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Hepatocellular carcinoma (HCC) is still one of the leading causes of tumor-related deaths. Accumulating evidence indicates that immunogenic cell death (ICD) could occur in tumor cells. However, ICD-related studies are limited in HCC. This study collected HCC RNA sequencing data from the Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R software was used to analyze the expression of ICD in HCC and to screen essential genes with prognostic value. qRT-PCR and WB determined the mRNA and protein expressions of hub gene. Cell viability assay, Clonal formation assay, and Live/dead staining assay were employed to determine the gene functions. After cross-analysis of differentially expressed genes (DEGs) and ICD-related genes (ICDRGs), 7 differentially expressed ICDRGs were identified in HCC. Of them, HSP90AA1, with the most excellent prognostic value in HCC, was selected, whose expression was also validated in public cohorts, cell lines, and clinical tissue samples. High HSP90AA1 expression indicated an inferior prognosis of HCC, and HSP90AA1 knockdown significantly suppressed cell viability and chemotherapy resistance of HCC. ICD-related gene HSP90AA1 was an unfavorable factor for HCC, and high HSP90AA1 expression contributed to tumor cell survival and chemotherapy resistance.

Polygala tenuifolia, commonly known as Yuanzhi (YZ) in Chinese, has been shown to possess anti-insomnia properties. However, the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear. Herein, we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging (MSI)-based spatial resolved metabolomics. According to the results, 17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain, which might be the major components contributing to the sedative-hypnotic effects. Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse, and dopaminergic synapse, among other pathways. LC-MS/MS-based targeted metabolomics and Western blot (WB) revealed that tryptophan-serotonin-melatonin (Trp-5-HT-Mel) and tyrosine-norepinephrine-adrenaline (Tyr-Ne-Ad) are the key regulated pathways. Dopa decarboxylase (DDC) upregulation and phenylethanolamine N-methyltransferase (PNMT) downregulation further confirmed these pathways. Furthermore, MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland (PG), and Ad in the brainstem, including the middle brain (MB), pons (PN), and hypothalamus (HY). In summary, this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine, YZ.

Evaluating toxicity and decoding the underlying mechanisms of active compounds are crucial for drug development. In this study, we present an innovative, integrated approach that combines air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and spatial metabolomics to comprehensively investigate the nephrotoxicity and underlying mechanisms of nitidine chloride (NC), a promising anti-tumor drug candidate. Our quantitive AFADESI-MSI analysis unveiled the region specific of accumulation of NC in the kidney, particularly within the inner cortex (IC) region, following single and repeated dose of NC. High spatial resolution ToF-SIMS analysis further allowed us to precisely map the localization of NC within the renal tubule. Employing spatial metabolomics based on AFADESI-MSI, we identified over 70 discriminating endogenous metabolites associated with chronic NC exposure. These findings suggest the renal tubule as the primary target of NC toxicity and implicate renal transporters (organic cation transporters, multidrug and toxin extrusion, and organic cation transporter 2 (OCT2)), metabolic enzymes (protein arginine N-methyltransferase (PRMT) and nitric oxide synthase), mitochondria, oxidative stress, and inflammation in NC-induced nephrotoxicity. This study offers novel insights into NC-induced renal damage, representing a crucial step towards devising strategies to mitigate renal damage caused by this compound.

A tunable tri-band terahertz refractive index sensor based on graphene is proposed and designed. The structure of the sensor comprises a gold (Au) substrate layer, a dielectric layer (Topas), and a graphene pattern layer. The numerical simulation results demonstrate that the sensor exhibits three narrowband absorption peaks at 1.68, 3.82, and 4.78 THz, and the corresponding absorption rate can reach 99.9%, 98.0%, and 97.9%, respectively. By adjusting the Fermi level of graphene, the resonant frequency of the sensor can be effectively tuned. Notably, due to the rotational symmetry of the structure, the sensor shows insensitivity to transverse magnetic and transverse electric polarizations of incident light. By varying the refractive index of surrounding analytes, the sensor’s sensitivity and Figure of Merit (FOM) are studied. The sensitivities of the three resonance peaks are 0.59, 1.19, and 1.38 THz/RIU, with corresponding FOM values of 2.57, 3.40, and 6.58, respectively. Furthermore, the feasibility and effectiveness of the designed sensor in practical applications are verified by testing five types of samples. These findings indicate that the proposed sensor has superior performance in sensitivity and selectivity, which makes it have a great potential for applications in the fields of material characterization, environmental monitoring, and biomedicine detection in the terahertz band.

