Biexcitons-plasmon coupling of Ag@Au hollow nanocube/MoS2 heterostructures based on scattering spectra.

The strong interaction between light and matter is one of the current research hotspots in the field of nanophotonics, and provides a suitable platform for fundamental physics research such as on nanolasers, high-precision sensing in biology, quantum communication and quantum computing. In this study, double Rabi splitting was achieved in a composite structure monolayer MoS2 and a single Ag@Au hollow nanocube (HNC) in room temperature mainly due to the two excitons in monolayer MoS2. Moreover, the tuning of the plasmon resonance peak was realized in the scattering spectrum by adjusting the thickness of the shell to ensure it matches the energy of the two excitons. Two distinct anticrossings are observed at both excitons resonances, and large double Rabi splittings (90 meV and 120 meV) are obtained successfully. The finite-difference time domain (FDTD) method was also used to simulate the scattering spectra of the nanostructures, and the simulation results were in good agreement with the experimental results. Additionally, the local electromagnetic field ability of the Ag@Au hollow HNC was proved to be stronger by calculating and comparing the mode volume of different nanoparticles. Our findings provides a good platform for the realization of strong multi-mode coupling and open up a new way to construct nanoscale photonic devices.

Programmed necrosis: backup to and competitor with apoptosis in the immune system.

Programmed cell death is essential for the development and maintenance of the immune system and its responses to exogenous and endogenous stimuli. Studies have demonstrated that in addition to caspase-dependent apoptosis, necrosis dependent on the kinases RIP1 and RIP3 (also called necroptosis) is a major programmed cell-death pathway in development and immunity. These two programmed cell-death pathways may suppress each other, and necroptosis also serves as an alternative when caspase-dependent apoptosis is inhibited or absent. Here we summarize recent advancements that have identified the molecular mechanisms that underlie necroptosis and explore the mechanisms that regulate the interplay between apoptosis and necroptosis.

Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia.

Hair cells of the inner ear are not normally replaced during an animal's life, and must continually renew components of their various organelles. Among these are the stereocilia, each with a core of several hundred actin filaments that arise from their apical surfaces and that bear the mechanotransduction apparatus at their tips. Actin turnover in stereocilia has previously been studied by transfecting neonatal rat hair cells in culture with a ß-actin-GFP fusion, and evidence was found that actin is replaced, from the top down, in 2-3 days. Overexpression of the actin-binding protein espin causes elongation of stereocilia within 12-24 hours, also suggesting rapid regulation of stereocilia lengths. Similarly, the mechanosensory 'tip links' are replaced in 5-10 hours after cleavage in chicken and mammalian hair cells. In contrast, turnover in chick stereocilia in vivo is much slower. It might be that only certain components of stereocilia turn over quickly, that rapid turnover occurs only in neonatal animals, only in culture, or only in response to a challenge like breakage or actin overexpression. Here we quantify protein turnover by feeding animals with a (15)N-labelled precursor amino acid and using multi-isotope imaging mass spectrometry to measure appearance of new protein. Surprisingly, in adult frogs and mice and in neonatal mice, in vivo and in vitro, the stereocilia were remarkably stable, incorporating newly synthesized protein at <10% per day. Only stereocilia tips had rapid turnover and no treadmilling was observed. Other methods confirmed this: in hair cells expressing ß-actin-GFP we bleached fiducial lines across hair bundles, but they did not move in 6 days. When we stopped expression of ß- or γ-actin with tamoxifen-inducible recombination, neither actin isoform left the stereocilia, except at the tips. Thus, rapid turnover in stereocilia occurs only at the tips and not by a treadmilling process.

Race, Exclusionary Discipline, and Connectedness to Adults in Secondary Schools.

This study examines racial differences in students' connectedness to school adults and considers the possibility that disparities in exclusionary discipline practices may reduce all students' sense of connection to educators, not just those who have been disciplined or are from racial groups overrepresented in out-of-school suspensions. Data sources include a self-report survey of secondary school students (n = 29,148) linked to administrative data (n = 107 schools) from a large urban district. Multilevel modeling techniques were used to estimate the relationships between students' racial background, youths' connection to school adults, and school-level racial discipline gaps. Controlling for school racial composition, gender, grade level and other covariates, students of color were significantly less likely to feel connected to school adults than their White peers. Additionally, the racial discipline gap was significantly and negatively associated with connectedness for all students. Results indicate that strategies to improve educational outcomes for youth of color need to attend to relational dynamics between students and school adults. Research findings also suggest that efforts to reduce discipline disparities may improve all students' connectedness.

