Differences and Similarities in Diabetes Research between China and the USA

Diabetes mellitus is one of the major non-communicable diseases (NCD) with increasing prevalence in China. There is a lack of high-quality research focusing on prevention and management of diabetes in low and middle income countries (LMICs) compared to developed countries. This comparative study aims to describe the characteristics of diabetes research conducted in China and the USA. The study included 800 studies on diabetes mellitus from both countries. Compared with studies in the USA, studies in China were more likely to be laboratory-based primary research (50.5% versus 30.8%), more likely to use animal subjects (47% versus 27.5%), more likely to focused on risk factors (22.7% versus. 14.7%), more likely to be case-controlled studies (17.7% versus 10.0%), and more likely to evaluate pharmacological treatments (36.5% versus 20.7%). Further, compared with studies in the USA, studies in China were less likely to involve patients (42.7% versus 60.7%), less likely to be clinical trials (6.2% versus 14.5%), less likely to be cohort studies (8.8% versus. 26.0%), and less likely to evaluate disease management interventions (3.3% versus 13.3%). Clinical studies in China should be more patient-based to facilitate more effective control and management of diabetes

Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

Use of Xinfeng capsule to treat abarticular pathologic changes in patients with rheumatoid arthritis

AbstractObjectiveTo observe the influence of Xinfeng-capsule (XFC) on abarticular pathologic changes (APCs) and other indices of patients with rheumatoid arthritis (RA) and explore the mechanism of action of XFC in improving such changes.MethodsThree-hundred RA patients were divided randomly into a treatment group (n=150) and control group (n=150). A normal control (NC) group (n=90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured. Curative effects of the two groups were compared, and comparison carried out with the NC group.ResultsIn 300 RA patients, late diastolic peak flow velocity (A peak) was much higher (P<0.01) and early diastolic peak flow velocity (E peak), E/A, and left ventricular fraction shortening much lower (P<0.01) than those in the NC group. Vital capacity (VC), forced vital capacity in one second, forced vital capacity (FVC), maximal voluntary ventilation (MVV), maximal expiratory flow in 50% of VC (FEF50) and FEF75 were lowered remarkably (P< 0.05 or P<0.01). Platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) increased markedly (P<0.05 or P<0.01), and hemoglobin (Hb) level decreased significantly (P<0.05). After XFC treatment, the A peak and PLT and PCT were much lower (P<0.05), and E/A and the number of red blood cells as well as Hb level were much higher (P< 0.05), as were FVC, MVV and FEF50 (P<0.05 or P< 0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints, uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 + CD25 + regulation T cells (Treg) and CD4 + CD25 + CD127-Treg were much higher (P<0.05 or P<0.01) in the treatment group than those in the NC group.ConclusionRA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients

Functional determination of calcium-binding sites required for the activation of inositol 1,4,5-trisphosphate receptors

Inositol 1,4,5-trisphosphate receptors (IP3Rs) initiate a diverse array of physiological responses by carefully orchestrating intracellular calcium (Ca2+) signals in response to various external cues. Notably, IP3R channel activity is determined by several obligatory factors, including IP3, Ca2+, and ATP. The critical basic amino acid residues in the N-terminal IP3-binding core (IBC) region that facilitate IP3 binding are well characterized. In contrast, the residues conferring regulation by Ca2+ have yet to be ascertained. Using comparative structural analysis of Ca2+-binding sites identified in two main families of intracellular Ca2+-release channels, ryanodine receptors (RyRs) and IP3Rs, we identified putative acidic residues coordinating Ca2+ in the cytosolic calcium sensor region in IP3Rs. We determined the consequences of substituting putative Ca2+ binding, acidic residues in IP3R family members. We show that the agonist-induced Ca2+ release, single-channel open probability (P0), and Ca2+ sensitivities are markedly altered when the negative charge on the conserved acidic side chain residues is neutralized. Remarkably, neutralizing the negatively charged side chain on two of the residues individually in the putative Ca2+-binding pocket shifted the Ca2+ required to activate IP3R to higher concentrations, indicating that these residues likely are a component of the Ca2+ activation site in IP3R. Taken together, our findings indicate that Ca2+ binding to a well-conserved activation site is a common underlying mechanism resulting in increased channel activity shared by IP3Rs and RyRs

Single-particle cryo-EM of the ryanodine receptor channel

Ryanodine receptors (RyRs) are tetrameric ligand-gated Ca2+ release channels that are responsible for the increase of cytosolic Ca2+ concentration leading to muscle contraction. Our current understanding of RyR channel gating and regulation is greatly limited due to the lack of a high-resolution structure of the channel protein. The enormous size and unwieldy shape of Ca2+ release channels make X-ray or NMR methods difficult to apply for high-resolution structural analysis of the full-length functional channel. Single-particle electron cryo-microscopy (cryo-EM) is one of the only effective techniques for the study of such a large integral membrane protein and its molecular interactions. Despite recent developments in cryo-EM technologies and break-through single-particle cryo-EM studies of ion channels, cryospecimen preparation, particularly the presence of detergent in the buffer, remains the main impediment to obtaining atomic-resolution structures of ion channels and a multitude of other integral membrane protein complexes. In this review we will discuss properties of several detergents that have been successfully utilized in cryo-EM studies of ion channels and the emergence of the detergent alternative amphipol to stabilize ion channels for structure-function characterization. Future structural studies of challenging specimen like ion channels are likely to be facilitated by cryo-EM amenable detergents or alternative surfactants

Single-particle cryo-EM of the ryanodine receptor channel in an aqueous environment.

Abstract Ryanodine receptors (RyRs) are tetrameric ligand-gated Ca 2+ release channels that are responsible for the increase of cytosolic Ca 2+ concentration leading to muscle contraction. Our current understanding of RyR channel gating and regulation is greatly limited due to the lack of a high-resolution structure of the channel protein. The enormous size and unwieldy shape of Ca 2+ release channels make X-ray or NMR methods difficult to apply for high-resolution structural analysis of the full-length functional channel. Single-particle electron cryomicroscopy (cryo-EM) is one of the only effective techniques for the study of such a large integral membrane protein and its molecular interactions. Despite recent developments in cryo-EM technologies and break-through single-particle cryo-EM studies of ion channels, cryospecimen preparation, particularly the presence of detergent in the buffer, remains the main impediment to obtaining atomic-resolution structures of ion channels and a multitude of other integral membrane protein complexes. In this review we will discuss properties of several detergents that have been successfully utilized in cryo-EM studies of ion channels and the emergence of the detergent alternative amphipol to stabilize ion channels for structurefunction characterization. Future structural studies of challenging specimen like ion channels are likely to be facilitated by cryo-EM amenable detergents or alternative surfactants

Overexpression of OsPT8 Increases Auxin Content and Enhances Tolerance to High-Temperature Stress in Nicotiana tabacum

Temperature is a primary factor affecting the rate of plant development; as the climate warms, extreme temperature events are likely to increasingly affect agriculture. Understanding how to improve crop tolerance to heat stress is a key concern. Wild plants have evolved numerous strategies to tolerate environmental conditions, notably the regulation of root architecture by phytohormones, but the molecular mechanisms of stress resistance are unclear. In this study, we showed that high temperatures could significantly reduce tobacco biomass and change its root architecture, probably through changes in auxin content and distribution. Overexpression of the OsPT8 phosphate transporter enhanced tobacco tolerance to high-temperature stress by changing the root architecture and increased the antioxidant ability. Molecular assays suggested that overexpression of OsPT8 in tobacco significantly increased the expression of auxin synthesis genes NtYUCCA 6, 8 and auxin efflux carriers genes NtPIN 1,2 under high-temperature stress. We also found that the expression levels of auxin response factors NtARF1 and NtARF2 were increased in OsPT8 transgenic tobacco under high-temperature stress, suggesting that OsPT8 regulates auxin signaling in response to high-temperature conditions. Our findings provided new insights into the molecular mechanisms of plant stress signaling and showed that OsPT8 plays a key role in regulating plant tolerance to stress conditions

Recent Advances and Perspective of Photonic Bound States in the Continuum

Recent advancements in photonic bound states in the continuum (BICs) have opened up exciting new possibilities for the design of optoelectronic devices with improved performance. In this perspective article, we provide an overview of recent progress in photonic BICs based on metamaterials and photonic crystals, focusing on both the underlying physics and their practical applications. The first part of this article introduces 2 different interpretations of BICs, based on far-field interference of multipoles and near-field analysis of topological charges. We then discuss recent research on manipulating the far-field radiation properties of BICs through engineering topological charges. The second part of the article summarizes recent developments in the applications of BICs, including chiral light and vortex beam generation, nonlinear optical frequency conversion, sensors, and nanolasers. Finally, we conclude with a discussion of the potential of photonic BICs to advance terahertz applications in areas such as generation and detection, modulation, sensing, and isolation. We believe that continued research in this area will lead to exciting new advancements in optoelectronics, particularly in the field of terahertz devices