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The development and function of the immune system are controlled by temporospatial gene expression programs, which are regulated by cis-regulatory elements, chromatin structure, and trans-acting factors. In this study, we cataloged the dynamic histone modifications and chromatin interactions at regulatory regions during T helper (Th) cell differentiation. Our data revealed that the H3K4me1 landscape established by MLL4 in naive CD4+ T cells is critical for restructuring the regulatory interaction network and orchestrating gene expression during the early phase of Th differentiation. GATA3 plays a crucial role in further configuring H3K4me1 modification and the chromatin interaction network during Th2 differentiation. Furthermore, we demonstrated that HSS3-anchored chromatin loops function to restrict the activity of the Th2 locus control region (LCR), thus coordinating the expression of Th2 cytokines. Our results provide insights into the mechanisms of how the interplay between histone modifications, chromatin looping, and trans-acting factors contributes to the differentiation of Th cells.
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Diferenciação Celular , Cromatina , Código das Histonas , Histonas , Células Th2 , Diferenciação Celular/imunologia , Animais , Cromatina/metabolismo , Camundongos , Células Th2/imunologia , Histonas/metabolismo , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Região de Controle de Locus Gênico , Citocinas/metabolismoRESUMO
Cis-regulatory elements have an important role in human adaptation to the living environment. However, the lag in population genomic cohort studies and epigenomic studies, hinders the research in the adaptive analysis of cis-regulatory elements in human populations. In this study, we collected 4,013 unrelated individuals and performed a comprehensive analysis of adaptive selection of genome-wide cis-regulatory elements in the Han Chinese. In total, 12.34% of genomic regions are under the influence of adaptive selection, where 1.00% of enhancers and 2.06% of promoters are under positive selection, and 0.06% of enhancers and 0.02% of promoters are under balancing selection. Gene ontology enrichment analysis of these cis-regulatory elements under adaptive selection reveals that many positive selections in the Han Chinese occur in pathways involved in cell-cell adhesion processes, and many balancing selections are related to immune processes. Two classes of adaptive cis-regulatory elements related to cell adhesion were in-depth analyzed, one is the adaptive enhancers derived from neanderthal introgression, leads to lower hyaluronidase level in skin, and brings better performance on UV-radiation resistance to the Han Chinese. Another one is the cis-regulatory elements regulating wound healing, and the results suggest the positive selection inhibits coagulation and promotes angiogenesis and wound healing in the Han Chinese. Finally, we found that many pathogenic alleles, such as risky alleles of type 2 diabetes or schizophrenia, remain in the population due to the hitchhiking effect of positive selections. Our findings will help deepen our understanding of the adaptive evolution of genome regulation in the Han Chinese.
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Diabetes Mellitus Tipo 2 , Homem de Neandertal , Humanos , Animais , Diabetes Mellitus Tipo 2/genética , Seleção Genética , Sequências Reguladoras de Ácido Nucleico , Regiões Promotoras Genéticas , Homem de Neandertal/genética , China , Elementos Facilitadores GenéticosRESUMO
Specific metabolites have been reported to be potentially associated with Alzheimer's disease (AD) risk. However, the comprehensive understanding of roles of metabolite biomarkers in AD etiology remains elusive. We performed a large AD metabolome-wide association study (MWAS) by developing blood metabolite genetic prediction models. We evaluated associations between genetically predicted levels of metabolites and AD risk in 39,106 clinically diagnosed AD cases, 46,828 proxy AD and related dementia (proxy-ADD) cases, and 401,577 controls. We further conducted analyses to determine microbiome features associated with the detected metabolites and characterize associations between predicted microbiome feature levels and AD risk. We identified fourteen metabolites showing an association with AD risk. Five microbiome features were further identified to be potentially related to associations of five of the metabolites. Our study provides new insights into the etiology of AD that involves blood metabolites and gut microbiome, which warrants further investigation.
