RVFV virulence factor NSs triggers the mitochondrial MCL-1-BAK axis to activate pathogenic NLRP3 pyroptosis.

Infection of Rift Valley fever virus (RVFV), a highly pathogenic mosquito-borne zoonotic virus, triggers severe inflammatory pathogenesis but the underlying mechanism of inflammation activation is currently unclear. Here, we report that the non-structural protein NSs of RVFV triggers mitochondrial damage to activate the NLRP3 inflammasome leading to viral pathogenesis in vivo. It is found that the host transcription inhibition effect of NSs causes rapid down-regulation of myeloid cell leukemia-1(MCL-1), a pro-survival member of the Bcl-2 (B-cell lymphoma protein 2) protein family. MCL-1 down-regulation led to BAK activation in the mitochondria, which triggered mtROS production and release of oxidized mitochondrial DNA (ox-mtDNA) into the cytosol. Cytosolic ox-mtDNA binds and activates the NLRP3 inflammasome triggering NLRP3-GSDMD pyroptosis in RVFV infected cells. A NSs mutant virus (RVFV-NSsRM) that is compromised in inducing transcription inhibition did not trigger MCL-1 down-regulation nor NLRP3-GSDMD pyroptosis. RVFV infection of the Nlrp3-/- mouse model demonstrated that the RVFV-triggered NLRP3 pyroptosis contributed to RVFV inflammatory pathogenesis and fatal infection in vivo. Infection with the RVFV-NSsRM mutant virus similarly showed alleviated inflammatory pathogenesis and reduced fatality rate. Taken together, these results revealed a mechanism by which a virulence factor activates the mitochondrial MCL-1-BAK axis through inducing host transcription inhibition to trigger NLRP3-dependent inflammatory pathogenesis.

Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Gibberellins regulate masculinization through the SpGAI-SpSTM module in dioecious spinach.

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3, showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.

Rift Valley Fever Virus Nucleoprotein Triggers Autophagy to Dampen Antiviral Innate Immune Responses.

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes severe and potentially fatal hemorrhagic fever in humans. Autophagy is a self-degradative process that can restrict viral replication at multiple infection steps. In this study, we evaluated the effects of RVFV-triggered autophagy on viral replication and immune responses. Our results showed that RVFV infection triggered autophagosome formation and induced complete autophagy. Impairing autophagy flux by depleting autophagy-related gene 5 (ATG5), ATG7, or sequestosome 1 (SQSTM1) or treatment with autophagy inhibitors markedly reduced viral RNA synthesis and progeny virus production. Mechanistically, our findings demonstrated that the RVFV nucleoprotein (NP) C-terminal domain interacts with the autophagy receptor SQSTM1 and promotes the SQSTM1-microtubule-associated protein 1 light chain 3 B (LC3B) interaction and autophagy. Deletion of the NP C-terminal domain impaired the interaction between NP and SQSTM1 and its ability to trigger autophagy. Notably, RVFV-triggered autophagy promoted viral infection in macrophages but not in other tested cell types, including Huh7 hepatocytes and human umbilical vein endothelial cells, suggesting cell type specificity of this mechanism. It was further revealed that RVFV NP-triggered autophagy dampens antiviral innate immune responses in infected macrophages to promote viral replication. These results provide novel insights into the mechanisms of RVFV-triggered autophagy and indicate the potential of targeting the autophagy pathway to develop antivirals against RVFV. IMPORTANCE We showed that RVFV infection induced the complete autophagy process. Depletion of the core autophagy genes ATG5, ATG7, or SQSTM1 or pharmacologic inhibition of autophagy in macrophages strongly suppressed RVFV replication. We further revealed that the RVFV NP C-terminal domain interacted with SQSTM1 and enhanced the SQSTM1/LC3B interaction to promote autophagy. RVFV NP-triggered autophagy strongly inhibited virus-induced expression of interferon-stimulated genes in infected macrophages but not in other tested cell types. Our study provides novel insights into the mechanisms of RVFV-triggered autophagy and highlights the potential of targeting autophagy flux to develop antivirals against this virus.

Preparation of Multistage Pore TS-1 with Enhanced Photocatalytic Activity, Including Process Studies and Artificial Neural Network Modeling for Synergy Assessment.

Antibiotic residues have been found in several aquatic ecosystems as a result of the widespread use of antibiotics in recent years, which poses a major risk to both human health and the environment. At present, photocatalytic degradation is the most effective and environmentally friendly method. Titanium silicon molecular sieve (TS-1) has been widely used as an industrial catalyst, but its photocatalytic application in wastewater treatment is limited due to its small pores and few active sites. In this paper, we report a method for preparing multistage porous TS-1 with a high specific surface area by alkali treatment. In the photocatalytic removal of CIP (ciprofloxacin) antibiotic wastewater experiments, the alkali-treated catalyst showed better performance in terms of interfacial charge transfer efficiency, which was 2.3 times higher than that of TS-1 synthesized by the conventional method, and it was found to maintain better catalytic performance in the actual water source. In addition, this research studied the effects of solution pH, contaminant concentration, and catalyst dosage on CIP degradation, while liquid chromatography-mass spectrometry (LC-MS) was used to identify intermediates in the degradation process and infer possible degradation pathways and the toxicity of CIP, and its degradation product was also analyzed using ECOSAR 2.2 software, and most of the intermediates were found to be nontoxic and nonharmful. Finally, a 3:5:1 artificial neural network model was established based on the experiments, and the relative importance of the influence of experimental conditions on the degradation rate was determined. The above results confirmed the feasibility and applicability of photocatalytic treatment of wastewater containing antibiotics using visible light excitation alkali post-treatment TS-1, which provided technical support and a theoretical basis for the photocatalytic treatment of wastewater containing antibiotics.

Biochar application regulates organic phosphorus fractions and the release of available phosphorus in farmland soil.

BACKGROUND: The relationship between phosphorus (P) related enzymatic activity and organic P turnover remains unclear, particularly in the context of biochar application. Field experiments were conducted on Phaeozem and Luvisol soil types to investigate the effects of biochar application rates - 0 t ha-1 (CK), 22.5 t ha-1 (D1), 67.5 t ha-1 (D2), and 112.5 t ha-1 (D3) - on soil organic fractions using 31P nuclear magnetic resonance (NMR) spectroscopy and relevant phosphatase activity. RESULTS: The application of biochar increased the soil organic carbon (SOC), pyrophosphate (pyro), and orthophosphate (ortho) content, as well as the acid phosphomonoesterase (AcP), alkaline phosphomonoesterase (AlP), inorganic pyrophosphatase (IPP), and phosphodiesterase (PD) activities. Biochar application also increased soil organic P (OPa), the sum of inorganic P forms (IP), ortho, monoesters, and myo-IHP contents, the pH value, AlP and PD activities in Phaeozem, but it significantly reduced diesters, polyphosphate (poly) contents, and IPP and AcP activities compared to those in Luvisol. Acid phosphomonoesterase and PD activities also showed an opposite trend in Luvisol. The structural equation model showed that the potential mechanism of organic P turnover in response to biochar application differed depending on the soil types, potentially influenced by P availability. CONCLUSION: Overall, the findings of this study enhance the comprehension of the variation of P fractions and their availability in the context of biochar application for agricultural production in northeastern China. © 2024 Society of Chemical Industry.

Lineage-specific amplification and epigenetic regulation of LTR-retrotransposons contribute to the structure, evolution, and function of Fabaceae species.

