ABSTRACT
Dysfunction of voltage-gated sodium channel Nav1.2 causes various epileptic disorders, and inhibition of the channel has emerged as an attractive therapeutic strategy. However, currently available Nav1.2 inhibitors exhibit low potency and limited structural diversity. In this study, a novel series of pyrimidine-based derivatives with Nav1.2 inhibitory activity were designed, synthesized, and evaluated. Compounds 14 and 35 exhibited potent activity against Nav1.2, boasting IC50 values of 120 and 65 nM, respectively. Compound 14 displayed favorable pharmacokinetics (F = 43%) following intraperitoneal injection and excellent brain penetration potency (B/P = 3.6). Compounds 14 and 35 exhibited robust antiepileptic activities in the maximal electroshock test, with ED50 values of 3.2 and 11.1 mg/kg, respectively. Compound 35 also demonstrated potent antiepileptic activity in a 6 Hz (32 mA) model, with an ED50 value of 18.5 mg/kg. Overall, compounds 14 and 35 are promising leads for the development of new small-molecule therapeutics for epilepsy.
Subject(s)
Anticonvulsants , Epilepsy , NAV1.2 Voltage-Gated Sodium Channel , Pyrimidines , Animals , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/pharmacokinetics , Pyrimidines/therapeutic use , Anticonvulsants/pharmacology , Anticonvulsants/chemistry , Anticonvulsants/chemical synthesis , Anticonvulsants/therapeutic use , Anticonvulsants/pharmacokinetics , Epilepsy/drug therapy , Epilepsy/metabolism , Mice , NAV1.2 Voltage-Gated Sodium Channel/metabolism , Structure-Activity Relationship , Humans , Disease Models, Animal , Male , Voltage-Gated Sodium Channel Blockers/pharmacology , Voltage-Gated Sodium Channel Blockers/chemistry , Voltage-Gated Sodium Channel Blockers/chemical synthesis , Voltage-Gated Sodium Channel Blockers/pharmacokinetics , Voltage-Gated Sodium Channel Blockers/therapeutic use , Drug Discovery , Electroshock , Molecular Docking SimulationABSTRACT
The plant MADS-box transcription factor family is a major regulator of plant flower development and reproduction, and the AGAMOUS-LIKE11/SEEDSTICK (AGL11/STK) subfamily plays conserved functions in the seed development of flowering plants. Camellia japonica is a world-famous ornamental flower, and its seed kernels are rich in highly valuable fatty acids. Seed abortion has been found to be common in C. japonica, but little is known about how it is regulated during seed development. In this study, we performed a genome-wide analysis of the MADS-box gene the in C. japonica genome and identified 126 MADS-box genes. Through gene expression profiling in various tissue types, we revealed the C/D-class MADS-box genes were preferentially expressed in seed-related tissues. We identified the AGL11/STK-like gene, CjSTK, and showed that it contained a typical STK motif and exclusively expressed during seed development. We found a significant increase in the CjSTK expression level in aborted seeds compared with normally developing seeds. Furthermore, overexpression of CjSTK in Arabidopsis thaliana caused shorter pods and smaller seeds. Taken together, we concluded that the fine regulation of the CjSTK expression at different stages of seed development is critical for ovule formation and seed abortion in C. japonica. The present study provides evidence revealing the regulation of seed development in Camellia.
