A Nicotiana benthamiana receptor-like kinase regulates Phytophthora resistance by coupling with BAK1 to enhance elicitin-triggered immunity.

Cell-surface-localized leucine-rich-repeat receptor-like kinases (LRR-RLKs) are crucial for plant immunity. Most LRR-RLKs that act as receptors directly recognize ligands via a large extracellular domain (ECD), whereas LRR-RLK that serve as regulators are relatively small and contain fewer LRRs. Here, we identified LRR-RLK regulators using high-throughput tobacco rattle virus (TRV)-based gene silencing in the model plant Nicotiana benthamiana. We used the cell-death phenotype caused by INF1, an oomycete elicitin that induces pattern-triggered immunity, as an indicator. By screening 33 small LRR-RLKs (≤6 LRRs) of unknown function, we identified ELICITIN INSENSITIVE RLK 1 (NbEIR1) as a positive regulator of INF1-induced immunity and oomycete resistance. Nicotiana benthamiana mutants of eir1 generated by CRISPR/Cas9-editing showed significantly compromised immune responses to INF1 and were more vulnerable to the oomycete pathogen Phytophthora capsici. NbEIR1 associates with BRI1-ASSOCIATED RECEPTOR KINASE 1 (NbBAK1) and a downstream component, BRASSINOSTEROID-SIGNALING KINASE 1 (NbBSK1). NbBSK1 also contributes to INF1-induced defense and P. capsici resistance. Upon INF1 treatment, NbEIR1 was released from NbBAK1 and NbBSK1 in vivo. Moreover, the silencing of NbBSK1 compromised the association of NbEIR1 with NbBAK1. We also showed that NbEIR1 regulates flg22-induced immunity and associates with its receptor, FLAGELLIN SENSING 2 (NbFLS2). Collectively, our results suggest that NbEIR1 is a novel regulatory element for BAK1-dependent immunity. NbBSK1-NbEIR1 association is required for maintaining the NbEIR1/NbBAK1 complex in the resting state.

Al2 O3 -coated BiVO4 Photoanodes for Photoelectrocatalytic Regioselective C-H Activation of Aromatic Amines.

Photoelectrochemistry is becoming an innovative approach to organic synthesis. Generally, the current photoelectrocatalytic organic transformations suffer from limited reaction type, low conversion efficiency and poor stability. Herein, we develop efficient and stable photoelectrode materials using metal oxide protective layer, with a focus on achieving regioselective activation of amine compounds. Notably, our photoelectrochemistry process is implemented under mild reaction conditions and does not involve any directing groups, transition metals or oxidants. The results demonstrate that beyond photocatalysis and electrocatalysis, photoelectrocatalysis exhibits high efficiency, remarkable repeatability and good functional group tolerance, highlighting its great potential for applications.

Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade.

BACKGROUND: Mutations in BRCA1 or BRCA2 (BRCA1/2) cause homologous recombination deficiency (HRD). Ovarian cancer (OvCa) patients harbouring HRD beyond BRCA1/2 mutation result in a state referred to as "BRCAness". OvCa with BRCAness could benefit from PARP inhibitors. This study aims to identify a signature to detect the BRCAness population at the transcriptome level. METHODS: We used a rank-based algorithm to develop a qualitative BRCAness signature for OvCa. Upregulation of CXCL1 with downregulation of SV2A and upregulation of LY9 with downregulation of CHRNB3 were constructed as the BRCAness signature (2 gene pairs, 2-GPS) for OvCa. RESULTS: OvCa samples that were classified as BRCAness by 2-GPS showed improved overall survival, progression-free survival and exhibited increased multi-omics alterations in homologous recombination genes and enhanced sensitivity to immune checkpoint blockade. BRCAness cells were sensitive to PARP inhibitors. By biological experiments, we validated SKOV3 cells and patients with HRD exhibited higher expression of CXCL1 than SV2A and higher expression of LY9 than CHRNB3 at mRNA level. Both SKOV3 and A2780 with HRD were sensitive to mitomycin C, cisplatin and olaparib. CONCLUSIONS: In conclusion, 2-GPS could robustly predict BRCAness OvCa at the individual level and extend the population who may benefit from PARP inhibitors.

