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History A 26-year-old man presented with a 1-month history of chest pain, a palpable and painful right inguinal mass, and edema in the right lower extremity. One month earlier, he started to experience left chest pain with no cough. Pulmonary CT angiography (CTA) revealed a left lower lobe segmental pulmonary embolus. The local hospital made a diagnosis of pulmonary embolism. He received anticoagulants, and his chest pain was gradually relieved. At the time of current presentation, the patient was experiencing right lower extremity swelling and pain. Physical examination revealed a 4 × 3 cm palpable right inguinal mass with no redness. His medical history and family history were negative. The results of laboratory work-up were normal, with a d-dimer level of 0.16 mg/L fibrinogen equivalent units (reference range

Environmentally benign synthesis of graphite at low temperatures is a great challenge in the absence of transition metal catalysts. Herein, we report a green and efficient approach of synthesizing graphite from carbon dioxide at ultralow temperatures in the absence of transition metal catalysts. Carbon dioxide is converted into graphite submicroflakes in the seconds timescale via reacting with lithium aluminum hydride as the mixture of carbon dioxide and lithium aluminum hydride is heated to as low as 126 °C. Gas pressure-dependent kinetic barriers for synthesizing graphite is demonstrated to be the major reason for our synthesis of graphite without the graphitization process of amorphous carbon. When serving as lithium storage materials, graphite submicroflakes exhibit excellent rate capability and cycling performance with a reversible capacity of ~320 mAh g–1 after 1500 cycles at 1.0 A g–1. This study provides an avenue to synthesize graphite from greenhouse gases at low temperatures. Green synthesis of graphite is a great challenge in the absence of the graphitization of amorphous carbon at high temperatures. Here, the authors report a green approach of synthesizing graphite from carbon dioxide at low temperature in seconds timescale.

Background: Type-2-diabetes mellitus is associated with many side effects affecting vital body organs, especially heart. Thiazolidinediones are potent antidiabetics. Studies have proven that amino-acids and peptides promote glucose transport, have antioxidant properties, and fewer side effects, thus we designed hybrids by combining amino-acid esters and peptide esters with 2, 4 thiazolidinedione acetic acid moiety which can act as antidiabetic agent with cardioprotection properties. Methodology: In vitro ADME, toxicity, and docking studies were performed using Qikprop3.1.OSIRIS, PROTOX (Prediction of Rodent Oral Toxicity), and FlexX 2.1.3, respectively. Results: All the designed molecules belong to three sub-series, i.e. 2, 4-dioxothiazolidine-5-acetic acid single amino acid hybrid methyl esters, 2, 4-dioxothiazolidine-5-acetic acid dipeptide hybrid methyl esters and 2, 4-dioxothiazolidine-5-acetic acid tripeptide hybrid methyl esters. All molecules were non-toxic. SSMA2, SSMA14, SSMA49, and SSDM50 showed good docking scores in 2PRG and 2UV4, respectively. Conclusion: The selected in silico studies helped to design hybrids with less toxicity, target specificity with dual activity as potential anti-diabetic and cardioprotective agents.

Ankylosing spondylitis (AS) is a chronic immune-mediated disease. Various immune cells play an essential role in the AS pathogenesis. However, the specific pathogenesis of AS has not been well understood. Proteomic profiles of peripheral blood mononuclear cells (PBMCs) were applied to reveal the specific pathogenesis of AS. Quantitative proteomic analyses were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methods to investigate the protein profiling of PBMCs from new-onset AS patients (n = 9) and healthy controls (n = 9). We identified 782 differentially expressed proteins (DEPs) and 527 differentially phosphorylated proteins (DPPs) between AS patients and healthy controls. The subcellular location of DEPs and DPPs showed that most of the DEPs were from the cytoplasm (n = 296, 38%), were extracellular (n = 141, 18%), and from the nucleus (n = 114, 15%); most of the DPPs were from the cytoplasm (n = 37, 34%), nucleus (n = 35, 32%), and plasma membrane (n = 10, 9%). We further identified 89 proteins with both expression and phosphorylation differences. The functional annotation of the 89 differentially expressed and phosphorylated proteins enriched in the antigen processing and presentation pathway. Four DEPs with six phosphorylated positions were found in the antigen processing and presentation pathway. The differentially expressed and phosphorylated proteins may be helpful to uncover the pathogenesis of AS. The six AS-specific proteins may serve as candidate markers for AS diagnosis and new treatment targets.