Subject(s)
Camellia , Gene Expression Regulation, Plant , MADS Domain Proteins , Plant Proteins , Seeds , Camellia/genetics , Camellia/metabolism , Camellia/growth & development , Seeds/genetics , Seeds/growth & development , MADS Domain Proteins/genetics , MADS Domain Proteins/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Phylogeny , Arabidopsis/genetics , Arabidopsis/metabolism , Gene Expression Profiling , Multigene Family , Genome, Plant , Genome-Wide Association StudyABSTRACT
PURPOSE: The relationship between vitamin intake and cancer risk in the chronic kidney disease (CKD) population is unknown. For this reason, we investigated the relationship between dietary vitamin intake and cancer risk in CKD patients and looked for effective vitamin dietary patterns. METHODS: This study included 3518 CKD patients from 2007 to 2018 National Health and Nutrition Examination Survey database. All participants were categorized into four groups based on vitamin intake by K-mean clustering. The data were collected and analyzed from June 2023 to December 2023. RESULTS: A total of 3518 CKD patients with a mean age of (61.8 ± 16.3) years were included in the study. During a median follow-up of 7.3 years, 137 participants died of cancer. In the multivariate adjusted cox proportional hazards model for single vitamin intake, vitamin E Q4 intake (reference Q1) reduced cancer mortality (HR (95% CI) = 0.45 (0.24-0.87), P = 0.018). Further plotting of the restricted cubic spline curve revealed a linearly decreasing relationship between vitamin E intake and cancer mortality (Poverall = 0.010 Pnon-linear = 0.163). In the multivariate adjusted cox proportional hazards model for multivitamin co-intake, the vitamin C/K intake group reduced cancer mortality compared to the low vitamin intake group (HR (95% CI) = 0.42 (0.20-0.88), P = 0.022). CONCLUSION: Increased vitamin C intake was independently associated with reduced cancer risk in CKD patients, and a vitamin dietary pattern with high vitamin C/K intake was also effective in reducing cancer risk.
Subject(s)
Diet , Neoplasms , Nutrition Surveys , Renal Insufficiency, Chronic , Vitamins , Humans , Renal Insufficiency, Chronic/complications , Male , Middle Aged , Female , Neoplasms/epidemiology , Vitamins/administration & dosage , Aged , Risk Assessment , Adult , United States/epidemiology , Time FactorsABSTRACT
CXC chemokine receptor 6 (CXCR6), a seven-transmembrane domain G-protein-coupled receptor, plays a pivotal regulatory role in inflammation and tissue damage through its interaction with CXC chemokine ligand 16 (CXCL16). This axis is implicated in the pathogenesis of various fibrotic diseases and correlates with clinical parameters that indicate disease severity, activity, and prognosis in organ fibrosis, including afflictions of the liver, kidney, lung, cardiovascular system, skin, and intestines. Soluble CXCL16 (sCXCL16) serves as a chemokine, facilitating the migration and recruitment of CXCR6-expressing cells, while membrane-bound CXCL16 (mCXCL16) functions as a transmembrane protein with adhesion properties, facilitating intercellular interactions by binding to CXCR6. The CXCR6/CXCL16 axis is established to regulate the cycle of damage and repair during chronic inflammation, either through modulating immune cell-mediated intercellular communication or by independently influencing fibroblast homing, proliferation, and activation, with each pathway potentially culminating in the onset and progression of fibrotic diseases. However, clinically exploiting the targeting of the CXCR6/CXCL16 axis requires further elucidation of the intricate chemokine interactions within fibrosis pathogenesis. This review explores the biology of CXCR6/CXCL16, its multifaceted effects contributing to fibrosis in various organs, and the prospective clinical implications of these insights.
Subject(s)
Chemokine CXCL16 , Fibrosis , Receptors, CXCR6 , Humans , Receptors, CXCR6/metabolism , Chemokine CXCL16/metabolism , Animals , Signal TransductionABSTRACT
FLOWERING LOCUS T (FT), belonging to the FT/TFL1 gene family, is an important gene regulating the flowering transition and inflorescence architecture during plant development. Given its importance to plant adaptation and crop improvement, FT has been extensively studied in related plant research; however, the specific role and underlying molecular mechanisms of FT in the continuous flowering of perennial plants remains elusive. Here, we isolated and characterized homologous FT genes from two Camellia species with different flowering-period phenotypes: CaFT was isolated from Camellia azalea, a precious species blooming in summer and flowering throughout the year, and CjFT was isolated from C. japonica, which blooms in winter and spring. The major difference in the genes between the two species was an additional five-amino acid repeat sequence in C. japonica. FT showed high expression levels in the leaves in both species from January to August, especially in April for C. japonica and in May for C. azalea. CaFT was expressed throughout the year in C. azalea, whereas CjFT was not expressed from September to December in C. japonica. The expression levels of FT in the floral buds were generally higher than those in the leaves. Overexpression of CaFT and CjFT in Arabidopsis indicated that both genes can activate downstream genes to promote flowering. Transgenic callus tissue was obtained by introducing the two genes into C. azalea through Agrobacterium-mediated transformation. Transcriptome and quantitative real-time polymerase chain reaction analyses indicated that both florigen FT genes promoted the expression of downstream genes such as AP1, FUL, and SEP3, and slightly up-regulated the expression of upstream genes such as CO and GI. The above results indicated that CaFT and CjFT played a role in promoting flowering in both camellia species. The expression pattern of CaFT in leaves suggested that, compared to CjFT, CaFT may be related to the annual flowering of C. azalea.
