Helicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic ...resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca
2+
release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans.
Abbreviations: 1,25D3: 1α, 25-dihydroxyvitamin D3; ATG5: autophagy related 5; Baf A1: bafilomycin A
1
; BECN1: beclin 1; CagA: cytotoxin-associated gene A; CFU: colony-forming unit; ChIP-PCR: chromatin immunoprecipitation-polymerase chain reaction; Con A: concanamycin A; CQ: chloroquine; CRISPR: clustered regularly interspaced short palindromic repeats; CTSD: cathepsin D; GPN: Gly-Phe-β-naphthylamide; H. pylori: Helicobacter pylori; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MCOLN1: mucolipin 1; MCOLN3: mucolipin 3; MCU: mitochondrial calcium uniporter; MOI: multiplicity of infection; NAGLU: N-acetyl-alpha-glucosaminidase; PDIA3: protein disulfide isomerase family A member 3; PMA: phorbol 12-myristate 13-acetate; PRKC: protein kinase C; SQSTM1: sequestosome 1; STAT3: signal transducer and activator of transcription 3; SS1: Sydney Strain 1; TRP: transient receptor potential; VacA: vacuolating cytotoxin; VD3: vitamin D3; VDR: vitamin D receptor
Correction for 'Analysis of the effects of acoustic levitation to simulate the microgravity environment on the development of early zebrafish embryos' by Li Li
et al.
,
RSC Adv.
, 2020,
10
, ...44593-44600, DOI:
10.1039/D0RA07344J
.
•Structural, magnetic and electric properties of Sr0.95Y0.05Fe12-xZrxO19 M−type hexaferrites.•Hard-magnetic and electric polarization behaviors change as increasing Zr-doping content.•Co-presence of ...Fe2 + and Fe3 + ions in M−type hexaferrites.
The ceramic technique has been utilized to fabricate Sr0.95Y0.05Fe12-xZrxO19 (x = 0–2) samples. Structural and Raman-scattering analyses have revealed that the samples with x = 0 and 0.5 possess the M−type hexagonal-ferrite phase, while the others have the additional Zr-related phase. All samples exhibit the hard-magnetic behavior and the magnetic parameters tend to decrease with increasing Zr-doping content. The study on the electric polarization has indicated that the sample with x = 0 shows the coexistence of paraelectric and weak ferroelectric behaviors, while the other samples (x = 0.5–2) show conductive behaviour with nearly circular loops. The changes in the magnetic and electrical properties mainly related to the co-presence of Fe2+ and Fe3+ ions, as evidenced from analyzing X-ray absorption data.
The dual-transducer support structure discussed has the advantages of a simple structure and low cost, as well as allowing for the use of both Traveling-Wave (TW) and Standing-Wave (SW) acoustic ...transportation, supporting its use in pharmaceutical and biochemical analysis, for example. By adjusting the distance between the vibrating plate and the reflector which forms SW field in the y direction, the control of the position of the SW nodes or the TW component along the x direction allows the formation of a Two-Dimensional Standing Wave (2D-SW) or a Traveling Wave (TW) acoustic field, and these could be used for transportation in the x direction. It has been found that the x position of the SW nodes can be adjusted through changing the temporal phase shift, θ, which permits multiple objects to be transported using the 2D-SW mode. By comparison, TWs in the opposite direction could be generated at a pair of specific temporal phase shifts, allowing fast transportation using the TW mode. In this research work, an experiment has been carried out to transport polystyrene spheres using the two modes by programming the temporal phase shift, θ, this illustrating that precise position control of the multiple objects transported was possible using the 2D-SW mode, while high-speed transportation (up to 540 mm/s) was realized using the TW mode, showing that the dual-transducer support structure could be used effectively for accurate and fast transportation. As a fully non-contact method, the dual-transducer support structure can be seen to work in the 2D-SW mode for reaction synthesis or detection applications, and also in TW mode for rapid sample transportation applications.
A fully microscopic model for the description of nuclear level density (NLD) in spherical nuclei is proposed. The model is derived by combining the partition function of the exact pairing solution ...plus the independent-particle model at finite temperature (EP+IPM) with that obtained by using the collective vibrational states calculated from the self-consistent Hartree-Fock mean field with MSk3 interaction plus the exact pairing and random-phases approximation (SC-HFEPRPA). Two important factors are taken into account in a fully microscopic way, namely the spin cut-off and vibrational enhancement factors are, respectively, calculated using the statistical thermodynamics and partition function of the SC-HFEPRPA without any fitting parameters. The numerical test for two spherical 60Ni and 90Zr nuclei shows that the collective vibrational enhancement is mostly dominated by the quadrupole and octupole excitations. This is the first microscopic model confirming such an effect, which was phenomenologically predicted long time ago and widely employed in several NLD models. In addition, the influence of collective vibrational enhancement on nuclear thermodynamic quantities such as excitation energy, specific heat capacity and entropy is also studied by using the proposed model.
This article proposes a novel highly sensitive humidity sensor with temperature compensation, mainly consisting of a special modal interferometer bonded with thick polyimide (PI) solid films. The ...modal interferometer is constructed by splicing a special dual-mode fiber (DMF) with two sections of regular single mode fiber (SMF), forming an SDS (SMF-DMF-SMF) structure. Due to the particular design of the refractive index of the DMF, only <inline-formula> <tex-math notation="LaTeX">{\text {LP}}_{{01}} </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">{\text {LP}}_{{02}} </tex-math></inline-formula> modes are transmitted, which causes a unique wavelength (UWL) to appear in the spectrum. The UWL breaks the periodicity of the conventional interferometric spectrum. More importantly, both sides of UWL respond differently to various measurands, which enables the interferometer to measure dual parameters simultaneously. To achieve a higher humidity sensitivity, the thick PI solid films are used for the first time to manufacture the interferometric humidity sensors. Their thickness is at least one order of magnitude greater than that of the PI coating used in the traditional humidity sensors, which enhances the sensor's response to humidity variation significantly. The performance of the proposed sensor is further improved with the aid of the varied period Vernier effect by paralleling a bare dual modal interferometer based on the SDS structure as a reference. Similar to the sensing modal interferometric spectrum, the output spectrum of the varied period Vernier effect scheme owns the UWL as well, which makes it easy to distinguish the wavelength shifts of the specific peaks to the measurands. The validity of the proposed scheme is verified by an experimental case, where the humidity sensitivity and the temperature sensitivity are achieved as 1044.26 pm/%RH and 1467.99 pm/°C, respectively.
Plasminogen activator inhibitor-1 (PAI-1), a crucial regulator of fibrinolysis, is increased in sepsis, but its values in predicting disease severity or mortality outcomes have been controversial. ...Therefore, we conducted a systematic review and meta-analysis of its predictive values in sepsis.
PubMed and Embase were searched until August 18, 2017 for studies that evaluated the relationships between PAI-1 levels and disease severity or mortality in sepsis.
A total of 112 and 251 entries were retrieved from the databases, of which 18 studies were included in the final meta-analysis. A total of 4,467 patients (36% male, mean age: 62 years, mean follow-up duration: 36 days) were analyzed. PAI-1 levels were significantly higher in non-survivors than survivors odds ratios (OR): 3.93, 95% confidence interval (CI): 2.31-6.67,
< 0.0001 and in patients with severe sepsis than in those less severe sepsis (OR: 3.26, 95% CI: 1.37-7.75,
= 0.008).
PAI-1 is a significant predictor of disease severity and all-cause mortality in sepsis. Although the predictive values of PAI-1 reached statistical significance, the clinical utility of PAI-1 in predicting outcomes will require carefully designed prospective trials.
Trabeculectomy is a surgical procedure for lowering intraocular pressure in glaucoma patients, in which excessive scarring leading to failure of the filtering bleb adversely affects the surgical ...outcome. Heightened Tenon's capsule fibroblast (TCF) proliferation and extracellular matrix (ECM) deposition are implicated in this process but endogenous factors that regulate TCF functions remain largely elusive. This study sought to elucidate the role of connective tissue growth factor (CTGF) in the regulation of TCF phenotypes and signaling.
Expression of CTGF in scarring and nonscarring Tenon's capsules was measured by real-time PCR and immunofluorescence. Knockdown of CTGC was achieved by lentivirus delivery of small-hairpin RNA. Cell proliferation was measured by CCK8, cell cycle progression, and apoptosis by flow cytometry, adhesion, migration, and invasion of TCF by functional assays in vitro. Proteins and cytokines related to fibrosis were measured by Western blot and ELISA, respectively.
Expression of CTGF was significantly upregulated in scarring Tenon's capsules and their isolated fibroblasts when compared with the nonfibrotic counterparts. Functionally, targeting CTGF with lentivirus-delivered small-hairpin RNA inhibited the proliferation, adhesion, migration, and invasion of TCFs, accompanied by downregulation of p38 and nuclear factor-κB as well as matrix metalloproteinase-2, cyclin D1, and collagen I. In addition, lentiviral targeting of CTGF reduced the release of fibrosis-related cytokines from TCFs and inhibited TCF-conditioned, medium-induced macrophage chemotaxis.
Our study supports a crucial role of CTGF in the regulation of TCF proliferation and ECM deposition. Targeting CTGF using lentiviral vector may be a promising approach for preventing excessive scarring after trabeculectomy.
This work reports the first observation of azimuthal asymmetries around the thrust axis in e+e− annihilation of pairs of back-to-back charged pions in one hemisphere, and π0 and η mesons in the ...opposite hemisphere. These results are complemented by a new analysis of pairs of back-to-back charged pions. The π0 and η asymmetries rise with the relative momentum z of the detected hadrons as well as with the transverse momentum with respect to the thrust axis. These asymmetries are sensitive to the Collins fragmentation function H1⊥ and provide complementary information to previous measurements with charged pions and kaons in the final state. In particular, the η final states will provide additional information on the flavor structure of H1⊥. This is the first measurement of the explicit transverse-momentum dependence of the Collins fragmentation function from Belle data. It uses a dataset of 980.4 fb−1 collected by the Belle experiment at or near a center-of-mass energy of 10.58 GeV.
Maize (
) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed
. Germination of
is induced by strigolactones exuded from maize ...roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, which stimulate less
germination than the major maize strigolactone, zealactone. We then showed that a single cytochrome P450, ZmCYP706C37, catalyzes a series of oxidative steps in the maize-strigolactone biosynthetic pathway. Reduction in activity of this enzyme and two others involved in the pathway, ZmMAX1b and ZmCLAMT1, can change strigolactone composition and reduce
germination and infection. These results offer prospects for breeding
-resistant maize.
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