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OBJECTIVE: To explore the clinical utility of ultrasound in evaluating and grading neuromuscular diseases in the lower extremities of patients with diabetes mellitus. METHODS: A total of 126 inpatients from the Department of Diabetes at Zhangzhou Affiliated Hospital of Fujian Medical University, China, were recruited from June 2020 to December 2022. The cohort included 69 patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN group) and 57 patients with T2DM but without DPN (non-DPN group). Additionally, 80 healthy controls were included. High-frequency ultrasound was used to scan the common peroneal, sural, and tibial nerves, measuring their transverse (D1) and anteroposterior (D2) diameters, and calculating the cross-sectional area (CSA). Changes in the internal echo of the extensor digitorum brevis (EDB) muscle, including maximum thickness and CSA, were also recorded. The DPN group was further subdivided based on disease duration to assess ultrasonic changes over time and the statistical significance of these variations. RESULTS: Ultrasonic changes such as uneven internal echo reduction, ill-defined epineurial boundaries, and obscured cribriform structures were most prevalent in the DPN group. Significant differences in ultrasound parameters (D1, D2, CSA) were observed among the groups (all P<0.05), with the most pronounced changes in the DPN group. In patients with a disease duration of over 15 years, a significant increase in CSA of lower extremity nerves and a decrease in CSA of the EDB were noted compared to those in the 5-10 years subgroup (19.89±0.98 vs 19.00±0.94; 5.25±0.74 vs 5.93±0.94; all P<0.05). CONCLUSIONS: High-frequency ultrasound provides a valuable imaging basis for diagnosing and monitoring DPN, demonstrating significant changes in nerve and muscle parameters among diabetic patients.
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METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase separation, by driving metabolic reprogramming. This correlates with an impairment of translation of cell-cycle related mRNAs harboring polymethylated m6A sites. In summary, our results report a coordination of m6A-dependent and -independent function of the methyltransferase complex in regulating senescence through phase separation driven by metabolic reprogramming.
Subject(s)
Cellular Senescence , Chromatin , Methyltransferases , Stress Granules , Methyltransferases/metabolism , Methyltransferases/genetics , Chromatin/metabolism , Humans , Stress Granules/metabolism , Stress Granules/genetics , Hexokinase/metabolism , Hexokinase/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics , Adenosine/metabolism , Adenosine/analogs & derivatives , HEK293 Cells , Metabolic Reprogramming , Phase SeparationABSTRACT
OBJECTIVES: To develop and evaluate a direct abdominal vein thrombus imaging (DATI) technique, based on a respiratory navigating SPACE sequence with DANTE black-blood preparation, for diagnosing abdominal vein thrombosis (AVT) without the use of exogenous contrast agents. METHODS: We prospectively enrolled 10 healthy subjects and 28 suspected AVT patients who underwent DATI scans on 3.0 T MRI. Contrast-enhanced CT venography (CTV) was also conducted on the suspected AVT patients for comparison. All images were analyzed by two blinded radiologists who independently evaluated randomized images and gave image quality and diagnostic confidence scores (1-poor, 4-excellent) for DATI and CTV. The accuracy (ACC), sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of CTV were calculated using CTV as a standard reference. The diagnostic agreement between DATI and CTV as well as the interobserver agreement were conducted using Cohen κ test. RESULTS: The patient study demonstrated that DATI can provide adequate thrombus signal intensity and the contrast between the thrombus to dark venous lumen for the diagnosis of AVT. It offers good to excellent image quality (reader1/reader2: 3.50 ± 0.64/3.42 ± 0.63, κ = 0.872) and diagnostic confidence (reader1/reader2: 3.71 ± 0.53/3.78 ± 0.42, κ = 0.804) for the diagnosis of AVT. Taking CTV as a reference, DATI has high accuracy (96.6%), SE (91.5%), SP (98.0%), PPV (92.3%), and NPV (97.8%). DATA CONCLUSION: DATI can provide good to excellent image quality, effective venous blood signal suppression, and definitive thrombus detection for the diagnosis of AVT without the use of exogenous contrast agents.
