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The association between daptomycin exposure and eosinophilic pneumonia (EP) is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics and provide more evidence for better identify and management of daptomycin-induced eosinophilic pneumonia in clinical practice.Literature from 1991 to October 31, 2021 on EP induced by daptomycin were collected for retrospective analysis.A total of 47 patients (40 male and 7 female) from 35 studies were included. The median age was 67 years (range 28-89), and 78.7% of patients were ≥60 years. Daptomycin was mainly used in patients undergoing osteoarticular infections (63.8%). Typical initial symptoms were fever (91.5%), cough (55.3%) and dyspnea (59.6%). The median onset time of symptom was 3 weeks. EP recurred in 14.9% of patients after the re-administration of daptomycin, and 57.1% of EP recurred within 24h. Most cases were accompanied by marked accumulation of eosinophils in peripheral (41 cases) and/or bronchoalveolar lavage fluid (27 cases). The main radiological features were pulmonary infiltration, ground glass opacity or consolidation in CT/CXR. All patients had symptom resolution after discontinuation of daptomycin except for one patient died due to the progression of the primary disease, the median time to symptoms relief was 3 days. Corticosteroids have been shown to help symptoms relief in some cases (59.6%).Daptomycin-induced eosinophilic pneumonia is a rare and serious complication. Physicians should consider eosinophilic pneumonia as a differential diagnosis when receiving daptomycin therapy, particularly in elderly male patients.

Scavenger receptors (SRs) have been shown to participate in regulating the immune response of macrophages, and fucoidan from Fucus vesiculosus has been verified as a ligand of class A SRs (SR-A). However, the roles of SRs in the immunomodulatory activity of fucoidan from Saccharina japonica are not clear. Thus, we performed a comparative study of the immunomodulatory activities of six different fucoidans from S. japonica on RAW 264.7 macrophages, and the roles of SRs in the processes were studied. Six fucoidans (0.5 M FPS, 1 M FPS, 2 M FPS, 0.5 M DFPS, 1 M DFPS and 2 M FPS) had different molecular weights and chemical compositions. Griess reagent system, ELISA and RT-qPCR results showed that different fucoidans displayed different stimulation of macrophages to secrete NO, IL-6, IL-1β and TNF-α, as well as differences in the upregulation of their gene expressiones. Flow cytometric analysis of the protein expression level indicated the upregulation of TLR4 after treatment with all the fucoidans but different expressions of SRs. Furthermore, only 0.5 M DFPS and 1 M DFPS were confirmed to be ligands of SR-A through the competitive binding assay with Ac-LDL bound to the fluorescent probe DiI by flow cytometry. Our results revealed that fucoidans with low molecular weight and heterogeneity more easily bound to SRs and contributed to their immunomodulatory effects. This comparative study might promote the biological study of targeted SRs and the discovery of new pharmacological mechanisms of different fucoidans.

Understanding the relationship between contrast agents and Kounis syndrome (KS) is mainly based on case reports. The purpose of this research is to explore the clinical characteristics of contrast media induced KS.We searched for contrast-induced KS case reports through Chinese and English databases from 1991 to October 31, 2021.A total of 26 patients (19 men and 7 women,) were included, with a median age of 60 years (range 30-83). The contrast agents that cause KS mainly included gadolinium-based contrast agent (7 cases), iodine-containing contrast media (12 cases). KS mainly occurred within 30 min after administration and mainly manifests as chest pain and allergic reactions. Electrocardiogram (ECG) mainly showed ST elevation. Echocardiography mainly revealed normal. Coronary angiography showed normal, coronary vasospasm, stent thrombosis, occlusion and stenosis. After treatment with steroids, antihistamines and anti-ischemic therapy, 24 patients recovered completely and 2 patients died.KS is a rare adverse reaction of contrast media. Radiologists should recognize this rare but serious disease to ensure rapid diagnosis and proper management.

Advanced functional materials, especially gel electrolytes, play a very important role in the preparation of electrochemical actuators and sensors, and have received extensive attention. In this review, a general classification of gel electrolytes is firstly introduced according to the type of medium. Then, the research progress of gel electrolytes with different types used to fabricate electrochemical actuators is summarized. Next, the current research progress of gel electrolytes used in different types of electrochemical sensors, including strain sensors, stress sensors, and gas sensors is introduced. Finally, the future challenges and development prospects of electrochemical actuators and sensors based on gel electrolytes are discussed. The huge application prospects of gel electrolyte are worthy of further focusing by researchers, which will have an indispensable impact on human life and development.

