A CC-NB-ARC-LRR Gene Regulates Bract Morphology in Cotton.

Bracts are leaf-like structures in flowering plants. They serve multiple functions such as attracting pollinators, aiding tolerance of abiotic stressors, and conducting photosynthesis. While previous studies extensively examine bract function, the molecular mechanisms underlying bract growth remain unknown. Here, the map-based isolation and characterization of a crucial factor responsible for cotton bract development, identified from a mutant known as frego bract (fg), discovered by Frego in 1945 are presented. This gene, named Ghfg, encodes a CC-NB-ARC-LRR (CNL) family protein. Through analysis of bract form in plants with virus-induced gene silencing (VIGS) and transgenic plants, this gene is confirmed to be the causal gene under the fg locus. Furthermore, high-resolution single-cell transcriptomic landscape of cotton bracts is generated, which reveals differences related to auxin in proliferating cells from TM-1 and T582; differences in auxin distribution and ROS accumulation are experimentally verified. These findings suggest that GhFG is in a self-activated state in the fg mutant, and its activity leads to ROS accumulation that impacts auxin distribution and transport. Finally, an island cotton variety with the frego bract trait is developed, demonstrating a novel solution for reducing the high impurity rate caused by bract remnants.

Investigation of bioactive components and metabolic pathways of Zhen-wu-tang in rat plasma and renal tissue by UPLC-Q-TOF/MS.

INTRODUCTION: Zhen-wu-tang (ZWT) is a traditional Chinese medicine (TCM) formula for the treatment of several kidney diseases. However, due to the complexity of the TCM formula, there is a lack of accurate knowledge of the chemical constituents of ZWT and its bioactive components, as well as in vivo metabolic pathway studies. OBJECTIVES: The chemical composition of ZWT and its bioactive components along with the metabolic pathways were investigated by a combination of chemical profiling and serum pharmacochemistry. METHODS: High-resolution ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to identify the chemical components of ZWT and its bioactive components and metabolites in vivo. RESULTS: As a result, a total of 110 chemical components were identified from ZWT solution, mainly amino acids, alkaloids, gingerols, monoterpene glycosides and terpenoids, and so on. In addition, 24 prototype components and 36 metabolites were detected in rat plasma. Meanwhile, 8 prototype components were detected in rat kidney tissue but no metabolites. Interestingly, 4 of the 28 bioactive components were detected in both plasma and renal tissue, which were atractylenolide III, trimethoxyaconitane, methyl gallate, and paeoniflorin. The metabolic pathways mainly involved Phases I and/or II metabolic reactions such as hydrolysis, oxidation, reduction and hydration, methylation/demethylation, sulphation, glucuronidation, acetylation, and glutathione conjugation. CONCLUSION: Overall, the present study has comprehensively elucidated the chemical composition of ZWT and its potential bioactive components and metabolites, which provides a basis for the basic study of its pharmacodynamic substances and a reference for the study of the bioactive components of TCM formulae.

Cobalt stress enhanced dendrobine-type total alkaloids biosynthesis of Trichoderma longibrachiatum UN32 through reactive oxygen species formation.