Metal oxides Y2Ce2-xRuxO7-δ (x = 0–0.4) with partial substitution of Run+ cations in the host structure were synthesized to study their catalytic activity on oxidative steam reforming of ethanol (OSRE). The samples were characterized using X-ray diffraction (XRD), X-ray photoelectron spectra (XPS) and temperature-programmed reduction (TPR). The performances investigated by varied temperatures, Ru ion content, carbon-to-oxygen ratios and long-term stability. The lowest activation temperature on OSRE is 300 °C, which is significantly lower than that of La2Ce2-xRuxO7-δ (400 °C). The cell dimension of Y2Ce2-xRuxO7-δ was reduced compare to La2Ce2-xRuxO7-δ for the replacement of the Y3+ ion with La3+ ion. The reduced unit cell in the host structure not only increase the surface composition of the Ce4+ ions, but also induce the synergetic effect of Run+/Ru4+ (n > 4) and Ce4+/Ce3+, which lead to the enhanced OSRE activity. The optimized catalyst Y2Ce1.6Ru0.4O7-δ showed selectivity of hydrogen SH2 = 84(4)% (YH2 = 2.5(1) mol/mol EtOH) and carbon monoxide SCO = 48(1)% for long-term stability test at T = 300 °C, C/O = 0.5, and O2/C2H5OH = 1.5.

The key to sustainable energy application is the rational utilization of abundant materials on the earth. Fe, Co, and Cu theoretically exhibit high oxygen reduction capability close to Pt. However, their high diffusion behaviors make it difficult to homogeneously incorporate with carbon at elevated fabrication temperature. Here, polyaniline is developed an incorporated frame to realize the homodisperse of Fe, Co, or Cu. Three efficient oxygen reduction catalysts, including Fe-polyaniline/carbon (Fe-N/C), Co-N/C, and Cu-N/C are synthesized by a three-step method combining polymerization, complexation, and pyrolysis. All catalysts with metal doping reveal high catalytic activity, good cyclic stability, and the activity varies with different doping metal. The Fe-doped catalyst exhibits the best oxygen reduction ability with onset and half-wave potentials of − 104 mV and − 199.5 mV. Furthermore, the influence of complexation time and the pyrolysis temperature on the oxygen reduction activity are also studied systematically. These interesting discoveries may contribute to provide important ideas to oxygen reduction catalysts.

Blending of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) would produce polylactide stereocomplex crystallites (PLA SC). In the PLLA/PDLA specimens prepared by solution mixing or melt blending,...

Objective: Curcumin possesses extensive therapeutic effects on several diseases and tumor cells, which has inhibitory effects on mammalian target of rapamycin (mTOR)-STAT3 signaling. Our study aims to explore the influences of curcumin on promoting the recovery of motor function after spinal cord injury (SCI) in rats through the mTOR-STAT3 signaling pathway. Methods : SCI rats were treated with rapamycin and curcumin followed by establishing rat models of SCI. The influences of rapamycin and curcumin on the protein expressions of PTEN, Akt, phosphorylated S6 and chondroitin sulphate proteoglycans (CSPGs) were measured by western blot. Means of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was used to assess motor function. Results: After SCI, curcumin promoted the expression of PTEN, reduced the proliferation of neuroglia cells, affected the expressions of CSPGs and improved the motor function. Conclusion: Curcumin can promote motor function recovery after SCI which is possibly by up-regulating the PTEN expression via the mTOR-STAT3 signaling pathway.

Near-infrared (NIR) fluorescent probes can deeply penetrate through tissues with little damage. To facilitate image-guided theranostics, researchers usually apply a desired amount of photosensitizers to achieve effective photothermal responses. However, these probes could easily suffer from low photostability and aggregated-caused quenching effect in high concentrations. In this paper, the rational incorporation of an aggregated-induced emission (AIE) unit into the structure of heptamethine cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens) via different linkages. The IR-780 derivatives all show enhanced AIE features, in which the probe with an ether linkage (IR780-O-TPE) is superior in rapid cell uptake, high targeting capacity, and good photostability. Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa cells (IC50 = 3.3 μM). The three IR-780 derivatives displayed a photothermal response in a concentration-dependent manner, in which IR-780 AIEgens are more cytotoxic than IR-780, with IC50 of 0.3 μM under 808 nm laser irradiation. In tumor-bearing mice, the optimal probe IR780-O-TPE also showed a more effective photothermal response than IR-780. By illustrating the relationship between aggregation state with photophysical properties, cell imaging, and cytotoxicity, this work is helpful in modulating NIR-based photosensitizers into AIE features for efficient image-guided theranostics.

The Mg­(NH2)2–2LiH system with KOH additive is a promising high-capacity hydrogen storage material in terms of low dehydrogenation temperatures, good reversibility, and excellent cycling stability. Various mechanisms have been reported to elucidate the reasons for the K-containing additive improving the hydrogen storage performance. Herein, the dehydrogenation performance of Mg­(NH2)2–2LiH–0.07KOH is found to be strongly associated with hydrogen pressures. The Li2K­(NH2)3 and KH produced from the reaction between KOH, LiH, and Mg­(NH2)2 in the ball milling process are converted into Li3K­(NH2)4, MgNH, and LiNH2 in the heating dehydrogenation process under Ar carrier gas or very low hydrogen pressure, exhibiting a two-peak dehydrogenation process. For the sample under high hydrogen pressure, Li2K­(NH2)3 can react with LiH to convert into Li3K­(NH2)4 and further to form KH and LiNH2 in the heating process, showing a one-peak dehydrogenation process under 5 bar hydrogen. The hydrogen pressure-dependent reactions of K-containing additives in the Mg­(NH2)2–2LiH system lead to a different hydrogen storage performance under different dehydrogenation conditions.

Cycle stability improvement of a high-capacity Si anode is a challenge for its wide application in high-energy-density lithium-ion batteries. Active amorphous/nanosized Si embedded in an inactive matrix is a strategy to improve the cycle stability of Si anodes. Ternary Si100-x-yTixBy (5 ≤ y ≤ x ≤ 20) alloys are designed and prepared by ball milling using elemental Si, Ti, and B as starting materials. The formation sequence of inactive phases during mechanical alloying is predicted by an effective heat-of-formation model and verified by microstructural characterization. The local-fine distribution of free amorphous and nanocrystalline Si in the Si100-x-yTixBy is analyzed by confocal μ-Raman spectroscopy. When used as lithium-ion anodes, the capacity and voltage affected by Si and inactive compounds in the Si100-x-yTixBy are concerned to assess their high energy density. Furthermore, the impact of free active Si, the inactive phase, and amorphous Si on the cyclability of Si100-x-yTixBy is studied. The results show that the Si100-x-yTixBy material is a potential anode for high-energy-density Li-ion batteries and could be used to guide the design of multi-component Si-alloy anodes.

Orderly arranged Silicon carbide (SiC)/epoxy (EP) composites were fabricated. SiC was made magnetically responsive by decorating the surface with iron oxide (Fe3O4) nanoparticles. Three treatment methods, including without magnetization, pre-magnetization and curing magnetization, were used to prepare SiC/EP composites with different filler distributions. Compared with unmodified SiC, magnetic SiC with core-shell structure was conducive to improve the breakdown strength of SiC/EP composites and the maximum enhancement rate was 20.86%. Among the three treatment methods, SiC/EP composites prepared in the curing-magnetization case had better comprehensive properties. Under the action of magnetic field, magnetic SiC were orderly oriented along the direction of an external field, thereby forming SiC chains. The magnetic alignment of SiC restricted the movement of EP macromolecules or polar groups to some extent, resulting in the decrease in the dielectric constant and dielectric loss. The SiC chains are equivalent to heat flow channels, which can improve the heat transfer efficiency, and the maximum improvement rate was 23.6%. The results prove that the orderly arrangement of SiC had a favorable effect on dielectric properties and thermal conductivity of SiC/EP composites. For future applications, the orderly arranged SiC/EP composites have potential for fabricating insulation materials in the power electronic device packaging field.

