Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis.

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.

Eupatilin attenuates doxorubicin-induced cardiotoxicity by activating the PI3K-AKT signaling pathway in mice.

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.

Associations between accelerometer-measured physical activity and sedentary behaviour with physical function among older women: a cross-sectional study.

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.

Efficient Photosynthesis of Hydrogen Peroxide by Cyano-Containing Covalent Organic Frameworks from Water, Air and Sunlight.

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 (1601 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.

An Investigation of All Fiber Free-Running Dual-Comb Spectroscopy.

A dual-comb spectroscopy (DCS) system uses two phase-locked optical frequency combs with a slight difference in the repetition frequency. The spectrum can be sampled in the optical frequency (OF) domain and reproduces the characteristics in the radio frequency (RF) domain through asynchronous optical sampling. Therefore, the DCS system shows great advantages in achieving precision spectral measurement. During application, the question of how to reserve the mutual coherence between the two combs is the key issue affecting the application of the DCS system. This paper focuses on a software algorithm used to realize the mutual coherence of the two combs. Therefore, a pair of free-running large anomalous dispersion fiber combs, with a center wavelength of approximately 1064 nm, was used. After the signal process, the absorption spectra of multiple species were simultaneously obtained (simulated using the reflective spectra of narrow-bandwidth fiber Bragg gratings, abbreviated as FBG). The signal-to-noise ratio (SNR) could reach 13.97 dB (25) during the 100 ms sampling time. In this study, the feasibility of the system was first verified through the simulation system; then, a principal demonstration experiment was successfully executed. The whole system was connected by the optical fiber without additional phase-locking equipment, showing promise as a potential solution for the low-cost and practical application of DCS systems.

Methane Emissions from Wetlands in China and Their Climate Feedbacks in the 21st Century.

Wetlands are large sinks of carbon dioxide (CO2) and sources of methane (CH4). Both fluxes can be altered by wetland management (e.g., restoration), leading to changes in the climate system. Here, we use multiple models to assess CH4 emissions and CO2 sequestration from the wetlands in China and the impacts on climate under three climate scenarios and four wetland management scenarios with various levels of wetland restoration in the 21st century. We find that wetland restoration leads to increased CH4 emissions with a national total of 0.32-11.31 Tg yr-1. These emissions induce an additional radiative forcing of 0.0005-0.0075 W m-2 yr-1 and global annual mean air temperature rise of 0.0003-0.0053 °C yr-1, across all future climate and management scenarios. However, wetland restoration also resulted in net CO2 sequestration, leading to a combined net greenhouse gas sink in all climate management scenarios, except in the highest restoration level combined with the hottest climate scenario. The highest climate cooling was achieved under medium restoration, with the climate scenario consistent with the Paris agreement target of below 2 °C, with a cumulative global warming potential of -3.2 Pg CO2-eq (2020-2100). Wetland restoration in the Qinghai-Tibet Plateau offers the greatest cooling effect.

Effects of low-carbohydrate vs low-fat diets on weight loss and metabolic risk factors in obese/overweight individuals with impaired glucose regulation: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the effects of low-carbohydrate diet (LCD) versus low-fat diet (LFD) on weight loss, glycemic control and metabolic risk factors in individuals with impaired glucose regulation (IGR) after 10-week intervention. METHODS AND STUDY DESIGN: In this 10-week randomized controlled trial, 90 obese/overweight adults with IGR were randomly assigned to consume either low-carbohydrate diet (20%-25% energy from carbohydrates, 30%-45% energy from fat, 40%-45% en-ergy from protein), or low-fat diet (40%-55% energy from carbohydrates, 20%-30% energy from fat, 20%-30% energy from protein), or heath education (HE) group. The anthropometry and body composition were collected at baseline, week 4, week 8 and week 10. The glycemia and metabolic indicators were assessed at baseline and week 10. RESULTS: A total of 69 participants (mean±SE age: 39.2±1.0 years, 72.5% women) completed the intervention and were included in the final analysis. At week 10, all three groups presented similar mean reduction in weight (LCD: 5.80±0.6 kg; LFD: 6.36±0.57 kg; HE: 4.49±0.98 kg), and fasting blood glucose (LCD: 0.73±0.13 mmol/L; LFD: 0.84±0.17 mmol/L; HE: 0.58±0.14 mmol/L). Additionally, there were no differences in the improvements of TG and liver function markers between diets, the low-fat diet exhibited more favorable effects on TC level. CONCLUSIONS: Both diets achieved similar weight loss, fasting glucose, and insulin reduction in short-term, suggesting each diet pattern could be an effective strategy for the prediabetes management.

Clinical significance of common-stem lenticulostriate arteries in patients with internal watershed infarction.

BACKGROUND: A common-stem origin of lenticulostriate arteries (CS-LSAs) is an anatomical variation that supplies a moderate to large section of the basal ganglia. We hypothesized that CS-LSAs with a patent orifice are located at distal positions of the acute-occluded middle cerebral artery (MCA) and that the blood flow of CS-LSAs is supplied by pail arterial anastomoses and results in hypoperfusion of CS-LSAs, similar to a deep watershed (DWS) infarction. OBJECTIVE: Our study evaluated the possibility of CS-LSAs in patients with DWS infarction and MCA occlusion and also assessed the safety of endovascular therapy (ET) in these patients. METHODS: A cohort of consecutive patients with DWS infarction and MCA occlusion and in whom full recanalization via ET was achieved were identified. Patients were divided into two groups based on the presence of CS-LSAs observed during ET. In addition, radiological and clinical data were retrospectively analyzed. RESULTS: Thirty-three patients were included, and CS-LSAs were observed in 48.5% (16/33) of patients. The possibility (72.2%, 13/18) of CS-LSAs was high in patients with DWS infarction companied with basal ganglia infarction. A good clinical outcome was similar in patients with CS-LSAs and basal ganglia infarction and in patients without CS-LSAs and basal ganglia infarction (69.2% vs. 81.8%, P = 0.649). CONCLUSIONS: The possibility of CS-LSAs was 48.5% in patients with DWS infarction and MCA occlusion, and the revascularization procedure was safe and feasible in these patients despite the moderate-to-large basal ganglia infarction.

[Association between the polymorphisms of TMPRSS6 and the levels of serum ferrtin and soluble transferrin receptor in pregnant women in Lüliang Area of Shanxi Province].

OBJECTIVE: To analysis the associations between the polymorphisms of TMPRSS6 and the levels of serum ferritin( SF) and soluble transferrin receptor( s TfR) in pregnant women. METHODS: A total of 807 pregnant women were recruited by using cluster random sampling method from Lüliang in Shanxi Province in 2014. Roche Tinaquant immunoturbidimetric assay was used to measure the level of SF and s TfR, then iron deficiency( ID) was identified by the criteria of SF < 25 ng/m L and s TfR > 4. 4 mg/L, respectively. Sequenom MassArray was used to genotype the 7 targeted single-nucleotide polymorphisms( SNPs)( rs11704654, rs1421312, rs2111833, rs2235321, rs2543519, rs4820268 and rs855791) of the subjects. The t test and ANOVA analysis were used to test the different levels of SF and s TfR among SNPs, and chi-square test and Logistic regression were conducted to detect the associations between genotypes of each locus and ID. RESULTS: The differences of the levels of Ln SF between genotypes in rs2111833 were significant( F = 3. 57, P = 0. 0287), and the Ln SF level of T allele carrier group was lower than CC group( t = 2. 03, P = 0. 0429). The Ln SF level of A allele carrier group was lower than GG carrier group in rs855791( t = 1. 97, P = 0. 0490). For rs11704654, the ratio of SF < 25 ng/m L of T allele carriers was higher than CC carriers( χ~2= 4. 5456, P = 0. 0330). For rs211183, the ratio of SF < 25 ng/m L of T allele carriers was higher than CC carriers( χ~2= 4. 6431, P = 0. 0312). For rs855791, the ratio of SF < 25 ng/m L of GG carriers was lower than A allele carriers( χ~2= 5. 0134, P = 0. 0263). rs11704654( T) and rs855791( A) were still shown the association with SF < 25 ng/m L status in logistic analysis adjusted by age and gestational weeks. The Ln s TfR level of T allele carrier group in rs11704654 was higher than CC carrier group( t =-2. 012, P = 0. 024), and the Ln s TfR level of G allele carrier group in rs2543519 was higher than AA carrier group( t =-1. 954, P = 0. 011). CONCLUSION: The associations between polymorphisms of TMPRSS6 and the levels of SF and s TfR are observed in pregnant women.

Recognition of objects in simulated irregular phosphene maps for an epiretinal prosthesis.

Visual prostheses offer a possibility of restoring vision to the blind. It is necessary to determine minimum requirements for daily visual tasks. To investigate the recognition of common objects in daily life based on the simulated irregular phosphene maps, the effect of four parameters (resolution, distortion, dropout percentage, and gray scale) on object recognition was investigated. The results showed that object recognition accuracy significantly increased with an increase of resolution. Distortion and dropout percentage had significant impact on the object recognition; with the increase of distortion level and dropout percentage, the recognition decreased considerably. The accuracy decreased significantly only at gray level 2, whereas the other three gray levels showed no obvious difference. The two image processing methods (merging pixels to lower the resolution and edge extraction before lowering resolution) showed significant difference on the object recognition when there was a high degree of distortion level or dot dropout.

Expertise and responsibility effects on pilots' reactions to flight deck alerts in a simulator.

INTRODUCTION: Flight deck alerts provide system malfunction information designed to lead corresponding pilot reactions aimed at guaranteeing flight safety. This study examined the roles of expertise and flight responsibility and their relationship to pilots' reactions to flight deck alerts. METHODS: There were 17 pilots composing 12 flight crews that were assigned into pairs according to flight hours and responsibilities. The experiment included 9 flight scenarios and was carried out in a CRJ-200 flight simulator. Pilot performance was recorded by a wide angle video camera, and four kinds of reactions to alerts were defined for analysis. RESULTS: Pilots tended to have immediate reactions to uninterrupted cautions, with a turning off rate as high as 75%. However, this rate decreased sharply when pilots encountered interrupted cautions and warnings; they also exhibited many wrong reactions to warnings. Pilots with more expertise had more reactions to uninterrupted cautions than those with less expertise, both as pilot flying and pilot monitoring. Meanwhile, the pilot monitoring, regardless of level of expertise, exhibited more reactions than the pilot flying. In addition, more experienced pilots were more likely to have wrong reactions to warnings while acting as the monitoring pilot. CONCLUSIONS: These results suggest that both expertise and flight responsibility influence pilots' reactions to alerts. Considering crew pairing strategy, when a pilot flying is a less experienced pilot, a more experience pilot is suggested to be the monitoring pilot. The results of this study have implications for understanding pilots' behaviors to flight deck alerts, calling for specialized training and design of approach alarms on the flight deck.

The effect of aspartame on accelerating caspase-dependent apoptosis of pancreatic islet via ZIPK/STAT3/caspase 3 signaling pathway.

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.

[Spatio-temporal Evolution and Driving Factors of Ecological Environment Quality in the Huaihe River Basin Based on RSEI].

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 engine（GEE） to establish a remote sensing ecological index （RSEI）, 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 that： ① 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%. ② In terms of spatial distribution, RSEI gradually deteriorated from east to west （except in the northwest and southwest marginal mountainous areas）. 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. ③ 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%.

A novel deep intronic variant introduce dystrophin pseudoexon in Becker muscular dystrophy: A case report.

Most pathogenic DMD variants are detectable and interpretable by standard genetic testing for dystrophinopthies. However, approximately 1∼3% 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.

A new pseudoexon activation due to ultrarare branch point formation in Duchenne muscular dystrophy.

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.

Clinical and genetic interpretation of uncertain DMD missense variants: evidence from mRNA and protein studies.

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.

A novel biomarker of fibrofatty replacement in dystrophinopathies identified by integrating transcriptome, magnetic resonance imaging, and pathology data.

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.

Epidemiology of twin births in southeast China: 1993-2005.

Recently, there has been a significant increase in the rate of multiple births in most developed countries. However, few population-based studies have been conducted in China regarding the epidemiology of twin births in recent years. We performed a descriptive analysis of twin births from 1993 to 2005 using data from a population-based perinatal care program in southeast China. The twin birth rate in southeast China was 0.65%, and the twin birth rates from 1993 to 2005 fluctuated between 0.60% and 0.70%. During the three periods of 1993-1996, 1997-2000, and 2001-2005, the twin birth rate increased from 0.57% to 0.71% in urban areas (p = .005) and from 0.59% to 0.68% in mothers who had an education level of high school or higher (p = .046). After 2000, the twin birth rate of primiparae 30 years of age and older significantly increased from 0.72% to greater than 1.20%. We concluded that the twin birth rates in southeast China from 1993 to 2005 stayed constant in the overall population but increased in certain subgroups of women, presumably due to increased use of fertility treatment and the development of assisted reproductive technology.

[Image processing strategies based on visual attention models under simulated prosthetic vision].

Visual prostheses have the potential to restore partial vision for the blinds. The stimulating electrodes generate reproducible phosphenes. Still limited by the low resolution vision used in visual prostheses nowadays, it is important to optimize the image processing strategies in order to deliver better visual information to the patients. This paper presents a review of the current research progress on the image processing strategies based on visual attention models under simulated prosthetic vision and related psychophysics.

Test Pilot and Airline Pilot Differences in Facing Unexpected Events.

BACKGROUND: Unexpected events in flight might decrease the transparency of the flying process and weaken the pilot's perception of the current state, or even erode manipulating skills. However, during the flight test of a new or modified aircraft, to verify the boundaries of aircraft aerodynamic performance and handling stability, unexpected events may be encountered that need to be handled by the test pilot. Therefore, studying the differences between test pilots and airline pilots could help improve flight safety.METHODS: Two kinds of physiological parameters, eye blink rate and average fixation duration and task-related performance of test pilots and airline pilots, were analyzed in three abnormal scenarios. A total of 16 pilots participated. The study was carried out in an A320 flight simulator.RESULTS: The differences were significant for both test pilots and airline pilots in eye blink rate and average fixation duration. Furthermore, the reaction time of test pilots (Mean = 23.38 s) was significantly shorter than airline pilots (Mean = 42.63 s) in Unreliable Airspeed condition, and the pitch angle deviations between them were significant in both Wind Shear and Unreliable Airspeed condition.DISCUSSION: The uncertainty of environmental change could create more severe pressure and mental workload influence than actual system failure. For airline pilots, compared with test pilots, the importance of practicing manual flight should still be emphasized. Improving reactions to unexpected ambient conditions and unannounced fault status could also contribute to flight safety.Zheng Y, Lu Y, Jie Y, Zhao Z, Fu S. Test pilot and airline pilot differences in facing unexpected events. Aerosp Med Hum Perform. 2023; 94(1):18-24.