Unique electronic and optical properties of stacking-modulated bilayer graphene under external magnetic fields.

This study delves into the magneto-electronic and magneto-optical properties of stacking-modulated bilayer graphene. By manipulating domain walls (DWs) across AB-BA domains periodically, we unveil oscillatory Landau subbands and the associated optical excitations. The DWs act as periodic potentials, yielding fascinating 1D spectral features. Our exploration reveals 1D phenomena localized to Bernal stacking, DW regions, and stacking boundaries, highlighting the intriguing formation of Landau state quantization influenced by the commensuration between the magnetic length and the system. The stable quantized localization within different regions leads to the emergence of unconventional quantized subbands. This study provides valuable insights into the essential properties of stacking-modulated bilayer graphene.

Photoreactive Mercury-Containing Metallosupramolecular Nanoparticles with Tailorable Properties That Promote Enhanced Cellular Uptake for Effective Cancer Chemotherapy.

A new potential route to enhance the efficiency of supramolecular polymers for cancer chemotherapy was successfully demonstrated by employing a photosensitive metallosupramolecular polymer (Hg-BU-PPG) containing an oligomeric poly(propylene glycol) backbone and highly sensitive pH-responsive uracil-mercury-uracil (U-Hg-U) bridges. This route holds great promise as a multifunctional bioactive nano-object for development of more efficient and safer cancer chemotherapy. Owing to the formation of uracil photodimers induced by ultraviolet irradiation, Hg-BU-PPG can form a photo-cross-linked structure and spontaneously forms spherical nanoparticles in aqueous solution. The irradiated nanoparticles possess many unique characteristics, such as unique fluorescence behavior, highly sensitive pH-responsiveness, and intriguing phase transition behavior in aqueous solution as well as high structural stability and antihemolytic activity in biological media. More importantly, a series of cellular studies clearly confirmed that the U-Hg-U photo-cross-links in the irradiated nanoparticles substantially enhance their selective cellular uptake by cancer cells via macropinocytosis and the mercury-loaded nanoparticles subsequently induce higher levels of cytotoxicity in cancer cells (compared to non-irradiated nanoparticles), without harming normal cells. These results are mainly attributed to cancer cell microenvironment-triggered release of mercury ions from disassembled nanoparticles, which rapidly induce massive levels of apoptosis in cancer cells. Overall, the pH-sensitive U-Hg-U photo-cross-links within this newly discovered supramolecular system are an indispensable factor that offers a potential path to remarkably enhance the selective therapeutic effects of functional nanoparticles toward cancer cells.

Conductive Supramolecular Polymer Nanocomposites with Tunable Properties to Manipulate Cell Growth and Functions.

Synthetic bioactive nanocomposites show great promise in biomedicine for use in tissue growth, wound healing and the potential for bioengineered skin substitutes. Hydrogen-bonded supramolecular polymers (3A-PCL) can be combined with graphite crystals to form graphite/3A-PCL composites with tunable physical properties. When used as a bioactive substrate for cell culture, graphite/3A-PCL composites have an extremely low cytotoxic activity on normal cells and a high structural stability in a medium with red blood cells. A series of in vitro studies demonstrated that the resulting composite substrates can efficiently interact with cell surfaces to promote the adhesion, migration, and proliferation of adherent cells, as well as rapid wound healing ability at the damaged cellular surface. Importantly, placing these substrates under an indirect current electric field at only 0.1 V leads to a marked acceleration in cell growth, a significant increase in total cell numbers, and a remarkable alteration in cell morphology. These results reveal a newly created system with great potential to provide an efficient route for the development of multifunctional bioactive substrates with unique electro-responsiveness to manipulate cell growth and functions.

Yohimbine, an α2-Adrenoceptor Antagonist, Suppresses PDGF-BB-Stimulated Vascular Smooth Muscle Cell Proliferation by Downregulating the PLCγ1 Signaling Pathway.

