Yb3+ doped gain guided index anti-guided fiber based on the nanoporous silica glass rod.

We report a heavily Yb3+/Al3+/B3+/F- co-doped high silica rod with a negative refractive index relative to pure silica. The high silica rod was fabricated from nanoporous silica rod using glass phase-separation technology. To lower the refractive index, B3+ and F- were simultaneously introduced into the silica rod and the optical properties of the silica rod were investigated. The fiber preform was prepared with the rod-in-tube method by which the Yb3+ doped high silica rod was only used as an active core. The fiber has a core diameter of 80 µm and a cladding diameter of 400 µm. The measurements show that the Yb3+ in the high silica fiber core is 15856 ppm by weight, while the refractive index is 0.0024 lower than that of the inner cladding. The amplification performance of the fiber was investigated. The results indicate that nanoporous silica glass based on the glass phase-separation technology has great potential for gain-guided index anti-guided high silica fiber.

Double negative curvature anti-resonance hollow core fiber.

We report on a double negative curvature anti-resonance hollow core fiber, in which, the cladding is constituted of 6 large tubes and 6 small tubes arranged in a staggered pattern. The simulation shows that the loss of the fiber can reach or even exceed the loss of double-clad negative curvature anti-resonance hollow core fibers in short wavelength band, due to the staggered arrangement of two kind of tubes and the double negative curvature on the core boundary. The best single mode performance with a loss ratio as high as 100,000 between LP11 mode and LP01 mode is obtained due to simultaneously inhibited LP11 modes and LP21 modes in the fiber structure. The reason for loss oscillations in long wavelength band and the fabrication feasibility of proposed fiber are also discussed.

High coupling efficiency technology of large core hollow-core fiber with single mode fiber.

With the research of hollow-core fiber with large core diameter, the coupling efficiency from hollow-core fiber with large core diameter to single-mode fiber is difficult to increase through the traditional technology, we proposed a novel coupling method to improve the coupling efficiency by attaching a pure silica small ball at the front end of single-mode fiber, the coupling efficiency of 50% from hollow-core fiber with a large core diameter of 110 µm to single-mode fiber can be achieved.

Temperature-Insensitive Refractive Index Sensor with Etched Microstructure Fiber.

A Mach-Zehnder interferometer (MZI) based on an etched all-solid microstructure fiber (MOF) has been demonstrated. The MZI works on the basis of interference between the vibrant core and cladding modes in the MOF. The all-solid MOF has a heterostructure cladding composed of Ge-doped rod arrays and pure silica, and thus can support and propagate a vibrant cladding mode with a large mode area. When the outermost cladding of MOF is etched, the cladding mode becomes sensitive to the ambient refractive index (RI). The etched MOF can work as a sensing head for RI sensing. By comparing the interference spectra, the extinction ratio has remained stable at around 20 dB after the MOF was etched. The RI sensing characteristics of the MZI with an etched MOF have also been investigated. The results show that the RI sensitivity can reach up to 2183.6 nm/RIU with a low-temperature coefficient (<10 pm/°C).

Design and fabrication of a heterostructured cladding solid-core photonic bandgap fiber for construction of Mach-Zehnder interferometer and high sensitive curvature sensor.

A heterostructured cladding solid-core photonic bandgap fiber (HCSC-PBGF) is designed and fabricated which supports strong core mode and cladding mode transmission in a wide bandgap. An in-line Mach-Zehnder interferometer (MZI) curvature sensor is constructed by splicing single mode fibers at both ends of a HCSC-PBGF. Theoretical analysis of this heterostructured cladding design has been implemented, and the simulation results are consistent with experiment results. Benefiting from the heterostructured cladding design, an enhanced curvature sensing sensitivity of 24.3 nm/m-1 in the range of 0-1.75 m-1 and a high quality interference spectrum with 20 dB fringe visibility are achieved. In order to eliminate the interference of longitudinal strain and transverse torsion on the result of the curvature sensing experiment, we measure the longitudinal strain and transverse torsion sensing properties of HCSC-PBGF, and the results show that the impact is negligible. It is obvious that this high-sensitivity and cost-effective all fiber sensor with a compact structure will have a promising application in fiber sensing.

Long-Acting Release Microspheres Containing Novel GLP-1 Analog as an Antidiabetic System.

