Silver-coated hollow fiber surface plasmon resonance sensor for glucose detection with enhanced limit of detection.

A fiber-optic surface plasmon resonance (SPR) biosensor based on a silver-coated hollow fiber (HF) structure for glucose detection is presented. The sensor surface was immobilized with 4-mercaptophenylboronic acid (PMBA) acting as a glucose recognition monolayer. Then, gold nanoparticles (AuNPs) modified with 2-aminoethanethiol (2-AET) and PMBA were introduced onto the sensor surface after glucose was captured to enhance the wavelength shift of the SPR phenomenon excited by the light transmitted in the wall of the HF sensor. Instead of the conventional one-step sensitization pretreatment commonly used in the deposition process of silver films for fiber-optic SPR sensors, a sensitization-activation two-step activation method was adopted in the fabrication of the proposed sensor. Experiments for glucose detection were performed on the fabricated sensors in the concentration range of 1 nM-1 mM. Results showed that the sensor fabricated by the two-step activation method has a much larger shift of resonance wavelength than the sensor fabricated using the one-step sensitization method. The resonance wavelength shift was found to be linear to the logarithm of the concentration in the range of 1 nM-1 mM. The sensor achieved a limit of detection (LOD) of as low as 1 nM, which is at least an order of magnitude lower than that of other fiber-optic sensors for glucose detection reported previously. The presented HF glucose sensor has the potential for biosensing applications and provides a large reference value in the study of optical fiber SPR sensors for biosensing.

Diallyl trisulfide and its active metabolite allyl methyl sulfone attenuate cisplatin-induced nephrotoxicity by inhibiting the ROS/MAPK/NF-κB pathway.

Cisplatin, a chemotherapy medication employed in the treatment of various solid tumors, is constrained in its clinical application due to nephrotoxicity. Diallyl trisulfide (DATS), a compound derived from garlic that possessed anticancer and antioxidant properties, can be combined with cisplatin without hindering its antitumor effects. The present investigation examined the defensive properties of DATS and its active metabolites against renal dysfunction caused by cisplatin. We created a mouse model to study renal injury caused by cisplatin and assessed kidney histology, immunochemistry, and serum cytokines. DATS treatment effectively reduced the pathological changes caused by cisplatin by decreasing the levels of renal function markers BUN, CRE, cystatin C, NGAL, inflammatory factors TNF-α, IL-6, and the protein expression of α-SMA, NF-κB, KIM-1. A pharmacokinetic evaluation of DATS found that allyl methyl sulfone (AMSO2) was the most abundant and persistent metabolite of DATS in vivo. Then, we examined the impact of AMSO2 on cell viability, apoptosis, ROS generation, and MAPK/NF-κB pathways in HK-2 cells treated with cisplatin. Cotreatment with AMSO2 effectively hindered the HK-2 cells alterations induced by cisplatin. Furthermore, AMSO2 mitigated oxidative stress through the modulation of MAPK and NF-κB pathways. Our findings indicated that DATS and its active derivative AMSO2 attenuated cisplatin-induced nephrotoxicity. DATS shows potential as a viable treatment for nephrotoxicity caused by cisplatin.

Prediction of the mechanism for the combination of diallyl trisulfide and cisplatin against gastric cancer: a network pharmacology study and pharmacological evaluation.