An F-box protein attenuates fungal xylanase-triggered immunity by destabilizing LRR-RLP NbEIX2 in a SOBIR1-dependent manner.

Receptor-like proteins (RLPs) lacking the cytoplasmic kinase domain play crucial roles in plant growth, development and immunity. However, what remains largely elusive is whether RLP protein levels are fine-tuned by E3 ubiquitin ligases, which are employed by receptor-like kinases for signaling attenuation. Nicotiana benthamiana NbEIX2 is a leucine-rich repeat RLP (LRR-RLP) that mediates fungal xylanase-triggered immunity. Here we show that NbEIX2 associates with an F-box protein NbPFB1, which promotes NbEIX2 degradation likely by forming an SCF E3 ubiquitin ligase complex, and negatively regulates NbEIX2-mediated immune responses. NbEIX2 undergoes ubiquitination and proteasomal degradation in planta. Interestingly, NbEIX2 without its cytoplasmic tail is still associated with and destabilized by NbPFB1. In addition, NbPFB1 also associates with and destabilizes NbSOBIR1, a co-receptor of LRR-RLPs, and fails to promote NbEIX2 degradation in the sobir1 mutant. Our findings reveal a distinct model of NbEIX2 degradation, in which an F-box protein destabilizes NbEIX2 indirectly in a SOBIR1-dependent manner.

A G-type lectin receptor-like kinase regulates the perception of oomycete apoplastic expansin-like proteins.

Phytophthora capsici is one of the most harmful pathogens in agriculture, which threatens the safe production of multiple crops and causes serious economic losses worldwide. Here, we identified a P. capsici expansin-like protein, PcEXLX1, by liquid chromatography-tandem mass spectrometry from Nicotiana benthamiana apoplastic fluid infected with P. capsici. Clustered regularly interspaced short palindromic repeats/crispr associated protein 9 (CRISPR/Cas9)-mediated PcEXLX1 knockout mutants exhibited significantly enhanced virulence, while the overexpression of PcEXLX1 impaired the virulence. Prokaryotically expressed PcEXLX1 activated multiple plant immune responses, which were BRI1-associated kinase 1 (BAK1)- and suppressor of BIR1-1 (SOBIR1)-dependent. Furthermore, overexpression of PcEXLX1 homologs in N. benthamiana could also increase plant resistance to P. capsici. A G-type lectin receptor-like kinase from N. benthamiana, expansin-regulating kinase 1 (ERK1), was shown to regulate the perception of PcEXLX1 and positively mediate the plant resistance to P. capsici. These results reveal that the expansin-like protein, PcEXLX1, is a novel apoplastic effector with plant immunity-inducing activity of oomycetes, perception of which is regulated by the receptor-like kinase, ERK1.

Transformation of Crowded Oligoarylene into Perylene-Cored Chiral Nanographene by Sequential Oxidative Cyclization and 1,2-Phenyl Migration.

Synthetic innovation for constructing sophisticated nanographenes is of fundamental significance for a variety of advanced applications. Herein, we report a distinctive method to prepare π-extended chiral nanographenes with 29 benzenoid rings and two helical breaches from a highly crowded perylene-cored oligoarylene precursor. Under Scholl's conditions, the reaction predominantly involves the regioselective and sequential cyclization in the peri- and bay regions of the perylene core, and the complanation of the 1-phenyl[5]helicene intermediate module via 1,2-phenyl migration. The resulting chiral nanographenes are configurationally stable at 180 °C due to the high diastereomerization barriers of ca. 45 kcal mol-1 . These molecules also possess globally delocalized π-systems with low HOMO/LUMO gaps, leading to nearly panchromatic absorption, intensive electronic circular dichroism signals and deep-red circularly polarized luminescence.

Cascaded stimulated Brillouin scattering erbium-doped fiber laser generating orbital angular momentum beams at tunable wavelengths.

We experimentally demonstrate a method to obtain central wavelength tunable orbital angular momentum beams with switchable topological charges (+1 or -1) in a stimulated Brillouin scattering erbium-doped fiber laser. Multiwavelength operation is achieved through cascaded stimulated Brillouin scattering in a single-mode fiber with a length of 6 km initiated by an external Brillouin pump. High-efficiency mode conversion between the fundamental mode and the orbital angular momentum modes is realized through a broadband two-mode long-period fiber grating. High-purity orbital angular momentum beams with up to 10 stable wavelength channels with a tuning range of 35 nm are achieved, which is the highest number of operating wavelengths and tuning range in an all-fiber laser for orbital angular momentum beam emission to the best of our knowledge. Both the operational central wavelength and number of operating wavelengths can be tuned by adjusting the primary pump power and the center wavelength of the tunable bandpass filter in conjunction with changing the Brillouin pump wavelength.

