Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is uncl...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent repro...Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent reprogramming within the tumor microenvironment(TME)into highly immunosuppressive phenotypes that facilitate cancer dissemination and immunotherapy resist-ance1,2.We contend that an underappreciated,upstream determinant of this divergence is the maturation stage of TANs3,4.The developmental stage of TANs determines the migration patterns and constrains the functional capacity,and the developmental stage also constrains the extent of TME-driven re-education,together shaping pro-or anti-tu-mor outcomes3-5.In this Perspective,we place maturation at the core of TAN biology and discuss current definitions for TAN developmental stages and the measurable mark-ers that researchers and clinicians can use(Figure 1).In addition,spatial and temporal transitions in TAN matu-ration stages and the factors that govern these transitions are elucidated.We explain how maturation status shapes TAN function and articulate the key differences between mouse and human TAN maturation systems to highlight the value of human immune system(HIS)mouse models.Based on this framework,functional biomarkers and signa-tures of TAN maturation are introduced and we show how to embed them into patient stratification and longitudinal monitoring.Finally,we outline immunotherapy strategies targeting TAN maturation,selecting interventions guided by maturation markers to reinforce treatment benefits for cancer patients.展开更多
Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biologica...Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biological maturity and the limitations of existing testing methods, particularly in adolescent sports contexts, there is a pressing need for a non-invasive method that is convenient, accurate, and broadly applicable to monitor the biological maturity of adolescent athletes comprehensively. In response to this need, a maturity assessment method based on the smartphone application Maturo has been developed. This study evaluates the accuracy and validity of the Maturo software, an automated tool for estimating biological age and related maturation metrics.Methods: A sample of 103 actively training teenage athletes aged 9-17 years. The sample included 76 males(age = 11.74 ± 1.55 years, mean ±SD) and 27 females(age = 13.95 ± 1.40 years), all without medical conditions that might impact growth or development.Results: Compared to traditional expert evaluations, the intraclass correlation coefficients(ICCs) and Pearson correlation coefficients demonstrated reliable positive correlations and significant agreement between the Maturo software and expert methods across multiple metrics, such as biological age(ICC = 0.965, R = 0.97), corrected biological age(ICC = 0.973, R = 0.99), predicted adult height(ICC = 0.991, R = 0.99), and percentage of adult height achieved(ICC = 0.955, R = 0.97). The Bland-Altman plots provided additional evidence of the validity of the Maturo software estimations, showing low systematic error in most measures. The linear regression analysis produced excellent adjusted R2values: 0.95for biological age and 0.99 for anticipated adult height. The Maturo approach demonstrated a high level of dependability in classifying teenagers into groups based on their maturity status and timing. The κ coefficients of 0.93 for maturity status and 0.82 for maturity timing indicate a nearly perfect agreement with the expert technique.Conclusion: While the Maturo software's non-invasive nature, cost-effectiveness, and ease of use could make it a potential tool for regular monitoring of growth and maturation in young athletes, its promising results in assessing maturation should be interpreted with caution due to limitations such as sample size and demographic constraints. Further longitude research with larger and more diverse populations is needed to validate these preliminary findings and strengthen the evidence for its broader applicability.展开更多
Sexual maturation heterosis has been widely exploited in animal crossbreeding.However,the underlying mechanism has been rarely explored in chicken.In the present study,we performed the reciprocal crossing between Whit...Sexual maturation heterosis has been widely exploited in animal crossbreeding.However,the underlying mechanism has been rarely explored in chicken.In the present study,we performed the reciprocal crossing between White Leghorn and Beijing You chicken to evaluate the phenotypes related to sexual maturation,and profiled the ovary circRNAs of purebreds(WW,YY)and crossbreds(WY,YW)to elucidate the molecular mechanism underlying heterosis for sexual maturation.Pubic space and oviduct length exhibited positive heterosis,and age at first egg(AFE)exhibited negative heterosis in the crossbreds.We identified 3,025 known circRNAs and 624 putative circRNAs,which were mainly derived from the exons.Among these circRNAs,141 and 178circRNAs were specially expressed in WY and YW,respectively.There were 52.38 and 64.63%of total circRNAs in WY and YW exhibited non-additive expression pattern,respectively.GO enrichment and KEGG pathway analysis showed that the host genes of non-additive circRNAs were mainly involved in TGF-beta signaling pathway,oocyte development,ATPase activator activity,oocyte