ABSTRACT
BACKGROUND: The formation and domestication of ornamental traits are influenced by various aspects, such as the recognition of esthetic values and cultural traditions. Camellia japonica is widely appreciated and domesticated around the world mainly due to its rich variations in ornamental traits. Ornamental camellias have a diverse range of resources, including different bud variations from Camellia spp. as well as inter- and intra- specific hybridization. Despite research on the formation of ornamental traits, a basic understanding of their genetics and genomics is still lacking. RESULTS: Here, we report the chromosomal-level reference genome of C. japonica through combining multiple DNA-sequencing technologies and obtain a high-density genetic linkage map of 4255 markers by sequencing 98 interspecific F1 hybrids between C. japonica and C. chekiangoleosa. We identify two whole-genome duplication events in C. japonica: one is a shared ancient γ event, and the other is revealed to be specific to genus Camellia. Based on the micro-collinearity analysis, we find large-scale segmental duplication of chromosome 8, resulting to two copies of the AGAMOUS loci, which may play a key role in the domestication of floral shapes. To explore the regulatory mechanisms of seasonal flowering, we have analyzed year-round gene expression patterns of C. japonica and C. azalea-a sister plant of continuous flowering that has been widely used for cross breeding. Through comparative analyses of gene co-expression networks and annual gene expression patterns, we show that annual expression rhythms of some important regulators of seasonal growth and development, including GIGANTEA and CONSTANS of the photoperiod pathway, have been disrupted in C. azalea. Furthermore, we reveal that the distinctive expression patterns of FLOWERING LOCUS T can be correlated with the seasonal activities of flowering and flushing. We demonstrate that the regulatory module involved in GIGANTEA, CONSTANS, and FLOWERING LOCUS T is central to achieve seasonality. CONCLUSIONS: Through the genomic and comparative genomics characterizations of ornamental Camellia spp., we propose that duplication of chromosomal segments as well as the establishment of gene expression patterns has played a key role in the formation of ornamental traits (e.g., flower shape, flowering time). This work provides a valuable genomic platform for understanding the molecular basis of ornamental traits.
Subject(s)
Camellia , Seasons , Camellia/genetics , Plant Breeding , Genomics , Flowers/genetics , Gene Expression , Gene Expression Regulation, PlantABSTRACT
AIM AND OBJECTIVES: The relationship between dietary metal intake and mortality risk is controversial, and we investigated the relationship between intake of five metals (iron, copper, selenium, zinc, and magnesium) and all-cause, cardiovascular mortality in the total population, gender subgroups, and age subgroups. MATERIALS AND METHODS: 17,207 participants from the National Health and Nutrition Examination Survey (NHANES) database from 2009 to 2016 were included in this study. Kaplan-Meier survival curves, multivariate Cox proportional hazards models, and restrictive cubic spline (RCS) curves were used to explore the association between metal intake and all-cause, cardiovascular mortality. RESULTS: In this study, the average dietary metal intake of men and older people was lower than that of women and younger people. The RCS curves found in the whole population that all-cause mortality was negative linearly associated with copper intakes, L-shaped with zinc and magnesium intakes. Further subgroup analyses of copper, zinc, and magnesium by age and gender revealed that only magnesium showed statistically significant differences in the age subgroups. In the 20-40 population, there was a non-linear increasing trend in magnesium intake and all-cause mortality, whereas there was a non-linear decreasing trend in the > 60 population. CONCLUSION: The relationship between metal intake and mortality is more than a simple linear correlation, and differences in age can affect this correlation. In metal exposure studies, different populations can be studied to better determine the effect of metal exposure on mortality. DATA AVAILABILITY: The dataset used for statistical analysis in this study is available on the NHANES website: https://www.cdc.gov/nchs/nhanes/index.htm.
