Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 733
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 170(5): 1000-1012.e19, 2017 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-28823555

RESUMO

The formation and retrieval of a memory is thought to be accomplished by activation and reactivation, respectively, of the memory-holding cells (engram cells) by a common set of neural circuits, but this hypothesis has not been established. The medial temporal-lobe system is essential for the formation and retrieval of episodic memory for which individual hippocampal subfields and entorhinal cortex layers contribute by carrying out specific functions. One subfield whose function is poorly known is the subiculum. Here, we show that dorsal subiculum and the circuit, CA1 to dorsal subiculum to medial entorhinal cortex layer 5, play a crucial role selectively in the retrieval of episodic memories. Conversely, the direct CA1 to medial entorhinal cortex layer 5 circuit is essential specifically for memory formation. Our data suggest that the subiculum-containing detour loop is dedicated to meet the requirements associated with recall such as rapid memory updating and retrieval-driven instinctive fear responses.


Assuntos
Córtex Entorrinal/metabolismo , Hipocampo/metabolismo , Memória Episódica , Vias Neurais , Animais , Corticosterona/metabolismo , Córtex Entorrinal/citologia , Expressão Gênica , Hipocampo/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética
2.
Immunity ; 55(3): 527-541.e5, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35231421

RESUMO

The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Estruturas Linfoides Terciárias , Carcinoma de Células Renais/terapia , Feminino , Humanos , Imunoglobulina G , Neoplasias Renais/terapia , Masculino , Plasmócitos , Estruturas Linfoides Terciárias/patologia , Microambiente Tumoral
3.
Nucleic Acids Res ; 51(D1): D1381-D1387, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36243962

RESUMO

Advances in sequencing technologies have led to the rapid growth of multi-omics data on rheumatoid arthritis (RA). However, a comprehensive database that systematically collects and classifies the scattered data is still lacking. Here, we developed the Rheumatoid Arthritis Bioinformatics Center (RABC, http://www.onethird-lab.com/RABC/), the first multi-omics data resource platform (data hub) for RA. There are four categories of data in RABC: (i) 175 multi-omics sample sets covering transcriptome, epigenome, genome, and proteome; (ii) 175 209 differentially expressed genes (DEGs), 105 differentially expressed microRNAs (DEMs), 18 464 differentially DNA methylated (DNAm) genes, 1 764 KEGG pathways, 30 488 GO terms, 74 334 SNPs, 242 779 eQTLs, 105 m6A-SNPs and 18 491 669 meta-mQTLs; (iii) prior knowledge on seven types of RA molecular markers from nine public and credible databases; (iv) 127 073 literature information from PubMed (from 1972 to March 2022). RABC provides a user-friendly interface for browsing, searching and downloading these data. In addition, a visualization module also supports users to generate graphs of analysis results by inputting personalized parameters. We believe that RABC will become a valuable resource and make a significant contribution to the study of RA.


Assuntos
Artrite Reumatoide , Bases de Dados Factuais , Humanos , Artrite Reumatoide/genética , Biomarcadores/metabolismo , Biologia Computacional/métodos , Metilação de DNA/genética , Perfilação da Expressão Gênica/métodos , Transcriptoma
4.
Nano Lett ; 24(25): 7645-7653, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38875704

RESUMO

Understanding the nucleation and growth mechanism of 3d transition bimetallic nanocrystals (NCs) is crucial to developing NCs with tailored nanostructures and properties. However, it remains a significant challenge due to the complexity of 3d bimetallic NCs formation and their sensitivity to oxygen. Here, by combining in situ electron microscopy and synchrotron X-ray techniques, we elucidate the nucleation and growth pathways of Fe-Ni NCs. Interestingly, the formation of Fe-Ni NCs emerges from the assimilation of Fe into Ni clusters together with the reduction of Fe-Ni oxides. Subsequently, these NCs undergo solid-state phase transitions, resulting in two distinct solid solutions, ultimately dominated by γ-Fe3Ni2. Furthermore, we deconvolve the interplays between local coordination and electronic state concerning the growth temperature. We directly visualize the oxidation-state distributions of Fe and Ni at the nanoscale and investigate their changes. This work may reshape and enhance the understanding of nucleation and growth in atomic crystallization.

5.
Proteomics ; 24(6): e2300235, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38197532

RESUMO

Changes in the structure of RNA and protein, have an important impact on biological functions and are even important determinants of disease pathogenesis and treatment. Some genetic variations, including copy number variation, single nucleotide variation, and so on, can lead to changes in biological function and increased susceptibility to certain diseases by changing the structure of RNA or protein. With the development of structural biology and sequencing technology, a large amount of RNA and protein structure data and genetic variation data resources has emerged to be used to explain biological processes. Here, we reviewed the effects of genetic variation on the structure of RNAs and proteins, and investigated their impact on several diseases. An online resource (http://www.onethird-lab.com/gems/) to support convenient retrieval of common tools is also built. Finally, the challenges and future development of the effects of genetic variation on RNA and protein were discussed.


Assuntos
Variações do Número de Cópias de DNA , RNA , RNA/genética , Proteínas/química
6.
Proteomics ; : e2300359, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522029

RESUMO

Risk prediction and disease prevention are the innovative care challenges of the 21st century. Apart from freeing the individual from the pain of disease, it will lead to low medical costs for society. Until very recently, risk assessments have ushered in a new era with the emergence of omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and so on, which potentially advance the ability of biomarkers to aid prediction models. While risk prediction has achieved great success, there are still some challenges and limitations. We reviewed the general process of omics-based disease risk model construction and the applications in four typical diseases. Meanwhile, we highlighted the problems in current studies and explored the potential opportunities and challenges for future clinical practice.

7.
J Biol Chem ; 299(1): 102775, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36493904

RESUMO

Phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] is a critical signaling phospholipid involved in endolysosome homeostasis. It is synthesized by a protein complex composed of PIKfyve, Vac14, and Fig4. Defects in PtdIns(3,5)P2 synthesis underlie a number of human neurological disorders, including Charcot-Marie-Tooth disease, child onset progressive dystonia, and others. However, neuron-specific functions of PtdIns(3,5)P2 remain less understood. Here, we show that PtdIns(3,5)P2 pathway is required to maintain neurite thickness. Suppression of PIKfyve activities using either pharmacological inhibitors or RNA silencing resulted in decreased neurite thickness. We further find that the regulation of neurite thickness by PtdIns(3,5)P2 is mediated by NSG1/NEEP21, a neuron-specific endosomal protein. Knockdown of NSG1 expression also led to thinner neurites. mCherry-tagged NSG1 colocalized and interacted with proteins in the PtdIns(3,5)P2 machinery. Perturbation of PtdIns(3,5)P2 dynamics by overexpressing Fig4 or a PtdIns(3,5)P2-binding domain resulted in mislocalization of NSG1 to nonendosomal locations, and suppressing PtdIns(3,5)P2 synthesis resulted in an accumulation of NSG1 in EEA1-positive early endosomes. Importantly, overexpression of NSG1 rescued neurite thinning in PtdIns(3,5)P2-deficient CAD neurons and primary cortical neurons. Our study uncovered the role of PtdIns(3,5)P2 in the morphogenesis of neurons, which revealed a novel aspect of the pathogenesis of PtdIns(3,5)P2-related neuropathies. We also identified NSG1 as an important downstream protein of PtdIns(3,5)P2, which may provide a novel therapeutic target in neurological diseases.


Assuntos
Neuritos , Fosfatos de Fosfatidilinositol , Humanos , Endossomos/metabolismo , Neuritos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Fosfatos de Fosfatidilinositol/biossíntese , Fosfatos de Fosfatidilinositol/metabolismo
8.
Plant Physiol ; 192(3): 2185-2202, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-36797801

RESUMO

Hydrogen sulfide (H2S) is a gaseous signaling molecule that delays color change during fruit ripening. Whether H2S affects anthocyanin biosynthesis in red-skinned pears (Pyrus L.) remains unclear. Here, we found that H2S substantially inhibits anthocyanin accumulation in red-skinned pears and the expression of several genes encoding transcription factors is affected in response to H2S signaling. For example, PyMYB10 and PyMYB73 were down-regulated, whereas PyMYB114 and PyMYB6 were up-regulated. Bioinformatics analysis showed that PyMYB73 and PyMYB6, each containing an EAR motif, may negatively regulate anthocyanin accumulation. Transient expression analysis showed that PyMYB73 substantially promotes anthocyanin biosynthesis by co-transforming with PyMYB10/PyMYB114 + PybHLH3; however, PyMYB6 inhibited anthocyanin biosynthesis in strawberry (Fragaria vesca) receptacles and pear fruits, and PyMYB73 interacted with PyMYB10 and PyMYB6 but not PyMYB114 or PybHLH3. Further investigation showed that Cys194 and Cys218 of PyMYB10 were modified by persulfidation and that PyMYB10Cys218Ala substantially increased anthocyanin accumulation by a transient transformation system. Co-transformation of PyMYB10Cys218Ala + PyMYB73/PyMYB6 also promoted anthocyanin accumulation in pear fruits. Yeast two-hybrid assays showed that the mutation of PyMYB10 did not affect the interaction between PyMYB10 and PyMYB73, but it inhibited interaction with PyMYB6. Moreover, H2S weakened the interaction between PyMYB10 and PyMYB73 but enhanced the interaction with PyMYB6. Thus, we provided a model in which PyMYB10 undergoes persulfidation at Cys218, enhancing the interaction with PyMYB6 and reducing the interaction with PyMYB73. These subsequently results in lower expression of the anthocyanin biosynthesis-related genes Pyrus dihydroflavonol 4-reductase (PyDFR), Pyrus anthocyanidin synthase (PyANS), Pyrus UDP-glucose: flavonoid 3-glucosyl transferase (PyUFGT) and Pyrus glutathione S-transferase (PyGST), thereby inhibiting anthocyanin accumulation in red-skinned pears. Our findings provided a molecular mechanism for H2S-mediated anthocyanin biosynthesis in red-skinned pears.


Assuntos
Pyrus , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Pyrus/genética , Pyrus/metabolismo , Antocianinas/metabolismo , Regulação da Expressão Gênica de Plantas , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Plant Physiol ; 192(1): 616-632, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732924

RESUMO

Hydrogen sulfide (H2S) is a gaseous signaling molecule reported to play multiple roles in fruit ripening. However, the molecular mechanisms underlying H2S-mediated delay in fruit ripening remain to be established. Here, the gene encoding a WRKY transcription factor, WRKY71, was identified as substantially upregulated in H2S-treated tomato (Solanum lycopersicum) via transcriptome profiling. The expression of WRKY71 was negatively associated with that of CYANOALANINE SYNTHASE1 (CAS1). Transient and stable genetic modification experiments disclosed that WRKY71 acts as a repressor of the tomato ripening process. CAS1 appears to play an opposite role, based on the finding that the ripening process was delayed in the cas1 mutant and accelerated in CAS1-OE tomatoes. Dual-luciferase reporter assay, yeast one-hybrid, electrophoretic mobility shift assay, and transient transformation experiments showed that WRKY71 bound to the CAS1 promoter and suppressed its activation. Moreover, the persulfidation of WRKY71 enhanced its binding ability to the CAS1 promoter. Data from luciferase complementation and Y2H assays confirmed that WRKY71 interacts with a BOI-related E3 ubiquitin-protein ligase 3 (BRG3) and is ubiquitinated in vitro. Further experiments showed that modification of BRG3 via persulfidation at Cys206 and Cys212 led to reduced ubiquitination activity. Our findings support a model whereby BRG3 undergoes persulfidation at Cys206 and Cys212, leading to reduced ubiquitination activity and decreased interactions with the WRKY71 transcript, with a subsequent increase in binding activity of the persulfidated WRKY71 to the CAS1 promoter, resulting in its transcriptional inhibition and thereby delayed ripening of tomatoes. Our collective findings provide insights into a mechanism of H2S-mediated regulation of tomato fruit ripening.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Frutas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Etilenos/metabolismo
10.
Acc Chem Res ; 56(4): 452-461, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36719833

RESUMO

ConspectusOrganolead halide-based photovoltaics are one of the state-of-the-art solar cell systems with efficiencies increasing to 25% over the past decade, ascribed to their high light-absorption coefficient, broad wavelength coverage, tunable band structure, and excellent carrier mobility. Indeed, these optical characteristics are highly demanding in photocatalysis and photoluminescence (PL), which also involve the solar energy utilization and charge transport. However, the vast majority of organolead halides are ionically bonded structures and susceptible to degradation upon high-polarity protic molecules (e.g., water (vapor) and alcohol), which are often inevitable in many photochemical applications. Encapsulation is a commonly used stabilization approach by coating protective layers, avoiding the direct contact between organolead halides and polar molecules. However, this may partially hinder the light penetration to the inner hybrid halide materials, and introduce new interface problems that are important in photocatalysis and luminescent sensing. Therefore, developing intrinsically stable organometal halide hybrids is a major target for their applications in optoelectronic applications.In this Account, recent research progress on the synthesis of organolead halide-based coordination polymers for a variety of photoactive applications is described. Herein, we propose a general strategy to advance the intrinsic stability of organometal halide crystalline materials by using coordinating anionic organic linkers, which occupy the excellent photophysical features analogous to those of perovskites. Unlike the organoammonium cations as for ionically bonded structures, the anionic structure-directing agents (e.g., organocarboxylates) render well-defined metal-carboxylate coordination motifs in extended architectures spanning from low-dimensional (0D, 1D) to high-dimensional cationic inorganic Pb-X-Pb (X = F-/Cl-/Br-/I-) sublattices. This family of organolead halide coordination polymers can endure chemically reactive environments over a wide range of pH and aqueous boiling condition, which have been systematically investigated by experimental studies and theoretical calculations. Many chloride/bromide-based coordination polymers show air-stable, broadband self-trapped emission with large Stokes shift and high color rendition, exhibiting the absolute quantum yields of 35-72%. Among them, the porous frameworks with low-dimensional (0D, 1D) inorganic blocks are recognized as a rare class of porous metal-organic frameworks (MOFs) constructed by lead halides as secondary building units (SBUs). They not only occupy substantially higher light-harvesting and carrier-transport properties than conventional metal oxide-based MOFs, but also allow for isoreticular modification to regulate the PL characteristics by guest molecules. More importantly, combining the high stability with excellent carrier characteristics, a layered organolead iodide coordination polymer shows the overall photocatalytic water splitting without the use of any sacrificial agent under simulated sunlight illumination. Given the wide choice of structurally diverse organocarboxylate linkers, we hope this Account provides deep insights on the importance of coordination chemistry in the discovery of a wide family of intrinsically stable organolead halides to expand their photophysical applications.

11.
Cancer Cell Int ; 24(1): 18, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191389

RESUMO

BACKGROUND: Although non-invasive radiological techniques are widely applied in kidney renal clear cell carcinoma (KIRC) diagnosis, more than 50% of KIRCs are detected incidentally during the diagnostic procedures to identify renal cell carcinoma (RCC). Thus, sensitive and accurate KIRC diagnostic methods are required. Therefore, in this study, we aimed to identify KIRC-associated microRNAs (miRNAs). METHODS: This three-phase study included 224 participants (112 each of patients with KIRC and healthy controls (NCs)). RT-qPCR was used to evaluate miRNA expression in KIRC and NC samples. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to predict the usefulness of serum miRNAs in KIRC diagnosis. In addition, we performed survival and bioinformatics analyses. RESULTS: We found that miR-1-3p, miR-129-5p, miR-146b-5p, miR-187-3p, and miR-200a-3p were significantly differentially expressed in patients with KIRC. A panel consisting of three miRNAs (miR-1-3p, miR-129-5p, and miR-146b-5p) had an AUC of 0.895, ranging from 0.848 to 0.942. In addition, using the GEPIA database, we found that the miRNAs were associated with CREB5. According to the survival analysis, miR-146b-5p overexpression was indicative of a poorer prognosis in patients with KIRC. CONCLUSIONS: The identified three-miRNA panel could serve as a non-invasive indicator for KIRC and CREB5 as a potential target gene for KIRC treatment.

12.
Chem Res Toxicol ; 37(6): 935-943, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38761382

RESUMO

Amitriptyline (ATL), a tricyclic antidepressant, has been reported to cause various adverse effects, particularly hepatotoxicity. The mechanisms of ATL-induced hepatotoxicity remain unknown. The study was performed to identify the olefin epoxidation metabolite of ATL and determine the possible toxicity mechanism. Two glutathione (GSH) conjugates (M1 and M2) and two N-acetylcysteine (NAC) conjugates (M3 and M4) were detected in rat liver microsomal incubations supplemented with GSH and NAC, respectively. Moreover, M1/M2 and M3/M4 were respectively found in ATL-treated rat primary hepatocytes and in bile and urine of rats given ATL. Recombinant P450 enzyme incubations demonstrated that CYP3A4 was the primary enzyme involved in the olefin epoxidation of ATL. Treatment of hepatocytes with ATL resulted in significant cell death. Inhibition of CYP3A attenuated the susceptibility to the observed cytotoxicity of ATL. The metabolic activation of ATL most likely participates in the cytotoxicity of ATL.


Assuntos
Amitriptilina , Citocromo P-450 CYP3A , Compostos de Epóxi , Hepatócitos , Microssomos Hepáticos , Ratos Sprague-Dawley , Animais , Amitriptilina/metabolismo , Ratos , Citocromo P-450 CYP3A/metabolismo , Microssomos Hepáticos/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Compostos de Epóxi/metabolismo , Compostos de Epóxi/toxicidade , Compostos de Epóxi/química , Glutationa/metabolismo , Células Cultivadas
13.
Biomarkers ; : 1-9, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38767408

RESUMO

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.


Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.

14.
J Oral Pathol Med ; 53(3): 182-192, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38438274

RESUMO

BACKGROUND: Burning mouth syndrome is a chronic pain syndrome mainly characterized by an intensive burning sensation of tongue. Previous studies have suggested that saliva/serum biomarkers in burning mouth syndrome might be associated with psychological disorders. The aim of systematic review was to observe whether the biomarkers in serum/saliva could be an alternative method to evaluate the psychological disorders in patients with burning mouth syndrome. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library databases were searched for papers published up to March 15, 2023. Risk of bias was measured by using the Newcastle-Ottawa Scale. RevMan was used for meta-analysis. RESULTS: A total of 467 articles were screened, which of 12 studies were included. These studies collected 43 different biomarkers in saliva and 35 in serum. Of these biomarkers, only three (cortisol, α-amylase, and IL-6) were analyzed in two or more studies. Only salivary cortisol levels were significantly higher in the patient group compared to the controls (Mean Difference = 1.39; 95% CI [0.80-1.97]; p < 0.001). Moreover, cortisol might be relevant to psychological scores, especially anxiety. CONCLUSION: Different papers have investigated salivary and serum biomarkers in burning mouth syndrome patients with controversial results. This meta-analysis showed that cortisol levels in saliva may be a potential biomarker to assess the psychological disorders in burning mouth syndrome patients.


Assuntos
Síndrome da Ardência Bucal , Humanos , Síndrome da Ardência Bucal/diagnóstico , Hidrocortisona/análise , Saliva/química , Biomarcadores/análise , Ansiedade
15.
Bioorg Chem ; 143: 107069, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38160477

RESUMO

Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity and potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide and sulfonate TET derivatives were designed, synthesized, and evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, ß-unsaturated carbonyl group exhibited the most potent activity against all tested tumor cell lines (including Hela, HCT116, HepG2, MCF-7, and SHSY5Y), as well as negligible toxicity against normal cell lines LO2 and HEK293. Additionally, compound 3c effectively inhibited HCT116 and CT26 cell proliferation in vitro with increased cell proportion in the G2/M phase, activated the mitochondrial apoptosis pathway, and induced colon cancer cell apoptosis by suppressing the PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that compound 3c is potentially bound to multiple residues in PI3K with a stronger binding affinity than TET. Ultimately, compound 3c dramatically suppressed tumor growth in the CT26 xenograft tumor model, without noticeable visceral toxicity detected in the high-dose group. In summary, compound 3c might present new insights for designing new PI3K inhibitors and be a potential candidate for colon cancer treatment.


Assuntos
Benzilisoquinolinas , Neoplasias do Colo , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Células HEK293 , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo
16.
Nature ; 560(7716): E4, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29930352

RESUMO

In this Letter, owing to an error during the production process, the author affiliations were listed incorrectly. Affiliation number 5 (Colleges of Nanoscale Science and Engineering, State University of New York (SUNY)) was repeated, and affiliation numbers 6-8 were incorrect. In addition, the phrase "two oxide thickness variants" should have been "two gate oxide thickness variants". These errors have all been corrected online.

17.
Nature ; 556(7701): 349-354, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29670262

RESUMO

Electronic and photonic technologies have transformed our lives-from computing and mobile devices, to information technology and the internet. Our future demands in these fields require innovation in each technology separately, but also depend on our ability to harness their complementary physics through integrated solutions1,2. This goal is hindered by the fact that most silicon nanotechnologies-which enable our processors, computer memory, communications chips and image sensors-rely on bulk silicon substrates, a cost-effective solution with an abundant supply chain, but with substantial limitations for the integration of photonic functions. Here we introduce photonics into bulk silicon complementary metal-oxide-semiconductor (CMOS) chips using a layer of polycrystalline silicon deposited on silicon oxide (glass) islands fabricated alongside transistors. We use this single deposited layer to realize optical waveguides and resonators, high-speed optical modulators and sensitive avalanche photodetectors. We integrated this photonic platform with a 65-nanometre-transistor bulk CMOS process technology inside a 300-millimetre-diameter-wafer microelectronics foundry. We then implemented integrated high-speed optical transceivers in this platform that operate at ten gigabits per second, composed of millions of transistors, and arrayed on a single optical bus for wavelength division multiplexing, to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing3,4. By decoupling the formation of photonic devices from that of transistors, this integration approach can achieve many of the goals of multi-chip solutions 5 , but with the performance, complexity and scalability of 'systems on a chip'1,6-8. As transistors smaller than ten nanometres across become commercially available 9 , and as new nanotechnologies emerge10,11, this approach could provide a way to integrate photonics with state-of-the-art nanoelectronics.

18.
Nature ; 557(7703): 43-49, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29695866

RESUMO

Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.


Assuntos
Produtos Agrícolas/classificação , Produtos Agrícolas/genética , Variação Genética , Genoma de Planta/genética , Oryza/classificação , Oryza/genética , Ásia , Evolução Molecular , Genes de Plantas/genética , Genética Populacional , Genômica , Haplótipos , Mutação INDEL/genética , Filogenia , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética
19.
Environ Res ; 249: 118360, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38325779

RESUMO

For human health and environment safety, it is of great significance to develop novel materials with high effectiveness for removal of lead from not only aqueous solutions but also human body and traditional Chinese medicines. Here, functional kiwi peel composite, manganese dioxide decorated kiwi peel powder (MKPP), is proposed for the removal of Pb2+ effectively. The adsorption of Pb2+ in aqueous solution is a highly selective and endothermic process and kinetically follows a pseudo-second-order model, which can reach equilibrium with the capacity of 192.7 mg/g within 10 min. Comprehensive factors of hydration energy, charge-to-radius ratio and softness of Pb2+ make a stronger affinity between MKPP and Pb2+. The possible adsorption mechanism involves covalent bond, electrostatic force and chelation, etc. MKPP can be efficiently regenerated and reused with high adsorption efficiency after five cycles. Besides, MKPP can remove over 97% of Pb2+ from real water samples. MKPP can also alleviate lead poisoning to a certain extent and make the Pb level of TCM extract meet the safety standard. This work highlights that MKPP is a promising adsorbent for the removal of Pb2+ and provides an efficient strategy for reusing kiwi peel as well as dealing with the problem of Pb pollution.


Assuntos
Medicamentos de Ervas Chinesas , Chumbo , Compostos de Manganês , Óxidos , Poluentes Químicos da Água , Chumbo/isolamento & purificação , Chumbo/química , Compostos de Manganês/química , Adsorção , Óxidos/química , Medicamentos de Ervas Chinesas/química , Humanos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Medicina Tradicional Chinesa , Purificação da Água/métodos
20.
Phytopathology ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749069

RESUMO

The previous studies revealed that the type VI secretion system (T6SS) has an essential role in bacterial competition and virulence in many gram-negative bacteria. However, the role of T6SS in virulence in Pectobacterium atrosepticum remains controversial. We examined a closely related strain, PccS1, and discovered that its T6SS comprises a single copy cluster of 17 core genes with a higher identity to homologs from P. atrosepticum. Through extensive phenotypic and functional analyses of over 220 derivatives of PccS1, we found that three of the five VgrGs could be classified into group I VgrGs. These VgrGs interacted with corresponding DUF4123 domain proteins, which were secreted outside of the membrane and were dependent on either T6SS or T4SS. This interaction directly governed virulence and competition. Meanwhile, supernatant proteomic analyses with stains defective in T6SS or/and T4SS confirm that effectors, such as FhaB, were secreted redundantly to control the virulence and suppress host callose-deposition in the course of infection. Notably, this redundant secretion mechanism between T6SS and T4SS is believed to be the first of its kind in bacteria.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA