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Repair of DNA double-strand breaks (DSBs) elicits three-dimensional (3D) chromatin topological changes. A recent finding reveals that 53BP1 assembles into a 3D chromatin topology pattern around DSBs. How this formation of a higher-order structure is configured and regulated remains enigmatic. Here, we report that SLFN5 is a critical factor for 53BP1 topological arrangement at DSBs. Using super-resolution imaging, we find that SLFN5 binds to 53BP1 chromatin domains to assemble a higher-order microdomain architecture by driving damaged chromatin dynamics at both DSBs and deprotected telomeres. Mechanistically, we propose that 53BP1 topology is shaped by two processes: (1) chromatin mobility driven by the SLFN5-LINC-microtubule axis and (2) the assembly of 53BP1 oligomers mediated by SLFN5. In mammals, SLFN5 deficiency disrupts the DSB repair topology and impairs non-homologous end joining, telomere fusions, class switch recombination, and sensitivity to poly (ADP-ribose) polymerase inhibitor. We establish a molecular mechanism that shapes higher-order chromatin topologies to safeguard genomic stability.
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Cromatina , Reparo do DNA , Animais , Cromatina/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Mamíferos/metabolismo , Proteínas de Ligação a Telômeros/genética , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMO
TGF-ß signaling is a key player in tumor progression and immune evasion, and is associated with poor response to cancer immunotherapies. Here, we identified ubiquitin-specific peptidase 8 (USP8) as a metastasis enhancer and a highly active deubiquitinase in aggressive breast tumors. USP8 acts both as a cancer stemness-promoting factor and an activator of the TGF-ß/SMAD signaling pathway. USP8 directly deubiquitinates and stabilizes the type II TGF-ß receptor TßRII, leading to its increased expression in the plasma membrane and in tumor-derived extracellular vesicles (TEVs). Increased USP8 activity was observed in patients resistant to neoadjuvant chemotherapies. USP8 promotes TGF-ß/SMAD-induced epithelial-mesenchymal transition (EMT), invasion, and metastasis in tumor cells. USP8 expression also enables TßRII+ circulating extracellular vesicles (crEVs) to induce T cell exhaustion and chemoimmunotherapy resistance. Pharmacological inhibition of USP8 antagonizes TGF-ß/SMAD signaling, and reduces TßRII stability and the number of TßRII+ crEVs to prevent CD8+ T cell exhaustion and to reactivate anti-tumor immunity. Our findings not only reveal a novel mechanism whereby USP8 regulates the cancer microenvironment but also demonstrate the therapeutic advantages of engineering USP8 inhibitors to simultaneously suppress metastasis and improve the efficacy of cancer immunotherapy.
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Vesículas Extracelulares , Neoplasias , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Ubiquitina Tiolesterase , Linfócitos T CD8-Positivos/metabolismo , Endopeptidases/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Ubiquitina Tiolesterase/metabolismoRESUMO
Domestication and artificial selection during production-oriented breeding have greatly shaped the level of genomic variability in sheep. However, the genetic variation associated with increased reproduction remains elusive. Here, two groups of samples from consecutively monotocous and polytocous sheep were collected for genome-wide association, transcriptomic, proteomic, and metabolomic analyses to explore the genetic variation in fecundity in Tibetan sheep. Genome-wide association study revealed strong associations between BMPR1B (p.Q249R) and litter size, as well as between PAPPA and lambing interval; these findings were validated in 1,130 individuals. Furthermore, we constructed the first single-cell atlas of Tibetan sheep ovary tissues and identified a specific mural granulosa cell subtype with PAPPA-specific expression and differential expression of BMPR1B between the two groups. Bulk RNA-seq indicated that BMPR1B and PAPPA expressions were similar between the two groups of sheep. 3D protein structure prediction and coimmunoprecipitation analysis indicated that mutation and mutually exclusive exons of BMPR1B are the main mechanisms for prolific Tibetan sheep. We propose that PAPPA is a key gene for stimulating ovarian follicular growth and development, and steroidogenesis. Our work reveals the genetic variation in reproductive performance in Tibetan sheep, providing insights and valuable genetic resources for the discovery of genes and regulatory mechanisms that improve reproductive success.
