A Paternò-Büchi Reaction of Aromatics with Quinones under Visible Light Irradiation.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

A Molecular Cage Accessed by Threefold Click Reaction of a C3v-Symmetric Triazido-Functionalized Tribenzotriquinacene.

The hitherto unknown hexakis(halomethyl)-functionalized tribenzotriquinacenes (TBTQs) 9 and 10 were synthesized from the key 4b,8b,12b-tribromo-TBTQ derivative 6 by an improved route in 67% overall yield. Extension of the bowl-shaped framework of 9 or 10 by threefold condensation with propargylamine or 2-azidoethylamine afforded the corresponding TBTQ-trialkyne 11 and TBTQ-triazide 12, respectively. While attempts to construct bis-TBTQ cages, including homodimerization of 11 and heterocoupling of 11 with 12, were unsuccessful, triazide 12 was found to undergo threefold [3 + 2]-cycloaddition with 3-ethynylaniline and phloroglucinol tripropargyl ether under click chemistry conditions. The latter reaction enabled facile capping of the TBTQ bowl to give the novel cage compound 5 in 22% yield.

Connexin26 Modulates Radiation-Induced Skin Damage by Regulating Chemokine CCL27 through MAPK Signaling.

Connexin26 (Cx26) plays an important role in ionizing radiation-induced damage, and CC chemokine ligand 27 (CCL27) regulates the skin immune response. However, the relationship between Cx26 and CCL27 in radiation-induced skin damage is unclear. After X-ray irradiation, clonogenic survival and micronucleus formation were assessed in immortalized human keratinocytes (HaCaT). Proteins in the mitogen activated protein kinase (MAPK) signaling pathway and CCL27-related proteins were detected by immunoblotting. HaCaTCx26-/- cells were constructed to verify the effects of Cx26 on CCL27 secretion. A mouse model was established to examine the expression of CCL27 and skin inflammation in vivo. The degree of skin injury induced by 6 MV of X rays was closely related to CCL27. The phosphorylation of ERK, p38 and NF-κB was significantly increased in irradiated cells. The secretion of CCL27 was significantly decreased in HaCaT wild-type cells relative to HaCaTCx26-/- cells. Whereas cell survival fractions decreased, and the micronuclei formation rate increased as a function of increasing X-ray dose in HaCaT cells, the opposite trend occurred in HaCaTCx26-/- cells. Our findings show that Cx26 likely plays a role in the activation of the MAPK and NF-κB/COX-2 signaling pathways and regulates the secretion of CCL27 in keratinocytes after X-ray radiation-induced skin damage.

Broadband and efficient multi-mode fiber-chip edge coupler on a silicon platform assisted with a nano-slot waveguide.

Mode-division multiplexing (MDM) has been extensively utilized to expand the capacity of chip-scale or fiber-based optical communication, whereas it is still challenging to implement the MDM for fiber-chip optical interconnects due to the huge mode mismatch between few-mode fiber (FMF) and multi-mode waveguide. In this work, we propose and design a silicon integrated six-mode edge coupler assisted with a slot waveguide, which achieves the efficient direct conversion of multiple modes between the waveguide and fiber in a broad bandwidth. Based on the principle of mode conversion, this edge coupler enables the mode conversion between six linear polarization (LP) modes (i.e. LPx/y01, LPx/y11a, LPx/y11b) in FMF and six on-chip waveguide modes (i.e. TE0, TE1, TE2, TM0, TM1, TM2) with low insertion loss, low mode crosstalk and broad bandwidth. The obtained results show that over the whole C-band the efficiency of mode conversion is higher than 98% and the mode crosstalk is low than -19 dB, while the total coupling loss is higher than 85%. The favorable results offer an important reference for designing related broadband photonic devices, and the presented scheme could be potentially exploited to further increase the transmission capability for prospective fiber-chip optical interconnections and communications.

Efficient mode coupling between a few-mode fiber and multi-mode photonic chip with low crosstalk.

The mode-division multiplexing technology has been developing slowly in the field of fiber-chip-fiber optical interconnects, mainly limited by the inefficient mode coupling between few-mode fiber and multi-mode photonic chip. Here we propose and design a multi-mode coupler composed of tapered few-mode fiber and silicon integrated multistage waveguide tapers, which allows the direct coupling between high-order fiber modes and high-order waveguide modes with high coupling efficiency and low crosstalk. Based on the edge coupling scheme, the six linear polarization modes (LP01x/y, LP11a x/y, LP11bx/y) in few-mode fiber are firstly coupled into the integrated waveguide with low insertion loss, then the input modes are converted to the desired waveguide modes (TE0, TE1, TE2, TM0, TM1, TM2) with low mode crosstalk relying on the mode evolution principle. The obtained results show that the coupling efficiency is higher than 87%, while for the mode conversion process, the efficiency is higher than 99% and the mode crosstalk is lower than -25 dB. The favorable performance achieved may open new perspectives for diverse mode-division multiplexing applications, enabling efficient capacity scaling in fiber-chip-fiber optical interconnects and optical communication systems.

