Leveraging Large Language Models for Improved Patient Access and Self-Management: Assessor-Blinded Comparison Between Expert- and AI-Generated Content.

BACKGROUND: While large language models (LLMs) such as ChatGPT and Google Bard have shown significant promise in various fields, their broader impact on enhancing patient health care access and quality, particularly in specialized domains such as oral health, requires comprehensive evaluation. OBJECTIVE: This study aims to assess the effectiveness of Google Bard, ChatGPT-3.5, and ChatGPT-4 in offering recommendations for common oral health issues, benchmarked against responses from human dental experts. METHODS: This comparative analysis used 40 questions derived from patient surveys on prevalent oral diseases, which were executed in a simulated clinical environment. Responses, obtained from both human experts and LLMs, were subject to a blinded evaluation process by experienced dentists and lay users, focusing on readability, appropriateness, harmlessness, comprehensiveness, intent capture, and helpfulness. Additionally, the stability of artificial intelligence responses was also assessed by submitting each question 3 times under consistent conditions. RESULTS: Google Bard excelled in readability but lagged in appropriateness when compared to human experts (mean 8.51, SD 0.37 vs mean 9.60, SD 0.33; P=.03). ChatGPT-3.5 and ChatGPT-4, however, performed comparably with human experts in terms of appropriateness (mean 8.96, SD 0.35 and mean 9.34, SD 0.47, respectively), with ChatGPT-4 demonstrating the highest stability and reliability. Furthermore, all 3 LLMs received superior harmlessness scores comparable to human experts, with lay users finding minimal differences in helpfulness and intent capture between the artificial intelligence models and human responses. CONCLUSIONS: LLMs, particularly ChatGPT-4, show potential in oral health care, providing patient-centric information for enhancing patient education and clinical care. The observed performance variations underscore the need for ongoing refinement and ethical considerations in health care settings. Future research focuses on developing strategies for the safe integration of LLMs in health care settings.

Dioscin Alleviates Periodontitis by Inhibiting NLRP3 Inflammasome Activation via Regulation of K+ Homeostasis and Mitochondrial Function.

Gingival inflammation and alveolar bone loss are characteristic manifestations of periodontitis. Interleukin (IL)-1ß, the maturation of which is mainly regulated by NOD-like receptor protein (NLRP) 3 inflammasome, not only amplifies the inflammatory response but also triggers osteoclastogenesis, thereby accelerating the progression of periodontitis. Dioscin, a natural steroid saponin, has been shown to inhibit NLRP3 inflammasome. Nevertheless, research on the effectiveness of Dioscin for the management of periodontitis remains scarce. In this study, Dioscin was found to dramatically reduce the integral components of NLRP3 inflammasome, ultimately limiting IL-1ß secretion. Notably, the inhibitory impact of Dioscin on NLRP3 inflammasome might be exerted by curbing the generation of mitochondrial (mt) reactive oxygen species (ROS) and oxidized (ox) mtDNA, which were mediated by inhibition of K+ efflux. Furthermore, Dioscin effectively alleviated periodontitis in mice. Overall, the results established that Dioscin could alleviate periodontitis by inhibiting NLRP3 inflammasome via modulation of the K+ efflux-mtROS-ox-mtDNA pathway, holding the potential to treat periodontitis and other NLRP3-driven inflammatory diseases.

An injectable gel based on photo-cross-linkable hyaluronic acid and mesoporous bioactive glass nanoparticles for periodontitis treatment.

