A Bioinformatic Strategy for Investigating the Mechanism of Hispolon in the Treatment of Triple-Negative Breast Cancer Combined with In vitro Experiments.

BACKGROUND: Hispolon, a phenolic compound isolated from the medicinal yellow fungal mulberry, exhibits a strong anti-triple-negative breast cancer (TNBC) effect. However, the antitumor mechanisms of Hispolon have not been fully explored. OBJECTIVE: In this study, we systematically investigated the mechanism of Hispolon against TNBC based on bioinformatics and in vitro experiments. METHODS: The Hispolon-related targets were first collected from the SwissTarget database. Differential Expression Genes (DEG) were screened between TNBC and normal breast tissue using the Gene Expression Comprehensive (GEO) dataset. The overlapping targets between Hispolon and DEG were analyzed by plotting Venn maps. Protein-protein interaction (PPI) network was constructed to analyze the interactions among these targets. The focus was on mining the core targets of anti-TNBC effects of Hispolon via the Cytohubba and MCODE plugin of Cytoscape 3.7.2 software. We performed survival analysis on these core targets to screen the best-matched targets, including EGFR, KIT, and PLAU. This correlated strongly with our validation of Hispolon by molecular docking. In addition, Gene Ontology (GO) anal-ysis and KEGG pathway analysis were performed using R software (ClusterProfiler package). Finally, in vitro experiments were performed to assess the accuracy of predicted target genes. RESULTS: The ADME results suggested that Hispolon has great potential to develop into a drug. Twenty overlapping targets were screened by matching the 107 targets of Hispolon to the 2,013 targets of TNBC DEG. Seven core targets of Hispolon against TNBC were initially identified, including EGFR, IGFBP3, MMP9, MMP2, MMP1, PLAU, and KIT. GO enrich-ment analysis demonstrated that the biological process of Hispolon acting on TNBC mainly involves lymphocyte activation in immune response and phosphatidylinositol-mediated signal-ing. Additionally, the relaxin signaling pathway, estrogen signaling pathway, proteoglycans in cancer, and others might be the key pathways of Hispolon against TNBC. Furthermore, Hispo-lon inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner and regulated the RNA and protein expression of the core targets EGFR, PLAU, and KIT for the treatment of TNBC. CONCLUSION: In this study, the polygenic pharmacological mechanism of action of Hispolon against TNBC was explored through network pharmacology and in vitro experiments, provid-ing a new insight into the mechanism of TCM monomer against TNBC.

Rapid quantitative analysis of coal composition using laser-induced breakdown spectroscopy coupled with random forest algorithm.

Coal is the primary energy source in China, widely used in energy production, industrial processes, and chemical engineering. Due to the complexity and diversity of coal quality, there is an urgent need for new technologies to achieve rapid and accurate detection and analysis of coal, aiming to improve coal resource utilization and reduce pollutant emissions. This study proposes a rapid quantitative analysis of coal using laser-induced breakdown spectroscopy combined with the random forest algorithm. Firstly, a Q-switched Nd: YAG laser at 1064 nm was employed to ablate coal samples, generating plasma, and spectral data were collected using a spectrometer. Secondly, the study explores the impact of different parameters in the preprocessing method (wavelet transform) on the predictive performance of the random forest model. It identifies elements related to coal ash content and calorific value along with their spectral information. Subsequently, to further validate the predictive performance of the model, a comparison is made with models established using support vector machine, artificial neural network, and partial least squares. Finally, under optimal parameters for spectral information preprocessing (wavelet transform with Db4 as the base function and 3 decomposition levels), a model combining wavelet transform with Random Forest is established to predict and analyze the ash content and calorific value of coal. The results demonstrate that the Wavelet Transform-Random Forest model exhibits excellent predictive performance (coal ash content: R2 = 0.9470, RMSECV = 4.8594, RMSEP = 4.8450; coal calorific value: R2 = 0.9485, RMSECV = 1.5996, RMSEP = 1.5949). Therefore, laser-induced breakdown spectroscopy combined with the random forest algorithm is an effective method for rapid and accurate detection and analysis of coal. The predicted coal composition values show high accuracy, providing insights and methods for coal composition monitoring and analysis.

Diffuse photon remission associated with the center-illuminated-area-detection geometry. III. Perspectives on the patterns of saturation.

Understanding scattering insensitiveness in diffuse reflectance spectroscopy (DRS) will be useful to enhancing the spectral specificity to absorption. In DRS based on center-illuminated-area-detection (CIAD), the scattering response can saturate as the relative strength of scattering with respect to the collection size, represented by a dimensionless reduced scattering, increases over a threshold. However, the formation of saturation versus the same range of dimensionless reduced scattering may differ between a fixed reduced scattering over an increasing collection size (case 1) and an increasing reduced scattering over a fixed collection size (case 2), due to the absorption. Part III demonstrates the differences of the scattering saturation as well as the effect of absorption on it in the CIAD geometry between the two cases while assessed over the same range of the dimensionless reduced scattering. A model allows predicting the absorption-dependent levels of saturation and the corner parameters of saturation transition. When assessed for the absorption coefficient to vary over [0.001,0.01,0.1,1]m m -1, the model-predicted levels of saturation agree with MC results with ≤2.2% error in both cases. In comparison, the model-predicted corner parameters of saturation show much different agreement with MC results in the two cases, suggesting that the saturation pattern is much better formed in one than in the other. Experiments conforming to the CIAD geometry support the discrepancy of the saturating patterns between the two cases.

Numerical Study on Enhanced Heat Transfer of Downhole Slotted-Type Heaters for In Situ Oil Shale Exploitation.

In order to improve the flow state of the heater shell side and enhance the performance evaluation of the heater, this paper proposes a perforated plate-type heater model. Based on Fluent, numerical studies are conducted on the heat transfer performance and shell-side fluid flow characteristics of a perforated plate-type heater. The variations of the heat transfer factor Nu, friction factor f, and evaluation parameter Nu/f1/3 are analyzed for different helix angles ß and ratios of the long and short semiaxes of the circular holes on the heating plate under different Reynolds numbers Re. The results reveal that under the same shell-side Reynolds number Re, the heat transfer factor Nu shows an increasing trend with the increase in the proportion of the helix angle ß. The heat transfer factor Nu for the heating plate with the hole shape ratio a/b = 1 does not exhibit significant improvement compared to hole shape ratios a/b = 0.8 and a/b = 0.6, but it increases by 4.87 to 7.07% compared to the hole shape ratio a/b = 0.4 in the perforated plate-type heater. On the other hand, the friction factor f decreases as the helix angle ß and the ratio of hole shapes on the heating plate increase. The lowest friction factor f is observed for the helix angle ß of 25° and the hole shape ratio a/b = 1 in the perforated plate-type heater. When the helix angle ß is 25° and the hole shape ratio is a/b = 1, the evaluation parameter Nu/f1/3 reaches its highest value, indicating the optimal overall performance of the perforated plate-type heater.

Diffuse photon remission associated with the center-illuminated-area-detection geometry. II. Approach to the time-domain model.

This part proposes a model of time-dependent diffuse photon remission for the center-illuminated-area-detection (CIAD) geometry, by virtue of area integration of the radially resolved time-dependent diffuse photon remission formulated with the master-slave dual-source scheme demonstrated in Part I for steady-state measurements. The time-domain model is assessed against Monte Carlo (MC) simulations limiting to only the Heyney-Greenstein scattering phase function for CIAD of physical scales and medium properties relevant to single-fiber reflectance (SfR) and over a 2 ns duration, in compliance with the timespan of the only experimental report of SfR demonstrated with a 50 µm gradient index fiber. The time-domain model-MC assessments are carried out for an absorption coefficient ranging three orders of magnitude over [0.001,0.01,0.1,1]m m -1 at a fixed scattering, and a reduced scattering coefficient ranging three orders of magnitude over [0.01,0.1,1,10]m m -1 at a fixed absorption, among others. Photons of shorter and longer propagation times, relative to the diameter of the area of collection, respond differently to the scattering and absorption changes. Limited comparisons of MC between CIAD and a top-hat geometry as the idealization of SfR reveal that the time-domain photon remissions of the two geometries differ appreciably in only the early arriving photons.

Identification of IKZF1 genetic mutations as new molecular subtypes in acute myeloid leukaemia.

BACKGROUND: Genetic mutations of IKZF1 have been frequently delineated in B-lineage acute leukaemia (B-ALL) but rarely elucidated in acute myeloid leukaemia (AML). IKZF1 mutations confer a poor prognosis in AML, and hotspot mutations of IKZF1, N159Y and N159S tend to occur in B-ALL and AML respectively. However, the pathogenesis of IKZF1 N159S in AML and IKZF1 lineage susceptibility are largely unknown. METHODS: The genetic and clinical characteristics of IKZF1-mutated AML patients were evaluated. Multi-omics analysis and functional assays were performed in vitro using IKZF1 mutations knock-in AML cell lines. RESULTS: 23 (4.84%) small sequence variants of IKZF1 were identified in 475 newly diagnosed AML (non-M3) patients. Based on RNA sequencing, three classes of IKZF1-related AML were defined, including 9 patients (39.13%) with IKZF1 N159S mutations, 10 (43.47%) with CEBPA mutations and 4 others (17.39%). IKZF1 N159S may define a unique subgroup with higher HOXA/B expression and native B-cell immune fractions. Gene expression data of multiple knock-in cell lines indicate that the lymphocyte differentiation-related MME and CD44 kept high expression in IKZF1 N159Y but were downregulated in N159S. CUT&TAG sequencing showed that IKZF1 N159S reshaped the binding profiles of IKZF1. Integration analysis suggested that the pathogenesis of IKZF1 N159S may depend on the deregulation of several cofactors, such as oncogenic MYC and CPNE7 targets. CONCLUSIONS: Collectively, we dissected the molecular spectrum and clinical features of IKZF1-related AML, which may promote an in-depth understanding of the pathogenesis, lineage susceptibility and clinical research of AML.

J-shaped association between uric acid and breast cancer risk: a prospective case-control study.

BACKGROUND/AIM: In terms of breast cancer risk, there is no consensus on the effect of uric acid (UA) levels. The aim of our study was to clarify the link between UA and breast cancer risk in a prospective case-control study and to find the UA threshold point. METHODS: We designed a case-control study with 1050 females (525 newly diagnosed breast cancer patients and 525 controls). We measured the UA levels at baseline and confirmed the incidence of breast cancer through postoperative pathology. We used binary logistic regression to study the association between breast cancer and UA. In addition, we performed restricted cubic splines to evaluate the potential nonlinear links between UA and breast cancer risk. We used threshold effect analysis to identify the UA cut-off point. RESULTS: After adjusting for multiple confounding factors, we found that compared with the referential level (3.5-4.4 mg/dl), the odds ratio (OR) of breast cancer was 1.946 (95% CI 1.140-3.321) (P < 0.05) in the lowest UA level and 2.245 (95% CI 0.946-5.326) (P > 0.05) in the highest level. Using the restricted cubic bar diagram, we disclosed a J-shaped association between UA and breast cancer risk (P-nonlinear < 0.05) after adjusting for all confounders. In our study, 3.6 mg/dl was found to be the UA threshold which acted as the optimal turning point of the curve. The OR for breast cancer was 0.170 (95% CI 0.056-0.512) to the left and 1.283 (95% CI 1.074-1.532) to the right of 3.6 mg/dl UA (P for log likelihood ratio test < 0.05). CONCLUSION: We found a J-shaped association between UA and breast cancer risk. Controlling the UA level around the threshold point of 3.6 mg/dl provides a novel insight into breast cancer prevention.

Emergence of a NDM-1-producing ST25 Klebsiella pneumoniae strain causing neonatal sepsis in China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) seriously threaten the efficacy of modern medicine with a high associated mortality rate and unprecedented transmission rate. In this study, we isolated a clinical K. pneumoniae strain DY1928 harboring bla NDM-1 from a neonate with blood infection. Antimicrobial susceptibility testing indicated that DY1928 was resistant to various antimicrobial agents, including meropenem, imipenem, ceftriaxone, cefotaxime, ceftazidime, cefepime, piperacillin-tazobactam, and amoxicillin-clavulanate. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE), southern blot and conjugation experiment revealed that the bla NDM-1 gene was located on a conjugative plasmid of IncA/C2 type with a 147.9 kb length. Whole-genome sequencing showed that there was a conservative structure sequence (bla NDM-1-ble-trpF-dsbD) located downstream of the bla NDM-1 gene. Multilocus sequence typing (MLST) classified DY1928 as ST25, which was a hypervirulent K. pneumoniae type. Phylogenetic analysis of genomic data from all ST25 K. pneumoniae strains available in the NCBI database suggested that all bla NDM-1 positive strains were isolated in China and had clinical origins. A mouse bloodstream infection model was constructed to test the virulence of DY1928, and 11 K. pneumoniae strains homologous to DY1928 were isolated from the feces of infected mice. Moreover, we found that DY1928 had a tendency to flow from the blood into the intestine in mice and caused multiple organ damage. To our knowledge, this is the first study to report an infection caused by bla NDM-1-positive ST25 K. pneumoniae in the neonatal unit. Our findings indicated that stricter surveillance and more effective actions were needed to reduce the risk of disseminating such K. pneumoniae strains in clinical settings, especially in neonatal wards.

Influence of dissolved organic matter on methylmercury transformation during aerobic composting of municipal sewage sludge under different C/N ratios.

Current knowledge about the transformation of total mercury and methylmercury (MeHg) in aerobic composting process is limited. In this study, the composition and transformation of mercury and dissovled organic matter (DOM) in aerobic composting process of municipal sewage sludge were were comprehensively characterized, and the differences among the three C/N ratio (20, 26 and 30) were investigated. The main form of mercury in C/N 20 and 26 was organo-chelated Hg (F3, 46%-60%); while the main form of mercury in C/N 30 was mercuric sulfide (F5, 64%-70%). The main component of DOM in C/N 20 and 26 were tyrosine-like substance (C1, 53%-76%) while the main fractions in C/N 30 were tyrosine-like substance (C1, 28%-37%) and fulvic-like substance (C2, 17%-39%). The mercury and DOM varied significantly during the 9 days composting process. Compared to C/N 20 and 26, C/N 30 produced the less MeHg after aerobic composting process, with values of 658% (C/N 20), 1400% (C/N 26) and 139% (C/N 30) of the initial, respectively. Meanwhile, C/N 30 produced the best compost showed greater degree of DOM molecular condensation and humification. Hg fraction had been altered by DOM, as indicated by a significant correlation between mercury species and DOM components. Notably, C/N 30 should be used as an appropriate C/N ratio to control the methylation processes of mercury and degration of DOM.

Modeling of Polycrystalline Material Microstructure with 3D Grain Boundary Based on Laguerre-Voronoi Tessellation.

Voronoi tessellations are shown to be statistically representative of polycrystalline microstructures, which have been widely accepted for the modeling of microstructures of metallurgic and ceramic materials. In this paper, a new implementation of the Voronoi diagram in Laguerre geometry is presented for the generation of numerical models of polycrystalline microstructures, where the size and shape of the grains can be controlled, and the 3D grain boundaries can be modeled with a specified thickness. The distribution of grain sizes in the models is fitted to a lognormal distribution, compared with the normal distribution in the Voronoi tessellation methods. Finally, statistical analyses of grain face and grain size distribution are performed with the models, and the macroscopic elastic properties of polycrystalline ceramic materials are simulated to verify the capability of the presented method.

Diffuse photon remission associated with the center-illuminated-area-detection geometry: Part I, an approach to the steady-state model.

Diffuse photon remission associated with the center-illuminated-area-detection (CIAD) geometry has been useful for non-contact sensing and may inform single-fiber reflectance (SfR). This series of work advances model approaches that help enrich the understanding and applicability of the photon remission by CIAD. The general approach is to derive the diffuse photon remission by the area integration of the radially resolved diffuse reflectance while limiting the analysis to a medium exhibiting only the Heyney-Greenstein (HG) scattering phase function. Part I assesses the steady-state photon remission in CIAD over a reduced scattering scaled diameter of µ s ' d a r e a ∈[0.5×10-3,103] that covers the range extensively modeled for SfR. The corresponding radially resolved diffuse reflectance is obtained by concatenating an empirical expression for the semi-ballistic region near the point-of-illumination and a formula utilizing a master-slave dual-source scheme over the semi-diffusive to a diffusive regime while being constrained by an extrapolated zero-boundary condition. The terminal algebraic photon remission is examined against Monte Carlo simulations for an absorption coefficient over [0.001,1]m m -1, a reduced scattering coefficient over [0.01,1000]m m -1, a HG scattering anisotropy factor within [0.5,0.95], and a diameter of the area of collection ranging [50,1000]µm. The algebraic model is also applied to phantom data acquired over a ∼2c m non-contact CIAD configuration and with a 200 µm SfR probe. The model approach will be extended in a subsequent work towards the time-of-flight characteristics of CIAD.

Diffuse photon-remission associated with single-fiber geometry may be a simple scaling of that collected over the same area when under centered-illumination.

Robust models for single-fiber reflectance (SFR) are relatively complex [Opt. Lett.45, 2078 (2020)OPLEDP0146-959210.1364/OL.385845] due to overlapping of the illumination and collection areas that entails probability weighting of the spatial integration of photon-remission. We demonstrate, via analytical means for limiting cases and Monte Carlo simulation of broader conditions, that diffuse photon-remission collected by single-fiber geometry may be scaled over the center-illuminated photon-remission. We specify for a medium revealing Henyey-Greenstein (HG) scattering anisotropy that the diffuse photon-remission from a sub-diffusive area of a top-hat illumination is ∼84.9% of that collected over the same area when under a centered-illumination. This ratio remains consistent over a reduced-scattering fiber-size product of µs'dfib=[10-5,100], for absorption varying 3 orders of magnitude. When applied to hemoglobin oxygenation changes induced in an aqueous phantom using a 200 µm single-fiber probe, the center-illumination-scaled model of SFR produced fitting results agreeing with reference measurements.

[Speciation and Ecological Risk Assessment of Heavy Metal(loid)s in the Municipal Sewage Sludge of China].

To reveal the speciation and pollution status of heavy metal(loid) s (HMs) in the dewatered sewage sludge(SS) of municipal wastewater treatment plants(MWTPs) in China, SS samples were collected from 40 MWTPs located in different regions of China. The total concentrations and geochemical fractions of As, Cd, Cr, Cu, Ni, Pb, and Zn in the SS samples were analyzed. The ecological risks induced by HMs in the SS were assessed based on the toxicity characteristic leaching procedure(TCLP), risk assessment code(RAC), and potential ecological risk index(RI). The median values of HMs in SS followed the order Zn > Cu > Cr > Pb > Ni > As > Cd. The general attainment rates of HMs in SS were satisfactory(>90%). As showed a generally even distribution among all the fractions; Cd and Zn mainly existed in the reducible fraction; Cr mainly occurred in the residual fraction, followed by oxidizable and reducible fractions; Cu mainly occurred in the oxidizable fraction; Ni occurred mainly as exchangeable forms; and Pb mainly occurred in the reducible and residual fractions, with its exchangeable form being the lowest fraction. According to the RAC method, the environmental risks induced by HMs in the SS followed the order Ni > As > Zn > Cd > Cu > Cr > Pb. The ecological risk of Ni was high; Zn, As, and Cd had a medium level of risk; Cr and Cu had a low level of risk; and the risk of Pb was negligible. According to the RI method, Cd and Cu showed the highest potential ecological risk, indicating that these are the primary HM pollutants in the SS. However, if the agricultural application of SS is carried out in accordance with the national standards, the overall level of risk from soil HM pollution is considered relatively low.

Empirical method for rapid quantification of intrinsic fluorescence signals of key metabolic probes from optical spectra measured on tissue-mimicking turbid medium.

SIGNIFICANCE: Optical fluorescence spectroscopy technique has been explored extensively to quantify both glucose uptake and mitochondrial metabolism with proper fluorescent probes in small tumor models in vivo. However, it remains a great challenge to rapidly quantify the intrinsic metabolic fluorophores from the optically measured fluorescence spectra that contain significant distortions due to tissue absorption and scattering. AIM: To enable rapid spectral data processing and quantify the in vivo metabolic parameters in real-time, we present an empirical ratio-metric method for rapid fluorescence spectra attenuation correction with high accuracy. APPROACH: A first-order approximation of intrinsic fluorescence spectra can be obtained by dividing the fluorescence spectra by diffuse reflectance spectra with some variable powers. We further developed this approximation for rapid extraction of intrinsic key metabolic probes (2-NBDG for glucose uptake and TMRE for mitochondrial function) by dividing the distorted fluorescence spectra by diffuse reflectance intensities recorded at excitation and emission peak with a pair of system-dependent powers. Tissue-mimicking phantom studies were conducted to evaluate the method. RESULTS: The tissue-mimicking phantom studies demonstrated that our empirical method could quantify the key intrinsic metabolic probes in near real-time with an average percent error of ∼5 % . CONCLUSIONS: An empirical method was demonstrated for rapid quantification of key metabolic probes from fluorescence spectra measured on a tissue-mimicking turbid medium. The proposed method will potentially facilitate real-time monitoring of key metabolic parameters of tumor models in vivo using optical spectroscopy, which will significantly advance translational cancer research.

Diffuse photon remission from thick opaque media of the high absorption/scattering ratio beyond what is accountable by the Kubelka-Munk function.

The Kubelka-Munk (KM) theory of diffuse photon remission from opaque media is widely applied to quality-control processes. Recent works based on radiative transfer revealed that the KM function as the backbone parameter of the method may saturate at strong absorption to cause the KM approach to be unfit to predict the change of diffuse reflectance from the medium at strong absorption. We demonstrate by empirical means based on Monte Carlo results that diffuse photon remission from a strong-absorbing medium depends simply upon the absorption/scattering ratio when evaluated over a large area centered at the point of illumination differing in geometry from those convenient for the KM approach. Our empirical prediction gives ∼11% mean errors of the diffuse photon remission from thick opaque medium having an absorption coefficient ranging 0.001 to up to 1000 times stronger than the reduced-scattering coefficient. A slight modification to the KM function in terms of the absorption weighting and absorption-scattering coupling for use within the KM approach also noticeably improves the prediction of diffuse photon remission from thick opaque medium of strong absorption. Our empirical model and the KM approach using the modified KM function were compared against measurements from a thick opaque medium, of which the absorption coefficient was changed over four orders of magnitude.

Heavy metal(loid)s in sewage sludge in China: concentrations and spatial-temporal variations.

Sewage sludge (SS) production in China has increased rapidly, accompanying the fast expansion of its sewage treatment capacity. Heavy metals (HMs) in SS have been a great concern, hampering the utilization and disposal of SS. In this study, heavy metal (HM) contents in SS from throughout China were determined. The median values of HMs in SS decreased in the order Zn > Cu > Cr > Pb > Ni > As > Hg > Cd. The general attainment rates of HMs in SS are satisfying (> 90%). Combining the present data with those obtained from references, spatial distributions and temporal trends of HMs in SS were analyzed. Depending on the specific HM element, the spatial variation trend might be decreasing trends from south to north and from east to west of China. The element-specific hot spots of SS with relatively high HM contents were identified. Analysis of the historical data in different time intervals reviewed obvious decreasing trends in HM contents of SS in China, indicating the well implementation of more and more stringent environmental regulations.

Leaching behavior and transformation of total mercury and methylmercury from raw and lime-conditioned sewage sludge under simulated rain.

Mercury (Hg) that leaches from municipal sewage sludge (MSS) landfill under natural rain is of increasing concern. The column leaching experiments were conducted to investigate the leaching characteristics of total mercury (THg) and methylmercury (MeHg) as well as pH, total organic carbon (TOC), and total suspended solids (TSS) in the raw sludge (RS) and lime-conditioned sludge (LCS) under simulated rain with different acidities (pH 6.5 and 2.9). Results showed the release of MeHg in the leachates presented different patterns from THg. And the final amounts of MeHg in the MSS columns were 1.49 (RS at pH = 6.5), 1.88 (RS at 2.9), 1.97 (LCS at pH = 6.5), and 2.06 times (LCS at pH = 2.9) higher than the initial amounts, suggesting methylation of inorganic Hg (IHg) occurred in the leaching process. The leaching efficiencies of THg and MeHg in RS was lower than that in LCS, indicating lime was more favorable for the release of THg and MeHg. And lower values of pH of the simulated rain promoted the release of THg and MeHg from RS while the opposite was true for LCS. This study provides a better understanding of the release and biogeochemical transformations of Hg in MSS.

Numerical investigation of depth-sensitive diffuse reflectance and fluorescence measurements on murine subcutaneous tissue with growing solid tumors.

In most biomedical optical spectroscopy platforms, a fiber-probe consisting of single or multiple illumination and collection fibers was commonly used for the delivery of illuminating light and the collection of emitted light. Typically, the signals from all collection fibers were combined and then sampled to characterize tissue samples. Such simple averaged optical measurements may induce significant errors for in vivo tumor characterization, especially in longitudinal studies where the tumor size and location vary with tumor stages. In this study, we utilized the Monte Carlo technique to optimize the fiber-probe geometries of a spectroscopy platform to enable tumor-sensitive diffuse reflectance and fluorescence measurements on murine subcutaneous tissues with growing solid tumors that have different sizes and depths. Our data showed that depth-sensitive techniques offer improved sensitivity in tumor detection compared to the simple averaged approach in both reflectance and fluorescence measurements. Through the numerical studies, we optimized the source-detector distances, fiber diameters, and numerical apertures for sensitive measurement of small solid tumors with varying size and depth buried in murine subcutaneous tissues. Our study will advance the design of a fiber-probe in an optical spectroscopy system that can be used for longitudinal tumor metabolism and vasculature monitoring.

Arabidopsis glucose-sensitive mutant 3 affects ABA biosynthesis and sensitivity during early seedling development.

In plants, glucose (Glc) plays pivotal roles in development and stress responses mainly by supplying fuel for growth and regulating expression of genes essential for crosstalk with hormonal, oxidative, and defense signaling. However, the complicated relationship between Glc and plant hormones is still not very clear. In this study, gsm3 (glucose-sensitive mutant 3), an Arabidopsis mutant with Glc-sensitive phenotype, was identified. Compared to wild type, the cotyledon expansion rate of gsm3 was significantly decreased under the condition of 4.5% Glc. Fluridone was able to rescue the Glc-induced defects of gsm3 in cotyledon expansion. AAO3 and ABI4 are key genes involved in abscisic acid (ABA) biosynthesis and signaling transduction, respectively. We found that inactivation of AAO3 or ABI4 in gsm3 background led to reduced sensitivity to Glc. These results indicated that increased ABA synthesis resulted in the sensitivity of gsm3 to Glc. Moreover, our results indicated that gsm3 mutant accumulated more ROS, which made it more sensitive to the application of exogenous H2O2. Overall, GSM3 plays an important role in Glc-ABA signaling cascade during seed germination and early seedling growth.