iPSCs from a Hibernator Provide a Platform for Studying Cold Adaptation and Its Potential Medical Applications.

Hibernating mammals survive hypothermia (<10°C) without injury, a remarkable feat of cellular preservation that bears significance for potential medical applications. However, mechanisms imparting cold resistance, such as cytoskeleton stability, remain elusive. Using the first iPSC line from a hibernating mammal (13-lined ground squirrel), we uncovered cellular pathways critical for cold tolerance. Comparison between human and ground squirrel iPSC-derived neurons revealed differential mitochondrial and protein quality control responses to cold. In human iPSC-neurons, cold triggered mitochondrial stress, resulting in reactive oxygen species overproduction and lysosomal membrane permeabilization, contributing to microtubule destruction. Manipulations of these pathways endowed microtubule cold stability upon human iPSC-neurons and rat (a non-hibernator) retina, preserving its light responsiveness after prolonged cold exposure. Furthermore, these treatments significantly improved microtubule integrity in cold-stored kidneys, demonstrating the potential for prolonging shelf-life of organ transplants. Thus, ground squirrel iPSCs offer a unique platform for bringing cold-adaptive strategies from hibernators to humans in clinical applications. VIDEO ABSTRACT.

Study on mechanism of removal of sudden Tetracycline by compound modified biological sand filtration process.

The removal of tetracycline from the sewage plant effluents through advanced treatment methods is key to controlling tetracycline levels in the water environment. In this study, modified quartz sands (QS) were used in a biological sand filter to remove tetracycline. The modified QS, with different surface characteristics, were prepared using glass etching technology combined with subsequent chemical modification methods, including hydroxylation treatment, metal ion modification, and amino modification. The adsorption efficiency of hydroxylated QS was higher than that of metal ion modified and amino modified QS, with adsorption efficiencies of 20.4331 mg/kg, 12.8736 mg/kg, and 10.1737 mg/kg, respectively. Results indicated that QS primarily reduce tetracycline through adsorption. Adsorption on ordinary QS fit the pseudo-first-order kinetic model, while adsorption on other modified QS and biofilm-coated QS fit the pseudo-second-order kinetics model. Biodegradation was identified as another mechanism for tetracycline reduction, which fit the zero-order kinetic model. Pseudomonas alcaligenes and unclassified Pseudomonas accounted for 96.6% of the total tetracycline-degrading bacteria. This study elucidates the effectiveness and mechanisms of five types of QS in treating tetracycline from sewage plant effluents. It provides a novel method for tetracycline reduction in real-world wastewater scenarios.

Comparative genome analyses uncovered the cadmium resistance mechanism of enterobacter cloacae.

Cadmium (Cd) can be transported into plants from polluted soils and may cause animal and human diseases through food chains, which requires the development of highly efficient methods for soil Cd remediation. Although we isolated an Enterobacter cloacae strain Cu6 with Cd resistance, this strain cannot be used for soil Cd remediation due to its lower resistance. Here, we domesticated Cu6 and obtained a highly Cd-resistant strain, LPY6, and found that this strain can attenuate the toxic effects of Cd on wheat seedling growth. We deciphered the high Cd-resistance mechanism of LPY6 by genome comparative and genetic analysis. Compared with Cu6, 75 genes were mutated in LPY6. Thirty-four of these genes were deleted, and 41 had single nucleotide polymorphisms (SNPs). Most of these mutated proteins are involved in basic metabolism, substrate transport, stress response and formate and hydrogen metabolism. RNA quantitative analysis and promoter activity assays showed that the transcription or mRNA levels of two operons (cadA and norVW) in these mutated genes were regulated by Cd, zinc (Zn) or lead (Pb) ions, suggesting that these two operons might be required for Cd, Zn or Pb resistance. Expression of cadA and norVW operons in LPY6 partially recovered Cd susceptibility, demonstrating that CadA and NorVW are involved in Cd resistance in E. cloacae. Our findings illustrate that E. cloacae acquires Cd resistance through different pathways and lay a foundation for developing highly efficient methods for soil Cd remediation.