Subject(s)
Cardiovascular Diseases , Copper , Male , Adult , Humans , Female , Aged , Nutrition Surveys , Magnesium , Prospective Studies , Zinc , Cardiovascular Diseases/epidemiologyABSTRACT
In trees, the annual cycling of active and dormant states in buds is closely regulated by environmental factors, which are of primary significance to their productivity and survival. It has been found that the parallel or convergent evolution of molecular pathways that respond to day length or temperature can lead to the establishment of conserved periodic gene expression patterns. In recent years, it has been shown in many woody plants that change in annual rhythmic patterns of gene expression may underpin the adaptive evolution in forest trees. In this review, we summarize the progress on the molecular mechanisms of seasonal regulation on the processes of shoot growth, bud dormancy, and bud break in response to day length and temperature factors. We focus on seasonal expression patterns of genes involved in dormancy and their associated epigenetic modifications; the seasonal changes in the extent of modifications, such as DNA methylation, histone acetylation, and histone methylation, at dormancy-associated loci have been revealed for their actions on gene regulation. In addition, we provide an outlook on the direction of research on the annual cycle of tree growth under climate change.
Subject(s)
Histones , Trees , Trees/physiology , Seasons , Histones/genetics , DNA Methylation , Gene Expression , Gene Expression Regulation, PlantABSTRACT
A convenient and reliable surface-enhanced Raman scattering (SERS) substrate has been developed for the surface corrosion analysis of bronze artifacts. The substrate consists of oriented alginate nanofiber membranes containing silver nanoparticles (Ag NPs), which were obtained through electrostatic spinning, ion exchange, and in-situ reduction. By controlling the reduction time, Ag/alginate nanofiber membranes with different contents, sizes, and distributions were obtained. The Ag/alginate nanofiber#20 membranes, obtained with a reduction time of 20 min, reached a detection limit of 10-12 M for R6G with an enhancement factor of 6.64 × 107. In the trace detection of bronze patina, the intensity of the characteristic peaks of harmful patina located at 513, 846, 911, and 974 cm-1 were increased by more than 500 %. This was due to the uniform loading of a large number of Ag NPs on the surface of the nanofiber membrane obtained by reduction for 20 min, and the formation of a large number of hot spots between the oriented nanofibers. This significantly improved the SERS performance of the flexible substrate layer under the joint action with the Ag NPs. These results indicate that the flexible substrate layer can greatly enhance the Raman characteristic peaks of alkali copper chloride and be effectively used for trace analysis of the surface composition of bronze artifacts.
ABSTRACT
Background: The relationship between vitamin E supplementation and the prevalence of chronic kidney disease (CKD) is unclear. We discussed the relationship between vitamin E intake and CKD prevalence and further investigated the effect on different CKD risk strata. Methods: We ultimately included 20 295 participants from the National Health and Nutrition Examination Survey (NHANES) database from 2009 to 2016. Multiple logistic regression and restricted cubic splines (RCS) were applied to explore the relationship between vitamin E intake and CKD prevalence and risk stratification. Subgroup analysis was applied to assess the stability of the association between vitamin E intake and CKD. Results: In the CKD prevalence study, we found a negative association between high vitamin E intake and CKD prevalence through an adjusted multiple logistic regression model, the odds ratio (OR) was 0.86 [95% confidence interval (CI) 0.74-1.00; P for trend = .041] and RCS showed a nonlinear negative correlation (P-nonlinear = .0002, <.05). In the CKD risk stratification study, we found that in very high-risk patients, the OR was 0.51 (95% CI 0.32-0.84; P for trend = .006) and the RCS also showed a nonlinear negative correlation (P-nonlinear <.0001, <.05). Subgroup analysis demonstrated that the correlations were stable across populations (P-values >.01 for all interactions). Conclusion: Dietary vitamin E intake was negatively associated with the prevalence of CKD in US adults. Increased vitamin E intake was a protective factor across CKD risk strata, and as vitamin E intake increased, there was a non-linear downward trend in the proportion progressing to very high-risk CKD.