Glucagon-like peptide 1 (GLP-1) has recently received significant attention as an efficacious way to treat diabetes mellitus. However, the short half-life of the peptide limits its clinical application in diabetes. In our previous study, a novel GLP-1 analog (PGLP-1) with a longer half-life was synthesized and evaluated. Herein, we prepared the PGLP-1-loaded poly(d,l-lactide- co-glycolide) microspheres to achieve long-term effects on blood glucose control. The incorporation of zinc ion into the formulation can effectively decrease the initial burst release, and a uniform drug distribution was obtained, in contrast to native PGLP-1 encapsulated microspheres. We demonstrated that the solubility of the drug encapsulated in microspheres played an important role in in vitro release behavior and drug distribution inside the microspheres. The Zn-PGLP-1 microspheres had a prominent acute glucose reduction effect in the healthy mice. A hypoglycemic effect was observed in the streptozotocin (STZ) induced diabetic mice through a 6-week treatment of Zn-PGLP-1-loaded microspheres. Meanwhile, the administration of Zn-PGLP-1 microspheres led to the ß-cell protection and stimulation of insulin secretion. The novel GLP-1 analog-loaded sustained microspheres may greatly improve patient compliance along with a desirable safety feature.

Yb3+ heavily doped photonic crystal fiber lasers prepared by the glass phase-separation technology.

We report a Yb3+ heavily doped photonic crystal fiber with 30 µm core diameter manufactured for the first time by an alternative technique. Silica core rods with a diameter of 3 mm and a length of 280 mm were prepared by the sodium-borosilicate glass phase-separation technology. The measurements show that the fiber has an Yb3+ concentration of 22810 ppm by weight, and a resultant absorption of approximately 8.5 dB/m at 976 nm. The Yb3+ ions are distributed throughout the fiber core with an excellent homogeneity. The laser performance demonstrates a high slope efficiency of 64.5% for laser emission at 1033.4 nm and a low power threshold of 3 W within a short fiber length of 1 m. This novel approach provides an alternative means of preparing large active silica rods with high doping levels and excellent material homogeneity for large mode area fibers with complex designs.

All fiber M-Z interferometer for high temperature sensing based on a hetero-structured cladding solid-core photonic bandgap fiber.

We proposed and experimentally demonstrated a high temperature fiber sensor using a hetero-structured cladding solid-core photonic bandgap fiber (HCSC-PBGF) for the first time to our knowledge. A hetero-structured cladding solid-core photonic bandgap fiber is designed and fabricated that supports vibrant core mode and cladding mode transmission. Then, an all fiber M-Z interference sensor is constructed by splicing single mode fiber at both ends of HCSC-PBGF without any other micromachining. The transmission characteristics of HCSC-PBGF are analyzed with a full-vector beam propagation method and a full-vector finite element method, and the simulation results are consistent with experiment results. The sensitivity of this fiber sensor is as high as 0.09 nm/°C when operating from room temperature to 1000 °C, and the fringe contrast keeps stable and clear. It is obvious that this all fiber sensor will have great application prospects in fiber sensing with the advantages of a compact structure, high sensitivity, and cost-effectiveness.

Yb³âº-doped large core silica fiber for fiber laser prepared by glass phase-separation technology.

We report on the preparation and optical characteristics of an Yb(3+)-doped large core silica fiber with the active core prepared from nanoporous silica rod by the glass phase-separation technology. The measurements show that the fiber has an Yb(3+) concentration of 9811 ppm by weight, a low background attenuation of 0.02 dB/m, and absorption from Yb(3+) about 5.5 dB/m at 976 nm. The laser performance presents a high slope efficiency of 72.8% for laser emission at 1071 nm and a low laser threshold of 3 W within only 2.3 m fiber length. It is suggested that the glass phase-separation technology shows great potential for realizing active fibers with larger core and complex fiber designs.

Synchronous microencapsulation of multiple components in silymarin into PLGA nanoparticles by an emulsification/solvent evaporation method.

The development of polymeric carriers loaded with extracts suffers from the drawback not to be able to incorporate simultaneously various pharmacological compounds into the formulation. The aim of this study was therefore to achieve synchronous microencapsulation of multiple components of silymarin into poly (lactic-co-glycolic acid) nanoparticle, the most commonly used polymeric carrier with biodegradability and safety. The main strategy taken was to improve the overall entrapment efficiency and to reduce the escaping ratio of the components of different physicochemical properties. The optimized nanoparticles were spherical in morphology with a mean particle size of 150 ± 5 nm. Under common preparative conditions, silybin and isosilybin were entrapped in high efficiency, whereas taxifolin, silychristin and silydianin, especially taxifolin, showed less entrapment because they were more hydrophilic. By changing the pH of the outer aqueous phase and saturating it with silymarin, the entrapment efficiency of taxifolin, silychristin and silydianin could be significantly improved to over 90%, the level similar to silybin and isosilybin, thereby achieving synchronous encapsulation. It could be concluded that synchronous encapsulation of multiple components of silymarin was achieved by optimizing the preparative variables.