Previous knowledge about the association between proton pump inhibitors (PPIs) exposure and subacute cutaneous lupus erythematosus (SCLE) was mainly based on limited case reports or few review studies. We aim to evaluate the clinical characteristics, management, and outcome in patients with PPIs-induced SCLE.Case reports and case series from 2000 to December 31, 2021, on SCLE induced by PPIs were collected and retrospectively analyzed.A total of 29 patients (6 male and 23 female) were included from 19 studies, the median age was 61 years (range 19-85), and 65.5% of patients were ≥60 years old. 37.9% of patients had the history of autoimmune diseases. The incubation period of PPIs intro to SCLE was 6 weeks for PPI-naive patients and 2 weeks for those re-administration of PPIs. The most common symptoms were annular and polycyclic erythematous (74.1%), rash or maculopapular (48.1%), and scaly plaques (40.7%). Trunk (69.2%), extremities (69.2%), face (26.9%), chest (26.9%), and back (26.9%) were common involved locations. Antinuclear antibodies, anti-Ro/SSA antibodies, and anti-La/SSB antibodies were positive in 24 patients (82.8%), 24 patients (82.8%), and 6 patients (20.7%), respectively. Direct immunofluorescence was positive in 50% of cases. Complete clinical remission (92.6%) was observed (median time: 4 weeks) with discontinuation of PPIs and treatment of oral corticosteroids (61.1%), hydroxychloroquine (44.4%), or topical steroids (16.7%).PPIs-related SCLE is a rare adverse reaction based on clinical manifestations associated with immunological abnormalities and suggestive histological findings. PPIs should be suspected when considering possible culprits for drug-related SCLE.

Chemotherapy resistance is one of the most critical challenges in colorectal cancer (CRC) treatment. The occurrence and development of chemotherapy resistance closely related to the tumor immune microenvironment (TIME). As the most important immunosuppressive immune cells infiltrating into the TIME, macrophages are essential for chemotherapy resistance in CRC treatment. In this study, we found that a kind of fucoidan (FPS1M) induced macrophages differentiation to the M1 phenotype, and this transformation promoted cancer cells apoptosis both in vitro and in vivo. TNFα is a key mediator of FPS1M-induced tumorcidal activity of macrophages. Mechanistically, as a stimulator of TLR4, FPS1M enhanced macrophages glycolysis and regulated macrophages differentiation to the M1 phenotype by the activation of TLR4 mediated PI3K/AKT/mTOR signaling axis. In addition, FPS1M improved the immunosuppressed tumor microenvironment by increasing the infiltration of M1 macrophages in tumor tissue, which was conducive to improving the sensitivity of tumor to chemotherapy. Collectively, our findings demonstrated that FPS1M has the great potential to be used in tumor immunotherapy. The results also suggested that the combination of FPS1M with capecitabine is an alternative therapy method for colon cancer.

Novel ternary nanohybrids, bifunctionalized graphene oxide/MnFe2O4 magnetic nanoparticles (PEHA-Phos-GO/MnFe2O4), were prepared by a facile method and applied for the removal of Pb(II) from aqueous solution. Attributing to the numerous amino and phosphate groups on the bifunctionalized GO nanosheets as well as the magnetic nanoparticles of MnFe2O4, PEHA-Phos-GO/MnFe2O4 demonstrated high removal efficiency of Pb(II) and rapid magnetic separation. The 366.4 mg/g maximum adsorption capacity of Pb(II) on PEHA-Phos-GO/MnFe2O4 was obtained at the optimal adsorption pH of 5.5, much higher than that on GO (212.1 mg/g). The kinetics and isotherm data indicated that the adsorption processes can be well described by the pseudo-second-order kinetics and the Langmuir model. For the adsorption of Pb(II) on PEHA-Phos-GO/MnFe2O4, thermodynamic studies revealed the endothermic nature of the spontaneous adsorption process. The exhibited adsorption capacity, easy magnetic separation and reusability make the PEHA-Phos-GO/MnFe2O4 nanohybrids very promising adsorbents for efficacious removal of heavy metals from aqueous solutions in environmental pollution cleanup.

Highlights • The detection rate of hock-a-loogie saliva was higher than nasopharyngeal swabs. • Hock-a-loogie saliva sample had a higher viral load than throat swab. • Hock-a-loogie saliva sampling for SARS-CoV-2 detection is reliable., To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P

Previous knowledge about the relationship between voriconazole exposure and periostitis was mainly based on limited case reports and few retrospective studies. The purpose of this study was to assess the clinical characteristics, diagnosis and management of voriconazole-associated periostitis.Case reports and case series from 1998 to November 30, 2021 on periostitis induced by voriconazole were collected for retrospective analysis.Forty four patients (18 male and 26 female) from 34 studies were included in total. The median age was 58 years (29-74). The majority of patients had undergone organ transplantation (50.0%) or suffered from hematologic malignancy (31.81%). The median onset time of symptoms was 6 months after the start of voriconazole. The most common initial symptom was diffuse skeletal pain (68.28%) which can be severe and even disabling (66.7%). Ribs (37.21%), femurs (32.56%), scapulae (25.58%), humerus (23.26%), and clavicle (23.26%) were the common involved locations. Most cases were accompanied by different degrees of elevated serum alkaline phosphatase and fluoride level, while some presented with elevated bone-specific alkaline phosphatase. The main radiological features included periosteal reaction and multifocal high radiotracer uptake on bone scintigraphy. The formation of new bone was characterized with bilateral, irregular, nodular, as well as high density. The resolution of symptoms was observed with discontinuation of voriconazole in all patients, of whom 18 patients (52.94%) were relieved within a week. Itraconazole, posaconazole or isavuconazole were safe alternatives to voriconazole in voriconazole-induced periostitis.Voriconazole-induced periostitis is an infrequent complication characterized by bone inflammation involving one or multiple skeletal areas. Bony pain, elevated serum alkaline phosphatase as well as fluoride level are suspicious signs during voriconazole treatment.

