Highly sensitive microfluidic sensor using integrated optical fiber and real-time single-cell Raman spectroscopy for diagnosis of pancreatic cancer.

Pancreatic cancer is notoriously lethal due to its late diagnosis and poor patient response to treatments, posing a significant clinical challenge. This study introduced a novel approach that combines a single-cell capturing platform, tumor-targeted silver (Ag) nanoprobes, and precisely docking tapered fiber integrated with Raman spectroscopy. This approach focuses on early detection and progression monitoring of pancreatic cancer. Utilizing tumor-targeted Ag nanoparticles and tapered multimode fibers enhances Raman signals, minimizes light loss, and reduces background noise. This advanced Raman system allows for detailed molecular spectroscopic examination of individual cells, offering more practical information and enabling earlier detection and accurate staging of pancreatic cancer compared to conventional multicellular Raman spectroscopy. Transcriptomic analysis using high-throughput gene screening and transcriptomic databases confirmed the ability and accuracy of this method to identify molecular changes in normal, early, and metastatic pancreatic cancer cells. Key findings revealed that cell adhesion, migration, and the extracellular matrix are closely related to single-cell Raman spectroscopy (SCRS) results, highlighting components such as collagen, phospholipids, and carotene. Therefore, the SCRS approach provides a comprehensive view of the molecular composition, biological function, and material changes in cells, offering a novel, accurate, reliable, rapid, and efficient method for diagnosing and monitoring pancreatic cancer.

Er3+/Yb3+ Co-Doped Fluorotellurite Glass Fiber with Broadband Luminescence.

In order to address the 'capacity crisis' caused by the narrow bandwidth of the current C band and the demand for wide-spectrum sensing sources and tunable fiber lasers, a broadband luminescence covering the C + L bands using Er3+/Yb3+ co-doped fluorotellurite glass fiber is investigated in this paper. The optimal doping concentrations in the glass host were determined based on the intensity, lifetime, and full width at half maximum (FWHM) of the fluorescence centered at 1.5 µm, which were found to be 1.5 mol% Er2O3 and 3 mol% Yb2O3. We also systematically investigated this in terms of optical absorption spectra, absorption and emission cross-sections, gain coefficients, Judd-Ofelt parameters, and up-conversion fluorescence. The energy transfer (ET) mechanism between the high concentrations of Er3+ and Yb3+ was summarized. In addition, a step-indexed fiber was prepared based on these fluorotellurite glasses, and a wide bandwidth of ~112.5 nm (covering the C + L bands from 1505.1 to 1617.6 nm) at 3 dB for the amplified spontaneous emission (ASE) spectra has been observed at a fiber length of 0.57 m, which is the widest bandwidth among all the reports based on tellurite glass. Therefore, this kind of Er3+/Yb3+ co-doped fluorotellurite glass fiber has great potential for developing broadband C + L band amplifiers, ultra-wide fiber sources for sensing, and tunable fiber lasers.

Correction: Characterization of a Polyethylene Glycol-Amphotericin B Conjugate Loaded with Free AMB for Improved Antifungal Efficacy.

[This corrects the article DOI: 10.1371/journal.pone.0152112.].

Investigation of a twisting-fused side-pump coupler based on tellurite fiber.

Fiber side-pump couplers can enhance the output power of fiber laser due to their dependable and efficient operation and impressive power handling capability. We developed a tellurite fiber side-pump coupler by twisting and fusing a tapered pump fiber onto a target fiber. The effect of twisting parameters on coupling efficiency was comprehensively investigated through theoretical simulations and experiments. Experimental results exhibited an impressive coupling efficiency of 76.5% and a root mean square stability of 0.086% and 0.091% before and after one month, respectively, driven by an incident pump power of up to 4.2 W.

High-efficiency and broadband tunable Raman fiber laser in a chalcogenide fiber based on the Fresnel reflection.

