ABSTRACT
Doxorubicin (DOX) is an important drug for cancer treatment, but its clinical application is limited due to its toxicity and side effects. Therefore, detecting the concentration of DOX during treatment is crucial for enhancing efficacy and reducing side effects. In this study, the authors developed a biophotonic fiber sensor based on localized surface plasmon resonance (LSPR) with the multimode fiber (MMF)-four core fiber (FCF)-seven core fiber (SCF)-MMF-based direct-taper and anti-taper structures for the specific detection of DOX. Compared to other detection methods, it has the advantages of high sensitivity, low cost, and strong anti-interference ability. In this experiment, multi-walled carbon nanotubes (MWCNTs), cerium-oxide nanorods (CeO2-NRs), and gold nanoparticles (AuNPs) were immobilized on the probe surface to enhance the sensor's biocompatibility. MWCNTs and CeO2-NRs provided more binding sites for the fixation of AuNPs. By immobilizing AuNPs on the surface, the LSPR was stimulated by the evanescent field to detect DOX. The sensor surface was functionalized with DOX aptamers for specific detection, enhancing its specificity. The experiments demonstrated that within a linear detection range of 0-10 µM, the sensitivity of the sensor is 0.77 nm/µM, and the limit of detection (LoD) is 0.42 µM. Additionally, the probe's repeatability, reproducibility, stability, and selectivity were evaluated, indicating that the probe has high potential for detecting DOX during cancer treatment.
Subject(s)
Doxorubicin , Gold , Metal Nanoparticles , Surface Plasmon Resonance , Doxorubicin/pharmacology , Humans , Surface Plasmon Resonance/instrumentation , Gold/chemistry , Metal Nanoparticles/chemistry , Neoplasms/drug therapy , Nanotubes, Carbon/chemistry , Biosensing Techniques/instrumentation , Optical Fibers , Equipment Design , Antibiotics, Antineoplastic/analysis , Cerium/chemistry , Fiber Optic Technology/instrumentationABSTRACT
Yb-doped sesquioxides represent one of the most excellent laser crystals applying for high-power ultrafast lasers owing to their very high thermal conductivities and broadband emission spectra. Pumped by a high-brightness Yb-fiber laser at 976â nm, the Yb:Lu2O3 laser delivers a maximum output power that amounts to 3.55â W in the continuous-wave regime with an optical efficiency of 75%. In the mode-locked regime, 90-fs pulses were generated via soft-aperture Kerr-lens mode-locking at 1080.6â nm with an average output power of 2.85â W, which corresponds to an optical efficiency of 60.3% and a slope efficiency of 68.8%. Average output power of the mode-locked Yb:Lu2O3 laser can be further scaled to 3.05â W at the expense of the pulse duration (178â fs), which corresponds to an optical efficiency as high as 64.5%. To the best of our knowledge, it is the highest optical efficiency ever reported from any solid-state Kerr-lens mode-locked Yb lasers.
ABSTRACT
CD38 is involved in immune responses, cell proliferation, and has been identified in the brain, where it is implicated in inflammation processes and psychiatric disorders. We hypothesized that dysfunctional CD38 activity in the brain may contribute to the pathogenesis of depression. To investigate the underlying mechanisms, we used a lipopolysaccharide (LPS)-induced depression-like model and conducted behavioral tests, molecular and morphological methods, along with optogenetic techniques. We microinjected adeno-associated virus into the hippocampal CA3 region with stereotaxic instrumentation. Our results showed a marked increase in CD38 expression in both the hippocampus and cortex of LPS-treated mice. Additionally, pharmacological inhibition and genetic knockout of CD38 effectively alleviated neuroinflammation, microglia activation, synaptic defects, and Sirt1/STAT3 signaling, subsequently improving depression-like behaviors. Moreover, optogenetic activation of glutamatergic neurons of hippocampal CA3 reduced the susceptibility of mice to depression-like behaviors, accompanied by reduced CD38 expression. We also found that (R)-ketamine, which displayed antidepressant effects, was linked to its anti-inflammatory properties by suppressing increased CD38 expression and reversing synaptic defects. In conclusion, hippocampal CD38 is closely linked to depression-like behaviors in an inflammation model, highlighting its potential as a therapeutic target for antidepressant development.