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Estudo de Associação Genômica Ampla , Multiômica , Humanos , Feminino , Ovinos/genética , Animais , Tibet , Proteômica , Reprodução , MutaçãoRESUMO
Optical spatial differentiation is a typical operation of optical analog computing and can single out the edge to accelerate the subsequent image processing, but in some cases, overall information about the object needs to be presented synchronously. Here, we propose a multifunctional optical device based on structured chiral photonic crystals for the simultaneous realization of real-time dual-mode imaging. This optical differentiator is realized by self-organized large-birefringence cholesteric liquid crystals, which are photopatterned to encode with a special integrated geometric phase. Two highly spin-selective modes of second-order spatial differentiation and bright-field imaging are exhibited in the reflected and transmitted directions, respectively. Two-dimensional edges of both amplitude and phase objects have been efficiently enhanced in high contrast and the broadband spectrum. This work extends the ingenious building of hierarchical chiral nanostructures, enriches their applications in the emerging frontiers of optical computing, and boasts considerable potential in machine vision and microscopy.
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Fanconi anemia (FA) is a rare genetic disease caused by a defect in DNA repair pathway for DNA interstrand crosslinks. These crosslinks can potentially impede the progression of the DNA replication fork, consequently leading to DNA double-strand breaks. Heterozygous RAD51-Q242R mutation has been reported to cause FA-like symptoms. However, the molecular defect of RAD51 underlying the disease is largely unknown. In this study, we conducted a biochemical analysis of RAD51-Q242R protein, revealing notable deficiencies in its DNA-dependent ATPase activity and its ATP-dependent regulation of DNA-binding activity. Interestingly, although RAD51-Q242R exhibited the filament instability and lacked the ability to form displacement loop, it efficiently stimulated the formation of displacement loops mediated by wild-type RAD51. These findings facilitate understanding of the biochemical properties of the mutant protein and how RAD51 works in the FA patient cells.
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Adenosina Trifosfatases , Reparo do DNA , Anemia de Fanconi , Rad51 Recombinase , Humanos , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , DNA/metabolismo , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Mutação , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismoRESUMO
BACKGROUND: Elucidating the genetic variation underlying phenotypic diversity will facilitate improving production performance in livestock species. The Tibetan sheep breed in China holds significant historical importance, serving as a fundamental pillar of Qinghai's animal husbandry sector. The Plateau-type Tibetan sheep, comprising 90% of the province's population, are characterized by their tall stature and serve as the primary breed among Tibetan sheep. In contrast, Zhashijia sheep exhibit larger size and superior meat quality. These two species provide an excellent model for elucidating the genetic basis of body size variation. Therefore, this study aims to conduct a comprehensive genome-wide association study on these two Tibetan sheep breeds to identify single nucleotide polymorphism loci and regulatory genes that influence body size traits in Tibetan sheep. RESULT: In this study, the phenotypic traits of body weight, body length, body height, chest circumference, chest depth, chest width, waist angle width, and pipe circumference were evaluated in two Tibetan sheep breeds: Plateau-type sheep and Zhashijia Tibetan sheep. Whole genome sequencing generated 48,215,130 high-quality SNPs for genome-wide association study. Four methods were applied and identified 623 SNPs significantly associated with body size traits. The significantly associated single nucleotide polymorphisms identified in this study are located near or within 111 candidate genes. These genes exhibit enrichment in the cAMP and Rap1 signaling pathways, significantly affecting animal growth, and body size. Specifically, the following genes were associated: ASAP1, CDK6, FRYL, NAV2, PTPRM, GPC6, PTPRG, KANK1, NTRK2 and ADCY8. CONCLUSION: By genome-wide association study, we identified 16 SNPs and 10 candidate genes associated with body size traits in Tibetan sheep, which hold potential for application in genomic selection breeding programs in sheep. Identifying these candidate genes will establish a solid foundation for applying molecular marker-assisted selection in sheep breeding and improve our understanding of body size control in farmed animals.
