Intensity Of Expression Research Articles

Alcohol increases social engagement in dyadic interactions: role of partner's drug state.

Alcohol is commonly used in social environments and is known to facilitate social behaviors. However, most controlled laboratory studies on alcohol have been conducted in isolated settings, limiting our understanding of its effects on social interactions. The current study was designed to examine the effects of alcohol on dyadic interactions in healthy volunteers (N = 37), with a focus on the influence of the conversation partner's drug state. Using a 4-session, placebo-controlled, within-subjects design, participants received a moderate dose of alcohol (0.8g/kg men) or placebo in randomized order before engaging in a 45-minute semi-structured conversation with a partner who received either alcohol or placebo. Partners were always strangers. Outcome measures included subjective responses to alcohol, self-reported closeness to partners, and facial expressions during interactions analyzed via a machine learning model. Alcohol produced its expected subjective effects, some of which were enhanced when the partner also received alcohol. Alcohol enhanced enjoyment of social interactions and feelings of connectedness, irrespective of the partner's drug condition. Facial expression analysis revealed that alcohol increased positive and decreased negative emotional expressions. For women but not men, these effects were more pronounced when their conversation partners also received alcohol. Individual emotion analysis revealed that alcohol increased the intensity of facial expressions associated with amusement, joy, and excitement, while reducing emotions such as awkwardness and contempt. Our findings show that alcohol increases feelings of social connectedness, and that responses to alcohol can be influenced by the drug state of interacting partners. The increased feelings of social connection may contribute to risk for escalation of use.

Coherent characteristics of broadband and extended light sources based on the Twyman–Green interferometer

The Twyman–Green interferometer, as a representative type of interferometric structure, possesses unique advantages in the field of interferometry due to its adjustable single optical path characteristic. However, using a laser as the light source for the Twyman–Green interferometer, with its long coherence length, can result in noisy fringes when measuring planar elements, including multiple surface interference fringes and speckle noise. To address these issues, this paper proposes the use of broadband extended light source as the coherent light source in the Twyman–Green interferometer to achieve short coherent source illumination, thereby eliminating interference fringes and coherent noise. This paper theoretically derives the coherence characteristics of broadband extended light sources and, in particular, quantitatively analyzes the influence of the thickness difference of glass in the Twyman–Green dual optical paths on the contrast of the interference fringe. The corresponding theoretical expressions for interference intensity are derived, and the validity of these theoretical findings is demonstrated through simulation analysis and experimental verification. This innovative research, to our knowledge, significantly supplements the existing coherence theory of light sources, offering substantial theoretical research insights and practical engineering applications.

Deployment of a Machine Learning Algorithm in a Real-World Cohort for Quality Control Monitoring of Human Epidermal Growth Factor-2-Stained Clinical Specimens in Breast Cancer.

Precise determination of biomarker status is necessary for clinical trial enrollment and endpoint analyses, as well as for optimal treatment determination in real-world practice. However, variabilities may be introduced into this process due to the processing of clinical specimens by different laboratories and assessment by distinct pathologists. Machine learning tools have the potential to minimize inconsistencies, although their use is not presently widespread. To assess the applicability of machine learning to the quality control process for biomarker scoring in oncology, we developed and validated an automated machine learning model to be applied as a quality control tool for monitoring the assessment of human epidermal growth factor-2 (HER2). The model was trained using whole slide images from multiple sources to quantify HER2 expression and measure immunohistochemistry stain intensity, tumor area, and the presence of artifacts or ductal carcinoma in situ across breast cancer phenotypes. The quality control tool was deployed in a real-world cohort of HER2-stained breast cancer sample images collected from routine diagnostic practice to evaluate trends in HER2 testing quality indicators and between pathology laboratories. Automated image analysis for HER2 scoring is consistent and reliable using this algorithm. Deployment of the HER2 quality control tool across 3 clinical laboratories revealed interlaboratory variability in HER2 scoring and inconsistencies in data reporting. These results support the future incorporation of quality control algorithms for real-time monitoring of clinical laboratories contributing to clinical trials in oncology and in the real-world setting of HER2 immunohistochemistry testing in local clinical laboratories and hospitals.