Surface modification of quartz sand: A review of its progress and its effect on heavy metal adsorption.

Quartz sand (SiO2) is a prevalent filtration medium, boasting wide accessibility, superior stability, and cost-effectiveness. However, its utility is often curtailed by its sleek surface, limited active sites, and swift saturation of adsorption sites. This review outlines the prevalent strategies and agents for quartz sand surface modification and provides a comprehensive analysis of the various modification reagents and their operative mechanisms. It delves into the mechanism and utility of surface-modified quartz sand for adsorbing heavy metal ions (HMIs). It is found that the reported modifiers usually form connections with the surface of quartz sand through electrostatic forces, van der Waals forces, pore filling, chemical bonding, and/or molecular entanglement. The literature suggests that these modifications effectively address issues inherent to natural quartz sand, such as its low superficial coarseness, rapid adsorption site saturation, and limited adsorption capacity. Regrettably, comprehensive investigations into the particle size, regenerative capabilities, and application costs of surface-modified quartz sand and the critical factors for its wider adoption are lacking in most reports. The adsorption mechanisms indicate that surface-modified quartz sand primarily removes HMIs from aqueous solutions through surface complexation, ion exchange, and electrostatic and gravitational forces. However, these findings were derived under controlled laboratory conditions, and practical applications for treating real wastewater necessitate overcoming further laboratory-scale obstacles. Finally, this review outlines the limitations of partially surface modified quartz sand and suggests potential venues for future developments, providing a valuable reference for the advancement of cost-effective, HMI-absorbing, surface-modified quartz sand filter media.

Transcriptome Landscape Analyses of the Regulatory Network for Zygotic Embryo Development in Paeonia ostii.

Paeonia ostii is a worldwide ornamental flower and an emerging oil crop. Zyotic embryogenesis is a critical process during seed development, and it can provide a basis for improving the efficiency of somatic embryogenesis (SE). In this study, transcriptome sequencing of embryo development was performed to investigate gene expression profiling in P. ostii and identified Differentially expressed genes (DEGs) related to transcription factors, plant hormones, and antioxidant enzymes. The results indicated that IAA (Indole-3-acetic acid), GA (Gibberellin), BR (Brassinosteroid) and ETH (Ethylene) were beneficial to early embryonic morphogenesis, while CTK (Cytokinin) and ABA (Abscisic Acid) promoted embryo morphogenesis and maturation. The antioxidant enzymes' activity was the highest in early embryos and an important participant in embryo formation. The high expression of the genes encoding fatty acid desaturase was beneficial to fast oil accumulation. Representative DEGs were selected and validated using qRT-PCR. Protein-protein interaction network (PPI) was predicted, and six central node proteins, including AUX1, PIN1, ARF6, LAX3, ABCB19, PIF3, and PIF4, were screened. Our results provided new insights into the formation of embryo development and even somatic embryo development in tree peonies.

Impacts, carbon effects, and forecasts for cropland expansion in the Northern Tianshan Mountain Economic Zone.

Increasing population growth and cropland occupation means that new cropland is needed to achieve the goal of food security. In order to achieve the goal of "carbon neutrality," the carbon effect and ecological effect brought about by the cropland area increase urgently need to be studied. Methods such as land use transfer matrix, land use information map, InVEST model, and the ecological risk index were used to analyze the impact of cropland change in the Northern Tianshan Mountain Economic Zone and calculated the carbon effect caused by its increasing cropland area. The Ca-Markov model was used to predict and analyze the impacts of future cropland distribution and area. The results showed that, between 2000 and 2020, the area of cropland in the study area increased 3926 km2, and the area of cropland occupation by built-up was 857 km2. The new increased cropland was predominantly derived from low-cover grassland and unused land. The quality and the carbon stock of the cropland increased. The ecological risk index of cropland was 0.2613, 0.2624, and 0.1187 in 2000, 2010, and 2020, respectively. The proportion of low-risk index area was 54.43%, 55.49%, and 87.22% in 2000, 2010, and 2020, respectively. According to the current development pattern of cropland, from 2000 to 2030, the area of occupation cropland and the area of cropland may increase, the carbon stock may increase by 941,650 Mg due to the change in land use types associated with cropland, the ecological risk index may be 0.1113, and the proportion of low-risk index cropland may be 80.08%. As a carbon sink, cropland is important for local carbon neutralization alongside the sustainable adjustment of planting structure and farming methods. The results could be helpful for land resource management policy, under the conditions of following natural laws; it is feasible to appropriately expand the cropland area in order to support the gradually increasing population.

Nitrogen deposition further increases Ambrosia trifida root exudate invasiveness under global warming.

Invasive plants can change the soil ecological environment in the invasion area to adapt to their growth and reproduction through root exudates. Root exudates are the most direct manifestation of plant responses to external environmental changes, but there is a lack of studies on root exudates of invasive plants in the context of inevitable global warming and nitrogen deposition. In this research, we used widely targeted metabolomics to investigate Ambrosia trifida root exudates during seedling and maturity under warming and nitrogen deposition to reveal the possible mechanisms of A. trifida adaptation to climate change. The results showed that the organic acids increased under warming condition but decreased after nitrogen addition in the seedling stage. Phenolic acids increased greatly after nitrogen addition in the mature stage. Most phenolic acids were annotated in the phenylpropane metabolic pathway and tyrosine metabolism. Therefore, nitrogen deposition may increase the adaptability of A. trifida through root exudates, making it more invasive under global warming. The results provide new ideas for preventing and controlling the invasion of A. trifida under climate change.

OCT biomarkers related to subthreshold micropulse laser treatment effect in central serous chorioretinopathy.

BACKGROUND: To identify the OCT biomarkers related to the anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) after subthreshold micropulse laser (SML) treatment. METHODS: Patients with CSCR underwent SML were enrolled in this retrospective study. Only patients who underwent enhanced depth imaging optical coherence tomography (EDI-OCT) examination before and after SML were selected. Patients were divided into two groups based on whether subretinal fluid (SRF) absorbed or not after SML. Group 1 was the SRF resolved group, and Group 2 was the SRF non-resolved group. Factors including age and gender, duration of symptoms, CSCR history, the height of SRF at baseline, retinal pigment epithelium (RPE) /inner choroid alterations, as well as subfoveal choroidal thickness (SFCT) of the affected eye and the fellow eye before and after SML were recorded and compared between two groups. Longitudinal change of SFCT of a subgroup of patients were analyzed. RESULTS: A total of 58 eyes of 58 patients were involved in this study. SRF of 31 eyes got completely absorbed, and SRF of 27 eyes was retained after SML. Logistic regression analysis revealed baseline SFCT of the affected eye (OR = 1.007, 95% CI: 1.001-1.012, P = 0.019) and RPE/inner choroid alterations (OR = 25.229, 95% CI: 2.890-220.281, P = 0.004) were correlated with SML efficacy. Thirty-three eyes of 33 patients were enrolled in the subgroup analysis. A significant difference of SFCT changes between two groups were demonstrated (P = 0.001). The difference of SFCT between baseline and three months after SML was also related to SRF resolution (OR = 0.952, 95% CI: 0.915-0.990, P = 0.014). CONCLUSION: Baseline SFCT, change of SFCT at 3-month after treatment, and RPE/inner choroid alterations were the OCT biomarkers related to SRF resolution after SML treatment.

Effect of AI-assisted software on inter- and intra-observer variability for the X-ray bone age assessment of preschool children.

