A Deep Learning-Based, Real-Time Image Report System for Linear Endoscopic Ultrasound.

BACKGROUND AND AIMS: The integrity of image acquisition is critical for biliopancreatic Endoscopic Ultrasonography (EUS) reporting, significantly affecting the quality of EUS examinations and disease-related decision-making. However, the quality of EUS reports varies among endoscopists. To address this, we developed a deep learning-based EUS automatic image reporting system (EUS-AIRS), aiming to achieve automatic photodocumentation in real-time during EUS, including capturing standard stations, lesions, and puncture procedures. METHODS: Eight deep learning models trained and tested using 235,784 images were integrated to construct the EUS-AIRS. We tested the performance of EUS-AIRS through man-machine comparison at two levels: retrospective test (include internal and external test), and prospective test. From May 2023 to October 2023, 114 patients undergoing EUS at Renmin Hospital of Wuhan University were consecutively recruited for prospective test. The primary outcome was the completeness of the EUS-AIRS for capturing standard stations. RESULTS: In terms of completeness in capturing biliopancreatic standard stations, EUS-AIRS exceeds the capabilities of endoscopists at all levels of expertise in retrospective internal (90.8% [95%CI 88.7%-92.9%] vs. 70.5% [95%CI 67.2%-73.8%], p<0.001), and external test (91.4% [95%CI 88.4%-94.4%] vs 68.2% [95%CI 63.3%-73.2%], p<0.001). EUS-AIRS demonstrated high accuracy and completeness in capturing standard station images. The completeness significantly outperformed manual endoscopist reports: 91.4% [95%CI, 89.4% - 93.4%] vs. 78.1% [95%CI, 75.1% - 81.0%), p<0.001. CONCLUSIONS: EUS-AIRS exhibits exceptional capabilities in real-time capturing high-quality and high-integrity biliopancreatic EUS images, showcasing the potential of applying an artificial intelligence image reporting system in the EUS field.

Topical hADSCs-HA Gel Promotes Skin Regeneration and Angiogenesis in Pressure Ulcers by Paracrine Activating PPARß/δ Pathway.

Background: Pressure ulcer is common in the bedridden elderly with high mortality and lack of effective treatment. In this study, human-adipose-derived-stem-cells-hyaluronic acid gel (hADSCs-HA gel) was developed and applied topically to treat pressure ulcers, of which efficacy and paracrine mechanisms were investigated through in vivo and in vitro experiments. Methods: Pressure ulcers were established on the backs of C57BL/6 mice and treated topically with hADSCs-HA gel, hADSCs, hyaluronic acid, and normal saline respectively. The rate of wound closure was observed continuously during the following 14 days and the wound samples were obtained for Western blot, histopathology, immunohistochemistry, and proteomic analysis. Human dermal fibroblasts (HDFs) and human venous endothelial cells (HUVECs) under normal or hypoxic conditions were treated with conditioned medium of human ADSCs (ADSC-CM), then CCK-8, scratch test, tube formation, and Western blot were conducted to evaluate the paracrine effects of hADSCs and to explore the underlying mechanism. Results: The in vivo data demonstrated that hADSCs-HA gel significantly accelerated the healing of pressure ulcers by enhancing collagen expression, angiogenesis, and skin proliferation. The in vitro data revealed that hADSCs strengthened the proliferation and wound healing capabilities of HDFs and HUVECs, meanwhile promoted collagen secretion and tube formation through paracrine mode. ADSC-CM was also proved to exert protective effects on hypoxic HDFs and HUVECs. Besides, the results of proteomic analysis and Western blot elucidated that lipid metabolism and PPARß/δ pathway mediated the healing effect of hADSCs-HA gel on pressure ulcers. Conclusion: Our research showed that topical application of hADSCs-HA gel played an important role in dermal regeneration and angiogenesis. Therefore, hADSCs-HA gel exhibited the potential as a novel stem-cell-based therapeutic strategy of treating pressure ulcers in clinical practices.

Possible Mechanism of Sucrose and Trehalose-6-Phosphate in Regulating the Secondary Flower on the Strong Upright Spring Shoots of Blueberry Planted in Greenhouse.