Subject(s)
Sensitivity and Specificity , Venous Thrombosis , Humans , Venous Thrombosis/diagnostic imaging , Male , Female , Middle Aged , Prospective Studies , Adult , Aged , Magnetic Resonance Imaging/methods , Abdomen/diagnostic imaging , Abdomen/blood supply , Contrast Media , Phlebography/methodsABSTRACT
Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their resistance to anti-PD-L1 by enhancing its binding with PD-1 on CD8+ T cells. In orthotopic, syngeneic EOC models in female mice, inhibiting branched N-glycans using 2-Deoxy-D-glucose sensitizes HR-proficient, but not HR-deficient EOCs, to anti-PD-L1. These findings indicate branched N-glycans as promising therapeutic targets whose inhibition sensitizes HR-proficient EOCs to ICB by overcoming immune evasion.
Subject(s)
BRCA1 Protein , Ovarian Neoplasms , Humans , Female , Animals , Mice , BRCA1 Protein/metabolism , Immune Checkpoint Inhibitors/therapeutic use , CD8-Positive T-Lymphocytes/metabolism , Glycosylation , BRCA2 Protein/metabolism , Ovarian Neoplasms/pathology , Carcinoma, Ovarian Epithelial/drug therapy , B7-H1 Antigen/metabolismABSTRACT
BACKGROUND: The purpose of this study was to evaluate the relationship between remnant cholesterol (RC) to high-density lipoprotein cholesterol (HDL-C) ratio and the risk of coronary artery disease (CAD). We also investigated the clinical value of RC/HDL-C ratio in evaluating the severity of CAD and in predicting the short-term prognosis of CAD patients. METHODS: In total, 615 patients were enrolled and they were classified into a CAD group (418 cases) and a normal group (197 cases) according to the results of coronary angiography. Serum RC/HDL-C ratio and Gensini score were calculated. Multivariate logistic regression and receiver operating characteristic (ROC) curves were employed to evaluate the association between RC/HDL-C ratio and CAD. The effect of RC/HDL-C ratio on the progression of major adverse cardiovascular events (MACEs) was also explored. RESULTS: Increased RC/HDL-C ratio was associated with an increased risk of CAD (OR: 11.122; 95% CI: 5.903-20.954; P â <â 0.001). When stratified by CAD subtypes, increased RC/HDL-C ratio was correlated with a greater risk of acute coronary syndrome (ACS) (OR:1.549; 95% CI: 1.014-2.364; P â <â 0.05). Compared with the first quartile, the 4th quartile of RC/HDL-C ratio had a 9.774-fold ( P â =â 0.000) increase in the odds ratio for CAD, and a 2.241-fold ( P â =â 0.017) increase in the odds ratio for ACS. RC/HDL-C ratio was an independent determinant of Gensini score ≥32 (OR: 2.138, 95% CI:1.389-3.292, P â <â 0.01), and multi-branch (MVD) (OR: 2.245; 95% CI: 1.468-3.443; P â <â 0.001). The prevalence of Gensini score ≥32 and MVD in the 4th quartile of RC/HDL-C ratio group were much higher than that of other quartile groups ( P â <â 0.01). Moreover, the areas under the ROC for the predictive value of RC/HDL-C ratio for CAD, ACS, Gensini score ≥32, and MVD were 0.702, 0.563, 0.602, and 0.669, respectively. Furthermore, the incidence of MACEs was significantly increased in CAD patients with levels of RC/HDL-C ratio ( P â <â 0.05). CONCLUSION: RC/HDL-C ratio plays an important role in the progression and severity of CAD.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Cholesterol, HDL , Cholesterol, LDL , Cholesterol , Coronary Angiography , Acute Coronary Syndrome/complications , Risk FactorsABSTRACT
Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating tissue aging has been attributed to its enzymatic role in cellular redox regulation. Here, we show that TXNRD1 drives the SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune response pathway independently of its enzymatic activity. TXNRD1 localizes to cytoplasmic chromatin fragments and interacts with cGAS in a senescence-status-dependent manner, which is necessary for the SASP. TXNRD1 enhances the enzymatic activity of cGAS. TXNRD1 is required for both the tumor-promoting and immune surveillance functions of senescent cells, which are mediated by the SASP in vivo in mouse models. Treatment of aged mice with a TXNRD1 inhibitor that disrupts its interaction with cGAS, but not with an inhibitor of its enzymatic activity alone, downregulated markers of inflammaging in several tissues. In summary, our results show that TXNRD1 promotes the SASP through the innate immune response, with implications for inflammaging. This suggests that the TXNRD1-cGAS interaction is a relevant target for selectively suppressing inflammaging.
Subject(s)
Signal Transduction , Thioredoxin Reductase 1 , Animals , Mice , Cellular Senescence/genetics , Immunity, Innate/genetics , Inflammation/genetics , Nucleotidyltransferases/genetics , Thioredoxin Reductase 1/metabolismABSTRACT
In the rapidly evolving field of thin-film electronics, the emergence of large-area flexible and wearable devices has been a significant milestone. Although organic semiconductor thin films, which can be manufactured through solution processing, have been identified, their utility is often undermined by their poor stability and low carrier mobility under ambient conditions. However, inorganic nanomaterials can be solution-processed and demonstrate outstanding intrinsic properties and structural stability. In particular, a series of two-dimensional (2D) nanosheet/nanoparticle materials have been shown to form stable colloids in their respective solvents. However, the integration of these 2D nanomaterials into continuous large-area thin with precise control of layer thickness and lattice orientation still remains a significant challenge. This review paper undertakes a detailed analysis of van der Waals thin films, derived from 2D materials, in the advancement of thin-film electronics and optoelectronic devices. The superior intrinsic properties and structural stability of inorganic nanomaterials are highlighted, which can be solution-processed and underscor the importance of solution-based processing, establishing it as a cornerstone strategy for scalable electronic and optoelectronic applications. A comprehensive exploration of the challenges and opportunities associated with the utilization of 2D materials for the next generation of thin-film electronics and optoelectronic devices is presented.
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BACKGROUND: Blood flow signals may be a confounder in quantifying T1 values of plaque or thrombus and how to realize black-blood T1 mapping remains a challenge task. PURPOSE: To develop a fast and three-dimensional black-blood T1 mapping technique for quantitative assessment of atherosclerosis and venous thrombosis. STUDY TYPE: Sequence development and optimization via phantoms and volunteers as well as pilot prospective. PHANTOM AND SUBJECTS: Numerical simulations, a standard phantom, 8 healthy volunteers (mean age, 22 ± 1 years; 5 males), and 19 patients (mean age, 57 ± 14 years; 13 males) with atherosclerosis or venous thrombosis. FIELD STRENGTH/SEQUENCE: 3T/inversion recovery spin-echo sequence (IR-SE), magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE), and black-blood prepared MP2RAGE (BB-MP2RAGE). ASSESSMENT: The black-blood preparation (i.e., delay alternating with nutation for tailored excitation, DANTE) was incorporated into MP2RAGE for black-blood T1 mapping. The BB-MP2RAGE was optimized numerically based on the Bloch equation, and then the phantom study was performed to verify the accuracy of T1 mapping by BB-MP2RAGE against IR-SE and MP2RAGE. Preliminary clinical validation was prospectively performed to assess the flow suppression effect and its potential application in plaque and thrombosis identification. STATISTICAL TESTS: Pearson correlation test, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. A P value <0.05 indicates a statistically significant difference. RESULTS: Phantom experiments showed comparable accuracy of T1 maps by BB-MP2RAGE with IR-SE and MP2RAGE (all r2 > 0.99); Compared to MP2RAGE, BB-MP2RAGE effectively nulled the blood flow signals, and had a significant improvement in contrast-to-noise ratio between static tissue and blood (250.5 ± 66.6 vs. 91.9 ± 35.9). BB-MP2RAGE can quantify plaque or thrombus T1 relaxation time with blood flow signal suppression. DATA CONCLUSION: Accurate T1 mapping with sufficient blood flow suppression was achieved by BB-MP2RAGE. BB-MP2RAGE has the potential to quantitatively characterize atherosclerosis and venous thrombosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.
