Carbon dots (CDs) are photoluminescent nanomaterials with wide-ranging applications. Despite their photoactivity, it remains unknown whether CDs degrade under illumination and whether such ...photodegradation poses any cytotoxic effects. Here, we show laboratory-synthesized CDs irradiated with light degrade into molecules that are toxic to both normal (HEK-293) and cancerous (HeLa and HepG2) human cells. Eight days of irradiation photolyzes 28.6-59.8% of the CDs to <3 kilo Dalton molecules, 1431 of which are detected by high-throughput, non-target high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Molecular network and community analysis further reveal 499 cytotoxicity-related molecules, 212 of which contain polyethylene glycol, glucose, or benzene-related structures. Photo-induced production of hydroxyl and alkyl radicals play important roles in CD degradation as affected by temperature, pH, light intensity and wavelength. Commercial CDs show similar photodegraded products and cytotoxicity profiles, demonstrating that photodegradation-induced cytotoxicity is likely common to CDs regardless of their chemical composition. Our results highlight the importance of light in cytocompatibility studies of CDs.
A room‐temperature, visible‐light‐driven N‐centered iminyl radical‐mediated and redox‐neutral C−C single bond cleavage/radical addition cascade reaction of oxime esters and unsaturated systems has ...been accomplished. The strategy tolerates a wide range of O‐acyl oximes and unsaturated systems, such as alkenes, silyl enol ethers, alkynes, and isonitrile, enabling highly selective formation of various chemical bonds. This method thus provides an efficient approach to various diversely substituted cyano‐containing alkenes, ketones, carbocycles, and heterocycles.
A visible‐light‐driven room‐temperature N‐centered iminyl radical‐mediated and redox‐neutral C−C single bond cleavage/radical addition cascade reaction of oxime esters and unsaturated systems has been accomplished. The strategy tolerates a wide range of O‐acyl oximes and alkenes, silyl enol ethers, alkynes, and isonitrile. This method allows access to various cyano‐containing alkenes, ketones, carbocycles, and heterocycles.
Verticillium dahliae isolates are most virulent on the host from which they were originally isolated. Mechanisms underlying these dominant host adaptations are currently unknown. We sequenced the ...genome of V. dahliae Vd991, which is highly virulent on its original host, cotton, and performed comparisons with the reference genomes of JR2 (from tomato) and VdLs.17 (from lettuce).
Pathogenicity-related factor prediction, orthology and multigene family classification, transcriptome analyses, phylogenetic analyses, and pathogenicity experiments were performed.
The Vd991 genome harbored several exclusive, lineage-specific (LS) genes within LS regions (LSRs). Deletion mutants of the seven genes within one LSR (G-LSR2) in Vd991 were less virulent only on cotton. Integration of G-LSR2 genes individually into JR2 and VdLs.17 resulted in significantly enhanced virulence on cotton but did not affect virulence on tomato or lettuce. Transcription levels of the seven LS genes in Vd991 were higher during the early stages of cotton infection, as compared with other hosts. Phylogenetic analyses suggested that G-LSR2 was acquired from Fusarium oxysporum f. sp. vasinfectum through horizontal gene transfer.
Our results provide evidence that horizontal gene transfer from Fusarium to Vd991 contributed significantly to its adaptation to cotton and may represent a significant mechanism in the evolution of an asexual plant pathogen.
Tapetum development and pollen production are regulated by a complex transcriptional network that consists of a group of tapetum-specific Arabidopsis transcription factors (TFs). Among these TFs, ...DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1) encodes an R2R3 MYB factor, and ABORTED MICROSPORE (AMS) encodes a basic helix-loop-helix (bHLH) factor. However, knowledge regarding the regulatory role of TDF1 in anther development remains limited.
Here, we discovered that TDF1 directly regulates AMS via an AACCT cis-element. We found the precocious AMS transcript and absence of AMS protein in ams
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gpTDF1:AMS-FLAG lines, suggesting the timing of the TDF1-regulated AMS expression is a prerequisite for AMS functioning.
We found that TDF1 interacts with AMS. Additionally, the TDF1–AMS complex additively promotes the expression of AMS-regulated genes, suggesting that TDF1 and AMS regulate the downstream genes through a feed-forward loop.
EPXB5, encoding a beta-expansin family protein, is another direct target of TDF1, and it is highly expressed in the tapetum and pollen grains. The TDF1–AMS complex acts in concert to activate EXPB5 expression through a feed-forward loop. The identification of the regulatory pathway between TDF1 and AMS provides an interlocked feed-forward loop circuit that precisely regulates the transcriptional cascades that support anther development.
Lithium metal is one of the most attractive anode materials for next-generation lithium batteries due to its high specific capacity and low electrochemical potential. However, the poor cycling ...performance and serious safety hazards, caused by the growth of dendritic and mossy lithium, has long hindered the application of lithium metal based batteries. Herein, we reported a rational design of free-standing Cu nanowire (CuNW) network to suppress the growth of dendritic lithium via accommodating the lithium metal in three-dimensional (3D) nanostructures. We demonstrated that as high as 7.5 mA h cm–2 of lithium can be plated into the free-standing copper nanowire (CuNW) current collector without the growth of dendritic lithium. The lithium metal anode based on the CuNW exhibited high Coulombic efficiency (average 98.6% during 200 cycles) and outstanding rate performance owing to the suppression of lithium dendrite growth and high conductivity of CuNW network. Our results demonstrate that the rational nanostructural design of current collector could be a promising strategy to improve the performance of lithium metal anode enabling its application in next-generation lithium–metal based batteries.
The tapetum plays a critical role during the development and maturation of microspores. DYSFUNCTIONAL TAPETUM 1 (DYT1) is essential for early tapetal development. Here, we determined that the ...promoter region (−550 to −463 bp) contains indispensable cis‐elements for DYT1 expression. Although DYT1 transcripts can be detected in both meiocytes and tapetal cells, localization of DYT1–GFP demonstrated that DYT1 is strictly located in tapetal cells during microsporogenesis. Chromatin immunoprecipitation (ChIP) analysis revealed that DYT1 directly binds the promoter region of Defective in Tapetal Development and Function 1 (TDF1), a transcription factor essential for tapetum development. When TDF1 driven by the DYT1 promoter is expressed in a dyt1 mutant, the expression of the transcription factors AMS, MS188/MYB80, TEK and MS1 and the pollen wall‐related genes are restored. Although the pollen wall is not formed and the microspores are ruptured, DIOC₂staining showed that fatty acids, the precursors of the pollen wall, were synthesized in the transgenic lines. These results indicate that DYT1 regulates the expression of AMS, MS188/MYB80, TEK and MS1 for pollen wall formation, primarily via TDF1.
Disulfide bonds play an important role in thiol‐based redox regulation. However, owing to the lack of analytical tools, little is known about how local O2 mediates the reversible thiol/disulfide ...cycle under protein confinement. In this study, a protein‐nanopore inside a glove box is used to control local O2 for single‐molecule reaction, as well as a single‐molecule sensor for real‐time monitoring of the reversible thiol/disulfide cycle. The results demonstrate that the local O2 molecules in protein nanopores could facilitate the redox cycle of disulfide formation and cleavage by promoting a higher fraction of effective reactant collisions owing to nanoconfinement. Further kinetic calculations indicate that the negatively charged residues near reactive sites facilitate proton‐involved oxygen‐induced disulfide cleavage under protein confinement. The unexpectedly strong oxidation ability of confined local O2 may play an essential role in cellular redox signaling and enzyme reactions.
The reversible thiol/disulfide cycle under protein confinement was monitored in real‐time using a mutant aerolysin nanopore. Experiments combined with kinetic calculations revealed that confined local O2 can lead to proton‐involved, oxygen‐induced disulfide bond cleavage. The negatively charged neighboring microenvironment facilitates disulfide bond cleavage, which plays a vital role in redox signaling and reactions.
The epidemiology on the human papillomavirus (HPV) among females in Southern China is not well-established. Baseline data on the prevalence of HPV infection in China prior to mass prophylactic HPV ...vaccination would be useful. Thus, this study aims to determine the type-specific HPV prevalence and distribution among females from Southern China prior to mass HPV vaccination.
A retrospective cross-sectional study employing 214,715 women attending ChenZhou NO.1 People's Hospital for cervical screening during 2012-2018 was conducted prior to widespread HPV vaccination. HPV genotype was detected using nucleic acid molecular diversion hybridization tests. The overall prevalence, age-specific prevalence, type distribution, and annual trend were analyzed.
The overall HPV prevalence was 18.71% (95% confidence interval CI, 18.55-18.88%) among Southern China females. During 2012-2018, the prevalence of HPV infection showed a downward tendency, from 21.63% (95% CI, 21.07-22.20%) in 2012 to 18.75% (95% CI, 18.35-19.16%) in 2018. Age-specific HPV distribution displayed a peak at young women aged less than 21 years (33.11, 95% CI, 31.13-35.15%), 20.07% (95% CI, 19.70-20.44%) among women aged 21-30 years, 17.29% (95% CI, 17.01-17.57%) among women aged 31-40 years, 17.23% (95% CI, 16.95-17.51%) among women aged 41-50 years, 21.65% (95% CI, 21.11-22.20%) among women aged 51-60 years, and 25.95% (95% CI, 24.86-27.07%) among women aged over 60 years. Of the 21 subtypes identified, the top three prevalent high-risk HPV (HR-HPV) genotypes were HPV52 (5.12%; 95% CI, 21.11-22.20%), - 16 (2.96%; 95% CI, 2.89-3.03%), and - 58 (2.51%; 95% CI, 2.44-2.58%); the predominant low-risk HPV (LR-HPV) genotypes were HPV81 (1.86%; 95%CI, 1.80-1.92%) and - 6 (0.69%; 95% CI, 0.66-0.73%) respectively. Incidence of HR-HPV only, LR-HPV only and mixed LR- and HR-HPV were 15.17, 2.07 and 1.47% respectively. Besides, single HPV infection accounted for 77.30% of all positive cases in this study.
This study highlights 1) a high prevalence of HPV infection among females with a decreasing tendency towards 2012-2018, especially for young women under the age of 21 prior to mass HPV vaccination; 2) HPV52, - 16 and - 58 were the predominant HPV genotypes, suggesting potential use of HPV vaccine covering these HPV genotypes in Southern China.
Abstract
Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and ...senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.
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