Evaluating imaging repeatability of fully self-service fundus photography within a community-based eye disease screening setting.

PURPOSE: This study aimed to investigate the imaging repeatability of self-service fundus photography compared to traditional fundus photography performed by experienced operators. DESIGN: Prospective cross-sectional study. METHODS: In a community-based eye diseases screening site, we recruited 65 eyes (65 participants) from the resident population of Shanghai, China. All participants were devoid of cataract or any other conditions that could potentially compromise the quality of fundus imaging. Participants were categorized into fully self-service fundus photography or traditional fundus photography group. Image quantitative analysis software was used to extract clinically relevant indicators from the fundus images. Finally, a statistical analysis was performed to depict the imaging repeatability of fully self-service fundus photography. RESULTS: There was no statistical difference in the absolute differences, or the extents of variation of the indicators between the two groups. The extents of variation of all the measurement indicators, with the exception of the optic cup area, were below 10% in both groups. The Bland-Altman plots and multivariate analysis results were consistent with results mentioned above. CONCLUSIONS: The image repeatability of fully self-service fundus photography is comparable to that of traditional fundus photography performed by professionals, demonstrating promise in large-scale eye disease screening programs.

Service Quality and Residents' Preferences for Facilitated Self-Service Fundus Disease Screening: Cross-Sectional Study.

BACKGROUND: Fundus photography is the most important examination in eye disease screening. A facilitated self-service eye screening pattern based on the fully automatic fundus camera was developed in 2022 in Shanghai, China; it may help solve the problem of insufficient human resources in primary health care institutions. However, the service quality and residents' preference for this new pattern are unclear. OBJECTIVE: This study aimed to compare the service quality and residents' preferences between facilitated self-service eye screening and traditional manual screening and to explore the relationships between the screening service's quality and residents' preferences. METHODS: We conducted a cross-sectional study in Shanghai, China. Residents who underwent facilitated self-service fundus disease screening at one of the screening sites were assigned to the exposure group; those who were screened with a traditional fundus camera operated by an optometrist at an adjacent site comprised the control group. The primary outcome was the screening service quality, including effectiveness (image quality and screening efficiency), physiological discomfort, safety, convenience, and trustworthiness. The secondary outcome was the participants' preferences. Differences in service quality and the participants' preferences between the 2 groups were compared using chi-square tests separately. Subgroup analyses for exploring the relationships between the screening service's quality and residents' preference were conducted using generalized logit models. RESULTS: A total of 358 residents enrolled; among them, 176 (49.16%) were included in the exposure group and the remaining 182 (50.84%) in the control group. Residents' basic characteristics were balanced between the 2 groups. There was no significant difference in service quality between the 2 groups (image quality pass rate: P=.79; average screening time: P=.57; no physiological discomfort rate: P=.92; safety rate: P=.78; convenience rate: P=.95; trustworthiness rate: P=.20). However, the proportion of participants who were willing to use the same technology for their next screening was significantly lower in the exposure group than in the control group (P<.001). Subgroup analyses suggest that distrust in the facilitated self-service eye screening might increase the probability of refusal to undergo screening (P=.02). CONCLUSIONS: This study confirms that the facilitated self-service fundus disease screening pattern could achieve good service quality. However, it was difficult to reverse residents' preferences for manual screening in a short period, especially when the original manual service was already excellent. Therefore, the digital transformation of health care must be cautious. We suggest that attention be paid to the residents' individual needs. More efficient man-machine collaboration and personalized health management solutions based on large language models are both needed.

[Pathogenesis of ferroptosis on chronic kidney disease and traditional Chinese medicine intervention: a review].