Subject(s)
ADP-ribosyl Cyclase 1 , Depression , Ketamine , Animals , Mice , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Antidepressive Agents/metabolism , Depression/metabolism , Hippocampus/metabolism , Inflammation/metabolism , Ketamine/pharmacology , Ketamine/therapeutic use , Ketamine/metabolism , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , ADP-ribosyl Cyclase 1/metabolismABSTRACT
BACKGROUND: Although Huaier granules can be used as prospective anti-cholangiocarcinoma drugs, the mechanism of action of Huaier granules in cholangiocarcinoma is not clear. The anti-cholangiocarcinoma effect of Huaier granules was validated in cell line research. In vitro experiments were conducted to investigate the signalling pathways affected by Huaier in CCA cells. METHODS AND RESULTS: Real-time quantitative PCR (RTâqPCR) and Western blot analysis were performed to analyse gene expression in CCA cells. MTT assays, scratch tests, and Transwell assays were used to explore the effects on the proliferation and metastasis of CCA cells. Chromatin immunoprecipitation assays were performed to reveal the potential underlying mechanisms involved. Twist1 was upregulated in human CCA tissues. In addition, its expression levels were negatively related to FBP1 expression levels. Mechanistically, Twist1 can bind to the region of the FBP1 promoter to reduce its expression. Huaier plays an indispensable role in suppressing Twist1 expression to inhibit the Twist1/FBP1/Wnt/ß-catenin axis. Then, we verified the effect of Huaier in vitro. CONCLUSIONS: These findings suggested that Huaier granules were capable of inhibiting CCA development through regulating the Twist1/FBP1/Wnt/ß-catenin signalling axis and provided a novel orientation for the development of novel anti-CCA drugs.
Subject(s)
Bile Duct Neoplasms , Cell Proliferation , Cholangiocarcinoma , Gene Expression Regulation, Neoplastic , Nuclear Proteins , Twist-Related Protein 1 , Wnt Signaling Pathway , beta Catenin , Humans , Twist-Related Protein 1/metabolism , Twist-Related Protein 1/genetics , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Cholangiocarcinoma/drug therapy , Wnt Signaling Pathway/drug effects , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Cell Line, Tumor , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Gene Expression Regulation, Neoplastic/drug effects , Cell Proliferation/drug effects , beta Catenin/metabolism , Cell Movement/drug effects , Cell Movement/geneticsABSTRACT
Yb-doped fluoride has been demonstrated to be potential crystals for application in efficient ultrafast lasers. However, the trade-off between the shorter pulses with higher efficiencies is a challenge. In this work, using Y b,G d:C a S r F 2 crystal, we report on a sub-50-fs Kerr-lens mode-locked oscillator with an optical efficiency up to 44%. Pumped by a 976-nm diffraction-limited fiber laser and using chirped mirrors combined with prism pairs for the dispersion compensation, a pulse as short as 46 fs was obtained with 620-mW output power, corresponding to an optical efficiency more than 40%. Stable Kerr-lens mode-locking with RMS of output power lower than 0.3% and beam quality factors M 2<1.14 were achieved. Moreover, a maximum output power of 780 mW was obtained in continuous-wave operation with 55.3% optical efficiency. To the best of our knowledge, the results in this work represent the shortest pulses generated from Yb-doped fluoride lasers as well as the highest optical efficiencies ever reported in sub-100 fs Yb bulk lasers.
ABSTRACT
In this work, we introduce a novel multimode fiber (MMF) - seven core fiber (SCF) - MMF (MCM) optical fiber biosensor, also known as the WaveFlex biosensor (plasma wave assisted fiber biosensor), based on localized surface plasmon resonance (LSPR) for qualitative detection of xanthine. Xanthine is a purine base widely distributed in human blood and tissues, and commonly used as an indicator for various disease detections. The MCM sensor incorporates a tapered optical fiber structure, fabricated using the combiner manufacturing system (CMS), and is designed with SCF and MMF. By effectively harnessing LSPR, the sensor boosts the attachment points of biomolecules on the probe surface through immobilized tungsten disulfide (WS2)-thin layers, gold nanoparticles (AuNPs), and carbon nitride quantum dots (C3N-QDs). The functionalization of xanthine oxidase (XO) on the sensing probe further enhances the sensor's specificity. The proposed WaveFlex biosensor exhibits a remarkable sensitivity of 3.2â nm/mM and a low detection limit of 96.75 µM within the linear detection range of 100 - 900 µM. Moreover, the sensor probe demonstrates excellent reusability, reproducibility, stability, and selectivity. With its sensitivity, biocompatibility, and immense potential for detecting human serum and fish products, this WaveFlex biosensor presents a promising platform for future applications.
Subject(s)
Biosensing Techniques , Metal Nanoparticles , Animals , Humans , Gold/chemistry , Xanthine , Reproducibility of Results , Metal Nanoparticles/chemistry , Surface Plasmon ResonanceABSTRACT
Terahertz waves are known for their bio-safety and spectral fingerprinting features, and terahertz spectroscopy technology holds great potential for both qualitative and quantitative identification in the biomedical field. There has been a substantial amount of research utilizing this technology in conjunction with machine learning algorithms for substance identification. However, due to the strong absorption of water for terahertz waves, the single-dimensional features of the sample become indistinct, thereby diminishing the efficiency of the algorithmic recognition. Building upon this, we propose a method that employs terahertz time-domain spectroscopy (THz-TDS) in conjunction with multidimensional feature spectrum identification for the detection of blood sugar and glucose mixtures. Our research indicates that combining THz-TDS with multidimensional feature spectrum and linear discriminant analysis (LDA) algorithms can effectively identify glucose concentrations and detect adulteration. By integrating the multidimensional feature spectrum, the identification success rate increased from 68.9% to 96.0%. This method offers an economical, rapid, and safe alternative to traditional methods and can be applied in blood sugar monitoring, sweetness assessment, and food safety.
ABSTRACT
Blood sugar is an important biomedical parameter of diabetic patients. The current blood sugar testing is based on an invasive method, which is not very friendly for patients who require long-term monitoring, while the non-invasive method is still in the developing stage. In this paper, we design a non-invasive and highly sensitive terahertz wave detector with Co3Sn2S2 semimetal thin film to test sugar concentration. As different concentrations have inconsistent responses to terahertz wave, we can deduce the concentration of the sugar solution to realize real-time highly sensitive detection of blood sugar concentration. This novel method can be further expanded to 6â G edge intelligence for non-invasive and real-time monitoring of blood sugar, and promote the development of 6â G technology.
ABSTRACT
Abnormal lipid metabolism promotes hepatocellular carcinoma (HCC) progression, which engenders therapeutic difficulties owing to unclear mechanisms of the phenomenon. We precisely described a special steatotic HCC subtype with HBV-related cirrhosis and probed its drivers. Hematoxylin-eosin (HE) staining of 245 HCC samples revealed a special HCC subtype (41 cases) characterized by HBV-related cirrhosis and intratumoral steatosis without fatty liver background, defined as steatotic HCC with HBV-related cirrhosis (SBC-HCC). SBC-HCC exhibits a larger tumor volume and worse prognosis than non-SBC-HCC. Screening for driver genes promoting fatty acid (FA) biosynthesis in the Gao's HBV-related cirrhosis HCC cases and GSE121248' HBV-related HCC cases revealed that high expression of SOCS5 predicts increased FA synthesis and that SOCS5 is upregulated in SBC-HCC. Through proteomics, metabolomics, and both in vivo and in vitro experiments, we demonstrated that SOCS5 induces lipid accumulation to promote HCC metastasis. Mechanistically, through co-IP and GST-pulldown experiments, we found that the SOCS5-SH2 domain, especially the amino acids Y413 and D443, act as critical binding sites for the RBMX-RRM domain. SOCS5-RBMX costimulates the promoter of SREBP1, inducing de novo lipogenesis, while mutations in the SH2 domain, Y413, and D443 reverse this effect. These findings precisely identified SBC-HCC as a special steatotic HCC subtype and highlighted a new mechanism by which SOCS5 promotes SBC-HCC metastasis.
ABSTRACT
Fano resonance with high Q-factor is considered to play an important role in the field of refractive index sensing. In this paper, we theoretically and experimentally investigate a refractive index sensor with high performance, realizing a new approach to excite multiple Fano resonances of high Q-factor by introducing an asymmetric parameter to generate a quasi-bound state in the continuum (BIC). Combined with the electromagnetic properties, the formation mechanism of Fano resonances in multiple different excitation modes is analyzed and the resonant modes of the three resonant peaks are analyzed as toroidal dipole (TD), magnetic quadrupole (MQ), and magnetic dipole (MD), respectively. The simulation results show that the proposed metastructure has excellent sensing properties with a Q-factor of 3668, sensitivity of 350â nm/RIU, and figure of merit (FOM) of 1000. Furthermore, the metastructure has been fabricated and investigated experimentally, and the result shows that its maximum Q-factor, sensitivity and FOM can reach 634, 233â nm/RIU and 115, respectively. The proposed metastructure is believed to further contribute to the development of biosensors, nonlinear optics, and lasers.
ABSTRACT
Metal coordination hydrogels (MC-HGs) that introduce dynamically coordinate bonds together with metal ionic conduction have attracted considerable attention in flexible electronics. However, the traditional soaking method alleged to have technical scalability faces the challenge of forming MC-HGs with a "core-shell" structure, which undoubtedly reduces the whole mechanical properties and ionic stimulation responsiveness required for flexible electronics materials. Herein, a novel strategy referred to as "masking" has been proposed based on the theory of the valence bond and coordination chemistry. By regulating the masking agents and their concentrations as well as pairing mode with the metal ions, the whole mechanical properties of the resulting composites (MC-HGsMasking) show nearly double the values of their traditional soaking samples (MC-HGsSoaking). For example, the fracture stress and toughness of Fe-HGsMasking(SA, 5.0 g/L) are 1.55 MPa and 2.14 MJ/m3, almost twice those of Fe-HGsSoaking (0.83 MPa and 0.93 MJ/m3, respectively). Microstructure characterization combined with finite element analysis, molecular dynamics, and first-principles simulations demonstrates that the masking strategy first facilitating interfacial permeation of metal complexes and then effective coordination with functional ligands (carboxylates) of the hydrogels is the mechanism to strengthen the mechanical properties of composites MC-HGsMasking, which has the potential to break through the limitations of current MC-HGs in flexible electronic sensor applications.