Huaier inhibits cholangiocarcinoma cells through the twist1/FBP1/Wnt/ß-catenin axis.

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 (RT‒qPCR) 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.

Development of a biophotonic fiber sensor using direct-taper and anti-taper techniques with seven-core and four-core fiber for the detection of doxorubicin in cancer treatment.

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.

Sub-50-fs Kerr-lens mode-locked Yb-doped fluoride laser with 44% optical efficiency.

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.

SOCS5-RBMX stimulates SREBP1-mediated lipogenesis to promote metastasis in steatotic HCC with HBV-related cirrhosis.

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.

High-precision sensor for glucose solution using active multidimensional feature THz spectroscopy.

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.

Non-contact, highly sensitive sugar concentration detection based on Co3Sn2S2 Weyl semimetal thin film sensor by terahertz wave.

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 6 G edge intelligence for non-invasive and real-time monitoring of blood sugar, and promote the development of 6 G technology.

High-Q Fano resonances in all-dielectric metastructures for enhanced optical biosensing applications.

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 350 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, 233 nm/RIU and 115, respectively. The proposed metastructure is believed to further contribute to the development of biosensors, nonlinear optics, and lasers.

Masking Strategy Constructed Metal Coordination Hydrogels with Improved Mechanical Properties for Flexible Electronic Sensors.

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.

The role of CD38 in inflammation-induced depression-like behavior and the antidepressant effect of (R)-ketamine.

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.

Sub-100-fs Kerr-lens mode-locked Yb:Lu2O3 laser with more than 60% optical efficiency.

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 976 nm, the Yb:Lu2O3 laser delivers a maximum output power that amounts to 3.55 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 1080.6 nm with an average output power of 2.85 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 3.05 W at the expense of the pulse duration (178 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.

Establishment and validation of a nomogram model for preoperative prediction of the risk of cholangiocarcinoma with perineural invasion.

OBJECTIVE: To establish and validate a nomogram model for predicting the risk of cholangiocarcinoma with perineural invasion. METHODS: We retrospectively collected the clinical data of 356 patients with surgically confirmed cholangiocarcinoma, including 98 cases of extrahepatic cholangiocarcinoma (eCCA), 197 cases of intrahepatic cholangiocarcinoma (iCCA), and 61 cases of perihilar cholangiocarcinoma (pCCA). RESULTS: Based on these data, we determined the influencing factors of preoperative perineural invasion risk in patients with cholangiocarcinoma by forward multivariate regression analysis. Based on these variables, we established two nomogram models. The model variables for predicting perineural invasion of eCCA included prothrombin time, high-density lipoprotein and tumor size (all P<0.05). The consistency index (C-index) of internal and external validation was 0.845 and 0.806, respectively. In addition, the model variables for predicting perineural invasion of iCCA included carcinoembryonic antigen, carbohydrate antigen 19-9 and tumor size (all P<0.05). The internal and external validation of the C-index was 0.735 and 0.886, respectively. Both models have considerable results in terms of calibration accuracy and clinical decision-making. Kaplan-Meier survival analysis showed that the survival time of patients with perineural invasion was significantly reduced (P=0.033). CONCLUSIONS: We established a predictive model for preoperative perineural invasion in patients with iCCA and eCCA, and this model can provide good predictive value for clinicians. However, we have not obtained relevant predictive variables for predicting perineural invasion of pCCA, and the number of modeling cases was relatively small, so this study needs to be further explored.

WaveFlex biosensor based on S-tapered and waist-expanded technique for detection of glycosylated hemoglobin.