BACKGROUND: With the rapid development of deep learning algorithms and the rapid improvement of computer hardware in the past few years, AI-assisted diagnosis software for bone age has achieved good diagnostic performance. The purpose of this study was to investigate the effect of AI-assisted software on residents' inter-observer agreement and intra-observer reproducibility for the X-ray bone age assessment of preschool children. METHODS: This prospective study was approved by the Institutional Ethics Committee. Six board-certified residents interpreted 56 bone age radiographs ranging from 3 to 6 years with structured reporting by the modified TW3 method. The images were interpreted on two separate occasions, once with and once without the assistance of AI. After a washout period of 4 weeks, the radiographs were reevaluated by each resident in the same way. The reference bone age was the average bone age results of the three experts. Both TW3-RUS and TW3-Carpal were evaluated. The root mean squared error (RMSE), mean absolute difference (MAD) and bone age accuracy within 0.5 years and 1 year were used as metrics of accuracy. Interobserver agreement and intraobserver reproducibility were evaluated using intraclass correlation coefficients (ICCs). RESULTS: With the assistance of bone age AI software, the accuracy of residents' results improved significantly. For interobserver agreement comparison, the ICC results with AI assistance among 6 residents were higher than the results without AI assistance on the two separate occasions. For intraobserver reproducibility comparison, the ICC results with AI assistance were higher than results without AI assistance between the 1st reading and 2nd reading for each resident. CONCLUSIONS: For preschool children X-ray bone age assessment, in addition to improving diagnostic accuracy, bone age AI-assisted software can also increase interobserver agreement and intraobserver reproducibility. AI-assisted software can be an effective diagnostic tool for residents in actual clinical settings.

Clinical evaluation of AI software for rib fracture detection and its impact on junior radiologist performance.

BACKGROUND: The detection of rib fractures (RFs) on computed tomography (CT) images is time-consuming and susceptible to missed diagnosis. An automated artificial intelligence (AI) detection system may be helpful to improve the diagnostic efficiency for junior radiologists. PURPOSE: To compare the diagnostic performance of junior radiologists with and without AI software for RF detection on chest CT images. MATERIALS AND METHODS: Six junior radiologists from three institutions interpreted 393 CT images of patients with acute chest trauma, with and without AI software. The CT images were randomly split into two sets at each institution, with each set assigned to a different radiologist First, the detection of all fractures (AFs), including displaced fractures (DFs), non-displaced fractures and buckle fractures, was analyzed. Next, the DFs were selected for analysis. The sensitivity and specificity of the radiologist-only and radiologist-AI groups at the patient level were set as primary endpoints, and secondary endpoints were at the rib and lesion level. RESULTS: Regarding AFs, the sensitivity difference between the radiologist-AI group and the radiologist-only group were significant at different levels (patient-level: 26.20%; rib-level: 22.18%; lesion-level: 23.74%; P < 0.001). Regarding DFs, the sensitivity difference was 16.67%, 14.19%, and 16.16% at the patient, rib, and lesion levels, respectively (P < 0.001). No significant difference was found in the specificity between the two groups for AFs and DFs at the patient and rib levels (P > 0.05). CONCLUSION: AI software improved the sensitivity of RF detection on CT images for junior radiologists and reduced the reading time by approximately 1 min per patient without decreasing the specificity.

Automatic detection of leakage point in central serous chorioretinopathy of fundus fluorescein angiography based on time sequence deep learning.

PURPOSE: To detect the leakage points of central serous chorioretinopathy (CSC) automatically from dynamic images of fundus fluorescein angiography (FFA) using a deep learning algorithm (DLA). METHODS: The study included 2104 FFA images from 291 FFA sequences of 291 eyes (137 right eyes and 154 left eyes) from 262 patients. The leakage points were segmented with an attention gated network (AGN). The optic disk (OD) and macula region were segmented simultaneously using a U-net. To reduce the number of false positives based on time sequence, the leakage points were matched according to their positions in relation to the OD and macula. RESULTS: With the AGN alone, the number of cases whose detection results perfectly matched the ground truth was only 37 out of 61 cases (60.7%) in the test set. The dice on the lesion level were 0.811. Using an elimination procedure to remove false positives, the number of accurate detection cases increased to 57 (93.4%). The dice on the lesion level also improved to 0.949. CONCLUSIONS: Using DLA, the CSC leakage points in FFA can be identified reproducibly and accurately with a good match to the ground truth. This novel finding may pave the way for potential application of artificial intelligence to guide laser therapy.

