We report a three-year-old male child who presented with congenital valvular defects,right ventricular malformation,and initial developmental delay.Genome sequencing showed rare deleterious biallelic missense variants...We report a three-year-old male child who presented with congenital valvular defects,right ventricular malformation,and initial developmental delay.Genome sequencing showed rare deleterious biallelic missense variants in PLD1.In his parents’second pregnancy,echocardiogram at 13 weeks gestation revealed right-sided cardiac malformations resembling the clinical presentation of the family’s first child.Targeted DNA analysis showed that the fetus carried the same biallelic PLD1 variants as their older sibling.This case helps to further delineate the clinical spectrum of PLD1-related defects and highlights the value of both genome sequencing in congenital heart disease and early fetal echocardiography to establish phenotype.展开更多
Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the...Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.展开更多
Phospholipase D （PLD） plays a critical role in plant growth and development, as well as in hormone and stress responses. PLD encoding genes constitute a large gene family that are present in higher plants. There are...Phospholipase D （PLD） plays a critical role in plant growth and development, as well as in hormone and stress responses. PLD encoding genes constitute a large gene family that are present in higher plants. There are 12 members of the PLD family in Arabidopsis thaliana and several of them have been functionally characterized; however, the members of the PLD family in Oryza sativa remain to be fully described. Through genome-wide analysis, 17 PLD members found in different chromosomes have been identified in rice. Protein domain structural analysis reveals a novel subfamily, besides the C2-PLDs and PXPH-PLDs, that is present in rice - the SP-PLD. SP-PLD harbors a signal peptide instead of the C2 or PXPH domains at the N-terminus. Expression pattern analysis indicates that most PLD-encoding genes are differentially expressed in various tissues, or are induced by hormones or stress conditions, suggesting the involvement of PLD in multiple developmental processes. Transgenic studies have shown that the suppressed expression office PLDβ1 results in reduced sensitivity to exogenous ABA during seed germination. Further analysis of the expression of ABA signaling-related genes has revealed that PLDβ1 stimulates ABA signaling by activating SAPK, thus repressing GAmyb exoression and inhibiting seed germination.展开更多
The CuxSi（1-x） thin films have been grown by pulsed laser deposition（PLD） with in situ annealing on Si（001） and Si（111）,respectively.The transformation of phase was detected by X-ray diffraction（XRD）.The res...The CuxSi（1-x） thin films have been grown by pulsed laser deposition（PLD） with in situ annealing on Si（001） and Si（111）,respectively.The transformation of phase was detected by X-ray diffraction（XRD）.The results showed that the as-deposited films were composed of Cu on both Si（001） and Si（111）.The annealed thin films consisted of Cu ＋η ＂-Cu3Si on Si（001） while Cu ＋η＇-Cu3Si on Si（111）,respectively,at annealed temperature（Ta）= 300-600℃.With the further increasing of Ta,at Ta= 700℃,there was only one main phase,η＂-Cu3Si on Si（001） while η＇-Cu3Si on Si（111）,respectively.The annealed thin films transformed from continuous dense structure to scattered-grain morphology with increasing Ta detected by field emission scanning electron microscope（FESEM）.It was also showed that the grain size would enlarge with increasing annealing time（ta）.展开更多
MicroRNAs （miRNAs） are a type of small non-coding RNAs that are often play important roles in carcinogene- sis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and...MicroRNAs （miRNAs） are a type of small non-coding RNAs that are often play important roles in carcinogene- sis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma （GC）. The expres- sion of miR-638 in GC and the DNA copy number of miR- 638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algo- rithms （TargetScan and miRanda）, luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues （NCTs）, and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Fur- thermore, we observed that PLD1 was overexpressed inGC tissues, and high expression of PLDt in GC predicted poor overall survival. In summary, we revealed that miR- 638 functions as a tumor suppressor in GC through inhibiting PLDI.展开更多
基金This work was funded by the Ted Rogers Centre for Heart Research.
文摘We report a three-year-old male child who presented with congenital valvular defects,right ventricular malformation,and initial developmental delay.Genome sequencing showed rare deleterious biallelic missense variants in PLD1.In his parents’second pregnancy,echocardiogram at 13 weeks gestation revealed right-sided cardiac malformations resembling the clinical presentation of the family’s first child.Targeted DNA analysis showed that the fetus carried the same biallelic PLD1 variants as their older sibling.This case helps to further delineate the clinical spectrum of PLD1-related defects and highlights the value of both genome sequencing in congenital heart disease and early fetal echocardiography to establish phenotype.
基金This work was supported by the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061)the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141)+2 种基金National Natural Science Foundation(82261160657)Chang Jiang Scholars Program(J.-X.B.)Special Support Program of Guangdong(J.-X.B.)。
文摘Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.
基金This work was supported by the State Key Project of Basic Research （2005CB 120803） and the National Natural Science Foundation of China （30425029, 30421001）. We thank Ms Shu-Ping Xu （Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences） for help on rice transformation.
文摘Phospholipase D （PLD） plays a critical role in plant growth and development, as well as in hormone and stress responses. PLD encoding genes constitute a large gene family that are present in higher plants. There are 12 members of the PLD family in Arabidopsis thaliana and several of them have been functionally characterized; however, the members of the PLD family in Oryza sativa remain to be fully described. Through genome-wide analysis, 17 PLD members found in different chromosomes have been identified in rice. Protein domain structural analysis reveals a novel subfamily, besides the C2-PLDs and PXPH-PLDs, that is present in rice - the SP-PLD. SP-PLD harbors a signal peptide instead of the C2 or PXPH domains at the N-terminus. Expression pattern analysis indicates that most PLD-encoding genes are differentially expressed in various tissues, or are induced by hormones or stress conditions, suggesting the involvement of PLD in multiple developmental processes. Transgenic studies have shown that the suppressed expression office PLDβ1 results in reduced sensitivity to exogenous ABA during seed germination. Further analysis of the expression of ABA signaling-related genes has revealed that PLDβ1 stimulates ABA signaling by activating SAPK, thus repressing GAmyb exoression and inhibiting seed germination.
基金Funded by National Natural Science Foundation of China(Nos.51102101,51272196,51372188,51521001)the 111 Project(No.B13035)+2 种基金the International Science&Technology Cooperation Program of China(No.2014DFA53090)the Natural Science Foundation of Hubei Province,China(No.2014CFB870)the Fundamental Research Funds for the Central Universities,China(No.WUT:2015III023)
文摘The CuxSi（1-x） thin films have been grown by pulsed laser deposition（PLD） with in situ annealing on Si（001） and Si（111）,respectively.The transformation of phase was detected by X-ray diffraction（XRD）.The results showed that the as-deposited films were composed of Cu on both Si（001） and Si（111）.The annealed thin films consisted of Cu ＋η ＂-Cu3Si on Si（001） while Cu ＋η＇-Cu3Si on Si（111）,respectively,at annealed temperature（Ta）= 300-600℃.With the further increasing of Ta,at Ta= 700℃,there was only one main phase,η＂-Cu3Si on Si（001） while η＇-Cu3Si on Si（111）,respectively.The annealed thin films transformed from continuous dense structure to scattered-grain morphology with increasing Ta detected by field emission scanning electron microscope（FESEM）.It was also showed that the grain size would enlarge with increasing annealing time（ta）.
文摘MicroRNAs （miRNAs） are a type of small non-coding RNAs that are often play important roles in carcinogene- sis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma （GC）. The expres- sion of miR-638 in GC and the DNA copy number of miR- 638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algo- rithms （TargetScan and miRanda）, luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues （NCTs）, and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Fur- thermore, we observed that PLD1 was overexpressed inGC tissues, and high expression of PLDt in GC predicted poor overall survival. In summary, we revealed that miR- 638 functions as a tumor suppressor in GC through inhibiting PLDI.