[Formation mechanism of Pickering emulsions induced by self-assembly of medium chain triglycerides and α-cyclodextrin].

In this study, the Pickering emulsions were prepared using medium chain triglycerides(MCT) and α-cyclodextrin(α-CD) and the formation mechanism was studied by means of several physicochemical techniques. The MCT/α-CD microparticles, which stabilized the emulsions, were characterized by the measurement of interfacial tension and the contact angle(θ(ow)), powder X ray diffraction(XRD), scanning electron microscope(SEM), high performance liquid chromatography(HPLC), differential interference microscope(DIM), Cryo-scanning electron microscopy(Cryo-SEM). The physical stability of emulsions with different α-CD content in the continuous aqueous phase was investigated by determination of the droplet size and sedimentation rate, combined with the observation of droplet morphologies by the inverted phase contrast microscope. As a result, it was observed that the amphiphilic supramolecule of MCT and α-CD were indeed formed. Furthermore, MCT/α-CD microparticles formed by the aggregation of MCT/α-CD supramolecule absorbed at the oil/water interface, and then forming a membrane structure to stabilize emulsion. In addition, the average θ(ow) for the MCT/α-CD microparticles was(46.1 ± 3.4)° which stabilized O/W emulsion. When the content of α-CD was increased in the continuous phase, there were more microparticles formed at the oil/water interface and in the continuous aqueous phase, which resulted in smaller particle size of droplet and higher viscosity of the continuous phase. In summary, the study suggest that α-CD/MCT/water emulsions were of O/W Pickering emulsions and the physical stability was better for emulsions with higher content of α-CD in the continuous phase.

Environment-responsive aza-BODIPY dyes quenching in water as potential probes to visualize the in vivo fate of lipid-based nanocarriers.

Environment-responsive near-infrared (NIR) aza-BODIPY dyes capable of fluorescence quenching in water were explored to visualize the in vivo fate of model lipid-based nanocarriers, solid lipid nanoparticles (SLNs). The water-quenching effect of the dyes was confirmed to be sensitive and remained stable for at least 24h. In vitro lipolysis measured by fluorescence quenching completed within 20min, which was in correlation with alkaline compensation results. In vivo live imaging indicated predominant digestion of SLNs within 2h and complete digestion within 4h, which correlated well to in vitro data. Rekindling of quenched dyes by mixed micelles was observed in vitro, but not in vivo. In sharp contrast, SLNs encapsulating another NIR dye DiR showed persistent fluorescence both in vitro and in vivo despite significant lipolysis. It was envisaged that water-quenching fluorescence dyes can be used as probes to monitor the in vivo fate of lipid-based nanocarriers. FROM THE CLINICAL EDITOR: Lipid-based drug delivery systems can provide an excellent nanocarrier platform for the delivery of poorly water-soluble drugs. Nonetheless, the mechanism of oral absorption and subsequent kinetics is poorly understood. In this article, the authors studied the novel use of near-infrared (NIR) aza-BODIPY dyes to visualize the fate of these lipid-based nanocarriers. The positive finding means that this approach may be useful for in-vivo monitoring of lipid-based nanocarriers.

Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Efficacy and safety of robotic versus laparoscopic liver resection for hepatocellular carcinoma: a propensity score-matched retrospective cohort study.