Yohimbine (YOH) has antiproliferative effects against breast cancer and pancreatic cancer; however, its effects on vascular proliferative diseases such as atherosclerosis remain unknown. Accordingly, we investigated the inhibitory mechanisms of YOH in vascular smooth muscle cells (VSMCs) stimulated by platelet-derived growth factor (PDGF)-BB, a major mitogenic factor in vascular diseases. YOH (5-20 µM) suppressed PDGF-BB-stimulated a mouse VSMC line (MOVAS-1 cell) proliferation without inducing cytotoxicity. YOH also exhibited antimigratory effects and downregulated matrix metalloproteinase-2 and -9 expression in PDGF-BB-stimulated MOVAS-1 cells. It also promoted cell cycle arrest in the initial gap/first gap phase by upregulating p27Kip1 and p53 expression and reducing cyclin-dependent kinase 2 and proliferating cell nuclear antigen expression. We noted phospholipase C-γ1 (PLCγ1) but not ERK1/2, AKT, or p38 kinase phosphorylation attenuation in YOH-modulated PDGF-BB-propagated signaling pathways in the MOVAS-1 cells. Furthermore, YOH still inhibited PDGF-BB-induced cell proliferation and PLCγ1 phosphorylation in MOVAS-1 cells with α2B-adrenergic receptor knockdown. YOH (5 and 10 mg/kg) substantially suppressed neointimal hyperplasia in mice subjected to CCA ligation for 21 days. Overall, our results reveal that YOH attenuates PDGF-BB-stimulated VSMC proliferation and migration by downregulating a α2B-adrenergic receptor-independent PLCγ1 pathway and reduces neointimal formation in vivo. Therefore, YOH has potential for repurposing for treating atherosclerosis and other vascular proliferative diseases.

Increased risk of pulmonary and extrapulmonary tuberculosis infection in patients with polycystic kidney disease: a nationwide population-based study with propensity score-matching analysis.

BACKGROUND: Polycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD. METHODS: A nationwide population-based cohort study was performed using Taiwan's National Health Insurance Research Database. We used patients' hospitalization files for the entire analysis during 2000-2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection. RESULTS: A total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51-2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46-4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29-2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69-4.30). CONCLUSIONS: Taken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.

Development of biotinylated and magnetic bead-immobilized enzymes for efficient glyco-engineering and isolation of antibodies.

The chemoenzymatic remodeled monoclonal antidodies with well-defined glycan structure at the Fc domain display improved biological activities, such as ADCC and ADCP, and are more likely to yield a better safety profile by eliminating the non-human glycans derived from CHO cell culture. We covalently immobilize wild type endoglycosidase S (EndoS), fucosidase, and EndoS2 mutant on magnetic beads through a linker to efficiently generate homogeneous antibody glycoforms without additional purification step to remove endoglycosidase and fucosidase. We also used the biotinylated wild type EndoS2 and EndoS2 mutant in combination with covalently immobilized fucosidase on magnetic beads to allow the sequential removal of endoglycosidases and fucosidase for efficient glyco-engineering and isolation of antibodies without purifying deglycosylated antibody intermediate. Notably, the relatively expensive fucosidase can be recovered to reduce the cost, and the strong affinity of streptavidin to biotin would complete the isolation of biotinylated enzymes. We used Trastuzumab as a model to demonstrate both approaches were reliable for the large-scale production and isolation of antibodies without the residual contamination of endoglycosidase to avoid deglycosylation over storage time.

Photosensitive Supramolecular Micelle-Mediated Cellular Uptake of Anticancer Drugs Enhances the Efficiency of Chemotherapy.

The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications.

Supramolecular Polymer Network-Mediated Self-Assembly of Semicrystalline Polymers with Excellent Crystalline Performance.