Global patterns in vision loss burden due to vitamin A deficiency from 1990 to 2017.

OBJECTIVE: To investigate the vision loss burden due to vitamin A deficiency (VAD) at the global, regional and national levels by year, age, sex and socio-economic status using prevalence and years lived with disability (YLD). DESIGN: International, retrospective, comparative burden-of-disease study. SETTING: Prevalence and YLD data were extracted from the Global Burden of Disease (GBD) Study 2017. The association of age-standardised YLD rates and human development index (HDI) was tested by Pearson correlation and linear regression analyses. The Gini coefficient and concentration index (CI) were calculated to demonstrate the trends in between-country inequality in vision loss burden due to VAD. PARTICIPANTS: All participants met the GBD inclusion criteria. RESULTS: The age-standardised prevalence rate increased by 9·2 %, while the age-standardised YLD rates rose by 10·8 % from 1990 to 2017. Notably, the vision loss burden caused by VAD showed a declining trend since 2014. The vision loss burden was more concentrated in the post-neonatal age group and decreased with increasing age. The age-standardised YLD rates were inversely correlated with HDI (r = -0·2417, P = 0·0084). The CI and Gini coefficients indicated that socio-economic-related and between-country inequality declined from 2000 to 2017. VAD was the eighth leading cause of the age-standardised prevalence rate and ninth leading cause of age-standardised YLD rate among fifteen causes of vision loss in 2017. CONCLUSION: VAD has become one of the significant leading causes of vision loss globally. Efforts to control vision impairment related to VAD are needed, especially for children in countries with lower socio-economic status.

Impacts of an azo food dye tartrazine uptake on intestinal barrier, oxidative stress, inflammatory response and intestinal microbiome in crucian carp (Carassius auratus).

Food dyes, or color additives, are often added into foods, cosmetics and beverages during processing to improve the sensory attributes of the final products. However, the toxicity of tartrazine (TZ), one of the most common azo-dyes, is still unclear, and needs to be ascertained by further study. Hence, in the present study, we aimed to evaluate the effects of TZ consumption on health by using a teleost, crucian carp (Carassius auratus) as the experimental fish. TZ consumption (1.4, 5.5 and 10 mg/kg bwt/day) could cause severe histopathological and cellular alterations in intestine and liver. The height of intestinal villus, thickness of intestinal muscle, and microvilli density were also affected. With the increasing of TZ concentrations, the activities of antioxidant enzymes (CAT, SOD and GSH-Px), exhibited a decreasing trend, while the contents of MDA elevated. Upregulations of pro-inflammatory cytokines (il6 and tnfα), anti-inflammatory cytokines (il8, and il10) and other immune related genes (complement component 3 (c3), lysozymes (lyz), ß-defensin 3 (defb3)), were observed after TZ uptake. In addition, TZ consumption also affected the community structure of the microbiota in the intestine of crucian carp. The amount of some probiotic bacteria (Roseomonas, Rhodococcus and Bacillus) and the bacteria (Bacteroides and Clostridium), producing short chain fatty acids, were significantly reduced, and some pathogenetic microorganisms (e.g. Bdellovibrio and Shewanella) were significantly increased after TZ uptake. In summary, the data in the present study indicate that TZ consumption, even at a low concentration, may lead to adverse effects on fish health. Therefore, in aquaculture, it is necessary to be informed about the hazardous effects of TZ, and more attentions should be focused on using natural substitutes.

KRT8 phosphorylation regulates the epithelial-mesenchymal transition in retinal pigment epithelial cells through autophagy modulation.

Proliferative vitreoretinopathy (PVR) is a severe ocular disease which results in complex retinal detachment and irreversible vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is considered to be critical in the pathogenesis of PVR. In this study, we focused on the potential impact of keratin 8 (KRT8) phosphorylation and autophagy on TGF-ß2-induced EMT of RPE cells and explored the relationship between them. Using immunofluorescence and Western blot analysis, the co-localization of KRT8 and autophagy marker, as well as the abundance of phosphorylated KRT8 (p-KRT8) expression, was observed within subretinal and epiretinal membranes from PVR patients. Moreover, during TGF-ß2-induced EMT process, we found that p-KRT8 was enhanced in RPE cells, which accompanied by an increase in autophagic flux. Inhibition of autophagy with pharmacological inhibitors or specific siRNAs was associated with a reduction in cell migration and the synthesis of several EMT markers. In the meantime, we demonstrated that p-KRT8 was correlated with the autophagy progression during the EMT of RPE cells. Knockdown the expression or mutagenesis of the critical phosphorylated site of KRT8 would induce autophagy impairment, through affecting the fusion of autophagosomes and lysosomes. Therefore, this study may provide a new insight into the pathogenesis of PVR and suggests the potential therapeutic value of p-KRT8 in the prevention and treatment of PVR.

The prognostic landscape of adaptive immune resistance signatures and infiltrating immune cells in the tumor microenvironment of uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and has a high mortality rate. Tumor microenvironment (TME) is crucial in controlling and influencing the behavior of malignant tumors. Thus, illustrating the prognostic values of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM may provide scientific rationales for immunotherapy. In this study, the gene expression data of 80 primary UM and 103 primary skin cutaneous melanoma (SKCM) samples with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. The TME was analyzed by the xCell, EPIC, ESTIMATE and TIMER algorithms. The relationships and prognostic values of immune infiltrates and mutated genes were further investigated. We found that primary UM and primary SKCM exhibited distinct TMEs. Higher levels of infiltrating stromal and immune cells in UM were related to more aggressive biology and poor prognosis. Increased CD8+ T cell level, as well as several adaptive immune resistance markers, was a predictive factor of poor prognosis in UM. Furthermore, some common mutations of UM were associated with its TME. This study analyzed the immune landscape of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM. Identification of these immune-related biomarkers may thus enable the prediction of prognosis and the selection of optimal immunotherapy strategies in UM.

The roles of two myostatins and immune effects after inhibition in Qi river crucian carp (Carassius auratus).

Myostatin, through type I receptor (kinase 4, 5, ALK4/5), functions to participate in the immune system and negatively regulate muscle growth in mammals. However, the role of myostatin (mstn) in the immune system of teleosts is largely unknown. In a previous study, we cloned the mstn1 cDNA encoding myostatin in Qi river crucian carp (Carassius auratus). In the present study, we have cloned mstn2 cDNA, which was characterized and analyzed together with mstn1. Tissue distribution analysis showed that both mstn genes are expressed in numerous tissues, with mstn1 dominantly expressed in the muscle and brain, whereas mstn2 is mainly expressed in the brain. During embryogenesis, mstn1 and mstn2 exhibit different expression patterns. Both mstn1 and mstn2 expression increased stepwise in the brain at different developmental stages. Furthermore, both genes are differentially regulated during different periods of fasting/re-feeding. Following the exposure of C. auratus to polyI:C, lipopolysaccharide (LPS), and Aeromonas hydrophila, both genes were upregulated in different tissues, which indicated that they might be involved in the immune response against pathogenic invasion. Blocking the Mstn signal pathway with SB-431542 (a chemical inhibitor of ALK4/5) resulted in significantly increased body length and weight. However, the mortality of SB-431542-treated fish was higher after A. hydrophila challenge. Moreover, decreased expression of lysozymes (lyz), complement component 3 (c3), ß-defensin 3 (defb3), and interferon γ (ifnγ) were exhibited in treated fish, compared with the controls. Furthermore, the expression of nf-κb1, three pro-inflammatory cytokines (il1ß, il6, and tnfα), and inflammatory cytokines (il8 and il10) were significantly increased in both the SB-431542-treated group and the control after A. hydrophila infection, suggesting that the NF-κB pathway was not suppressed in the SB-431542-treated fish. Taken together, our data suggest that both mstn1 and mstn2 play important roles in early body development, muscle growth, and the immune system by acting downstream of the NF-κB signal pathway.