A high-efficiency and broadband tunable chalcogenide fiber Raman laser with the Fabry-Perot (F-P) cavity formed by the Fresnel reflection was established. A maximum average power slope efficiency of around 43% and a maximum output peak power of about 2.9 W at 2148 nm were demonstrated by using a 2 µm nanosecond pump source. The laser shows a broadened pulse width of 674 ns and a broadband tunability of the central wavelength from 2100 to 2186 nm. The Raman Fabry-Perot cavity constituted by the Fresnel reflection from chalcogenide fiber endfaces can operate at any wavelength without the aid of any additional optical feedback element. This will facilitate the realization of fiber lasers with excellent performance and compact system, especially in the mid-infrared region.

High Q-factor, ultrasensitivity slot microring resonator sensor based on chalcogenide glasses: erratum.

We correct the error in [Opt. Express30, 3866 (2022)10.1364/OE.450092], Fig. 6(c). The unit of the vertical axis in the figure should be arbitrary units, not dB. All the conclusions are unchanged after the correction.

Advances in the pharmacological study of Chinese herbal medicine to alleviate diabetic nephropathy by improving mitochondrial oxidative stress.

Diabetic nephropathy (DN) is one of the serious complications of diabetes mellitus, primarily arising from type 2 diabetes (T2DM), and can progress to chronic kidney disease (CKD) and end stage renal disease (ESRD). The pathogenesis of DN involves various factors such as hemodynamic changes, oxidative stress, inflammatory response, and lipid metabolism disorders. Increasing attention is being given to DN caused by oxidative stress in the mitochondrial pathway, prompting researchers to explore drugs that can regulate these target pathways. Chinese herbal medicine, known for its accessibility, rich historical usage, and remarkable efficacy, has shown promise in ameliorating renal injury caused by DN by modulating oxidative stress in the mitochondrial pathway. This review aims to provide a reference for the prevention and treatment of DN. Firstly, we outline the mechanisms by which mitochondrial dysfunction impairs DN, focusing on outlining the damage to mitochondria by oxidative stress. Subsequently, we describe the process by which formulas, herbs and monomeric compounds protect the kidney by ameliorating oxidative stress in the mitochondrial pathway. Finally, the rich variety of Chinese herbal medicine, combined with modern extraction techniques, has great potential, and as we gradually understand the pathogenesis of DN and research techniques are constantly updated, there will be more and more promising therapeutic targets and herbal drug candidates. This paper aims to provide a reference for the prevention and treatment of DN.

Fiber Optic SERS Sensor with Silver Nanocubes Attached Based on Evanescent Wave for Detecting Pesticide Residues.

Surface-enhanced Raman scattering (SERS) has great potential in the field of rapid detection of pesticide residues in food. In this paper, a fiber optic SERS sensor excited by evanescent waves was proposed for efficient detection of thiram. Silver nanocubes (Ag NCs) were prepared as SERS active substrates, which had much stronger electromagnetic field intensity than nanospheres under laser excitation due to much more "hot spots". By using the method of electrostatic adsorption and laser induction, Ag NCs were uniformly assembled at the fiber taper waist (FTW) for enhancing the Raman signal. Different from the traditional way of stimulation, evanescent wave excitation greatly increased the interaction area between the excitation and analyte, while reducing the damage of the excited light to the metal nanostructures. The methods proposed in this work have been successfully used to detect the pesticide residues of thiram and showed good detection performance. The detection limits for 4-Mercaptobenzoic acid (4-MBA) and thiram were determined to be 10-9 and 10-8 M, the corresponding enhancement factor could be 1.64 × 105 and 6.38 × 104. Low concentration of thiram was detected in the peels of tomatoes and cucumbers, indicating its feasibility in actual sample detection. The combination of evanescent waves and SERS provides a new direction for the application of SERS sensors, which had great application potential in the field of pesticide residue detection.

Fabrication of a tellurite-fiber-based side-pump coupler based on the tapered-fused method.

