Design of robust superhydrophobic surfaces.

The ability of superhydrophobic surfaces to stay dry, self-clean and avoid biofouling is attractive for applications in biotechnology, medicine and heat transfer1-10. Water droplets that contact these surfaces must have large apparent contact angles (greater than 150 degrees) and small roll-off angles (less than 10 degrees). This can be realized for surfaces that have low-surface-energy chemistry and micro- or nanoscale surface roughness, minimizing contact between the liquid and the solid surface11-17. However, rough surfaces-for which only a small fraction of the overall area is in contact with the liquid-experience high local pressures under mechanical load, making them fragile and highly susceptible to abrasion18. Additionally, abrasion exposes underlying materials and may change the local nature of the surface from hydrophobic to hydrophilic19, resulting in the pinning of water droplets to the surface. It has therefore been assumed that mechanical robustness and water repellency are mutually exclusive surface properties. Here we show that robust superhydrophobicity can be realized by structuring surfaces at two different length scales, with a nanostructure design to provide water repellency and a microstructure design to provide durability. The microstructure is an interconnected surface frame containing 'pockets' that house highly water-repellent and mechanically fragile nanostructures. This surface frame acts as 'armour', preventing the removal of the nanostructures by abradants that are larger than the frame size. We apply this strategy to various substrates-including silicon, ceramic, metal and transparent glass-and show that the water repellency of the resulting superhydrophobic surfaces is preserved even after abrasion by sandpaper and by a sharp steel blade. We suggest that this transparent, mechanically robust, self-cleaning glass could help to negate the dust-contamination issue that leads to a loss of efficiency in solar cells. Our design strategy could also guide the development of other materials that need to retain effective self-cleaning, anti-fouling or heat-transfer abilities in harsh operating environments.

METTL3 protects METTL14 from STUB1-mediated degradation to maintain m6 A homeostasis.

N6 -Methyladenosine (m6 A) is an important RNA modification catalyzed by methyltransferase-like 3 (METTL3) and METTL14. m6 A homeostasis mediated by the methyltransferase (MTase) complex plays key roles in various biological processes. However, the mechanism underlying METTL14 protein stability and its role in m6 A homeostasis remain elusive. Here, we show that METTL14 stability is regulated by the competitive interaction of METTL3 with the E3 ligase STUB1. STUB1 directly interacts with METTL14 to mediate its ubiquitination at lysine residues K148, K156, and K162 for subsequent degradation, resulting in a significant decrease in total m6 A levels. The amino acid regions 450-454 and 464-480 of METTL3 are essential to promote METTL14 stabilization. Changes in STUB1 expression affect METTL14 protein levels, m6 A modification and tumorigenesis. Collectively, our findings uncover an ubiquitination mechanism controlling METTL14 protein levels to fine-tune m6 A homeostasis. Finally, we present evidence that modulating STUB1 expression to degrade METTL14 could represent a promising therapeutic strategy against cancer.

Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

Quantum Induced Coherence Light Detection and Ranging.

Quantum illumination has been proposed and demonstrated to improve the signal-to-noise ratio (SNR) in light detection and ranging (LiDAR). When relying on coincidence detection alone, such a quantum LiDAR is limited by the timing jitter of the detector and suffers from jamming noise. Inspired by the Zou-Wang-Mandel experiment, we design, construct, and validate a quantum induced coherence (QuIC) LiDAR which is inherently immune to ambient and jamming noises. In traditional LiDAR the direct detection of the reflected probe photons suffers from deteriorating SNR for increasing background noise. In QuIC LiDAR we circumvent this obstacle by only detecting the entangled reference photons, whose single-photon interference fringes are used to obtain the distance of the object, while the reflected probe photons are used to erase path information of the reference photons. In consequence, the noise accompanying the reflected probe light has no effect on the detected signal. We demonstrate such noise resilience with both LED and laser light to mimic the background and jamming noise. The proposed method paves a new way of battling noise in precise quantum electromagnetic sensing and ranging.