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OBJECTIVE: This study assesses the difference in professional attitudes among medical students, both before and after coronavirus disease 2019 (COVID-19), and identifies the determinants closely associated with it, while providing precise and scientific evidence for implementing precision education on such professional attitudes. METHODS: A pre-post-like study was conducted among medical students in 31 provinces in mainland China, from March 23, to April 19, 2021. RESULTS: The proportion of medical students whose professional attitudes were disturbed after the COVID-19 pandemic, was significantly lower than before the COVID-19 pandemic (χ2 = 15.6216; P < 0.0001). Compared with the "undisturbed -undisturbed" group, the "undisturbed-disturbed" group showed that there was a 1.664-fold risk of professional attitudes disturbed as grade increased, 3.269-fold risk when others suggested they choose a medical career rather than their own desire, and 7.557-fold risk for students with COVID-19 in their family, relatives, or friends; while the "disturbed-undisturbed" group showed that students with internship experience for professional attitudes strengthened was 2.933-fold than those without internship experience. CONCLUSIONS: The professional attitudes of medical students have been strengthened during the COVID-19 pandemic. The results provide evidence of the importance of education on professional attitudes among medical students during public health emergencies.
Subject(s)
COVID-19 , Students, Medical , Humans , COVID-19/epidemiology , SARS-CoV-2 , Pandemics , Educational StatusABSTRACT
As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.
ABSTRACT
Bacillus subtilis is an important part of the gut microbiota and a commonly used probiotic. In the present study, to assess the biological characteristics and probiotic properties of B. subtilis derived from mink, we isolated B. subtilis MG-1 isolate from mink fecal samples, characterized its biological characteristics, optimized the hydrolysis of casein by its crude extract, and comprehensively analyzed its potential as a probiotic in combination with whole-genome sequencing. Biological characteristics indicate that, under low-pH conditions (pH 2), B. subtilis MG-1 can still maintain a survival rate of 64.75%; under the conditions of intestinal fluid, gastric acid, and a temperature of 70 °C, the survival rate was increased by 3, 1.15 and 1.17 times compared with the control group, respectively. This shows that it can tolerate severe environments. The results of hydrolyzed casein in vitro showed that the crude bacterial extract of isolate MG-1 exhibited casein hydrolyzing activity (21.56 U/mL); the enzyme activity increased to 32.04 U/mL under optimized reaction conditions. The complete genome sequencing of B. subtilis MG-1 was performed using the PacBio third-generation sequencing platform. Gene annotation analysis results revealed that B. subtilis MG-1 was enriched in several Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways, and most genes were related to Brite hierarchy pathways (1485-35.31%) and metabolism pathways (1395-33.17%). The egg-NOG annotation revealed that most genes were related to energy production and conversion (185-4.10%), amino acid transport and metabolism (288-6.38%), carbohydrate transport and metabolism (269-5.96%), transcription (294-6.52%), and cell wall/membrane/envelope biogenesis (231-5.12%). Gene Ontology (GO) annotation elucidated that most genes were related to biological processes (8230-45.62%), cellular processes (3582-19.86%), and molecular processes (6228-34.52%). Moreover, the genome of B. subtilis MG-1 was predicted to possess 77 transporter-related genes. This study demonstrates that B. subtilis MG-1 has potential for use as a probiotic, and further studies should be performed to develop it as a probiotic additive in animal feed to promote animal health.
