Correction: Yang et al. Construction and Evaluation of Chitosan-Based Nanoparticles for Oral Administration of Exenatide in Type 2 Diabetic Rats. Polymers 2022, 14, 2181.

The authors wish to make the following corrections to this paper [...].

Optical determination of layered-materials InSe thickness via RGB contrast method and regression analysis.

Indium selenide (InSe) features intriguing thickness-dependent optoelectronic properties, and a simple, and precise way to identify the thickness is essential for the rapid development of InSe research. Here, a red, green, and blue (RGB) color contrast method with regression analysis for quantitative correlation of three optical contrasts from RGB channels with the InSe thickness (1-35 nm), is demonstrated. The lower accuracy of the thickness identification obtained from the individual channels was discussed. Moreover, the effective refractive indices in the three RGB regions can be extracted from the Fresnel equation and numerical analysis by finding the best fit to the experimental optical contrast. After further consideration of the wavelength-dependent refractive indices, the slope of the regression line between the estimated thickness and that obtained from the atomic force microscope was improved from 1.59 ± 0.05 to 0.97 ± 0.02. The complex refractive index spectra of InSe (1-10 layers) generated fromab initionumerical calculation results were also adopted to identify the InSe thickness. Compared to dispersion, the evolution of the band structure had less effect on thickness identification. This work could be extended to other layered materials, facilitate the thickness-dependent study of layered materials, and expedite the realization of their practical applications.

Operando photoelectron spectroscopy analysis of graphene field-effect transistors.

In this study, operando photoelectron spectroscopy was used to characterize the performance of graphene field-effect transistors under working conditions. By sweeping the back-gate voltages, the carrier concentration of the graphene channel on the 150 nm Si3N4/Si substrate was tuned. From the C1s core level spectra acquired under the application of different gate voltages, the binding energy shifts caused by electric-field effects were obtained and analyzed. Together with the C1s peak shape information and the photoluminescence spectrum of the Si3N4/Si substrate, the presence of local potential across the x-ray beam spot associated with defects and gate leakage current in amorphous Si3N4was identified. The presence of defects in Si3N4/Si substrate could not only screen the partial electric field generated by the back gate but also serve as long-range scattering centers to the carriers, thus affecting charge transport in the graphene channel. Our findings will help further investigate the dielectric/graphene interface properties and accelerate the utilization of graphene in real device applications.

Construction and Evaluation of Chitosan-Based Nanoparticles for Oral Administration of Exenatide in Type 2 Diabetic Rats.

Oral delivery of therapeutic peptides has been a daunting challenge due to poor transport across the tight junctions and susceptibility to enzymatic degradation in the gastrointestinal tract. Numerous advancement in nanomedicine has been made for the effective delivery of protein and peptide. Owing to the superior performance of chitosan in opening intercellular tight junctions of epithelium and excellent mucoadhesive properties, chitosan-based nanocarriers have recently garnered considerable attention, which was formulated in this paper to orally deliver the GLP-1 drug (Exenatide). Against this backdrop, we used chitosan (CS) polymers to encapsulate the exenatide, sodium tripolyphosphate (TPP) as the cross-linking agent and coated the exterior with sodium alginate (ALG) to impart the stability in an acidic environment. The chitosan/alginate nanoparticles (CS-TPP-ALG) functioned as a protective exenatide carrier, realized efficient cellular uptake and controlled release, leading to a steady hypoglycemic effect and a good oral bioavailability in vivo. Trimethyl chitosan (TMC), a chitosan derivative with stronger positive electrical properties was additionally selected as a substitute for chitosan to construct the TMC-TPP-ALG nanoparticle, and its oral peptide delivery capacity was explored in terms of both characterization and pharmacodynamics studies. Overall, our study demonstrated that functional chitosan/alginate nanoparticles can protect proteins from enzymatic degradation and enhance oral absorption, which presents important research value and application prospects.

Formulation and Evaluation of Chitosan/NaCl/Maltodextrin Microparticles as a Saltiness Enhancer: Study on the Optimization of Excipients for the Spray-Drying Process.

Spray-dried chitosan/NaCl/maltodextrin microparticles have the potential to be used to enhance saltiness; however, its notable hygroscopicity results in handling and storage problems, thus limiting its application. In the present study, we attempted to introduce maltodextrin, microcrystalline cellulose (MCC), and waxy starch (WS) as excipients into the spray drying formulation of microparticles to reduce the cohesiveness and caking behavior and improve the yield simultaneously by ameliorating the moisture absorption tendency. The prepared microparticles showed a spherical appearance and had particle sizes ranging from 6.29 to 7.64 µm, while the sizes of the NaCl crystals embedded in the microparticles were 0.36 to 1.24 µm. The crystalline reflections of WS and MCC were retained in the microparticles after the spray-drying process. The handling properties were assessed to be acceptable. The formulation with only maltodextrin as the excipient showed a high moisture absorption rate of 2.83 g/100 g·h and a caking strength of 3.27 kg. The addition of MCC and WS significantly reduced the hygroscopic rate and caking strength. The spray-dried products provided better saltiness perception than native NaCl; as such, they may be promising for seasoning dry food products to achieve sodium intake reduction in the food industry.

