ABSTRACT
Membrane distillation (MD) has great potential in the management of hypersaline water for zero liquid discharge (ZLD) due to its high salinity tolerance. However, the membrane wetting issue significantly restricts its practical application. In this study, a composite membrane tailored for extreme concentrations and even crystallization of hypersaline water is synthesized by coating a commercial hydrophobic porous membrane with a composite film containing a dense polyamide layer, a cation exchange layer (CEL), and an anion exchange layer (AEL). When used in direct contact MD for treating a 100 g L-1 NaCl hypersaline solution, the membrane achieves supersaturation of feed solution and a salt crystal yield of 38.0%, with the permeate concentration at <5 mg L-1. The composite membrane also demonstrates ultrahigh antiwetting stability in 360 h of long-term operation. Moreover, ion diffusion analysis reveals that the ultrahigh wetting resistance of the composite membrane is attributed to the bipolar AEL and CEL that eliminate ion crossover. The literature review elucidates that the composite membrane is superior to state-of-the-art membranes. This study demonstrates the great potential of the composite membrane for direct crystallization of hypersaline water, offering a promising approach to filling the gap between reverse osmosis and conventional thermal desalination processes for ZLD application.
Subject(s)
Crystallization , Distillation , Membranes, Artificial , Salinity , Water/chemistry , Water Purification/methodsABSTRACT
Introduction: To investigate the causal associations between accelerometer-based physical activity (PA), sedentary behavior (SB), and seven common geriatric syndromes (GSs) (frailty, falls, delirium, urinary incontinence, dysphagia, hearing loss, and visual impairment) by Mendelian randomization (MR) analysis. Methods: Instrumental variables from a genome-wide association study were used for MR analysis. The exposure factors were three PA phenotypes (average acceleration, overall activity, and moderate-intensity activity) and one SB phenotype (SB). The outcome variables were seven common GSs. The inverse variance weighted (IVW) method was utilized for the primary MR analysis. Additionally, sensitivity, pleiotropy, and heterogeneity analyses were subsequently conducted to assess the robustness of the present study's findings. Results: According to the primary MR results obtained using the IVW method, genetically predicted PA (average acceleration) decreased the risk of two GSs (frailty, p = 0.01; dysphagia, p = 0.03). Similarly, overall activity decreased the risk of two GSs (frailty, p = 0.01; delirium, p = 0.03), and moderate-intensity activity reduced the risk of three GSs (urinary incontinence, p = 0.04; hearing loss, p = 0.02; visual impairment, p = 0.01). Furthermore, SB was causally correlated with a greater risk for three GSs (frailty, p = 0.03; fall, p = 0.01; dysphagia, p = 0.04). Conclusion: This study provided evidence that accelerometer-based PA may be causally associated with a lower risk of GSs, while SB may increase the risk of GSs.
Subject(s)
Accelerometry , Exercise , Mendelian Randomization Analysis , Sedentary Behavior , Humans , Aged , Female , Genome-Wide Association Study , Male , Frailty , SyndromeABSTRACT
INTRODUCTION: The benefits of using head-up displays (HUDs) include reducing head-down time during critical flight phases, enhancing awareness of the external environment, and improving in-flight crew performance. However, the monochromatic nature of HUDs, increased head rotation, and longer gaze movement paths might affect pilots' reactions to different types of alerts.METHODS: Pilot workload and behavior differences were examined between HUD and head-down display (HDD) configurations in three alert scenarios. The study was carried out in an A320 flight simulator and 12 pilots participated.RESULTS: Except for one engine-on-fire scenario, pilot workload when using a HUD was significantly lower than using an HDD. In one engine-on-fire (3.98 s vs. 3.57 s) and one gear-disagree (5.42 s vs. 4.69 s) scenario, pilot response time to alerts using HUD was significantly longer than using an HDD. The angle deviations were significantly smaller when using HUDs in both go-around-under-crosswind (2.67° vs. 3.37°) and one engine-on-fire scenario (1.22° vs. 1.89°).DISCUSSION: The HUD is suitable for a lengthy process of manual flight control inputs, which not only reduces workload but also promotes control accuracy. For tasks that rely on automation, the benefits for workload become less obvious. In addition, head rotation and reorientation of attention adversely affected the response time to non-time-critical warnings and cautions. For instantaneous control with high precision requirements, HUDs did not demonstrate a significant advantage.Zheng Y, Lu Y, Jie Y, Fu S. Pilots' reactions to different types of alerts when using head-up displays. Aerosp Med Hum Perform. 2024; 95(9):688-694.
Subject(s)
Pilots , Workload , Humans , Adult , Male , Aerospace Medicine , Reaction Time/physiology , Computer Simulation , Female , Data Display , Task Performance and Analysis , Aviation , Young AdultABSTRACT
BACKGROUND: This study aimed to investigate the relationships between accelerometer-measured physical activity (PA) and sedentary behaviour (SB) with physical function (PF) among older Chinese women in the community. METHODS: The present study comprised 1,113 community-dwelling older females, with an average age of 65 ± 2 years. We employed a linear regression analysis to investigate the relationship between patterns of PA and SB with PF. PA variables consisted of total PA time, bouted PA time (a continuous PA that lasts equal to or more than 10 min), and sporadic PA time (a continuous PA that lasts less than 10 min). SB variables included total SB time, 30-min bout of SB (a continuous SB that lasts equal to or more than 30 min), and 60-min bout of SB (a continuous SB that lasts equal to or more than 60 min). PF variables comprised handgrip strength (HGS), one-legged stance test with eyes closed (OLSTEC), usual walking speed (UWS), maximum walking speed (MWS) and chair-stand time (CT). To explore the joint effects of moderate-to-vigorous-intensity PA (MVPA) and SB on PF, we divided the duration of SB and MVPA participation in older women into different combinations: low MVPA & high SB, low MVPA & low SB, high MVPA & high SB, high MVPA & low SB. RESULTS: The study revealed a significant association between 30-min bout of SB and CT, which remained after adjusting for total MVPA time (P = 0.021). Both total MVPA and bouted MVPA were found to be positively associated with better UWS, MWS, CT, and PF Z-score. When the combination of low MVPA & high SB was used as a reference, the regression coefficients for PF ascended by 1.32 (P < 0.001) in the high MVPA & high SB group and by 1.13 (P < 0.001) in the high MVPA & low SB group. CONCLUSIONS: A significant association was observed between poorer lower limb function and prolonged, uninterrupted SB in older women, rather than with the total SB time. Concurrently, the insufficient engagement in MVPA may also be a crucial factor contributing to poorer PF in older women. Engaging in longer durations and higher intensity of PA, such as bouts of MVPA lasting a minimum of 10 min or longer, may contribute to better PF.
Subject(s)
Accelerometry , Exercise , Sedentary Behavior , Humans , Female , Cross-Sectional Studies , Aged , Exercise/physiology , Middle Aged , Independent Living , ChinaABSTRACT
Clarifying the spatio-temporal evolution of the ecological environment quality of a watershed and its response to the natural environment and human factors are crucial for policy implementation in the ecological environment of the watershed. Using the Google earth engineï¼GEEï¼ to establish a remote sensing ecological index ï¼RSEIï¼, the spatio-temporal changes in the ecological environment quality of the Huaihe River Basin from 2002 to 2022 were evaluated combined with trend analysis, variation coefficient, and Hurst index. The main driving factors of spatial differentiation of RSEI were explored using the geographic detector. The results showed thatï¼ â In the past 21 years, RSEI of the Huaihe River Basin had generally improved, but it showed a gradual upward-downward trend. Overall, the area of poor and less poor grades decreased, the area of medium grades increased, and the area of good and excellent grades increased. The improved area accounted for 55.93%, and the degraded area accounted for 22.01%. â¡ In terms of spatial distribution, RSEI gradually deteriorated from east to west ï¼except in the northwest and southwest marginal mountainous areasï¼. The stability was better in the east and worse in the western and central areas. In the future, the ecological quality change in the basin was prone to be anti-sustainable and mainly improved. ⢠Factor detection results showed that the spatial differentiation of RSEI in the basin was mainly driven by vegetation factors, followed by altitude. The interaction between two factors enhanced the driving force for RSEI spatial differentiation, in which the interaction between vegetation factor and elevation had the strongest driving force for RSEI spatial differentiation, reaching 86.3%.
ABSTRACT
Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.
Subject(s)
Cardiotoxicity , Ferroptosis , Ginsenosides , Animals , Mice , Apoptosis/drug effects , Autophagy/drug effects , Cardiotoxicity/drug therapy , Cardiotoxicity/metabolism , Cardiotoxicity/prevention & control , Doxorubicin/adverse effects , Doxorubicin/toxicity , Ginsenosides/pharmacology , Myocytes, Cardiac/metabolism , Oxidative StressABSTRACT
BACKGROUND: Pathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies. METHODS: Nine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them. RESULTS: Three of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn't reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively. CONCLUSION: Our study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.
Subject(s)
Dystrophin , Muscular Dystrophy, Duchenne , Humans , Dystrophin/genetics , Muscular Dystrophy, Duchenne/genetics , Mutation, Missense/genetics , RNA, Messenger/genetics , Sarcoglycans/geneticsABSTRACT
Most pathogenic DMD variants are detectable and interpretable by standard genetic testing for dystrophinopthies. However, approximately 1â¼3% of dystrophinopthies patients still do not have a detectable DMD variant after standard genetic testing, most likely due to structural chromosome rearrangements and/or deep intronic pseudoexon-activating variants. Here, we report on a boy with a suspected diagnosis of Becker muscular dystrophy (BMD) who remained without a detectable DMD variant after exonic DNA-based standard genetic testing. Dystrophin mRNA studies and genomic Sanger sequencing were performed in the boy, followed by in silico splicing analyses. We successfully detected a novel deep intronic disease-causing variant in the DMD gene (c.2380 + 3317A > T), which consequently resulting in a new dystrophin pseudoexon activation through the enhancement of a cryptic donor splice site. The patient was therefore genetically diagnosed with BMD. Our case report further emphasizes the significant role of disease-causing splicing variants within deep intronic regions in genetically undiagnosed dystrophinopathies.
ABSTRACT
Aspartame (ASP) as an important sugar substitute is widely used in pharmaceutical and food processing. Here, we compared the effects of ASP and sucrose on mice pancreatic islet cells in vivo and observed that ASP with the condition of high concentration and long-term exposure (HASP) could cause insulin secretion (500 mg/kg for 1 month). Next, we conducted iTRAQ mass spectrometry to profile the global phosphoproteome and found that phosphorylation of zipper-interacting protein kinase (ZIPK) in murine pancreatic islet tissues were induced at Thr197, Thr242, Thr282, and Ser328 by high-sucrose (HS) treatment, but only induced at Thr197 and Ser328 by HASP treatment. Simultaneously, phosphorylation of STAT3 could be induced at Tyr705 and Ser727 by HS but not by HASP. Furthermore, presence of activated STAT3 accompanied with autophagy was observed in HS treatment. In turn, the inactivation of STAT3 as well as enhanced expression of caspase 3 was observed in HASP treatment. We generated Thr242APro and Thr282Pro on ZIPK using CRISPR-Cas9 in β-TC3 cells and found the weakened interaction with STAT3 as well as the reduced phosphorylation of STAT3 even under HS stimulation. Finally, we observed that ankyrin repeat domain containing 11 (ANKRD11) could interact with ZIPK and play an inhibitory role in the phosphorylation of Thr242APro and Thr282Pro of ZIPK. However, HASP can induce the retention of ANKRD11 in the cytoplasm by phenylpyruvic acid (the metabolite of ASP). Taken together, this study determined that ASP with high concentration and long-term exposure could lead to caspase-dependent apoptosis of pancreatic islet cells through ANKRD11/ZIPK/STAT3 inhibition. Our results give evidence of adverse effects of aspartame on islet cells in some extreme conditions, which might help people to reconsider the biosafety of non-nutritive sweeteners. (AU)
Subject(s)
Aspartame , Apoptosis , Caspase 3ABSTRACT
Aspartame (ASP) as an important sugar substitute is widely used in pharmaceutical and food processing. Here, we compared the effects of ASP and sucrose on mice pancreatic islet cells in vivo and observed that ASP with the condition of high concentration and long-term exposure (HASP) could cause insulin secretion (500 mg/kg for 1 month). Next, we conducted iTRAQ mass spectrometry to profile the global phosphoproteome and found that phosphorylation of zipper-interacting protein kinase (ZIPK) in murine pancreatic islet tissues were induced at Thr197, Thr242, Thr282, and Ser328 by high-sucrose (HS) treatment, but only induced at Thr197 and Ser328 by HASP treatment. Simultaneously, phosphorylation of STAT3 could be induced at Tyr705 and Ser727 by HS but not by HASP. Furthermore, presence of activated STAT3 accompanied with autophagy was observed in HS treatment. In turn, the inactivation of STAT3 as well as enhanced expression of caspase 3 was observed in HASP treatment. We generated Thr242APro and Thr282Pro on ZIPK using CRISPR-Cas9 in β-TC3 cells and found the weakened interaction with STAT3 as well as the reduced phosphorylation of STAT3 even under HS stimulation. Finally, we observed that ankyrin repeat domain containing 11 (ANKRD11) could interact with ZIPK and play an inhibitory role in the phosphorylation of Thr242APro and Thr282Pro of ZIPK. However, HASP can induce the retention of ANKRD11 in the cytoplasm by phenylpyruvic acid (the metabolite of ASP). Taken together, this study determined that ASP with high concentration and long-term exposure could lead to caspase-dependent apoptosis of pancreatic islet cells through ANKRD11/ZIPK/STAT3 inhibition. Our results give evidence of adverse effects of aspartame on islet cells in some extreme conditions, which might help people to reconsider the biosafety of non-nutritive sweeteners. (AU)
Subject(s)
Aspartame , Apoptosis , Caspase 3ABSTRACT
Deep-intronic variants that create or enhance a splice site are increasingly reported as a significant cause of monogenic diseases. However, deep-intronic variants that activate pseudoexons by affecting a branch point are extremely rare in monogenic diseases. Here, we describe a novel deep-intronic DMD variant that created a branch point in a Duchenne muscular dystrophy (DMD) patient. A 7.0-year-old boy was enrolled because he was suspected of DMD based on his clinical, muscle imaging, and pathological features. Routine genetic testing did not discover a pathogenic DMD variant. We then performed muscle-derived dystrophin mRNA analysis and detected an aberrant pseudoexon-containing transcript. Further genomic Sanger sequencing and bioinformatic analyses revealed a novel deep-intronic splicing variant in DMD (NM_004006.2:c.5325+1759G>T), which created a new branch point sequence and thus activated a new dystrophin pseudoexon (NM_004006.2:r.5325_5326ins5325+1779_5325+1855). Our study highlights the significant role of branch point alterations in the pathogenesis of monogenic diseases.
Subject(s)
Muscular Dystrophy, Duchenne , Humans , Male , Child , Muscular Dystrophy, Duchenne/genetics , Dystrophin/genetics , Mutation , RNA Splicing , Genetic TestingABSTRACT
Aspartame (ASP) as an important sugar substitute is widely used in pharmaceutical and food processing. Here, we compared the effects of ASP and sucrose on mice pancreatic islet cells in vivo and observed that ASP with the condition of high concentration and long-term exposure (HASP) could cause insulin secretion (500 mg/kg for 1 month). Next, we conducted iTRAQ mass spectrometry to profile the global phosphoproteome and found that phosphorylation of zipper-interacting protein kinase (ZIPK) in murine pancreatic islet tissues were induced at Thr197, Thr242, Thr282, and Ser328 by high-sucrose (HS) treatment, but only induced at Thr197 and Ser328 by HASP treatment. Simultaneously, phosphorylation of STAT3 could be induced at Tyr705 and Ser727 by HS but not by HASP. Furthermore, presence of activated STAT3 accompanied with autophagy was observed in HS treatment. In turn, the inactivation of STAT3 as well as enhanced expression of caspase 3 was observed in HASP treatment. We generated Thr242APro and Thr282Pro on ZIPK using CRISPR-Cas9 in ß-TC3 cells and found the weakened interaction with STAT3 as well as the reduced phosphorylation of STAT3 even under HS stimulation. Finally, we observed that ankyrin repeat domain containing 11 (ANKRD11) could interact with ZIPK and play an inhibitory role in the phosphorylation of Thr242APro and Thr282Pro of ZIPK. However, HASP can induce the retention of ANKRD11 in the cytoplasm by phenylpyruvic acid (the metabolite of ASP). Taken together, this study determined that ASP with high concentration and long-term exposure could lead to caspase-dependent apoptosis of pancreatic islet cells through ANKRD11/ZIPK/STAT3 inhibition. Our results give evidence of adverse effects of aspartame on islet cells in some extreme conditions, which might help people to reconsider the biosafety of non-nutritive sweeteners.
Subject(s)
Apoptosis , Aspartame , Islets of Langerhans , Animals , Mice , Apoptosis/drug effects , Aspartame/adverse effects , Aspartame/metabolism , Caspase 3/metabolism , Death-Associated Protein Kinases/drug effects , Death-Associated Protein Kinases/pharmacology , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Phosphorylation , Signal Transduction , STAT3 Transcription Factor/metabolism , Sucrose/metabolism , Sucrose/pharmacology , Transcription Factors/metabolismABSTRACT
Eupatilin is a pharmacologically active flavonoid with a variety of biological activities, such as anticancer, anti-inflammatory, antioxidant, neuroprotective, anti-allergic and cardioprotective effects. However, whether eupatilin has protective effects on doxorubicin-induced cardiotoxicity remains unknown. Thus, this study aimed to investigate the role of eupatilin in doxorubicin-induced cardiotoxicity. Mice were exposed to a single dose of doxorubicin (15 mg/kg) to generate doxorubicin-induced cardiotoxicity or normal saline as a control. To explore the protective effects, mice were intraperitoneally injected with eupatilin daily for 7 days. Then, we examined the changes in cardiac function, inflammation, apoptosis, and oxidative stress to evaluate the effects of eupatilin on doxorubicin-induced cardiotoxicity. Additionally, RNA-seq analysis was introduced to explore the potential molecular mechanisms. Eupatilin ameliorated doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and cardiomyocyte apoptosis and ameliorated doxorubicin-induced cardiac dysfunction. Mechanistically, eupatilin activated the PI3K-AKT signaling pathway, as evidenced by RNA-seq analysis and Western blot analysis. This study provides the first evidence that eupatilin ameliorates doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and apoptosis. Pharmacotherapy with eupatilin provides a novel therapeutic regimen for doxorubicin-induced cardiotoxicity.
Subject(s)
Cardiotoxicity , Proto-Oncogene Proteins c-akt , Mice , Animals , Cardiotoxicity/drug therapy , Cardiotoxicity/prevention & control , Cardiotoxicity/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Doxorubicin/toxicity , Flavonoids/metabolism , Oxidative Stress , Inflammation/metabolism , Apoptosis , Myocytes, Cardiac/metabolismABSTRACT
The insufficient exciton (e- -h+ pair) separation/transfer and sluggish two-electron water oxidation are two main factors limiting the H2 O2 photosynthetic efficiency of covalent organic frameworks (COFs) photocatalysts. Herein, we present an alternative strategy to simultaneously facilitate exciton separation/transfer and reduce the energy barrier of two-electron water oxidation in COFs via a dicyano functionalization. The in situ characterization and theoretical calculations reveal that the dicyano functionalization improves the amount of charge transfer channels between donor and acceptor units from two in COF-0CN without cyano functionalization to three in COF-1CN with mono-cyano functionalization and four in COF-2CN with dicyano functionalization, leading to the highest separation/transfer efficiency in COF-2CN. More importantly, the dicyano group activates the neighbouring C atom to produce the key *OH intermediate for effectively reducing the energy barrier of rate-determining two-electron water oxidation in H2 O2 photosynthesis. The simultaneously enhanced exciton separation/transfer and two-electron water oxidation in COF-2CN result in high H2 O2 yield (1601â µmol g-1 h-1 ) from water and oxygen without using sacrificial reagent under visible-light irradiation. COF-2CN can effectively yield H2 O2 in water with wide pH range, in different real water samples, in scaled-up reactor under natural sunlight irradiation, and in continuous-flow reactor for consecutively producing H2 O2 solution for water decontamination.