Chronic kidney disease(CKD) is an insidious disease that has become a significant global public health issue due to its high incidence rate, low awareness, low diagnostic rate, poor prognosis, and high medical costs. Recent studies have shown that CKD development is associated with varying degrees of ferroptosis features. Traditional Chinese medicine(TCM) can regulate iron metabolism, lipid peroxidation, antioxidant systems to inhibit ferroptosis and delay the progression of CKD. Consequently, the intervention mechanism of ferroptosis has become one of the focuses of CKD research. TCM has thousands of years of traditional experience and wisdom. It focuses on the overall regulation of human body functions and can stimulate the body's disease resistance and recovery capabilities, which has certain advantages in treating CKD. However, there is currently a lack of comprehensive articles on the application of TCM in intervening ferroptosis to treat CKD and the pathogenesis of ferroptosis in CKD. Therefore, this article summarizes the latest research progress both domestically and internationally, briefly introduces the main mechanisms of ferroptosis, and systematically reviews the relationship between ferroptosis and CKD. The article integrates TCM theories related to ferroptosis in CKD, including "deficiency" "stasis" "phlegm turbidity" and "toxins" and summarizes the research status of active ingredients and herbal formulas in intervening ferroptosis to treat CKD. By considering ferroptosis from a new perspective, this article aims to provide new targets and directions for the application of TCM in treating CKD.

Genomic analyses provide insights into the polyploidization-driven herbicide adaptation in Leptochloa weeds.

Polyploidy confers a selective advantage under stress conditions; however, whether polyploidization mediates enhanced herbicide adaptation remains largely unknown. Tetraploid Leptochloa chinensis is a notorious weed in the rice ecosystem, causing severe yield loss in rice. In China, L. chinensis has only one sister species, the diploid L. panicea, whose damage is rarely reported. To gain insights into the effects of polyploidization on herbicide adaptation, we first assembled a high-quality genome of L. panicea and identified genome structure variations with L. chinensis. Moreover, we identified herbicide-resistance genes specifically expanded in L. chinensis, which may confer a greater herbicide adaptability in L. chinensis. Analysis of gene retention and loss showed that five herbicide target-site genes and several herbicide nontarget-site resistance gene families were retained during polyploidization. Notably, we identified three pairs of polyploidization-retained genes including LcABCC8, LcCYP76C1 and LcCYP76C4 that may enhance herbicide resistance. More importantly, we found that both copies of LcCYP76C4 were under herbicide selection during the spread of L. chinensis in China. Furthermore, we identified another gene potentially involved in herbicide resistance, LcCYP709B2, which is also retained during polyploidization and under selection. This study provides insights into the genomic basis of the enhanced herbicide adaptability of Leptochloa weeds during polyploidization and provides guidance for the precise and efficient control of polyploidy weeds.

Whole transcriptome analysis resulted in the identification of Chinese sprangletop (Leptochloa chinensis) genes involved in cyhalofop-butyl tolerance.

BACKGROUND: Chinese sprangletop [Leptochloa chinensis (L.) Nees] is an annual malignant weed, which can often be found in paddy fields. Cyhalofop-butyl is a specialized herbicide which is utilized to control L. chinensis. However, in many areas, L. chinensis has become tolerant to this key herbicide due to its continuous long-term use. RESULTS: In this study, we utilized a tolerant (LC18002) and a sensitive (LC17041) L. chinensis populations previously identified in our laboratory, which were divided into four different groups. We then employed whole transcriptome analysis to identify candidate genes which may be involved in cyhalofop-butyl tolerance. This analysis resulted in the identification of six possible candidate genes, including three cytochrome P450 genes and three ATP-binding cassette transporter genes. We then carried out a phylogenetic analysis to identify homologs of the differentially expressed cytochrome P450 genes. This phylogenetic analysis indicated that all genes have close homologs in other species, some of which have been implicated in non-target site resistance (NTSR). CONCLUSIONS: This study is the first to use whole transcriptome analysis to identify herbicide non-target resistance genes in L. chinensis. The differentially expressed genes represent promising targets for better understanding herbicide tolerance in L. chinensis. The six genes belonging to classes already associated in herbicide tolerance may play important roles in the metabolic resistance of L. chinensis to cyhalofop-butyl, although the exact mechanisms require further study.

Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-containing pyrazolo[3,4-b]pyridinones as a new series of AMPKɑ1ß1γ1 activators.

