands theoretical foundations for implementation.It must not be easily equated with human resource management activities.HCM must include initiatives directly focused on the knowledge resources that are at the organization’s disposal.However,using only internal knowledge resources is not enough to raise the level of competitiveness.Organizations must reach outside their environment.It has been adopted that,in instrumental terms,HCM is based on intentionally selected and applied organizational,technical,social,formal,and legal,as well as economic and financial instruments in a manner that enables the organization’s goals to be achieved.At the inter-organizational level,HCM was included in the organization’s business ecosystem as the organization gains new opportunities to use the knowledge and human capital of its stakeholders thanks to its network connections.It is from this perspective that the article proposes the main concepts,goals and practices,methods that HCM can serve.
基金the National Natural Science Foundation of China,No.82360148Guizhou Science&Technology Department,No.QKHPTRC2018-5636-2 and No.QKHPTRC2020-2201.
文摘Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.
文摘What is summarized as'harmony is of paramount importance' is a most prominent philosophical approach embraced by China's Confucian culture. This is an extension of the approach summarized as 'the people are of paramount importance.' It calls for harmonious human relations, obliging one to respect others' rights and interests while protecting the rights and interests of one's own. Harmony as a philosophical approach manifests itself, in many ways, in the realm of human rights in China today. To name just a few: the country's political system of multi-party cooperation under the leadership of the Chinese Communist Party, harmony that prevails between different religions in the country, and the country's call for international dialogue and cooperation to promote the human rights cause. As a fine Chinese tradition, this philosophical approach is being carried forward.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘The China Society of Human Rights Studies and the Human Rights Research Center at Nankai University jointly hosted a seminar on"The 10th Anniversary of the Blue Book on Human Rights and the Chinese Human Rights Concept,Discourse and Theory"on December 19th,2020.Experts at the meeting expressed their views and discussed the organization,style,and system of the Blue Book on Human Rights;the concept,expression,and dissemination of the Chinese human rights discourse;the paradigm,principle,and structure of the Chinese human rights theory;and the objectives,paths,and development of the Chinese human rights enterprise.
文摘Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.