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The gut microbiome plays an important role in human health. However, its response to external intervention is complex. A previous study showed that the response to Clostridium butyricum (CB) treatment of irritable bowel syndrome (IBS) is heterogeneous. We proposed that mathematical model simulation of the microbiota may help to optimize the management of IBS-associated microbiota. In this study, a novel mathematical non-extinction and defecation normalized (NEDN) model was generated for stable simulation of the dynamic nature of gut microbiota. In silico simulation revealed that a laxative may create a favourable opportunity for Clostridium cluster XIVa to shift the microbiota. An explorative clinical trial was conducted to compare three CB regimens in an IBS cohort: laxative, interval of 2 weeks and CB administration for 2 weeks (L2P); laxative immediately followed by CB administration (LP) for 2 weeks; and CB administration for 2 weeks (P). The LP regimen optimally relieved the IBS symptoms and shifted the microbiota closer to those of the healthy subjects during 2 weeks of CB intake. These results indicate that integration of biological/mathematical approaches and clinical scenarios is a promising method for management of microbiota. Additionally, the optimal effect of sequential laxative-CB usage for IBS treatment warrants further validation.Clinical trial registration numbers: NCT02254629.Date of registration: October 2, 2014.

Different fertilization regimes can substantially influence soil fungal community composition, yet fewer studies try to control for the effects of nitrogen input. Here, we investigated the impact of fertilization with equal nitrogen upon soil properties and soil fungal diversity and community composition in the North China Plain in a long-term field experiment. Long-term (32 years) fertilization regimes were applied with equal amounts of nitrogen: no chemical fertilizer or organic manure; chemical fertilization only; organic manure fertilization only, and; combination of 1/2 chemical fertilizer and 1/2 organic manure. Then we investigated the influence of these four fertilization regimes to soil properties, fungal diversity and community composition. The results showed that applying organic manure significantly influenced soil properties. Illumina MiSeq sequencing and its analysis revealed that organic manure fertilization significantly changed soil fungal alpha diversity, but chemical fertilization did not. Although soil fungal community composition did not differ significantly among all the fertilization regimes at the phylum and class levels, they did show differences in the abundance of dominant fungi. Yet at the genus level, soil fungal community composition, abundance, and beta diversity was affected by all fertilization regimes. Application of organic manure also reduced the abundance of soil-born fungal pathogens such as Fusarium. Our results suggest that long-term application of organic manure could markedly improve soil properties, altering soil fungal community composition and its diversity. Moreover, organic manure fertilization could limit soil-born fungal diseases, to further contribute to soil ecosystem sustainability.

We investigated the effect of CYP2C19 polymorphisms on the clinical outcomes of clopidogrel therapy in patients after stenting procedure for cerebral artery stenosis in northeast China. 568 patients performed CYP2C19 genotype screening in the neurosurgery department of our hospital; 154 patients were finally recruited according to the inclusion and exclusion criteria, and followed-up for 6 months. Ischemic events including (1) transient ischemic attack (TIA); (2) stent thrombosis; (3) ischemic stroke; and (4) death were defined as primary clinical endpoints. The frequencies of CYP2C19*1, *2 and *3 alleles in 568 patients were 63.1%, 31.1% and 5.8%, respectively. 154 patients were classified into extensive (65 patients; 42.2%), intermediate (66 patients; 42.9%), and poor (23 patients; 14.9%) metabolizer groups. A χ2 test showed a significant difference in primary clinical endpoints at 6 months (P = 0.04), and a multivariate Cox regression analysis indicated that the CYP2C19 loss-of-function (LOF) alleles associated with post-procedure prognosis. The Kaplan–Meier curve revealed that there was no significant difference in ischemic events between *2 and *3 alleles carriers. Our study verifies that CYP2C19 *2 and *3 have significant impact on the clinical outcomes of clopidogrel therapy in patients with stenting procedure for cerebral artery stenosis in China.

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the destruction of interlobular biliary ductules, which progressively leads to cholestasis, hepatic fibrosis, cirrhosis, and eventually liver failure. Several mouse models have been used to clarify the pathogenesis of PBC and are generally considered reflective of an autoimmune cholangitis. Most models focus on issues of molecular mimicry between the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC and xenobiotic cross reactive chemicals. None have focused on the classic models of breaking tolerance, namely immunization with self-tissue. Here, we report a novel mouse model of autoimmune cholangitis via immunization with syngeneic bile duct protein (BDP). Our results demonstrate that syngeneic bile duct antigens efficiently break immune tolerance of recipient mice, capturing several key features of PBC, including liver-specific inflammation focused on portal tract areas, increased number and activation state of CD4 and CD8 T cells in the liver and spleen. Furthermore, the germinal center (GC) responses in the spleen were more enhanced in our mouse model. Finally, these mice were 100% positive for anti-mitochondrial antibodies (AMAs). In conclusion, we developed a novel mouse model of PBC that may help to elucidate the detailed mechanism of this complex disease.