Accelerating H2 Evolution by Anodic Semi-dehydrogenation of Tetrahydroisoquinolines in Water over Co3 O4 Nanoribbon Arrays Decorated Nickel Foam.

Coupling the H2 evolution reaction in water with thermodynamically favorable organic oxidation reactions is highly desirable, because it can enhance the energy conversion efficiency compared with electrocatalytic water splitting, and produce value-added chemicals instead of O2 in the anodic reaction. Herein, Co3 O4 nanoribbon arrays in situ grown on nickel foam (Co3 O4 @NF) was employed as an effective electrocatalyst for the selective oxidation of tetrahydroisoquinolines (THIQs). Various value-added semi-dehydrogenation products including dihydroisoquinolines with electro-deficient or -rich groups could be obtained with moderate yields and faradaic efficiencies. Benefitting from the rich surface active sites of Co3 O4 @NF, a two-electrode (Co3 O4 @NF||Pt) electrolytic system drove a benchmark current density of 10 mA cm-2 at a cell voltage as low as 1.446 V in 1.0 M KOH aqueous solution containing 0.02 M THIQ, which was reduced by 174 mV in comparison with that of overall water splitting.

Neuropeptide Y mediates cardiac hypertrophy through microRNA-216b/FoxO4 signaling pathway.

Cardiac hypertrophy (CH) is a major risk factor for heart failure accompanied by maladaptive cardiac remodeling. The role and potential mechanism of neuropeptide Y (NPY) in CH are still unclear. We will explore the role and the mechanism of NPY inactivation (NPY-I) in CH caused by pressure overload. Abdominal aortic constriction (AAC) was used to induce CH model in rats. NPY or angiotensin II (Ang II) was used to trigger CH model in vitro in neonatal rat ventricular myocytes (NRVMs). We found that NPY was increased in the heart and plasma of hypertrophic rats. However, Ang II did not increase NPY expression in cardiomyocytes. NPY-I attenuated CH as decreasing CH-related markers (ANP, BNP and ß-MHC mRNA) level, reducing cell surface area, and restoring cardiac function. NPY inactivation increased miR-216b and decreased FoxO4 expression in CH heart. Moreover, NPY decreased miR-216b and increased FoxO4 expression in NRVMs which were reversed by NPY type 1 receptor (NPY1R) antagonist BIBO3304. MiR-216b mimic and FoxO4 siRNA (small interfering RNA) inhibited NPY/Ang II-induced myocardial hypertrophy in vitro. Meanwhile, BIBO3304 reversed the pro-hypertrophy effect of NPY in vitro. Collectively, NPY deficiency attenuated CH by NPY1R-miR-216b-FoxO4 axis. These findings suggested that NPY would be a potential therapeutic target for the prevention and treatment of cardiac hypertrophy.

A novel Danshensu/tetramethylpyrazine protects against Myocardial Ischemia Reperfusion Injury in rats.

A new Danshensu/tetramethylpyrazine derivative (ADTM) with cardio-protection effects such as antioxidant, arterial relaxation, pro-angiogenesis and antiplatelet activities. Platelet activating factor receptor (PAFR) plays a key role in myocardial ischemia reperfusion (MIR) injury. This study aims to investigate the protective role of ADTM in MIR injury and clarify the potential role of PAFR. We measured the effects of ADTM on MIR injury in rats in vivo and hypoxia re-oxygenation (HR) injury in neonatal rat ventricular myocytes (NRVMs) in vitro. The results show that ADTM can significantly improve the IR-induced decline in heart function as increasing EF and FS, and restore the decreased cardiac hemodynamic parameters (LVSP, ± dp/dt max) and increased the level of LVEDP, decrease the infarct size of damaged myocardium and lactate dehydrogenase (LDH) activity in serum. Additionally, ADTM inhibits cardiomyocytes apoptosis, caspase-3 activity, and inflammatory response as well as down-regulates the MIR-induced IL-1ß and TNFα production. Next, PAFR expression was significantly down-regulated in cardiomyocytes of MIR model in vivo and in vitro after treated with ADTM compare to IR group. At the same time, ADTM and PAFR small interfering RNA (siRNA) could inhibit cardiomyocytes apoptosis and inflammation during HR, while PAF presents the opposite effect. Furthermore, the above effects of PAF in HR induced cardiomyocytes were reversed by co-treatment of ADTM. Our findings demonstrate for the first time that ADTM protects against MIR injury through inhibition of PAFR signaling, which provides a new treatment for MIR.

