Breakthroughs in the generation of programmable sequence-specific nucleases (SSNs), such as zinc finger nucleases (ZFNs),TAL effector nucleases (TALENs) and the RNA-directed nuclease CRISPR-associated protein 9 (Cas9)...Breakthroughs in the generation of programmable sequence-specific nucleases (SSNs), such as zinc finger nucleases (ZFNs),TAL effector nucleases (TALENs) and the RNA-directed nuclease CRISPR-associated protein 9 (Cas9), have greatly increased the ease of plant genome engineering (Voytas, 2013; Malzahn et al.,2017). Programmable SSNs introduce a DNA double-strand break展开更多
Summary:The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease.Understanding the dysregulated human immune ...Summary:The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease.Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic.In this study,we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia(FOP)patients who underwent lung surgery and served as controls.We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients.In contrast to the FOP patients,Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients.This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients.In summary,our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity.Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.展开更多
Genetically modified pigs represent a great promise for generating models of human diseases and producing new breeds.Generation of genetically edited pigs using somatic cell nuclear transfer(SCNT)or zygote cytoplasmic...Genetically modified pigs represent a great promise for generating models of human diseases and producing new breeds.Generation of genetically edited pigs using somatic cell nuclear transfer(SCNT)or zygote cytoplasmic microinjection is a tedious process due to the low developmental rate or mosaicism of the founder(FO).Herein,we developed a method termed germinal vesicle oocyte gene editing(GVGE)to produce non-mosaic porcine embryos by editing maternal alleles during the GV to MII transition.Injection of Cas9 mRNA and X-linked Dmd gene-specific gRNA into GV oocytes did not affect their developmental potential.The MII oocytes edited during in vitro maturation(IVM)could develop into blastocysts after parthenogenetic activation(PA)or in vitro fertilization(IVF).Genotyping results indicated that the maternal gene X-linked Dmd could be efficiently edited during oocyte maturation.Up to81.3% of the edited IVF embryos were non-mosaic Dmd gene mutant embryos.In conclusion,GVGE might be a valuable method for the generation of non-mosaic maternal allele edited FO embryos in a short simple step.展开更多
Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antib...Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes. Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes, little is known about how the GC-associated cell cycle is orchestrated. The D-type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes. Cell type- and developmental stage-specific roles of D-type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed. In this study, we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells. In contrast, GC development in Ccnd3^-/- mice is markedly impaired, as is the T cell-dependent antibody response. Within the GC, although both switched and unswitched B cells are affected by cyclin D3 inactivation, the IgM^- pool is more severely reduced. Interestingly, despite a compensatory increase in cyclln D2 expression, a significant number of Ccnd3^-/- GC B cells accumulate in quiescent GO state. Lastly, although cyclin D3 inactivation did not disrupt BCL6 expression in GC B cells, it completely blocked the GC promoting effect of BCL6 overexpression, suggesting that cyclin D3 acts downstream of BCL6 to regulate GC formation. This is the first demonstration that cyclin D3 plays an important and unique role at the GC stage of B cell development.展开更多
The purpose of this study was to evaluate the viability and subsequent developmental ability of porcine germinal vesicle(GV) oocytes vitrified step-wise exposure to cryoprotectants. Oocytes were transferred to a vit...The purpose of this study was to evaluate the viability and subsequent developmental ability of porcine germinal vesicle(GV) oocytes vitrified step-wise exposure to cryoprotectants. Oocytes were transferred to a vitrification solution composed of 10% ethylene glycol(EG),10% dimethyl sulfoxide(DMSO), 300 g/L-1 Ficoll and 0.5 mol/L-1 sucrose(EDFS40) in a direct manner (non-preequilibrium) or in step-wise manner( single- and two-step preequilibrium). After vitrification and storage in liquid nitrogen, the oocytes were thawed,washed and in vitro maturation, fertilization and culture. In the non-preequilibrium group, the rates of post-thawed oocytes surviving, maturing to metaphase-Ⅱ, cleavage rate and blastocysts rate was significantly lower than that of sigle- and two-step preequilubrium groups(P<0.05). In the single- and two- step groups, the rates of metaphase-Ⅱ stage were 46.8%, 42.7% and 49.7%, respectively, the rates which developed to blastocysts were 10.5%,11.1% and 14.8%, respectivaly. In the non-vitrified control group,the rates of oocytes maturing to metaphase-Ⅱ, developing to blastocysts was significantly higher than that vitrified groups(P<0.05). The present study shows that the vitrification of porcine GV oocytes by a step-wise method involving two-steps preequilibrium may have advantage in maintaining the viability and subsequent production of blastocysts.展开更多
Monoclonal antibodies were used to label cutaneous germinal center cell-derived lymphomas <CGCCL) obtained from 10 patients. According to the Kiel classification, they were classified into 2 types. Eight patients h...Monoclonal antibodies were used to label cutaneous germinal center cell-derived lymphomas <CGCCL) obtained from 10 patients. According to the Kiel classification, they were classified into 2 types. Eight patients had centroblastic/centrocytic <CB/CC) lymphomas while 2 patients and centrocytic (CC) lymphomas. After monoclonal antibody labelling, the results were consistent with those of the clinical and morphologic analyses. Of the 10 cases, 9 were B1 positive, 6 were K positive, and 4 were λ positive. In 8 cases labeled with immunoglobulin, 6 were IgGFab positive, 2 were IgM positive and 8 were IgA negative. Five cases (CB/CC 3, CC 2) were both Bl, K and IgG positive (γ K). Four cases CB/CC were both Bl and A positive. Only one case (CB/CC) was both K and IgM positive (μ K). Two cases (CB CC) were both A and IgG positive (γ λ). The results indicate that Bl, K and A are the most important markers to phenotype cutaneous B-cell lymphomas. Our findings also show a higher percentage of y K types in CGCCL as compared with Western countries.展开更多