Isotypes of autoantibodies against novel differential 4-hydroxy-2-nonenal-modified peptide adducts in serum is associated with rheumatoid arthritis in Taiwanese women.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients. METHODS: Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Four novel differential HNE-modified peptide adducts, complement factor H (CFAH)1211-1230, haptoglobin (HPT)78-108, immunoglobulin (Ig) kappa chain C region (IGKC)2-19, and prothrombin (THRB)328-345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546) from RA patients vs. HCs. Further, we determined serum protein levels of CFAH, HPT, IGKC and THRB, HNE-protein adducts, and autoantibodies against unmodified and HNE-modified peptides. Significant correlations and odds ratios (ORs) were calculated. RESULTS: Levels of HPT in RA patients were greatly higher than the levels in HCs. Levels of HNE-protein adducts and autoantibodies in RA patients were significantly greater than those of HCs. IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgM anti-IGKC2-19 HNE may be considered as diagnostic biomarkers for RA. Importantly, elevated levels of IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 were positively correlated with the disease activity score in 28 joints for C-reactive protein (DAS28-CRP). Further, the ORs of RA development through IgM anti-HPT78-108 HNE (OR 5.235, p < 0.001), IgM anti-IGKC2-19 (OR 12.655, p < 0.001), and IgG anti-THRB328-345 (OR 5.761, p < 0.001) showed an increased risk. Lastly, we incorporated three machine learning models to differentiate RA from HC and OA, and performed feature selection to determine discriminative features. Experimental results showed that our proposed method achieved an area under the receiver operating characteristic curve of 0.92, which demonstrated that our selected autoantibodies combined with machine learning can efficiently detect RA. CONCLUSIONS: This study discovered that some IgG- and IgM-NAAs and anti-HNE M-NAAs may be correlated with inflammation and disease activity in RA. Moreover, our findings suggested that IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 may play heavy roles in RA development.

Engineering an Indium Selenide van der Waals Interface for Multilevel Charge Storage.

As the continuous miniaturization of floating-gate transistors approaches a physical limit, new innovations in device architectures, working principles, and device materials are in high demand. This study demonstrated a nonvolatile memory structure with multilevel data storage that features a van der Waals gate architecture made up of a partially oxidized surface layer/indium selenide (InSe) van der Waals interface. The key functionality of this proof-of-concept device is provided through the generation of charge-trapping sites via an indirect oxygen plasma treatment on the InSe surface layer. In contrast to floating-gate nonvolatile memory, these sites have the ability to retain charge without the help of a gate dielectric. Together with the layered structure, the surface layer with charge-trapping sites facilitates continual electrostatic doping in the underlying InSe layers. The van der Waals gating effect is further supported by trapped charge-induced core-level energy shifts and relative work function variations obtained from operando scanning X-ray photoelectron spectroscopy and Kelvin probe microscopy, respectively. On modulating the amount of electric field-induced trapped electrons by the electrostatic gate potential, eight distinct storage states remained over 3000 s. Moreover, the device exhibits a high current switching ratio of 106 within 11 cycles. The demonstrated characteristics suggest that the engineering of an InSe interface has potential applications for nonvolatile memory.

Mitochondrial targeted doxorubicin derivatives delivered by ROS-responsive nanocarriers to breast tumor for overcoming of multidrug resistance.

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by 1H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

Intracellular Restructured Reduced Glutathione-Responsive Peptide Nanofibers for Synergetic Tumor Chemotherapy.

Self-assembled peptide nanofibers have been widely studied in cancer nanotherapeutics with their excellent biocompatibility and low toxicity of degradation products, showing the significant potential in inhibiting tumor progression. However, poor solubility prevents direct intravenous administration of nanofibers. Although water-soluble peptide precursors have been formed via the method of phosphorylation for intravenous administration, their opportunities for broad in vivo application are limited by the weak capacity of encapsulating drugs. Herein, we designed a novel restructured reduced glutathione (GSH)-responsive drug delivery system encapsulating doxorubicin for systemic administration, which achieved the intracellular restructuration from three-dimensional micelles into one-dimensional nanofibers. After a long blood circulation, micelles endocytosed by tumor cells could degrade in response to high GSH levels, achieving more release and accumulation of doxorubicin at desired sites. Further, the synergistic chemotherapy effects of self-assembled nanofibers were confirmed in both in vitro and in vivo experiments.

Doxorubicin derivative loaded acetal-PEG-PCCL micelles for overcoming multidrug resistance in MCF-7/ADR cells.

Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor. Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR. Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo. Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs. Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.

Dipolar magnetism in assembled Co nanoparticles on graphene.

The magnetic properties of the assembled Co nanoparticles on graphene were studied using X-ray magnetic circular dichroism (XMCD), magneto-optical Kerr effects, and a modeling simulation. We demonstrate that the superparamagnetic nanoparticles reveal a ferromagnetic phase when they are assembled on graphene. The moderate increase of the XMCD asymmetry and magnetization with coverage for this assembly indicates a dipolar-mediated magnetism, which is further verified by a model simulation considering the dipolar interaction between neighboring nanoparticles. Furthermore, C K-edge spectra reveal visible dichroism at the π* state of graphene, which indicates the existence of a spin-polarized interface state, while the assembled Co nanoparticles reveal a ferromagnetic phase. These results suggest an efficient route to stabilize the ferromagnetic phase of nanostructures on graphene by tailoring dipolar interactions, which is essential to realize a higher efficiency of spin injection in graphene-based spintronics.

Isotypes of autoantibodies against differentially expressed novel malondialdehyde-modified peptide adducts in serum of Taiwanese women with rheumatoid arthritis.

This study identified and validated four differentially expressed novel malondialdehyde (MDA)-modified peptide adducts and evaluated autoantibodies against native and MDA-modified peptides among Taiwanese women patients with rheumatoid arthritis (RA), osteoarthritis (OA) and healthy controls (HCs). Ig kappa chain C region76-99, alpha-1-antitrypsin284-298, alpha-2-macroglobulin824-841, and apolipoprotein B-1004022-4040 exhibiting 2-fold differences in relative modification ratios were identified by concanavalin A (Con A) affinity chromatography, 1D SDS-PAGE, in-gel digestion, nano-LC/MS/MS and nano-LC/MS using pooled serum-derived Con A-captured proteins from 9 RA and 9 age-matched HCs. Furthermore, the levels of proteins, serum MDA, and MDA-modified protein adducts were further validated against individual serum from 20 RA and 20 HCs, and autoantibodies against native and their MDA-modified peptides used 45 RA, 30 OA and 45 HCs. Levels of serum MDA and MDA-modified protein adducts were significantly higher in RA than HCs but protein levels were not significantly different. Serum Igs G and M against MDA-modified peptides showed better diagnostic performance in differentiating among patients with RA, OA and HCs, with an area under the receiver operating characteristic curve of 0.96-0.98, sensitivity of 88.9%-97.8%, and specificity of 88.9%-100%. Autoantibodies against MDA-modified epitopes become useful clinical biomarkers for RA. BIOLOGICAL SIGNIFICANCE: By using a label-free relative quantitative proteomic analysis of concanavalin A (Con A)-bound serum samples, the current study discovered and validated malondialdehyde (MDA)-modified peptide adducts as novel biomarkers for differentiating between rheumatoid arthritis (RA) patients and healthy controls (HCs). In addition, the serum levels of MDA, proteins, and MDA-modified protein adducts as well as the MDA modification of proteins were determined. Isotypes of autoantibodies against MDA-modified peptide adducts can be used as serological biomarkers for further discriminating among RA patients, osteoarthritis patients and HCs. This strategy can become the basis for identifying potential diagnostic and pathological biomarkers for RA.

Low Levels of IgG Recognizing the α-1-Antitrypsin Peptide and Its Association with Taiwanese Women with Primary Sjögren's Syndrome.

The aim of this study was to examine oxidative stress and low level of α-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, α-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Our study suggests that elevated HNE-protein adduct, oxidative stress, level (odds ratio (OR) 4.877, p = 0.003), lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

High photosensitivity and broad spectral response of multi-layered germanium sulfide transistors.

In this paper, we report the optoelectronic properties of multi-layered GeS nanosheet (∼28 nm thick)-based field-effect transistors (called GeS-FETs). The multi-layered GeS-FETs exhibit remarkably high photoresponsivity of Rλ ∼ 206 A W(-1) under 1.5 µW cm(-2) illumination at λ = 633 nm, Vg = 0 V, and Vds = 10 V. The obtained Rλ ∼ 206 A W(-1) is excellent as compared with a GeS nanoribbon-based and the other family members of group IV-VI-based photodetectors in the layered-materials realm, such as GeSe and SnS2. The gate-dependent photoresponsivity of GeS-FETs was further measured to be able to reach Rλ ∼ 655 A W(-1) operated at Vg = -80 V. Moreover, the multi-layered GeS photodetector holds high external quantum efficiency (EQE ∼ 4.0 × 10(4)%) and specific detectivity (D* ∼ 2.35 × 10(13) Jones). The measured D* is comparable to those of the advanced commercial Si- and InGaAs-based photodiodes. The GeS photodetector also shows an excellent long-term photoswitching stability over a long period of operation (>1 h). These extraordinary properties of high photocurrent generation, broad spectral range, and long-term stability make the GeS-FET photodetector a highly qualified candidate for future optoelectronic applications.