Defect driven physics-informed neural network framework for fatigue life prediction of additively manufactured materials.

Additive manufacturing (AM) has attracted many attentions because of its design freedom and rapid manufacturing; however, it is still limited in actual application due to the existing defects. In particular, various defect features have been proved to affect the fatigue performance of components and lead to fatigue scatter. In order to properly assess the influences of these defect features, a defect driven physics-informed neural network (PiNN) is developed. By embedding the critical defects information into loss functions, the defect driven PiNN is enhanced to capture physical information during training progress. The results of fatigue life prediction for different AM materials show that the proposed PiNN effectively improves the generalization ability under small samples condition. Compared with the fracture mechanics-based PiNN, the proposed PiNN provides physically consistent and higher accuracy without depending on the choice of fracture mechanics-based model. Moreover, this work provides a scalable framework being able to integrate more prior knowledge into the proposed PiNN. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Preface to the theme issue 'physics-informed machine learning and its structural integrity applications'.

The issue focuses on physics-informed machine learning and its applications for structural integrity and safety assessment of engineering systems/facilities. Data science and data mining are fields in fast development with a high potential in several engineering research communities; in particular, advances in machine learning (ML) are undoubtedly enabling significant breakthroughs. However, purely ML models do not necessarily carry physical meaning, nor do they generalize well to scenarios on which they have not been trained on. This is an emerging field of research that potentially will raise a huge impact in the future for designing new materials and structures, and then for their proper final assessment. This issue aims to update the current research state of the art, incorporating physics into ML models, and providing tools when dealing with material science, fatigue and fracture, including new and sophisticated algorithms based on ML techniques to treat data in real-time with high accuracy and productivity. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Physics-informed machine learning and its structural integrity applications: state of the art.

The development of machine learning (ML) provides a promising solution to guarantee the structural integrity of critical components during service period. However, considering the lack of respect for the underlying physical laws, the data hungry nature and poor extrapolation performance, the further application of pure data-driven methods in structural integrity is challenged. An emerging ML paradigm, physics-informed machine learning (PIML), attempts to overcome these limitations by embedding physical information into ML models. This paper discusses different ways of embedding physical information into ML and reviews the developments of PIML in structural integrity including failure mechanism modelling and prognostic and health management (PHM). The exploration of the application of PIML to structural integrity demonstrates the potential of PIML for improving consistency with prior knowledge, extrapolation performance, prediction accuracy, interpretability and computational efficiency and reducing dependence on training data. The analysis and findings of this work outline the limitations at this stage and provide some potential research direction of PIML to develop advanced PIML for ensuring structural integrity of engineering systems/facilities. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Computational characterization of homologous ligands binding to a deep hydrophobic pocket in Shigella flexneri pilot protein MxiM.

The type III secretion system (T3SS) is an important molecular machinery in gram-negative bacteria Shigella flexneri as it provides ways for translocating virulence factors from the bacteria into host cells, eventually leading to severe disease symptoms such as bacillary dysentery. Due to the rising concerns of antibiotics resistance in bactericidal strategy, the anti-virulence strategy that primarily targets the T3SS components becomes an attractive alternative. MxiM, the secretin pilot protein of Shigella flexneri, binds the secretin MxiD and facilitates the formation of the secretin ring in outer membrane in T3SS assembly. MxiM harbors a large hydrophobic pocket that has been shown to be important in MxiM-MxiD interaction. In this work, I examined the ligand binding property of MxiM by performing molecular dynamics (MD) simulations of the association between MxiM and a series of hydrophobic ligands, with simulation time amounted to 30 µs. MD simulations successfully captured spontaneous ligand binding events in 153 of the 300 trajectories. The ligand binding can be categorized into two types: a fast type, in which the ligand binds quickly into the hydrophobic pocket and a slow type, in which the ligand forms an encounter complex with the protein before binding into the hydrophobic pocket. Using the MxiM-ligand binding poses captured in MD simulations, I additionally performed umbrella-sampling MD simulations with total simulation time amounted to 63 µs to obtain protein-ligand binding free energies. The relationship between the ligand binding free energy and ligand size appears to be nonlinear and exhibits an exponential decay pattern. In summary, I performed computational characterization of MxiM-hydrophobic ligand binding capabilities and properties, which may provide valuable insights into designing anti-bacterial medicine against antibiotics resistance in Shigella flexneri.

