Degradation and humification of steroidal estrogens in the soil environment: A review.

Emerging pollutants are toxic and harmful chemical substances characterized by environmental persistence, bioaccumulation and biotoxicity, which can harm the ecological environment and even threaten human health. There are four categories of emerging pollutants that are causing widespread concern, namely, persistent organic pollutants, endocrine disruptors, antibiotics, and microplastics. The distribution of emerging pollutants has spatial and temporal heterogeneity, which is influenced by factors such as geographical location, climatic conditions, population density, emission amount, etc. Steroidal estrogens (SEs) discussed in this paper belong to the category of endocrine disruptors. There are generally three types of fate for SEs in the soil environment: sorption, degradation and humification. Humification is a promising pathway for the removal of SEs, especially for those that are difficult to degrade. Through humification, these difficult-to-degrade SEs can be effectively transferred or fixed, thus reducing their impact on the environment and organisms. Contrary to the well-studied process of sorption and degradation, the role and promise of the humification process for the removal of SEs has been underestimated. Based on the existing research, this paper reviews the sources, classification, properties, hazards and environmental behaviors of SEs in soil, and focuses on the degradation and humification processes of SEs and the environmental factors affecting their processes, such as temperature, pH, etc. It aims to provide references for the follow-up research of SEs, and advocates further research on the humification of organic pollutants in future studies.

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).

Effect of Kasai procedure on liver transplantation in children with biliary atresia: a systematic review and updated meta-analysis.

Background: Kasai procedure and liver transplantation are effective ways to save the life of children with biliary atresia (BA). However, with the gradual development of liver transplantation technology, scholars have questioned the necessity of the Kasai procedure. Therefore, we conducted a meta-analysis to evaluate the effect of previous Kasai procedures on liver transplantation in children with BA. Methods: Seven databases were searched and screened from the establishment of the database to May 3, 2023. The data in the included literature were extracted for meta-analysis to compare the differences between the Kasai group and the non-Kasai group. Finally, a publication bias test, sensitivity analysis, subgroup analysis, and systematic review were performed. Results: A total of 26 studies were included in which 6,522 children with BA underwent liver transplantation, including 4,989 in the Kasai group. Compared with the non-Kasai group, the Kasai group had older age [standardized mean difference (SMD) =0.64; 95% confidence interval (CI): 0.46, 0.82; P<0.001] (I2=78.6%), heavier weight (SMD =0.41; 95% CI: 0.33, 0.48; P<0.001) (after sensitivity analysis, I2=0.0%), lower pediatric end-stage liver disease (PELD) (SMD =-0.41; 95% CI: -0.48, -0.35; P<0.001) (I2=20.1%), longer operation time (SMD =0.33; 95% CI: 0.01, 0.65; P<0.001) (I2=83.2%), more intraoperative blood loss (SMD =0.26; 95% CI: 0.06, 0.46; P=0.012) (I2=19.1%), shorter intensive care unit (ICU) stay (SMD =-0.09; 95% CI: -0.34, 0.15; P=0.027) (I2=68.6%) and higher incidence of intestinal perforation [odds ratio (OR) =1.96; 95% CI: 1.20, 3.18; P=0.007] (I2=7.4%) and biliary complications (OR =1.41; 95% CI: 1.05, 1.89; P=0.024) (I2=31.4%). In the "Asia" subgroup, the Kasai group was older (SMD =0.68; 95% CI: 0.52, 0.84; P<0.001) (I2=28.2%). In the "Cases since 2000" subgroup, there was no significant difference in operation time between the two groups (I2=28.5%). In the "Other" and the "non-Asia" subgroup, there was no significant difference in length of intensive care unit (ICU) stay between the two groups (I2=0.0%). However, there were no significant differences in other postoperative complications and prognostic indicators between the two groups. Conclusions: For children with BA undergoing liver transplantation, although previous Kasai procedure may increase the risk of intraoperative bleeding, biliary complications, and intestinal perforation, it does not affect the main clinical outcomes, and can even delay the timing of liver transplantation and improve the preoperative status of children. Therefore, when BA children have no obvious contraindications to Kasai procedure, the sequential treatment of Kasai procedure-liver transplantation should be supported first.

Biliary atresia: the development, pathological features, and classification of the bile duct.