A novel application of supramolecular interactions within semicrystalline polymers, capable of self-assembling into supramolecular polymer networks via self-complementary multiple hydrogen-bonded complexes, is demonstrated for efficient construction of highly controlled self-organizing hierarchical structures to offer a direct, efficient nucleation pathway resulting in superior crystallization performance. Herein, a novel functionalized poly(ε-caprolactone) containing self-complementary sextuple hydrogen-bonded uracil-diamidopyridine (U-DPy) moieties is successfully developed and demonstrated excellent thermal and viscoelastic properties as well as high dynamic structural stability in the bulk state due to physical cross-linking created by reversible sextuple hydrogen bonding between U-DPy units. Due to the ability to vary the extent of the reversible network by tuning the U-DPy content, this newly developed material can be readily adjusted to obtain the desired crystalline products with specific characteristics. Importantly, incorporating only 0.1% U-DPy resulted in a polymer with a high crystallization rate constant, short crystallization half-time, and much more rapid crystallization kinetics than pristine PCL, indicating a low content of U-DPy moieties provides highly efficient nucleation sites that manipulate the nucleation and growth processes of polymer crystals to promote crystallization and chain alignment in bulk. This new system is suggested as a potential new route to substantially improve the performance of polymer crystallization.

Differential proteomics of monosodium urate crystals-induced inflammatory response in dissected murine air pouch membranes by iTRAQ technology.

The precipitation of monosodium urate crystals within joints triggers an acute inflammatory reaction that is the root cause of gout. The inflammation induced by the injection of MSU crystals into the murine air pouch for 1, 3, and 5 h was examined by iTRAQ-based proteomic profiling. The iTRAQ-labeled peptides were fractionated by SCX, basic-RP or solution-IEF, followed by LC-MS/MS analysis. A total of 951 proteins were quantified from the total combined fractions. Among them, 317 proteins exhibited a differential expression, compared to that of the controls at one time point or more. The majority of the differentially expressed proteins were found in the sample after a 5-h MSU treatment. Western blot revealed that the expression levels of cathelin-related antimicrobial peptide and S100A9 were positively correlated with the time-course treated with MSU. Further analysis of GeneGO pathway demonstrated that these differentially expressed proteins are primarily related to the immune-related complement system and the tricarboxylic acid cycle. Moreover, seven genes from the TCA cycle were found to be significantly downregulated at the transcriptional level and its correlation with gout and possible therapeutic applications are worth further investigation. Last, we found that pyruvate carboxylation could be potential targets for antigout treatment.

Immobilization of silver nanoparticles on exfoliated mica nanosheets to form highly conductive nanohybrid films.

Highly electrically conductive films were prepared by coating organic/inorganic nanohybrid solutions with a polymeric dispersant and exfoliated mica nanosheets (Mica) on which silver nanoparticles (AgNPs) had been dispersed in various components. Transmission electronic microscopy showed that the synthesized AgNPs had a narrow size distribution and a diameter of approximately 20 nm. Furthermore, a 60 µm thick film with a sheet resistance as low as 4.5 × 10(-2) Ω/sq could be prepared by controlling the heating temperature and by using AgNPs/POE-imide/Mica in a weight ratio of 20:20:1. During the heating process, the surface color of the hybrid film changed from dark golden to white, suggesting the accumulation of the AgNPs through surface migration and their melting to form an interconnected network. These nanohybrid films have potential for use in various electrically conductive devices.

Multimode Friedel oscillations in monolayer and bilayer graphene.

This study systematically explores the influence of charged impurities on static screening in monolayer graphene and extends the investigation to AA-stacked and AB-stacked bilayer graphene (BLG). Applying the random phase approximation (RPA), monolayer graphene displays unique beating Friedel oscillations (FOs) in inter-valley and intra-valley channels. Shifting to BLG, the study emphasizes layer-specific responses on each layer by considering self-consistent field interactions between layers. It also explores the derived multimode FOs, elucidating distinctions from monolayer behavior. In AA-stacked BLG, distinct metallic screening behaviors are revealed, uncovering unique oscillatory patterns in induced charge density, providing insights into static Coulomb scattering effects between two Dirac cones. The exploration extends to AB-stacked BLG, unveiling layer-specific responses of parabolic bands in multimode FOs with increasing Fermi energy. This comprehensive investigation, integrating RPA considerations, significantly advances our understanding of layer-dependent static screening in the broader context of FOs in graphene, providing valuable contributions to the field of condensed matter physics.

Flexible nanohybrid substrates utilizing gold nanocubes/nano mica platelets with 3D lightning-rod effect for highly efficient bacterial biosensors based on surface-enhanced Raman scattering.

In this study, gold nanocubes (AuNCs) were quickly synthesized using the seed-mediated growth method and reduced onto the surface of two-dimensional (2D) delaminated nano mica platelets (NMPs), enabling the development of AuNCs/NMPs nanohybrids with a 3D lightning-rod effect. First, the growth-solution amount can be changed to easily adjust the AuNCs average-particle size within a range of 30-70 nm. The use of the cationic surfactant cetyltrimethylammonium chloride as a protective agent allowed the surface of AuNCs and nanohybrids to be positively charged. Positively charged nanohybrid surfaces presented a good adsorption effect for detecting molecules with negative charges on the surface. Additionally, the NMP surfaces were rich in ionic charges and provided a large specific surface area for stabilizing the growth of AuNCs. Delaminated AuNCs/NMPs nanohybrids can generate a 3D hotspot effect through self-assembly to enhance the Raman signal. Surface-enhanced Raman scattering (SERS) is highly sensitive in detecting adenine biomolecules. Its limit of detection (LOD) and Raman enhancement factor reached 10-9 M and 3.6 × 108, respectively. Excellent reproducibility was obtained owing to the relatively regular arrangement of AuNC particles, and the relative standard deviation (RSD) was 10.7%. Finally, the surface of NMPs was modified by adding the hydrophilic poly(oxyethylene)-diamine (POE2000) and amphiphilic PIB-POE-PIB copolymer at different weight ratios. The adjustment of the surface hydrophilicity and hydrophobicity of AuNCs/NMPs nanohybrids led to better adsorption and selectivity for bacteria. AuNCs/POE/NMPs and AuNCs/PIB-POE-PIB/NMPs were further applied to the SERS detection of hydrophilic Staphylococcus aureus and hydrophobic Escherichia coli, respectively. The SERS-detection results suggest that the LOD of hydrophilic Staphylococcus aureus and hydrophobic Escherichia coli reached 92 CFU mL-1 and 1.6 × 102 CFU mL-1, respectively. The AuNCs/POE/NMPs and AuNCs/PIB-POE-PIB/NMPs nanohybrids had different hydrophilic-hydrophobic affinities, which greatly improved the selectivity and sensitivity for detecting bacteria with different hydrophilicity and hydrophobicity. Therefore, fast, highly selective, and highly sensitive SERS biological-detection results were obtained.

Application of Nanohybrid Substrates with Layer-by-Layer Self-Assembling Properties to High-Sensitivity Surface-Enhanced Raman Scattering Detection.

The present study was conducted to prepare and investigate large-area, high-sensitivity surface-enhanced Raman scattering (SERS) substrates. Organic/inorganic nanohybrid dispersants consisting of an amphiphilic triblock copolymer (hereafter referred to simply as "copolymer") and graphene oxide (GO) were used to stabilize the growth and size of gold nanoparticles (AuNPs). Ion-dipole forces were present between the AuNPs and copolymer dispersants, while the hydrogen bonds between GO and the copolymer prevented the aggregation of GO, thereby stabilizing the AuNP/GO nanohybrids. Transmission electron microscopy (TEM) revealed that the AuNPs had particle sizes of 25-35 nm and a relatively uniform size distribution. The AuNP/GO nanohybrids were deposited onto the glass substrate by using the solution drop-casting method and employed for SERS detection. The self-assembling properties of two-dimensional sheet-like GO led to a regular lamellar arrangement of AuNP/GO nanohybrids, which could be used for the preparation of large-area SERS substrates. Following removal of the copolymer by annealing at 300 °C for 2 h, measurements were obtained under scanning electron microscopy. The results confirmed that 2D GO nanosheets were capable of stabilizing AuNPs, with the final size reaching approximately 40 nm. These AuNPs were adsorbed on both sides of the GO nanosheets. Because the GO nanosheets were merely 5 nm-thick, a good three-dimensional hot-junction effect was generated along the z-axis of the AuNPs. Lastly, the prepared material was used for the SERS detection of rhodamine 6G (R6G), a commonly used highly fluorescent dye. An enhancement factor (EF) of up to 3.5 × 106 was achieved, and the limit of detection was approximately 10-10 M. Detection limits of 10-10 M and < 10-10 M were also observed with the detection of Direct Blue 200 and the biological molecule adenine. It is therefore evident that AuNP/copolymer/GO nanohybrids are large-area flexible SERS substrates that hold great potential in environmental monitoring and biological system detection applications.

Risk of Diabetic Retinopathy in Patients With Type 2 Diabetes After SGLT-2 Inhibitors: A Nationwide Population Cohort Study.

Diabetic retinopathy (DR) accounts for 80% of cases of vision loss in patients with type 2 diabetes mellitus (T2DM). Interventional treatments are only indicated in advanced DR and are ineffective in some patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are used to attenuate T2DM-associated cardiovascular complications. We conducted the cohort study to investigate the effect of SGLT2is on DR development. Data (May 2016-December 2018) obtained from the Taiwan National Health Insurance Research Database were analyzed in this nationwide retrospective cohort study. After propensity score matching, a total of 31,764 patients receiving SGLT2is and another 31,764 patients receiving dipeptidyl peptidase 4 inhibitors (DPP4is) were included in this study. Multiple Cox proportional-hazards regression models were used to evaluate DR risk. Overall DR incidence among SGLT2i or DPP4i users was 10.9 or 15.6 per 10,000 patient-years, respectively. After covariate adjustment, DR (both early and late stage) risk was substantially lower in SGLT2i users (adjusted hazard ratio: 0.68, 95% confidence interval: 0.6-0.78) than in DPP4i users. DR risk appears to be considerably lower in SGLT2i users than in DPP4i users. Glycemic control measurement with HbA1C level was unavailable in this claim database.

Differential proteomic analysis of cancer stem cell properties in hepatocellular carcinomas by isobaric tag labeling and mass spectrometry.

Malignant tumors are relatively resistant to treatment due to their heterogeneous nature, drug resistance, and tendency for metastasis. Recent studies suggest that a subpopulation of cancer cells is responsible for the malignant outcomes. These cells are considered as cancer stem cells (CSC). Although a number of molecules have been identified in different cancer cells as markers for cancer stem cells, no promising markers are currently available for hepatocellular carcinoma cells. In this study, two clones of Hep3B cell lines were functionally characterized as control or CSC-like cells, based on properties including spheroid formation, drug resistance, and tumor initiation. Furthermore, their protein expression profiles were investigated by isobaric tags for relative and absolute quantitation (iTRAQ), and a total of 1,127 proteins were identified and quantified from the combined fractions; 50 proteins exhibited at least 2-fold differences between these two clones. These 50 proteins were analyzed by GeneGo and were found to be associated with liver neoplasms, hepatocellular carcinoma (HCC), and liver diseases. They were also components of metabolic pathways, immune responses, and cytoskeleton remodeling. Among these proteins, the expressions of S100P, S100A14, and vimentin were verified in several HCC cell lines, and their expressions were correlated with tumorigenicity in HCC cell lines. The functional significance of vimentin and S100A14 were also investigated and verified.

Highly photoactive novel NiS/BiOI nanocomposite photocatalyst towards efficient visible light organic pollutant degradation and carcinogenetic Cr (VI) reduction for environmental remediation.

Heterojunction engineering in catalyst structures is a promising approach for solving the main restriction of the narrow photoabsorption range and quick recombination of photogenerated charge carriers in the photocatalysts. Herein, a simple, eco-friendly, non-toxic, and novel Z-scheme heterojunction of nanoflower-like NiS/BiOI was systematically designed using the low-temperature solvothermal and precipitation methods. The physicochemical and photo-electrochemical properties of the as-synthesized nanomaterials were characterized using XRD, FESEM, FT-IR, XPS, BET, UV-vis, PL, and EIS. NiS/BiOI nanomaterials exhibited a wide photoabsorption range (200-1000 nm), a narrow bandgap energy (1.76 eV), a large surface area (35.82 m2 g-1), and a low charge carrier recombination rate because of the synergistic effects of the NiS and BiOI photocatalysts, which could be the basis for superior photocatalytic efficiency. Particularly, the optimal 40% NiS/BiOI nanocomposite exhibited better stability and efficiency than the pure NiS and BiOI. The maximum degradation efficiency of rhodamine B (RhB) was 99.8% after 200 min, tetracycline (TC) was 96.3% after 140 min, and the photoreduction of Cr(VI) was 92.8% after 180 min rather than the pure NiS and BiOI under visible light irradiation. The constant rate (k) of RhB was approximately 10 and 4, TC was 12 and 4, and Cr(VI) was 10 and 8 times that of pristine NiS and BiOI, respectively. Radical trapping experiments and Tauc plot analysis proposed the design of the plausible Z-scheme reaction mechanism between NiS and BiOI, which has a crucial role in the rate of transportation and separation of electron/hole pairs. This investigation provides a venue for the design of a photoactive NiS-based nanocomposite for environmental remediation.

Photocurable Carbon Nanotube/Polymer Nanocomposite for the 3D Printing of Flexible Capacitive Pressure Sensors.

A photocurable resin/carbon nanotube (CNT) nanocomposite was fabricated from aligned CNTs in an acrylic matrix. The conductivity of the nanocomposite increased rapidly and then stabilized when the CNT content was increased up to and beyond the percolation threshold. Various structures were created using a digital light processing (DLP) 3D printer. Various polymeric dispersants (SMA-amide) were designed and synthesized to improve the CNT dispersion and prevent aggregation. The benzene rings and lone electron pairs on the dispersant interacted with aromatic groups on the CNTs, causing the former to wrap around the latter. This created steric hindrance, thereby stabilizing and dispersing the CNTs in the solvent. CNT/polymer nanocomposites were created by combining the dispersant, CNTs, and a photocurable resin. The CNT content of the nanocomposite and the 3D printing parameters were tuned to optimize the conductivity and printing quality. A touch-based human interface device (HID) that utilizes the intrinsic conductivity of the nanocomposite and reliably detects touch signals was fabricated, enabling the free design of sensors of various styles and shapes using a low-cost 3D printer. The production of sensors without complex circuitry was achieved, enabling novel innovations.

Denosumab treatment and infection risks in patients with osteoporosis: propensity score matching analysis of a national-wide population-based cohort study.