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Tamanho Corporal , Estudo de Associação Genômica Ampla , Fenótipo , Polimorfismo de Nucleotídeo Único , Animais , Tamanho Corporal/genética , Ovinos/genética , Ovinos/anatomia & histologia , Tibet , Locos de Características QuantitativasRESUMO
DNAzyme-based assays have found extensive utility in pathogenic bacteria detection but often suffer from limited sensitivity and specificity. The integration of a signal amplification strategy could address this challenge, while the existing combination methods require extensive modification to accommodate various DNAzymes, limiting the wide-spectrum bacteria detection. We introduced a novel hook-like DNAzyme-activated autocatalytic nucleic acid circuit for universal pathogenic bacteria detection. The hook-like connector DNA was employed to seamlessly integrate the recognition element DNAzyme with the isothermal enzyme-free autocatalytic hybridization chain reaction and catalytic hairpin assembly for robust exponential signal amplification. This innovative autocatalytic circuit substantially amplifies the output signals from the DNAzyme recognition module, effectively overcoming DNAzyme's inherent sensitivity constraints in pathogen identification. The biosensor exhibits a strong linear response within a range of 1.5 × 103 to 3.7 × 107 CFU/mL, achieving a detection limit of 1.3 × 103 CFU/mL. Noted that the sensor's adaptability as a universal detection platform is established by simply modifying the hook-like connector module, enabling the detection of various pathogenic bacteria of considerable public health importance reported by the World Health Organization, including Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Salmonella typhimurium. Additionally, the specificity of DNAzyme in bacterial detection is markedly improved due to the signal amplification process of the autocatalytic circuit. This hook-like DNAzyme-activated autocatalytic platform presents a versatile, sensitive, and specific approach for pathogenic bacteria detection, promising to significantly expand the applications of DNAzyme in bacteria detection.
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Técnicas Biossensoriais , DNA Catalítico , DNA Catalítico/química , DNA Catalítico/metabolismo , Técnicas Biossensoriais/métodos , Bactérias/isolamento & purificação , Bactérias/genética , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico , Escherichia coli/isolamento & purificação , Escherichia coli/genéticaRESUMO
MAIN CONCLUSION: The transcription factor LiNAC100 has a novel function of regulating floral fragrance by directly regulating linalool synthase gene LiLiS. Lilium 'Siberia', an Oriental hybrid, is renowned as both a cut flower and garden plant, prized for its color and fragrance. The fragrance comprises volatile organic compounds (VOCs), primarily monoterpenes found in the plant. While the primary terpene synthases in Lilium 'Siberia' were identified, the transcriptional regulation of these terpene synthase (TPS) genes remains unclear. Thus, understanding the regulatory mechanisms of monoterpene biosynthesis is crucial for breeding flower fragrance, thereby improving ornamental and commercial values. In this study, we isolated a nuclear-localized LiNAC100 transcription factor from Lilium 'Siberia'. The virus-induced gene silencing (VIGS) of LiNAC100 was found to down-regulate the expression of linalool synthase gene (LiLiS) and significantly inhibit linalool synthesis. Conversely, transient overexpression of LiNAC100 produced opposite effects. Additionally, yeast one-hybrid and dual-luciferase assays confirmed that LiNAC100 directly activates LiLiS expression. Our findings reveal that LiNAC100 plays a key role in monoterpene biosynthesis in Lilium 'Siberia', promoting linalool synthesis through the activation of LiLiS expression. These results offer insights into the molecular mechanisms of terpene biosynthesis in Lilium 'Siberia' and open avenues for biotechnological enhancement of floral scent.
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Lilium , Lilium/genética , Lilium/metabolismo , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Monoterpenos Acíclicos/metabolismo , Monoterpenos/metabolismo , Flores/genética , Fatores de Transcrição/genéticaRESUMO
MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.
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MicroRNAs , Rhododendron , Transcriptoma/genética , Rhododendron/genética , Rhododendron/metabolismo , Ecossistema , Resposta ao Choque Térmico/genética , MicroRNAs/genética , Perfilação da Expressão GênicaRESUMO
Plants trigger a robust immune response by activating massive transcriptome reprogramming through crosstalk between PTI and ETI. However, how PTI and ETI contribute to the quantitative or/and qualitative output of immunity and how they work together when both are being activated were unclear. In this study, we performed a comprehensive overview of pathogen-triggered transcriptomic reprogramming by analyzing temporal changes in the transcriptome up to 144 h after Colletotrichum gloeosporioides inoculated in Populus. Moreover, we constructed a hierarchical gene regulatory network of PagWRKY18 and its potential target genes to explore the underlying regulatory mechanisms of PagWRKY18 that are not yet clear. Interestingly, we confirmed that PagWRKY18 protein can directly bind the W-box elements in the promoter of a transmembrane leucine-rich repeat receptor-like kinase, PagSOBIR1 gene, to trigger PTI. At the same time, PagWRKY18 functions in disease tolerance by modulation of ROS homeostasis and induction of cell death via directly targeting PagGSTU7 and PagPR4 respectively. Furthermore, PagPR4 can interact with PagWRKY18 to inhibit the expression of PagPR4 genes, forming a negative feedback loop. Taken together, these results suggest that PagWRKY18 may be involved in regulating crosstalk between PTI and ETI to activate a robust immune response and maintain intracellular homeostasis.
