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.

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.

Humanβ-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long noncoding RNA TCONS_00014506

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.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

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.

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

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.

Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

The relationship between DNA fragmentation and the intensity of morphologically abnormal human spermatozoa

Objective:To determine the relationship between teratozoospermia and sperm DNA fragmentation(SDF)in the human ejaculate.Methods:This retrospective study included 100 normozoospermic men as a control cohort(abnormal forms>14%),210 patients with a high level of abnormal forms(≤4%)and 65 patients presenting with a moderate level of abnormal forms(>4%to≤14%)based on the World Health Organization definitions.Sperm morphology was assessed using bright field microscopy.Sperm DNA fragmentation was assessed using the sperm chromatin dispersion assay.Non-parametric analyses were conducted to examine the relationship between abnormal sperm morphology and sperm DNA fragmentation;receiver operating characteristic(ROC)analyses were conducted to assess sensitivity and specificity of this relationship.Results:A correlation analysis revealed that the higher the proportion of abnormal spermatozoa in the ejaculate,the higher the level of SDF(Spearman's Rho=-0.230;P<0.001).Significant differences in the proportion of SDF were found when all cohorts were compared(P<0.001);these significant differences were also retained when the different cohorts were compared pairwise.ROC analysis showed a moderate but significant predictive value for SDF to differentiate patients with different levels of teratozoospemia.Conclusions:Although analysis of a more continuous range of values for teratozoospermia would help further clarify any causal relationship with SDF,there is clearly a synergistic or coincident affiliation between these variables that needs to be acknowledged by the clinician when interpreting the spermiogram.

Study on the spatial and temporal evolutionary characteristics of ozone concentration and the impact of human activities in China in 2019

Ozone(O_(3))pollution has a profound impact on human health,vegetation development,and the ecological environment,making it a critical focus of global academic research.In recent years,O_(3)pollution in China has been on a steady rise,with ozone emerging as the sole conventional pollutant to consistently increase in concentration without any decline.This study conducted a quantitative analysis of O_(3)concentrations across 367 Chinese cities in 2019,examining spatial autocorrelation and local clustering of O_(3)levels,and investigated the diverse relationships between human activity factors and O_(3)concentration.The seasonal fluctuation of O_(3)exhibited the“M-type”pattern,with peak concentrations in winter and the lowest levels in summer.The center of O_(3)pollution migrated southeastward,with the area of highest concentration progressively shifting south along the eastern coast.Moreover,O_(3)concentration showed a strong positive correlation with population density,road freight volume,and industrial emissions,suggesting that human activities,vehicle emissions,and industrial operations are significant contributors to O_(3)production.The results provide comprehensive information on the characteristics,causes,and occurrence mechanism of O_(3)in Chinese cities that can be utilized by global government departments to formulate strategies to prevent and control O_(3)pollution.

Homozygous CCDC146 mutation causes oligoasthenoteratozoospermia in humans and mice

Infertility represents a significant health concern,with sperm quantity and quality being crucial determinants of male fertility.Oligoasthenoteratozoospermia(OAT)is characterized by reduced sperm motility,lower sperm concentration,and morphological abnormalities in sperm heads and flagella.Although variants in several genes have been implicated in OAT,its genetic etiologies and pathogenetic mechanisms remain inadequately understood.In this study,we identified a homozygous nonsense mutation(c.916C>T,p.Arg306*)in the coiled-coil domain containing 146(CCDC146)gene in an infertile male patient with OAT.This mutation resulted in the production of a truncated CCDC146 protein(amino acids 1-305),retaining only two out of five coiled-coil domains.To validate the pathogenicity of the CCDC146 mutation,we generated a mouse model(Ccdc146^(mut/mut))with a similar mutation to that of the patient.Consistently,the Ccdc146mut/mut mice exhibited infertility,characterized by significantly reduced sperm counts,diminished motility,and multiple defects in sperm heads and flagella.Furthermore,the levels of axonemal proteins,including DNAH17,DNAH1,and SPAG6,were significantly reduced in the sperm of Ccdc146^(mut/mut) mice.Additionally,both human and mouse CCDC146 interacted with intraflagellar transport protein 20(IFT20),but this interaction was lost in the mutated versions,leading to the degradation of IFT20.This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility,potentially by disrupting axonemal protein transportation.These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.

