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Diazirine-tagged d- and l-adrenaline derivatives formed abundant noncovalent gas-phase ion complexes with peptides N-Ac-SSIVSFY-NH2 (peptide S) and N-Ac-VYILLNWIGY-NH2 (peptide V) upon electrospray ionization. These peptide sequences represent the binding motifs in the β2-adrenoreceptor. The structures of the gas-phase complexes were investigated by selective laser photodissociation of the diazirine chromophore at 354 nm, which resulted in a loss of N2 and formation of a transient carbene intermediate in the adrenaline ligand without causing its expulsion. The photolyzed complexes were analyzed by collision-induced dissociation (CID-MS3 and CID-MS4) in an attempt to detect cross-links and establish the binding sites. However, no cross-linking was detected in the complexes regardless of the peptide and d- or l-configuration in adrenaline. Cyclic ion mobility measurements were used to obtain collision cross sections (CCS) in N2 for the peptide S complexes. These showed identical values, 334 ± 0.9 A2, for complexes of the l- and d-adrenaline derivatives, respectively. Identical CCS were also obtained for peptide S complexes with natural l- and d-adrenaline, 317 ± 1.2 A2, respectively. Born-Oppenheimer molecular dynamics (BOMD) in combination with full geometry optimization by density functional theory calculations provided structures for the complexes that were used to calculate theoretical CCS with the ion trajectory method. A close match (337 A2) was found for a single low Gibbs energy structure that displayed a binding pocket with Ser 2 and Ser 5 residues forming hydrogen bonds to the adrenaline catechol hydroxyls. Analysis of the BOMD trajectories revealed a small number of contacts between the incipient carbene carbon atom in the ligand and X-H bonds in the peptide, which was consistent with the lack of cross-linking. Temperature dependence of the internal dynamics of peptide S-adrenaline complexes as well as the specifics of the adrenaline carbene reactions are discussed. In particular, peptide amide hydrogen transfer to the carbene carbon atom was calculated to require crossing a potential energy barrier, which may hamper cross-linking in competition with carbene internal rearrangements.

Nano-TiO2 was prepared with butyl titanate as a precursor by sol-gel method. The samples were analysed by TG-DTA, X-ray diffraction, TEM and so on to assess the effects of different temperatures on the crystal structure, grain size, and microstructure of nano-TiO2. Meanwhile, the catalytic effect of heat treatment temperature on the degradation performance of TiO2 to methyl orange was investigated. The dynamic process of grain growth was preliminarily analysed by Eastman’s particle growth theory. The result shows that TiO2 particle size gradually increases with the heat treatment temperature. At 450 to 550°C, the grain is mainly anatase phase, a mixture of anatase and rutile phase was found at 650°C (mass ratio A:R = 9:1), and the degradation rate of nano-TiO2 on methyl orange reaches 97.75%. When the calcination temperature exceeds 850°C, TiO2 particles almost entirely are composed of rutile phase, and the photocatalytic activity decreases significantly. At 730°C, half of the crystalline TiO2 is transformed from anatase to rutile form. The apparent activation energies of the anatase and rutile crystals of nano-TiO2 are 18.15 kJ/mol and 42.56 kJ/mol, and the fastest grain growth occurs at 546°C and 1280°C respectively.

We determined the role of endophytic bacteria of C. equietifolia, involved in synthesis of allelochemicals. The root endophytic bacteria were isolated and their biological activity was studied to determine their allelopathic potential in fermentation broth. Twenty one species of endophytic bacteria were isolated from the C. equisetifolia roots, of which Bacillus were the dominant genus, Acinetobacter and Staphylococcus were other dominant genera. These 21 endophytic bacteria inhibited the seeds germination of C. equisetifolia, among which Bacillus amyloliquefaciens was most inhibitory. Main allelopathic components of fermentation broth of 3-endophytic bacteria (Bacillus amyloliquefaciens, Bacillus aryabhattai and Paenibacillus glycanilyticus) with strongest allelopathic potential were rich in phenols, esters, organic acids, aldehydes, alcohols, ketones etc. Among them, two allelopathic substances [2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-Phenol and 1,2,3,4-Butanetetrol] were present in both endophytic bacteria fermentation broth and in root and soil extracts. These results confirmed that the secondary metabolites of C. equisetifolia root endophytic bacteria were allelopathic.