meiosis,progesterone-mediated oocyte maturation and GnRH signaling pathway.Weighted gene co-expression network analysis identified that 4 modules were significantly(P<0.05)correlated with oviduct length and pubic space.The host genes of non-additive circRNAs harbored in the 4 modules were associated with MAPK signaling pathway and Wnt signaling pathway.Furthermore,competing endogenous RNAs(ceRNA)network analysis characterized non-additive circRNAs gal-FGFR2_0005 and galMAPKAP1_0004 could interact with gga-miR-1612 and gga-miR-12235-5p to regulate CNOT6,COL8A1,and FHL2,which were essential for ovary development,indicating that the non-additive circRNAs involved in the formation of sexual maturation heterosis through regulating genes related to the reproductive and developmental process.The findings would provide a deeper understanding of the molecular mechanism underlying sexual maturation heterosis from a novel perspective.展开更多
Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures.Cranial neural crest cells are specified at the neural plate border,migrate to pharyngeal arches,and differentiate into pharyn...Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures.Cranial neural crest cells are specified at the neural plate border,migrate to pharyngeal arches,and differentiate into pharyngeal chondrocytes,which subsequently flatten,elongate,and stack like coins during maturation.Although the developmental processes prior to chondrocyte maturation have been extensively studied,their subsequent changes in morphology and organization remain largely elusive.Here,we show that wnt2bb is expressed in the pharyngeal ectoderm adjacent to the chondrogenic precursor cells in zebrafish.Inactivation of Wnt2bb leads to a reduction in nuclearβ-catenin,which impairs chondrogenic precursor proliferation and disrupts chondrocyte morphogenesis and organization,eventually causing a severe shrinkage of pharyngeal cartilages.Moreover,the decrease ofβ-catenin in wnt2bb^(-/-)mutants is accompanied by the reduction of Yap expression.Reactivation of Yap can restore the proliferation of chondrocyte progenitors as well as the proper size,shape,and stacking of pharyngeal chondrocytes.Our findings suggest that Wnt/β-catenin signaling promotes Yap expression to regulate pharyngeal cartilage formation in zebrafish.展开更多
Seed maturation is a critical development transition and it largely affects the final yield and quality of crops.Abscisic acid(ABA)-activated sucrose-non-fermentation kinase subfamily 2(SnRK2s)constitute a well-known ...Seed maturation is a critical development transition and it largely affects the final yield and quality of crops.Abscisic acid(ABA)-activated sucrose-non-fermentation kinase subfamily 2(SnRK2s)constitute a well-known regulatory network that modulate seed maturation in Arabidopsis;however,the underlying genetic and regulatory mechanisms in cereal crops remain largely unknown.Here,we found that ABA levels exhibited two distinct peaks during kernel development in maize,corresponding to the lag and maturation phase,respectively.Integrated transcriptome and proteome profiling of kernels treated with exogenous ABA at the pre-maturation stage suggested that the second peak of ABA acts as a trigger for kernel maturation program.Knockout of ZmSnRK2s demonstrated that subclassⅢZmSnRK2s are required for kernel maturation in maize,and the loss-of-function of subclassⅢZmSnRK2s showed a disruption in kernel dehydration and dormancy.We identified a conserved ABA–SnRK2–b ZIP signaling pathway mediating this process in maize.Additionally,ZmSnRK2.10 overexpression accelerates kernel dehydration during maturity,achieving reduced kernel moisture content(KMC)at physiological maturity(PM).Overall,our findings establish ABA-activated SnRK2s as central regulators of kernel maturation in maize and provide valuable genetic resources for breeding maize varieties with low moisture content at harvest.展开更多
Rising global energy needs have intensified the search for unconventional hydrocarbon sources,especially in under-selected areas like the Northeast Java Basin.This region harbors promising unconventional hydrocarbon r...Rising global energy needs have intensified the search for unconventional hydrocarbon sources,especially in under-selected areas like the Northeast Java Basin.This region harbors promising unconventional hydrocarbon reserves,where source rocks function as dual-phase systems for both hydrocarbon generation and storage.This research investigates how metal-based catalysts,particularly iron(Fe),can expedite hydrocarbon maturation in such reservoirs.Combining well logging,geochemical assessments,seismic data,and advanced lab techniques,including X-ray Diffraction(XRD),we pinpoint optimal zones for exploration.Results indicate that the Tuban,Kujung,and Ngimbang formations contain economically viable unconventional deposits,exhibiting tight reservoir properties(permeability:0.01–1 md)and moderate to good Total Organic Carbon(TOC)levels(1%–2%).Spatial analysis reveals elevated density concentrations in the northern sector,indicative of high-viscosity hydrocarbons typical of unconventional plays.Crucially,Fe additives were found to markedly enhance organic matter conversion,shortening maturation periods and boosting hydrocarbon yield.XRD data confirms that Fe alters crystalline configurations,increasing reactivity and speeding up thermal breakdown(shifting immature organic compounds toward maturity at an accelerated rate).These findings contribute to the evolving discourse on unconventional resource exploitation by proposing an innovative recovery enhancement strategy.The study also sets a precedent for investigating metal-assisted hydrocarbon conversion in geologically comparable basins globally.展开更多