Heterogeneity of the Alpha-Smooth Muscle Actin Tumor Score in Breast Cancer Cells Significantly Affects Tumor Invasiveness, Recurrence, and Patient Survival.

Alpha-smooth muscle actin (αSMA) has been widely investigated in malignancies, primarily concerning its expression in cancer-associated fibroblasts (CAFs) inside the tumor stroma. Microscopic examination indicates that αSMA expression is not confined to the tumor stromal compartment but is also present in a subset of tumor cells, and this expression correlates with an enhanced invasive phenotype of malignant cells from lung, liver, or ovarian malignancies. Information on actin expression in breast cancer (BC) cells is scarce, and its influence on clinicopathological characteristics remains ambiguous due to conflicting findings in the literature. To examine the αSMA tumor score in breast cancer cells utilizing digital image analysis (DIA) methodologies and to critically analyze the varying effects of αSMA tumor score values on clinicopathologic parameters, particularly focusing on tumor cell invasiveness, recurrence, and survival. Double immunostaining for CD34 and αSMA was conducted on 53 breast cancer cases that were thoroughly characterized in relation to clinicopathologic data. Double immunostaining for CD34 and αSMA demonstrated different distribution patterns of both markers in normal and breast cancer tissues. DIAdata about αSMA tumor cell density, intensity, tumor score, and histological score were correlated with clinicopathological factors. We delineated three unique breast cancer subgroups based on αSMA tumor scores: a 9.43% low-expressing subgroup (αSMA_TSlow, score 4), a 35.07% medium-expressing subgroup (αSMA_TSmed, scores 5 and 6), and a 55.5% high-expressing subgroup (αSMA_TShigh, scores 7 and 8). Stromal immature vessels and tertiary lymphoid structures (TLS) exhibited a strong correlation with αSMA_TSlow, whereas recurrence, perineural, and lymphovascular invasion strongly influenced the αSMA_TSmed and αSMA_TShigh subgroups. The αSMA_TSmed subgroup demonstrated the most heterogeneity with the influence of αSMA-expressing breast cancer cells on tumor size, nodal status, perineural and lymphovascular invasion, menopausal status, recurrence, and survival. Most of the cases from the αSMA_TSlow subgroup had Luminal B and Luminal B-HER2 phenotypes, while triple-negative breast cancer (TNBC) represented one-third of all cases in the αSMA_TShigh subgroup. αSMA-expressing breast cancer cells variably affect malignant growth, invasion, and recurrence, highly contingent upon their density and expression intensity. The current investigation identified an αSMA_TSmed BC subgroup that appears to promote invasiveness, recurrence, and survival in breast cancer. Our data indicate that αSMA BC-expressing cells play a dual role in BC progression, contingent upon their percentage and expression intensity; however, further research is required to elucidate the factors and mechanisms responsible for their accumulation and/or transdifferentiation in malignant breast tissue.

An Innovative 3D-IDE Design and Adaptive Signal Extraction Algorithm for Efficient Ovarian Cancer Detection.

This work presents a facile, ultrasensitive, and selective chemiresistive biosensor assisted by an adaptive signal extraction algorithm (ASEA) for detecting vimentin, a potential biomarker for ovarian cancer detection. The low-cost device, fabricated on a PCB substrate through sacrificial copper etching, features a 3D-IDE design with interwoven comb-like structures mimicking the natural symmetry of a droplet. An unequal count of positive and negative concentric circle fingers ensures a uniform, higher electric field over the sensor's surface, as verified by COMSOL Multiphysics 3D simulation. This optimal electric field elegantly reflects changes in the IV characteristics, even with minor variations in surface charge density from probe-target interactions. Graphene oxide, functionalized with a heterobifunctional linker, serves as the sensing nanomaterial. A detailed study examines the device's response with interdigitated gaps from 30 to 150 μm. A wider interdigitated gap introduces greater variability in the response across different voltage levels. To address this, the Python-based ASEA meticulously scans the entire voltage range, isolating the segment of the signal that best balances both the intensity and extension for optimal expression. ASEA boosts the limit of detection (LOD) by five times for sensors with gaps of over 100 μm. The biosensor achieves a minimum LOD of 9.45 fg mL-1 and a highest sensitivity of (ΔR/R) 477 ng mL-1 cm2. The biosensor exhibits excellent selectivity, strong resistance to interfering proteins, and commendable stability, showcasing its potential for on-field and point-of-care testing.

