ABSTRACT
BACKGROUND: Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China. METHOD: Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment. RESULTS: The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = -3.161, p = 0.007] and 16 (LS mean difference = -3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed. CONCLUSIONS: Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.
Subject(s)
Depressive Disorder, Major , Psychotherapy, Psychodynamic , Humans , Depressive Disorder, Major/drug therapy , Antidepressive Agents/therapeutic use , Treatment Outcome , Combined Modality TherapyABSTRACT
BACKGROUND: Spinal tumor surgery usually involved long operation time, large area of soft tissue resection and long wound, and was prone to hypothermia during the operation. Therefore, actively promoting insulation and optimizing the intraoperative insulation program have great potential in reducing the incidence of hypothermia and reducing the incidence of postoperative complications. In this study, we compared patients who did not implement multi-mode nursing insulation program (MNIP) with those who implemented MNIP, observing and comparing clinical outcomes, and complications in both groups, with the aim of developing an optimal management plan for the preoperative, intraoperative, and postoperative periods, respectively. METHODS: We selected 2 periods of 1 year, before (n = 120 patients) and after MINP implementation (n = 120 patients). Data were collected on patient demographics, operative, perioperative details, temperature changes, anesthesia recovery effect, incidence of postoperative wound infection, length of hospital stay and complications. PS analyses were used for dealing with confounding bias in this retrospective observational study. RESULTS: After PS matching, the outcomes of 120 well-balanced pairs of patients were compared (No-MNIP vs MNIP). There was no significant difference concerning the satisfaction survey. The results indicated that the MNIP had better insulation effect at 90 min, 120 min, 150 min after anesthesia induction and after surgery. There were 16 cases of complications in the No-MNIP group and 5 cases in the MNIP group postoperative, which have significant statistical difference. CONCLUSION: In this study, the incidence of intraoperative hypothermia was effectively reduced by adopting the multi-mode insulation scheme, thus reducing the incidence of incision infection and shortening the length of hospital stay of patients.
Subject(s)
Hypothermia , Humans , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Propensity Score , Retrospective Studies , SpineABSTRACT
The FH gene encodes the fumarate hydratase of the Krebs cycle and functions as a homotetramer to catalyze the hydration of fumarate to malate. Mutations in FH result in uterine leiomyomas, a rare autosomal dominant inherited metabolic disease. However, how FH mutations result in this disease is poorly understood. Here, the FH mutation c.557G>A (p.S186N) was identified in a family with uterine leiomyomas phenotype. A series of studies were performed to confirm the pathogenicity of this mutation. Results showed that the FH mutant exhibited significantly lower fumarase enzyme activity and increased the fumarates level compared with the wildtype, which might be due to the impaired homotetramer formation in the native gel electrophoresis. Interestingly, the immunofluorescence study revealed that the overexpressed FH mutant exhibited puncta structures compared with the evenly expressed FH wildtype in cytoplasm suggesting that the altered amino acid might result in dysfunctional proteins which were accumulated to reduce its cytotoxicity. Importantly, the cells overexpressing the FH mutant exhibited higher proliferation and extracellular acidification rate value (ECAR) which might be caused by the upregulated HIF-1α indicating the tumor phenotype. Notably, phospho-mTOR was significantly increased and autophagy was inhibited in the FH mutant overexpression cells compared with the wildtype. Our work provides new insight into the FH mutation c.557G>A (p.S186N) underlies uterine leiomyomas and important information for accurate genetic counseling and clinical diagnosis of the disease.