Acute effects of Rho-kinase inhibitor fasudil on pulmonary arterial hypertension in patients with congenital heart defects.

BACKGROUND: We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group. CONCLUSIONS: Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2.

Promotion of artery occlusion in dogs by percutaneous rotational atherectomy.

BACKGROUND: This study aims to offer experimental data and indirect evidences for the application of percutaneous rotational atherectomy to treat patent ductus arteriosus (PDA). METHODS: Eleven dogs (6 male dogs and 5 female dogs; aged 14-20 months, with an average of 16.7±3.2 months; weight 20-25 kg, with an average of 22.7±2.5 kg) were enrolled in this study. The diameters of the left and right arteries ranged from 3.2 to 4.8 mm (average 3.9±0.6 mm) on percutaneous angiography. Percutaneous rotational atherectomy with proper rotablator (the size was 1-1.5 mm larger than the artery diameter) was performed in the arterial intima. After 4 weeks from percutaneous rotational atherectomy, arteriography was conducted to observe the changes in artery diameter. Then all dogs were sacrificed and the pathologic examination was conducted on the left and right axillary arteries. RESULTS: There were obvious changes with different degrees in 22 arteries, including 8 arteries with complete occlusion and 12 arteries with stenosis (≥2/3, 1/2, and 1/3 stenosis in 4, 4, and 4 arteries, respectively). The occlusion rate was 36.4% and the total effective rate was 90.9%. It was considered failure in other 2 arteries with <1/3 of stenosis. CONCLUSIONS: Percutaneous rotational atherectomy of arterial intima can promote the occlusion of arteries. This has provided a new choice for the treatment of PDA.

Severe cough and hemoptysis induced reopening of patent foramen ovale leading to significant decrease in pulmonary artery pressure in a patient with idiopathic pulmonary arterial hypertension： A case report.

Pulmonary arterial hypertension (PAH) is a perilous disease that precipitates right ventricular hypertrophy, induces right heart failure, and exerts deleterious ramifications on prognostic outcomes. The establishment of atrial communication can create a right-to-left shunt, thereby ameliorating hemodynamic parameters. Previous reports suggested that opening of a patent foramen ovale (PFO) was common in patients with severe PAH, but exhibited no discernible impact on long-term survival. We reported the case of a 39-year-old man with severe idiopathic PAH, who underwent reopening of the PFO due to severe cough and hemoptysis, followed by a marked amelioration in symptoms and a substantial decrease in pulmonary arterial pressure. The patient has survived for more than 12 years, persisting in World Health Organization functional class Ⅱ with mild PAH.

Diverse alkaloids from the aerial parts of Aconitum carmichaelii and antiproliferative activity of costemline via inhibiting SIRT1/ROCK1/P-STAT3 pathways.

Six undescribed alkaloids together with 15 known alkaloids were isolated from the aerial parts of Aconitum carmichaelii. Their structures were elucidated extensively by NMR and HRESIMS spectroscopy. The absolute configurations of N-formyllaurotetanine, and the known compounds glaucine-ß-N-oxide and glaucine-α-N-oxide were established by electronic circular dichroism (ECD) spectra. Notably, it was the discovery of rare indole alkaloids from the genus Aconitum, and biosynthetic pathway of compounds 1 and 6 was deduced. Evaluation of the antiproliferative activity of these alkaloids demonstrated that costemline exhibited significant anti-proliferation effects against HCT116, SKOV3, and A549 cells with IC50 values of 5.6, 14.2, and 6.8 µM, respectively. Costemline could also inhibit the cell invasion activity of HCT116 cells. Mechanistic studies in HCT116 cells suggested that the antiproliferative activity of costemline was attributable to SIRT1/ROCK1/P-STAT3 pathways regulation. This study revealed the potential for developing and utilizing the aerial parts of Aconitum carmichaelii.

Epithelial p38alpha controls immune cell recruitment in the colonic mucosa.

Intestinal epithelial cells (IECs) compose the first barrier against microorganisms in the gastrointestinal tract. Although the NF-kappaB pathway in IECs was recently shown to be essential for epithelial integrity and intestinal immune homeostasis, the roles of other inflammatory signaling pathways in immune responses in IECs are still largely unknown. Here we show that p38alpha in IECs is critical for chemokine expression, subsequent immune cell recruitment into the intestinal mucosa, and clearance of the infected pathogen. Mice with p38alpha deletion in IECs suffer from a sustained bacterial burden after inoculation with Citrobacter rodentium. These animals are normal in epithelial integrity and immune cell function, but fail to recruit CD4(+) T cells into colonic mucosal lesions. The expression of chemokines in IECs is impaired, which appears to be responsible for the impaired T cell recruitment. Thus, p38alpha in IECs contributes to the host immune responses against enteric bacteria by the recruitment of immune cells.

In Situ Microfluidic SERS Chip for Ultrasensitive Hg2+ Sensing Based on I--Functionalized Silver Aggregates.

Mercury(II) ions are causing serious environmental pollution and health damage. Developing a simple, rapid, and sensitive sensor for Hg2+ detection is of great significance. Herein, we demonstrate an I--functionalized surface-enhanced Raman scattering (SERS) substrate for rapid and sensitive Hg2+ sensing on a highly integrated microfluidic platform. Based on the combination reaction between I- and Hg2+, the Hg2+ sensing is achieved via the SERS intensity "turn-off" strategy, where HgI2 precipitation is formed on an SERS substrate interface, dissociating the Raman reporters that coadsorbed with I-. Owing to the strong binding constant between I- and Hg2+, our I--functionalized substrate demonstrates a very fast sensing response (∼150 s). Through reliable in situ SERS detection, a robust calibration curve between the "turn-off" signal and "lgC" is obtained in a broad concentration range of 10-9 to 10-13 M. Additionally, the detectable Hg2+ concentration can be as low as 1 fM. The good selectivity toward Hg2+ is also verified by testing about a dozen common metal ions in water, such as K+, Na+, Ca2+, Mg2+, and so forth. Furthermore, we apply the SERS sensor for real tap and lake water sample detection, and good recoveries of 113, 97, and 107% are obtained. With its advantages of high integration, simple preparation, fast response, high sensitivity, and reliability, the proposed I--functionalized SERS sensor microfluidic chip can be a promising platform for real-time and on-site Hg2+ detection in natural water.

Plasmon-driven photocatalytic properties based on the surface of gold nanostar particles.

Surface plasmon resonance (SPR) generated in gold nanoparticles can induce the conversion of p-Aminothiophenol (PATP) molecules into p,p'-dimercaptoazobenzene (DMAB) molecules by coupling reaction under the action of excitation light. Molecular detection of samples by surface enhanced Raman spectroscopy (SERS) techniques allows the study of their plasma-driven photocatalytic reaction processes. In this study, we used gold nanostars (GNS) as the substrate to study its catalytic performance and sensitivity. On this basis, catalytic substrates of gold nanospheres (GNPs) were prepared for comparison. The catalytic reactions of PATP molecules on each of the above two substrates were systematically investigated under 633 nm laser irradiation. The reduction process was subsequently observed by introducing NaBH4 solution. The results show that photocatalytic reactions can be achieved on both substrates under laser excitation at the same wavelength. However, the catalytic and reduction reaction rates on GNSs as a substrate are much faster than those of GNPs. This phenomenon may be due to the abundant nano-branched microstructures on the surface of GNSs, which will generate more and stronger local surface plasma hot spots under the irradiation of excitation light. In order to test the above hypothesis, the surface electromagnetic field distribution of two nanostructures was numerically simulated using the finite-difference time domain (FDTD) method. It is found that the star-like nanostructures not only have the same inter-particle hot spot system as the spherical nanostructures, but also have a large number of high-intensity single-particle hot spot systems arising from the abundance of branched nanostructures on their own surfaces. Compared with the spherical nanostructures, they are characterized by a dual hot spot system, which accelerates the photocatalytic reaction rate. The above experiments are of some reference significance for the in-depth study of multi-branched nanostructures and surface plasma distribution properties and their applications.

Resonance Photoluminescence Enhancement of Monolayer MoS2 via a Plasmonic Nanowire Dimer Optical Antenna.