TGF-β1 has long been considered as a key mediator in diabetic kidney disease (DKD) but anti-TGF-β1 treatment fails clinically, suggesting a diverse role for TGF-β1 in DKD. In the present study, we examined a novel hypothesis that latent TGF-β1 may be protective in DKD mice overexpressing human latent TGF-β1. Streptozotocin-induced Type 1 diabetes was induced in latent TGF-β1 transgenic (Tg) and wild-type (WT) mice. Surprisingly, compared to WT diabetic mice, mice overexpressing latent TGF-β1 were protected from the development of DKD as demonstrated by lowing microalbuminuria and inhibiting renal fibrosis and inflammation, although blood glucose levels were not altered. Mechanistically, the renal protective effects of latent TGF-β1 on DKD were associated with inactivation of both TGF-β/Smad and nuclear factor-κB (NF-κB) signaling pathways. These protective effects were associated with the prevention of renal Smad7 from the Arkadia-induced ubiquitin proteasomal degradation in the diabetic kidney, suggesting protection of renal Smad7 from Arkadia-mediated degradation may be a key mechanism through which latent TGF-β1 inhibits DKD. This was further confirmed in vitro in mesangial cells that knockdown of Arkadia failed but overexpression of Arkadia reversed the protective effects of latent TGF-β1 on high glucose-treated mesangial cells. Latent TGF-β1 may protect kidneys from TGF-β1/Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation in diabetes through inhibiting Arkadia-mediated Smad7 ubiquitin degradation.

We herein report the results of a facile two-step surfactant assisted reflux synthesis of bismuth telluride (Bi2Te3) nanowires (NWs). The as-synthesised NWs had diameters ranging from 70 to 110 nm with a length varying between 0.4 and 3 µm and a preferential lattice orientation of (0 1 5) as determined by grazing incidence x-ray diffraction. We demonstrate for the first time that a solvent/binder paste formulation of N-methyl-2-pyrrolidone/polyvinylidene fluoride (PVDF) is suitable for screen-printing the Bi2Te3 NWs with the potential for the fabrication of flexible thermoelectric (TE) materials. The wt% of PVDF in the composite films was varied from 10% to 20% to identify the optimal composition with a view to achieving maximum film flexibility whilst retaining the best TE performance. The films were screen-printed onto Kapton substrates and subjected to a post-printing annealing process to improve TE performance. The annealed and screen printed Bi2Te3/PVDF NW composites yielded a maximum Seebeck coefficient −192 µV K−1 with a power factor of 34 µW m−1K−2 at 225 K. The flexible screen printed composite films were flexible and found to be intact even after 2000 bending cycles.

BACKGROUND AND PURPOSE: Efficient detection of metastases is important for patient’ treatment. This prospective study was to explore the clinical value of contrast-enhanced T2 FLAIR in imaging brain metastases using half-dose gadobenate dimeglumine. MATERIALS AND METHODS: In vitro signal intensity of various gadolinium concentrations was explored by spin-echo T1-weighted imaging and T2 FLAIR. Then, 46 patients with lung cancer underwent nonenhanced T2 FLAIR before administration of half-dose gadobenate dimeglumine and 3 consecutive contrast-enhanced T2 FLAIR sequences followed by 1 spin-echo T1WI after administration of half-dose gadobenate dimeglumine. After an additional dose of 0.05 mmol/kg, 3D brain volume imaging was performed. All brain metastases were classified as follows: solid-enhancing, ≥ 5 mm (group A); ring-enhancing, ≥ 5 mm (group B); and lesion diameter of

Five isonitrogenous and isocaloric diets containing dietary lipid concentrations from 71.90 to 142.70 g/kg were formulated and fed to Chinese rice field eel Monopterus albus fingerlings (5.00 ± 0.50 g). The highest values of weight gain, specific growth rate (SGR), together with the lowest feed conversion ratio (FCR) were found in fish fed with 89.10 g/kg lipid diet. Fish fed with 71.90 g/kg diet (F1) had higher hepatosomatic index, viscerosomatic index and whole‐body crude lipid than fish in the other four treatments (p

Oxidation of nontraditional nucleobases 1-methylcytosine (hachimoji base S) and isoguanine (hachimoji base B) in gas-phase ternary complexes with CuII(terpyridine)2+ formed cation radicals that wer...