Subject(s)
Fumarate Hydratase/genetics , Leiomyomatosis/genetics , Mutation/genetics , Uterine Neoplasms/genetics , Adult , Autophagy , Base Sequence , Female , Fumarate Hydratase/chemistry , Fumarates/metabolism , HEK293 Cells , Humans , Male , Pedigree , Protein Multimerization , Signal Transduction , TOR Serine-Threonine Kinases/metabolismABSTRACT
Yes-associated protein 1 (YAP1), the core downstream effector of the Hippo signaling cascade, was involved in the regulation of osteoblast and osteoclast differentiation and in bone metabolism. However, the regulatory effects and mechanisms of YAP1 on bone-remodeling molecules in osteoblasts under inflammation remain unknown. In this study, YAP1 expression level was downregulated after treatment with inflammatory cytokine tumor necrosis factor-α (TNF-α) in MC3T3-E1 cells. The key osteoclastogenic molecules induced by TNF-α, namely, interleukin-6 and receptor activator of nuclear factor-κB (NF-κB) ligand, were suppressed after lentivirus-induced YAP1 overexpression, which dramatically increased the expression level of osteoprotegerin. Conversely, the expression levels of the above factors showed opposite trends in the YAP1 small interfering RNA and YAP1 inhibitor (verteporfin) group. Mechanistically, YAP1 attenuated the TNF-α-induced activation of the NF-κB signaling pathway as revealed by the reduced expression of phosphorylated-p65 and NF-κB reporter activity and the nuclear translocation of p65. Moreover, the expression level of YAP1 suppressed by TNF-α was reversed by berberine in concentration-dependent manner. Taken together, our study suggests that YAP1 plays a critical role in the regulation of bone metabolism and is a potential therapeutic target for treating inflammatory bone resorption.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Bone Remodeling/drug effects , Bone Resorption/metabolism , Cell Cycle Proteins/metabolism , NF-kappa B/metabolism , Osteoblasts/drug effects , Tumor Necrosis Factor-alpha/pharmacology , 3T3 Cells , Adaptor Proteins, Signal Transducing/genetics , Animals , Bone Resorption/genetics , Bone Resorption/physiopathology , Cell Cycle Proteins/genetics , Interleukin-6/genetics , Interleukin-6/metabolism , Mice , NF-kappa B/genetics , Osteoblasts/metabolism , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Signal Transduction , YAP-Signaling ProteinsABSTRACT
Local injection of tumor necrosis factor-alpha (TNF-α) at bone fracture sites during the early stage of the inflammatory response is reported to improve fracture repair in a murine model. However, the underlying mechanism is unclear. Endochondral bone formation, a process that is highly related to fracture repair, requires a certain amount of chondrocyte hypertrophy. This study aimed to investigate the effect of TNF-α on the differentiation of murine chondrogenic ATDC5 cells and the underlying mechanism. In this study, improved chondrogenic differentiation of ATDC5 cells was achieved by brief TNF-α stimulation. Moreover, the expression of Yes-associated protein 1 (YAP1) was suppressed after brief TNF-α stimulation. The expressions of inflammatory mediators and chondrogenic and hypertrophic-associated genes in ATDC5 cells triggered by TNF-α were suppressed in the YAP1 overexpression group but enhanced in the YAP1 knockdown group. Mechanistically, TNF-α-induced activation of the 5' AMP-activated protein kinase (AMPK) signaling pathway was regulated by YAP1, as revealed by the phosphorylated-AMPK/AMPK change ratios in the YAP1 overexpression and knockdown groups, respectively. Moreover, the potential for TNF-α to enhance chondrogenic differentiation could be partially reversed with an AMPK inhibitor. Taken together, we demonstrate, for the first time, that YAP1 modulates the ability of TNF-α to enhance chondrocyte differentiation partly through AMPK signaling.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Cell Differentiation , Chondrocytes/cytology , Chondrogenesis , Inflammation/drug therapy , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Animals , Cell Cycle Proteins/metabolism , Cell Line , Cell Proliferation , Chondrocytes/drug effects , Chondrocytes/metabolism , Humans , Inflammation/immunology , Inflammation/metabolism , Mice , Signal Transduction , YAP-Signaling ProteinsABSTRACT
DDIT3 is of great importance in endoplasmic reticulum stress and is involved in many inflammatory diseases and mineralization processes. The cementum protects teeth from periodontitis and provides attachment for Sharpey's fibers of the periodontal ligament. However, the effect of DDIT3 on cementoblast differentiation remains largely unknown. In this study, we found that DDIT3 was suppressed during cementoblast differentiation. Knockdown of DDIT3 increased the messenger RNA (mRNA) and protein levels of several key osteogenic markers in vitro, including alkaline phosphatase, runt-related transcription factor 2, and osteocalcin (OCN). In addition, isocitrate dehydrogenase 1 (IDH1) was increased during cementoblast differentiation, and knockdown of DDIT3 increased the protein and mRNA levels of IDH1. Furthermore, inhibition of IDH1 could partially reduce the effect of DDIT3 on cementoblast differentiation. The DDIT3 knockdown activated nuclear factor-κB (NF-κB) transcriptional activity and upregulated the expression of p-p65 and p-IκBα. The increased osteogenic differentiation ability and IDH1 expression, as induced by the DDIT3 knockdown, could be partially turned over by the addition of NF-κB inhibitor BAY 11-7082. Overall, our data clarified that DDIT3 suppresses cementoblast differentiation through IDH1, via the NF-κB pathway.
