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Summary: Using microscopy to investigate stomatal behaviour is common in plant physiology research. Manual inspection and measurement of stomatal pore features is low throughput, relies upon expert knowledge to record stomatal features accurately, requires significant researcher time and investment, and can represent a significant bottleneck to research pipelines.To alleviate this, we introduce StomaAI (SAI): a reliable, user‐friendly and adaptable tool for stomatal pore and density measurements via the application of deep computer vision, which has been initially calibrated and deployed for the model plant Arabidopsis (dicot) and the crop plant barley (monocot grass).SAI is capable of producing measurements consistent with human experts and successfully reproduced conclusions of published datasets.SAI boosts the number of images that can be evaluated in a fraction of the time, so can obtain a more accurate representation of stomatal traits than is routine through manual measurement. An online demonstration of SAI is hosted at https://sai.aiml.team, and the full local application is publicly available for free on GitHub through https://github.com/xdynames/sai‐app. [ABSTRACT FROM AUTHOR]

Repeated low-intensity noise exposure is prevalent in industrialized societies. It has long been considered risk-free until recent evidence suggests that the temporary threshold shift (TTS) induced by such exposure might be a high-risk factor for hearing loss. This study was conducted to further investigate the manner in which repeated low-intensity noise exposure contributed to hearing damage. Two-month-old C57BL/6 J mice were exposed to white noise at 96 dB SPL for 8 h per day over 7 days to induce TTS. Auditory brainstem response (ABR) was monitored to assess changes in hearing thresholds, tracking the effects of noise exposure until the mice reached 12 months of age. Our results indicated that noise-exposed mice exhibited accelerated age-related hearing loss spanning from high to low frequencies. Proteomics analysis revealed an upregulation in the receptor for the advanced glycation end-products (RAGE) signaling pathway, which was associated with an activated inflammatory response, vascular injury, and mitochondrial and synaptic dysfunction. Further analysis confirmed increased levels of inflammatory cytokines in the cochlear lymph fluid and significant macrophages infiltration in the cochlear lateral wall, accompanied by hyperpermeability of the blood-labyrinth barrier. Additionally, degenerated mitochondria in the outer hair cells and decreased synaptic ribbons in the inner hair cells were also observed. These pathological changes indicated that noise exposure damages the cochlear cellular components, increasing the cochlear susceptibility to age-related stress. Our findings suggest that TTS caused by repeated low-intensity noise exposure correlates with a severe sensorineural hearing loss during aging; targeting the RAGE signaling pathway may be a promising strategy to mitigate damage from low-intensity noise and slow down the progression of age-related hearing loss. [Display omitted] • Repeated low-intensity noise exposure impairs suprathreshold hearing in the short term and accelerates age-related hearing loss in the long run. • Low-intensity noise may exert an additive effect on the development of age-related hearing loss via RAGE pathway. • Cochlear injury caused by repeated low-intensity noise is different from acute high-intensity noise, in which microcirculation is typically affected. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the molecular mechanisms of acute noise-induced hearing loss and recovery of steady-state noise-induced hearing loss using miniature pigs. We used miniature pigs exposed to white noise at 120 dB (A) as a model. Auditory brainstem response (ABR) measurements were made before noise exposure, 1 day and 7 days after noise exposure. Proteomic Isobaric Tags for Relative and Absolute Quantification (iTRAQ) was used to observe changes in proteins of the miniature pig inner ear following noise exposure. Western blot and immunofluorescence were performed for further quantitative and qualitative analysis of proteomic changes. The average ABR-click threshold of miniature pigs before noise exposure, 1 day and 7 days after noise exposure, were 39.4 dB SPL, 67.1 dB SPL, and 50.8 dB SPL, respectively. In total, 2,158 proteins were identified using iTRAQ. Both gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses showed that immune and metabolic pathways were prominently involved during the impairment stage of acute hearing loss. During the recovery stage of acute hearing loss, most differentially expressed proteins were related to cholesterol metabolism. Western blot and immunofluorescence showed accumulation of reactive oxygen species and nuclear translocation of NF-κB (p65) in the hair cells of miniature pig inner ears during the acute hearing loss stage after noise exposure. Nuclear translocation of NF-κB (p65) may be associated with overexpression of downstream inflammatory factors. Apolipoprotein (Apo) A1 and Apo E were significantly upregulated during the recovery stage of hearing loss and may be related to activation of cholesterol metabolic pathways. This is the first study to use proteomics analysis to analyze the molecular mechanisms of acute noise-induced hearing loss and its recovery in a large animal model (miniature pigs). Our results showed that activation of metabolic, inflammatory, and innate immunity pathways may be involved in acute noise-induced hearing loss, while cholesterol metabolic pathways may play an important role in recovery of hearing ability following noise-induced hearing loss. [ABSTRACT FROM AUTHOR]

Optimal stomatal regulation is important for plant adaptation to changing environmental conditions and for maintaining crop yield. The guard cell signal γ-aminobutyric acid (GABA) is produced from glutamate by glutamate decarboxylase (GAD) during a reaction that generates CO2 as a by-product. Here, we investigated a putative connection between GABA signalling and the more clearly defined CO2 signalling pathway in guard cells. The GABA-deficient mutant Arabidopsis lines gad2-1 , gad2-2 , and gad1/2/4/5 were examined for stomatal sensitivity to various CO2 concentrations. Our findings show a phenotypical discrepancy between the allelic mutant lines gad2-1 and gad2-2 —a weakened CO2 response in gad2-1 (GABI_474_E05) in contrast to a wild-type response in gad2-2 (SALK_028819) and gad1/2/4/5. Through transcriptomic and genomic investigation, we traced the response of gad2-1 to a deletion of full-length Mitogen-activated protein kinase 12 (MPK12) in the GABI-KAT line, thereafter renamed as gad2-1 *. Guard cell-specific complementation of MPK12 in gad2-1* restored the wild-type CO2 phenotype, which confirms the proposed importance of MPK12 in CO2 sensitivity. Additionally, we found that stomatal opening under low atmospheric CO2 occurs independently of the GABA-modulated opening channel ALUMINIUM-ACTIVATED MALATE TRANSPORTER 9 (ALMT9). Our results demonstrate that GABA has a role in modulating the rate of stomatal opening and closing, but not in response to CO2 per se. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A novel PC biosensor was developed for the sensitive detection of Ab. • The MPC characterized by the high ordered P(MMA-AM-GA-HP) microgels array. • The Ab was sensitively recognized and created optical signals using the biosensor. • The biosensor avoided the extra functionalization and the bulk hydrogel interference. Abstract In this study, a easy-to-prepare biosensor for the sensitive detection of the antibody (Ab) protein was developed using a novel microgel photonic crystal (MPC). The MPC was fabricated by the spin-coated self-assembly method with the monodisperse Ab-sensitive poly (methyl methacrylate-acrylamide-glutaraldehyde-hapten) (P(MMA-AM-GA-HP)) microgels. Morphology characterization showed that the P(MMA-AM-GA-HP) microgels possessed round shapes and the large specific surface area, and the formed MPC had a highly ordered three dimensional (3D) periodically-ordered structure with the desired structural color. The Ab-response event of the P(MMA-AM-GA-HP) microgels can be directly transferred into a readable optical signal through a change in Bragg reflection of the periodic structure of the MPC. With the sensory system, the sensitive and selective detection of Ab was achieved without labeling techniques and expensive instruments. Therefore, this easy and sensitive detection system has great potential for next generation of the bioassay platform for clinical diagnosis and other applications. [ABSTRACT FROM AUTHOR]

