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The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.
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Instabilidade Genômica , Regiões Promotoras Genéticas , Estruturas R-Loop , Terminação da Transcrição Genética , Humanos , DNA de Cadeia Simples/metabolismo , Instabilidade Genômica/genética , Mutação , Estruturas R-Loop/genética , RNA Polimerase II/metabolismo , Regiões Promotoras Genéticas/genética , Genoma Humano , Proteínas de Ligação a DNA/metabolismoRESUMO
Heat stress poses a significant threat to maize, especially when combined with drought. Recent research highlights the potential of water replenishment to ameliorate grain weight loss. However, the mitigating mechanisms of heat in drought stress, especially during the crucial early grain-filling stage, remain poorly understood. We investigated the mechanism for mitigating heat in drought stress by water replenishment from the 12th to the 32nd days after silking in a controlled greenhouse experiment (Exp. I) and field trial (Exp. II). A significant reduction in grain weight was observed in heat stress compared to normal conditions. When water replenishment was applied to increase soil water content (SWC) under heat stress, the grain yield exhibited a notable increase ranging from 28.4 to 76.9%. XY335 variety was used for transcriptome sequencing to analyze starch biosynthesis and amino acid metabolisms in Exp. I. With water replenishment, the transcripts of genes responsible for trehalose 6-phosphate phosphates (TPP), alpha-trehalase (TRE), ADP-glcpyrophosphorylase, and starch synthase activity were stimulated. Additionally, the expression of genes encoding TPP and TRE contributed to an enhanced conversion of trehalose to glucose. This led to the conversion of sucrose from glucose-1-phosphate to ADP-glucose and ADP-glucose to amylopectin, ultimately increasing starch production by 45.1%. Water replenishment to boost SWC during heat stress also elevated the levels of essential amino acids in maize, including arginine, serine, tyrosine, leucine, glutamic acid, and methionine, providing valuable support to maize plants in adversity. Field trials further validated the positive impact of water replenishment on SWC, resulting in a notable increase in grain yield ranging from 7.1 to 9.2%. This study highlights the vital importance of adapting to abiotic stress and underscores the necessity of developing strategies to counteract its adverse effects on crop yield.
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Aminoácidos , Secas , Sacarose , Água , Zea mays , Zea mays/genética , Zea mays/fisiologia , Zea mays/metabolismo , Aminoácidos/metabolismo , Água/metabolismo , Sacarose/metabolismo , Grão Comestível/fisiologia , Grão Comestível/genética , Temperatura Alta , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico/fisiologiaRESUMO
Low temperature (LT) greatly restricts grain filling in maize (Zea mays L.), but the relevant molecular mechanisms are not fully understood. To better understand the effect of LT on grain development, 17 hybrids were subjected to LT stress in field trials over 3 years, and two hybrids of them with contrasting LT responses were exposed to 30/20°C and 20/10°C for 7 days during grain filling in a greenhouse. At LT, thousand-kernel weight declined, especially in LT-sensitive hybrid FM985, while grain-filling rate was on average about 48% higher in LT-tolerant hybrid DK159 than FM985. LT reduced starch synthesis in kernel mainly by suppression of transcript levels and enzyme activities for sucrose synthase and hexokinase. Brassinolide (BR) was abundant in DK159 kernel, and genes involved in BR and cytokinin signals were inducible by stress. LT downregulated the genes in light-harvesting complex and photosystem I/II subunits, accompanied by reduced photosynthetic rate and Fv/Fm in ear leaf. The LT-tolerant hybrid could maintain a high soluble sugar content and fast interconversion between sucrose and hexose in the stem internode and cob, improving assimilate allocation to kernel at LT stress and paving the way for simultaneous growth and LT stress responses.
