Permanent magnetic materials capable of operating at high temperature up to 500℃ have wide potential applications in fields such as aeronautics, space, and electronic cars. SmCo alloys are candidates ...for high temperature applications, since they have large magnetocrystalline anisotropy field (6-30 T), high Curie temperature (720-920℃), and large energy product (〉200 kJ.m-3) at room temperature. However, the highest service temperature of commercial 2:17 type SmCo magnets is only 300℃, and many efforts have been devoted to develop novel high temperature permanent magnets. This review focuses on the development of three kinds of SmCo based magnets: 2:17 type SmCo magnets, nanocrystalline SmCo magnets, and nanocomposite SmCo magnets. The oxidation protection, including alloying and surface modification, of high temperature permanent magnets is discussed as well.
Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and ...oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.
Although it is known that ataxia‐telangiectasia mutated (ATM) and interleukin 6 (IL‐6) contribute to multiple drug resistance (MDR) in tumor chemotherapy, the exact role of ATM activation in MDR ...resulting from increased IL‐6 expression is still unclear. In the present study, we demonstrate that the activation of the ATM‐NF‐kappaB pathway, resulting from increased IL‐6 expression, plays a central role in augmented chemoresistance in lung cancer cell lines. This result was supported by the increased expressions of Bcl‐2, Mcl‐1, Bcl‐xl, and the upregulation of MDR‐associated protein ABCG2. The higher level of IL‐6 reveals not only higher ATM/NF‐kappaB activity but also increased expressions of ABCG2, Bcl‐2, Mcl‐1 and Bcl‐xl. Most importantly, lung cancer cells themselves upregulated IL‐6 secretion by activating the p38/NF‐kappaB pathway through treatment with cisplatin and camptothecin. Taken together, these findings demonstrate that chemotherapeutic agents increase IL‐6 expression, hence activating the ATM/NF‐kappaB pathway, augmenting anti‐apoptotic protein expression and contributing to MDR. This indicates that both IL‐6 and ATM are potential targets for the treatment of chemotherapeutic resistance in lung cancer.
We demonstrate that the activation of ATM‐NF‐κB pathway play a central role in IL‐6 augmented chemoresistance in lung cancer cells, which was supported by the increased expression of Bcl‐2, Mcl‐1, Bcl‐xl and the upregulation of MDR associated protein ABCG2.
Suicide is the fourth leading cause of death for individuals aged 15-29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is ...convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk.
Sixty-four college students with high suicidal ideation (aged 18-30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries.
Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency.
BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.
Background Peroral endoscopic myotomy (POEM) has been developed to provide a less-invasive myotomy for achalasia in adults but seldom has been used in pediatric patients. Objective To evaluate the ...feasibility, safety, and efficacy of POEM for pediatric patients with achalasia. Design Single-center, prospective study. Setting Academic medical center. Patients A total of 27 pediatric patients (mean age 13.8 years, range 6-17 years) with achalasia. Interventions POEM. Main Outcome Measurements The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤3. Secondary outcomes were procedure-related adverse events, clinical reflux adverse events, and lower esophageal sphincter (LES) pressure on manometry before and after POEM. Results A total of 26 cases (96.3%) underwent successful POEM. A submucosal tunnelling attempt failed in 1 case because of serious inflammation and adhesion. No serious adverse events related to POEM were encountered. During a mean follow-up period of 24.6 months (range 15-38 months), treatment success was achieved in all patients (mean score before vs after treatment 8.3 vs 0.7; P < .001). Mean LES pressure also decreased from a mean of 31.6 mm Hg to 12.9 mm Hg after POEM ( P < .001). Five patients developed clinical reflux adverse events (19.2%). Limitations Single center and lack of some objective evaluations. Conclusion This relatively long-term follow-up study adds to the evidence that POEM seems to be a promising new treatment for pediatric patients with achalasia, resulting in long-term symptom relief in all cases and without serious adverse events.
Background
MIKC type MADS-box transcription factors are one of the largest gene families and play a pivotal role in flowering time and flower development.
Chimonanthus salicifolius
belongs to the ...family Calycanthaceae and has a unique flowering time and flowering morphology compared to other
Chimonanthus
species, but the research on MIKC type MADS-box gene family of
C. salicifolius
has not been reported.
Objective
Identification, comprehensive bioinformatic analysis, the expression pattern of MIKC-type MADS-box gene family from different tissues of
C. salicifolius
.
Methods
Genome-wide investigation and expression pattern under different tissues of the MIKC-type MADS-box gene family in
C. salicifolius
, and their phylogenetic relationships, evolutionary characteristics, gene structure, motif distribution, promoter
cis
-acting element were performed.
Results
A total of 29 MIKC-type MADS-box genes were identified from the whole genome sequencing. Interspecies synteny analysis revealed more significant collinearity between
C. salicifolius
and the magnoliids species compared to eudicots and monocots. MIKC-type MADS-box genes from the same subfamily share similar distribution patterns, gene structure, and expression patterns. Compared with
Arabidopsis thaliana
,
Nymphaea colorata
, and
Chimonanthus praecox
, the
FLC
genes were absent in
C. salicifolius
, while the
AGL6
subfamily was expanded in
C. salicifolius
. The selectively expanded promoter (
AGL6
) and lack of repressor (
FLC
) genes may explain the earlier flowering in
C. salicifolius
. The loss of the
AP3
homologous gene in
C. salicifolius
is probably the primary cause of the morphological distinction between
C. salicifolius
and
C. praecox
.
The csAGL6a
gene is specifically expressed in the flowering process and indicates the potential function of promoting flowering.
Conclusion
This study offers a genome-wide identification and expression profiling of the MIKC-types MADS-box genes in the
C. salicifolius
, and establishes the foundation for screening flowering development genes and understanding the potential function of the MIKC-types MADS-box genes in the
C. salicifolius
.
Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane ...depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI). C57BL/6 mice underwent lateral fluid percussion TBI. TBI mice were transfected with a lentivirus carrying the DCX-ChR2-EGFP gene. We observed that not only immature neurons but also type-2b intermediate progenitor (IPs) and neuroblasts expressed DCX-EGFP, indicating that DCX-expressing newborn cells could provide a long time window for electrical activity regulation. Quantitative results showed that the number of EGFP-expressing cells began to rise at 3 days after TBI and peaked at 9 days after TBI. By optical depolarization of DCX-EGFP-expressing cells between 3 and 12 days, we observed significantly improved cognitive deficits after TBI with enhanced survival and maturation of newborn cells in the dentate gyrus. We also investigated the role of optical depolarization in neural stem cells transfected with a lentivirus carrying the ChR2-DCX-EGFP gene in vitro. By administrating verapamil to block L-type calcium channels, we verified that the up-regulation of MAP2, NeuN, Neurog2, NeuroD1 and GluR2 in newborn cells was mediated by ChR2-elicted depolarization. By using β-catenin inhibitor Dkk1, we demonstrated that optical depolarization of DCX-EGFP-expressing cells facilitated survival and maturation probably through the Wnt/β-catenin signaling cascade.
Radiofrequency ablation (RFA) is one of the effective therapeutic modalities in patients with hepatocellular carcinoma (HCC). However, there is no proper method to evaluate the HCC response to RFA. ...This study aimed to establish and validate a clinical prediction model based on dual-energy computed tomography (DECT) quantitative-imaging parameters, clinical variables, and CT texture parameters.
We enrolled 63 patients with small HCC. Two to four weeks after RFA, we performed DECT scanning to obtain DECT-quantitative parameters and to record the patients’ clinical baseline variables. DECT images were manually segmented, and 56 CT texture features were extracted. We used LASSO algorithm for feature selection and data dimensionality reduction; logistic regression analysis was used to build a clinical model with clinical variables and DECT-quantitative parameters; we then added texture features to build a clinical-texture model based on clinical model.
A total of six optimal CT texture analysis (CTTA) features were selected, which were statistically different between patients with or without tumor progression (P < 0.05). When clinical variables and DECT-quantitative parameters were included, the clinical models showed that albumin-bilirubin grade (ALBI) odds ratio (OR) = 2.77, 95% confidence interval (CI): 1.35-6.65, P = 0.010, λAP (40-100 keV) (OR = 3.21, 95% CI: 3.16-5.65, P = 0.045) and ICAP (OR = 1.25, 95% CI: 1.01-1.62, P = 0.028) were associated with tumor progression, while the clinical-texture models showed that ALBI (OR = 2.40, 95% CI: 1.19-5.68, P = 0.024), λAP (40-100 keV) (OR = 1.43, 95% CI: 1.10-2.07, P = 0.019), and CTTA-score (OR = 2.98, 95% CI: 1.68-6.66, P = 0.001) were independent risk factors for tumor progression. The clinical model, clinical-texture model, and CTTA-score all performed well in predicting tumor progression within 12 months after RFA (AUC = 0.917, 0.962, and 0.906, respectively), and the C-indexes of the clinical and clinical-texture models were 0.917 and 0.957, respectively.
DECT-quantitative parameters, CTTA, and clinical variables were helpful in predicting HCC progression after RFA. The constructed clinical prediction model can provide early warning of potential tumor progression risk for patients after RFA.
Abundant evidence suggests that the prevalence and risk of depression in people with diabetes is high. However, the pathogenesis of diabetes-related depression remains unclear. Since ...neuroinflammation is associated with the pathophysiology of diabetic complications and depression, this study aims to elucidate the neuroimmune mechanism of diabetes-related depression.
Male C57BL/6 mice were injected with streptozotocin to establish a diabetes model. After screening, diabetic mice were treated with the NLRP3 inhibitor MCC950. Then, metabolic indicators and depression-like behaviors were evaluated in these mice, as well as their central and peripheral inflammation. To explore the mechanism of high glucose-induced microglial NLRP3 inflammasome activation, we performed in vitro studies focusing on its canonical upstream signal I (TLR4/MyD88/NF-κB) and signal II (ROS/PKR/P2X7R/TXNIP).
Diabetic mice exhibited depression-like behaviors and activation of NLRP3 inflammasome in hippocampus. In vitro high-glucose (50 mM) environment primed microglial NLRP3 inflammasome by promoting NF-κB phosphorylation in a TLR4/MyD88-independent manner. Subsequently, high glucose activated the NLRP3 inflammasome via enhancing intracellular ROS accumulation, upregulating P2X7R, as well as promoting PKR phosphorylation and TXNIP expression, thereby facilitating the production and secretion of IL-1β. Inhibition of NLRP3 with MCC950 significantly restored hyperglycemia-induced depression-like behavior and reversed the increase in IL-1β levels in the hippocampus and serum.
The activation of NLRP3 inflammasome, probably mainly in hippocampal microglia, mediates the development of depression-like behaviors in STZ-induced diabetic mice. Targeting the microglial inflammasome is a feasible strategy for the treatment of diabetes-related depression.
Schematic diagram of the role and molecular mechanisms of microglial NLRP3 inflammasome activation in mediating diabetes-related depression. IL-1β: interleukin-1 beta; NLRP3: NOD-, leucine-rich repeat (LRR)-, and pyrin domain (PYD)-containing protein 3; ASC: apoptosis-associated speck-like protein containing a caspase recruitment domain; TLR4: Toll-like receptor 4; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; ROS: reactive oxygen species; TXNIP: thioredoxin-interacting protein; PKR: double-stranded RNA-dependent protein kinase; P2X7R: purinergic receptor P2X, ligand-gated ion channel 7; ATP: adenosine triphosphate. Display omitted
•Inhibiting NLRP3 inflammasome alleviates diabetes-induced depression-like behavior.•Glucose overload primes NLRP3 inflammasomes via enhancing NF-κB phosphorylation.•High glucose triggers microglial NLRP3 inflammasome activation by various pathways.
Microbial lipopeptides have been proposed to adsorb at interface rapidly and have synergistic effect with synthetic surfactant, and we assumed that stable droplets of oil would generate and ...oil-in-water emulsion with good stability would be obtained using the mixture of microbial lipopeptides and synthetic surfactant in short time scale. Here, the interfacial properties of the mixture of microbial lipopeptide and petroleum sulphonates has been evaluated using the coalescence frequency of the micro-droplets of crude oil in surfactant solutions in flow state and within sub-second period based on a microfluidic method. Results showed that partial substitution of petroleum sulphonates by lipopeptide enhanced the stability of micro-droplets of crude oil in surfactant solutions. To form stable micro-droplets of crude oil, less lipopeptide/petroleum sulphonates mixture (m:m=1:1) was needed than petroleum sulphonates. Moreover, higher salt tolerance, less demand of alkali, and shorter adsorption time were obtained for lipopeptide/petroleum sulphonates mixture to form stable emulsion comparing with that of individual petroleum sulphonates mixture. The present study provide novel information of lipopeptide/petroleum sulphonates mixture in generating stable crude oil-in-water emulsion at flow state.
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