Rotating cantilever-based low-frequency double-fiber grating acceleration sensor.

Acceleration sensors play an important role in bridges, dams, seismic monitoring, geological exploration, and more. Aiming at the problem that it is still difficult to accurately measure low-frequency vibration signals with low-frequency acceleration sensors, a high-sensitivity, wide-low-band fiber Bragg grating (FBG) acceleration sensor incorporating a rotating cantilever and springs was proposed. A sensor mechanics model was built, and its key parameters were analyzed theoretically and optimized in size. ANSYS Workbench was used for simulation analysis, and the physical sensor was developed while a low-frequency test platform was established for performance tests. The experimental results suggested that the natural frequency of the sensor was 78 Hz, the operating frequency band was 1-55 Hz, the sensitivity was 1127.2 pm/g, the transverse interference immunity was less than 5.45%, and the dynamic range was 86.45 dB. With high sensitivity, wide low frequency band, and excellent temperature compensation characteristics, the designed sensor could provide a reference for the design of like FBG acceleration sensors.

TCL1A acts as a tumour suppressor by modulating gastric cancer autophagy via miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop.

Gastric cancer is the third most commonly cause of tumour-related death worldwide and one of the most prevalent malignancies in China. TCL1A, TCL1 family Akt coactivator A, can active Akt/mTOR pathway and regulate the autophagy. However, the action of TCL1A in gastric cancer is not well understood. The present study is investigating the mechanism of action of TCL1A in gastric cancer. TCL1A was lowly expressed in gastric cancer tissues. Subsequent experiments demonstrated that miR-181a-5p can regulate c-MYC through the TCL1A-Akt/mTOR pathway and c-MYC can in turn affect the expression of miR-181a-5p, thus confirming the existence of the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop. Flow cytometric apoptosis assay and mRFP-eGFP-LC3 autophagy assay demonstrated that both miR-181a-5p and TCL1A can affect autophagy and apoptosis of gastric cancer cells through the loop. In vivo experiments confirmed that TCL1A can affect the proliferation of gastric cancer. These results illustrate that TCL1A can exert tumour suppressive effects and affect gastric cancer autophagy and progression via the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop, which could be a potential therapeutic target for gastric cancer.

Cryo-EM structures of LolCDE reveal the molecular mechanism of bacterial lipoprotein sorting in Escherichia coli.

Bacterial lipoproteins perform a diverse array of functions including bacterial envelope biogenesis and microbe-host interactions. Lipoproteins in gram-negative bacteria are sorted to the outer membrane (OM) via the localization of lipoproteins (Lol) export pathway. The ATP-binding cassette (ABC) transporter LolCDE initiates the Lol pathway by selectively extracting and transporting lipoproteins for trafficking. Here, we report cryo-EM structures of LolCDE in apo, lipoprotein-bound, and AMPPNP-bound states at a resolution of 3.5 to 4.2 Å. Structure-based disulfide crosslinking, photo-crosslinking, and functional complementation assay verify the apo-state structure and reveal the molecular details regarding substrate selectivity and substrate entry route. Our studies snapshot 3 functional states of LolCDE in a transport cycle, providing deep insights into the mechanisms that underlie LolCDE-mediated lipoprotein sorting in E. coli.

Obesity-related genetic polymorphisms are associated with the risk of early puberty in Han Chinese girls.

OBJECTIVE: To explore the association between obesity and precocious puberty from the perspective of genetic polymorphism. DESIGN: Two hundred and ninety-eight pairs of girls in early puberty and age-matched controls (±3 months) were recruited. The genotypes of four obesity-related single-nucleotide polymorphism (SNP) loci (rs10968576, rs12935153, rs4674340 and rs7635103) were determined and the effect of variation on early puberty in Chinese Han girls was evaluated. The unstimulated luteinizing hormone (LH), follicle-stimulating hormone and estradiol levels were also measured to determine the relationship with SNP polymorphisms. RESULTS: The effect allele A of rs12935153 was associated with early puberty (odds ratio [OR] = 1.256, 95% confidence interval [CI]: 1.010-1.585), but the significance disappeared after multiple comparisons. After adjusting for body mass index, rs12935153 variation increased the risk of early puberty in additive (OR = 1.589, 95% CI: 1.222-2.066), dominant (OR = 1.788, 95% CI: 1.210-2.642) and recessive (OR = 1.915, 95% CI: 1.207-3.038) models of inheritance. Individuals harbouring AA genotype in rs12935153 had a risk of higher LH levels than that of wild type (OR = 1.668, 95% CI: 1.093-2.546). CONCLUSIONS: The association between obesity and precocity can be explained from a genetic perspective. Our study suggests that variations in rs12935153 increase the risk of early puberty in Chinese girls. Further studies are needed to verify our findings.

