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Cough variant asthma (CVA) is one of the primary causes of chronic cough. And we found that Fritillariae thunbergii Bulbus (FTB) exhibited promising antitussive and expectorant functions. Thus, we explore the role and mechanism of FTB on CVA based on metabolomics. CVA mice models were established using ovalbumin and treated with different concentrations of FTB (1–4 g/kg). Then cough numbers, airway resistance, inflammatory factor levels, inflammatory cell numbers, EOS contents, and lung histopathology were determined. Furthermore, TLR4-MyD88-NF-κB pathway-related protein expressions were evaluated. Besides, UPLC-MS/MS analysis was applied to detect serum differential metabolites of CVA mice with FTB treatment. We found that FTB showed obvious effects on CVA mice by reducing cough number and airway resistance, alleviating inflammation response in serum and BALF, and improving lung pathological damage. Furthermore, FTB decreased TLR4-MyD88-NF-κB pathway-associated protein expressions in the lung tissue of CVA mice. The results of metabolomics found that FTB recovered the levels of nucleosides, analogues, organic acids and derivatives as well as organoheterocyclic compounds in CVA mice serum, the modulation may relate to metabolic pathways, purine metabolism and regulation of lipolysis in adipocytes. FTB suppressed inflammation in CVA via inhibiting TLR4-MyD88-NF-κB signaling pathway and serum metabolic levels, indicating that FTB might act as a novel drug for treating CVA.

Ophiopogon japonicas has a protective effect on myocardial ischemia/reperfusion injury-related diseases. Using network pharmacology and molecular docking approaches, we aimed to investigate the potential role of OJPs in myocardial damage. Also, the effects of OJPs and verapamil on cardiac function, cardiac marker enzymes, oxidative stress, inflammation, histopathological changes, apoptosis, TLR4/Myd88/NF-κB, PI3K/AKT/mTOR, as well Nrf2/HO-1 pathways were determined by echocardiography, hematoxylin-eosin and staining, Enzyme-Linked Immunosorbnent Assay, TdT-mediated dUTP nick end labeling, IHC and Western blot assays in MI/RI rats, respectively. A total of 28 absorbable compounds of OJPs and 65 OJPs-MI/RI-related targets were screened. Regulation of inflammatory response and apoptotic signaling pathway might contribute to OJPs against MI/RI. Besides, molecular docking presented that there are 6 core targets including AKT1, IL6, TNF, VEGFA, EGFR, and Caspase 3 with a certain binding affinity on the absorbable components of OJPs. The in vivo experiments illustrated that OJPs ameliorated cardiac function, oxidative stress, inflammation, and histopathological injury in I/R rats. Moreover, OJPs also could repress levels of apoptosis and TLR4/Myd88/NF-κB-related targets, as well as activate PI3K/AKT/mTOR and Nrf2/HO-1 pathways. Collectively, our findings suggest OJPs could attenuate MI/RI by weakening the TLR4/Myd88/NF-κB signaling, as well as activating PI3K/AKT/mTOR and Nrf2/HO-1 pathways.

Strict air pollution control strategies have been implemented in recent decades in the North China Plain (NCP), previously one of the most polluted regions in the world, and have resulted in considerable changes in emissions of air pollutants. However, little is so far known about the long-term trends of the regional background level of NOx and SO2, along with the increase and decrease processes of regional emissions. In this study, the seasonal and diurnal variations of NOx and SO2 as well as their long-term trends at a regional background station in the NCP were characterized from 2004 to 2016. On average, SO2 and NOx mixing ratios were 5.7 ± 8.4 and 14.2 ± 12.4 ppb, respectively. The seasonal variations in SO2 and NOx mixing ratios showed a similar pattern, with a peak in winter and a valley in summer. However, the diurnal variations in SO2 and NOx mixing ratios greatly differed for all seasons, indicating different sources for SO2 and NOx and meteorological effects on their concentrations. Overall, the annual mean SO2 exhibited a significant decreasing trend of −6.1 % yr−1 (R = −0.84, P

The human vaginal microbiota plays essential roles in preventing pathogenic bacteria, fungi, and viruses from invading. The dominant vaginal Lactobacillus species show great potential to be developed as probiotics.