Guided bone regeneration (GBR) is an effective strategy to promote periodontal tissue repair. The current study aimed to develop an injectable gel for GBR, composed of photo-cross-linkable hyaluronic acid and mesoporous bioactive glass nanoparticles (MBGNs) loaded with antibacterial minocycline hydrochloride (MNCl). Hyaluronic acid modified with methacrylic anhydride (MHA) that could be cross-linked under UV irradiation was first synthesized. Dynamic rheological evaluation of MHA under UV was carried out to determine its in-situ gelling feasibility and stability. Morphological and mechanical characterization was performed to determine the optimal concentration of MHA gels. Sol-gel derived MBGNs loaded with MNCl were further incorporated into MHA gels to obtain the injectable drug-loaded MBGN-MNCl/MHA gels. In vitro antibacterial, anti-inflammatory and osteogenic effects of this gel were evaluated. It was shown that the MHA gel obtained from 3 % MHA under UV treatment of 30s exhibited a suitable porous structure with a compressive strength of 100 kPa. MBGNs with particle size of ∼120 nm and mesopores were confirmed by TEM and SEM. MBGNs had a loading capacity of ∼120 mg/g for MNCl, exhibiting a sustained release behavior. The MBGN-MNCl/MHA gel was shown to effectively inhibit the proliferation of Streptococcus mutans and the expression of pro-inflammatory factors IL-6 and TNF-α by macrophages. It could on the other hand significantly promote the expression of osteogenic-related genes ALP, Runx2, OPN, and osterix of MC3T3-E1 cells. In conclusion, the current design using photo-crosslinkable MHA gel embedded with MNCl loaded MBGNs can serve as a promising injectable formulation for GBR treatment of irregular periodontal defects.

One-piece versus two-piece zirconia abutment supported single implant crown in the esthetic region: 3-Year results from a split-mouth randomized controlled clinical trial.

OBJECTIVES: To compare the clinical, radiographic, and immunological outcomes between one-piece versus two-piece zirconia abutments supported single implant crowns in the esthetic region. MATERIALS AND METHODS: The study followed a split-mouth, double-blind, and randomized controlled clinical design for a duration of 3 years. Twenty-two eligible patients with 44 implants were randomly assigned to two groups: Group 1 (one-piece zirconia abutment with zirconia base, n = 22) and Group 2 (two-piece zirconia abutment with titanium base, n = 22). The primary outcome was the technical complication rate. Additionally, survival rates, cytokines concentrations in peri-implant crevicular fluid (PICF), peri-implant conditions, marginal bone loss, and pink/white esthetics score (PES/WES) were assessed as secondary outcomes. RESULTS: Twelve of 22 patients attended the 1-year follow-up (due to the COVID pandemic), and 19 patients attended the 3-year examination. Two abutments in Group 1 were fractured after 10 and 12 months in function. Additionally, one screw loosening occurred in Group 1 at 1-year follow-up. The 3-year technical complication rate was significantly higher in Group 1 than that in Group 2 (15.79% vs. 0%, p < .001). The 3-year implant survival rate was 100% in both groups. The concentration of IFN-γ in PICF was significantly upregulated in Group 2 (p = .018). Furthermore, the IL-6 concentration was positively correlated with BOP% (p = .020). CONCLUSIONS: Two-piece zirconia abutments exhibited superior technical performance compared to one-piece designs during a 3-year follow-up in the anterior region. However, further long-term research is necessary to verify the immunological stability of two-piece zirconia abutments.

Application of Levosimendan in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Patients with Myocardial Injury.

Objective: This study aims to investigate the effectiveness of levosimendan in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection complicated by cardiac insufficiency and myocardial injury. Methods: A total of 22 patients with SARS-CoV-2 infection and myocardial injury, admitted to the Cardiology Department of our hospital between December 2022 and February 2023, are randomly divided into two groups: a dobutamine general treatment group and a levosimendan observation treatment group. The treatment outcomes of the two groups are compared and analyzed. Results: The overall improvement rate in the general treatment group is 80%, while the levosimendan treatment group shows a 100% improvement rate. There is a statistically significant difference between the two groups (P < .05). Post-treatment, the left ventricular ejection fraction for the general treatment group and the levosimendan treatment group are (48 ± 7)% and (54 ± 6)%, respectively. Additionally, the left ventricular end-diastolic diameter is (55.0 ± 3.0) mm in the general treatment group and (51 ± 5.0) mm in the levosimendan group, with a statistically significant difference (P < .05). After active treatment, the plasma levels of B-type natriuretic peptide (Brain Natriuretic Peptide, NT-proBNP) are significantly lower in the levosimendan treatment group than in the general treatment group (P < .05). Moreover, the plasma levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the levosimendan group decrease slightly faster than those in the general treatment group, with a statistically significant difference (P < .05). The length of hospital stay in the levosimendan group is (12 ± 3) days, significantly lower than the general treatment group (16 ± 5) days, with a statistically different result (P < .05). Conclusions: Levosimendan demonstrates significant efficacy in patients with novel coronavirus infection complicated by myocardial injury, resulting in improved clinical symptoms, enhanced cardiac function, shorter hospital stays, early discharge, and cost savings.

