The preparation and expression of replication- deficient human interleukin-2 recombinant adenoviruses

Interleukin-2(IL-2) has been demonstrated to beone of the most effective target genes in cancerimmunogene therapy. There are more than 20 clinicalprotocols of cancer gene therapy introducing IL-2 intotumor patients to treat melanoma, renal carcinoma,prostate carcinoma, colon carcinoma,

An In-depth Interpretation of the Universal Declaration of Human Rights With the Common Values of Humanity As the Research Paradigm

Interpreting the Universal Declaration of Human Rights from political,juridical and philosophical perspectives is es-sential for promoting the guiding principles of the Declaration,build-ing consensus on human rights,and advancing human rights practice in the new historical context.To conduct an academic,systematic in-terpretation of the Declaration that conforms to the trends of the times and answers the fundamental questions of the world,it is necessary to find a new research paradigm.The common values of humanity,namely peace,development,equity,justice,democracy and freedom,put forward by Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,provide the most explanatory and penetrating scientific paradigm for reaching the issue.This paper an-alyzes and reflects on the views,value foundation and principled(con-tractual)consensus of human rights in the Declaration,and narrates and foresees the far-reaching significance of the three global initia-tives(namely,the Global Development Initiative,the Global Security Initiative,and the Global Civilization Initiative)with the common val-ues of humanity as the soul in advancing the modernization of global human rights governance and building a new form of human rights civilization.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,biochemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

The Historical Position and Value Dimensions of Human Rights Civilization

Human beings are the mainstay and the ultimate goal of civilization.The history of human civilization is a continuous struggle to realize the respect,liberation,protection,and development of humanity.Human rights are an achievement of humanity and a symbol of progress,and the human rights civilization is an important component of human civilization.Understanding and interpreting human rights from the perspective of human rights civilization means that human rights are not only a concept or an idea but also a grand historical and long-term social practice.Up to now,the development of human rights civilization has roughly experienced four awakening eras:initialization,revolution,popularization,and globalization.In terms of its value dimensions,it has the characteristics of progressiveness,diversity,commonality,inclusiveness,indivisibility,openness,and so on.The historical position of human rights civilization and the development of its value dimensions have shown to the world that human rights are the common wealth of humanity,and human rights belong to all mankind;human rights are historical,concrete,and developmental;the concept of human rights is constantly evolving,and its connotations and categories are constantly expanding;achieving the free and well-rounded development of every person is the highest value realm of human rights civilization.The Chinese modernization endows Chinese civilization with modern strength and opens up new horizons for human rights civilization.The new pattern of human rights civilization to be created by Chinese modernization not only possesses the common characteristics of human rights civilization but also enjoys Chinese characteristics based on its own national conditions,enriching and developing the diversity of human rights civilization for all mankind.

Human Rights and Development:China's Contributions Based on a Larger Concept of Human Rights

The Western liberal view of global governance can no longer effectively address the challenges facing the world today or respond to the demands of developing countries in the fields of human rights and development.Meanwhile,the United Nations human rights and development agenda also has its limitations.Against such a backdrop,China's path of human rights development has avoided the trap of human rights confrontation and the clash of civilizations.It has set an example of complementarity and positive interaction between human rights and development by unifying collective human rights with individual human rights and integrating the universality and particularity of human rights.Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,delivered a speech at the 37th group study session of the Political Bureau of the CPC Central Committee on China's Path of Human Rights Development.This elevated China's human rights development to a new historical height.Practice has proved that China's concept and path of human rights in the new era have not only effectively promoted the development of its human rights cause,but also contributed Chinese wisdom to the global cause of human rights and development with a larger concept of human rights.Under the framework of the concept of building a community with a shared future for mankind,the Belt and Road Initiative,and the Global Development Initiative,China has contributed to enhancing the discourse power of developing countries in human rights and building a fairer,more just,more reasonable and more inclusive system for global human rights governance.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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.

Pioneering a New Realm of Human Rights Civilization in the Chinese Path to Modernization——An Overview of the Symposium on“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”

On October 14,2023,a symposium themed“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”was held in Changchun,Jilin Province,China.More than fifty experts,scholars,and researchers from national institutions and universities engaged in discussions and exchanges on human rights on the Chinese path to modernization,including the path,practice,knowledge systems,and civilization forms of human rights.This symposium played a significant role in advancing the construction of the disciplinary system,academic system,and discourse system of human rights in China.

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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.

Expression rates of p16,p53 in head and neck cutaneous squamous cell carcinoma based on human-papillomavirus positivity

BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

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.

Revisiting the Spirit of the UDHR and Discussing Human Rights Development——Summary of Views from the Seminar Commemorating the 75th Anniversary of the Universal Declaration of Human Rights

On December 4,2023,the China Society for Human Rights Studies hosted a seminar in Beijing commemorating the 75^(th) Anniversary of the Universal Declaration of Human Rights.Participants discussed topics such as the significance of the Universal Declaration of Human Rights,China’s theories and practices in respecting and safeguarding human rights,the three global initiatives and global human rights governance,human rights protection in the digital age,and telling Chinese stories of human rights in the new era.The discussions led to a broad consensus and achieved positive results.

Insights into gastrointestinal manifestation of human immunodeficiency virus:A narrative review

Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.