Background: In this research, we aimed to explore the efficacy of diallyl trisulfide (DATS) combined with cisplatin (DDP) for gastric cancer treatment and its underlying mechanism based on network pharmacology. Methods: First, the pharmacological mechanism by which DATS combined with DDP acts against gastric cancer was predicted using network pharmacology. The TTD, GeneCards, and OMIM databases were used to extract drug and disease targets. The David Bioinformatics Resources 6.8 database was used to conduct GO and KEGG analyses. We investigated the efficacy of DATS combined with DDP against gastric cancer in SGC7901 cells and a xenograft model. Furthermore, the specific mechanism of DATS combined with DDP, inferred by network pharmacology, was identified by Western blotting and immunohistochemistry. Results: The combination of DDP and DATS significantly increased cytotoxicity and cell apoptosis compared to the DATS or DDP treatment group in vitro. In addition, continuous intraperitoneal injection of DATS markedly improved the tumor inhibitory effect of DDP in the SGC-7901 tumor-bearing mouse model. Furthermore, network pharmacology and experimental validation studies revealed that the combination of DATS and DDP synergistically enhanced antitumor activity by regulating endoplasmic reticulum stress and inhibiting STAT3/PKC-δ and MAPK signaling pathways. Conclusion: Our study showed that the combination of DATS and DDP could exert outstanding therapeutic effects in gastric cancer. Moreover, network pharmacology coupled with experimental validation revealed the molecular mechanisms of combination therapy for gastric cancer. This study offers a new adjuvant strategy based on DATS and DDP for the treatment of gastric cancer.

Long-range surface plasmon resonance-based hollow fiber temperature sensor with ultrahigh sensitivity and tunable detection range.

A dielectric/Ag-coated hollow fiber (HF) temperature sensor based on long-range surface plasmon resonance (LRSPR) is proposed and experimentally demonstrated. The structural parameters, including the dielectric material and layer thicknesses, are optimized through comprehensive theoretical analysis to achieve the best performance. By filling it with a high refractive index (RI) thermosensitive liquid, the GK570/Ag-coated HF temperature sensor with optimal structural parameters is fabricated. Due to the high sensitivity of the LRSPR sensor and the optimized design, the fabricated sensor achieves a temperature sensitivity of 3.6∼20.5 nm/°C, which is almost the highest among the optical fiber temperature sensors based on surface plasmon resonance reported experimentally. Moreover, the detection range of the proposed sensor can be easily tuned up to 170°C by varying the RI of the filled thermosensitive liquid, and the sensor performance remains stable. Considering that most temperature sensors using polydimethylsiloxane have a fixed detection range, this is an outstanding advantage that could expand the application field of the optical fiber temperature sensor.

Flexible Hollow Core Fiber Photoacoustic Gas Sensor Based on Embedded Acoustic Resonant Structure.

In this paper, we demonstrate a flexible leaky hollow core fiber (LHCF) photoacoustic (PA) gas sensor based on an embedded acoustic resonant structure. The sensor employs a part of a gas conduit as the buffer chamber to construct an equivalent T-type half-open PA cell. The LHCF is installed inside of the gas conduit and the LHCF is hence replaceable. Also, the flexibility of the LHCF and the gas conduit make the gas sensor flexible to reduce spatial size. The inner diameter and length of the LHCF are 1.6 mm and 70 mm, respectively. The inner diameter and length of the gas conduit are 4 mm and 210 mm, respectively. The total gas volume of the sensor is only ∼2.6 mL. Trace acetylene (C2H2) is selected as the target gas to evaluate the performance of the PA gas sensor. A near-infrared distributed feedback (DFB) laser is utilized to generate the PA signal, and an electrical micro-electro-mechanical system (MEMS) microphone is employed to extract the PA signal. The experimental results show that the minimum detection limit (MDL) can be as low as 21.1 ppb when the lock-in integration time is 200 s. And the normalized noise equivalent absorption coefficient (NNEA) is calculated to be 5.7 × 10-9·W/cm-1·Hz-1/2.

Low-frequency Resonant Photoacoustic Gas Sensor by Employing Hollow Core Fiber-Based O-Shaped Multipass Cells.