Total iron binding capacity (TIBC) is a potential biomarker of left ventricular remodelling for patients with iron deficiency anaemia.

BACKGROUND: Preclinical studies indicate iron deficiency (ID) plays an important role in cardiac remodelling. However, the relationship between ID and cardiac remodelling remains unknown in clinical setting. This retrospective study aims to identify a potential biomarker for the myocardial remodelling in patients with ID. Due to limited patients with ID are identified without iron deficiency anaemia (IDA), we analyse the relationship of total iron binding capacity (TIBC) and the left ventricular mass index (LVMI) in patients with iron deficiency anaemia. METHODS: A total of 82 patients with IDA exhibiting the diagnostic criteria for IDA were enrolled in the study. Among the patients, 65 had reported LVMI values. Subsequently, these patients were divided into two groups according to abnormal LVMI (> 115 g/m2 in men and > 95 g/m2 in women). Linear bivariate analysis was performed to detect the associations of haemoglobin or TIBC with clinical and echocardiographic characteristics. Simple linear regression analysis was used to evaluate the correlation between LVMI and the parameters of IDA, while multivariable linear analysis was used to assess the association of LVMI with age, TIBC and haemoglobin. Logistic regression analysis was utilized to determine the relationship of LV remodelling with anaemia severity and TIBC. RESULTS: As compared with control group, the levels of TIBC in abnormal LVMI group are increased. Using log transformed LVMI as the dependent variable, simultaneously introducing age, TIBC, and haemoglobin into the simple linear regression or multivariable linear regression analysis confirmed the positive association among these factors. Bivariate correlation analysis reveals the irrelevance between haemoglobin and TIBC. In logistic regression analysis, TIBC is associated with the risk of LV remodelling. CONCLUSIONS: Results of study indicate that TIBC exhibit an explicit association with LVMI in patients with iron deficiency anaemia. Logistic analysis further confirms the contribution of TIBC to abnormal LVMI incidence among this population with IDA.

Multi-label classification of retinal lesions in diabetic retinopathy for automatic analysis of fundus fluorescein angiography based on deep learning.

PURPOSE: To automatically detect and classify the lesions of diabetic retinopathy (DR) in fundus fluorescein angiography (FFA) images using deep learning algorithm through comparing 3 convolutional neural networks (CNNs). METHODS: A total of 4067 FFA images from Eye Center at the Second Affiliated Hospital of Zhejiang University School of Medicine were annotated with 4 kinds of lesions of DR, including non-perfusion regions (NP), microaneurysms, leakages, and laser scars. Three CNNs including DenseNet, ResNet50, and VGG16 were trained to achieve multi-label classification, which means the algorithms could identify 4 retinal lesions above at the same time. RESULTS: The area under the curve (AUC) of DenseNet reached 0.8703, 0.9435, 0.9647, and 0.9653 for detecting NP, microaneurysms, leakages, and laser scars, respectively. For ResNet50, AUC was 0.8140 for NP, 0.9097 for microaneurysms, 0.9585 for leakages, and 0.9115 for laser scars. And for VGG16, AUC was 0.7125 for NP, 0.5569 for microaneurysms, 0.9177 for leakages, and 0.8537 for laser scars. CONCLUSIONS: Experimental results demonstrate that DenseNet is a suitable model to automatically detect and distinguish retinal lesions in the FFA images with multi-label classification, which lies the foundation of automatic analysis for FFA images and comprehensive diagnosis and treatment decision-making for DR.