Metabolic syndrome (MetS) is a pathological state of multiple metabolic abnormalities. Dietary fibers (DFs) has been widely concerned about its positive role in MetS. Different from the DFs of terrestrial plants, the DFs of seaweeds has unique composition and structural characteristics. The aim of this study is to investigate the composition and microstructures of DF derived from Saccharina japonica, and its positive effects on MetS mice induced by high fat diet (HFD). We extracted DF from S. japonica (DFSJ). DFSJ has a high proportion of soluble dietary fiber (SDF) and it shows good water holding capacity (11.34 ± 1.63 g/g) and swelling property (32.9 ± 2.52 mL/g). Supplementing DFSJ can significantly improve insulin resistance (IR), dyslipidemia in HFD mice. Besides, DFSJ can reduce inflammatory factors (TNF-α, MCP-1 and IL-6), improve the hepatic oxidative stress and protect visceral organs from the injury of HFD. Finally, 16S rDNA high-throughput sequencing was used to further analyze the profile changes of gut microbiota. The results indicated that supplementing DFSJ can effectively ameliorate gut microbiota dysbiosis. In particular, DFSJ can increase the relative abundance of some beneficial bacteria, such as Bifidobacterium, Turicibacter and Akkermansia. Our results indicated that DFSJ has a comprehensive regulatory effect on MetS, and it is involved in various regulatory pathways, such as antioxidant, anti-inflammatory, hypoglycemic and hypolipidemic pathways in HFD-induced MetS mice. Our results reveal the great potential of DFSJ as an effective regulator on various metabolic abnormalities of MetS.

Metabolic syndrome (MetS) is a pathological condition of a variety of metabolic abnormalities, which requires more urgent treatment and intervention. Fucoidan has been recommended as a supplement for health enhancement and disease management. Here, we first propose that the beneficial effect of low molecular weight fucoidan fraction LF2 in regulating metabolic syndrome induced by high-fat diet is similar to that of metformin, in terms of molecular mechanism and gut microbiota. The study found that LF2 significantly reduces fasting blood glucose, enhances insulin sensitivity and restores insulin homeostasis and lipid homeostasis. Moreover, LF2 reduced liver oxidative stress and inflammation, and improved hepatocyte steatosis. To decipher the mechanism behind this therapeutic effect, both the molecular mechanisms and gut microbiota were further analyzed. LF2 inhibited the activation of PI3K-Akt-mTOR axis and decreased the expression of SREBP-1c and PPARγ in liver. Interestingly, we found that LF2 and metformin have similar effects on gut microbiota, increasing the proportion of Verrucomicrobia and enriching the abundance of Akkermansia muciniphila, which is beneficial to host health. Collectively, our research clarifies the new application of fucoidan as a functional food for anti-MetS, and provides a new insight for fucoidan to exert systemic therapeutic effects from the perspective of molecular mechanism and gut microbiota.

Diffuse alveolar injury and pulmonary fibrosis (PF) are the main causes of death of Covid-19 cases. In this study a low molecular weight fucoidan (LMWF) with unique structural was obtained from Laminaria japonica, and its anti- PF and anti-epithelial-mesenchymal transition (EMT) bioactivity were investigated both in vivo and in vitro. After LWMF treatment the fibrosis and inflammatory factors stimulated by Bleomycin (BLM) were in lung tissue. Immunohistochemical and Western-blot results found the expression of COL2A1, β-catenin, TGF-β, TNF-α and IL-6 were declined in mice lung tissue. Besides, the phosphorylation of PI3K and Akt were inhibited by LMWF. In addition, the progression of EMT induced by TGF-β1 was inhibited by LMWF through down-regulated both TGF-β/Smad and PI3K/AKT signaling pathways. These data indicate that unique LMWF can protect the lung from fibrosis by weakening the process of inflammation and EMT, and it is a promising therapeutic option for the treatment of PF.

Porphyran, derived from the marine red algae Porphyra and Pyropia, is a type of polysaccharide. Oligo-porphyran (OP) was prepared from porphyran (isolated from Pyropia yezoensis) through the acidolysis reaction containing a linear backbone of alternating 3-linked β-d-galactose and 4-linked α-l-galactose-6-sulfate. Our previous studies have shown that oligo-porphyran could attenuate MPTP-induced behavioral deficits in mice by inhibiting the tyrosine hydroxylase (TH) loss. In the present study, we further investigated how OP protects the dopamine neurons from loss in PC12 cells. OP significantly attenuated LDH release and the production of reactive oxygen species (ROS) lesioned by 6-OHDA. Moreover, OP alleviated the mitochondrial membrane potential (MMP) loss, the ratio of Bax/Bcl-2, and upregulated the PI3K/ Akt/PKC pathway, the level of tyrosine hydroxylase (TH), and dopamine transporter (DAT). Furthermore, OP decreased the production of proinflammatory cytokines. Terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining further indicated that OP treatment inhibited apoptosis. These results might contribute to the overall understanding of the potential health benefits of OP for food and drug applications.

Parkinson&rsquo, s disease (PD), one of the most common neurodegenerative disorders, is caused by dopamine depletion in the striatum and dopaminergic neuron degeneration in the substantia nigra. In our previous study, we hydrolyzed the fucoidan from Saccharina japonica, obtaining three glucuronomannan oligosaccharides (GMn, GM1, GM2, and GM3) and found that GMn ameliorated behavioral deficits in Parkinsonism mice and downregulated the apoptotic signaling pathway, especially with GM2 showing a more effective role in neuroprotection. However, the neuroprotective mechanism is unclear. Therefore, in this study, we aimed to assess the neuroprotective effects of GM2 in vivo and in vitro. We applied GM2 in 1-methyl-4-phenylpyridinium (MPP+)-treated PC12 cells, and the results showed that GM2 markedly improved the cell viability and mitochondrial membrane potential, inhibited MPP+-induced apoptosis, and enhanced autophagy. Furthermore, GM2 contributed to reducing the loss of dopaminergic neurons in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice through enhancing autophagy. These data indicate that a possible protection of mitochondria and upregulation of autophagy might underlie the observed neuroprotective effects, suggesting that GM2 has potential as a promising multifunctional lead disease-modifying therapy for PD. These findings might pave the way for additional treatment strategies utilizing carbohydrate drugs in PD.

Parkinson&rsquo, s disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra and dopamine depletion in the striatum, affects up to 1% of the global population over 50 years of age. Our previous study found that a heteropolysaccharide from Saccharina japonica exhibits neuroprotective effects through antioxidative stress. In view of its high molecular weight and complex structure, we degraded the polysaccharide and subsequently obtained four oligosaccharides. In this study, we aimed to further detect the neuroprotective mechanism of the oligosaccharides. We applied MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to induce PD, and glucuronomannan oligosaccharides (GMn) was subsequently administered. Results showed that GMn ameliorated behavioral deficits in Parkinsonism mice. Furthermore, we observed that glucuronomannan oligosaccharides contributed to down-regulating the apoptotic signaling pathway through enhancing the expression of tyrosine hydroxylase (TH) in dopaminergic neurons. These results suggest that glucuronomannan oligosaccharides protect dopaminergic neurons from apoptosis in PD mice.

DNA functionalized nanomaterials have attracted tremendous attention for bioanalytical applications. Owing to exceptional fluorescence quenching ability, most DNA-based nanoprobes were designed with turn-on signals for target gene detection, while only a few of them could simultaneously achieve gene detection and regulation in one system. In this study, we explored the use of nanoscale zeolitic imidazolate framework-8 (ZIF-8) as a building block to construct a DNA-based nanoprobe. We found ZIF-8 could stably adsorb DNA to resist the dissociation by various biological ligands, enabling potential biological applications. However, ZIF-8 was not a nano-quencher to turn off the fluorophore labeling on the adsorbed DNA. We therefore designed a DNAzyme embedded molecular beacon (DMB) to functionalize ZIF-8. After endocytosis, ZIF-8 was disintegrated to release DMB for target mRNA detection, and the co-released Zn2+ acted as an effective cofactor to activate the embedded DNAzyme for mRNA regulation. This study provides a versatile nano-platform to realize multiple functions inside cells by using functional nucleic acids, which holds great promise for theranostic applications.