The germinal matrix being an accumulation of immature blood vessels in the premature infant brain is known to be the main cause of the intracranial hemorrhage. To investigate the injuring mechanism to the blood vessel...The germinal matrix being an accumulation of immature blood vessels in the premature infant brain is known to be the main cause of the intracranial hemorrhage. To investigate the injuring mechanism to the blood vessels of the germinal matrix, a modeling scenario that consists of three basic steps is proposed. First, the cerebral blood flow that depends on autoregulation, CO2 reactivity, and variations of intracranial pressure is modeled. Second, the chaotic blood vessel network of the germinal matrix is generated, and blood pressures in the vessels of this network are computed dependent on the outcome of the first step. In the third step, the pressures computed on the second step are used in finite element simulations of separate blood vessels of the germinal matrix to detect critical values for vessels impairment.展开更多
B cells,a pivotal constituent of the lymphatic system,undergo differentiation into plasma cells and memory B cells upon antigen stimulation,thereby primarily facilitating humoral immunity(Zhang et al.,2024).Most B cel...B cells,a pivotal constituent of the lymphatic system,undergo differentiation into plasma cells and memory B cells upon antigen stimulation,thereby primarily facilitating humoral immunity(Zhang et al.,2024).Most B cells necessitate transit through germinal centers(GCs)to achieve complete differentiation and maturation.Abnormal transformation of GC B cells represents a fundamental etiological factor in the development of diffuse large B-cell lymphoma(DLBCL)(Mlynarczyk et al.,2019)and multiple myeloma(MM)(Rizq et al.,2023).展开更多
Pulmonary T and B cells are important for protection of this mucosal barrier site.While viral infections lead to the development of ectopic lymphoid structures highly similar to those in germinal centers in secondary ...Pulmonary T and B cells are important for protection of this mucosal barrier site.While viral infections lead to the development of ectopic lymphoid structures highly similar to those in germinal centers in secondary lymphoid organs,little is known about how T/B cooperation occurs in the unstructured,diffuse tissue infiltrates characteristic of autoimmune diseases and nonviral infections.Using a mouse model of interstitial lung inflammation,we found that naive B cells are directly activated in lung tissue.Despite the absence of any germinal center-like structures,the interaction of B cells with peripheral T helper cells results in efficient somatic hypermutation and class switching.As antigen-presenting cells,macrophages are critical for this process.Unique B-cell repertoires indicated that the lung response was autonomous from the lung-draining lymph node.Only lung GC-like B cells were switched to IgA and had a broader repertoire,making them ideal candidates for producing broadly neutralizing immunoglobulins against respiratory pathogens.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
The transcriptional repressor B cell lymphoma 6(BCL6) controls a large transcriptional network that is required for the formation and maintenance of germinal centers(GC). GC B cells represent the normal counterpart of...The transcriptional repressor B cell lymphoma 6(BCL6) controls a large transcriptional network that is required for the formation and maintenance of germinal centers(GC). GC B cells represent the normal counterpart of most human B-cell lymphomas, which are often characterized by deregulated BCL6 expression or BCL6-mediated pathways. BCL6 suppresses gene transcription largely through recruitment of its co-repressors through its distinct repression domain. Understanding the precise biological roles of each repression domain in normal and malignant B cells is helpful for development of targeted inhibition of BCL6 functions that is emerging as the basis for design of anti-lymphoma therapies. This review focuses on recent progress in the molecular mechanisms of action of BCL6 in B cells and discusses remaining unresolved questions related to how these mechanisms are linked to normal and malignant B cell development.展开更多
B cells play essential roles in immunity,mainly through the production of high affinity plasma cells(PCs)and memory B(Bmem)cells.The affinity maturation and differentiation of B cells rely on the integration of B-cell...B cells play essential roles in immunity,mainly through the production of high affinity plasma cells(PCs)and memory B(Bmem)cells.The affinity maturation and differentiation of B cells rely on the integration of B-cell receptor(BCR)intrinsic and extrinsic signals provided by antigen binding and the microenvironment,respectively.In recent years,tumor infiltrating B(TIL-B)cells and PCs(TIL-PCs)have been revealed as important players in antitumor responses in human cancers,but their interplay and dynamics remain largely unknown.In lymphoid organs,B-cell responses involve both germinal center(GC)-dependent and GC-independent pathways for Bmem cell and PC production.Affinity maturation of BCR repertoires occurs in GC reactions with specific spatiotemporal dynamics of signal integration by B cells.In general,the reactivation of high-affinity Bmem cells by antigens triggers GC-independent production of large numbers of PC without BCR rediversification.Understanding B-cell dynamics in immune responses requires the integration of multiple tools and readouts such as single-cell phenotyping and RNA-seq,in situ analyses,BCR repertoire analysis,BCR specificity and affinity assays,and functional tests.Here,we review how those tools have recently been applied to study TIL-B cells and TIL-PC in different types of solid tumors.We assessed the published evidence for different models of TIL-B-cell dynamics involving GC-dependent or GC-independent local responses and the resulting production of antigen-specific PCs.Altogether,we highlight the need for more integrative B-cell immunology studies to rationally investigate TIL-B cells as a leverage for antitumor therapies.展开更多