ACTN3 is associated with children's physical fitness in Han Chinese.

The ACTN3 gene locates on 11q13-q14 and encodes the α-actinin-3 protein, which is only expressed in human skeletal muscle and influenced muscle function and metabolism. The previous studies reported that SNP rs1815739 is associated with elite power athletes' performance. In this study, we investigated the association between five SNPs within the ACTN3 gene and Chinese children physical fitness. We recruited 2244 Han Chinese children participants, and measured their 25-m run, stand broad jump, 10-m shuttle run, handgrip, BMI (calculated by weight and height) data. SNPs rs1671064, rs2275998, rs2290463, rs10791881, and rs1815739 of ACTN3 gene were genotyped and analyzed in five physical fitness data. QTL analysis on genotype and physical fitness data was carried out in all samples. Furthermore, a dichotomous division of samples into an overweight group (543) and a normal group (1701) was used for an association study of overweight. In the QTL analysis, we found rs2290463 was significantly associated with stand broad jump (corrected P value = 0.009, beta = 2.692). After added age and gender as covariates in the regression test, the association became more significant (P value = 5.80 × 10- 5, corrected P value = 4.06 × 10- 4); when we used BMI as a covariate, the association still existed (P value = 4.65 × 10- 4, corrected P value = 0.001). In the association study of overweight, rs2275998 was found to be significant (OR, 95% CI = 0.733 [0.6-0.895]; Pallele = 0.011, Pgenotype = 0.024) after the Bonferroni correction, and the association did not change much after a further correction for gender, age, and stand broad jump performance. Our results showed that common variants in ACTN3 are significantly associated with both stand broad jump performance and overweight in Han Chinese children.

Cloning and characterization of wnt4a gene in a natural triploid teleost, Qi river crucian carp (Carassius auratus).

WNT4 (wingless-type MMTV integration site family, member 4) plays a key role in the ovarian differentiation and development in mammals. However, the possible roles of Wnt4 during gonadal differentiation and development need further clarification in teleosts. In this study, we cloned and characterized the full-length cDNA of Qi river crucian carp (Carassius auratus) wnt4a gene (CA-wnt4a). The cDNA of CA-wnt4a is 2337 bp, including the ORF of 1059 bp, encoding a putative protein with a transmembrane domain and a WNT family domain. Sequence and phylogenetic analyses revealed that the CA-Wnt4a identified is a genuine Wnt4a. Tissue distribution analysis showed that CA-wnt4a is expressed in all the tissues examined, including ovary. CA-wnt4a undergoes a stepwise increase in the embryonic stages, suggesting that CA-wnt4a might be involved in the early developmental stage. Ontogenic analysis demonstrated that CA-wnt4a expression is upregulated in the ovaries at 30-50 days after hatching (dah), the critical period of sex determination/differentiation in Qi river crucian carp. From 90 dah, the expression of CA-wnt4a was gradually downregulated in the developing ovaries. Immunohistochemistry demonstrated that CA-Wnt4a was expressed in the somatic and germ cells of the ovary by 30 dah, thereafter, positive signals of Wnt4a were detected in the somatic cells, oogonia and primary growth oocytes from 60 dah. In the sex-reversed testis induced by letrozole treatment, the expression level of CA-wnt4a was significantly downregulated. When CA-wnt4a expression was inhibited by injection of FH535 (an inhibitor of canonical Wnt/ß-catenin signal pathway) in the ovaries, levels of cyp19a1a, foxl2 mRNA were significantly downregulated, while sox9b and cyp11c1 were upregulated, which suggested that together with Foxl2-leading estrogen pathway, CA-wnt4a signaling pathway might be involved in ovarian differentiation and repression of the male pathway gene expression in Qi river crucian carp.