ABSTRACT
GATA4 plays a pivotal role in the reproductive processes of mammals. However, the research on GATA4 in goat ovary is limited. This study aimed to study the expression and function of GATA4 in goat ovary. Utilizing real-time PCR and western blot analysis, we studied the expression and regulatory mechanisms of GATA4 in goat ovary and granulosa cells (GCs). We found that GATA4 was expressed in all follicle types in the goat ovary, with significantly higher levels in GCs of larger follicles (>3 mm) compared to those in smaller follicles (<3 mm). Additionally, we demonstrated that human chorionic gonadotrophin (hCG) induced GATA4 mRNA expression via the activation of PKA, MEK, p38 MAPK, PKC, and PI3K pathways in vitro. Our study also showed that hCG suppressed the levels of miR-200b and miR-429, which in turn directly target GATA4, thereby modulating the basal and hCG-induced expression of GATA4. Functionally, we examined the effect of siRNA-mediated GATA4 knockdown on cell proliferation and hormone secretion in goat GCs. Our results revealed that knockdown of GATA4, miR-200b, and miR-429 suppressed cell proliferation. Moreover, knockdown of GATA4 decreased estradiol and progesterone production by inhibiting the promoter activities of CYP11A1, CYP19A1, HSD3B, and StAR. Collectively, our findings suggest a critical involvement of GATA4 in regulating goat GC survival and steroidogenesis.
Subject(s)
Chorionic Gonadotropin , GATA4 Transcription Factor , Gene Expression Regulation , Goats , Granulosa Cells , Animals , Granulosa Cells/metabolism , Granulosa Cells/drug effects , Granulosa Cells/physiology , Goats/physiology , Female , GATA4 Transcription Factor/genetics , GATA4 Transcription Factor/metabolism , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Chorionic Gonadotropin/pharmacology , MicroRNAs/genetics , MicroRNAs/metabolism , Progesterone/metabolism , Cells, Cultured , Estradiol/pharmacology , Estradiol/metabolism , Cell ProliferationABSTRACT
Dance and music are well known to improve sensorimotor skills and cognitive functions. To reveal the underlying mechanism, previous studies focus on the brain plastic structural and functional effects of dance and music training. However, the discrepancy training effects on brain structure-function relationship are still blurred. Thus, proficient dancers, musicians, and controls were recruited in this study. The graph signal processing framework was employed to quantify the region-level and network-level relationship between brain function and structure. The results showed the increased coupling strength of the right ventromedial putamen in the dance and music groups. Distinctly, enhanced coupling strength of the ventral attention network, increased coupling strength of the right inferior frontal gyrus opercular area, and increased function connectivity of coupling function signal between the right and left middle frontal gyrus were only found in the dance group. Besides, the dance group indicated enhanced coupling function connectivity between the left inferior parietal lobule caudal area and the left superior parietal lobule intraparietal area compared with the music groups. The results might illustrate dance and music training's discrepant effect on the structure-function relationship of the subcortical and cortical attention networks. Furthermore, dance training seemed to have a greater impact on these networks.
Subject(s)
Music , Brain/diagnostic imaging , Brain Mapping , Parietal Lobe , Frontal Lobe , Magnetic Resonance Imaging/methodsABSTRACT
Our objective was to determine effects of supplemental dietary riboflavin on meat quality, antioxidant capacity, fatty acid composition, lipidomic, volatilomic, and proteomic profiling of duck breast muscle. The results showed that dietary riboflavin supplementation significantly increased growth performance, breast meat yield, intramuscular fat content, polyunsaturated fatty acid (PUFA), n3-PUFA, n6-PUFA, redness (a*), and pH24h, but decreased lightness (L*) and yellowness (b*). Furthermore, riboflavin supplementation significantly improved muscle antioxidant capacity based on various biochemical parameters. Lipidomic and volatilomic analyses revealed that riboflavin supplementation markedly increased breast meat phosphatidylglycerol and coenzyme Q contents and two favourable key odorants, citronellyl acetate and 3-(methylthio)-propanal. Proteomics analyses confirmed that riboflavin supplementation activated mitochondrial aerobic respiration, including fatty acid beta oxidation, the tricarboxylic acid cycle, and oxidative phosphorylation. In conclusion, supplementing duck diets with riboflavin enhanced breast meat quality, attributed to increases in antioxidant capacity and mitochondrial functions.