Cytosine and adenine base editors are promising new tools for introducing precise genetic modifications that are required to generate disease models and to improve traits in pigs. Base editors can catalyze the convers...Cytosine and adenine base editors are promising new tools for introducing precise genetic modifications that are required to generate disease models and to improve traits in pigs. Base editors can catalyze the conversion of C→T(C>T) or A→G(A>G) in the target site through a single guide RNA. Injection of base editors into the zygote cytoplasm can result in the production of offspring with precise point mutations, but most F0 are mosaic, and breeding of F1 heterozygous pigs is time-intensive. Here, we developed a method called germinal vesicle oocyte base editing(GVBE) to produce point mutant F0 porcine embryos by editing the maternal alleles during the GV to MⅡ transition. Injection of cytosine base editor 3(BE3) mRNA and X-linked Dmdspecific guide RNAs into GVoocytes efficiently edited maternal Dmd during in vitro maturation and did not affect the maturation potential of the oocytes. The edited MⅡ oocytes developed into blastocysts after parthenogenetic activation(PA) or in vitro fertilization(IVF). However, BE3 may reduce the developmental potential of IVF blastocysts from 31.5%±0.8% to 20.4%±2.1%. There 40%–78.3% diploid PA blastocysts had no more than two different alleles, including up to 10% embryos that had only C>T mutation alleles. Genotyping of IVF blastocysts indicated that over 70% of the edited embryos had one allele or two different alleles of Dmd. Since the male embryos had only a copy of Dmd allele, all five(5/19) F0 male embryos are homozygous and three of them were Dmd precise C>T mutation. Nine(9/19) female IVF embryos had two different alleles including a WT and a C>T mutation. DNA sequencing showed that some of them might be heterozygous embryos. In conclusion, the GVBE method is a valuable method for generating F0 embryos with maternal point mutated alleles in a single step.展开更多
Germinal centers(GCs)are essential for the establishment of long-lasting antibody responses.GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into funct...Germinal centers(GCs)are essential for the establishment of long-lasting antibody responses.GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome.However,the critical proteins driving these key mechanisms are still unknown.Here,we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses.TIA1-and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection,expansion and differentiation into B-cell clones producing high-affinity antibodies.Mechanistically,TIA1 and TIAL1 control the transcriptional identity of dark-and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1.Thus,we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.展开更多
Germinal center kinases (GCKs) participate in a variety of signaling pathways needed to regulate cellular functions including apoptosis, cell proliferation, polarity and migration. Recent studies have shown that GCK...Germinal center kinases (GCKs) participate in a variety of signaling pathways needed to regulate cellular functions including apoptosis, cell proliferation, polarity and migration. Recent studies have shown that GCKs are participants in both adaptive and innate immune regulation. However, the differential activation and regulatory mechanisms of GCKs, as well as upstream and downstream signaling molecules, remain to be fully defined. It remains unresolved whether and how GCKs may cross-talk with existing signaling pathways. This review stresses the progresses in research of GCKs relevant to the immune system.展开更多
Initially,identified as a Hodgkin lymphoma marker,CD30 was subsequently detected on a subset of human B cells within and around germinal centers(GCs).While CD30 expression is typically restricted to a few B cells,expa...Initially,identified as a Hodgkin lymphoma marker,CD30 was subsequently detected on a subset of human B cells within and around germinal centers(GCs).While CD30 expression is typically restricted to a few B cells,expansion of CD30-expressing B cells occurs in certain immune disorders and during viral infections.The role of CD30 in B cells remains largely unclear.To address this gap in knowledge,we established a conditional CD30-knockin mouse strain.In these mice,B-cell-specific CD30 expression led to a normal B-cell phenotype in young mice,but most aged mice exhibited significant expansion of B cells,T cells and myeloid cells and increased percentages of GC B cells and IgG1-switched cells.This may be driven by the expansion of CD4+senescence-associated T cells and T follicular helper cells,which partially express CD30-L(CD153)and may stimulate CD30-expressing B cells.Inducing CD30 expression in antigen-activated B cells accelerates the GC reaction and augments plasma cell differentiation,possibly through the posttranscriptional upregulation of CXCR4.Furthermore,CD30 expression in GC B cells promoted the expansion of IgG1-switched cells,which displayed either a GC or memory-like B-cell phenotype,with abnormally high IgG1 levels compared with those in controls.These findings shed light on the role of CD30 signaling in GC B cells and suggest that elevated CD30+B-cell numbers lead to pathological lymphocyte activation and proliferation.展开更多
Gibberellins(GAs)and auxin play central regulatory roles in seed germination and root system development,respectively,so that the application of these phytohormones to crops would be worthwhile,with an increasing pote...Gibberellins(GAs)and auxin play central regulatory roles in seed germination and root system development,respectively,so that the application of these phytohormones to crops would be worthwhile,with an increasing potential demand in agriculture.However,there are few effective chemicals that simultaneously enhance both GA and auxin signaling.Here,we report on an artificial thiourea derivative chemical,Y21,that serves as both a GA-signaling agonist and an auxin analog,promoting seed germination and root development,as well as low-phosphorus tolerance.Phenotypic,biochemical,and genetic evidence demonstrated that Y21 enhances the interaction between GA and its receptor GID1C via the Val239 amino acid residue and consequently promotes degradation of the DELLA proteins REPRESSOR OF ga1-3(RGA)and RGA-LIKE 2.Furthermore,we found that Y21 interacts with the auxin receptor TIR1 via the Cys405 residue and thus promotes the turnover of the auxinresponsive Aux/IAA proteins.Consequently,Y21significantly increases low-phosphorus tolerance of treated plants by positively regulating lateral root development.To our knowledge,Y21 is the first GA-signaling agonist to be identified,and our results also demonstrate that this potent synthetic chemical,identified by chemical genetic screening,is effective at modulating plant development and stress tolerance.展开更多
Seaweed extract contains plant growth regulators and bio-stimulants that enhance plant growth and development.In Bangladesh,winter rice(Boro rice)in the nursery bed often shows poor seed emergence and weak seedling gr...Seaweed extract contains plant growth regulators and bio-stimulants that enhance plant growth and development.In Bangladesh,winter rice(Boro rice)in the nursery bed often shows poor seed emergence and weak seedling growth due to low temperature.This problem can be addressed by using seaweed extract as a seed priming agent and bio-stimulant.The objective of this study was to evaluate the effectiveness of seaweed extract(Crop Plus)on seed emergence,seedling growth,and vigor of winter rice in the nursery.Two experiments were conducted at Bangladesh Agricultural University using BRRI dhan89.The laboratory experiment consisted of 17 treatments combining three concentrations of Crop Plus(5000,10,000 and 15,000 ppm)and four priming durations(6,12,18,and 24 h),along with hydro-priming and a no priming as control.Seed priming with 15,000 ppm for 24 h produced the highest germination percentage and superior seedling growth traits.The nursery bed experiment comprised 11 treatments combining two doses(1 mL m^(−2)and 2 mL m^(−2))of Crop Plus and five different foliar application schedules,along with a control.All treatments outperformed the control,with the best results from Crop Plus@2 mL m^(−2)applied at 20 and 30 days after sowing(DAS).Overall,the treatment involving seed priming with 15,000 ppm seaweed extract for 24 h,followed by nursery application at 2 mL m^(−2)at 20 and 30 DAS,resulted in higher germination and improved early growth of winter rice.However,further validation across multiple locations,seasons,and rice cultivars is recommended.展开更多
Seed vigor is critical for uniform germination and emergence,directly influencing subsequent seedling development.This is especially important under both normal and stress conditions that may arise post-sowing.Chillin...Seed vigor is critical for uniform germination and emergence,directly influencing subsequent seedling development.This is especially important under both normal and stress conditions that may arise post-sowing.Chilling stress during emergence and early growth poses significant challenges for tomato seedlings,potentially leading to uneven emergence,abnormal growth,and higher seedling mortality.This study evaluated the effectiveness of combining drum-priming with melatonin to alleviate chilling stress during these two critical stages.Tomato seeds were primed with melatonin at various concentrations and compared to untreated controls under chilling stress conditions.Higher concentrations of melatonin significantly accelerated emergence and improved early growth under stress.These stress-mitigating effects were evidenced by reductions in oxidative stress markers,such as malondialdehyde and hydrogen peroxide,along with increased total polyphenol and flavonoid contents.Furthermore,melatonin priming preserved photosynthetic efficiency,typically reduced by chilling stress,and enhanced the activities of antioxidant enzymes,including catalase and peroxidase.These biochemical changes reduced oxidative damage and promoted stress resilience.Melatonin also accelerated the expression of genes within the C-repeat binding factor pathway,which is crucial for cold acclimation.This suggests that melatonin priming enabled quicker adaptation to chilling stress following sowing and bolstered seedling resilience during subsequent growth stages.Overall,our results demonstrate that melatonin priming not only enhances germination but also significantly supports seedling growth under adverse conditions.The findings highlight melatonin as a promising tool in crop management strategies to improve resilience against sudden chilling stress.展开更多
Subject Code:C08With the support by the National Natural Science Foundation of China,a study by the research group led by Prof.Qi Hai(祁海)from the School of Medicine,Tsinghua University revealed a novel mechanism tha...Subject Code:C08With the support by the National Natural Science Foundation of China,a study by the research group led by Prof.Qi Hai(祁海)from the School of Medicine,Tsinghua University revealed a novel mechanism that regulates the germinal center reaction,aphysiological process that underlies high-quality展开更多
基金supported by a Collaborative Funding Grant from North Carolina Biotechnology Center and Syngenta Biotechnology (2016-CFG-8003)startup funds provided by East Carolina University and University of Maryland to Y.Q.a grant from the National Science Foundation (IOS-1339209)
文摘Breakthroughs in the generation of programmable sequence-specific nucleases (SSNs), such as zinc finger nucleases (ZFNs),TAL effector nucleases (TALENs) and the RNA-directed nuclease CRISPR-associated protein 9 (Cas9), have greatly increased the ease of plant genome engineering (Voytas, 2013; Malzahn et al.,2017). Programmable SSNs introduce a DNA double-strand break
基金The study was funded by grants from the Special R&D Program of Ministry of Science and Technology(No.2019YFC1316203)Ministry of Science and Technology(No.2020YFC0844700)Clinical Foundation of Tongji Hospital(No.XXGZBDYJ010).
文摘Summary:The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease.Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic.In this study,we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia(FOP)patients who underwent lung surgery and served as controls.We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients.In contrast to the FOP patients,Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients.This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients.In summary,our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity.Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.
基金supported by the National Key R&D Program of China(2017YFC1001901 and 2017YFA0102801)the National Natural Science Foundation of China (31671540)+3 种基金the National Transgenic Major Program (2016ZX08006003-006)the Natural Science Foundation of Guangdong Province (2015A020212005 and 2014A030312011)the Key R&D Program of Guangdong Province (2018B020203003)the Guangzhou Science and Technology Project (201803010020)
文摘Genetically modified pigs represent a great promise for generating models of human diseases and producing new breeds.Generation of genetically edited pigs using somatic cell nuclear transfer(SCNT)or zygote cytoplasmic microinjection is a tedious process due to the low developmental rate or mosaicism of the founder(FO).Herein,we developed a method termed germinal vesicle oocyte gene editing(GVGE)to produce non-mosaic porcine embryos by editing maternal alleles during the GV to MII transition.Injection of Cas9 mRNA and X-linked Dmd gene-specific gRNA into GV oocytes did not affect their developmental potential.The MII oocytes edited during in vitro maturation(IVM)could develop into blastocysts after parthenogenetic activation(PA)or in vitro fertilization(IVF).Genotyping results indicated that the maternal gene X-linked Dmd could be efficiently edited during oocyte maturation.Up to81.3% of the edited IVF embryos were non-mosaic Dmd gene mutant embryos.In conclusion,GVGE might be a valuable method for the generation of non-mosaic maternal allele edited FO embryos in a short simple step.
文摘Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes. Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes, little is known about how the GC-associated cell cycle is orchestrated. The D-type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes. Cell type- and developmental stage-specific roles of D-type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed. In this study, we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells. In contrast, GC development in Ccnd3^-/- mice is markedly impaired, as is the T cell-dependent antibody response. Within the GC, although both switched and unswitched B cells are affected by cyclin D3 inactivation, the IgM^- pool is more severely reduced. Interestingly, despite a compensatory increase in cyclln D2 expression, a significant number of Ccnd3^-/- GC B cells accumulate in quiescent GO state. Lastly, although cyclin D3 inactivation did not disrupt BCL6 expression in GC B cells, it completely blocked the GC promoting effect of BCL6 overexpression, suggesting that cyclin D3 acts downstream of BCL6 to regulate GC formation. This is the first demonstration that cyclin D3 plays an important and unique role at the GC stage of B cell development.
基金Item supported by international coopera-tion programme of science and technology of Shanghai (No.015407005)
文摘The purpose of this study was to evaluate the viability and subsequent developmental ability of porcine germinal vesicle(GV) oocytes vitrified step-wise exposure to cryoprotectants. Oocytes were transferred to a vitrification solution composed of 10% ethylene glycol(EG),10% dimethyl sulfoxide(DMSO), 300 g/L-1 Ficoll and 0.5 mol/L-1 sucrose(EDFS40) in a direct manner (non-preequilibrium) or in step-wise manner( single- and two-step preequilibrium). After vitrification and storage in liquid nitrogen, the oocytes were thawed,washed and in vitro maturation, fertilization and culture. In the non-preequilibrium group, the rates of post-thawed oocytes surviving, maturing to metaphase-Ⅱ, cleavage rate and blastocysts rate was significantly lower than that of sigle- and two-step preequilubrium groups(P<0.05). In the single- and two- step groups, the rates of metaphase-Ⅱ stage were 46.8%, 42.7% and 49.7%, respectively, the rates which developed to blastocysts were 10.5%,11.1% and 14.8%, respectivaly. In the non-vitrified control group,the rates of oocytes maturing to metaphase-Ⅱ, developing to blastocysts was significantly higher than that vitrified groups(P<0.05). The present study shows that the vitrification of porcine GV oocytes by a step-wise method involving two-steps preequilibrium may have advantage in maintaining the viability and subsequent production of blastocysts.
文摘Monoclonal antibodies were used to label cutaneous germinal center cell-derived lymphomas <CGCCL) obtained from 10 patients. According to the Kiel classification, they were classified into 2 types. Eight patients had centroblastic/centrocytic <CB/CC) lymphomas while 2 patients and centrocytic (CC) lymphomas. After monoclonal antibody labelling, the results were consistent with those of the clinical and morphologic analyses. Of the 10 cases, 9 were B1 positive, 6 were K positive, and 4 were λ positive. In 8 cases labeled with immunoglobulin, 6 were IgGFab positive, 2 were IgM positive and 8 were IgA negative. Five cases (CB/CC 3, CC 2) were both Bl, K and IgG positive (γ K). Four cases CB/CC were both Bl and A positive. Only one case (CB/CC) was both K and IgM positive (μ K). Two cases (CB CC) were both A and IgG positive (γ λ). The results indicate that Bl, K and A are the most important markers to phenotype cutaneous B-cell lymphomas. Our findings also show a higher percentage of y K types in CGCCL as compared with Western countries.
文摘The germinal matrix being an accumulation of immature blood vessels in the premature infant brain is known to be the main cause of the intracranial hemorrhage. To investigate the injuring mechanism to the blood vessels of the germinal matrix, a modeling scenario that consists of three basic steps is proposed. First, the cerebral blood flow that depends on autoregulation, CO2 reactivity, and variations of intracranial pressure is modeled. Second, the chaotic blood vessel network of the germinal matrix is generated, and blood pressures in the vessels of this network are computed dependent on the outcome of the first step. In the third step, the pressures computed on the second step are used in finite element simulations of separate blood vessels of the germinal matrix to detect critical values for vessels impairment.
基金supported by the Research Center for Brain Cognition and Human Development,Guangdong,China(2024B0303390003)Special Funds for the Cultivation of Guangdong College Students’Scientific and Technological Innovation(“Climbing Program”Special Funds pdjh2024b118)+2 种基金Autism Research Special Fund of Zhejiang Foundation For Disabled Persons(2023003)Scientific Research Innovation Project of Graduate School of South China Normal University(43204021)Startup Fund for Talented Scholars of South China Normal University.
文摘B cells,a pivotal constituent of the lymphatic system,undergo differentiation into plasma cells and memory B cells upon antigen stimulation,thereby primarily facilitating humoral immunity(Zhang et al.,2024).Most B cells necessitate transit through germinal centers(GCs)to achieve complete differentiation and maturation.Abnormal transformation of GC B cells represents a fundamental etiological factor in the development of diffuse large B-cell lymphoma(DLBCL)(Mlynarczyk et al.,2019)and multiple myeloma(MM)(Rizq et al.,2023).
基金supported by the German Research Foundation(DFG),project ID 509546995supported by DFG grants HU 1294/8-1,HU 1294/8-2,and SFB 1526-A08(project ID 454193335)+2 种基金funded by the Federal Ministry of Education and Research(BMBF)as part of the German Center for Child and Adolescent Health(DZKJ)under funding codes 01GL2401C,CONAN and TreATgrants from the Leibniz Association(Leibniz Collaborative Excellence,TargArt and ImpACt)supported by Germany’s Excellence Strategy grants EXC2151 and EXC2047.
文摘Pulmonary T and B cells are important for protection of this mucosal barrier site.While viral infections lead to the development of ectopic lymphoid structures highly similar to those in germinal centers in secondary lymphoid organs,little is known about how T/B cooperation occurs in the unstructured,diffuse tissue infiltrates characteristic of autoimmune diseases and nonviral infections.Using a mouse model of interstitial lung inflammation,we found that naive B cells are directly activated in lung tissue.Despite the absence of any germinal center-like structures,the interaction of B cells with peripheral T helper cells results in efficient somatic hypermutation and class switching.As antigen-presenting cells,macrophages are critical for this process.Unique B-cell repertoires indicated that the lung response was autonomous from the lung-draining lymph node.Only lung GC-like B cells were switched to IgA and had a broader repertoire,making them ideal candidates for producing broadly neutralizing immunoglobulins against respiratory pathogens.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
文摘The transcriptional repressor B cell lymphoma 6(BCL6) controls a large transcriptional network that is required for the formation and maintenance of germinal centers(GC). GC B cells represent the normal counterpart of most human B-cell lymphomas, which are often characterized by deregulated BCL6 expression or BCL6-mediated pathways. BCL6 suppresses gene transcription largely through recruitment of its co-repressors through its distinct repression domain. Understanding the precise biological roles of each repression domain in normal and malignant B cells is helpful for development of targeted inhibition of BCL6 functions that is emerging as the basis for design of anti-lymphoma therapies. This review focuses on recent progress in the molecular mechanisms of action of BCL6 in B cells and discusses remaining unresolved questions related to how these mechanisms are linked to normal and malignant B cell development.
基金We acknowledge all members of the Milpied and Vivier laboratories at CIML for fruitful discussionsEP is supported by a fellowship funded by Innate Pharma and the RHU PIONeeR project(ANR-17-RHUS-00XX-08)This work was supported by grants from ITMO Cancer and the RHU PIONeeR project.
文摘B cells play essential roles in immunity,mainly through the production of high affinity plasma cells(PCs)and memory B(Bmem)cells.The affinity maturation and differentiation of B cells rely on the integration of B-cell receptor(BCR)intrinsic and extrinsic signals provided by antigen binding and the microenvironment,respectively.In recent years,tumor infiltrating B(TIL-B)cells and PCs(TIL-PCs)have been revealed as important players in antitumor responses in human cancers,but their interplay and dynamics remain largely unknown.In lymphoid organs,B-cell responses involve both germinal center(GC)-dependent and GC-independent pathways for Bmem cell and PC production.Affinity maturation of BCR repertoires occurs in GC reactions with specific spatiotemporal dynamics of signal integration by B cells.In general,the reactivation of high-affinity Bmem cells by antigens triggers GC-independent production of large numbers of PC without BCR rediversification.Understanding B-cell dynamics in immune responses requires the integration of multiple tools and readouts such as single-cell phenotyping and RNA-seq,in situ analyses,BCR repertoire analysis,BCR specificity and affinity assays,and functional tests.Here,we review how those tools have recently been applied to study TIL-B cells and TIL-PC in different types of solid tumors.We assessed the published evidence for different models of TIL-B-cell dynamics involving GC-dependent or GC-independent local responses and the resulting production of antigen-specific PCs.Altogether,we highlight the need for more integrative B-cell immunology studies to rationally investigate TIL-B cells as a leverage for antitumor therapies.
基金supported by the National Key R&D Program of China (2017YFC1001901 and 2017YFA0102801)the National Natural Science Foundation (31671540)+3 种基金the National Transgenic Major Program (2016ZX08006003-006)the Natural Science Foundation of Guangdong Province (2015A020212005 and 2014A030312011)the Key R&D Program of Guangdong Province (2018B020203003)the Guangzhou Science and Technology Project (201803010020)。
文摘Cytosine and adenine base editors are promising new tools for introducing precise genetic modifications that are required to generate disease models and to improve traits in pigs. Base editors can catalyze the conversion of C→T(C>T) or A→G(A>G) in the target site through a single guide RNA. Injection of base editors into the zygote cytoplasm can result in the production of offspring with precise point mutations, but most F0 are mosaic, and breeding of F1 heterozygous pigs is time-intensive. Here, we developed a method called germinal vesicle oocyte base editing(GVBE) to produce point mutant F0 porcine embryos by editing the maternal alleles during the GV to MⅡ transition. Injection of cytosine base editor 3(BE3) mRNA and X-linked Dmdspecific guide RNAs into GVoocytes efficiently edited maternal Dmd during in vitro maturation and did not affect the maturation potential of the oocytes. The edited MⅡ oocytes developed into blastocysts after parthenogenetic activation(PA) or in vitro fertilization(IVF). However, BE3 may reduce the developmental potential of IVF blastocysts from 31.5%±0.8% to 20.4%±2.1%. There 40%–78.3% diploid PA blastocysts had no more than two different alleles, including up to 10% embryos that had only C>T mutation alleles. Genotyping of IVF blastocysts indicated that over 70% of the edited embryos had one allele or two different alleles of Dmd. Since the male embryos had only a copy of Dmd allele, all five(5/19) F0 male embryos are homozygous and three of them were Dmd precise C>T mutation. Nine(9/19) female IVF embryos had two different alleles including a WT and a C>T mutation. DNA sequencing showed that some of them might be heterozygous embryos. In conclusion, the GVBE method is a valuable method for generating F0 embryos with maternal point mutated alleles in a single step.
基金We thank all personnel from the Toulouse animal facility CREFRE and from the flow cytometry,imaging,transcriptomics and bioinformatics technical platforms of INFINITy.M.D.D-M.is supported by ATIP-Avenir-Plan Cancer(C18003BS),ANR(ANR-20-CE15-0007)foundation ARSEP R19201BB,foundation ARC,La Ligue Contre Le Cancer and INSPIRE(Region Occitanie,Inserm and CHU Toulouse)M.T.is supported with a BBSRC core funding grant and a Wellcome Investigator award(200823/Z/16/Z).D.C.-S.is supported by Boehringer Ingelheim Fonds.
文摘Germinal centers(GCs)are essential for the establishment of long-lasting antibody responses.GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome.However,the critical proteins driving these key mechanisms are still unknown.Here,we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses.TIA1-and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection,expansion and differentiation into B-cell clones producing high-affinity antibodies.Mechanistically,TIA1 and TIAL1 control the transcriptional identity of dark-and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1.Thus,we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.
基金This work was supported by the 973 Program of the Ministry of Science and Technology of China (2010CB529700 and 2012CB910204), the National Natural Science Foundation of China (NSFC10979005 and NSFC30970566) and the Science and Technology Commission of Shanghai Municipality (11JC14140000). Dr ZZ is a scholar of the Hundred Talents Program of the Chinese Academy of Sciences. Dr Greene is supported by grants from the NIH, NCI, the Abramson Family Research Institute and the BCRF.
文摘Germinal center kinases (GCKs) participate in a variety of signaling pathways needed to regulate cellular functions including apoptosis, cell proliferation, polarity and migration. Recent studies have shown that GCKs are participants in both adaptive and innate immune regulation. However, the differential activation and regulatory mechanisms of GCKs, as well as upstream and downstream signaling molecules, remain to be fully defined. It remains unresolved whether and how GCKs may cross-talk with existing signaling pathways. This review stresses the progresses in research of GCKs relevant to the immune system.
基金supported by the Deutsche Krebshilfe,Nr.70113859 to U.Z.-S.and H.A.,the Wilhelm-Sander-Stiftung Nr.2022.128.1 to A.Ö.Y and U.Z.-S.and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI170965。
文摘Initially,identified as a Hodgkin lymphoma marker,CD30 was subsequently detected on a subset of human B cells within and around germinal centers(GCs).While CD30 expression is typically restricted to a few B cells,expansion of CD30-expressing B cells occurs in certain immune disorders and during viral infections.The role of CD30 in B cells remains largely unclear.To address this gap in knowledge,we established a conditional CD30-knockin mouse strain.In these mice,B-cell-specific CD30 expression led to a normal B-cell phenotype in young mice,but most aged mice exhibited significant expansion of B cells,T cells and myeloid cells and increased percentages of GC B cells and IgG1-switched cells.This may be driven by the expansion of CD4+senescence-associated T cells and T follicular helper cells,which partially express CD30-L(CD153)and may stimulate CD30-expressing B cells.Inducing CD30 expression in antigen-activated B cells accelerates the GC reaction and augments plasma cell differentiation,possibly through the posttranscriptional upregulation of CXCR4.Furthermore,CD30 expression in GC B cells promoted the expansion of IgG1-switched cells,which displayed either a GC or memory-like B-cell phenotype,with abnormally high IgG1 levels compared with those in controls.These findings shed light on the role of CD30 signaling in GC B cells and suggest that elevated CD30+B-cell numbers lead to pathological lymphocyte activation and proliferation.
基金supported by grants from the National Natural Science Foundation of China(32470364,31872850,and 31872804)the Natural Science Basic Research Program of Shaanxi(2025JC-JCQN-056 and 2024JC-YBMS-151)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2025A1515012749)the China Postdoctoral Science Foundation(2025M774348)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(22JHZ007and 22JHQ054)。
文摘Gibberellins(GAs)and auxin play central regulatory roles in seed germination and root system development,respectively,so that the application of these phytohormones to crops would be worthwhile,with an increasing potential demand in agriculture.However,there are few effective chemicals that simultaneously enhance both GA and auxin signaling.Here,we report on an artificial thiourea derivative chemical,Y21,that serves as both a GA-signaling agonist and an auxin analog,promoting seed germination and root development,as well as low-phosphorus tolerance.Phenotypic,biochemical,and genetic evidence demonstrated that Y21 enhances the interaction between GA and its receptor GID1C via the Val239 amino acid residue and consequently promotes degradation of the DELLA proteins REPRESSOR OF ga1-3(RGA)and RGA-LIKE 2.Furthermore,we found that Y21 interacts with the auxin receptor TIR1 via the Cys405 residue and thus promotes the turnover of the auxinresponsive Aux/IAA proteins.Consequently,Y21significantly increases low-phosphorus tolerance of treated plants by positively regulating lateral root development.To our knowledge,Y21 is the first GA-signaling agonist to be identified,and our results also demonstrate that this potent synthetic chemical,identified by chemical genetic screening,is effective at modulating plant development and stress tolerance.
基金funded by Bangladesh Agricultural University Research System(BAURES)through the Project No.2024/48/BAU.
文摘Seaweed extract contains plant growth regulators and bio-stimulants that enhance plant growth and development.In Bangladesh,winter rice(Boro rice)in the nursery bed often shows poor seed emergence and weak seedling growth due to low temperature.This problem can be addressed by using seaweed extract as a seed priming agent and bio-stimulant.The objective of this study was to evaluate the effectiveness of seaweed extract(Crop Plus)on seed emergence,seedling growth,and vigor of winter rice in the nursery.Two experiments were conducted at Bangladesh Agricultural University using BRRI dhan89.The laboratory experiment consisted of 17 treatments combining three concentrations of Crop Plus(5000,10,000 and 15,000 ppm)and four priming durations(6,12,18,and 24 h),along with hydro-priming and a no priming as control.Seed priming with 15,000 ppm for 24 h produced the highest germination percentage and superior seedling growth traits.The nursery bed experiment comprised 11 treatments combining two doses(1 mL m^(−2)and 2 mL m^(−2))of Crop Plus and five different foliar application schedules,along with a control.All treatments outperformed the control,with the best results from Crop Plus@2 mL m^(−2)applied at 20 and 30 days after sowing(DAS).Overall,the treatment involving seed priming with 15,000 ppm seaweed extract for 24 h,followed by nursery application at 2 mL m^(−2)at 20 and 30 DAS,resulted in higher germination and improved early growth of winter rice.However,further validation across multiple locations,seasons,and rice cultivars is recommended.
文摘Seed vigor is critical for uniform germination and emergence,directly influencing subsequent seedling development.This is especially important under both normal and stress conditions that may arise post-sowing.Chilling stress during emergence and early growth poses significant challenges for tomato seedlings,potentially leading to uneven emergence,abnormal growth,and higher seedling mortality.This study evaluated the effectiveness of combining drum-priming with melatonin to alleviate chilling stress during these two critical stages.Tomato seeds were primed with melatonin at various concentrations and compared to untreated controls under chilling stress conditions.Higher concentrations of melatonin significantly accelerated emergence and improved early growth under stress.These stress-mitigating effects were evidenced by reductions in oxidative stress markers,such as malondialdehyde and hydrogen peroxide,along with increased total polyphenol and flavonoid contents.Furthermore,melatonin priming preserved photosynthetic efficiency,typically reduced by chilling stress,and enhanced the activities of antioxidant enzymes,including catalase and peroxidase.These biochemical changes reduced oxidative damage and promoted stress resilience.Melatonin also accelerated the expression of genes within the C-repeat binding factor pathway,which is crucial for cold acclimation.This suggests that melatonin priming enabled quicker adaptation to chilling stress following sowing and bolstered seedling resilience during subsequent growth stages.Overall,our results demonstrate that melatonin priming not only enhances germination but also significantly supports seedling growth under adverse conditions.The findings highlight melatonin as a promising tool in crop management strategies to improve resilience against sudden chilling stress.
文摘Subject Code:C08With the support by the National Natural Science Foundation of China,a study by the research group led by Prof.Qi Hai(祁海)from the School of Medicine,Tsinghua University revealed a novel mechanism that regulates the germinal center reaction,aphysiological process that underlies high-quality