Subject(s)
Dental Cementum/metabolism , Isocitrate Dehydrogenase/metabolism , NF-kappa B/metabolism , Transcription Factor CHOP/metabolism , Animals , Cell Differentiation , Cell Line , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Humans , Isocitrate Dehydrogenase/genetics , Mice , NF-kappa B/genetics , Nitriles/pharmacology , Sulfones/pharmacology , Transcription Factor CHOP/geneticsABSTRACT
Yes-associated protein 1 (YAP1) transcriptional coactivator has recently been identified to regulate skeletal lineage cell differentiation and bone development. However, the role and molecular mechanisms of YAP1 in the regulation of osteoblastic differentiation remains to be elucidated. In this study, we demonstrated that YAP1 expression was increased during osteogenic differentiation of rat bone mesenchymal stem cells and MC3T3-E1. YAP1 overexpression MC3T3-E1 showed increased expression of osteogenesis markers, such as runt-related transcription factor 2, osteocalcin, and osteopontin, as well as alkaline phosphatase and alizarin red staining. Conversely, YAP1 knockdown significantly suppressed MC3T3-E1 osteoblastic differentiation. Mechanistically, we found that YAP1 overexpression upregulated the mRNA and protein expression of the inhibitor of differentiation/DNA binding 1 (ID1), which was contrary to the results of YAP1-knockdown group. Moreover, the early osteogenic differentiation of MC3T3-E1 cells was enhanced by ID1 overexpression. Furthermore, transient transfection with exogenous ID1 overexpression plasmid completely recaptured the decreased effects of YAP1 knockdown on MC3T3-E1 cell differentiation. In addition, ß-catenin and AMP-activated protein kinase signaling pathways participated in YAP1 regulation processes. Taken together, our study suggests that YAP1 is a crucial modulator of osteoblast differentiation in vitro, and provides insight into the mechanism by which YAP1 regulates osteoblast differentiation.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cell Cycle Proteins/metabolism , Cell Differentiation , Osteoblasts/cytology , Osteoblasts/metabolism , Osteogenesis , Adenylate Kinase/metabolism , Animals , Cell Differentiation/genetics , Cell Line , Cell Proliferation , Down-Regulation/genetics , Inhibitor of Differentiation Protein 1/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Models, Biological , Osteogenesis/genetics , Rats, Sprague-Dawley , Signal Transduction , Transcription, Genetic , Up-Regulation/genetics , YAP-Signaling Proteins , beta Catenin/metabolismABSTRACT
Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of mechanosensitive signaling. Cementum, which covers the tooth root surface, continuously senses external mechanical stimulation. Cementoblasts are responsible for the mineralization and maturation of the cementum. However, the effect of YAP1 on cementoblast differentiation remains largely unknown. In this study, we initially demonstrated that YAP1 overexpression enhanced the mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein expression of several cementogenesis markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix acidic phosphoprotein 1 (DMP1). The YAP1 overexpression group showed higher intensities of ALP and Alizarin red stain than the YAP1-knockdown group. Unexpectedly, a sharp increase in the expression of dentin sialophosphoprotein (DSPP) was induced by the overexpression of YAP1. Knockdown of YAP1 suppressed DSPP transcriptional activity. YAP1 overexpression activated Smad-dependent BMP signaling and slightly inhibited Erk1/2 signaling pathway activity. Treatment with specific BMP antagonist (LDN193189) prevented the upregulation of the mRNA levels of ALP, RUNX2, and OCN, as well as intensity of ALP-stained and mineralized nodules in cementoblasts. The Erk1/2 signaling pathway inhibitor (PD 98,059) upregulated these cementogenesis markers. Thus, our study suggested that YAP1 enhanced cementoblast mineralization in vitro. YAP1 exerted its effect on the cementoblast partly by regulating the Smad-dependent BMP and Erk1/2 signaling pathways.