Enhancing protective immunity against SARS-CoV-2 with a self-amplifying RNA lipid nanoparticle vaccine.

RNA-based vaccines against SARS-CoV-2 have demonstrated promising protective immunity against the global COVID-19 epidemic. Enhancing the intensity and duration of mRNA antigen expression is anticipated to markedly boost antiviral immune responses. Self-amplifying RNA (saRNA) represents a next-generation platform for RNA-based vaccines, amplifying transcripts in situ to augment the expression of encoded immunogens. Here, we develop a saRNA nanovaccine, formulated with a mutated saRNA encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, encapsulated within a lipid nanoparticle (LNP-saRNA-RBD). This LNP-saRNA vaccine platform enables efficient delivery of saRNA-RBD, inducing enhanced and prolonged expression of the RBD antigen. LNP-saRNA-RBD vaccination stimulated the generation of antigen-specific T cells, promoting their differentiation into a long-lived effector memory phenotype. Immunization with LNP-saRNA-RBD induced a germinal center response in draining lymph nodes, leading to the production of anti-RBD IgG antibodies with the ability to neutralize SARS-CoV-2 pseudovirus. Furthermore, prime-boost immunizations with LNP-saRNA-RBD conferred protection to mice against SARS-CoV-2 challenge by suppressing viral infection and replication, as well as pulmonary inflammatory responses and associated damage. Taken together, these findings provide strong support for advancing the development of LNP-saRNA-RBD as a safe and efficacious vaccine candidate against SARS-CoV-2 infection.

P53 marker expression in epithelial ovarian tumours in a centre in Nigeria – a descriptive study

Backgroundp53 is a tumor suppressor gene. p53 expression in epithelial ovarian tumors (EOTs) is correlated with their biological behavior and predicts patient overall survival. However, there is a dearth of knowledge regarding p53 expression in these tumors among women from southwest Nigeria. Our study aimed to determine the patterns of p53 expression in various types of epithelial ovarian tumours.MethodsWe conducted a retrospective study of epithelial ovarian tumours. We retrieved formalin-fixed, paraffin-embedded (FFPE) tissue blocks of previously diagnosed epithelial tumors from the departmental archive. We performed immunohistochemical analysis using p53 antibodies. We scored the expression and staining intensity of p53 as follows: negative (0), focal/weakly positive (1 +), and diffuse/strongly positive (2 +) on the basis of the recommended Cytomation scoring system.ResultsThe spectrum of p53 expression in the 51 histologically diagnosed cases revealed that 29 cases had no expression, consisting of 21 benign EOTs, two borderline EOTs, and six malignant EOTs. Nine cases exhibited wild-type expression, including six serous carcinomas, two mucinous carcinomas, and one signet ring cell carcinoma. p53 overexpression was observed in 13 patients overall, with 12 having serous carcinomas and one having endometrioid carcinoma. Among the 21 serous carcinoma patients, 28.6% (6 patients) presented with wild-type p53 expression, 57.1% (12 patients) presented with p53 overexpression, and 14.3% (three patients) presented negative p53 expression. There was a significant association between p53 expression and the histological grade of serous carcinoma.ConclusionMost epithelial ovarian carcinomas in our hospital are high grade, with many serous carcinomas showing either p53 overexpression or loss of expression. This may contribute to the poor patient survival rate.