PurposeTumor-associated macrophages (TAMs) play a crucial role in shaping various tumor microenvironments. However, their recruitment in Wilms tumor (WT), the predominant malignant renal tumor in children, has been inadequately explored. This retrospective cohort study involved the analysis of 148 WT samples to investigate the recruitment and polarization typing of TAMs in WT tissues.MethodsWT tissues underwent Western blotting (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence (IF) to measure the expression of TAM markers CD68, CD86, and CD163. Statistically analyze the relationship between TAM recruitment levels and patient clinical characteristics, and use Kaplan-Meier curves and the log-rank test to evaluate the association between TAM levels and survival outcomes.ResultsThe findings indicated a positive correlation between the recruitment levels of total macrophages (Mtotal) and M2 tumor-associated macrophages (M2 TAM) in both chemotherapy and non-chemotherapy groups with the clinical stage. Elevated recruitment of Mtotal and M2 TAM in tumor tissues was linked to a poorer prognosis. Notably, patients with persistently higher recruitment of M2 TAM following preoperative chemotherapy exhibited the worst prognosis.ConclusionsThe recruitment and polarization typing of TAM exhibit significant differences in WT patients with various stages and prognosis outcomes, suggesting a potential avenue for future diagnosis and treatment of WT.

PurposeWilms' tumor (WT), also known as nephroblastoma, is the predominant form of primary malignant renal cancer. The unfavorable prognoses linked to anaplastic nephroblastoma and recurrent nephroblastoma emphasize the crucial requirement for the exploration of innovative treatment modalities for WT.MethodsOur study conducted one-way Cox regression and Kaplan-Meier analyses using TARGET-WT nephroblastoma data to identify differentially expressed genes in nephroblastoma and evaluate their prognostic relevance. Utilizing the Connectivity Map database, ZSTK474 emerged as a viable therapeutic option for WT. The effect of ZSTK474 on WT and related underlying mechanisms were further investigated through in vitro and in vivo investigations.ResultsThe in vivo experiment results indicated that ZSTK474 effectively inhibited subcutaneous tumor growth in WT mice. CCK-8 assays revealed two nephroblastoma cell lines exhibited half-inhibitory concentrations of 2μM and 2.51μM for ZSTK474, respectively. ZSTK474 was shown to inhibit the migration and invasion capabilities of WT cells in both Transwell and wound healing assays. Flow cytometry apoptosis and TUNEL assays demonstrated that ZSTK474 induced apoptosis in WT cells. Cell cycle analysis revealed that ZSTK474 led to the induction of G0/G1 phase arrest. Sequencing of ZSTK474-treated WiT49 cells suggested that the impact of ZSTK474 on WT might be mediated by the PI3K/Akt pathway, specifically by inhibiting PIK3R3. Knock-down of PIK3R3 confirmed that ZSTK474 downregulated PIK3R3, reducing Akt phosphorylation, cyclin D and CDK4 levels and elevating P21 expression in nephroblastoma cells. However, current research has limitations, including a lack of understanding of the long-term effects and potential resistance mechanisms of new therapies.ConclusionThis research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma.