Mulberry leaf (Morus alba L.): A review of its potential influences in mechanisms of action on metabolic diseases.

The leaves of Morus alba L. (called Sangye in Chinese, ML), which belong to the genus Morus., are highly valuable edible plants in nutrients and nutraceuticals. In Asian countries including China, Japan and Korea, ML are widely used as functional foods including beverages, noodles and herbal tea because of its biological and nutritional value. Meanwhile, ML-derived products in the form of powders, extracts and capsules are widely consumed as dietary supplements for controlling blood glucose and sugar. Clinical studies showed that ML play an important role in the treatment of metabolic diseases including the diabetes, dyslipidemia, obesity, atherosclerosis and hypertension. People broadly use ML due to their nutritiousness, deliciousness, safety, and abundant active benefits. However, the systematic pharmacological mechanisms of ML on metabolic diseases have not been fully revealed. Therefore, in order to fully utilize and scale relevant products about ML, this review summarizes the up-to-date information about the ML and its constituents effecting on metabolic disease.

MTERF3 contributes to MPP+-induced mitochondrial dysfunction in SH-SY5Y cells.

Parkinson's disease (PD) is a neurodegenerative disorder causing severe social and economic burdens. The origin of PD has been usually attributed to mitochondrial dysfunction. To this end, mitochondrial transcription regulators become attractive subjects for understanding PD pathogenesis. Previously, we found that the expression of mitochondrial transcription termination factor 3 (MTERF3) was reduced in MPP+-induced mice model of PD. In the present study, we probe the function of MTERF3 and its role in MPP+-induced cellular model of PD. Initially, we observe that MTERF3 expression is also reduced in MPP+-induced cellular model of PD, which can be mainly attributed to the increase of MTERF3 degradation. Next, we examine the effect of MTERF3 knockdown and overexpression on the replication, transcription, and translation of mitochondrial DNA (mtDNA). We show that knockdown and overexpression of MTERF3 have opposite effects on mtDNA transcript level but similar effects on mtDNA expression level, in line with MTERF3's dual roles in mtDNA transcription and translation. In addition, we examine the effect of MTERF3 knockdown and overexpression on mitochondrial function with and without MPP+ treatment, and find that MTERF3 seems to play a generally protective role in MPP+-induced mitochondrial dysfunction. Together, this work suggests a regulatory role of MTERF3 in MPP+-induced cellular model of PD and may provide clues in designing novel therapeutics against PD.

A Regulatory Loop Involving miR-200c and NF-κB Modulates Mortalin Expression and Increases Cisplatin Sensitivity in an Ovarian Cancer Cell Line Model.

Ovarian cancer is currently the most lethal gynecological cancer. At present, primary debulking surgery combined with platinum-based chemotherapy is the standard treatment strategy for ovarian cancer. Although cisplatin-based chemotherapy has greatly improved the prognosis of patients, the subsequent primary or acquired drug resistance of cancer cells has become an obstacle to a favorable prognosis. Mortalin is a chaperone that plays an important role in multiple cellular and biological processes. Our previous studies have found that mortalin is associated with the proliferation and migration of ovarian cancer cells and their resistance to cisplatin-based chemotherapy. In this study, microRNA (miR)-200b/c downregulated mortalin expression and inhibited the proliferation and migration of the paired cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) epithelial ovarian cancer cell lines. Moreover, miR-200c increased the sensitivity of ovarian cancer cells to cisplatin treatment by regulating mortalin levels. Nuclear factor (NF)-κB directly regulated mortalin and miR-200b/c expression levels, while NF-κB and miR-200b/c jointly regulated the expression of mortalin. The combination of cisplatin and miR-200c significantly enhanced the therapeutic effects on ovarian cancer in vivo, suggesting that miR-200c may serve as a potential therapeutic agent for ovarian cancer.

Chrysin Alleviates Chronic Hypoxia-Induced Pulmonary Hypertension by Reducing Intracellular Calcium Concentration in Pulmonary Arterial Smooth Muscle Cells.

Chrysin (CH), the main ingredient of many medicinal plants, has been reported to be a very potent flavonoid possessing a large number of pharmacological activities. Recent studies have shown that CH significantly improves hemodynamic parameters such as right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in a rat model of chronic hypoxia-induced pulmonary hypertension (CHPH). These improvements are through the inhibition of NOX4 expression, reactive oxygen species and malondialdehyde production, pulmonary arterial smooth muscle cell (PASMC) proliferation, and collagen accumulation. In this study, we investigated another mechanism by which CH alleviates CHPH by regulating intracellular calcium concentrations ([Ca]i) in PASMCs, as well as the underlying signaling pathway. The results show that (1) in CHPH model rats, CH substantially attenuated elevated right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) in cultured rat distal PASMCs, CH inhibited the hypoxia-triggered promotion of cell proliferation, store-operated Ca entry and [Ca]i; and (3) CH significantly suppressed the hypoxia-upregulated HIF-1α, BMP4, TRPC1, and TRPC6 expression in distal pulmonary arteries (PAs) and cultured rat distal PASMCs. These results indicate that CH likely exerts its CHPH protective activity by regulating [Ca]i, which may result from the downregulation of HIF-1α, BMP4, TRPC1, and TRPC in PASMCs.

Validation of the Generalized Force Fields GAFF, CGenFF, OPLS-AA, and PRODRGFF by Testing Against Experimental Osmotic Coefficient Data for Small Drug-Like Molecules.

Accurate force field parameters for proteins and drugs are of fundamental importance for predicting protein-drug binding poses and binding free energies in structure-based drug design. Osmotic pressure simulations have recently gained popularity as a means to validate common force fields for biomolecules such as proteins; up to now, however, little such effort has been made to use these methods to validate common force fields for small drug-like molecules. In this work, osmotic coefficients of 16 drug-like molecules were calculated from osmotic pressure molecular dynamics simulations using four common force fields for drug-like molecules: GAFF, CGenFF, OPLS-AA, and PRODRGFF. While GAFF, CGenFF, and OPLS-AA produced osmotic coefficients that are in good agreement with the corresponding experimental osmotic coefficients, PRODRGFF, which attempts to use GROMOS parameters, often produced osmotic coefficients that are in poor agreement. All four force fields poorly reproduced the experimental osmotic coefficients of purine-derived molecules including purine, 6-methylpurine, and caffeine, suggesting common issues in describing interactions of this particular molecule type. The poor overall performance of PRODRGFF can be mainly attributed to the poor results with two macrocyclic molecules HMT and TAT, which can be significantly improved by reparameterizing the van der Waals (vdW) parameters of alkyl carbons and using lower solute concentration. In addition, the recently developed GAFF2 with revamped vdW parameters was found to produce osmotic coefficients that are in slightly better agreement with experiments than GAFF. Overall, the four common force fields for drug-like molecules tested in this study performed reasonably well at reproducing experimental osmotic coefficients of drug-like molecules, although failures of certain force fields on certain molecules suggest that further force field reparameterizations, especially for vdW parameters, might be required to improve their accuracy.

Association Between the Lipid Profile and Renal Dysfunction in the Heart Failure Patients.

