Unveiling Immune Infiltration Characterizing Genes in Hypertrophic Cardiomyopathy Through Transcriptomics and Bioinformatics.

Background: Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways. Methods: First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database. Results: Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings. Conclusion: Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications.

Identification of serum exosomal miRNA biomarkers for diagnosis of Rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation-induced joint damage, which can cause lasting disability. Therefore, early diagnosis and treatment of RA are crucial. Herein, we evaluated whether exosomal microRNAs (miRNAs) could be served as promising biomarkers that can accelerate the diagnosis of RA and development of therapies for RA. METHODS: First, we performed small RNA sequencing to determine the miRNA profiles of serum exosomes within a screening cohort comprised of 18 untreated active RA patients, along with 18 age and gender-matched healthy controls (HCs). Subsequently, the miRNA profiles were then validated in a training cohort consisting of 24 RA patients and 24 HCs by RT-qPCR. Finally, the selected exosomal miRNAs were validated in a larger cohort comprising 108 RA patients and 103 HCs. The diagnostic efficacy of the exosomal miRNAs was evaluated by receiver operating characteristic (ROC) curve analysis. Biological functions of the miRNAs were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Our results first demonstrated a noteworthy upregulation of three candidate miRNAs (miR-885-5p, miR-6894-3p, and miR-1268a) in the RA patients' serum exosomes compared to HCs. The combination of three miRNAs along with anti- citrullinated peptide antibodies (ACPA) exhibited excellent diagnostic accuracy, yielding an area under the curve (AUC) of 0.963 (95 % CI : 0.941-0.984), sensitivity of 87.96 %, and specificity of 93.20 %. Notably, miR-885-5p exhibited remarkable discriminatory capacity by itself in indistinguishing ACPA- negative RA patients from HCs, with an AUC of 0.993 (95 % CI : 0.978-1.000), sensitivity of 96.67 %, and specificity of 100 %. Moreover, the expression of miR-1268a in the assessment of therapeutic effectiveness displayed significant reduction on 29th day of Methotrexate (MTX) treatment in RA patients. This decreased expression paralleled with trends observed in tender 28-joint count (TJC28), swollen 28-joint count (SJC28), and disease activity score with 28-joint count using C-reactive protein (DAS28-CRP), all of which are indicative of RA disease activity. Finally, predictive analysis indicated that, these three exosomal miRNAs target pivotal signaling molecules involved in inflammatory pathways, thereby demonstrating effective modulation of the immune system. CONCLUSIONS: In this study, we successfully demonstrated the promising potential for serum exosomal miRNAs, particularly miR-885-5p, miR-6894-3p and miR-1268a as biomarkers for early diagnosis and prediction of RA for the first time.

High Circulating FGF-23 and Its Relationship with Severity of Spinal Involvement in Diffuse Idiopathic Skeletal Hyperostosis.

The primary objective of this study was to determine the role of fibroblast growth factor 23 (FGF-23) in the pathogenesis of diffuse idiopathic skeletal hyperostosis (DISH). A total of 61 patients with DISH and 61 age- and sex-matched control patients without DISH were included in this study. The serum FGF-23, creatinine, inorganic phosphate, calcium, albumin, albumin-adjusted calcium and alkaline phosphatase, and C-reactive protein were assessed in both groups. Based on the extent of ossification, DISH group was further divided into T-DISH and L-DISH subgroups. Data were comparatively analyzed between DISH and Non-DISH groups and among T-DISH, L-DISH, and Non-DISH groups, respectively. Besides, the number of ossification segments of all DISH patients was quantified and the correlation between the number of ossification segments and the serum concentration of FGF-23 was analyzed. The results revealed that serum FGF-23 was significantly higher in DISH group than in Non-DISH group, regardless of gender. Interestingly, serum Pi was significantly lower in DISH group than in Non-DISH group. Moreover, a significant difference in serum FGF-23 among T-DISH, L-DISH, and Non-DISH groups was also observed. In contrast to Non-DISH group, both T-DISH and L-DISH subgroups displayed significantly higher serum FGF-23 level. Although the mean value was relatively higher in L-DISH subgroup, no statistically significant difference was found between T-DISH and L-DISH subgroups. In addition, a moderately positive correlation was identified between the number of ossification segments and the serum level of FGF-23. It can be concluded that serum FGF-23 could serve as a positive biomarker for DISH and may play a significant role in ectopic ossification in DISH.