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Bone Morphogenetic Protein 1/metabolism , Cementogenesis/physiology , Dental Cementum/cytology , Extracellular Signal-Regulated MAP Kinases/metabolism , Phosphoproteins/metabolism , Smad Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Alkaline Phosphatase/biosynthesis , Animals , Bone Morphogenetic Protein 1/antagonists & inhibitors , Cell Cycle Proteins , Cell Differentiation , Cell Line , Core Binding Factor Alpha 1 Subunit/biosynthesis , Extracellular Matrix Proteins/biosynthesis , Extracellular Matrix Proteins/genetics , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Flavonoids/pharmacology , Mice , Osteocalcin/biosynthesis , Phosphoproteins/biosynthesis , Phosphoproteins/genetics , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Sialoglycoproteins/biosynthesis , Sialoglycoproteins/genetics , YAP-Signaling ProteinsABSTRACT
OBJECTIVE: To investigate the expansion of hematopoietic stem/progenitor cells (HSPCs) from umbilical cord blood using extracellular matrix (ECM) protein-coated three-dimensional hierarchical scaffolds. RESULTS: The expansion of HSPCs was evaluated through total nucleated cell (TNC) expansion, immuno-phenotypic analysis, and clonogenic ability. After 7 days of culture, three-dimensional cultures with fibronectin-coated scaffolds achieved the highest fold increase in TNCs (164 ± 6.9 fold) and the highest CD45(+)CD34(+) (35 %) and CD34(+)CD38(-) (32 %) ratios. CONCLUSION: Three-dimensional hierarchical scaffolds were coated with ECM protein to simulate a biomimetic environment or niche, and had a significant effect on the expansion potential of HSPCs without changing their phenotype.
Subject(s)
Biocompatible Materials/chemical synthesis , Cell Culture Techniques/methods , Fibronectins/metabolism , Hematopoietic Stem Cells/cytology , Umbilical Cord/cytology , ADP-ribosyl Cyclase 1/metabolism , Antigens, CD34/metabolism , Cell Culture Techniques/instrumentation , Cell Proliferation , Hematopoietic Stem Cells/immunology , Humans , Leukocyte Common Antigens/metabolism , Stem Cell Niche , Surface PropertiesABSTRACT
Sirtuin 6 (SIRT6) is a NAD-dependent deacetylase involved in lifespan regulation. To evaluate the effect of SIRT6 on osteogenesis, rat bone marrow mesenchymal stem cells (rBMSCs) with enhanced or reduced SIRT6 function were developed. We observed that SIRT6 knockdown significantly reduced the mRNA levels of several key osteogenic markers in vitro, including alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin, while overexpression of SIRT6 enhanced their expression. Additionally, SIRT6 knockdown activated nuclear factor-κB (NF-κB) transcriptional activity and upregulated the expression of acetyl-NF-κB p65 (Lys310). The decreased osteogenic differentiation ability of rBMSCs could be partially rescued by the addition of NF-κB inhibitor BAY 11-7082. Furthermore, SIRT6 overexpression in rBMSCs combined with the use of collagen/chitosan/hydroxyapatite scaffold could significantly boost new bone formation in rat cranial critical-sized defects, as determined by microcomputed tomography and histological examination. These data confirm that SIRT6 is mainly located in the nuclei of rBMSCs and plays an essential role in their normal osteogenic differentiation, partly by suppressing NF-κB signaling.