Background: Some reports have indicated a high expression level of ASB3 in various cancers, but its role in hepatocellular carcinoma (HCC) remains elusive. Methods: ASB3 levels and clinical features were obtained from the TCGA database. Meanwhile, the expression levels of ASB3 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Imunohistochemistry (IHC). ASB3-related downstream molecular analysis was carried out with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Pathways linked to ASB3 expression were identified by means of gene set enrichment analysis (GSEA). Single-sample GSEA (ssGSEA) aided in conducting a correlation analysis of ASB3 with immune infiltration. Functional experiments were performed in HepG2 cells by using the small interfering RNA. Results: ASB3 expression was remarkably higher in HCC tissues. Its remarkable precision in forecasting cancer suggests that ASB3 might serve as an unidentified diagnostic and prognostic indicator of HCC. Higher ASB3 expression led to worse overall survival (OS), particularly in various clinical subgroups of HCC. GO/KEGG analysis indicated that critical biological activities, such as the activation of complement systems and humoral immune response, could potentially underlie the progression of HCC. Furthermore, GSEA demonstrated enrichment of certain pathways, including the MAPK, IL17, and fibrinolysis pathways, in samples with elevated ASB3 levels. ASB3 exhibited a substantial association with T helper cells, dendritic cells (DCs), and central memory T (Tcm) cell infiltration level. Cell function experiments confirmed elevated ASB3 levels in HCC cell lines as opposed to hepatic epithelial cell lines. Moreover, the ability of HCC cells to proliferate and invade was remarkably reduced by ASB3 knockdown. Conclusion: Summarize briefly, we found that ASB3 can be a promising biomarker in HCC.

Abstract With a pair of high‐resolution (HR, 10 km ocean and 25 km atm) and low‐resolution (LR, 100 km ocean and 100 km atm) Community Earth System Model (CESM) simulations, we investigate and compare the long‐term mean Northern Hemisphere (NH) wintertime storm tracks against reanalysis data. Based on several Eulerian measures, the CESM‐HR shows a poleward shift of the NH storm tracks and a reduced equatorward bias in the North Pacific relative to the CESM‐LR. Those may be associated with the refined topography of the Tibetan Plateau as well as the improved subtropical jet, stationary planetary waves, atmospheric baroclinity, and baroclinic energy conversion over the North Pacific. We also find that sharper oceanic fronts along the Kuroshio Extension accompanied by enhanced local atmospheric baroclinity and strengthened eddy heat flux over the northern North Pacific could be related to those improvements. Nevertheless, the North Atlantic storm track in HR is placed too north, leading to a larger negative bias over the subtropical zone than in LR. The simulated insufficient subtropical sensible and latent heat fluxes and northward zonal winds in HR seemingly coincide with the deficits in the North Atlantic storm track. The stronger NH branch of the Hadley cell and its poleward expansion in HR may be linked to the changes in the tropical precipitation and the poleward shift of the NH storm tracks. Further studies of attributing these biases to a specific aspect of the climate model by sensitivity experiments are warranted for further clarification of the mechanisms.

A novel method of optical Nyquist pulse generation based on recirculating frequency shift loop (RFSL) is proposed and experimentally demonstrated. In this article, a large number of flat phase-locked comb lines output from RFSL are used to synthesize Nyquist pulse, which has ultra-narrow and flexible tunable pulse width. It is the first time to theoretically analyze the condition of Nyquist pulse generation by RFSL in detail. In the experiment, the number of flat spectral lines is continuously tuned in the range of 10 to 40 corresponding to the pulse width of 8.9 ps to 2.4 ps. Meanwhile, Nyquist pulses with tunable repetition rate from 7.5 GHz to 15 GHz are obtained experimentally.

A tunable dual-band terahertz sensor based on graphene is proposed. The sensor consists of a metal bottom layer, a middle dielectric layer, and single-layer graphene patterned with four strips on the top. The numerical simulations results show that the proposed sensor exhibits two significant absorption peaks at 2.58 THz and 6.07 THz. The corresponding absorption rates are as high as nearly 100% and 98%, respectively. The corresponding quality factor (Q) value is 11.8 at 2.58 THz and 29.6 at 6.07 THz. By adjusting the external electric field or chemical doping of graphene, the positions of the dual-frequency resonance peak can be dynamically tuned. The excitation of plasma resonance in graphene can illustrate the mechanism of the sensor. To verify the practical application of the device, the terahertz response of different kinds and different thicknesses of the analyte is investigated and analyzed. A phenomenon of obvious frequency shifts of the two resonance peaks can be observed. Therefore, the proposed sensor has great potential applications in terahertz fields, such as material characterization, medical diagnosis, and environmental monitoring.