[Objective] The study aimed to provide references for the time of oocyte maturation in vitro and enucleation in the course of sheep nuclear transfer(NT).[Method] Compared the effects of different maturation time of oo...[Objective] The study aimed to provide references for the time of oocyte maturation in vitro and enucleation in the course of sheep nuclear transfer(NT).[Method] Compared the effects of different maturation time of oocytes on enucleation efficiency and reconstructed embryo development by means of blind enucleation and fluorescence microscopy.[Result] Treatment of IVM(in vitro maturation)19-21 h was significantly higher than IVM 16-18 h treatment in oocyte maturation rate(P<0.05)and was significantly higher than IVM 22-24 h treatment in enucleation rate(P<0.05).Three treatments had no significant difference in cleavage rate and blastocyst rate(P>0.05),but IVM 19-21 h treatment was significantly higher than the other 2 treatments in average cell number of blastocysts(P<0.05).[Conclusion] The appropriate in vitro maturation time of oocytes was 19-21 h for sheep nuclear transfer,which could significantly improve the quality of blastocysts according to the cell number per blastocyst(P<0.05).展开更多
p28, a 28kD protein from toad (Bufo bufo gargarizans) oocytes, was identified by using p13sucl-agarose affinity chromatography. Sequence homology analysis of the full-length cDNA of p28 (Gene Bank accession number: AF...p28, a 28kD protein from toad (Bufo bufo gargarizans) oocytes, was identified by using p13sucl-agarose affinity chromatography. Sequence homology analysis of the full-length cDNA of p28 (Gene Bank accession number: AF 314091) indicated that it encodes a protein containing 224 amino-acids with about 55% identities and more than 70% positives to human, rat or mouse UCH-L1, and contains homological functional domains of UCH family. Anti-p28 monoclonal antibody, on injecting into the oocytes, could inhibit the progesterone-induced resumption of meiotic division in a dose-dependent manner. The recombinant protein p28 showed similar SDS/PAGE behaviors to the native one, and promoted ubiquitin ethyl ester hydrolysis, a classical catalytic reaction for ubiquitin carboxyl terminal hydrolases (UCHs). The results in this paper reveal that a novel protein, p28, exists in the toad oocytes, is a UCH L1 homolog, was engaged in the process of progesterone-induced oocyte maturation possibly through an involvement in protein turnover and degradation.展开更多
[Objective] This study aimed to improve the in vitro maturation quality of denuded porcine oocytes and provide scientific basis for establishing a stable and efficient denuded oocyte culture system. [Method] The first...[Objective] This study aimed to improve the in vitro maturation quality of denuded porcine oocytes and provide scientific basis for establishing a stable and efficient denuded oocyte culture system. [Method] The first polar body extrusion rate, oocyte glutathione （GSH） content, positive rate of brilliant cresyl blue （BCB） staining and development potential of activated oocytes or fertilized oocytes were employed as main indicators to investigate the effects of follicular mural granulosa cell （MGC） coculture on cytoplasmic maturation of cumulus cell-removal oocytes （Denuded Oocyte, DO）. [Result] According to in vitro maturation results, compared with DO group, the first polar body extrusion rate of porcine oocytes in DO＋MGC group was not significantly different, but the nuclear maturation process was improved and was more similar to that in COC （cumulus-oocyte complex） group. Detection of GSH content in mature oocytes showed that there was no significant difference between DO＋ MGC group （optical density of 1 053.67） and COC group （optical density of 1 426.00） or between DO＋MGC group and COC＋GC group （optical density of 1 541.00）, however, GSH content in mature oocytes of DO group （optical density of 724.67） was significantly lower than that of COC group and COC＋GC group （P0.05）. Detection of glucose-6-phosphate dehydrogenase （G6PDH） activity showed that there was no significant difference in BCB positive oocyte rate between DO ＋MGC group （88.26% ） and COC group （92.75%） or between DO＋MGC group and DO group （82.86% ）, however, BCB positive oocyte rate of DO group was significantly lower than that of COC group （P0.05）. Furthermore, the cleavage rate and blastocyst rate of activated mature oocytes derived from DO ＋MGC group （94.98% and 43.67% , respectively） were significantly higher than those from DO group （52.54% and 8.97%, respectively） （P0.05）, and were not significantly different compared with those from COC group （97.11% and 38.30%, respectively）. In addition, the cleavage rate of fertilized oocytes derived from DO＋MGC group （72.65%） showed no significant difference compared with that from DO group （63.59%）, but the blastocyst rate of DO＋MGC group was significantly higher than that of DO group （9.88%） （P0.05）. [Conclusion] MGC coculture can significantly improve the in vitro cytoplasmic maturation quality of denuded porcine oocytes, thereby enhancing the subsequent developmental potential.展开更多