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Regulação da Expressão Gênica de Plantas , Imunidade Vegetal , Proteínas de Plantas , Populus , Populus/genética , Populus/imunologia , Populus/microbiologia , Imunidade Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Colletotrichum/fisiologia , Transcriptoma , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Redes Reguladoras de Genes , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism. METHODS: Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis. RESULTS: 398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90-1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99-1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01-2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03-2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables. CONCLUSIONS: In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.
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Doenças Cardiovasculares , Pessoa de Meia-Idade , Idoso , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Glucose , Fatores de Risco , Estudos Longitudinais , Triglicerídeos , China/epidemiologiaRESUMO
The complexity of microvascular circulation has led to the development of advanced imaging techniques and biomimetic models. This study developed a multifaceted microfluidic-based microdevice as an in vitro model of microvasculature to replicate important geometric and functional features of in vivo perfusion in mice. The microfluidic device consisted of a microchannel for blood perfusion, mirroring the natural hierarchical branching vascular structures found in mice. Additionally, the device incorporated a steady gradient of oxygen (O2) which diffused through the polydimethylsiloxane (PDMS) layer, allowing for dynamic blood oxygenation. The assembled multi-layered microdevice was accompanied by a dual-modal imaging system that combined laser speckle contrast imaging (LSCI) and intrinsic signal optical imaging (ISOI) to visualize full-field blood flow distributions and blood O2 profiles. By closely reproducing in vivo blood perfusion and oxygenation conditions, this microvasculature model, in conjunction with numerical simulation results, can provide quantitative information on physiologically relevant hemodynamics and key O2 transport parameters that are not directly measurable in traditional animal studies.
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Hemodinâmica , Microfluídica , Camundongos , Animais , Oxigênio , MicrovasosRESUMO
BACKGROUND: Pien Tze Huang (PZH), a traditional Chinese medicine formulation, is recognized for its therapeutic effect on colitis and colorectal cancer. However, its protective role and underlying mechanism in colitis-associated colorectal cancer (CAC) remain to be elucidated. METHODS: A CAC mouse model was established using AOM/DSS. Twenty mice were randomly divided into four groups (n = 5/group): Control, PZH, AOM/DSS, and AOM/DSS + PZH groups. Mice in the PZH and AOM/DSS + PZH group were orally administered PZH (250 mg/kg/d) from the first day of experiment, while the control and AOM/DSS group received an equivalent volume of distilled water. Parameters such as body weight, disease activity index (DAI), colon weight, colon length, colon histomorphology, intestinal tumor formation, serum concentrations of pro-inflammatory cytokines, proliferation and apoptosis in colon tissue were assessed. RNA sequencing was employed to identify the differentially expressed transcripts (DETs) in colonic tissues and related signaling pathways. Wnt/ß-Catenin Pathway-Related genes in colon tissue were detected by QPCR and immunohistochemistry (IHC). RESULTS: PZH significantly attenuated AOM/DSS-induced weight loss, DAI elevation, colonic weight gain, colon shortening, histological damage, and intestinal tumor formation in mice. PZH also notably decreased serum concentration of IL-6, IL-1ß, and TNF-α. Furthermore, PZH inhibited cell proliferation and promote apoptosis in tumor tissues. RNA-seq and KEGG analysis revealed key pathways influenced by PZH, including Wnt/ß-catenin signaling pathway. IHC staining confirmed that PZH suppressed the expression of ß-catenin, cyclin D1 and c-Myc in colonic tissues. CONCLUSIONS: PZH ameliorates AOM/DSS-induced CAC in mice by suppressing the activation of Wnt/ß-catenin signaling pathway.
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The chemical composition and physical properties of secondary organic aerosol (SOA) generated through OH-initiated oxidation of mixtures containing ß-myrcene, an acyclic monoterpene, and d-limonene, a cyclic monoterpene, were investigated to assess the extent of the chemical interactions between their oxidation products. The SOA samples were prepared in an environmental smog chamber, and their composition was analyzed offline using ultraperformance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UPLC-ESI-HRMS). Our results suggested that SOA containing ß-myrcene showed a higher proportion of oligomeric compounds with low volatility compared to that of SOA from d-limonene. The formula distribution and signal intensities of the mixed SOA could be accurately predicted by a linear combination of the mass spectra of the SOA from individual precursors. Effects of cross-reactions were observed in the distribution of isomeric oxidation products within the mixed SOA, as made evident by chromatographic analysis. On the whole, ß-myrcene and d-limonene appear to undergo oxidation by OH largely independently from each other, with only subtle effects from cross-reactions influencing the yields of specific oxidation products.