Fundamental analyses of fabrication-tolerant high-performance silicon mode (de)multiplexer.

Mode-division multiplexing (MDM) has been extensively exploited to expand the capacity of chip-scale optical interconnects, whereas high-volume manufacturing of on-chip mode (de)multiplexers is still full of challenges. In this paper, we analyze the fabrication errors (sidewall, width, height) of silicon mode (de)multiplexer and present two cases of fabrication-tolerant high-performance silicon mode (de)multiplexer. The presented mode (de)multiplexer could eliminate the mode mismatch and mode hybridization caused by the fabrication errors. When sidewall errors are 0°, 5°, width errors are 0, ± 20, ± 30 nm, and height errors are 0, ± 10 nm, the designed fabrication-tolerant high-performance silicon mode (de)multiplexer can achieve low excess loss less than 2.5 dB and low inter-mode crosstalk less than -15 dB over a broad bandwidth from 1500 to 1600 nm. The obtained results provide an important guideline for designing fabrication-tolerant photonic integrated circuits on silicon platform, which could be applied to the prospective high-volume manufacturing and large-scale integration.

LEAF TIP RUMPLED 1 Regulates Leaf Morphology and Salt Tolerance in Rice.

Leaf morphology is one of the important traits related to ideal plant architecture and is an important factor determining rice stress resistance, which directly affects yield. Wax layers form a barrier to protect plants from different environmental stresses. However, the regulatory effect of wax synthesis genes on leaf morphology and salt tolerance is not well-understood. In this study, we identified a rice mutant, leaf tip rumpled 1 (ltr1), in a mutant library of the classic japonica variety Nipponbare. Phenotypic investigation of NPB and ltr1 suggested that ltr1 showed rumpled leaf with uneven distribution of bulliform cells and sclerenchyma cells, and disordered vascular bundles. A decrease in seed-setting rate in ltr1 led to decreased per-plant grain yield. Moreover, ltr1 was sensitive to salt stress, and LTR1 was strongly induced by salt stress. Map-based cloning of LTR1 showed that there was a 2-bp deletion in the eighth exon of LOC_Os02g40784 in ltr1, resulting in a frameshift mutation and early termination of transcription. Subsequently, the candidate gene was confirmed using complementation, overexpression, and knockout analysis of LOC_Os02g40784. Functional analysis of LTR1 showed that it was a wax synthesis gene and constitutively expressed in entire tissues with higher relative expression level in leaves and panicles. Moreover, overexpression of LTR1 enhanced yield in rice and LTR1 positively regulates salt stress by affecting water and ion homeostasis. These results lay a theoretical foundation for exploring the molecular mechanism of leaf morphogenesis and stress response, providing a new potential strategy for stress-tolerance breeding.

Efficacy and safety of Shenfu injection in the treatment of sepsis: A protocol for systematic review and meta-analysis.

BACKGROUND: Sepsis is a syndrome of infection-induced systemic inflammatory response. Conventional treatment combined with Shenfu injection (SFI) has been previously validated clinical effective in alleviating inflammatory response in patients with septic shock. However, evidence-based medical evidence is scant. Herein, we designed the protocol of a proposed study based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, aiming to systematically evaluate the efficacy and safety of SFI in patients with sepsis. METHODS: Eligible studies reporting the efficacy and safety of SFI in the treatment of sepsis published before August 2021 will be searched from online databases, including the PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The literature selection process will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. After data extraction and methodological quality evaluation, Stata 12.0 software will be used to synthesize the data through fixed/random effects of meta-analysis models. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide reliable evidence-based basis for the clinical application of SFI in the treatment of sepsis. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KCMDQ.

Long non-coding RNA CHRF accelerates LPS-induced acute lung injury through microRNA-146a/Notch1 axis.

BACKGROUND: The present study sought to investigate the regulatory role of the long non-coding RNA (lncRNA) cardiac hypertrophy-related factor (CHRF) in a mouse model of acute lung injury (ALI) and in primary mouse pulmonary microvascular endothelial cells (MPVECs) treated with lipopolysaccharide (LPS). METHODS: C57BL/6 mice were given adenovirus (Ad) sh-CHRF or negative control (NC) before undergoing cecal ligation and perforation. MPVECs transfected with Adsh-CHRF or NC were treated with LPS. Double luciferase assay was used to detect the binding of miR-146a to CHRF or Notch1. Subsequently, MPVECs were co-transfected with miR-146a inhibitor and sh-CHRF for 24 hours, and then treated with LPS. RESULTS: High expression of CHRF was detected in septic mice. Cecal ligation and perforation induced ALI and apoptosis in mice, whereas, CHRF knockout could inhibit ALI. The protein expression levels of TNF-α, IL-1ß and IL-6 in the lung and bronchoalveolar lavage fluid of the CLP group were up-regulated, whereas the expression of IL-4 and IL-10 was down-regulated. CHRF inhibition reduced the production of proinflammatory cytokines in septic mice. The inhibitory effect of CHRF gene knockdown on lung inflammation and apoptosis was confirmed in the septic cell model. Mechanistic investigation showed that CHRF up-regulated the level of Notch1 by sponging miR-146a. Additionally, the low expression of miR-146a reversed the inhibitory effect of CHRF gene knockout on LPS-induced inflammatory response and apoptosis. Together, in vivo and in vitro results demonstrated that CHRF enhanced sepsis-induced ALI by targeting miR-146a and up-regulating Notch1. CONCLUSIONS: CHRF can induce inflammation and apoptosis caused by sepsis by miR-146a/Notch1 axis. Therefore, it may serve as a potential drug target for treating sepsis-induced ALI.

Organochlorine Pesticide Ban Facilitated Reproductive Recovery of Chinese Striped Hamsters.

Organochlorine pesticides (OCPs) have been used worldwide on an enormous scale over the last century but are banned globally due to environmental persistence and ecotoxicity in recent decades. The long-term effects of OCP ban for agricultural use in China since 1983 on the reproductive health of small terrestrial mammals have never been evaluated in the field. We examined the residue dynamics of OCPs and the reproductive performance of Chinese striped hamsters (Cricetulus barabensis) in North China Plain during 1983-2010 and concluded that the exposure levels of OCPs in hamsters drastically decreased from 2900 ± 740 to 25.2 ± 6.88 ng/g with an average half-life of 5.08 yrs, coinciding with the observed reproductive recovery of hamsters. The population-based reproductive performance of hamsters was significantly and negatively associated with OCP exposure levels after adjusting the contributions from climate and population density factors, indicating that the ban of OCPs has facilitated the reproductive recovery of hamsters by up to 81% contribution. Our findings suggest that the OCP ban is effective to restore reproduction of small terrestrial mammals. Integration of population biology and environmental science is essential to assess the impacts of persistent organic pollutants on ecological safety and biodiversity loss under accelerated global change.

Synthesis of Enantiopure Hydrocarbon Cages Based on an Optically Resolved C3-Symmetric Triaminotribenzotriquinacene.

The synthesis of the enantiomerically pure, D3-symmetric covalent hydrocarbon cages (+)-(M,M)-4 and (-)-(P,P)-4 bearing two C3-symmetrically functionalized tribenzobenzotriquinacene (TBTQ) vertices is reported. The enantiomerically pure TBTQ building blocks (+)-(M)-5 and (-)-(P)-5 were prepared via the diastereomeric TBTQ triamides obtained by use of both Boc-d- and Boc-l-phenylglycine as chiral auxiliaries.

Ligustilide modulates oxidative stress, apoptosis, and immunity to avoid pathological damages in bleomycin induced pulmonary fibrosis rats via inactivating TLR4/MyD88/NF-KB P65.

