γ-aminobutyric acid treatment inhibits browning and promotes storage quality by regulating reactive oxygen species and membrane lipid metabolism in fresh-cut stem lettuce.

The effects of γ-aminobutyric (GABA) on enzymatic browning, storage quality, membrane and reactive oxygen species (ROS) metabolism in fresh-cut stem lettuce were investigated. The results illustrated that GABA treatment delayed browning degree, polyphenol oxidase (PPO) activity and the expression of LsPPO. Meanwhile, higher chlorophyll and ascorbic acid contents were exhibited in GABA-treated stem lettuce, as well as the slower microbial propagation. Further investigation revealed that exogenous GABA application declined malondialdehyde content, electrolyte leakage and the enzyme activities of membrane metabolism, and the expression levels of related genes were also downregulated. In addition, GABA treatment scavenged ROS and strengthened the enzyme activities of ROS metabolism, as well as the expression levels of corresponding genes. Taken together, these findings implied that the repressed enzymatic browning and microbial propagation in GABA-treated stem lettuce were due to the inhibition of ROS accumulation, enhancement of membrane stability and increased resistance to oxidation.

Corrigendum: Glutamatergic and GABAergic neurons in the preoptic area of the hypothalamus play key roles in menopausal hot flashes.

[This corrects the article DOI: 10.3389/fnagi.2022.993955.].

Development and biological evaluation of 68Ga-labeled peptides for potential application in HER2-positive colorectal cancer.

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world. Human epidermal growth factor receptor 2 (HER2) is a promising target for the diagnosis and treatment of CRC. In this study, we aimed to design, synthesize and label peptide-based positron emission tomography (PET) tracers targeting HER2-positive CRC, namely [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02. The results show that [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [68Ga]Ga-ES-02 demonstrated higher binding affinity (Kd = 24.29 ± 4.95 nM) toward the HER2 in CRC. In HER2-positive HT-29 CRC xenograft mouse model, PET study showed specific tumor uptake after injection of [68Ga]Ga-ES-02 (SUV15min max = 0.87 ± 0.03; SUV30min max = 0.64 ± 0.02). In biodistribution study, the T/M ratios of 68Ga-ES-02 at 30 min after injection reached a maximum of 4.07 ± 0.34. In summary, we successfully synthesized and evaluated two novel peptide-based PET tracers. Our data demonstrate that [68Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [68Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.

Prediction of Freezing of Gait in Parkinson's disease based on multi-channel time-series neural network.

Freezing of Gait (FOG) is a noticeable symptom of Parkinson's disease, like being stuck in place and increasing the risk of falls. The wearable multi-channel sensor system is an efficient method to predict and monitor the FOG, thus warning the wearer to avoid falls and improving the quality of life. However, the existing approaches for the prediction of FOG mainly focus on a single sensor system and cannot handle the interference between multi-channel wearable sensors. Hence, we propose a novel multi-channel time-series neural network (MCT-Net) approach to merge multi-channel gait features into a comprehensive prediction framework, alerting patients to FOG symptoms in advance. Owing to the causal distributed convolution, MCT-Net is a real-time method available to give optimal prediction earlier and implemented in remote devices. Moreover, intra-channel and inter-channel transformers of MCT-Net extract and integrate different sensor position features into a unified deep learning model. Compared with four other state-of-the-art FOG prediction baselines, the proposed MCT-Net obtains 96.21% in accuracy and 80.46% in F1-score on average 2 s before FOG occurrence, demonstrating the superiority of MCT-Net.

Single-cell hdWGCNA reveals metastatic protective macrophages and development of deep learning model in uveal melanoma.

BACKGROUND: Although there has been some progress in the treatment of primary uveal melanoma (UVM), distant metastasis remains the leading cause of death in patients. Monitoring, staging, and treatment of metastatic disease have not yet reached consensus. Although more than half of metastatic tumors (62%) are diagnosed within five years after primary tumor treatment, the remainder are only detected in the following 25 years. The mechanisms of UVM metastasis and its impact on prognosis are not yet fully understood. METHODS: scRNA-seq data of UVM samples were obtained and processed, followed by cell type identification and characterization of macrophage subpopulations. High-dimensional weighted gene co-expression network analysis (HdWGCNA) was performed to identify key gene modules associated with metastatic protective macrophages (MPMφ) in primary samples, and functional analyses were conducted. Non-negative matrix factorization (NMF) clustering and immune cell infiltration analyses were performed using the MPMφ gene signatures. Machine learning models were developed using the identified metastatic protective macrophages related genes (MPMRGs) to distinguish primary from metastatic patients. A deep learning convolutional neural network (CNN) model was constructed based on MPMRGs and cell type associations. Lastly, a prognostic model was established using the MPMRGs and validated in independent cohorts. RESULTS: Single-cell RNA-seq analysis revealed a unique immune microenvironment landscape in primary samples compared to metastatic samples, with an enrichment of macrophage cells. Using HdWGCNA, MPMφ and marker genes were identified. Functional analysis showed an enrichment of genes related to antigen processing progress and immune response. Machine learning and deep learning models based on key genes showed significant effectiveness in distinguishing between primary and metastatic patients. The prognostic model based on key genes demonstrated substantial predictive value for the survival of UVM patients. CONCLUSION: Our study identified key macrophage subpopulations related to metastatic samples, which have a profound impact on shaping the tumor immune microenvironment. A prognostic model based on macrophage cell genes can be used to predict the prognosis of UVM patients.

FOXP4 is a Direct YAP1 Target that Promotes Gastric Cancer Stemness and Drives Metastasis.

The Hippo-YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo-YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer (GC). As the Hippo-YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it. Here, we identified a vital role of FOXP4 in YAP1-driven gastric carcinogenesis by maintaining stemness and promoting peritoneal metastasis. Loss of FOXP4 impaired GC spheroid formation and reduced stemness marker expression, while FOXP4 upregulation potentiated cancer cell stemness. RNA-seq analysis revealed SOX12 as downstream target of FOXP4, and functional studies established that SOX12 supports stemness in YAP1-induced carcinogenesis. A small molecule screen identified 42-(2-Tetrazolyl)rapamycin as a FOXP4 inhibitor, and targeting FOXP4 suppressed GC tumor growth and enhanced the efficacy of 5-FU chemotherapy in vivo. Collectively, these findings revealed that FOXP4 upregulation by YAP1 in GC regulates stemness and tumorigenesis by upregulating SOX12. Targeting the YAP1-FOXP4-SOX12 axis represents a potential therapeutic strategy for GC.

Exposures to particulate matters and childhood sleep disorders-A large study in three provinces in China.

OBJECTIVES: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter <2.5 µm and <1 µm, respectively) with sleep disorders in children. METHODS: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM2.5 and PM1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments. RESULTS: Long-term PM2.5 and PM1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM2.5 and PM1 per 10 µg/m3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM1 were found than that of PM2.5 in southeast region. CONCLUSION: Long-term PM2.5 and PM1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region.

Lignin-derivable alternatives to bisphenol A with potentially undetectable estrogenic activity and minimal developmental toxicity.

Lignin-derivable bisguaiacols/bissyringols are viable alternatives to commercial bisphenols; however, many bisguaiacols/bissyringols (e.g., bisguaiacol F [BGF]) have unsubstituted bridging carbons between the aromatic rings, making them more structurally similar to bisphenol F (BPF) than bisphenol A (BPA) - both of which are suspected endocrine disruptors. Herein, we investigated the estrogenic activity (EA) and developmental toxicity of dimethyl-substituted bridging carbon-based lignin-derivable bisphenols (bisguaiacol A [BGA] and bissyringol A [BSA]). Notably, BSA showed undetectable EA at seven test concentrations (from 10-12 M to 10-6 M) in the MCF-7 cell proliferation assay, whereas BPA had detectable EA at five concentrations (from 10-10 M to 10-6 M). In silico results indicated that BSA had the lowest binding affinity with estrogen receptors. Moreover, in vivo chicken embryonic assay results revealed that lignin-derivable monomers had minimal developmental toxicity vs. BPA at environmentally relevant test concentrations (8.7-116 µg/kg). Additionally, all lignin-derivable compounds showed significantly lower expression fold changes (from ∼1.81 to ∼4.41) in chicken fetal liver tests for an estrogen-response gene (apolipoprotein II) in comparison to BPA (fold change of ∼11.51), which was indicative of significantly reduced estrogenic response. Altogether, the methoxy substituents on lignin-derivable bisphenols appeared to be a positive factor in reducing the EA of BPA alternatives.

Role of microRNAs in pituitary gonadotrope cells.