ABSTRACT
New stable frictional materials based on metal-organic frameworks (MOFs) are greatly desired for applications in self-powered systems. This work reports an ionic MOF material with efficient charge separation mediated by charge induction. ZUT-iMOF-1(Cu) is chemically stable and its triboelectric output performance surpasses those of traditional MOF materials. The short-circuit current of the iMOF triboelectric nanogenerator is 73.79 µA at 5 Hz. The output performance remains stable over 50 000 cycles of continuous operation. The charge and power densities peak at 123.20 µC m-2 and 3133.23 mW m-2. Owing to its high output performance, ZUT-iMOF-1(Cu) effectively prevents metal corrosion in cathodic-protection systems. Theoretical calculations show that increasing the charge-separation effect promotes the frictional electricity generation behaviour. This study provides research suggestions for ionic MOF frictional materials and will promote their application in self-powered electrochemical cathodic-protection systems.
ABSTRACT
Androgen insensitivity syndrome (AIS) is a rare genetic disorder that affects the development of the male reproductive system in individuals with a 46,XY karyotype. In addition to physical impacts, patients with AIS may face psychological distress and social challenges related to gender identity and acceptance. The major molecular etiology of AIS results from hormone resistance caused by mutations in the X-linked androgen receptor (AR) gene. Depending on the severity of androgen resistance, the wide spectrum of AIS can be divided into complete AIS (CAIS), partial AIS (PAIS), or mild AIS (MAIS). Open issues in the treatment and management of AIS include decisions about reconstructive surgery, genetic counseling, gender assignment, timing of gonadectomy, fertility and physiological outcomes. Although new genomic approaches have improved understanding of the molecular causes of AIS, identification of individuals with AIS can be challenging, and molecular genetic diagnosis is often not achievable. The relationship between AIS genotype and phenotype is not well established. Therefore, the optimal management remains uncertain. The objective of this review is to outline the recent progress and promote understanding of AIS related to the clinical manifestation, molecular genetics and expert multidisciplinary approach, with an emphasis on genetic etiology.
ABSTRACT
This study was to determine the effects of riboflavin deficiency (RD) on intestinal development, jejunum mucosa proteome, cecal short-chain fatty acids (SCFA) profiling, and cecal microbial diversity and community of starter Pekin ducks. Male white Pekin ducks (1 d old, n = 240) were allocated into 2 groups, with 12 replicates and 10 birds per replicate in each group. For 21 d, all ducks had ad libitum access to either an RD or a riboflavin adequate (control, CON) diet, formulated by supplementing a basal diet with 0 or 10 mg riboflavin per kg of diet, respectively. Compared to the CON group, growth retardation, high mortality, and poor riboflavin status were observed in the RD group. Furthermore, RD reduced the villus height and the ratio of villus height to crypt depth of jejunum and ileum (P < 0.05), indicating morphological alterations of the small intestine. In addition, dietary RD enhanced relative cecum weight and decreased cecal SCFA concentrations (P < 0.05), including propionate, isobutyrate, butyrate, and isovalerate. The jejunum mucosa proteomics showed that 208 proteins were upregulated and 229 proteins were downregulated in the RD group compared to those in the CON group. Among these, RD mainly suppressed intestinal absorption and energy generation processes such as glycolysis and gluconeogenesis, fatty acid beta oxidation, tricarboxylic acid cycle, and oxidative phosphorylation, leading to impaired ATP generation. In addition, RD decreased the community richness and diversity of the bacterial community in the cecum of ducks. Specifically, RD reduced the abundance of butyrate-producing bacteria in the cecum (P < 0.05), such as Eubacterium coprostanoligenes, Prevotella and Faecalibacterium. Dietary RD resulted in growth depression and intestinal hypofunction of Pekin ducks, which could be associated with impaired intestinal absorption and energy generation processes in intestinal mucosa, as well as gut microbiota dysbiosis. These findings contribute to our understanding of the mechanisms of intestinal hypofunction due to RD.
ABSTRACT
N6-methyladenosine (m6A) is a common chemical modification for mammalian mRNA and exhibits high dynamics in various biological processes. However, dynamics of m6A RNA methylome during leukemogenesis remains unknown. Here, we delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6 as a key for maintaining AML stem cells. We observe an obvious change in m6A methylome during leukemogenesis and find that protein arginine methyltransferase PRMT6 and m6A reader IGF2BP2 maintain the function of human and murine leukemia stem cells (LSCs). Genetic deletion or pharmacological inhibition of PRMT6 damages AML development and LSC function. Mechanistically, IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner, which catalyzes H3R2me2a and suppresses lipid transporter MFSD2A expression. PRMT6 loss upregulates MFSD2A expression that increases docosahexaenoic acid levels and impairs LSC maintenance. Collectively, our findings reveal a critical role of PRMT6-MFSD2A signaling axis in AML development and provide a therapeutic strategy for targeting LSCs.
Subject(s)
Leukemia, Myeloid, Acute , RNA , Humans , Animals , Mice , RNA/metabolism , Epigenome , RNA, Messenger/metabolism , Neoplastic Stem Cells/metabolism , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Lipids , Mammals/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Nuclear Proteins/metabolism , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolismABSTRACT
Triboelectric nanogenerators (TENGs) based on contact electrification and electrostatic induction can effectively convert low-frequency mechanical energy into electrical energy and has attracted considerable attention. However, the low current output performance seriously hinders the wide application of TENGs. Herein, a 3D nanocrystalline metal-organic framework (Cd-MOF) with a specific structure and morphology was reasonably designed as a high-performance triboelectric positive electrode material. The triboelectric test results showed that the maximum instantaneous short-circuit current of Cd-MT was 55.32 µA and the stable output performance maintained a long-term continuous operation for 10 000 s. The peak values of the charge density and electric power density were 102.39 µC m-2 and 2451.04 mW m-2, respectively. In addition, the Cd-MT could quickly fully charge commercial capacitors and light a large number of LED lamps. This work provides a new idea for the development and design of functional MOF triboelectric materials.
ABSTRACT
The development of novel metal organic framework (MOF) friction power generation materials with high stability is important. This paper reports the first example of a double-helix metal chain organic framework with a network structure (ZUT-8). ZUT-8 shows high chemical stability, functional adjustability, and excellent output performance of friction power generation, which is superior to traditional coordination polymer materials. The cathodic protection system with ZUT-8 can prevent metal corrosion significantly. The output performance can be improved effectively by enhancing the conjugate effect of the linker. The theoretical calculation results showed that an increase in the degree of conjugation could significantly reduce the band gap, thereby affecting the friction power output signal. This study opens the door to constructing MOF materials with a double-helix metal chain and will promote their potential applications in self-powered electrochemical cathodic protection.
ABSTRACT
Riboflavin is an essential micronutrient and a precursor of flavin mononucleotide and flavin adenine dinucleotide for maintaining cell homeostasis. Riboflavin deficiency (RD) induces cell apoptosis. Endoplasmic reticulum (ER) stress is considered to induce apoptosis, and C/EBP homologous protein (CHOP) is a key pathway involved in this process. However, whether RD-induced apoptosis is mediated by ER stress and the CHOP pathway remains unclear and needs further investigation. Therefore, the current study presents the effect of RD on ER stress and apoptosis in the human hepatoma cell line (HepG2). Firstly, cells were cultured in a RD medium (4.55 nM riboflavin) and a control (CON) medium (1005 nM riboflavin). We conducted an observation of cell microstructure characterization and determining apoptosis. Subsequently, 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, was used in HepG2 cells to investigate the role of ER stress in RD-induced apoptosis. Finally, CHOP siRNA was transfected into HepG2 cells to validate whether RD triggered ER stress-mediated apoptosis by the CHOP pathway. The results show that RD inhibited cell proliferation and caused ER stress, as well as increased the expression of ER stress markers (CHOP, 78 kDa glucose-regulated protein, activating transcription factor 6) (p < 0.05). Furthermore, RD increased the cell apoptosis rate, enhanced the expression of proapoptotic markers (B-cell lymphoma 2-associated X, Caspase 3), and decreased the expression of the antiapoptotic marker (B-cell lymphoma 2) (p < 0.05). The 4-PBA treatment and CHOP knockdown markedly alleviated RD-induced cell apoptosis. These results demonstrate that RD induces cell apoptosis by triggering ER stress and the CHOP pathway.
Subject(s)
Apoptosis , Endoplasmic Reticulum Stress , Riboflavin Deficiency , Riboflavin , Transcription Factor CHOP , Apoptosis/genetics , Endoplasmic Reticulum Stress/genetics , Hep G2 Cells , Humans , Proto-Oncogene Proteins c-bcl-2/metabolism , Riboflavin/genetics , Riboflavin/metabolism , Riboflavin/pharmacology , Riboflavin Deficiency/genetics , Riboflavin Deficiency/physiopathology , Signal Transduction , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolismABSTRACT
PURPOSE: To summarize the clinical characteristics and surgical option of Robert's uterus. METHODS: We reported a rare case of Robert's uterus with severe uterine adhesion with successive laparoscopic and hysteroscopic surgery. To our knowledge, such a case has not been reported previously. We also performed a systematic literature review from the PubMed, Embase, and Cochrane databases. RESULTS: Our patient with Robert's uterus with severe uterine adhesions was successfully treated with hysteroscopic septal resection and hysteroscopic adhesiolysis, and the intractable dysmenorrhea disappeared after the hysteroscopic septal resection. In our study, we analyzed the selected 22 reported cases, 10/22 cases (45.5%) were diagnosed before age 20; 20/22 cases (90.91%) experienced dysmenorrhea, 19/22 cases (86.36%) were with hematometra. 5/22 cases (22.73%) underwent re-operation or a third surgery before diagnosis and management. CONCLUSION: Robert's uterus, a rare congenital abnormality of Mullerian duct development, consists of an oblique septum and non-communicating asymmetrical uterine hemi-cavity. The main symptoms are the presence of hematometra and severe dysmenorrhea. Septal resection is the main surgical procedure; however, the rarity and difficulty obtaining a pre-operative diagnosis lead to a high rate of misdiagnosis and second surgery.
Subject(s)
Hematometra , Uterine Diseases , Adult , Dysmenorrhea/etiology , Dysmenorrhea/pathology , Dysmenorrhea/surgery , Female , Hematometra/complications , Hematometra/surgery , Humans , Hysteroscopy/methods , Pregnancy , Tissue Adhesions/complications , Tissue Adhesions/diagnosis , Tissue Adhesions/surgery , Uterine Diseases/complications , Uterine Diseases/diagnosis , Uterine Diseases/surgery , Uterus/abnormalities , Young AdultABSTRACT
NAD+ metabolism is involved in many biological processes. However, the underlying mechanism of how NAD+ metabolism is regulated remains elusive. Here, we find that PTIP governs NAD+ metabolism in macrophages by regulating CD38 expression and is required for macrophage inflammation. Through integrating histone modifications with NAD+ metabolic gene expression profiling, we identify PTIP as a key factor in regulating CD38 expression, the primary NAD+-consuming enzyme in macrophages. Interestingly, we find that PTIP deletion impairs the proinflammatory response of primary murine and human macrophages, promotes their metabolic switch from glycolysis to oxidative phosphorylation, and alters NAD+ metabolism via downregulating CD38 expression. Mechanistically, an intronic enhancer of CD38 is identified. PTIP regulates CD38 expression by cooperating with acetyltransferase p300 in establishing the CD38 active enhancer with enriched H3K27ac. Overall, our findings reveal a critical role for PTIP in fine-tuning the inflammatory responses of macrophages via regulating NAD+ metabolism.
Subject(s)
Macrophages , NAD , Animals , DNA-Binding Proteins , Humans , Inflammation , Macrophages/metabolism , Mice , NAD/metabolism , Oxidative Phosphorylation , p38 Mitogen-Activated Protein KinasesABSTRACT
N6-methyladenosine (m6A) on mRNA plays critical roles in various cellular processes. However, the landscape and dynamics of m6A modification in hematopoietic system remain unknown. Here, we delineate a comprehensive m6A landscape across hematopoietic hierarchy and uncover that IGF2BP2 is required for preserving the function of hematopoietic stem cells (HSCs). Our data reveal a cell-type-specific m6A landscape in hematopoiesis. m6A modifications arise mostly in the early stage of hematopoiesis and prefer to play distinct roles for determining mRNA fates in HSCs and committed progenitors. Mechanistically, increased m6A-IGF2BP2 expression controls transcriptional state and maintenance of HSCs. IGF2BP2 deficiency induces quiescence loss and impairs HSC function. Moreover, IGF2BP2 loss increases mitochondrial activity of HSCs by accelerating Bmi1 mRNA decay, leading to de-repression of mitochondria-related genes. Collectively, our results present a fascinating portrait of m6A modification of hematopoietic hierarchy and reveal a key role of IGF2BP2 in maintaining HSC function by restraining mitochondrial activity.
Subject(s)
Hematopoiesis , RNA , Cell Division , Hematopoiesis/genetics , Hematopoietic Stem Cells/metabolism , Mitochondria , RNA/metabolismABSTRACT
Green development is a strategy for China's sustainable economic growth, and improving green total factor energy efficiency (GTFEE) is the key to achieving the dual goals of energy conservation, emission reduction, and economic development. This paper takes panel data of 267 prefecture-level cities in China from 2004 to 2019 as samples to explore how heterogeneous environmental regulation can have the effects of FDI on GTFEE. The results show that, first, except for environmental regulation and FDI independently affecting GTFEE, there is a synergistic effect between environmental regulation and FDI, and their interaction can also significantly affect GTFEE. Secondly, FDI has no significant impact on GTFEE when environmental regulation is low, but FDI can significantly improve GTFEE when environmental regulation is high. Thirdly, market-based environmental regulations (MER) have a better improvement effect on GTFEE than command-based environmental regulations (CER). Therefore, it is necessary to pay attention to the benign interaction between FDI and environmental regulation, especially giving full play to the role of market-based environmental regulation and further improving the design of command-based environmental regulation.
Subject(s)
Conservation of Energy Resources , Investments , China , Economic Development , EfficiencyABSTRACT
An organophotocatalyzed C(sp2)-H/N-H cross-dehydrogenative coupling of cyclic aldimines with aliphatic amines has been developed, which represents the first example of visible-light-induced C-H amination of N-sulfonylated imines. This methodology enables the streamline assembly of amine derivatives via radical mediated C-N bond formation. The current protocol features transition-metal-free, mild conditions, good functional group tolerance and good yields.
ABSTRACT
RNA-binding proteins (RBPs) are critical regulators of transcription and translation that are often dysregulated in cancer. Although RBPs are increasingly recognized as being important for normal hematopoiesis and for hematologic malignancies as oncogenes or tumor suppressors, RBPs that are essential for the maintenance and survival of leukemia remain elusive. Here we show that YBX1 is specifically required for maintaining myeloid leukemia cell survival in an N6-methyladenosine (m6A)-dependent manner. We found that expression of YBX1 is significantly upregulated in myeloid leukemia cells, and deletion of YBX1 dramatically induces apoptosis and promotes differentiation coupled with reduced proliferation and impaired leukemic capacity of primary human and mouse acute myeloid leukemia cells in vitro and in vivo. Loss of YBX1 has no obvious effect on normal hematopoiesis. Mechanistically, YBX1 interacts with insulin-like growth factor 2 messenger RNA (mRNA)-binding proteins (IGF2BPs) and stabilizes m6A-tagged RNA. Moreover, YBX1 deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and BCL2 in an m6A-dependent manner, which contributes to the defective survival that results from deletion of YBX1. Thus, our findings have uncovered a selective and critical role of YBX1 in maintaining myeloid leukemia survival, which might provide a rationale for the therapeutic targeting of YBX1 in myeloid leukemia.
Subject(s)
Adenosine/analogs & derivatives , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Y-Box-Binding Protein 1/metabolism , Adenosine/metabolism , Animals , Apoptosis/genetics , Cell Survival/genetics , Gene Deletion , Gene Expression Regulation, Leukemic , Hematopoiesis/genetics , Humans , Leukemia, Myeloid, Acute/genetics , Mice, Inbred C57BL , Protein Stability , Proto-Oncogene Proteins c-myc/metabolism , RNA, Neoplasm/metabolism , RNA-Binding Proteins/metabolism , Y-Box-Binding Protein 1/geneticsABSTRACT
The rapidly developmental RNA-guided CRISPR/Cas system is a powerful tool for RNA and DNA editing in a variety of cells from different species and makes a great contribution to gene function research, disease model generation and gene therapy development in the past few years. The ease of use, low cost and high efficiency of CRISPR/Cas make it commonly used in various conditions. In this review, we introduce the CRISPR/Cas system and its diverse applications in nervous system briefly, which provides a better understanding for its potential application values.
ABSTRACT
PTX3, a member of the pentraxin protein family, plays important roles in ovulation as a marker of cumulus cell-oocyte complex expansion. However, the expression and function of PTX3 in goat ovarian GCs remain unclear. We isolated GCs from small and large follicles and found that PTX3 expression was significantly decreased and miR-29 mRNA expression was significantly increased during the growth of antral follicles. MiR-29 decreased PTX3 expression by targeting its 3' untranslated. Furthermore, miR-29 promoted GC proliferation, suppressed steroidogenesis and apoptosis by targeting PTX3 via the activation of the PI3K/AKT/mTOR and Erk1/2 signaling pathways. Treatment with inhibitors also verified these results. Meanwhile, we found that PI3K/AKT/mTOR and Erk1/2 signaling pathways had different role in secretion of E2 and P4 by regulating differently various steroidogenic enzyme (CYP19A1, CYP11A1, StAR and HSD3B) expression. These outcomes indicate the potential role of PTX3 in goat follicular growth and atresia.
Subject(s)
C-Reactive Protein/metabolism , Granulosa Cells/metabolism , MicroRNAs/genetics , Serum Amyloid P-Component/metabolism , Animals , Apoptosis , C-Reactive Protein/genetics , Cell Proliferation , Estradiol/metabolism , Female , Goats , HEK293 Cells , Humans , MAP Kinase Signaling System , Phosphatidylinositol 3-Kinases/metabolism , Progesterone/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Serum Amyloid P-Component/genetics , TOR Serine-Threonine Kinases/metabolismABSTRACT
N6-methyladenosine (m6A) is a commonly present modification of mammalian mRNAs and plays key roles in various cellular processes. m6A modifiers catalyze this reversible modification. However, the underlying mechanisms by which these m6A modifiers are regulated remain elusive. Here we show that expression of m6A demethylase ALKBH5 is regulated by chromatin state alteration during leukemogenesis of human acute myeloid leukemia (AML), and ALKBH5 is required for maintaining leukemia stem cell (LSC) function but is dispensable for normal hematopoiesis. Mechanistically, KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing H3K9me3 levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Thus, our findings link chromatin state dynamics with expression regulation of m6A modifiers and uncover a selective and critical role of ALKBH5 in AML that might act as a therapeutic target of specific targeting LSCs.