Circulating exosomal microRNAs as biomarkers of lupus nephritis.

Objective: Disruption in the delicate symphony of genes, microRNA (miRNA), or protein expression can result in the dysregulation of the immune system, leading to the devastating consequences such as lupus nephritis (LN). The capacity of exosomes to transport miRNAs between cells and modify the phenotype of recipient cells implies their involvement in persistent kidney inflammation. This study unveils identifying two previously undiscovered exosomal miRNAs in the serum of LN patients, offering potential solutions to the current challenges in LN diagnosis and management. Methods: Initially, we used a reagent-based kit to isolate serum exosomes from patients with Systemic lupus erythematosus (SLE) and used Trizol method for total RNA extraction. Subsequently, we employed small RNA sequencing to screen for differential expression profiles of exosomal small RNAs. The RT-qPCR method was used to individually validate samples in both the screening and validation cohorts, enabling the identification of candidate small RNAs; specific to LN. We assessed the diagnostic potency using receiver operating characteristic (ROC) curve, and explored the biological roles of miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Compared to SLE patients without LN, SLE patients accompanied by LN exhibited significantly spiked levels of exosomal hsa-miR-4796-5p and hsa-miR-7974. The duo of miRNAs, hsa-miR-4796-5p and hsa-miR-7974, exhibited promising potential as biomarkers for diagnosing LN, with an AUC exceeding 0.8. Correlation analysis revealed a strong positive association between these miRNAs and proteinuria, as well as the SLE Disease Activity Index (SLEDAI) score. Moreover, the levels of two miRNAs in LN patients were significantly elevated in comparison to other autoimmune nephritis conditions, such as immunoglobulin A nephropathy (IgAN) and diabetic nephropathy (DN). Furthermore, the bioinformatics analysis indicated that this miRNAs duo can play a pivotal role in the regulation of immune processes by modulating signal pathways, such as the mTOR and PI3K-Akt signaling pathway. Conclusion: This study provides a new ground that serum exosomal miRNAs can effectively identify and predict LN in SLE patients.

Exosomes based advancements for application in medical aesthetics.

Beauty is an eternal pursuit of all people. Wound repair, anti-aging, inhibiting hyperpigmentation and hair loss are the main demands for medical aesthetics. At present, the repair and remodeling of human body shape and function in medical aesthetics are often achieved by injection of antioxidants, hyaluronic acid and botulinum toxin, stem cell therapy. However, there are some challenges, such as difficulty controlling the injection dose, abnormal local contour, increased foreign body sensation, and the risk of tumor occurrence and deformity induced by stem cell therapy. Exosomes are tiny vesicles secreted by cells, which are rich in proteins, nucleic acids and other bioactive molecules. They have the characteristics of low immunogenicity and strong tissue penetration, making them ideal for applications in medical aesthetics. However, their low yield, strong heterogeneity, and long-term preservation still hinder their application in medical aesthetics. In this review, we summarize the mechanism of action, administration methods, engineered production and preservation technologies for exosomes in medical aesthetics in recent years to further promote their research and industrialization in the field of medical aesthetics.

[Retrospective study of temporomandibular joint dislocation by surgical treatment].

OBJECTIVE: This study aimed to retrospectively analyze temporomandibular joint dislocation by surgical treatment and evaluate the treatment effect. METHODS: From May 2012 to April 2016, a total of 17 cases of temporomandibular joint dislocation were surgically treated, including 8 cases of irreducible dislocation (ID) and 9 cases of recurrent dislocation (RD). Synovial injection of sclerosing agent by arthroscope was performed in 5 cases, 9 sides; augmentation of the articular eminence by titanium plate implantation was performed in 7 cases, 12 sides; iliac bone transplantation was performed in 1 case, 1 side; Medpore implantation was performed in 3 cases, 6 sides; and eminectomy and capsular tightening were performed in 1 case, 2 sides. Follow-up was conducted 1-5 years after the operation, and the success rate statistics was obtained. RESULTS: The cure rate of synovial injection of sclerosing agent by arthroscope was 77.8% (7/9), and the effective rate was 100%. The cure rate of titanium plate implantation was 75% (9/12), and the effective rate was 100%. The cure rates of augmentation of the articular eminence by Medpore implantation (6/6), iliac bone graft (1/1), and eminectomy (2/2) were 100%. CONCLUSIONS: The surgical method of temporomandibular joint dislocation was selected according to the state of the patients. The postoperative recurrent patients were advised to undergo augmentation of the articular eminence by Medpore implantation, which offered a reduced chance of recurrence and relatively less injury, as well as a simple operative method.