Ischemia/reperfusion (I/R) is a primary cause of morbidity and mortality in acute myocardial infarction (AMI). L-Borneol 7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside (LBAG), extracted from the Radix Ophiopogonis, is the main bioactive component that may be exerting cardiovascular protection in AMI. The purpose was to examine the effects of LBAG on myocardial I/R injury (MIRI) in rats and H9c2 cells treated with hypoxia/reoxygenation (H/R). MIRI was induced through the combination of ischemia with reperfusion for 30 min and 24 h, respectively. LBAG was administered 7 days before vascular ligation. Myocardial function was detected by an electrocardiograph, histological, TTC, and TUNEL staining analyses. The influences of LBAG on the content concentration of cardiac enzymes in the serum were measured by ELISA. Moreover, H9c2 cells were exposed to LBAG or combined with AKT inhibitor (perifosine) and then exposed to H/R for simulating the cardiac injury process. Afterward, cell viability, LDH, CD-KM release, apoptosis, and autophagy were evaluated by CCK-8 and ELISA assays, flow cytometry, TUNEL, and immunofluorescence staining, respectively. Additionally, the proteins of apoptosis, autophagy, and PI3K/mTOR pathway were determined by western blotting. In I/R rats, LBAG pretreatment significantly ameliorated cardiac function, as illustrated by reducing the infarct size, myocardial autophagy, and apoptosis levels. In H/R-induced H9c2 cells, LBAG pretreatment significantly decreased cell apoptosis, LC3 II/I, and Beclin 1 levels, elevated the Bcl-2 levels, attenuated LDH, and CD-KM production. Moreover, LBAG pretreatment markedly increased the PI3K/mTOR pathway activation, and the protective influences of LBAG were partly abolished with the AKT inhibitor perifosine treatment. These findings demonstrated the protective functions of LBAG on I/R by regulating apoptosis and autophagy in vitro and in vivo by activating the PI3K/mTOR pathway.

ε-N-l-Lactyllysine (LacK) is site-specifically incorporated into proteins and utilized to develop fluorescent and luminescent probes for detecting delactylases in living cells.

To explore the causative mutation for autosomal recessive inheritance factor V (FV) deficiency in a Chinese family. Relative coagulation indexes and the FV antigen were tested by the one-stage clotting method and ELISA, respectively. At the same time, the calibrated automated thrombogram (CAT) was used to analyze the mutant protein function. All 25 exons, flanking sequences, 5' and 3' untranslated regions of the F5 were amplified by PCR and sequenced directly, while each suspected variant was verified by reverse sequencing. The possible impact of the mutant was analyzed by the corresponding bioinformatics software. The phenotypic tests showed that the proband's FV activity has decreased to 24%, whereas the FV antigen has also reduced to 28%. The genetic analysis revealed that she was a compound heterozygote for a frameshift variant from small deletion in the exon 13 (c.2390_2390delC, p.Pro798Leufs∗13) and a missense mutation in the exon 25 (c.6665A>G, p.Asp2222Gly). Meanwhile, the online bioinformatics software indicated that the frameshift variant was disease-causing. The pathogenic variant p.Pro798Leufs∗13 and the benign variant p.Asp2222Gly largely account for the decrease of the FV deficiency in this Chinese family, of which the pathogenic variant is firstly reported in the world.

