Ace Deficiency Induces Intestinal Inflammation in Zebrafish.

Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable. The understanding of the pathogenesis of IBD remains unclear. In this study, we found that ace (angiotensin-converting enzyme), expressed abundantly in the intestine, plays an important role in IBD. The deletion of ace in zebrafish caused intestinal inflammation with increased expression of the inflammatory marker genes interleukin 1 beta (il1b), matrix metallopeptidase 9 (mmp9), myeloid-specific peroxidase (mpx), leukocyte cell-derived chemotaxin-2-like (lect2l), and chemokine (C-X-C motif) ligand 8b (cxcl8b). Moreover, the secretion of mucus in the ace-/- mutants was significantly higher than that in the wild-type zebrafish, validating the phenotype of intestinal inflammation. This was further confirmed by the IBD model constructed using dextran sodium sulfate (DSS), in which the mutant zebrafish had a higher susceptibility to enteritis. Our study reveals the role of ace in intestinal homeostasis, providing a new target for potential therapeutic interventions.

The role of E2F2 in cancer progression and its value as a therapeutic target.

The E2F family of transcription factors plays a crucial role in the regulation of cell cycle progression and cell proliferation. Accumulative evidence indicates that aberrant expression or activation of E2F2 is a common phenomenon in malignances. E2F2 has emerged as a key player in the development and progression of various types of tumors. A wealth of research has substantiated that E2F2 could contribute to the enhancement of tumor cell proliferation, angiogenesis, and invasiveness. Moreover, E2F2 exerts its influence on a myriad of cellular processes by engaging with a spectrum of auxiliary factors and downstream targets, including apoptosis and DNA repair. The dysregulation of E2F2 in the context of carcinogenesis may be attributable to a multitude of mechanisms, which encompass modifications in upstream regulatory elements or epigenetic alterations. This review explores the function of E2F2 in cancer progression and both established and emerging therapeutic strategies aiming at targeting this oncogenic pathway, while also providing a strong basis for further research on the biological function and clinical applications of E2F2.

Nkx1.2 deletion decreases fat production in zebrafish.

OBJECTIVE: This study aimed to investigate the role of Nkx1-2, a transcription factor with the NK homeobox domain, in the regulation of fat production. METHODS: Gene expression was analyzed using quantitative real-time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate nkx1.2 knockout zebrafish and nkx1.2-deleted 3T3-L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3-L1 cells were stained with Oil red O. The binding of Nkx1-2 to the promoter was verified through an electrophoretic mobility shift assay experiment. RESULTS: Nkx1-2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of nkx1.2 in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3-L1 preadipocytes, Nkx1-2 induces differentiation into mature adipocytes by binding to the cebpa promoter, thereby activating its transcription. Additionally, the expression of nkx1.2 is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3-L1 cells. CONCLUSIONS: Our findings suggest that Nkx1-2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis.

Identification, Expression and Evolutional Analysis of Two cyp19-like Genes in Amphioxus.

The mechanism of sex determination and differentiation in animals remains a central focus of reproductive and developmental biology research, and the regulation of sex differentiation in amphioxus remains poorly understood. Cytochrome P450 Family 19 Subfamily A member 1 (CYP19A1) is a crucial sex differentiation gene that catalyzes the conversion of androgens into estrogens. In this study, we identified two aromatase-like genes in amphioxus: cyp19-like1 and cyp19-like2. The cyp19-like1 is more primitive and may represent the ancestral form of cyp19 in zebrafish and other vertebrates, while the cyp19-like2 is likely the result of gene duplication within amphioxus. To gain further insights into the expression level of these two aromatase-like, we examined their expression in different tissues and during different stages of gonad development. While the expression level of the two genes differs in tissues, both are highly expressed in the gonad primordium and are primarily localized to microsomal membrane systems. However, as development proceeds, their expression level decreases significantly. This study enhances our understanding of sex differentiation mechanisms in amphioxus and provides valuable insights into the formation and evolution of sex determination mechanisms in vertebrates.

A Gradient Composite Structure Enables a Stable Microsized Silicon Suboxide-Based Anode for a High-Performance Lithium-Ion Battery.

The practical application of microsized anodes is hindered by severe volume changes and fast capacity fading. Herein, we propose a gradient composite strategy and fabricate a silicon suboxide-based composite anode (d-SiO@SiOx/C@C) consisting of a disproportionated microsized SiO inner core, a homogeneous composite SiOx/C interlayer (x ≈ 1.5), and a highly graphitized carbon outer layer. The robust SiOx/C interlayer can realize a gradient abatement of stress and simultaneously connect the inner SiO core and carbon outer layer through covalent bonds. As a result, d-SiO@SiOx/C@C delivers a specific capacity of 1023 mAh/g after 300 cycles at 1 A/g with a retention of >90% and an average Coulombic efficiency of >99.7%. A full cell assembled with a LiNi0.8Co0.15Al0.05O2 cathode displays a remarkable specific energy density of 569 Wh/kg based on total active materials as well as excellent cycling stability. Our strategy provides a promising alternative for designing structurally and electrochemically stable microsized anodes with high capacity.

The Effects of Radix isatidis Raw Material on Egg Quality, Serum Biochemistry, Gut Morphology and Gut Flora.

China produces more than 30 million tons of drug residues every year. Therefore, innovative solutions are needed to mitigate environmental damage. Certain plant compounds boost hens' health and performance. Radix isatidis is promising for layer production. This study elucidates the multidimensional impact of Radix isatidis residual material (RIHR) on laying hens, focusing on the egg quality, intestinal health and the microbial landscape. A total of 288 55-week-old Peking powder laying hens with similar laying rates and body weights were randomly divided into four groups, with eight replicates per group and nine hens per replicate. The groups were divided into a control group, an RIHR low-dose group, a medium-dose group and a high-dose group according to a single-factor, completely randomized design. For the three RIHR treatment groups, the added amounts were 5 kg/t, 10 kg/t and 15 kg/t, respectively. Liquid chromatography- mass spectrometry (LC-MS), molecular docking, fluorescence quantitative PCR and other methods were used. The results showed that three main anti-inflammatory and antiviral compounds were identified in RIHR-indirubin (0.21 µg/g), deoxyvasicinone (0.18 µg/g) and epigoitrin (0.39 µg/g). RIHR significantly increased the eggshell thickness, Haugh unit and protein height (p < 0.05). It also had significant antioxidant and anti-inflammatory effects on ilea and ceca (p < 0.05). The microbial analysis demonstrated that RIHR supplementation led to a significant reduction in foregut Lactobacillus levels (p < 0.05). In the hindgut, a significant increase in pathogenic bacteria was observed (p < 0.05). The study concludes that RIHR's anti-inflammatory compounds may directly act on the intestinal tract to modulate inflammation, highlighting its potential for targeted interventions in poultry health and nutrition.

Sleep characteristics before assisted reproductive technology treatment predict reproductive outcomes: a prospective cohort study of Chinese infertile women.

Sleep disorders affect mental and physical health. Infertile women undergoing assisted reproductive technology (ART) treatment are prone to sleep disorders. Sleep condition, its influencing factors, and the association between sleep condition and ART treatment outcomes before treatment have not been explored within a population with a large sample size. Therefore, we investigated the sleep characteristics of 1002 Chinese infertile women before ovulation induction and investigated the influencing factors (negative and positive psychological factors, demographics, and fertility characteristics). We also examined whether sleep conditions before treatment predicted reproductive outcomes. We found that 24.1% of participants reported poor sleep quality. Women with primary infertility reported poorer sleep than women with secondary infertility. Negative psychological factors, including depression, anxiety, and perceived stress were associated with poor sleep, whereas positive affect was linked with good sleep. Adverse sleep characteristics, including poor subjective sleep quality, sleep disturbances, and poor sleep efficiency, decreased the quantity and quality of oocytes retrieved, fertilization rates, and clinical pregnancy rates. This study indicates that before ART treatment, a large number of females with infertility suffer from sleep problems, which are affected by psychological factors and infertility type, and unhealthy sleep characteristics may impair treatment outcomes. Our findings highlight the importance of screening and treatment for sleep disorders before the enrollment of ART treatment in infertile women.