In this study, (1 + 1) × 1 side-pump couplers made of tellurite fibers were fabricated and investigated. The whole optical design of the coupler was established on the basis of ray tracing models and validated by experimental results. By optimizing the preparation conditions and structural parameters, the tested component achieved a coupling efficiency of 67.52% and an insertion loss of 0.52 dB. To the best of our knowledge, this is the first time a tellurite-fiber-based side-pump coupler was developed. The fused coupler presented will simplify many mid-infrared fiber lasers or amplifier architectures.

Detection of copper ions in an aqueous solution by a dual-peak long period fiber grating functionalized with a polypyrrole-chitosan composite.

A dual-peak long period fiber grating (DP-LPFG) sensor functionalized by polypyrrole-chitosan composite was proposed for sensitive detection of Cu2+ ions in aqueous solution. The nitrogen atom on the polypyrrole ring and the amino group on the chitosan chain in the complex matrix can chelate the Cu2+ ions. Thus, the refractive index of the overlay changed and further modulated the transmission spectrum of DP-LPFG. After special design, the double peaks can move in opposite directions with the increase of Cu2+ ion concentration, thereby greatly improving detection sensitivity. The linear sensitivity of the fabricated sensor was measured to be 9.12 and 2.14 nm/ppm (0.61 and 0.14 nm/µM) for concentrations of 0.1-0.5 (1.5 µM-7.5 µM) and 0.5-2 ppm (7.5 µM-30 µM), respectively. In addition, the Langmuir isothermal model was used to evaluate the overall response of the sensor to Cu2+ ions quantitatively, and the detection limit was determined to be 0.05 ppb (0.75 nM). This ingenious sensor offers a new solution for sensitive detection of heavy metal ions in environmental water.

Design and fabrication of large-mode-area multicore chalcogenide fiber with low bending loss.

Multicore fiber (MCF) has a larger mode-area (LMA) compared to traditional single-core fiber, making it easy to get a mode area of more than 3000 µm2 with an optimized MCF structure. Here, a fine-structured 19-core fiber based on chalcogenide glass was fabricated using a combined method involving extrusion, drilling, and rod-in-tube for the first time. The fiber has a minimum transmission loss of 1.8 dB/m at 6.7 µm. When the bending radius exceeds 6 cm, a low bending loss of about 0.6 dB appears, and the experimental data are in good agreement with the simulation results. In addition, the supermode characteristics of the 19-core fiber are analyzed from both perspectives of simulation and experiment, and these results are perfectly in good agreement. We believe it opens a new way to develop high-power and bend-resisting fiber with such kind of multicore structure.

Rapid and sensitive detection of ammonia in water by a long period fiber grating sensor coated with sol-gel silica.

A sensitive ammonia sensor based on long-period fiber grating (LPFG) is designed and manufactured for the detection of ammonia concentration in water. Femtosecond laser direct writing technology is used to write LPFGs on standard single-mode silica fiber. A thin layer doped with basic dyes is coated on the optical fiber for sensing by using the sol-gel method. The thicknesses of sol-gel layers, which play a key role in the sensitivity of the LPFG sensor, were carefully studied. Experimental results show that LPFG with a functional layer of ∼340 nm has the best sensing performance, and the detection limit is 0.08 ppm. The response time of the sensor is less than one minute, and the sensor has good repeatability with a short recovery time. Compared with other organic molecules and ions in water, the proposed LPFG sensor has not only good reusability, but also selectivity for the detection of ammonia.

Efficacy and Safety of Glycosides of Tripterygium wilfordii Combined with Renin-Angiotensin System in the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis.