Trichoderma longibrachiatum UN32 is a well-documented mutant strain known to produce dendrobine-type total alkaloids (DTTAs). It was serendipitously observed that the addition of Co2+ to the medium resulted in a notable enhancement in DTTAs production in the T. longibrachiatum UN32 strain, accompanied by an upregulating effect on the expression of antioxidase-related genes. Hence, the objective of the present work was to ascertain whether ROS (intracellular levels of hydrogen peroxide) induced by Co2+ treatment has a beneficial or detrimental impact on DTTAs biosynthesis. A comparison of the intracellular levels of hydrogen peroxide (H2O2) and DTTAs treated with CoCl2 and CH3COOH revealed that CoCl2 was the optimal inducer for investigating the relationship between ROS formation and DTTAs production. This was due to the observation that ROS formation was reduced by approximately 4% and DTTAs production was increased by 12.55% in comparison to the CH3COOH treatment. The physiological results revealed that the introduction of Co2+ resulted in the oxidative damage and activation of the expression of intracellular superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). Furthermore, it was confirmed that ROS induced by Co2+ was beneficial to DTTAs production by adding exogenous ROS scavengers. The inclusion of all ROS scavengers, including vitamin C, tocopherol, melatonin, mannitol, and sesamol, resulted in a reduction in ROS accumulation and a concomitant decrease in DTTAs production. Specifically, the addition of melatonin at a concentration of 0.4 mg/L demonstrated significant effects, resulting in a 32.53% (P < 0.01) decrease in ROS accumulation and a 45.22% (P < 0.01) reduction in DTTAs production. Subsequently, the timelines of accumulation of intracellular H2O2 and DTTAs content indicated that ROS are also crucial for normal fermentation without CoCl2 addition. Specifically, the proper H2O2 dose for DTTAs accumulation is between 8.82 and 18.86 µmol/g. The present study offers the initial experimental evidence indicating that CoCl2 enhance DTTAs production during the culture of T. longibrachiatum UN32 via leading an increase in intracellular ROS, which is conductive to DTTAs production and can be inhibited by the ROS scavengers. Our results provide insights into the mechanistic study of DTTAs biosynthesis.

Dynamic patterns of gene expressional and regulatory variations in cotton heterosis.

Purpose: Although the application of heterosis has significantly increased crop yield over the past century, the mechanisms underlying this phenomenon still remain obscure. Here, we applied transcriptome sequencing to unravel the impacts of parental expression differences and transcriptomic reprogramming in cotton heterosis. Methods: A high-quality transcriptomic atlas covering 15 developmental stages and tissues was constructed for XZM2, an elite hybrid of upland cotton (Gossypium hirsutum L.), and its parental lines, CRI12 and J8891. This atlas allowed us to identify gene expression differences between the parents and to characterize the transcriptomic reprogramming that occurs in the hybrid. Results: Our analysis revealed abundant gene expression differences between the parents, with pronounced tissue specificity; a total of 1,112 genes exhibited single-parent expression in at least one tissue. It also illuminated transcriptomic reprogramming in the hybrid XZM2, which included both additive and non-additive expression patterns. Coexpression networks between parents and hybrid constructed via weighted gene coexpression network analysis identified modules closely associated with fiber development. In particular, key regulatory hub genes involved in fiber development showed high-parent dominant or over dominant patterns in the hybrid, potentially driving the emergence of heterosis. Finally, high-depth resequencing data was generated and allele-specific expression patterns examined in the hybrid, enabling the dissection of cis- and trans-regulation contributions to the observed expression differences. Conclusion: Parental transcriptional differences and transcriptomic reprogramming in the hybrid, especially the non-additive upregulation of key genes, play an important role in shaping heterosis. Collectively, these findings provide new insights into the molecular basis of heterosis in cotton.

Impacts of parental genomic divergence in non-syntenic regions on cotton heterosis.