LncRNA Miat knockdown alleviates endothelial cell injury through regulation of miR-214-3p/Caspase-1 signalling during atherogenesis.

Atherosclerosis is a common problem in healthy people around the world. Long noncoding RNAs (lncRNAs) play important roles in atherosclerosis. Myocardial infarction-associated transcript (Miat) is a cardiovascular disease-associated lncRNA. Its role and mechanism in atherosclerosis is still not fully clarified. Our study aims to explore the role and mechanism of lncRNA Miat in atherosclerosis. The atherosclerosis models were established both in vitro and in vivo. Real-time PCR was used to measure the expression of lncRNA Miat, miR-214, Caspase-1 and IL-1ß. Western blot was performed to detect the protein expression of Caspase-1. CCK-8 assay, Tunel staining, and flow cytometry analysis were conducted to detect proliferation and apoptosis of human aortic endothelial cells (HAECs), respectively. Oil red O staining and HE staining were used to evaluated the histological changes of the aorta. The results found that lncRNA Miat was upregulated in ox-LDL-induced atherosclerosis model in vitro. The inhibition of lncRNA Miat protects against ox-LDL-induced HAEC injury, presented as increased cell viability and decreased apoptosis. LncRNA Miat and miR-214 has binding site, and CASP1, which encodes Caspase-1, is a target of miR-214. The downregulation of lncRNA Miat increased the expression of miR-214-3p and decreased the expression of Caspase-1, as well as its downstream molecule IL-1ß in HAECs. However, the inhibition of miR-214-3p attenuated the effect of lncRNA Miat downregulation on HAECs. Furthermore, the downregulation of lncRNA Miat alleviated atherosclerosis in ApoE-deficient mice. Correspondingly, the expression of miR-214-3p was upregulated and Caspase-1 was downregulated after knockdown of lncRNA Miat. In conclusion, downregulation of lncRNA Miat exerts a protective effect against atherosclerosis through the regulation miR-214-3p/Caspase-1 signalling pathway. Therefore, the inhibition of lncRNA Miat expression may be an effective strategy in the treatment of atherosclerosis.

Molybdenum contamination dispersion from mining site to a reservoir.

This study was conducted to assess heavy metals in the overlying water and sediments of Luhun Reservoir, Henan Province, China, which is positioned downstream from a molybdenum (Mo) mining area. The pollution indexes indicated that deposition of all metals may have been affected by the mining area. The single element pollution factor (Pi) of Mo was the highest among all heavy metals, with a mean value of 2.05. However, the sediments were subject to long-term accumulation of metals, particularly Mo, Cd, Pb, and Zn, which originated from anthropogenic sources. The mean individual element potential ecological risk index values for Cd were above 385, while the mean value comprehensive potential ecological risk index was 465, which indicates a high ecological risk. Moreover, the enriched heavy metals had different spatial distributions in the Luhun Reservoir sediments. Finally, Pearson correlation analysis indicated that the Pb was mainly affected by different anthropogenic sources and had no relationship with other metals, which suggests that the influence of mining area on heavy metal concentrations in the reservoir is difficult to disentangle.

Electron transfer involved in bio-Pd (0) synthesis by Citrobacter freundii at different growth phases.