BACKGROUND: Evidence concerning long-term outcome of robotic liver resection (RLR) and laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) patients is scarce. METHODS: This study enrolled all patients who underwent RLR and LLR for resectable HCC between July 2016 and July 2021. Propensity score matching (PSM) was employed to create a 1:3 match between the RLR and LLR groups. A comprehensive collection and analysis of patient data regarding efficacy and safety have been conducted, along with the evaluation of the learning curve for RLR. RESULTS: Following PSM, a total of 341 patients were included, with 97 in the RLR group and 244 in the LLR group. RLR group demonstrated a significantly longer operative time (median [IQR], 210 [152.0-298.0] min vs. 183.5 [132.3-263.5] min; p = 0.04), with no significant differences in other perioperative and short-term postoperative outcomes. Overall survival (OS) was similar between the two groups (p = 0.43), but RLR group exhibited improved recurrence-free survival (RFS) (median of 65 months vs. 56 months, p = 0.006). The estimated 5-year OS for RLR and LLR were 74.8% (95% CI: 65.4-85.6%) and 80.7% (95% CI: 74.0-88.1%), respectively. The estimated 5-year RFS for RLR and LLR were 58.6% (95% CI: 48.6-70.6%) and 38.3% (95% CI: 26.4-55.9%), respectively. In the multivariate Cox regression analysis, RLR (HR: 0.586, 95% CI (0.393-0.874), p = 0.008) emerged as an independent predictor of reducing recurrence rates and enhanced RFS. The operative learning curve indicates that approximately after the 11th case, the learning curve of RLR stabilized and entered a proficient phase. CONCLUSIONS: OS was comparable between RLR and LLR, and while RFS was improved in the RLR group. RLR demonstrates oncological effectiveness and safety for resectable HCC.

Case Report: Long-term survival of a patient with advanced rectal cancer and multiple pelvic recurrences after seven surgeries.

Background: Rectal cancer has a high risk of recurrence and metastasis, with median survival ranging from 24 months to 36 months. K-RAS mutation is a predictor of poor prognosis in rectal cancer. Advanced rectal cancer can be stopped in its tracks by pelvic exenteration. Case summary: A 51-year-old woman was diagnosed with advanced rectal cancer (pT4bN2aM1b, stage IV) with the KRAS G12D mutation due to a change in bowel habits. The patient had experienced repeated recurrences of rectal cancer after initial radical resection, and the tumor had invaded the ovaries, sacrum, bladder, vagina and anus. Since the onset of the disease, the patient had undergone a total of seven surgeries and long-term FOLFIRI- or XELOX-based chemotherapy regimens, with the targeted agents bevacizumab and regorafenib. Fortunately, the patient was able to achieve intraoperative R0 resection in almost all surgical procedures and achieve tumor-free survival after pelvic exenteration. The patient has been alive for 86 months since her diagnosis. Conclusions: Patients with advanced rectal cancer can achieve long-term survival through active multidisciplinary management and R0 surgery.

Multifunctional theragnostic ultrasmall gold nanodot-encapsuled perfluorocarbon nanodroplets for laser-focused ultrasound sequence irradiation (LFSI)-based enhanced tumor ablation.

Despite the substantial potential of focused ultrasound therapy, its efficacy in cancer therapy has been limited due to the high cavitation threshold and safety concerns regarding the use of high-intensity energy pulses. Here, ultrasmall Au nanodot-loaded PEG-modified perfluorocarbon nanodroplets (Au-PFCnDs) were prepared and used as a therapeutic enhancer. A LFSI method was designed to achieve enhanced tumor ablation at a mild focused ultrasound (FUS) energy pulse with the assistance of the instinct photothermal effect of intratumor-permeable ultrasmall Au nanodots under 808 nm NIR laser irradiation. In addition to their therapeutic function, Au-PFCnDs can also generate multimodal images to provide information for tumor surveillance and treatment guidance. The experimental results also showed that the cRGD-targeted Au-PFCnDs could be more efficiently delivered into the tumor and selectively destroy tumors with no observable side effects on normal tissue under LFSI treatment.

A Preliminary Study of miR-144 Inhibiting the Stemness of Colon Cancer Stem Cells by Targeting Krüppel-Like Factor 4.

Colon cancer is a prevalent clinical malignant tumor of the digestive system. The current study aims to explore the miR-144 expression in colorectal cancer (CRC) cell lines and CRC stem cells (CSCs) and to explore its effect on the stemness of CSCs and the targeted regulation of Krüppel-like factor 4 (KLF4). Use qRT-PCR to detect the expression level of miR-144 in CRC cells SW480, HCT116, and H129 and the healthy colon cell NCM460. The CSCs that were used were cultured in HCT116 cells. Use western blot to explore the expressions of Nanog, SOX2, and OCT4 stemness marker protein. After it was transfected with miR-144 mimics or KLF4 plasmid, use MTT to explore the cell viability of CSCs, use flow cytometry to evaluate apoptosis, and use transwell assay to evaluate the ability of invasive of CSCs. The targeting effect of miR-144 on the KLF4 gene was verified using TargetScan prediction and the double-luciferase reporter gene test. Use qRT-PCR to evaluate the role of miR-144 mimics on KLF4 mRNA expression in CSCs. The qRT-PCR results exhibited that the miR-144 expression in CRC cells was higher than that in the healthy colon cell line. The expressions of OCT4, Nanog, and SOX2 stem cell markers were up-regulated in CSCs, and the expression of miR144 increased in CSCs. The cell viability, apoptosis, and invasion of CSCs increased after miR-144 was transfected. The TargetScan prediction and double-luciferase reporter gene assay confirmed that miR-144 was targeted by KLF4, and the expression of KLF4 mRNA in the miR-144 mimics group reduced. Moreover, the overexpression of KLF4 could partially reverse the role of miR-144 mimics on CSCs. In summary, miR-144 was highly expressed in CRC cell lines and CSCs, and the overexpression of miR-144 in CSCs significantly promoted the proliferation of CSCs, inhibited its apoptosis, and promoted its invasion ability. In addition, its preliminary mechanism, possibly through negative regulation KLF4, promotes the stemness of CSCs, and miR-144 is likely to be a potential target for eliminating CSC from CRC treatment.

Glutathione responsive cubic gel particles cyclodextrin metal-organic frameworks for intracellular drug delivery.

Novel cubic gel particles (ssCGP) with Glutathione (GSH) triggered drug release features were prepared by crosslinking the cyclodextrin based metal-organic frameworks (CD-MOFs) templets with a newly synthesized biodegradable disulfide bond-bearing linker and removing of the potassium ion in sequence. The morphology and size of ssCGP were investigated by field emission scanning electron microscope (FESEM) and dynamic light scattering. Energy dispersive x-ray spectroscopy (EDX), fourier transform infrared spectroscopy (FT-IR), powder x-ray diffraction (PXRD) and Brunauer-Emmett-Teller (BET) were employed to characterize the structure of ssCGP. ssCGP have regular hexahedron shape with edge length about 200-400 nm. Excellent ability of drug adsorption was achieved by using doxorubicin (DOX) as a model drug. The GSH triggered drug release of ssCGP was observed both in GSH contained solutions and intracellular environments. ssCGP have been demonstrated as a biocompatible porous nanocarrier, particular for intracellular drug delivery.

A Privacy-Preserving Multi-Task Learning Framework for Face Detection, Landmark Localization, Pose Estimation, and Gender Recognition.

Recently, multi-task learning (MTL) has been extensively studied for various face processing tasks, including face detection, landmark localization, pose estimation, and gender recognition. This approach endeavors to train a better model by exploiting the synergy among the related tasks. However, the raw face dataset used for training often contains sensitive and private information, which can be maliciously recovered by carefully analyzing the model and outputs. To address this problem, we propose a novel privacy-preserving multi-task learning approach that utilizes the differential private stochastic gradient descent algorithm to optimize the end-to-end multi-task model and weighs the loss functions of multiple tasks to improve learning efficiency and prediction accuracy. Specifically, calibrated noise is added to the gradient of loss functions to preserve the privacy of the training data during model training. Furthermore, we exploit the homoscedastic uncertainty to balance different learning tasks. The experiments demonstrate that the proposed approach yields differential privacy guarantees without decreasing the accuracy of HyperFace under a desirable privacy budget.

ATP Aptamer-Modified Quantum Dots with Reduced Glutathione/Adenosine Triphosphate Dual Response Features as a Potential Probe for Intracellular Drug Delivery Monitoring of Vesicular Nanocarriers.

Nanoparticles have great promise in drug delivery, but their functional mechanisms are very complicated. Monitoring the payloads or carriers by conventional labeling strategies may result in an inaccurate perception of the effectiveness of nano drug delivery systems (NDDSs). A GSH/ATP dual-responsive fluorescence enhancement probe was developed by manipulating the electron transfer pathways of surface-modified quantum dots (QDs). Because the intracellular concentrations of GSH and ATP are one hundred times greater than those in the extracellular environment, the intracellular drug release process could be observed by the fluorescence signal of this probe after it is loaded into NDDSs as drug simulants. As a proof-of-concept investigation, the intracellular drug release behaviors of classical liposomes were studied by loading this probe, and the observed results strongly support the known drug delivery mechanism of these systems. Although more studies are needed to investigate the in vivo performance of the probe, this study may encourage further investigations of other intracellular environment-responsive smart probes for deciphering the in vivo fate of NDDSs.