Secondary flowering is the phenomenon in which a tree blooms twice or more times a year. Along with the development of blueberry (Vaccinium corymbosum L.) fruits in spring, a large number of secondary flowers on the strong upright spring shoots were noticed in blueberries planted in the greenhouse. To reveal the cause and possible regulatory mechanism of the phenomenon, we clarified the phenological characteristics of flower bud differentiation and development on the spring shoots by combining phenological phenotype with anatomical observation. Furthermore, the changes in carbohydrates, trehalose-6-phosphate (Tre6P), and the relationship among the key enzyme regulatory genes for Tre6P metabolism and the key regulatory genes for flower formation during the differentiation process of apical buds and axillary buds were investigated. The results showed that the process of flower bud differentiation and flowering of apical and axillary buds was consistent, accompanied by a large amount of carbohydrate consumption. This process was positively correlated with the expression trends of VcTPS1/2, VcSnRK1, VcFT, VcLFY2, VcSPL43, VcAP1, and VcDAM in general, and negatively correlated with that of VcTPP. In addition, there is a certain difference in the differentiation progress of flower buds between the apical and axillary buds. Compared with axillary buds, apical buds had higher contents of sucrose, fructose, glucose, Tre6P, and higher expression levels of VcTPS2, VcFT, VcSPL43, and VcAP1. Moreover, VcTPS1 and VcTPS2 were more closely related to the physiological substances (sucrose and Tre6P) in axillary bud and apical bud differentiation, respectively. It was suggested that sucrose and trehalose-6-phosphate play a crucial role in promoting flower bud differentiation in strong upright spring shoots, and VcTPS1 and VcTPS2 might play a central role in these activities. Our study provided substantial sight for further study on the mechanism of multiple flowering of blueberries and laid a foundation for the regulation and utilization of the phenomenon of multiple flowering in a growing season of perennial woody plants.

High-Efficient Electrochemiluminescence of DNA-Au Ag Nanoclusters with Au NPs@Ti3C2 as a Novel Coreaction Accelerator for Ultrasensitive Biosensing.

In this work, an ultrasensitive electrochemiluminescence (ECL) biosensor was constructed based on DNA-stabilized Au Ag nanoclusters (DNA-Au Ag NCs) as the efficient luminophore and Au NPs@Ti3C2 as a new coreaction accelerator for determining microRNA-221 (miRNA-221) related to liver cancer. Impressively, DNA-Au Ag NCs were stabilized by the high affinity of the periodic 3C sequence, exhibiting an excellent ECL efficiency of 27% compared with classical BSA-Au Ag NCs (16%). Moreover, the Au NPs@Ti3C2 nanocomposites, as a new coreaction accelerator, were first introduced to accelerate the production of abundant sulfate free radicals (SO4•-) for promoting the ECL efficiency of DNA-Au Ag NCs in the DNA-Au Ag NCs/Au NPs@Ti3C2/S2O82- ternary system due to the energy band of Au NPs@Ti3C2 being well-matched with the frontier orbital of S2O82-. Furthermore, the trace target (miRNA-221) could drive the rolling circle amplification to generate an amount of output DNA with periodic 3C and 10A sequences. Through covalent bonds on the surface of poly A and Au NPs, the distance between the luminophor and the coreaction accelerator could be narrowed to further enhance the detection sensitivity. As a result, the constructed sensor has been applied for the ultrasensitive detection of miRNA-221 with a low detection limit of 50 aM and successfully monitored miRNA-221 in MHCC-97L and HeLa cell lysates. This strategy could be utilized for guiding the synthesis of light-emitting DNA-metal NCs, which has great potential in the construction of ultrasensitive biosensors for the early diagnosis of diseases.

Non-coding RNAs in hepatocellular carcinoma metastasis: Remarkable indicators and potential oncogenic mechanism.