A novel reactive phosphorus and sulfur-containing monomer (bis(acryloxyethyldiphenylphosphate)sulfone, BADPS) was synthesized to enhance the comprehensive performance of unsaturated polyester resin (UPR), and corresponding flame-retardant unsaturated polyester resins (FR-UPRs) with various amounts of BADPS were prepared by radical bulk polymerization. The flame retardancy and thermal and mechanical properties of the UPR samples were investigated by limiting oxygen index (LOI) measurements, cone calorimetry, differential scanning calorimetry (DSC), a thermogravimetric analysis (TGA), and a tension test. The results showed that the introduction of BADPS remarkably enhanced the flame resistance and high-temperature stability, as well as the tensile performance of UPR. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and Raman spectroscopy studies revealed that BADPS can efficaciously promote the formation of UPR char residue with an improved microstructure and increased graphitization degree, which enhancedthe high-temperature stability and char yield of UPR. Additionally, a thermogravimetry-Fourier transform infrared (TG-FTIR) analysis corroborated that the evolution of combustible volatiles from UPR decomposition was substantially restrained by the incorporation of BADPS, which is beneficial for the suppression of fire hazards in UPR.

Novel ternary nanohybrids, bifunctionalized graphene oxide/MnFe

Revealing the relationship between the enzyme and substrate could provide insights into signaling networks. Mass spectrometry has been widely applied for the large scale interrogation of biological systems in proteomics, and also has taken an important role in determination of enzyme activities and screening of enzyme inhibitors. In this review, we introduced the recent advance in the mass spectrometry based methods for enzyme substrate screening and enzyme kinetics analysis, including in vitro substrate screening using protein-derived library and peptide-derived library, in vivo substrate screening and high-throughput kinetics analysis, and then gave our opinions on the outlook of mass spectrometry in the study of enzyme kinetics in complex system.

Covalently-functionalized graphene oxide (FGO) was successfully prepared by grafting a novel phosphorus-containing flame retardant, [2-((6-oxidodibenzo[c,e][1,2]oxaphosphinin-6-yl)methoxy)acryloxyethylchlorophosphate, PACP], to graphene oxide (GO). The resulting FGO demonstrated hydrophobicity and stability in polar solvents such as N,N-dimethylformamide (DMF). The reactive vinyl groups of PACP attached to FGO further copolymerized with styrene to produce polystyrene-FGO (PS-FGO) nanocomposites. PS-FGO samples showed obviously improved fire-resistance, thermal behavior and glass transition temperature in comparison with those of neat PS and PS-GO samples, due to the good dispersion of FGO in PS as well as the strong interfacial bonds between FGO and the matrix. In addition, thermogravimetry-Fourier transform infrared (TG-FTIR) results indicated that the evolution of volatile products from PS decomposition was significantly inhibited by the introduction of FGO. Furthermore, scanning electron microscopy (SEM) and FTIR and Raman spectroscopy were employed to investigate the char residue, elaborating the flame-retardance mechanism.

The enzymatic process involving the incubation of a library of substrates with an enzyme is the key step for a few important experiments for bioanalytical chemistry including proteomics analysis, enzymatic labeling, substrate screening, etc. The relationship between the substrates’ consumption and their abundances in a complex enzymatic system with a huge number of coexisting substrates of different abundances was not well-known. In this study, we have demonstrated theoretically and experimentally that the priority of substrate consumption depended on their specificity constants but not abundances. We derived the expression between the fractions of the substrates consumed (pi) and their specificity constants. Using the enzymatic system of five synthetic peptide substrates of trypsin, we validated through 24 experiments that the ln(1 – pi) values of competing substrates have linear correlation with their specificity constants, and thus, the priority of substrate depletion has no relation with their abundan...

Background/Aims: Basophils have been reported to infiltrate skin lesions in various skin diseases, but not in systemic lupus erythematosus (SLE). This study investigated basophil infiltration in SLE and its mechanism. Methods: Twenty newly diagnosed SLE patients and twenty healthy controls were enrolled. Nine SLE patients underwent skin biopsies. Flow cytometric analysis the phenotype of peripheral basophils and their migration rate toward RANTES and MCP-1 were analyzed with the transwell culture system, also the expression of these two chemokines in skin tissue were analyzed with immunohistochemistry. Results: Increased activation and decreased numbers of peripheral basophils were observed in SLE patients compared with controls. Basophil migration into skin lesions of SLE patients were observed, but not in normal skin tissue. This migration was related to the upregulation of chemokine receptors CCR1 and CCR2 on basophils. In vitro studies showed that migration rate toward RANTES and MCP-1 increased significantly in basophils from SLE patients compared with those from controls. Consistently, high levels of RANTES and MCP-1 expression were observed in skin lesions from SLE patients but not in normal skin tissue. Conclusion: Basophil recruitment to skin lesions of SLE patients mediated by CCR1 and CCR2, which may contribute to tissue damage in SLE.

Sphenophyllum was an important and long-surviving sphenopsid genus in the Paleozoic floras, with a worldwide distribution. A new species, Sphenophyllum changxingense sp. nov., is described from the Upper Devonian Wutong Formation of Changxing County, Zhejiang Province, China. This plant is characterized by two orders of slender axes and wedge-shaped leaves borne in whorls. The axes bear short spines and show longitudinal ridges and furrows on surface. Three to eight isophyllous leaves, with one, two, or no second-order axes, are attached at each node of first-order axes. Leaves bear spines and show a bilobate morphology; the two leaf lobes divide distally to form several marginal segments, each segment with a leaf vein. Sphenophyllum changxingense represents an early and primitive species within the genus, in light of the absence of heterophylly and specialized hook-like leaves. Like some Carboniferous and Permian species, it appears to have formed dense mats with mutually supportive axes. This pl...

