TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Palladium-Catalyzed Intermolecular Dearomatization Annulation Cascade Reaction of Furans for Stereoselective Access to 2,5-Dihydrofurans.

A novel palladium-catalyzed intermolecular dearomatization of furans with alkynes via a three-component formal [3 + 2] spiroannulation/allylic substitution cascade reaction has been successfully developed for the stereoselective assembly of spiro 2,5-dihydrofuran frameworks. High step economy and efficacy as well as excellent stereoselectivity were achieved for a broad substrate scope. Two new C-C bonds and one new C-O bond were generated sequentially in a one-pot manipulation. The yielded spiro 2,5-dihydrofuran skeleton bearing a tetrasubstituted carbon center constitutes the core structure for plenty of useful natural products or corresponding analogues. This work represents a significant advancement in the dearomatization strategy for furan heterocycles and provides a practical methodology for expedited access to complex spiro dihydrofuran scaffolds.

Compact, ultrabroadband and temperature-insensitive arbitrary ratio power splitter based on adiabatic rib waveguides.

We propose a compact, ultrabroadband and temperature-insensitive adiabatic directional coupler based on rib silicon waveguide-enabling arbitrary splitting ratios. Simulation results show that the device can achieve arbitrary splitting ratios from 1400 to 1600 nm, equal to 50%:50%, 60%:40%, 70%:30%, 80%:20%, and 90%:10% for the fundamental transverse electric mode. The designed device has an excess loss of less than 0.19 dB on the operational waveband. Furthermore, the proposed device shows a great robustness to fabrication imperfection, with a waveguide width deviation of 50 nm and ambient temperature change from 0°C to 200°C. These properties make the design a potential candidate for ultrahigh-density photonic integration chips.

High-efficiency and CMOS compatible out-of-plane light emission based on a silicon coupler.

Photonic antennas are critical in applications such as spectroscopy, photovoltaics, optical communications, holography, and sensors. Metal antennas are widely used because of their small size, but they are difficult to be compatible with a CMOS. All-dielectric antennas are easier to integrate with Si waveguides, but are generally larger in size. In this paper, we propose the design of a small-sized, high-efficiency semicircular dielectric grating antenna. The antenna's key size is only 2.37µm×4.74µm, and the emission efficiency reaches over 64% in the wavelength range from 1.16 to 1.61 µm. The antenna provides a new, to the best of our knowledge, approach for three-dimensional optical interconnections between different decks of integrated photonic circuits.

Three-Component Synthesis of Dioxaphosphorane-Fused Diphosphacycles Exhibiting Unique Dynamic Fluorescence "On/Off" Properties.

Rigidly planar polycyclic phosphacycles featuring an internal dioxaphosphorane are promising photofunctional materials. However, the lack of efficient synthetic methods resulted in limited structural diversities which significantly hampered extensive study. Herein, we report a straightforward three-component synthesis of novel dioxaphosphorane-fused diphosphacycles with distinctive photophysical properties. Control experiments and theory calculations were performed to account for a plausible reaction mechanism. We also systematically investigated the structure-property relationships of these unprecedented platforms by combining experiments (X-ray analysis, optical and redox properties) and theoretical computations. Based on their unique structure and properties, a novel fluorescent switch for pH sensing was revealed by a dynamic ring-opening/ring-closing process.

Silicon modulator based on omni junctions by effective 3D Monte-Carlo method.

3D doping structure has significant advantages in modulation efficiency and loss compared with 2D modulator doping profiles. However, to the best of our knowledge, previous work on 3D simulation methods for interdigitated doping designs applied simplified models, which prohibited complex 3D doping. In this work, innovative omni junctions, based on the effective 3D Monte-Carlo method, are believed to be the first proposed for high-performance modulators. Simulation results show that the modulation efficiency reaches 0.88 V·cm, while the loss is only 16 dB/cm, with capacitance below 0.42 pF/mm. This work provides a modulator design with superior modulation efficiency and serviceability for high-speed datacom.

Synthesis of (Thio)Furan-Fused Phospholes via Phosphonation Cyclization and a Base-Promoted Phospha-Friedel-Crafts Reaction.

Herein, we developed a novel strategy for synthesizing ladder (thio)furan-fused phospholes via intermolecular phosphonation cyclization and a base-promoted phospha-Friedel-Crafts reaction under mild conditions. The starting substrates are readily available phosphinic acids and easy-to-handle alkynes. The details of the reaction mechanism were further rationalized using theoretical calculations. This protocol can be widely applied to synthesize furan- and thiofuran-fused phospholes as well as the corresponding large π-extended derivatives, which are of great interest in the domain of organic functional materials.