Adenosine monophosphate-activated protein kinase (AMPK) plays a key role in maintaining whole-body homeostasis and has been regarded as a therapeutic target for the treatment of diabetic nephropathy (DN). Herein, a series of 1,2,4-oxadiazole-containing pyrazolo[3,4-b]pyridinone derivatives is reported as AMPKɑ1ß1γ1 activators. The in vitro biological assay demonstrated that compounds 12k (EC50 [AMPKα1γ1ß1] = 180 nM) and 13q (EC50 [AMPKα1γ1ß1] = 2 nM) displayed significant enzyme activation. Mechanism studies indicated that both compounds reduced the levels of reactive oxygen species in a rat kidney fibroblast cell line (NRK-49F) stimulated by transforming growth factor-ß and induced early apoptosis of NRK-49F cells at 10 µM. Molecular docking studies suggested that 13q exhibited critical hydrogen-bond interactions with the critical amino acid residues Lys29, Lys31, Asn111, and Asp88 at the binding site of the AMPK protein. These results enrich the structure pool of AMPK activators and provide novel lead compounds for the subsequent development of compounds with a promising therapeutic potential against DN.

Diversity and bioactivities of fungal endophytes from Distylium chinense, a rare waterlogging tolerant plant endemic to the Three Gorges Reservoir.

BACKGROUND: The present study involves diversity and biological activities of the endophytic fungal community from Distylium chinense, a rare waterlogging tolerant plant endemic to the Three Gorges Reservoir. This study has been conducted hypothesizing that the microbial communities in the TGR area would contribute to the host plant tolerating a range of abiotic stress such as summer flooding, infertility, drought, salinity and soil erosion etc., and they may produce new metabolites, which may possess plentiful bioactive property, especially antioxidant activity. Therefore in the current study, the antioxidant, antimicrobial and anticancer activities of 154 endophytes recovered from D. chinense have been investigated. Furthermore, the active metabolites of the most broad-spectrum bioactive strain have also been studied. RESULTS: A total of 154 fungal endophytes were isolated from roots and stems. They were categorized into 30 morphotypes based on cultural characteristics and were affiliated with 27 different taxa. Among these, the most abundant fungal orders included Diaporthales (34.4%) and Botryosphaeriales (30.5%), which were predominantly represented by the species Phomopsis sp. (24.7%) and Neofusicoccum parvum (23.4%). Fermentation extracts were evaluated, screening for antioxidant, antimicrobial and anticancer activities. Among the 154 isolates tested, 99 (64.3%) displayed significant antioxidant activity, 153 (99.4%) exhibited inclusive antimicrobial activity against at least one tested microorganism and 27 (17.5%) showed exclusive anticancer activity against one or more cancer cell lines. Specifically, the crude extract of Irpex lacteus DR10-1 exhibited note-worthy bioactivities. Further chemical investigation on DR10-1 strain resulted in the isolation and identification of two known bioactive metabolites, indole-3-carboxylic acid (1) and indole-3-carboxaldehyde (2), indicating their potential roles in plant growth promotion and human medicinal value. CONCLUSION: These results indicated that diverse endophytic fungal population inhabits D. chinense. One of the fungal isolate DR10-1 (Irpex lacteus) exhibited significant antioxidant, antimicrobial and anticancer potential. Further, its active secondary metabolites 1 and 2 also showed antioxidant, antimicrobial and anticancer potential.

Synthesis and structure-activity relationships of pyrazolo-[3,4-b]pyridine derivatives as adenosine 5'-monophosphate-activated protein kinase activators.

A series of pyrazolo[3,4-b]pyridine derivatives were designed, synthesized, and evaluated for their activation activity toward adenosine 5'-monophosphate-activated protein kinase (AMPK). According to the enzyme activity, the pyrazole N-H exposure and para substitution on the diphenyl group were proved to be essential for the activation potency. Compound 17f showed equal activation compared with A-769662. In the molecular modeling study, compound 17f exhibited important hydrogen bond interaction with Lys29, Asp88, and Arg83. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays on the NRK-49F cell line showed that potent enzyme activators could effectively inhibit cell proliferation, especially for 17f (EC50 [AMPKα1γ1ß1] = 0.42 µM, efficacy = 79%; IC50 [NRK-49F cell line] = 0.78 µM). These results might provide new insights to explore novel AMPK activators.

Manipulation of the spontaneous parametric down-conversion process in space and frequency domains via wavefront shaping.