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Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Zea mays , Zea mays/crescimento & desenvolvimento , Zea mays/genética , Zea mays/metabolismo , Zea mays/fisiologia , Glucosiltransferases/metabolismo , Glucosiltransferases/genética , Fotossíntese , Amido/metabolismo , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/genética , Grão Comestível/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sementes/crescimento & desenvolvimento , Sementes/genética , Sementes/metabolismo , Brassinosteroides/metabolismo , Esteroides Heterocíclicos/farmacologia , Esteroides Heterocíclicos/metabolismoRESUMO
The endoplasmic reticulum-localized DnaJ family 3B (ERdj3B), is a component of the stromal cell-derived factor 2 (SDF2)-ERdj3B-binding immunoglobulin protein (BiP) chaperone complex, which functions in protein folding, translocation, and quality control. We found that ERdj3B mutations affected integument development in the Ler ecotype but not in the Col-0 ecotype of Arabidopsis (Arabidopsis thaliana). Map-based cloning identified the ERECTA (ER) gene as a natural modifier of ERdj3B. The double mutation of ERdj3B and ER caused a major defect in the inner integument under heat stress. Additional mutation of the ER paralog ERECTA-LIKE 1 (ERL1) or ERL2 to the erdj3b er double mutant exacerbated the defective integument phenotype. The double mutation of ER and SDF2, the other component of the SDF2-ERdj3B-BiP complex, resulted in similar defects in the inner integument. Furthermore, both the protein abundance and plasma membrane partitioning of ER, ERL1, and ERL2 were markedly reduced in erdj3b plants, indicating that the SDF2-ERdj3B-BiP chaperone complex might control the translocation of ERECTA-family proteins from the endoplasmic reticulum to the plasma membrane. Our results suggest that the SDF2-ERdj3B-BiP complex functions in ovule development and the heat stress response in coordination with ERECTA-family receptor kinases.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Resposta ao Choque Térmico , Óvulo Vegetal/metabolismo , Proteínas Serina-Treonina QuinasesRESUMO
Contact electrification between water and a solid surface is crucial for physicochemical processes at water-solid interfaces. However, the nature of the involved processes remains poorly understood, especially in the initial stage of the interface formation. Here we report that H2O2 is spontaneously produced from the hydroxyl groups on the solid surface when contact occurred. The density of hydroxyl groups affects the H2O2 yield. The participation of hydroxyl groups in H2O2 generation is confirmed by mass spectrometric detection of 18O in the product of the reaction between 4-carboxyphenylboronic acid and 18O-labeled H2O2 resulting from 18O2 plasma treatment of the surface. We propose a model for H2O2 generation based on recombination of the hydroxyl radicals produced from the surface hydroxyl groups in the water-solid contact process. Our observations show that the spontaneous generation of H2O2 is universal on the surfaces of soil and atmospheric fine particles in a humid environment.
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Eletricidade , Peróxido de Hidrogênio , Radical Hidroxila , Água , Atmosfera/química , Umidade , Peróxido de Hidrogênio/síntese química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Espectrometria de Massas , Isótopos de Oxigênio/análise , Isótopos de Oxigênio/química , Tamanho da Partícula , Solo/química , Água/químicaRESUMO
Drought is a major abiotic stress reducing maize (Zea mays) yield worldwide especially before and during silking. The mechanism underlying drought tolerance in maize and the roles of different organs have not been elucidated. Hence, we conducted field trials under pre-silking drought conditions using two maize genotypes: FM985 (drought-tolerant) and ZD958 (drought-sensitive). The two genotypes did not differ in plant height, grain number, and yield under control conditions. However, the grain number per ear and the yield of FM985 were 38.1 and 35.1% higher and plants were 17.6% shorter than ZD958 under drought conditions. More 13 C photosynthates were transported to the ear in FM985 than in ZD958, which increased floret fertility and grain number. The number of differentially expressed genes was much higher in stem than in other organs. Stem-ear interactions are key determinants of drought tolerance, in which expression of genes related to abscisic acid, lignin, and flavonoid biosynthesis and carbon metabolism in the stem was induced by drought, which inhibited stem elongation and promoted assimilate allocation to the ear in FM985. In comparison with ZD958, the activities of trehalose 6-phosphate phosphatase and sucrose non-fermentation-associated kinase 1 were higher in the stem and lower in the kernel of FM985, which facilitated kernel formation. These results reveal that, beyond the ear response, stem elongation is involved in the whole process of drought tolerance before silking. Abscisic acid together with trehalose 6-phosphate, lignin, and flavonoid suppresses stem elongation and allocates assimilates into the ear, providing a novel and systematic regulatory pathway for drought tolerance in maize.
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Ácido Abscísico , Resistência à Seca , Ácido Abscísico/metabolismo , Zea mays/metabolismo , Lignina/metabolismo , Flavonoides/metabolismo , Trealose/metabolismo , Grão Comestível , Secas , Fosfatos/metabolismo , Estresse FisiológicoRESUMO
Exosomes have been established as a valuable tool for clinical applications for the purpose of liquid biopsy and therapy. However, the clinical practice of exosomes as cancer biopsy markers is still to a very low extent. Active mode optical microcavity with microlaser emission has aroused as a versatile approach for chemical and biological sensing due to its benefits of larger photon population, increased effective Q-factor, decreased line width, and improved sensitivity. Herein, we report a label-free and precise quantification of exosome vesicles and surface protein profiling of breast cancer exosomes using functionalized active whispering gallery mode (WGM) microlaser probes. A detection limit of 40 exosomes per microresonator was achieved. The proposed system enabled a pilot assay of quantitative exosome analysis in cancer patients' blood with only a few microliters of sample consumption, holding good potential for large-scale cancer liquid biopsy. Multiplexed functionalization of the optical microresonator allowed us to profile cancer exosomal surface markers and distinct subclasses of breast cancer-associated exosomes and monitor drug treatment outcomes. Our findings speak volumes about the advantages of the WGM microlaser sensor, including very small sample consumption, low detection limit, high specificity, and ease of operation, offering a promising means for precious clinical sample analysis.
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Neoplasias da Mama , Exossomos , Humanos , Feminino , Exossomos/metabolismo , Biópsia Líquida , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , LasersRESUMO
Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.
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Análise Espectral Raman , Análise Espectral Raman/métodos , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/química , Aprendizado de Máquina , Melanoma/patologia , Melanoma/diagnóstico , Melanoma/classificação , Vesículas Extracelulares/química , Máquina de Vetores de Suporte , Bactérias/classificação , Bactérias/isolamento & purificação , Inteligência ArtificialRESUMO
BACKGROUND: The pollution of soil by heavy metals, particularly Cd, is constitutes a critical international environmental concern. Willow species are renowned for their efficacy in the phytoremediation of heavy metals owing to their high Cd absorption rate and rapid growth. However, the mechanisms underlying microbial regulation for high- and low-accumulating willow species remain poorly understood. Therefore, we investigated the responses of soil and rhizosphere microbial communities to high- and low-Cd-accumulating willows and Cd contamination. We analyzed soil properties were analyzed in bulk soil (SM) and rhizosphere soil (RM) planted with high-accumulating (H) and low-accumulating (L) willow species. RESULTS: Rhizosphere soil for different willow species had more NH4+ than that of bulk soil, and RM-H soil had more than RM-L had. The available phosphorus content was greater in hyper-accumulated species than it was in lower-accumulated species, especially in RM-H. Genome sequencing of bacterial and fungal communities showed that RM-L exhibited the highest bacterial diversity, whereas RM-H displayed the greatest richness than the other groups. SM-L exhibited the highest diversity and richness of fungal communities. Ralstonia emerged as the predominant bacterium in RM-H, whereas Basidiomycota and Cercozoa were the most enriched fungi in SM-H. Annotation of the N and C metabolism pathways revealed differential patterns: expression levels of NRT2, NarB, nirA, nirD, nrfA, and nosZ were highest in RM-H, demonstrating the effects of NO3-and N on the high accumulation of Cd in RM-H. The annotated genes associated with C metabolism indicated a preference for the tricarboxylic pathway in RM-H, whereas the hydroxypropionate-hydroxybutyrate cycle was implicated in C sequestration in SM-L. CONCLUSIONS: These contribute to elucidation of the mechanism underlying high Cd accumulation in willows, particularly in respect of the roles of microbes and N and C utilization. This will provide valuable insights for repairing polluted soil using N and employing organic acids to improve heavy metal remediation efficiency.
