The Therapeutic Effectiveness of Laparoscopic Sleeve Gastrectomy Among Individuals with Low BMI Obesity (30-35 Kg/m2) and the Relationship of BMI to Weight Loss.

Purpose: Investigating the therapeutic efficacy of Laparoscopic Sleeve Gastrectomy (LSG) in low BMI (30-35 kg/m2) patients with obesity, and exploring the correlation between patients' preoperative BMI and postoperative weight loss. Methods: Comparing the weight loss, remission of comorbidities, occurrence of complications, and quality of life among the different BMI patients who underwent LSG. Analyzing the relationship between BMI and percentage of excess weight loss (%EWL) by using Spearman correlation analysis and linear regression analysis. Results: The %EWL at 12 months after the surgical procedure was (104.26±16.41)%, (90.36±9.98)%, and (78.30±14.64)% for patients with Class I, II, and III obesity, respectively, P<0.05. Spearman correlation coefficients between %EWL and BMI at 1, 3, 6, and 12 months after surgery were R=-0.334 (P<0.001), R=-0.389 (P<0.001), and R=-0.442 (P<0.001), R=-0.641 (P<0.001), respectively. The remission of hypertension, diabetes and dyslipidaemia did not differ significantly between groups (P>0.05). Conclusion: Individuals with obesity for varying BMI can experience favorable outcomes following LSG surgery. It is advisable to consider LSG treatment for patients with Class I obesity.

The imaging dynamic changes in the malignant transformation of an epidermoid cyst: a case report and literature review.

Malignant transformation of epidermoid cysts is a rare complication. Most of the previously reported cases have involved postoperative malignant transformations. We present a case of malignant transformation of a nonpostoperative epidermoid tumor into squamous cell carcinoma (SCC) that occurred in a 61-year-old Chinese woman. The patient's initial cranial MRI scan showed an epidermoid cyst with marginal enhancement in the pre-pontine cistern, and the lesion gradually enlarged after 10 months. A craniotomy was performed using to remove part of the tumor via the right retrosigmoid approach, and postoperative pathology confirmed that the transformation of the epidermoid cyst was malignant. Our case study suggests that the possibility of malignant transformation of epidermoid cyst should not be ignored on the basis of enhanced imaging features, regardless of whether they are nodular, annular, or patchy, as is the case for inflammation. Strict follow-up is required for early detection of malignant transformation to prompt correspondingly early clinical treatment.

Psychromicrobium Xiongbiense sp. nov., an Actinobacterium Isolated from Forest Soil.

A novel Gram-stain-positive, oval-shaped, and non-flagellated bacterial strain YIM S02556T was isolated from forest soil in Xiongbi Town, Shizong County, Qujing City, Yunnan Province, southwestern China. The strain exhibited high pairwise 16 S rRNA gene sequence similarity with Psychromicrobium lacuslunae (97.3%) and Psychromicrobium silvestre (96.3%). Strain YIM S02556T exhibited an average nucleotide identity (ANI) of 72.5% with P. lacuslunae IHBB 11,108T and 72.8% ANI with P. silvestre AK 20-18T. The digital DNA-DNA hybridization (dDDH) value between strain YIM S02556T and P. lacuslunae IHBB 11,108T was 20.2%, while with P. silvestre AK 20-18T, the dDDH value was 20.8%. Strain YIM S02556T exhibited optimal growth at 28 °C, pH 7.0, without NaCl. Growth occurred within 10-37 ℃, pH 5.0-8.0, and in the presence of up to 5% w/v NaCl concentration. The genome size was 3.1 Mbp with 64.2% G + C content. The predominant menaquinone was MK-8(H4). The major cellular fatty acid was anteiso-C15:0. Based on the polyphasic analysis, strain YIM S02556T (= KCTC 49,805T = CCTCC AB2020166T) represents a novel Psychromicrobium species in which the name Psychromicrobium xiongbiense sp.nov. was proposed.

Coupled Poly(ethylenimine) Coreactant to Enhance Electrochemiluminescence of Polymer Dots for Array Imaging of Protein Biomarkers.

Traditional electrochemiluminescent (ECL) bioanalysis suffers from the demand for excessive external coreactants and the damage of reaction intermediates. In this work, a poly(ethylenimine) (PEI)-coupled ECL emitter was proposed by covalently coupling tertiary amine-rich PEI to polymer dots (Pdots). The coupled PEI might act as a highly efficient coreactant to enhance the ECL emission of Pdots through intramolecular electron transfer, reducing the electron transfer distance between emitter and coreactant intermediates and avoiding the disadvantages of traditional ECL systems. Through modification of the PEI-Pdots with tDNA, a sequence partially complementary to cDNA that was complementary to the aptamer of target protein biomarker (aDNA), tDNA-PEI-Pdots were obtained. The biosensors were produced using Au/indium tin oxide (ITO) with an aDNA/cDNA hybrid, and an ECL imaging biosensor array was constructed for ultrasensitive detection of protein biomarkers. Using vascular endothelial growth factor 165 (VEGF165) as a protein model, the proposed ECL imaging method containing two simple incubations with target samples and then tDNA-PEI-Pdots showed a detectable range of 1 pg mL-1 to 100 ng mL-1 and a detection limit of 0.71 pg mL-1, as well as excellent performance such as low toxicity, high sensitivity, excellent selectivity, good accuracy, and acceptable fabrication reproducibility. The PEI-coupled Pdots provide a new avenue for the design of ECL emitters and the application of ECL imaging in disease biomarker detection.

Modular Engineering of Aptamer-Based Nanobiotechnology for Conditional Control of ATP Sensing.

Dynamic changes of intracellular, extracellular, and subcellular adenosine triphosphates (ATPs) have fundamental interdependence with the physio-pathological states of cells. Spatially selective in situ imaging of such ATP dynamics offers valuable mechanistic insights into the related biological activities. Despite significant advances in the design of aptamer sensors for ATP detection, the dearth of methods that enable precise ATP imaging in specific cellular locations remains a challenge in this field. This review focuses on the modular engineering of regulatable sensing technology via the integration of aptamer probe designs with advanced functional nanomaterials, allowing conditional control of ATP sensing and imaging with high spatial precision from subcellular organelles to living animals. Highlighting the recent advances in the design of photo-triggered nanosensors for spatiotemporally controlled ATP imaging, endogenously-triggered ATP sensing in a cell-selective manner, and spatially-controlled nanodevices for ATP imaging in specific organelles and extracellular microenvironments. Emphasis will be put on elucidating the principles of how nanotechnology can be applied to regulate the spatial precision of aptamer-based ATP sensing activities. The authors envision that this perspective provides insights into the engineering of aptamer-based nanobiotechnology for opening new frontiers in precise molecular sensing and other bio-applications.

Graphene/metal-organic framework nano-sandwiches derived N, P-codoped porous carbon nanosheets as robust material for electrochemical analysis.

Construction of novel two-dimensional porous carbon nanosheets with superior electrochemical activity is of great challenge. Here, graphene/ZIF-8 nano-sandwiches derived N, P-codoped porous carbon nanosheets (N, P-codoped PCN) was easily obtained by sequential room temperature self-assembly and high-temperature carbonization method. Relative to the widely used physically exfoliated graphene nanosheets (GN) and graphene/ZIF-8 derived N-doped porous carbon nanosheets (N-doped PCN), N, P-codoped PCN displayed larger active surface, faster electron transport ability and stronger physical adsorption ability, which can be ascribed to the dual doping effect of heteroatoms N and P. As a result, N, P-codoped PCN exhibited remarkable oxidation signal enhancement for tumor marker (8-hydroxy-2'-deoxyguanosine), analgesic and antipyretic drug (acetaminophen) and organic pesticide (benomyl). Besides, the limits of detection were measured as low as 1.58 nM, 7.50 nM and 2.10 nM with sensitivity of 270.00 µA µM-1 cm-2, 757.14 µA µM-1 cm-2 and 272.86 µA µM-1 cm-2 for 8-hydroxy-2'-deoxyguanosine, acetaminophen and benomyl, respectively. Basing on this, a novel and highly sensitive electrochemical sensing platform was developed. It is believed that the reported two-dimensional N, P-codoped PCN with unique structure and composition is highly valuable for the development of carbon-based electrochemical sensors.