Background We examine whether working conditions in different types of charter schools lead to different levels of teacher turnover. We consider two types of teacher turnover behaviors. One is teacher migration, which refers to the transfer of teachers from one school to another. The other one is teacher attrition, which describes the phenomenon of teachers leaving the profession entirely. We distinguish among charter schools managed by for-profit education management organizations (EMOs), those managed by non-profit charter management organizations (CMOs), and regular charter schools. Method/analysis Our data come from the 2011–12 Schools and Staffing Survey (SASS). We estimate multi-level models with hierarchical linear modeling (HLM) software. Findings and implications We find that teachers in charter schools managed by EMOs and CMOs have higher levels of migration and attrition intention than do teachers in regular charter schools. Teachers, particularly in EMO-managed charter schools, are more likely to consider moving to another school or to leave the teaching profession. Our analyses suggest that the increased migration and attrition among teachers in MO-managed charter schools can be partially explained by the differences in working conditions, such as the degree of administrative support in the school, the degrees of classroom control and school-wide influence of teachers, salary, opportunities of professional development, the quality of the student body, and the degree of student misbehavior. [ABSTRACT FROM AUTHOR]

We examine whether working conditions in charter schools and traditional public schools lead to different levels of job satisfaction among teachers. We distinguish among charter schools managed by for-profit education management organizations (EMOs) and non-profit charter management organizations (CMOs) and stand-alone charter schools. We investigate our research question using data from the School and Staffing Survey. We find that teachers in charter schools are less satisfied with their jobs than teachers in traditional public schools. We also find that teachers in EMO-managed schools appear less satisfied than those in stand-alone charter schools. Our analyses suggest that lower salaries and limited union memberships help drive these lower levels of satisfaction, particularly among stand-alone charter schools and charter schools managed by EMOs. [ABSTRACT FROM AUTHOR]

A sensitive competitive inhibition enzyme-linked immunosorbent assay (CIELISA) for the detection of parathion has been developed. In this assay, a small molecule hapten II (O,O-diethyl O-4-aminophenyl phosphorothioate) was covalent linked to glutaric dialdehyde treated-microtiter plates. In addition, 4-(ethoxy(4-nitrophenoxy) phosphorothioylamino) butanoic acid-ovalbumin (hapten I-OVA) conjugate served as the coating antigen for comparison with directly hapten II covalent linked plates in the CIELISA format. The developed assay demonstrated highly sensitivity (IC was 0.08 ng mL) selectivity and stability. In samples analysis, the results of parathion detected by this assay were in accordance with which obtained by high-performance liquid chromatography. [ABSTRACT FROM AUTHOR]

A novel photonic crystal (PC) for the enrichment and detection of trace chloramphenicol (Cm) was constructed based on the combination of the imprinted crystalline colloidal array (ICCA) and the enrichment effect induced by wettability differences. The enrichment ICCA (E-ICCA) material had a highly ordered opal structure consisted of hydrophilic molecular imprinting polymer (MIP) spheres and the surrounding hydrophobic polydimethylsiloxane (PDMS) matrix, thus showing the desired structural color but also possessing the large hydrophilicity/hydrophobicity (HP) interaction area to enable efficient enrichment of the target Cm molecules from a highly dilute solution to the MIP sphere surface. The sensitive Cm recognition of MIP spheres finally caused the reduced reflection intensity and a red shift of the material due to changes of the periodic structure. Using this sensing platform, the highly sensitive detection of Cm (as low as 1.5×10 −9 M) with high selectivity was achieved without using label techniques and expensive detection instruments. Furthermore, the developed method successfully used to screen Cm in drinking water samples. Therefore, this approach is extensible to the construction of many sensor systems for the sensitive detection of drugs, diseases, and pollutions of food and the environment. [ABSTRACT FROM AUTHOR]

A new enzyme-linked immunosorbent assay (ELISA) for atrazine was developed based on covalent bonding of the small molecule hapten, 2-mercaptopropionic acid-4-ethylamino-6-isopropylamino-1,3,5-triazine (MPA–atrazine), to urea-glutaraldehyde (UGA)-treated microtiter plates. In this assay, the microtiter plate surface was treated with the UGA network to both introduce amino groups, which were used to cross-link with the hapten carboxylate groups, and efficiently prevent non-specific adsorption of antibodies, which successfully eliminated the time-consuming routine blocking step. Compared with HNO 3 -H 2 SO 4 -APTES-hapten coated ELISA (modified with a HNO 3 -H 2 SO 4 -APTES mixture and covalent-linked hapten) and conventional ELISA (coated with hapten–carrier protein conjugates), the novel ELISA format increased the sensitivity by approximately 3.5-fold and 7.5-fold, respectively, and saved 2.5 h and 34 h of coating hapten time, respectively. The method's 50% inhibition concentration for atrazine was 5.54 ng mL − 1 , and the limit of detection was 0.16 ng mL − 1 after optimization of reaction conditions. Furthermore, the ELISA was adapted for analysis of atrazine in corn, rice, and water samples, demonstrating recoveries of 90%–108%. Thus, the assay provides a convenient alternative to conventional, laborious immunoassays for routine supervision of residue detection in food and the environment. [ABSTRACT FROM AUTHOR]