Non-coding RNAs (ncRNAs), as key regulators involving in intercellular biological processes, are more prominent in many malignancies, especially for hepatocellular carcinoma (HCC). Herein, we conduct a comprehensive review to summarize diverse ncRNAs roles in HCC metastatic mechanism. We focus on four signaling pathways that predominate in HCC metastatic process, including Wnt/ß-catenin, HIF-1α, IL-6, and TGF-ß pathways. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) employed different mechanisms to participate in the regulation of the key genes in these pathways, typical as interaction with DNA to control transcription, with RNA to control translation, and with protein to control stability. Therefore, ncRNAs may become potential biomarkers and therapeutic targets for HCC metastasis.

Dietary Inulin to Improve SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients: The RIVASTIM-Inulin Randomised Controlled Trial.

Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically inadequate to generate protective immunity. Gut dysbiosis, which is common among kidney transplant recipients and known to effect systemic immunity, may be a contributing factor to a lack of vaccine immunogenicity in this at-risk cohort. The gut microbiota modulates vaccine responses, with the production of immunomodulatory short-chain fatty acids by bacteria such as Bifidobacterium associated with heightened vaccine responses in both observational and experimental studies. As SCFA-producing populations in the gut microbiota are enhanced by diets rich in non-digestible fibre, dietary supplementation with prebiotic fibre emerges as a potential adjuvant strategy to correct dysbiosis and improve vaccine-induced immunity. In a randomised, double-bind, placebo-controlled trial of 72 kidney transplant recipients, we found dietary supplementation with prebiotic inulin for 4 weeks before and after a third SARS-CoV2 mRNA vaccine to be feasible, tolerable, and safe. Inulin supplementation resulted in an increase in gut Bifidobacterium, as determined by 16S RNA sequencing, but did not increase in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third vaccination. Dietary fibre supplementation is a feasible strategy with the potential to enhance vaccine-induced immunity and warrants further investigation.

Neuroprotective effects of anti-TRAIL-ICG nanoagent and its multimodal imaging evaluation in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is a major challenge to neuronal survival in acute ischemic stroke (AIS). However, effective neuroprotective agents remain to be developed for the treatment of CIRI. In this work, we have developed an Anti-TRAIL protein-modified and indocyanine green (ICG)-responsive nanoagent (Anti-TRAIL-ICG) to target ischemic areas and then reduce CIRI and rescue the ischemic penumbra. In vitro and in vivo experiments have demonstrated that the carrier-free nanoagent can enhance drug transport across the blood-brain barrier (BBB) in stroke mice, exhibiting high targeting ability and good biocompatibility. Anti-TRAIL-ICG nanoagent played a better neuroprotective role by reducing apoptosis and ferroptosis, and significantly improved ischemia-reperfusion injury. Moreover, the multimodal imaging platform enables the dynamic in vivo examination of multiple morphofunctional information, so that the dynamic molecular events of nanoagent can be detected continuously and in real time for early treatment in transient middle cerebral artery occlusion (tMCAO) models. Furthermore, it has been found that Anti-TRAIL-ICG has great potential in the functional reconstruction of neurovascular networks through optical coherence tomography angiography (OCTA). Taken together, our work effectively alleviates CIRI after stoke by blocking multiple cell death pathways, which offers an innovative strategy for harnessing the apoptosis and ferroptosis against CIRI.

Effect of γ-tACS on prefrontal hemodynamics in bipolar disorder: A functional near-infrared study.

OBJECTIVES: Transcranial alternating current stimulation (tACS) is a potential therapeutic psychiatric tool that has been shown to modulate clinical symptoms and brain function by inducing brain oscillations. However, direct evidence on the effects of gamma-tACS (γ-tACS) on Bipolar I Disorder (BD-I) is limited. In the present study we used functional near-infrared spectroscopy to explore prefrontal hemodynamic changes in BD-I patients receiving combined γ-tACS intervention in addition to pharmacological treatment. METHODS: Only 39 male patients with BD-I in the acute manic phase were included, and they were randomly divided into an intervention group (n = 18) and a control group (n = 21). The intervention group received γ-tACS treatment on a weekday for a total of 10 sessions in the right prefrontal cortex and left prefrontal cortex. All participants were pretested (baseline) and posttested (2 weeks after) with questionnaires to assess clinical symptoms and cognitive abilities, and with functional near infrared spectroscopy (fNIRS) to assess spontaneous cortical hemodynamic activities. RESULTS: Compared to the control group, the intervention group had greater increases in Montreal Cognitive Assessment (MoCA) scores, and greater decreases in Bech-Rafaelsen Mania Rating Scale (BRMS) scores. In the intervention group, functional connectivity (FC) was significantly greater in the left hemisphere. γ-tACS treatment resulted in a left hemispheric lateralization effect of resting state FC in BD-I patients, increasing the hemodynamic activity of the patient's left prefrontal cortex. CONCLUSIONS: γ-tACS can improve cognitive impairment and mood symptoms with BD-I patients in an acute manic episode by enhancing FC in the patients' left prefrontal cortex.

