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A self-propelled nanoparticle system composed of a tissue factor (TF) integrated into a liposome and a CaCO3 shell was developed, showing superior hemostatic capacity by delivering the lipidated TF deep into bleeding wounds with good biocompatibility.

Autism spectrum disorder (ASD) has become one of the most common neurological developmental disorders in children. However, the study of ASD diagnostic markers faces significant challenges due to the existence of heterogeneity. In this study, genetic testing was performed on children who were clinically diagnosed with ASD. Children with ASD susceptibility genes and healthy controls were studied. The proteomics of plasma and peripheral blood mononuclear cells (PBMCs) as well as plasma metabolomics were carried out. The results showed that although there was genetic heterogeneity in children with ASD, the differentially expressed proteins (DEPs) in plasma, peripheral blood mononuclear cells, and differential metabolites in plasma could still effectively distinguish autistic children from controls. The mechanism associated with them focuses on several common and previously reported mechanisms of ASD. The biomarkers for ASD diagnosis could be found by taking differentially expressed proteins and differential metabolites into consideration. Integrating omics data, glycerophospholipid metabolism and N-glycan biosynthesis might play a critical role in the pathogenesis of ASD.

Existing data demonstrate a significant correlation between autism spectrum disorder (ASD) and the status of biologically essential and toxic trace elements. However, there is still a lack of data on the steady state of trace elements in ASD. We performed a case-control study to explore the association between the risk of ASD and 23 trace elements in plasma. The results showed that children with ASD had considerably decreased lithium (Li), manganese (Mn), selenium (Se), barium (Ba), mercury (Hg), and tin (Sn) levels when compared to their age- and sex-matched controls. Meanwhile, children with ASD had considerably increased plasma chromium (Cr) and vanadium (V) concentrations. We also divided each group into subgroups based on age and gender and created element-related networks for each subgroup. We detected significant element correlations within or between subgroups, as well as changes in correlations that included all elements examined. Finally, more element correlations were observed among males, which may open a new avenue for understanding the complicated process behind the sex ratio of children with ASD. Overall, our data revealed a novel relationship between elements and ASD, which may extend current understanding about ASD.

Exosomes are often a promising source of biomarkers for cancer diagnosis in the early stages. Therefore, it is important to develop a sensitive and low-cost detection method. Here, we introduce a new substrate using gold nanorods (GNRs) on a silver-island film that produces a 360-fold AF647 molecule fluorescence enhancement compared to glass. The amplified fluorescence was proven theoretically by using finite difference time-domain simulation (FDTD). Utilizing the enhanced fluorescence from the substrate, GNRs attached with the biomolecules and created a sandwich immunoassay that can significantly detect human CD63 antigen on the exosome. By applying the method, the detection limit of mouse IgG goes down to 0.3 ng/mL, which is considerably better than the existing methods. Moreover, the sensitivity and accuracy for clinical plasma from six patients confirm its diagnostic feasibility. The proposed substrate can be uniformly extended to the identification of other biomarkers by modifying the antibodies on the surfaces of the GNRs.

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social and communication difficulties. Valproic acid (VPA) injection during pregnancy elicits autism-like behavior in the offspring, making it a classic animal model of ASD. However, the mechanisms involved have not yet been determined. In this study, we used iTRAQ (isobaric tags for relative and absolute quantification) proteomics analysis of the cerebral cortex of a VPA rat model (VPA group) and controls (CON group). The results showed that 79 differentially expressed proteins (DEPs) were identified between the VPA group and the CON group. Based on bioinformatics analysis, the DEPs were mainly enriched at synapses, especially glutamatergic synapses and GABAergic synapses. Some DEPs were involved in energy metabolism, thyroid hormone synthesis pathway, and Na

Background: Autism spectrum disorder (ASD) has become one of the most common neurological developmental disorders in children. However, the study of ASD diagnostic markers faces significant challenges due to the existence of heterogeneity. Methods: In this study, genetic testing was performed on children who were clinically diagnosed with ASD. Children with ASD susceptibility genes and healthy controls were studied. The proteomics of plasma and peripheral blood mononuclear cells (PBMCs) as well as plasma metabolomics were carried out. Results: The results showed that although there was genetic heterogeneity in children with ASD, the differentially expressed proteins (DEPs) in plasma, PBMCs, and differential metabolites in plasma could still effectively distinguish autistic children from controls. The mechanism associated with them focus on several common and previously reported mechanisms of ASD. Limitations: The number of samples carrying risk genes in omics research is limited. In further research, a large sample size is required. A group of children who have been diagnosed with ASD but have not been detected to carry risk genes should also be included.Conclusion: The biomarkers for ASD diagnosis could be found by taking DEPs and differential metabolites into consideration. Integrating omics data, glycerophospholipid metabolism and N-glycan biosynthesis might play a critical role in the pathogenesis of ASD.

Intrahepatic cholestasis of pregnancy (ICP) is one of the more common complications in the middle and late stages of pregnancy, which requires early detection and intervention. The aim of the study is to investigate the changes in the metabolic profile of bile acids (BAs) in plasma of pregnant women with ICP and to look biomarkers for the diagnosis and grading of ICP, and to explore the disease mechanism. The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze plasma BAs. Twenty-seven BAs can be quantified in all participants. Among them, 22 BAs were identified as differential BAs between ICP and control groups. Five BAs include 3β-CA, 3β-DCA, CDCA-3Gln, NCA, and Tβ-MCA, were found to be associated with ICP for the first time. Nine BAs include NCA, GCA, GCDCA, GHCA, GUDCA, HCA, TCA, TCDCA and THCA, can be used as possible ICP diagnostic biomarkers. Four BAs, i.e., GLCA, THCA, GHCA and TLCA-3S may be used as potential biomarkers for ICP grading. There were significant differences in plasma BA profiles between ICP patients and the control. The BA profiles of mild ICP group and severe ICP group partially overlapped. Potential diagnostic and grading BA markers were identified. A significant characteristic of ICP group was the increase of conjugated BAs. A mechanism to sustain the equilibrium of BA metabolism and adaptive response has been developed in ICP patients to accelerate excretion and detoxification.

Sulfides play an important role in the photobiological production of H2 from microalgae. Apart from the conventional sulfur deprivation strategy, the addition of sulfides is also found to promote the hydrogen production and biomass of microalgae. However, it is still unclear that how different sulfides influence the biomass and hydrogen production of algae. Here, an evaluation of various sulfides for enhancing the photobiological hydrogen production by co-cultivation of Chlamydomonas reinhardtii and Thiomonas intermedia was systematically investigated. Our results show that the addition of different sulfides can improve the biomass and photobiological hydrogen production of algae, and sodium thiosulfate (Na2S2O3) displays the best efficacy with a maximum H2 photoproduction rate of 255.52 μmol/mg Chl, which was 5.9 times higher than that of the pure algal culture. Notably, sustained H2 production can be achieved by intermittent supplement of sulfides. Moreover, the effects of different sulfides on various physiological factors, such as starch accumulation, respiration rate and hydrogenase activity of the algae were also evaluated. This report provides the fundamental information for an enhanced and sustainable photobiological production of renewable hydrogen using microalgae.

Our understanding of molecular chaperone function in membrane protein biogenesis lags far behind that in soluble protein biogenesis. Through a combined approach including isothermal titration calorimetry, UV–Vis spectroscopy, and fluorescence spectroscopy, the behavior of ATP-dependent chaperonin GroEL–GroES, a paradigmatic chaperone of soluble protein folding, was investigated in the refolding of membrane protein bacteriorhodopsin (BR) and its membrane insertion. We found that BR bound asymmetrically to the double-ring GroEL, with a much higher affinity when it was partially denatured. GroEL alone showed a clear influence on BR refolding, but the presence of ATP was necessary to significantly enhance both the rate and yield of the GroEL-mediated folding, in contrast to the adverse effect of GroES on the folding yield. However, synergy between ATP and GroES was shown to be required not only for releasing high-affinity BR species from GroEL, but also for unfolding and rescuing the misfolded conformers complexed to GroEL. This is consistent with the observation that maximum rate enhancement of BR refolding or assembly with the prepared inverted membrane vesicles was achieved when the complete chaperonin system was used. Our results support the iterative unfolding mechanism of GroEL activity previously proposed for soluble proteins, whereby GroEL might perform repeated unfolding and release of BR, thus offering additional opportunities for timely folding or membrane integration. This work provides important information on the convergence of folding of membrane and soluble proteins in light of folding pathways and the role of molecular chaperones.