High performance and bendable few-layered InSe photodetectors with broad spectral response.

Two-dimensional crystals with a wealth of exotic dimensional-dependent properties are promising candidates for next-generation ultrathin and flexible optoelectronic devices. For the first time, we demonstrate that few-layered InSe photodetectors, fabricated on both a rigid SiO2/Si substrate and a flexible polyethylene terephthalate (PET) film, are capable of conducting broadband photodetection from the visible to near-infrared region (450-785 nm) with high photoresponsivities of up to 12.3 AW(-1) at 450 nm (on SiO2/Si) and 3.9 AW(-1) at 633 nm (on PET). These photoresponsivities are superior to those of other recently reported two-dimensional (2D) crystal-based (graphene, MoS2, GaS, and GaSe) photodetectors. The InSe devices fabricated on rigid SiO2/Si substrates possess a response time of ∼50 ms and exhibit long-term stability in photoswitching. These InSe devices can also operate on a flexible substrate with or without bending and reveal comparable performance to those devices on SiO2/Si. With these excellent optoelectronic merits, we envision that the nanoscale InSe layers will not only find applications in flexible optoelectronics but also act as an active component to configure versatile 2D heterostructure devices.

Cyclometalated iridium(III)-ß-carboline complexes as potent autophagy-inducing agents.

Two cyclometalated Ir(III)-ß-carboline complexes were identified as potent inducers of autophagic cell death. Autophagy induced by these complexes is ROS-mediated and caspase-independent.

Metallomics insights into the programmed cell death induced by metal-based anticancer compounds.

Since the discovery of cisplatin more than 40 years ago, enormous research efforts have been dedicated to developing metal-based anticancer agents and to elucidating the mechanisms involved in the action of these compounds. Abnormal metabolism and the evasion of apoptosis are important hallmarks of malignant transformation, and the induction of apoptotic cell death has been considered to be a main pathway by which cytotoxic metal complexes combat cancer. However, many cancers have cellular defects involving the apoptotic machinery, which results in an acquired resistance to apoptotic cell death and therefore reduced chemotherapeutic effectiveness. Over the past decade, it has been revealed that a growing number of cell death pathways induced by metal complexes are not dependent on apoptosis. Metal complexes specifically triggering these alternative cell death pathways have been identified and explored as novel cancer treatment options. In this review, we discuss recent examples of metallomics studies on the different types of cell death induced by metal-based anticancer drugs, especially on the three major forms of programmed cell death (PCD) in mammalian cells: apoptosis, autophagy and regulated necrosis, also called necroptosis.

Chemical vapor deposition synthesis and Raman spectroscopic characterization of large-area graphene sheets.

We present a chemical vapor deposition (CVD) method to catalytically synthesize large-area, transferless, single- to few-layer graphene sheets using hexamethyldisilazane (HMDS) on a SiO2/Si substrate as a carbon source and thermally evaporated alternating Ni/Cu/Ni layers as a catalyst. The as-synthesized graphene films were characterized by Raman spectroscopic imaging to identify single- to few-layer sheets. This HMDS-derived graphene layer is continuous over the entire growth substrate, and single- to trilayer mixed sheets can be up to 30 µm in the lateral dimension. With the synthetic CVD method proposed here, graphene can be grown into tailored shapes directly on a SiO2/Si surface through vapor priming of HMDS onto predefined photolithographic patterns. The transparent and conductive HMDS-derived graphene exhibits its potential for widespread electronic and opto-electronic applications.

Sunlight-activated long-persistent luminescence in the near-infrared from Cr(3+)-doped zinc gallogermanates.

Visible-light persistent phosphors are being widely used as self-sustained night-vision materials because of their sufficiently strong and long afterglow (>10 h) and their ability to be excited by sunlight as well as room light. In contrast, persistent phosphors for near-infrared (NIR) wavelengths are lacking. Here we report a series of Cr(3+)-doped zinc gallogermanate NIR persistent phosphors that exhibit strong emission at 650-1,000 nm, extending beyond the typical 690-750 nm, and with a super-long afterglow of more than 360 h. These new NIR persistent phosphors are all-weather materials that can be rapidly, effectively and repeatedly charged by natural sunlight in almost all kinds of outdoor environment. Seconds to minutes of sunlight activation can result in more than two weeks of persistent NIR light emission. This new series of NIR persistent materials have potential applications in night-vision surveillance, solar energy utilization and in vivo bio-imaging.