INTRODUCTION: Heterosis has revolutionized crop breeding, enhancing global agricultural production. However, the mechanisms underlying heterosis remain obscure. Xiangzamian 2# (XZM2), a super hybrid upland cotton (Gossypium hirsutum L.) characterized by high-yield heterosis, has been developed and extensively planted in China. OBJECTIVES: We conducted a systematic analysis of CRI12 and J8891, two parents of XZM2. We aimed to reveal the precise genetic information and the role of non-syntenic divergence in shaping heterosis, laying a foundation for advancing understanding of heterosis. METHODS: We de novo assembled high-quality genomes of CRI12 and J8891, and further uncovered abundant genetic variations and non-syntenic regions between the parents. Whole-genome comparison, association analysis, transcriptomic analysis and relative identity-by-descent (rIBD) estimation were conducted to identify structural variations (SVs) and introgressions within non-syntenic blocks and to analyze their impacts on promoting heterosis. RESULTS: Parental genetic divergence increased in non-syntenic regions. Furthermore, these regions, accounting for only 16.71% of the total genome, contained more loci with significantly higher heterotic effects, far exceeding the syntenic background. SVs covered 97.26% of non-syntenic sequences and caused widespread gene expression differences in these regions, driving dynamic complementation of gene expression in the hybrid. A set of SVs were responsible for trait improvement and had positive effects on heterosis, contributing larger heritability than short variations. We characterized numerous parental-specific introgressions from G. barbadense. Specifically, a functional introgression segment within non-syntenic blocks introduced an elite haplotype, which significantly increased lint yield and enhanced heterosis. CONCLUSION: Our study clarified non-syntenic regions to harbor more loci with higher heterotic effects, revealed their importance in promoting heterosis and supported the crucial role of genetic complementation in heterosis. SVs and introgressions were identified as key factors responsible for non-syntenic divergence between the parents. They had important effects on gene expression and trait improvement, positively contributing to heterosis.

Variation of mesophyll conductance mediated by nitrogen form is related to changes in cell wall property and chloroplast number.

Plants primarily incorporate nitrate (NO3 -) and ammonium (NH4 +) as the primary source of inorganic nitrogen (N); the physiological mechanisms of photosynthesis (A) dropdown under NH4 + nutrition has been investigated in many studies. Leaf anatomy is a major determinant to mesophyll conductance (g m) and photosynthesis; however, it remains unclear whether the photosynthesis variations of plants exposed to different N forms is related to leaf anatomical variation. In this work, a common shrub, Lonicera japonica was hydroponically grown under NH4 +, NO3 - and 50% NH4 +/NO3 -. We found that leaf N significantly accumulated under NH4 +, whereas the photosynthesis was significantly decreased, which was mainly caused by a reduced g m. The reduced g m under NH4 + was related to the decreased intercellular air space, the reduced chloroplast number and especially the thicker cell walls. Among the cell wall components, lignin and hemicellulose contents under NH4 + nutrition were significantly higher than those in the other two N forms and were scaled negatively correlated with g m; while pectin content was independent from N forms. Pathway analysis further revealed that the cell wall components might indirectly regulate g m by influencing the thickness of the cell wall. These results highlight the importance of leaf anatomical variation characterized by modifications of chloroplasts number and cell wall thickness and compositions, in the regulation of photosynthesis in response to varied N sources.

Examining chronic kidney disease screening frequency among diabetics: a POMDP approach.

Forty percent of diabetics will develop chronic kidney disease (CKD) in their lifetimes. However, as many as 50% of these CKD cases may go undiagnosed. We developed screening recommendations stratified by age and previous test history for individuals with diagnosed diabetes and unknown proteinuria status by race and gender groups. To do this, we used a Partially Observed Markov Decision Process (POMDP) to identify whether a patient should be screened at every three-month interval from ages 30-85. Model inputs were drawn from nationally-representative datasets, the medical literature, and a microsimulation that integrates this information into group-specific disease progression rates. We implement the POMDP solution policy in the microsimulation to understand how this policy may impact health outcomes and generate an easily-implementable, non-belief-based approximate policy for easier clinical interpretability. We found that the status quo policy, which is to screen annually for all ages and races, is suboptimal for maximizing expected discounted future net monetary benefits (NMB). The POMDP policy suggests more frequent screening after age 40 in all race and gender groups, with screenings 2-4 times a year for ages 61-70. Black individuals are recommended for screening more frequently than their White counterparts. This policy would increase NMB from the status quo policy between $1,000 to  $8,000 per diabetic patient at a willingness-to-pay of $150,000 per quality-adjusted life year (QALY).

Determination of Azole Fungicide Residues in Fresh Juice by Magnetic Solid Phase Extraction Based on Fe3O4@ZnAl-LDH@MIL-53(Al) Sorbent in Combination with High-Performance Liquid Chromatograph.