ABSTRACT
BACKGROUND: The literature describes a case of systemic lupus erythematosus (SLE) complicated with Castleman's disease (CD) and secondary paraneoplastic pemphigus (PNP). CASE PRESENTATION: A 12-year-old female presented with a neck mass, rash, arthralgia, and skin and mouth ulceration for 5 years were admitted. All blood cells were low. Multiple autoantibodies associated with SLE were positive. The pathology of the neck mass revealed the classical manifestations of CD. She was treated with prednisone, hydroxychloroquine, leflunomide, thalidomide, and dressings. Pathological examination of the skin revealed PNP. The neck mass was removed and continued to take antirheumatic drugs. At subsequent follow-up, the patient's disease status was stable and the skin mucosal lesion did not recur. CONCLUSION: The case of simultaneous SLE, CD, and PNP in children was rarely reported, and the correct diagnosis of the disease will help to take timely treatment.
Subject(s)
Castleman Disease , Lupus Erythematosus, Systemic , Pemphigus , Female , Child , Humans , Pemphigus/diagnosis , Pemphigus/etiology , Castleman Disease/complications , Castleman Disease/diagnosis , Neoplasm Recurrence, Local/complications , Neoplasm Recurrence, Local/pathology , Skin/pathology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/pathologyABSTRACT
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon. CASE PRESENTATION: We described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now. CONCLUSIONS: The main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.
Subject(s)
Kidney Transplantation , Lupus Nephritis , Lymphohistiocytosis, Hemophagocytic , Virus Diseases , Humans , Child , Female , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Kidney Transplantation/adverse effects , Lupus Nephritis/complications , Lupus Nephritis/diagnosis , Lupus Nephritis/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney , Virus Diseases/complicationsABSTRACT
The exact pathogenesis of epilepsy, one of the most common and devastating diseases of the nervous system, is not fully understood. Syntaxin7 (STX7) is a member of the SNARE superfamily, which mediates membrane fusion events in all cells. However, the role STX7 plays in epilepsy remains unclear. Therefore, this study investigates the role of STX7 in epilepsy. Our study found that the expression of STX7 was reduced in the epileptic brain and that overexpression of STX7 decreased the susceptibility to epileptic seizures and alleviated epileptic activity in a kainic acid-induced model and pentylenetetrazole-induced kindling model of epilepsy, whereas the downregulation of STX7 showed opposite effects. Whole-cell patch-clamp recordings showed that STX7 does not affect the intrinsic excitability of neurons, but rather the excitation/inhibition ratio mediated by affecting the release of presynaptic γ-aminobutyric acid neurotransmitters. Transmission electron microscopy results showed that STX7 did not affect the density of inhibitory synapses but could affect the density of inhibitory vesicles. Taken together, these results reveal a previously unknown function of STX7 in epilepsy and suggest that STX7 may serve as a novel target for epilepsy therapy.
Subject(s)
Epilepsy , Humans , Carrier Proteins , Epilepsy/metabolism , Neurons/metabolism , Qa-SNARE Proteins/metabolism , Seizures/metabolism , Animals , MiceABSTRACT
A superior semiconductor material with efficient charge separation and easy reuse could be a promising route for efficient photocatalytic hydrogen evolution and pollutant degradation. AgVO3 is one of the best visible light active materials which has attracted much attention for several biological and environmental applications. In the aim of enhancing its stability and recyclability a novel AgVO3/rGO/CuFe2O4 heterojunction was prepared by hydrothermal method for hydrogen generation (H2) and 4-nitrophenol (4-NP) degradation as well. The composite was well characterized by XRD, SEM, HR-TEM, XPS and VSM. The morphological images suggested the rod shaped AgVO3 and irregular shaped CuFe2O4 are unevenly distributed on reduced graphene oxide (rGO) layers. The hydrogen evolution results indicated that the composite showed around 8.937 mmol g-1h-1 of H2 generation which was â¼2.3 times and â¼9.2 times higher than pure AgVO3 (3.895 mmol g-1h-1) and CuFe2O4 (0.96 mmol g-1h-1) respectively. The 4-NP degradation efficiency of the prepared composite was observed as 94.7% (k = 0.01841 min-1) which is much higher than the AgVO3 (66.3%) and CuFe2O4 (38.2%) after 4 h of irradiation. The higher efficiency could be attributed to the heterojunction formation and faster charge separation. The radical trapping results indicated that the â¢OH, O2â¢- and photogenerated h+ are the main species responsible for efficient activity. The AgVO3/rGO/CuFe2O4 heterojunction showed 49.6 emu/g of saturation magnetization and confirms that it could be easily separated with an external magnet, and showed 85.3% of degradation efficiency even after 6 recycles which indicated its higher stability and recyclability. Thus, our study provides new insight into hydrogen generation and phenol degradation using AgVO3 based recyclable composites.
Subject(s)
Graphite , Hydrogen , Light , CatalysisABSTRACT
Background: Stewart-Treves Syndrome in Primary Limb Lymphedema (STS-PLE) is an extremely rare malignant tumor. A retrospective analysis was conducted to elucidate the relationship between magnetic resonance imaging (MRI) findings and signs compared to pathology. Methods: Seven patients with STS-PLE were enrolled at Beijing Shijitan Hospital, Capital Medical University, from June 2008 to March 2022. All cases were examined by MRI. The surgical specimens were subjected to histopathological and immunohistochemical staining for CD31, CD34, D2-40, and Ki-67. Results: There were two different types of MRI findings. One was mass shape (STS-PLE I type) in three male patients, and the other was the "trash ice" d sign (STS-PLE II type) observed in four female patients. The average duration of lymphedema (DL) of STS-PLE I type (18 months) was shorter than that of STS-PLE II type (31 months). The prognosis for the STS-PLE I type was worse than that for the STS-PLE II type. Regarding overall survival (OS), the STS-PLE I type (17.3 months) was three times shorter than that of the STS-PLE II type (54.5 months). For STS-PLE I type, the older the STS-PLE onset, the shorter the OS. However, there was no significant correlation in STS-PLE II type. MRI was compared to histological results to provide an explanation for the differences in MR signal changes, especially on T2WI. Against a background of dense tumor cells, the richer the lumen of immature vessels and clefts, the higher the T2WI MRI signal (taking muscle signal as the internal reference standard) and the worse the prognosis, and vice versa. We also found that younger patients with a lower Ki-67 index (<16%) had better OS, especially for the STS-PLE I type. Those with stronger positive expression of CD31 or CD34 had shorter OS. However, the expression of D2-40 was positive in nearly all cases, and seemed not to be associated with prognosis. Conclusions: In lymphedema, the richer the lumen of immature vessels and clefts based on dense tumor cells, the higher the T2WI signal on the MRI. In adolescent patients, the tumor often showed a "trash ice" sign (STS-PLE II-type) and prognosis was better than for the STS-PLE I type. While in middle-aged and older patients, tumors showed a mass shape (STS-PLE I type). The expression of immunohistochemical indicators (CD31, CD34, and KI-67) correlated with clinical prognosis, especially decreased Ki-67 expression. In this study, we determined it was possible to predict prognosis comparing MRI findings with pathological results.
ABSTRACT
Drought has severe effects on plant growth, forest productivity, and survival throughout the world. Understanding the molecular regulation of drought resistance in forest trees can enable effective strategic engineering of novel drought-resistant genotypes of tree species. In this study, we identified a gene, PtrVCS2, encoding a zinc finger (ZF) protein of the ZF-homeodomain transcription factor in Populus trichocarpa (Black Cottonwood) Torr. & A. Gray. ex Hook. Overexpression of PtrVCS2 (OE-PtrVCS2) in P. trichocarpa resulted in reduced growth, a higher proportion of smaller stem vessels, and strong drought-resistance phenotypes. Stomatal movement experiments revealed that the OE-PtrVCS2 transgenics showed lower stomata apertures than wild-type plants under drought conditions. RNA-seq analysis of the OE-PtrVCS2 transgenics showed that PtrVCS2 regulates the expression of multiple genes involved in regulation of stomatal opening and closing, particularly the PtrSULTR3;1-1 gene, and several genes related to cell wall biosynthesis, such as PtrFLA11-12 and PtrPR3-3. Moreover, we found that the water use efficiency of the OE-PtrVCS2 transgenic plants was consistently higher than that of wild type plants when subjected to chronic drought stress. Taken together, our results suggest that PtrVCS2 plays a positive role in improving drought adaptability and resistance in P. trichocarpa.