[Objective] This study aimed to investigate the appropriate concentrations of follicle-stimulating hormone（FSH）, luteotropic hormone（LH） and estrodiol（E2） during in vitro maturation of Tan sheep oocytes. [Method...[Objective] This study aimed to investigate the appropriate concentrations of follicle-stimulating hormone（FSH）, luteotropic hormone（LH） and estrodiol（E2） during in vitro maturation of Tan sheep oocytes. [Method] Tan sheep oocytes were divided into five groups for in vitro maturation culture： control group, FSH group（10,50, 100, 200 and 300 μg/ml FSH, respectively）, LH group（5, 10, 20, 50 and 100μg/ml LH, respectively）, E2group（5, 10, 25, 50 and 100 μg/ml E2, respectively）, and FSH ＋ LH group（100 μg/ml FSH ＋ 20 μg/ml LH）. The releasing rate of first polar bodies was analyzed. [Result] The maturation rate of Tan sheep oocytes in 100 μg/ml FSH ＋ 20 μg/ml LH group reached the highest（64.64%）, which was significantly higher than that in other four groups（P〈0.05）; among different FSH concentrations,100 μg/ml FSH was superior to other four concentrations and the control group, exhibiting significant differences（P〈0.05）; among different LH concentrations, 20 μg/ml LH was superior to other four concentrations and the control group, exhibiting significant differences（P〈0.05）; among different E2 concentrations, 50 μg/ml E2 was superior to other four concentrations and the control group, exhibiting significant differences（P〈0.05）. [Conclusion] Under the experimental conditions, 100 μg/ml FSH ＋20 μg/ml LH was the most appropriate hormone combination for in vitro maturation of Tan sheep oocytes.展开更多
Casein kinase G (CKG) with more than 2500-fold enrichment was purified from Bufo bufo gargarizans ovaries. The catalytic activity of the enzyme was found to be associated with its 42 kD subunit, and its 26 kD subunit ...Casein kinase G (CKG) with more than 2500-fold enrichment was purified from Bufo bufo gargarizans ovaries. The catalytic activity of the enzyme was found to be associated with its 42 kD subunit, and its 26 kD subunit was found to be the major target for the enzyme auto-phosphorylation. Each full-grown oocyte contained 1.9 units of CKG corresponding to an intracellular concentration of 93 nM. After injecting an amount of 0.38 units of the enzyme into the oocyte, approximately 50% of the progesterone-induced maturation was inhibited. The inhibitory effect was enhanced in oocytes pretreated with spermine, which was consistent with the results that the enzyme was activated in vitro in the presence of spermine. The MPF-induced oocyte maturation was delayed and even prohibited in the kinase-microinjected oocytes. A 55 kD oocyte protein was identified as an substrate of CKG both in vivo and in vitro, and the enhancement of the 55 kD protein phosphorylation was associated with kinase inhibition on maturation and on protein synthesis in kinase-microinjected oocytes. As the endogenous spermine level decreased in the course of progesterone-induced oocyte maturation, 55 kD protein was dephospho-rylated. Heparin, a specific inhibitor of CKG, potentiated the progesterone-induced oocyte maturation. Altogether the experimental results indicated strongly that CKG may be the physiological target of spermine.展开更多
Spermidine or spermine but not putrescine inhibited progesterone induced Bufo bufo gargarizans oocyte maturation. The ID50 for spermine inhibition via intra - oocyte mi-croinjection on maturation induced by progestero...Spermidine or spermine but not putrescine inhibited progesterone induced Bufo bufo gargarizans oocyte maturation. The ID50 for spermine inhibition via intra - oocyte mi-croinjection on maturation induced by progesterone was 6. 8 mM(100 nl). Spermine could inhibit MPF induced toad oocyte maturation with a much higher ID50.A 55 kD protein was dephosphorylated during the process of progesterone induced oocyte maturation. Spermine selectively promoted the level of phosphorylation of ?this protein in both progesterone - stimulated and hormone - untreated oocytes. The extent of its dephosphorylation was fairly correlated with the percentage of GVBD in the hormone stimulated oocytes.The level of endogenous spermine was reduced by 28% between the period of 0. 40 GVBD50 and 0. 60 GVBD50, at which 55 kD protein was dephosphorylated.Spermine inhibited progesterone - stimulated protein synthesis in almost the same dose dependent manner as its inhibitory effect on the hormone - induced maturation. The endogenous spermine regulated 55 kD protein dephosphorylation which may trigger the increase of protein synthesis and in turn promote the activation of MPF. It is possible that 55 kD protein may be one of the components of messenger ribonucleoprotein (mRNP) particles.展开更多
文摘Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
基金funded by grants from the National Natural Science Foundation of China(Grant Nos.82373263 and 82403835)the National Key Research and Development Program of China(Grant No.2023YFC2506400)+2 种基金China Postdoctoral Science Foundation(Grant No.2024M751405)Jiangsu Provincial Natural Science Foundation Youth Project(Grant No.BK20240247)General Project of Nanjing Health Science and Technology Development Program(Grant No.YKK24084).
文摘Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent reprogramming within the tumor microenvironment(TME)into highly immunosuppressive phenotypes that facilitate cancer dissemination and immunotherapy resist-ance1,2.We contend that an underappreciated,upstream determinant of this divergence is the maturation stage of TANs3,4.The developmental stage of TANs determines the migration patterns and constrains the functional capacity,and the developmental stage also constrains the extent of TME-driven re-education,together shaping pro-or anti-tu-mor outcomes3-5.In this Perspective,we place maturation at the core of TAN biology and discuss current definitions for TAN developmental stages and the measurable mark-ers that researchers and clinicians can use(Figure 1).In addition,spatial and temporal transitions in TAN matu-ration stages and the factors that govern these transitions are elucidated.We explain how maturation status shapes TAN function and articulate the key differences between mouse and human TAN maturation systems to highlight the value of human immune system(HIS)mouse models.Based on this framework,functional biomarkers and signa-tures of TAN maturation are introduced and we show how to embed them into patient stratification and longitudinal monitoring.Finally,we outline immunotherapy strategies targeting TAN maturation,selecting interventions guided by maturation markers to reinforce treatment benefits for cancer patients.
文摘Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biological maturity and the limitations of existing testing methods, particularly in adolescent sports contexts, there is a pressing need for a non-invasive method that is convenient, accurate, and broadly applicable to monitor the biological maturity of adolescent athletes comprehensively. In response to this need, a maturity assessment method based on the smartphone application Maturo has been developed. This study evaluates the accuracy and validity of the Maturo software, an automated tool for estimating biological age and related maturation metrics.Methods: A sample of 103 actively training teenage athletes aged 9-17 years. The sample included 76 males(age = 11.74 ± 1.55 years, mean ±SD) and 27 females(age = 13.95 ± 1.40 years), all without medical conditions that might impact growth or development.Results: Compared to traditional expert evaluations, the intraclass correlation coefficients(ICCs) and Pearson correlation coefficients demonstrated reliable positive correlations and significant agreement between the Maturo software and expert methods across multiple metrics, such as biological age(ICC = 0.965, R = 0.97), corrected biological age(ICC = 0.973, R = 0.99), predicted adult height(ICC = 0.991, R = 0.99), and percentage of adult height achieved(ICC = 0.955, R = 0.97). The Bland-Altman plots provided additional evidence of the validity of the Maturo software estimations, showing low systematic error in most measures. The linear regression analysis produced excellent adjusted R2values: 0.95for biological age and 0.99 for anticipated adult height. The Maturo approach demonstrated a high level of dependability in classifying teenagers into groups based on their maturity status and timing. The κ coefficients of 0.93 for maturity status and 0.82 for maturity timing indicate a nearly perfect agreement with the expert technique.Conclusion: While the Maturo software's non-invasive nature, cost-effectiveness, and ease of use could make it a potential tool for regular monitoring of growth and maturation in young athletes, its promising results in assessing maturation should be interpreted with caution due to limitations such as sample size and demographic constraints. Further longitude research with larger and more diverse populations is needed to validate these preliminary findings and strengthen the evidence for its broader applicability.
基金funded by the National Natural Science Foundation of China(32172721)the China Agriculture Research System(CARS-40)+1 种基金the Central Publicinterest Scientific Institution Basal Research Fund,China(2021-YWF-ZYSQ-12)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(ASTIP-IAS04)。
文摘Sexual maturation heterosis has been widely exploited in animal crossbreeding.However,the underlying mechanism has been rarely explored in chicken.In the present study,we performed the reciprocal crossing between White Leghorn and Beijing You chicken to evaluate the phenotypes related to sexual maturation,and profiled the ovary circRNAs of purebreds(WW,YY)and crossbreds(WY,YW)to elucidate the molecular mechanism underlying heterosis for sexual maturation.Pubic space and oviduct length exhibited positive heterosis,and age at first egg(AFE)exhibited negative heterosis in the crossbreds.We identified 3,025 known circRNAs and 624 putative circRNAs,which were mainly derived from the exons.Among these circRNAs,141 and 178circRNAs were specially expressed in WY and YW,respectively.There were 52.38 and 64.63%of total circRNAs in WY and YW exhibited non-additive expression pattern,respectively.GO enrichment and KEGG pathway analysis showed that the host genes of non-additive circRNAs were mainly involved in TGF-beta signaling pathway,oocyte development,ATPase activator activity,oocyte meiosis,progesterone-mediated oocyte maturation and GnRH signaling pathway.Weighted gene co-expression network analysis identified that 4 modules were significantly(P<0.05)correlated with oviduct length and pubic space.The host genes of non-additive circRNAs harbored in the 4 modules were associated with MAPK signaling pathway and Wnt signaling pathway.Furthermore,competing endogenous RNAs(ceRNA)network analysis characterized non-additive circRNAs gal-FGFR2_0005 and galMAPKAP1_0004 could interact with gga-miR-1612 and gga-miR-12235-5p to regulate CNOT6,COL8A1,and FHL2,which were essential for ovary development,indicating that the non-additive circRNAs involved in the formation of sexual maturation heterosis through regulating genes related to the reproductive and developmental process.The findings would provide a deeper understanding of the molecular mechanism underlying sexual maturation heterosis from a novel perspective.
基金support of the National Natural Science Foundation of China(32025014 and 32330029 to Q.W.)the National Key Research and Development Program of China(2020YFA0804000 to Q.W.)+2 种基金Guangdong Excellent Youth Team Project(2024B1515040019 to Q.W.)Guangzhou Science and Technology Plan Project(202201010323 to X.H.)the Fundamental Research Funds for the Central Universities(to Q.W.).
文摘Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures.Cranial neural crest cells are specified at the neural plate border,migrate to pharyngeal arches,and differentiate into pharyngeal chondrocytes,which subsequently flatten,elongate,and stack like coins during maturation.Although the developmental processes prior to chondrocyte maturation have been extensively studied,their subsequent changes in morphology and organization remain largely elusive.Here,we show that wnt2bb is expressed in the pharyngeal ectoderm adjacent to the chondrogenic precursor cells in zebrafish.Inactivation of Wnt2bb leads to a reduction in nuclearβ-catenin,which impairs chondrogenic precursor proliferation and disrupts chondrocyte morphogenesis and organization,eventually causing a severe shrinkage of pharyngeal cartilages.Moreover,the decrease ofβ-catenin in wnt2bb^(-/-)mutants is accompanied by the reduction of Yap expression.Reactivation of Yap can restore the proliferation of chondrocyte progenitors as well as the proper size,shape,and stacking of pharyngeal chondrocytes.Our findings suggest that Wnt/β-catenin signaling promotes Yap expression to regulate pharyngeal cartilage formation in zebrafish.
基金supported by the National Natural Science Foundation of China(32201696)the Natural Science Foundation of Sichuan Province(23NSFSC4071)。
文摘Seed maturation is a critical development transition and it largely affects the final yield and quality of crops.Abscisic acid(ABA)-activated sucrose-non-fermentation kinase subfamily 2(SnRK2s)constitute a well-known regulatory network that modulate seed maturation in Arabidopsis;however,the underlying genetic and regulatory mechanisms in cereal crops remain largely unknown.Here,we found that ABA levels exhibited two distinct peaks during kernel development in maize,corresponding to the lag and maturation phase,respectively.Integrated transcriptome and proteome profiling of kernels treated with exogenous ABA at the pre-maturation stage suggested that the second peak of ABA acts as a trigger for kernel maturation program.Knockout of ZmSnRK2s demonstrated that subclassⅢZmSnRK2s are required for kernel maturation in maize,and the loss-of-function of subclassⅢZmSnRK2s showed a disruption in kernel dehydration and dormancy.We identified a conserved ABA–SnRK2–b ZIP signaling pathway mediating this process in maize.Additionally,ZmSnRK2.10 overexpression accelerates kernel dehydration during maturity,achieving reduced kernel moisture content(KMC)at physiological maturity(PM).Overall,our findings establish ABA-activated SnRK2s as central regulators of kernel maturation in maize and provide valuable genetic resources for breeding maize varieties with low moisture content at harvest.
文摘Rising global energy needs have intensified the search for unconventional hydrocarbon sources,especially in under-selected areas like the Northeast Java Basin.This region harbors promising unconventional hydrocarbon reserves,where source rocks function as dual-phase systems for both hydrocarbon generation and storage.This research investigates how metal-based catalysts,particularly iron(Fe),can expedite hydrocarbon maturation in such reservoirs.Combining well logging,geochemical assessments,seismic data,and advanced lab techniques,including X-ray Diffraction(XRD),we pinpoint optimal zones for exploration.Results indicate that the Tuban,Kujung,and Ngimbang formations contain economically viable unconventional deposits,exhibiting tight reservoir properties(permeability:0.01–1 md)and moderate to good Total Organic Carbon(TOC)levels(1%–2%).Spatial analysis reveals elevated density concentrations in the northern sector,indicative of high-viscosity hydrocarbons typical of unconventional plays.Crucially,Fe additives were found to markedly enhance organic matter conversion,shortening maturation periods and boosting hydrocarbon yield.XRD data confirms that Fe alters crystalline configurations,increasing reactivity and speeding up thermal breakdown(shifting immature organic compounds toward maturity at an accelerated rate).These findings contribute to the evolving discourse on unconventional resource exploitation by proposing an innovative recovery enhancement strategy.The study also sets a precedent for investigating metal-assisted hydrocarbon conversion in geologically comparable basins globally.
基金Supported by School Program of Henan Institute of Science and Technology(20060516)~~
文摘[Objective] The study aimed to provide references for the time of oocyte maturation in vitro and enucleation in the course of sheep nuclear transfer(NT).[Method] Compared the effects of different maturation time of oocytes on enucleation efficiency and reconstructed embryo development by means of blind enucleation and fluorescence microscopy.[Result] Treatment of IVM(in vitro maturation)19-21 h was significantly higher than IVM 16-18 h treatment in oocyte maturation rate(P<0.05)and was significantly higher than IVM 22-24 h treatment in enucleation rate(P<0.05).Three treatments had no significant difference in cleavage rate and blastocyst rate(P>0.05),but IVM 19-21 h treatment was significantly higher than the other 2 treatments in average cell number of blastocysts(P<0.05).[Conclusion] The appropriate in vitro maturation time of oocytes was 19-21 h for sheep nuclear transfer,which could significantly improve the quality of blastocysts according to the cell number per blastocyst(P<0.05).
基金This work is supported by National Natural Sci-ence Fundation of China (Grant 39770370), and National Laboratory of Contraceptives and Devices Re-search affiliated with Shanghai lnstitute of Planned Parenthood Research.
文摘p28, a 28kD protein from toad (Bufo bufo gargarizans) oocytes, was identified by using p13sucl-agarose affinity chromatography. Sequence homology analysis of the full-length cDNA of p28 (Gene Bank accession number: AF 314091) indicated that it encodes a protein containing 224 amino-acids with about 55% identities and more than 70% positives to human, rat or mouse UCH-L1, and contains homological functional domains of UCH family. Anti-p28 monoclonal antibody, on injecting into the oocytes, could inhibit the progesterone-induced resumption of meiotic division in a dose-dependent manner. The recombinant protein p28 showed similar SDS/PAGE behaviors to the native one, and promoted ubiquitin ethyl ester hydrolysis, a classical catalytic reaction for ubiquitin carboxyl terminal hydrolases (UCHs). The results in this paper reveal that a novel protein, p28, exists in the toad oocytes, is a UCH L1 homolog, was engaged in the process of progesterone-induced oocyte maturation possibly through an involvement in protein turnover and degradation.
基金Supported by National Natural Science Foundation of China (30871431)Outstanding Youth Fund of Heilongjiang Province (JC200905)~~
文摘[Objective] This study aimed to improve the in vitro maturation quality of denuded porcine oocytes and provide scientific basis for establishing a stable and efficient denuded oocyte culture system. [Method] The first polar body extrusion rate, oocyte glutathione （GSH） content, positive rate of brilliant cresyl blue （BCB） staining and development potential of activated oocytes or fertilized oocytes were employed as main indicators to investigate the effects of follicular mural granulosa cell （MGC） coculture on cytoplasmic maturation of cumulus cell-removal oocytes （Denuded Oocyte, DO）. [Result] According to in vitro maturation results, compared with DO group, the first polar body extrusion rate of porcine oocytes in DO＋MGC group was not significantly different, but the nuclear maturation process was improved and was more similar to that in COC （cumulus-oocyte complex） group. Detection of GSH content in mature oocytes showed that there was no significant difference between DO＋ MGC group （optical density of 1 053.67） and COC group （optical density of 1 426.00） or between DO＋MGC group and COC＋GC group （optical density of 1 541.00）, however, GSH content in mature oocytes of DO group （optical density of 724.67） was significantly lower than that of COC group and COC＋GC group （P0.05）. Detection of glucose-6-phosphate dehydrogenase （G6PDH） activity showed that there was no significant difference in BCB positive oocyte rate between DO ＋MGC group （88.26% ） and COC group （92.75%） or between DO＋MGC group and DO group （82.86% ）, however, BCB positive oocyte rate of DO group was significantly lower than that of COC group （P0.05）. Furthermore, the cleavage rate and blastocyst rate of activated mature oocytes derived from DO ＋MGC group （94.98% and 43.67% , respectively） were significantly higher than those from DO group （52.54% and 8.97%, respectively） （P0.05）, and were not significantly different compared with those from COC group （97.11% and 38.30%, respectively）. In addition, the cleavage rate of fertilized oocytes derived from DO＋MGC group （72.65%） showed no significant difference compared with that from DO group （63.59%）, but the blastocyst rate of DO＋MGC group was significantly higher than that of DO group （9.88%） （P0.05）. [Conclusion] MGC coculture can significantly improve the in vitro cytoplasmic maturation quality of denuded porcine oocytes, thereby enhancing the subsequent developmental potential.