Subject(s)
Cell Differentiation , Mesenchymal Stem Cells/physiology , NF-kappa B/metabolism , Sirtuins/physiology , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Bone Regeneration , Cell Adhesion , Cell Nucleus/enzymology , Cell Proliferation , Cells, Cultured , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Gene Expression , Humans , Male , Mesenchymal Stem Cell Transplantation , Osteocalcin/genetics , Osteocalcin/metabolism , Osteogenesis , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Induced pluripotent stem cells (iPSCs) have great potential in bone tissue engineering to repair large bone defects. Before their clinical application, investigations are needed to discover the genes and osteoconductive scaffolds that influence their differentiation toward an osteogenic lineage. Alox5 plays controversial and complex roles in the regulation of bone and fat metabolism. To detect the effect of Alox5 on osteogenic and adipogenic differentiation of iPSCs, both Alox5 knockout mouse iPSCs (Alox5-KO-iPSCs) and wild-type mouse iPSCs (Wild-iPSCs) were developed. The mRNA levels of many osteogenic markers in Alox5-KO-iPSCs were significantly reduced, while many adipogenic markers were enhanced. Furthermore, when implanted in rat cranial critical-sized defects with collagen/chitosan/hydroxyapatite scaffolds (CCHS), Alox5-KO-iPSCs produced significantly less new bone than Wild-iPSCs and both cell-scaffold groups had no tumor formation. There was a significant difference in the expression of Cox2 during the osteogenic and adipogenic differentiation between the two kinds of iPSCs in vitro. In conclusion, firstly, Alox5 knockout reduced the osteogenic but increased the adipogenic differentiation potential of mouse iPSCs. These disorders might be related to the change of Cox2 expression. Secondly, combined with iPSCs, CCHS can serve as a potential substrate to repair critical-sized bony defects. However, more studies are required to confirm the mechanisms through which Alox5 affects the osteogenic and adipogenic abilities of iPSCs in vivo and the effect of Cox2 inhibition in this system.
Subject(s)
Adipogenesis/physiology , Arachidonate 5-Lipoxygenase/metabolism , Cell Differentiation/physiology , Induced Pluripotent Stem Cells/enzymology , Osteogenesis/physiology , Animals , Arachidonate 5-Lipoxygenase/genetics , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Induced Pluripotent Stem Cells/cytology , Mice , Mice, Knockout , Mice, Nude , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVES: With the development of online technology and the increase in real-world needs, conducting psychotherapy on online platforms has become a popular trend. The present study followed the schedule and content of Mindfulness-based Cognitive Therapy (MBCT), and only changed the treatment format (from offline to online) to investigate the effectiveness of online group MBCT for Chinese outpatients with depression. METHODS: The study used before-and-after controlled design, and included 88 depressed outpatients, of which 75 formally underwent a 10-week online group MBCT. The 24-item Hamilton Depression Scale (HAMD-24), Hamilton Anxiety Scale (HAMA), Self-Depression Rating Scale (SDS), Mindful Attention Awareness Scale (MAAS), and Self-Acceptance Questionnaire (SAQ) were administered to patients one week prior to treatment, the fifth week of treatment, and the tenth week of treatment. Repeated-measures data were processed using linear mixed-effects models. RESULTS: 75 patients (85.23 %) attended >4 sessions, 44 of whom were taking psychotropic medication during treatment. HAMD-24 and HAMA scores decreased significantly in both medicated and unmedicated patients (w10 < w1, p < 0.05). HAMD-24 and HAMA scores declined more rapidly in patients taking medication, with significant decreases in the fifth week (w5 < w1, p < 0.05). The remarkable effectiveness of treatment (HAMD-24 score reduction >50 %) was >30 %, but there were no significant changes in patients' SDS, MAAS, or SAQ scores. CONCLUSIONS: This study supports the effectiveness of online group MBCT for outpatients with depression and the adherence of depressed patients to participate in online group MBCT was high.
Subject(s)
Cognitive Behavioral Therapy , Mindfulness , Humans , Depression/therapy , Depression/psychology , Outpatients , Treatment OutcomeABSTRACT
This study aims to investigate the functional connectivity (FC) changes of the habenula (Hb) among patients with major depressive disorder (MDD) after 12 weeks of duloxetine treatment (MDD12). Patients who were diagnosed with MDD for the first time and were drug-naïve were recruited at baseline as cases. Healthy controls (HCs) matched for sex, age, and education level were also recruited at the same time. At baseline, all participants underwent resting-state functional MRI. FC analyses were performed using the Hb seed region of interest, and three groups including HCs, MDD group and MDD12 group were compared using whole-brain voxel-wise comparisons. Compared to the HCs, the MDD group had decreased FC between the Hb and the right anterior cingulate cortex at baseline. Compared to the HCs, the FC between the Hb and the left medial superior frontal gyrus decreased in the MDD12 group. Additionally, the FC between the left precuneus, bilateral cuneus and Hb increased in the MDD12 group than that in the MDD group. No significant correlation was found between HDRS-17 and the FC between the Hb, bilateral cuneus, and the left precuneus in the MDD12 group. Our study suggests that the FC between the post-default mode network and Hb may be the treatment mechanism of duloxetine and the treatment mechanisms and the pathogenesis of depression may be independent of each other.
Subject(s)
Depressive Disorder, Major , Habenula , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/drug therapy , Duloxetine Hydrochloride/pharmacology , Duloxetine Hydrochloride/therapeutic use , Default Mode Network , Magnetic Resonance Imaging , Rest/physiologyABSTRACT
Veratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both target natural products by utilizing a biomimetic rearrangement to form the C-nor-D-homo steroid core and a stereoselective reductive coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.
Subject(s)
Veratrum Alkaloids , Veratrum Alkaloids/chemical synthesis , Veratrum Alkaloids/chemistry , Stereoisomerism , Cyclization , Biological Products/chemical synthesis , Biological Products/chemistry , Molecular StructureABSTRACT
Our study aims to explore the differences in functional connectivity in the nucleus accumbens (NAc) between patients with melancholic depression and non-melancholic depression (NMD) and their relation to melancholic depression's pathogenesis. We recruited 60 melancholic depression, 58 NMD, and 80 healthy controls, all matched for gender, age, and education. Functional connectivity analysis focused on bilateral NAc as the region of interest, comparing it with the whole brain and correlating significant differences with clinical scores. Melancholic depression patients showed reduced functional connectivity between the left NAc and anterior brain regions, and between the right NAc and temporal and frontal areas, compared to healthy controls. In contrast, NMD patients displayed reduced functional connectivity only between the left NAc and the posterior cingulate cortex. Melancholic depression patients also exhibited increased functional connectivity between the right NAc and the middle frontal gyrus, unlike NMD patients. The findings suggest that melancholic depression patients exhibit unique NAc functional connectivity patterns, particularly with the default mode network and prefrontal areas, suggesting atypical reward-circuitry interactions. The right NAc's connection to the prefrontal gyrus may distinguish melancholic depression from NMD.