A low-frequency flexible resonant photoacoustic (PA) gas sensor using an O-shaped multipass cell is demonstrated. The PA sensor employed a flexible gradually tapered leaky hollow core fiber (LHCF). The LHCF was bent to be an end-to-end structure to make full use of the incident light. Additionally, the two ends of the LHCF were put inside a single buffer chamber, yielding an equivalent H-type acoustic resonator. The geometric size was reduced thanks to the bending structure. The geometric length of the LHCF was 500 mm. A micro-electro-mechanical-systems electrical microphone was installed at the center of the resonant tube to detect the PA signal. The proposed PA gas sensor exhibited a first-order longitudinal resonance frequency of 408 Hz. Trace acetylene (C2H2) was used as the target gas. The minimum detectable limit was calculated to be 25.8 parts-per-billion (ppb) with an average time of 400 s, which was 1.93 times higher than that of a single-pass PA gas sensor. The normalized noise-equivalent absorption coefficient and the PA cell constant were calculated to be 9.6 × 10-9 W·cm-1·Hz-1/2 and 8295 Pa/W·cm-1, respectively. The PA gas sensor owns a low resonance frequency and can be used for detection of most of the polar gaseous molecules, especially suitable for gas molecules with a long V-T relation time, such as carbon monoxide and carbon dioxide.

High harmonic generation in solids: particle and wave perspectives.

High harmonic generation (HHG) from gas-phase atoms (or molecules) has opened up a new frontier in ultrafast optics, where attosecond time resolution and angstrom spatial resolution are accessible. The fundamental physical pictures of HHG are always explained by the laser-induced recollision of particle-like electron motion, which lay the foundation of attosecond spectroscopy. In recent years, HHG has also been observed in solids. One can expect the extension of attosecond spectroscopy to the condensed matter if a description capable of resolving the ultrafast dynamics is provided. Thus, a large number of theoretical studies have been proposed to understand the underlying physics of solid HHG. Here, we revisit the recollision picture in solid HHG and show some challenges of current particle-perspective methods, and present the recently developed wave-perspective Huygens-Fresnel picture for understanding dynamical systems within the ambit of strong-field physics.

Highly sensitive photoacoustic gas sensor with micro-embedded acoustic resonator for gas leakage detection.

In this work, a photoacoustic (PA) gas sensor with a micro-embedded acoustic resonator for gas leakage detection was demonstrated. The micro-embedded acoustic resonator was fabricated by putting a leaky hollow-core fiber (L-HCF) into a cylindrical buffer chamber. The L-HCF was utilized as the PA cavity and the light transmission media simultaneously. The optimal inner diameter of the L-HCF was 1.7 mm. The embedded acoustic resonator was experimentally proven to be equivalent to a T-type half-open acoustic resonator, but the structure became much more compact. The volume of the amount of gas in the cell was only ∼0.3 mL, and the gas diffusion time to fill the sensor under room temperature (25°C) and ambient pressure (101 kPa) was ∼44 s. Trace acetylene (C2H2) in pure nitrogen (N2) was chosen as the target gas, and the minimum detectable limit (MDL) reached 29 ppb when the lock-in integration time was 1 s. The normalized noise equivalent absorption (NNEA) coefficient was calculated to be 3.0 × 10-9 W·cm-1·Hz-1/2. The micro-resonant PA gas sensor, with merits of compactness, low gas consumption, and low cost, has the potential to be a remote gas sensing scheme in fields of environmental protection, industrial process monitoring, and so on.

CH4, C2H6, and CO2 Multi-Gas Sensing Based on Portable Mid-Infrared Spectroscopy and PCA-BP Algorithm.

A multi-gas sensing system was developed based on the detection principle of the non-dispersive infrared (NDIR) method, which used a broad-spectra light source, a tunable Fabry-Pérot (FP) filter detector, and a flexible low-loss infrared waveguide as an absorption cell. CH4, C2H6, and CO2 gases were detected by the system. The concentration of CO2 could be detected directly, and the concentrations of CH4 and C2H6 were detected using a PCA-BP neural network algorithm because of the interference of CH4 and C2H6. The detection limits were achieved to be 2.59 ppm, 926 ppb, and 114 ppb for CH4, C2H6, and CO2 with an averaging time of 429 s, 462 s, and 297 s, respectively. The root mean square error of prediction (RMSEP) of CH4 and C2H6 were 10.97 ppm and 2.00 ppm, respectively. The proposed system and method take full advantage of the multi-component gas measurement capability of the mid-infrared broadband source and achieve a compromise between performance and system cost.

[Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor].

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Surface-Enhanced Raman Scattering in Silver-Coated Suspended-Core Fiber.

In this paper, the silver-coated large-core suspended-core fiber (LSCF) probe was fabricated by the dynamic chemical liquid phase deposition method for surface-enhanced Raman scattering (SERS) sensing. The 4-mercaptophenylboronic acid (4-MPBA) monolayer was assembled in the LSCF as the recognition monolayer. Taking advantage of the appropriate core size of the LSCF, a custom-made Y-type optical fiber patch cable was utilized to connect the semiconductor laser, Raman spectrometer, and the proposed fiber SERS probe. The SERS signal is propagated in the silver-coated air channels, which can effectively reduce the Raman and fluorescence background of the silica core. Experiments were performed to measure the Raman scattering spectra of the 4-MPBA in the silver-coated LSCF in a non-enhanced and enhanced case. The experiment results showed that the Raman signal strength was enhanced more than 6 times by the surface plasmon resonance compared with the non-enhanced case. The proposed LSCF for SERS sensing technology provides huge research value for the fiber SERS probes in biomedicine and environmental science. The combination of SERS and microstructured optical fibers offers a potential approach for SERS detection.

Surface plasmon resonance temperature sensor with tunable detection range based on a silver-coated multi-hole optical fiber.

A novel surface plasmon resonance (SPR) temperature sensor based on a silver-coated multi-hole optical fiber (SMHOF) is presented. The central and surrounding air holes of the SMHOF are filled with two kinds of thermosensitive liquid with high and low refractive index (RI), respectively. Two separated resonance dips, which are related to the high and low RI filled liquid respectively, are observed at different wavelength in the transmission spectrum. Advantageously, the two dips move towards opposite direction with the temperature variation. The interval between the two SPR dips is measured under different environmental temperature and exhibits a good linearity. The proposed sensor with different detection range is fabricated by changing the RIs of the filled thermosensitive liquids. The temperature sensitivity of 7.72 nm/°C and -7.81 nm/°C is obtained in the range of 20-60 °C and -20-20 °C, respectively. Owing to the high temperature sensitivity and tunable detection range, the proposed sensor is expected to find potential applications in biomedicine, health care and environmental monitoring.

Fleck-like lesions in CEP290-associated leber congenital amaurosis: a case series.

PURPOSE: To provide a detailed ophthalmic phenotype of a small cohort of patients with Leber Congenital Amaurosis (LCA) caused by mutations in CEP290 (CEP290-LCA) with a focus on elucidating the origin of yellow-white lesions observed in 30% of patients with this condition. METHODS: This is a retrospective review of records of five patients with CEP290-LCA. Patients had comprehensive ophthalmic evaluations. Visual function was assessed with full-field electroretinograms (ffERGs) and full-field sensitivity testing (FST). Multimodal imaging was performed with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation wavelengths. RESULTS: All patients showed relative structural preservation of the foveal and near midperipheral retina separated by a pericentral area of photoreceptor loss. Yellow-white, fleck-like lesions in an annular distribution around the near midperiphery co-localized with hyperreflective lesions on SD-OCT. The lesions located between the inner segment ellipsoid signal and the apical retinal pigment epithelium (RPE). The inner retina was normal. Longitudinal observations in one of the patients indicates the abnormalities may represent an intermediate stage in the degenerative process between the near normal appearing retina previously documented in young CEP290-LCA patients and the pigmentary retinopathy observed along the same region in older individuals. CONCLUSIONS: We speculate that fleck-like lesions in CEP290-LCA correspond to malformed, rudimentary or degenerated, including shed, photoreceptor outer segments. The topography and possible origin of the abnormalities may inform the planning of evolving genetic therapies for this disease.

Pivotal interplays between fecal metabolome and gut microbiome reveal functional signatures in cerebral ischemic stroke.