The spontaneous parametric down-conversion (SPDC) source of entangled-photon pairs is important for applications in the quantum information process and quantum communication, but suffers from scattering by sample defect and air impurity. Here, we proposed an alternative scheme to manipulate the scattered SPDC process, where only a spatial light modulator was used to control the incident wavefront. The scheme was experimentally tested and also applied on the manipulation of photon pairs through the SPDC process with spectral control. This work proved the feasibility of manipulating nonlinear signals at quantum level with feedback-based wavefront shaping and also indicated applications in long-distance quantum key distribution, quantum communications, and quantum imaging, especially in complex environments.

Adaptive pumping for spectral control of broadband second-harmonic generation.

Second-harmonic generation (SHG) is always a significant frequency conversion process in nonlinear optics for many great applications but can be limited when broadband spectral laser sources are involved, e.g., femtosecond pulses. The conversion efficiency can be high, but the spectral control is hard because of the phase-matching (PM) limitation. Recently, a random quasi-phase-matching (QPM) scheme was proposed to make use of highly nonlinear materials that are difficult to be phase matched under traditional configurations. The spectral control is even harder in anisotropic random materials, and the coherence is completely lost. Here, we proposed an approach to solve this problem by coherent light control via feedback-based wavefront shaping. We utilized this method for spectral control of broadband SHG, which can be efficient even in strongly scattering media. Randomly selected wavelengths in the broadband spectra were enhanced with a good selectivity, and the direction was also controlled in a three-dimensional (3D) configuration. This technique paves the way for convenient spatial and spectral control of both linear and nonlinear emissions and a local enhancement of their conversion efficiency, indicating great progress in both random and ultrafast nonlinear optics.

Second-harmonic focusing by a nonlinear turbid medium via feedback-based wavefront shaping.

Scattering has usually been considered detrimental for optical focusing or imaging. Recently, more and more research has shown that strongly scattering materials can be utilized to focus coherent light by controlling or shaping the incident light. Here, purposeful focusing of second-harmonic waves, which are generated and scattered from nonlinear turbid media via feedback-based wavefront shaping, is presented. This Letter shows a flexible manipulation of both disordered linear and nonlinear scattering signals, indicating more controllable degrees of freedom for the description of turbid media. This technique also provides a possible way to an efficient transmission of nonlinear signal at a desired location in the form of a focal point or other patterns. With the combination of random nonlinear optics and wavefront shaping methods, more interesting applications can be expected in the future, such as nonlinear transmission matrix, multi-frequency imaging, and phase-matching-free nonlinear optics.

Weed biology and management in the multi-omics era: Progress and perspectives.

Weeds pose a significant threat to crop production, resulting in substantial yield reduction. In addition, they possess robust weedy traits that enable them to survive in extreme environments and evade human control. In recent years, the application of multi-omics biotechnologies has helped to reveal the molecular mechanisms underlying these weedy traits. In this review, we systematically describe diverse applications of multi-omics platforms for characterizing key aspects of weed biology, including the origins of weed species, weed classification, and the underlying genetic and molecular bases of important weedy traits such as crop-weed interactions, adaptability to different environments, photoperiodic flowering responses, and herbicide resistance. In addition, we discuss limitations to the application of multi-omics techniques in weed science, particularly compared with their extensive use in model plants and crops. In this regard, we provide a forward-looking perspective on the future application of multi-omics technologies to weed science research. These powerful tools hold great promise for comprehensively and efficiently unraveling the intricate molecular genetic mechanisms that underlie weedy traits. The resulting advances will facilitate the development of sustainable and highly effective weed management strategies, promoting greener practices in agriculture.

RETFound-enhanced community-based fundus disease screening: real-world evidence and decision curve analysis.