Background: IgA nephropathy (IgAN) is currently the most common primary glomerular disease, accounting for approximately 36.7% to 58.2% of primary glomerular disease in kidney biopsies in China. Definitive diagnosis depends on immunopathological examination of the kidney. The prognosis of this disease was generally considered to be good, but recent studies have found that about half of patients can progress to end-stage renal disease within 30 years of onset. Because the pathogenesis is unknown, there is no specific treatment. Objective: To evaluate the efficacy and safety of glycosides of Tripterygium wilfordii (GTW) in combination with renin-angiotensin system (RAS) inhibitors for the treatment of IgAN. Methods: Search Embase, Pubmed, Cochrane, CNKI, Web of Science, Wanfang, and VIP for all randomized controlled trials (RCTs) on treating IgAN with RASI from the self-built database to December 2021. Relevant data were searched and collected separately by two reviewers. The Cochrane risk of bias model was used for quality assessment, and RevMan 5.3 was used for data analysis. Results: Thirteen Chinese publications with a total of 958 patients were finally included. There was no statistically significant difference in baseline information (including laboratory data and clinical parameters) between the two groups of patients. The urine protein quantification in both groups showed a significant decreasing trend as the treatment duration increased. At 3, 6, 9, and 12 months after treatment, urine protein was significantly lower than the baseline value in both the observation and control groups (P < 0.05). During the follow-up period, there was no statistical difference in blood creatinine (Scr) and eGFR values between the two groups compared with the baseline values (P > 0.05). Patients with CKD stage 2 achieved a higher remission rate compared with patients with CKD stage 3, with a statistically significant difference (P < 0.05), and the difference between the two groups was not significant for patients in the same stage. There was no statistically significant difference in the total effective rate between the two groups (P > 0.05). During the follow-up period, there was no statistically significant difference in urine protein quantification, Scr, and eGFR between the two groups. In terms of the incidence of adverse reactions, the observation group was less than the control group, and there was a significant difference between the two groups (P < 0.05). Conclusion: GTW combined with RASI is one of the safe and effective treatment modes for IgAN nephropathy. It can not only effectively reduce the excretion of urinary protein in patients and delay the progression of chronic kidney disease but also has less serious side effects and is well tolerated by patients, so it can be a new choice of therapeutic drugs for this group of patients.

Se-H-free As2Se3 fiber and its spectral applications in the mid-infrared.

The complete removal of the impurities like Se-H in Se-based chalcogenide glasses has been challenging in the development of highly transparent chalcogenide glass fiber. In this paper, several purification methods, including dynamic distillation, static distillation, and combined distillation method, were adopted with an aim of purifying arsenic selenide glass with ultra-low content of the impurities. The experimental results demonstrated that the Se-H can be completely eliminated in the arsenic selenide glass host and fiber without the introduction of any chloride. We further explored the applications of such low loss and Se-H-free chalcogenide glass fiber in the mid-infrared. It was found that, using such a Se-H free fiber, a flattened supercontinuum spectrum above the -30 dB level from 1.2 to 13 µm was generated from the Se-H free fiber with a 5.5 µm laser pumping. The sensitivity was found to be improved 5.1 times for CO2 gas in the 3 to 6 µm wavelength range.

Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model.

COVID-19 and chronic kidney disease (CKD) share similarity in sex bias and key genes in the disease pathway of sex difference. We investigated the sex difference of molecular pathways of four key players of these two diseases using an existing large set of whole genome expression profiles from the kidneys of female and male mouse models. Our data show that there is little to no correlation at the whole genome expression level between female and male mice among these four genes. There are considerable sex differences among genes in upstream regulation, Ace2 complex interaction, and downstream pathways. Snap25 and Plcb4 may play important roles in the regulation of the expression level of Adam17, Tmprss2, and Cd146 in females. In males, Adh4 is a candidate gene for the regulation of Adam17, while Asl, Auts2, and Rabger1 are candidates for Tmprss2. Within the Ace2 complex, Cd146 directly influences the expression level of Adam17 and Ace2 in the female, while in the male Adam potentially has a stronger influence on Ace2 than that of Tmprss2. Among the top 100 most related genes, only one or two genes from four key genes and 11 from the control B-Actin were found to be the same between sexes. Among the top 10 sets of genes in the downstream pathway of Ace2, only two sets are the same between the sexes. We concluded that these known key genes and novel genes in CKD may play significant roles in the sex difference in the CKD and COVID-19 disease pathways.