BACKGROUND: Long terminal repeat (LTR)-retrotransposons (LTR-RTs) are ubiquitous and make up the majority of nearly all sequenced plant genomes, whereas their pivotal roles in genome evolution, gene expression regulation as well as their epigenetic regulation are still not well understood, especially in a large number of closely related species. RESULTS: Here, we analyzed the abundance and dynamic evolution of LTR-RTs in 54 species from an economically and agronomically important family, Fabaceae, and also selected two representative species for further analysis in expression of associated genes, transcriptional activity and DNA methylation patterns of LTR-RTs. Annotation results revealed highly varied proportions of LTR-RTs in these genomes (5.1%~68.4%) and their correlation with genome size was highly positive, and they were significantly contributed to the variance in genome size through species-specific unique amplifications. Almost all of the intact LTR-RTs were inserted into the genomes 4 Mya (million years ago), and more than 50% of them were inserted in the last 0.5 million years, suggesting that recent amplifications of LTR-RTs were an important force driving genome evolution. In addition, expression levels of genes with intronic, promoter, and downstream LTR-RT insertions of Glycine max and Vigna radiata, two agronomically important crops in Fabaceae, showed that the LTR-RTs located in promoter or downstream regions suppressed associated gene expression. However, the LTR-RTs within introns promoted gene expression or had no contribution to gene expression. Additionally, shorter and younger LTR-RTs maintained higher mobility and transpositional potential. Compared with the transcriptionally silent LTR-RTs, the active elements showed significantly lower DNA methylation levels in all three contexts. The distributions of transcriptionally active and silent LTR-RT methylation varied across different lineages due to the position of LTR-RTs located or potentially epigenetic regulation. CONCLUSION: Lineage-specific amplification patterns were observed and higher methylation level may repress the activity of LTR-RTs, further influence evolution in Fabaceae species. This study offers valuable clues into the evolution, function, transcriptional activity and epigenetic regulation of LTR-RTs in Fabaceae genomes.

A rapid method for assembly of single chromosome and identification of sex determination region based on single-chromosome sequencing.

The sex-determining-region (SDR) may offer the best prospects for studying sex-determining gene, recombination suppression, and chromosome heteromorphism. However, current progress of SDR identification and cloning showed following shortcomings: large near-isogenic lines need to be constructed, and a relatively large population is needed; the cost of whole-genome sequencing and assembly is high. Herein, the X/Y chromosomes of Spinacia oleracea L. subsp. turkestanica were successfully microdissected and assembled using single-chromosome sequencing. The assembly length of X and Y chromosome is c. 192.1 and 195.2 Mb, respectively. Three large inversions existed between X and Y chromosome. The SDR size of X and Y chromosome is c. 13.2 and 24.1 Mb, respectively. MSY region and six male-biased genes were identified. A Y-chromosome-specific marker in SDR was constructed and used to verify the chromosome assembly quality at cytological level via fluorescence in situ hybridization. Meanwhile, it was observed that the SDR located on long arm of Y chromosome and near the centromere. Overall, a technical system was successfully established for rapid cloning the SDR and it is also applicable to rapid assembly of specific chromosome in other plants. Furthermore, this study laid a foundation for studying the molecular mechanism of sex chromosome evolution in spinach.

Virulence, antimicrobial resistance, and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae in a hospital in Shijiazhuang City from China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), as one of the most common drug-resistant bacteria threatening human health, is hyper-resistant to multiple antimicrobial drugs and carbapenems, which can be dealt with only limited clinical treatment options. This study described the epidemiological characteristics of CRKP in this tertiary care hospital from 2016 to 2020. Specimen sources included blood, sputum, alveolar lavage fluid, puncture fluid, secretions from a burn wound, and urine. Among the 87 carbapenem-resistant strains, ST11 was the predominant isolate, followed by ST15, ST273, ST340, and ST626. These STs were in broad agreement with the STs defined by pulsed-field gel electrophoresis clustering analysis in discriminating clusters of related strains. Most CRKP isolates contained the blaKPC-2 gene, some isolates carried the blaOXA-1, blaNDM-1, and blaNDM-5 genes, and the isolates carrying carbapenem resistance genes were more resistant to the antimicrobials of ß-lactams, carbapenems, macrolides, and fluoroquinolone. The OmpK35 and OmpK37 genes were detected in all CRKP strains, and the Ompk36 gene was detected in some CRKP strains. All detected OmpK37 had 4 mutant sites, and OmpK36 had 11 mutant sites, while no mutant sites were found in OmpK35. More than half of the CRKP strains contained the OqxA and OqxB efflux pump genes. The virulence genes were most commonly combined with urea-wabG-fimH-entB-ybtS-uge-ycf. Only one CRKP isolate was detected with the K54 podoconjugate serotype. This study elucidated the clinical epidemiological features and molecular typing of CRKP, and grasped the distribution of drug-resistant genotypes, podocyte serotypes, and virulence genes of CRKP, providing some guidance for the subsequent treatment of CRKP infection.