Many important experiments in proteomics including protein digestion, enzyme substrate screening, enzymatic labeling, etc., involve the enzymatic reactions in a complex system where numerous substrates coexists with an enzyme. However, the enzyme kinetics in such a system remains unexplored and poorly understood. Herein, we derived and validated the kinetics equations for the enzymatic reactions in complex system. We developed an iteration approach to depict the enzymatic reactions in complex system. It was validated by 630 time-course points from 24 enzymatic reaction experiments and was demonstrated to be a powerful tool to simulate the reactions in the complex system. By applying this approach, we found that the ratio of substrate depletion is independent of other coexisted substrates under specific condition. This observation was then validated by experiments. Based on this striking observation, a simplified model was developed to determine the catalytic efficiencies of numerous competing substrates presented in the complex enzyme reaction system. When coupled with high-throughput quantitative proteomics technique, this simplified model enabled the accurate determination of catalytic efficiencies for 2369 peptide substrates of a protease by using only one enzymatic reaction experiment. Thus, this study provided, in the first time, a validated model for the large scale determination of specificity constants which could enable the enzyme substrate screening approach turned from a qualitative method of identifying substrates to a quantitative method of identifying and prioritizing substrates. Data are available via ProteomeXchange with identifier PXD004665.

The sphenopsids first appeared in the Late Devonian, becoming diverse in the Carboniferous and Permian, but are represented now by the single genus Equisetum . In this article, morphologically preserved material of the novel sphenopsid plant, Xihuphyllum megalofolium (Wu) Chen emend. Huang et al., is described from the Upper Devonian Wutong Formation of Zhejiang Province, China, providing new data on the early evolutionary history of this group. This plant is characterized by a hierarchical branching pattern, with robust nodose stems up to 42.5 mm wide and two orders of lateral branches. Morphometric studies show that the internode width of stems and first-order branches are correlated with the internode length. Leaves, cuneate, broadly cuneate, or spatulate in shape and highly variable in size, are arranged in whorls at the nodes of stems and branches. The leaves of Xihuphyllum reach over 80 mm in length and > 3000 mm 2 in area, an unusually large size for Paleozoic sphenopsids. Xihuphyllum is reconstructed as having a stature 2–3 m in height, and represents an early, large-bodied member within the extinct Sphenophyllales. The occurrence of Xihuphyllum and contemporaneous members of the same group, including Eviostachya , Hamatophyton , Rotafolia and Sphenophyllum , indicates early diversification of sphenopsids in South China.

The colonization of terrestrial environments by rooted vascular plants had far-reaching impacts on the Earth system. However, the belowground structures of early vascular plants are rarely documented, and thus the plant−soil interactions in early terrestrial ecosystems are poorly understood. Here we report the earliest rooted paleosols (fossil soils) in Asia from Early Devonian deposits of Yunnan, China. Plant traces are extensive within the soil and occur as complex network-like structures, which are interpreted as representing long-lived, belowground rhizomes of the basal lycopsid Drepanophycus. The rhizomes produced large clones and helped the plant survive frequent sediment burial in well-drained soils within a seasonal wet−dry climate zone. Rhizome networks contributed to the accumulation and pedogenesis of floodplain sediments and increased the soil stabilizing effects of early plants. Predating the appearance of trees with deep roots in the Middle Devonian, plant rhizomes have long functioned in the belowground soil ecosystem. This study presents strong, direct evidence for plant−soil interactions at an early stage of vascular plant radiation. Soil stabilization by complex rhizome systems was apparently widespread, and contributed to landscape modification at an earlier time than had been appreciated.

A variety of biologically active products have been isolated from Gracilariopsis lemaneiformis. In the present study, two novel angiotensin-converting enzyme (ACE) inhibitory peptides, FQIN [M(O)] CILR, and TGAPCR, were screened and identified from G. lemaneiformis protein hydrolysates by LC-MS/MS. The IC50 values of FQIN [M(O)] CILR and TGAPCR were 9.64 &plusmn, 0.36 &mu, M and 23.94 &plusmn, 0.82 &mu, M, respectively. In the stability study, both peptides showed stabilities of pH, temperature, simulated gastrointestinal digestion, and ACE hydrolysis. The Lineweaver&ndash, Burk plot showed that the two peptides were noncompetitive inhibitors of ACE. Molecular docking simulated the intermolecular interactions of two peptides and ACE, and the two peptides formed hydrogen bonds with the active pockets of ACE. However, FQIN [M(O)] CILR was more closely linked to the active pockets of ACE, thereby exerting better ACE inhibition. Spontaneously hypertensive rats (SHRs) were studied with an oral dose of 10 mg/kg body weight. Both peptides reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) in SHRs, of which FQIN [M(O)] CILR was able to reduce the systolic blood pressure by 34 mmHg (SBP) (p &lt, 0.05). Therefore, FQIN [M(O)] CILR was an excellent ACE inhibitory peptide.

