Immunoglobulin M perception by FcµR.

Immunoglobulin M (IgM) is the first antibody to emerge during embryonic development and the humoral immune response1. IgM can exist in several distinct forms, including monomeric, membrane-bound IgM within the B cell receptor (BCR) complex, pentameric and hexameric IgM in serum and secretory IgM on the mucosal surface. FcµR, the only IgM-specific receptor in mammals, recognizes different forms of IgM to regulate diverse immune responses2-5. However, the underlying molecular mechanisms remain unknown. Here we delineate the structural basis of the FcµR-IgM interaction by crystallography and cryo-electron microscopy. We show that two FcµR molecules interact with a Fcµ-Cµ4 dimer, suggesting that FcµR can bind to membrane-bound IgM with a 2:1 stoichiometry. Further analyses reveal that FcµR-binding sites are accessible in the context of IgM BCR. By contrast, pentameric IgM can recruit four FcµR molecules to bind on the same side and thereby facilitate the formation of an FcµR oligomer. One of these FcµR molecules occupies the binding site of the secretory component. Nevertheless, four FcµR molecules bind to the other side of secretory component-containing secretory IgM, consistent with the function of FcµR in the retrotransport of secretory IgM. These results reveal intricate mechanisms of IgM perception by FcµR.

Deletion of Dux ameliorates muscular dystrophy in mdx mice by attenuating oxidative stress via Nrf2.

DUX4 has been widely reported in facioscapulohumeral muscular dystrophy, but its role in Duchenne muscular dystrophy (DMD) is unclear. Dux is the mouse paralog of DUX4. In Dux-/- mdx mice, forelimb grip strength test and treadmill test were performed, and extensor digitorum longus (EDL) contraction properties were measured to assess skeletal muscle function. Pathological changes in mice were determined by serum CK and LDH levels and muscle Masson staining. Inflammatory factors, oxidative stress, and mitochondrial function indicators were detected using kits. Primary muscle satellite cells were isolated, and the antioxidant molecule Nrf2 was detected. MTT assay and Edu assay were used to evaluate proliferation and TUNEL assay for cell death. The results show that the deletion of Dux enhanced forelimb grip strength and EDL contractility, prolonged running time and distance in mdx mice. Deleting Dux also attenuated muscle fibrosis, inflammation, oxidative stress, and mitochondrial dysfunction in mdx mice. Furthermore, Dux deficiency promoted proliferation and survival of muscle satellite cells by increasing Nrf2 levels in mdx mice.

Heterogeneous Rhodium Single-Atom-Site Catalyst Enables Chemoselective Carbene N-H Bond Insertion.

Transition-metal-catalyzed carbene insertion reactions of a nitrogen-hydrogen bond have emerged as robust and versatile methods for the construction of C-N bonds. While significant progress of homogeneous catalytic metal carbene N-H insertions has been achieved, the control of chemoselectivity in the field remains challenging due to the high electrophilicity of the metal carbene intermediates. Herein, we present an efficient strategy for the synthesis of a rhodium single-atom-site catalyst (Rh-SA) that incorporates a Rh atom surrounded by three nitrogen atoms and one phosphorus atom doped in a carbon support. This Rh-SA catalyst, with a catalyst loading of only 0.15 mol %, exhibited exceptional catalytic performance for heterogeneous carbene insertion with various anilines and heteroaryl amines in combination with diazo esters. Importantly, the heterogeneous catalyst selectively transformed aniline derivatives bearing multiple nucleophilic moieties into single N-H insertion isomers, while the popular homogeneous Rh2(OAc)4 catalyst produced a mixture of overfunctionalized side products. Additionally, similar selectivities for N-H bond insertion with a set of stereoelectronically diverse diazo esters were obtained, highlighting the general applicability of this heterogeneous catalysis approach. On the basis of density functional theory calculations, the observed selectivity of the Rh-SA catalyst was attributed to the insertion barriers and the accelerated proton transfer assisted by the phosphorus atom in the support. Overall, this investigation of heterogeneous metal-catalyzed carbene insertion underscores the potential of single-atom-site catalysis as a powerful and complementary tool in organic synthesis.

Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.

BACKGROUND: Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency. METHODS: We treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA. Data from the two U.S. studies (in which fresh and cryopreserved formulations were used) at 24 months of follow-up were analyzed alongside data from the U.K. study (in which a fresh formulation was used) at 36 months of follow-up. RESULTS: Overall survival was 100% in all studies up to 24 and 36 months. Event-free survival (in the absence of reinitiation of enzyme-replacement therapy or rescue allogeneic hematopoietic stem-cell transplantation) was 97% (U.S. studies) and 100% (U.K. study) at 12 months; 97% and 95%, respectively, at 24 months; and 95% (U.K. study) at 36 months. Engraftment of genetically modified HSPCs persisted in 29 of 30 patients in the U.S. studies and in 19 of 20 patients in the U.K. study. Patients had sustained metabolic detoxification and normalization of ADA activity levels. Immune reconstitution was robust, with 90% of the patients in the U.S. studies and 100% of those in the U.K. study discontinuing immunoglobulin-replacement therapy by 24 months and 36 months, respectively. No evidence of monoclonal expansion, leukoproliferative complications, or emergence of replication-competent lentivirus was noted, and no events of autoimmunity or graft-versus-host disease occurred. Most adverse events were of low grade. CONCLUSIONS: Treatment of ADA-SCID with ex vivo lentiviral HSPC gene therapy resulted in high overall and event-free survival with sustained ADA expression, metabolic correction, and functional immune reconstitution. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01852071, NCT02999984, and NCT01380990.).

Deep sequencing of 1320 genes reveals the landscape of protein-truncating variants and their contribution to psoriasis in 19,973 Chinese individuals.

Protein-truncating variants (PTVs) have important impacts on phenotype diversity and disease. However, their population genetics characteristics in more globally diverse populations are not well defined. Here, we describe patterns of PTVs in 1320 genes sequenced in 10,539 healthy controls and 9434 patients with psoriasis, all of Han Chinese ancestry. We identify 8720 PTVs, of which 77% are novel, and estimate 88% of all PTVs are deleterious and subject to purifying selection. Furthermore, we show that individuals with psoriasis have a significantly higher burden of PTVs compared to controls (P = 0.02). Finally, we identified 18 PTVs in 14 genes with unusually high levels of population differentiation, consistent with the action of local adaptation. Our study provides insights into patterns and consequences of PTVs.

miR-92b-3p protects retinal tissues against DNA damage and apoptosis by targeting BTG2 in experimental myopia.

BACKGROUND: Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2. METHODS: Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting. RESULTS: Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia. CONCLUSION: In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.

Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review.

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.

One-Pot Synthesis of C@BiOBr for Efficient Photocatalytic Degradation of Phenol.

This work describes the synthesis of C@BiOBr using glucose as the carbon precursor by a repeatable one-step hydrothermal method. Characterization studies indicate that the structure of BiOBr did not change after the carbon layer was encapsulated on the surface. The highest activity is achieved at 1.2-C@BiOBr, with 97% of phenol (50 mg·L-1) degrading within 90 min, and the degradation amount of phenol is determined to be 48.5 mg·g-1 with a speed of 0.54 mg·g-1·min-1. The useful species of phenol degradation are studied and assigned to •O2-, 1O2, and h+. The effect of coated carbon layer for photocatalytic degradation of phenol over BiOBr is studied by photoelectrochemical experiments, fluorescence spectra, and density functional theory (DFT) calculations. It is attributed to the good conductivity of carbon, enhanced separation of the photocarriers by carbon coating, and thermodynamically favorable reactive oxygen species (ROS) production on the surface of carbon. This work demonstrates that carbon coating is an effective strategy to improve the photocatalytic activity of BiOBr and reveals the detailed mechanism.

Highly Sensitive, Stable InP Quantum Dot Fluorescent Probes for Quantitative Immunoassay Through Nanostructure Tailoring and Biotin-Streptavidin Coupling.

Nontoxic, highly sensitive InP quantum dot (QD) fluorescent immunoassay probes are promising biomedical detection modalities due to their unique properties. However, InP-based QDs are prone to surface oxidation, and the stability of InP QD-based probes in biocompatible environments remains a crucial challenge. Although the thick shell can provide some protection during the phase transfer process of hydrophobic QDs, the photoluminescence quantum yield (PLQY) is generally decreased because of the contradiction between lattice stress relaxation and thick shell growth. Herein, we developed thick-shell InP-based core/shell QDs by inserting a ZnSeS alloy layer. The ternary ZnSeS intermediate shell could effectively facilitate lattice stress relaxation and passivate the defect states. The synthesized InP/ZnSe/ZnSeS/ZnS core/alloy shell/shell QDs (CAS-InP QDs) with nanostructure tailoring revealed a larger size, high PLQY (90%), and high optical stability. After amphiphilic polymer encapsulation, the aqueous CAS-InP QDs presented almost constant fluorescence attenuation and stable PL intensity under different temperatures, UV radiation, and pH solutions. The CAS-InP QDs were excellent labels of the fluorescence-linked immunosorbent assay (FLISA) for detecting C-reactive protein (CRP). The biotin-streptavidin (Bio-SA) system was first introduced in the FLISA to further improve the sensitivity, and the CAS-InP QDs-based SA-Bio sandwich FLISA realized the detection of CRP with an impressive limit of detection (LOD) of 0.83 ng/mL. It is believed that the stable and sensitive InP QD fluorescent probes will drive the rapid development of future eco-friendly, cost-effective, and sensitive in vitro diagnostic kits.

The role of oxidative stress in the pathogenesis of ocular diseases: an overview.

Dysregulation of oxidative stress serves as a pivotal predisposing or exacerbating factor in the intricate development of numerous pathological processes and diseases. In recent years, substantial evidence has illuminated the crucial role of reactive oxygen species (ROS) in many fundamental cellular functions, including proliferation, inflammation, apoptosis, and gene expression. Notably, producing free radicals within ROS profoundly impacts a wide range of biomolecules, such as proteins and DNA, instigating cellular damage and impairing vital cellular functions. Consequently, oxidative stress emerges as a closely intertwined factor across diverse disease spectra. Remarkably, the pathogenesis of several eye diseases, including age-related macular degeneration, glaucoma, and diabetic retinopathy, manifests an intrinsic association with oxidative stress. In this comprehensive review, we briefly summarize the recent progress in elucidating the intricate role of oxidative stress in the development of ophthalmic diseases, shedding light on potential therapeutic avenues and future research directions.

A Correlation Analysis Between Adult Hepatic Fibrosis and Bone Mineral Density of the Lumbar Spine and Hip.

Context: Osteoporosis (OP) is a common complication for patients who have liver cirrhosis or cholestatic liver disease or who have received a liver transplantation. Osteoporotic fractures are serious clinical consequences of OP, and they often occur in the spine, hip, and wrist; have a high disability and mortality rate; cause a serious, social, medical burden; and threaten people's health. Objective: The study intended to explore the correlation between different degrees of liver fibrosis and bone mineral density (BMD) of the lumbar spine and hip as well as the factors influencing those differences. Design: The research team performed a retrospective observational study. Setting: The study took place at the First Affiliated Hospital of the Medical College at Ningbo University (Bund Courtyard) in Ningbo, China. Participants: Participants were 164 patients who had received two-dimensional shear wave elastography (2D-SWE) to measure liver stiffness and dual-energy X-ray absorptiometry (DEXA) to measure bone density at the First Affiliated Hospital of Ningbo University (Bund Courtyard) in Ningbo from May 2020 to April 2022. Groups: According to the liver-stiffness value, the research team divided participants into three groups: (1) the F0-F1 group with no or mild liver fibrosis, (2) the F2 group with significant liver fibrosis, and (3) F3-F4 group with severe liver fibrosis. For the three groups, the research team also compared the differences between the groups-F0-F1 to F2, F0-F1 to F3-F4, and F2 to F3-F4-in the BMD of the lumbar spine-Total, L2, L3, L4-and of the hip-Total, Neck, and Troch. Outcome Measures: The research team: (1) determined participants' degrees of liver fibrosis to create the F0-F1, F2, and F3-F4 groups and compared the BMDs of the lumbar spine and hip among those groups; (2) compared the degrees of liver fibrosis for three age groups-<40, 40-60, and ≥60 years old; (3) compared the degrees of liver fibrosis for participants with two etiologies of the disease-hepatitis or other causes; and (4) analyzed the correlations between different degrees of liver fibrosis and BMD of the lumbar spine and hip and the factors influencing those relationships. Results: The study revealed significant differences among the F0-F1, F2, and F3-F4 groups in terms of age group, degree of liver fibrosis, and bone mineral density (BMD) at various sites. Specifically, there were significant age group differences between individuals aged 40-60 years and those aged ≥60 years (P < .05). There were also significant differences noted in the degree of liver fibrosis with mean values of 5.59 ± 0.81, 7.43 ± 0.26, and 15.48 ± 10.02 for the F0-F1, F2, and F3-F4 groups, respectively (P < .05). The BMDs of the lumbar spine (L2, L3, L4, and Total values) and hip (Total values, right femoral neck (Neck), and trochantor (Troch)) showed significant differences (all P < .05). However, no significant differences were found in the BMDs for the L1 vertebra and Ward's triangle among the groups (both P > .05). The analysis also revealed that the mean BMDs of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups. Furthermore, there was a positive correlation between the F2 and F0-F1 groups and a negative correlation between the F2 and F3-F4 groups (P < .05). The logistic regression analysis showed that age group (OR = 2.047, 95% CI: 0.135-1.298, P = .016) and Total BMD for the hip (OR = 176.368, 95% CI: 0.233-10.112, P = .040) were significantly, independently correlated with the degree of liver fibrosis. Conclusions: According to the findings of the present study, a positive correlation was observed between liver stiffness and bone mineral density (BMD) values in patients at the F0-F1 to F2 stage of liver fibrosis. In contrast, a significant negative correlation was identified between these parameters in patients at the F2 to F3-F4 stage, indicating that BMD tends to decrease as the degree of liver fibrosis increases. These results suggest a potential link between liver fibrosis and bone health. The comparisons between groups F0-F1 and F3-F4 with group F2. Specifically, the study found that the BMD values of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups.