Aim: Acute kidney injury (AKI), a global public health issue, not only causes millions of deaths every year, but is also a susceptible factor for chronic kidney disease (CKD). Nephrotoxic drugs are an important cause of AKI. There is still a lack of effective and satisfactory prevention method in clinical practice. This study investigated the protective effect of the exosomes derived from urine of premature infants on cisplatin-induced acute kidney injury. Methods: Isolation of exosomes from fresh urine of premature infants: The characteristics of exosomes were determined by flow cytometry, transmission electron microscopy and Western blotting. A C57BL/6 mice model of cisplatin-induced acute kidney injury was established. The mice in the experimental group were given 100ug exosomes dissolved in 200ul solution. The mice in the control group were given normal saline (200ul). These treatments were performed 24 hours after AKI was induced by intraperitoneal injection of cisplatin. To evaluate renal function, blood was drawn 24 hours after AKI model was established and serum creatinine (sCr) was measured. The mice were euthanized 72 hours after exosome treatment. The kidneys were collected for pathological examination, RNA and protein extraction, and the evaluation of renal tubular damage and apoptosis. In the in-vitro experiment, human renal cortex/proximal tubular cells (HK2) was induced by cisplatin to assess the protective ability of the exosomes derived from urine of premature infants. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blotting were used to evaluate the effect of exosomes treatment on the apoptosis of HK2 cells induced by cisplatin. Exosome microRNA sequencing technology and bioinformatics analysis method were applied to investigate the miRNAs enriched in exosomes and their target genes. The dual luciferase gene reporter system was used to detect the interaction of target genes. Results: Treatment of exosomes derived from urine of premature infants could decrease the level of serum creatinine and the apoptosis of renal tubular cell, inhibit the infiltration of inflammatory cell, protect mice from acute kidney injury induced by cisplatin and reduce mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes derived from urine of premature infants. It protected HK2 cells from cisplatin-induced apoptosis by targeting and down-regulating the 3'UTR of mitogen-activated protein kinases (MAPK8) mRNA. Conclusions: According to our results, the exosomes derived from urine of premature infants alleviated cisplatin-induced acute kidney injury in mice and inhibited the apoptosis of human proximal tubular cells (HK2) induced by cisplatin in vitro. MiR-30a-5p in exosomes inhibited cisplatin-induced MAPK activation, ameliorated apoptosis, and protected renal function. The exosomes derived from urine of premature infants provided a promising acellular therapy for AKI.

Internal tandem duplications of FLT3 (FLT3-ITD) occur in approximately 25% of all acute myeloid leukemia (AML) cases and confer a poor prognosis. Optimization of the screening hit 1 from our in-house compound library led to the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives as potent and selective FLT3-ITD inhibitors. Compounds 17 and 19 displayed potent FLT3-ITD activities both with IC50 values of 0.4 nM and excellent antiproliferative activities against AML cell lines. Especially, compounds 17 and 19 inhibited the quizartinib resistance- conferring mutations, FLT3D835Y, both with IC50 values of 0.3 nM. Moreover, western blot analysis indicated that compounds 17 and 19 potently inhibited the phosphorylation of FLT3 and attenuated downstream signaling in AML cells. These results indicated that pyrazolo[1,5-a]pyrimidine derivatives could be promising FLT3-ITD inhibitors for the treatment AML.

The antibiotic sulfadiazine (SDZ) is a challenging threat to the health of aquatic organisms, as it frequently occurs in aquatic ecosystems. Tolerance mechanisms and accumulation of SDZ in a floating macrophyte (Eichhornia crassipes) under hydroponic conditions were investigated in this study to provide more insight into the SDZ removal process. Results show that the presence of 1 mg L−1 SDZ decreased the quickest and ranged from 669.45 to 165.34 μg L−1 from days 5 to 25. Exposing E. crassipes to SDZ ( aerial parts under all treatments. These findings suggest that E. crassipes has the ability to phytoremediation SDZ contaminated water.

For micro-arc oxidation (MAO) coating on aluminium alloys, the corrosion medium can permeate through the microvoids and cracks in it to decrease its corrosion resistance. In this study, a method of...

Mitochondria are crucial in the process of oxidative metabolism and apoptosis. Their morphology is greatly associated with the development of certain diseases. For specific and long-term imaging of mitochondrial morphology, we synthesized a new mitochondria-targeted near-infrared (NIR) fluorescent probe (TPE-Xan-In) by incorporating TPE with a NIR merocyanine skeleton (Xan-In). TPE-Xan-In displayed both absorption (660 nm) and emission peaks (743 nm) in the NIR region. Moreover, it showed aggregation-induced emission properties at neutral pH and specifically illuminated mitochondria with good biocompatibility, superior photostability, and high tolerance to mitochondrial membrane potential changes. With a pH-responsive unit, hydroxyl xanthene (Xan), the probe exhibited a pH-sensitive fluorescence emission in the range of pH 4.0-7.0, which indicated its potential in long-term tracking of pH and morphology changes of mitochondria in the biomedical research studies.

The SiO2/C composites with submicron SiO2 particles fully embedded into the porous carbon are prepared via a facile, environmentally benign and cost-effective method. The electrochemical performances of the SiO2/C composites are found to be related to its carbon content. For the SiO2/C composites with C contents ranging from 5 wt% to 23 wt%, the sample with 14 wt % carbon delivers the highest reversible capacity of 653 mAh/g (based on the mass of the SiO2/C composite) at 100 mA/g and retained the reversible capacity of 620 mAh/g after 150 cycles. Even at a current density of 1.0 A/g, it still delivers a reversible capacity of 534 mAh/g over 1000 cycles, which is the best cycle performance reported for the SiO2 anode materials. The ultralong cycle life and excellent rate capability can be attributed to both the porous carbon matrix and the favorable connection between SiO2 particles and porous carbon.