Compact, broadband, and low-loss silicon photonic arbitrary ratio power splitter using adiabatic taper.

The arbitrary ratio power splitter is widely used in photonic integrated circuits (PICs), for signal monitoring, power equalization, signal feedback, and so on. Here we designed a fabrication-tolerant, compact, broadband, and low-loss arbitrary ratio power splitter. The proposed arbitrary ratio power splitter was realized with an adiabatically tapered silicon rib waveguide with 70 nm shallow etches and an Si3N4 waveguide. The fabrication analysis confirmed that both of them are robust to fabrication errors. 3D finite-difference time-domain simulations show a very low excess loss (less than 0.02 dB for Si3N4 waveguide and 0.05 dB for Si rib waveguide), and a broadband operating wavelength range (100 nm). Good fabrication tolerance and standard critical dimensions make the arbitrary ratio power splitter compatible with the standard fabrication process of commercial silicon photonic foundries.

Broadband and CMOS compatible polarization splitter-rotator based on a bi-level taper.

A silicon-on-insulator polarization diversity scheme is proposed. Based on an asymmetrical evanescent coupler, a broadband and compact polarization splitter-rotator comprising mode conversion tapers and mode sorting asymmetric Y junctions is optimized with silicon dioxide upper cladding and a silicon nitride waveguide. The simulation results show mode conversion loss is less than 0.2 dB, and the extinction ratio is lower than -17dB in the wavelength range of 1.48µm to 1.67µm.

First Total Synthesis of 5'-O-α-d-Glucopyranosyl Tubercidin.

The first total synthesis of 5'-O-α-d-glucopyranosyl tubercidin was successfully developed. It is a structurally unique disaccharide 7-deazapurine nucleoside exhibiting fungicidal activity, and was isolated from blue-green algae. The total synthesis was accomplished in eight steps with 27% overall yield from commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-ß-d-ribose. The key step involves stereoselective α-O-glycosylation of the corresponding 7-bromo-6-chloro-2',3'-O-isopropylidene-ß-d-tubercidin with 2,3,4,6-tetra-O-benzyl-glucopyranosyl trichloroacetimidate. All spectra are in accordance with the reported data for natural 5'-O-α-d-glucopyranosyl tubercidin. Meanwhile, 5'-O-ß-d-glucopyranosyl tubercidin was also prepared using the same strategy.

CRISPR/Cas9-based genome engineering of zebrafish using a seamless integration strategy.

Numerous feasible methods for inserting large fragments of exogenous DNA sequences into the zebrafish genome have been developed, as has genome editing technology using programmable nucleases. However, the coding sequences of targeted endogenous genes are disrupted, and the expression patterns of inserted exogenous genes cannot completely recapitulate those of endogenous genes. Here we describe the establishment of a novel strategy for endogenous promoter-driven and microhomology-mediated end-joining-dependent integration of a donor vector using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9. We successfully integrated mCherry into the final coding sequence of targeted genes to generate seamless transgenic zebrafish lines with high efficiency. This novel seamless transgenesis technique not only maintained the integrity of the endogenous gene but also did not disrupt the function of targeted gene. Therefore, our microhomology-mediated end-joining-mediated transgenesis strategy may have broader applications in gene therapy. Moreover, this novel seamless gene-editing strategy in zebrafish provides a valuable new transgenesis technique, which was driven by endogenous promoters and in vivo animal reporter modes for translational medicine. It is expected to be a standard gene-editing technique in the field of zebrafish, leading to some important breakthroughs for studies in early embryogenesis.-Luo, J.-J., Bian, W.-P., Liu, Y., Huang, H.-Y., Yin, Q., Yang, X.-J., Pei, D.-S. CRISPR/Cas9-based genome engineering of zebrafish using a seamless integration strategy.

Machine learning guided rapid focusing with sensor-less aberration corrections.

Non-invasive, real-time imaging and deep focus into tissue are in high demand in biomedical research. However, the aberration that is introduced by the refractive index inhomogeneity of biological tissue hinders the way forward. A rapid focusing with sensor-less aberration corrections, based on machine learning, is demonstrated in this paper. The proposed method applies the Convolutional Neural Network (CNN), which can rapidly calculate the low-order aberrations from the point spread function images with Zernike modes after training. The results show that approximately 90 percent correction accuracy can be achieved. The average mean square error of each Zernike coefficient in 200 repetitions is 0.06. Furthermore, the aberration induced by 1-mm-thick phantom samples and 300-µm-thick mouse brain slices can be efficiently compensated through loading a compensation phase on an adaptive element placed at the back-pupil plane. The phase reconstruction requires less than 0.2 s. Therefore, this method offers great potential for in vivo real-time imaging in biological science.