Objective. We examine how the working conditions in charter schools managed by management organizations (MOs) compare to those that teachers experience in stand-alone charter schools. We consider differences in the degree of autonomy within the schools, professional development, levels of administrative support, support from teachers and parents, and teachers' work hours and levels of compensation. Methods. Our data come from the 2011-2012 Schools and Staffing Survey (SASS). We estimate multilevel models using the hierarchical linear modeling software, while controlling for the composition of the teachers and school context. Results. We find that teachers in charter schools managed by education MOs have lower levels of autonomy than teachers in other charter schools. They also receive lower levels of compensation than other charter school teachers. Conclusion. ForprofitMOs appear to constrain the charter schools that they manage, limiting the ability of teachers to determine how students are taught within their classrooms. [ABSTRACT FROM AUTHOR]

A novel opal closest-packing (OCP) photonic crystal (PC) was prepared by the introduction of molecular imprinting technique into the OCP PC. This molecular imprinted (MI)-OCP PC was fabricated via a vertical convective self-assembly method using 17β-estradiol (E2) as template molecules for monitoring E2 in aqueous solution. Morphology characterization showed that the MI-OCP PC possessed a highly ordered three-dimensional (3D) periodically-ordered structure, showing the desired structural color. The proposed PC material displayed a reduced reflection intensity when detecting E2 in water environment, because the molecular imprinting recognition events make the optical characteristics of PC change. The Bragg diffraction intensity decreased by 19.864 a.u. with the increase of E2 concentration from 1.5 ng mL −1 to 364.5 ng mL −1 within 6 min, whereas there were no obvious peak intensity changes for estriol, estrone, cholesterol, testosterone and diethylstilbestrol, indicating that the MI-OCP PC had selective and rapid response for E2 molecules. The adsorption results showed that the OCP structure and homogeneous layers were created in the MI-OCP PC with higher adsorption capacity. Thus, it was learned the MI-OCP PC is a simple prepared, sensitive, selective, and easy operative material, which shows promising use in routine supervision for residue detection in food and environment. [ABSTRACT FROM AUTHOR]

Based on a combination of the molecular imprinting technique and polymerized crystalline colloidal array, we have developed an imprinted crystalline colloidal array (ICCA) chemical-sensing material for the real-time and label-free detection of diethylstilbestrol (DES) in aqueous solution. This novel sensing material was prepared by a noncovalent and self-assembly approach using liquid monodispersed DES-imprinted colloidal spheres and was characterized by a three-dimensional (3D) ordered opal structure in which numerous nanocavities were derived from DES imprinting. Thus, the inherent high affinity of the nanocavities allowed ICCA to recognize DES with high specificity, and changes of the ordered periodic structure enabled ICCA to transfer the recognition events into readable optical signals (label-free). Owing to the special opal structure and without interference from the bulk hydrogel film, the ICCA enabled the rapid and sensitive detection of the target analyte. The understanding of the recognizing response has also been advanced by using molecular modeling software to compute rational interaction between the template molecules and the function monomers. After careful optimization of the assay conditions, the ICCA could decrease its diffraction intensity within just 7 min according to the DES concentration from 2 ng mL−1 to 8.192 μg mL−1, whereas there were no obvious diffraction intensity changes for the DES analogues. The adsorption results showed that the homogenous structure and large surface area of ICCA could improve its adsorption capacity. Therefore, such a sensing material with high selectivity, high sensitivity, high stability, and easy operation might offer an attractive alternative for establishing optical sensors for the rapid real-time monitoring of different residues in food and the environment. [ABSTRACT FROM AUTHOR]

MAXI J1348−630 is a low-mass X-ray black hole binary located in the Galaxy and undergone the X-ray outburst in 2019. We analysed the observation data in very soft state during the outburst between MJD 58588 and MJD 58596 based on the Insight - HXMT observations from 2 to 20 keV via the continuum fitting method to measure the spin of the stellar-mass black hole in MAXI J1348−630. The inner disc temperature and the apparent inner disc radius were found to be |$0.47\pm 0.01 \rm \,\rm \,keV$| and 5.33 ± 0.10  Rg from the observation data modeled by the multicolour disc blackbody model. Assuming the distance of the source |$D\sim 3.4 \rm \,kpc$| , the mass of the black hole M ∼ 11 M⊙, and the inclination of the system i ∼ 29.2°, the spin is determined to be a ⋆ = 0.41 ± 0.03 for fixing hardening factor at 1.6 and |$n_{H}=8.6\times 10^{21} \rm cm^{-2}$|. Besides, considering the uncertainty of the parameters D, M, i of this system, with the Monte Carlo analysis, we still confirm the moderate spin of the black hole as |$a_{\star }=0.42^{+0.13}_{-0.50}$|. Some spectral parameters (e.g. column density and hardening factor) which could affect the measurements of the BH spin are also briefly discussed. [ABSTRACT FROM AUTHOR]

Organic-inorganic donor-acceptor interfaces are gaining growing attention in organic photovoltaic applications as each component of the interface offers unique attributes. Here we use hybrid density functional theory to examine the electronic structure of sexithiophene/ZnO interfaces. We find that interfacial molecular orientations strongly influence the adsorption energy, the energy level alignment, and the open-circuit voltage. We attribute the orientation dependence to the varied strength of electronic coupling between the molecule and the substrate. Our study suggests that photovoltaic performance can be optimized by controlling the interfacial design of molecular orientations. [ABSTRACT FROM AUTHOR]

Abstract: A novel enzyme liked immunosorbent assay (ELISA) was developed for the detection of chloramphenicol (CAP). In this assay, the small molecular hapten (Hap) was directly coated on the surface of microtiter plates and biotin–streptavidin system (BSAS) was employed to improve the sensitivity of immunoassay (BSAS-direct Hap coated ELISA). The surface of microtiter plates was treated with glutaraldehyde (GA) polymer network to introduce aldehyde group, which was used to cross-link with amino group of CAP. Compared with conventional ELISA (the plates were coated with Hap–carrier protein conjugates), the modified plates presented significantly high antibody and antigen (Ab–Ag) affinity and showed excellent stability. And then the biotinylated monoclonal antibody (mAb) and HRP-labeled streptavidin were employed in this assay for amplification of signals. The sensitivity of BSAS-direct Hap coated ELISA was increased by approximately 20-folds and the stability was also improved greatly compared to conventional ELISA. Its 50% inhibition concentration (IC50) for CAP was 10.5ngmL−1 and the limit of detection (LOD) was 0.2ngmL−1 after optimization of reaction conditions. To our knowledge, this was one of the most sensitive immunoassay for CAP yet reported. In sample analysis, the results of CAP detected by this assay were in accordance with which obtained by conventional ELISA and high performance liquid chromatography (HPLC). Therefore, it is an attractive alternative compared to conventional immunoassays in routine supervision for residue detection in food and environment. [ABSTRACT FROM AUTHOR]