Bmp4 in Zebrafish Enhances Antiviral Innate Immunity through p38 MAPK (Mitogen-Activated Protein Kinases) Pathway.

Bone morphogenetic proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-ß superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidence is emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here, we identified the zebrafish bmp4 ortholog, whose expression is up-regulated through challenge with grass carp reovirus (GCRV) or its mimic poly(I:C). The overexpression of bmp4 in epithelioma papulosum cyprini (EPC) cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild-type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through the p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 plays an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.

Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation.

The role of bone morphogenetic proteins (BMPs) in regulating adipose has recently become a field of interest. However, the underlying mechanism of this effect has not been elucidated. Here we show that the anti-fat effect of Bmp8a is mediated by promoting fatty acid oxidation and inhibiting adipocyte differentiation. Knocking out the bmp8a gene in zebrafish results in weight gain, fatty liver, and increased fat production. The bmp8a-/- zebrafish exhibits decreased phosphorylation levels of AMPK and ACC in the liver and adipose tissues, indicating reduced fatty acid oxidation. Also, Bmp8a inhibits the differentiation of 3T3-L1 preadipocytes into mature adipocytes by activating the Smad2/3 signaling pathway, in which Smad2/3 binds to the central adipogenic factor PPARγ promoter to inhibit its transcription. In addition, lentivirus-mediated overexpression of Bmp8a in 3T3-L1 cells significantly increases NOD-like receptor, TNF, and NF-κB signaling pathways. Furthermore, NF-κB interacts with PPARγ, blocking PPARγ's activation of its target gene Fabp4, thereby inhibiting adipocyte differentiation. These data bring a signal bridge between immune regulation and adipocyte differentiation. Collectively, our findings indicate that Bmp8a plays a critical role in regulating lipid metabolism and adipogenesis, potentially providing a therapeutic approach for obesity and its comorbidities.

Engineering the Structural Uniformity of Gel Polymer Electrolytes via Pattern-Guided Alignment for Durable, Safe Solid-State Lithium Metal Batteries.

Ultrathin and super-toughness gel polymer electrolytes (GPEs) are the key enabling technology for durable, safe, and high-energy density solid-state lithium metal batteries (SSLMBs) but extremely challenging. However, GPEs with limited uniformity and continuity exhibit an uneven Li+ flux distribution, leading to nonuniform deposition. Herein, a fiber patterning strategy for developing and engineering ultrathin (16 µm) fibrous GPEs with high ionic conductivity (≈0.4 mS cm-1 ) and superior mechanical toughness (≈613%) for durable and safe SSLMBs is proposed. The special patterned structure provides fast Li+ transport channels and tailoring solvation structure of traditional LiPF6 -based carbonate electrolyte, enabling rapid ionic transfer kinetics and uniform Li+ flux, and boosting stability against Li anodes, thus realizing ultralong Li plating/stripping in the symmetrical cell over 3000 h at 1.0 mA cm-2 , 1.0 mAh cm-2 . Moreover, the SSLMBs with high LiFePO4 loading of 10.58 mg cm-2 deliver ultralong stable cycling life over 1570 cycles at 1.0 C with 92.5% capacity retention and excellent rate capacity of 129.8 mAh g-1 at 5.0 C with a cut-off voltage of 4.2 V (100% depth-of-discharge). Patterned GPEs systems are powerful strategies for producing durable and safe SSLMBs.

Optical diffraction tomography and Raman spectroscopy reveal distinct cellular phenotypes during white and brown adipocyte differentiation.

White adipose tissue (WAT) and brown adipose tissue (BAT) are the primary types of fats in humans, and they play prominent roles in energy storage and thermogenesis, respectively. While the mechanisms of terminal adipogenesis are well understood, much remains unknown about the early stages of adipogenic differentiation. Label-free approaches, such as optical diffraction tomography (ODT) and Raman spectroscopy, offer the ability to retrieve morphological and molecular information at the single cell level without the negative effects of photobleaching and system perturbation due to introduction of fluorophores. In this study, we employed 3D ODT and Raman spectroscopy to gain deeper insights into the early stages of differentiation of human white preadipocytes (HWPs) and human brown preadipocytes (HBPs). We utilized ODT to retrieve morphological information, including cell dry mass and lipid mass, and Raman spectroscopy to obtain molecular information about lipids. Our findings reveal that HWPs and HBPs undergo dynamic and differential changes during the differentiation process. Notably, we found that HBPs accumulated lipids more rapidly and had a higher lipid mass than HWPs. Additionally, both cell types experienced an increase and subsequent decrease in cell dry mass during the first seven days, followed by an increase after day 7, which we attribute to the transformation of adipogenic precursors in the early stages. Finally, HBPs had higher lipid unsaturation levels than HWPs for the same differentiation timepoints. The insights gained from our study provide crucial contributions towards the advancement of new therapies for obesity and related diseases.

The genetic spectrum and clinical features of X-linked juvenile retinoschisis in Central China.

PURPOSE: X-linked juvenile retinoschisis (XLRS) is the most common congenital retinoschisis in rare vitreoretinopathy and causes visual disturbances. The study aimed to explore possible genetic mutations associated with XLRS and assess the clinical characteristics in Chinese families. METHODS: Seventeen cases and thirty-four eyes of probands and thirty-nine cases and seventy-eight eyes of their guardians were recruited. Peripheral blood DNA was extracted and PCR-amplified for retinal disease second-generation panel sequencing to screen for mutated genes. Pathogenicity was referred to the guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: A total of 17 male patients were included, with an average age of 9.73 years (range, 5 ~ 27 years). Clinical data indicate typical macular retinoschisis (97.06%), peripheral retinoschisis (46.67%), retinal holes (32.35%). Fifteen mutations (10 missense mutations, 4 shift mutations, and 3 nonsense mutations) of RS1 gene were identified, including 5 novel mutations. In novel mutations, amino acid conservation analysis shows W33, W50, E62, and G70 were highly conserved, and software predicts mutations to be pathogenic. SWISS-MODEL protein prediction software showed protein structural changes in proband 13. CONCLUSIONS: We have identified and described five novel mutations in the RS1 gene and their corresponding clinical manifestations. These findings not only expand the range of known RS1 mutations and associated clinical phenotypes but also provide a basis for mechanistic studies and diagnosis of XLRS.

Peripheral complete blood cell count indices and serum lipid levels in polypoidal choroidal vasculopathy.

CLINICAL RELEVANCE: Systemic inflammation factors (e.g. white blood cells and neutrophils), high level of triglyceride and high neutrophil-to-lymphocyte ratio have significant associations with the risk of polypoidal choroidal vasculopathy (PCV). BACKGROUND: This study aimed to investigate associations of complete blood cell count-derived indicators and serum lipid levels with PCV. METHODS: Forty-eight patients with PCV and 54 age- and gender-matched control group participants were included in the study. Records of demographic characteristics and the results of ophthalmic examinations and haematologic parameters for the participants were collected retrospectively. Blood cell count-derived indicators and serum lipid levels were calculated and were compared between the two groups. RESULTS: The PCV group had higher white blood cell, neutrophils, triglyceride, and neutrophil-to-lymphocyte ratio levels and lower mean corpuscular volume level, compared with the control group (P = 0.002, P < 0.001, P = 0.003, P = 0.002, and P = 0.027, respectively). White blood cell, neutrophil, triglyceride, and neutrophil-to-lymphocyte ratio were independent risk factors for PCV (odds ratio [OR] = 1.668, 2.324, 2.846, and 2.543, respectively; P = 0.003, P = 0.001, P = 0.005, and P = 0.004, respectively). Mean corpuscular volume was an independent protective factor against PCV (OR = 0.902; P = 0.031). Receiver operating characteristic curve analysis revealed that the area under the curve values for white blood cell, neutrophil, triglyceride, neutrophil-to-lymphocyte ratio, and mean corpuscular volume was 0.656, 0.687, 0.660, 0.659, and 0.633, respectively (P< 0.05, respectively). The combined area under the curve value was 0.772 (P < 0.001). CONCLUSIONS: White blood cells, neutrophils, triglycerides, and the neutrophil-to-lymphocyte ratio were the risk factors for PCV. Mean corpuscular volume was a protective factor against PCV. These results suggested that the combination of white blood cells, neutrophils, triglyceride, neutrophil-to-lymphocyte ratio, and mean corpuscular volume can be used to predict PCV.

Tuning Mass Transport in Electrocatalysis Down to Sub-5†nm through Nanoscale Grade Separation.

Nano and single-atom catalysis open new possibilities of producing green hydrogen (H2 ) by water electrolysis. However, for the hydrogen evolution reaction (HER) which occurs at a characteristic reaction rate proportional to the potential, the fast generation of H2 nanobubbles at atomic-scale interfaces often leads to the blockage of active sites. Herein, a nanoscale grade-separation strategy is proposed to tackle mass-transport problem by utilizing ordered three-dimensional (3d) interconnected sub-5 nm pores. The results reveal that 3d criss-crossing mesopores with grade separation allow efficient diffusion of H2 bubbles along the interconnected channels. After the support of ultrafine ruthenium (Ru), the 3d mesopores are on a superior level to two-dimensional system at maximizing the catalyst performance and the obtained Ru catalyst outperforms most of the other HER catalysts. This work provides a potential route to fine-tuning few-nanometer mass transport during water electrolysis.

BMP8B Activates Both SMAD2/3 and NF-κB Signals to Inhibit the Differentiation of 3T3-L1 Preadipocytes into Mature Adipocytes.

Bone morphogenetic protein 8B (BMP8B) has been found to regulate the thermogenesis of brown adipose tissue (BAT) and the browning process of white adipose tissue (WAT). However, there is no available information regarding the role of BMP8B in the process of adipocyte differentiation. Here, we showed that BMP8B down-regulates transcriptional regulators PPARγ and C/EBPα, thereby impeding the differentiation of 3T3-L1 preadipocytes into fully mature adipocytes. BMP8B increased the phosphorylation levels of SMAD2/3, and TP0427736 HCl (SMAD2/3 inhibitor) significantly reduced the ability of BMP8B to inhibit adipocyte differentiation, suggesting that BMP8B repressed adipocyte differentiation through the SMAD2/3 pathway. Moreover, the knockdown of BMP I receptor ALK4 significantly reduced the inhibitory effect of BMP8B on adipogenesis, indicating that BMP8B triggers SMAD2/3 signaling to suppress adipogenesis via ALK4. In addition, BMP8B activated the NF-κB signal, which has been demonstrated to impede PPARγ expression. Collectively, our data demonstrated that BMP8B activates both SMAD2/3 and NF-κB signals to inhibit adipocyte differentiation. We provide previously unidentified insight into BMP8B-mediated adipogenesis.

Insm1 promotes differentiation of retinal progenitor cells toward photoreceptor cells in the developing retina through up-regulation of SHH.

This article investigated the effect of Insm1 on RPC differentiation in mice and the underlying mechanism. The retinal tissues of mouse embryo at 12.5 days (E12.5) and postnatal 14 days (P14) were collected, following by the detection of Insm1 and corresponding markers by immunofluorescent staining. RPCs isolated from retinal tissues at P1 were cultured in culture medium for 7 days. The differentiation of photoreceptor and glial cells was assessed after RPCs transferred to the differentiation medium for 20 days. Next, the effect of Insm1 overexpression on the differentiation of RPCs toward rod photoreceptor and glial cells were assessed. Insm1 was highly expressed in RPCs of retinal tissues and decline in photoreceptor cells, while hardly expressed in glial cells. Based on the results of Pax-6 positive immunofluorescent staining and flow cytometry detection, RPCs were successfully isolated from retinal tissues. After the culture in differentiation medium, RPCs showed positive staining of Rhodopsin and glial fibrillary acidic protein (GFAP). Further results showed that overexpression of Insm1 significantly increased the percentage of Rhodopsin positive cells, and up-regulated Sonic Hedgehog (SHH), hairy and enhancer of split homolog-1(Hes1), S-opsin and Rhodopsin levels, while decreased the percentage of Glutamine synthetase positive cells, and reduced Glutamine synthetase and GFAP levels. Whereas, the effect of Insm1 overexpression on these protein levels were partly abolished by the knockdown of SHH or Hes1. We conclude that Insm1 promotes the differentiation of RPCs into photoreceptor cells in the developing retina through up-regulation of SHH.

Elevated neutrophil counts, triglycerides, monocyte/high-density lipoprotein (HDL) ratios, and lower HDL in patients with retinal vein occlusion.

Introduction Aim to evaluate associations of peripheral blood immune cells and blood lipid profile levels with retinal vein occlusion (RVO). Methods This retrospective study included 127 patients with RVO and 108 controls. Patients with RVO were divided into branch RVO (BRVO), central RVO (CRVO), ischemic RVO, or non-ischemic RVO groups. Medical records were collected and analyzed. Results The RVO group had higher mean neutrophil, triglyceride (TG), and monocyte/high-density lipoprotein (HDL) ratio (MHR) levels and lower HDL levels (P=0.037, P<0.001, P=0.004, and P=0.002, respectively). TG and MHR levels were significantly higher in the BRVO and CRVO groups compared with the control group (P<0.001, P=0.016, respectively), but there was no difference in BRVO and CRVO group (P=0.972, P=0.916, respectively). Mean HDL levels were significantly lower in the BRVO and CRVO groups than in the control group (P=0.005), but the difference between the BRVO group and CRVO group was not significant (P=0.290). Neutrophils, TG, and MHR were independent risk factors for RVO. HDL was an independent protective factor for RVO. Age was an independent risk factor for ischemic RVO. Conclusions Lower HDL, and higher neutrophil, TG and MHR levels are associated with RVO. Age is an independent risk factor for ischemic RVO.

Preparation and Performances of Polyether Polytriazole Elastomers Based on Click Chemistry.

Since the polyurethane elastomer synthesis process is susceptible to moisture, polytriazole polyethylene oxide-tetrahydrofuran (PTPET) elastomer was used as a replacement owing to its mild production environment. In contrast to the conventional flask-synthesis method, the twin-screw reactor instrument could provide more meaningful data in the synthesis. In this study, PTPET elastomer was prepared by the MiniLab twin-screw reactor method for the first time, and the activation energy of the PTPET elastomer was calculated using the torque variation obtained from the MiniLab twin-screw reactor during the synthesis process at two different temperatures. The addition of flame retardants could endow the composites with more useful properties. The PTPET composites poly (phenylsilsesquioxane) (PTPET-PPSQ), octaphenyl polyhedral oligomeric silsesquioxane (PTPET-OPS) and PTPET-PhVPOSS (phenyl/vinyl polysilsesquioxane) were synthesized by using the MiniLab twin-screw reactor. The prepared PTPET elastomer and composites were fully characterized by FT-IR, TG, DSC, swelling test, mechanical test, SEM and combustion test. The characterization results show that the addition of the flame retardants has little influence on the original structure and properties of PTPET elastomer. The flame retardancy was characterized by the combustion test showing that all PTPET composites form a certain thickness of char layer during the burning process. These results indicate that the addition of flame retardants maintains the outstanding properties of PTPET elastomer and also endows the materials with a certain extent of flame retardancy; thus, it is believed to be a good engineering material that could be applied in many realms.

Various configuration types of the foveal avascular zone with related factors in normal Chinese adults with or without myopia assessed by swept-source OCT angiography.

AIM: To describe the morphological characteristics of foveal avascular zone (FAZ) in normal Chinese adults with or without myopia by swept-source optical coherence tomography angiography (SS-OCTA) and analyze the possible associated factors. METHODS: Normal Chinese adults with or without myopia aged between 18 and 60y were recruited into the study. One eye in each individual was randomly selected for scanning using SS-OCTA. FAZ parameters, central retinal thickness (CRT) and central choroidal thickness (CCT) were then analyzed. Correlations between systemic and ocular variables and FAZ parameters were subsequently evaluated. The subgroup analysis based on refractive error was also carried out. RESULTS: In total, 127 eyes out of 127 normal subjects were finally included in the study (mean age 29.5±8.22y, 61 males and 66 females). The pattern of FAZ was variable: round configuration in 28 eyes (22%), quadrilateral configuration in 23 eyes (18%), pentagonal configuration in 20 eyes (16%), oval configuration in 15 eyes (12%), triangular configuration in 6 eyes (5%) and irregular configuration in 35 eyes (28%). The mean area of FAZ was 0.37±0.12 mm2. Females had a larger FAZ (0.41±0.11 mm2 vs 0.32±0.11 mm2) compared with that of males (P<0.01). All myopic individuals showed smaller FAZ area and perimeter compared with that of normal individuals (P<0.01). There was no obvious correlation between age and FAZ. In the univariate regression analysis, both axial length (AL) and refractive error were significantly related to FAZ parameters. However, only CRT showed negative correlation with FAZ in the multivariate regression analysis. CONCLUSION: The pattern of FAZ configuration in normal Chinese adults with or without myopia is highly variable. Establishing quantitative parameters of FAZ would not only provide details of macular pathophysiology but could possibly contribute as a biomarker in disease staging.

Raman spectroscopy reveals phenotype switches in breast cancer metastasis.

The accurate analytical characterization of metastatic phenotype at primary tumor diagnosis and its evolution with time are critical for controlling metastatic progression of cancer. Here, we report a label-free optical strategy using Raman spectroscopy and machine learning to identify distinct metastatic phenotypes observed in tumors formed by isogenic murine breast cancer cell lines of progressively increasing metastatic propensities. Methods: We employed the 4T1 isogenic panel of murine breast cancer cells to grow tumors of varying metastatic potential and acquired label-free spectra using a fiber probe-based portable Raman spectroscopy system. We used MCR-ALS and random forests classifiers to identify putative spectral markers and predict metastatic phenotype of tumors based on their optical spectra. We also used tumors derived from 4T1 cells silenced for the expression of TWIST, FOXC2 and CXCR3 genes to assess their metastatic phenotype based on their Raman spectra. Results: The MCR-ALS spectral decomposition showed consistent differences in the contribution of components that resembled collagen and lipids between the non-metastatic 67NR tumors and the metastatic tumors formed by FARN, 4T07, and 4T1 cells. Our Raman spectra-based random forest analysis provided evidence that machine learning models built on spectral data can allow the accurate identification of metastatic phenotype of independent test tumors. By silencing genes critical for metastasis in highly metastatic cell lines, we showed that the random forest classifiers provided predictions consistent with the observed phenotypic switch of the resultant tumors towards lower metastatic potential. Furthermore, the spectral assessment of lipid and collagen content of these tumors was consistent with the observed phenotypic switch. Conclusion: Overall, our findings indicate that Raman spectroscopy may offer a novel strategy to evaluate metastatic risk during primary tumor biopsies in clinical patients.