BackgroundRibonucleotide reductase regulatory subunit M2 (RRM2) has been reported to be an oncogene in some malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, the clinical significance of RRM2 in hepatocellular carcinoma has been less studied. The aim of this study was to assess the importance of RRM2 in hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database.MethodsThe RRM2 expression levels and clinical features were downloaded from the TCGA database. Immunohistochemistry results between tumor tissues and normal tissues were downloaded from the Proteinatlas database. Meanwhile, the expression levels of RRM2 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Western Blotting. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein-interactions (PPI) network were constructed to analyze RRM2-related downstream molecules. In addition, RRM2 expression-related pathways performed by gene set enrichment analysis (GSEA). Association analysis of RRM2 gene expression and immune infiltration was performed by single-sample GSEA (ssGSEA).ResultsThe RRM2 expression level in tumor tissues was higher than normal tissues (P

Composition analysis in wine is gaining increasing attention because it can provide information about the wine quality, source, and nutrition. In this work, in situ liquid secondary ion mass spectrometry (SIMS) was applied to 14 representative wines, including six wines manufactured by a manufacturer in Washington State, United States, four Cabernet Sauvignon wines, and four Chardonnay wines from other different manufacturers and locations. In situ liquid SIMS has the unique advantage of simultaneously examining both organic and inorganic compositions from liquid samples. Principal component analysis (PCA) of SIMS spectra showed that red and white wines can be clearly differentiated according to their aromatic and oxygen-contained organic species. Furthermore, the identities of different wines, especially the same variety of wines, can be enforced with a combination of both organic and inorganic species. Meanwhile, in situ liquid SIMS is sample-friendly, so liquid samples can be directly analyzed without any prior sample dilution or separation. Taken together, we demonstrate the great potential of in situ liquid SIMS in applications related to the molecular investigation of various liquid samples in food science.

Background. Long-term extensive use of glucocorticoids will lead to hormonal necrosis of the femoral head, and osteoblasts play an important role in the prevention of osteonecrosis. However, there is no complete cure for necrosis of the femoral head. Mesenchymal stem cell- (MSCs-) derived exosomes are widely used for the repair of various tissue lesions. Therefore, the aim of this study was to investigate the mechanism of dexamethasone- (DEX-) induced osteoblast apoptosis and the therapeutic effect of human umbilical cord MSC- (hucMSC-) derived exosome mimetic vesicles (EMVs) on osteoblast-induced apoptosis by DEX. Methods. The viability and apoptosis of primary MC3T3-E1 cells were determined by the Cell Counting Kit-8 (CCK-8), FITC-Annexin V/PI staining and immunoblot. The intracellular levels of reactive oxygen species (ROS) after DEX treatment were measured by 2′, 7′ -dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In this study, hucMSC-EMVs and N-acetyl-l-cysteine (NAC) were used as therapeutic measures. The expression of B-cell lymphoma 2-associated X, Bcl 2, HO-1, and nuclear factor erythroid-derived 2-like 2 and MAPK- signaling pathway in osteogenic cell MC3T3-E1 cells treated with Dex was analyzed by the immunoblotting. Results. DEX significantly induced osteoblasts MC3T3-E1 apoptosis and ROS accumulation. MAPK-signaling pathway was activated in MC3T3-E1 after DEX treatment. hucMSC-EMVs intervention significantly downregulated DEX-induced MAPK-signaling pathway activation and ROS accumulation. In addition, hucMSC-EMVs can reduce the apoptosis levels in osteoblast MC3T3-E1 cells induced by DEX. Conclusions. Our study confirmed that hucMSC-EMVs regulates MAPK-signaling pathway and ROS levels to inhibit DEX-induced osteoblast apoptosis.

Large-scale physical models of landslides can potentially accurately reflect the interactions between many internal and external factors and elucidate the process of slope deformation and failure. In order to reveal the mechanism of deformation of the reservoir bank accumulation layer, in this study, a large-scale physical test model with a similarity ratio of 1:200 was constructed based on the actual engineering geological section. Two reservoir water level cycle fluctuation conditions were simulated, and the reservoir water level drop rate was strictly controlled to be two times the rise rate. This study analyzed pore water pressure and deformation characteristics in the accumulation layer in relation to fluctuating reservoir water levels. The results showed that the rise in reservoir water level will make landslides more stable. The periodic sudden drop in water level seriously endangers the stability of landslides. The deformation and failure of landslides are more likely to occur in the weak interlayer area. The failure mode of the accumulation body in the test was traction failure. It is suggested that the front part of the accumulation body can be reinforced in practical engineering. To reveal the progression of instability and movement during accumulation layer large-scale landslides, a numerical model was constructed using the material point method. The accumulation layer sliding process could be divided into three stages: acceleration sliding, deceleration sliding and stabilization. After destabilization, the river channel may be altered by the landslide mass to form a landslide dam, potentially threatening the integrity of the dam via impulse waves generated during destabilization. The research results provide technical support for reservoir scheduling in major water conservancy and hydroelectric power station reservoirs as well as engineering risk assessment and prevention.

A novel scheme of self-oscillation multicarrier light source based on recirculating frequency shift loop (RFSL) is proposed and experimentally demonstrated in this paper. Compared with conventional RFSL-based multicarrier generation schemes, the radio frequency (RF) signal for driving the modulator in RFSL is generated by an internal self-oscillation of the optical carrier instead of the external commercial RF source device. The self-oscillation method significantly reduces the cost of the light source and decreases the phase noise of RF signal and multicarrier signal. In the experiment, we successfully generate a single-mode oscillation RF signal with the phase noise of −85.10 dBc/Hz at 10 kHz offset frequency. A total of 49 multicarrier optical signals from 1550.59 nm to 1554.44 nm with the power fluctuation as low as 3 dB are obtained. The frequency interval is approximately 10.014 GHz, which is equal to the oscillation frequency of the RF signal.

A novel frequency quasi-linear swept light source based on multi-frequency time-matched spectrum stitching and recirculating frequency shifter loop (RFSL) is proposed and successfully demonstrated. The seed light with different frequencies enters RFSL in turn through optical delay line to complete the frequency sweep and spectrum stitching of each band. Spectrum stitching can effectively reset the noise, suppress the accumulation of amplified spontaneous emission (ASE) noise and the spectral sideband noise in RFSL, and expand the sweep range several times without affecting the sweep linearity. A swept range of 5.227 nm is experimentally achieved with the noise range of 7.78 dB. Compared with the single-frequency sweep scheme that the noise variation is 9.03 dB, the sweep range is extended by more than three times. The Pearson's correlation coefficients (r) of the output swept signal is higher than -0.99996.

Understanding the renal region-specific metabolic alteration in different animal models of diabetic nephropathy (DN) is critical for uncovering the underlying mechanisms and for developing effective treatments. In the present study, spatially resolved metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to compare the local metabolic changes in the kidneys of HFD/STZ-induced diabetic rats and db/db mice. As a result, a total of 67 and 59 discriminating metabolites were identified and visualized in the kidneys of the HFD/STZ-induced diabetic rats and db/db mice, respectively. The result showed that there were significant region-specific changes in the glycolysis, TCA cycle, lipid metabolism, carnitine metabolism, choline metabolism, and purine metabolism in both DN models. However, the regional levels of the ten metabolites, including glucose, AMP, eicosenoic acid, eicosapentaenoic acid, Phosphatidylserine (36:1), Phosphatidylserine (36:4), Phosphatidylethanolamine (34:1), Phosphatidylethanolamine (36:4), Phosphatidylcholine (34:2), Phosphatidylinositol (38:5) were changed in reversed directions, indicating significant differences in the local metabolic phenotypes of these two commonly used DN animal models. This study provides comprehensive and in-depth analysis of the differences in the tissue and molecular pathological features in diabetic kidney injury in HFD/STZ-induced diabetic rats and db/db mice.

A polarization-insensitive broadband terahertz absorber with a sandwich structure of metal–dielectric-graphene is designed and simulated. The graphene is patterned as an array of graphene square blocks with circular apertures. The results of the simulations and theoretical analysis show that the absorption exceeds 99% from 0.93 to 1.65 THz while 90% from 0.80 to 1.87 THz, and a broad relative bandwidth of 80.2% is achieved. The absorption performance is passively enhanced by altering physical dimensions of the graphene pattern and actively adjusted by changing the chemical potential of graphene. When the chemical potential increases from 0.1 eV to 0.7 eV, the corresponding terahertz absorption increases from 59.1% to 99%. The mechanism of absorption is disclosed by analyzing the impedance matching theory and distribution of electric-field intensity. In addition, different polarization modes and incident angles are also studied. The proposed absorber has the superiorities of broad relative bandwidth, high absorption rate, polarization insensitivity, and a wide incident angle, which offers some potential applications in the field of terahertz technology such as imaging, detection, and cloaking.

Heating, ventilation and air-conditioning (HVAC) system is favourable for regulating indoor temperature, relative humidity, airflow pattern and air quality. However, HVAC systems may turn out to be the culprit of microbial contamination in enclosed spaces and deteriorate the environment due to inappropriate design and operation. In the context of COVID-19, significant transformations and new requirements are occurring in HVAC systems. Recently, several updated operational guidelines for HVAC systems have been issued by various institutions to control the airborne transmission and mitigate infection risks in enclosed environments. Challenges and innovations emerge in response to operational variations of HVAC systems. To efficiently prevent the spread of the pandemic and reduce infection risks, it is essential to have an overall understanding of impacts caused by COVID-19 on HVAC systems. Therefore, the objectives of this article are to: (a) provide a comprehensive review of the airborne transmission characteristics of SARS-CoV-2 in enclosed spaces and a theoretical basis for HVAC operation guideline revision; (b) investigate HVAC-related guidelines to clarify the operational variations of HVAC systems during the pandemic; (c) analyse how operational variations of HVAC systems affect energy consumption; and (d) identify the innovations and research trends concerning future HVAC systems. Furthermore, this paper compares the energy consumption of HVAC system operation during the normal times versus pandemic period, based on a case study in China, providing a reference for other countries around the world. Results of this paper offer comprehensive insights into how to keep indoor environments safe while maintaining energy-efficient operation of HVAC systems.

An ultrafast wavenumber linear-step-swept source based on a synchronous lightwave synthesized frequency sweeper (SLSFS) is demonstrated. A multi-wavelength source is used as a seed source. In SLSFS, the swept range of different wavelength components is precisely controlled by a stable programmable radio frequency signal applied on a dual-parallel Mach-Zehnder modulator instead of a conventional wavelength filter. The identical frequency shifting step of all the wavelength components promises high linear sweeping in the frequency domain. The key significance of this technique is that the swept rate and the swept range increases as the number of the seed wavelengths increases. Experimentally, a 120 kHz swept rate over the 4.75 nm range with a 8.6 GHz swept step is achieved when using two coupled DFB-LDs as the seed source. The K-linearity of Pearson's correlation coefficients is 0.99999. We also acquired the swept rates of 400 kHz, 800 kHz, and 1.23 MHz over the 7.86 nm range with a 8.6 GHz swept step using an F-P LD as a seed source.

Modafinil is a mild psychostimulant-like drug enhancing wakefulness, improving attention and developing performance in various cognitive tasks, but its mechanism of action is not completely understood. This is the first combination of amperometry, electrochemical cytometry and mass spectrometry to interrogate the mechanism of action of a drug, here modafinil, at cellular and sub-cellular level. We employed single-cell amperometry (SCA) and intracellular vesicle impact electrochemical cytometry (IVIEC) to investigate the alterations in exocytotic release and vesicular catecholamine storage following modafinil treatment. The SCA results reveal that modafinil slows down the exocytosis process so that, the number of catecholamines released per exocytotic event is enhanced in the modafinil-treated cells. Also, IVIEC results offer an upregulation effect of modafinil on the vesicular catecholamine storage. Mass spectrometry imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS) illustrates that treatment with modafinil reduces the cylindrical-shaped phosphatidylcholine at the cellular membrane, while the high curvature lipids with conical structures such as phosphatidylethanolamine and phosphatidylinositol are elevated after modafinil treatment. Combining the results obtained by SCA, IVIEC and ToF-SIMS suggests that modafinil-treated cells release a larger portion of their vesicular content at least in part by changing the lipid composition of the cell membrane, suggesting regulation of cognition.

Platinum(II) terpyridine complexes has attracted increasing attention as they have displayed great potential as antitumor agents due to their high intercalation affinity with nucleic acids. Epidermal growth factor receptor (EGFR) is often overexpressed in various tumor cells, leading to uncontrolled growth of tumor, and is regarded as an important target for developing novel antitumor drugs. Herein, we report four platinum(II) terpyridine complexes bearing EGFR inhibiting 4-anilinoquinazoline derivatives as potent multi-targeting antiproliferation agents against a series of cancer cells. EGFR inhibition assay revealed that these complexes are highly potent EGFR inhibitors. But competitive DNA binding assay and docking simulations also suggested that these complexes exhibited multiple modes of DNA interaction, especially great affinity toward DNA minor groove. Finally, cellular uptake and distribution measurements by inductively coupled plasma mass spectrometry (ICP-MS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) demonstrated that both nucleus DNA and membrane proteins are important targets for their anticancer mechanisms. The complexes herein can therefore be regarded as promising multi-targeting anticancer agents.

Analogous coherent states are deduced from classical optical fields on curved surface in this paper. The Gaussian laser beam, as a fundamental mode, cannot be adequately simulated by coherent states due to their inherent diffraction in flat space. But it differs when propagating on a surface with the uniform curvature, the constant Gaussian curvature surface (CGCS). By generalizing the method of Feynman path integral, an equivalent coherent states solution is demonstrated to describe the beam propagation. The temporal evolution of the Schrödinger equation is analogously translated into a spatial transmission in this derivation, and we obtain the expression of quantized momentum transmitted on curved surface, which is proportional to the square root of the Gaussian curvature K . In addition to that, a physical picture of beam propagation that is identical to the squeezed state is also built. We hope this research can offer a new view on the quantum field in curved space.

Ultrafast linear frequency modulated continuous-wave (FMCW) lasers are a special category of CW lasers. The linear FMCW laser is the light source for many sensing applications, especially for light detection and ranging (LiDAR). However, systems for the generation of high quality linear FMCW light are limited and diverse in terms of technical approaches and mechanisms. Due to a lack of characterization methods for linear FMCW lasers, it is difficult to compare and judge the generation systems in the same category. We propose a novel scheme for measuring the mapping relationship between instantaneous frequency and time of a FMCW laser based on a modified coherent optical spectrum analyzer (COSA) and digital signal processing (DSP) method. Our method has the potential to measure the instantaneous frequency of a FMCW laser at an unlimited sweep rate. In this paper, we demonstrate how to use this new method to precisely measure a FMCW laser at a large fast sweep rate of 5000 THz/s by both simulation and experiments. We find experimentally that the uncertainty of this method is less than 100 kHz and can be improved further if a frequency feedback servo system is introduced to stabilize the local CW laser.

A wavelength step-swept light source (WSSL) using a recirculating frequency shifter loop (RFSL) based on a single-side-band (SSB) modulator is proposed, in order to achieve a linear and fast wavelength-sweeping. The swept step can be tuned from 1.2 pm to 128 pm by adjusting a precise and stable radio frequency (RF) signal that is applied to the SSB modulator. The swept rate can be tuned up to 99 kHz in a range of over 5.12 nm. Wavelength-to-time mapping is used to measure static strain-induced or temperature-induced shifting of the reflected central wavelength of a fiber Bragg grating (FBG). Because of the high linearity of the light source, the interrogation linearity of the strain and the temperature are as high as 0.99944 and 0.99946, respectively. When a dynamic periodic strain applied to FBG sensor, the dynamic performance of the FBG sensor is successfully recorded in the time domain and its power spectral density of a fast Fourier transform (FFT) is calculated. The signal-to-noise ratio (SNR) of the power spectral density is over 40 dB for a 100 Hz dynamic strain and the calculated sensitivity is 0.048 με/Hz1/2. A sharp change in the strain frequency from 100 Hz to 500 Hz is captured in real time.