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Abstract Delay-bandwidth product (DBP) is a key metric in slow light waveguides, requiring a balance between a large group index and broad bandwidth—two parameters that often involve a trade-off. Here, we propose and demonstrate a slow light waveguide with large DBP using a pseudospin-polarized transverse electromagnetic mode. This waveguide features a folded edge configuration that supports a 200% relative bandwidth from quasistatic limit (zero frequency) and an arbitrarily large group index. Owing to the pseudospin-polarized design, the dense folding would not introduce backscattering and the associated group velocity dispersion (GVD). The resulting gapless linear dispersion and pulse transmission behavior in folded edge waveguide are observed in microwave experiments. Our scheme provides a way to overcome the trade-off between group index and working bandwidth in slow light waveguide, which has potential applications in broadband optical buffering, light-matter interaction enhancement, terahertz radiation source and time domain processing.

Small cell lung cancer (SCLC) is highly lethal due to its prevalent metastasis. Most SCLCs have inactivating mutations in TP53 and RB1. We find that loss of YAP expression is key for SCLC cells to acquire rapid ameboid migration and high metastatic potential. YAP functions through its target genes CCN1/CCN2 to inhibit SCLC ameboid migration. RB1 mutation contributes to YAP transcriptional silencing via E2F7, which recruits the RCOR co-repressor complex to YAP promoter. We discover that benzamide family HDAC inhibitors stimulate YAP expression by inhibiting the RCOR-HDAC complex, thereby suppressing SCLC metastasis and improving survival in a mouse model. Our study unveils the molecular and cellular basis underlying SCLCs high metastatic potential, the previously unrecognized role of YAP in suppressing ameboid migration and tumor metastasis, and the mechanism of YAP transcription regulation involving E2F7, RCOR, and Sin3 HDAC. This study reveals a therapeutic potential of benzamides for SCLC treatment.

To enhance the sensitivity, signal-to-noise ratio and durance of electrospray mass spectrometer, an off-axis ion guide combining a traveling-wave (TW) stacked-ring and a shaped ion funnel has been designed, which is capable of filtering out the neutral contaminants and charged droplets entrained in the electrospray plume. According to its structural characteristics, the corresponding TW and radio frequency (RF) coupling power supply and measurement as well as control system were designed. Customizable Ethernet communication protocol was used to control the field-programmable logic gate array (FPGA) for full-circuit signal control and generation, and an 8-channel traveling-wave amplitude monitoring was achieved through a 12-bit analog-to-digital converter (ADC) and a 16-bit digital-to-analog converter (DAC). In addition, dual-plane transformer coupling circuit was designed. The use of traveling wave changed the central reference frame of the RF, achieving the purpose of programmed RF and the effect of TW in the stacked-ring to provide axial kinetic energy. The stability and accuracy of the electrical parameters of the hardware system on the off-axis transmission structure were tested. The results showed that the controllable voltage range of TW power supply is 0.1-100 V and the controlled DC power supply’s full range detection and control absolute error are less than 0.04 V. The frequency of TW up to 400 kHz, both rising edge and falling edge are less than 30 ns. Furthermore, the waveforms of TW, RF and post-coupling waveform are sufficiently smooth. The test results also showed that the performance of the power supply and measurement and control system are stable and reliable, and their accuracy and range can satisfy the design requirements. Then, the performance of off-axis structure was tested under rough vacuum using reserpine ions. It was found that the reference voltage difference between the upper and lower traveling-waves (the voltage which the ions were extracted), the voltage of the upper traveling-waves, and the traveling-wave duty cycle of the off-axis ion transmitter have more significant effects on the off-axis transmission of ions than other electrical parameters. The experimental results provide a fundamental understanding of ion transport and off-axis separation of traveling-wave stacked-ring structures, which is valuable for the development of high signal-to-noise mass spectrometry system. In the future, this novel traveling-wave off-axis transmitter and its coupling power supply system will be applied to homemade mass spectrometry instruments. Besides, we will compare the developed device with the mainstream ion transmission devices in the market so as to further improve the device structure and power supply parameters, and deeply explore the role of traveling-wave off-axis transmitter in different ionization sources and different detectors.