Performance Optimization Design for a High-Speed Weak FBG Interrogation System Based on DFB Laser.

A performance optimization design for a high-speed fiber Bragg grating (FBG) interrogation system based on a high-speed distributed feedback (DFB) swept laser is proposed. A time-division-multiplexing sensor network with identical weak FBGs is constituted to realize high-capacity sensing. In order to further improve the multiplexing capacity, a waveform repairing algorithm is designed to extend the dynamic demodulation range of FBG sensors. It is based on the fact that the spectrum of an FBG keeps stable over a long period of time. Compared with the pre-collected spectra, the distorted spectra waveform are identified and repaired. Experimental results show that all the identical weak FBGs are distinguished and demodulated at the speed of 100 kHz with a linearity of above 0.99, and the range of dynamic demodulation is extended by 40%.

ZrO2 thin-film-based sapphire fiber temperature sensor.

A submicrometer-thick zirconium dioxide film was deposited on the tip of a polished C-plane sapphire fiber to fabricate a temperature sensor that can work to an extended temperature range. Zirconium dioxide was selected as the thin film material to fabricate the temperature sensor because it has relatively close thermal expansion to that of sapphire, but more importantly it does not react appreciably with sapphire up to 1800 °C. In order to study the properties of the deposited thin film, ZrO2 was also deposited on C-plane sapphire substrates and characterized by x-ray diffraction for phase analysis as well as by atomic force microscopy for analysis of surface morphology. Using low-coherence optical interferometry, the fabricated thin-film-based sapphire fiber sensor was tested in the lab up to 1200 °C and calibrated from 200° to 1000 °C. The temperature resolution is determined to be 5.8 °C when using an Ocean Optics USB4000 spectrometer to detect the reflection spectra from the ZrO2 thin-film temperature sensor.

Decoding the spectra of low-finesse extrinsic optical fiber Fabry-Perot interferometers.

A theoretical model is developed to address the fringe visibility and additional phase in the interference spectra of low-finesse extrinsic optical fiber excited Fabry-Pérot interferometers. The model described in the paper applies to both single-mode and multimode fiber excitations; according to the theory, the fringe visibility and additional phase term are primarily determined by the working wavelength and angular power density distribution outputting from the excitation fiber, rather than based on spatial and temporal degree of coherence. Under certain approximations, the output interference intensity and the spatial power density distribution projected onto the fiber axis form a Fourier-transform pair, which potentially provides a tool for spatial density distribution analysis of fiber output. With excellent agreement with experiments, the theory presented in this paper leads to design guidelines for Fabry-Pérot interferometric sensors and insightful physical understanding of such devices.

Fully distributed fiber-optic temperature sensing using acoustically-induced rocking grating.

A highly sensitive fully distributed fiber-optic temperature sensing technique is proposed and demonstrated based on a transient and traveling rocking grating. The rocking grating is generated by pulsed acoustic torsional waves propagating along the fiber. The measured temperature sensitivity is 1000 ppm/°C and is experimentally demonstrated mainly due to the temperature dependence of the fiber birefringence. This traveling rocking grating based sensing technique may also serve other fully-distributed sensing applications by using specially designed fibers.

Method of multiple references for 3D imaging with Fourier transform interferometry.

This letter presents an improved phase referencing technique, called Method of Multiple References, for optical profilometry. Based on a lookup table, the method eliminates several major drawbacks of single-reference Fourier Transform Interferometry by enabling surface error correction for steep slopes and step discontinuities, and by allowing mapping of multiple discrete objects using a single image set. The algorithm is tested using a fiber optic coupler-based FTI system and shown to have RMS surface error less than 0.03 mm.

Compact optical path scanner and its application for decoding fiber-optic interferometers.

This Letter describes a compact optical path scanner for decoding fiber-optic interferometers. The active component of the scanner is a segment of liquid sealed in a fused silica hollow fiber. When the volume of the liquid is changed by an attached thermoelectric cooler, one end facet of the liquid moves along the hollow fiber, and the optical path of the light reflected by the end facet is thus tuned, with a continuous tuning range of a few hundred micrometers. We used the optical path scanner for demodulating the optical path difference of a Fabry-Perot interferometric sensor, and the resulted decoding accuracy is 14 nm over a measurement range of 50 mum. The compact optical path scanner has the advantages of compact size, high precision, flexible scanning range, low cost, insensitivity to vibration, and ease of fabrication.

Multiplexed high temperature sensing with sapphire fiber air gap-based extrinsic Fabry-Perot interferometers.

In this Letter we present a high temperature multipoint sensing method using sapphire fiber air gap-based extrinsic Fabry-Perot interferometers. Three sensors are fabricated and tested in a single sensing link. Experimental results show that the air gap-based high temperature sensors have a very high temperature sensitivity (>20 nm/ degrees C) and resolution (<0.3 degrees C) and are capable of operating at temperatures well above 1000 degrees C. The multiplexed sapphire sensors present a significant advancement over traditional single-point sensors for critical high temperature applications.

Analyzing absorption and scattering spectra of micro-scale structures with spectroscopic optical coherence tomography.

We demonstrate the feasibility of characterizing the absorption and scattering spectra of micron-scale structures in a turbid medium using a spectroscopic optical coherence tomography (SOCT) system with a bandwidth of 430-650 nm. SOCT measurements are taken from phantoms composed of fluorescent microspheres. The absorption and scattering spectra are recovered with proper selections of spatial window width in the post processing step. Furthermore, we present an analysis using numerical OCT simulation based on full-wave solutions of the Maxwell's Equation to elucidate the origination of the multiple peaks in the OCT image for a single microsphere. Finally, we demonstrate the possibility of identifying contrast agents concentrated in micron-sized scale in an SOCT image. Two different types of microspheres in gel phantom are discriminated based on their distinguished absorbent feature.

Characterization of malignant brain tumor using elastic light scattering spectroscopy.

We report a pilot study designed to test elastic light-scattering (ELS) spectroscopy for characterizing normal, tumor, and tumor-infiltrated brain tissues. ELS spectra were measured from 393 sites on 36 ex vivo tissue specimen obtained from 29 patients. We employed and compared the performances of three methods of spectral classification for tissue characterization, including spectral slope analysis, principle component analysis (PCA), and artificial neural network (ANN) classification. The ANN classifier yielded the best correlation between spectral pattern and histopathological diagnosis, with a typical sensitivity of 80% and specificity of 93% for differentiating tumor from normal brain tissues. We also demonstrate that all three classification methods discriminate between tumor and normal tissue and have the potential to identify and quantitatively characterize tumor-infiltrated brain tissues.

Optimal spectral reshaping for resolution improvement in optical coherence tomography.

We analyze the resolution limit that can be achieved by means of spectral reshaping in optical coherence tomography images and demonstrate that the resolution can be improved by means of modelessly reshaping the source spectrum in postprocessing. We show that the optimal spectrum has a priori surprising "crater-like" shape, providing 0.74 micron axial resolution in free space. This represents ~50% improvement compared to resolution using the original spectrum of a white light lamp.

Analytical techniques for addressing forward and inverse problems of light scattering by irregularly shaped particles.

Understanding light scattering by nonspherical particles is crucial in modeling the transport of light in realistic structures such as biological tissues. We report the application of novel analytical approaches based on modified Wentzel-Kramers-Brillouin and equiphase-sphere methods that facilitate accurate characterization of light scattering by a wide range of irregularly shaped dielectric particles. We also demonstrate that these approaches have the potential to address the inverse-scattering problem by means of a spectral analysis of the total scattering cross section of arbitrarily shaped particles.