Effectiveness of Er:YAG Laser Combined with Photobiomodulation on Periodontitis Based on 3-month Observation.

PURPOSE: The effectiveness of using different laser therapy strategies in adjunct to scaling and root planing (SRP) for treatment of periodontitis remains unclear. This study compared the treatment outcome of SRP and its combination with Er:YAG laser and/or photobiomodulation on patients with severe periodontitis. MATERIALS AND METHODS: A total of 50 patients were included, whose teeth were divided into 4 quadrants: 1. SRP+Er:YAG laser irradiation+photobiomodulation treatment; 2. SRP+Er:YAG laser irradiation treatment; 3. SRP+photobiomodulation treatment; 4. SRP treatment only. An Er:YAG laser at powers of 50 or 40 mJ and an Nd:YAG laser at 50 mJ were used. Patients were followed-up for 3 months. Periodontal clinical parameters (probing depth [PD], clinical attachment level [CAL], plaque index [PLI] and bleeding index [BI]), inflammation factors (melatonin and MMP-8 levels) and pain intensity were compared among the 4 quadrants. RESULTS: The quadrant treated by SRP combined with Er:YAG laser irradiation and photobiomodulation had statistically significantly lower PD? (p = 0.0081 at 1 month; p < 0.0001 at 3 months), CAL? (p = 0.003), PLI ?(p = 0.0011) and BI levels ?(p = 0.005 at 1 month; p = 0.0236 at 3 months) compared with the other 3 quadrants. In addition, melatonin ?(p = 0.0006 at 1 month; p = 0.0002 at 3 months) and MMP-8 levels ?(p = 0.0012; only at 1 month) were also statistically significantly higher. CONCLUSION: Of the treatments tested here, SRP combined with Er:YAG laser irradiation and photobiomodulation had the best short-term outcome for severe periodontitis.

Efficacy and safety of Abelmoschus manihot in treating chronic kidney diseases: A multicentre, open-label and single-arm clinical trial.

RATIONALE AND OBJECTIVE: The efficacy of Abelmoschus manihot (AM) in treating of chronic kidney disease (CKD) has been confirmed by prior trials. AM is also commonly combined to other medicines among CKD patients in clinic. This trial aimed at evaluating the safety of AM combination application, and further verifying the efficacy of AM in treating various types of CKD. STUDY DESIGN: A multicentre, prospective, open-label, single-arm trial SETTING AND PARTICIPANTS: Approximately 2000 CKD patients with proteinuria (≥ 150 mg/d), from 105 centres across China INTERVENTIONS: AM was administered to patients three times per day for 24 weeks: the daily dose was based on age (> 12 years old: 2.5 g tid; 6∼12 years old: 1.5 g tid; 2∼6 years old: 1 g tid) OUTCOMES: The efficacy outcomes were the change in 24-hour proteinuria and estimated glomerular filtration rate (eGFR) from baseline to week 24. Safety outcomes included adverse events and laboratory tests. RESULTS: 2054 CKD patients from 105 centres were enrolled in this trial, with 1843 (89.7%) completing the 24-week follow-up. The participants' median age was 44 years old and 44.6% were female. Compared to baseline, 24-hour proteinuria decreased 471 mg (95% confident interval, 367 to 575, p < 0.001) at week 24. eGFR did not change significantly relative to baseline with the mean increase as 1.7 ml/min/1.73 m2 (95% confident interval, -0.3 to 3.7, p = 0.09). 902 (43.9%) participants combined medication to AM during follow-up. The total incidence of adverse events was 12.9%; and the most common adverse events were hyperlipidaemia (4.1%), abnormal liver function (2.3%), upper respiratory infection (1.8%), and hyperglycaemia (1.1%). Combined medications did not change the risk for hyperlipidaemia and upper respiratory infection. The combination application with antiplatelet reagents increased the risk of abnormal liver function, and with calcium channel blockers increased the risk of hyperglycaemia. LIMITATIONS: Single-arm clinical trial and short observation time CONCLUSION: We have provided safety information of AM on various types of CKD in a large trial, especially when combination to medications most commonly prescribed to CKD patients. AM also showed to decrease proteinuria with stable kidney function during follow up. AM is a promising treatment for CKD patients.

Single-mode suspended large-core chalcohalide fiber with a low zero-dispersion wavelength for supercontinuum generation.

Chalcogenide glass possesses outstanding advantages, such as supercontinuum generation, but its nonlinear applications were limited by large zero-dispersion wavelength (ZDW). Traditional suspended-core fibers can shift the ZDW to near IR with a tiny core size of less than 5 µm but a large evanescent wave loss exists in these fibers. In this paper, we prepared a novel suspended-core fiber (SCF) based on chalcohalide glasses for the first time via the extrusion method, in which the ZDW of the fundamental mode in the fiber with a core size of larger than 30 µm was successfully shifted to 2.6 µm. We also calculated confinement loss (CL) of propagation modes and fundamental mode energy ratio in the fiber. We found that the minimum CL ratio of the high order modes (LP11) to the CL of the fundamental mode is 124, indicating that the single-mode operation condition is satisfied when the wavelength is more than 4.6 µm. The lowest transmission loss is 1.2 dB/m at 6.5 µm. An ultra-broad supercontinuum spectrum, covering from 1.6 to 12 µm was generated in this suspended-core fiber pumped by a 5 µm femtosecond laser. Such a wide SC in the chalcogenide SCF is due to the large core size. All these results demonstrate the potential to use the large core SCF in the application of a mid-IR laser.

High Q-factor, ultrasensitivity slot microring resonator sensor based on chalcogenide glasses.

In this article, the chalcogenide slot waveguide is theoretically studied, and the highest power confinement factors of the slot region and the cladding region are obtained to be 36.3% and 56.7%, respectively. A high-sensitivity chalcogenide slot microring resonator sensor is designed and fabricated by electron-beam lithography and dry etching. The structure increases the sensitivity of the sensor compared with the conventional evanescent field waveguide sensor. The cavity has achieved a quality factor of 1 × 104 by fitting the resonant peaks with the Lorentzian profile, one of the highest quality factors reported for chalcogenide slot microring resonators. The sensor sensitivity is measured to be 471 nm/RIU, which leads to an intrinsic limit of detection of 3.3 × 10--4 RIU.

Rapid and sensitive detection of Staphylococcus aureus by using a long-period fiber grating immunosensor coated with egg yolk antibody.

The rapid and reliable detection of bacteria plays an important role in clinical and veterinary practice. A stable, label free, compact, and sensitive long-period fiber grating (LPFG) sensor based on egg yolk antibody (IgY) was proposed for the detection of Staphylococcus aureus (S. aureus). LPFG was fabricated with laser writing technology, and specific IgY was further immobilized on the grating region and then combined with the corresponding bacteria. S. aureus was detected by tracking the change of resonance wavelength in the LPFG transmission spectrum caused by bacteria-antibody interaction induced by the increase of biological cover thickness and density after the immune reaction. The testing results showed that the proposed sensor was selective and sensitive to S. aureus measurement, and the detection limit is approximately 33 CFU/ml. The proposed antibody immobilization method is very simple, and the optical fiber can be manufactured in batch to reduce the cost. The detection time of the sensor is around 20 min, which is fast and suitable for detection. The assay was successfully applied for the quantitative analysis of S. aureus in natural waters and met the needs of on-site screening trace pathogenic bacteria in food safety control.