ABSTRACT
Ethylene response factors have been shown to be involved in the effects of plant developmental processes and to regulate stress tolerance. The aim of this study was to recognize the regulatory mechanisms of ethylene response factors on tobacco plant height. In this study, a gene-edited mutant (ERF10-KO) and wild type (WT) were utilized as experimental materials. Transcriptome and metabolome analyses were used to investigate the regulatory mechanism of NtERF10 gene editing on plant height in tobacco. Here, through the analysis of differentially expressed genes (DEGs), 2051 genes were upregulated and 1965 genes were downregulated. We characterized the different ERF10-KO and WT plant heights and identified key genes for photosynthesis, the plant hormone signal transduction pathway and the terpene biosynthesis pathway. NtERF10 was found to affect the growth and development of tobacco by regulating the expression levels of the PSAA, PSBA, GLY17 and GGP3 genes. Amino acid metabolism was analyzed by combining analyses of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). In addition, we found that members of the bHLH, NAC, MYB, and WRKY transcription factor families have vital roles in regulating plant height. This study not only provides important insights into the positive regulation of the ethylene response factor NtERF10 on plant height during plant growth and development but also provides new research ideas for tobacco molecular breeding.
Subject(s)
Gene Expression Regulation, Plant , Nicotiana , Plant Proteins , Transcription Factors , Nicotiana/genetics , Nicotiana/growth & development , Nicotiana/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Growth Regulators/metabolism , Plant Growth Regulators/genetics , Ethylenes/metabolism , Plants, Genetically Modified/growth & development , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , TranscriptomeABSTRACT
Electrochemical water oxidation is known as the anodic reaction of water splitting. Efficient design and earth-abundant electrocatalysts are crucial to this process. Herein, we report a family of catalysts (1-3) bearing bis(benzimidazole)pyrazolide ligands (H 2 L1-H 2 L3). H 2 L3 contains electron-donating substituents and noninnocent components, resulting in catalyst 3 exhibiting unique performance. Kinetic studies show first-order kinetic dependence on [3] and [H2O] under neutral and alkaline conditions. In contrast to previously reported catalyst 1, catalyst 3 exhibits an insignificant kinetic isotope effect of 1.25 and zero-order dependence on [NaOH]. Based on various spectroscopic methods and computational findings, the L3Co2 III(µ-OH) species is proposed to be the catalyst resting state and the nucleophilic attack of water on this species is identified as the turnover-limiting step of the catalytic reaction. Computational studies provided insights into how the interplay between the electronic effect and ligand noninnocence results in catalyst 3 acting via a different reaction mechanism. The variation in the turnover-limiting step and catalytic potentials of species 1-3 leads to their catalytic rates being independent of the overpotential, as evidenced by Eyring analysis. Overall, we demonstrate how ligand design may be utilized to retain good water oxidation activity at low overpotentials.
ABSTRACT
Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.
Subject(s)
Aconitum , Gerbillinae , Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Animals , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Male , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stroke/metabolism , Stroke/prevention & control , Signal Transduction/drug effects , Oxidative Stress/drug effects , Ischemic Stroke/metabolism , Ischemic Stroke/prevention & controlABSTRACT
Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.
ABSTRACT
With the use of metagenomic next-generation sequencing, patients diagnosed with Whipple pneumonia are being increasingly correctly diagnosed. We report a series of 3 cases in China that showed a novel pattern of movable infiltrates and upper lung micronodules. After treatment, the 3 patients recovered, and lung infiltrates resolved.
Subject(s)
Tomography, X-Ray Computed , Whipple Disease , Aged , Humans , Male , Middle Aged , Anti-Bacterial Agents/therapeutic use , China , High-Throughput Nucleotide Sequencing , Lung/diagnostic imaging , Lung/pathology , Pneumonia, Bacterial/diagnostic imaging , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/diagnosis , Tropheryma/genetics , Tropheryma/isolation & purification , Whipple Disease/diagnosis , Whipple Disease/drug therapy , Whipple Disease/diagnostic imagingABSTRACT
BACKGROUND: A fish spike stuck in the throat is a common ear, nose, and throat (ENT) emergency. However, it is very rare for a fish spike to reach the thyroid tissue through the throat, which is very dangerous and can lead to pharyngeal fistula, cervical abscess, mediastinal abscess, and thyroid abscess. Proper and timely management can help reduce complications, especially in elderly patients. CASE SUMMARY: In the case presented here, the causative factor was dentures, but improper management aggravated the condition. In the case presented here, an elderly woman with a history of accidentally swallowing fish bones for 20 d had a sensation of foreign bodies in her throat. Eventually, computed tomography (CT) of the neck showed that the left side of the thyroid gland had a dense shadow in the form of a stripe. CONCLUSION: If a fishbone foreign body is not visible during endoscopic examination but the patient has significant symptoms, the surgeon should be aware that the fishbone may be lodged in the thyroid. To avoid a misdiagnosis, ultrasound, CT, and other tests can be used to clarify the diagnosis. T The first step in treating a fish bone in the thyroid gland is to determine the position of the foreign body and the extent of the infection, and to develop a personalized surgical plan for its removal. At the same time, scientific information should be made available to the general public so that people know that if a fish bone is accidentally lodged, they should not force it to be swallowed or be spit out by inducing vomiting, which are incorrect methods and may aggravate the condition or even cause it to migrate outside the cavity, leading to serious complications, as in this reported case.
ABSTRACT
Wild plants represent a potential source of urban landscape trees. Stranvaesia davidiana Dcne. is a member of the Stranvaesia Lindl. Genus, which belongs to family Rosaceae Juss. It has great ornamental value. It can contribute to urban color foliage and fruit species. However, the most effective fertilizer application strategy required for its cultivation is unknown. Therefore, we conducted an orthogonal experiment to investigate the fertilizer type and level (pure nitrogen) using ten experimental groups, including an untreated control group. Pot experiments were used to determine the growth indices of seedlings, including plant height, basal diameter, and chlorophyll content post-fertilizer treatment. This study explored the most appropriate fertiler application model for the growth of S. davidiana seedlings. The results revealed that enhanced seedling growth depended on the type and amount of fertilizer used, and their interaction. Fertilizer application increased the plant height by 2.67 cm to 12.26 cm, basal diameter by 0.39 cm to 0.75 cm, and chlorophyll content by 5.66 to 19.86. Among the different types of fertilizer, organic fertilizer increased the plant height by 0.42 cm to 9.59 cm and basal diameter by 0.01 cm to 0.05 cm, compared with the control group. Organic fertilizer had the maximum effect on seedling growth, especially at medium levels. The total growth of basal diameter and chlorophyll content was 1.58 ± 0.04 cm and 39.53 ± 2.37, respectively. Basal diameter is the most critical index in seedling reproduction . The study results suggest that the application of 4.06 g of organic fertilizer per plant was the most effective, and served as a basis for further field trials.
Subject(s)
Rosaceae , Seedlings , Fertilizers , Chlorophyll , Control GroupsABSTRACT
Sexually dimorphic behaviors are ubiquitous throughout the animal kingdom. Although both sex-specific and sex-shared neurons have been functionally implicated in these diverse behaviors, less is known about the roles of sex-shared neurons. Here, we discovered sexually dimorphic cholinergic synaptic transmission in C. elegans occurring at neuromuscular junctions (NMJs), with males exhibiting increased release frequencies, which result in sexually dimorphic locomotion behaviors. Scanning electron microscopy revealed that males have significantly more synaptic vesicles (SVs) at their cholinergic synapses than hermaphrodites. Analysis of previously published transcriptome identified the male-enriched transcripts and focused our attention on UNC-43/CaMKII. We ultimately show that differential accumulation of UNC-43 at cholinergic neurons controls axonal SV abundance and synaptic transmission. Finally, we demonstrate that sex reversal of all neurons in hermaphrodites generates male-like cholinergic transmission and locomotion behaviors. Thus, beyond demonstrating UNC-43/CaMKII as an essential mediator of sex-specific synaptic transmission, our study provides molecular and cellular insights into how sex-shared neurons can generate sexually dimorphic locomotion behaviors.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Neuromuscular Junction , Synaptic Transmission , Animals , Female , Male , Caenorhabditis elegans/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Neurons , Caenorhabditis elegans Proteins/geneticsABSTRACT
OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.
Subject(s)
HELLP Syndrome , Placenta Previa , Pregnancy Complications , Premature Birth , Infant, Newborn , Pregnancy , Female , Humans , Retrospective Studies , Fetal DistressABSTRACT
BACKGROUND: Previous studies have indicated that pain-related diseases can result in significant functional alterations in the brain. However, differences in spontaneous brain activity in toothache (TA) patients remain unclear. OBJECTIVE: To investigate altered spontaneous brain activity in patients with TA and its underlying mechanisms using the resting-state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF) technique. METHODS: Twelve patients with TA and 12 non-toothache controls (NTCs) (matched for sex, age, and level of education) were enrolled. Spontaneous cerebral activity variations were investigated using the rsfMRI-fALFF technique in all individuals. The mean fALFF values of the TA patients and NTCs were classified using receiver operating characteristic (ROC) curves. The correlations between fALFF signals of distinct brain regions and clinical manifestations of TA patients were evaluated using Pearson's correlation analysis. RESULTS: TA patients showed lower fALFF values in the left superior frontal gyrus, medial; right superior frontal gyrus, dorsolateral; and left median cingulate and paracingulate gyri (LDCG) than the NTCs. Moreover, ROC curve analysis indicated that the area under the curve of each cerebral region studied had high accuracy. Besides, in the TA group, the visual analog scale score was negatively correlated with fALFF signal values of the LDCG (r = .962, p < .001). CONCLUSION: Abnormal spontaneous activity was detected in numerous brain regions in patients with TA, which may be valuable for understanding the brain processing mechanism underlying TA. These regional changes in brain activity may serve as effective clinical indicators of TA.
Subject(s)
Brain Mapping , Brain , Humans , Brain Mapping/methods , Magnetic Resonance Imaging/methods , Prefrontal Cortex , Correlation of DataABSTRACT
Disturbed inhibitory synaptic transmission has functional impacts on neurodevelopmental and psychiatric disorders. An essential mechanism for modulating inhibitory synaptic transmission is alteration of the postsynaptic abundance of GABAARs, which are stabilized by postsynaptic scaffold proteins and recruited by presynaptic signals. However, how GABAergic neurons trigger signals to transsynaptically recruit GABAARs remains elusive. Here, we show that UNC-43/CaMKII functions at GABAergic neurons to recruit GABAARs and modulate inhibitory synaptic transmission at C. elegans neuromuscular junctions. We demonstrate that UNC-43 promotes presynaptic MADD-4B/Punctin secretion and NRX-1α/Neurexin surface delivery. Together, MADD-4B and NRX-1α recruit postsynaptic NLG-1/Neuroligin and stabilize GABAARs. Further, the excitation of GABAergic neurons potentiates the recruitment of NLG-1-stabilized-GABAARs, which depends on UNC-43, MADD-4B, and NRX-1. These data all support that UNC-43 triggers MADD-4B and NRX-1α, which act as anterograde signals to recruit postsynaptic GABAARs. Thus, our findings elucidate a mechanism for pre- and postsynaptic communication and inhibitory synaptic transmission and plasticity.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Animals , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , gamma-Aminobutyric Acid/metabolism , Neuromuscular Junction/metabolism , Synapses/metabolism , Synaptic Transmission/physiologyABSTRACT
Because hydrogen sulfide (H2S) is classified as a gaseous signaling molecule, protein S-sulfhydration is known to be one of the mechanisms by which H2S signals are conducted. PTP1B, a negative regulator in insulin signaling, has been found to be S-sulfhydrated at Cys215-SH to form Cys215-SSH in response to endoplasmic reticulum (ER) stress. Therefore, we aimed to understand the change in PTP1B S-sulfhydration and cellular redox homeostasis in response to insulin stimulation. We demonstrated a feasible PEG-switch method to determine the levels of PTP1B S-sulfhydration. According to the results obtained from HEK293T and MDA-MB-231 cells, insulin induced a change in PTP1B S-sulfhydration that was similar to the change in Insulin receptor substrate 1 (IRS1) phosphorylation in both cell lines. However, insulin-induced PTP1B S-sulfhydration and IRS1 phosphorylation were only significantly affected by metformin in HEK293T cells. Insulin also induced an increase in reactive oxygen species (ROS) in both cell lines. However, the level of H2S, GSH, and GSSG was only significantly affected by insulin and metformin in HEK293T cells. HEK293T cells maintained high levels of H2S and cysteine, but low levels of GSSG and GSH in general compared to MDA-MB-231 cells. From these findings, we suggest that PTP1B activity is modulated by H2S and redox-regulated S-sulfhydration during insulin signaling.
Subject(s)
Hydrogen Sulfide , Insulin , Humans , Glutathione Disulfide/metabolism , HEK293 Cells , Hydrogen Sulfide/pharmacology , Hydrogen Sulfide/metabolism , Insulin/metabolism , Oxidation-Reduction , Sulfides/metabolismABSTRACT
The optimal pharmaceutical regimen for advanced thymic epithelial tumors (TETs) remains controversial when first-line chemotherapy fails. This retrospective study aims to evaluate the efficacy and safety of anlotinib treatment for patients with relapsed and refractory TETs. Patients with progressive disease after failure of platinum-based chemotherapy were enrolled in this study. Anlotinib was orally taken once a day at an initial dose of 12 mg (10 mg when body weight <60 kg). The cycle was repeated every 3 weeks (2 weeks of treatment followed by 1-week rest). Objective response rate (ORR) and progression-free survival (PFS) were recorded as primary endpoints. There were 50 patients enrolled in this study from October 2018 to June 2021 at a median age of 50 (range 23-79) years old. Patients with thymoma and thymic carcinoma were 33 (66%) and 17 (34%), respectively. The ORR in thymoma and thymic carcinoma patients were 33% (11/33) and 41% (7/17), respectively. The median PFS (mPFS) was 7 (95% CI, 5.9-10.2) months in thymoma patients and 6 (95% CI, 4.6-9.3) months in the thymic carcinoma group. Eleven patients experienced dose reduction due to toxicities, among whom, eight patients discontinued treatment even after dose reduction. Six patients with thymoma showed myasthenia gravis deterioration during treatment, and two of them died of myasthenia gravis crisis. Anlotinib is active in patients with advanced TETs refractory to routine chemotherapy. Prescription of anlotinib to patients with myasthenia gravis should be made cautiously.
Subject(s)
Myasthenia Gravis , Neoplasms, Glandular and Epithelial , Thymoma , Thymus Neoplasms , Humans , Young Adult , Adult , Middle Aged , Aged , Thymoma/drug therapy , Thymoma/pathology , Retrospective Studies , Thymus Neoplasms/drug therapy , Thymus Neoplasms/pathology , Neoplasms, Glandular and Epithelial/drug therapyABSTRACT
Compared with the traditional liquid-liquid extraction method, solid-phase extraction agents are of great significance for the recovery of indium metal due to their convenience, free of organic solvents, and fully exposed activity. In this study, P2O4 (di-2-ethylhexyl phosphoric acid) was chemically modified by using UiO-66 to form the solid-phase extraction agent P2O4-UiO-66-MOFs (di-2-ethylhexyl phosphoric acid-UiO-66-metal-organic frameworks) to adsorb In(III). The results show that the Zr of UiO-66 bonds with the P-OH of P2O4 to form a composite P2O4-UiO-66-MOF, which was confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). The adsorption process of indium on P2O4-UiO-66-MOFs followed pseudo first-order kinetics, and the adsorption isotherms fit the Langmuir adsorption isotherm model. The adsorption capabilities can reach 192.8 mg/g. After five consecutive cycles of adsorption-desorption-regeneration, the indium adsorption capacity by P2O4-UiO-66-MOFs remained above 99%. The adsorption mechanism analysis showed that the P=O and P-OH of P2O4 molecules coated on the surface of P2O4-UiO-66-MOFs participated in the adsorption reaction of indium. In this paper, the extractant P2O4 was modified into solid P2O4-UiO-66-MOFs for the first time. This work provides a new idea for the development of solid-phase extractants for the recovery of indium.
Subject(s)
Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Indium , Spectroscopy, Fourier Transform Infrared , Solid Phase Extraction/methods , AdsorptionABSTRACT
Hedgehog (Hh) signaling pathway plays a pivotal role in embryonic development. Hh binding to Patched1 (PTCH1) derepresses Smoothened (SMO), thereby activating the downstream signal transduction. Covalent SMO modification by cholesterol in its cysteine-rich domain (CRD) is essential for SMO function. SMO cholesterylation is a calcium-accelerated autoprocessing reaction, and STIM1-ORAI1-mediated store-operated calcium entry promotes cholesterylation and activation of endosome-localized SMO. However, it is unknown whether the Hh-PTCH1 interplay regulates the activity of the endoplasmic reticulum (ER)-localized SMO. Here, we found that PTCH1 inhibited the COPII-dependent export of SMO from the ER, whereas Hh promoted this process. The RRxWxR amino acid motif in the cytosolic tail of SMO was essential for COPII recognition, ciliary localization, and signal transduction activity. Hh and PTCH1 regulated cholesterol modification of the ER-localized SMO, and SMO cholesterylation accelerated its exit from ER. The GRAMD1/ASTER sterol transport proteins facilitated cholesterol transfer to ER from PM, resulting in increased SMO cholesterylation and enhanced Hh signaling. Collectively, we reveal a regulatory role of GRAMD-mediated cholesterol transport in ER-resident SMO maturation and Hh signaling.
Subject(s)
Calcium , Hedgehog Proteins , Biological Transport , Calcium/metabolism , Cholesterol/metabolism , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/physiology , Smoothened Receptor/genetics , Smoothened Receptor/metabolism , Membrane Proteins/metabolismABSTRACT
BACKGROUND: Antenatal depression might cause adverse pregnancy outcomes. However, previous study results were inconsistent, especially in the low- and middle- income countries. We aimed to study the association between antenatal depression and adverse perinatal outcomes in a Chinese population. METHODS: We performed a prospective cohort study and enrolled pregnant women from January 2020 to January 2021. Antenatal depressive symptoms in the third trimester of pregnancy were evaluated by the Edinburgh Postpartum Depression Scale (EPDS). Baseline characteristics and pregnancy outcomes were recorded. After adjusting for confounding factors (age, occupation, education level, and annual income), multivariate logistic regression analysis was applied to evaluate the associations between antenatal depression and pregnancy outcomes. RESULTS: Among the 5209 participants, 1448 (27.7 %) pregnant women were positive for depression. After adjusting for potential confounders, women with antenatal depressive symptoms were significantly more likely to deliver prematurely [Odds ratio (OR) = 1.404, 95 % confidence interval (CI) = 1.020-1.933, P = 0.037] and receive cesarean section (OR = 1.154, 95 % CI = 1.002-1.331, P = 0.048). LIMITATIONS: EPDS, not a structured diagnostic interview, was used for psychological assessment. In addition, we only screened the women in their third trimester in a single research center. The association between the duration of antenatal depression and perinatal outcomes was not evaluated. CONCLUSIONS: Depressive symptoms were common among Chinese women in their third trimester of pregnancy. Women with antenatal depressive symptoms had increased cesarean section and preterm delivery risks. Screening and treatment for antenatal depression are needed during the prenatal care.
Subject(s)
Depression, Postpartum , Pregnancy Complications , Infant, Newborn , Pregnancy , Female , Humans , Depression/epidemiology , Depression/diagnosis , Depression, Postpartum/diagnosis , Depression, Postpartum/epidemiology , Depression, Postpartum/psychology , Prospective Studies , Cesarean Section , Pregnancy Complications/psychology , ParturitionABSTRACT
Magnolia sieboldii K. Koch is a deciduous tree species. However, the wild resource of M. sieboldii has been declining due to excessive utilization and seed dormancy. In our previous research, M. sieboldii seeds have morphophysiological dormancy and low germination rates under natural conditions. The aim of the present study was to identify the genes involved in dormancy maintenance. In this study, the germination percentage of M. sieboldii seeds negatively correlated with the content of endogenous abscisic acid (ABA). The hydration of seeds for germination showed three distinct phases. Five key time points were identified: 0 h imbibition (dry seed, GZ), 0 day after imbibition (DAI), 16 DAI, 40 DAI, and 56 DAI. The comprehensive transcript profiles of M. sieboldii seeds treated with ABA and water at the five key germinating stages were obtained. A total of 9641 differentially expressed genes (DEGs) were identified, and 208 and 197 common DEGs were found throughout the ABA and water treatments, respectively. Compared with that in the GZ, 518, 696, 2133, and 1535 DEGs were identified in the SH group at 0, 16, 40 and 56 DAI, respectively. 666, 1725, 1560 and 1415 DEGs were identified in the ABA group at 0, 16, 40, and 56 DAI, respectively. Among the identified DEGs, 12 722 were annotated with GO terms, the top three enriched GO terms were different among the DEGs at 56 DAI in the ABA vs. SH treatments. KEGG pathway enrichment analysis for DEGs indicated that oxidative phosphorylation, protein processing in endoplasmic reticulum, starch and sucrose metabolism play an important role in seed response to ABA. 1926 TFs are obtained and classified into 72 families from the M. sieboldii transcriptome. Results of differential gene expression analysis together with qRT-PCR indicated that phase II is crucial for rapid and successful seed germination. This study is the first to present the global expression patterns of ABA-regulated transcripts in M. sieboldii seeds at different germinating phases.
Subject(s)
Abscisic Acid , Magnolia , Humans , Abscisic Acid/pharmacology , Abscisic Acid/metabolism , Germination/genetics , Transcriptome , Magnolia/genetics , Gene Expression Profiling , Plant Dormancy/genetics , Seeds/metabolism , Gene Expression Regulation, PlantABSTRACT
Cilia are conserved organelles found in many cell types in eukaryotes, and their dysfunction causes defects in environmental sensing and signaling transduction; such defects are termed ciliopathies. Distinct cilia have cell-specific morphologies and exert distinct functions. However, the underlying mechanisms of cell-specific ciliogenesis and regulation are unclear. Here, we identified a WD40-repeat (WDR) protein, NMTN-1 (the homolog of mammalian WDR47), and show that it is specifically required for ciliogenesis of AWB chemosensory neurons in C. elegans. NMTN-1 is expressed in the AWB chemosensory neuron pair, and is enriched at the basal body (BB) of the AWB cilia. Knockout of nmtn-1 causes abnormal AWB neuron cilia morphology, structural integrity, and induces aberrant AWB-mediated aversive behaviors. We further demonstrate that nmtn-1 deletion affects movement of intraflagellar transport (IFT) particles and their cargo delivery in AWB neurons. Our results indicate that NMTN-1 is essential for AWB neuron ciliary morphology and function, which reveal a novel mechanism for cell-specific ciliogenesis. Given that WDR47/NMTN-1 is conserved in mammals, our findings may help understanding of the process of cell-specific ciliogenesis and provide insights for treating ciliopathies.
Subject(s)
Caenorhabditis elegans , Ciliopathies , Animals , Biological Transport , Cilia/metabolism , Neurons/metabolism , Ciliopathies/metabolism , MammalsABSTRACT
Changes in neurotransmitter receptor abundance at post-synaptic elements play a pivotal role in regulating synaptic strength. For this reason, there is significant interest in identifying and characterizing the scaffolds required for receptor localization at different synapses. Here we analyze the role of two C. elegans post-synaptic scaffolding proteins (LIN-2/CASK and FRM-3/FARP) at cholinergic neuromuscular junctions. Constitutive knockouts or muscle specific inactivation of lin-2 and frm-3 dramatically reduced spontaneous and evoked post-synaptic currents. These synaptic defects resulted from the decreased abundance of two classes of post-synaptic ionotropic acetylcholine receptors (ACR-16/CHRNA7 and levamisole-activated AChRs). LIN-2's AChR scaffolding function is mediated by its SH3 and PDZ domains, which interact with AChRs and FRM-3/FARP, respectively. Thus, our findings show that post-synaptic LIN-2/FRM-3 complexes promote cholinergic synaptic transmission by recruiting AChRs to post-synaptic elements.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Neuromuscular Junction/metabolism , Receptors, Cholinergic/genetics , Receptors, Cholinergic/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Synaptic Transmission/genetics , Cholinergic Agents/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Helminth Proteins/metabolismABSTRACT
Hexamethyldisilazane was reacted with formamides to generate N,N-disubstituent formimidamide, after which a reaction with sulfonamides was induced to form sulfonylformamidines. This protocol can be applied for arylformamidine formation in which anilines are used as substrates under optimized conditions. The advantages of this method are high efficiency, structural diversity in products with good yields, and applicability in large-scale operations.