A Multitask Network for People Counting, Motion Recognition, and Localization Using Through-Wall Radar.

Due to the outstanding penetrating detection performance of low-frequency electromagnetic waves, through-wall radar (TWR) has gained widespread applications in various fields, including public safety, counterterrorism operations, and disaster rescue. TWR is required to accomplish various tasks, such as people detection, people counting, and positioning in practical applications. However, most current research primarily focuses on one or two tasks. In this paper, we propose a multitask network that can simultaneously realize people counting, action recognition, and localization. We take the range-time-Doppler (RTD) spectra obtained from one-dimensional (1D) radar signals as datasets and convert the information related to the number, motion, and location of people into confidence matrices as labels. The convolutional layers and novel attention modules automatically extract deep features from the data and output the number, motion category, and localization results of people. We define the total loss function as the sum of individual task loss functions. Through the loss function, we transform the positioning problem into a multilabel classification problem, where a certain position in the distance confidence matrix represents a certain label. On the test set consisting of 10,032 samples from through-wall scenarios with a 24 cm thick brick wall, the accuracy of people counting can reach 96.94%, and the accuracy of motion recognition is 96.03%, with an average distance error of 0.12 m.

Molecular Defensive Mechanism of Echinacea purpurea (L.) Moench against PAH Contaminations.

The understanding of the molecular defensive mechanism of Echinacea purpurea (L.) Moench against polycyclic aromatic hydrocarbon (PAH) contamination plays a key role in the further improvement of phytoremediation efficiency. Here, the responses of E. purpurea to a defined mixture of phenanthrene (PHE) and pyrene (PYR) at different concentrations or a natural mixture from an oilfield site with a history of several decades were studied based on transcriptomics sequencing and widely targeted metabolomics approaches. The results showed that upon 60-day PAH exposure, the growth of E. purpurea in terms of biomass (p < 0.01) and leaf area per plant (p < 0.05) was negatively correlated with total PAH concentration and significantly reduced at high PAH level. The majority of genes were switched on and metabolites were accumulated after exposure to PHE + PYR, but a larger set of genes (3964) or metabolites (208) showed a response to a natural PAH mixture in E. purpurea. The expression of genes involved in the pathways, such as chlorophyll cycle and degradation, circadian rhythm, jasmonic acid signaling, and starch and sucrose metabolism, was remarkably regulated, enhancing the ability of E. purpurea to adapt to PAH exposure. Tightly associated with transcriptional regulation, metabolites mainly including sugars and secondary metabolites, especially those produced via the phenylpropanoid pathway, such as coumarins, flavonoids, and their derivatives, were increased to fortify the adaptation of E. purpurea to PAH contamination. These results suggest that E. purpurea has a positive defense mechanism against PAHs, which opens new avenues for the research of phytoremediation mechanism and improvement of phytoremediation efficiency via a mechanism-based strategy.

Fine-Grained Radio Frequency Fingerprint Recognition Network Based on Attention Mechanism.

With the rapid development of the internet of things (IoT), hundreds of millions of IoT devices, such as smart home appliances, intelligent-connected vehicles, and wearable devices, have been connected to the network. The open nature of IoT makes it vulnerable to cybersecurity threats. Traditional cryptography-based encryption methods are not suitable for IoT due to their complexity and high communication overhead requirements. By contrast, RF-fingerprint-based recognition is promising because it is rooted in the inherent non-reproducible hardware defects of the transmitter. However, it still faces the challenges of low inter-class variation and large intra-class variation among RF fingerprints. Inspired by fine-grained recognition in computer vision, we propose a fine-grained RF fingerprint recognition network (FGRFNet) in this article. The network consists of a top-down feature pathway hierarchy to generate pyramidal features, attention modules to locate discriminative regions, and a fusion module to adaptively integrate features from different scales. Experiments demonstrate that the proposed FGRFNet achieves recognition accuracies of 89.8% on 100 ADS-B devices, 99.5% on 54 Zigbee devices, and 83.0% on 25 LoRa devices.

Identification of Sex Differentiation-Related microRNAs in Spinach Female and Male Flower.

Sex determination and differentiation is an important biological process for unisexual flower development. Spinach is a model plant to study the mechanism of sex determination and differentiation of dioecious plant. Till now, little is known about spinach sex determination and differentiation mechanism. MicroRNAs are key factors in flower development. Herein, small RNA sequencing was performed to explore the roles of microRNAs in spinach sex determination and differentiation. As a result, 92 known and 3402 novel microRNAs were identified in 18 spinach female and male flower samples. 74 differentially expressed microRNAs were identified between female and male flowers, including 20 female-biased and 48 male-biased expression microRNAs. Target prediction identified 22 sex-biased microRNA-target pairs, which may be involved in spinach sex determination or differentiation. Among the differentially expressed microRNAs between FNS and M03, 55 microRNAs were found to reside in sex chromosome; one of them, sol-miR2550n, was functionally studied via genetic transformation. Silencing of sol-miR2550n resulted in abnormal anther while overexpression of sol-miR2550n induced early flowering, indicating sol-miR2550n was a male-promoting factor and validating the reliability of our small RNA sequencing data. Conclusively, this work can supply valuable information for exploring spinach sex determination and differentiation and provide a new insight in studying unisexual flower development.

Impact of LTR-Retrotransposons on Genome Structure, Evolution, and Function in Curcurbitaceae Species.

Long terminal repeat (LTR)-retrotransposons (LTR-RTs) comprise a major portion of many plant genomes and may exert a profound impact on genome structure, function, and evolution. Although many studies have focused on these elements in an individual species, their dynamics on a family level remains elusive. Here, we investigated the abundance, evolutionary dynamics, and impact on associated genes of LTR-RTs in 16 species in an economically important plant family, Cucurbitaceae. Results showed that full-length LTR-RT numbers and LTR-RT content varied greatly among different species, and they were highly correlated with genome size. Most of the full-length LTR-RTs were amplified after the speciation event, reflecting the ongoing rapid evolution of these genomes. LTR-RTs highly contributed to genome size variation via species-specific distinct proliferations. The Angela and Tekay lineages with a greater evolutionary age were amplified in Trichosanthes anguina, whereas a recent activity burst of Reina and another ancient round of Tekay activity burst were examined in Sechium edule. In addition, Tekay and Retand lineages belonging to the Gypsy superfamily underwent a recent burst in Gynostemma pentaphyllum. Detailed investigation of genes with intronic and promoter LTR-RT insertion showed diverse functions, but the term of metabolism was enriched in most species. Further gene expression analysis in G.pentaphyllum revealed that the LTR-RTs within introns suppress the corresponding gene expression, whereas the LTR-RTs within promoters exert a complex influence on the downstream gene expression, with the main function of promoting gene expression. This study provides novel insights into the organization, evolution, and function of LTR-RTs in Cucurbitaceae genomes.

The effect of nursing intervention based on the staged behaviour change on recovery, quality of life, and self-efficacy of diabetic patients with scalds.

This study aimed to explore the impact of nursing intervention based on staged behaviour change (SBC) on the quality of life (QoL) and self-efficacy of diabetic patients with scalds. From January 2020 to January 2021, a total of 82 consecutive cases with diabetes and scalds were prospectively enrolled in this study. They were divided into the SBC group (41 cases were given SBC-based nursing intervention) and the control group (41 cases were given routine intervention) using the random number table method. The granulation tissue growth time and wound healing time were compared between the two groups. Pain intensity, QoL, self-efficacy, and score of wound exudation at 3, 7, and 15 days after intervention were observed. The granulation tissue growth time and wound healing time of the SBC group were lower than those of the control group with statistical difference (P < 0.05). The 3-, 5-, and 7-day pain intensity of the SBC group were all lower than those of the control group, with statistical difference (P < 0.05, respectively). Before intervention, there were no significant differences in mental health, role emotional, social function, vitality status, physical pain, role physical, physical function, and general health between the two groups (P > 0.05, respectively). After intervention, the above indicators of the SBC group were significantly higher than those of the control group (P < 0.05, respectively). Before intervention, there were no significant differences between the two groups in communication with doctors, emotional communication, role function, symptom management, medication as prescribed, and control of water and salt intake and nutrition (P > 0.05, respectively). After intervention, the above indicators in the SBC group were all significantly higher than those in the control group (P < 0.05, respectively). The score of wound exudation of the SBC group was lower than that of the control group after intervention (P < 0.05). SBC-based nursing intervention can effectively improve the QoL and self-efficacy of diabetic patients with scalds and can effectively promote wound healing, and can be recommended for clinical use.

Ultra-compact silicon-microcap based improved Michelson interferometer high-temperature sensor.

An ultra-short high-temperature fiber-optic sensor based on a silicon-microcap created by a single-mode fiber (SMF) and simple fusion splicing technology is proposed and experimentally demonstrated. A section of the SMF with a silicon-microcap at one end is connected to the "peanut" structure to build the microcap-based optical fiber improved Michelson interferometer (MI). The optimal discharge parameters of microcap and length of SMF has been investigated to achieve the best extinction ratio of 6.61 dB. The size of this microcap-based improved MI sensor is 560 µm and about 18 times shorter compared to the current fiber tip interferometers (about 10 mm). Meanwhile, it showed good robustness during the two heating-cooling cycles and the duration period stability test at 900 °C. This microcap-based improved MI sensor with the smaller size, simple fabrication, low cost, high reliability, and good linearity within a large dynamic range is beneficial to practical temperature measurement and massive production.

Discovery of novel 2H-chromene-3-carbonyl derivatives as selective estrogen receptor degraders (SERDs): Design, synthesis and biological evaluation.

Selective estrogen receptor degraders (SERDs) not only block ERα activity but degrade this receptor at the same time and are effective in relapsed ERα positive breast cancer patients who have accepted other endocrine therapies. Herein, through scaffold hopping of coumarin skeleton, a series of 2H-chromene-3-carbonyl-based SERDs with phenyl acrylic acid group as the side chain were designed and synthesized. Compound XH04 containing 7-hydroxy-2H-chromene-3-carbonyl skeleton exhibited the most potent activities in 2D (IC50 = 0.8 µM) and 3D cells culture models (MCF-7) and had the best ERα binding affinity as well. Furthermore, the significant antiestrogen property of compound XH04 was confirmed by inhibiting the expression of progesterone receptor (PgR) mRNA in MCF-7 cells. On the other hand, the outgoing ERα degradation property of compound XH04 was qualitatively and quantificationally verified by immunofluorescence analysis and Western blot assay in MCF-7 cells. Besides, compound XH04 repressed the expression level of Ki67 in MCF-7 cells and induced the apoptosis increase of this tumor cells in a dose-dependent manner like approved-SERD fulvestrant (2), while compound XH04 exhibited better preliminary pharmacokinetics in human and rat liver microsomes in vitro and a lower LogD7.4 value than fulvestrant. And further molecular docking study revealed that compound XH04 possessed a proverbial and typical binding model with ERα like other reported SERD. All these results confirmed that 7-hydroxy-2H-chromene-3-carbonyl structure could be a feasible skeleton for design of ERα antagonists including SERDs and compound XH04 is a promising candidate for further development of ERα + breast cancer therapy agents.

Simultaneous temperature and refractive index sensor based on an L-like Michelson interferometer.

We experimentally demonstrate, to the best of our knowledge, temperature and refractive index (RI) sensing with a novel L-like Michelson interferometer (MI). Two MIs are designed based on single-mode fiber (SMF) and multimode fiber (MMF), respectively, fabricated via an oxyhydrogen flame and a rotatable platform. By comparative experiments on the size and bent degree of the sensor, the corresponding parameters of the sensor with excellent performance are determined for measurement experiments. The RI sensitivity of the SMF L-like MI reaches -131.0nm/RIU, and the highest temperature sensitivity is 94.17 pm/°C. The highest RI of the MMF L-like MI is 176.5 nm/RIU, and the temperature sensitivity is 104.2 pm/°C. The L-like MI has advantages of low cost and easy fabrication, and is a promising temperature and RI sensor in a wide range of measurements.

High-sensitivity transverse-load and high-temperature sensor based on the cascaded Vernier effect.

In this paper, we demonstrate a novel, to the best of our knowledge, transverse-load and high-temperature sensor based on the cascaded Vernier effect. Two Fabry-Perot interferometers fabricated by a piece of hollow-core fiber (HCF) and a piece of polarization-maintaining photonic crystal fiber (PM-PCF) are connected by a long part of single-mode fiber with a length of 1 m, and play the roles of transverse-load sensor and high-temperature sensor, respectively. The sensitivity of not only the transverse load but also that of temperature can be enhanced by the Vernier effect. The sensitivity of the transverse load is raised by 7.7 times to 5.84 nm/N, and the temperature sensitivities increased by 5.5 and 5.9 times to -0.0689nm/∘C and -0.1038nm/∘C within the temperature range of 50-400°C to 400-900°C. Moreover, both the HCF cavity and PM-PCF cavity can be split and combined flexibly. Hence, such a sensor could have great potential in sensing applications.

Comparative transcriptome analysis of male and female flowers in Spinacia oleracea L.

BACKGROUND: Dioecious spinach (Spinacia oleracea L.), a commercial and nutritional vegetable crop, serves as a model for studying the mechanisms of sex determination and differentiation in plants. However, this mechanism is still unclear. Herein, based on PacBio Iso-seq and Illumina RNA-seq data, comparative transcriptome analysis of male and female flowers were performed to explore the sex differentiation mechanism in spinach. RESULTS: Compared with published genome of spinach, 10,800 transcripts were newly annotated; alternative splicing, alternative polyadenylation and lncRNA were analyzed for the first time, increasing the diversity of spinach transcriptome. A total of 2965 differentially expressed genes were identified between female and male flowers at three early development stages. The differential expression of RNA splicing-related genes, polyadenylation-related genes and lncRNAs suggested the involvement of alternative splicing, alternative polyadenylation and lncRNA in sex differentiation. Moreover, 1946 male-biased genes and 961 female-biased genes were found and several candidate genes related to gender development were identified, providing new clues to reveal the mechanism of sex differentiation. In addition, weighted gene co-expression network analysis showed that auxin and gibberellin were the common crucial factors in regulating female or male flower development; however, the closely co-expressed genes of these two factors were different between male and female flower, which may result in spinach sex differentiation. CONCLUSIONS: In this study, 10,800 transcripts were newly annotated, and the alternative splicing, alternative polyadenylation and long-noncoding RNA were comprehensively analyzed for the first time in spinach, providing valuable information for functional genome study. Moreover, candidate genes related to gender development were identified, shedding new insight on studying the mechanism of sex determination and differentiation in plant.