BACKGROUND Primary insomnia is a worldwide problem and it has a considerable negative impact on one's physical and mental health. Studies have shown that non-synonymous Single-nucleotide polymorphisms in 5-hydroxytryptamine (serotonin or 5-HT) are related to primary insomnia. Previous studies have shown that 5-HT polymorphism (rs140700) is related to depression, and insomnia is often accompanied by depression and anxiety. The relationship between this site and primary insomnia is unknown. We speculated that this site may be related to primary insomnia, so we investigated the relationship between rs140700 and primary insomnia. AIMS To explore the relationship between the 5-HT gene polymorphism rs140700 and primary insomnia. METHODS In this study, we included 57 patients with primary insomnia and 54 age- and gender-matched normal controls. The subjects who belonged to the Chinese population were subjected to polysomnography for three consecutive nights. Their sleep quality was assessed, and the genotypes of the 5-hydroxytryptamine (5-HT) gene polymorphism rs140700 were determined by the flight mass spectrometry. RESULTS The genotype distributions of the 5-HT gene polymorphism rs140700 were in Hardy-Weinberg equilibrium in both patients and controls (P > 0.05). The allele and genotype distributions of this variant were comparable between the patients and controls in all subjects and between genders (all P > 0.05). The influence of rs140700 on percentage of stage 1 (P = 0.015) change and arousal index (P = 0.028) of primary insomnia was statistically significant. The logistic multi-factor regression analysis results revealed that 5-HT gene polymorphism rs140700 was not a risk factor for primary insomnia in the Chinese population (P = 0.589). CONCLUSIONS The 5-HT gene polymorphism rs140700 may not be a susceptibility locus for primary insomnia in the Chinese population.

Palmitic acid (PA), the most common statured fatty acid in diets, is involved in peripheral as well as central inflammation. The M1 polarization of microglia plays an important role in PA-induced neuroinflammation. However, it is still unclear on the key factor and molecule mechanism of microglial polarization among it. Thus, we investigated whether the release of self-DNA into the cytoplasm of microglia was a consequence of PA treatment, as in aortic endothelial cells and adipocytes. RT-qPCR and immunofluorescence were performed to detect the status of cytosolic DNA and microglial polarization after PA treatment. We found that the content of cytosolic nDNA rather than mtDNA increased after PA treatment and the M1 polarization of microglia was associated with this. Moreover, the knockdown of cGAS in BV2 microglial cells demonstrated that the cGAS-STING pathway is involved in polarization process. Our results revealed that nDNA and cGAS-STING pathway are critically involved in PA-induced microglial M1 polarization. This mechanism may pose a new insight on targeting microglia may be a promising way to mitigate diet-induced early neuroinflammation.

Age-related osteoporosis is characterized by the deterioration in bone volume and strength, partly due to the dysfunction of bone marrow mesenchymal stromal/stem cells (MSCs) during aging. Alpha-ketoglutarate (αKG) is an essential intermediate in the tricarboxylic acid (TCA) cycle. Studies have revealed that αKG extends the lifespan of worms and maintains the pluripotency of embryonic stem cells (ESCs). Here, we show that the administration of αKG increases the bone mass of aged mice, attenuates age-related bone loss, and accelerates bone regeneration of aged rodents. αKG ameliorates the senescence-associated (SA) phenotypes of bone marrow MSCs derived from aged mice, as well as promoting their proliferation, colony formation, migration, and osteogenic potential. Mechanistically, αKG decreases the accumulations of H3K9me3 and H3K27me3, and subsequently upregulates BMP signaling and Nanog expression. Collectively, our findings illuminate the role of αKG in rejuvenating MSCs and ameliorating age-related osteoporosis, with a promising therapeutic potential in age-related diseases., α-ketoglutarate is an intermediate of the Krebs Cycle that was recently reported to extend lifespan in C.Elegans. Here, the authors show that administration of α-ketoglutarate to mice reduces age-related bone loss, by ameliorating senescence of bone-marrow derived mesenchymal stem cells.

Social behaviors do not exist only in higher organisms but are also present in microbes that interact for the common good. Here, we report that budding yeast cells interact with their neighboring cells after exposure to DNA damage. Yeast cells irradiated with DNA-damaging UV light secrete signal peptides that can increase the survival of yeast cells exposed to DNA-damaging stress. The secreted peptide is derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and it induced cell death of a fraction of yeast cells in the group. The data suggest that the GAPDH-derived peptide serves in budding yeast’s social interaction in response to DNA-damaging stress. IMPORTANCE Many studies have shown that microorganisms, including bacteria and yeast, display increased tolerance to stress after exposure to the same stressor. However, the mechanism remains unknown. In this study, we report a striking finding that Saccharomyces cerevisiae cells respond to DNA damage by secreting a peptide that facilitates resistance to DNA-damaging stress. Although it has been shown that GAPDH possesses many key functions in cells aside from its well-established role in glycolysis, this study demonstrated that GAPDH is also involved in the social behaviors response to DNA-damaging stress. The study opens the gate to an interesting research field about microbial social activity for adaptation to a harsh environment.