Gram-negative Citrobacter freundii with high Pd (II) reduction capacity was isolated from electroplating wastewater, and the electron transfer involved in Pd (II) bio-reduction by C. freundii JH was investigated in phosphate buffer saline solution with sodium formate as sole electron donor under anaerobic condition. FTIR spectra indicated that hydroxyl and amine groups on cell wall participated Pd (II) bio-sorption. TEM, XRD, XPS results confirmed that Pd (0) nanoparticles (NPs) could be bio-synthesized intra/extracellularly. Meanwhile, pH turn-over were observed owing to the reduction of cytochrome c (c-Cyt) in bio-reduction process. EPR spectra indicated that free radicals (OH) was generated from high concentration Pd (II), which would cause seriously damage to cell. Despite of the lower tolerance to Pd (II), the cells at logarithmic phase exhibited higher Pd (II) reduction capacity (72.21%) than that at stationary phase (56.21%), which might be related to the relatively stronger proton motive force (PMF) created by the substrate oxidation and the electron transfer, as evidenced by electrochemical experiments (CV, DPV, amperometric I-t curves) and protein denaturalization experiments. Additionally, c-Cyt and riboflavin were confirmed to be important participants in electron transfer. Finally, a putative synthesis mechanism of Pd (0)-NPs was deduced. This study contributed to further understanding the electron transfer in Pd (II) reduction, and provided more information for the bio-synthetic of metal nanoparticles.

Direct Arylation of Unactivated Alkanes with Heteroarenes by Visible-Light Catalysis.

The functionalization of aliphatic C-H bonds is both a major challenge and a desirable goal in organic synthesis. Here, we describe the successful arylation of unactivated alkanes with heteroarenes by using iridium polypyridyl complexes as the photocatalyst and persulfate as the HAT catalyst precursor under visible-light irradiation. This reaction features good functional group tolerance and broad scope with regard to both alkane and heteroarene substrates (37 examples), which allows direct access to alkyl-substituted N-heteroarenes, a key structural motif in natural products and bioactive molecules.

Surface-emitting distributed feedback laser based on high-order gratings.

This paper reports a surface-emitting (SE) distributed feedback laser based on high-order surface gratings. The proposed device not only retains the advantages of edge-emitting lasers such as excellent single-mode property, high internal quantum efficiency, and high output power but also obtains other appealing characteristics, such as easy realization of the hybrid integration, the simple fabrication process, etc. The SE distributed feedback laser is analyzed and optimized for better performances using an improved traveling wave model.

High efficiency all-fiber cylindrical vector beam laser using a long-period fiber grating.

We demonstrate a novel all-fiber laser generating cylindrical vector beams with high slope efficiency and low threshold by introducing a long-period fiber grating into the laser cavity. Highly efficient mode conversion is realized by an LPFG at ∼1548 nm. Mode selection and spectrum filtering are achieved in combination with a two-mode fiber Bragg grating (TM-FBG). The fiber laser operates at a single wavelength of 1547.95 nm with a 30 dB linewidth of less than 0.18 nm and a side-mode suppression ratio (SMSR) of more than 56 dB. The lasing threshold and slope efficiency of the laser are 24.5 mW and 35.41%, respectively. The output power is 72 mW with an absorbed pump power of 225 mW. The variation of slope efficiency with respect to the reflectivity of the TM-FBG is investigated. Through adjusting the intra-cavity polarization controller, high-purity radially and azimuthally polarized beams are both obtained.

Suppression of AKT expression by miR-153 produced anti-tumor activity in lung cancer.

Lung cancer is one of the leading causes of cancer death worldwide. microRNAs have been shown to be a novel class of regulators in lung cancer. Here, we explored the role of miR-153 in the pathogenesis of lung cancer and its therapeutic potential. miR-153 was significantly decreased in lung cancer tissues than the adjacent tissues. The protein and mRNA levels of protein kinase B (AKT), which were shown to promote tumor growth, were both increased in lung cancer tissues than adjacent tissues. Overexpression of miR-153 significantly inhibited AKT protein expression, which were abrogated by co-transfection of AMO-153, the specific inhibitor of miR-153. Luciferase assay showed that transfection of miR-153 markedly suppressed the fluorescent intensity of chimeric vectors carrying the 3'UTR of AKT1, while produced no effect on the mutant construct, indicating that AKT is regulated by miR-153. Overexpression of miR-153 significantly inhibited the proliferation and migration, and promoted apoptosis of cultured lung cancer cells in vitro, and suppressed the growth of xenograft tumors in vivo. Interestingly, lung cancer cells with lower endogenous miR-153 expression are more sensitive to ectopic overexpressed miR-153. The IC50 of miR-153 on lung cancer cells is positive correlated with the endogenous miR-153 level, while negative correlated with AKT level. Knockdown of AKT expression suppressed lung cancer cell proliferation. In summary, miR-153 exerted anti-tumor activity in lung cancer by targeting on AKT. The sensitivity of lung cancer cells to miR-153 is determined by its endogenous miR-153 level.

The human epididymis protein 4 acts as a prognostic factor and promotes progression of gastric cancer.

Human epididymis protein 4 (HE4), represented as an epididymis-specific gene and designated a WAP four-disulfide core domain protein 2 (WFDC2), is amplified in many tumors. However, little is known about its clinical significance and biological function in gastric carcinomas. We found that HE4 was more commonly observed in gastric carcinoma tissues than in normal tissues and was significantly correlated with Lauren classification, TNM stage, and tumor size by immunohistochemistry. The overall survival rate of patients with HE4 low expression was significantly higher than that of the patients with HE4 high expression. In addition, silencing of HE4 expression inhibits cell proliferation and migration and enhances cell apoptosis. Subsequent studies reveal that the Src, Akt, and Erk1/2 signaling may be involved with pro-survival and anti-apoptotic effects of the HE4 on gastric cancer cells. Taken together, this study provides new evidence on promotive effects of the HE4 on gastric cancer progression and indicates that HE4 might be a promising prognostic factor for gastric cancer diagnosis.

TRPV3 regulates Breast Cancer Cell Proliferation and Apoptosis by EGFR/AKT pathway.

Breast cancer (BC) is one of the most common cancer types worldwide and the first cause of cancer-related deaths in women. Transient receptor potential vanillin 3 (TRPV3) has been preliminarily discovered to play an important role in various cancers, including BC. Here, we explored the effect of TRPV3 on breast cancer cells and its potential mechanism. TRPV3 level was measured in BC tissue and adjacent noncancerous breast tissue using real-time RT-PCR and Western blot. Wound healing was used to detect cell migration. MTT and EDU were detected cell proliferation. TUNEL and Caspase-3 activity were used to detect cell apoptosis. We found that TRPV3 expression significantly increased in both human BC tissues and breast cells line. TRPV3 siRNA (TRPV3 inhibition) dramatically suppressed cell migration and proliferation, promoted the apoptosis, and decreased [Ca2+]i; whereas Carvacrol (TRPV3 agonist) has opposite effect in MCF-7 cells. We validated EGFR (Epidermal growth factor receptor) is a direct target protein of TRPV3. Mechanism studies have shown that Carvacrol increased phosphorylation levels of EGFR and AKT, and were decreased by suppression of TRPV3. Moreover, Erlotinib (EGFR inhibitor) and LY294002 (PI3K inhibitor) diminished Carvacrol induced cell migration and proliferation, promoted cell apoptosis, and increased [Ca2+]i in Carvacrol group. Our results collectively suggest that TRPV3 siRNA inhibits migration and proliferation, and promoted apoptosis in breast cancer cells by EGFR/AKT pathway. These findings indicate that TRPV3 may represent a novel therapeutic strategy for breast cancer.

Using GC-O-MS, GC-IMS, and chemometrics to investigate flavor component succession regularity in the Niulanshan Erguotou Baijiu brewing process.

The volatile compounds in Dacha liquor (DL) and Ercha liquor (EL) from Niulanshan Erguotou Baijiu (NEB) were analyzed. The results demonstrated that a total of 34 odorants were identified. For the first time, the products of different brewing stages were analyzed using temperature-programmed headspace gas chromatography-ion mobility spectrometry (TP-HS-GC-IMS). The 3D fingerprint obtained revealed that the compounds exhibited different change patterns during the brewing process. Furthermore, the results of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) revealed that hexanal, 3-hydroxy-2-butanone, trans-2-pentenal, and ethyl hexanoate could be used to distinguish different types of fermented grains; and hexanal, 1-pentanol, methyl isovalerate, isoamyl acetate, 3-hydroxy-2-butanone, ethyl hexanoate, ethyl acetate, ethyl 2-methylbutanoate, and ethyl pentanoate could be used to distinguish different types of distilled spirits. This study serves as a useful reference for enhancing quality control measures in the production of NEB.