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Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients. Pompe disease (PD) is a rare disorder that leads to progressive muscle weakness if left untreated. Here, the authors use multispectral optoacoustic tomography (MSOT) to map and quantify the composition of affected muscle tissue to determine disease severity and potentially monitor future therapies. [ABSTRACT FROM AUTHOR]

The efficiency of perovskite solar cells (PSCs) is hindered by substantial defects within the grain boundaries (GBs) of polycrystalline perovskite films. Conventional post‐treatment strategies struggle to precisely repair these defects at GBs. Here, a targeted grain boundary passivation strategy through solvent effects by incorporating symmetrical biphenyl molecules is proposed, 4,4′‐diaminodiphenyl sulfone (DDS) and 4,4′‐sulfodiphenol (SDP), aiming to mitigate defects at GBs and optimize energy level arrangements through their electric dipole effects. Compared to the pristine device, the SDP‐modified device exhibits significant improvements, including a champion efficiency of 24.39% and an impressive fill factor, along with excellent operation stability. This work provides an effective and straightforward solution for improving the performance of PSCs. [ABSTRACT FROM AUTHOR]

Driven by their many unique features, perovskite solar cells (PSCs) have become one of the most promising candidates in the photovoltaic field. Two‐step preparation of perovskite film is advantageous for its higher stability and reproducibility compared to the one‐step method, which is more suitable for practical application. However, the incomplete conversion of the dense lead iodide (PbI2) layer during the sequential spin‐coating of formamidinium/methylammonium (FA+/MA+) organic amine salts severely affect the performance of PSCs. Herein, sodium bicarbonate (NaHCO3) is used to induce the formation of porous PbI2, which facilitates the penetration of the FA+/MA+ ions and the formation of a perovskite film with high crystallinity and large grain microstructure. Meanwhile, the introduction of Na+ not only improves the energetic alignment of the PSC, but also increases the conductivity via p‐doping. As a result, the optimized NaHCO3‐modified PSC achieves a champion power conversion efficiency of 24.0% with suppressed hysteresis. Moreover, the significant reduction in defect density and ion migration as well as a mild alkaline environment enhance the stability of device. The unencapsulated NaHCO3‐modified PSCs maintain over 90% of their original efficiency upon storage in ambient air (30%–40% relative humidity) for 2160 h. We have demonstrated an ingenious strategy for controlling the quality of perovskite and improving the performance of device by low‐temperature foaming of simple inorganic molecules of NaHCO3. [ABSTRACT FROM AUTHOR]

Objective. Explore the ultrasound characteristics of early postpartum Diastasis Recti Abdominis (DRA) and provide effective data support for its clinical diagnosis and treatment. Method. A total of 458 parturients who were diagnosed with DRA in the Chongqing Maternal and Child Health Hospital from December 2017 to September 2020 underwent postpartum ultrasound examinations. All of which were located at four points: 6 cm above the umbilicus (point 1), 3 cm above the umbilicus (point 2), umbilicus (point 3), and 3 cm below the umbilicus (point 4) to detect the interrectus distance (IRD) in the resting and sit-up state of the parturients postpartum and to study the differences in maternal age, weight, and ultrasound diagnosis of IRD at different stages after delivery. Results. The IRD values of the four measurement points in the resting state of the parturient were significantly greater than the IRD values in the sit-up state. And in the resting state, the IRD value (4.31 ± 1.07 cm) of the point 3 region was the largest, and there were significant differences at different stages of the postpartum women. At the same time, the IRD values of points 3 and 4 have significant differences in parturient of different ages. In addition, the IRD values of the four measurement points of overweight women were higher than those of nonoverweight women. Conclusion. The umbilicus is the best ultrasound evaluation point for early postpartum DRA. The IRD value at this point in the resting state can be used as reference data for evaluating early postpartum DRA, which provides a useful reference for rapid postpartum recovery of parturients. [ABSTRACT FROM AUTHOR]

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that most commonly affects the apocrine glands of older men and women. Because it is associated with other cancers, early diagnosis and evaluation are needed. This study is to evaluate the value of reflectance confocal microscopy (RCM) in diagnosing EMPD. A total of 73 patients with clinically suspicious diagnosis of EMPD were enrolled in this study, and the RCM device imaged their lesions. Moreover, 67 patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then evaluated the RCM value of biopsy‐confirmed lesions. Based on the RCM image analysis, 54 of 73 (74.0%) patients were diagnosed with EMPD. Of all 67 biopsied lesions, 52 (77.6%) were EMPD. Then, we analyzed the RCM characteristics of 52 cases of biopsy‐confirmed EMPD, compared their RCM image characteristics of three different lesions of EMPD, and further concluded the key points of EMPD under RCM microscopy based on the 52 EMPD cases. Finally, we focused on the differential diagnosis of EMPD from other skin diseases. RCM showed great diagnostic value in diagnosing EMPD. [ABSTRACT FROM AUTHOR]

Background: Actinic keratosis (AK) occurs frequently in sun‐exposed skin while its diagnosis and treatment were still in exploration. Materials and methods: Thirty two patients with facial AK lesions were selected and examined with reflective confocal microscopy (RCM) firstly, followed by biopsy at the same site. RCM was used to observe AK lesions before 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) treatment, after the first treatment, after 4 treatments, and at 1 and 6 months follow‐up. Retrospective analysis of RCM images was performed. Results: Thirty two AK cases showed initial RCM microscopic features including disorderly arranged epidermal cells (100%), atypical keratinocytes (100%), and blurry border between the epidermis and dermis (100%). 4 patients quitted trail. After treatments, 24 cases showed basically regular arrangement of epidermal cells, absent atypical keratinocytes, and clear border between epidermis and dermis, while 4 cases improved little. At 1 and 6 months follow‐up, 23 cases remained relapse‐free while 1 case developed recurrent symptoms. Effective rate of 4 ALA‐PDT treatments for AK was 100%; recurrence and cure rates were 4.2% and 82.1%, respectively. Conclusion: ALA‐PDT is effective to treat AK, while RCM can be recommended for in vivo evaluating and monitoring the effect of ALA‐PDT on AK. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic immune‐mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL‐17 and IL‐22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down‐regulated KRT6 mRNA and protein expression while up‐regulated KRT10 mRNA and protein expression within IL‐22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63‐mediated transcription of KRT10, therefore improving psoriasis. [ABSTRACT FROM AUTHOR]

Solid-state fluorescence switches have attracted tremendous attention in recent years owing to their applications in fluorescent sensors, security inks and data storage. Herein, we report a novel molecule (2NR) composed of two naphthalimide moieties and a Rhodamine 6G (R6G) unit linked by a branched amidoamine spacer. 2NR exhibits excellent acid and force dual-stimuli-responsive behaviour in the solid state: (i) exposing 2NR powder to HCl vapour results in fluorescence off–on switching, because protonation of the tertiary amine by acid impedes the photoinduced electron transfer process; (ii) further treatment with grinding, the force-induced open-ring reaction of R6G and subsequent efficient fluorescence resonance energy transfer from naphthalimide to the open-ring form of R6G realizes a high-contrast fluorescent colour change. Moreover, the branched amidoamine spacer induces a twisted conformation of naphthalene moieties, which provides considerable free volume and significantly facilitates the isomerization process of R6G from spirolactam to open-ring amide. Both fluorescence switches have good reversibility. Consequently, the excellent solid-state fluorescent switching of 2NR is highly applicable for anti-counterfeiting materials. [ABSTRACT FROM AUTHOR]

Reducing costs is a pragmatic method for promoting the widespread usage of indoor localization technology. Conventional indoor localization systems (ILSs) exploit relatively expensive wireless chips to measure received signal strength for positioning. Our work is based on a cheap and widely-used commercial off-the-shelf (COTS) wireless chip, i.e., the Nordic Semiconductor nRF24LE1, which has only several output power levels, and proposes a new power level based-ILS, called Plils. The localization procedure incorporates two phases: an offline training phase and an online localization phase. In the offline training phase, a self-organizing map (SOM) is utilized for dividing a target area into k subregions, wherein their grids in the same subregion have similar fingerprints. In the online localization phase, the support vector machine (SVM) and back propagation (BP) neural network methods are adopted to identify which subregion a tagged object is located in, and calculate its exact location, respectively. The reasonable value for k has been discussed as well. Our experiments show that Plils achieves 75 cm accuracy on average, and is robust to indoor obstacles. [ABSTRACT FROM AUTHOR]

Exosomes are small membrane-bound vesicles (30-100 nm) that are secreted by different types of cells and they have been well documented to resemble saucers or flattened spheres under the electron microscope. Recently, evidence indicates that exosomes play important roles in the immune modulation and are associated with the immune pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA), Sjogren’s syndrome (SS) and systemic lupus erythematosus (SLE). In this review, we will summarize current research advances of exosomes in immunoregulation, pathogenesis, diagnosis and therapeutics of autoimmune diseases. [ABSTRACT FROM AUTHOR]

DNA methylation plays an important role in the epigenetic regulation of mammalian gene expression. TET (ten-eleven translocation) proteins, newly discovered demethylases, have sparked great interest since their discovery. TET proteins catalyze 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in 3 consecutive Fe(II)- and 2-oxoglutarate (2-OG)-dependent oxidation reactions. TET proteins dynamically regulate global or locus-specific 5-methylcytosine and/or 5-hydroxymethylcytosine levels by facilitating active DNA demethylation. In fact, in addition to their role as methylcytosine dioxygenases, TET proteins are closely related to histone modification, interact with metabolic enzymes as well as other proteins, and cooperate in transcriptional regulation. In this review, we summarize the recent progress in this exciting field, highlighting the molecular mechanism by which TET enzymes regulate gene expression and their functions in health and disease. We also discuss the therapeutic potential of targeting TET proteins and aberrant DNA modifications. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease of multifactorial pathoaetiology. One of the most serious manifestations is lupus nephritis. The pathogenesis of SLE has not been well elucidated, but it has been reported that interleukin-17 (IL-17) and Th17 cells play important roles in the pathogenesis of SLE. IL-17A, a member of IL-17 family, amplifies the immune response by inducing the local production of chemokines and cytokines, recruiting neutrophils and monocytes, augmenting the production of autoantibodies, and aggravating the inflammation and damage of target organs such as the kidney in SLE. In recent years, several IL-17A pathway inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibody and the anti-17RA monoclonal antibody. Several agents have shown great success in Phase II trials in multiple autoimmune diseases such as psoriasis, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and non-infectious uveitis, which has sparked the urgent need of anti-IL-17A as innovative therapeutic option in controlling disease activity of moderate-to-severe SLE. Here, we review and summarize current progress in IL-17A and SLE fromin vitrostudies, human expression studies, and animal models, providing novel insight into its therapeutic potential. [ABSTRACT FROM AUTHOR]

Highlights: [•] One session of PDT plus CO2 laser may be enough for some patients with fewer warts. [•] Response rate and recurrence rate are the same in perianal and external genital CA. [•] CO2 laser vaporation plus ALA-PDT is a highly effective modality for treating CA. [Copyright &y& Elsevier]

Objective: Acute mixed-lineage leukemia (AMLL) is characterized as the acute leukemia involved with acute myeloid cells and lymphoid cells at the same time. The AMLL is easily misdiagnosed because of a dual character involved with lymphoid and myeloid cells. At present, researches of AMLL in adults are more common. Only some are reported for children. Therefore, our aim was to study clinical characteristics of the childhood AMLL. Methods: From January 2000 to July 2009, 14 cases of AMLL children were selected by morphological and immunophenotyping methods from 185 cases of childhood acute leukemia admitted to the Department of Pediatrics, Tongji Hospital, Tongji Medical College of Science and Technology of Huazhong University. Medical records of all AMLL cases were reviewed for clinical characteristics. Findings: Fourteen cases of AMLL were screened from 185 cases of acute leukemia by morphology, immunology, cytogenetics and molecular (MICM). The rate of childhood AMLL accounted for 7.57% of pediatric acute leukemia (AL) diagnosed in the research period; white blood cell count in most of the patients was normal, the average value being 31.0×109/L in the first visit. In the 14 cases of AMLL, 8 cases were B-Ly+/My+, 2 cases were T-Ly+/My+B, and 4 were T+B-Ly+/My+. Among them, nine cases received treatment. Consequently, 6 cases reached complete remission (CR); 1 case had not complete remission; 2 cases did not complete the treatment. Conclusion: The diagnosis of AMLL should depend on the comprehensive evaluation of MICM. As there are still many problems concerning AMLL, it is very necessary that the research units collaborate with each other to improve the prognosis of childhood AMLL. The limitations and applications of the results are that they are only based on the patients of one hospital. [ABSTRACT FROM AUTHOR]

Far less has been unveiled about the functions of lncRNAs on cancers yet. Here, we reported that lncRNA FAM87A, as a ceRNA of miR-424-5p, played a vital role in glioma development. qRT-PCR result indicated that FAM87A was abnormally downregulated in glioma tissue and cells. Survival analysis suggested that the FAM87A expression was negatively correlated with the survival rate. Effects of FAM87A on human glioma cell lines were also analyzed by MTT, Edu, and transwell assays. FAM87A hastened proliferation and migration of glioma cells. MiR-424-5p, predicted target of FAM87A, was fostered in glioma, which was examined by qRT-PCR. A negative correlation was indicated between FAM87A and miR-424-5p. Results of bioinformatics, dual luciferase, and RIP assays unveiled that FAM87A and miR-424-5p act upon each other. In addition, miR-424-5p targeted 3 ′ -UTR of PPM1H. Also, effects of miR-424-5p/FAM87A on glioma cells were identified via the cell function experiments. FAM87A suppressed PPM1H by binding to miR-424-5p competitively, thereby restraining cell proliferation, migration, and invasion. Collectively, these findings illuminated a new mechanism for glioma progression. Therefore, FAM87A may act as a feasible target for glioma treatment. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement. It is characterized by abundant autoantibodies that form immune complex with autoantigens and deposit in organs and cause tissue damage by inducing inflammation. The pathogenesis of SLE has been intensively studied but remains unclear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are believed to contribute to the initiation and development of SLE. The up-to-date research findings point to the relationship between abnormal DNA methylation and SLE, which has attracted considerable interest worldwide. Besides the global hypomethylation on lupus T and B cells, the gene specific and site-specific methylation has been identified and documented to be responsible for SLE. The purpose of this review was to present and summarize the association between aberrant DNA methylation of immune cells and SLE, the possible mechanisms of immune dysfunction caused by DNA methylation, and to better understand the roles of aberrant DNA methylation in the initiation and development of SLE and to provide an insight into the related diagnosis biomarkers and therapeutic options in SLE. [ABSTRACT FROM AUTHOR]

Depression is the most common comorbidities associated with rheumatoid arthritis (RA). We aimed to explore the mechanism of association between RA and depression. 120 subjects were enrolled and depression was diagnosed and assessed using DSM-5 and 24-item version of Hamilton Depression Scale. Pain intensity and joint function in patients with RA were assessed using the visual analog scale (VAS) and health assessment questionnaire (HAQ). Serum levels of interferon-gamma (IFN-γ), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), tryptophan (TRP), and quinolinic acid (QUIN)were detected. In animal experiments, K/BxN mice with RA-like phenotype was used and depressive behavior was observed. The protein expression level of N-methyl -D- aspartate receptor 2B (NR2B) in the hippocampus was detected. In this study, 36.67 % of patients with RA also had depression. The working status, month family income, tender joint count, the VAS and HAQ score were the main factors influencing the depression in RA patients. HAQ score was found to be an independent risk factor for depression in RA. Serum IDO, IFN-γ, KYN were increased and TRP contents were decreased in RA group. K/BxN mice with RA-like phenotype showed depressive behavior. However, injection of IFN-γ neutralizing antibody could inhibit kynurenine pathway and reverse the depressive behavior in mice. The levels of QUIN in the neurotoxic metabolic pathway were increased and N-methyl -D- aspartate receptors (NMDAR) were activated, which may be the mechanism behind the onset of depression. From clinical and preclinical aspects, the occurrence of depression in RA was explored and the related mechanism was revealed. [Display omitted] • 36.67% of RA patients developed depression, and HAQ scores were found to be an independent risk factor. • In RA group, serum IDO, IFN-γ, KYN were increased and TRP decreased. • K/BxN mice with RA- like phenotype showed depressive behavior. • The injection of IFN-γ neutralizing antibody can inhibit the kynurenine pathway and reverse the depressive behavior. • The IFN-γ-induced kynurenine pathway, which activates NMDAR via QUIN, may be the pathogenesis of depression in RA. [ABSTRACT FROM AUTHOR]