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BACKGROUND: Bronchoscopic lung volume reduction (LVR) could significantly improve pulmonary function and quality of life in patients with emphysema. We aimed to assess the efficacy and safety of bronchoscopic thermal vapor ablation (BTVA) on LVR in patients with emphysema at different stage. METHODS: A systematic search of database including PubMed, Embase and Cochrane library was conducted to determine all the studies about bronchoscopic thermal vapor ablation published through Dec 1, 2022. Related searching terms were "lung volume reduction", "bronchoscopic thermal vapor ablation", "bronchial thermal vapor ablation" "BTVA" and "emphysema", "efficacy" and"safety". We used standardized mean difference (SMD) to analyze the summary estimates for BTVA therapy. RESULTS: We retrieved 30 records through database search, and 4 trials were selected for meta-analysis, including 112 patients with emphysema. Meta-analysis of the pooled effect showed that levels of forced expiratory volume in 1 s (FEV1), residual volume (RV), total lung capacity (TLC), 6-min walk distance (6MWD) and St George's Respiratory Questionnaire (SGRQ) were significantly improved in patients with emphysema following BTVA treatment between 6 months vs. baseline. Additionally, no significant changes in FEV1, RV, TLC and SGRQ occurred from 3 to 6 months of follow-up except for 6MWD. The magnitude of benefit was higher at 3 months compared to 6 months. The most common complications at 6 months were treatment-related chronic obstructive pulmonary disease (COPD) exacerbations (RR: 12.49; 95% CI: 3.06 to 50.99; p < 0.001) and pneumonia (RR: 9.49; 95% CI: 2.27 to 39.69; p < 0.001). CONCLUSIONS: Our meta-analysis provided clinically relevant information about the impact and safety of BTVA on predominantly upper lobe emphysema. Particularly, short-term significant improvement of lung function and quality of life occurred especially within the initial 3 months. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.
Subject(s)
Ablation Techniques , Emphysema , Pulmonary Emphysema , Humans , Pneumonectomy/adverse effects , Quality of Life , Ablation Techniques/adverse effects , Forced Expiratory Volume , Bronchoscopy/adverse effects , Treatment OutcomeABSTRACT
Duck breed Longshengcui (Anas platyrhynchos Linnaeus, 1758 breed Longshengcui, LSC) is one of the famous native breed of the Guangxi Zhuang Nationality Autonomous Region in China. In this study, we report the complete mitochondrial genome of LSC. The mitogenome (GenBank accession no. MZ895120) has 16,602 bp in length and consisted of the well-known 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and the control region. The phylogenetic analysis showed that LSC and Zhijiang duck have highly similar genetic relationship. These results are helpful for the conservation of genetic resources and phylogeny of this species.
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Background: Peer victimization is a harmful experience that contributed to one's psychological problems, physical health deterioration, and so on. Quality of life (QoL) is an important indicator of adolescent health assessment. To identify potential pathways of positive experiences in preventing peer victimization's detrimental effects and then provide intervention ideas for adolescent health, this study was conducted to examine the relationship between peer victimization and QoL in Chongqing adolescents and discover whether resilience plays a mediating role and positive childhood experiences (PCEs) act as a moderating role in the relationship. Methods: Data were the first follow-up of a cohort study conducted in four complete middle schools in two districts of Chongqing, China. Self-designed peer victimization items, the Connor-Davidson Resilience Scale, the Adolescent Quality of Life Scale, and the Benevolent Childhood Experiences Scale were used. We investigated the differences and correlations in peer victimization, QoL, and resilience between the two PCEs groups. Mplus version 8.3 was used to analyze the mediating role of resilience and the moderating role of PCEs in peer victimization and QoL. Results: Peer victimization, resilience, and QoL differed between the two PCEs groups (P < 0.001). Peer victimization negatively correlated with QoL and resilience, while resilience positively correlated with QoL (P < 0.001). In the models with total QOL as the dependent variable, the indirect effect was -0.431 (8.08% of the total effect) in the low-PCEs group vs. -2.077 (41.97% of the total effect) in the high-PCEs group. In the models with four dimensions of QOL as the dependent variable, the indirect effects ranged from -0.054 to -0.180 (6.07-12.95% of the total effects) in the low-PCEs group and from 0.295 to -0.823 in the high-PCEs group (35.89-68.76% of the total effects). Both total and indirect effects were significant (P < 0.05). In addition, the differences in indirect effects were significant between the two PCEs groups (P < 0.05), while differences in total and direct effects were almost not apparent. Conclusion: Resilience partially mediated the effect of peer victimization on QoL in Chongqing adolescents, and PCEs moderated this mediation. Schools, families, and society should focus on resilience intervention and prioritize the enhancement of PCEs for improving adolescent QoL.
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Acute ischemic stroke (AIS) is a serious cardiovascular and cerebrovascular disease; Oxidative stress and neuroinflammation are important factors which destroy blood-brain barrier (BBB) in AIS. In the study, a series of 1,3,5-triphenyl-1,2,4-triazole derivatives were designed and synthesized; the optimal compound 9 was obtained by screening their anti-oxidant and anti-inflammatory effects; the neuroprotection effect of compound 9 was evaluated with a rat middle cerebral artery occlusion (MCAO) model. Subsequently, the mechanism of neuroprotection were explored via Western blot. The results prompt compound 9 maybe exert anti-AIS neuroprotection by inhibiting oxidative stress and neuroinflammation inhibition by inhibiting Keap1, COX-2 and iNOS. At the same time, it can protect BBB by reducing glycocalyx degradation and matrix metallopeptidase-9 levels. Its LD50 > 1000 mg/kg on mice and hERG channel inhibition IC50 > 30 µM, which lower acute toxicity and hERG channel inhibition would make compound 9 a promising stroke treatment candidate.
Subject(s)
Blood-Brain Barrier , Ischemic Stroke , Animals , Mice , Rats , Kelch-Like ECH-Associated Protein 1 , Neuroprotection , Neuroinflammatory Diseases , NF-E2-Related Factor 2 , Oxidative Stress , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic useABSTRACT
A two-dimensional (2D) silicene-germanene alloy, siligene (SixGey), a single-phase material, has attracted increased attention due to its two-elemental low-buckled composition and unique physics and chemistry. This 2D material has the potential to address the challenges caused by low electrical conductivity and the environmental instability of corresponding monolayers. Yet, the siligene structure was studied in theory, demonstrating the material's great electrochemical potential for energy storage applications. The synthesis of free-standing siligene remains challenging and therefore hinders the research and its application. Herein we demonstrate nonaqueous electrochemical exfoliation of a few-layer siligene from a Ca1.0Si1.0Ge1.0 Zintl phase precursor. The procedure was conducted in an oxygen-free environment applying a -3.8 V potential. The obtained siligene exhibits a high quality, high uniformity, and excellent crystallinity; the individual flake is within the micrometer lateral size. The 2D SixGey was further explored as an anode material for lithium-ion storage. Two types of anode have been fabricated and integrated into lithium-ion battery cells, namely, (1) siligene-graphene oxide sponges and (2) siligene-multiwalled carbon nanotubes. The as-fabricated batteries both with/without siligene exhibit similar behavior; however there is an increase in the electrochemical characteristics of SiGe-integrated batteries by 10%. The corresponding batteries exhibit a 1145.0 mAh·g-1 specific capacity at 0.1 A·g-1. The SiGe-integrated batteries demonstrate a very low polarization, confirmed by their good stability after 50 working cycles and a decrease in the solid electrolyte interphase level that occurs after the first discharge/charge cycle. We anticipate the growing potential of emerging two-component 2D materials and their great promise for energy storage and beyond.
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BACKGROUND: Internet addiction has emerged as a major global concern as a potential adverse impact of internet exposure on adolescents. Internet addiction is associated with many demographic variables; however, there is a lack of consensus on its relationship with health literacy. Therefore, the aim of the present study was to assess the rates of internet addiction and health literacy level among middle school students (grades 7 to 12) in Chongqing, China, as well as to investigate the association between them. METHODS: A cross-sectional, questionnaire-based study was conducted among 8971 students who were randomly selected by using stratified cluster sampling between November and December 2019. The Internet Addiction Diagnostic Questionnaire, Adolescent Health Literacy Scale and a self-designed basic information questionnaire were used to collect data. Chi-square tests were performed to compare the differences in the distribution of internet addiction across health literacy levels as well as some sociodemographic characteristics. Multivariate logistic regression analyses were conducted to identify the association between health literacy and internet addiction. RESULTS: The prevalence of internet addiction among middle school students in Chongqing was 6.1%. The percentage of the students who spent more than 4 hours online every day in the past week was 14.3%. In addition, 26.7%, 26.0%, 28.3% and 26.3% of the participants reported low functional, interactive, critical and total health literacy, respectively. After adjusting for the confounding effects of demographics, multivariate regression analysis showed that critical health literacy was a protective variable for internet addiction, while functional, and interactive health literacy were the risk variable (P<0.05). Furthermore, the internet addiction rates were higher among boys, students with good peer relationships, and students without parental supervision, whereas internet addiction rates were lowest among students in grade 12. CONCLUSIONS: The prevalence of internet addiction among middle school students in Chongqing is relatively high. Internet addiction is strongly negatively associated with critical health literacy, but it is positively associated with functional and interactive health literacy but not total health literacy. This study provides preliminary evidence for the predictive role of health literacy in internet addiction of adolescents.
Subject(s)
Behavior, Addictive , Health Literacy , Male , Adolescent , Humans , Cross-Sectional Studies , Internet Addiction Disorder , China/epidemiology , Surveys and Questionnaires , Students , Behavior, Addictive/epidemiology , InternetABSTRACT
Black phosphorus (BP), a promising 2D material for electronics, energy storage, catalysis, and sensing, has sparked a research boom. However, exfoliated thin-layered BP is unstable and can easily be degraded under environmental conditions, severely limiting its practical applications. In this context, a simple and cost-effective method has been proposed that involves electrochemically exfoliating BP and simultaneously electrochemically depositing aluminum oxide (AlO x ) for passivation of the exfoliated BP. The ambient stability of the exfoliated BP is studied using a time-dependent atomic force microscope (AFM). The AlO x capping layer significantly improves the environmental stability of BP compared to uncapped BP. The thermal stability of the resulting BP is evaluated using power-dependent Raman spectroscopy. The results show that the AlO x -passivated BP has increased thermal stability, with only a slight shift in peak position toward higher Raman power intensity. These properties can make the material suitable for stable energy storage devices. Interestingly, the electrochemical exfoliation and passivation processes resulted in the BP with a twist angle (9.86°), which is expected to exhibit unique electronic properties similar to those of graphene with a twist angle.
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ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in â¼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune checkpoint blockade (ICB) by driving inflammasome-regulated immunomodulating pyroptosis in ARID1A-inactivated OCCCs. SWI/SNF inactivation downregulates the rate-limiting enzymes in the mevalonate pathway such as HMGCR and HMGCS1, which creates a dependence on the residual activity of the pathway in ARID1A-inactivated cells. Inhibitors of the mevalonate pathway such as simvastatin suppresses the growth of ARID1A mutant, but not wild-type, OCCCs. In addition, simvastatin synergizes with anti-PD-L1 antibody in a genetic OCCC mouse model driven by conditional Arid1a inactivation and in a humanized immunocompetent ARID1A mutant patient-derived OCCC mouse model. Our data indicate that inhibition of the mevalonate pathway simultaneously suppresses tumor cell growth and boosts antitumor immunity by promoting pyroptosis, which synergizes with ICB in suppressing ARID1A-mutated cancers.