Glycosylated hemoglobin (HbA1c) is considered a new standard for the detection of diabetes mellitus because it is more accurate than regular blood sugar tests and there is no need to take blood on an empty stomach or at a specific time. In this work, we have developed a novel optical fiber biosensor, referred to as the "WaveFlex biosensor," which operates on the principles of localized surface plasmon resonance (LSPR) plasmonic wave. The sensor is fabricated using an innovative S-tapered and waist-expanded technique, enabling it to effectively detect HbA1c. Compared to the HbA1c sensors currently in use, HbA1c optical fiber sensors possess the characteristics of high sensitivity, low cost, and strong anti-interference ability. The gold nanoparticles (AuNPs), cerium oxide (CeO2) nanorods (NRs), and tungsten disulfide (WS2) nanosheets (NSs) are functionalized to improve the effectiveness of the fiber sensor on the probe surface. AuNPs are utilized to generate LSPR by the excitation of evanescent waves to amplify the sensing signal. The CeO2-NRs can have a strong metal-carrier interaction with AuNPs, enhancing the cascade of CeO2-NRs and AuNPs. The WS2-NSs with layered fold structure have a large specific surface area. Therefore, the combination of CeO2-NRs and WS2-NSs is conducive to the binding of antibodies and the addition of sites. The functionalized antibodies on the fiber make the sensor probe capable of specific selection. The developed probe is applied to test the HbA1c solution over concentrations of 0-1000 µg/mL, and the sensitivity and limits of detection of 1.195×10-5 a.u./(µg/mL) and 1.66 µg/mL are obtained, respectively. The sensor probe is also evaluated using assays for reproducibility, reusability, selectivity, and pH. According to the findings, a novel method for detecting blood glucose based on a plasmonic biosensor is proposed.

Humanoid-shaped WaveFlex biosensor for the detection of food contamination.

High-toxicity secondary metabolites called aflatoxin are naturally produced by the fungus Aspergillus. In a warm, humid climate, Aspergillus growth can be considerably accelerated. The most dangerous chemical among all aflatoxins is aflatoxin B1 (AFB1), which has the potential to cause cancer and several other health risks. As a result, food forensicists now urgently need a method that is more precise, quick, and practical for aflatoxin testing. The current study focuses on the development of a highly sensitive, specific, label-free, and rapid detection method for AFB1 using a novel humanoid-shaped fiber optic WaveFlex biosensor (refers to a plasmon wave-based fiber biosensor). The fiber probe has been functionalized with nanomaterials (gold nanoparticles, graphene oxide and multiwalled carbon nanotubes) and anti-AFB1 antibodies to enhance the sensitivity and specificity of the developed sensor. The findings demonstrate that the developed sensor exhibits a remarkable low detection limit of 34.5 nM and exceptional specificity towards AFB1. Furthermore, the sensor demonstrated exceptional characteristics such as high stability, selectivity, reproducibility, and reusability. These essential factors highlight the significant potential of the proposed WaveFlex biosensor for the accurate detection of AFB1 in diverse agricultural and food samples.

Effective splicing technique of different cladding diameter-based optical fibers and performance evaluation.

In this work, the fabrication and sensing performance of fusion structures based on single-mode fiber (SMF) and multimode fiber (MMF) with different cladding diameters are discussed, and the effects of different lengths of MMF and fiber etching on sensing performance are analyzed. First, the transmitted intensity measurement experiment is performed, and the results indicate that the performance of the SMF-MMF-SMF(SMS)-based structure is better for sensing purposes. In addition, the results demonstrate that the performance of etched fiber is better than that of non-etched fiber. The etched fiber structure with lower fiber diameters produces more evanescent waves and is better for sensing purposes. Therefore, the proposed structure has certain development potential as an application of future optical fiber sensors.

Development and stability analysis of an S-tapered optical fiber-based sensor structure.

In this paper, three S-tapered fiber (STF) structures with different diameters (40, 60, and 80 µm) are fabricated using conventional single-mode fiber. First, the reproducibility of the proposed S-tapered structure is confirmed through an analysis of the diameter distribution. Considering the transmitted intensities of the three various diameter, S-tapered structures reveal that the STF with a 40 µm diameter produces more evanescent waves and is more sensitive to external refractive index variations. Therefore, the STF structure with a 40 µm diameter was evaluated for the detection of different concentration of glucose solutions, demonstrating that the structure has the potential to be utilized to develop a highly sensitive fiber sensor.

Homemade low-cost fabrication technique and stability analysis of a U-shaped fiber sensor structure.

In this work, the fabrication method of a U-shaped optical fiber (UOF) structure using single-mode fiber is proposed. Few UOF sensors have been developed to date, but the fabrication process has not been described in detail. Here, its subsequent homemade fabrication, optimization strategies, and analysis are thoroughly explored. Further, the influence of transmission on U-shaped diameter is explored. The transmitted intensity is mainly used to assess the strength of the evanescent field. For this purpose, three different diameters of 2 mm, 4 mm, and 6 mm UOFs are fabricated. The results show that the transmission of the U-shaped structure is dependent on the diameter of the UOF. Thereafter, different concentrations of glucose solutions are detected using the optimized stable UOF structure to showcase the sensing properties. Overall, this work is essential for beginners who want to conduct research on optical fiber sensors with a curved shape.

Slide-type waveflex biosensor based on signal enhancement technology for alpha-fetoprotein detection.

The development of signal enhancement technology in optical fiber biosensors is beneficial for the accurate measurement of low-concentration samples. Here, a localized surface plasmon resonance (LSPR)-based fiber biosensor combining a slide-type fiber structure (thus named WaveFlex Biosensor) and low-dimensional materials is proposed for alpha-fetoprotein (AFP) detection. A symmetric transverse offset splicing technology was used to fabricate the multi-mode fiber (MMF-multi-core fiber (MCF)-MMF structure. Furthermore, the MMF on one side was prepared into an S-taper, forming a slide-type fiber structure to generate more energy leakage. The LSPR signal generated by gold nanoparticles (AuNPs) was enhanced by the CeO2 NPs and C3N quantum dots functionalized on the fiber probe. The excellent performance of NPs was conducive to improving the sensitivity of the WaveFlex biosensor and enabling the rapid detection of samples. An AFP antibody was used to identify AFP micro-biomolecules in a specific manner. Based on the combination of the above two methods, the developed fiber probe was applied to detect AFP, and the sensitivity and limit of detection were 32 pm/(ng/mL) and 6.65 ng/mL, respectively. The experimental results demonstrate that the signal-enhanced AFP WaveFlex biosensor has great potential for the rapid and accurate detection of AFP.

ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells.

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA.In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells.In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.

Fascinating Pathway to Facilitate the Photoisomerization of Spiropyran-Based Nanocomposites.

Recently, spiropyran-based composites have gained more attention on account of their stimuli-responsive essence, especially of the fascinating and green photo stimulus. However, the great dipole moment change between the ring-opened merocyanine and ring-closed spiropyran requires a large free volume available for isomerization, which significantly restrains the photoisomerization of spiropyran-based nanocomposites. Herein, a fascinating pathway by regulating the states both of spiropyran and the immobilized nanoparticle supports was put forward to facilitate the photoisomerization. The results demonstrated that the spiropyran grafting percentage of 5.18% and immobilized supports with less aggregation, high specific surface area, large pore size, and noncrystalline structure were suitable to fabricate spiropyran-based nanocomposites, which showed a significant improvement for Pb2+ and Cr3+ removal from aqueous solution on account of free photoisomerization of spiropyran on the support's surface. This work will pave the pathway to extend the exploitation of spiropyran-based nanocomposites in various fields such as biotechnology, physiology, and electronics to photonics and environmental-friendly fields.

Role of GABAergic system in the comorbidity of pain and depression.

Patients with chronic pain often suffer with depressive symptoms, and these two conditions can be aggravated by each other over time, leading to an increase in symptom intensity and duration. The comorbidity of pain and depression poses a significant challenge to human health and quality of life, as it is often difficult to diagnose early and treat effectively. Therefore, exploring the molecular mechanisms underlying the comorbidity of chronic pain and depression is crucial to identifying new therapeutic targets for treatment. However, understanding the pathogenesis of comorbidity requires examining interactions among multiple factors, which calls for an integrative perspective. While several studies have explored the role of the GABAergic system in pain and depression, fewer have examined its interactions with other systems involved in their comorbidity. Here, we review the evidence that the role of GABAergic system in the comorbidity of chronic pain and depression, as well as the interactions between the GABAergic system and other secondary systems involved in pain and depression comorbidity, providing a comprehensive understanding of their intricate interplay.