Amniotic fluid-derived stem cells: potential factories of natural and mimetic strategies for congenital malformations

Background:Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy.Methods:MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. A physicochemical, structural, and molecular comparison was conducted with exosomes (EXOs) released from the same batch of cells. Additionally, their distribution patterns in female mice were evaluated following in vivo administration, along with an assessment of their safety profile throughout gestation in a mouse strain predisposed to neural tube defects (NTDs). The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake in two different cell types(fibroblasts, and macrophages) and mRNA functionality overtime in an in vitro experimental setting as well as in an ex vivo, whole embryo culture using pregnant C57BL6 dams.Results:Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a threefold greater yield. Biodistribution patterns following intraperitoneal administration were comparable between the two particle types, with the uterus being among targeted organs. No toxic effects were observed in the dams during gestation, nor were there any malformations or significant differences in the number of viable versus dead fetuses detected. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein in macrophages and fibroblasts. An ex-vivo whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo.Conclusions:The present data confirms the potential application of EXOs and MIMs as suitable tools for prevention and treatment of NTDs and proposes MIMs as prospective vehicles to prevent congenital malformations caused by in utero exposure to drugs.

Molecular Ultrasound Imaging With Clinically Translatable cRGD-Coated Microbubbles to Assess αvβ3-Integrin Expression in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) subdivides into Crohn disease (CD) and ulcerative colitis (UC), and is characterized by unpredictable periods of inflammation and results in significant patient suffering and even death. Conventional diagnostic methods, for example, colonoscopy, computed tomography, or magnetic resonance imaging, have limitations such as invasiveness, patient discomfort, and limited sensitivity and accuracy. Therefore, we propose ultrasound molecular imaging (USMI) to detect and characterize IBD. First, we evaluated integrin-αvβ3 as a biomarker of IBD in human samples and then used clinically translatable cyclic Arg-Gly-Asp-D-Phe-Lys (cRGDfK)-coupled poly(butyl)cyanoacrylate microbubbles (cRGD-MB) to assess IBD in mice. Vascular integrin-αvβ3 expression in human colon tissue samples (healthy, CD and UC, n = 10 per group) was analyzed by immunofluorescence staining. In mice, acute colitis was induced by administration of 4% dextran sodium sulfate in drinking water for 5 days. On day 7, USMI with cRGD-MB was performed in colitis (n = 6) and healthy (n = 5) mice. The signal of bound cRGD-MB was assessed by the destruction-replenishment method. Ex vivo analysis of mouse colon tissue was performed to assess the degree of colitis by hematoxylin-eosin staining and the vascular expression of integrin-αv by immunofluorescence. Human samples showed a significantly higher vascular integrin-αvβ3 expression in CD and UC tissue, when compared with healthy samples (P < 0.005). In mice, a higher binding of cRGD-MB to inflamed colon was detected by USMI compared with healthy controls (P < 0.005). Immunofluorescence staining confirmed these findings, showing stronger integrin-αv expression in acute colitis, with a good correlation between USMI signal intensity and integrin-αv expression (r = 0.8, P = 0.0016). Integrin-αvβ3 on vessels is a suitable marker for IBD. USMI using cRGD-MB accurately detects this marker and correlates well with histology. These encouraging results support clinical translation of this imaging method as a noninvasive and cost-effective monitoring tool.

The Intensity of BCL2A1 Expression Increases According to the Stage Progression of Acute Histologic Chorioamnionitis in the Extra-Placental Membranes of Spontaneous Preterm Birth

The Intensity of BCL2A1 Expression Increases According to the Stage Progression of Acute Histologic Chorioamnionitis in the Extra-Placental Membranes of Spontaneous Preterm Birth

Risk-free rate caplets pricing by CTMC approximation

The benchmark rate reform has significant impact on fixed income derivatives markets, and poses challenges in pricing risk-free rate (RFR) instruments. We propose a unified framework for pricing RFR caplets, including forward-looking, backward-looking and barrier caplets, under general Markov short rate models. Our approach is to approximate the RFR process using continuous-time Markov chain (CTMC). We derive an explicit expression of T-forward intensity and transition probability under CTMC for general interest rate derivatives, and use Laplace transform to price caplets with backward-looking rates. The framework offers a comprehensive and efficient approach to accurately price RFR caplets across various short rate models, and can be potentially extended to other types of RFR derivatives. Numerical experiments demonstrate the efficiency and accuracy of our pricing method under popular short rate models including the Vasicek model, CIR model, and jump-extended CEV model.