In this work, a magnetic adsorption material based on metal-organic framework (Fe3O4@ZnAl-LDH@MIL-53(Al)) was synthesized and used as an adsorbent in the process of magnetic solid phase extraction. Then, a high-performance liquid chromatograph was used to quantitatively detect triazole fungicides in samples. In order to verify the successful preparation of the material, a series of characterization analyses were carried out. Besides, the key parameters that may affect the extraction efficiency have been optimized, and under optimal conditions the three triazole fungicides showed good linearity in the range of 10-1000 µg/L (R2 ≥ 0.9796); Limit of detections were ranged from 0.013 to 0.030 µg/mL. Finally, the established method was applied to the detection of triazole fungicides in four fresh juice samples. The results showed that the target analyte was not detected in all the test samples. By detecting the recoveries (73.3-104.3%) and coefficient variation (RSD ≤ 6.8%) of triazole fungicides in fortified samples, it proved that this established method meets the requirements of pesticide residue analysis and showed excellent application potential.

UDP-glucosyltransferase 71C4 controls the flux of phenylpropanoid metabolism to shape cotton seed development.

Seeds play a crucial role in plant reproduction, making it essential to identify genes that affect seed development. In this study, we focused on UDP-glucosyltransferase 71C4 (UGT71C4) in cotton, a member of the glycosyltransferase family that shapes seed width and length, thereby influencing seed index and seed cotton yield. Overexpression of UGT71C4 results in seed enlargement owing to its glycosyltransferase activity on flavonoids, which redirects metabolic flux from lignin to flavonoid metabolism. This shift promotes cell proliferation in the ovule via accumulation of flavonoid glycosides, significantly enhancing seed cotton yield and increasing the seed index from 10.66 g to 11.91 g. By contrast, knockout of UGT71C4 leads to smaller seeds through activation of the lignin metabolism pathway and redirection of metabolic flux back to lignin synthesis. This redirection leads to increased ectopic lignin deposition in the ovule, inhibiting ovule growth and development, and alters yield components, increasing the lint percentage from 41.42% to 43.40% and reducing the seed index from 10.66 g to 8.60 g. Our research sheds new light on seed size development and reveals potential pathways for enhancing seed yield.

Xuebijing injection and its bioactive components alleviate nephrotic syndrome by inhibiting podocyte inflammatory injury.

Xuebijing injection (XBJ) is widely used to treat nephrotic syndrome (NS) in clinic, but its bioactive components and therapeutic mechanism are still unclear. In this study, the bioactive components of XBJ were determined by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The therapeutic effect of XBJ on NS was evaluated in BALB/c mice induced by adriamycin (ADR, 10 mg/kg) via a single tail vein. The protective effect of XBJ and its bioactive components on podocytes was demonstrated using mouse podocytes (MPC-5) induced by lipopolysaccharide (LPS, 4 µg/mL). The results show that 33 components of XBJ were identified. Furthermore, 12 bioactive components were detected in blood, including protocatechuic acid, salvianolic acid C, benzoyloxypaeoniflorin, danshensu, salvianolic acid A, salvianolic acid B, catechin, caffeic acid, galloylpaeoniflorin, oxypaeoniflorin, hydroxysafflor yellow A, rosmarinic acid. The relative content (%) of the bioactive components were 59.32, 16.01, 9.97, 9.73, 8.72, 8.31, 7.92, 6.54, 1.54, 1.30, 0.68 and 0.59 in this order. After XBJ treatment, the renal function, hyperlipidemia and renal pathological damage were improved in NS model mice. Moreover, the levels of nephrin and desmin which are functional proteins in podocytes were reversed, and the levels of pro-inflammatory factors were reduced by XBJ. Interestingly, protocatechuic acid and salvianolic acid C also showed good protective effects on podocyte function and reduced the level of inflammation in LPS-induced MPC-5. The study is the first time to elucidate the bioactive components of XBJ and its potential therapeutic mechanism for treating NS by protecting podocyte function.