Cryo-EM structures of LptB2FG and LptB2FGC from Klebsiella pneumoniae in complex with lipopolysaccharide.

Lipopolysaccharide (LPS) is an essential component of the outer membrane (OM) in most Gram-negative bacteria. LPS transport from the inner membrane (IM) to the OM is achieved by seven lipopolysaccharide transport proteins (LptA-G). LptB2FG, an type VI ATP-binding cassette (ABC) transporter, forms a stable complex with LptC, extracts LPS from the IM and powers LPS transport to the OM. Here we report the cryo-EM structures of LptB2FG and LptB2FGC from Klebsiella pneumoniae in complex with LPS. The KpLptB2FG-LPS structure provides detailed interactions between LPS and the transporter, while the KpLptB2FGC-LPS structure may represent an intermediate state that the transmembrane helix of LptC has not been fully inserted into the transmembrane domains of LptB2FG.

Structures of the ß-barrel assembly machine recognizing outer membrane protein substrates.

ß-barrel outer membrane proteins (ß-OMPs) play critical roles in nutrition acquisition, protein import/export, and other fundamental biological processes. The assembly of ß-OMPs in Gram-negative bacteria is mediated by the ß-barrel assembly machinery (BAM) complex, yet its precise mechanism remains elusive. Here, we report two structures of the BAM complex in detergents and in nanodisks, and two crystal structures of the BAM complex with bound substrates. Structural analysis indicates that the membrane compositions surrounding the BAM complex could modulate its overall conformations, indicating low energy barriers between different conformational states and a highly dynamic nature of the BAM complex. Importantly, structures of the BAM complex with bound substrates and the related functional analysis show that the first ß-strand of the BamA ß-barrel (ß1BamA ) in the BAM complex is associated with the last but not the first ß-strand of a ß-OMP substrate via antiparallel ß-strand interactions. These observations are consistent with the ß-signal hypothesis during ß-OMP biogenesis, and suggest that the ß1BamA strand in the BAM complex may interact with the last ß-strand of an incoming ß-OMP substrate upon their release from the chaperone-bound state.

Association of PLCB1 gene polymorphism with the risk of central precocious puberty in Chinese Han girls / 中国学校卫生

Objective@#To investigate the association between mutation of PLCB1, the downstream gene of KISS1/GPR54 pathway, and the risk of central precocious puberty (CPP) in Chinese Han girls.@*Methods@#Totally 169 pairs of CPP girls on their first visit to hospital and age-matched controls (± 3 months) were recruited. The genotypes of rs6140544, rs11476922, rs3761170 and rs2235613 were determined and the effect of loci variations on CPP was investigated.@*Results@#After adjusting for confounding factors (BMI, maternal age at menarche, maternal age at birth, and time for bed), rs2235613 variation was significantly negative associated with CPP in recessive models(OR=0.46，95%CI=0.24-0.91), and mutation in rs3761170 increased the risk of CPP in dominant models (OR=1.99，95%CI=1.01-3.93).@*Conclusion@#The study suggests that mutation in rs3761170 increases the risk of CPP and rs2235613 variation may have a protective effect on the risk of CPP.

Influencing factors of myopia among primary and secondary school students in Shenzhen / 中国学校卫生

Objective@#To investigate the associated factors of myopia among primary and secondary school students in Shenzhen, and to provide reference for the prevention and control of myopia.@*Methods@#By stratified cluster sampling, 3 073 students of 14 schools including primary,junior,regular and vocational senior schools from two districts in Shenzhen were selected and investigated.@*Results@#For primary school students, the time of using computer for 2-<3 hours per day (OR=2.23，95%CI=1.19-4.20) , and no physical education class(2 sections per week OR=0.34, 95%CI=0.13-0.91; 4 sections per week OR=0.23, 95%CI=0.08-0.62; 5 sections or more per week OR=0.33, 95%CI=0.11-0.97) were positively associated with myopia. Teachers finishing class on time at break (occasionally delaying OR=1.99, 95%CI=1.51-2.63; frequently delaying OR=2.07, 95%CI=1.29-3.30), taking 0.5-1 hour break when using eyes at close range (1-<2 hours OR=1.33，95%CI=1.03-1.70; ≥3 hours OR=1.87, 95%CI=1.17-3.00), no parents with myopia(one parent with myopia OR=1.69, 95%CI=1.32-2.17; two parents with myopia OR=2.13, 95%CI=1.50-3.02) were negatively associated with myopia. For junior high school students, without parents with myopia (one parent with myopia OR=3.27, 95%CI=2.17-4.94; two parents with myopia OR=5.38, 95%CI=2.78-10.42) was the protective factor of myopia. For senior high school students, male (female OR=1.52, 95%CI=1.07-2.14), doing eye exercises twice a day in school (OR=0.41, 95%CI=0.23-0.75), and accumulating outdoor activities for ≥2 hours a day (OR=0.70, 95%CI=0.49-1.00) were negatively associated with myopia.@*Conclusion@#There are different risk factors for myopia among different students in Shenzhen. Students with high risk factors are the key objects of prevention and control.

Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG.

After biosynthesis, bacterial lipopolysaccharides (LPS) are transiently anchored to the outer leaflet of the inner membrane (IM). The ATP-binding cassette (ABC) transporter LptB2FG extracts LPS molecules from the IM and transports them to the outer membrane. Here we report the crystal structure of nucleotide-free LptB2FG from Pseudomonas aeruginosa. The structure reveals that lipopolysaccharide transport proteins LptF and LptG each contain a transmembrane domain (TMD), a periplasmic ß-jellyroll-like domain and a coupling helix that interacts with LptB on the cytoplasmic side. The LptF and LptG TMDs form a large outward-facing V-shaped cavity in the IM. Mutational analyses suggest that LPS may enter the central cavity laterally, via the interface of the TMD domains of LptF and LptG, and is expelled into the ß-jellyroll-like domains upon ATP binding and hydrolysis by LptB. These studies suggest a mechanism for LPS extraction by LptB2FG that is distinct from those of classical ABC transporters that transport substrates across the IM.

Structural basis for lipopolysaccharide insertion in the bacterial outer membrane.

One of the fundamental properties of biological membranes is the asymmetric distribution of membrane lipids. In Gram-negative bacteria, the outer leaflet of the outer membrane is composed predominantly of lipopolysaccharides (LPS). The export of LPS requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS from the inner membrane, through the periplasm to the surface. Of the seven Lpt proteins, the LptD-LptE complex is responsible for inserting LPS into the external leaflet of the outer membrane. Here we report the crystal structure of the ∼110-kilodalton membrane protein complex LptD-LptE from Shigella flexneri at 2.4 Å resolution. The structure reveals an unprecedented two-protein plug-and-barrel architecture with LptE embedded into a 26-stranded ß-barrel formed by LptD. Importantly, the secondary structures of the first two ß-strands are distorted by two proline residues, weakening their interactions with neighbouring ß-strands and creating a potential portal on the barrel wall that could allow lateral diffusion of LPS into the outer membrane. The crystal structure of the LptD-LptE complex opens the door to new antibiotic strategies targeting the bacterial outer membrane.

[Influence of Pr3+ on Eu3+ luminescence in three component complex system of Eu(ClO4)3-DPSO-phen].

Different nuclear [(Eu(1 - x)Pr(x))(DPSO)(phen)3(ClO4)2]ClO4 x nH2O (x = 0.000-0.200, DPSO as the abbreviation for diphenyl sulfoxide and phen for 1,10-phenanthroline, n = 1-6) coordination compounds were synthesized, and were studied by means of composition analysis, conductance, IR spectra and fluorescence excitation and emission spectra. In the fluorescence spectra it was found that Pr3+ has a great influence on the luminescence of Eu3+. The fluorescence emission intensity of europium perchlorate was enhanced when doped with 0.001-->0.100 mol Pr3+. The local symmetry of Eu3+ site is low in this coordination compounds.