Visual impairments and blindness are major public health concerns globally. Effective eye disease screening aided by artificial intelligence (AI) is a promising countermeasure, although it is challenged by practical constraints such as poor image quality in community screening. The recently developed ophthalmic foundation model RETFound has shown higher accuracy in retinal image recognition tasks. This study developed an RETFound-enhanced deep learning (DL) model for multiple-eye disease screening using real-world images from community screenings. Our results revealed that our DL model improved the sensitivity and specificity by over 15% compared with commercial models. Our model also shows better generalisation ability than AI models developed using traditional processes. Additionally, decision curve analysis underscores the higher net benefit of employing our model in both urban and rural settings in China. These findings indicate that the RETFound-enhanced DL model can achieve a higher net benefit in community-based screening, advocating its adoption in low- and middle-income countries to address global eye health challenges.

Influence of cover crops at the four spheres: A review of ecosystem services, potential barriers, and future directions for North America.

Cover crops have been studied for over a century, but the recognition of a complex interaction of cover crop on the Earth's biosphere, lithosphere, hydrosphere, and atmosphere is relatively recent. Furthermore, previously published cover crop research has largely focused on evaluating cover crop impacts on subsequent crop yield. Understanding the cover crop-induced benefits on soil organic carbon (SOC) sequestration, nitrous oxide (N2O) emissions, wind and water erosion, weed control, and soil microbial communities has gained considerable attention in the last few decades, which is crucial to make progress towards developing sustainable agricultural production systems. New research is continuously published to gain a comprehensive understanding of the multiple ecosystem services provided by cover crops. Here, in this review, we aimed to (a) summarize current knowledge related to cover crop impacts on agroecosystem functioning and explore the potential mechanisms responsible for those effects, and (b) identify the key factors limiting the adoption of cover crops into agroecosystems and the conspicuous knowledge gaps in cover crop research. Overall, the review results suggest that cover crops increased subsequent crop yield, increased SOC storage, increased weed suppression, mitigated N2O emissions, reduced wind and water erosion, suppressed plant pathogens, and increased soil microbial activity and wildlife biodiversity. However, the magnitude of benefits observed with cover crops varied with cover crop type, location, and the duration of cover cropping. Notably, cover crop termination methods, designing crop rotations to fit cover crops, additional costs associated with cover crop integration, and uncertainty related to economic returns with cover crops are some of the major barriers limiting the adoption of cover crops into production systems, particularly in North America. In addition to long-term effects, future research on cover crop agronomy, breeding cover crop cultivars, and interactive effects of cover crops with other sustainable land management practices is needed.

Effect of long-term application of bioorganic fertilizer on the soil property and bacteria in rice paddy.

The application of novel bioorganic fertilizer (BIO) has been established as a weed biocontrol strategy, and reduce herbicides pollution and negatively effects on agricultural ecosystems. However, its long-term influences on soil bacterial communities are unknown. Here, 16 S rRNA sequencing to identify the changes that occur in soil bacterial community and enzyme under BIO treatments after five years in a field experiment. BIO application effectively controlled weeds, however no obvious differences between treatments were observed under BIO-50, BIO-100, BIO-200 and BIO-400 treatment. Anaeromyxobacter and Clostridium_ sensu_ stricto_1 were the two dominant genera among BIO-treated soil samples. The BIO-800 treatment had a slight influence on the species diversity index, which was more remarkable after five years. The seven significantly-different genera between BIO-800 treatment and untreated soils included C._sensu_stricto_1, Syntrophorhabdus, Candidatus_Koribacter, Rhodanobacter, Bryobacter, Haliangium, Anaeromyxobacter. In addition, BIO application had different effects on soil enzymatic activities and chemical properties. The extractable P and pH saliency correlated with Haliangium and C._Koribacter, and C._sensu_stricto_1 observably correlated with exchangeable K, hydrolytic N and organic matter. Taken together, our data suggest that BIO application effectively controlled weeds and a slight influence on soil bacterial communities and enzymes. These findings expand our knowledge of the application of BIO as widely used as a sustainable weed control in rice paddy.

Artificial Intelligence in Community-Based Diabetic Retinopathy Telemedicine Screening in Urban China: Cost-effectiveness and Cost-Utility Analyses With Real-world Data.