Covalently-functionalized graphene oxide (FGO) was successfully prepared by grafting a novel phosphorus-containing flame retardant, [2-((6-oxidodibenzo[

Selective enrichment of specific peptides is an effective way to identify low abundance proteins. Fractionation of peptides prior to mass spectrometry is another widely used approach to reduce sample complexity in order to improve proteome coverage.In this study, we designed a multi-stage digestion strategy to generate peptides with different trypsin cleavage kinetics. It was found that each of the collected peptide fractions yielded many new protein identifications compared to the control group due to the reduced complexity. The overlapping peptides identified between adjacent fractions were very low, indicating that each fraction had different sets of peptides. The multi-stage digestion strategy separates tryptic peptides with different cleavage kinetics while RPLC separates peptides with different hydrophobicity. These two separation strategies were highly orthogonal, and showed an effective multidimensional separation to improve proteome coverage.

Albeit much less abundant than Ser/Thr phosphorylation (pSer/pThr), Tyr phosphorylation (pTyr) is considered as a hallmark in cellular signal transduction. However, its analysis at the proteome level remains challenging. The conventional immunopurification (IP) approach using antibodies specific to pTyr sites is known to have low sensitivity, poor reproducibility and high cost. Our recent study indicated that SH2 domain-derived pTyr-superbinder is a good replacement of pTyr antibody for the specific enrichment of pTyr peptides for phosphoproteomics analysis. In this study, we presented an efficient SH2 superbinder based workflow for the sensitive analysis of tyrosine phosphoproteome. This new method can identify 41% more pTyr peptides than the previous method. Its excellent performance was demonstrated by the analysis of a variety of different samples. For the highly tyrosine phosphorylated sample, for example, pervanadate-treated Jurkat T cells, it identified over 1800 high confident pTyr sites from only 2 mg of proteins. For the unstimulated Jurkat cells, where the pTyr events rarely occurred, it identified 343 high confident pTyr sites from 5 mg of proteins, which was 31% more than that obtained by the antibody-based method. For the heterogeneous sample of tissue, it identified 197 high confident pTyr sites from 5 mg protein digest of mouse skeletal muscle. In general, it is a sensitive, robust and cost-effective approach and would have wide applications in the study of the regulatory role of tyrosine phosphorylation in diverse physiological and pathological processes.

Tyrosine phosphorylation (pTyr) is important for normal physiology and implicated in many human diseases, particularly cancer. Identification of pTyr sites is critical to dissecting signaling pathways and understanding disease pathologies. However, compared with serine/threonine phosphorylation (pSer/pThr), the analysis of pTyr at the proteome level is more challenging due to its low abundance. Here, we developed a biphasic affinity chromatographic approach where Src SH2 superbinder was coupled with NeutrAvidin affinity chromatography, for tyrosine phosphoproteome analysis. With the use of competitive elution agent biotin-pYEEI, this strategy can distinguish high-affinity phosphotyrosyl peptides from low-affinity ones, while the excess competitive agent is readily removed by using NeutrAvidin agarose resin in an integrated tip system. The excellent performance of this system was demonstrated by analyzing tyrosine phosphoproteome of Jurkat cells from which 3,480 unique pTyr sites were identified. The biphasic affinity chromatography method for deep Tyr phosphoproteome analysis is rapid, sensitive, robust, and cost-effective. It is widely applicable to the global analysis of the tyrosine phosphoproteome associated with tyrosine kinase signal transduction.

Objective Autoantibody and inflammatory cytokines play crucial roles in the development of systemic lupus erythematosus (SLE); however, the regulation of their production warrants further investigation. This study aimed to investigate the role of basophil activation in the development of SLE based on studies in patients with SLE and spontaneous lupus-prone MRL-lpr/lpr mice. Methods The phenotypes of peripheral basophils and the production of autoantibody and interleukin (IL)-17 in patients with SLE were determined by flow cytometry and enzyme-linked immunosorbent assay, and also their correlations were investigated by statistical analysis. Thereafter, the effect of basophils on autoantibody production by B cells and Th17 differentiation in SLE were evaluated in vitro. Finally, the effect of basophil depletion on the development of autoimmune disorders in spontaneous lupus-prone MRL-lpr/lpr mice was examined. Results The decreased numbers and an increased activation of peripheral basophils were found to be correlated with increased autoantibody production and disease activity in patients with SLE. Correspondingly, in vitro coculture studies showed that basophils obtained from patients with SLE promoted autoantibody production by SLE B cells and promoted Th17 differentiation from SLE naïve CD4+ T cells. The decrease of peripheral basophils in patients with SLE might be due to their migration to lymph nodes post their activation mediated by (autoreactive) IgE as supported by their increased CD62L and CCR7 expressions and accumulation in the lymph nodes of MRL-lpr/lpr mice. Furthermore, an increased activation of peripheral basophils was identified in MRL-lpr/lpr mice. Importantly, basophil-depleted MRL-lpr/lpr mice exhibited an extended life span, improved renal function, and lower serum levels of autoantibodies and IL-17, while basophil-adoptive-transferred mice exhibited the opposite results. Conclusion These finding suggest that basophil activation-dependent autoantibody and IL-17 production may constitute a critical pathogenic mechanism in SLE.

The city of Lanzhou in northwestern China experiences serious air pollution episodes in the form of PM10 that is characterized by having high levels of heavy metals. The Xigu District represents the industrial core area of Lanzhou City and is denoted by having the largest petrochemical bases in western China. This study investigates heavy metal compositions and oxidative potential of airborne PM10 (particulate matter with aerodynamic diameter of 10 μm or less) collected in Xigu District in the summer and winter of 2010. An in vitro plasmid scission assay (PSA) was employed to study the oxidative potential of airborne PM10 and inductively coupled plasma-mass spectrometry (ICP-MS) was used to examine heavy metal compositions. Transmission electron microscopy coupled with energy-dispersive X-ray spectrometry (TEM/EDX) was used to investigate elemental compositions and mixing states of PM10. The average mass concentrations of PM10 collected in Xigu District were generally higher than the national standard for daily PM10 (150 μg/m3). Cr, Zn, Pb and Mn were the most abundant metals in the intact whole particles of PM10. Zn, Mn and As was the most abundant metal in the water-soluble fraction, while Cr, Pb, and V existed primarily in insoluble forms. TD20 values (i.e. toxic dosage of PM10 causing 20% of plasmid DNA damage) varied considerably in both winter and summer (from 19 μg/mL to >1000 μg/mL) but were typically higher in summer, suggesting that the winter PM10 exhibited greater bioreactivity. In addition, the PM10 collected during a dust storm episode had a highest TD20 value and thus the least oxidative damage to supercoiled plasmid DNA, while the particles collected on a hazy day had a lowest TD20 value and thus the highest oxidative damage to supercoiled plasmid DNA. The particles collected on the first day after snow fall and on a day of cold air intrusion exhibited minor oxidative potential (i.e. caused limited DNA damage). The water-soluble Zn, Mn, As, and Cu displayed a significant negative correlation with TD20 values, suggesting that these heavy metals were responsible for the increase of oxidative potential. The high mass concentration of PM10 and resulting high oxidative potential in Xigu District may be due to the constant low wind speed and high relative humidity, particularly in winter. Finally, TEM analysis suggested that the oxidative potential of PM10 may be associated with its degree of internal mixing, whereby the heterogeneous assortment of soot, mineral and metals created a highly reactive moiety.

Although geographical fieldwork can be viewed as an integral component of geographical education, it fell out of favor in Chinese secondary schools in the recent past. However, the new junior high school geography standards established in 2001 stress the importance of conducting geographical fieldwork for students’ learning of geography. Now nearly 10 years after the implementation of the standards, this study attempted to ascertain teachers’ views and attitudes toward geographical fieldwork in the secondary schools that have attempted field activities. Information was gathered via questionnaires and interviews. The results reveal that the teachers in China share many perceptions regarding the importance, value, and cognitive and affective benefits as well as perceptions of constraints such as examination requirements, large class size, limited time, overemphasis on classroom learning, liability for student safety, and lack of software and hardware. However, it is also found that there are some difference...

To evaluate the effect of four widely used red blood cell lysing solutions on counting and measurement of activation marker of peripheral basophils in normals and systemic lupus erythematosus (SLE) patients by flow cytometry. Our results showed that the light scatter properties including FS and SS value of leukocytes in whole blood were preserved when whole blood samples were lysed in RBC Lysis Buffer and FACS Lysing Solution, while were affected when lysed in distilled water or ACK. By counting basophils, RBC Lysis Buffer and FACS Lysing Solution were almost the same level, while were significantly lower when lysed in distilled water or ACK. The expressions of CD203c on peripheral basophils of SLE patients were significantly higher than those of normals. Comparing the data of CD203c expression obtained demonstrated that there were no significant differences among them, while FACS Lysing Solution treatment leads to a slightly lower staining intensity of CD203c. We provide a solid description that the widely used red blood cell lysing reagents may influence the light scatter properties of leukocytes, the accuracy of quantity of absolute number of the existence of basophil subsets and the quantity of staining intensity of cell-activated marker CD203c fluorescence when measured by flow cytometry.