Abstract The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Semaphorins were originally identified as axonal guidance molecules, but they also control processes such as vascular development and tumorigenesis. The downstream signaling cascades of Semaphorins in these biological processes remain unclear. Here, we show that the class 3 Semaphorins (SEMA3s) activate the Hippo pathway to attenuate tissue growth, angiogenesis, and tumorigenesis. SEMA3B restoration in lung cancer cells with SEMA3B loss of heterozygosity suppresses cancer cell growth via activating the core Hippo kinases LATS1/2 (large tumor suppressor kinase 1/2). Furthermore, SEMA3 also acts through LATS1/2 to inhibit angiogenesis. We identified p190RhoGAPs as essential partners of the SEMA3A receptor PlexinA in Hippo regulation. Upon SEMA3 treatment, PlexinA interacts with the pseudo-guanosine triphosphatase (GTPase) domain of p190RhoGAP and simultaneously recruits RND GTPases to activate p190RhoGAP, which then stimulates LATS1/2. Disease-associated etiological factors, such as genetic lesions and oscillatory shear, diminish Hippo pathway regulation by SEMA3. Our study thus discovers a critical role of Hippo signaling in mediating SEMA3 physiological function.

Abstract Small cell lung cancer (SCLC) is highly lethal due to its prevalent metastasis. Most SCLCs have inactivating mutations in TP53 and RB1. We find that loss of YAP expression is key for SCLC cells to acquire rapid ameboid migration and high metastatic potential. YAP functions through its target genes CCN1/CCN2 to inhibit SCLC ameboid migration. RB1 mutation contributes to YAP transcriptional silencing via E2F7, which recruits the RCOR co-repressor complex to YAP promoter. We discover that benzamide family HDAC inhibitors stimulate YAP expression by inhibiting the RCOR-HDAC complex, thereby suppressing SCLC metastasis and improving survival in a mouse model. Our study unveils the molecular and cellular basis underlying SCLC’s high metastatic potential, the previously unrecognized role of YAP in suppressing ameboid migration and tumor metastasis, and the mechanism of YAP transcription regulation involving E2F7, RCOR, and Sin3 HDAC. This study reveals a therapeutic potential of benzamides for SCLC treatment.

Abstract The development of chemically recyclable polymers serves as an attractive approach to address the global plastic pollution crisis. Monomer design principle is the key to achieving chemical recycling to monomer. Herein, we provide a systematic investigation to evaluate a range of substitution effects and structure−property relationships in the ɛ-caprolactone (CL) system. Thermodynamic and recyclability studies reveal that the substituent size and position could regulate their ceiling temperatures (T c). Impressively, M4 equipped with a tert-butyl group displays a T c of 241 °C. A series of spirocyclic acetal-functionalized CLs prepared by a facile two-step reaction undergo efficient ring-opening polymerization and subsequent depolymerization. The resulting polymers demonstrate various thermal properties and a transformation of the mechanical performance from brittleness to ductility. Notably, the toughness and ductility of P(M13) is comparable to the commodity plastic isotactic polypropylene. This comprehensive study is aimed to provide a guideline to the future monomer design towards chemically recyclable polymers.

Abstract Besides chiral edge states, the hallmark of quantum Hall insulators, antichiral edge states can exhibit unidirectional transport behavior but in topological semimetals. Although such edge states provide more flexibility for molding the flow of light, their realization usually suffers from time-reversal breaking. In this study, we propose the realization of antichiral surface states in a time-reversal-invariant manner and demonstrate our idea with a three-dimensional (3D) photonic metacrystal. Our system is a photonic semimetal possessing two asymmetrically dispersed Dirac nodal lines. Via dimension reduction, the nodal lines are rendered a pair of offset Dirac points. By introducing synthetic gauge flux, each two-dimensional (2D) subsystem with nonzero k z is analogous to a modified Haldane model, yielding a k z -dependent antichiral surface transport. Through microwave experiments, the bulk dispersion with asymmetric nodal lines and associated twisted ribbon surface states are demonstrated in our 3D time-reversal-invariant system. Although our idea is demonstrated in a photonic system, we propose a general approach to realize antichiral edge states in time-reversal-invariant systems. This approach can be easily extended to systems beyond photonics and may pave the way for further applications of antichiral transport.

Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in nature and possess a variety of biological activities. Up to date, only five fusicoccane-type diterpene synthases have been identified. Here, we identify a two-gene biosynthetic gene cluster containing a new fusicoccane-type diterpene synthase gene tadA and an associated cytochrome P450 gene tadB from Talaromyces wortmannii ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. D2O isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known fusicoccane-type diterpene synthases, in which a neutral intermediate is firstly formed and then protonated by an environmental proton. In addition, we demonstrate that the associated cytochrome P450 enzyme TadB is able to catalyze multiple oxidation of talaro-7,13-diene to yield talaro-6,13-dien-5,8-dione.

Ion mobility (IM) coupled mass spectrometry (MS) is a versatile tool for analytical separations, characterization, and detection by measuring collision cross-sections and mass-to-charge (m/z) ratios. Traveling wave (TW)-based structures for lossless ion manipulations (TW-SLIM) is an innovative ion drift tube for complex gas phase ion manipulations, which is the key component of traveling wave ion mobility spectrometry (TWIMS). TW-SLIM combines flexible ion path design and traveling wave technology. The traveling wave pulse power supply is used to provide an oscillatory electric fields. Ions in TWIMS are propelled and separated by traveling wave. The operating pressure, TW amplitude and TW frequency of TW pulse have effect on ion motion in TWIMS. In this work, a traveling wave pulse power supply was developed, which mainly consisted of field programmable gate array (FPGA), half-bridge gate driver integrated circuit (IC), metal-oxide-semiconductor field effect transistor (MOSFET), adjustable high voltage module and external trigger signal. The frequency of TW pulse power supply was up to 100 kHz, both rising edge and falling edge were less than 20 ns. The influence of TW amplitude and TW frequency on ions transmission and separation was explored on the home-built instrument platform. The experimental results presented here provide a fundamental understanding of the transmission and separation mechanism in TWIMS. The maximum signal intensity of hexakis (2, 2-difluoroethoxy) phosphazene was at amplitude of 35 V and frequency of 10 kHz. As the traveling wave frequency increased at a fixed traveling wave amplitude, signal intensity of hexakis (2, 2-difluoroethoxy) phosphazene decreased. Ions separations was positively related to frequency when traveling wave amplitude was fixed, while traveling wave amplitude was opposite. The development of traveling wave pulse power supply is valuable for research and development of high resolution TWIMS instrument.

Reliable photonuclear reaction rates in stellar conditions are essential for understanding the origin of the heavy stable neutron-deficient isotopes between ^74 Se and ^196 Hg, i.e., p -nuclei. However, many reaction rates of relevance still have to rely on the Hauser–Feshbach (HF) model due to the rarity of experimental progress. One such case is in the mass range of 160 for Dy, Er, Ho, and Tm isotopes. In this work we attempt to constrain the HF model in the TALYS package by reproducing the available experimental data on ^160 Dy( p , γ ) ^161 Ho and ^162 Er( p , γ ) ^163 Tm in the A ∼ 160 mass region, and examine the effects of level density, gamma strength function, and the optical model potential. The constrained model then allows us to calculate the reaction rates of ^157,159 Ho( γ , p ) and ^163,165 Tm( γ , p ) for the γ -process nucleosynthesis in a carbon-deflagration model for Type Ia supernovae. Our recommended rates differ from the JINA REACLIB by more than one order of magnitude in the temperature range 2–3 GK. This results in changes in the final abundance of p -nuclei in the A ∼ 160 mass range by −5.5% to 3% from those with JINA, which means that the uncertainty of ( γ , p ) reactions is not predominant for the synthesis of these nuclei.