Stereolithography (SL) based 3D printing is promising to produce of next-generation dielectric materials because of its high geometric accuracy, less internal defect and high flexibility. Polymer matrix composites (PMCs) are widely used in the 3D printing of dielectric materials. However, the loading of high-refractive-index ceramic filler in PMCs significantly reduces their process compatibility, making it difficult to successfully fabricate the 3D printing materials. In this study, silane-coupling-agent (SCA) treated barium titanate microspheres (BT-S) were prepared using radio-frequency thermal plasma spheroidization (RF-TPS) and KH570 silane treatment. Experimental results showed that the prepared BT-S particles have spherical shape and impact structure. This enhances the 3D printability of UV curable PMCs by the improvement of UV curing performance and fluidity. Finally, 3D printing of UV/BT-S composites were successfully printed using stereolithography (SLA) 3D printing technique.

Platelet-rich fibrin (PRF) is a natural fibrin meshwork material with multiple functions that are suitable for tissue engineering applications. PRF provides a suitable scaffold for critical-size bone defect treatment due to its platelet cytokines and rich growth factors. However, the structure of PRF not only promotes cell attachment but also, due to its density, provides a pool for cell migration into the PRF to facilitate regeneration. In our study, we used repeated freeze drying to enlarge the pores of PRF to engineer large-pore PRF (LPPRF), a type of PRF that has expanded pores for cell migration. Moreover, a biodegradable Mg ring was used to provide stability to bone defects and the release of Mg ions during degradation may enhance osteoconduction and osteoinduction. Our results revealed that cell migration was more extensive when LPPRF was used rather than when PRF was used and that LPPRF retained the growth factors present in PRF. Moreover, the Mg ions released from the Mg ring during degradation significantly enhanced the calcium deposition of MC3T3-E1 preosteoblasts. In the present study, a bone substitute comprising LPPRF combined with a Mg ring was demonstrated to have much potential for critical-size bone defect repair.

Liquid biopsy is becoming an innovative tool in precision oncology owing to its noninvasive identification of biomarkers circulating in the body fluid at various time points for continuous and real-time analysis of disease progression. MicroRNAs in blood exosomes are identified as a new promising class of potential biomarkers for cancer diagnostics and prognostics. Conventional detection of blood exosomal microRNAs need multiple-step, complicated, costly, and time-consuming sample preparation of exosomes isolation and RNA extract, which affect the accuracy and reproducibility of analytical results. In this work, we set up an in situ quantitative analysis of human plasma exosomal miR-1246 by a probe of 2'-O-methyl and phosphorothioate modified molecular beacon. The probe has outstanding nuclease resistance in highly active RNase A/T1/I, which makes it stable for direct application in blood samples. With rapid rupture of exosomes membrane by Triton X-100, the probe can enter exosomes to specifically target miR-1246 exhibiting quantitative fluorescent signals. Using the output signals as a diagnostic marker, we differentiated 33 breast cancer patients from 37 healthy controls with 97.30% sensitivity and 93.94% specificity at the best cutoff. The blood biopsy is simple without extracting plasma exosomes and their nucleic acids content, time-saving in about 2 h of total analysis process, and microvolumes needed for plasma sample, suggesting its good potential to clinical application.

MicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generated. We found that cardiac-specific miR-125b-1 knockout mice displayed half the miR-125b expression of control mice resulting in a 60% perinatal death rate. However, the surviving mice developed hearts with cardiac hypertrophy. The cardiomyocytes in both neonatal and adult mice displayed abnormal mitochondrial morphology. In the deficient neonatal hearts, there was an increase in mitochondrial DNA, but total ATP production was reduced. In addition, both the respiratory complex proteins in mitochondria and mitochondrial transcription machinery were impaired. Mechanistically, using transcriptome and proteome analysis, we found that many proteins involved in fatty acid metabolism were significantly downregulated in miR-125b knockout mice which resulted in reduced fatty acid metabolism. Importantly, many of these proteins are expressed in the mitochondria. We conclude that miR-125b deficiency causes a high mortality rate in neonates and cardiac hypertrophy in adult mice. The dysregulation of fatty acid metabolism may be responsible for the cardiac defect in the miR-125b deficient mice.