Assessment of the role of false-positive alerts in computer-aided polyp detection for assistance capabilities.

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

Long-term Intravital Investigation of an Orthotopic Glioma Mouse Model via Optical Coherence Tomography Angiography.

BACKGROUND/AIM: Probing brain tumor microvasculature holds significant importance in both basic cancer research and medical practice for tracking tumor development and assessing treatment outcomes. However, few imaging methods commonly used in clinics can noninvasively monitor the brain microvascular network at high precision and without exogenous contrast agents in vivo. The present study aimed to investigate the characteristics of microvasculature during brain tumor development in an orthotopic glioma mouse model. MATERIALS AND METHODS: An orthotopic glioma mouse model was established by surgical orthotopic implantation of U87-MG-luc cells into the mouse brain. Then, optical coherence tomography angiography (OCTA) was utilized to characterize the microvasculature progression within 14 days. RESULTS: The orthotopic glioma mouse model evaluated by bioluminescence imaging and MRI was successfully generated. As the tumor grew, the microvessels within the tumor area slowly decreased, progressing from the center to the periphery for 14 days. CONCLUSION: This study highlights the potential of OCTA as a useful tool to noninvasively visualize the brain microvascular network at high precision and without any exogenous contrast agents in vivo.

Characteristics and effects on daily lives of pelvic girdle pain during early postpartum in Beijing women, China.

Pelvic girdle pain (PGP) is a common problem during pregnancy and postpartum and negatively affects women's well-being. Yet it is not well known in China. This study assessed PGP's intensity, location, and quality and the status of daily activities on postpartum women with pain, and explored the relationship between pain and the prevalence of depressive symptoms. A cross-sectional study recruiting 1,038 eligible women at 6 weeks postpartum from the obstetric clinic of a hospital was conducted in Beijing, China. Data were collected using self-reported questionnaires, including Introductory information form, Body chart, Number Rating Scale, McGill Pain Questionnaire-2, Pelvic Girdle Questionnaire, and Edinburgh Postnatal Depression Scale. In this study, 32.2 percent women experienced pain. The mean (SD) pain intensity score was 3.07 ± 1.60. About 50.6 percent women experienced sacroiliac joint pain, and 25.5 percent women experienced pain in a combination of locations. About 73.1 percent women experienced aching pain, and 57.5 percent experienced more than one kind of pain quality. The mean total score, which assesses activity and symptom limitations, was 21.93 ± 17.35 (percent), of which a normal sex life (1.29 ± 0.94) was made more challenging due to pain. In mental health, the prevalence of depressive symptoms coincided with the prevalence of pain (p = 0.008). Postpartum PGP still needs to be taken seriously, and women with pain require further support. The above knowledge offers information to manage pain, daily lives and depressive symptoms, contributes to think about strategies to better promote postpartum women physical and mental health in the future.

Regulatory mechanism of the Glabrene against non-small cell lung cancer by suppressing FGFR3.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3. METHODS: HCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9 days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1/2, and p-ERK1/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E-cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E-cadherin, ERK1/2, and p-ERK1/2 were detected via qPCR and Western blot. IGF-1, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA). RESULTS: This study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over-expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF-1, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p-ERK1/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p-ERK1/2 expression, as well as contents of IGF-1, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E-cadherin. CONCLUSION: Glabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial-mesenchymal transition (EMT).