BACKGROUND: Community-based telemedicine screening for diabetic retinopathy (DR) has been highly recommended worldwide. However, evidence from low- and middle-income countries (LMICs) on the choice between artificial intelligence (AI)-based and manual grading-based telemedicine screening is inadequate for policy making. OBJECTIVE: The aim of this study was to test whether the AI model is more worthwhile than manual grading in community-based telemedicine screening for DR in the context of labor costs in urban China. METHODS: We conducted cost-effectiveness and cost-utility analyses by using decision-analytic Markov models with 30 one-year cycles from a societal perspective to compare the cost, effectiveness, and utility of 2 scenarios in telemedicine screening for DR: manual grading and an AI model. Sensitivity analyses were performed. Real-world data were obtained mainly from the Shanghai Digital Eye Disease Screening Program. The main outcomes were the incremental cost-effectiveness ratio (ICER) and the incremental cost-utility ratio (ICUR). The ICUR thresholds were set as 1 and 3 times the local gross domestic product per capita. RESULTS: The total expected costs for a 65-year-old resident were US $3182.50 and US $3265.40, while the total expected years without blindness were 9.80 years and 9.83 years, and the utilities were 6.748 quality-adjusted life years (QALYs) and 6.753 QALYs in the AI model and manual grading, respectively. The ICER for the AI-assisted model was US $2553.39 per year without blindness, and the ICUR was US $15,216.96 per QALY, which indicated that AI-assisted model was not cost-effective. The sensitivity analysis suggested that if there is an increase in compliance with referrals after the adoption of AI by 7.5%, an increase in on-site screening costs in manual grading by 50%, or a decrease in on-site screening costs in the AI model by 50%, then the AI model could be the dominant strategy. CONCLUSIONS: Our study may provide a reference for policy making in planning community-based telemedicine screening for DR in LMICs. Our findings indicate that unless the referral compliance of patients with suspected DR increases, the adoption of the AI model may not improve the value of telemedicine screening compared to that of manual grading in LMICs. The main reason is that in the context of the low labor costs in LMICs, the direct health care costs saved by replacing manual grading with AI are less, and the screening effectiveness (QALYs and years without blindness) decreases. Our study suggests that the magnitude of the value generated by this technology replacement depends primarily on 2 aspects. The first is the extent of direct health care costs reduced by AI, and the second is the change in health care service utilization caused by AI. Therefore, our research can also provide analytical ideas for other health care sectors in their decision to use AI.

Multi-omics analyses reveal the crosstalk between the circadian clock and the response to herbicide application in Oryza sativa.

Plants have evolved circadian clock systems that enable biological processes to occur in tandem with periodic changes in the environment. However, it is largely unknown whether crosstalk occurs between the circadian clock and the response to herbicide in rice. We identified 19 conserved rhythmic metabolites which were response to pesticide application and their metabolic abundance peaked mainly at ZT2 or ZT14-ZT18. We found a series of glyphosate, s-Metolachlor, fenclorim, metcamifen and GA3 response genes were expressed following stable circadian rhythms. In order to determine the patterns of their temporal expression, co-expression network analysis was done on 10,467 genes that were periodically expressed throughout a 24-hour period. Next, we identified 4,031 potential direct target genes of OsCCA1 in using DAP-seq data for OsCCA1. Of these, 339, 22, 53, 53 and 63 genes showed a response to glyphosate, s-Metolachlor, fenclorim, metcamifen and GA3 application, respectively. And they were mainly phased from dusk to midnight. Interestingly, we identified significant OsCCA1 binding peaks in the promoter regions of four herbicide resistance genes, including OsCYP81A12, OsCYP81E22, OsCYP76C2, and OsCYP76C4. Finally, we found that herbicide application could affects the expression of some of the central oscillator genes of the rice circadian clock. Here, we used multi-omics data to reveal the crosstalk between the circadian clock and herbicide response processes at the epigenomics, transcriptome, and metabolome levels in rice. This work will serve as a theoretical guide for identifying rhythmic herbicide targets, leading to the creation of new herbicides or the breeding of crops resistant to herbicides.

Zuogui-Jiangtang-Yishen decoction prevents diabetic kidney disease: Intervene pyroptosis induced by trimethylamine n-oxide through the mROS-NLRP3 axis.

BACKGROUND: Nowadays, diabetic kidney disease (DKD) has become one of the most threatening to the end-stage renal diseases, and the early prevention of DKD is inevitable for Diabetes Mellitus (DM) patients. AIMS: Pyroptosis, a programmed cell death that mediates renal inflammation induced early renal injury. The trimethylamine n-oxide (TMAO) was also an independent risk factor for renal injury. Here, the associations between TMAO-induced pyroptosis and pathogenesis of DKD were studied, and the potential mechanism of Zuogui-Jiangtang-Yishen (ZGJTYS) decoction to prevent DKD was further investigated. METHOD: Using Goto-Kakizaki (GK) rats to establish the early DKD models. The 16S-ribosomal RNA (16S rRNA) sequencing, fecal fermentation and UPLC-MS targeted metabolism techniques were combined to explore the changes of gut-derived TMAO level under the background of DKD and the effects of ZGJTYS. The proximal convoluted tubule epithelium of human renal cortex (HK-2) cells was adopted to explore the influence of pyroptosis regulated by TMAO. RESULTS: It was demonstrated that ZGJTYS could prevent the progression of DKD by regulating glucolipid metabolism disorder, improving renal function and delaying renal pathological changes. In addition, we illustrated that gut-derived TMAO could promote DKD by activating the mROS-NLRP3 axis to induce pyroptosis. Furthermore, besides interfering with the generation of TMAO through gut microbiota, ZGJTYS inhibited TMAO-induced pyroptosis with a high-glucose environment and the underlying mechanism was related to the regulation of mROS-NLRP3 axis. CONCLUSION: Our results suggested that ZGJTYS inhibited the activation of pyroptosis by gut-derived TMAO via the mROS-NLRP3 axis to prevent DKD.

Potential Choroidal Mechanisms Underlying Atropine's Antimyopic and Rebound Effects: A Mediation Analysis in a Randomized Clinical Trial.

Purpose: To investigate whether choroidal vascularity participates in high-dose atropine's antimyopia and rebound mechanisms. Methods: A mediation analysis was embedded within a randomized controlled trial. In total, 207 myopic children were assigned randomly to group A/B. Participants in group A received 1% atropine weekly (phase 1) and 0.01% atropine daily (phase 2) for 6 months each. Those in group B received 0.01% atropine daily for 1 year. Four plausible intervention mediators were assessed: total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI). Results: In group A, LA, SA, and TCA increased significantly after receiving 1% atropine for 6 months. The increment diminished after tapering to 0.01% atropine. In group B, those parameters remained stable. TCA mediated approximately one-third of 1% atropine's effect on spherical equivalent progression in both phases. In phase 1, the mediation effect of TCA was shared by LA and SA, while only that of LA remained significant in phase 2. No mediation effect of CVI was found. Conclusions: One percent atropine induced choroidal thickening by increasing both LA and SA, while 0.01% atropine had little choroidal response. The choroidal changes following 1% atropine treatment diminished after switching to 0.01% atropine. TCA, but not CVI, partially explains atropine's antimyopic and myopic-rebound mechanisms. SA may serve as a potential biomarker to predict the postrebound treatment efficacy of high-dose atropine. (ClinicalTrials.gov number, NCT03949101.).

Altered microRNA expression profiles in retinas with diabetic retinopathy.

Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to ascertain miRNAs associated with DR. Histopathologically, we observed characteristic features of DR in rats at 10 weeks after STZ injection. Investigation of miRNA expression profiles in the retinas of control and diabetic rats using miRNA microarrays revealed that many miRNAs were abnormally expressed in DR. On the basis of their fold changes and probability values, a total of 37 miRNAs were selected for further validation by real-time PCR analysis. The results showed that 11 miRNAs were significantly upregulated and 6 miRNAs were notably downregulated in DR. Furthermore, these changes in retinal miRNA expression levels paralleled the course of DR. Levels of miR-182, miR-96, miR-183, miR-211, miR-204, and miR-124 were significantly increased during the progress of DR, whereas miR-10b, miR-10a, miR-219-2-3p, miR-144, miR-338, and miR-199a-3p were significantly decreased. Our data indicate that the aberrant miRNA expression profiles in DR are associated with the development of DR. Modulation of retinal miRNA expression levels may provide a potential therapeutic strategy for DRs.