Quantitative contributions of climate change and human activities to vegetation dynamics in the Zoige Plateau from 2001 to 2020

Climate change and human activities such as overgrazing and rapid development of tourism simultaneously affected the vegetation of the Zoige Plateau.However,the spatiotemporal variations of vegetation and the relative contributions of climate change and human activities to these vegetation dynamics remain unclear.Therefore,clarifying how and why the vegetation on the Zoige Plateau changed can provide a scientific basis for the sustainable development of the region.Here,we investigate NDVI trends using the Normalized Difference Vegetation Index(NDVI)as an indicator of vegetation greenness and distinguish the relative effects of climate changes and human activities on vegetation changes by utilizing residual trend analysis and the Geodetector.We find a tendency of vegetation greening from 2001 to 2020,with significant greening accounting for 21.44%of the entire region.However,browning area expanded rapidly after 2011.Warmer temperatures are the primary driver of vegetation changes in the Zoige Plateau.Climatic variations and human activities were responsible for 65.57%and 34.43%of vegetation greening,and 39.14%and 60.86%of vegetation browning,respectively,with browning concentrated along the Yellow,Black and White Rivers.Compared to 2001-2010,the inhibitory effect of human activity and climate fluctuations on vegetation grew dramatically between 2011 and 2020.

Changes in human settlement environments and their drivers in valley cities located in arid and semi-arid regions:A case study of Lanzhou in Western China

Development of urban human settlement environments(HSEs)is an integral part of promoting high-quality and sustainable regional development and constructing a beautiful China.The city of Lanzhou,located at the geometric center of China,is the only provincial capital traversed by the Yellow River.Given the constraints posed by the valley topography and the need for economic development,the development of this HSE,which is located within an arid region,poses considerable challenges.Evidently,an understanding of the evolution of HSEs and drivers of changes in them contributes to high-quality,sustainable urban development in arid and semi-arid regions.An analytical model was developed using the parameters of relief degree of land surface,human comfort days,the land cover index,nighttime light index,and precipitation.This model was used in combination with population density and the gross domestic product to analyze the spatial distribution of Lanzhou's HSE and its drivers.The results showed that landscapes in Lanzhou underwent significant changes between 2000 and 2022,with an increase in building-up land(+0.946%),cultivated land(+0.134%),and forest land(+0.018%)and a decrease in grassland(-1.10%).There was significant outward expansion of the main urban zone of Lanzhou and of various county towns,with the increase in building-up land being most prominent.During this period,there were significant changes in the periphery of the core urban area and county towns in Lanzhou,with decreases moving from the urban center(the highest value)to the surrounding areas(Yongdeng County had the lowest value).The correlation between the HSE and population density grew stronger in Anning and Chengguan Districts but became weaker in Xigu and Qilihe Districts.Spatiotemporal variations in the HSE were primarily caused by climate change,followed by human activities,and were also influenced by the valley topography.Overall,the spatial distribution of population density and the HSE in Lanzhou demonstrated good consistency under the in-fluence of economic development and urbanization.

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae plants.It also has anti-infection,antitumor,and immunomodulatory effects.In this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and U251-MG.However,the mechanism through which honokiol regulates glioma cell apoptosis is still unknown.Methods:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control cells.Protein-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative PCR.Furthermore,MAPK signaling and ferroptosis were detected via western blotting.Results:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased genes.Analysis of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were verified.Conclusion:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling pathways.These data could lead to new ideas for future research and therapy for patients with glioma.

Erratum to “The enriched gut commensal Faeciroseburia intestinalis contributes to the anti-metabolic disorders effects of the Ganoderma meroterpene derivative” [Food Science and Human Wellness 11 (2022) 85-96]

The authors were contacted after publication to request a replacement of Fig.2M in the manuscript.Unfortunately,the authors inadvertently used an image of the model(Vehicle)group liver histopathology section that matches an image published in Fig.2D of Cell Reports(Volume 26,Issue 1,pages 222–235.e5).

Coupled effects of climate change and human activities on vegetation dynamics in the Southwestern Alpine Canyon Region of China

The driving effects of climate change and human activities on vegetation change have always been a focal point of research.However,the coupling mechanisms of these driving factors across different temporal and spatial scales remain controversial.The Southwestern Alpine Canyon Region of China(SACR),as an ecologically fragile area,is highly sensitive to the impacts of climate change and human activities.This study constructed a vegetation cover dataset for the SACR based on the Enhanced Vegetation Index(EVI)from 2000 to 2020.Spatial autocorrelation,Theil-Sen trend,and Mann-Kendall tests were used to analyze the spatiotemporal characteristics of vegetation cover changes.The main drivers of spatial heterogeneity in vegetation cover were identified using the optimal parameter geographic detector,and an improved residual analysis model was employed to quantify the relative contributions of climate change and human activities to interannual vegetation cover changes.The main findings are as follows:Spatially,vegetation cover exceeds 60%in most areas,especially in the southern part of the study area.However,the border area between Linzhi and Changdu exhibits lower vegetation cover.Climate factors are the primary drivers of spatial heterogeneity in vegetation cover,with temperature having the most significant influence,as indicated by its q-value,which far exceeds that of other factors.Additionally,the interaction q-value between the two factors significantly increases,showing a relationship of bivariate enhancement and nonlinear enhancement.In terms of temporal changes,vegetation cover shows an overall improving trend from 2000 to 2020,with significant increases observed in 68.93%of the study area.Among these,human activities are the main factors driving vegetation cover change,with a relative contribution rate of 41.31%,while climate change and residual factors contribute 35.66%and 23.53%,respectively.By thoroughly exploring the coupled mechanisms of vegetation change,this study provides important references for the sustainable management and conservation of the vegetation ecosystem in the SACR.

Spatial distribution of soil salinization under the influence of human activities in arid areas,China

The Hotan Prefecture of Xinjiang Uygur Autonomous Region,China belongs to arid desert climate,with significant soil salinization issues.The study selected six rivers in Hotan Prefecture(Pishan,Qaraqash,Yurungqash,Celle,Kriya,and Niya rivers)to explore the spatial distribution of soil salinization in this area and its underlying mechanisms.Sampling was conducted along each river's watershed,from the Gobi in the upper reaches,through the anthropogenic impact area in the middle reaches,to the desert area in the lower reaches.Soil physical-chemical indicators,including total soluble salts,pH,K+,Na+,Ca2+,Mg2+,SO42-,Cl-,CO32-,HCO3-,organic matter,available nitrogen,available phosphorus,and available potassium,were tested,along with the total dissolved solids of surface water and groundwater.The results revealed that the soil water and nutrient contents in anthropogenic impact area were higher than those in Gobi and desert areas,while the pH and total soluble salts were lower than those in Gobi and desert areas.The ions in the soil of the study area were primarily Cl-,SO42-,K+,and Na+,and the ion concentration of soil salt were positively correlated with surface water and groundwater.Overall,the study area exhibited low soil water content,low clay content,infertile soil,and high soil salinization,dominated by weak to moderate chloride-sulfate types.Compared with Gobi and desert areas,the soil in anthropogenic impact area had higher soil water content,lower pH,lower soluble salts,and higher nutrients,indicating that human farming activities help mitigate salinization.These findings have practical implications for guiding the scientific prevention and control of soil salinization in the arid areas and for promoting sustainable agricultural development.