• Zn and Ru doping decreases the coercivity in SrFe 12-2 x Zn x Ru x O 19. • In x = 0.5, under 1.7–4.8 mm, the absorption bandwidth (RL < −10 dB) is broader than 13.7 GHz. • For RL < −10 dB, the impedance matching of 0.5–1.5 is acceptable and the attenuation is higher than 75. The magnetic resonance frequency of SrFe 12 O 19 hexaferrites is above 40 GHz due to a very high magnetic anisotropy. Therefore, they are not suitable as absorbing materials in the frequency range of 1–18 GHz. Doping with Zn and Ru (SrFe 12-2 x Zn x Ru x O 19) decreases the magnetic anisotropy and can bring the resonance frequency below 18 GHz improving the microwave absorption in lower frequency band. Both the imaginary and real parts of the permittivity increase and the magnetic loss tangent has a wide peak for x ≥ 0.3, which is twice the dielectric loss tangent. Both of them contribute to the microwave absorption. For this level of doping, the microwave absorption is significant in a wide frequency range. For x = 0.5 and the sample layer of 1.7–4.8 mm thick, the absorption bandwidth (RL < −10 dB) is from 4.3 GHz to 18 GHz. For a single-layer of 1.9 mm, the absorption bandwidth is from 10.1 to 18 GHz. The broad absorption is due to tunable magnetic anisotropic field by the Zn and Ru doping. The detailed analysis also shows that the impedance matching plays an important role in improving the absorbing band. [ABSTRACT FROM AUTHOR]

We report on the structural and electronic properties of the interface between the multiferroic oxide YMnO3 and semiconductor GaN studied with the Hubbard-corrected local-spin-density approximation to density-functional theory. We find that the band offsets at the interface between antiferromagnetically ordered YMnO3 and GaN are different for spin-up and spin-down states. This behavior is due to the spin splitting of the valence band induced by the interface. The energy barrier depends on the relative orientation of the electric polarization with respect to the polarization direction of the GaN substrate suggesting an opportunity to create magnetic tunnel junctions in this material system. [ABSTRACT FROM AUTHOR]

Curcumin (Cur) is a naturally hydrophobic polyphenol with potential pharmacological properties. However, the poor aqueous solubility and low bioavailability of curcumin limits its ocular administration. Thus, the aim of this study was to prepare a mixed micelle in situ gelling system of curcumin (Cur-MM-ISG) for ophthalmic drug delivery. The curcumin mixed micelles (Cur-MMs) were prepared via the solvent evaporation method, after which they were incorporated into gellan gum gels. Characterization tests showed that Cur-MMs were small in size and spherical in shape, with a low critical micelle concentration. Compared with free curcumin, Cur-MMs improved the solubility and stability of curcumin significantly. The ex vivo penetration study revealed that Cur-MMs could penetrate the rabbit cornea more efficiently than the free curcumin. After dispersing the micelles in the gellan gum solution at a ratio of 1:1 (v/v), a transparent Cur-MM-ISG with the characteristics of a pseudoplastic fluid was formed. No obvious irritations were observed in the rabbit eyes after ocular instillation of Cur-MM-ISG. Moreover, Cur-MM-ISG showed a longer retention time on the corneal surface when compared to Cur-MMs using the fluorescein sodium labeling method. These findings indicate that biocompatible Cur-MM-ISG has great potential in ophthalmic drug therapy. [ABSTRACT FROM AUTHOR]

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5–KRP1–STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency. Abscisic acid (ABA) signaling regulates reproductive development under water-deficient conditions in Arabidopsis via ABA- and meristem-related transcription factors and a cyclin-dependent kinase. [ABSTRACT FROM AUTHOR]

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human β-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells. [ABSTRACT FROM AUTHOR]

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1–GRF5–phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation. This study reveals how sugar signaling under subterranean darkness is sensed, amplified, and relayed to determine skototophotomorphogenesis upon exposure to light irradiation. [ABSTRACT FROM AUTHOR]

We analyse a Neutron Star Interior Composition Explorer observation of the black hole X-ray binary MAXI J1820+070 during a transition from type-C to type-B quasi-periodic oscillations (QPOs). We find that below ∼2 keV, for the type-B QPOs the rms amplitude is lower and the magnitude of the phase lags is larger than for the type-C QPOs. Above that energy, the rms and phase-lag spectra of the type-B and type-C QPOs are consistent with being the same. We perform a joint fit of the time-averaged spectra of the source, and the rms and phase-lag spectra of the QPOs with the time-dependent Comptonization model vkompth to study the geometry of the corona during the transition. We find that the data can be well fitted with a model consisting of a small and a large corona that are physically connected. The sizes of the small and large coronae increase gradually during the type-C QPO phase whereas they decrease abruptly at the transition to type-B QPO. At the same time, the inner radius of the disc moves inward at the QPO transition. Combined with simultaneous radio observations showing that discrete jet ejections happen around the time of the QPO transition, we propose that a corona that expands horizontally during the type-C QPO phase, from ∼104 km (⁠|$\sim 800\, R_{\rm g}$|⁠) to 105 km (⁠|$\sim 8000\, R_{\rm g}$|⁠) overlying the accretion disc, transforms into a vertical jet-like corona extending over ∼104 km (⁠|$\sim 800\, R_{\rm g}$|⁠) during the type-B QPO phase. [ABSTRACT FROM AUTHOR]

Background: Iatrogenic facial nerve injury is one of the severest complications of middle ear surgery, this study aims to evaluate surgical management and prognosis in the era of improved surgical instruments. Methods: Patients suffered from facial nerve paralysis after middle ear surgery between January 2000 and December 2019 were retrospectively collected. Demographic characters, primary disease and surgery, details of revision surgery were analyzed. Results: Forty-five patients were collected, of whom 8 were injured at our center and 37 were transferred. For 8 patients injured at our center, seven (87.5%) ranked House-Brackmann (H-B) grade V and one (12.5%) ranked H-B VI before revision surgery; postoperatively, two (25.0%) patients recovered to H-B grade I, four (50.0%) recovered to H-B II, and the other two (25.0%) recovered to H-B III. For 37 patients transferred, thirteen (35.1%) ranked H-B grade V and 24 (64.9%) ranked H-B VI preoperatively, final postoperative grade ranked from H-B grade I to grade V, with H-B I 6 (16.2%) cases, H-B II 6 (16.2%) cases, H-B III 18 (48.6%) cases, H-B IV 5 (13.5%) cases and H-B V 2 (5.4%) cases. The most vulnerable site was tympanic segment (5, 62.5% and 27, 73.0% respectively). Twenty-one (46.7%) patients suffered from mild injury and 24 (53.3%) suffered from partial or complete nerve transection. For surgical management, twenty-one (46.7%) patients received decompression, nineteen (42.2%) received graft and 5 (11.1%) received anastomosis. Those decompressed within 2 months after paralysis had higher possibility of H-B grade I or II recovery (P = 0.026), those received graft within 6 months were more likely to get H-B grade III recovery (P = 0.041), and for patients underwent anastomosis within 6 months, all recovered to H-B grade III. Conclusions: Tympanic segment is the vulnerable site. If facial nerve paralysis happens, high-resolution computed tomography could help identify the injured site. Timely treatment is important, decompression within 2 months after paralysis, graft and anastomosis within 6 months lead to better recovery. [ABSTRACT FROM AUTHOR]

Post-stroke depression (PSD), the most frequent psychiatric complication following stroke, could have a negative impact on the recuperation of stroke patients. Hyperhomocysteinemia (HHCY) has been reported to be a modifiable risk factor of stroke. The study tries to explore the effect of HHCY on PSD and the role of N-methyl-d-aspartate receptors (NMDARs)-mediated synaptic alterations. Forty-five adult male Sprague–Dawley rats were randomly allocated into five groups: sham operation group, middle cerebral artery occlusion group (MCAO), HCY-treated MCAO group HCY and MK-801 co-treated MCAO group and MK-801-treated MCAO group. 1.6 mg/kg/d D, L-HCY was administered by tail vein injection for 28 d prior to SHAM or MCAO operationand up to 14 d after surgery. The MK-801 (3 mg/kg) was administered by intraperitoneal injection 15 min prior to MCAO operation. HCY treatment aggravated depressive-like disorders of post-stroke rats by the open field test and sucrose preference test. Further, HCY significantly decreased central monoamines levels in the MCAO rats by HPLC. The transmission electron microscopy results showed that the number of synapses and the area of postsynaptic density decreased in the hippocampus of the HCY-treated MCAO rats. Additionally, HCY augmented ischemia-induced up-regulation of NMDARs, decreased the levels of synaptic structure-related marker PSD-95and the synaptic transmission-associated synaptic proteins (VGLUT1, SNAP-25 and Complexin Ι/ΙΙ). These effects of HCY were partly reversed by the NMDA antagonist MK-801. The current study suggested that NMDARs-mediated synaptic plasticity may be involved in the adverse effect of HCY on PSD. [ABSTRACT FROM AUTHOR]

A novel biomimetic molecular imprinted polymer chip with fluorescence (FL) and structural (STR) states, inspired by color patterns of chameleon skin, is fabricated for detecting diethylstilbestrol (DES). The chip features a regularly structured, non-closed-packed (NCP) colloidal photonic crystal (CPC) lattice made monodisperse MIP spheres containing fluorescence poly ionic liquid (FPIL) pigments. The FL color originates from FPIL pigments and is further enhanced by the Purcell effect, while the STR color results from the periodic arrangement of the NCP CPC structure. Upon the addition of DES, the molecular imprinting recognition events of the chip induce bicolored responses. These color variations are observable to the naked eye. Based on a self-correction function of colors, the chip showed direct, sensitive (as low as 0.5 ng/mL), rapid (6 min), selective and stable detection of DES. In sample analysis, the results of DES detected by the chip were by which obtained by the HPLC-MS/MS method. [Display omitted] • Inspired chameleon skin, the novel biomimetic MIP chip was developed. • The chip had a NCP CPC structure with FPIL pigments. • The chip can detect DES by FL and STR responses. • Color changes of the chip can be observed by the naked eye. • The chip had higher sensitive, rapid, selective and stable detection of DES. [ABSTRACT FROM AUTHOR]

[Display omitted] • Inspired by the back of the desert beetle, a novel biomimetic chip was developed. • The chip featured a periodic array with AuNPs semi-embedded on PMMA spheres. • The chip had functions of hydrophilic-hydrophobic enrichment and LSPR enhancement. • The chip had sensitive, rapid, selective CP detection and good recovery. • Color changes on the chip can be seen with the naked eye during the detection. Inspired by the desert beetle, a novel biomimetic chip was developed to detect chloramphenicol (CP). The chip was characterized by a periodic array in which hydrophobic Au nanoparticles (AuNPs) were semi-embedded on hydrophilic polymethyl methacrylate (PMMA) spheres. Among them, the AuNPs exhibited both a localized surface plasmon resonance effect to amplify the reflected signal and a synergistic effect with PMMA spheres to create a significant hydrophilic-hydrophobic interface, which facilitated the enrichment of target CP molecules and improved sensitivity. After optimization, the chip showed direct, ultrasensitive (as low as 0.2 ng/mL), fast (5 min), and selective detection of CP with a wide concentration range extending from 0.2 ng/mL to 1000 ng/mL. During detection, color changes of the chip were observed by naked eyes without any color display equipment. The recovery of CP was between 94.65 % and 108.70 % in chicken and milk samples. [ABSTRACT FROM AUTHOR]

Xiaoer Huanglong Granule is the only Chinese Patent Medicine widely used for treating attention deficit hyperactivity disorder. However, not much is known about the bioactive components and pharmacokinetics of Xiaoer Huanglong Granule even after it was successfully introduced into clinical use. This study analyzed the components in the medication and rat plasma after oral administration with the help of the UNIFI platform and Masslynx. A total of 119 and 37 components were detected in the medication and plasma, respectively, using an ultra‐performance liquid chromatography‐tandem mass spectrometer. We established a rapid and sensitive simultaneous determination of one triterpene saponin, three monoterpene glycosides, and three lignans in rat plasma by solid‐phase extraction. The determination was accomplished within 7.50 min via gradient elution. The values of the lower limit of quantitation were validated at 0.08 ng/ml for tenuifolin, 0.8 ng/ml for lactiflorin, 1.828 ng/ml for albiflorin, 2 ng/ml for paeoniflorin, gomisin B, and gomisin D, 10 ng/ml for schisandrin. The results from validations of other methods were all acceptable (relative standard deviation ≤ 14.94%). This is the first report on the identification and pharmacokinetics studies of components in Xiaoer Huanglong Granule. Moreover, the pharmacokinetic behavior of lactiflorin was studied for the first time. [ABSTRACT FROM AUTHOR]

We propose a new substitutional impurity complex in diamond composed of a lithium atom that is tetrahedrally coordinated by four nitrogen atoms (LiN4). Density functional calculations are consistent with the hydrogenic impurity model, both supporting the prediction that this complex is a shallow donor with an activation energy of 0.27 ± 0.06 eV. Three paths to the experimental realization of the LiN4 complex in diamond are proposed and theoretically analyzed. [ABSTRACT FROM AUTHOR]