Cation radicals of adenine (A•+) and 9-methyladenine (MA•+) were generated in the gas phase by collision-induced intramolecular electron transfer in copper-terpyridine-nucleobase ternary complexes and characterized by collision-induced dissociation (CID) mass spectra and UV-vis photodissociation action spectroscopy in the 210-700 nm wavelength region. The action spectra of both A•+ and MA•+ displayed characteristic absorption bands in the near-UV and visible regions. Another tautomer of A•+ was generated as a minor product by multistep CID of protonated 9-(2-bromoethyl)adenine. Structure analysis by density functional theory and coupled-clusters ab initio calculations pointed to the canonical 9-H-tautomer Ad1•+ as the global energy minimum of adenine cation radicals. The canonical tautomer MA1•+ was also calculated to be a low-energy structure among methyladenine cation radicals. However, two new noncanonical tautomers were found to be energetically comparable to MA1•+. Vibronic absorption spectra were calculated for several tautomers of A•+ and MA•+ and benchmarked on equation-of-motion coupled-clusters excited-state calculations. Analysis of the vibronic absorption spectra of A•+ tautomers pointed to the canonical tautomer Ad1•+ as providing the best match with the action spectrum. Likewise, the canonical tautomer MA1•+ was the unequivocal best match for the MA•+ ion generated in the gas phase. According to potential-energy mapping, MA1•+ was separated from energetically favorable noncanonical cation radicals by a high-energy barrier that was calculated to be above the dissociation threshold for loss of a methyl hydrogen atom, thus preventing isomerization. Structures and energetics of all four DNA nucleobase cation radicals are compared and discussed.

Bacteria have evolved diverse mechanisms to fend off predation by bacteriophages. We previously identified the Dnd system, which uses DndABCDE to insert sulfur into the DNA backbone as a double-stranded phosphorothioate (PT) modification, and DndFGH, a restriction component. Here, we describe an unusual SspABCD-SspE PT system in Vibrio cyclitrophicus, Escherichia coli and Streptomyces yokosukanensis, which has distinct genetic organization, biochemical functions and phenotypic behaviour. SspABCD confers single-stranded and high-frequency PTs with SspB acting as a nickase and possibly introducing nicks to facilitate sulfur incorporation. Strikingly, SspABCD coupled with SspE provides protection against phages in unusual ways: (1) SspE senses sequence-specific PTs by virtue of its PT-stimulated NTPase activity to exert its anti-phage activity, and (2) SspE inhibits phage propagation by introducing nicking damage to impair phage DNA replication. These results not only expand our knowledge about the diversity and functions of DNA PT modification but also enhance our understanding of the known arsenal of defence systems.

To analyze the polymorphism ofThe blood samples and epidemiological characteristics were collected from malaria cases in Yunnan Province registered in the National Notifiable Disease Report System. TheThe sequences ofThe

We used single-molecule picometer-resolution nanopore tweezers (SPRNT) to resolve the millisecond single-nucleotide steps of superfamily 1 helicase PcrA as it translocates on, or unwinds, several kilobase-long DNA molecules. We recorded more than two million enzyme steps under various assisting and opposing forces in diverse adenosine tri- and diphosphate conditions to comprehensively explore the mechanochemistry of PcrA motion. Forces applied in SPRNT mimic forces and physical barriers PcrA experiences in vivo , such as when the helicase encounters bound proteins or duplex DNA. We show how PcrA’s kinetics change with such stimuli. SPRNT allows for direct association of the underlying DNA sequence with observed enzyme kinetics. Our data reveal that the underlying DNA sequence passing through the helicase strongly influences the kinetics during translocation and unwinding. Surprisingly, unwinding kinetics are not solely dominated by the base pairs being unwound. Instead, the sequence of the single-stranded DNA on which the PcrA walks determines much of the kinetics of unwinding.