Cell Responses to Calcium- and Protein-Conditioned Titanium: An In Vitro Study.

Dental implants have become the leading choice for patients who lose teeth; however, dental implantation is challenged by peri-implant infections. Here, calcium-doped titanium was fabricated by the combinational use of thermal evaporation and electron beam evaporation in a vacuum; then, the material was immersed in a calcium-free phosphate-buffered saline solution containing human plasma fibrinogen and incubated at 37 °C for 1 h, creating calcium- and protein-conditioned titanium. The titanium contained 12.8 ± 1.8 at.% of calcium, which made the material more hydrophilic. Calcium release by the material during protein conditioning was able to change the conformation of the adsorbed fibrinogen, which acted against the colonization of peri-implantitis-associated pathogens (Streptococcus mutans, UA 159, and Porphyromonas gingivalis, ATCC 33277), while supporting the adhesion and growth of human gingival fibroblasts (hGFs). The present study confirms that the combination of calcium-doping and fibrinogen-conditioning is a promising pathway to meeting the clinical demand for suppressing peri-implantitis.

Effects of diabetes/hyperglycemia on peri-implant biomarkers and clinical and radiographic outcomes in patients with dental implant restorations: A systematic review and meta-analysis.

OBJECTIVE: The objective of this study is to systematically analyze the effects of diabetes mellitus/hyperglycemia (DM/HG) on peri-implant biomarkers and clinical and radiographic outcomes in patients undergoing implant treatment. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched up to March 2022. Studies reporting on peri-implant biomarkers, and clinical and radiographic outcomes in patients with different glycemic status levels (HbA1c) were included. Several analyses were conducted, such as meta-analysis, sensitivity analysis, dose-response meta-analysis (DRMA), and robust error meta-regression (REMR). RESULTS: A total of 10 studies and 634 participants were included for analysis, with a maximum follow-up of six years in function. The level of advanced glycation end products (AGEs) in peri-implant crevicular fluid (PICF) was significantly higher in the DM/HG group than in the healthy group (p < .01). Subgroup analyses showed that a set of negative regulators of bone metabolism (including IL-6, TNF-α, IL-8, and RANKL) were significantly higher in the DM/HG group (p = .01). Implant survival rate (100%) was not compromised in patients with an HbA1c level less than 10%. Outcomes of implant stability quotient (ISQ) values, bleeding on probing rate (BOP%), probing depth (PD), and marginal bone loss (MBL) in the DM/HG group were significantly worse than those in the healthy group (p = .04, <0.01, 0.01, <0.01, respectively). DRMA results showed AGE accumulation in PICF, PD, and MBL worsened in a dose-response dependent manner with elevated HbA1c levels (<6%, 6-8%, >8%; p = .04, 0.02, <0.01, respectively). CONCLUSIONS: DM/HG can upregulate negative regulators of bone metabolism and compromise peri-implant health. In addition, there are dose-response relationships between HbA1c levels and AGE accumulation in PICF, PD, and MBL.

A Novel DEM Block Adjustment Method for Spaceborne InSAR Using Constraint Slices.

The lack and uneven distribution of Ground Control Points (GCPs) will lead to the deterioration of Digital Elevation Model (DEM) block adjustment results in the bistatic Interferometric Synthetic Aperture Radar (InSAR) system. Given this issue, we first explain the relationship between the stability of adjustment parameters and the GCP distribution pattern theoretically using matrix perturbation theory. Second, we put forward the Constraint Slices (CSs) concept and first introduce CSs into the adjustment optimization model as constraint conditions rather than actual values as GCPs. Finally, we propose a novel DEM block adjustment method for spaceborne InSAR using CSs based on an optimization model with nonlinear constraints. The simulated experiment shows the instability of the conventional method and validates the proposed method under different parallel baseline errors. Four groups of real experiments were carried out according to the size of the uncontrolled area using twelve Co-registered Single-look Slant-range Complex (CoSSC) datasets for Henan Province, China. The adjustment results verified by the ICESat-2 ATL08 data demonstrate that the performance of the proposed method is better than the conventional method in the uncontrolled area; the corresponding improvements in adjustment accuracies compared with the conventional method are 0.13 m, 1.02 m, 2.12 m, and 8.18 m, respectively. At the same time, the proposed method can enhance the height consistency in overlapping areas, which is vital for seamless DEM production.