Enhanced neural sensitivity to brief changes of happy over angry facial expressions in preschoolers: A fast periodic visual stimulation study.

Across childhood, emotion perception from facial expressions has traditionally been studied with event-related potentials (ERP). Here, we explored the novel fast periodic visual stimulation (FPVS) electroencephalography (EEG) approach to provide information about how brief changes in facial expressions are processed implicitly in young children's brains. Utilizing two FPVS tasks for the first time in preschoolers, we examined brain responses to (1) the discrimination of brief changes in facial expressions at maximum intensity and (2) thresholds for discrimination of gradual increasing facial expression intensities. Within a stream of neutral faces at 6 Hz, happy and angry faces were embedded with a frequency of 1.2 Hz. Additionally, children performed an emotion recognition task (ERT). Data were collected in the context of a training study for socio-emotional competencies with typically developing children (N = 74; 5.1[0.9] years; 34 females). FPVS data were collected post-training, where training was included as a controlling factor. Across FPVS tasks, we detected robust expression change responses, particularly with larger responses for happy versus angry faces in the maximum intensity task. ERT results paralleled neural findings with faster reaction times and higher accuracy rates for happy versus angry faces. For gradual increases in emotional intensity, we found linear increases in responses across emotions. The majority of the sample showed a significant expression change at 60% intensity. With its implicit nature, short duration, and robustness of individual responses, our results highlight the potential of FPVS in comparison to classical ERP methods to study neural mechanisms of emotion perception in preschool samples.

Verba Emosi Marah Dalam Bahasa Aceh: Kajian Metabahasa Semantik Alami

This article aims to look at the representation of reality in language, especially in the context of using words to express emotions, focusing on the word "angry" in the Acehnese language. Natural Semantic Metalanguage Theory (MSA) is used as a theoretical framework to analyze the meaning of these words. The research method used is qualitative descriptive with data collection through interviews, textbooks, and videos in Acehnese. The results of the analysis show that the words used to express angry emotions in Acehnese, such as "bingeing", "cat", "dam", "tune", "as a", "chicken", and "lust", have basic meanings—the same but different in the context and intensity of emotional expression. The meaning component analysis highlights differences in the experience and expression of angry emotions and strengthens understanding of the variation and complexity of human emotions in specific cultural contexts. This research provides a deeper understanding of the role of language in representing emotional reality and enriches the study of emotional semantics in the Acehnese cultural context.

Damage quantification using spectral response of a multi-degree-of-freedom system with spatial and temporal stiffness variations: Application to shear-type frames

The present study is aiming to develop a spectral response-based closed-form expression of maximum damage intensity in a multi-degree-of-freedom system considering temporal and spatial variations of stiffness. The time-dependent variation of stiffness is incorporated in the formulation to simulate opening–closing mechanism of crack. In addition, an expression for multiple damage severity at consecutive stories is also derived. For the validation of the present method, numerical model of a shear-type frame is thoroughly investigated. It is observed from the analysis that incorporation of spectral amplitudes at modulated frequencies in the formulation, improves the assessment of damage severity. Further, an experiment on a scale-down 6-story steel building is performed for practical insights followed by two case studies with real data of a full-scale tower and an instrumented building. As the assumed temporal variation of stiffness is not generic, it may mislead the accuracy of estimated damage quantity in other incompatible scenarios.

Abstract 4121527: Empagliflozin Improves Mitochondrial Biogenesis in Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by endothelial proliferation and progressive pulmonary vascular (PV) remodeling. Empagliflozin (EMPA), a sodium glucose cotransporter 2 (SGLT2) inhibitor, benefits heart failure patients, potentially mediated by improved mitochondrial function. This study aimed to explore the impact of EMPA in PAH. Methods and Results: Immunohistochemistry of pulmonary arteries revealed the expression of SGLT2 in the intima of PAH patients. Microvascular endothelial cells (MVECs) were isolated from lungs of control subjects (CTRL) and PAH patients and found intense expression of SGLT2 in PAH MVECs. Western blot showed significantly higher expression of SGLT2, while PGC-1α, a transcriptional coactivator known as a master regulator of mitochondrial biogenesis, was lower in PAH MVECs compared to CTRL (Image 1). PAH MVECs were treated with EMPA (1 μM) and observed a significant increase of PGC-1α and BMPR2-pSmad1/5/9. Similarly, knockdown of SGLT2 using siRNA resulted in enhanced expression of PGC-1α. Moreover, Seahorse analysis revealed increased oxygen consumption rate and reduced extracellular acidification rate by EMPA, suggesting that EMPA improved mitochondrial respiration. In addition, EMPA attenuated reactive oxygen species and proliferation of PAH MVECs, as revealed by MitoTracker analysis and MTT assay respectively. For the in vivo study, Sprague-Dawley rats (120-180 gram) were injected with SU5416 (Week-0) and exposed to hypoxia for 3 weeks followed by normoxia. After randomization at Week-4, rats were treated with EMPA (300 mg/kg in chow, n=12) or placebo (PLAC, n=12). Catheterization and histological analysis were performed at Week-8. EMPA decreased PV resistance index (0.21±0.02 vs. 0.37±0.05 mmHg/mL/min/mm 2 , p=0.01), ameliorated intima thickening (21.0±7.5 vs. 40.0±7.8%, p&lt;0.01) and vessel occlusion (Image 2). We further conducted a single-center, open-label, single-arm interventional proof-of-concept study to assess the tolerability of 12 weeks of treatment with 10mg of EMPA as add-on therapy in eight patients with a prior PAH diagnosis. There were no treatment related adverse events during the study time course. Conclusions: EMPA directly improved mitochondrial biogenesis and attenuated proliferation of MVECs from PAH patients and reversed PV remodeling in experimental PAH. EMPA treatment was feasible in patients with PAH. EMPA may serve as a new therapeutic option for PAH.

Propagation properties of two types of sinc Schell-model beams in oceanic turbulence

Abstract The evolution of two types of sinc Schell-model (SSM) beams, each considered with both circular and rectangular symmetries, is investigated during their propagation in oceanic turbulence. The expressions for the spectral intensity and spectral coherence of the transmitted optical field are derived using the extended Huygens-Fresnel principle. Based on these expressions, numerical simulations are carried out to explore how source and turbulence parameters influence the transmitted field. The results demonstrate that the spectral intensity distribution of the SSM1 beam evolves from an initial Gaussian profile into a circular or rectangular flat-topped shape during propagation, while the SSM2 beam develops into a ring-shaped or array-like pattern. As the dissipation rate of turbulent kinetic energy decreases, or the mean square temperature dissipation rate and the strength of temperature and salinity fluctuations increase, the energy of these beams disperses from its concentrated regions to the surrounding areas, causing the characteristic intensity distributions to become blurred. Additionally, the coherence of these beams exhibits oscillatory distributions, with the SSM2 beam showing stronger oscillations compared to the SSM1 beam and displaying greater sensitivity to changes in turbulence parameters. The intensity and coherence distributions are also affected by source parameters, which play a dominant role at shorter propagation distances. However, as the distance increases, turbulence parameters gradually become the primary influence. The results presented here may be applied to oceanic optical communication and remote sensing.

Stimulated Brillouin scattering in plasmonic nanofiber containing an ensemble of metallic nanorods

A theory of stimulated Brillouin scattering (SBS) has been developed for metallic nanohybrid fiber, which is made of an ensemble of metallic nanoparticles doped in a dielectric nanofiber. We consider that input probe light photons scatter within the nanohybrid and produce stimulated Brillouin scattered photons and acoustic phonons. The coupled-mode formalism based on Maxwell’s equations is used to obtain the SBS intensity, the SBS energy, and the SBS absorption coefficient. It is found that the SBS depends on the third-order susceptibility, which is evaluated by the density matrix method. An analytical expression of the SBS intensity, energy, and absorption coefficient is calculated in the presence of surface plasmon polaritons (SPPs) and dipole-dipole interactions (DDI) between nanoparticles in the ensemble. Next, we have compared our theory with the experimental data for a nanohybrid made of an ensemble of Au-nanorods doped in water. A good agreement between theory and experiment is found. We have also performed the numerical simulations to study the effect of SPP and DDI fields on the SBS intensity. We have predicted an enhancement in the SBS intensity due to the SPP and DDI couplings. The enhancement is due to not only the scattering mechanisms of the probe photons with acoustic phonons but also the extra scattering mechanisms from the SPP and DDI polaritons with acoustic phonons. The SBS analytical expressions can be useful for experimental scientists and engineers who can use them to plan new experiments and make new types of plasmonic devices. The enhancement effect can be used to fabricate new types of SBS nanosensors and amplifiers.

Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models

Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC.

Hyperresponsiveness of Corticoid-Resistant Th17/Tc-17 Cells to TLR-2 and TLR-4 Ligands is a Feature of Multiple Sclerosis Patients at Higher Risk of Therapy Failure.

The presence of T cells expressing TLR-2 and TLR-4 has been associated with relapsing-remitting multiple sclerosis (RRMS) pathogenesis. Here, we evaluated whether the effectiveness of DMT in controlling clinical activity of the disease would be associated with modulation of proportion of TLRs+ T cells. Whole peripheral blood mononuclear cells, purified CD4+ and CD8+ T cells from RRMS patients were cultured with different stimuli. The frequency of IL-17-secreting CD4+ and CD8+ T cells positive for TLR-2 and TLR-4 was determined by flow cytometry. The cytokine profile of these T cells following TLR-2 and TLR-4 stimulation was determined by Multiplex. Some of these T cell cultures were treated with hydrocortisone. The levels of LPS-binding protein (LBP) were dosed by ELISA. Clinical (occurrence of relapses) and radiological (number of active brain lesions) activity were evaluated during the 1-year follow-up. Despite DMT, high intensity of TLR-2 and TLR-4 expression on (CD4+ and CD8+) T-cells, as well as the frequency of IL-17-secreting (CD4+ and CD8+) T-cells, are predictive of future RRMS relapses. Moreover, higher cytokine production related to Th17/Tc-17 phenotypes in response to TLR-2 and TLR-4 agonists was observed in DMT-treated patients and displayed an elevated number of brain lesions. The hyperresponsiveness of MS-derived T-cells to TLR-2 and TLR-4 ligands, with high levels of IL-1β, IL-6, IL-17, IFN-γ and GM-CSF in response to both TLR agonists, positively correlated with plasma LBP levels. Interestingly, corticoid was less efficient in reducing Th17 and Tc-17 cytokine production induced by TLR-2 and TLR-4 ligands in DMT-treated patients who relapsed during follow-up. Collectively, the data suggested that persistence of circulating Th17 and Tc17 cells expressing elevated levels of functional TLR-2 and TLR-4 could indicate high disease activity and lower therapeutic efficacy in RRMS patients.

Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products.

Microbial genetic circuits are vital for regulating gene expression and synthesizing bioactive compounds. However, assessing their strength and timing, especially in multicellular fungi, remains challenging. Here, an advanced microfluidic platform is combined with a mathematical model enabling precise characterization of fungal gene regulatory circuits (GRCs) at the single-cell level. Utilizing this platform, the expression intensity and timing of 30 transcription factor-promoter combinations derived from two representative fungal GRCs, using the model fungus Aspergillus nidulans are determined. As a proof of concept, the selected GRC combination is utilized to successfully refactor the biosynthetic pathways of bioactive molecules, precisely control their production, and activate the expression of the silenced biosynthetic gene clusters (BGCs). This study provides insights into microbial gene regulation and highlights the potential of platform in fungal synthetic biology applications and the discovery of novel natural products.