[Image: see text] Interleukin-1 receptor associated kinase 4 (IRAK4) is a promising therapeutic target for diffuse large B-cell lymphoma driven by MYD88 L265P mutant, acting both as a kinase and a scaffolding protein for downstream signaling molecules. While previous efforts to modulate IRAK4 activity with kinase inhibitors alone displayed moderate efficacy, protein degradation may offer a solution to blocking both IRAK4 kinase activity and scaffolding capabilities. To this end, the potent IRAK4 degrader 9 was discovered, and it effectively inhibited the activation of downstream NF-κB signaling and outperformed the parent compound 1. In addition, compound 9 displayed a substantial advantage in reduction of the viability of OCI-LY10 and TMD8 cells over the parent compound 1. These results underline the potential that eliminating both the kinase and scaffolding functions of IRAK4 may result in superior and broader efficacy than inhibiting the kinase activity alone.

Nanoparticles are expected to play a vital role in the management of future plant diseases, and they are expected to provide an environmentally friendly alternative to traditional synthetic fungicides. In the present study, silver nanoparticles (AgNPs) were green synthesized through the mediation by using the endophytic bacterium Pseudomonas poae strain CO, which was isolated from garlic plants (Allium sativum). Following a confirmation analysis that used UV&ndash, Vis, we examined the in vitro antifungal activity of the biosynthesized AgNPs with the size of 19.8&ndash, 44.9 nm, which showed strong inhibition in the mycelium growth, spore germination, the length of the germ tubes, and the mycotoxin production of the wheat Fusarium head blight pathogen Fusarium graminearum. Furthermore, the microscopic examination showed that the morphological of mycelia had deformities and collapsed when treated with AgNPs, causing DNA and proteins to leak outside cells. The biosynthesized AgNPs with strong antifungal activity were further characterized based on analyses of X-ray diffraction, transmission electron microscopy, scanning electron microscopy, EDS profiles, and Fourier transform infrared spectroscopy. Overall, the results from this study clearly indicate that the biosynthesized AgNPs may have a great potential in protecting wheat from fungal infection.

One of the most significant challenges in boron neutron capture therapy (BNCT) is to have an ideal boron delivery agent which can deliver sufficient numbers of boron atoms to designated tumor cells. In this work, mild synthetic conditions for synthesis of dipeptidyl multiple boron-containing analogs under microwave-assisted condition were investigated. The results showed that the reaction generally took place at 50 °C, but higher reaction temperature was required when a fluorinated building block was used. The resulting peptidyl skeletons generated by Ugi four-component reaction resemble basic cell metabolites and could potentially be used as alternative replacements for current boron carrier agents in BNCT.

Objective: The dysregulation of neuro-inflammation is one of the attributes of the pathogenesis of Alzheimer’s disease (AD). Over-expression of complement proteins co-localizes with neurofibrillary tangles, thereby indicating that a complement system may be involved in neuro-inflammation. Here, we report the influence of complement activation on the neuro-inflammation using a microglial cell line. Methods: first, we performed a cytotoxic assay using the microglial cells BV-2. Second, after treatment of BV-2 cells with Aβ42 and/ or C5a, the anaphylatoxin derived from C5, we determined the expression levels of the pro-inflammatory factors TNF-α, IL-1β, and IL-6. Finally, we explored whether this neuroinflammatory response was mediated by JAK/ STAT3 signaling. Results: C5a had an enhanced effect on the neural cell viability of BV-2 cells treated with Aβ42. In addition, C5a also increased the Aβ-induced neuro-inflammatory response, and these effects were blocked by the C5aR antagonist, PMX205. Finally, we demonstrated that the neuro-inflammatory responses induced by Aβ and C5a were mediated through JAK/STAT3 signaling. By blocking this pathway with an antagonist, AG490, the expression of TNF-α, IL-1β, and IL-6 was alleviated. Conclusion: The complement protein C5a could exaggerate the Aβ-induced neuroinflammatory response in microglia, and C5aR may be a potential therapeutic tool for AD treatment.

Nine new minor diterpenoids, jatrogossones A-I (1-9), and six known analogues (10-15) were separated from an extract of the branches and leaves of Jatropha gosspiifolia. Compounds 4-6 and 10, possessing a 5/11 fused-ring skeleton, and 8, 9, and 13, with a 5/9/5 fused-ring skeleton, represent rare diterpenoid skeletons that have been found only in compounds isolated from plants of the Jatropha genus. The absolute configurations of 1-10 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicity of the diterpenoids was evaluated using RKO and LOVO colon cancer cells in which regenerating islet-derived protein 3-alpha (Reg3A) is highly expressed. Compound 12 exhibited cytotoxicity against RKO colon cancer cells with an IC50 value of 2.6 μM. Morphological features of apoptosis and antimigration activities were evaluated in 12-treated RKO cells. Compound 12 effectively induced apoptosis of RKO, which was associated with G2/M-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 12 significantly induced RKO cell apoptosis in a dose-dependent manner.

Molecular dynamics (MD) simulation was used to investigate the microstructure and mechanical properties of pure polyvinylidene fluoride (PVDF) and PVDF/carbon nanotube (CNT) composites with and without a polarization process. After annealing, the trans percentages of non-polarized PVDF and composites are improved by about 25% compared to the initial model of α-phase PVDF. For PVDF and composites with polarization process, the PVDF trans percentages can be further enhanced by around 10% compared to those without the polarization process. The mechanical properties of pure PVDF can be improved by blending the PVDF with CNTs and with the polarization process. The local shear strain analysis shows that the strength of PVDF around the CNTs have been enhanced, leading to higher brittleness of the composites at increasing CNT weight fractions. During the tensile process, the trans percentage of PVDF increases in the non-polarized cases with increasing strain, but are less sensitive to polarized cases.

BACKGROUND Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive type of the disease. To date, much evidence has indicated that accurate HER2 status detection is crucial for prognosis and treatment strategy selection. Thus, bioanalytical techniques for early and accurate detection of HER2 have the potential to improve patient care. Currently, the widely used immunohistochemical staining normally has problems with reproducibility and lack of standardization, resulting in poor concordance between laboratories. Aptamers are a good alternative, but the extent of their use in quantitative analysis of HER2 is limited because of the lack of effective detection methods. METHODS We developed a quasi-targeted proteomics assay and converted the HER2 signal into the mass response of reporter peptide by a combination of aptamer–peptide probe and LC-MS/MS. RESULTS The selected aptamer–peptide probe consisted of aptamer HB5 and the substrate peptide GDKAVLGVDPFR that contained the reporter peptide AVLGVDPFR. After characterization of this newly synthesized probe (e.g., conjugation efficiency, stability, binding affinity, specificity, and digestion efficiency), probe binding and trypsin shaving conditions were optimized. The resulting limit of quantification for HER2 was 25 pmol/L. Then, the quasi-targeted proteomics assay was applied to determine the HER2 concentrations in the HER2-positive breast cancer cells BT474 and SK-BR-3, the HER2-negative breast cancer cells MDA-MB-231 and MCF-7, and 36 pairs of human breast primary tumors and adjacent normal tissue samples. The results were highly concordant with those obtained by immunohistochemistry with reflex testing by fluorescent in situ hybridization. CONCLUSIONS Quasi-targeted proteomics can be a quantitative alternative for HER2 detection.

To enhance the electrical and mechanical properties of silicone rubber (SIR) in the field of high-voltage insulation, conventional fillers such as aluminum hydroxide (ATH), fumed silica and precipitated silica have been used for many years. In this work, SIR composites filled with ATH, irregular SiO 2 (IS) and sphere SiO 2 (SS) were prepared by mechanical blending, and the effects of filler type and filler shape on mechanical, electrical and thermal properties of SIR composites were systematically investigated. Compared with ATH-SIR composites, SS-SIR composite exhibited better electrical and mechanical properties. It showed that the tensile strength of SS-SIR composites was up to 6.6 MPa, which was nearly 2-folded compared to ATH-SIR composite. According to the loss tangent results in combination with tensile fracture surface observation, the interfacial interaction between SiO 2 fillers and SIR is stronger than that between ATH and SIR, and the dispersion is better in SiO 2 fillers filled SIR composites than that in ATH filled composite. The breakdown strength of ATH-SIR composite is only 18.9 kV mm −1 , while those of IS-SIR and SS-SIR composites are 24.9 and 24.8 kV mm −1 , respectively. Among the three SIR composites, SS-SIR composite has lowest dielectric permittivity and dielectric loss. Compared with ATH-SIR composite, the SiO 2 fillers filled SIR composites have the lower thermal conductivity ranging from 30 °C to 150 °C, but they exhibit the better arc aging resistance due to the good thermal stability and thermal conducting property at high temperature. Moreover, the SS-SIR composite exhibits the better arc aging resistance than IS-SIR composite.

An integrated approach based on organic petrographic and geochemical proxies along with palynological and palynofacies analysis were employed using 24 rock samples representing the upper part of the Quse and Sewa formations in the southern Qiangtang Basin, Tibetan Plateau, SW China. This interval was deposited during the Early Jurassic Toarcian Oceanic Anoxic Event (T-OAE) and is investigated to assess the biostratigraphic age control based on palynomorphs composition. The current approach allows for the interpretation of the local paleoenvironmental response to T-OAE climate variability that still unraveled based on palynofacies analysis of the Bilong co succession. Visual palynofacies analysis, vitrinite reflectance (VRo), and total organic carbon (TOC)/Rock-Eval pyrolysis parameters enables a detailed assessment of probable source rock characterization. The palynomorph content comprises mainly terrestrially-derived land-plants, mostly sphaeromorphs pollen grains, with minor content of marine dinoflagellate cysts (dinocysts). Marker dinocysts and pollen taxa allow the subdivision of the studied succession into two age-distinctive units of early Toarcian and late Bajocian-Bathonian. Additionally, carbon isotope profile of the studied succession observed a large negative carbon isotope excursion (CIE) within the lower Toarcian oil shale interval, which is compatible with regional δ13Corg records from adjacent basins at this time. The regional TOC contents of lower Toarcian reached up to 21 wt% in areas of the eastern Tethys compared to lower values in the western Tethys and Boreal (ca. 3 wt%). Two palynofacies assemblages revealed deposition of these deposits in distal inner neritic to fluvio-deltaic environment and to some extent in brackish marginal marine setting. Geochemical screening indicated that most samples were dominated by very good to excellent organic matter richness of kerogen Type II and mixed Type II/III with very good to excellent hydrocarbon generation. The calculated VRo-eq from Rock-Eval Tmax and measured VRo values are in good agreement and showed that the organic matter of the studied interval is in the early to middle stages of the oil window.

The emergence of non-coding RNAs (ncRNAs) has challenged the central dogma of molecular biology that dictates that the decryption of genetic information starts from transcription of DNA to RNA, with subsequent translation into a protein. Large numbers of ncRNAs with biological significance have now been identified, suggesting that ncRNAs are important in their own right and their roles extend far beyond what was originally envisaged. ncRNAs do not only regulate gene expression, but are also involved in chromatin architecture and structural conformation. Several studies have pointed out that ncRNAs participate in heart disease; however, the functions of ncRNAs still remain unclear. ncRNAs are involved in cellular fate, differentiation, proliferation and tissue regeneration, hinting at their potential therapeutic applications. Here, we review the current understanding of both the biological functions and molecular mechanisms of ncRNAs in heart disease and describe some of the ncRNAs that have potential heart regeneration effects. Keywords: Non-coding RNAs, Cardiac regeneration, Cardiac fate, Proliferation, Differentiation, Reprograming

SnO2-nanorods coupled by reduced graphene oxide (rGO) nanostructures were synthesized through a hydrothermal method, and their NH3 sensing properties were studied. The uniform SnO2 nanorods randomly grew on the reduced graphene oxide (rGO) substrate and formed a network structure. The microstructure and morphology of the as-prepared materials were characterized by various techniques. A gas sensor fabricated from the as-prepared SnO2-nanorods coupled by rGO was investigated the ammonia sensing properties. Most importantly, the sensor exhibited good sensitivity to NH3 at room temperature. This sensor performed a fast response and recovery time for 200 ppm NH3 at room temperature, which were 8 s and 13 s, respectively. The response value (Ra/Rg) of the SnO2-nanorods coupled by rGO up to 1.9 for 500 ppm NH3 at room temperature, indicated that the quite good NH3 sensing performance at room temperature by the structure of SnO2-nanorod coupled by rGO.

Hierarchical porous carbon (HPC) has attracted much attention in tackling global environmental and energy problems. For the state-of-the-art routes to synthesize HPC from organic compounds, the emission of carbon dioxide (CO2) and gaseous pollutants is inevitable during thermal carbonization. Herein, we report an environmentally benign and high-yield route to synthesize HPC from CO2via H2O-induced self-propagating reactions. By introducing an initiator of H2O, CO2 can react with lithium hydride (LiH) to produce HPC in 13 seconds at low temperatures. The as-synthesized HPC exhibits an interconnected micro–meso–macropore network structure with a high porosity of 83%. The formation mechanism of HPC is discussed on the basis of the conversion reactions from CO2 to C and the gas blowing effect in producing hierarchical porosity. The HPC evaluated as an anode material for lithium-ion batteries not only delivers a high reversible capacity of ∼1150 mA h g−1 at a current density of 0.2 A g−1, but also exhibits superior rate capability (∼825 mA h g−1 at 1.0 A g−1) and excellent cycling properties (up to 2000 cycles). This research opens a new avenue both to synthesize HPC from CO2 on a large scale and to mitigate greenhouse gas from the atmosphere.