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Biodegradação Ambiental , Cádmio , Microbiota , Rizosfera , Salix , Microbiologia do Solo , Poluentes do Solo , Salix/microbiologia , Salix/metabolismo , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Fungos/metabolismo , Fungos/genética , Solo/químicaRESUMO
Polarization-sensitive broadband optoelectronic detection is crucial for future sensing, imaging, and communication technologies. Narrow bandgap 2D materials, such as Te and PdSe2, show promise for these applications, yet their polarization performance is limited by inherent structural anisotropies. In this work, a self-powered, broadband photodetector utilizing a Te/PdSe2 van der Waals (vdWs) heterojunction, with orientations meticulously tailored is introduced through polarized Raman optical spectra and tensor calculations to enhance linear polarization sensitivity. The device exhibits anisotropy ratios of 1.48 at 405 nm, 3.56 at 1550 nm, and 1.62 at 4 µm, surpassing previously-reported photodetectors based on pristine Te and PdSe2. Additionally, it exhibits high responsivity (617 mA W-1 at 1550 nm), specific detectivity (5.27 × 1010 Jones), fast response (≈4.5 µs), and an extended spectral range beyond 4 µm. The findings highlight the significance of orientation-engineered heterostructures in enhancing polarization-sensitive photodetectors and advancing optoelectronic technology.
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Peroxydisulfate (PDS), a popular molecule that is able to oxidize organic compounds, is garnering attention across various disciplines of chemistry, materials, pharmaceuticals, environmental remediation, and sustainability. Methylene blue (MB) is a model pollutant that can be readily oxidized by PDS-derived radicals. Unlike the conventional degradation process, here a reversible "dissolution-precipitation" phenomenon is discovered, triggered by a simple mixing of PDS and MB, revealing a novel application of PDS in fabricating self-assembled ultra-long nanowires with MB. This phenomenon is unique to PDS and MB, different from the traditional salting out or self-aggregation of dyes. Formation of nanowires facilitated by electrostatic interaction between S+ and O- moieties and π-π stacking is reversible, controlled by temperature and the solvent polarity. MB1-PDS-MB2 configuration (MB: PDS = 2:1) is theoretically predicted by density functional theory (DFT) calculations and further validated by stoichiometric ratios of carbon, sulfur, and nitrogen in the obtained precipitates (MBO). This untapped feature of PDS enables the development of colorimetric quantitative detection of PDS and sustainable dye recycling. Far more than those demonstrated cases, the potentialities of MBO as a nanomaterial merit further exploration.
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We report a 4.3â µm mid-infrared (mid-IR) high-power amplified spontaneous emission (ASE) fiber source based on CO2-filled nested hollow-core anti-resonant fiber (Nested HC-ARF). The pump source is a homemade hundred-watt-level wavelength-tunable 2â µm single-frequency fiber laser. A 5.7 m long 8-tube Nested HC-ARF is used as the gas cell, with a core diameter of 110â µm and cladding diameter of 400â µm, which exhibits transmission loss of 0.1â dB/m at 2 µm and 0.24â dB/m at 4.3â µm respectively. To improve the coupling efficiency of the high-power pump laser and reduce the influence of the thermal effect at the input end of the hollow-core fiber, the fiber is designed for multimode transmission at the pump wavelength. A continuous wave output power of 6.6 W at 4.3 µm is achieved, and the slope efficiency is 17.05%. To the best of our knowledge, it is the highest output power for such gas-filled HC-ARF ASE sources in 4â¼5â µm. This work demonstrates the great potential of gas-filled HC-ARF generating high-power mid-IR emission.
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The escalation in the intensity, frequency, and duration of high-temperature (HT) stress is currently unparalleled, which aggravates the challenges for crop production. Yet, the stage-dependent responses of reproductive organs to HT stress at the morphological, physiological, and molecular levels remain inadequately explored in pivotal staple crops. This review synthesized current knowledge regarding the mechanisms by which HT stress induces abnormalities and aberrations in reproductive growth and development, as well as by which it alters the morphology and function of florets, flowering patterns, and the processes of pollination and fertilization in maize (Zea mays L.). We identified the stage-specific sensitivities to HT stress and accurately defined the sensitive period from a time scale of days to hours. The microspore tetrad phase of pollen development and anthesis (especially shortly after pollination) are most sensitive to HT stress, and even brief temperature spikes during these stages can lead to significant kernel loss. The impetuses behind the heat-induced impairments in seed set are closely related to carbon, reactive oxygen species, phytohormone signals, ion (e.g. Ca2+) homeostasis, plasma membrane structure and function, and others. Recent advances in understanding the genetic mechanisms underlying HT stress responses during maize sexual reproduction have been systematically summarized.