Introduction: Denosumab demonstrates efficacy in reducing the incidence of hip, vertebral, and nonvertebral fractures in postmenopausal women with osteoporosis. We present a population-based national cohort study to evaluate the infection risks in patients with osteoporosis after long-term denosumab therapy. Methods: We used the Taiwan National Health Insurance Research Database (NHIRD) to identify patients with osteoporosis. The case cohort comprised patients treated with denosumab. Propensity score (PS) matching was used to select denosumab nonusers for the control cohort. The study period was between August 2011 and December 2017. Our study comprised 30,106 pairs of case and control patients. Results: Patients receiving denosumab therapy had high risks of the following infections: pneumonia and influenza (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI]: 1.27 -1.39), urinary tract infection (aHR: 1.36; 95% CI:1.32 -1.40), tuberculosis (aHR: 1.60; 95% CI: 1.36 -1.87), fungal infection (aHR: 1.67; 95% CI:1.46 -1.90), candidiasis (aHR: 1.68; 95% CI: 1.47 -1.93), herpes zoster infection (aHR: 1.27; 95% CI: 1.19 -1.35), sepsis (aHR: 1.54; 95% CI:1.43 -1.66), and death (aHR: 1.26; 95% CI: 1.20 -1.32). However, the longer the duration of denosumab treatment, the lower the risk patients had of developing infections. Discussion: Denosumab therapy is associated with a higher infection risk at the early periods of treatment. Nevertheless, the risk attenuates significantly after the 2nd year of therapy. Clinicians should closely monitor infection status in patients with osteoporosis during the initial stages of denosumab therapy.

Evaluation of peptide fractionation strategies used in proteome analysis.

Peptide fractionation is extremely important for the comprehensive analysis of complex protein mixtures. Although a few comparisons of the relative separation efficiencies of 2-D methodologies using complex biological samples have appeared, a systematic evaluation was conducted in this study. Four different fractionation methods, namely strong-cation exchange, hydrophilic interaction chromatography, alkaline-RP and solution isoelectric focusing, which can be used prior to LC-MS/MS analysis, were compared. Strong-cation exchange × RPLC was used after desalting the sample; significantly more proteins were identified, compared with the nondesalted sample (1990 and 1375). We also found that the use of a combination of analytical methods resulted in a dramatic increase in the number of unique peptides that could be identified, compared with only a small increase in protein levels. The increased number of distinct peptides that can be identified is especially beneficial, not only for unequivocally identifying proteins but also for proteomic studies involving posttranslational modifications and peptide-based quantification approaches using stable isotope labeling. The identification and quantification of more peptides per protein provide valuable information that improves both the quantification of, and confidence of protein identification.

Au Nanorods on Carbon-Based Nanomaterials as Nanohybrid Substrates for High-Efficiency Dynamic Surface-Enhanced Raman Scattering.

Gold nanorods (AuNRs) with different aspect ratios were prepared by the seed-mediated growth method and combined with three carbon-based nanomaterials of multiple dimensions (i.e., zero-dimensional (0D) carbon black (CB), one-dimensional (1D) carbon nanotubes (CNTs), and two-dimensional (2D) graphene oxide (GO)). The AuNR/carbon-based nanomaterial hybrids were utilized in dynamic surface-enhanced Raman scattering (D-SERS). First, cetyltrimethylammonium bromide (CTAB) was used to stabilize and coat the AuNRs, enabling them to be dispersed in water and conferring a positive charge to the surface. AuNR/carbon-based nanomaterial hybrids were then formed via electrostatic attraction with the negatively charged carbon-based nanomaterials. Subsequently, the AuNR/carbon-based nanomaterial hybrids were utilized as large-area and highly sensitive Raman spectroscopy substrates. The AuNR/GO hybrids afforded the best signal enhancement because the thickness of GO was less than 5 nm, which enabled the AuNRs adsorbed on GO to produce a good three-dimensional hotspot effect. The enhancement factor (EF) of the AuNR/GO hybrids for the dye molecule Rhodamine 6G (R6G) reached 1 × 107, where the limit of detection (LOD) was 10-8 M. The hybrids were further applied in D-SERS (detecting samples transitioning from the wet state to the dry state). During solvent evaporation, the system spontaneously formed many hotspots, which greatly enhanced the SERS signal. The final experimental results demonstrated that the AuNR/GO hybrids afforded the best D-SERS signal enhancement. The EF value for R6G reached 1.1 × 108 after 27 min, with a limit of detection of 10-9 M at 27 min. Therefore, the AuNR/GO nanohybrids have extremely high sensitivity as molecular sensing elements for SERS and are also very suitable for the rapid detection of single molecules in water quality and environmental management.