Characterization of the MIKCC-type MADS-box gene family in blueberry and its possible mechanism for regulating flowering in response to the chilling requirement.

MAIN CONCLUSION: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4+7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKCC-type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKCC-type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds.

Intravital photoacoustic brain stimulation with high-precision.

Significance: Neural regulation at high precision vitally contributes to propelling fundamental understanding in the field of neuroscience and providing innovative clinical treatment options. Recently, photoacoustic brain stimulation has emerged as a cutting-edge method for precise neuromodulation and shows great potential for clinical application. Aim: The goal of this perspective is to outline the advancements in photoacoustic brain stimulation in recent years. And, we also provide an outlook delineating several prospective paths through which this burgeoning approach may be substantively refined for augmented capability and wider implementations. Approach: First, the mechanisms of photoacoustic generation as well as the potential mechanisms of photoacoustic brain stimulation are provided and discussed. Then, the state-of-the-art achievements corresponding to this technology are reviewed. Finally, future directions for photoacoustic technology in neuromodulation are provided. Results: Intensive research endeavors have prompted substantial advancements in photoacoustic brain stimulation, illuminating the unique advantages of this modality for noninvasive and high-precision neuromodulation via a nongenetic way. It is envisaged that further technology optimization and randomized prospective clinical trials will enable a wide acceptance of photoacoustic brain stimulation in clinical practice. Conclusions: The innovative practice of photoacoustic technology serves as a multifaceted neuromodulation approach, possessing noninvasive, high-accuracy, and nongenetic characteristics. It has a great potential that could considerably enhance not only the fundamental underpinnings of neuroscience research but also its practical implementations in a clinical setting.

Antagonistic Activity of Streptomyces alfalfae 11F against Fusarium Wilt of Watermelon and Transcriptome Analysis Provides Insights into the Synthesis of Phenazine-1-Carboxamide.

Streptomyces alfalfa strain 11F has inhibitory effects on many phytopathogenic fungi and improves the establishment and biomass yield of switchgrass. However, the antagonistic effects of strain 11F on Fusarium wilt of watermelon and its secondary metabolites that contribute to its biocontrol activity are poorly understood. We evaluated the antagonistic and growth-promoting effects of strain 11F and conducted a transcriptome analysis to identify the metabolites contributing to antifungal activity. Strain 11F had marked inhibitory effects on six fungal pathogens. The incidence of Fusarium wilt of watermelon seedlings was decreased by 46.02%, while watermelon seedling growth was promoted, as indicated by plant height (8.7%), fresh weight (23.1%), and dry weight (60.0%). Clean RNA-sequencing data were annotated with 7553 functional genes. The 2582 differentially expressed genes (DEGs) detected in the Control vs. Case 2 comparison were divided into 42 subcategories of the biological process, cellular component, and molecular function Gene Ontology categories. Seven hundred and forty functional genes (55.47% of the DEGs) were assigned to Kyoto Encyclopedia of Genes and Genomes metabolic pathways, reflecting the complexity of the strain 11F metabolic regulatory system. The expression level of the gene phzF, which encodes an enzyme essential for phenazine-1-carboxylic acid (PCA) synthesis, was downregulated 3.7-fold between the 24 h and 48 h fermentation time points, suggesting that strain 11F can produce phenazine compounds. A phenazine compound from 11F was isolated and identified as phenazine-1-carboxamide (PCN), which contributed to the antagonistic activity against Fusarium oxysporum f. sp. niveum. PCA was speculated to be the synthetic precursor of PCN. The downregulation in phzF expression might be associated with the decrease in PCA accumulation and the increase in PCN synthesis in strain 11F from 24 to 48 h. Streptomyces alfalfae 11F protects watermelon seedlings from Fusarium wilt of watermelon and promotes seedling growth. The transcriptome analysis of strain 11F provides insights into the synthesis of PCN, which has antifungal activity against F. oxysporum f. sp. niveum of watermelon.

Development of an ultrasensitive sandwich immunoassay for detecting small molecule semicarbazide.