Incorporation of human β-defensin-1 into immunoliposomes to facilitate targeted autophagy therapy of colon carcinoma

Based on the discovery that humanβ-defensin-1(hBD-1)triggers autophagy in colon cancer cells and inhibits proliferation,we proposed the consideration of its druggability.As a protein,its stability,targetability and bioavailability must be improved.Compared with the traditional medicinal chemistry technology,nano-technology is more economical for increasing the druggability of hBD-1 and can be readily scaled up.Here,we propose an immunoliposome system containing hBD-1 to improve its stability and bioavailability.To enhance its targetability,anti-epidermal growth factor receptor(EGFR)antibodies were conjugated to the liposomal bilayer to produce immunoliposomes that can target EGFR,which is highly expressed in colon cancer cells.Although more studies are needed to su-pport clinical trials and large-scale manufacturing,these immunoliposomes have great potential as therapeutics.Thus,immunoliposomes are suitable nanovesicles to improve the druggability of hBD-1;however,additional basic and translational research of these systems is warranted.

Addressing Japan’s disposal of nuclear-contaminated water from the perspective of international human rights law

The discharge of nuclear-contaminated water containing radionuclides into the ocean by Japan will lead to its integration into the entire ecosystem through processes of circulation and biomagnification,eventually entering the human body via the food chain.This poses a substantial risk of irreversible damage to both the ecosystem and human health,a situation that will worsen with the ongoing discharge of such water.The respect and protection of human rights represent an international consensus,and safeguarding fundamental human rights is a substantial obligation that states must undertake in accordance with both international and domestic law.Since the Fukushima nuclear disaster,Japan has continuously violated its international legal obligations to protect human rights in several areas,including the resettlement of disaster victims,the reduction of nuclear radiation levels,and the handling of contaminated water.Such actions have compromised and will continue to compromise the basic human rights of not only its citizens but also those of people worldwide,including environmental rights,the right to life,development rights,and food rights.In the aftermath of the Fukushima meltdown,the public and workers involved in handling nuclear contaminants have been continually exposed to high radiation levels,endangering their rights to life,development,and health.Japan’s inadequate efforts in victim resettlement and environmental restoration have jeopardized the environmental and food rights of its citizens to live healthily and access food in an environment unaffected by nuclear radiation.The release of nuclear-contaminated water poses a risk of Japan’s nuclear pollution to the people of neighboring countries and the global population at large.The principle of human rights underpins the theory of a community with a shared future for humanity,and human rights are a crucial area of China’s active participation in United Nations affairs and global governance.By voicing concerns over Japan’s potential human rights violations globally,China demonstrates its role as a responsible major country.In response to Japan’s breach of legal obligations and human rights violations,China can adopt a reasoned and beneficial approach,including calling on the international community to hold Japan criminally accountable for crimes against humanity under the Rome Statute and advancing scholarly discussions on ecocide and crimes against the marine environment.Furthermore,China should persist in seeking advisory opinions from the International Court of Justice and strive for substantive accountability,utilizing the mechanisms of international human rights organizations to make its voice heard.

On the Theoretical System Development of Contemporary Chinese Outlook on Human Rights

Centering on the systematic construction of human rights theories,Xi Jinping’s discourses on respecting and protecting human rights creatively put forward a series of original theoretical viewpoints and academic propositions,profoundly revealing the basic connotation of a contemporary Chinese outlook on human rights and realizing all-around and deep-level innovation in the construction of a contemporary human rights theoretical system.In ontology,the four-in-one view of human rights of the political party,the government,society,and the people goes beyond the dichotomy between the political state and civil society.In element theory,the substantive view of human rights surpasses the formalist view of human rights.In category theory,the view of human rights focusing on the right to sub-sistence and the right to development transcends the view of human rights based on the individual’s right to freedom.In operation theory,the“development-based human rights path”goes beyond the“human rights-based development path.”In practice,the positive view of human rights based on the rule of law surpasses the negative view of human rights based on the rule of law.

“One Core,Two Sources”:The Endogenous Logic of China’s Path to Develop Human Rights from the Perspective of“Two Integrations”

The development of China’s human rights path is driven by both external and internal factors,influenced by general principles of human rights worldwide while also following China’s own endogenous logic.The concept of the“Two Integrations”reflects the continuous theoretical innovation of the Chinese Communist Party based on China’s national conditions,significantly illustrating the endogenous logic of China’s human rights path.Among these,the“basic principles of Marxism”occupy a“core”position within the endogenous logic of China’s human rights path,and to some extent,embody an understanding of the inherent laws of human rights.Meanwhile,“China’s specific realities”and“fine traditional Chinese culture”serve as the“living water sources”for the ongoing advancement of China’s human rights.The“Two Integrations”represent an intrinsic requirement of historical materialism and practical materialism.The logical structure of“One Core,Two Sources”explains the endogenous nature of China’s human rights path,offering both an interpretation of the driving forces behind China’s human rights path and a defense of its rationality.

Research on the Constitutional,Historical and Practical Logic of the Chinese Path of Human Rights Development——From the Perspective of the Inclusion of Human Rights Clause in the Constitution

The inclusion of the human rights clause in the Chi-nese Constitution is a concern and expression of the spirit of the Con-stitution,which has laid the institutional regulations of the fundamen-tal law for the development of human rights in China,provided the principles and value norms of the highest level of effectiveness for the legal protection of human rights,and built a profound constitutional basis for the formation and improvement of the Chinese path of human rights development.The human rights clause is not only a summariza-tion and affirmation of the historical practice of Chinese human rights development under the leadership of the Communist Party of China,but also a new starting point for the development of human rights in China under the leadership of the Communist Party of China.It marks that the development of human rights in China has entered a new era.The Party and the state have finally embarked on a path of human rights development with Chinese characteristics by formulating and implementing the Human Rights Action Plan of China,eliminating ab-solute poverty through the national poverty alleviation campaign,and promoting human rights protection through the rule of law.

Subclinical hepatitis E virus genotype 1 infection:The concept of“dynamic human reservoir”

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.