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Pivotal enhancements in electronic minimization algorithms, which are vital for the advancement of computational materials science, are introduced in this research. Our research is dedicated to refining the DIIS algorithm specifically for electronic structure calculations of silicon (Si) and gallium arsenide (GaAs) solar cells, aiming to enhance their efficiency and stability. We have enriched DIIS by integrating a weight regularization factor, significantly bolstering its convergence stability. This modification enhances iteration robustness and curtails the average iteration duration, thus streamlining the convergence process. Furthermore, we have incorporated the conjugate gradient (CG) algorithm to proficiently resolve symmetric positive definite residual matrices. This inclusion substantially accelerates the solution-finding process within the DIIS framework. A novel aspect of our research is the application of reverse automatic differentiation (AD), deployed in two distinct methodologies: the construction of the Jacobian matrix and direct chain rule application for gradient computation. These approaches involve sophisticated mathematical techniques that enhance computational precision and efficiency specifically for Si and GaAs solar cell materials in determining the optimal weights for residual combinations during DIIS iterations. The integration of these advanced methods into the DIIS algorithm not only augments its convergence stability but also ensures a substantial reduction in total computational time. Our findings demonstrate that the enhanced DIIS, CG-enhanced DIIS, and AD-integrated DIIS methods collectively lead to a more efficient electronic minimization process. This balance of stability and efficiency is crucial in high-performance computational materials science, particularly for complex systems analysis. The findings of this research represent a notable advancement in computational strategies for Si and GaAs solar cell materials, providing enhanced methodologies and insights that significantly improve the efficiency and stability of electronic structure calculations in these critical components of renewable energy technologies.
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Pesticides play an important role in the development of agriculture, as they can prevent and control crop diseases and pests, improve crop yield and quality. However, the abuse and improper use of pesticides can lead to negative impacts such as environmental pollution and pest resistance issues. There is an urgent need to develop green, safe, and efficient pesticides. In this work, natural product arecoline was selected as parent structure, a series of arecoline derivatives were designed, synthesized, and systematically investigated antiviral activities against tobacco mosaic virus (TMV). These compounds were found to have good to excellent anti-TMV activities for the first time. The antiviral activities of 4a, 4 h, 4 l, 4p, 6a, 6c, and 6f are higher than that of ningnanmycin. Compounds 4 h (EC50 value 146 µg/mL) and 4p (EC50 value 161 µg/mL) with simple structures and excellent activities emerged as new antiviral candidates. We chose 4 h to further investigate the antiviral mechanism, which revealed that it can cause virus fragmentation by acting on the viral coat protein (CP). We further validated this result through molecular docking. These compounds also displayed broad-spectrum fungicidal activities against 8 plant pathogenic fungi. This work lays the theoretical foundation for the application of arecoline derivatives in the agricultural field.
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Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus, or corded and hyalinized endometrioid adenocarcinoma (CHEC), is a rare morphological variant of endometrioid carcinoma, for which there is limited literature and few cases reports. Most researchers tend to consider CHEC as a low-grade cancer with a favorable prognosis. Full-staging surgery is the primary choice for this disease, and no case of CHEC has been previously reported to be treated conservatively. Here, we present the following case to explore the possibility of fertility-preserving treatment for young women with CHEC. A 23-year-old nulliparous patient diagnosed with presumed stage IA CHEC received fertility-sparing treatment at the Obstetrics and Gynecology Hospital of Fudan University and got a complete response (CR) after 10 months of conservative treatment. The patient subsequently became pregnant spontaneously, successfully conceived, and gave birth to a healthy male neonate without any sign of recurrence during 37 months follow-up after CR. The patient's postpartum follow-up is continuing. Presently, CHEC is not included in the fertility-sparing field of any available guidelines. This case indicates that fertility-sparing treatment may be an option for highly selected patients with CHEC. Continuous follow-up remains mandatory to observe long-term outcomes.
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Carcinoma Endometrioide , Neoplasias do Endométrio , Gravidez , Recém-Nascido , Feminino , Humanos , Masculino , Adulto Jovem , Adulto , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/patologia , Tratamento Conservador , Útero/patologia , PrognósticoRESUMO
PURPOSE: To investigate the capacity of critical flicker frequency (CFF) in discriminating cataract eyes with or without macula disease using trichromatic flickers, and to develop a model to predict postoperative best corrected visual acuity (BCVA). METHODS: Patients were divided into two groups based on the presence or absence of macular disease. CFF threshold measurements of red (R-CFF), green (G-CFF), and yellow (Y-CFF) flickers were conducted both preoperatively and postoperatively. A generalized estimating equations model (GEE) was employed to examine the relationship between CFF threshold and 3-month postoperative BCVA. RESULTS: A total of 115 eyes were enrolled, with 59 eyes in the cataract alone group and 56 eyes in the cataract with macular disease group completing the follow-up. R-CFF was found to be consistent before and after cataract removal (P = 0.06), even in cases where OCT was not performed successfully (P > 0.05). Y-CFF showed the highest AUC (0.798) for differentiating ocular comorbidities. According to the GEE model, in patients with a CFF threshold below 26 Hz, the odds ratios for achieving a postoperative VA of 20/40 or better were 34.8% for R-CFF, 26.0% for G-CFF, and 24.5% for Y-CFF. CONCLUSION: CFF emerges as a promising tool for predicting postoperative BCVA, providing valuable supplementary insights when fundus examination is obstructed. R-CFF demonstrates the best resistance to cataracts, while Y-CFF exhibits the highest sensitivity both in identifying macular diseases and predicting postoperative BCVA of 20/40 or better.
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Catarata , Acuidade Visual , Humanos , Feminino , Masculino , Catarata/fisiopatologia , Catarata/complicações , Catarata/diagnóstico , Acuidade Visual/fisiologia , Idoso , Pessoa de Meia-Idade , Macula Lutea/fisiopatologia , Macula Lutea/diagnóstico por imagem , Macula Lutea/patologia , Seguimentos , Doenças Retinianas/fisiopatologia , Doenças Retinianas/diagnóstico , Tomografia de Coerência Óptica/métodos , Curva ROC , Estudos Prospectivos , Testes Visuais/métodosRESUMO
OBJECTIVES: Older people are more likely to have digital exclusion, which is associated with poor health. This study investigated the relationship between digital exclusion and cognitive impairment in older adults from 23 countries across five longitudinal surveys. DESIGN AND MEASUREMENTS: Digital exclusion is defined as self-reported non-use of the Internet. We assessed cognitive impairment on three dimensions: orientation, memory, and executive function. We used generalized estimation equations fitting binary logistic regression with exchangeable correlations to study the relationship between digital exclusion and cognitive impairment, and apply the minimum sufficiently adjusted set of causally directed acyclic graphs as the adjusted variable. SETTING AND PARTICIPANTS: We pooled a nationally representative sample of older adults from five longitudinal studies, including the China Health and Retirement Longitudinal study (CHARLS), the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), the Mexican Health and Ageing Study (MHAS) and the Survey of Health, Ageing and Retirement in European (SHARE). RESULTS: We included 62,413 participants from five longitudinal studies. Digital exclusion varied by country, ranging from 21.69% (SHARE) in Denmark to 97.15% (CHARLS) in China. In the original model, digital exclusion was significantly associated with cognitive impairment in all five studies. In the adjusted model, these associations remained statistically significant: CHARLS (Odds ratio [OR] = 2.81, 95% confidence interval [CI] 1.84-4.28, ELSA (1.92 [1.70-2.18]), HRS(2.48[2.28-2.71), MHAS (1.92 [1.74-2.12]), and SHARE (2.60 [2.34-2.88]). CONCLUSION: Our research shows that a significant proportion of older people suffer from digital exclusion, especially in China. Digital exclusion was positively correlated with cognitive impairment. These findings suggest that digital inclusion could be an important strategy to improve cognitive function and reduce the risk of cognitive impairment in older adults.
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Disfunção Cognitiva , Humanos , Idoso , Estudos Longitudinais , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , China/epidemiologia , Uso da Internet/estatística & dados numéricosRESUMO
Masspersonal communication has emerged as a compelling alternative persuasive approach in response to the widespread use of social media. It is crucial to comprehend how observing online interpersonal interactions regarding the fear appeal of climate change can foster pro-environmental behaviors among users. This study examines the effects of vicarious message interactivity in promoting actions against climate change and the underlying mechanisms behind this effect. The results of an online experiment conducted in China (N = 236) revealed that psychological reactance and message elaboration mediated the effects of vicarious message interactivity on behavioral intention in a serial indirect effect. In comparison to static fear appeal, interactive fear appeal proves effective in reducing psychological reactance, promoting message elaboration, and ultimately increasing intention to take actions against climate change. Our findings not only contribute to the literature on interactive communication but also provide insights for environmental-health campaigns on social media.