基金Supported by Natural Science Foundation of Ningxia Hui Autonomous Region(NZ12150)~~
文摘[Objective] This study aimed to investigate the appropriate concentrations of follicle-stimulating hormone（FSH）, luteotropic hormone（LH） and estrodiol（E2） during in vitro maturation of Tan sheep oocytes. [Method] Tan sheep oocytes were divided into five groups for in vitro maturation culture： control group, FSH group（10,50, 100, 200 and 300 μg/ml FSH, respectively）, LH group（5, 10, 20, 50 and 100μg/ml LH, respectively）, E2group（5, 10, 25, 50 and 100 μg/ml E2, respectively）, and FSH ＋ LH group（100 μg/ml FSH ＋ 20 μg/ml LH）. The releasing rate of first polar bodies was analyzed. [Result] The maturation rate of Tan sheep oocytes in 100 μg/ml FSH ＋ 20 μg/ml LH group reached the highest（64.64%）, which was significantly higher than that in other four groups（P〈0.05）; among different FSH concentrations,100 μg/ml FSH was superior to other four concentrations and the control group, exhibiting significant differences（P〈0.05）; among different LH concentrations, 20 μg/ml LH was superior to other four concentrations and the control group, exhibiting significant differences（P〈0.05）; among different E2 concentrations, 50 μg/ml E2 was superior to other four concentrations and the control group, exhibiting significant differences（P〈0.05）. [Conclusion] Under the experimental conditions, 100 μg/ml FSH ＋20 μg/ml LH was the most appropriate hormone combination for in vitro maturation of Tan sheep oocytes.
文摘Casein kinase G (CKG) with more than 2500-fold enrichment was purified from Bufo bufo gargarizans ovaries. The catalytic activity of the enzyme was found to be associated with its 42 kD subunit, and its 26 kD subunit was found to be the major target for the enzyme auto-phosphorylation. Each full-grown oocyte contained 1.9 units of CKG corresponding to an intracellular concentration of 93 nM. After injecting an amount of 0.38 units of the enzyme into the oocyte, approximately 50% of the progesterone-induced maturation was inhibited. The inhibitory effect was enhanced in oocytes pretreated with spermine, which was consistent with the results that the enzyme was activated in vitro in the presence of spermine. The MPF-induced oocyte maturation was delayed and even prohibited in the kinase-microinjected oocytes. A 55 kD oocyte protein was identified as an substrate of CKG both in vivo and in vitro, and the enhancement of the 55 kD protein phosphorylation was associated with kinase inhibition on maturation and on protein synthesis in kinase-microinjected oocytes. As the endogenous spermine level decreased in the course of progesterone-induced oocyte maturation, 55 kD protein was dephospho-rylated. Heparin, a specific inhibitor of CKG, potentiated the progesterone-induced oocyte maturation. Altogether the experimental results indicated strongly that CKG may be the physiological target of spermine.
文摘Spermidine or spermine but not putrescine inhibited progesterone induced Bufo bufo gargarizans oocyte maturation. The ID50 for spermine inhibition via intra - oocyte mi-croinjection on maturation induced by progesterone was 6. 8 mM(100 nl). Spermine could inhibit MPF induced toad oocyte maturation with a much higher ID50.A 55 kD protein was dephosphorylated during the process of progesterone induced oocyte maturation. Spermine selectively promoted the level of phosphorylation of ?this protein in both progesterone - stimulated and hormone - untreated oocytes. The extent of its dephosphorylation was fairly correlated with the percentage of GVBD in the hormone stimulated oocytes.The level of endogenous spermine was reduced by 28% between the period of 0. 40 GVBD50 and 0. 60 GVBD50, at which 55 kD protein was dephosphorylated.Spermine inhibited progesterone - stimulated protein synthesis in almost the same dose dependent manner as its inhibitory effect on the hormone - induced maturation. The endogenous spermine regulated 55 kD protein dephosphorylation which may trigger the increase of protein synthesis and in turn promote the activation of MPF. It is possible that 55 kD protein may be one of the components of messenger ribonucleoprotein (mRNP) particles.