The gonadotrope cells within the pituitary control vital processes of reproduction by producing follicle stimulating hormone (FSH) and luteinizing hormone (LH). Both external stimuli and internal regulatory factors contribute to the regulation of gonadotrope development and function. In recent years, growing evidences indicate that microRNAs (miRNAs), which regulate gene expression post-transcriptionally, play critical roles in multiple processes of gonadotrope development and function, including the syntheses of α or ß subunits of FSH and LH, the secretion of LH, the regulation of GnRH signaling, and the maintenance of gonadotrope cell kinetics. Here, we review recent advances of miRNAs' expression, functions and mechanisms approached by using miRNA knockout mouse models, in silico analysis and the in vitro cultures of primary pituitary cells and gonadotrope-derived cell lines. By summarizing and discussing different roles of miRNAs in gonadotropes, this minireview helps to gain insights into the complex molecular network in gonadotropes and reproduction.

Exogenous CaCl2 reduces the oxidative cleavage of carotenoids in shredded carrots by targeting CAMTA4-mediated transcriptional repression of carotenoid degradation pathway.

Carotenoid oxidative cleavage is a significant factor contributing to the color changes of shredded carrots and treatment with calcium chloride (CaCl2, 1% w/v) has been observed to alleviate the whitening symptom and color loss. However, the specific mechanism by which CaCl2 treatment suppresses carotenoid degradation remains unclear. In this study, the effect of CaCl2 and EGTA (calcium ion chelating agent) treatment on carotenoid biosynthesis and degradation in shredded carrots and the mechanism involved was investigated. CaCl2 treatment promoted the expression and activity of carotenoid biosynthetic enzyme (phytoene synthase, PSY), but inhibited the increases of the degradative enzyme activity of carotenoid cleavage dioxygenase (CCD) and down-regulated the corresponding transcripts, thus delayed the degradation of total carotenoid and maintaining higher levels of major carotenoid compounds including ß-carotene, α-carotene, lycopene, and lutein in shredded carrots during storage. However, EGTA treatment promoted the gene expression and enzyme activity of CCD and increased the degradation of carotenoid compounds in shredded carrots during storage. Furthermore, the CaCl2 treatment induced DcCAMTA4, identified as a calcium decoder in shredded carrots, which, in turn, suppressed the expressions of DcCCD1 and DcCCD4 by interacting with their promoters. The transient overexpression of DcCAMTA4 in tobacco leaves led to reduced expression of NtCCD1 and NtCCD4, maintaining a higher content of carotenoids. Thus, CaCl2 alleviated the oxidative cleavage of carotenoids in shredded carrots through the DcCAMTA4-mediated carotenoid degradation pathway.

A sensing label or gel loaded with an NIR emission fluorescence probe for ultra-fast detection of volatile amine and fish freshness.

A simple benzopyran-based fluorescence probe DCA-Apa detection of volatile amine has been synthesized. DCA-Apa can recognize volatile amines by dual channel mode (changing from blue to light yellow in sunlight, and from weak pink to orange under 365 nm) in pure water system. DCA-Apa has the advantages of ultra-fast response (∼6 s), NIR emission (655 nm), and a good fluorescence response for many amines. The sensing label or gel loaded with DCA-Apa was prepared by the dipping or mixing method using filter paper or gelatin as solid carriers, which can identify volatile amine vapor and monitor the freshness of salmon by colorimetric and fluorescent dual channels. When the color of the label changes to light yellow-green or the fluorescence of the label becomes orange fluorescence (365 nm UV lamp), it indicates that the fish has rotted. The two-channel method makes up for the deficiency of the single colorimetric method, and establishes a theoretical foundation for more precise assessment of fish freshness.

Caspase-8 promotes NLRP3 inflammasome activation mediates eye development defects in zebrafish larvae exposed to perfulorooctane sulfonate (PFOS).

Epidemiological evidence showed that serum high perfluorooctane sulfonate (PFOS) levels are associated with multiple eye related diseases, but the potential underlying molecular mechanisms remain poorly understood. Zebrafish and photoreceptor cell (661w) models were used to investigate the molecular mechanism of PFOS induced eye development defects. Our results showed a novel molecular mechanism of PFOS-induced inflammation response-mediated photoreceptor cell death associated with eye development defects. Inhibition of Caspase-8 activation significantly decreased photoreceptor cell death in PFOS exposure. Mechanistically, Toll-like receptor 4 (TLR4) mediates activation of Caspase-8 promote activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome to elicit maturation of interleukin-1 beta (IL-1ß) via Caspase-1 activation, facilitating photoreceptor cell inflammation damage in PFOS exposure. In addition, we also made a novel finding that Caspase-3 activation was increased via Caspase-8 activation and directly intensified cell death. Our results show the important role of Caspase-8 activation in PFOS induced eye development defects and highlight Caspase-8 mediated activation of the NLRP3 inflammation triggers activation of Caspase-1 and promote the maturation of IL-1ß in retinal inflammatory injury.

Prediction of Visual Outcome After Rhegmatogenous Retinal Detachment Surgery Using Artificial Intelligence Techniques.

Purpose: This study aimed to develop artificial intelligence models for predicting postoperative functional outcomes in patients with rhegmatogenous retinal detachment (RRD). Methods: A retrospective review and data extraction were conducted on 184 patients diagnosed with RRD who underwent pars plana vitrectomy (PPV) and gas tamponade. The primary outcome was the best-corrected visual acuity (BCVA) at three months after the surgery. Those with a BCVA of less than 6/18 Snellen acuity were classified into a vision impairment group. A deep learning model was developed using presurgical predictors, including ultra-widefield fundus images, structural optical coherence tomography (OCT) images of the macular region, age, gender, and preoperative BCVA. A fusion method was used to capture the interaction between different modalities during model construction. Results: Among the participants, 74 (40%) still had vision impairment after the treatment. There were significant differences in age, gender, presurgical BCVA, intraocular pressure, macular detachment, and extension of retinal detachment between the vision impairment and vision non-impairment groups. The multimodal fusion model achieved a mean area under the curve (AUC) of 0.91, with a mean accuracy of 0.86, sensitivity of 0.94, and specificity of 0.80. Heatmaps revealed that the macular involvement was the most active area, as observed in both the OCT and ultra-widefield images. Conclusions: This pilot study demonstrates that artificial intelligence techniques can achieve a high AUC for predicting functional outcomes after RRD surgery, even with a small sample size. Machine learning methods identified The macular region as the most active region. Translational Relevance: Multimodal fusion models have the potential to assist clinicians in predicting postoperative visual outcomes prior to undergoing PPV.

Taurine Alleviates Experimental Colitis by Enhancing Intestinal Barrier Function and Inhibiting Inflammatory Response through TLR4/NF-κB Signaling.

Taurine (Tau) is a semiessential amino acid in mammals with preventive and therapeutic effects on several intestinal disorders. However, the exact function of taurine in ulcerative colitis (UC) is still largely unclear. In this study, we used two taurine-deficient mouse models (CSAD-/- and TauT-/- mice) to explore the influence of taurine on the progression of UC in both dextran sulfate sodium (DSS)-induced colitis and LPS-stimulated Caco-2 cells. We found that cysteine sulfinic acid decarboxylase (CSAD) and taurine transporter (TauT) expressions and taurine levels were markedly reduced in colonic tissues of mice treated with DSS. The CSAD and TauT knockouts exacerbated DSS-induced clinical symptoms and pathological damage and aggravated the intestinal barrier dysfunction and the colonic mucosal inflammatory response. Conversely, taurine pretreatment enhanced the intestinal barrier functions by increasing goblet cells and upregulating tight junction protein expression. Importantly, taurine bound with TLR4 and inhibited the TLR4/NF-κB pathway, ultimately reducing proinflammatory factors (TNF-α and IL-6) and oxidative stress. Our findings highlight the essential role of taurine in maintaining the intestinal barrier integrity and inhibiting intestinal inflammation, indicating that taurine is a promising supplement for colitis treatment.

Phosphatidylinositol-specific phospholipase C-associated phospholipid metabolism mediates DcGLRs channel to promote calcium influx under CaCl2 treatment in shredded carrots during storage.

The rapid activation of phosphatidylinositol-specific phospholipase C (PI-PLC) occurs early after the stimulation of biotic and abiotic stress in plants, which directly associated with the calcium channel-induced calcium ion (Ca2+) influx. Exogenous calcium chloride (CaCl2) mediates the calcium signaling transduction to promote the γ-aminobutyric acid accumulation and nutritional quality in shredded carrots whereas the generation mechanism remains uncertain. Therefore, the involvement of PI-PLC-associated phospholipid metabolism was investigated in present study. Our result revealed that CaCl2 treatment promoted the expression and activity of PI-PLC and increased the inositol 1,4,5-trisphosphate and hexakisphosphate content in shredded carrots. The transcripts of multi-glutamate receptor-like channels (DcGLRs), the glutamate and γ-aminobutyric acid (GABA) content, and Ca2+ influx were induced by CaCl2 treatment in shredded carrots during storage. However, PI-PLC inhibitor (U73122) treatment inhibited the activation of PI-PLC, the increase of many DcGLRs family genes expression levels, and Ca2+ influx. Moreover, the identification of DcPI-PLC4/6 and DcGLRs proteins, along with the analysis of characteristic domains such as PLCXc, PLCYc, C2 domain, transmembranous regions, and ligand binding domain, suggests their involvement in phospholipid catalysis and calcium transport in carrots. Furthermore, DcPI-PLC4/6 overexpression in tobacco leaves induced the Ca2+ influx by activating the expressions of NtGLRs and the accumulation of glutamate and GABA. These findings collectively indicate that CaCl2 treatment-induced PI-PLC activation influences DcGLRs expression levels to mediate cytosolic Ca2+ influx, thus, highlighting the "PI-PLC-GLRs-Ca2+" pathway in calcium signaling generation and GABA biosynthesis in shredded carrots.

Oxidative stress plays an important role in the central regulatory mechanism of orofacial hyperalgesia under low estrogen conditions.

Hyperalgesia occurs in the orofacial region of rats when estrogen levels are low, although the specific mechanism needs to be investigated further. Furthermore, oxidative stress plays an important role in the transmission of pain signals. This study aimed to explore the role of oxidative stress in orofacial hyperalgesia under low estrogen conditions. We firstly found an imbalance between oxidative and antioxidant capacity within the spinal trigeminal subnucleus caudalis (SP5C) of rats after ovariectomy (OVX), resulting in oxidative stress and then a decrease in the orofacial pain threshold. To investigate the mechanism by which oxidative stress occurs, we used virus as a tool to silence or overexpress the excitatory amino acid transporter 3 (EAAT3) gene. Further investigation revealed that the regulation of glutathione (GSH) and reactive oxygen species (ROS) can be achieved by regulating EAAT3, which in turn impacts the occurrence of oxidative stress. In summary, our findings suggest that reduced expression of EAAT3 within the SP5C of rats in the low estrogen state may decrease GSH content and increase ROS levels, resulting in oxidative stress and ultimately lead to orofacial hyperalgesia. This suggests that antioxidants could be a potential therapeutic direction for orofacial hyperalgesia under low estrogen conditions, though more research is needed to understand its mechanism.

The effect of duration between sessions on microperimetric biofeedback training in patients with maculopathies.

Aim of this study was to explore the optimal training interval and times of microperimetric biofeedback training (MBFT) in maculopathies. Twenty-nine patients with maculopathies were divided into two groups: daily training (Group A) or alternate daily training (Group B). Both groups underwent 15 MBFT sessions. We compared the BCVA, reading speed, and fixation stability at baseline, after 5, 10, 15 sessions. After 15 sessions of MBFT, all visual parameters in both groups improved. There was a significant increase in BCVA after 5 sessions in both groups (P=0.016, and P<0.001 respectively), but Group A showed further improvement after 10 sessions (P<0.001). Regarding reading speed, Group A showed significant improvement from baseline after 15 sessions(P=0.020), Group B improved significantly after 5 sessions (P=0.047) and continued to improve after 10 sessions (P=0.030). Additionally, P1 and LgBCEA of Group A significantly improved after 10 sessions (P=0.001, and P=0.001 respectively), while Group B significantly improved after 5 sessions (P=0.002, and P<0.001 respectively). There was no significant difference in visual outcomes between the two groups (P>0.05) except LgBCEA (P=0.046) after 15 sessions. We concluded that the both MBFT frequencies are effective at improving vision and quality of life in patients with maculopathies. The alternate daily training group showed less time-dependent of improvement in all parameters and a greater benefit in fixation stability. Ten sessions are the optimal number of treatment sessions for alternate daily training.

Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

A novel fluorescence probe for ultrafast detection of SO2 derivatives/biogenic amines and its multi-application: Detecting food and fish freshness, fluorescent dye and bioimaging.

In this study, we have effectively prepared a novel fluorescent probe named HDXM based on benzopyran derivatives for the ultrafast detection (within 3 s) of SO2 derivatives or biogenic amines. HDXM showed a noticeable color change after the addition of SO2 derivatives (from purple to colorless) or biogenic amines (from purple to blue), indicating that HDXM can identify two analytes with the naked eye. It is worth noting that HDXM can be used to detect SO2 derivatives in actual sugar samples, and to image HSO3-/SO32- in living cells. More importantly, sensing labels (HDXM-loaded filter paper or agarose hydrogel) enable real-time visual monitoring of salmon freshness through colorimetric and fluorescence dual channels. Compared with the Chinese national standard method, the sensing label is an effective tool for evaluating the freshness of fish. Benefiting from its excellent solubility and fluorescence performance, HDXM can be used as a versatile fluorescent material in various applications, including flexible films, glass coatings, impregnating dyes, printing, and fingerprint ink. HDXM is expected to be a promising and valuable multifunctional tool for food safety and fluorescent materials.