INTRODUCTION Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Looking for reliable diagnostic markers for early diagnosis can reduce the impact of the disease on the fetus OBJECTIVE: The present study is designed to find plasma metabolites that can be used as potential biomarkers for GDM, and to clarify GDM-related mechanisms METHODS: By non-target metabolomics analysis, compared with their respective controls, the plasma metabolites of GDM pregnant women at 12-16 weeks and 24-28 weeks of pregnancy were analyzed. Multiple reaction monitoring (MRM) analysis was performed to verify the potential marker RESULTS: One hundred and seventy-two (172) and 478 metabolites were identified as differential metabolites in the plasma of GDM pregnant women at 12-16 weeks and 24-28 weeks of pregnancy, respectively. Among these, 40 metabolites were overlapped. Most of them are associated with the mechanism of diabetes, and related to short-term and long-term complications in the perinatal period. Among them, 7 and 10 differential metabolites may serve as potential biomarkers at the 12-16 weeks and 24-28 weeks of pregnancy, respectively. By MRM analysis, compared with controls, increased levels of 17(S)-HDoHE and sebacic acid may serve as early prediction biomarkers of GDM. At 24-28 weeks of pregnancy, elevated levels of 17(S)-HDoHE and L-Serine may be used as auxiliary diagnostic markers for GDM CONCLUSION: Abnormal amino acid metabolism and lipid metabolism in patients with GDM may be related to GDM pathogenesis. Several differential metabolites identified in this study may serve as potential biomarkers for GDM prediction and diagnosis.

Alzheimer’s disease (AD) is the most common age-associated dementia with complex pathological hallmarks. Mitochondrion, synaptosome, and myelin sheath appear to be vulnerable and play a key role in the pathogenesis of AD. To clarify the early mechanism associated with AD, followed by subcellular components separation, we performed iTRAQ (isobaric tags for relative and absolute quantification)-based proteomics analysis to simultaneously investigate the differentially expressed proteins (DEPs) within the mitochondria, synaptosome, and myelin sheath in the cerebrum of the 6-month-old triple transgenic AD (3 × Tg-AD) and 6-month-old wild-type (WT) mice. A large number of DEPs between the AD and WT mice were identified. Most of them are related to mitochondria and synaptic dysfunction and cytoskeletal protein change. Differential expressions of Lrpprc, Nefl, and Sirpa were verified by Western blot analysis. The results suggest that decreased energy metabolism, impaired amino acid metabolism and neurotransmitter synthesis, increase compensatory fatty acid metabolism, up-regulated cytoskeletal protein expression, and oxidative stress are the early events of AD. Among these, mitochondrial damage, synaptic dysfunction, decreased energy metabolism, and abnormal amino acid metabolism are the most significant events. The results indicate that it is feasible to separate and simultaneously perform proteomics analysis on the three subcellular components.

Autism spectrum disorder (ASD) is a common childhood neurodevelopmental disorder that may be related to trace elements. However, reports on the relationship between them are still inconsistent. In this article, we conducted a meta-analysis on this issue. We searched the PubMed, EMBASE, and Cochrane databases as of November 15, 2019. A random-effects model was used, and subgroups of studies were analyzed using samples of different measurements. Twenty-two original articles were identified (18 trace elements, including a total of 1014 children with ASD and 999 healthy controls). In autistic children, the overall levels of barium (Ba), mercury (Hg), lithium (Li), and lead (Pb) were higher. There were significant differences in the levels of copper (Cu) in the hair and serum between autistic children and the control group. The levels of Hg, Li, Pb and selenium (Se) in the hair of autistic children were higher than those of healthy children, while the levels of zinc (Zn) in the blood were lower. Excessive exposure to toxic heavy metals and inadequate intake of essential metal elements may be associated with ASD. Preventing excessive exposure to toxic metals and correcting poor dietary behaviors may be beneficial for the prevention and treatment of the disease.

Diabetic nephropathy (DN) is a serious complication of diabetes caused by changes in the structure and function of the kidneys. It is important to detect diagnostic biomarkers of DN at an early stage, in which the drug can slow the loss of kidney function and prevent disease progression. In recent years, a variety of biological markers related to DN have been discovered, which is of great significance for predicting the occurrence and development of diseases. Due to the simplicity of non-invasive collection, urine is an ideal biological sample for the discovery of new biomarkers of kidney disease. We reviewed some new urinary biomarkers related to early DN patients, including urinary proteins, peptides, and exosomes biomarkers. We also highlight the proteins associated with tubular damage, glomerular damage, inflammation and oxidative stress marker. Despite the promise of these new urinary biomarkers, we next proposed a review of the most recent publications reporting on larger cohorts, focusing on those that aim at qualification or validation. This review provides important data to better understand biomarkers related to the pathophysiology of DN, and these markers have been increasingly studied for disease progression to provide effective human treatment.

Malaria is a serious worldwide disease, caused by a bite of a female Anopheles mosquito. The parasite transferred into complex life round in which it is grown and reproduces into the human body. The detection and recognition of Plasmodium species are possible and efficient through a process called staining (Giemsa). The staining process slightly colorizes the red blood cells (RBCs) but highlights Plasmodium parasites, white blood cells and artifacts. Giemsa stains nuclei, chromatin in blue tone and RBCs in pink color. It has been reported in numerous studies that manual microscopy is not a trustworthy screening technique when performed by nonexperts. Malaria parasites host in RBCs when it enters the bloodstream. This paper presents segmentation of Plasmodium parasite from the thin blood smear points on region growing and dynamic convolution based filtering algorithm. After segmentation, malaria parasite classified into four Plasmodium species: Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, and Plasmodium malaria. The random forest and K-nearest neighbor are used for classification base on local binary pattern and hue saturation value features. The sensitivity for malaria parasitemia (MP) is 96.75% on training and testing of the proposed approach while specificity is 94.59%. Beside these, the comparisons of the two features are added to the proposed work for classification having sensitivity is 83.60% while having specificity is 94.90% through random forest classifier based on local binary pattern feature.

Nanotechnology-enhanced drug delivery via receptor-mediated endocytosis provides a promising and clinically translatable strategy to targeted diagnosis and precise therapy, yet an in-depth understanding of this process is technically limited by our inability to probe the nanocarrier distributions at the cell surface and inside the cell at nanoscale resolution. Here, we report small blinking single-layer graphene oxide nanosheet (GONS) that serves both as a nanoscopy fluorophore and as a drug-bearing nanocarrier for addressing such a task. The GONS blinks spontaneously with a low duty cycle (∼0.003), high photon output (∼3000 photons per switching event), and higher photostability than organic dyes, thus affording well for single molecule localization-based super-resolution imaging. Applying the localization analysis, we reveal GONS clustering size, GONS number in each cluster, and the number fraction of GONSs that participate in clustering at the cell surface and in the cytoplasm, respectively, and track their evolutions over 24 h. The data suggest that the nanocarrier clustering and distribution at the cell surface control their endocytosis and accumulation inside the cell. This process is drug-independent during which drug transportation into the destination relies on its own loading and escaping capability. Thus, this work demonstrates the great potential of the dual-functional GONS in quantitative super-resolution imaging of drug carriers in cells, which is helpful for the rational design of a smart drug delivery system aiming at achieving full therapeutic capacity.

Photosystem I (PSI) generates the most negative redox potential found in nature, and the performance of solar energy conversion into alternative energy sources in artificial systems highly depends on the thermal stability of PSI. Thus, understanding thermal denaturation is an important prerequisite for the use of PSI at elevated temperatures. To assess the thermal stability of surfactant-solubilized PSI from cyanobacteria Arthrospira Platensis, the synergistic denaturation effect of heat and surfactant was studied. At room temperature, surfactant n-dodecyl-β-d-maltoside solubilized PSI trimer gradually disassembles into PSI monomers and free pigments over long time. In the solubilizing process of PSI particles, surfactant can uncouple pigments of PSI, and the high concentration of surfactant causes the pigment to uncouple more; after the surfactant-solubilizing process, the uncoupling is relatively slow. During the heating process, changes were monitored by transmittance T800nm, ellipticity θ686nm and θ222nm, upon slow heating (1.5 °C per minute) of samples in Tris buffer (20 mM, pH 7.8) from 20 to 95 °C. The thermal denaturation of surfactant-solubilized PSI is a much more complicated process, which includes the uncoupling of pigments by surfactants, the disappearance of surrounding surfactants, and the unfolding of PSI α-helices. During the heating process, the uncoupling chlorophyll a (Chla) and converted pheophytin (Pheo) can form excitons of Chla–Pheo. The secondary structure α-helix of PSI proteins is stable up to 87–92 °C in the low-concentration surfactant solubilized PSI, and high-concentration surfactant and pigments uncoupling can accelerate the α-helical unfolding.

Tumor markers have been regularly detected for early cancer diagnosis in clinical oncology. The development of facile and low cost technology has become an important challenge for their diagnosis. We here report a low-cost plasmonic silver needle (PSN) for immunofluorescence detection of tumor biomarkers. The fluorescence signal is enhanced on the needle by up to 220-fold, allowing high-performance detection of tumor markers down to 0.08 ng mL-1. To assess the clinical potential of the proposed assay technique, PSN-based sandwich immunoassay for the detection of alpha-fetoprotein and carcinoembryonic antigen were performed for blood as well as for serum sample. The results from serum sample have an excellent agreement with an electrochemluminecence assay. The small relative error and a good linear correlation suggest that the accuracy and precision of this analytical technology are satisfactory. This assay technique with lower cost, use of less sample, higher sensitivity and easier procedure shows great promise for the facile and early cancer diagnosis.

An ultra-high fluorescence enhancement for two dyes on photonic crystal films was achieved to construct a two-color immuno-dot blot assay. This assay was demonstrated to simultaneously detect chemokine receptor co-expressed in cancer cells and reveal their co-operative and subtle changes after binding with respective ligands and drugs.

Background Chemokines and their cognate receptors play important role in the control of leukocyte chemotaxis, HIV entry and other inflammatory diseases. Developing an effcient method to investigate the functional expression of chemokines and its interactions with specific receptors will be helpful to asses the structural and functional characteristics as well as the design of new approach to therapeutic intervention. Results By making systematic optimization study of expression conditions, soluble and functional production of chemokine C-C motif ligand 8 (CCL8) in Escherichia coli (E. coli) has been achieved with approx. 1.5 mg protein/l culture. Quartz crystal microbalance (QCM) analysis exhibited that the purified CCL8 could bind with C-C chemokine receptor type 3 (CCR3) with dissociation equilibrium constant (K D) as 1.2 × 10−7 M in vitro. Obvious internalization of CCR3 in vivo could be detected in 1 h when exposed to 100 nM of CCL8. Compared with chemokine C-C motif ligand 11 (CCL11) and chemokine C-C motif ligand 24 (CCL24), a weaker chemotactic effect of CCR3 expressing cells was observed when induced by CCL8 with same concentration. Conclusion This study delivers a simple and applicable way to produce functional chemokines in E. coli. The results clearly confirms that CCL8 can interact with chemokine receptor CCR3, therefore, it is promising area to develop drugs for the treatment of related diseases. Electronic supplementary material The online version of this article (10.1186/s12865-017-0237-5) contains supplementary material, which is available to authorized users.