ABSTRACT
BACKGROUND: We aimed to analyse genome-wide transcriptome differences between Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients and identify biomarkers that correlate well with muscle magnetic resonance imaging (MRI) and histological fibrofatty replacement in both patients, which have not been reported. METHODS: One hundred and one male patients with dystrophinopathies (55 DMD and 46 BMD) were enrolled. Muscle-derived genome-wide RNA-sequencing was performed in 31 DMD patients, 29 BMD patients, and 11 normal controls. Fibrofatty replacement was scored on muscle MRI and histological levels in all patients. A unique pipeline, single-sample gene set enrichment analysis combined with Spearman's rank correlations (ssGSEA-Cor) was developed to identify the most correlated gene signature for fibrofatty replacement. Quantitative real-time PCR (qRT-PCR) analysis, western blot analysis, and single-nucleus RNA-sequencing (snRNA-seq) were performed in the remaining patients to validate the most correlated gene signature. RESULTS: Comparative transcriptomic analysis revealed that 31 DMD muscles were characterized by a significant increase of inflammation/immune response and extracellular matrix remodelling compared with 29 BMD muscles (P < 0.05). The ssGSEA-Cor pipeline revealed that the gene set of CDKN2A and CDKN2B was the most correlated gene signature for fibrofatty replacement (histological rs = 0.744, P < 0.001; MRI rs = 0.718, P < 0.001). Muscle qRT-PCR confirmed that CDKN2A mRNA expression in both 15 DMD (median = 25.007, P < 0.001) and 12 BMD (median = 5.654, P < 0.001) patients were significantly higher than that in controls (median = 1.101), while no significant difference in CDKN2B mRNA expression was found among DMD, BMD, and control groups. In the 27 patients, muscle CDKN2A mRNA expression respectively correlated with muscle MRI (rs = 0.883, P < 0.001) and histological fibrofatty replacement (rs = 0.804, P < 0.001) and disease duration (rs = 0.645, P < 0.001) and North Star Ambulatory Assessment total scores (rs = -0.698, P < 0.001). Muscle western blot analysis confirmed that both four DMD (median = 2.958, P < 0.05) and four BMD (median = 1.959, P < 0.01) patients had a significantly higher level of CDKN2A protein expression than controls (median = 1.068). The snRNA-seq analysis of two DMD muscles revealed that CDKN2A was mainly expressed in fibro-adipogenic progenitors, satellite cells, and myoblasts. CONCLUSIONS: We identify CDKN2A expression as a novel biomarker of fibrofatty replacement, which might be a new target for antifibrotic therapy in dystrophinopathies.
Subject(s)
Muscular Dystrophy, Duchenne , Transcriptome , Humans , Male , Muscular Dystrophy, Duchenne/diagnostic imaging , Muscular Dystrophy, Duchenne/genetics , Muscle, Skeletal/pathology , Biomarkers , Magnetic Resonance Imaging , RNA, Messenger , RNA , RNA, Small NuclearABSTRACT
2,4,6-Trinitrotoluene (TNT) production processes generate a substantial amount of toxic wastewater. Therefore, it is crucial to identify efficient and sustainable methods for treating this wastewater. This paper explores the application of sustainable biomass-derived carbon produced from rice straw for the adsorption of 2,4,6-trinitrotoluene (TNT) red water. The rice straw-derived biochar (SBC) materials were synthesized by two-step reactions through hydrothermal carbonization and chemical activation with KOH. Characterization of the fabricated biochar was conducted using various techniques. Here, the chemical oxygen demand (COD) was used as an evaluation index for adsorption efficiency. The adsorption kinetics showed a good fit with the pseudo-second-order model, and the adsorption equilibrium was achieved in 30 min. The biochar's high surface area (1319 m2/g) and large pore volume (1.058 cm3/g) gave it a large adsorption capacity. The Langmuir model exhibited better correlation for equilibrium data analysis, with a maximum adsorption capacity of 173.9 mg/g at 298 K. The SBC was found to have a high removal effect over a wide pH range (from 1 to 13) and showed remarkable stability after undergoing five desorption-adsorption cycles using ethanol and acetone as eluent. The results provide a simple and low-cost method for the efficient treatment of TNT red water.
Subject(s)
Oryza , Trinitrotoluene , Water Pollutants, Chemical , Wastewater , Water , Water Pollutants, Chemical/chemistry , Adsorption , Porosity , Charcoal/chemistry , KineticsABSTRACT
We aimed to investigate the clinical, pathological, and genetic characteristics of Chinese female dystrophinopathy and to identify possible correlations among them. One hundred forty genetically and/or pathologically confirmed female DMD variant carriers were enrolled, including 104 asymptomatic carriers and 36 symptomatic carriers. Twenty of 36 symptomatic and 16 of 104 asymptomatic carriers were sporadic with no family history. Muscle pathological analysis was performed in 53 carriers and X chromosome inactivation (XCI) analysis in 19 carriers. In asymptomatic carriers, the median age was 35.0 (range 2.0-58.0) years, and the serum creatine kinase (CK) level was 131 (range 60-15,745) IU/L. The median age, age of onset, and CK level of symptomatic carriers were 15.5 (range 1.8-62.0) years, 6.3 (range 1.0-54.0) years, and 6,659 (range 337-58,340) IU/L, respectively. Four female carriers with X-autosome translocation presented with a Duchenne muscular dystrophy (DMD) phenotype. Skewed XCI was present in 70.0% of symptomatic carriers. Compared to Becker muscular dystrophy (BMD)-like carriers, DMD-like carriers were more likely to have an early onset age, rapidly progressive muscle weakness, delayed walking, elevated CK levels, severe reduction of dystrophin, and skewed XCI. Our study reports the largest series of symptomatic female DMD carriers and suggests that delayed walking, elevated CK levels, severe reduction of dystrophin, X-autosome translocation, and skewed XCI pattern are associated with a severe phenotype in female dystrophinopathy.
Subject(s)
Dystrophin , Muscular Dystrophy, Duchenne , Humans , Female , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Infant , Dystrophin/genetics , East Asian People , Heterozygote , Mutation , Muscular Dystrophy, Duchenne/geneticsABSTRACT
BACKGROUND: A considerable number of people suffered from mental disorders due to coronavirus disease 2019 (COVID-19). As the virus mutated, the effect of COVID-19 changed. This study intends to compare the mental health between the medical staff and non-medical staff during the Omicron pandemic, and to analyze the relevant risk factors. METHODS: The cross-sectional study was conducted by a set of online questionnaires, 1246 medical staff and 1246 non-medical staff were selected after a 1:1 propensity score matching. The questionnaires included the demographic characteristics, the Coronavirus Anxiety Scale (CAS), the Center for Epidemiologic Studies Depression Scale (CES-D), the Insomnia Severity Index Scale (ISI), and the Psychological Resilience Scale(CD-RISC). RESULTS: Compared with medical staff, non-medical staff scored higher on CAS and CES-D (both P < 0.001). Non-medical staff had higher prevalence of anxiety (55.0 % versus 47.3 %; adjusted OR = 1.45, 95 % CI = 1.23-1.70), depression (62.4 % versus 53.4 %; adjusted OR = 1.46, 95 % CI = 1.23-1.73) and insomnia (46.5 % versus 43.4 %; adjusted OR = 1.21, 95 % CI = 1.02-1.43). Multivariate logistic regression analysis showed that being female, being younger than 40 years, having an annual income of <50,000 yuan, paying attention to omicron, in the course of an infection and below bachelor degree influenced anxiety, depression and insomnia of the medical staff and non-medical staff to different degree. LIMITATIONS AND CONCLUSIONS: This study only collected data through the network. Therefore, the validity was reduced to some extent. The outbreak of the Omicron epidemic posed a significant challenge to public mental health, with non-medical staff at the highest risk for mental health problems.
Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Humans , Female , Male , COVID-19/epidemiology , Mental Health , Pandemics , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/epidemiology , Cross-Sectional Studies , Anxiety/psychology , Depression/psychology , China/epidemiologyABSTRACT
Objectives: This study aimed to investigate the relationship between frailty and all-cause mortality in hypertensive population. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 and mortality data from the National Death Index. Frailty was assessed using the revised version of the Fried frailty criteria (weakness, exhaustion, low physical activity, shrinking, and slowness). This study aimed to evaluate the association between frailty and all-cause mortality. Cox proportional hazard models were used to evaluate the association between frailty category and all-cause mortality, adjusted for age, sex, race, education, poverty-income ratio, smoking, alcohol, diabetes, arthritis, congestive heart failure, coronary heart disease, stroke, overweight, cancer or malignancy, chronic obstructive pulmonary disease, chronic kidney disease, and taking medicine for hypertension. Results: We gathered data of 2,117 participants with hypertension; 17.81%, 28.77%, and 53.42% were classified as frail, pre-frail, and robust, respectively. We found that frail [hazard ratio (HR) = 2.76, 95% confidence interval (CI) = 2.33-3.27] and pre-frail (HR = 1.38, 95% CI = 1.19-1.59] were significantly associated with all-cause mortality after controlling for variables. We found that frail (HR = 3.02, 95% CI = 2.50-3.65) and pre-frail (HR = 1.35, 95% CI = 1.15-1.58) were associated with all-cause mortality in the age group ≥65â years. For the frailty components, weakness (HR = 1.77, 95% CI = 1.55-2.03), exhaustion (HR = 2.25, 95% CI = 1.92-2.65), low physical activity (HR = 2.25, 95% CI = 1.95-2.61), shrinking (HR = 1.48, 95% CI = 1.13-1.92), and slowness (HR = 1.44, 95% CI = 1.22-1.69) were associated with all-cause mortality. Conclusion: This study demonstrated that frailty and pre-frailty were associated with an increased risk of all-cause mortality in patients with hypertension. More attention should be paid to frailty in hypertensive patients, and interventions to reduce the burden of frailty may improve outcomes in these patients.
ABSTRACT
Objectives: Infection is one of the major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE), and as a new diagnostic technique, metagenomic next-generation sequencing (mNGS) is increasingly used for the pathogenetic detection of co-infected SLE patients. However, conventional microbiological testing (CMT) is still the gold standard for pathogenic diagnosis, and the specific diagnostic efficacy of mNGS versus CMT in such patients is not known. In addition, there are few studies on the short-term prognosis of co-infected SLE patients. Methods: This study retrospectively included 58 SLE patients with co-infection admitted to the First Affiliated Hospital of Zhengzhou University from October 2020 to August 2022. Patients were divided into a survivors (n=27) and a non-survivors (n=31) according to their discharge status. Baseline characteristics and etiological data were collected and statistically analyzed for all patients during their hospitalization. The sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE) II and systemic lupus erythematosus disease activity index (SLEDAI) were calculated for each patient to assess the predictive ability of the 3 scores on the short-term prognosis of SLE patients. The mNGS and CMT culture results were also compared to clarify the flora characteristics of patients with SLE infection. Results: More patients in the non-survivors had renal impairment, neurological manifestations, multiplasmatic cavity effusion and gastrointestinal manifestations compared to the survivors (p < 0.05). The SOFA score, APACHE II and SLEDAI were significantly higher in the non-survivors than in the survivors (p < 0.01). There were also significant differences between the two groups in several tests such as hemoglobin, platelets, albumin, total bilirubin, C-reactive protein (CRP), procalcitonin (PCT), and complement C3 (p < 0.05). In addition, the absolute values of T lymphocytes, CD4+ T cells and CD8+ T cells were smaller in the non-survivors than in the survivors (p < 0.05). The most common type of infection in this study was pulmonary infection, followed by bloodstream infection. mNGS and CMT positivity rates were not significantly different among patients in the non-survivors, but were significantly different among patients in the survivors (p=0.029). In-hospital survival of patients with SLE infection could be predicted based on the SOFA score in relation to 6. For patients with SOFA <6, we recommend earlier mNGS testing to identify the pathogen and improve patient prognosis. Conclusions: For SLE patients with co-infection, in-hospital survival can be predicted based on SOFA score. For patients with SOFA <6, advising them to complete mNGS testing as early as possible may improve the prognosis to some extent.