Ultrasensitive sandwich immunoassays for detecting the small molecule semicarbazide (SEM) were developed based on derivatization. Several SEM derivatizing agents were synthesized by linking o-nitrobenzaldehyde (NBA) and biotin with dihydroxyalkanes (different lengths), which were then used to evaluate the distance effect of two epitopes. Sandwich ELISA for SEM derivatives was developed using an anti-SEM-NBA antibody and horseradish peroxidase-labeled avidin or anti-biotin antibody as a secondary conjugate. The advantageous distances of the two epitopes under the double-antibody sandwich and antibody-avidin sandwich modes were ≥12 and ≥13 Å, respectively. Under the distances, the sensitivities of the sandwich ELISA were no lower than those of competitive ELISA. The obtained optimal EC50 values were 11.2 pg/mL (double-antibody sandwich with the epitope distance ≥16 Å) and 7.3 pg/mL (antibody-avidin sandwich with the epitope distance ≥17 Å). Compared with competitive ELISA, the developed method achieved a 30-fold improvement in sensitivity, with simpler aquatic product pretreatment.

Evaluation of a computer-aided diagnostic model for corneal diseases by analyzing in vivo confocal microscopy images.

Objective: In order to automatically and rapidly recognize the layers of corneal images using in vivo confocal microscopy (IVCM) and classify them into normal and abnormal images, a computer-aided diagnostic model was developed and tested based on deep learning to reduce physicians' workload. Methods: A total of 19,612 corneal images were retrospectively collected from 423 patients who underwent IVCM between January 2021 and August 2022 from Renmin Hospital of Wuhan University (Wuhan, China) and Zhongnan Hospital of Wuhan University (Wuhan, China). Images were then reviewed and categorized by three corneal specialists before training and testing the models, including the layer recognition model (epithelium, bowman's membrane, stroma, and endothelium) and diagnostic model, to identify the layers of corneal images and distinguish normal images from abnormal images. Totally, 580 database-independent IVCM images were used in a human-machine competition to assess the speed and accuracy of image recognition by 4 ophthalmologists and artificial intelligence (AI). To evaluate the efficacy of the model, 8 trainees were employed to recognize these 580 images both with and without model assistance, and the results of the two evaluations were analyzed to explore the effects of model assistance. Results: The accuracy of the model reached 0.914, 0.957, 0.967, and 0.950 for the recognition of 4 layers of epithelium, bowman's membrane, stroma, and endothelium in the internal test dataset, respectively, and it was 0.961, 0.932, 0.945, and 0.959 for the recognition of normal/abnormal images at each layer, respectively. In the external test dataset, the accuracy of the recognition of corneal layers was 0.960, 0.965, 0.966, and 0.964, respectively, and the accuracy of normal/abnormal image recognition was 0.983, 0.972, 0.940, and 0.982, respectively. In the human-machine competition, the model achieved an accuracy of 0.929, which was similar to that of specialists and higher than that of senior physicians, and the recognition speed was 237 times faster than that of specialists. With model assistance, the accuracy of trainees increased from 0.712 to 0.886. Conclusion: A computer-aided diagnostic model was developed for IVCM images based on deep learning, which rapidly recognized the layers of corneal images and classified them as normal and abnormal. This model can increase the efficacy of clinical diagnosis and assist physicians in training and learning for clinical purposes.

Short-chain fatty acids directly exert anti-inflammatory responses in podocytes and tubular epithelial cells exposed to high glucose.