Super electro-optic modulation in bulk KTN:Cu based on electric-field-enhanced permittivity.

The electric-field-enhanced effect of permittivity can improve the performance of electro-optic modulators and deflectors. A theoretical model of super electro-optic modulation based on the field-enhanced effect of the permittivity was proposed. Results showed that a strong field-enhanced effect can greatly reduce the half-wave voltage and increase the modulation depth as a result of increased relative dielectric permittivity and permittivity gradient to the electric field. For bulk paraelectric KTN:Cu near the Curie temperature, we found a novel phenomenon that the response of relative dielectric permittivity to the bias electric field was closely related to the frequency, including attenuation, invariance, and enhancement. We effectively selected the frequencies corresponding to the strong field-enhanced effect by measuring the dielectric-frequency spectrum under the bias voltage. At these frequencies, a phase retardation of π was achieved through 2Vpp AC modulation voltage, indicating that the half-wave voltage was reduced by one order of magnitude.

Clinical, radiographic, and immunological evaluation of angulated screw-retained and cemented single-implant crowns in the esthetic region: A 1-year randomized controlled clinical trial.

BACKGROUND: Screw-retained implant crowns are considered more biologically compatible than cemented crowns due to the absence of excess cement. However, traditional screw-retained implant crowns are not viable when the access hole of the screw channel would need to be located in an esthetic area, which would compromise the esthetic outcome of the treatment. PURPOSE: To evaluate the clinical, radiographic, and immunological outcomes of angulated screw-retained and cemented single-implant crowns in the esthetic region. MATERIALS AND METHODS: The study was a single-center, open-label, randomized controlled clinical trial. Eligible patients were randomly placed in two groups: angulated screw-retained group (AG) and cemented group (CG). Implant survival rate, bleeding on probing rate (BOP%), probing depth (PD), modified plaque index (mPI), marginal bone loss (MBL), concentrations of pro-inflammatory cytokines (TNF-α, IL-6) in peri-implant crevicular fluid (PICF), mechanical complications, and pink esthetic score/white esthetic score (PES/WES) were evaluated. RESULTS: Fifty-six patients (AG: 29, CG: 27) attended the 1-year examination. The drop-out rate was 6.67%. No implant failure was found in both groups during the observation period. BOP% was significantly lower in the AG than that in the CG (mean, 21.84% ± 19.97% vs. 37.04% ± 26.28%, p = 0.018). The concentration of TNF-α in PICF was significantly higher in the AG than that in the CG (median, 13.54 vs. 4.62, p = 0.019). No significant difference of PD, mPI, MBL, IL-6, or mechanical complication rates was found between the two groups. Mean scores for PES/WES were 21.71 and 21.64 in the AG and CG, respectively. CONCLUSION: Based on the present results, both treatment options showed acceptable clinical outcomes in the short term. Angulated screw-retained crowns might benefit the peri-implant soft tissue. However, studies with long-term follow-up are needed to confirm whether the higher concentration of TNF-α will compromise the long-term outcomes of treatment.

Potassium tantalate niobate (KTN) crystal-based polarization-modulated 3D ladar with a large field of view.

An innovative 3D ladar that utilizes potassium tantalate niobate (KTN) crystal as a polarization modulator is proposed in this Letter. The optical isotropy of KTN in cubic phase can effectively suppress the range errors induced by the incident angles of collected beams in 3D imaging. The giant quadratic electro-optic coefficient can dramatically lower the voltage that is required to modulate the polarization so that a high voltage amplifier with less noise can be used to improve the ranging performances. By virtue of these two advantages, a range error of 4.8 cm and a range precision of 4.4 cm at 15 m have been achieved under a large field of view of 20° (about 0.35 rad) and a maximum detection range without ambiguity of 60 m.