BACKGROUND: Integrative analysis approaches of metagenomics and metabolomics have been widely developed to understand the association between disease and the gut microbiome. However, the different profiling patterns of different metabolic samples in the association analysis make it a matter of concern which type of sample is the most closely associated with gut microbes and disease. To address this lack of knowledge, we investigated the association between the gut microbiome and metabolomic profiles of stool, urine, and plasma samples from ischemic stroke patients and healthy subjects. METHODS: We performed metagenomic sequencing (feces) and untargeted metabolomics analysis (feces, plasma, and urine) from ischemic stroke patients and healthy volunteers. Differential analyses were conducted to find key differential microbiota and metabolites for ischemic stroke. Meanwhile, Spearman's rank correlation and linear regression analyses were used to study the association between microbiota and metabolites of different metabolic mixtures. RESULTS: Untargeted metabolomics analysis shows that feces had the most abundant features and identified metabolites, followed by urine and plasma. Feces had the highest number of differential metabolites between ischemic stroke patients and the healthy group. Based on the association analysis between metagenomics and metabolomics of fecal, urine, and plasma, fecal metabolome showed the strongest association with the gut microbiome. There are 1073, 191, and 81 statistically significant pairs (P < 0.05) in the correlation analysis for fecal, urine, and plasma metabolome. Fecal metabolites explained the variance of alpha-diversity of the gut microbiome up to 31.1%, while urine and plasma metabolites only explained the variance of alpha-diversity up to 13.5% and 10.6%. Meanwhile, there were more significant differential metabolites in feces than urine and plasma associated with the stroke marker bacteria. CONCLUSIONS: The systematic association analysis between gut microbiome and metabolomics reveals that fecal metabolites show the strongest association with the gut microbiome, followed by urine and plasma. The findings would promote the association study between the gut microbiome and fecal metabolome to explore key factors that are associated with diseases. We also provide a user-friendly web server and a R package to facilitate researchers to conduct the association analysis of gut microbiome and metabolomics.

Filming movies of attosecond charge migration in single molecules with high harmonic spectroscopy.

Electron migration in molecules is the progenitor of chemical reactions and biological functions after light-matter interaction. Following this ultrafast dynamics, however, has been an enduring endeavor. Here we demonstrate that, by using machine learning algorithm to analyze high-order harmonics generated by two-color laser pulses, we are able to retrieve the complex amplitudes and phases of harmonics of single fixed-in-space molecules. These complex dipoles enable us to construct movies of laser-driven electron migration after tunnel ionization of N2 and CO2 molecules at time steps of 50 attoseconds. Moreover, the angular dependence of the migration dynamics is fully resolved. By examining the movies, we observe that electron holes do not just migrate along the laser polarization direction, but may swirl around the atom centers. Our result establishes a general scheme for studying ultrafast electron dynamics in molecules, paving a way for further advance in tracing and controlling photochemical reactions by femtosecond lasers.

Spinal Cord Stimulation Improved Freezing of Gait and Hypokinetic Dysarthria of a Patient with Dopamine-Resistant Multiple System Atrophy-Parkinsonian Type.

Background: Multiple system atrophy parkinsonian type (MSA-P) patients with resistance to dopamine have highly limited treatment options. This calls for further study of spinal cord stimulation (SCS) as a potential nondopaminergic therapy to improve motor and speech functions of patients with dopamine-resistant parkinsonism. Case Presentation: A 58-year-old male with MSA-P had hypokinetic dysarthria, freezing of gait (FOG), and spinal disc herniation with refractory back pain. SCS was used to treat his refractory back pain. Serendipitously, after the surgery, the patient reported not only a reduction in pain but also rapid improvement of FOG and hypokinetic dysarthria. Conclusion: SCS has been found in some cases to improve FOG and hypokinetic dysarthria. It is necessary to further study the potential of and the mechanism behind SCS as a potential nondopaminergic therapy to improve motor and speech functions of patients with dopamine-resistant parkinsonism.

Design, fabrication, and characterization of a single-polarization single-mode flexible hollow waveguide for low loss millimeter wave propagation.