Abstract: A new opal photonic crystal sensor (OPCS) that allows the detection of label-free bisphenol A (BPA) is proposed in the current study. The concept of developing photonic-based sensors using combined photonic crystal technology and molecular imprinting techniques is introduced. First batches of the BPA-imprinted monodisperse PMMA spheres with a diameter of 220 (±5)nm were prepared based on the suspension polymerization, so numerous nanocavities derived from BPA imprinting were distributed in the PMMA spheres. The liquid monodisperse microspheres were made into a polymerized crystalline colloidal array (PCCA) opal photonic crystal sensor. The inherent high affinity of the nanocavities distributed in the sphere allows OPCS to recognize BPA specifically. The sensor is characterized by a 3D-ordered interconnected lattice structure. Between the monospheres, there are well-arranged pores allowing the target molecules to embed and transport. As a result, changes in diffraction intensity which are related to BPA concentrations can be observed with the sensor. The detection ranges of OPCS are at 1ng/ml–1μg/ml level. The new sensory system has high selectivity of the target molecules in their natural forms, is easy to use, and costs low. Overall, the proposed approach provides a versatile analytical system for the establishment of a new sensor for the detection of endocrine-disrupting chemicals. [Copyright &y& Elsevier]

[Display omitted] • A reflection-fluorescence ratios probe was developed for the ratiometric detection of glucose. • The probe had a highly ordered periodic structure emitting both of reflection and fluorescence. • With the increase of glucose concentration, the reflection and fluorescence of the probe were attenuated simultaneously. • The probe showed simple operation, great stability and reusability, and was successfully used in the real blood serum samples. Herein, an optical ratios probe with reflection (RE) and fluorescence (FL), named as RE-FL ratios probe, has been developed for the ratiometric detection of glucose (GLU). This probe was prepared through self-assembling monodisperse colloids into opal photonic crystal and immobilizing fluorescence imidazolium ionic liquids as molecular recognition elements. So there was a periodic three-dimensional face-centered cubic arrayed structure and emissions of strong RE and FL in the probe, which allowed dual optical detection of the target analyte. From the results, it was learned that RE and FL emissions of RE-FL ratios probe were decreased when an increase of GLU concentration, and the resulting ratiometric optical changes can be quantitatively correlated to GLU concentration from 1 to 64 mM. The detection of probe was characterized by simple operation, stability, reusability and glucose oxidase independence. Furthermore, the probe successfully used to detect GLU in the real serum sample and showed great stability compared with the only FL pattern. Different types of appropriated recognition elements are expected to be introduced into opal photonic crystals to construct variety ratiometric optical probes in the wide of applications. [ABSTRACT FROM AUTHOR]

Can damaged or degenerated vessels be regenerated in the ear? The question is clinically important, as disruption of cochlear blood flow is seen in a wide variety of hearing disorders, including in loud sound-induced hearing loss (endothelial injury), ageing-related hearing loss (lost vascular density), and genetic hearing loss (e.g., Norrie disease: strial avascularization). Progression in cochlear blood flow (CBF) pathology can parallel progression in hair cell and hearing loss. However, neither new vessel growth in the ear, nor the role of angiogenesis in hearing, have been investigated. In this study, we used an established ex vivo tissue explant model in conjunction with a matrigel matrix model to demonstrate for the first time that new vessels can be generated by activating a vascular endothelial growth factor (VEGF-A) signal. Most intriguingly, we found that the pattern of the newly formed vessels resembles the natural 'mesh pattern' of in situ strial vessels, with both lumen and expression of tight junctions. Sphigosine-1-phosphate (S1P) in synergy with VEGF-A control new vessel size and growth. Using transgenic neural/glial antigen 2 (NG2) fluorescent reporter mice, we have furthermore discovered that the progenitors of " de novo " strial vessels are NG2-derived cells. Taken together, our data demonstrates that damaged strial microvessels can be regenerated by reprogramming NG2-derived angiogenic cells. Restoration of the functional vasculature may be critical for recovery of vascular dysfunction related hearing loss. • Vascular regeneration ex vivo from adult mouse stria vascularis. • Vascular regeneration signaled by VEGF-A 165. • NG2-derived mural cells as tip cells leading the angiogenesis. [ABSTRACT FROM AUTHOR]

Rhizoma Paridis, a traditional Chinese medicine, has shown promise in cancer prevention and therapy. Polyphyllin II is one of the most significant saponins in Rhizoma Paridis and it has toxic effects on kinds of cancer cells. However, our results in this study proved that the polyphyllin II has hepatotoxicity in vitro through caspases activation and cell‐cycle arrest. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide results indicated polyphyllin II inhibited proliferation, induced apoptosis in HepaRG cells and HL‐7702 cells and showed a concentration and time‐dependent. Then, we selected the innovative cell model‐HepaRG cells to explore the mechanism of hepatotoxicity. Our data showed the reactive oxygen species (ROS) increased and the mitochondrial membrane potential decreased in HepaRG cells after administration of polyphyllin II. Besides, with the increase of concentration, the release of lactate dehydrogenase increased and the S phase of the cell cycle was arrested. Nevertheless, when pretreatment with antioxidant N‐acetylcysteine, apoptotic cells decreased significantly, inhibited the production of ROS and improved the decrease of membrane potential in HepaRG cells. Moreover, polyphyllin II treatment increased levels of Fas, Bax, cytochrome c, activated caspase‐3, ‐8, ‐9, cleaved poly(ADP‐ribose) polymerase and decreased Bcl‐2 expression levels. Finally, we identified two signal pathways of apoptosis induced by polyphyllin II including the death receptor pathway and the mitochondria pathway. This study confirmed the hepatotoxicity of the polyphyllin II in vitro, which has never been discovered and gave a wake‐up call for the clinical application of Rhizoma Paridis. This study confirmed the hepatotoxicity of the polyphyllin II in vitro, which has never been discovered and gave a wake‐up call for the clinical application of Rhizoma Paridis. Moreover, we identified two signaling pathways of apoptosis induced by polyphyllin II including death receptor pathway and the mitochondria pathway. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood.Methods: The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry.Results: Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment.Conclusions: STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke. [ABSTRACT FROM AUTHOR]

In this study, a homogeneous enzyme-free ratiometric (HOMO- EF-RA) immunoassay was developed for the sensitive detection of C-peptide. In the immunoassay, there have been a miscible detection system by mixing with the fluorescent quantum dots conjugated antigen (QD-Ag conjugates) and the dylight dye conjugated antibody (DL-Ab conjugates). When connecting between Ag-QD conjugate and Ab-DL conjugate by specific recognition, the system emitted fluorescence resonant energy transfer (FRET). The target C-peptide can inhibit the connection and FRET formation between QD-Ag conjugates and DL-Ab conjugates, thus changing the dual fluorescence. By measuring the ratio dual fluorescence changes of the system, the content of C-peptide was evaluated without any enzyme used and multiple incubation and washing steps. This immunoassay realized the highly sensitive (as low as 0.12 ng mL−1), selective and rapid (as less as 6 min) detection of C-peptide. Furthermore, the simple and convenient immunoassay was applied successfully to the determination of C-peptide in real serum samples. [Display omitted] • A homogeneous enzyme-free ratiometric immunoassay was developed for the detection of C-peptide. • The immunoassay was composed of a miscible detection system by mixing QD-Ag conjugates and DL-Ab conjugates. • The detection processes had the detection signals self-correction effect based on the dual-fluorescence-output. • With this immunoassay the highly sensitive, selective, rapid and stable detection of C-peptide was achieved. [ABSTRACT FROM AUTHOR]

Photocurrent generation in organic photovoltaics (OPVs) relies on the dissociation of excitons into free electrons and holes at donor/acceptor heterointerfaces. The low dielectric constant of organic semiconductors leads to strong Coulomb interactions between electron-hole pairs that should in principle oppose the generation of free charges. The exact mechanism by which electrons and holes overcome this Coulomb trapping is still unsolved, but increasing evidence points to the critical role of hot charge-transfer (CT) excitons in assisting this process. Here we provide a real-time view of hot CT exciton formation and relaxation using femtosecond nonlinear optical spectroscopies and non-adiabatic mixed quantum mechanics/molecular mechanics simulations in the phthalocyanine-fullerene model OPV system. For initial excitation on phthalocyanine, hot CT excitons are formed in 10?13?s, followed by relaxation to lower energies and shorter electron-hole distances on a 10?12?s timescale. This hot CT exciton cooling process and collapse of charge separation sets the fundamental time limit for competitive charge separation channels that lead to efficient photocurrent generation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A dual-QDs ratios fluorescent probe was fabricated for the detection of insulin. • The probe consisted of two colored GQD and SQD. • The ratios responses were correlated quantitatively to insulin concentration. • The sensitive, rapid response and stable detection of insulin was achieved. In this work, immune modified graphene quantum dot (GQD) and semiconductor quantum dot (SQD) with blue and red emission respectively were synthesized to assemble a dual-QDs ratios fluorescent probe, which could be efficient used for insulin determination. There may be the dynamic equilibrium of förster resonance energy transfer (FRET) and aggregation-induced emission (AIE) in the internal of the probe, thus emitted special dual fluorescent lights. However, this sate of probe was cleaved upon exposure to target insulin, resulting in changing of the dual fluorescent lights. The resulting ratios response can be correlated quantitatively to the concentration of insulin, and was found to have a detection limit (as low as 0.045 ng mL−1) and rapid response time (as short as 5 min). It has been preliminarily used for ratiometric sensing of insulin in biological samples and exhibited consistency of the insulin detected results and higher stability compared with conventional ELISA. Therefore, this sensitive, rapid and stable detection system has great potential for next generation of the bioassay platform for clinical diagnosis and other applications. [ABSTRACT FROM AUTHOR]

Ischemic stroke represents a major cause of mortality worldwide. An elevated level of homocysteine (Hcy) is recognized as a powerful risk factor of ischemic stroke. We previously reported that Hcy induces cytotoxicity and proliferation inhibition in neural stem cells (NSCs) derived from the neonatal rat hippocampus in vitro. However, the toxic potential of Hcy on NSCs and its underlying mechanisms are not entirely clear in ischemic brain. Since DNA methylation is critical for establishing the diverse cell fates in the central nervous system, we hypothesized that negative effect of Hcy (an intermediate in the one-carbon metabolism) on neurogenesis might be link to DNA methylation in ischemic stroke. In our study, the rats in Hcy intervention group were intraperitoneally injected with 2% Hcy solution (5 mL/kg/d) for 7 consecutive days before MCAO surgery until they were sacrificed. Our study indicated that Hcy inhibited NSCs self-renewal capacity, which was exhibited by lowering the number of DCX+/BrdU+ and NeuN+/BrdU+ in ischemic brain hippocampus. A reduction in the activity of the DNA methyltransferases (DNMTs), total methylation level and the number of 5mC+/NeuN+ and DCX+/5mC+ cells was observed in Hcy-treated ischemic brains. Additionally, Hcy also induced an increase in S-adenosylhomocysteine (SAH), and a decrease in the ratio of S-adenosylmethionine (SAM) to SAH. These results suggest that the alterations in DNA methylation may be an important mechanism by which Hcy inhibits neurogenesis after stroke. Hcy-induced DNA hypomethylation may be mainly caused by a reduction in the DNMT activity which is regulated by the concentrations of SAM and SAH. Maintaining normal DNA methylation by lowering Hcy level may possess therapeutic potential for promoting neurological recovery and reconstruction after stroke. • Homocysteine inhibits the proliferation and differentiation of hippocampal neural stem cells in ischemic brain. • Homocysteine resulted in DNA hypomethylation and ultimately inhibited the neurogenesis in ischemic brain. • Homocysteine-induced DNA hypomethylation may be caused by a reduction in the DNA methyltransferases activity. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common cancers with the highest morbidity and mortality. It is necessary to develop new anti-liver cancer drugs. Itraconazole is a popular systemic anti-fungal drug with a strong anti-tumor effect. However, so far, it is not clear whether itraconazole has specific anti-tumor effect on liver cancer. The purpose of this study was to investigate itraconazole resistant effect of liver cancer and to explore its potential anti-cancer mechanism. The effect of itraconazole on the proliferation of liver cancer cells was studied with MTT assay. Flow cytometry was used to determine the effect of itraconazole on apoptosis, cell cycle distribution, changes in intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). In addition, after DAPI staining, nuclear morphological changes were observed under the fluorescent microscope, and the release of lactate dehydrogenase (LDH) was measured using the microplate reader. Finally, the expressions of proteins related to the anti-tumor signaling pathway were determined by Western blotting. The results showed that itraconazole significantly inhibited the proliferation of HepG2 and Bel-7405 cells. In addition, the data showed that itraconazole induced apoptosis in HepG2 cells, increased the production of ROS, blocked cell cycle, and decreased MMP. Furthermore, itraconazole inhibited HCC cell growth and promoted apoptosis through the Hh, Wnt/catenin, AKT/mTOR/S6K, ROS and death receptor pathways. Finally, we come to the conclusion that itraconazole exerts anti-liver cancer effect, and has potential for use as a new drug for liver cancer in clinic. [ABSTRACT FROM AUTHOR]

Rhizoma paridis is a popularly-used Chinese medicine in clinics, based on the pharmacodynamic properties of its saponin components. The four main saponins in Rhizoma paridis are designated saponins I, II, VI, and VII. At present, much attention is focused on the anticancer effect of Rhizoma paridis which is manifested in its cytotoxicity to various cancer cells. The purpose of this study was to investigate the hepatocellular toxicities of the four saponins in Rhizoma paridis and the relative intensities of their cytotoxic effects. It was found that the four saponins were cytotoxic to two types of hepatocytes-HL-7702 and HepaRG cells. The cytotoxicities of the four saponins to the two cell models were compared. One of the most cytotoxic saponins was Rhizoma paridis saponin I (PSI). This was used to determine the mechanism of hepatocellular toxicity. Results from MTT assays demonstrated that the four saponins induced apoptosis of the two hepatocyte models in a dose-dependent and time-dependent manner. In addition, fluorescent 4′,6-diamidino-2-phenylindole (DAPI) staining was used to observe the morphological changes of HepaRG cells after saponin administration. Further, as the concentration increased, PSI-induced lactate dehydrogenase (LDH) release from HepaRG cells increased gradually. In addition, PSI enhanced the levels of reactive oxygen species (ROS) and blocked the S and G2 phases of the cell cycle in HepaRG cells. A western blot indicated that PSI upregulated the protein expression levels of p53, p21, and Fas. Furthermore, the PSI-induced changes in the p53 protein increased the Bax/bcl-2 ratio, resulting in enhancement of the release of mitochondrial cytochrome c, activation of caspases-3, -8, and -9, poly-ADP ribose polymerase (PARP), and ultimately apoptosis. Increased Fas protein activated caspase-8, which led to the activation of caspase-3 and its downstream PARP protein, resulting in cell apoptosis. These results indicate that PSI induced apoptosis in HepaRG cells through activation of ROS and death receptor pathways. The results obtained in this study suggest that the hepatocellular toxicity of saponins in Rhizoma paridis should be considered during the clinical application of this drug. In addition, they provide a reference for future anti-cancer studies on Rhizoma paridis. [ABSTRACT FROM AUTHOR]

Sustained-release preparation is a hot spot in antitumor drug research, where the first task is to select suitable drug carriers. Research has revealed that carboxylic acid iron metal–organic frameworks (MOFs), constructed from iron (Fe) ions and terephthalic acid, are nontoxic and biocompatible. Due to the breathing effect, the skeleton of this mesoporous material is flexible and can reversibly adapt its pore size through drug adsorption. Therefore, we chose one kind of Fe-MOF, MIL-53(Fe), as a carrier for the anticancer drug oridonin (Ori). In this work, we report the design and synthesis of MIL-53(Fe) and explore its ability as a transport vehicle to deliver Ori. MIL-53(Fe) is characterized by scanning electron microscopy and X-ray powder diffraction. A loading capacity of 56.25 wt % was measured by high performance liquid chromatography. This carrier was safe and nontoxic (cell viability > 95.27%), depending on the results of 3-(4,5-dimethylthiazol-2-yl)--2,5-diphenyltetrazolium bromide assays, lactate dehydrogenase assays, and Annexin V-fluoresce isothiocyanate/propidium iodide double-staining assays. After loading the drug, the structure of the MIL-53(Fe) was not destroyed, and Ori was amorphous in MIL-53(Fe). Based on an analysis of the Ori release profile, results suggest that it lasts for more than seven days in vitro. The cumulative release rate of Ori at the seventh day was about 82.23% and 91.75% in phosphate buffer saline solution at 37 °C under pH 7.2 and pH 5.5, respectively. HepG2 cells were chosen to study the cytotoxicity of Ori@MIL-53(Fe), and the results show that the anticancer ratio of Ori@MIL-53(Fe) system reaches 90.62%. Thus, MIL-53 can be used as a carrier for anticancer drugs and Ori@MIL-53(Fe) is a promising sustained-release drug delivery system for the cancer therapy. [ABSTRACT FROM AUTHOR]

Polyphyllin VI, which is an active saponin, is mainly isolated from traditional medicinal plant Paris polyphylla, which causes liver damage in rats. In the present study, we aimed to explore the potential cytotoxicity of polyphyllin VI on the growth of HepaRG cells and to determine the molecular mechanism. The results revealed that polyphyllin VI changed cell morphology and induced apoptosis in HepaRG cells. Flow cytometric assay displayed that polyphyllin VI promoted the generation of reactive oxygen species (ROS), depolarized the mitochondrial membrane potential (MMP), and induced S phase cell cycle arrest by decreasing the expression of cyclin A2 and CDK2, while significantly increasing the expression of p21 protein. Polyphyllin VI induced the release of cytochrome c from the mitochondria to the cytosol and activated Fas, caspase-3, -8, -9, and PARP proteins. Pretreatment with NAC and Z-VAD-FMK (ROS scavenger and caspase inhibitor, respectively) on HepaRG cells increased the percentage of viable cells, which indicated that polyphyllin VI induced cell apoptosis through mitochondrial pathway by the generation of ROS and Fas death-dependent pathway. All of the effects are in dose- and time-dependent manners. Taken together, these findings emphasize the necessity of risk assessment to polyphyllin VI and offer an insight into polyphyllin VI-induced apoptosis of HepaRG cells. [ABSTRACT FROM AUTHOR]

Heterophyllin B (HB), an active cyclic peptide, is a compound existing in the ethyl acetate extract of Pseudostellaria heterophylla (Miq.) Pax and exhibited the activity of inhibiting the production of NO and cytokines, such as IL-1β and IL-6, in LPS-stimulated RAW 264.7 macrophages. In addition, HB suppressed the production of ROS and the apoptosis induced by LPS in RAW 264.7 macrophages. The underlying mechanism was investigated in the LPS-induced RAW 264.7 cells. The results showed that HB decreased the level of IL-1β and IL-6 expression by qRT-PCR analysis. HB up-regulated the relative ratio of p-AKT/AKT and p-PI3K/PI3K as indicated by western blot analysis. In summary, HB inhibited the LPS-induced inflammation and apoptosis through the PI3K/Akt signaling pathways and represented a potential therapeutic target for treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]