Angulated screw-retained and cemented implant crowns following flapless immediate implant placement in the aesthetic region: A 1-year prospective cohort study.

PURPOSE: To compare the short-term clinical and radiographic outcomes of angulated screw-retained and cemented implant crowns following flapless immediate implant placement. MATERIALS AND METHODS: The study was designed as a prospective cohort study with 1-year follow-up. Eligible patients were divided into two groups according to restoration type: the angulated screw group (AG) and the cemented group (CG). Implant survival, marginal bone loss, mechanical complications, probing depth, bleeding on probing% and pink aesthetic score were evaluated. RESULTS: After 1 year of loading, the implant survival rate was 100% in both groups (AG, n = 23; CG, n = 20). A significantly lower bleeding on probing% was found in the AG than in the CG (11.6 ± 19.1% vs. 33.3 ± 33.8%, P = 0.04). No significant differences in marginal bone loss, probing depth and mechanical complication rates were found between the two groups (P = 0.53, 0.48, 0.41, respectively). The overall pink aesthetic score value was 8.96 ± 0.88 in the AG and 8.98 ± 0.62 in the CG at 1-year examination (P = 0.96). The percentage of excellent pink aesthetic scores (≥ 9) value increased from 48% at baseline to 83% at 1 year in the AG, and from 45% at baseline to 85% at 1 year in the CG. CONCLUSION: Based on the 1-year results, both treatment options provide high implant survival, a stable marginal bone level and excellent aesthetic outcomes in the short term. Angulated screw-retained crowns might benefit the long-term peri-implant conditions.

Overexpression of the bioactive lunasin peptide in soybean and evaluation of its anti-inflammatory and anti-cancer activities in vitro.

Lunasin, a bioactive peptide with a variety of physiological functions, was overexpressed in soybean to generate a transgenic soybean. Polymerase chain reaction (PCR) analysis suggested that lunasin was successfully inserted into the soybean genome, and three transgenic lines, L12, L43, and L45, were selected for further study. Lunasin expression was characterized in the lines by Western blot and ultra-performance liquid chromatography with tandem mass spectrometry. Enzyme-linked immunosorbent assay showed that lunasin content in L12, L43, and L45 lines was 1.47 mg g-1, 1.32 mg g-1 and 1.98 mg g-1, respectively; these values were significantly higher than that in wild-type soybean (0.94 mg g-1). Lunasin enrichments from transgenic soybean (LET) exhibited stronger DPPH, ABTS+, and oxygen radical scavenging activity than lunasin enrichments from wild-type soybean (LEW). Further, LET presented superior anti-inflammatory activity on lipopolysaccharide-induced macrophage cells compared to LEW, and it significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines including interleukin-1 and -6. Moreover, LET showed higher anti-proliferation activity on MDA-MB-231 cells than LEW. Immunofluorescence staining showed that LET could internalize into NIH-3T3 cells, and localize in the nucleus. In conclusion, it is feasible and efficient to produce lunasin through a transgenic soybean expression system. Lunasin overexpressing soybean could be consumed as a functional food in the diets of patients with cancer and obesity in the future.

LINC-PINT Activates the Mitogen-Activated Protein Kinase Pathway to Promote Acute Myocardial Infarction by Regulating miR-208a-3p.

BACKGROUND: This study is performed to explore the differential expression of long intergenic non-coding-p53 induced non-coding transcript, miR-208a-3p and JUN in acute myocardial infarction (AMI) and their potential mechanisms. Methods and Results: Gene Expression Omnibus, R software, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis were used for analyzing the differentially expressed genes (DEGs) and pathways. The differential expressions of LINC-PINT and miR-208a-3p were examined by qRT-PCR. The expressions of JUN and the mitogen-activated protein kinase (MAPK) pathway-related proteins were analyzed by Western blot. The triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining methods were used to measure the myocardial infarction size and tissue apoptosis respectively. The targeted relationships between miR-208a-3p and LINC-PINT or JUN were confirmed using a dual luciferase reporter assay. DEGs were significantly enriched in the MAPK signaling pathway. LINC-PINT could sponge miR-208a-3p, which targeted and regulated JUN. LINC-PINT and JUN were confirmed to be overexpressed in AMI tissues. Silencing LINC-PINT and JUN could exert a protective influence against AMI. The expression of miR-208a-3p was significantly decreased in AMI tissues, and miR-208a-3p reduced myocardial ischemia-reperfusion injury and apoptosis. Downregulation of LINC-PINT facilitated miR-208a-3p expression and suppressed the protein level of JUN, contributing to the inactivation of the MAPK pathway in the AMI tissues and thus generating protective effects. CONCLUSIONS: Knockdown of LINC-PINT inactivated the MAPK pathway by releasing miR-208a-3p and suppressing the JUN, protecting the injury during the process of AMI.