ABSTRACT
In this study, the influence of fasting on hepatic glucose and lipid metabolism was explored by examining biochemical, antioxidative, and morphological indicators and transcriptional expression in the liver of javelin goby (Synechogobius hasta) after 0, 3, 7, or 14 days of starvation. Marked reductions in hepatic glycogen and triglycerides occurred from the seventh day of starvation until the end of the trial (p < 0.05). However, no alterations in hepatic cholesterol or protein were detected throughout the entire experiment (p > 0.05). During fasting, the activities of pyruvate kinase, lactate dehydrogenase, and glycogen phosphorylase a all rose firstly and then fell (p < 0.05). The activities of hepatic fatty acid synthase and acetyl-CoA carboxylase were minimized to their lowest levels at the end of food deprivation (p < 0.05), while lipase was elevated after 7-14 days of fasting (p < 0.05). Catalase, glutathione, and the total antioxidative capacity were increased and maintained their higher values in the later stage of fasting (p < 0.05), whereas malondialdehyde was not significantly changed (p > 0.05). Hepatic vein congestion, remarkable cytoplasmic vacuoles, and irregular cell shape were present in S. hasta which endured 3-7 days of fasting and were less pronounced when food shortage was prolonged. In terms of genes associated with glucose and lipid metabolism, the hepatic phosphofructokinase gene was constantly up-regulated during fasting (p < 0.05). However, the mRNA levels of glycogen synthase and glucose-6-phosphatase were obviously lower when the food scarcity extended to 7 days or more (p < 0.05). Fatty acid synthase, stearoyl-CoA desaturase 1, and peroxisome proliferator-activated receptor γ were substantially down-regulated in S. hasta livers after 7-14 days of food deprivation (p < 0.05). However, genes involved in lipolysis and fatty acid transport were transcriptionally enhanced to varying extents and peaked at the end of fasting (p < 0.05). Overall, starvation lasting 7 days or more could concurrently mobilize hepatic carbohydrates and fat as energy resources and diminished their hepatic accumulation by suppressing biosynthesis and enhancing catabolism and transport, ultimately metabolically and structurally perturbing the liver in S. hasta. This work presents preliminary data on the dynamic characteristics of hepatic glucose and lipid metabolism in S. hasta in response to starvation, which may shed light on the sophisticated mechanisms of energetic homeostasis in fish facing nutrient unavailability and may benefit the utilization/conservation of S. hasta.
ABSTRACT
This paper employs low-field nuclear magnetic resonance (LF-NMR) technology to meticulously analyze and explore the intricate soybean infiltration process. The methodology involves immersing soybeans in distilled water, with periodic implementation of Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence experiments conducted at intervals of 20 to 30 minutes to determine the relaxation time T2. Currently, magnetic resonance imaging (MRI) is conducted every 30 minutes. The analysis uncovers the existence of three distinct water phases during the soybean infiltration process: bound water denoted as T21, sub-bound water represented by T22, and free water indicated as T23. The evolution of these phases unfolds as follows: bound water T21 displays a steady oscillation within the timeframe of 0 to 400 minutes; sub-bound water T22 and free water T23 exhibit a progressive pattern characterized by a rise-stable-rise trajectory. Upon scrutinizing the magnetic resonance images, it is discerned that the soybean infiltration commences at a gradual pace from the seed umbilicus. The employment of LF-NMR technology contributes significantly by affording an expeditious, non-destructive, and dynamic vantage point to observe the intricate motion of water migration during soybean infiltration. This dynamic insight into the movement of water elucidates the intricate mass transfer pathway within the soybean-water system, thus furnishing a robust scientific foundation for the optimization of processing techniques.
Subject(s)
Glycine max , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy/methods , Water/chemistry , MotionABSTRACT
BACKGROUND: China has thousands years of goat breeding and abundant goat genetic resources. Additionally, the Hainan black goat is one of the high-quality local goat breeds in China. In order to conserve the germplasm resources of the Hainan black goat, facilitate its genetic improvement and further protect the genetic diversity of goats, it is urgent to develop a single nucleotide polymorphism (SNP) chip for Hainan black goat. RESULTS: In this study, we aimed to design a 10K liquid chip for Hainan black goat based on genotyping by pinpoint sequencing of liquid captured targets (cGPS). A total of 45,588 candidate SNP sites were obtained, 10,677 of which representative SNP sites were selected to design probes, which finally covered 9,993 intervals and formed a 10K cGPS liquid chip for Hainan black goat. To verify the 10K cGPS liquid chip, some southern Chinese goat breeds and a sheep breed with similar phenotype to the Hainan black goat were selected. A total of 104 samples were used to verify the clustering ability of the 10K cGPS liquid chip for Hainan black goat. The results showed that the detection rate of sites was 97.34% -99.93%. 84.5% of SNP sites were polymorphic. The heterozygosity rate was 3.08%-36.80%. The depth of more than 99.4% sites was above 10X. The repetition rate was 99.66%-99.82%. The average consistency between cGPS liquid chip results and resequencing results was 85.58%. In addition, the phylogenetic tree clustering analysis verified that the SNP sites on the chip had better clustering ability. CONCLUSION: These results indicate that we have successfully realized the development and verification of the 10K cGPS liquid chip for Hainan black goat, which provides a useful tool for the genome analysis of Hainan black goat. Moreover, the 10K cGPS liquid chip is conducive to the research and protection of Hainan black goat germplasm resources and lays a solid foundation for its subsequent breeding work.
Subject(s)
Goats , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Animals , Goats/genetics , Polymorphism, Single Nucleotide/genetics , Oligonucleotide Array Sequence Analysis/methods , China , Genotyping Techniques/methods , Genotype , Sequence Analysis, DNA/methods , Breeding/methodsABSTRACT
INTRODUCTION: Anxiety disorder is one of the most prevalent mental disorders in China. However, there are obvious subjective factors in the current assessment of anxiety disorders, which may lead to certain diagnostic errors. The identification and diagnosis of anxiety disorders can be further improved if objective biological indicators are added in the assessment process. The current research validates facial expression recognition as a screening tool to assist in detecting generalized anxiety disorder. METHODS: Based on the International Affective Picture System, we constructed an aided diagnostic experimental paradigm and recorded their facial expression. The split-half reliability was displayed by the Pearson correlation heatmap. The paradigm, GAD-7 and HAMA scales were administered to 60 generalized anxiety disorder patients and 60 matched healthy controls to evaluate the criterion-related validity. Additionally, we conducted a diagnostic study by using MINI as a gold standard and calculated ROC analysis to examine the screening performance of the facial expressions. RESULTS: The heatmap showed very high correlations (r > 0.60, PS < 0.05) along the diagonal of the square heatmap (from the bottom left corner to the top right). The Pearson correlation coefficients between the GAD-7, HAMA and seven facial expressions ranged from -0.35(neutral, P < 0.01) to 0.34(angry, P < 0.01). The intergroup effects of neutral, anger and fear emotions were statistically significant (F = 18.893, P < 0.001; F = 20.535, P < 0.001; F = 9.091, P = 0.003). ROC analysis showed AUC for neutral, angry and scared facial expressions were 0.723, 0.792 and 0.727 respectively. CONCLUSION: This study constructed a tool for auxiliary screening of GAD patients and provided an objective automatic facial expression recognition method to assist psychological diagnosis.
ABSTRACT
BACKGROUND: Flight accidents caused by spatial disorientation (SD) greatly affect flight safety. OBJECTIVE: Few studies have been devoted to the evaluation of SD. METHODS: 10 pilots and 10 non-pilots were recruited for the experimental induction of SD. Videos for giving optical flow stimuli were played at two different flow speeds to induce SD. Subjective judgment and center of foot pressure (CoP) data were collected from the tests. The data were combined to determine the occurrence of SD and analyze the SD types. RESULTS: The number of self-reported SD events was slightly smaller in the pilots than in the non-pilots. The average upper bound of the confidence interval for the standard deviation of CoP was 0.32 ± 0.09 cm and 0.38 ± 0.12 cm in the pilots and non-pilots, respectively. This indicator was significantly lower in the pilots than in the non-pilots (P= 0.03). The success rate of the experimental induction of unrecognized SD was 26.7% and 45.0% in the pilots and non-pilots, respectively. CONCLUSION: The method offered a new to analyze unrecognized SD. We could determine the occurrence unrecognized SD. This is an essential means of reducing flight accidents caused by unrecognized SD.