Photoinduced Low-Valent Zirconium Catalysis for Cross-Electrophile Coupling of Ethers.

Accessing versatile C(sp3)-C(sp3) bond through the cross-electrophile coupling of two distinct etheric C-O bonds is crucial in organic synthesis but remains barely explored. Herein, we report an innovative photoinduced low-valent zirconocene catalysis enabling the reductive coupling of ethers with high activity and cross-selectivity. Mechanistic investigation suggests that photoexcitation of low-valent zirconocene facilitates the C(sp3)-O bond scission of benzylic ethers, leading to the benzylic radicals intermediate via a single-electron reduction pathway. The subsequent recombination of this benzylic radical with the Zr center followed by carbomagnesiation generates benzylic Grignard reagents for downstream coupling with aliphatic ethers through an SN2-like mechanism. In application, a wide range of ethers readily in situ derived from aldehydes and ketones becomes feasible with high functional group compatibility as well as excellent cross-selectivity.

Stability of collagen heterotrimer with same charge pattern and different charged residue identities.

Salt bridges are important factors in maintaining the stability of proteins, and their contribution to protein folding has received much attention. Although the interaction energies, or stabilizing contributions, of individual salt bridges have been measured in various proteins, a systematic assessment of various types of salt bridges in a relatively uniform environment is still a valuable analysis. Here, we used a collagen heterotrimer as a host-guest platform to construct 48 heterotrimers with the same charge pattern. A variety of salt bridges were formed between the oppositely charged residues Lys, Arg, Asp, and Glu. The melting temperature (Tm) of the heterotrimers was measured with circular dichroism. The atomic structures of 10 salt bridges were shown in three x-ray crystals of heterotrimer. Molecular dynamics simulation based on the crystal structures indicated that strong, intermediate, and weak salt bridges have distinctive N-O distances. A linear regression model was used to predict the stability of heterotrimers with high accuracy (R2 = 0.93). We developed an online database to help readers understand how a salt bridge stabilizes collagen. This work will help us better understand the stabilizing mechanism of salt bridges in collagen folding and provide a new strategy to design collagen heterotrimers.

Femtosecond-laser-based full-field three-dimensional imaging with phase compensation.

Coherence scanning interferometer (CSI) enables 3D imaging with nanoscale precision. However, the efficiency of such a system is limited because of the restriction imposed by the acquisition system. Herein, we propose a phase compensation method that reduces the interferometric fringe period of femtosecond-laser-based CSI, resulting in larger sampling intervals. We realize this method by synchronizing the heterodyne frequency with the repetition frequency of the femtosecond laser. The experimental results show that our method can keep the root-mean-square axial error down to 2 nm at a high scanning speed of 6.44 µm per frame, which enables fast nanoscale profilometry over a wide area.

Absolute angular position measurement by dual-comb spectroscopy of an autocollimation diffracted beam.

The dual-comb technique is a powerful tool in industrial inspection and scientific research and is capable of realizing ultrahigh-resolution and fast broadband spectral measurements. We propose an absolute angular-position measurement method based on dual-comb spectroscopy. With a simple layout, the absolute angular position can be naturally determined through the traceable and wide-amplitude spectra of the autocollimation diffracted beams of the target grating. We experimentally demonstrate that a precision of 0.12 arcsec in the dynamic range of approximately 6660 arcsec, along with a 1 kHz repetition rate difference, is achieved. Compared with a commercial autocollimator, over 1000 arcsec, the comparison residuals are kept within ±0.3 arcsec.

Hypothalamic hypernatremic myopathy: A single-center case series.

INTRODUCTION/AIMS: Hypernatremia myopathy is a rare disease often unrecognized by clinicians. This study aimed to present a case series of hypernatremic myopathy with an emphasis on profiling its clinical characteristics and exploring its pathogenesis. METHODS: We reviewed seven patients with hypernatremic myopathy and reported their demographic data, etiology, clinical manifestations, and laboratory and electrophysiological characteristics. A muscle biopsy was performed on one patient. RESULTS: All patients had hypothalamic lesions as the cause of the hypernatremia including craniopharyngioma, germinoma, pituitary adenoma, Langerhans cell histiocytosis, and glioma. The clinical manifestations varied from mild weakness to complete paralysis. Myalgia and muscle cramps were also observed. Four of the patients had rhabdomyolysis on admission and developed acute kidney injury. All patients had markedly elevated serum creatine kinase (CK) and sodium levels. There was a significant positive correlation between serum sodium and CK levels. A high prevalence of hypopituitarism in different axes was observed in our study. Central hypogonadism (5 of 7), central hypothyroidism (3 of 7), and central diabetes insipidus (3 of 7) were the most common manifestations of hypothalamic dysfunction. Myopathic changes were observed on needle electromyography. The muscle biopsy of one patient showed diffuse necrotic fibers and scattered hypercontracted fibers with increased ragged red fibers. DISCUSSION: Hypernatremia myopathy should be considered in hypernatremic patients with muscle weakness and myalgia. Rhabdomyolysis frequently occurs and may lead to acute kidney injury in hypernatremia myopathy. Testing of hormone levels and performance of brain magnetic resonance imaging for possible hypothalamic lesions is strongly recommended.

Risk factors for self-reported medication adherence in community-dwelling older patients with multimorbidity and polypharmacy: a multicenter cross-sectional study.

BACKGROUND: Medication nonadherence is a significant public health problem as it contributes to poor clinical outcomes and increased healthcare costs. Older patients with multimorbidity and polypharmacy often have low medication adherence. These patients also have a high prevalence of potentially inappropriate medication (PIM) use. AIM: To explore risk factors related to medication nonadherence in older patients with multimorbidity and polypharmacy and examine the association between medication nonadherence and PIM use. METHOD: A multicenter cross-sectional study was conducted from May to December 2019 in 16 tertiary hospitals from 12 provinces and cities in China. Data were collected from outpatients 65 years or older with multimorbidity and polypharmacy. The PIMs were evaluated using the 2019 Beers Criteria. Self-reported medication adherence was assessed using the Visual Analog Scale (VAS). RESULTS: A total of 773 outpatients were recruited. The prevalence of medication nonadherence was 31.8%. In the univariate analysis, nonadherence was significantly associated with sex, cognitive impairment, stroke, visiting the same physicians, self-administration of medication, the percentage of drug costs ≥ 10% of the medical expenses, and PIMs for the alimentary tract and metabolism. In the multivariate analysis, the results almost paralleled those of the univariate associations. Notably, the use of PIM was significantly associated with medication adherence. CONCLUSION: Several factors that influence medication adherence were identified. Targeted interventions can be implemented to improve medication adherence, such as encouraging self-administering medications and reducing medication expenses.

Identification of Potential Differentially-Methylated/Expressed Genes in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. DNA methylation can regulate gene expression. Understanding the potential molecular mechanism of COPD is of great importance. The aim of this study was to find differentially methylated/expressed genes in COPD. DNA methylation and gene expression profiles in COPD were downloaded from the dataset, followed by functional analysis of differentially-methylated/expressed genes. The potential diagnostic value of these differentially-methylated/expressed genes was determined by receiver operating characteristic (ROC) analysis. Expression validation of differentially-methylated/expressed genes was performed by in vitro experiment and extra online datasets. Totally, 81 hypermethylated-low expression genes and 121 hypomethylated-high expression genes were found in COPD. Among which, 9 core hypermethylated-low expression genes (CD247, CCR7, CD5, IKZF1, SLAMF1, IL2RB, CD3E, CD7 and IL7R) and 8 core hypomethylated-high expression genes (TREM1, AQP9, CD300LF, CLEC12A, NOD2, IRAK3, NLRP3 and LYZ) were identified in the protein-protein interaction (PPI) network. Moreover, these genes had a potential diagnostic utility for COPD. Some signaling pathways were identified in COPD, including T cell receptor signaling pathway, cytokine-cytokine receptor interaction, hematopoietic cell lineage, HTLV-I infection, endocytosis and Jak-STAT signaling pathway. In conclusion, differentially-methylated/expressed genes and involved signaling pathways are likely to be associated with the process of COPD.

Predictive value of hemoglobin-to-red blood cell distribution width ratio for contrast-induced nephropathy after emergency percutaneous coronary intervention.

BACKGROUND: Although the relationship of either hemoglobin or red blood cell distribution width (RDW) with contrast-induced nephropathy (CIN) has been reported individually. To date, no studies have evaluated the predictive value of hemoglobin-to-red blood cell distribution width ratio (HRR) for CIN. METHODS: A total of 1658 elderly patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) were retrospectively screened. Preoperative complete blood count was collected and the HRR was calculated as the ratio of hemoglobin to RDW. CIN was defined as an absolute ≥0.5 mg/dL (44.2 µmol/L) or a relative ≥25% increase in creatinine level at 72 h after contrast administration. Univariate and multivariate regression analysis were conducted to determine the effective predictors for CIN. The ROC curve analysis was plotted to determine the optimal cutoff value for HRR in predicting CIN. RESULTS: The overall incidence of CIN was 8.38%. The HRR was significantly lower in the CIN group compared with the non-CIN group (0.87 ± 0.15 vs 1.24 ± 0.23, p < 0.001). After multivariate regression analysis was performed, HRR was noted to be an effective predictor for the development of CIN (OR 1.617, 95% CI 1.439-2.706, p = 0.014), along with age, creatinine, eGFR, hs-CRP and contrast volume. An optimal cutoff value of 0.94 or lower for HRR was identified with 82.4% sensitivity and 63.5% specificity to predict CIN. CONCLUSION: Lower HRR on admission was an effective predictor for CIN in elderly patients with STEMI undergoing emergency PCI. HRR may be a convenient, economical and reliable biomarker for risk stratification.

Assessment of Cu(II) Removal from Aqueous Solutions by Modified Pomelo Peels: Experiments and Modelling.

In this study, low-cost pomelo peel wastes were used as a bio-sorbent to remove copper ions (e.g., Cu(II)) from aqueous solutions. Prior to testing its Cu(II) removal capability, the structural, physical and chemical characteristics of the sorbent were examined by scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, and Brunauer-Emmett-Teller (BET) surface area analysis. The impacts of the initial pH, temperature, contact time and Cu(II) feed concentration on the Cu(II) biosorption using modified pomelo peels were then assessed. Thermodynamic parameters associated to the biosorption clearly demonstrate that this biosorption is thermodynamically feasible, endothermic, spontaneous and entropy driven. Furthermore, adsorption kinetic data were found to fit very well with the pseudo-second order kinetics equation, highlighting that this process is driven by a chemical adsorption. Finally, an artificial neural network with a 4:9:1 structure was then established for describing the Cu(II) adsorption using modified pomelo peels with R2 values close to 0.9999 and to 0.9988 for the training and testing sets, respectively. The results present a big potential use of the as-prepared bio-sorbent for the removal of Cu(II), as well as an efficient green technology for ecological and environmental sustainability.