Enzyme and MicroRNA Dual-Regulated Photodynamic Molecular Beacons for Cell-Selective Amplification of Antitumor Efficacy.

Photodynamic molecular beacons (PMBs) are highly appealing for activatable photodynamic therapy (PDT), but their applications are hindered by limited therapeutic efficacy. Here, by molecular engineering of enzyme-responsive units in the loop region of DNA-based PMBs, we present for the first time the modular design of an enzyme/microRNA dual-regulated PMB (D-PMB) to achieve cancer-cell-selective amplification of PDT efficacy. In the design, the "inert" photosensitizers in D-PMB could be repeatedly activated in the presence of both tumor-specific enzyme and miRNA, leading to amplified generation of cytotoxic singlet oxygen species and therefore enhanced PDT efficacy in vitro and in vivo. By contrast, low photodynamic activity could be observed in healthy cells, as D-PMB activation has been largely avoided by the dual-regulatable design. This work presents a cooperatively activated PDT strategy, which enables enhanced therapeutic efficacy with improved tumor-specificity and thus conceptualizes an approach to expand the repertoire of designing smart tumor treatment modality.

Enzyme-Triggered DNA Sensor Technology for Spatially-Controlled, Cell-Selective Molecular Imaging.

With unparalleled programmability, DNA has evolved as a powerful scaffold for engineering intricate and dynamic systems that can perform diverse tasks. By allowing serial detection of molecular targets in complex cellular milieus, increasingly sophisticated DNA sensors have not only promoted significant advances in unveiling the fundamental mechanisms of various pathophysiological processes but also provided a useful toolkit for disease diagnostics based on molecular signatures. Despite much progress, an inherent limitation of DNA-based sensors is that they often lack spatial control and cell-type selectivity for the sensing activity because of their "always active" design mechanism. Since most molecular targets of interests are not exclusive to disease cells, they are also shared by normal cells, the application of such biosensors for disease-specific imaging is limited by inadequate signal-to-background ratios due to indistinguishable signal response in both disease and normal cells. Therefore, imparting biosensors with spatial controllability remains a key issue to achieve molecular imaging with high sensitivity and cell specificity.As a biocatalyst, enzyme has been found to be closely related with the pathological conditions of numerous diseases. For example, many nucleases, protease, and kinases have been identified overexpressed in disease cells and considered as important biomarkers of cancer, inflammation, and neurological diseases. Recently, we have envisioned that such pathophysiology-associated enzymes could be leveraged as endogenous triggers to achieve spatial control over the molecular imaging activity of the DNA-based sensors with improved cell-specificity. In this Account, we outline the research efforts from our group on the development of endogenous enzyme-triggered, DNA-based sensor technology that enables spatially controlled, cell-type selective molecular imaging. With programmable DNA design and further engineering of enzymatically cleavable sites, a series of DNAzyme- and aptamer-based sensors have been developed for enzyme-controlled imaging of various molecular targets (e.g., metal ions and small molecules) in a cancer cell-selective manner. In particular, by introduction of PNA as bridge molecules to engineer DNA-based sensors with functional peptides, the conceptual design of protease-activated DNA biosensors has been established for spatioselective molecular imaging in cancer cells and extracellular tumor microenvironments. Furthermore, enzyme-triggered signal amplification approaches, such as enzymatically activated molecular beacon and catalytic hairpin assembly, have been developed for spatially selective RNA imaging in specific disease cells (e.g., inflammatory cells and cancer cells), which enables enhanced disease-site specificity and thus improved signal-to-background ratio. The signal amplification strategy is further expanded to cell-selective amplified imaging of non-RNA species through the combination with functional DNA design. Finally, the challenges and potential future directions in this burgeoning field are discussed. We hope this Account offers insights into rational design of enzymatically controlled, DNA-based sensor platforms for opening new frontiers in spatially resolved, cell-selective molecular imaging. We believe that the continuing advances in DNA-based molecular sensing technology together with the discoveries of diverse disease-associated enzymes will promise to usher a new era of diagnosis.