Influence of excessive exercise on immunity, metabolism, and gut microbial diversity in an overtraining mice model.

The purpose of this study was to evaluate the negative influence of excessive exercise on immunity, substance and energy metabolism as well as gut microbiota in mice. Firstly, an overtraining model of Male Kunming mice was established by high-intensity swimming exercise for 4 weeks. Then, a series of evaluation indicators, including the routine blood analysis, immune organ coefficient, digestive enzymes, and aquaporins expression levels of small intestine and colon tissue, histological examinations of liver, spleen, small intestine, and colon, were determined based on this model. Furthermore, 16S rRNA gene sequencing was also employed to measure the microbial composition in gut. The results found that immune parameters, substance and energy metabolism of all mice was altered and disturbed after high-intensity swimming for 4 weeks, led to an atrophy of thymus and spleen as well as abnormal structural changes in liver when compared to non-swimming mice. Besides, excessive swimming mice had lower microbial diversity compared to non-swimming mice. However, there was no significant difference in gut microbial taxa between the two groups. The data indicated that excessive exercise exhibits negative impacts on immunity, substance and energy metabolism as well as gut microbial diversity.

Routing light with ultrathin nanostructures beyond the diffraction limit.

An open nanostructure consisting of a periodic chain of subwavelength-nanoparticles for compressing and routing light beyond the diffraction limit is proposed. The open nanostructure is ultrathin and compact, with a size much smaller than the wavelength of light. We demonstrate that our ultrathin open nanostructure provides functions that can route and manipulate light at the subwavelength scale and can also sharply bend and split light beams below the diffraction limit while exhibiting broadband, incident-angle-tolerant, and robust against disorder. A physical picture based on all-angle self-collimation is presented to understand the manipulation of light using the ultrathin open nanostructure. Experimental and numerical observations validate our findings. This approach provides great flexibility in the design of nanophotonic devices for routing and manipulating light beyond the diffraction limit.

Fasudil inhibits tissue factor and plasminogen activator Inhibitor-1 secretion by peripheral blood mononuclear cells in CAPD patients.

Disturbances in hemostasis are common complications of kidney diseases and correlate well with cardiovascular mortality. Little is known about the effects of fasudil on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression in peripheral blood mononuclear cells (PBMCs) in CAPD patients. PBMCs were isolated from 13 individuals with CAPD and 13 healthy subjects. After 4 h of incubation with or without LPS (10 ng/mL), TF and PAI-1 mRNA of PBMCs were detected by RT-PCR. The levels of TF and PAI-1 in culture supernatants of PBMCs were determined by ELISA. Compared with healthy controls, CAPD patients had increased TF, PAI-1 protein and mRNA expression by PBMCs at baseline and after stimulated by LPS (10 ng/mL) [p < 0.001]. The fasudil treatment resulted in a significant effect in decreasing TF and PAI-1 [p < 0.05] synthesis in PBMCs. TF and PAI-1 mRNA expression and activities in PBMCs were increased in CAPD patients. Fasudil reduced LPS-mediated TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of fasudil in the treatment of CAPD patients.

A silicon-on-insulator polarization diversity scheme in the mid-infrared.

We propose a silicon-on-insulator (SOI) polarization diversity scheme in the mid-infrared wavelength range. In consideration of absorption loss in silicon dioxide (SiO2), the polarization splitter-rotator (PSR) is designed and optimized with silicon nitride (SiN) upper-cladding and SiO2 lower-cladding. This asymmetry allows the PSR, which consists of mode-conversion tapers and subsequent mode-sorting asymmetric Y-junctions, to be fabricated with a simple one-step etching process. Simulation shows that our PSR has good performance with low mode conversion loss (< 0.25 dB) and low crosstalk (< -18 dB) in a very large wavelength range from 4.0 µm to 4.4 µm. The PSR also exhibits large fabrication tolerance with respect to the size deviations in waveguide width, height and refractive index of the upper-cladding. Additionally, PSR devices based on Y-junctions with SiO2 upper-cladding, and SiN upper- and lower-claddings are designed for potential applications at shorter and longer wavelengths, respectively. These PSR devices could facilitate the development of silicon photonic devices in the mid-infrared.