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Resposta ao Choque Térmico , Reprodução , Zea mays , Zea mays/fisiologia , Zea mays/crescimento & desenvolvimento , Resposta ao Choque Térmico/fisiologia , Temperatura Alta , Pólen/fisiologiaRESUMO
Esophageal squamous cell carcinoma (ESCC) presents a five-year survival rate below 20%, underscoring the need for improved prognostic markers. Our study analyzed ESCC-specific datasets to identify consistently differentially expressed genes. A Venn analysis followed by gene network interactions revealed 23 key genes, from which we built a prognostic model using the COX algorithm (p = 0.000245, 3-year AUC = 0.967). This model stratifies patients into risk groups, with high-risk individuals showing worse outcomes and lower chemotherapy sensitivity. Moreover, a link between risk scores and M2 macrophage infiltration, as well as significant correlations with immune checkpoint genes (e.g., SIGLEC15, PDCD1LG2, and HVCR2), was discovered. High-risk patients had lower Tumor Immune Dysfunction and Exclusion (TIDE) values, suggesting potential responsiveness to immune checkpoint blockade (ICB) therapy. Our efficient 23-gene prognostic model for ESCC indicates a dual utility in assessing prognosis and guiding therapeutic decisions, particularly in the context of ICB therapy for high-risk patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Prognóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Biomarcadores Tumorais/genética , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Resistencia a Medicamentos Antineoplásicos/genética , Pessoa de Meia-Idade , Redes Reguladoras de GenesRESUMO
We report a 20-W-level acetylene-filled nested hollow-core anti-resonant fiber (nested HC-ARF) amplified spontaneous emission (ASE) source at 3.1â µm. A 1535â nm hundred-watt wavelength tunable single-frequency fiber laser with a high signal-to-noise ratio and narrow linewidth is built for pumping acetylene molecules. Simultaneously, a homemade 120â µm core diameter eight-tube nested HC-ARF is used as a gas chamber to obtain high pump laser coupling efficiency. The mid-infrared (mid-IR) ASE source output power of 21.8â W is achieved at 3.1â µm through the low-pressure acetylene gas-filled nested HC-ARF, and the slope efficiency is 25.1%. In addition, the ASE source features an excellent beam quality of Mx 2 = 1.16 and My 2 = 1.13. To the best of our knowledge, for the first time, it is a record output power for such mid-infrared ASE sources while maintaining excellent beam quality. This work provides a new way to achieve high-power mid-infrared emission.
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Mid-infrared hollow-core fiber (HCF) gas lasers based on a population inversion regime of gas molecules have made advanced development in recent years, but mostly with single-pass cavity-free structures. Here, we demonstrated a 3.1â µm high-power acetylene-filled HCF continuous wave (CW) laser and a self-Q-switched pulse laser with a linear-cavity structure. This configuration not only facilitates the transformation of amplified spontaneous emission into the laser output but also enhances the coherence of the light source and imparts distinct cavity mode characteristics. Harnessing a homemade high-power 1535â nm single-frequency fiber laser that served as the pump source, a CW laser output of 8.23â W at 3.1â µm was achieved, which is over three orders of magnitude higher than those in reported works so far. The corresponding slope efficiency of 31.8% and beam quality of Mx 2 = 1.18 and My 2 = 1.15 were characterized. When the gas pressure was up to 50â mbar, the laser generated a 3.1â µm self-Q-switched pulse with an output power of 1.98â W as well as a pulse width of 45â ns under the repetition rate of 4.59â MHz. To the best of our knowledge, this is the first time that an HCF gas laser achieves a self-Q-switched pulse. Future studies will aim to further optimize the experimental setup, potentially enabling the direct generation of picosecond pulses in the mid-infrared wavelength band.
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We conducted a joint theoretical and experimental study to investigate the collisional dissipation of molecular alignment. By comparing experimental measurements to the quantum simulations, the nonsecular effect in the collision dissipation of molecular alignment was unveiled from the gas-density-dependent decay rates of the molecular alignment revival signals. Different from the conventional perspective that the nonsecular collisional effect rapidly fades within the initial few picoseconds following laser excitation, our simulations of the time-dependent decoherence process demonstrated that this effect can last for tens of picoseconds in the low-pressure regime. This extended timescale allows for the distinct identification of the nonsecular effect from molecular alignment signals. Our findings present the pioneering evidence that nonsecular molecular collisional dissipation can endure over an extended temporal span, challenging established concepts and strengthening our understanding of molecular dynamics within dissipative environments.
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Flavin-dependent halogenase (FDH) is highly prized in pharmaceutical and chemical industries for its exceptional capacity to produce halogenated aromatic compounds with precise regioselectivity. This study has devised a multi-enzyme self-assembly strategy to construct an effective and reliable in vitro coenzyme cycling system tailored for FDHs. Initially, tri-enzyme self-assembling nanoclusters (TESNCs) were developed, comprising glucose dehydrogenase (GDH), flavin reductase (FR) and FDH. The TESNCs exhibited enhanced thermal stability and conversion efficiency compared to free triple enzyme mixtures during the conversion of L-Trp to 6-Cl-L-Trp, resulting in a 2.1-fold increase in yield. Subsequently, an ordered co-immobilization of GDH, FR, and FDH was established, further amplifying the stability and catalytic efficiency of the FDH coenzyme cycle system. Compared to the free TESNCs, the immobilized TESNCs demonstrated a 4.2-fold increase in catalytic efficiency in a 5 mL reaction system. This research provides an effective strategy for developing a robust and efficient coenzyme recycling system for FDHs.
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Based on the concept of "Evolutionary Traps", targeting survival essential genes obtained during tumor drug resistance can effectively eliminate resistant cells. While, it still faces limitations. In this study, lapatinib-resistant cells were used to test the concept of "Evolutionary Traps" and no suitable target stand out because of the identified genes without accessible drug. However, a membrane protein PDPN, which is low or non-expressed in normal tissues, is identified as highly expressed in lapatinib-resistant tumor cells. PDPN CAR-T cells were developed and showed high cytotoxicity against lapatinib-resistant tumor cells in vitro and in vivo, suggesting that CAR-T may be a feasible route for overcoming drug resistance of tumor based on "Evolutionary Trap". To test whether this concept is cell line or drug dependent, we analyzed 21 drug-resistant tumor cell expression profiles reveal that JAG1, GPC3, and L1CAM, which are suitable targets for CAR-T treatment, are significantly upregulated in various drug-resistant tumor cells. Our findings shed light on the feasibility of utilizing CAR-T therapy to treat drug-resistant tumors and broaden the concept of the "Evolutionary Trap".
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Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Imunoterapia Adotiva , Humanos , Animais , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Imunoterapia Adotiva/métodos , Lapatinib/farmacologia , Lapatinib/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/terapia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Camundongos Nus , Camundongos Endogâmicos BALB C , Camundongos , FemininoRESUMO
Anxiety is a common psychological disorder associated with other mental disorders, with depression being the most common comorbidity. Few studies have examined the neural mechanisms underlying anxiety after controlling for depression. This study aimed to explore whether there are differences in cortical activation in anxiety patients with different severities whose depression are normal. In the current study, depression levels were normal for 366 subjects-139 healthy subjects, 117 with mild anxiety, and 110 with major anxiety. Using the Hospital Anxiety and Depression Scale (HADS) and a verbal fluency task (VFT) to test subjects' anxiety and depression and cognitive function, respectively. A 53-channel guided near-infrared spectroscopic imaging technology (fNIRS) detected the concentration of oxyhemoglobin (oxy-Hb). Correlation analysis between anxiety severity and oxy-Hb concentration in the brain cortex was performed, as well as ANOVA analysis of oxy-Hb concentration among the three anxiety severity groups. The results showed that anxiety severity was significantly and negatively correlated with oxy-Hb concentrations in the left frontal eye field (lFEF) and in the right dorsolateral prefrontal area (rDLPFC). The oxy-Hb concentration in the lFEF and the rDLPFC were significantly lower in the major anxiety disorder group than that in the control group. This suggests that decreased cortical activity of the lFEF and rDLPFC may be neural markers of anxiety symptoms after controlling for depression. Anxiety symptoms without depression may be result from the dysfunction of the cognitive control network (CCN) which includes the lFEF and rDLPFC.