Metal halide perovskite nanocrystals (NCs) as a new kind of promising optoelectronic material have attracted wide attention due to their high photoluminescence (PL) quantum yield, narrow emission linewidth and wideband color tunability. Since the PL intensity always has a direct influence on the performance of optoelectronic devices, it is of vital importance to improve the perovskite NCs’ fluorescence emission efficiency. Here, we synthesize three inorganic perovskite NCs and experimentally demonstrate a broadband fluorescence enhancement of perovskite NCs by exploiting plasmonic nanostructured surface consisting of nanogrooves array. The strong near-field optical localization associated with surface plasmon polariton-coupled emission effect generated by the nanogrooves array can significantly boost the absorption of perovskite NCs and tailor the fluorescence emissions. As a result, the PL intensities of perovskite NCs are broadband enhanced with a maximum factor higher than 8-fold achieved in experimental demonstration. Moreover, the high efficiency PL of perovskite NCs embedded in the polymer matrix layer on the top of plasmonic nanostructured surface can be maintained for more than three weeks. These results imply that plasmonic nanostructured surface is a good candidate to stably broadband enhance the PL intensity of perovskite NCs and further promote their potentials in the application of visible-light-emitting devices.

Stimulated Brillouin scattering (SBS) via electrostrictive force is a fundamental interaction between light and sound which limits the power in conventional optical fibers. The emergence of optical microfibers with subwavelength diameter, ultralight mass and an intense light field, provides a new platform for photon–phonon coupling, resulting in the radiation pressure mediated contribution of SBS. This study examines the optomechanical system in cylindrical coordinates, reveals the theoretically radiation pressure induced analogous, and demonstrates contrary effect compared with electrostrictive force in solid or hollow silica microfibers. The finding shows that the photon-phonon coupling, which is related to SBS, can be suppressed in a solid microfiber, and even be completely cancelled in a hollow microfiber.

An environment-friendly fluorescent nano-hybrid hydrogel has been synthesized successfully, from cellulose nanocrystal (CNC), acrylic acid (AA) and phosphorescent Eu2+/Dy3+ doped SrAl2O4 via free radical polymerization. The hydrogel network matrix fixed Eu2+/Dy3+ doped SrAl2O4 nanoparticles by polymer chains with coordinate bonds that prevented particles from aggregating and quenching in water. The fluorescent nano-hybrid hydrogel exhibited extremely high water absorption of which the swelling ratio in distilled water and NaCl salt solution were respectively of 323.35 g/g and 32.65 g/g. Furthermore, the hydrogel displayed excellent water retention property that can keep half of the moisture even exposed to 80 °C for 210 min. Besides, the hydrogel had bright green fluorescence under the sunlight or ultraviolet excitation, and the fluorescence intensity was up to 125477 after swelling 50 times in water. The time-resolved photoluminescence (TRPL) afterglow decay examination showed that the fluorescent emission persisted for 4 h after hydrogels excited at 368 nm wavelength UV-light for 10 min. The fluorescence intensity behaved significant linear relationship with the swelling ratio. As a result, these hydrogels were considered as promising candidates for the preparation of stable and sensitive sensor materials in green water detection.

We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.

Stimulated Brillouin scattering (SBS) via electrostrictive force is a fundamental interaction between light and sound which limits the power in conventional optical fibers. The emergence of optical microfibers with subwavelength diameter, ultralight mass and an intense light field, provides a new platform for photon–phonon coupling, resulting in the radiation pressure mediated contribution of SBS. This study examines the optomechanical system in cylindrical coordinates, reveals the theoretically radiation pressure induced analogous, and demonstrates contrary effect compared with electrostrictive force in solid or hollow silica microfibers. The finding shows that the photon-phonon coupling, which is related to SBS, can be suppressed in a solid microfiber, and even be completely cancelled in a hollow microfiber.

Plasmonic spectrum filtering devices based on metallic nanostructures have attracted wide attention due to their good reliability, ease of fabrication, and wideband tunability. However, the presence of thick substrate significantly limits the structure’s longitudinal size for further optoelectronic integration and reduces the devices’ performance. Here we propose and demonstrate an ultra-thin plasmonic bandpass filter based on free-standing periodic metal-dielectric-metal stack geometry working in the near-infrared wavelength range. The coupling between free-space electromagnetic waves and spatially confined plasmonic modes in the designed structure is systematically investigated. As demonstrated in the calculation and experiment, the free-standing plasmonic filters have more than 90% transmission efficiency and superior angular tolerance. The experimental results are in good agreement with the theoretical calculations. These artificial nanostructured filtering devices may find potential applications in the extremely compact device architectures.

We propose a method to convert linearly polarized incident electromagnetic waves fed by a single source into multi-beam reflections with independent control of polarizations based on anisotropic metasurface at microwave frequencies. The metasurface is composed of Jerusalem Cross structures and grounded plane spaced by a dielectric substrate. By designing the reflection-phase distributions of the anisotropic metasurface along the x and y directions, the x- and y-polarized incident waves can be manipulated independently to realize multi-beam reflections. When the x- and y-polarized reflected beams are designed to the same direction with equal amplitude, the polarization state of the beam will be only controlled by the phase difference between the x- and y-polarized reflected waves. Three examples are presented to show the multi-beam reflections with flexible control of polarizations by using anisotropic metasurfaces and excellent performance. Particularly, we designed, fabricated, and measured an anisotropic metasurface for two reflected beams with one linearly polarized and the other circularly polarized. The measurement results have good agreement with the simulations in a broad bandwidth.

Optical-quality single-crystal LiB3O5 (LBO) nanowires are synthesized for the first time using a sol–gel method. The LBO nanowires possess diameters ranging from 200 to 800 nm and lengths of up to 200 μm, and exhibit excellent uniformity, smooth surfaces, and good mechanical properties. A typical propagating loss of 0.038 dB/μm at 532 nm is obtained for a 620 nm-diameter nanowire. This is a decrease of one order of magnitude compared with that of a β-BaB2O4 (BBO) nanowire with similar diameter, which makes the LBO nanowire a promising candidate to construct miniaturized nonlinear photonic devices.

The influence of nanocellulose on oil well cement (OWC) properties is not known in detail, despite recent advances in nanocellulose technology and its related composite materials. The effect of cellulose nanofibers (CNFs) on flow, hydration, morphology, and strength of OWC was investigated using a range of spectroscopic methods coupled with rheological modelling and strength analysis. The Vom-Berg model showed the best fitting result of the rheology data. The addition of CNFs increased the yield stress of OWC slurry and degree of hydration value of hydrated CNF-OWC composites. The flexural strength of hydrated OWC samples was increased by 20.7% at the CNF/OWC ratio of 0.04 wt%. Excessive addition of CNFs into OWC matrix had a detrimental effect on the mechanical properties of hydrated CNF-OWC composites. This phenomenon was attributed to the aggregation of CNFs as observed through coupled morphological and elemental analysis. This study demonstrates a sustainable reinforcing nano-material for use in cement-based formulations.

Curcumin has been shown to possess strong anti-inflammatory activity in many diseases. It has been demonstrated that the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade and the NAcht leucine-rich-repeat protein 1 (NALP1) inflammasome are important for the synthesis of Pro-Interleukin (IL)-1β and the processing of the inactive protein to its mature form, which plays an active role in the pathogenesis of neuropathic pain. The present study showed that repeated intraperitoneal injection of curcumin ameliorated SNI-induced mechanical and cold allodynia in a dose-dependent manner and inhibited the elevation of spinal mature IL-1β protein levels. Additionally, repeated curcumin treatment significantly inhibited the aggregation of the NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in spinal astrocytes. Furthermore, the genetic down-regulation of NALP1 inflammasome activation by NALP1 siRNA and the pharmacological inhibition of the JAK2-STAT3 cascade by AG490 markedly inhibited IL-1β maturation and Pro-IL-1β synthesis, respectively and reduced SNI-induced pain hypersensitivity. Our results suggest that curcumin attenuated neuropathic pain and down-regulated the production of spinal mature IL-1β by inhibiting the aggregation of NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in astrocytes.

The Feynman relation, a much celebrated condensed matter physics gemstone for more than 70 years, predicts that the density excitation spectrum and structure factor of a condensed Bosonic system in the phonon regime drops linear and continuously to zero. Until now, this widely accepted monotonic excitation energy drop as the function of reduced quasi-momentum has never been challenged in a spin-preserving process. We show rigorously that in a light-matter wave-mixing process in a Bosonic quantum gas, an optical-dipole potential arising from the internally-generated field can profoundly alter the Feynman relation and result in a new dynamic relation that exhibits an astonishing non-Feynman-like onset and cut-off in the excitation spectrum of the ground state energy of spin-preserving processes. This is the first time that a nonlinear optical process is shown to actively and significantly alter the density excitation response of a quantum gas. Indeed, this dynamic relation with a non-Feynman onset and cut-off has no correspondence in either nonlinear optics of a normal gas or a phonon-based condensed matter Bogoliubov theory.

Optical beam shaping plays a key role in optics and photonics. In this work, meta-q-plate featured by arbitrarily space-variant optical axes is proposed and demonstrated via liquid crystal photoalignment based on a polarization-sensitive alignment agent and a dynamic micro-lithography system. Meta-q-plates with multiple-, azimuthally/radially variant topological charges and initial azimuthal angles are fabricated. Accordingly, complex beams with elliptical, asymmetrical, multi-ringed and hurricane transverse profiles are generated, making the manipulation of optical vortex up to an unprecedented flexibility. The evolution, handedness and Michelson interferogram of the hurricane one are theoretically analysed and experimentally verified. The design facilitates the manipulation of polarization and spatial degrees of freedom of light in a point-to-point manner. The realization of meta-q-plate drastically enhances the capability of beam shaping and may pave a bright way towards optical manipulations, OAM based informatics, quantum optics and other fields.

The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota.

The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity and this process is likely initiated by BDNF-TrkB pathway activation.

Multiple mechanisms exist in regulation of host responses to massive challenges from microbiota to maintain immune homeostasis in the intestines. Among these is the enriched Th17 cells in the intestines, which regulates intestinal homeostasis through induction of antimicrobial peptides and secretory IgA among others. However, the means by which Th17 cells develop in response to microbiota is still not completely understood. Although both TLR5 and CD172α+ lamina propria dendritic cells (LPDC) have been shown to promote Th17 cell development, it is still unclear whether TLR5 mediates the CD172α+LPDC induction of Th17 cells. By using a microbiota antigen-specific T cell reporter mouse system, we demonstrated that microbiota antigen-specific T cells developed into Th17 cells in the intestinal LP, but not in the spleen when transferred into TCRβxδ−/− mice. LPDCs expressed high levels of TLR5 and most CD172α+LPDCs also co-expressed TLR5. LPDCs produced high levels of IL-23, IL-6 and TGFβ when stimulated with commensal flagellin and promoted Th17 cell development when cultured with full-length CBir1 flagellin but not CBir1 peptide. Wild-type CD172α+, but not CD172α−, LPDCs induced Th17 cells, whereas TLR5-deficient LPDC did not induce Th17 cells. Our data thereby demonstrated that TLR5 mediates CD172α+LPDC induction of Th17 cells in the intestines.

Researches on Airy beams have grown explosively since the first demonstration in 2007 due to the distinguishing properties of nondiffraction, transverse acceleration and self-healing. To date, a simple and compact approach for generating Airy beams in high quality and efficiency has remained challenging. Here, we propose and demonstrate a liquid crystal (LC) polarization Airy mask (PAM) featured by spatially variant LC azimuthal director. The PAM is fabricated through photoaligning LC via a polarization-sensitive alignment agent suophonic azo dye SD1. Thanks to the special design, a novel feature of polarization-controllable switch between dual Airy beams of orthogonal circular polarization is presented. The molecular-level continuity of LC director significantly improves the quality and efficiency of resultant Airy beams. Besides, the PAM can handle intense light due to the absence of absorptive electrodes. Additional merits of compact size, low cost and broad wavelength tolerance are also exhibited. This work settles a fundamental requirement for Airy beam applications of optical manipulations, biology science and even some uncharted territories.

Hepatic fibrosis is associated with bone marrow derived mesenchymal stem cells (BM-MSCs). In this study, we aimed to determine what role MSCs play in the process and how they mobilize from bone marrow (BM). We employed a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis. Frozen section was used to detect MSCs recruited to mice and human fibrotic liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected to assess liver function. It was found that MSCs of both exogenous and endogenous origin could aggravate liver fibrosis and attenuate liver damage as indicated by lower serum ALT and AST levels. Stromal cell–derived factor-1 (SDF-1α)/ CXCR4 was the most important chemotactic axis regulating MSCs migration from BM to fibrotic liver. Frozen section results showed that the migration did not start from the beginning of liver injury but occured when the expression balance of SDF-1α between liver and BM was disrupted, where SDF-1α expression in liver was higher than that in BM. Our findings provide further evidence to show the role of BM-MSCs in liver fibrosis and to elucidate the mechanism underlying MSCs mobilization in our early liver fibrosis mice model induced by CCl4.