Wound healing in diabetic skin is impaired by excessive activation of matrix metalloproteinase-9 (MMP-9). MMP-9 transcription is activated by Ten-eleven translocation 2 (TET2), a well-known DNA demethylation protein that induces MMP-9 promoter demethylation in diabetic skin tissues. However, how TET2 is targeted to specific loci in the MMP-9 promoter is unknown. Here, we identified a TET2-interacting long noncoding RNA (TETILA) that is upregulated in human diabetic skin tissues. TETILA regulates TET2 subcellular localization and enzymatic activity, indirectly activating MMP-9 promoter demethylation. TETILA also recruits thymine-DNA glycosylase (TDG), which simultaneously interacts with TET2, for base excision repair-mediated MMP-9 promoter demethylation. Together, our results suggest that the TETILA serves as a genomic homing signal for TET2-mediated demethylation specific loci in MMP-9 promoter, thereby disrupting the process of diabetic skin wound healing.

Introduction: The incidence of infection by Ralstonia is increasing. Several reports describing infection by these bacteria in immunocompromised patients have been published. In this study, we reported a case of Ralstonia pickettii infection in a patient with normal immunity. Case Presentation: A woman presented with fever after thyroid surgery. We identified R. pickettii in her blood culture using 16S rRNA gene sequencing. The patient’s condition improved clinically upon treatment with levofloxacin. Conclusions: Our report highlights the potential of Ralstonia to cause sepsis in patients with normal immunity and emphasizes the importance of blood culture testing when a hospitalized patient has an unexplained high fever.

Fragment size distribution, the important biological properties of cell-free DNA (cfDNA), provides useful information required for diagnostic assay development. However, besides methodological discrepancies, it varies due to the complicated origins and occurrences of in vivo cfDNA. In addition, limited data are available concerning the cfDNA associated with autophagy and distributional difference between cf-mitochondrial DNA (cf-mtDNA) and cf-nuclear DNA (cf-nDNA) fragments. Here we developed an in vitro model of mouse microglial cell (BV-2) with starvation-induced autophagy, in which cfDNA was isolated from the cell supernatant by ultrafiltration (UF) and column-based commercial kit (CC), respectively. Using Agilent 2100 Bioanalyzer, a DNA ladder pattern as the presence of peaks corresponding to mono-, di- and tri-nucleosomes was clearly visualized both in isolation products of UF and CC. However, we also detected shorter fragments than mono-nucleosome by UF. In comparing the UF and CC, we found that the former produced the higher recovery efficiency for spiked-in DNA of shorter fragments than mono-nucleosome in both water and medium, but the latter was superior for spiked-in DNA fragments which were longer than or equal to mono-nucleosome in medium. Combined with these two isolation methods, we have observed that autophagy-associated cf-mtDNA and cf-nDNA were both highly enriched inmono-nucleosomes fragments more than 71%, and showed no significant differences in the relative percentages for these four fragment sizes. These results have improved our understanding of the fragment size distribution of autophagy-derived cf-mtDNA and cf-nDNA in vitro, and might further develop application of cfDNA as a diagnostic tool.

TPS2694 Background: Folate-receptor 1 (FOLR1) and prostate specific membrane antigen (PSMA) are overexpressed on tumor and angiogenic endothelial cells in solid tumors, including prostate cancer, renal cell cancer and lung cancer. CBP-1018 is a first-in-class bi-ligand drug conjugate targeting to both FOLR1 and PSMA, with a tubulin inhibitor payload, monomethyl auristatin E (MMAE). We herein introduce its first-in-human study which is designed based on the significant anti-tumor potency and acceptable safety profile in nonclinical studies. Methods: This study is a phase Ⅰa/Ⅰb, multicenter, open-label study enrolling patients with advanced solid tumor relapsed after previous standard therapies. The primary objective is to assess CBP-1018 safety, tolerability, dose limiting toxicity and maximum tolerated dose. Preliminary efficacy including objective response rate, duration of response and progression-free survival will be observed. Pharmacokinetics, immunogenicity and biomarkers will be also evaluated. This study includes 2 parts: Ⅰa (Dose Escalation) and Ⅰb (Dose Expansion). CBP-1018 is administrated iv Q2W (4 weeks/cycle) in Ⅰa, with accelerated titration at lower doses (0.03 mg/kg and 0.06 mg/kg) and an i3+3 design at following doses (0.08 mg/kg, 0.10 mg/kg, 0.12 mg/kg and 0.14mg/kg, etc.). Subjects will be enrolled in 4 cohorts in Ⅰb: metastatic castration resistant prostate cancer, advanced renal cell cancer, advanced lung squamous cell cancer, and other advanced solid tumors. Efficacy will be assessed every 8 weeks (±7days) according to RECIST 1.1, PCWG3 and PSA assessment (only for prostate cancer). Treatment will be continued untill disease progression or intolerable toxicity. Enrollment has been started in Nov. 2021 and is ongoing. Clinical trial information: NCT04928612.

Short text analysis is a challenging task as far as the sparsity and limitation of semantics. The semantic extension approach learns the meaning of a short text by introducing external knowledge. However, for the randomness of short text descriptions in microblogs, traditional extension methods cannot accurately mine the semantics suitable for the microblog theme. Therefore, we use the prominent and refined hashtag information in microblogs as well as complex social relationships to provide implicit guidance for semantic extension of short text. Specifically, we design a deep hash model based on social and conceptual semantic extension, which consists of dual semantic extension and deep hashing representation. In the extension method, the short text is first conceptualized to achieve the construction of hashtag graph under conceptual space. Then, the associated hashtags are generated by correlation calculation based on the integration of social relationships and concepts to extend the short text. In the deep hash model, we use the semantic hashing model to encode the abundant semantic features and form a compact and meaningful binary encoding. Finally, extensive experiments demonstrate that our method can learn and represent the short texts well by using more meaningful semantic signal. It can effectively enhance and guide the semantic analysis and understanding of short text in microblogs.

Ground-basedMulti-AXis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements were performed at Shangdianzi (SDZ) regional atmospheric background station in northern China from March 2009 to February 2011. The tropospheric NO2 vertical column densities (VCDs) were retrieved to investigate the background condition of the Beijing–Tianjin–Hebei developed economic circle in China. The seasonal variation of mean NO2 tropospheric VCDs (VCDTrop) at SDZ is apparent, with the maximum (1.3 × 1016 molec/cm2) in February and the minimum (3.5 × 1015 molec/cm2) in August, much lower than those observed at the Beijing city center. The average daytime diurnal variations of NO2 VCDTrop are rather consistent for all four seasons, presenting the minimum at noon and the higher values in the morning and evening. The largest and lowest amplitudes of NO2 VCDTrop diurnal variation appear in winter and in summer, respectively. The diurnal pattern at SDZ station is similar to those at other less polluted stations, but distinct from the ones at the urban or polluted stations. Tropospheric NO2 VCDs at SDZ are strongly dependent on the wind, with the higher values being associated with the pollution plumes from Beijing city. Tropospheric NO2 VCDs derived from ground-based MAX-DOAS at SDZ show to be well correlated with corresponding OMI (Ozone Monitoring Instrument) satellite products with a correlation coefficient R = 0.88. However, the OMI observations are on average higher than MAX-DOAS NO2 VCDs by a factor of 28%, probably due to the OMI grid cell partly covering the south of SDZ which is influenced more by the pollution plumes from the urban areas.