The levels of serine proteases in colon tissue interstitial fluid and serum serve as an indicator of colorectal cancer progression.

The proteins in tissue interstitial fluids (TIFs) can spread into the blood and have been proposed as an ideal material to find blood biomarkers. The colon TIFs were collected from 8-, 13-, 18-, and 22-week ApcMin/+, a typical mouse model of colorectal cancer (CRC), and wild-type mice. iTRAQ-based quantification proteomics was conducted to survey the TIF proteins whose abundance appeared to depend on tumor progression. A total of 46 proteins that exhibited consecutive changes in abundance were identified, including six serine proteases, chymotrypsin-like elastase 1 (CELA1), chymotrypsin-like elastase 2A (CEL2A), chymopasin, chymotrypsinogen B (CTRB1), trypsin 2 (TRY2), and trypsin 4 (TRY4). The observed increases in the abundance of serine proteases were supported in another quantitative evaluation of the individual colon TIFs using a multiple reaction monitor (MRM) assay. Importantly, the increases in the abundance of serine proteases were also verified in the corresponding sera. The quantitative verification of the serine proteases was further extended to the clinical sera, revealing significantly higher levels of CELA1, CEL2A, CTRL/chymopasin, and TRY2 in CRC patients. The receiver operating characteristic analysis illustrated that the combination of CELA1 and CTRL reached the best diagnostic performance, with 90.0% sensitivity and 80.0% specificity. Thus, the quantitative target analysis demonstrated that some serine proteases are indicative of CRC progression.

Discovery of potential colorectal cancer serum biomarkers through quantitative proteomics on the colonic tissue interstitial fluids from the AOM-DSS mouse model.

Quantitative proteomic analysis was performed using iTRAQ to discover colorectal cancer (CRC)-related proteins in tissue interstitial fluids (TIFs). A typical inflammation-related CRC mouse model was generated using azoxymethane-dextran sodium sulfate (AOM-DSS), and TIFs were collected from these mice in four stages during CRC development. Using stringent criteria, a total of 144 proteins displayed changes in their abundances during tumor growth, including 45 that consecutively increased, 17 that consecutively decreased and 82 that changed irregularly. Of these 144 proteins, 24 of the consecutively changed proteins were measured using MRM in individual TIF samples, and 18 were verified. Twelve proteins verified to be consecutively increased in TIFs were examined using MRM to evaluate changes in their abundance in individual mouse serum samples. The abundances of leucine-rich alpha-2-glycoprotein 1 (LRG1), tubulin beta-5 chain (TUBB5) and immunoglobulin J chain (IGJ) were significantly higher in CRC mice than in control mice. Using clinical samples and MRM, we further verified that LRG1 and TUBB5 are potential CRC serum biomarkers. These data demonstrate that coupling dynamic TIF proteomics with targeted serum proteomics in an animal model is a promising avenue for pursuing the discovery of tumor serum biomarkers. BIOLOGICAL SIGNIFICANCE: Colorectal cancer (CRC) is one of the most dangerous diseases worldwide. However, few of CRC biomarkers possess satisfied specificity and sensitivity in clinical practices. Exploration of more CRC biomarkers, especially in serum, is an urgent and also a time-consuming campaign in the CRC study. Our study demonstrates that quantitatively evaluating the phase-dependent proteins in colonic tissue interstitial fluids from AOM-DSS mice is a feasible and effective way for exploration of the CRC-related proteins and the potential serum biomarkers. We identified two proteins, LRG1 and TUBB5, which may be practicable in human clinical samples as CRC serum biomarkers. To sum up, this study provides a novel angle to explore the critical factors in tumorigenesis and a new pipeline for potential serum biomarker discovery and verification.