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Doença de Alzheimer , Biomarcadores , Genômica , Metabolômica , Humanos , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Metabolômica/métodos , Biomarcadores/sangue , Feminino , Masculino , Genômica/métodos , Idoso , Metaboloma , Estudo de Associação Genômica Ampla/métodos , Microbioma Gastrointestinal/fisiologia , Microbioma Gastrointestinal/genética , Fatores de Risco , Pessoa de Meia-Idade , Estudos de Casos e ControlesRESUMO
Development of mRNA therapeutics necessitates targeted delivery technology, while the clinically advanced lipid nanoparticles face difficulty for extrahepatic delivery. Herein, we design highly branched poly(ß-amino ester)s (HPAEs) for efficacious organ-selective mRNA delivery through tailoring their chemical compositions and topological structures. Using an "A2+B3+C2" Michael addition platform, a combinatorial library of 219 HPAEs with varied backbone structures, terminal groups, and branching degrees are synthesized. The branched topological structures of HPAEs provide enhanced serum resistance and significantly higher mRNA expression in vivo. The terminal amine structures of HPAEs determine the organ-selectivity of mRNA delivery following systemic administration: morpholine facilitates liver targeting, ethylenediamine favors spleen delivery, while methylpentane enables mRNA delivery to the liver, spleen, and lungs simultaneously. This study represents a comprehensive exploration of the structure-activity relationship governing both the efficiency and organ-selectivity of mRNA delivery by HPAEs, suggesting promising candidates for treating various organ-related diseases.
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Polímeros , RNA Mensageiro , RNA Mensageiro/genética , Animais , Humanos , Polímeros/química , Camundongos , Nanopartículas/química , Fígado/metabolismo , Baço/metabolismo , Técnicas de Transferência de Genes , Pulmão/metabolismoRESUMO
The emergence of one-dimensional van der Waals heterostructures (1D vdWHs) opens up potential fields with unique properties, but precise synthesis remains a challenge. The utilization of mixed conductive types of carbon nanotubes as templates has imposed restrictions on the investigation of the electrical behavior and interlayer interaction of 1D vdWHs. In this study, we efficiently encapsulated silver iodide in high-purity semiconducting single-walled carbon nanotubes (sSWCNTs), forming 1D AgI@sSWCNT vdWHs. We characterized the semiconductor-metal transition and increased the carrier concentration of individual AgI@sSWCNTs via sensitive dielectric force microscopy and confirmed the results through electrical device tests. The electrical behavior transition was attributed to an interlayer charge transfer, as demonstrated by Kelvin probe force microscopy. Furthermore, we showed that this method of synthesizing 1D heterostructures can be extended to other metal halides. This work opens the door for the further exploration of the electrical properties of 1D vdWHs.
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Probabilistic bits (p-bits) with thermal- and spin torque-induced nondeterministic magnetization switching are promising candidates for performing probabilistic computing. Previously reported spin torque p-bits include volatile low-energy barrier nanomagnets (LBNMs) with spontaneously fluctuating magnetizations and initialization-necessary nonvolatile magnets. However, initialization-free nonvolatile spin torque p-bits are still lacking. Here, we demonstrate moderately thermal stable spin-orbit torque (SOT) p-bits with non-consecutively deposited Pt//Pt/Co/Pt stacks. Backhopping-like (BH) magnetization switching with a wide range current-tunable probability of final up and down magnetization states from 0% to 100% was achieved, regardless of the initial magnetization state, which was attributed to the interplay of SOT and thermal contributions. Integer factorization using such BH-SOT p-bits in zero magnetic field was demonstrated at times that are significantly shorter than those of existing nonvolatile STT or volatile LBNMs p-bits. Our realization of initialization-free and magnetic field-free moderately thermally stable BH-SOT p-bits opens up a new perspective for probabilistic spintronic applications.
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Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.
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Desenho de Fármacos , Descoberta de Drogas , Estereoisomerismo , Humanos , AnimaisRESUMO
One-dimensional (1D) high-entropy compounds (HECs) with subnano diameters are highly attractive because long-range electron delocalization may occur along the high-entropy atomic chain, which results in extraordinary properties. Nevertheless, synthesizing such 1D HECs presents a substantial challenge, and the physicochemical attributes of these novel structures remain ambiguous. Herein, we developed a comelting-filling-freezing-modification (co-MFFM) method for synthesizing 1D high-entropy metal phosphide (HEP) by simultaneously encapsulating various metal cations within single-walled carbon nanotubes (SWCNTs) followed with a phosphorization process. The resulting 1D HEP nanowires confined within SWCNTs exhibit crucial features, including an ultrafine, high-entropy, and amorphous structure, along with a core-shell arrangement. The SWCNT as a shell could donate π electrons to 1D HEP for enhanced electron delocalization and protect 1D HEP as an atomically single-layered protective covering, thus boosting high electrocatalytic activity and stability. Moreover, the co-MFFM method demonstrates scalability for mass production and displays universal applicability to the synthesis of various 1D HECs.
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In central nervous system (CNS), demyelination is a pathological process featured with a loss of myelin sheaths around axons, which is responsible for the diseases of multiple sclerosis, neuromyelitis optica, and so on. Transforming growth factor-beta1 (TGF-ß1) is a multifunctional cytokine participating in abundant physiological and pathological processes in CNS. However, the effects of TGF-ß1 on CNS demyelinating disease and its underlying mechanisms are controversial and not well understood. Herein, we evaluated the protective potential of TGF-ß1 in a rodent demyelinating model established by lysophosphatidylcholine (LPC) injection. It was identified that supplement of TGF-ß1 evidently rescued the cognitive deficit and motor dysfunction in LPC modeling mice assessed by novel object recognition and balance beam behavioral tests. Besides, quantified by luxol fast blue staining, immunofluorescence, and western blot, administration of TGF-ß1 was found to significantly ameliorate the demyelinating lesion and reactive astrogliosis by suppressing p38 MAPK pathway. Mechanistically, the results of in vitro experiments indicated that treatment of TGF-ß1 could directly promote the differentiation and migration of cultured oligodendrocytes. Our study revealed that modulating TGF-ß1 activity might serve as a promising and innovative therapeutic strategy in CNS demyelinating diseases.
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Lesões Encefálicas , Substância Branca , Animais , Camundongos , Gliose/prevenção & controle , Inflamação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Roedores , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Substância Branca/metabolismoRESUMO
BACKGROUND: Baolia H.W.Kung & G.L.Chu is a monotypic genus only known in Diebu County, Gansu Province, China. Its systematic position is contradictory, and its morphoanatomical characters deviate from all other Chenopodiaceae. Recent study has regarded Baolia as a sister group to Corispermoideae. We therefore sequenced and compared the chloroplast genomes of this species, and resolved its phylogenetic position based on both chloroplast genomes and marker sequences. RESULTS: We sequenced 18 chloroplast genomes of 16 samples from two populations of Baolia bracteata and two Corispermum species. These genomes of Baolia ranged in size from 152,499 to 152,508 bp. Simple sequence repeats (SSRs) were primarily located in the LSC region of Baolia chloroplast genomes, and most of them consisted of single nucleotide A/T repeat sequences. Notably, there were differences in the types and numbers of SSRs between the two populations of B. bracteata. Our phylogenetic analysis, based on both complete chloroplast genomes from 33 species and a combination of three markers (ITS, rbcL, and matK) from 91 species, revealed that Baolia and Corispermoideae (Agriophyllum, Anthochlamys, and Corispermum) form a well-supported clade and sister to Acroglochin. According to our molecular dating results, a major divergence event between Acroglochin, Baolia, and Corispermeae occurred during the Middle Eocene, approximately 44.49 mya. Ancestral state reconstruction analysis showed that Baolia exhibited symplesiomorphies with those found in core Corispermoideae characteristics including pericarp and seed coat. CONCLUSIONS: Comparing the chloroplast genomes of B. bracteata with those of eleven typical Chenopodioideae and Corispermoideae species, we observed a high overall similarity and a one notable noteworthy case of inversion of approximately 3,100 bp. of DNA segments only in two Atriplex and four Chenopodium species. We suggest that Corispermoideae should be considered in a broader sense, it includes Corispermeae (core Corispermoideae: Agriophyllum, Anthochlamys, and Corispermum), as well as two new monotypic tribes, Acroglochineae (Acroglochin) and Baolieae (Baolia).
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Amaranthaceae , Genoma de Cloroplastos , Filogenia , Amaranthaceae/genética , Amaranthaceae/anatomia & histologia , Amaranthaceae/classificação , Repetições de Microssatélites , China , DNA de Cloroplastos/genética , Análise de Sequência de DNA , Marcadores GenéticosRESUMO
High-quality-factor microring resonators are highly desirable in many applications. Fabricating a microring resonator typically requires delicate instruments to ensure a smooth side wall of waveguides and 100-nm critical feature size in the coupling region. In this work, we demonstrate a new method "damascene soft nanoimprinting lithography" that can create high-fidelity waveguide by simply backfill an imprinted cladding template with a high refractive index polymer core. This method can easily realize high Q-factor polymer microring resonators (e.g., ~5 x 105 around 770 nm wavelength) without the use of any expensive instruments and can be conducted in a normal lab environment. The high Q-factors can be attributed to the residual layer-free feature and controllable meniscus cross-section profile of the filled polymer core. Furthermore, the new method is compatible with different polymers, yields low fabrication defects, enables new functionalities, and allows flexible substrate. These benefits can broaden the applicability of the fabricated microring resonator.
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The applications of natural laccases are greatly restricted because of their drawbacks like poor biostability, high costs, and low recovery efficiency. M/NC single atom nanozymes (M/NC SAzymes) are presenting as great substitutes due to their superior enzyme-like activity, excellent selectivity and high stability. In this work, inspired by the catalytic active center of natural enzyme, a biomimetic Fe/NC SAzyme (Fe-SAzyme) with O2-Fe-N4 coordination is successfully developed, exhibiting excellent laccase-like activity. Compared with their natural counterpart, Fe-SAzyme has shown superior catalytic efficiency and excellent stability under a wide range of pH (3.0-9.0), temperature (4-80 °C) and NaCl strength (0-300 mm). Interestingly, density functional theory (DFT) calculations reveal that the high catalytic performance is attributed to the activation of O2 by O2-Fe-N4 sites, which weakened the OâO bonds in the oxygen-to-water oxidation pathway. Furthermore, Fe-SAzyme is successfully applied for efficient aflatoxin B1 removal based on its robust laccase-like catalytic activity. This work provides a strategy for the rational design of laccase-like SAzymes, and the proposed catalytic mechanism will help to understand the coordination environment effect of SAzymes on laccase-like catalytic processes.
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Post-transplant lymphoproliferative disorders (PTLDs) are associated with Epstein-Barr virus (EBV) infection in transplant recipients. Most of lymphoblastoid cell lines (LCLs) derived from EBV-immortalized B cells or PTLDs are sensitive to CD95-mediated apoptosis and cytotoxic T cell (CTL) killing. CD95 ligand (CD95L) exists as a transmembrane ligand (mCD95L) or a soluble form (sCD95L). Using recombinant mCD95L and sCD95L, we observed that sCD95L does not affect LCLs. While high expression of mCD95L in CTLs promotes apoptosis of LCLs, low expression induces clathrin-dependent CD19 internalization, caspase-dependent CD19 cleavage, and proteasomal/lysosomal-dependent CD19 degradation. The CD95L/CD95-mediated CD19 degradation impairs B cell receptor (BCR) signaling and inhibits BCR-mediated EBV activation. Interestingly, although inhibition of the caspase activity restores CD19 expression and CD19-mediated BCR activation, it fails to rescue BCR-mediated EBV lytic gene expression. EBV-specific CTLs engineered to overexpress mCD95L exhibit a stronger killing activity against LCLs. This study highlights that engineering EBV-specific CTLs to express a higher level of mCD95L could represent an attractive therapeutic approach to improve T cell immunotherapy for PTLDs.
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Infecções por Vírus Epstein-Barr , Humanos , Proteína Ligante Fas , Herpesvirus Humano 4/fisiologia , Caspases , Receptores de Antígenos de Linfócitos B/metabolismoRESUMO
Worldwide food security is severely threatened by the devastating wheat stripe rust disease. The utilization of resistant wheat cultivars represents the most cost-effective and efficient strategy for combating this disease. However, the lack of resistant resources has been a major bottleneck in breeding for wheat disease resistance. Therefore, revealing novel gene resources for combating stripe rust and elucidating the underlying resistance mechanism is of utmost urgency. In this study, we identified that the soybean NF-YB transcription factor GmNF-YB20 in wheat provides resistance to the stripe rust fungus (Puccinia striiformis f. sp. tritici, Pst). Wheat lines with stable overexpression of the GmNF-YB20 enhanced resistance against multiple Pst races. Transcriptome profiling of GmNF-YB20 transgenic wheat under Pst infection unveiled its involvement in the lipid signaling pathway. RT-qPCR assays suggested that GmNF-YB20 increased transcript levels of multiple nonspecific lipid transfer protein (LTP) genes during wheat-Pst interaction, luciferase reporter analysis illustrates that it activates the transcription of TaLTP1.50 in wheat protoplast, and GmNF-YB20 overexpressed wheat plants had higher total LTP content in vivo during Pst infection. Overexpression of TaLTP1.50 in wheat significantly increased resistance to Pst, whereas knockdown of TaLTP1.50 exhibited the opposite trends, indicating that TaLTP1.50 plays a positive role in wheat resistance. Taken together, our findings provide perspective regarding the molecular mechanism of GmNF-YB20 in wheat and highlight the potential use for wheat breeding.
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The line optical tweezers (LOT) has been proven to be an alternative technique to manipulating the biological cells because of the bigger potential compared with traditional optical tweezers with a highly focused spot. We deduce the 4 × 4 optical matrix of the astigmatic LOT to investigate the optical characteristics related to the systematic parameters. The comparison of the initial and scattered electric fields by the cell under the astigmatic and stigmatic LOT is implemented to illustrate that the forward scattered light from the astigmatic LOT is much stronger than that from the stigmatic LOT, so as to the cell deformations. It is demonstrated that the astigmatic LOT could provide a more efficient way to deform the cell not only in the focal plane, but also along the optical axis to screen large biomaterials in biomechanics.
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Laser-scanning confocal hyperspectral microscopy is a powerful technique to identify the different sample constituents and their spatial distribution in three-dimensional (3D). However, it suffers from low imaging speed because of the mechanical scanning methods. To overcome this challenge, we propose a snapshot hyperspectral confocal microscopy imaging system (SHCMS). It combined coded illumination microscopy based on a digital micromirror device (DMD) with a snapshot hyperspectral confocal neural network (SHCNet) to realize single-shot confocal hyperspectral imaging. With SHCMS, high-contrast 160-bands confocal hyperspectral images of potato tuber autofluorescence can be collected by only single-shot, which is almost 5 times improvement in the number of spectral channels than previously reported methods. Moreover, our approach can efficiently record hyperspectral volumetric imaging due to the optical sectioning capability. This fast high-resolution hyperspectral imaging method may pave the way for real-time highly multiplexed biological imaging.
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This study aimed to evaluate whether there is a causal relationship between autoimmune thyroid disorders (AITDs) and telomere length (TL) in the European population and whether there is reverse causality. In this study, Mendelian randomization (MR) and colocalization analysis were conducted to assess the potential causal relationship between AITDs and TL using summary statistics from large-scale genome-wide association studies, followed by analysis of the relationship between TL and thyroid stimulating hormone and free thyroxine (FT4) to help interpret the findings. The inverse variance weighted (IVW) method was used to estimate the causal estimates. The weighted median, MR-Egger and leave-one-out methods were used as sensitivity analyses. The IVW method results showed a significant causal relationship between autoimmune hyperthyroidism and TL (ß = -1.93 × 10-2 ; p = 4.54 × 10-5 ). There was no causal relationship between autoimmune hypothyroidism and TL (ß = -3.99 × 10-3 ; p = 0.324). The results of the reverse MR analysis showed that genetically TL had a significant causal relationship on autoimmune hyperthyroidism (IVW: odds ratio (OR) = 0.49; p = 2.83 × 10-4 ) and autoimmune hypothyroidism (IVW: OR = 0.86; p = 7.46 × 10-3 ). Both horizontal pleiotropy and heterogeneity tests indicated the validity of our bidirectional MR study. Finally, colocalization analysis suggested that there were shared causal variants between autoimmune hyperthyroidism and TL, further highlighting the robustness of the results. In conclusion, autoimmune hyperthyroidism may accelerate telomere attrition, and telomere attrition is a causal factor for AITDs.
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Doença de Graves , Doença de Hashimoto , Hipotireoidismo , Tireoidite Autoimune , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Telômero/genética , Hipotireoidismo/genéticaRESUMO
Graphene is a kind of two-dimensional material with a single-layer carbon structure and has been investigated in many high-performance photodetectors. The lateral photovoltaic effect (LPE) is widely used in the position-sensitive detectors (PSDs) owing to its linear response of photovoltage to the light position. In this Letter, a type of graphene-enhanced LPE is observed in the Ag nanoparticle-covered graphene/n-type Si. The LPE sensitivity can reach 97.3â mV/mm, much higher than the sensitivity of 1.3â mV/mm in the control sample of Ag/Si and 5.2â mV/mm of graphene/Si. Based on the photocarriers' diffusion mechanism, tailoring a photocarrier transfer at the interface of a heterojunction plays a key role for the enhancement. These findings exhibit great application potential of graphene in the field of PSDs and offer an effective method for the optimization of LPE devices.
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Cisplatin (CDDP)-based chemotherapy resistance is a major challenge for lung cancer treatment. PKM2 is the rate-limiting enzyme of glycolysis, which is associated with CDDP resistance. KAT8 is an acetyltransferase that regulates lung cancer progression. Thus, we aimed to explore whether KAT8 regulates PKM2 acetylation to participate in CDDP resistance. CDDP resistance was analyzed by CCK-8, flow cytometry and western blotting. To explore the regulation of KAT8 on PKM2, coimmunoprecipitation (Co-IP), immunofluorescence and immunoprecipitation followed by western blotting were performed. Glycolysis was determined using glucose consumption, lactate production, ATP level detection kits and extracellular acidification rate assay. We observed that KAT8 levels were downregulated in CDDP-treated A549 and PC9 cells. Interference with KAT8 inhibited cell viability, promoted apoptosis and upregulated PARP1 and cleaved-PARP1 levels of A549 cells treated with CDDP, suggesting the sensitivity to CDDP was enhanced, while KAT8 overexpression attenuated the CDDP sensitivity. Moreover, KAT8 interacted with PKM2 to promote the PKM2 K433 acetylation. PKM2 K433 mutated plasmids inhibited the si-KAT8-regulated cell viability, apoptosis and glycolysis compared with PKM2-WT. Besides, KAT8 reversed the inhibition of tumor growth caused by CDDP. In conclusion, KAT8-mediated PKM2 K433 acetylation was associated with the resistance of lung cancer cells to CDDP. The findings may provide a new idea for the treatment of CDDP-resistant lung cancer.
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Antineoplásicos , Proteínas de Transporte , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Proteínas de Membrana , Proteínas de Ligação a Hormônio da Tireoide , Hormônios Tireóideos , Humanos , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Acetilação , Hormônios Tireóideos/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Antineoplásicos/farmacologia , Animais , Camundongos , Apoptose/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Linhagem Celular Tumoral , Células A549 , Camundongos Nus , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
Coral reefs are declining due to the rising seawater temperature. Bacteria within and surrounding corals play key roles in maintaining the homeostasis of the coral holobiont. Research on coral-related bacteria could provide benefits for coral reef restoration. During the isolation of coral-associated bacteria, a Gram-stain-negative, motile bacterium (D5M38T) was isolated from seawater surrounding corals in Daya Bay, Shenzhen, PR China. Phylogenetic analysis revealed that strain D5M38T represents a novel species in the genus Cognatishimia. The temperature range for strain D5M38T growth was 10-40â°C, and the optimum temperature was 37â°C. The salinity range for the growth of this isolate was from 0 to 4.0â%, with an optimal salinity level of 0.5 %. The pH range necessary for strain D5M38T growth was between pH 5.0 and 9.0, with an optimal pH being 7.5. The predominant fatty acid was summed feature 8 (65.0â%). The major respiratory quinone was Q-10. The DNA G+C content was 56.8 %. The genome size was 3.88 Mb. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strain D5M38T and its two closest neighbours, Cognatishimia activa LMG 29900T and Cognatishimia maritima KCTC 23347T, were 73.2/73.6%, 73.2/73.6% and 19.7/19.5%, respectively. Strain D5M38T was clearly distinct from its closest neighbours C. activa LMG 29900T and C. maritima KCTC 23347T, with 16S rRNA gene sequence similarity values of 97.5 and 97.3â%, respectively. The phylogenetic analysis, along with the ANI, AAI, and dDDH values, demonstrated that strain D5M38T is a member of the genus Cognatishimia, and is distinct from the other two recognized species within this genus. The physiological, biochemical and chemotaxonomic characteristics also supported the species novelty of strain D5M38T. Thus, strain D5M38T is considered to be classified as representing a novel species in the genus Cognatishimia, for which the name Cognatishimia coralii sp. nov. is proposed. The type strain is D5M38T (=MCCC 1K08692T=KCTC 8160T).