Biliary atresia is an occlusive biliary disease involving intrahepatic and extrahepatic bile ducts. Its etiology and pathogenesis are unclear. There are many manifestations of bile duct involvement in biliary atresia, but little is known about its occurrence and development. In addition, different classification methods have been proposed in different periods of biliary atresia, each with its advantages and disadvantages. The combined application of biliary atresia classification will help to improve the survival rate of patients with native liver. Therefore, this article reviews the development, pathological features, and classification of intrahepatic and extrahepatic bile ducts in biliary atresia, to provide a reference for the study of the pathogenesis and the choice of treatment methods.

Association between behavioral patterns and depression symptoms: dyadic interaction between couples.

Background: Behavioral patterns are sometimes associated with depression symptoms; however, few studies have considered the intra-couple effects. This study examined the effect of a spouses' behavioral patterns on depression symptoms within themself and in their spouse. Methods: A total of 61,118 childbearing age participants (30,559 husband-wife dyads) were surveyed. The depression symptoms were assessed using the nine-item Patient Health Questionnaire (PHQ-9). The behavioral patterns were identified by the latent class analysis. The effects of behavioral patterns on the couple's own depression symptoms (actor effect) and their partner's depression symptoms (partner effect) were analyzed using the Actor-Partner Interdependence Model (APIM). Results: Three behavioral patterns were identified: low-risk group, moderate-risk group, and high-risk group. The high risk of these behavior patterns would be associated with a higher score on the PHQ-9; for both husbands and wives, their behavioral patterns were positively associated with PHQ-9 scores (ßhusband = 0.53, P < 0.01; ßwife = 0.58, P < 0.01). Wives' behavioral patterns were also positively associated with their husbands' PHQ-9 scores (ß = 0.14, P < 0.01), but husbands' behavioral patterns were not associated with their wives' PHQ-9 scores. Conclusions: Wives' depression symptoms were affected only by their own behavioral patterns, whereas husbands' depression symptoms were influenced by both their own and their spouses' behavioral patterns.

Preconception exposure to environmental antibiotics among childbearing couples in Anhui and health risk assessment: A multicenter population-based representative study.

Only few studies have assessed the health effects due to preconception exposure to antibiotics among childbearing couples. This study investigated the status of preconception exposure to antibiotics among childbearing couples in Anhui, associated with health risks, and influencing factors. Overall, 1500 childbearing couples were randomly selected from the Reproductive Health of Childbearing Couples - Anhui Cohort (RHCC-AC). The urinary levels of 40 antibiotics and 2 metabolites were determined, and specific gravity (SG) adjusted concentrations of antibiotics were measured to assess health risks. Generalized linear models were used to assess the associations of urinary SG-adjusted concentration of antibiotics with demographic parameters and diet frequency. The total detection rates of all antibiotics were 98.9 % and 99.3 % in wives and husbands, respectively. The detection rates of veterinary antibiotics (VAs) and preferred as VAs (PVAs) were above 90 %. Among eight antibiotics, sulfonamides (95.1 %) and fluoroquinolones (87.6 %) had the highest detection rates in couples. Approximately four-fifths of couples were simultaneously exposed to at least three different antibiotics, and more than half of them were exposed to low concentrations of antibiotics. 8.9 % and 9.2 % of wives and husbands had hazard index value of antibiotics exposure greater than 1. Antibiotic concentrations were associated with residence, sampling season, and diet frequency. In Anhui, nearly 98 % of childbearing couples have environmental exposure to antibiotics, and VAs and PVAs are the primary antibiotics. More than 8 % of couples had health risks due to antibiotic exposure. Several potential determinants of urinary antibiotics deserve more attention in future research.

Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age.

BACKGROUND: This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association. METHODS: This study is a population-based case-control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package "mediation". RESULTS: The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01-0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%. CONCLUSION: These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

ZmAGO18b negatively regulates maize resistance against southern leaf blight.

KEY MESSAGE: Here, we report that ZmAGO18b encoding an argonaute protein is a negative regulator of maize resistance against southern leaf blight. Southern leaf blight caused by fungal pathogen Cochliobolus heterostrophus is a destructive disease on maize throughout the world. Argonaute (AGO) proteins, key regulators in small RNA pathway, play important roles in plant defense. But whether they have function in maize resistance against C. heterostrophus is unknown. Association analysis between the nucleic variation of 18 ZmAGO loci with disease phenotype against C. heterostrophus was performed, and the ZmAGO18b locus was identified to be associated with resistance against C. heterostrophus. Overexpression of ZmAGO18b gene suppresses maize resistance against C. heterostrophus, and mutation of ZmAGO18b enhances maize resistance against C. heterostrophus. Further, we identified the resistant haplotype of ZmAGO18b by association analysis of natural variation in ZmAGO18b genomic DNA sequences with seedling resistance phenotypes against C. heterostrophus and confirmed the resistant haplotype is co-segregated with resistance phenotypes against C. heterostrophus in two F2 populations. In sum, this study reports that ZmAGO18b negatively regulates maize resistance against C. heterostrophus.

The reciprocal changes in dominant species with complete metabolic functions explain the decoupling phenomenon of microbial taxonomic and functional composition in a grassland.

The decoupling of microbial functional and taxonomic components refers to the phenomenon that a drastic change in microbial taxonomic composition leads to no or only a gentle change in functional composition. Although many studies have identified this phenomenon, the mechanisms underlying it are still unclear. Here we demonstrate, using metagenomics data from a steppe grassland soil under different grazing and phosphorus addition treatments, that there is no "decoupling" in the variation of taxonomic and metabolic functional composition of the microbial community within functional groups at species level. In contrast, the high consistency and complementarity between the abundance and functional gene diversity of two dominant species made metabolic functions unaffected by grazing and phosphorus addition. This complementarity between the two dominant species shapes a bistability pattern that differs from functional redundancy in that only two species cannot form observable redundancy in a large microbial community. In other words, the "monopoly" of metabolic functions by the two most abundant species leads to the disappearance of functional redundancy. Our findings imply that for soil microbial communities, the impact of species identity on metabolic functions is much greater than that of species diversity, and it is more important to monitor the dynamics of key dominant microorganisms for accurately predicting the changes in the metabolic functions of the ecosystems.

G-Protein ß-Subunit Gene TaGB1-B Enhances Drought and Salt Resistance in Wheat.

In the hexaploid wheat genome, there are three Gα genes, three Gß and twelve Gγ genes, but the function of Gß in wheat has not been explored. In this study, we obtained the overexpression of TaGB1 Arabidopsis plants through inflorescence infection, and the overexpression of wheat lines was obtained by gene bombardment. The results showed that under drought and NaCl treatment, the survival rate of Arabidopsis seedlings' overexpression of TaGB1-B was higher than that of the wild type, while the survival rate of the related mutant agb1-2 was lower than that of the wild type. The survival rate of wheat seedlings with TaGB1-B overexpression was higher than that of the control. In addition, under drought and salt stress, the levels of superoxide dismutase (SOD) and proline (Pro) in the wheat overexpression of TaGB1-B were higher than that of the control, and the concentration of malondialdehyde (MDA) was lower than that of the control. This indicates that TaGB1-B could improve the drought resistance and salt tolerance of Arabidopsis and wheat by scavenging active oxygen. Overall, this work provides a theoretical basis for wheat G-protein ß-subunits in a further study, and new genetic resources for the cultivation of drought-tolerant and salt-tolerant wheat varieties.

Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study.

BACKGROUND: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. METHODS: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20-49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). RESULTS: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. CONCLUSION: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.

Research on Assistant Diagnosis of Fundus Optic Neuropathy Based on Deep Learning.

PURPOSE: The purpose of this study was to use the neural network to distinguish optic edema (ODE), and optic atrophy from normal fundus images and try to use visualization to explain the artificial intelligence methods. METHODS: Three hundred and sixty-seven images of ODE, 206 images of optic atrophy, and 231 images of normal fundus were used, which were provided by two hospitals. A set of image preprocessing and data enhancement methods were created and a variety of different neural network models, such as VGG16, VGG19, Inception V3, and 50-layer Deep Residual Learning (ResNet50) were used. The accuracy, recall, F1-score, and ROC curve under different networks were analyzed to evaluate the performance of models. Besides, CAM (class activation mapping) was utilized to find the focus of neural network and visualization of neural network with feature fusion. RESULTS: Our image preprocessing and data enhancement method significantly improved the accuracy of model performance by about 10%. Among the networks, VGG16 had the best effect, as the accuracy of ODE, optic atrophy and normal fundus were 98, 90, and 95%, respectively. The macro-average and micro-average of VGG16 both reached 0.98. From CAM we can clearly find out that the focus area of the network is near the optic cup. From feature fusion images, we can find out the difference between the three types fundus images. CONCLUSION: Through image preprocessing, data enhancement, and neural network training, we applied artificial intelligence to identify ophthalmic diseases, acquired the focus area through CAM, and identified the difference between the three ophthalmic diseases through neural network middle layers visualization. With the help of assistant diagnosis, ophthalmologists can evaluate cases more precisely and more clearly.