Aims: Gut-microbiome derived short-chain fatty acids exert anti-inflammatory effects and delay progression of kidney disease in diabetic nephropathy. The aim of this study was to examine the impact in vivo and in vitro of short-chain fatty acid treatment on cellular pathways involved in the development of experimental diabetic nephropathy. Methods: To determine the effect of short-chain fatty acids in diabetic nephropathy, we compared wildtype, GPR43-/- and GPR109A-/- mice diabetic mice treated with acetate or butyrate and assessed variables of kidney damage. We also examined the impact of short-chain fatty acid treatment on gene expression in renal tubular cells and podocytes under high glucose conditions. Results: Short-chain fatty acid treatment with acetate or butyrate protected wild-type mice against development of diabetic nephropathy, exhibiting less glomerular hypertrophy, hypercellularity and interstitial fibrosis compared to diabetic controls. Acetate and butyrate treatment did not provide the same degree of protection in diabetic GPR43-/- and GPR109A-/- diabetic mice respectively. Consistent with our in vivo results, expression of pro-inflammatory genes in tubular epithelial cells exposed to high glucose were attenuated by acetate and butyrate treatment. Acetate did not reduce inflammatory or fibrotic responses in glucose stimulated GPR43-/- TECs. Butyrate mediated inhibition of pro-fibrotic gene expression in TECs through GPR109A, and in podocytes via GPR43. Conclusion: SCFAs protect against progression of diabetic nephropathy and diminish podocyte and tubular epithelial injury and interstitial fibrosis via direct, GPR-pathway dependent effects on intrinsic kidney cells. GPR43 and GPR109A are critical to short-chain fatty acid mediated reno-protection and have potential to be harnessed as a therapeutic target in diabetic nephropathy.

Classification of normal and abnormal fetal heart ultrasound images and identification of ventricular septal defects based on deep learning.

OBJECTIVES: Congenital heart defects (CHDs) are the most common birth defects. Recently, artificial intelligence (AI) was used to assist in CHD diagnosis. No comparison has been made among the various types of algorithms that can assist in the prenatal diagnosis. METHODS: Normal and abnormal fetal ultrasound heart images, including five standard views, were collected according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Practice guidelines. You Only Look Once version 5 (YOLOv5) models were trained and tested. An excellent model was screened out after comparing YOLOv5 with other classic detection methods. RESULTS: On the training set, YOLOv5n performed slightly better than the others. On the validation set, YOLOv5n attained the highest overall accuracy (90.67 %). On the CHD test set, YOLOv5n, which only needed 0.007 s to recognize each image, had the highest overall accuracy (82.93 %), and YOLOv5l achieved the best accuracy on the abnormal dataset (71.93 %). On the VSD test set, YOLOv5l had the best performance, with a 92.79 % overall accuracy rate and 92.59 % accuracy on the abnormal dataset. The YOLOv5 models achieved better performance than the Fast region-based convolutional neural network (RCNN) & ResNet50 model and the Fast RCNN & MobileNetv2 model on the CHD test set (p<0.05) and VSD test set (p<0.01). CONCLUSIONS: YOLOv5 models are able to accurately distinguish normal and abnormal fetal heart ultrasound images, especially with respect to the identification of VSD, which have the potential to assist ultrasound in prenatal diagnosis.

Relationships between circulating metabolites and facial skin aging: a Mendelian randomization study.

BACKGROUND: Blood metabolites are important to various aspects of our health. However, currently, there is little evidence about the role of circulating metabolites in the process of skin aging. OBJECTIVES: To examine the potential effects of circulating metabolites on the process of skin aging. METHOD: In the primary analyses, we applied several MR methods to study the associations between 249 metabolites and facial skin aging risk. In the secondary analyses, we replicated the analyses with another array of datasets including 123 metabolites. MR Bayesian model averaging (MR-BMA) method was further used to prioritize the metabolites for the identification of predominant metabolites that are associated with skin aging. RESULTS: In the primary analyses, only the unsaturation degree of fatty acids was found significantly associated with skin aging with the IVW method after multiple testing (odds ratio = 1.084, 95% confidence interval = 1.049-1.120, p = 1.737 × 10-06). Additionally, 11 out of 17 unsaturation-related biomarkers showed a significant or suggestively significant causal effect [p < 0.05 and > 2 × 10-4 (0.05/249 metabolites)]. In the secondary analyses, seven metabolic biomarkers were found significantly associated with skin aging [p < 4 × 10-4 (0.05/123)], while six of them were related to the unsaturation degree. MR-BMA method validated that the unsaturation degree of fatty acids plays a dominant role in facial skin aging. CONCLUSIONS: Our study used systemic MR analyses and provided a comprehensive atlas for the associations between circulating metabolites and the risk of facial skin aging. Genetically proxied unsaturation degree of fatty acids was highlighted as a dominant factor correlated with the risk of facial skin aging.