The S-nitrosylation status of PCNA localized in cytosol impacts the apoptotic pathway in a Parkinson's disease paradigm.

It is generally accepted that nitric oxide (NO) or its derivatives, reactive nitrogen species (RNS), are involved in the development of Parkinson's disease (PD). Recently, emerging evidence in the study of PD has indicated that protein S-nitrosylation triggers the signaling changes in neurons. In this study, SH-SY5Y cells treated with rotenone were used as a model of neuronal death in PD. The treated cells underwent significant apoptosis, which was accompanied by an increase in intracellular NO in a rotenone dose-dependent manner. The CyDye switch approach was employed to screen for changes in S-nitrosylated (SNO) proteins in response to the rotenone treatment. Seven proteins with increased S-nitrosylation were identified in the treated SH-SY5Y cells, which included proliferating cell nuclear antigen (PCNA). Although PCNA is generally located in the nucleus and participates in DNA replication and repair, significant PCNA was identified in the SH-SY5Y cytosol. Using immunoprecipitation and pull-down approaches, PCNA was found to interact with caspase-9; using mass spectrometry, the two cysteine residues PCNA-Cys81 and -Cys162 were identified as candidate S-nitrosylated residues. In addition, the evidence obtained from in vitro and the cell model studies indicated that the S-nitrosylation of PCNA-Cys81 affected the interaction between PCNA and caspase-9. Furthermore, the interaction of PCNA and caspase-9 partially blocked caspase-9 activation, indicating that the S-nitrosylation of cytosolic PCNA may be a mediator of the apoptotic pathway.

ISAR imaging of maneuvering targets based on the range centroid Doppler technique.

A new inverse synthetic aperture radar (ISAR) imaging approach is presented for application in situations where the maneuverability of noncooperative target is not too severe and the Doppler variation of subechoes from scatterers can be approximated as a first-order polynomial. The proposed algorithm is referred to as the range centroid Doppler (RCD) ISAR imaging technique and is based on the stretch Keystone-Wigner transform (SKWT). The SKWT introduces a stretch weight factor containing a range of chirp rate into the autocorrelation function of each cross-range profile and uses a 1-D interpolation of the phase history which we call stretch keystone formatting. The processing simultaneously eliminates the effects of linear frequency migration for all signal components regardless of their unknown chirp rate in time-frequency plane, but not for the noise or for the cross terms. By utilizing this novel technique, clear ISAR imaging can be achieved for maneuvering targets without an exhaustive search procedure for the motion parameters. Performance comparison is carried out to evaluate the improvement of the RCD technique versus other methods such as the conventional range Doppler (RD) technique, the range instantaneous Doppler (RID) technique, and adaptive joint time-frequency (AJTF) technique. Examples provided demonstrate the effectiveness of the RCD technique with both simulated and experimental ISAR data.

Effects of methotrexate on plasma cytokines and cardiac remodeling and function in postmyocarditis rats.

Excessive immune activation and inflammatory mediators may play a critical role in the pathogenesis of chronic heart failure. Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to investigate the effects of low-dose methotrexate (0.1 mg/kg/d for 30 d) on the plasma level of cytokines and cardiac remodeling and function. Our study showed that levels of tumor necrosis factor-(TNF-)alpha and interleukin-6 (IL-6) are significantly increased in postmyocarditis rats, compared with the control rats. Methotrexate treatment reduced the plasma levels of TNF-alpha and IL-6 and increased IL-10 level, compared to saline treatment. In addition, postmyocarditis rats showed significant cardiac fibrosis characterized by increased myocardial collagen volume fraction, perivascular collagen area, and the ratio of collagen type I to type III, compared with the control rats. However, MTX treatment not only markedly attenuated cardiac fibrosis, diminished the left ventricular end-diastolic dimension, but also increased the left ventricular ejection fraction and fractional shortening. Collectively, these results suggest that low-dose methotrexate has ability to regulate inflammatory responses and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy.