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Nucleotide analog inhibitors, including broad-spectrum remdesivir and favipiravir, have shown promise in in vitro assays and some clinical studies for COVID-19 treatment, this despite an incomplete mechanistic understanding of the viral RNA-dependent RNA polymerase nsp12 drug interactions. Here, we examine the molecular basis of SARS-CoV-2 RNA replication by determining the cryo-EM structures of the stalled pre- and post- translocated polymerase complexes. Compared with the apo complex, the structures show notable structural rearrangements happening to nsp12 and its co-factors nsp7 and nsp8 to accommodate the nucleic acid, whereas there are highly conserved residues in nsp12, positioning the template and primer for an in-line attack on the incoming nucleotide. Furthermore, we investigate the inhibition mechanism of the triphosphate metabolite of remdesivir through structural and kinetic analyses. A transition model from the nsp7-nsp8 hexadecameric primase complex to the nsp12-nsp7-nsp8 polymerase complex is also proposed to provide clues for the understanding of the coronavirus transcription and replication machinery.
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Betacoronavirus/química , Betacoronavirus/enzimología , ARN Polimerasa Dependiente del ARN/química , Proteínas no Estructurales Virales/química , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/química , Adenosina Monofosfato/metabolismo , Adenosina Monofosfato/farmacología , Alanina/análogos & derivados , Alanina/química , Alanina/metabolismo , Alanina/farmacología , Antivirales/química , Antivirales/metabolismo , Antivirales/farmacología , Dominio Catalítico , ARN Polimerasa Dependiente de ARN de Coronavirus , Microscopía por Crioelectrón , Modelos Químicos , Modelos Moleculares , ARN Viral/metabolismo , SARS-CoV-2 , Transcripción Genética , Replicación ViralRESUMEN
Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.
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Melatonina/metabolismo , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Diferenciación Celular , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Femenino , Humanos , Luz , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos C57BL , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Recurrencia , Estaciones del Año , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/citología , Células Th17/inmunología , Células Th17/metabolismoRESUMEN
Th17 cells play a critical role in host defense against extracellular pathogens and tissue homeostasis but can induce autoimmunity. The mechanisms implicated in balancing "pathogenic" and "non-pathogenic" Th17 cell states remain largely unknown. We used single-cell RNA-seq to identify CD5L/AIM as a regulator expressed in non-pathogenic, but not in pathogenic Th17 cells. Although CD5L does not affect Th17 differentiation, it is a functional switch that regulates the pathogenicity of Th17 cells. Loss of CD5L converts non-pathogenic Th17 cells into pathogenic cells that induce autoimmunity. CD5L mediates this effect by modulating the intracellular lipidome, altering fatty acid composition and restricting cholesterol biosynthesis and, thus, ligand availability for Rorγt, the master transcription factor of Th17 cells. Our study identifies CD5L as a critical regulator of the Th17 cell functional state and highlights the importance of lipid metabolism in balancing immune protection and disease induced by T cells.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Metabolismo de los Lípidos , Receptores Inmunológicos/metabolismo , Células Th17/patología , Animales , Diferenciación Celular , Sistema Nervioso Central/patología , Colesterol/biosíntesis , Encefalomielitis Autoinmune Experimental/inmunología , Ácidos Grasos Insaturados/metabolismo , Humanos , Ganglios Linfáticos/patología , Ratones , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Receptores Depuradores , Análisis de la Célula Individual , Células Th17/inmunologíaRESUMEN
Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung tissues from 116 individuals of Chinese ancestry, which resulted in the identification of 1,385 sQTL-harboring genes (sGenes) containing 378,210 significant variant-intron pairs. A comprehensive characterization of these sQTLs showed that they were enriched in actively transcribed regions, genetic regulatory elements, and splicing-factor-binding sites. Moreover, sQTLs were largely distinct from expression quantitative trait loci (eQTLs) and showed significant enrichment in potential risk loci of NSCLC. We also integrated sQTLs into NSCLC GWAS datasets (13,327 affected individuals and 13,328 control individuals) by using splice-transcriptome-wide association study (spTWAS) and identified alternative splicing events in 19 genes that were significantly associated with NSCLC risk. By using functional annotation and experiments, we confirmed an sQTL variant, rs35861926, that reduced the risk of lung adenocarcinoma (rs35861926-T, OR = 0.88, 95% confidence interval [CI]: 0.82-0.93, p = 1.87 × 10-5) by promoting FARP1 exon 20 skipping to downregulate the expression level of the long transcript FARP1-011. Transcript FARP1-011 promoted the migration and proliferation of lung adenocarcinoma cells. Overall, our study provided informative lung sQTL resources and insights into the molecular mechanisms linking sQTL variants to NSCLC risk.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Sitios de Carácter Cuantitativo/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudio de Asociación del Genoma Completo/métodos , Neoplasias Pulmonares/genética , Empalme Alternativo/genética , Adenocarcinoma del Pulmón/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
CRISPR-Cas12f nucleases are currently one of the smallest genome editors, exhibiting advantages for efficient delivery via cargo-size-limited adeno-associated virus delivery vehicles. Most characterized Cas12f nucleases recognize similar T-rich protospacer adjacent motifs (PAMs) for DNA targeting, substantially restricting their targeting scope. Here we report the cryogenic electron microscopy structure and engineering of a miniature Clostridium novyi Cas12f1 nuclease (CnCas12f1, 497 amino acids) with rare C-rich PAM specificity. Structural characterizations revealed detailed PAM recognition, asymmetric homodimer formation and single guide RNA (sgRNA) association mechanisms. sgRNA engineering transformed CRISPR-CnCas12f1, which initially was incapable of genome targeting in bacteria, into an effective genome editor in human cells. Our results facilitate further understanding of CRISPR-Cas12f1 working mechanism and expand the mini-CRISPR toolbox.
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Sistemas CRISPR-Cas , ARN Guía de Sistemas CRISPR-Cas , Humanos , Sistemas CRISPR-Cas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , ADN/química , Genoma , Endonucleasas/genética , Endonucleasas/metabolismo , Edición GénicaRESUMEN
Accumulating evidence has substantiated the potential of ambient particulate matter (PM) to elicit detrimental health consequences in the respiratory system, notably airway inflammation. Macrophages, a pivotal component of the innate immune system, assume a crucial function in responding to exogenous agents. However, the roles and detailed mechanisms in regulating PM-induced airway inflammation remain unclear. The current study revealed that PM had the ability to stimulate the formation of macrophage extracellular traps (METs) both in vitro and in vivo. This effect was dependent on peptidylarginine deiminase type 4 (PAD4)-mediated histone citrullination. Additionally, reactive oxygen species were involved in the formation of PM-induced METs, in parallel with PAD4. Genetic deletion of PAD4 in macrophages resulted in an up-regulation of inflammatory cytokine expression. Moreover, mice with PAD4-specific knockout in myeloid cells exhibited exacerbated PM-induced airway inflammation. Mechanistically, inhibition of METs suppressed the phagocytic ability in macrophages, leading to airway epithelial injuries and an aggravated PM-induced airway inflammation. The present study demonstrates that METs play a crucial role in promoting the phagocytosis and clearance of PM by macrophages, thereby suppressing airway inflammation. Furthermore, it suggests that activation of METs may represent a novel therapeutic strategy for PM-related airway disorders.
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Trampas Extracelulares , Macrófagos , Material Particulado , Arginina Deiminasa Proteína-Tipo 4 , Animales , Trampas Extracelulares/metabolismo , Material Particulado/efectos adversos , Ratones , Arginina Deiminasa Proteína-Tipo 4/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Inflamación/patología , Inflamación/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BL , Fagocitosis , Especies Reactivas de Oxígeno/metabolismo , CitrulinaciónRESUMEN
Th1 cells are critical in experimental autoimmune encephalomyelitis (EAE). Serine protease inhibitor clade E1 (Serpine1) has been posited as an inhibitor of IFN-γ from T cells, although its role in autoimmunity remains unclear. In this study, we show that Serpine1 knockout (KO) mice develop EAE of enhanced severity relative to wild-type (WT) controls. Serpine1 overexpression represses Th1 cell cytokine production and pathogenicity, whereas Serpine1-KO:2D2 Th1 cells transfer EAE of increased severity in comparison with WT 2D2 Th1 cells. Notably, polarized Serpine1-KO Th1 cells display delayed expression of the Th1-specific inhibitory receptor, Tim-3 (T cell Ig and mucin-domain containing-3). Serpine1-KO:Tim-3-Tg Th1 cells, which transgenically overexpress Tim-3, showed increased expression of IFN-γ and reduced expression of the checkpoint molecules Lag-3 and PD-1 relative to WT Tim-3-Tg counterparts. Furthermore, Serpine1 deficiency restored the EAE phenotype of Tim-3-Tg mice that normally develop mild disease. Taken together, we identify Serpine1 as a negative regulator of Th1 cells.
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Encefalomielitis Autoinmune Experimental , Ratones , Animales , Células TH1 , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Inhibidores de Serina Proteinasa , Ratones Noqueados , Ratones Endogámicos C57BL , Células Th17RESUMEN
Communication between interacting organisms via bioactive molecules is widespread in nature and plays key roles in diverse biological processes. Small RNAs (sRNAs) can travel between host plants and filamentous pathogens to trigger transkingdom RNA interference (RNAi) in recipient cells and modulate plant defense and pathogen virulence. However, how fungal pathogens counteract transkingdom antifungal RNAi has rarely been reported. Here we show that a secretory protein VdSSR1 (secretory silencing repressor 1) from Verticillium dahliae, a soil-borne phytopathogenic fungus that causes wilt diseases in a wide range of plant hosts, is required for fungal virulence in plants. VdSSR1 can translocate to plant nucleus and serve as a general suppressor of sRNA nucleocytoplasmic shuttling. We further reveal that VdSSR1 sequesters ALY family proteins, adaptors of the TREX complex, to interfere with nuclear export of the AGO1microRNA (AGO1miRNA) complex, leading to a great attenuation in cytoplasmic AGO1 protein and sRNA levels. With this mechanism, V. dahliae can suppress the accumulation of mobile plant miRNAs in fungal cells and succedent transkingdom silencing of virulence genes, thereby increasing its virulence in plants. Our findings reveal a mechanism by which phytopathogenic fungi antagonize antifungal RNAi-dependent plant immunity and expand the understanding on the complex interaction between host and filamentous pathogens.
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MicroARNs , Verticillium , Transporte Activo de Núcleo Celular , Antifúngicos , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades de las Plantas/microbiología , Plantas/genética , ARN de Planta , Verticillium/metabolismoRESUMEN
Plant embryogenic calli (ECs) can undergo somatic embryogenesis to regenerate plants. This process is mediated by regulatory factors, such as transcription factors and specifically expressed genes, but the precise molecular mechanisms underlying somatic embryogenesis at the single-cell level remain unclear. In this study, we performed high-resolution single-cell RNA sequencing analysis to determine the cellular changes in the EC of the woody plant species Dimocarpus longan (longan) and clarify the continuous cell differentiation trajectories at the transcriptome level. The highly heterogeneous cells in the EC were divided into 12 putative clusters (e.g., proliferating, meristematic, vascular, and epidermal cell clusters). We determined cluster-enriched expression marker genes and found that overexpression of the epidermal cell marker gene GDSL ESTERASE/LIPASE-1 inhibited the hydrolysis of triacylglycerol. In addition, the stability of autophagy was critical for the somatic embryogenesis of longan. The pseudo-timeline analysis elucidated the continuous cell differentiation trajectories from early embryonic cell division to vascular and epidermal cell differentiation during the somatic embryogenesis of longan. Moreover, key transcriptional regulators associated with cell fates were revealed. We found that ETHYLENE RESPONSIVE FACTOR 6 was characterized as a heat-sensitive factor that negatively regulates longan somatic embryogenesis under high-temperature stress conditions. The results of this study provide new spatiotemporal insights into cell division and differentiation during longan somatic embryogenesis at single-cell resolution.
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Sapindaceae , Transcriptoma , Transcriptoma/genética , Sapindaceae/genética , Perfilación de la Expresión Génica , Análisis de Secuencia de ARN , Desarrollo Embrionario , Técnicas de Embriogénesis Somática de Plantas , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Analyzing the molecular structure-photophysical property correlations of metal nanoclusters to accomplish function-oriented photocatalysis could be challenging. Here, the selective heteroatom alloying has been exploited to a Au15 nanocluster, making up a structure-correlated nanocluster series, including homogold Au15, bimetallic AgxAu15-x and CuxAu15-x, trimetallic AgxCuyAu15-x-y, and tetrametallic Pt1AgxCuyAu15-x-y. Their structure-dependent photophysical properties were investigated due to the atomically precise structures of these nanoclusters. Cu-alloyed CuxAu15-x showed intense phosphorescence and the highest singlet oxygen production efficiency. Moreover, the generation of 1O2 species from excited nanoclusters enabled CuxAu15-x as a suitable catalyst for efficient photocatalytic oxidation of silyl enol ethers to produce α,ß-unsaturated carbonyl compounds. The generality and applicability of the CuxAu15-x catalysts toward different photocatalytic oxidations were assessed. Overall, this study presents an intriguing Au15-based cluster series enabling an atomic-level understanding of structure-photophysical property correlations, which hopefully provides guidance for the fabrication of cluster-based catalysts with customized photocatalytic performance.
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INTRODUCTION: Breast cancer is a significant contributor to female mortality, exerting a public health burden worldwide, especially in China, where risk-prediction models with good discriminating accuracy for breast cancer are still scarce. METHODS: A multicenter screening cohort study was conducted as part of the Cancer Screening Program in Urban China. Dwellers aged 40-74 years were recruited between 2014 and 2019 and prospectively followed up until June 30, 2021. The entire data set was divided by year of enrollment to develop a prediction model and validate it internally. Multivariate Cox regression was used to ascertain predictors and develop a risk-prediction model. Model performance at 1, 3, and 5 years was evaluated using the area under the curve, nomogram, and calibration curves and subsequently validated internally. The prediction model incorporates selected factors that are assigned appropriate weights to establish a risk-scoring algorithm. Guided by the risk score, participants were categorized into low-, medium-, and high-risk groups for breast cancer. The cutoff values were chosen using X-tile plots. Sensitivity analysis was conducted by categorizing breast cancer risk into the low- and high-risk groups. A decision curve analysis was used to assess the clinical utility of the model. RESULTS: Of the 70,520 women enrolled, 447 were diagnosed with breast cancer (median follow-up, 6.43 [interquartile range, 3.99-7.12] years). The final prediction model included age and education level (high, hazard ratio [HR], 2.01 [95% CI, 1.31-3.09]), menopausal age (≥50 years, 1.34 [1.03-1.75]), previous benign breast disease (1.42 [1.09-1.83]), and reproductive surgery (1.28 [0.97-1.69]). The 1-year area under the curve was 0.607 in the development set and 0.643 in the validation set. Moderate predictive discrimination and satisfactory calibration were observed for the validation set. The risk predictions demonstrated statistically significant differences between the low-, medium-, and high-risk groups (p < .001). Compared with the low-risk group, women in the high- and medium-risk groups posed a 2.17-fold and 1.62-fold elevated risk of breast cancer, respectively. Similar results were obtained in the sensitivity analyses. A web-based calculator was developed to estimate risk stratification for women. CONCLUSIONS: This study developed and internally validated a risk-adapted and user-friendly risk-prediction model by incorporating easily accessible variables and female factors. The personalized model demonstrated reliable calibration and moderate discriminative ability. Risk-stratified screening strategies contribute to precisely distinguishing high-risk individuals from asymptomatic individuals and prioritizing breast cancer screening. PLAIN LANGUAGE SUMMARY: Breast cancer remains a burden in China. To enhance breast cancer screening, we need to incorporate population stratification in screening. Accurate risk-prediction models for breast cancer remain scarce in China. We established and validated a risk-adapted and user-friendly risk-prediction model by incorporating routinely available variables along with female factors. Using this risk-stratified model helps accurately identify high-risk individuals, which is of significant importance when considering integrating individual risk assessments into mass screening programs for breast cancer. Current clinical breast cancer screening lacks a constructive clinical pathway and guiding recommendations. Our findings can better guide clinicians and health care providers.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Estudios Prospectivos , Estudios de Cohortes , Detección Precoz del Cáncer , Medición de RiesgoRESUMEN
OBJECTIVES: T helper 9 (Th9) cells are recognised for their characteristic expression of the transcription factor PU.1 and production of interleukin-9 (IL-9), which has been implicated in various autoimmune diseases. However, its precise relationship with rheumatoid arthritis (RA) pathogenesis needs to be further clarified. METHODS: The expression levels of PU.1 and IL-9 in patients with RA were determined by ELISA, western blotting (WB) and immunohistochemical staining. PU.1-T cell-conditional knockout (KO) mice, IL-9 KO and IL-9R KO mice were used to establish collagen antibody-induced arthritis (CAIA), respectively. The inhibitor of PU.1 and IL-9 blocking antibody was used in collagen-induced arthritis (CIA). In an in vitro study, the effects of IL-9 were investigated using siRNAs and IL-9 recombinant proteins. Finally, the underlying mechanisms were further investigated by luciferase reporter analysis, WB and Chip-qPCR. RESULTS: The upregulation of IL-9 expression in patients with RA exhibited a positive correlation with clinical markers. Using CAIA and CIA model, we demonstrated that interventions targeting PU.1 and IL-9 substantially mitigated the inflammatory phenotype. Furthermore, in vitro assays provided the proinflammatory role of IL-9, particularly in the hyperactivation of macrophages and fibroblast-like synoviocytes. Mechanistically, we uncovered that PU.1 and IL-9 form a positive feedback loop in RA: (1) PU.1 directly binds to the IL-9 promoter, activating its transcription and (2) Th9-derived IL-9 induces PU.1 via the IL-9R-JAK1/STAT3 pathway. CONCLUSIONS: These results support that the PU.1-IL-9 axis forms a positive loop in Th9 dysregulation of RA. Targeting this signalling axis presents a potential target approach for treating RA.
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CD4(+) interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are instrumental in the immune response to pathogens. However, an overactive T(H)17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of T(H)17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during T(H)7 differentiation is not understood. Here we report that under T(H)17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting T(H)17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of T(H)17 cells that actively limits IL-2 production and promotes their differentiation.
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Interleucina-2/biosíntesis , Activación de Linfocitos , Células Th17/metabolismo , Transactivadores/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Diferenciación Celular , Células Cultivadas , Colitis/inmunología , Regulación de la Expresión Génica , Factor de Transcripción Ikaros , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Hidrocarburo de Aril/metabolismo , Factor de Transcripción STAT3/metabolismo , Células Th17/citología , Células Th17/inmunología , Transactivadores/deficiencia , Transactivadores/genéticaRESUMEN
Microsphere photolithography (MPL) is a promising technique for cost-effective fabrication of large-scale metasurfaces. This approach generates an array of photonic jets by the collimated illumination of self-assembled microspheres. The photonic jets can be precisely steered within the unit cell defined by each microsphere by changing the angle of incidence. This allows for the creation of complex metasurface element geometries. Computer controlled articulation of the substrate relative to a static UV source allows the direct-write of different metasurface elements. However, this is time-consuming and requires registration between each exposure for complex features. This paper investigates a single exposure method with the dynamic continuous angle of incidence control provided by a Digital Micromirror Device (DMD) in the front Fourier plane of the projection system. The grayscale values of the DMD pixels can be adjusted to provide optical proximity correction. Larger patterns can be achieved by scanning the substrate relative to the exposure beam. This approach is demonstrated with the creation of hierarchical patterns. This work greatly simplifies the MPL exposure process for complex resonators and provides potential for full light field control.
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Sapphire fiber Bragg gratings (FBGs) have demonstrated their efficacy in sensing at high-temperature harsh environments owing to their elevated melting point and outstanding stability. However, due to the extremely high volume of modes supported by the clad-less sapphire fiber, the demodulation capability of the reflected spectra is hindered due to their irregular and somewhat complicated shapes. Hence, a mode-stripping or scrambling step is typically employed beforehand, albeit at the expense of sensor robustness. Additionally, conventional interrogation of sapphire FBG sensors relies on an optical spectrum analyzer due to the high sensitivity provided by the spectrum analyzer, where the long data acquisition time restricts the system from detecting instantaneous temperature variations. In this study, we present a simple sensor configuration by directly butt-coupling the sapphire FBG multi-mode lead-out fiber to a single-mode lead-in fiber, and detect its reflected spectra via a low-cost, fast, and coarsely resolved (166 pm) spectrometer. We leverage machine learning to compensate for the under-sampling of the measured FBG spectra and achieve a temperature accuracy of 0.23 °C at a high data acquisition rate of 5 kHz (limited by the spectrometer). This represents a tenfold improvement in accuracy compared to conventional peak-searching and curve-fitting methods, as well as a significant enhancement in measurement speed that enables dynamic sensing. We further assess the robustness of our sensor by attaching one side of the sensor to a vibrator and still observe good performance (0.43 °C) even under strong shaking conditions. The introduced demodulation technology opens up opportunities for the broader use of sapphire FBG sensors in noisy and high-temperature harsh environments.
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A novel fiber Bragg grating (FBG) sensing system, based on an optically injected distributed feedback laser diode (DFB-LD) with an optoelectronic oscillating (OEO) loop, is proposed and experimentally demonstrated for temperature measurements with high and tunable sensitivity. The FBG sensor device works as an edge filter to adjust the optical power of the injected beam in response to temperature variations. The optically injected DFB-LD works at Period-one (P1) oscillating state, and the central wavelength of the oscillating mode of the DFB-LD can be tuned by the variable power of the injected beam. Furthermore, an OEO loop is implemented to improve the signal quality of the generated P1 microwave signal. Hence, the sensing parameter of temperature is converted to the frequency variation of the generated P1 microwave signal in the proposed sensing system. In the proof-of-concept experiment, a series of P1 microwave signals are generated while different temperatures are applied to the FBG sensor. The sensitivity of the proposed FBG sensing system for temperature measurements can be tuned from 0.44322â GHz/°C to 1.25952â GHz/°C. The stability and repeatability experiments are also performed, demonstrating the high measurement accuracy (0.0629°C) and low error of the system. The proposed FBG-based sensing and interrogation system exhibits high sensitivity, large tunability, good linearity, and flexible sensing generality.
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Allometric rules provide insights into the structure-function relationships across species and scales and are commonly used in ecology. The fields of agronomy, plant phenotyping and modeling also need simplifications such as allometric rules to reconcile data at different temporal and spatial levels (organs/canopy). This paper explores the variations in relationships for wheat regarding (i) the distribution of crop green area between leaves and stems, and (ii) the allocation of above-ground biomass between leaves and stems during the vegetative period, using a large dataset covering different years, countries, genotypes and management practices. Our results show that the relationship between leaf and stem area was linear, genotype-specific, and sensitive to radiation. The relationship between leaf and stem biomass depended on genotype and nitrogen fertilization. The mass per area, associating area and biomass for both leaf and stem, varied strongly by developmental stage and was significantly affected by environment and genotype. These allometric rules were evaluated with satisfactory performance, and their potential use is discussed with regard to current phenotyping techniques and plant/crop models. Our results enable the definition of models and minimum datasets required for characterizing diversity panels and making predictions in various G × E × M contexts.
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Feline coronavirus (FCoV) infection is a leading cause of death in cats. In this study, we produced FCoV-I virus-like particles (VLPs) containing E, M, N, and S proteins using a baculovirus expression system and mixed VLPs with the adjuvants MF59 and CpG 55.2 to prepare an VLP/MF59/CpG vaccine. After immunization of mice with the vaccine, IgG specific antibodies titers against S and N proteins increased to 1:12,800, and IFN-γ+ and IL-4+ splenocytes were significantly increased. Following immunization of FCoV-negative cats, the S protein antibodies in immunized cats (5/5) increased significantly, with a peak of 1:12,800. Notably, after booster vaccination in FCoV-positive cats, a significant reduction in viral load was observed in the feces of partial cats (4/5), and the FCoV-I negative conversion was found in two immunized cats (2/5). Therefore, the VLP/MF59/CpG vaccine is a promising candidate vaccine to prevent the FCoV infection.
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A new cross-coupling of trifluoromethyl arenes has been realized via multiphoton photoredox catalysis. Trifluoromethyl arenes were demonstrated to undergo selective mono-defluorinative alkylation under mild reaction conditions providing access to a series of valuable α,α-difluorobenzylic compounds. The reaction shows broad substrate scope and general functional group tolerance. In addition to the electron-deficient trifluoromethyl arenes that are easily reduced to the corresponding radical anion, more challenging electron-rich substrates were also successfully applied. Steady-State Stern-Volmer quenching studies indicated that the trifluoromethyl arenes were reduced by the multiphoton excited Ir-based photocatalyst.