Two-dimensional transition-metal dichalcogenides (TMDs) such as monolayer MoS2 exhibit remarkable optical properties. However, the intrinsic absorption and emission rates of MoS2 are very low, thus severely hindering its application in electronics and photonics. Combining MoS2 with a plasmonic optical antenna is an alternative solution to enhance the emission rates of the 2D semiconductor, and this can drastically increase the photoresponsivity of the corresponding photodetector. Herein, we have constructed a plasmonic gap cavity of a nanowire dimer (NWD) system as an optical antenna to brighten the emission of MoS2 off the hot spot. Different from the conventional enhancement concept which occurred in the plasmonic hot spot, the light emission off the nanogap hot spot was thoroughly investigated. We demonstrate that this new plasmonic optical nanostructure leads to a strong enhancement due to the Purcell effect. The NWD optical antenna can trap light to the near field through a high-efficiency plasmonic gap mode (PGM); then the PL emission was enhanced drastically up to 14.5-fold due to the resonance of the plasmonic gap mode (PGM) in the NWD with the excitonic band of monolayer MoS2. Theoretical simulations reveal that this NWD can alter the efficiency of convergence and excitation, which was consistent with our experimental results. This study can provide a pathway toward enhancing and controlling PGM-enhanced light emission of TMD materials beyond the plasmonic hot spot.

[Preliminary study on the efficacy and safety of oral sildenafil in pulmonary arterial hypertension in China].

OBJECTIVE: Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH has been under-investigated in China. The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China. METHODS: In this prospective, open-label and multi-center study, 90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks. They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks. The primary endpoint was the changes in exercise capacity as assessed by SMWT. And the secondary endpoints included assessment of functional class, evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death, transplantation and re-hospitalization for PAH). Drug safety and tolerability were also examined. RESULTS: There were 19 males and 71 females with an average age of 32.5 ± 12.1 years old (range: 18 - 61). Their etiologies were idiopathic (n = 15), related with congenital heart disease (n = 60), or related with connective tissue disease (n = 9) and chronic thromboembolic pulmonary hypertension (n = 6). Oral sildenafil significantly increased the SMWT distances [(342 ± 93) m vs. (403 ± 88) m, P < 0.001]. There was also remarkable improvement in Borg dyspnea score (2.9 ± 2.6 vs. 2.4 ± 2.0, P = 0.005). Furthermore, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found (mean pulmonary artery pressure, P < 0.001; cardiac index, P < 0.001; pulmonary vascular resistance, P < 0.001). Side effects were mild and consistent with other reports. CONCLUSION: This study confirms and extends previous studies. Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.

[Clinical analysis of transcatheter closure of atrial septal defects in elderly patients].

OBJECTIVE: To evaluate the clinical feature of patients with atrial septal defects (ASD) and the safety and efficacy of transcatheter closure of ASD in elderly patients. METHODS: Between May 2000 and June 2010, 82 patients aged (64.5 ± 3.8) years underwent attempted transcatheter ASD closure. Right heart catheterization was performed before intervention. Echocardiography was made at 1 day, 1, 3, 6 months after the procedure. The pre- and post-closure clinical feature, pulmonary artery pressure (PAP) and cardiac function were evaluated. RESULTS: In 82 patients, 37 (45.1%) patients were associated with pulmonary arterial hypertension (PAH). The systolic PAP and mean PAP [(44.1 ± 12.4) mm Hg (1 mm Hg = 0.133 kPa) and (25.2 ± 6.8) mm Hg, respectively] were measured by right heart catheterization before the procedure. One patient was unsuitable for closure because of severe PAH. The remaining 81 patients underwent successful ASD closure without major complications. After closuring, systolic PAP decreased from (52.7 ± 10.3) mm Hg to (31.8 ± 6.3) mm Hg (P < 0.05), and mean PAP descended from (30.9 ± 4.7) mm Hg to (21.8 ± 3.4) mm Hg (P < 0.05) in the 36 patients with PAH. The cardiac function improved post procedure. There were 6 new-onset atrial fibrillations during follow up. CONCLUSIONS: ASD in elderly patients are commonly associated with PAH. Transcatheter ASD closure is safe and effective in the majority of elderly patients.

Plasma-Driven Photocatalysis Based on Gold Nanoporous Arrays.

Various effects caused by surface plasmons including enhanced electromagnetic field, local heating, and excited electrons/holes can not only redistribute the electromagnetic field in the time domain and space but also redistribute the excited carriers and drive chemical reactions. In this study, firstly, an Au nanoporous array photocatalyst with the arrayed gauge was prepared by means of the anodic alumina template. Then, the formation of 4,4'-dimercaptoazobenzene (DMAB) by the surface plasmon-driven photocatalysis under 633 nm laser irradiation was investigated by means of Raman spectroscopy using aminothiophenol (PATP) as a probe molecule on gold nananoporous arrays. In addition, sodium borohydride was introduced in situ to realize the reverse photocatalytic reaction driven by the surface plasma. With the help of FDTD software, the plasma distribution characteristics on the surface of Au nanoporous arrays were simulated and analyzed. Through this practical method, it is expected to draw specific graphics, letters, and Chinese characters on the micro/nano scale, and realize the functions of graphics drawing, information encryption, reading, and erasing on the micro/nano scale.

Graphene/SnS2 van der Waals Photodetector with High Photoresponsivity and High Photodetectivity for Broadband 365-2240 nm Detection.

The fabrication of graphene/SnS2 van der Waals photodetectors and their photoelectrical properties are systematically investigated. It was found that a dry transferred graphene/SnS2 van der Waals heterostructure had a broadband sensing range from ultraviolet (365 nm) to near-infrared (2.24 µm) and respective improved responsivities and photodetectivities of 7.7 × 103 A/W and 8.9 × 1013 jones at 470 nm and 2 A/W and 1.8 × 1010 jones at 1064 nm. Moreover, positive and negative photoconductance effects were observed when the photodetectors were illuminated by photon sources with energies greater and smaller than the bandgap of SnS2, respectively. The photoresponsivity (R) versus incident power density (P) follows the empirical law R ∝ Pinß, with ß > -1 for positive photoconductance effects and ß < -1 for negative photoconductance effects. On the basis of the Fowler-Nordheim tunneling model and a Poisson and drift-diffusion simulation, we show quantitatively that the barrier height and barrier width of the heterostructure photodetector could be controlled by a laser and an external electrical field through a photogating effect generated by carriers trapped at the interface, which could be used to tune the separation and transport of photogenerated carriers. Our results may be useful for the design of high performance van der Waals heterojunction photodetectors.

Giant gauge factor of Van der Waals material based strain sensors.

There is an emergent demand for high-flexibility, high-sensitivity and low-power strain gauges capable of sensing small deformations and vibrations in extreme conditions. Enhancing the gauge factor remains one of the greatest challenges for strain sensors. This is typically limited to below 300 and set when the sensor is fabricated. We report a strategy to tune and enhance the gauge factor of strain sensors based on Van der Waals materials by tuning the carrier mobility and concentration through an interplay of piezoelectric and photoelectric effects. For a SnS2 sensor we report a gauge factor up to 3933, and the ability to tune it over a large range, from 23 to 3933. Results from SnS2, GaSe, GeSe, monolayer WSe2, and monolayer MoSe2 sensors suggest that this is a universal phenomenon for Van der Waals semiconductors. We also provide proof of concept demonstrations by detecting vibrations caused by sound and capturing body movements.

TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.

TRPA1, a member of the transient receptor potential (TRP) family of ion channels, is expressed by dorsal root ganglion neurons and by cells of the inner ear, where it has proposed roles in sensing sound, painful cold, and irritating chemicals. To test the in vivo roles of TRPA1, we generated a mouse in which the essential exons required for proper function of the Trpa1 gene were deleted. Knockout mice display behavioral deficits in response to mustard oil, to cold ( approximately 0 degrees C), and to punctate mechanical stimuli. These mice have a normal startle reflex to loud noise, a normal sense of balance, a normal auditory brainstem response, and normal transduction currents in vestibular hair cells. TRPA1 is apparently not essential for hair-cell transduction but contributes to the transduction of mechanical, cold, and chemical stimuli in nociceptor sensory neurons.

TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells.

Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transduction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted. Inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.

Fracturing and Damage of 3D-Printed Materials with Two Intermittent Fissures under Compression.

The crack propagation and failure of 3D-printed samples with prefabricated K-S fissures (a kinked fissure and a straight fissure) were observed under uniaxial compression, and the strain and displacement of the sample surface were quantified by the digital image correlation (DIC) method. The experimental results show that the branch inclination angle of the kinked fissure is an important factor affecting the crack initial position, and the evolution of the strain field during the failure process of the sample can better reflect the cracking law of the internal fissures. Furthermore, two coalescence modes are classified: Mode I is a tension-shear composite failure formed by the penetration of the tension-shear composite crack; Mode II is a tensile failure that penetrates the whole samples during the failure process without rock bridge damage. In addition, the numerical simulation results were well consistent with the cracking and failure modes.