The aim of this study was to construct a simple, rapid and ultra-sensitive optical biosensing technique based on rolling circle amplification (RCA), and to apply it to multiple detection of drug-resistant genes of mycobacterium tuberculosis. The common mutation sites of isoniazid, rifampicin and streptomycin resistance genes are katG315 (AGC➝ACC), rpoB531 (CAC➝TAC) and rpsL43 (AAG➝AGG). For these three gene sites, from February 2020 to May 2021, in the Department of Laboratory Medicine of the First Affiliated Hospital of Army Military Medical University, the padlock probe (PLP), primers and capture probes were designed. And a solid-phase RCA constant temperature amplification reaction system based on magnetic beads was constructed and the experimental parameters were optimized. The RCA products were accurately captured by the multicolor fluorescent probes (Cy3/Cy5/ROX), and the single-tube multiple detection of three mutation genes was realized. The sensitivity, specificity and linear range of this method were further verified. The results showed that the response range of katG315 in the same reaction system ranged from 1.0 pmol/L to 0.1 nmol/L. The response range of rpoB531 and rpsL43 ranged from 1.0 pmol/L to 50.0 pmol/L and 1.0 pmol/L to 20.0 pmol/L, and the method had good specificity and sensitivity, and could accurately identify single base mutations in mixed targets, with the minimum detection limit as low as 1.0 pmol/L. The recoveries of simulated serum samples were 95.0%-105.2%. In conclusion, the constant temperature amplification multiple detection method constructed in this study can quickly realize the single-tube multiple detection of three drug resistance mutation sites. This technology is low-cost, simple and rapid, and does not rely on large equipment, providing a new analysis method for pathogen drug resistance gene detection.本研究旨在构建基于核酸滚环扩增（RCA）的简便快速、超灵敏的光学生物传感技术，并将其运用于结核杆菌耐药相关基因的多重检测。本研究在2020年2月至2021年5月期间，于陆军军医大学第一附属医院检验科，针对异烟肼、利福平和链霉素耐药的高频基因突变位点katG315（AGC➝ACC）、rpoB531（CAC➝TAC）和rpsL43（AAG➝AGG），分别设计锁式探针（padlock probe，PLP）、引物和捕获探针，构建了基于磁珠的固相RCA恒温扩增反应体系，并进行了实验参数的优化。通过多色荧光探针（Cy3/Cy5/ROX）对RCA产物精准捕获与信号放大，实现了对3种突变基因的单管多重检测。进一步对该方法的灵敏度、特异性与线性范围等分析性能进行验证，结果显示同一反应体系中katG315的响应范围为1.0 pmol/L至0.1 nmol/L，rpoB531和rpsL43的响应范围为1.0 pmol/L至50.0 pmol/L和1.0 pmol/L至20.0 pmol/L，且该方法具有较好的特异度与灵敏度，在混合靶标中可精确识别单碱基突变，最低检出限低至1.0 pmol/L；在模拟血清样本的回收实验中，回收率可达95.0%~105.2%。综上，本研究构建的恒温扩增型多重检测方法可快速实现3种耐药突变位点的单管多重检测，该技术成本低廉、简便快速、不依赖大型设备，为病原体耐药基因检测提供了一种新的分析方法。.

Phonon lasers, exploiting coherent amplifications of phonons, have been a cornerstone for exploring quantum phononics, imaging nanomaterial structures, and realizing force sensors or phonon frequency combs. Single-mode phonon lasers, governed by dispersive optomechanical coupling, have been recently demonstrated via levitating a nanoparticle using an optical tweezer. Such levitated optomechanical (LOM) devices, with fundamental minimum of noises in high vacuum, can flexibly control large-mass objects with no internal discrete energy levels. However, it is still elusive to realize nonlinear multi-frequency phonon lasing with levitated microscale objects, dominated instead by dissipative LOM coupling due to much stronger optical scattering loss. Here, we report such a nonlinear phonon laser by employing a Yb3+-doped active LOM system. We observe a 3-order of magnitude enhancement for the fundamental-mode phonon lasing, compared with that in its passive counterparts. Above the lasing threshold, higher-order mechanical sidebands emerge spontaneously. Coherent correlations are also identified for the phonon modes. Our gain-assisted dissipative LOM platform no longer relies on any complicated external feedback control. Our work drives LOM into a new regime where it becomes promising to study mechanical properties or quantum entanglement of typical micro-size objects, such as atmospheric particulates and living cells, and build levitated force sensors with these objects for biomedical or astronomical applications.

Body sizes in endothermic species tend to increase as temperature decreases in accordance with Bergmann’s rule. However, why do some species support Bergmann’s clines while others reverse it? This question should be solved by considering the relative contributions of mean age and growth rate on adult ectotherm body size. Here we studied altitudinal variation in mean body size, age, and growth rate in Rana kukunoris through 16 sites at different altitudes in the eastern Tibetan Plateau. Our results revealed that mean body size decreased as altitude increased in each sex, which fails to obey Bergmann’s rule, but supports the converse Bergmann’s rule. Frogs at lower altitudes tended to grow faster than individuals of the same species at higher altitudes. Conversely, age of adults did not significantly increase as altitude increased. Therefore, we suggest that lower growth rate limits the mean individual body size at the altitudes, explaining why this species follows the converse Bergmann’s rule. The effect of age cannot be ignored because decreasing body length with increasing altitudes is not significant when removing the effect of age.

The CUPID-Mo experiment to search for 0$$\nu \beta \beta $$ ν β β decay in $$^{100}$$ 100 Mo has been recently completed after about 1.5 years of operation at Laboratoire Souterrain de Modane (France). It served as a demonstrator for CUPID, a next generation 0$$\nu \beta \beta $$ ν β β decay experiment. CUPID-Mo was comprised of 20 enriched $$\hbox {Li}_{{2}}$$ Li 2 $$^{100}$$ 100 $$\hbox {MoO}_4$$ MoO 4 scintillating calorimeters, each with a mass of $$\sim 0.2$$ ∼ 0.2 kg, operated at $$\sim 20$$ ∼ 20 mK. We present here the final analysis with the full exposure of CUPID-Mo ($$^{100}$$ 100 Mo exposure of 1.47 $$\hbox {kg} \times \hbox {year}$$ kg × year ) used to search for lepton number violation via 0$$\nu \beta \beta $$ ν β β decay. We report on various analysis improvements since the previous result on a subset of data, reprocessing all data with these new techniques. We observe zero events in the region of interest and set a new limit on the $$^{100}$$ 100 Mo 0$$\nu \beta \beta $$ ν β β decay half-life of $$T_{1/2}^{0\nu }$$ T 1 / 2 0 ν $$> {1.8}\times 10^{24}$$ > 1.8 × 10 24 year (stat. + syst.) at 90% CI. Under the light Majorana neutrino exchange mechanism this corresponds to an effective Majorana neutrino mass of $$\left$$ m β β $$ < ( 0.28 - 0.49 ) eV, dependent upon the nuclear matrix element utilized.

人脸识别作为快速、简便的身份识别手段，广泛应用于生活的多个领域。阻塞性睡眠呼吸暂停部分患者伴随着面部结构的异常，成为人脸识别的潜在应用场景。本文综述了人脸识别在成人阻塞性睡眠呼吸暂停筛查和诊断的相关研究进展，以期提供新的诊疗思路。.

ObjectivesTo understand the crosstalk between the host and microbiota in psoriatic skin, using a systems biology approach based on transcriptomics and microbiome profiling.MethodsWe collected the skin tissue biopsies and swabs in both lesion and non-lesion skin of 13 patients with psoriasis (PsO), 15 patients with psoriatic arthritis (PsA), and healthy skin from 12 patients with ankylosing spondylitis (AS). We performed transcriptome sequencing and metagenomics profiling on the local skin sites to study the similarities and differences in the molecular profiles between the three conditions, and the associations between the host defense and microbiota dynamic.ResultsWe found that lesion and non-lesional samples were remarkably different in terms of their transcriptome profiles. Functional annotation of differentially expressed genes (DEGs) showed a major enrichment in neutrophil activation. By using coexpression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we extracted a “core” set of genes that were functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundance of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the “core network” of genes.ConclusionsWe identified a core network that regulates inflammation and hyper-keratinization in psoriatic skin, and is associated with local disease severity and microbiome composition.