BACKGROUND/AIMS: In heart failure patients with high prevalence of chronic renal disease (CKD), hospitalization and mortality, whether the lipid profile was associated with renal dysfunction remained unknown. The present study intended to clarify the association between the lipid profile and renal dysfunction in the heart failure patients. METHODS: 336 hospitalized heart failure patients with left ventricle ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. The estimated glomerular filtration rate (eGFR) < 90 mL/min·1.73 m2 was defined as renal dysfunction. The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with eGFR. The significantly correlated factors were enrolled in Logistic regression as confounding factors to determine the association between the lipid profile and renal dysfunction in the heart failure patients. RESULTS: 182 patients (54.2%) had renal dysfunction and 154 patients (45.8%) did not have renal dysfunction. The waist circumference, platelet counts, platelet distribution width (PDW), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1), albumin and left ventricular ejection fraction (LVEF) are positively correlated with eGFR (all P< 0.05). Meanwhile, the age, mean platelet volume (MPV), neutrophilic granulocyte percentage (NEUT%), urea nitrogen (BUN), creatinine and total bilirubin (TBIL) are negatively correlated with eGFR (all P< 0.05). The total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) show no correlation with eGFR. After the adjustment of sex, hypertension, diabetes mellitus, age, waist circumference, platelet counts, MPV, PDW, NEUT%, TBIL, albumin and LVEF, HDL-C is the only lipid factor still significantly associated with renal dysfunction in hospitalized heart failure patients (OR=0.119, P=0.003). CONCLUSION: Among the lipid profile of TC, triglyceride, LDL-C, HDL-C, apo A1 and apo B, the HDL-C is the only lipid factor significantly associated with renal dysfunction in hospitalized heart failure patients.

Intrahepatic Cholestasis of Pregnancy as a Clinical Manifestation of Sodium-Taurocholate Cotransporting Polypeptide Deficiency.

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder. Although the etiology of ICP is not fully understood thus far, some genetic factors might contribute to the development of this condition. Sodium-taurocholate cotransporting polypeptide (NTCP), the protein encoded by the gene Solute Carrier Family 10, Member 1 (SLC10A1), is the primary transporter expressed in the basolateral membrane of the hepatocyte to uptake conjugated bile salts from the plasma. NTCP deficiency arises from biallelic SLC10A1 mutations which impair the NTCP function and cause intractably elevated levels of total bile acids (TBA) in the plasma (hypercholanemia). In this study, all the SLC10A1 exons and their flanking sequences were analyzed by Sanger sequencing to investigate the etiology for hypercholanemia in two male infants aged 2 and 20 months, respectively, from two unrelated families. As a result, both patients are homozygous for the reported pathogenic variant c.800C>T (p.Ser267Phe) that could impair the NTCP function to uptake bile acids, and the diagnosis of NTCP deficiency was thus made. Their mothers are also homozygotes of the same variant and both had been diagnosed to have ICP in the third trimester, with one of them undergoing cesarean section. The father of the first patient in this paper has the same SLC10A1 genotype c.800C>T/c.800C>T, also exhibiting slight hypercholanemia with a plasma TBA level of 21.5 µmol/L. In conclusion, we suggest that with hypercholanemia being a common laboratory change, NTCP deficiency may be a genetic factor leading to ICP and even cesarean section in clinical practice.

Features of Ebola Virus Disease at the Late Outbreak Stage in Sierra Leone: Clinical, Virological, Immunological, and Evolutionary Analyses.

We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.8%. Fatal cases exhibited significantly higher levels of viral loads, cytokines, and chemokines at late stages of infection versus early stage compared with survivors. The viruses converged in a new clade within sublineage 3.2.4, which had a significantly lower case fatality rate.

[Artesunate inhibits proliferation of glioblastoma cells by arresting cell cycle].

Glioblastoma is a common brain tumor and the overall survival rate of the patients is very low, so it is an effective way to develop the potential chemotherapy or adjuvant chemotherapy drugs in glioblastoma treatment. As a well-known antimalarial drug, artesunate(ARTs) has clear side effects, and recently it has been reported to have antitumor effects, but rarely reported in glioblastoma. Different concentrations of ARTs were used to treat the glioblastoma cells, and then the inhibitory effect of ARTs on glioblastoma proliferation was detected by MTT assay; Ki67 immunofluorescence assay was used to detect the proliferation of cells; Soft agar experiment was used to explain the clonal formation abilities in vitro; Flow Cytometry was used to detect the cell cycle; and Western blot assay was used to determine the expression of key cell cycle protein. MTT assay results indicated that ARTs-treated glioblastoma cell A172, U251, U87 were significantly inhibited in a time-and-dose dependent manner as compared to the control group(DMSO treatment group). Soft agar experiment showed that ARTs could significantly reduce the clonal formation ability of glioblastoma. Furthermore, Flow cytometry analysis showed that ARTs could obviously increase the cell proportion in G0/G1 phase and reduce the cell proportion in S phase. Western blot results showed that the expressions of cell cycle-related proteins CDK2, CDK4, cyclin D1 and cyclin B1 were all obviously down-regulated. Above all, ARTs may inhibit the proliferation of glioblastoma cells by arresting cell cycle in G0/G1 phase through down-regulating the expression of CDK2, CDK4, cyclin D1, cyclin B1. These results may not only provide a novel method for rediscovering and reusing ARTs but also provide a new potential drug for treating glioblastoma.

MTERF2 contributes to MPP(+)-induced mitochondrial dysfunction and cell damage.

Parkinson's disease (PD) is a common neurodegenerative disorder whose pathogenesis is under intense investigation. Substantial evidence indicates that mitochondrial dysfunction plays a central role in the pathophysiology of PD. Several mitochondrial internal regulating factors act to maintain the mitochondrial function. However, how these internal regulating factors contribute to mitochondrial dysfunction in PD remains elusive. One of these factors, mitochondrial transcription termination factor 2 (MTERF2), has been implicated in the regulation of oxidative phosphorylation by modulating mitochondrial DNA transcription. Here, we discovered a new role of MTERF2 in regulating mitochondrial dysfunction and cell damage induced by MPP(+) in SH-SY5Y cells. We found that MPP(+) treatment elevated MTERF2 expression, induced mitochondrial dysfunction and cell damage, which was alleviated by MTERF2 knockdown. These findings demonstrate that MTERF2 contributes to MPP(+)-induced mitochondrial disruption and cell damage. This study indicates that MTERF2 is a potential therapeutic target for environmentally induced Parkinson's disease.

Association between neutrophilic granulocyte percentage and depression in hospitalized patients with heart failure.

BACKGROUND: Previous researches reveal that depression is associated with increased inflammatory markers. As a simple and cheap inflammatory marker, we hypothesize that neutrophilic granulocyte percentage is associated with depression in hospitalized heart failure patients, whose prevalence of depression is at a very high level. METHODS: Three hundred sixty-six cases of hospitalized heart failure patients with left ventricular ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. All the enrolled patients received Hamilton Rating Scale for Depression (24-items) (HAM-D24). The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with HAM-D24 depression index. The significantly correlated factors were enrolled as independent variables in Logistic regression to determine the risk or protective factors for depression, which was taken as dependent variable. RESULTS: Two hundred ten cases of hospitalized heart failure patients (57.4%) had depression. Among them, 134 patients (63.8%) had mild depression, 58 patients (27.6%) had moderate depression and 18 patients (8.6%) had severe depression. Pearson simple linear correlation revealed that in hospitalized patients with heart failure, the neutrophils granulocyte percentage was positively correlated with the HAM-D24 depression index (r = .435, p < .001). After the adjustment of age, BMI, number of members of the household, smoking index, New York Heart Association (NYHA) classification, hemoglobin, TC, LDL-C, creatinine, cystatin-C, TBIL and albumin, the neutrophils granulocyte percentage is still significantly associated with depression in hospitalized heart failure patients (OR = 1.046, p < .001). CONCLUSIONS: The neutrophils granulocyte percentage may be used as a new marker for depression in hospitalized heart failure patients.

Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions.

The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26 °C for more than 9 d and at 37 °C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures.