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.

Expression of hepatitis B virus genes in early embryonic cells originated from hamster ova and human spermatozoa transfected with the complete viral genome

Aim： To detect the expression of hepatitis B virus （HBV） genes （HB S and C genes） in early embryonic cells after introducing motile human sperm carrying HBV DNA into zona-free hamster oocytes via the in vitro fertilization （IVF） technique. Methods： Human sperm-mediated HBV genes were delivered into zona-free hamster oocytes by the IVF method. Polymerase chain reaction （PCR） was used to detect HB S and pre-Core/Core （pre-C/C） coding genes both in one- and two-cell embryos. Reverse transcription-PCR （RT-PCR） analysis was used to study the expression of the two genes. Fluorescence in situ hybridization （FISH） analysis using the full-length HBV DNA as the hybridization probe was performed to confirm the integration of viral DNA in the host embryonic genome. Results： Both HB S and pre-C/C coding genes are present and transcribed in one- and two-cell embryos originated from hamster ova IVF with human spermatozoa carrying HBV DNA sequences. Conclusion： Sperm-mediated HBV genes are able to replicate and express themselves in early embryonic cells. These results provide direct evidence that HBV DNA could transmit vertically to the next generation via the male germ line.

The expression and significance of CATSPER1 in human testis and ejaculated spermatozoa

Aim： To investigate the distribution of cation channel of sperm 1 （CATSPER1） protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon human sperm motility was used to evaluate the function of human CATSPER1 and to estimate its possible use as a target for immunocontraception. Methods： Human ejaculated sperm from normozoospermic donors （n = 12） and liquid nitrogen frozen human testis were used for the study of mRNA and protein expression of CATSPER1 by reverse transcription polymerase chain reaction （RT-PCR） and immunohistochemistry, respectively. Spermatozoa from normozoospermic donors （n = 12） were individually processed using a swim-up procedure and were then incubated with CATSPER1 antibody at final concentrations of 20, 4 and 0.8 μg/mL. After 1, 2 and 6 h incubation, progressive motility and fast progressive motility were measured by means of computer-assisted semen analysis. Results： CATSPER1 transcript was detected in both human testis and each human ejaculated semen sample. CATSPER1 protein expressed in the membrane of spermatid and was localized in the principal piece of the sperm tail. The application of CATSPER1 antibody at all concentrations significantly inhibited both progressive motility and fast progressive motility after 1, 2 and 6 h incubation, and significant dose-dependent changes were observed. Conclusion： CATSPER1 is meiotically and post-meiotically expressed in human testis tissue. CATSPER1 mRNA in human ejaculated spermatozoa could be a more feasible target for study and infertility screening than testis biopsy. In addition, our results suggest that human CATSPER1 could be a possible target for immunocontraception.

Cryopreservation-induced decrease in heat-shock protein 90 in human spermatozoa and its mechanism

<abstract>Aim: To study the protein changes of spermatozoa associated with sperm motility during sperm cryopreservation and its mechanism. Methods: In 18 healthy men, the seminal sperm motility and HSP90 levels were studied before and after cryopreservation using SDS-PAGE, Western blotting and computerized image analysis. Results: The sperm motility declined significantly after cryopreservation (P<0.01). The average grey level and the integrated grey level of sperm HSP90 before cooling were 34.1±3.2 and 243.0±21.6, respectively, while those after thawing were 23.2±2.5 and 105.7±28.5, respectively. Both parameters were decreased significantly (P<0.01). No HSP90 was found in the seminal plasma before and after cryopreservation. Conclusion: HSP90 in human spermatozoa was decreased substantially after cryopreservation. This may result from protein degradation, rather than leakage into the seminal plasma.

Estimate of oxygen consumption and intracellular zinc concentration of human spermatozoa in relation to motility

<abstract>Aim: To investigate the human sperm oxygen/energy consumption and zinc content in relation to motility. Methods: In washed spermatozoa from 67 ejaculates, the oxygen consumption was determined. Following calculation of the total oxygen consumed by the Ideal Gas Law, the energy consumption of spermatozoa was calculated. In addition, the zinc content of the sperm was determined using an atomic absorption spectrometer. The resulting data were correlated to the vitality and motility. Results: The oxygen consumption averaged 0.24μmol/106 sperm×24 h, 0.28μmol/106 live sperm×24 h and 0.85μmol/106 live & motile sperm×24 h. Further calculations revealed that sperm motility was the most energy consuming process (164.31 mJ/106 motile spermatozoa×24 h), while the oxygen consumption of the total spermatozoa was 46.06 mJ/106 spermatozoa×24 h. The correlation of the oxygen/ energy consumption and zinc content with motility showed significant negative correlations (r= -0.759; P<0.0001 and r=-0.441; P<0.0001, respectively). However, when correlating sperm energy consumption with the zinc content, a significant positive relation (r=0.323; P=0.01) was observed. Conclusion: Poorly motile sperm are actually wasting the available energy. Moreover, our data clearly support the 'Geometric Clutch Model' of the axoneme function and demonstrate the importance of the outer dense fibers for the generation of sperm motility, especially progressive motility.

Destabilization of acrosome and elastase influence mediate the release of secretory phospholipase A2 from human spermatozoa

Aim： To determine the cellular distribution of secretory phospholipase A2 （sPLA2） in dependence on the acrosomal state and under the action of elastase released under inflammatory processes from leukocytes. Methods： Acrosome reaction of spermatozoa was triggered by calcimycin. Human leukocyte elastase was used to simulate inflammatory conditions. To visualize the distribution of sPLA2 and to determine the acrosomal state, immunofluorescence techniques and lectin binding combined with confocal laser scanning fluorescence microscopy and flow cytometry were used. Results： Although sPLA2 was detected at the acrosome and tail regions in intact spermatozoa, it disappeared from the head region after triggering the acrosome reaction. This release of sPLA2 was associated with enhanced binding of annexin V-fluoroscein isothiocyanate （FITC） to spermatozoa surfaces, intercalation of ethidium-homodimer I, and binding of FITC-labelled concanavalin A at the acrosomal region. Spermatozoa from healthy subjects treated with elastase were characterized by release of sPLA2, disturbance of acrosome structure, and loss of vitality. Conclusion： The ability of spermatozoa to release secretory phospholipase A2 is related to the acrosomal state. Premature destabi- lization of the acrosome and loss of sPLA2 can occur during silent inflammations in the male genital tract. The distribution pattern of sPLA2 in intact spermatozoa might be an additional parameter for evaluating sperm quality.

Acetyl-L-carnitine:An Effective Antioxidant against Cryo-damage on Human Spermatozoa with Asthenospermia

A variety of natural and artificial cryoprotectant extenders have been explored to enhance sperm recovery following cryopreservation-thawing process. The current investigation is aimed at evaluating the effect of acetyl-L-carnitine on human spermatozoa and reactive species oxygen（ROS） level after freezing-thawing process. The spermatozoa were collected from 35 male patients diagnosed as having asthenospermia. The cryopreservation of human spermatozoa treated with acetyl-L-carnitine at different concentrations（group B： 2.5 mmol/L, group C： 7.5 mmol/L, group D： 15 mmol/L） was compared with control（group A： no acetyl-L-carnitine given）. For the frozen-thawed spermatozoa, the viability, motility and DNA integrity were measured by comet assay, acrosome integrity by FITC-PNA staining and ROS level was determined in each group. The results showed that there were no significant differences in motility and viability between group A and group B, while the motility and viability of spermatozoa in group C and group D were significantly increased as compared with those in group A. As compared with group A, the values for DNA integrity parameters including comet rate（CR）, tail DNA percentage（TD）, tail length（TL） and Oliver tail moment（OTM） were significantly reduced in group C and group D. Group C and group D also displayed a higher proportion of intact acrosome than group A. No significant difference in ROS level was found between group A and group B, while with the increase in acetyl-L-carnitine concentration, the ROS level in groups C and D was significantly reduced as compared with that in group A. In conclusion, acetyl-L-carnitine at a concentration of 7.5 mmol/L is an effective antioxidant against cryo-damage on post-thawed human spermatozoa.

Shortening of alkaline DNA unwinding time does not interfere with detecting DNA damage to mouse and human spermatozoa in the comet assay

The comet assay was performed on mouse and human spermatozoa to examine the effect of alkaline DNA unwinding time. The spermatozoa were treated in vitrowith the DNA-damaging agents, methyl methanesulfonate （MMS） or hydrogen peroxide （Hz02）, and then embedded in agarose gel on glass sl ides. The slides were immersed in alkaline solution （〉pH 13） for 1, 5, 10 and 20 min, and then subjected to the electrophoresis under neutral conditions. In mouse spermatozoa, comet tails seen in solvent controls became brighter and longer as the alkaline DNA unwinding time increased. However, in the MMS-treated mouse spermatozoa, a smaller difference in the damage from that in the solvent control was seen with time within a dose. DNA damage induced by H2O2 could also be detected accurately after alkali treatment for 1-20 min. In human spermatozoa, DNA damage induced by MMS and H2O2 could be detected in a dose-dependent manner after alkali treatment for 1 min. The ability of the comet assay to detect DNA damage was not adversely affected by the short period （1 min） of the alkaline DNA unwinding time.

Adriamycin induces H2AX phosphorylation in human spermatozoa

Aim： To investigate whether adriamycin induces DNA damage and the formation of γH2AX （the phosphorylated form of histone H2AX） foci in mature spermatozoa. Methods： Human spermatozoa were treated with adriamycin at different concentrations, γH2AX was analyzed by immunofluorescent staining and flow cytometry and doublestrand breaks （DSB） were detected by the comet assay. Results： The neutral comet assay revealed that the treatment with adriamycin at 2 μg/mL for different times （0.5, 2, 8 and 24 h）, or for 8 h at different concentrations （0,4, 2 and 10 μg/mL）, induced significant DSB in spermatozoa. Immunofluorent staining and flow cytometry showed that the expression of γH2AX was increased in a dose-dependent and time-dependant manner after the treatment of adriamycin. Adriamycin also induced the concurrent appearance of DNA maintenance/repair proteins RAD50 and 53BP 1 with γH2AX in spermatozoa. Wortmannin, an inhibitor of the phosphatidylinositol 3-kinase （PI3K） family, abolished the co-appearance of these two proteins with γH2AX. Conclusion： Human mature spermatozoa have the same response to DSB-induced H2AX phosphorylation and subsequent recruitment of DNA maintenance/ repair proteins as somatic cells.

Establishment of a high-resolution 2-D reference map of human spermatozoal proteins from 12 fertile sperm-bank donors

Aim： To extend the analysis of the proteome of human spermatozoa and establish a 2-D gel electrophoresis （2-DE） reference map of human spermatozoal proteins in a pH range of 3.5-9.0. Methods： In order to reveal more protein spots, immobilized pH gradient strips （24 cm） of broad range of pH 3-10 and the narrower range of pH 6-9, as well as different overlapping narrow range pH immobilized pH gradient （IPG） strips, including 3.5-4.5, 4.0-5.0, 4.5-5.5, 5.0-6.0 and 5.5-6.7, were used. After 2-DE, several visually identical spots between the different pH range 2-D gel pairs were cut from the gels and confirmed by mass spectrometry and used as landmarks for computer analysis. Results： The 2-D reference map with pH value from 3.5 to 9.0 was synthesized by using the ImageMaster analysis software. The overlapping spots were excluded, so that every spot was counted only once. A total of 3 872 different protein spots were identified from the reference map, an approximately 3-fold increase compared to the broad range pH 3-10 IPG strip （1 306 spots）. Conclusion： The present 2-D pattern is a high resolution 2-D reference map for human fertile spermatozoal protein spots. A comprehensive knowledge of the protein composition of human spermatozoa is very meaningful in studying dysregulation of male fertility.

The expression of vitronectin,a ligand of integrin,on human spermatozoa and its role in fertilization

Objective: To study the vitronectin expression in human spermato-zoa and its role in fertilization. Methods: Spermatozoa from 14 fer-tile and 8 infertile men with normal semen data were studied. Follow-ing recovery of motile populations by swim-up, spermatozoa were ca-pacitated and immunostained with rabbit anti-human Vn polyclonal an-tibody and goat anti-rabbit IgG-FTTC second antibody. The percentageof spermatozoa expressing Vn was determined using a FAScan flowcytometer. Meanwhile, the fertilizing ability of capacitated spermato-zoa was determined with human spermatozoa zona-free hamster eggpenetration assay (SPA). Results: The mean ± s proportion ofspermatozoa expressing Vn of fertile men was 21.24% ± 11.70% and3.64±3.27% for infertile men (P<0.05). The penetration rate ofSPA in the fertile group was > 10%, but that in the infertile group ,< 10%. There is a correlation between positive sperm Vn expressionand percentage of eggs penetrated (r=0.476). Conclusion: Theseresults indicate the expression of Vn in human capacitated spermatozoaand its correlation with the fertilizing ability. The abnormal expressionof Vn on human spermatozoa may be one of the unexplained infertilereasons. (Reprod Contracep 2001; 21: 24-28)

Expression of hepatitis B virus genes in early embryonic cells originated from hamster ova and human spermatozoa transfected with the complete viral genome

Aim:To detect the expression of hepatitis B virus(HBV)genes(HB S and C genes)in early embryonic cells after introducing motile human sperm carrying HBV DNA into zona-free hamster oocytes via the in vitro fertilization(IVF) technique.Methods:Human sperm-mediated HBV genes were delivered into zona-free hamster oocytes by the IVF method.Polymerase chain reaction(PCR)was used to detect HB S and pre-Core/Core(pre-C/C)coding genes both in one-and two-cell embryos.Reverse transcription-PCR(RT-PCR)analysis was used to study the expression of the two genes.Fluorescence in situ hybridization(FISH)analysis using the full-length HBV DNA as the hybridization probe was performed to confirm the integration of viral DNA in the host embryonic genome.Results:Both HB S and pre-C/C coding genes are present and transcribed in one-and two-cell embryos originated from hamster ova IVF with human spermatozoa carrying HBV DNA sequences.Conclusion:Sperm-mediated HBV genes are able to replicate and express themselves in early embryonic cells.These results provide direct evidence that HBV DNA could transmit vertically to the next generation via the male germ line.

From Digital Human Modeling to Human Digital Twin: Framework and Perspectives in Human Factors

The human digital twin(HDT)emerges as a promising human-centric technology in Industry 5.0,but challenges remain in human modeling and simulation.Digital human modeling(DHM)provides solutions for modeling and simulating human physical and cognitive aspects to support ergonomic analysis.However,it has limitations in real-time data usage,personalized services,and timely interaction.The emerging HDT concept offers new possibilities by integrating multi-source data and artificial intelligence for continuous monitoring and assessment.Hence,this paper reviews the evolution from DHM to HDT and proposes a unified HDT framework from a human factors perspective.The framework comprises the physical twin,the virtual twin,and the linkage between these two.The virtual twin integrates human modeling and AI engines to enable model-data-hybrid-enabled simulation.HDT can potentially upgrade traditional ergonomic methods to intelligent services through real-time analysis,timely feedback,and bidirectional interactions.Finally,the future perspectives of HDT for industrial applications as well as technical and social challenges are discussed.In general,this study outlines a human factors perspective on HDT for the first time,which is useful for cross-disciplinary research and human factors innovation to enhance the development of HDT in industry.

Apoptosis and DNA damage in human spermatozoa

DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apeptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.

Relationship between acrosin activity of human spermatozoa and oxidative stress

Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P <0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.

Preparation and incubation conditions affect the DNA integrity of ejaculated human spermatozoa

Appropriate semen processing and assessment are critical for successful infertility treatment. We investigated whether laboratory procedures including semen preparation and incubation affect sperm DNA integrity. A total of 153 infertile men were involved. Conventional semen parameters and sperm chromatin structure assay （SCSA） parameters, that is, DNA fragmentation index （%DFI） and high DNA stainability （%HDS）, were assessed on the flesh ejaculated semen samples, which were treated and incubated under different conditions. Negative correlations were identified between the %DFI and sperm concentration, motility, progressive motility and morphology. A lower percentage of DFI was detected in spermatozoa when density gradient centrifugation （DGC） was followed by swimup treatment in comparison with DGC alone （P 〈 0.01）. Although the %DFI increased in a time-dependent manner with incubation both at room temperature （RT） and at 37℃ in air, the %DFI after 24 h at RT was significantly lower than that at 37℃ （P 〈 0.05）. Incubation with 5% CO2 was effective in maintaining sperm motility （P 〈 0.01）; however, it induced further elevation of %DFI （P 〈 0.001）. Thus, sperm DNA damage was associated with longer incubation periods. Interestingly, common culture conditions, such as maintaining pH and temperature, compromised the sperm DNA integrity.

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects, In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included （i） the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; （ii） the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and （iii） inhibition of hydrogen peroxide diffusion across the sperm membrane.

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.

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.