Responses of runoff to changes in climate and human activities in the Liuhe River Basin, China

Since the 1950s,numerous soil and water conservation measures have been implemented to control severe soil erosion in the Liuhe River Basin(LRB),China.While these measures have protected the upstream soil and water ecological environment,they have led to a sharp reduction in the downstream flow and the deterioration of the river ecological environment.Therefore,it is important to evaluate the impact of soil and water conservation measures on hydrological processes to assess long-term runoff changes.Using the Soil and Water Assessment Tool(SWAT)models and sensitivity analyses based on the Budyko hypothesis,this study quantitatively evaluated the effects of climate change,direct water withdrawal,and soil and water conservation measures on runoff in the LRB during different periods,including different responses to runoff discharge,hydrological regime,and flood processes.The runoff series were divided into a baseline period(1956-1969)and two altered periods,i.e.,period 1(1970-1999)and period 2(2000-2020).Human activities were the main cause of the decrease in runoff during the altered periods,contributing 86.03%(-29.61 mm),while the contribution of climate change was only 13.70%(-4.70 mm).The impact of climate change manifests as a decrease in flood volume caused by a reduction in precipitation during the flood season.Analysis of two flood cases indicated a 66.00%-84.00%reduction in basin runoff capacity due to soil and water conservation measures in the upstream area.Soil and water conservation measures reduced the peak flow and total flood volume in the upstream runoff area by 77.98%and 55.16%,respectively,even with nearly double the precipitation.The runoff coefficient in the reservoir area without soil and water conservation measures was 4.0 times that in the conservation area.These results contribute to the re-evaluation of soil and water conservation hydrological effects and provide important guidance for water resource planning and water conservation policy formulation in the LRB.

The Crested Ibises expanding to plain areas exhibit a higher tolerance of human proximity

Animals must strike a balance between anti-predation behavior and other essential behaviors,such as foraging.Within the same species,strategies may vary on individuals’risk-taking preferences,and in this process the environment is a determinant,in addition to predator regime.The Crested Ibis(Nipponia nippon)exhibits such tendency.This is an endangered species,once inhabiting exclusively in China’s Qinling Mountain.This used to be the sole remaining wild population.However,over recent decades,this population has expanded.A portion has relocated to breed in the lower plain area,which is characterized by elevated level of human activities and landscape complexity.We used flight initiation distance(FID)as an indicator of the ibises’risk-taking preference,particularly their response to human proximity.Additionally,we examined the environmental factors influencing their foraging site selection,including altitude,terrain openness,human activity intensity and human construction.Our findings revealed a significantly shorter FID among individuals relocating to plain habitats,indicating a higher tolerance of human proximity.The results showed that FID decreased with distance to the nearest human settlement.Another finding is that FID was independent of instant human activity intensity and environmental factors(altitude and terrain openness).These different may arise from various combinations of human activity,predation risk,and food abundance within the two habitats.These results provide insights into the in situ conservation of the threatened species within the context of global urbanization.

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.

Against all odds:The road to success in the development of human immune reconstitution mice

The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.

Inhibition of viability of human retinal microvascular endothelial cells by vialinin A under high glucose condition

AIM:To investigate the effects of vialinin A on viability of human retinal endothelial cells(HRECs)under high glucose condition and its potential mechanism.METHODS:The HRECs were divided into four groups:normal glucose control group(NG,5 mmol/L D-glucose),high glucose group(HG,30 mmol/L D-glucose),HG+1μmol/L vialinin A group,and HG+5μmol/L vialinin A group.The cell viabilities were measured with cell counting kit-8(CCK-8)assay for proliferation,with scratch assay for migration,and tube formation,for evaluation of the impact of vialinin A on cellular behaviour.Real-time PCR and Western blotting were used to determine the expression level of vascular endothelial growth factor(VEGF).RESULTS:The proliferative capacity and migration of HRECs was reduced by 5μmol/L vialinin A in high glucose environment(both P<0.05).Vialinin A also inhibited highglucose-induced tube formation of HRECs.The expression level of VEGF and PI3K in HRECs was also significantly decreased by vialinin A(P<0.05).CONCLUSION:Vialinin A inhibits the cell viability of HRECs.It may serve as a potential target for anti-angiogenic therapy.