Subject(s)
Carcinoma , Ovarian Neoplasms , Humans , Female , Mice , Animals , Mevalonic Acid , Pyroptosis , Nuclear Proteins/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Mutation , DNA-Binding Proteins/genetics , Transcription Factors/geneticsABSTRACT
Adolescents are prone to multiple health risk behaviors. These might lead to insufficient sleep, which is inconducive to adolescent growth. Therefore, this study explored the impact of a cluster of adolescent health risk behaviors on sleep time, providing a reference for designing relevant intervention measures. From November to December 2019, a stratified cluster sampling method was used to sample middle and high schools in 4 functional districts of Chongqing, China. A total of 8546 participants were selected for a questionnaire survey. Two-step clustering helped identify the health risk behavior clusters. Multivariate logistic regression models helped examine the association between the different clusters and sleep time. The rate of insufficient sleep was 65.8%. Three types of clusters were identified, namely (1) high-risk (poor) cluster (17.3%), (2) low physical activity (medium) cluster (55.1%), and (3) low-risk (good) cluster (27.6%). The high-risk and low physical activity clusters showed that the adjusted OR values of 1.471 (1.266-1.710) and 1.174 (1.052-1.310) were significantly associated with insufficient sleep (P < .001). Adolescent health risk behaviors were clustered, and different clusters had different sleep time. Schools authorities and healthcare practitioners should formulate effective intervention measures according to the characteristics of different clusters to promote healthy growth among adolescents.
Subject(s)
Adolescent Behavior , Health Risk Behaviors , Humans , Adolescent , Sleep Deprivation , Exercise , Sleep , Cluster AnalysisABSTRACT
Currently, China is experiencing a phase of rapid urbanization. With the frequent occurrence of extreme rainfall events within the context of climate change, the problem of heavy rainfall and waterlogging in many cities is very prominent. In November 2020, China issued a proposal for the construction of sponge cities across the entire region to significantly enhance the rainfall flood prevention and drainage capacity of cities and effectively improve the resilience of sponge city systems for flooding management. Therefore, this paper selected the Zhu pai-chong watershed in Nanning with frequent waterlogging disasters as an example. Based on underlying surface information, We used a coupled SWMM-LISFOOD model to simulate runoff and waterlogging processes and analyze the spatial and temporal evolution characteristics of the basin under 10 designed rainstorm return periods (0.25a-50a). The results confirm the substantial spatial and temporal variabilities of the runoff coefficient in the study area; impermeability was the main factor contributing to high runoff coefficient values. The spatial distribution characteristics of inundation area was general dispersion and local linear aggregation. Furthermore, this study assessed the effect of the control rate of blueâgreenâgray facilities on the actual storms, and the value ranged from only 48.6% (0.25a)-24.05% (50a). This study quantified the two-dimensional distribution of rainfall storage volume thresholds with or without considering the discharged from the pipe network. Quantitative mapping between the elements of "rainfall-storage volume of blueâgreenâgray facilities-runoff-drainage capacity of the pipe network-waterlogging level" was conducted within the study area as an example. Finally, an overall technical process scheme for rainfall and waterlogging management was proposed. The scheme covered the hydrologicalâhydraulic mechanism, storage function of sponge facilities, engineering control response, nonengineering measures and intelligent management of rainfall and waterlogging during sponge city construction, which could provide critical scientific support for effective promotion of the construction of sponge cities in China.
Subject(s)
Rain , Water Movements , China , Cities , Adaptation, PsychologicalABSTRACT
Purpose: To evaluate the early response of chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC) based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional pseudo-continuous arterial spin labeling (3D pCASL). Materials and methods: Forty patients diagnosed with NPC were recruited and divided into complete remission (CR) and partial remission (PR) group after CRT. All patients underwent IVIM and ASL and the related parameters was obtained. These parameters include pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), average blood flow ( BFavg), minimum blood flow (BFmin), and maximum blood flow (BFmax). Student's t test was used to compare the difference in ASL and IVIM derived parameters between CR and PR. The Areas under curve (AUC) of the receiver operating characteristic (ROC) was used to analyze the diagnostic performance of each parameter of ASL and IVIM to the treatment outcome. Results: the D value of IVIM in CR group was lower than that of the PR group ( P = 0.014),. Among the parameters of ASL, the BFavg and BFmax of the CR group were higher than those of the PR group(p = 0.004,0.013), but the BFmin had no statistical significance in the two groupsï¼P = 0.54ï¼. AUC of D, BFavg, and BFmax is about 0.731, 0.753, and 0.724, respectively, all of their combined AUC diagnosis was 0.812. Conclusion: The early response of NPC after CRT can predict by IVIM's diffusion parameters and ASL-related blood flow parameters.
ABSTRACT
ABSTRACT Introduction Suspension training develops the physical fitness of a swimmer and improves his or her abilities. The specific fitness of a swimmer is the body's ability to adapt to load in swimming. This is also a comprehensive reflection of their physical function, conditioning, athletic ability, and overall health. Objective This study aimed to analyze the effect of suspension training on swimmers' balance, abdominal center strength, and athletic performance. Methods This paper selects several swimmers as research volunteers. They were randomly divided into experimental and control groups. Both of them underwent physical training for three months. The experimental group adopted the suspension training method. The control group used traditional training methods. Mathematical statistics performed data analysis in both groups. Results The physical fitness of the two groups of swimmers was improved substantially after the experiment (P<0.05). The strength balance ability of the experimental group showed better performance(P<0.05). There was a significant difference between the experimental and control groups in the results of fitness index tests (P<0.01). Conclusion Suspension training has a prominent effect on the physical development of swimmers. This modality proved a better efficacy on swimmers' performance. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução O treinamento em suspensão desenvolve a aptidão física de um nadador e aprimora suas habilidades. A aptidão física específica de um nadador é a capacidade corporal de adaptação à carga na natação. Isto é também um reflexo abrangente de sua função física, condicionamento, habilidade atlética e saúde geral. Objetivo Este estudo teve como objetivo analisar o efeito do treinamento em suspensão no equilíbrio da força do centro abdominal e no desempenho atlético dos nadadores. Métodos Este artigo seleciona vários nadadores como voluntários de pesquisa. Eles foram divididos aleatoriamente em grupo experimental e grupo de controle. Ambos foram submetidos a treinamento físico durante três meses. O grupo experimental adotou o método de treinamento em suspensão. O grupo de controle utilizou métodos de treinamento tradicionais. A análise dos dados nos dois grupos foi executada por estatísticas matemáticas. Resultados A aptidão física dos dois grupos de nadadores foi aprimorada substancialmente após o experimento (P<0,05). A capacidade de equilíbrio de força do grupo experimental demonstrou um melhor desempenho(P<0,05). Houve uma diferença significativa entre os grupos experimental e de controle nos resultados dos testes de índice de aptidão física (P<0,01). Conclusão O treinamento de suspensão tem um efeito destacado sobre o desenvolvimento físico dos nadadores. Esta modalidade comprovou uma melhor eficácia sobre o desempenho dos nadadores.Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción El entrenamiento en suspensión desarrolla la aptitud física de un nadador y mejora sus habilidades. La condición física específica de un nadador es la capacidad del cuerpo para adaptarse a la carga en la natación. También es un reflejo exhaustivo de su función física, su acondicionamiento, su capacidad atlética y su salud en general. Objetivo Este estudio tiene como objetivo analizar el efecto del entrenamiento en suspensión sobre el equilibrio de la fuerza del centro abdominal y el rendimiento deportivo de los nadadores. Métodos Este trabajo selecciona a varios nadadores como voluntarios para la investigación. Se dividieron aleatoriamente en grupo experimental y grupo de control. Ambos fueron sometidos a un entrenamiento físico durante tres meses. El grupo experimental adoptó el método de entrenamiento en suspensión. El grupo de control utilizó métodos de entrenamiento tradicionales. El análisis de los datos en ambos grupos se realizó mediante estadística matemática. Resultados La aptitud física de los dos grupos de nadadores mejoró sustancialmente después del experimento (P<0,05). La capacidad de equilibrio de la fuerza del grupo experimental mostró un mejor rendimiento (P<0,05). Hubo una diferencia significativa entre los grupos experimental y de control en los resultados de las pruebas del índice de aptitud física (P<0,01). Conclusión El entrenamiento en suspensión tiene un efecto destacado en el desarrollo físico de los nadadores. Esta modalidad demostró una mayor eficacia en el rendimiento de los nadadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.