Direct measurement of the Raman enhancement factor of rhodamine 6G on graphene under resonant excitation

Graphene substrates have recently been found to generate Raman enhancement. Systematic studies using different Raman probes have been implemented, but one of the most commonly used Raman probes, rhodamine 6G (R6G), has yielded controversial results for the enhancement effect on graphene. Indeed, the Raman enhancement factor of R6G induced by graphene has never been measured directly under resonant excitation because of the presence of intense fluorescence backgrounds. In this study, a polarization-difference technique is used to suppress the fluorescence background by subtracting two spectra collected using different excitation laser polarizations. As a result, enhancement factors are obtained ranging between 1.7 and 5.6 for the four Raman modes of R6G at 611, 1,183, 1,361, and 1,647 cm[superscript −1] under resonant excitation by a 514.5 nm laser. By comparing these results with the results obtained under non-resonant excitation (632.8 nm) and pre-resonant excitation (593 nm), the enhancement can be attributed to static chemical enhancement (CHEM) and tuning of the molecular resonance. Density functional theory simulations reveal that the orbital energies and densities for R6G are modified by graphene dots.National Natural Science Foundation (China) (Nos. 21233001, 50972001, and 21129001)China. Ministry of Science and Technology (Nos. 2011YQ0301240201 and 2011CB932601)Beijing Natural Science Foundation (No. 2132056

Simultaneous bond-selective deuterium-based isotopic labeling sensing with disposable ultra-miniature CARS fiber probe

Deuterium-based isotopic labeling is an important technique for tracking cellular metabolism with the Raman signals analysis of low-wavenumber (LW) C–D bonds and high-wavenumber (HW) C–H bonds. We propose and demonstrate a disposable ultra-miniature fiber probe to detect LW and HW coherent anti-Stokes Raman scattering (CARS) spectra for deuterated compounds simultaneously and bond-selectively sensing. The 10.78 µm diameter disposable fiber probe, comprised of focusing taper as fiber probe head and time-domain walk-off eliminating fiber section with designed length, realizes wide-frequency-interval dual Stokes pulse delivering and focusing. The fiber probe enables quantitative concentration determination with resolution down to 11 mM. The chemical vibration modes of LW region C–D bonds and HW region C–H bonds of the mixture samples of organic compounds and their deuterated counterparts in a simulated cell are simultaneously excited and characterized. The CARS disposable fiber probe introduces a promising handle for in vivo biochemical detection based on isotopic labeling sensing

AI of Brain and Cognitive Sciences: From the Perspective of First Principles

Nowadays, we have witnessed the great success of AI in various applications, including image classification, game playing, protein structure analysis, language translation, and content generation. Despite these powerful applications, there are still many tasks in our daily life that are rather simple to humans but pose great challenges to AI. These include image and language understanding, few-shot learning, abstract concepts, and low-energy cost computing. Thus, learning from the brain is still a promising way that can shed light on the development of next-generation AI. The brain is arguably the only known intelligent machine in the universe, which is the product of evolution for animals surviving in the natural environment. At the behavior level, psychology and cognitive sciences have demonstrated that human and animal brains can execute very intelligent high-level cognitive functions. At the structure level, cognitive and computational neurosciences have unveiled that the brain has extremely complicated but elegant network forms to support its functions. Over years, people are gathering knowledge about the structure and functions of the brain, and this process is accelerating recently along with the initiation of giant brain projects worldwide. Here, we argue that the general principles of brain functions are the most valuable things to inspire the development of AI. These general principles are the standard rules of the brain extracting, representing, manipulating, and retrieving information, and here we call them the first principles of the brain. This paper collects six such first principles. They are attractor network, criticality, random network, sparse coding, relational memory, and perceptual learning. On each topic, we review its biological background, fundamental property, potential application to AI, and future development.Comment: 59 pages, 5 figures, review articl

Combination of Neutrophil Count and Gensini Score as a Prognostic Marker in Patients with ACS and Uncontrolled T2DM Undergoing PCI

Background: Several biomarkers have been studied as prognostic indicators among people with diabetes and coronary artery disease (CAD). The purpose of this study was to determine the prognostic value of neutrophil counts and the Gensini score in patients with diabetes and ACS undergoing percutaneous coronary intervention (PCI). Methods: A total of 694 people with ACS and T2DM who simultaneously had elevated HBA1c received PCI. Spearman rank correlation estimates were used for correlation evaluation. Multivariate Cox regression and Kaplan-Meier analysis were used to identify characteristics associated with major adverse cardiovascular and cerebrovascular events (MACCEs) and patient survival. The effects of single- and multi-factor indices on MACCEs were evaluated through receiver operating characteristic curve analysis. Results: The Gensini score and neutrophil count significantly differed between the MACCE and non-MACCE groups among patients receiving PCI who had concomitant ACS and T2DM with elevated HBA1c (P<0.001). The Gensini score and neutrophil count were strongly associated with MACCEs (log-rank, P<0.001). The Gensini score and neutrophil count, alone or in combination, were predictors of MACCEs, according to multivariate Cox regression analysis (adjusted hazard ratio [HR], 1.005; 95% confidence interval [CI], 1.002–1.008; P=0.002; adjusted HR, 1.512; 95% CI, 1.005–2.274; P=0.047, respectively). The Gensini score was strongly associated with neutrophil count (variance inflation factor ≥ 5). Area under the curve analysis revealed that the combination of multivariate factors predicted the occurrence of MACCEs better than any single variable. Conclusion: In patients with T2DM and ACS with elevated HBA1c who underwent PCI, both the Gensini score and neutrophil count were independent predictors of outcomes. The combination of both predictors has a higher predictability

Gene Expression Profiling for Diagnosis of Triple-Negative Breast Cancer: A Multicenter, Retrospective Cohort Study

Background: Triple-negative breast cancer (TNBC) accounts for 12–20% of all breast cancers. Diagnosis of TNBC is sometimes quite difficult based on morphological assessment and immunohistochemistry alone, particularly in the metastatic setting with no prior history of breast cancer.Methods: Molecular profiling is a promising diagnostic approach that has the potential to provide an objective classification of metastatic tumors with unknown primary. In this study, performance of a novel 90-gene expression signature for determination of the site of tumor origin was evaluated in 115 TNBC samples. For each specimen, expression profiles of the 90 tumor-specific genes were analyzed, and similarity scores were obtained for each of the 21 tumor types on the test panel. Predicted tumor type was compared to the reference diagnosis to calculate accuracy. Furthermore, rank product analysis was performed to identify genes that were differentially expressed between TNBC and other tumor types.Results: Analysis of the 90-gene expression signature resulted in an overall 97.4% (112/115, 95% CI: 0.92–0.99) agreement with the reference diagnosis. Among all specimens, the signature correctly classified 97.6% of TNBC from the primary site (41/42) and lymph node metastasis (41/42) and 96.8% of distant metastatic tumors (30/31). Furthermore, a list of genes, including AZGP1, KRT19, and PIGR, was identified as differentially expressed between TNBC and other tumor types, suggesting their potential use as discriminatory markers.Conclusion: Our results demonstrate excellent performance of a 90-gene expression signature for identification of tumor origin in a cohort of both primary and metastatic TNBC samples. These findings show promise for use of this novel molecular assay to aid in differential diagnosis of TNBC, particularly in the metastatic setting

Association of serum chemerin and inflammatory factors with type 2 diabetes macroangiopathy and waist-to-stature ratio

Chemerin is an adipocytokine that participates in glycolipid metabolism; however, its association with type 2 diabetes (T2DM) with lower extremity macroangiopathy (T2DM-V) has rarely been reported. This study explored the association of chemerin and inflammatory factors with body fat parameters, glucolipid metabolism, and insulin resistance (IR) in T2DM and T2DM-V. Patients were classified into normal glucose regulation (NGR), T2DM, and T2DM-V groups. Serum chemerin, glucolipid metabolic parameters, transforming growth factor (TGF)-β, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and fasting insulin levels were measured along with HOMA-IR, body mass index (BMI), and waist-to-stature ratio (WSR). Serum chemerin, TGF-β, IL-6 and MCP-1 levels were significantly higher in T2DM groups than in NGR group, and BMI, WSR, fasting plasma glucose (FPG), 2hPG, glycated hemoglobin (HbA1c), triglycerides (TG) and HOMA-IR were higher in T2DM-V subgroups with moderate or severe lower extremity macroangiopathy than in NGR group, simple T2DM group, and T2DM-V subgroup with mild macroangiopathy. FPG, 2hPG, HbA1c, TG and HOMA-IR were higher in T2DM-V subgroup with severe macroangiopathy than in T2DM-V with moderate macroangiopathy (p < 0.05). In all groups, serum chemerin levels were positively correlated with BMI, WSR, FPG, 2hPG, HbA1c, fasting insulin, aspartate transaminase, TG, TGF-β, IL-6 and HOMA-IR (p < 0.05) and negatively correlated with high-density lipoprotein cholesterol [HDL-c] (p < 0.05). Multiple stepwise regression analysis showed that 2hPG, HbA1c, and HDL-c were independent predictors of serum chemerin levels (β = -0.768, -0.122, -0.115, and 3.261, respectively; p < 0.01). Collectively, chemerin, factors associated with obesity, pathological and physiological changes in glucolipid metabolism, and inflammatory factors may promote the development of T2DM macroangiopathy

Impact of CRAMP-34 on Pseudomonas aeruginosa biofilms and extracellular metabolites

Biofilm is a structured community of bacteria encased within a self-produced extracellular matrix. When bacteria form biofilms, they undergo a phenotypic shift that enhances their resistance to antimicrobial agents. Consequently, inducing the transition of biofilm bacteria to the planktonic state may offer a viable approach for addressing infections associated with biofilms. Our previous study has shown that the mouse antimicrobial peptide CRAMP-34 can disperse Pseudomonas aeruginosa (P. aeruginosa) biofilm, and the potential mechanism of CRAMP-34 eradicate P. aeruginosa biofilms was also investigated by combined omics. However, changes in bacterial extracellular metabolism have not been identified. To further explore the mechanism by which CRAMP-34 disperses biofilm, this study analyzed its effects on the extracellular metabolites of biofilm cells via metabolomics. The results demonstrated that a total of 258 significantly different metabolites were detected in the untargeted metabolomics, of which 73 were downregulated and 185 were upregulated. Pathway enrichment analysis of differential metabolites revealed that metabolic pathways are mainly related to the biosynthesis and metabolism of amino acids, and it also suggested that CRAMP-34 may alter the sensitivity of biofilm bacteria to antibiotics. Subsequently, it was confirmed that the combination of CRAMP-34 with vancomycin and colistin had a synergistic effect on dispersed cells. These results, along with our previous findings, suggest that CRAMP-34 may promote the transition of PAO1 bacteria from the biofilm state to the planktonic state by upregulating the extracellular glutamate and succinate metabolism and eventually leading to the dispersal of biofilm. In addition, increased extracellular metabolites of myoinositol, palmitic acid and oleic acid may enhance the susceptibility of the dispersed bacteria to the antibiotics colistin and vancomycin. CRAMP-34 also delayed the development of bacterial resistance to colistin and ciprofloxacin. These results suggest the promising development of CRAMP-34 in combination with antibiotics as a potential candidate to provide a novel therapeutic approach for the prevention and treatment of biofilm-associated infections

Association between plasma trimethylamine N -oxide and neoatherosclerosis in patients with very late stent thrombosis

Abstract(#br)Background(#br)Trimethylamine N -oxide (TMAO) has been shown to promote the development of atherosclerosis. However, the relationship between plasma TMAO and neoatherosclerosis, an important underlying mechanism of very late stent thrombosis (VLST), is unknown.(#br)Methods(#br)This post hoc study investigated the association between TMAO and neoatherosclerosis in two independent cohorts. These included a control group of 50 healthy volunteers and a study cohort of 50 patients with VLST who presented with ST-segment elevation myocardial infarction and underwent optical coherence tomography examination. Of the 50 patients with VLST, 23 had neoatherosclerosis and 27 did not have neoatherosclerosis. Patients with neoatherosclerosis were further divided into two subgroups, including 14 patients with plaque rupture and 9 without plaque rupture.(#br)Results(#br)The plasma TMAO levels, detected using mass spectrometry, were significantly higher in patients with VLST than in healthy individuals (median [interquartile range]: 2.50 [1.67-3.84] vs. 1.32 [0.86-2.44] μM; P < 0.001). Among the VLST patients, the plasma TMAO levels were significantly higher in patients with neoatherosclerosis than in those without neoatherosclerosis (3.69 [2.46-5.29] vs. 1.96 [1.39-2.80] μM; P<0.001). In addition, in patients with neoatherosclerosis, patients with plaque rupture had significantly higher plasma TMAO concentrations than those without plaque rupture (4.51 [3.41-5.85] vs. 2.46 [2.05-3.55] μM; P=0.005). Multivariate analysis indicated that TMAO was an independent predictor of neoatherosclerosis (odds ratio 3.41; 95% confidence interval: 1.59-7.30; P=0.002). Moreover, the area under the receiver operating characteristic curve for TMAO, differentiated by neoatherosclerosis, was 0.85.(#br)Conclusions(#br)Plasma TMAO was significantly correlated with neoatherosclerosis and plaque rupture in patients with VLST