GHCU, a Molecular Chaperone, Regulates Leaf Curling by Modulating the Distribution of KNGH1 in Cotton.

Leaf shape is considered to be one of the most significant agronomic traits in crop breeding. However, the molecular basis underlying leaf morphogenesis in cotton is still largely unknown. In this study, through genetic mapping and molecular investigation using a natural cotton mutant cu with leaves curling upward, the causal gene GHCU is successfully identified as the key regulator of leaf flattening. Knockout of GHCU or its homolog in cotton and tobacco using CRISPR results in abnormal leaf shape. It is further discovered that GHCU facilitates the transport of the HD protein KNOTTED1-like (KNGH1) from the adaxial to the abaxial domain. Loss of GHCU function restricts KNGH1 to the adaxial epidermal region, leading to lower auxin response levels in the adaxial boundary compared to the abaxial. This spatial asymmetry in auxin distribution produces the upward-curled leaf phenotype of the cu mutant. By analysis of single-cell RNA sequencing and spatiotemporal transcriptomic data, auxin biosynthesis genes are confirmed to be expressed asymmetrically in the adaxial-abaxial epidermal cells. Overall, these findings suggest that GHCU plays a crucial role in the regulation of leaf flattening through facilitating cell-to-cell trafficking of KNGH1 and hence influencing the auxin response level.

A study on the relationship between recreational physical activity and audiovisual difficulty for older adults.

Audiovisual difficulty are especially common in older adults. Audiovisual difficulty seriously affect the quality of life of older adults in their later years. It is a top priority to find out the related factors, and to intervene and prevent them. The purpose of this study was to explore the relationship between recreational physical activities and audiovisual difficulty in older adults. We hope that older adults can reduce the risk of hearing and visual difficulty through scientific physical activity. A total of 4,886 people were sampled from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. Recreational physical activity was assessed through the Global Physical Activity Questionnaire (GPAQ); Hearing and visual difficulty were assessed using the Disability Questionnaire (DLQ). Chi-square test was used for categorical variables and rank sum test was used for measurement variables. P < 0.05 was considered statistically significant (bilateral test). After univariate analysis, binary Logistic regression analysis was performed with recreational physical activity as the independent variable, statistically significant demographic variable as the covariate, and hearing and visual difficulty as the dependent variable, respectively. (1) After excluding all confounding variables, recreational physical activity was significantly associated with hearing difficulty (P < 0.001), odds ratio (OR) 0.657 (95% CI 0.5899-0.733); (2) Recreational physical activity was significantly associated with visual difficulty (P < 0.001), OR 0.731 (95% CI 0.630-0.849). (1) Recreational physical activity is the protective factor of hearing difficulty in older adults; (2) Recreational physical activity is a protective factor for visual difficulty in older adults.

Assessment of the effects of myopic and hyperopic anisometropia on choroidal vascular structure in children using SS-OCTA.

OBJECTIVE: To compare large- and medium-sized choroidal vascularity and the choriocapillaris (CC) flow area in children with different refractive errors using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Forty-two anisometropic children were enrolled and divided into hyperopic anisometropia (HA) and myopic anisometropia (MA) groups. SS-OCTA was performed to analyse choroidal vascularity. Mean choroidal thickness (CT), choroidal vascularity volume (CVV), choroidal vascularity index (CVI) and CC flow area were compared between the two eyes. The inter-ocular differences between the two groups were also determined. RESULTS: Mean CT and CVV were highest in eyes with shorter axial lengths in both refractive groups, and the difference between the two eyes was positively correlated with the difference in axial length at the foveal region. Significant differences in the CVI in the MA group were only found in the parafoveal region. Inter-ocular differences in the CC were significantly reduced in eyes with longer axial lengths in the foveal and parafoveal regions of the HA and MA groups, respectively. Comparing inter-ocular differences, CC was significantly greater in the parafoveal region of the MA group than the HA group. CONCLUSIONS: All layers of choroidal vasculature were thinner in eyes with longer axial lengths in all groups. The inter-ocular CC difference was greater in the MA than in the HA group, with similar differences in axial length. This suggests that both medium-to-large choroidal vascular and choroidal capillaries may play a role in myopia development.