Chitinolyticbacter albus sp. Nov., A Novel Chitin-Degrading Bacterium Isolated from Ancient Wood Rhizosphere Soil.

In this study, a novel aerobic mesophilic bacterial strain with capable of degrading chitin, designated YIM B06366T, was isolated and classified. The rod-shaped, Gram-stain-negative, on-spore-forming bacterium originated from rhizosphere soil sample collected in Kunming City, Yunnan Province, southwest PR China. Strain YIM B06366T exhibited growth at temperatures between 20 and 35 °C (optimum, 30 °C) and at pH 6.0-8.0 (optimum, pH 6.0). The analysis of 16S rRNA gene sequence similarity revealed that strain YIM B06366T was most closely related to type strain Chitinolyticbacter meiyuanensis SYBC-H1T (98.9%). Phylogenetic analysis based on genome data indicated that strain YIM B06366T should be assigned to the genus Chitinolyticbacter. The Average Nucleotide Identity (ANI) and digital DNA-DNA Hybridization (dDDH) values between strain YIM B06366T and the reference strain Chitinolyticbacter meiyuanensis SYBC-H1T were 84.4% and 27.7%, respectively. The major fatty acids included Summed Feature 3 (C16:1 ω6c/C16:1 ω7c), Summed Feature 8 (C18:1 ω6c/C18:1 ω7c), and C16:0. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, aminophospholipids, and two unidentified phospholipids. The predominant menaquinone was Q-8, and the genomic DNA G + C content was 64.1%. Considering the polyphasic taxonomic evidence, strain YIM B06366T is proposed as a novel species within the genus Chitinolyticbacter, named Chitinolyticbacter albus sp. nov. (type strain YIM B06366T = KCTC 92434T = CCTCC AB 2022163T).

Selective In Situ Analysis of Mature microRNAs in Extracellular Vesicles Using a DNA Cage-Based Thermophoretic Assay.

Mature microRNAs (miRNAs) in extracellular vesicles (EVs) are involved in different stages of cancer progression, yet it remains challenging to precisely detect mature miRNAs in EVs due to the presence of interfering RNAs (such as longer precursor miRNAs, pre-miRNAs) and the low abundance of tumor-associated miRNAs. By leveraging the size-selective ability of DNA cages and polyethylene glycol (PEG)-enhanced thermophoretic accumulation of EVs, we devised a DNA cage-based thermophoretic assay for highly sensitive, selective, and in situ detection of mature miRNAs in EVs with a low limit of detection (LoD) of 2.05 fM. Our assay can profile EV mature miRNAs directly in serum samples without the interference of pre-miRNAs and the need for ultracentrifugation. A clinical study showed that EV miR-21 or miR-155 had an overall accuracy of 90 % for discrimination between breast cancer patients and healthy donors, which outperformed conventional molecular probes detecting both mature miRNAs and pre-miRNAs. We envision that our assay can advance EV miRNA-based diagnosis of cancer.

Lycopene inhibits endothelial-to-mesenchymal transition of choroidal vascular endothelial cells in laser-induced mouse choroidal neovascularization.

Choroidal neovascularization (CNV), is a major cause of irreversible blindness among the elderly population in developed countries, which is resulted from subretinal fibrosis without effective therapeutic strategies. Endothelial-to-mesenchymal transition (EndMT) of choroidal vascular endothelial cells (CVECs) contributes to subretinal fibrosis. Lycopene (LYC), a non-pro-vitamin A carotenoid, plays an anti-fibrotic role. Herein, we explored the effect and mechanism of LYC on the EndMT of CVECs during CNV. Firstly, LYC inhibited EndMT in hypoxic human choroidal endothelial cells (HCVECs). Meanwhile, LYC inhibited proliferation, androgen receptor (AR) expression and nuclear localization in hypoxic HCVECs. Then LYC-inhibited AR promotes the activation of microphthalmia-associated transcription factor (MITF) in hypoxic HCVECs. In addition, LYC down-regulated AR and induced MITF up-regulated pigment epithelium-derived factor (PEDF) transcription and expression in hypoxic HCVECs. Moreover, LYC-induced PEDF bound to laminin receptor (LR), inhibiting EndMT of hypoxic HCVECs via down-regulating protein kinase B (AKT)/ß-catenin pathway. In vivo, LYC alleviated mouse laser-induced subretinal fibrosis secondary to CNV via up-regulating PEDF without any ocular or systemic toxicity. These results indicate that LYC inhibits EndMT of CVECs via modulating AR/MITF/PEDF/LR/AKT/ß-catenin pathway, showing LYC is a promising therapeutic agent for CNV.

Regulation of Target-activated CRISPR/Cas12a on Surface Binding of Polymer Dots for Sensitive Electrochemiluminescence DNA Analysis.

Polymer dots (Pdots) have emerged as a type of attractive electrochemiluminescence (ECL) emitter. However, the low ECL efficiency severely limits their practicability. In this work, we develop a sensitive ECL biosensing strategy for the detection of human papilloma virus subtype (HPV-16) DNA by using target-activated CRISPR/Cas12a to regulate the binding of Pdots-DNA to biosensor and local surface plasmon resonance (LSPR) effect of electrochemically deposited Au nanoparticles (depAuNPs) to enhance the ECL emission of Pdots bound on biosensor. The biosensor is prepared by simply assembling hairpin DNA on depAuNPs modified electrode. In the presence of target DNA, the designed specific CRISPR/Cas12a can be activated to digest single-stranded assistant DNA, which decreases the amount of hairpin DNA opened by assistant DNA to bind Pdots-DNA on the biosensor surface, thus reduces the ECL emission. The integration of target DNA-triggered catalysis and the LSPR effect of depAuNPs greatly improves the sensitivity of ECL analysis. Using HPV-16 DNA as a target model, the proposed method shows a limit of detection (LOD) of 3.2 fM at a signal-to-noise ratio of 3 and a detectable concentration range of 5.0 fM to 50 pM. The high sensitivity, excellent selectivity, good testing stability, and acceptable fabrication reproducibility of the designed ECL biosensing strategy demonstrate its potential application in DNA bioanalysis.

Protease-Triggered, Spatially Controlled DNA Assembly in Apoptotic Cells for Early Evaluation of Therapeutic Efficacy.

Despite numerous advances in the use of DNA as building blocks to assemble complex structures, the dearth of strategies that allow for protease-controlled in situ DNA assembly in living cells remains a bottleneck in this field. Here, we present a modular engineering approach to achieve protease-triggered self-assembly of DNA in apoptotic cells for early evaluation of tumor response to drug treatment. In the design, peptide nucleic acid is introduced as a building bridge to engineer DNA building blocks with peptides and thus to suppress their self-assembly activity, while caspase-3 (Casp-3) protease-mediated enzymatic cleavage of the peptide substrate enables the activation of the DNA assembly, generating fluorescence signal output for real-time monitoring of Casp-3 activity. Furthermore, the specific protease triggering imparts DNA assembly with spatial selectivity to apoptotic cells in vivo, allowing for early evaluation of tumor therapeutic efficacy. Moreover, the strategy is extended to probe the activity of MMP-2 for lymph node metastasis imaging, demonstrating the universality of this approach. This work highlights protease-controlled DNA assembly in ways that are simple and versatile, with the potential to expand the repertoire of DNA nanotechnology for diverse biomedical applications.

A Remotely Controlled Nanosystem for Spatiotemporally Specific Gene Regulation and Combinational Tumor Therapy.

The dearth of technologies that allow gene modulation and therapy with high spatiotemporal precision remains a bottleneck in biomedical research and applications. Here we present a near-infrared (NIR) light-controlled nanosystem that allows spatiotemporally controlled regulation of gene expression and thus combinational tumor therapy. The nanosystem is built by engineering of an enzyme-activatable antisense oligonucleotide and further combination with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal. The system relies on photodynamic effect-induced translocation of a DNA repair enzyme from nucleus into mitochondria, which enables spatially selective gene regulation via enzymatic reactions. We demonstrate that the NIR light-induced mitochondrial photodamage and gene regulation enable enhanced antitumor effect. Our approach may enable the specific gene regulation and tumor treatment with high precision both spatially and temporally.

Endogenous Enzyme-Operated Spherical Nucleic Acids for Cell-Selective Protein Capture and Localization Regulation.

Precise regulation of protein activity and localization in cancer cells is crucial to dissect the function of the protein-involved cellular network in tumorigenesis, but there is a lack of suitable methodology. Here we report the design of enzyme-operated spherical nucleic acids (E-SNAs) for manipulation of the nucleocytoplasmic translocation of proteins with cancer-cell selectivity. The E-SNAs are constructed by programmable engineering of aptamer-based modules bearing enzyme-responsive units in predesigned sites and further combination with SNA nanotechnology. We demonstrate that E-SNAs are able to regulate cytoplasmic-to-nuclear shuttling of RelA protein efficiently and specifically in tumor cells, while they remain inactive in normal cells due to insufficient enzyme expression. We further confirmed the generality of this strategy by investigating the enzyme-modulated inhibition/activation of thrombin activity by varying the aptamer-based design.

Enzyme Translocation-Mediated Signal Amplification for Spatially Selective Aptasensing of ATP in Inflammatory Cells.

Amplified ATP imaging in inflammatory cells is highly desirable. However, the spatial selectivity of current amplification methods is limited, that is, signal amplification is performed systemically and not in a disease site-specific manner. Here we present a versatile strategy, termed enzymatically triggerable, aptamer-based signal amplification (ETA-SA), that enables inflammatory cell-specific imaging of ATP through spatially-resolved signal amplification. The ETA-SA leverages a translocated enzyme in inflammatory cells to activate DNA aptamer probes and further drive cascade reactions through the consumption of hairpin fuels, which, however, exerts no ATP response activity in normal cells, leading to a significantly improved sensitivity and spatial specificity for the inflammation-specific ATP imaging in vivo. Benefiting from the improved spatial selectivity, enhanced signal-to-background ratios were achieved for ATP imaging during acute hepatitis.

PD-L1 Aptamer-Functionalized Metal-Organic Framework Nanoparticles for Robust Photo-Immunotherapy against Cancer with Enhanced Safety.

Immune checkpoint blockade has become a paradigm-shifting treatment modality to combat cancer, while conventional administration of immune checkpoint inhibitors, such as anti-PD-L1 antibody (α-PD-L1), often shows unsatisfactory immune responses and lead to severe immune-related adverse effects (irAEs). Herein, we develop a PD-L1 aptamer-based spherical nucleic acids (SNAs), which consists of oxaliplatin (OXA) encapsulated in a metal-organic framework nanoparticle core and a dense shell of aptPD-L1 (denoted as M@O-A). Upon light irradiation, this nanosystem enables concurrent photodynamic therapy (PDT), chemotherapy, and enhanced immunotherapy in one shot to inhibit both primary colorectal tumors and untreated distant tumors in mice. Notably, M@O-A shows scarcely any systemic immunotoxicity in a clinical irAEs-mimic transgenic mouse model. Collectively, this study presents a novel strategy for priming robust photo-immunotherapy against cancer with enhanced safety.

An Enzymatically Gated Catalytic Hairpin Assembly Delivered by Lipid Nanoparticles for the Tumor-Specific Activation of Signal Amplification in miRNA Imaging.

MicroRNA (miRNA) imaging in disease sites is vital to elucidate their role in cancer progression. However, limited tumor specificity remains a major barrier for traditional amplification approaches due to associated background signal leakage. Here, we report a generalizable approach via the combination of enzymatically triggered catalytic hairpin assembly with lipid nanoparticles (LNPs)-based delivery strategy for tumor-specific activation of signal amplification and therefore sensitive miRNA imaging. The signal amplification is established via engineering of traditional catalytic hairpin assembly with enzymatically activated motifs to achieve triggable miRNA imaging in cancer cells. Furthermore, by the introduction of LNPs to combat biological barriers, we demonstrate that the system enables amplified miRNA imaging in vivo with reduced off-tumor signal, leading to enhanced tumor-to-background contrast compared with traditional methods. This approach that relies on specific triggers and controlled delivery to distinguish miRNA in cancer cells from normal cells should be useful in tumor diagnosis.

Peripheral white blood cell subtypes and the development/progression of diabetic macular edema in type 2 diabetic patients: a comparative study.

BACKGROUND: Inflammation and immune dysregulation are involved in the pathogenesis of diabetic macular edema (DME). The progressive increase of neutrophils in peripheral blood can lead to the increase of the number of neutrophils in the retina, thus leading to the sustained damage of the retinal vascular system and the destruction of the blood retinal barrier (BRB); lymphocytes play a protective role in vascular diseases caused by type 2 diabetes mellitus (T2DM). The purpose of this study was to study the relationship between the changes of leukocytes and their classification in peripheral blood and the occurrence and progression of DME in patients with T2DM. METHODS: A retrospective analysis was made on 81 patients with T2DM with DME (DME group) hospitalized in our hospital from January 2019 to December 2020. According to the morphological characteristics of macular edema in optical coherence tomography (OCT), they were divided into early DME group (n=33) and late DME group (n=48); 33 patients with diabetes retinopathy (DR) but without DME matched in age and course of disease served as the control group (NO-DME group). The clinical parameters assessed included eye examination, OCT results, WBCs and subtypes, blood glucose, and glycosylated hemoglobin. RESULTS: Compared with NO-DME group (n=33), Neutrophils% in DME group (n=81) was higher (57.37±9.52 vs. 63.27±7.85; P=0.001); Monocyte% (7.63±1.77 vs. 6.88±1.83; P=0.047) and lymphocyte% (30.35±9.51 vs. 27.26±6.59; P=0.032) were decreased. The optimal model was obtained with R 4.0.5 software. With other relevant variables being the same, females had a significantly increased risk of DME (b=1.273, P=0.015), %neutrophils was significantly associated with increased risk of DME (b=0.152, P=0.0006), and %lymphocytes was significantly associated with a reduced risk of DME (b=-0.027, P=0.179). However, in the early and late DME groups, no significant differences in biological markers were found, and a high-quality model was not obtained. CONCLUSIONS: In this preliminary study, %neutrophils is associated with increased risk of DME, whereas %lymphocytes is associated with a reduced risk of DME.

Spatially resolved in vivo imaging of inflammation-associated mRNA via enzymatic fluorescence amplification in a molecular beacon.

The in vivo optical imaging of RNA biomarkers of inflammation is hindered by low signal-to-background ratios, owing to non-specific signal amplification in healthy tissues. Here we report the design and in vivo applicability, for the imaging of inflammation-associated messenger RNAs (mRNAs), of a molecular beacon bearing apurinic/apyrimidinic sites, whose amplification of fluorescence is triggered by human apurinic/apyrimidinic endonuclease 1 on translocation from the nucleus into the cytoplasm specifically in inflammatory cells. We assessed the sensitivity and tissue specificity of an engineered molecular beacon targeting interleukin-6 (IL-6) mRNA in live mice, by detecting acute inflammation in their paws and drug-induced inflammation in their livers. This enzymatic-amplification strategy may enable the specific and sensitive imaging of other disease-relevant RNAs in vivo.