Impact of dietary sucralose and sucrose-sweetened water intake on lipid and glucose metabolism in male mice.

AIMS: Overconsumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of metabolic disorders, including obesity and diabetes. However, accumulating evidence also suggests the potential negative impact of consuming nonnutritive sweeteners (NNSs) on weight and glycaemic control. The metabolic effects of sucralose, the most widely used NNS, remain controversial. This study aimed to compare the impact of intake of dietary sucralose (acceptable daily intake dose, ADI dose) and sucrose-sweetened water (at the same sweetness level) on lipid and glucose metabolism in male mice. MATERIALS AND METHODS: Sucralose (0.1 mg/mL) or sucrose (60 mg/mL) was added to the drinking water of 8-week-old male C57BL/6 mice for 16 weeks, followed by oral glucose and intraperitoneal insulin tolerance tests, and measurements of bone mineral density, plasma lipids, and hormones. After the mice were sacrificed, the duodenum and ileum were used for examination of sweet taste receptors (STRs) and glucose transporters. RESULTS: A significant increase in fat mass was observed in the sucrose group of mice after 16 weeks of sweetened water drinking. Sucrose consumption also led to increased levels of plasma LDL, insulin, lipid deposition in the liver, and increased glucose intolerance in mice. Compared with the sucrose group, mice consuming sucralose showed much lower fat accumulation, hyperlipidaemia, liver steatosis, and glucose intolerance. In addition, the daily dose of sucralose only had a moderate effect on T1R2/3 in the intestine, without affecting glucose transporters and plasma insulin levels. CONCLUSION: Compared with mice consuming sucrose-sweetened water, daily drinking of sucralose within the ADI dose had a much lower impact on glucose and lipid homeostasis.

Cloning southern corn rust resistant gene RppK and its cognate gene AvrRppK from Puccinia polysora.

Broad-spectrum resistance has great values for crop breeding. However, its mechanisms are largely unknown. Here, we report the cloning of a maize NLR gene, RppK, for resistance against southern corn rust (SCR) and its cognate Avr gene, AvrRppK, from Puccinia polysora (the causal pathogen of SCR). The AvrRppK gene has no sequence variation in all examined isolates. It has high expression level during infection and can suppress pattern-triggered immunity (PTI). Further, the introgression of RppK into maize inbred lines and hybrids enhances resistance against multiple isolates of P. polysora, thereby increasing yield in the presence of SCR. Together, we show that RppK is involved in resistance against multiple P. polysora isolates and it can recognize AvrRppK, which is broadly distributed and conserved in P. polysora isolates.

Low and mismatched socioeconomic status between newlyweds increased their risk of depressive symptoms: A multi-center study.

Background: While there is evidence that low socioeconomic status (SES) increases susceptibility to depression, few studies have focused on the effect of marital SES matching on depression. This study aimed to explore the impact of SES indicator matching on depressive symptoms in newlyweds and clarify the interaction of depressive symptoms between couples. Methods: We assessed the depressive symptoms of newlyweds (N = 28, 179 couples) using a 9-item Patient Health Questionnaire. Logistic regression models and restricted cubic splines were used to explore the association between SES indicator matching and depressive symptoms and the interaction of depressive symptoms in newlyweds, respectively. Results: Compared with newlyweds with both high-level SES, the newlyweds with both low-level SES, male higher SES, or female higher SES had an increased risk of depressive symptoms in husbands (OR = 1.31; 1.22; 1.30), wives (OR = 1.30; 1.36; 1.32), and couples (OR = 1.48; 1.56; 1.57) (all P < 0.05). In addition, as the level of depression in one partner increases, the risk of depression in the other partner also increases. Conclusion: Mismatched SES and low-level SES between couples have adverse effects on depressive symptoms in newlyweds, with depressive symptoms having a positive association between newlyweds.

Genome-Wide Identification of the HMA Gene Family and Expression Analysis under Cd Stress in Barley.

In recent years, cadmium (Cd) pollution in soil has increased with increasing industrial activities, which has restricted crop growth and agricultural development. The heavy metal ATPase (HMA) gene family contributes to heavy metal stress resistance in plants. In this study, 21 HMA genes (HvHMAs) were identified in barley (Hordeumvulgare L., Hv) using bioinformatics methods. Based on phylogenetic analysis and domain distribution, barley HMA genes were divided into five groups (A-E), and complete analyses were performed in terms of physicochemical properties, structural characteristics, conserved domains, and chromosome localization. The expression pattern analysis showed that most HvHMA genes were expressed in barley and exhibited tissue specificity. According to the fragments per kilobase of exon per million fragments values in shoots from seedlings at the 10 cm shoot stage (LEA) and phylogenetic analysis, five HvHMA genes were selected for expression analysis under Cd stress. Among the five HvHMA genes, three (HvHMA1, HvHMA3, and HvHMA4) were upregulated and two (HvHMA2 and HvHMA6) were downregulated following Cd treatments. This study serves as a foundation for clarifying the functions of HvHMA proteins in the heavy metal stress resistance of barley.

Association of VEGF Gene Polymorphisms with Susceptibility to Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

The associations between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of type 2 diabetic retinopathy (DR) - proliferative diabetic retinopathy (PDR), and nonproliferative diabetic retinopathy (NPDR) - remain unclear. A systematic search and meta-analysis using odds ratio (OR) with 95% confidence interval (CI) was performed to evaluate the association. Our study concluded 26 studies containing 10 single nucleotide polymorphisms (SNPs). In Asian populations, rs3025039 polymorphism was associated with DR risk, while in overall populations and Caucasians, the DR risk was increased by association with rs2010963. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. DR risks were found to be significantly associated between rs3025021, rs13207351, and rs2146323 in either overall populations, Caucasians or Asians. Besides, in overall and Asian populations, rs699947 and rs3025039 were associated with PDR risk. rs1570360, rs3025039, and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039, and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR, and NPDR.

PF4 antagonizes retinal neovascularization via inhibiting PRAS40 phosphorylation in a mouse model of oxygen-induced retinopathy.

Retinal neovascularization (RNV) is a common pathology of blinding proliferative retinopathies. The current treatments to RNV, however, are hindered by limited efficacy, side effects, and drug resistance. A naturally-occurring cytokine in retina that is amicable to immune system and possesses robust anti-neovascular function would facilitate to overcome the hurdles. In this study, retinas from a mouse model of oxygen-induced retinopathy (OIR) underwent a protein array to screen the naturally-occurring cytokines that may antagonize RNV. Among the 62 angiogenesis-associated cytokines, platelet factor 4 (Pf4) stood out with the most prominent upregulation and statistical significance. Moreover, an intravitreal injection of mouse Pf4 demonstrated dramatic anti-vaso-obliteration and anti-neovascularization effects dose dependently in the OIR model; whereas human PF4 inhibited the proliferation, migration, and tubulogenesis of monkey retinal vascular endothelial cells treated with VEGF and TNF-α. These previously undescribed angiostatic effects of PF4 in OIR retinas and retinal vascular endothelial cells support translation of this naturally-occurring chemokine into a therapeutic modality to RNV supplementary to the anti-VEGFs. Mechanistically, a phosphorylation array and western blots indicated that downregulation of proline-rich Akt substrate of 40 kDa (Pras40) and its phosphorylation were necessary for Pf4's anti-neovascular effects in the OIR retinas. Indeed, overexpression of the wildtype Pras40 and the mutant version with deficient phosphorylation abolished and mimicked the Pf4's angiostatic effects in the OIR retinas, respectively. The similar effects were also observed in vitro. This study, for the first time, links PF4's anti-RNV function to an intracellular signaling molecule PRAS40 and its phosphorylation.

Prevalence of diabetic retinopathy, proliferative diabetic retinopathy and non-proliferative diabetic retinopathy in Asian T2DM patients: a systematic review and Meta-analysis.

AIM: To investigate the pooled prevalence of diabetic retinopathy (DR), proliferative DR (PDR) and nonproliferative DR (NPDR) in Asian type 2 diabetes mellitus (T2DM) patients. METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2DM patients. Effect size (ES) with 95% confidence interval (CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2DM patients, respectively. RESULTS: There were 41 references and 48 995 T2DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients (45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients (74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2DM from India was higher than patients from other locations of Asia, and the same results were also observed in NPDR patients. CONCLUSION: In either T2DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2DM patients, and we also recommend suitable interventions to prevent its progression.