Broadband and fabrication-tolerant on-chip scalable mode-division multiplexing based on mode-evolution counter-tapered couplers.

A broadband and fabrication-tolerant on-chip scalable mode-division multiplexing (MDM) scheme based on mode-evolution counter-tapered couplers is designed and experimentally demonstrated on a silicon-on-insulator (SOI) platform. Due to the broadband advantage offered by mode evolution, the two-mode MDM link exhibits a very large, -1 dB bandwidth of >180 nm, which is considerably larger than most of the previously reported MDM links whether they are based on mode-interference or evolution. In addition, the performance metrics remain stable for large-device width deviations from the designed valued by -60 nm to 40 nm, and for temperature variations from -25°C to 75°C. This MDM scheme can be readily extended to higher-order mode multiplexing and a three-mode MDM link is measured with less than -10 dB crosstalk from 1.46 to 1.64 µm wavelength range.

A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia.

Gain-of-function mutations in fibroblast growth factor receptor-3 (FGFR3) lead to several types of human skeletal dysplasia syndromes including achondroplasia, hypochondroplasia and thanatophoric dysplasia (TD). Currently, there are no effective treatments for these skeletal dysplasia diseases. In this study, we screened, using FGFR3 as a bait, a random 12-peptide phage library and obtained 23 positive clones that share identical amino acid sequences (VSPPLTLGQLLS), named as peptide P3. This peptide had high binding specificity to the extracellular domain of FGFR3. P3 inhibited tyrosine kinase activity of FGFR3 and its typical downstream molecules, extracellular signal-regulated kinase/mitogen-activated protein kinase. P3 also promoted proliferation and chondrogenic differentiation of cultured ATDC5 chondrogenic cells. In addition, P3 alleviated the bone growth retardation in bone rudiments from mice mimicking human thanatophoric dysplasia type II (TDII). Finally, P3 reversed the neonatal lethality of TDII mice. Thus, this study identifies a novel inhibitory peptide for FGFR3 signaling, which may serve as a potential therapeutic agent for the treatment of FGFR3-related skeletal dysplasia.

Intermittent PTH (1-34) injection rescues the retarded skeletal development and postnatal lethality of mice mimicking human achondroplasia and thanatophoric dysplasia.

Achondroplasia (ACH) and thanatophoric dysplasia (TD) are caused by gain-of-function mutations of fibroblast growth factor receptor 3 (FGFR3) and they are the most common forms of dwarfism and lethal dwarfism, respectively. Currently, there are few effective treatments for ACH. For the neonatal lethality of TD patients, no practical effective therapies are available. We here showed that systemic intermittent PTH (1-34) injection can rescue the lethal phenotype of TD type II (TDII) mice and significantly alleviate the retarded skeleton development of ACH mice. PTH-treated ACH mice had longer naso-anal length than ACH control mice, and the bone lengths of humeri and tibiae were rescued to be comparable with those of wild-type control mice. Our study also found that the premature fusion of cranial synchondroses in ACH mice was partially corrected after the PTH (1-34) treatment, suggesting that the PTH treatment may rescue the progressive narrowing of neurocentral synchondroses that cannot be readily corrected by surgery. In addition, we found that the PTH treatment can improve the osteopenia and bone structure of ACH mice. The increased expression of PTHrP and down-regulated FGFR3 level may be responsible for the positive effects of PTH on bone phenotype of ACH and TDII mice.

Proposal for fabrication-tolerant SOI polarization splitter-rotator based on cascaded MMI couplers and an assisted bi-level taper.

A novel silicon-on-insulator (SOI) polarization splitter-rotator (PSR) with a large fabrication tolerance is proposed based on cascaded multimode interference (MMI) couplers and an assisted mode-evolution taper. The tapers are designed to adiabatically convert the input TM(0) mode into the TE(1) mode, which will output as the TE(0) mode after processed by the subsequent MMI mode converter, 90-degree phase shifter (PS) and MMI 3 dB coupler. The numerical simulation results show that the proposed device has a < 0.5 dB insertion loss with < -17 dB crosstalk in C optical communication band. Fabrication tolerance analysis is also performed with respect to the deviations of MMI coupler width, PS width, slab height and upper-cladding refractive index, showing that this device could work well even when affected by considerable fabrication errors. With such a robust performance with a large bandwidth, this device offers potential applications for CMOS-compatible polarization diversity, especially in the booming 100 Gb/s coherent optical communications based on silicon photonics technology.