BACKGROUND: Pulmonary fibrosis (PF) is a fatal disease with increasing incidence. Ligustilide (LIG) has been shown to inhibit oxidative stress, apoptosis, and inflammation. Here we investigated the possible effect of LIG on bleomycin-induced PF in Sprague-Dawley rats. METHODS: PF rats were set up through a single endotracheal injection of bleomycin (5 mg/kg). Then rats were treated with 20, 40, and 80 mg/kg LIG for four weeks, and the effects were estimated. RESULTS: Overall, LIG significantly improved ventilation and reduced hyperplasia, and treatment of LIG reduced fibrosis as indicated by Masson staining and reduced expression of transforming growth factor-beta (TGF-ß), Fibronectin, and alpha-smooth muscle actin (α-SMA). Oxidative stress was induced with bleomycin while inhibited with LIG, as showed with rebalanced serum lactate dehydrogenase (LDH), and tissue superoxide dismutase (SOD), glutathione peroxidase (GSH) and malondialdehyde (MDA). Apoptosis was further inhibited with LIG, as shown with Terminal dUTP nick-end labeling (TUNEL) staining and expression of Caspase-3, Caspase-9, Bax, and Bcl-2. Th1/Th2 balance was also rebuilt as evaluated with CD4 and IFNγ/IL-4 labeled flow cytometry of peripheral blood mononuclear cells (PBMCs) and expression of inducible nitric oxide synthase (iNOS) and IL-10 in the serum and lung. Protein expression of Toll-like receptor 4 (TLR4), HSP60-TLR4-myeloid differentiation factor 88 (Myd88) and nuclear factor-kappa B (NF-κB) p-P65/P65 was significantly reduced with LIG treatment. All the effects of LIG exhibited in a dose-dependent way. CONCLUSIONS: LIG improved bleomycin-induced PF with improved ventilation, reduced fibroblast, reduced oxidative stress and apoptosis, and rebalanced Th1/Th2 immunity, through TLR4/MyD88/NF-κB P65 signaling.

Releasing the light field in subwavelength grating slot microring resonators for athermal and sensing applications.

Silicon-on-insulator (SOI) platforms have attracted increasing interest for photonic integrated devices with an ultra-small footprint. The distinct feature is the strong light confinement in the silicon region due to a high refractive-index-contrast. In contrast, releasing the light field out of the silicon region is also of great significance for providing a useful supplement to existing light guiding mechanisms and for facilitating versatile applications. Here, subwavelength grating slot (SWGS) microring resonators, which can effectively release light out of the silicon region for athermal and sensing applications, are proposed and demonstrated. The mechanism of releasing light relies on the combination of a surface enhanced supermode in a slot waveguide and a Bloch mode in a subwavelength grating waveguide. Four types of racetrack microring resonators (strip, slot, strip-SWGS, and slot-SWGS) were fabricated for comparison. The slot-SWGS microring resonator shows the best performance for athermal and sensing applications. The demonstrations may be useful for new releasing-light-enabled devices and applications.

Innate lymphoid cells regulate radiation-induced skin damage via CCR10 signaling.

OBJECTIVE: To assess the role of CCR10 in innate lymphoid cells (ILCs) response in radiation-induced skin damage. MATERIAL AND METHODS: CCR10+/- and CCR10-/- mice were treated with either a single dose of 5 Gy or 5 Gy everyday for 6 days with a total dose of 30 Gy with X-ray. ILCs from the skin were isolated and analyzed by flow cytometry 3 and 10 days after irradiation. A mouse model of radio-dermatitis was used to assess the skin damage 10 days after 6 × 5 Gy irradiation. RESULTS: Skin ILCs were decreased in both CCR10+/- and CCR10-/- mice 3 days after single irradiation (p < .05). However, the skin inflammation disappeared and ILCs returned to normal levels 10 days after single irradiation. ILCs of both genotypes were also decreased after 6 × 5 Gy irradiation, but the percentage of skin ILCs in CCR10-/- mice was lower than that in CCR10+/- mice 10 days after irradiation. The immunohistochemistry results showed that CCR10-/- mice had more severe skin inflammation than CCR10+/- mice. CONCLUSION: CCR10-/- mice had lower percentages of ILCs and more skin damage than CCR10+/- mice after irradiation. These findings indicate that skin ILCs are regulated by CCR10, which might be a potential target for reducing the radio-dermatitis.

Chiral Derivatives of 2-Aminotribenzotriquinacene: Synthesis and Optical Resolution.

Starting from a hitherto unknown 2-aminotribenzotriquinacene, several 2-amino-3-X-substituted TBTQ derivatives, all bearing a single ortho-difunctionalized indane wing, were synthesized as rigid and chiral building blocks for the potential construction of complex supramolecular architectures. Efficient access to two pairs of enantiomeric TBTQ derivatives, namely, the peripheral ortho-nitroaniline (X = NO2) and the related anthranilic acid (X = CO2H), was developed using chiral auxiliaries as the resolving reagents. The structure of the intermediate diastereomers was confirmed by 1H and 13C NMR spectroscopy, high-resolution mass spectroscopy (HRMS), and polarimetry. The absolute configuration of the optically active derivatives was confirmed by quantum chemical time-dependent density functional theory (TD-DFT) calculations of the theoretical electronic circular dichroism (ECD) spectra and by single-crystal X-ray structure analysis of a synthesis intermediate.

Multimode Fano resonances for low-power mode switching.

Intensive research in photonics has discovered many original and fascinating optical phenomena associated with the physics of Fano resonances. Here we extend the research of Fano resonance to on-chip multiple modes and high-order mode, which can be called multimode Fano resonance. By exploiting both wavelength and mode degrees of freedom, we demonstrate a compact structure to engineer wavelength- and shape-controlled multimode Fano resonances on an integrated photonic platform. Both simulated and experimental results indicate that the unambiguous asymmetric spectra line shapes for both transverse electric modes (${{\rm TE}_0}$TE0 and ${{\rm TE}_1}$TE1) can be further applied to low-power mode switching. The demonstrated on-chip multimode Fano resonances scheme may provide a new perspective for exploring the advantages and applications of multimode Fano resonances in integrated photonics.

Enantioselective Formal Synthesis of (+)-Cycloclavine and Total Synthesis of (+)-5-epi-Cycloclavine.

Starting from the commercially available 4-bromoindole, a concise and efficient enantioselective formal synthesis of (+)-cycloclavine (1) in 13 steps with 2.0% overall yield and a total synthesis of (+)-5-epi-cycloclavine (2) in 14 steps with 3.3% overall yield were achieved. Key features of the syntheses include the addition of a Grignard reagent to the C═N/Heck reaction sequence to construct the fused 6-5-6 ring systems, cyclopropanation, an ester aminolysis reaction, and the first example of the construction of a 3-azabicyclo[3,1,0]hexane through an intramolecular [3 + 2] cycloaddition/nitrogen extrusion.

Access to Benzylic Quaternary Carbons from Aromatic Ketones.

The construction of benzylic all-carbon quaternary stereocenters, which are ubiquitous in biomolecules and drugs, is a task of high practical significance. Herein, we disclose a highly efficient one-pot method of constructing all-carbon quaternary structural units from aryl ketones, revealing that the entire process involves three consecutive chemical events, namely nucleophilic addition, Meinwald 1,2-hydrogen migration, and alkylation. Interestingly, dimerization of acetophenones results in formation of 2,4-diarylfurans under the employed conditions rather than the quaternary carbon products.

Ultra-compact broadband polarization diversity orbital angular momentum generator with 3.6 × 3.6 µm2 footprint.

Orbital angular momentum (OAM), one fundamental property of light, has been of great interest over the past decades. An ideal OAM generator, fully compatible with existing physical dimensions (wavelength and polarization) of light, would offer the distinct features of broadband, polarization diversity, and ultra-compact footprint. Here, we propose, design, fabricate, and demonstrate an ultra-compact chip-scale broadband polarization diversity OAM generator on a silicon platform with a 3.6 × 3.6 µm2 footprint. The silicon OAM chip is formed by introducing a subwavelength surface structure (superposed holographic fork gratings) on top of a silicon waveguide, coupling the in-plane waveguide mode to the out-plane free-space OAM mode. We demonstrate in theory and experiment the broadband generation of polarization diversity OAM modes (x-/y-polarized OAM+1/OAM-1) from 1500 to 1630 nm with high purity and efficiency. The demonstrations of an ultra-compact broadband polarization diversity OAM generator may open up new perspectives for OAM-assisted N-dimensional optical multiplexing communications/interconnects and high-dimensional quantum communication systems.

Feedback-enabled adaptive underwater twisted light transmission link utilizing the reflection at the air-water interface.

Line-of-sight link is widely used in common free-space optical (FSO) laser communications between two fixed locations. While in practical underwater wireless optical communications (UWOC), the environment is relatively complicated. In some scenarios there exist irremovable obstacles, which block the line-of-sight optical link. Fortunately, the air-water interface can function as a natural mirror to enable non-line-of-sight optical link using the total internal reflection. Very recently, twisted light beams carrying orbital angular momentum (OAM) have attracted researchers' great attention to improve the transmission capacity in UWOC. Here, we propose and experimentally demonstrate a non-line-of-sight underwater twisted light transmission link utilizing the total internal reflection at the air-water interface. To overcome the beam fluctuation and drift caused by the change of interface states, we develop a proof-of-concept adaptive feedback system to provide a stable output. Moreover, we study the degrading effects of the slight wind effect, the salinity (turbidity) effect, and the vertical thermal gradient-induced turbulence effect. The results show that the water wave caused by the slight wind causes the most beam drift, the thermal gradient causes the most distortions, and the salinity causes the most power loss.