Family Environment and Community Context for Longitudinal Cigarette Smoking Trajectories Among Chinese Young People.

Tobacco use is the leading cause of preventable death, and China accounts for about 30% of worldwide smokers and 40% of global tobacco consumption. This study examines socioeconomic and community disparities in smoking among young Chinese people from 2010 to 2016. Data were from 953 people aged 16 to 25 in four waves of the China Family Panel Studies (CFPS). Two-level logistic regressions were fitted to account for both inter-individual and intra-individual differences over time. Weight-adjusted multilevel regression results showed a decrease in cigarette smoking among rural young people (OR = 0.71, 95% CI = [0.52, 0.98]) from 2010 to 2016. Higher family income was related to higher odds of cigarette smoking among young people (OR = 1.75, 95% CI = [1.10, 2.80]). Cigarette smoking among young people in families with higher incomes increased over time. Policies and interventions targeting the young should consider the socioeconomic disparities and multilevel context.

Perfluoroalkyl-Decorated Noble-Metal-Free MOFs for the Highly Efficient One-Pot Four-Component Coupling between Aldehydes, Amines, Alkynes, and Flue Gas CO2.

The non-noble-metal catalysed-multicomponent reactions between flue gas CO2 and cheap industrial raw stocks into high value-added fine chemicals is a promising manner for the ideal CO2 utilization route. To achieve this, the key fundamental challenge is the rational development of highly efficient and facile reaction pathway while establishing compatible catalytic system. Herein, through the stepwise solvent-assisted linker installation, post-synthetic fluorination and metalation, we report the construction of a series of perfluoroalkyl-decorated noble-metal-free metal-organic frameworks (MOFs) PCN-(BPY-CuI)-(TPDC-Fx ) [BPY=2,2'-bipyridine-5,5'-dicarboxylate, TPDC-NH2 =2'-amino-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid] that can catalyze the one-pot four-component reaction between alkyne, aldehyde, amine and flue gas CO2 for the preparation of 2-oxazolidinones. Such assembly endows the MOFs with superhydrophobic microenvironment, superior water resistance and highly stable catalytic site, leading to 21 times higher turnover numbers than that of homogeneous counterparts. Mechanism investigation implied that the substrates can be efficiently enriched by the MOF wall and then the adsorbed amine species act as an extrinsic binding site towards dilute CO2 through their strong preferential formation to carbamate acid. Moreover, density functional theory calculations suggest the tetrahedral geometry of Cu in MOF offers special resistance towards amine poisoning, thus maintaining its high efficiency during the catalytic process.

The association between different types of physical activity and smoking behavior.

BACKGROUND: Smoking is harmful, which has become a major public health burden. Physical activity may be related to smoking. Physical activity is one of the current methods for smoking control and smoking cessation. Different types of physical activity may have different effect on smoking behavior. OBJECTIVE: The purpose of this study was to identify the direction and extent of the impact of different types of physical activity above moderate intensity (including work physical activity, recreational physical activity, commuter physical activity and sedentary behavior) on smoking behavior. MATERIALS AND METHODS: In this study, a total of 2,015 individuals (1,233 males and 782 females, mean age 54.02±17.31 years) was selected from the representative population aged 20 and above in the National Health and Nutrition Survey of the United States from 2017 to 2018. Physical activity was assessed using the Global Physical Activity Questionnaire (GPAQ) ; the tobacco use questionnaire (SMQ) was used to determine whether the sample had smoking behavior at this stage. Binary Logistic regression analysis was performed with various physical activities as independent variables and smoking behavior as dependent variables. All data were analyzed through Statistical Product and Service Solutions (SPSS) 26.0. RESULTS: After adjusted for all confounding variables, physical activity at work was close to significantly associated with smoking behavior (P=0.053), odds ratio (OR) =1.135 (95%Cl: 0.999-1.289). Recreational physical activity was significantly associated with smoking behavior (P < 0.001), OR=0.729 (95%Cl: 0.639-0.832). Commuting physical activity was significantly associated with smoking behavior (P < 0.001), OR=1.214 (95%Cl:1.048-1.405). Sedentary behavior was significantly associated with smoking behavior (P < 0.001), OR=1.363 (95%Cl: 1.154-1.611). CONCLUSIONS: Given that different types of physical activity have different associations with smoking behavior. Therefore, when physical activity is used as a tobacco control measurement, it is necessary to pay attention to the type and environment of physical activity. Recreational physical activities should be appropriately increased, sedentary behavior should be reduced, and smoking prohibit environment should be expanded as far as possible to achieve better clinical intervention effects.

Choroid vascular changes in hyperopic anisometropia amblyopia using SS-OCTA.

PURPOSE: To observe and understand the structural changes in choroidal vessels in eyes with hyperopic anisometropic amblyopia using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: A total of 44 patients were enrolled in this study: 22 children with hyperopic anisometropic amblyopia and 22 age-matched controls. SS-OCTA was used to scan the 6*6 mm macular area of their eyes. The average choroidal thickness (CT) and choroidal capillary flow area (CC) in a 3 mm diameter area centered on the macular area were obtained. The choroidal vascularity volume (CVV) was automatically extracted and 3D reconstructed by inbuild software, and the three-dimensional choroidal vascularity index (3D-CVI) was calculated. The effect of amblyopia on the choroidal vessel structure was assessed using generalized linear estimating equations (GEEs) corrected for axial length, sex, age, and best-corrected visual acuity. RESULTS: The CC was greater in amblyopic eyes than in fellow eyes (P = 0.014) but was not significantly different from that in control eyes (P = 0.963). After correcting for sex, age, axial length, and visual acuity using GEEs, the mean CT in the amblyopic eyes was greater than that in the fellow eyes (P = 0.030) but was not significantly different from that in the control eyes (P = 0.160). The 3D-CVI in amblyopic eyes was higher than that in control eyes (P = 0.038) but was not significantly different from that in fellow eyes (P = 0.407). The three-dimensional choroidal vascularity volume (3D-CVV) was higher in amblyopic eyes than in fellow eyes (P = 0.046) and control eyes (P = 0.023). CONCLUSIONS: We found that eyes with hyperopic anisometropic amblyopia demonstrated higher CT, CC and 3D-CVV values than the contralateral eyes after correction, while the 3D-CVI was unchanged. Compared with control eyes, amblyopic eyes had higher 3D-CVV and 3D-CVI values but similar CT and CC values. Amblyopic eyes may have different choroidal vascular structures from fellow and control eyes.

Paeoniflorin suppresses kidney inflammation by regulating macrophage polarization via KLF4-mediated mitophagy.

BACKGROUND: Macrophages M1 polarization involved in the process of renal inflammatory injury, is a well-established hallmark of chronic kidney disease (CKD). Paeoniflorin (PF), a water-soluble monoterpene glycoside extracted from Paeonia lactiflora, revealed renal anti-inflammatory activities in our previous study. However, the potential molecular mechanism of PF on CKD remains unknown. PURPOSE: The present study aims to investigate the regulation of PF on macrophage polarization in CKD. METHODS: A CKD model was established by cationic bovine serum albumin and a murine macrophage cell line RAW264.7 induced with lipopolysaccharide (LPS) were used to clarify the underlying mechanisms of PF in CKD. RESULTS: Results showed that PF exhibited favorable protective effects on CKD model mice by promoting renal function, ameliorating renal pathological injury and podocyte damage. Furthermore, PF inhibited the infiltration of M1 macrophage marker CD68 and iNOS in kidney tissue, but increased the proportion of M2 macrophage marker CD206. In RAW264.7 cells stimulated with LPS, the levels of cytokines including IL-6, IL-1ß, TNF-α, MCP-1 were lessened under PF treatment, while the levels of Arg1, Fizz1, IL-10 and Ym-1 were augmented. These results indicated that PF promoted macrophage polarization from M1 to M2 in vivo and in vitro. More importantly, PF repaired the damaged mitochondria through increasing mitochondrial membrane potential and reducing ROS accumulation. The mitophagy-related proteins PINK1, Parkin, Bnip3, P62 and LC3 were up-regulated by PF, accompanied by the incremental expressions of Krüppel-like transcription factor 4 (KLF4). Moreover, the promotion of mitophagy and inhibition of M1 macrophage polarization owing to PF were reversed by mitophagy inhibitor Mdivi-1 or silencing KLF4. CONCLUSION: Overall, PF suppressed renal inflammation by promoting macrophage polarization from M1 to M2 and inducing mitophagy via regulating KLF4. It is expected to provide a new strategy for exploring the effects of PF in treating CKD.

Highly Stretchable and Stimulus-Free Self-Healing Hydrogels with Multiple Signal Detection Performance for Self-Powered Wearable Temperature Sensors.

A flexible wearable temperature sensor is a novel electronic sensor that can monitor real-time changes in human body temperature in a variety of application scenarios and is regarded as the "crown jewel" of information collection technology. Although flexible strain sensors based on hydrogels have excellent self-healing effects and mechanical durability, their widespread application is still limited by external power sources. Herein, a novel self-energizing hydrogel was developed by embellishing cellulose nanocrystals (CNC) with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). The resultant thermoelectrically conductive CNC was then employed as a booster for poly(vinyl alcohol) (PVA)/borax hydrogels. The obtained hydrogels exhibit remarkable self-healing performance (92.57%) and exceptional stretchability (989.60%). Additionally, the hydrogel was capable of accurately and reliably identifying human motion. Most importantly, it exhibits excellent thermoelectric performance, capable of generating stable and reproducible voltages. It shows a large Seebeck coefficient of 1.31 mV k-1 at ambient temperatures. When subjected to a temperature difference of 25 K, the output voltage reaches 31.72 mV. CNC-PEDOT:PSS/PVA conductive hydrogel is multifunctional with self-healing, self-powering, and temperature sensing, which has the potential to be used for the preparation of intelligent wearable temperature-sensing devices.

Real-world dose escalation of biologics for moderate-to-severe psoriasis in the United States.

AIM: To compare real-world dose escalation of risankizumab with other US Food and Drug Administration (FDA)-approved biologic treatments for management of moderate-to-severe psoriasis (PsO) in the United States. METHODS: The Merative® MarketScan® Research Database was used to identify adults with ≥2 medical claims for PsO, ≥3 claims of the index biologic medication in the maintenance period, and ≥6 months continuous enrollment pre-induction and ≥6 months after initiation of the maintenance period. Dose escalation was defined as ≥2 dosing intervals where the average daily dose was ≥30% higher than the expected daily dose (per FDA-approved dosing). Comparisons between risankizumab and other cohorts were made using chi-square tests and logistic regression models. RESULTS: At the 30% threshold, the percentage of patients with dose escalation in the full maintenance period was significantly lower with risankizumab (2.0%) compared with other drug classes (tumor necrosis factor, interleukin (IL)-12/23, IL-17, or other IL-23 inhibitors: 17.6%, 10.0%, 18.3%, or 7.1%, respectively; p < 0.0001 for each) and individual biologics (adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; 17.9%, 10.0%, 15.7%, 18.0%, and 7.2%, respectively; p < 0.0001). CONCLUSION: A significantly lower proportion of risankizumab-treated patients with PsO had dose escalations compared with patients treated with other biologics.