Tungsten Disulfide (WS2) is considered to be a promising Hydrogen Evolution Reaction (HER) catalyst to replace noble metals (such as Pt and Pd). However, progress in WS2 research has been impeded by the inertness of the in-plane atoms during HER. Although it is known that microstructure and defects strongly affect the electrocatalytic performance of catalysts, the understanding of such related catalytic origin still remains a challenge. Here, we combined a one-pot synthesis method with wet chemical etching to realize controlled cobalt doping and tunable morphology in WS2. The etched products, which composed of porous WS2, CoS2 and a spot of WOx, show a low overpotential and small Tafel slope in 0.5 M H2SO4 solution. The overpotential could be optimized to −134 mV (at 10 mA/cm2) with a Tafel slope of 76 mV/dec at high loadings (5.1 mg/cm2). Under N2 adsorption analysis, the treated WS2 sample shows an increase in macropore (>50 nm) distributions, which may explain the increase inefficiency of HER activity. We applied electron holography to analyze the catalytic origin and found a low surface electrostatic potential in Co-doped region. This work may provide further understanding of the HER mechanism at the nanometer scale, and open up new avenues for designing catalysts based on other transition metal dichalcogenides for highly efficient HER.

Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. Here, we identified a novel lncRNA MRAK052872, named lnc-URIDS (lncRNA UpRegulated in Diabetic Skin), which regulates wound healing in diabetes mellitus. Lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). Lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment in vitro and accelerated diabetic wound healing in vivo. Mechanistically, lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. The findings of the present study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Peroxyacetyl nitrate (PAN) is one of the most important photochemical pollutants and has aroused much concern in China in recent decades. However, few studies described the long-term variations in PAN in China. In this study, we continuously monitored the PAN, O3 and NOx concentrations at a regional background site near Beijing from August 2015 to February 2019. Based on the observed concentrations and climate data, we analyzed the seasonal PAN variations. The results revealed that the monthly mean PAN concentration ranged from 0.33–2.41 ppb, with an average value of 0.94 ppb. The PAN concentration exhibited a distinct seasonal variation, with high values in spring and low values in winter. After analyzing the corresponding meteorological data, we found that stronger ultraviolet (UV) radiation, a relatively longer lifetime and a higher background PAN concentration contributed to the high PAN concentrations in spring. In addition, with the utilization of the WRF-Chem (Weather Research and Forecasting with Chemistry) model, the cause of the extremely high PAN concentration in spring 2018 was determined. The model results demonstrated that an anomalously low pressure and the southwesterly winds in northern China might be the main causes of the increased PAN concentration in Beijing and its surrounding area in spring 2018.

Impaired wound healing is one of the main causes of diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes is not fully understood. Long noncoding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. In this study, we identified a novel lncRNA, MRAK052872, named lncRNA UpRegulated in Diabetic Skin (lnc-URIDS), which regulates wound healing in diabetes. lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment in vitro and accelerated diabetic wound healing in vivo. Mechanistically, lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. The findings of the current study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.

The Kondo effect offers an important paradigm to understand strongly correlated many-body physics. Although under intensive study, some of the important properties of the Kondo effect, in systems where both itinerant coupling and localized coupling play significant roles, are still elusive. Here we report the evolution and universality of the two-stage Kondo effect, the simplest form where both couplings are important using single molecule transistor devices incorporating Manganese phthalocyanine molecules. The Kondo temperature T* of the two-stage Kondo effect evolves linearly against effective interaction of involved two spins. Observed Kondo resonance shows universal quadratic dependence with all adjustable parameters: temperature, magnetic field and biased voltages. The difference in nonequilibrium conductance of two-stage Kondo effect to spin 1/2 Kondo effect is also identified. Messages learned in this study fill in directive experimental evidence of the evolution of two-stage Kondo resonance near a quantum phase transition point, and help in understanding sophisticated molecular electron spectroscopy in a strong correlation regime., The Kondo effect can serve as a powerful paradigm to understand strongly correlated many-body processes in physics. Here, Guo et al. utilize single molecule transistor devices as a testbed to study multi-level Kondo correlation and show electrical gate evolution and the universality of the two-stage Kondo effect.

Plasmonic nanomaterials, along with their assemblies, provide numerous applications due to their profound optical properties. In this work, we report the self-assembly of Au@Ag core-shell nanocuboids (NCs) into staircase superstructures in both vertical and horizontal orientations through two-stage droplet evaporation. Each stair is composed of a uniform well-aligned monolayer of NCs. The gap distance between NCs can be greatly shrunk to boost the corresponding surface-enhanced Raman scattering (SERS) performance using an ethanol wash method. The SERS performance of the assembled NCs is calculated by finite-difference time-domain (FDTD) simulation, and studied against the step number using 4-mercaptobenzoic acid as a Raman reporter molecule. The increasing EF with the increase of layer number proves that the plasmon mode propagates well in our uniformly aligned assemblies.

Quantum dot devices have been viewed as one of solutions for the next step in the development of integrated circuit. Two-dimensional (2D) layered semiconductors such as tin sulfide (SnS) and tin disulfide (SnS 2 ) are promising materials for fabricating quantum dots (QDs) devices. However, the challenges in the synthesis of QDs with pure phases severely limit applications in such fields. In this work, uniform SnS and SnS 2 QDs were synthesized via a convenient and facile ultrasonic method. TEM and AFM images confirmed the morphology of the SnS and SnS 2 QDs. The optical characteristics of the QDs were obtained via UV–vis absorption and Raman spectroscopy. Finally, volt-current measurements of devices fabricated using the SnS and SnS 2 QDs were carried out. Our results demonstrate the potential of SnS and SnS 2 QDs for optical and electronic applications.

Recently, layered IV–VI metal monochalcogenides have attracted a lot of attention because of their unique properties. Among them, tin monoxide (SnO) has been widely studied as thin films for the application in high-mobility p-channel transistor and photoelectricity device fabrication. In this work, we successfully synthesized SnO nanoshells through a facile solution chemical method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images confirmed the morphology of these nanoshells. The surface chemical composition was investigated by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Raman and photoluminescence spectra were used to study the optical properties of nanoshells with different sizes, which were formed in different concentrations. We found that the special nanostructure may result in abundant Sn or O vacancies on the surface of nanoshells, and these defects resulted in a broad photoluminescent signal. This work provided a solution synthesis method to prepare SnO and other IV–VI metal monochalcogenides as well as their promising applications in optical device.

Optimization design of energy management strategy (EMS) for plug-in hybrid electric vehicle (PHEV), which significantly affects the vehicle performance on fuel economy and pollutant emission, has always been a focal issue. Of various EMSs, rule-based strategies are dominant in practical applications due to their relatively low computational burden, but to obtain the optimum control parameters precisely and efficiently remains an unsolved problem. In this paper, a novel combinatorial algorithm utilizing the historical data from remote monitoring platform is proposed for the EMS optimization of PHEV. Firstly, the historical driving data are processed, and then a table which records different conditions at different time is built for reflecting the future PHEV operation schedule. Based on the historical data, a combinatorial algorithm which combines the advantages of genetic algorithm (GA) with enhanced ant colony algorithm (EACA) is proposed to optimize the control parameters. The principle of algorithm transformation from GA to EACA is when the objective function value is smaller than the default value after five generations of changing continuously in GA optimization process, and then the control parameter combinations can be regarded as the pheromone for EACA. Results show that the combinatorial algorithm successfully overcomes the low solution precision by GA and the slow resolving speed by EACA. The energy consumption of PHEV on a specific bus route can be reduced greatly by the proposed method, and it can provide a theoretical guidance for practical applications.

Weibo has become preferred media for people to expose events, express opinions and share experiences. Many real-world events are first revealed on Weibo. Bursty event detection based on microblog has become a research hotspot in the area of recent event detection. This paper proposes a bursty event detection method (Burst_NBT) based on enhanced bursty term detection which is composed of construction of meaningful string dictionary and calculation of bursty term score. To utilize the feature of hashtags in Weibo and features of titles’ mark in Chinese, Burst_NBT adopts meaningful strings between “#”s and meaningful strings between quotation marks as a heuristic method. The enhanced bursty term detection method takes three factors into consideration, word frequency, associated users and number of comments. Based on this, a hotspot computational model for bursty events is further developed, which uses the indexes such as bursty term frequency, associated users and hotness of associated posts. Experiments on the Sina Weibo corpus prove that Burst_NBT exceeds the other four bursty event detection methods.

The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro, while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. STATEMENT OF SIGNIFICANCE: In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.

Background Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor-β superfamily, has recently been suggested as an anti-aging factor that declines with age in the bloodstream, and restoration of the youthful level by administration of its recombinant protein could reverse age-related dysfunctions. However, its effects on titanium implant osseointegration and mandibular bone during aging remain unknown. Methods Two-month-old and 18-month-old C57BL male mice were given daily intraperitoneal injections of recombinant GDF11 (rGDF11) or vehicle for 6 weeks. Experimental titanium implants were inserted into femurs on the fourth week. Inhibition of GDF11 function was achieved by GDF11 antibody. Implant-bearing femurs were subjected to histomorphometric analysis and biomechanical evaluation. Mandibles were scanned with micro-CT and decalcified for histological measurements. Results In both young adult and aged mice, supraphysiologic GDF11 leads to a significantly decreased bone-to-implant contact ratio (BIC) and peri-implant bone volume/total volume (BV/TV) at the histologic level and reduced resistance at the biomechanical level, indicating weakened implant fixation. Moreover, rGDF11 administration resulted in less trabecular bone volume and thinner cortical thickness in the mandible, which was further compromised in the old animals. In contrast, inhibition of GDF11 improved peri-implant bone healing in old mice. Conclusions Rather than functioning as a rejuvenating factor, exogenous GDF11 negatively affects not only titanium implant healing but also mandibular bone in both young and old mice. In contrast, neutralization of endogenous GDF11 has positive effects on implant fixation in aged mice.

Different site selectivities have been reported for indoles with different directing groups in copper-catalyzed site-selective C-H arylations. Computational and mass spectrometric studies have been conducted in an effort to understand the origin of site selectivity and the effects of the directing groups. A Heck-like mechanism involving a four-membered ring is found in all three of the cases studied. For N-acetyl indole with a weak directing group, a neutral Heck-like mechanism is controlled by an electronic effect resulting in C2 site selectivity. In contrast, indole with a N-P(O) tBu2 group and N-benzyl-3-pivaloyl indole prefer a cationic Heck-like reaction in which a favorable six-membered chelation between the directing group and the CuIII center determines the C6 and C5 site selectivities.

Ground-basedMulti-AXis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements were performed at Shangdianzi (SDZ) regional atmospheric background station in northern China from March 2009 to February 2011. The tropospheric NO

Recently, the single-shaft series-parallel powertrain of Plug-in Hybrid Electric Bus (PHEB) has become one of the most popular powertrains due to its alterable operating modes, excellent fuel economy and strong adaptability for driving cycles. Nevertheless, for configuring the PHEB with single-shaft series-parallel powertrain in the development stage, it still faces greater challenge than other configurations when choosing and matching the main component parameters. Motivated by this issue, a comprehensive multi-objectives optimization strategy based on Genetic Algorithm (GA) is developed for the PHEB with the typical powertrain. First, considering repeatability and regularity of bus route, the methods of off-line data processing and mathematical statistics are adopted, to obtain a representative driving cycle, which could well reflect the general characteristic of the real-world bus route. Then, the economical optimization objective is defined, which is consist of manufacturing costs of the key components and energy consumption, and combined with the dynamical optimization objective, a multi-objective optimization function is put forward. Meanwhile, GA algorithm is used to optimize the parameters, for the optimal components combination of the novel series-parallel powertrain. Finally, a comparison with the prototype is carried out to verify the performance of the optimized powertrain along driving cycles. Simulation results indicate that the parameters of powertrain components obtained by the proposed comprehensive multi-objectives optimization strategy might get better fuel economy, meanwhile ensure the dynamic performance of PHEB. In contrast to the original, the costs declined by 18%. Hence, the strategy would provide a theoretical guidance on parameter selection for PHEB manufacturers.