A flexible metallic waveguide with elliptical core that achieves single-polarization single-mode (SPSM) propagation at millimeter wave was designed, fabricated, and characterized. In order to achieve SPSM propagation, optimization of the lengths of major/minor axes of elliptical core was conducted to cut off one of the two orthogonally polarized fundamental modes and all high-order modes. A one-meter long hollow elliptical waveguide (HEW) with major/minor axis length of 1.5/2.7 mm was fabricated. The substrate tube was a flexible elliptical polycarbonate (PC) tube, which was fabricated through glass-draw technique. Silver film was then coated on the inner surface of the tube. Simulation results show that the 1.5/2.7 mm HEW maintains SPSM propagation in the frequency band from 66.5 to 114 GHz. The SPSM operation was experimentally discussed in detail at 100 GHz. The measured loss of 2.58 dB/m and the output polarization ratio of 99.9% was obtained after propagating one meter. Furthermore, the waveguide was robust to bending and twisting. The additional loss was as small as 0.2 dB/m even when the waveguide was coiled into a circle. The potential application of HEWs as polarizers was demonstrated by using a 10 cm long waveguide for polarization detection and extinction ratio of 22.3 dB was achieved at 100 GHz.

Artesunate induces ferroptosis via modulation of p38 and ERK signaling pathway in glioblastoma cells.

Ferroptosis is implicated in various tumors, including glioblastoma. Artesunate (ART), an anti-malarial drug, exerted antitumor properties in several cancer types. However, the role of ferroptosis in the inhibiting effect of artesunate on glioblastoma remains unclear. The purpose of this study was to investigate the effects of ART on the ferroptosis of glioblastoma and to elucidate the underlying mechanisms. We found that ART inhibited the proliferation of glioblastoma cells in vitro and glioblastoma tumorigenesis in vivo. Characteristic changes of ferroptosis were observed in ART group, including GSH depletion, lipid peroxidation and iron overload. Meanwhile, the protein level of GPX4 were lower in ART group than that in control group. Ferrostatin-1, a ferroptosis inhibitor, could rescue the cell death induced by ART in U251 cells. Further examination of the mechanism revealed that the effect of ART on ferroptosis was partially governed by regulating iron homeostasis and p38 and ERK signaling pathway. These findings support that ART triggers ferroptosis in glioblastoma and might be a potential therapeutic agent for glioblastoma treatment.

Control of the Geometric Phase and Nonequivalence between Geometric-Phase Definitions in the Adiabatic Limit.

If the time evolution of a quantum state leads back to the initial state, a geometric phase is accumulated that is known as the Berry phase for adiabatic evolution or as the Aharonov-Anandan (AA) phase for nonadiabatic evolution. We evaluate these geometric phases using Floquet theory for systems in time-dependent external fields with a focus on paths leading through a degeneracy of the eigenenergies. Contrary to expectations, the low-frequency limits of the two phases do not always coincide. This happens as the degeneracy leads to a slow convergence of the quantum states to adiabaticity, resulting in a nonzero finite or divergent contribution to the AA phase. Steering the system adiabatically through a degeneracy provides control over the geometric phase as it can cause a π shift of the Berry phase. On the other hand, we revisit an example of degeneracy crossing proposed by AA. We find that, at suitable driving frequencies, both geometric-phase definitions give the same result and the dynamical phase is zero due to the symmetry of time evolution about the point of degeneracy, providing an advantageous setup for manipulation of quantum states.

Fingerprint of the Interbond Electron Hopping in Second-Order Harmonic Generation.

We experimentally explore the fingerprint of the microscopic electron dynamics in second-order harmonic generation (SHG). It is shown that the interbond electron hopping induces a novel source of nonlinear polarization and plays an important role even when the driving laser intensity is 2 orders of magnitude lower than the characteristic atomic field. Our model predicts anomalous anisotropic structures of the SHG yield contributed by the interbond electron hopping, which is identified in our experiments with ZnO crystals. Moreover, a generalized second-order susceptibility with an explicit form is proposed, which provides a unified description in both the weak and strong field regimes. Our work reveals the nonlinear responses of materials at the electron scale and extends the nonlinear optics to a previously unexplored regime, where the nonlinearity related to the interbond electron hopping becomes dominant. It paves the way for realizing controllable nonlinearity on an ultrafast time scale.