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The mutation of SARS-CoV-2 influences viral function as residue replacements affect both physiochemical properties and folding conformations. Although a large amount of data on SARS-CoV-2 is available, the investigation of how viral functions change in response to mutations is hampered by a lack of effective structural analysis. Here, we exploit the advances of protein structure fingerprint technology to study the folding conformational changes induced by mutations. With integration of both protein sequences and folding conformations, the structures are aligned for SARS-CoV to SARS-CoV-2, including Alpha variant (lineage B.1.1.7) and Delta variant (lineage B.1.617.2). The results showed that the virus evolution with change in mutational positions and physicochemical properties increased the affinity between spike protein and ACE2, which plays a critical role in coronavirus entry into human cells. Additionally, these structural variations impact vaccine effectiveness and drug function over the course of SARS-CoV-2 evolution. The analysis of structural variations revealed how the coronavirus has gradually evolved in both structure and function and how the SARS-CoV-2 variants have contributed to more severe acute disease worldwide.

Cytokines play a critical role in the pathogenesis and development of cardiovascular diseases. However, data linking cytokines to risk and severity of acute coronary syndrome (ACS) are still limited. We measured plasma profile of 280 cytokines using a quantitative protein microarray in 12 ACS patients and 16 healthy controls, and identified 15 differentially expressed cytokines for ACS. Osteopontin, chemokine ligand 23, brain derived neurotrophic factor and C-reactive protein (CRP) were further validated using immunoassay in two independent case-control studies with a total of 210 ACS patients and 210 controls. We further examined their relations with incident ACS among 318 case-control pairs nested within the Dongfeng-Tongji cohort, and found plasma osteopontin and CRP concentrations were associated with incident ACS, and the multivariable-adjusted odds ratio (95% confidence interval) was 1.29 (1.06–1.57) per 1-SD increase for osteopontin and 1.30 (1.02–1.66) for CRP, respectively. Higher levels of circulating osteopontin were also correlated with higher severity of ACS, and earlier ACS onset time. Adding osteopontin alone or in combination with CRP modestly improved the predictive ability of ACS beyond the Framingham risk scores. Our findings suggested that osteopontin might be a biomarker for incident ACS, using osteopontin adds moderately to traditional cardiovascular risk factors.

This study aimed to investigate the clinical characteristics and predictors of increased rapid eye movement (REM) sleep or slow wave sleep (SWS) in patients with obstructive sleep apnea (OSA) following positive airway pressure (PAP) therapy. The study retrospectively analyzed data from patients with OSA who underwent both diagnostic polysomnography (PSG) and pressure titration PSG at the Tangdu Hospital Sleep Medicine Center from 2011–2016. Paired diagnostic PSG and pressure titration studies from 501 patients were included. REM rebound was predicted by a higher oxygen desaturation index, lower REM proportion, higher arousal index, lower mean pulse oxygen saturation (SpO2), higher Epworth sleepiness score and younger age (adjusted R2 = 0.482). The SWS rebound was predicted by a longer total duration of apneas and hypopneas, lower N3 duration, lower SpO2 nadir, lower REM proportion in diagnostic PSG and younger age (adjusted R2 = 0.286). Patients without REM rebound or SWS rebound had a high probability of comorbidities with insomnia and mood complaints. Some parameters (subjective and objective insomnia, excessive daytime sleepiness, age and OSA severity) indicate changes in REM sleep and SWS between diagnostic and titration PSG tests. Treatment of insomnia and mood disorders in patients with OSA may helpful to improve the use PAP.

Paper has been pursued as an interesting substrate material for sensors in applications such as microfluidics, bio-sensing of analytes and printed microelectronics. It offers advantages of being inexpensive, lightweight, environmentally friendly and easy to use. However, currently available paper-based mechanical sensors suffer from inadequate range and accuracy. Here, using the principle of supercapacitive sensing, we fabricate force sensors from paper with ultra-high sensitivity and unprecedented configurability. The high sensitivity comes from the sensitive dependence of a supercapacitor’s response on the contact area between a deformable electrolyte and a pair of electrodes. As a key component, we develop highly deformable electrolytes by coating ionic gel on paper substrates which can be cut and shaped into complex three-dimensional geometries. Paper dissolves in the ionic gel after determining the shape of the electrolytes, leaving behind transparent electrolytes with micro-structured fissures responsible for their high deformability. Exploiting this simple paper-based fabrication process, we construct diverse sensors of different configurations that can measure not just force but also its normal and shear components. The new sensors have range and sensitivity several orders of magnitude higher than traditional MEMS capacitive sensors, in spite of their being easily fabricated from paper with no cleanroom facilities.

Interleukin-13 (IL-13) has important functions in atherosclerosis, but its role in coronary artery disease (CAD) is unclear. Here, we studied the genetic role of IL-13 in CAD in a Chinese Han population using tag SNPs covering the whole IL13 gene (i.e., rs1881457, rs2069744 and rs20541) and a two-stage cohort containing 1863 CAD cases and 1841 controls. Traditional risk factors for CAD, such as age, BMI, and other factors, were used as covariates in logistic regression analysis. In the total population, we found that two haplotypes of IL13 (ATG and ATA, ordered rs1881457C-rs2069744T-rs20541A) significantly contributed to the risk of CAD with adjusted p values less than 0.05 (padj = 0.019 and padj = 0.042, respectively). In subgroup population analyses, the variant rs1881457C was found to significantly contribute to a nearly two fold increase in the risk of CAD in men (padj = 0.023, OR = 1.91, 95% CI: 1.09-3.33). The variant rs1881457C also significantly contributed to a nearly twofold risk of late-onset CAD (padj = 0.024, OR = 1.93, 95% CI: 1.09-3.42). In conclusion, IL13 might be involved in CAD via different mechanisms under different conditions in the Chinese Han population.

Atrial fibrillation (AF) is the most common arrhythmia. In 2014, two new meta-GWAS identified 5 AF loci, including the NEURL locus, GJA1 locus, CAND2 locus, and TBX5 locus in the European ancestry populations and the NEURL locus and CUX2 locus in a Japanese population. The TBX5 locus for AF was reported by us in 2013 in the Chinese population. Here we assessed the association between AF and SNPs in the NEURL, GJA1, CAND2 and CUX2 loci in the Chinese Han population. We carried out a large case-control association study with 1,164 AF patients and 1,460 controls. Significant allelic and genotypic associations were identified between NEURL variant rs6584555 and GJA1 variant rs13216675 and AF. Significant genotypic association was found between CUX2 SNP rs6490029 and AF. No association was found between CAND2 variant rs4642101 and AF, which may be due to an insufficient power of the sample size for rs4642101. Together with our previous findings, seven of fifteen AF loci (

Otitis media (OM) is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by mucous cell hyperplasia that is thought to produce mucins from the middle ear mucosa. We are interested in the role of Notch signalling pathway in this inflammatory process. Using an acute otitis media (AOM) mouse model through injection of Streptococcus Pneumoniae into the middle ear, histopathologic examination and quantitative RT-PCR, acute inflammation with the thickness of mucosa, Goblet cell hyperplasia, and cilia loss were determined and gene expression related to the Notch signaling pathway were evaluated. Upregulation of the mucous cell markers, Argr2 and Muc5AC, and downregulation of the cilia cell marker, Foxj1 and Dnai2, were observed in AOM. In addition, genes encoding Notch receptors and ligands (Notch1, Notch2, Notch3, Notch4 and Dll1) and the Notch target genes (Hes1, Hes5, Hey1, NRARP) in AOM decreased significantly. The expression of the Notch1 and Jagged1 also showed down-regulation throughout the mouse middle ear epithelium. Taken together, this study suggests that downregulation of the Notch signaling pathway is involved in the mucosa hyperplasia during AOM.

B cells contribute to the development of dilated cardiomyopathy (DCM) by inducing myocyte injuries and myocardial fibrosis. Our recent research indicated that microRNA (miR) -185 participated in human B-cell activation. Thus, this study was aimed to explore the relationship between miR-185 and DCM progression. Forty-one healthy volunteers and fifty newly diagnosed DCM patients were enrolled. The levels of plasma miR-185, TNF-α secreting B cells and anti-heart autoantibody were detected. We found that the mean levels of plasma miR-185 in DCM patients were significantly higher than those in healthy controls. Furthermore, these DCM patients could be divided into miR-185high and miR-185low groups according to the cluster distribution. During one-year follow-up period, the miR-185high group showed apparent improvements in left ventricular ejection fraction, left ventricular end diastolic diameter and NT-proBNP, accompanied by significant declines in both cardiovascular mortality and total admissions for heart failure re-hospitalizations. In addition, the levels of anti-β1-AR antibody and TNF-α secreting B cells were also reduced in miR-185high group. These findings suggested that high miR-185 levels might be associated with a favorable prognosis by repressing B cell function in DCM. The findings of this study need to be confirmed with larger sample size and longer duration of observation.

Here, we successfully welded two bulk metallic glass (BMG) materials, Zr51Ti5Ni10Cu25Al9 and Zr50.7Cu28Ni9Al12.3 (at. %), using a liquid-solid joining process. An atomic-scale metallurgical bonding between two BMGs can be achieved. The interface has a transition layer of ~50 μm thick. The liquid-solid joining of BMGs can shed more insights on overcoming their size limitation resulting from their limited glass-forming ability and then promoting their applications in structural components.

Lovastatin is a member of Statins, which are beneficial in a lot of immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles in the activation and proliferation of T cells, and have become attractive target for immune-related disorders. The present study was designed to examine the block effect of Lovastatin on Kv1.3 channel in human T cells, and to clarify its new immunomodulatory mechanism. We found that Lovastatin inhibited Kv1.3 currents in a concentration- and voltage-dependent manner, and the IC50 for peak, end of the pulse was 39.81 ± 5.11, 6.92 ± 0.95 μM, respectively. Lovastatin also accelerated the decay rate of current inactivation and negatively shifted the steady-state inactivation curves concentration-dependently, without affecting the activation curve. However, 30 μM Lovastatin had no apparent effect on KCa current in human T cells. Furthermore, Lovastatin inhibited Ca2+ influx, T cell proliferation as well as IL-2 production. The activities of NFAT1 and NF-κB p65/50 were down-regulated by Lovastatin, too. At last, Mevalonate application only partially reversed the inhibition of Lovastatin on IL-2 secretion, and the siRNA against Kv1.3 also partially reduced this inhibitory effect of Lovastatin. In conclusion, Lovastatin can exert immunodulatory properties through the new mechanism of blocking Kv1.3 channel.

Interleukin-27 (IL-27) is an important cytokine in inflammatory diseases, including coronary artery disease (CAD). To explore the precise role of IL-27 in CAD, we investigated the genetic association between IL27 and CAD in the GeneID Chinese Han population. A two-stage case control association analysis was performed for 3075 CAD cases and 2802 controls. Logistic regression analysis was used to adjust the traditional risk factors for CAD. Results showed that a promoter variant, rs153109, tended to be marginally associated with CAD in the discovery population (Padj = 0.028, OR = 1.27, 95%CI: 1.03–1.58). However, this association was not replicated in the validation stage (Padj = 0.559, OR = 1.04, 95%CI: 0.90–1.21). In addition, when we classified the combined population into two subgroups according to the age at disease onset or disease state, we again obtained no significant associations. Finally, we estimated the severity of coronary stenosis using the Gensini Scoring system and determined that the rs153109 genotypes were still not associated with the Gensini scores of the CAD patients. In conclusion, our study failed to find an association between common variants in the functional region of IL27 and CAD in a Chinese Han population, which indicated that IL-27 might only be an inflammatory marker during the development of CAD.

Lovastatin is a member of Statins, which are beneficial in a lot of immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles in the activation and proliferation of T cells and have become attractive target for immune-related disorders. The present study was designed to examine the block effect of Lovastatin on Kv1.3 channel in human T cells and to clarify its new immunomodulatory mechanism. We found that Lovastatin inhibited Kv1.3 currents in a concentration- and voltage-dependent manner and the IC50 for peak, end of the pulse was 39.81 ± 5.11, 6.92 ± 0.95 μM, respectively. Lovastatin also accelerated the decay rate of current inactivation and negatively shifted the steady-state inactivation curves concentration-dependently, without affecting the activation curve. However, 30 μM Lovastatin had no apparent effect on KCa current in human T cells. Furthermore, Lovastatin inhibited Ca2+ influx, T cell proliferation as well as IL-2 production. The activities of NFAT1 and NF-κB p65/50 were down-regulated by Lovastatin, too. At last, Mevalonate application only partially reversed the inhibition of Lovastatin on IL-2 secretion and the siRNA against Kv1.3 also partially reduced this inhibitory effect of Lovastatin. In conclusion, Lovastatin can exert immunodulatory properties through the new mechanism of blocking Kv1.3 channel.