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1.
J Biol Chem ; 300(9): 107672, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39128723

RESUMO

The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinates (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.


Assuntos
Neoplasias da Mama , Movimento Celular , Invasividade Neoplásica , Peptidase 7 Específica de Ubiquitina , Ubiquitinação , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Peptidase 7 Específica de Ubiquitina/metabolismo , Peptidase 7 Específica de Ubiquitina/genética , Feminino , Linhagem Celular Tumoral , Epigênese Genética , Células HEK293 , Proteína 7 com Repetições F-Box-WD/metabolismo , Proteína 7 com Repetições F-Box-WD/genética , Proteínas Supressoras de Tumor
2.
J Biol Chem ; 300(10): 107768, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270819

RESUMO

Basal-like breast cancer may originate from luminal epithelial or cancerous cells. Inadequately repaired DNA damage impairs luminal differentiation and promotes aberrant luminal to basal trans-differentiation in mammary epithelial cells (MECs). Ubiquitin-specific peptidase 11 (USP11), a deubiquitinase, plays a critical role in DNA damage repair. The role of USP11 in controlling mammary cell differentiation and tumorigenesis remains poorly understood. We generated Usp11 knockout mice and breast cancer cell lines expressing wild-type (WT) and mutant forms of USP11. By using these mutant mice, cell lines, and human USP11-deficient and -proficient breast cancer tissues, we tested how USP11 controls mammary cell fate. We generated Usp11 knock-out mice and found that deletion of Usp11 reduced the expression of E-cadherin and promoted DNA damage in MECs. Overexpression of WT USP11, but not a deubiquitinase-inactive mutant form of USP11, promoted luminal differentiation, enhanced DNA damage repair, and suppressed tumorigenesis in mice. Mechanistically, we found that USP11 enhanced the protein expression of E-cadherin dependent on its deubiquitinase activity and that USP11 deubiquitinated E-cadherin at K738. We discovered that USP11 is bound to E-cadherin through its C-terminal region. In human breast cancers, expression of USP11 was positively correlated with that of E-cadherin, and high USP11 predicted better recurrence-free survival. Our findings provide compelling genetic and biochemical evidence that USP11 not only promotes DNA damage repair but also deubiquitinates E-cadherin and maintains the luminal feature of mammary tumor cells, thereby suppressing luminal breast cancer.

3.
BMC Biol ; 22(1): 85, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627785

RESUMO

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.


Assuntos
Neoplasias Mamárias Animais , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Camundongos , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Dano ao DNA , Reparo do DNA , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia
4.
BMC Genomics ; 25(1): 727, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060939

RESUMO

BACKGROUND: Acinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province. RESULTS: Non-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained blaADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite. CONCLUSIONS: This study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Genótipo , Tipagem de Sequências Multilocus , Fenótipo , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/efeitos dos fármacos , Humanos , China , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Antibacterianos/farmacologia , Hospitais , Farmacorresistência Bacteriana Múltipla/genética , Infecção Hospitalar/microbiologia , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto
5.
J Am Chem Soc ; 146(37): 25852-25859, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39226029

RESUMO

Organocatalytic ring-opening polymerization (ROP) of lactones is a green method for accessing renewable and biodegradable polyesters. Developing new organocatalysts with high activity and controllability is a major and challenging research topic in this field. Here, we report a series of organocatalysts to achieve a fast and controlled ROP of lactones. These catalysts incorporate (thio)urea and alkoxide in one molecule and act as initiators in the ROP. Such catalysts enable an effective intramolecular activation of initiator/chain end, as revealed by computational studies, resulting in higher activity and fewer (thio)urea loads than existing (thio)urea/alkoxide binary systems. These organocatalysts exhibit ultrahigh activity comparable to metal complexes, i.e., turnover number up to 900 and turnover of frequency up to 4860 min-1, affording polyesters with tailor-made structure, predicted molecular weights, narrow dispersity, less epimerization, and minimal transesterification. The catalyst synthesis is simple and scalable, allowing widely tuned activities of the ROP.

6.
J Am Chem Soc ; 146(15): 10889-10898, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38584517

RESUMO

Full-color luminophores have advanced applications in materials and engineering, but constructing color-tunable clusteroluminescence (CL) from nonconjugated polymers based on through-space interactions remains a huge challenge. Herein, we develop phosphine-capped nonconjugated polyesters exhibiting blue-to-red CL (400-700 nm) based on phosphine-initiated copolymerization of epoxides and cyclic anhydrides, especially P1-0.5TPP, which exhibits red CL (610 nm) with a high quantum yield of 32%. Experiments and theoretical calculations disclose that the phosphine-capped effect in polyesters brings about conformational changes and induces phosphine-ester clusters by through-space (n,π*) interactions. Moreover, CL colors and efficiencies can be easily tailored by types of phosphines, compositions and structures of polyesters, and concentration. Significantly, the role of polymer motions (group, segmental, and chain motions) on CL originating from microregions inside polyesters is revealed. Further, phosphine-capped nonconjugated polyesters are demonstrated to be nonconjugated dyes and fluorescent fibers and are also used for multicolor light-emitting diodes including white light. This work not only provides an engineering strategy based on the end-group effect to prepare full-color clusteroluminogens but also broadens the prospects for material applications.

7.
BMC Plant Biol ; 24(1): 387, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724946

RESUMO

BACKGROUND: Woody bamboos are the only diverse large perennial grasses in mesic-wet forests and are widely distributed in the understory and canopy. The functional trait variations and trade-offs in this taxon remain unclear due to woody bamboo syndromes (represented by lignified culm of composed internodes and nodes). Here, we examined the effects of heritable legacy and occurrence site climates on functional trait variations in leaf and culm across 77 woody bamboo species in a common garden. We explored the trade-offs among leaf functional traits, the connection between leaf nitrogen (N), phosphorus (P) concentrations and functional niche traits, and the correlation of functional traits between leaves and culms. RESULTS: The Bayesian mixed models reveal that the combined effects of heritable legacy (phylogenetic distances and other evolutionary processes) and occurrence site climates accounted for 55.10-90.89% of the total variation among species for each studied trait. The standardized major axis analysis identified trade-offs among leaf functional traits in woody bamboo consistent with the global leaf economics spectrum; however, compared to non-bamboo species, the woody bamboo exhibited lower leaf mass per area but higher N, P concentrations and assimilation, dark respiration rates. The canonical correlation analysis demonstrated a positive correlation (ρ = 0.57, P-value < 0.001) between leaf N, P concentrations and morphophysiology traits. The phylogenetic principal components and trait network analyses indicated that leaf and culm traits were clustered separately, with leaf assimilation and respiration rates associated with culm ground diameter. CONCLUSION: Our study confirms the applicability of the leaf economics spectrum and the biogeochemical niche in woody bamboo taxa, improves the understanding of woody bamboo leaf and culm functional trait variations and trade-offs, and broadens the taxonomic units considered in plant functional trait studies, which contributes to our comprehensive understanding of terrestrial forest ecosystems.


Assuntos
Nitrogênio , Folhas de Planta , Folhas de Planta/fisiologia , Folhas de Planta/genética , Nitrogênio/metabolismo , Sasa/genética , Sasa/fisiologia , Poaceae/genética , Poaceae/fisiologia , Fósforo/metabolismo , Filogenia , Teorema de Bayes
8.
Small ; 20(34): e2400272, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38623970

RESUMO

Polymer-in-salt solid-state electrolytes (PIS SSEs) are emerging for high room-temperature ionic conductivity and facile handling, but suffer from poor mechanical durability and large thickness. Here, Al2O3-coated PE (PE/AO) separators are proposed as robust and large-scale substrates to trim the thickness of PIS SSEs without compromising mechanical durability. Various characterizations unravel that introducing Al2O3 coating on PE separators efficiently improves the wettability, thermal stability, and Li-dendrite resistance of PIS SSEs. The resulting PE/AO@PIS demonstrates ultra-small thickness (25 µm), exceptional mechanical durability (55.1 MPa), high decomposition temperature (330 °C), and favorable ionic conductivity (0.12 mS cm-1 at 25 °C). Consequently, the symmetrical Li cells remain stable at 0.1 mA cm-2 for 3000 h, without Li dendrite formation. Besides, the LiFePO4|Li full cells showcase excellent rate capability (131.0 mAh g-1 at 10C) and cyclability (93.6% capacity retention at 2C after 400 cycles), and high-mass-loading performance (7.5 mg cm-2). Moreover, the PE/AO@PIS can also pair with nickel-rich layered oxides (NCM811 and NCM9055), showing a remarkable specific capacity of 165.3 and 175.4 mAh g-1 at 0.2C after 100 cycles, respectively. This work presents an effective large-scale preparation approach for mechanically durable and ultrathin PIS SSEs, driving their practical applications for next-generation solid-state Li-metal batteries.

9.
Small ; : e2405587, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350451

RESUMO

Solar-powered interfacial water evaporation is a promising technique for alleviating freshwater stress. However, the evaporation performance of solar evaporators is still constrained by low photothermal conversion efficiency and high water evaporation enthalpy. Herein, 0D carbon quantum dots (CQDs) are combined with 2D MXene to serve as a hybrid photothermal material to enhance the light absorption and photothermal conversion ability, meanwhile sodium carboxymethyl cellulose (CMC)/polyacrylamide (PAM) hydrogels are used as a substrate material for water transport to reduce the enthalpy of water evaporation. The synergistic effect in 0D CQDs/2D MXene hybrid photothermal materials accelerate the carrier transfer, inducing efficient localized surface plasmon resonance (LSPR) effect. This results in the enhanced photothermal conversion efficiency. The integrated hydrogel evaporators demonstrate a high evaporation rate (1.93 and 2.86 kg m-2 h-1 under 1 and 2 sunlights, respectively) and low evaporation enthalpy (1485 J g-1). In addition, the hydrogel evaporators are applied for photothermal sensing and temperature difference power generation (TEG). The TEG device presents an efficient output power density (230.7 mW m-2) under 1 sunlight. This work provides a feasible approach for regulating and controlling the evaporation performances of hydrogel evaporators, and gives a proof-of-concept for the design of multipurpose solar evaporation systems.

10.
Cytotherapy ; 26(6): 641-648, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38506770

RESUMO

Ex vivo resting culture is a standard procedure following genome editing in hematopoietic stem and progenitor cells (HSPCs). However, prolonged culture may critically affect cell viability and stem cell function. We investigated whether varying durations of culture resting times impact the engraftment efficiency of human CD34+ HSPCs edited at the BCL11A enhancer, a key regulator in the expression of fetal hemoglobin. We employed electroporation to introduce CRISPR-Cas9 components for BCL11A enhancer editing and compared outcomes with nonelectroporated (NEP) and electroporated-only (EP) control groups. Post-electroporation, we monitored cell viability, death rates, and the frequency of enriched hematopoietic stem cell (HSC) fractions (CD34+CD90+CD45RA- cells) over a 48-hour period. Our findings reveal that while the NEP group showed an increase in cell numbers 24 hours post-electroporation, both EP and BCL11A-edited groups experienced significant cell loss. Although CD34+ cell frequency remained high in all groups for up to 48 hours post-electroporation, the frequency of the HSC-enriched fraction was significantly lower in the EP and edited groups compared to the NEP group. In NBSGW xenograft mouse models, both conditioned with busulfan and nonconditioned, we found that immediate transplantation post-electroporation led to enhanced engraftment without compromising editing efficiency. Human glycophorin A+ (GPA+) red blood cells (RBCs) sorted from bone marrow of all BCL11A edited mice exhibited similar levels of γ-globin expression, regardless of infusion time. Our findings underscore the critical importance of optimizing the culture duration between genome editing and transplantation. Minimizing this interval may significantly enhance engraftment success and minimize cell loss without compromising editing efficiency. These insights offer a pathway to improve the success rates of genome editing in HSPCs, particularly for conditions like sickle cell disease.


Assuntos
Edição de Genes , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Animais , Humanos , Edição de Genes/métodos , Camundongos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Transplante de Células-Tronco Hematopoéticas/métodos , Sistemas CRISPR-Cas/genética , Eletroporação/métodos , Xenoenxertos , Sobrevivência Celular , Antígenos CD34/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
11.
Phys Rev Lett ; 132(6): 066602, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394559

RESUMO

It is commonly believed that topologically nontrivial one-dimensional systems support edge states rather than bulk states at zero energy. In this work, we find an unanticipated case of topological Anderson insulator (TAI) phase where two bulk modes are degenerate at zero energy, in addition to degenerate edge modes. We term this "ungapped TAI" to distinguish it from the previously known gapped TAIs. Our experimental realization of both gapped and ungapped TAIs relies on coupled photonic resonators, in which the disorder in coupling is judiciously engineered by adjusting the spacing between the resonators. By measuring the local density of states both in the bulk and at the edges, we demonstrate the existence of these two types of TAIs, together forming a TAI plateau in the phase diagram. Our experimental findings are well supported by theoretical analysis. In the ungapped TAI phase, we observe stable coexistence of topological edge states and localized bulk states at zero energy, highlighting the distinction between TAIs and traditional topological insulators.

12.
J Org Chem ; 89(2): 918-927, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38154059

RESUMO

Catalytic and asymmetric domino Michael/aldol reaction of 1,2-dicarbonyl compounds with α,ß-unsaturated ketones under the synergetic catalysis of chiral-at-metal rhodium complexes and pyrrolidine to deliver tertiary α-hydroxylation-cyclopentanones (45-89% yields with 81-99% ee and up to >20:1 dr) bearing three contiguous stereogenic centers had been established. Moreover, the scalability and practical utility of this protocol were well demonstrated by employing a gram-scale reaction and some representative transformations.

13.
J Pathol ; 259(2): 163-179, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36420735

RESUMO

Invadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they have been visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Podossomos , Humanos , Carcinoma Nasofaríngeo/patologia , Podossomos/metabolismo , Podossomos/patologia , Herpesvirus Humano 4/metabolismo , Neoplasias Nasofaríngeas/patologia , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas de Membrana/metabolismo , Proteínas da Matriz Viral/metabolismo , Microambiente Tumoral
14.
J Biomed Inform ; 154: 104627, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38561170

RESUMO

OBJECTIVE: Designing a new clinical trial entails many decisions, such as defining a cohort and setting the study objectives to name a few, and therefore can benefit from recommendations based on exhaustive mining of past clinical trial records. This study proposes an approach based on knowledge graph embeddings and semantics-driven inductive inference for generating such recommendations. METHOD: The proposed recommendation methodology is based on neural embeddings trained on first-of-its-kind knowledge graph constructed from clinical trials data. The methodology includes design of a knowledge graph for clinical trial data, evaluation of various knowledge graph embedding techniques for it, application of a novel inductive inference method using these embeddings, and generation of recommendations for clinical trial design. The study uses freely available data from clinicaltrials.gov and related sources. RESULTS: The proposed approach for recommendations obtained relevance scores ranging from 70% to 83%. These scores were determined by evaluating the text similarity of recommended elements to actual elements used in clinical trials that are in progress. Furthermore, the most pertinent recommendations were consistently located towards the top of the list, indicating the effectiveness of our method. CONCLUSION: Our study suggests that inductive inference using node semantics is a viable approach for generating recommendations using graphs neural embeddings, and that there is a potential for improvement in training graph embeddings using node semantics.


Assuntos
Ensaios Clínicos como Assunto , Semântica , Humanos , Mineração de Dados/métodos , Algoritmos , Redes Neurais de Computação , Projetos de Pesquisa
15.
Am J Otolaryngol ; 45(5): 104373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38838480

RESUMO

BACKGROUND: With advancements in medicine and economy, it would be expected that there will be changes in the clinical characteristics of upper respiratory papillomatosis. The aim of this study was to examine the current clinical characteristics of upper respiratory papillomatosis, as there are no recent data in the literature. METHODS: The medical records of 1894 patients with upper respiratory papillomatosis were retrospectively reviewed. Data extracted included clinical features, laryngoscopy images, and surgical procedure data. RESULTS: The upper frequency of upper respiratory papillomatosis in the oropharynx was 69.1 %, and in the larynx was held 28.9 %. The overall postoperative relapse rate was 2.4 %. The relapse rate of laryngeal papillomatosis was 6.5 %. Approximately 2.6 % of cases were in children. All postoperative recurrences in children were laryngeal, and the recurrence rate was 30.4 %. CONCLUSION: The oropharynx has the highest frequency of upper respiratory papillomatosis. The larynx, however, has the highest rate of postoperative recurrence. Compared to adults, children are more likely to experience a postoperative recurrence.


Assuntos
Neoplasias Laríngeas , Humanos , Estudos Retrospectivos , Masculino , Feminino , Criança , Adulto , Pré-Escolar , Pessoa de Meia-Idade , Adolescente , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/diagnóstico , Idoso , Adulto Jovem , Infecções por Papillomavirus , Laringoscopia , Lactente , Recidiva Local de Neoplasia/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Papiloma/cirurgia , Papiloma/epidemiologia , Papiloma/patologia , Idoso de 80 Anos ou mais
16.
Angew Chem Int Ed Engl ; 63(24): e202403827, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38589299

RESUMO

Organic radicals with narrow energy gaps are highly sought-after for the production of near-infrared (NIR) fluorophores. However, the current repertoire of developed organic radicals is notably limited, facing challenges related to stability and low fluorescence efficiency. This study addresses these limitations by achieving stable radicals in nonconjugated poly(diphenylmethane) (PDPM). Notably, PDPM exhibits a well-balanced structural flexibility and rigidity, resulting in a robust intra-/inter-chain through-space conjugation (TSC). The stable radicals within PDPM, coupled with strong TSC, yield a remarkable full-spectrum emission spanning from blue to NIR beyond 900 nm. This extensive tunability is achieved through careful adjustments of concentration and excitation wavelength. The findings highlight the efficacy of polymerization in stabilizing radicals and introduce a novel approach for developing nonconjugated NIR emitters based on triphenylmethane subunits.

17.
J Physiol ; 601(1): 83-98, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36420836

RESUMO

Autosomal dominant polycystic kidney disease is caused by mutations in the membrane receptor PKD1 or the cation channel PKD2. TACAN (also termed TMEM120A), recently reported as an ion channel in neurons for mechanosensing and pain sensing, is also distributed in diverse non-neuronal tissues, such as kidney, heart and intestine, suggesting its involvement in other functions. In this study, we found that TACAN is in a complex with PKD2 in native renal cell lines. Using the two-electrode voltage clamp in Xenopus oocytes, we found that TACAN inhibits the channel activity of PKD2 gain-of-function mutant F604P. TACAN fragments containing the first and last transmembrane domains interacted with the PKD2 C- and N-terminal fragments, respectively. The TACAN N-terminus acted as a blocking peptide, and TACAN inhibited the function of PKD2 by the binding of PKD2 with TACAN. By patch clamping in mammalian cells, we found that TACAN inhibits both the single-channel conductance and the open probability of PKD2 and mutant F604P. PKD2 co-expressed with TACAN, but not PKD2 alone, exhibited pressure sensitivity. Furthermore, we found that TACAN aggravates PKD2-dependent tail curvature and pronephric cysts in larval zebrafish. In summary, this study revealed that TACAN acts as a PKD2 inhibitor and mediates mechanosensitivity of the PKD2-TACAN channel complex. KEY POINTS: TACAN inhibits the function of PKD2 in vitro and in vivo. TACAN N-terminal S1-containing fragment T160X interacts with the PKD2 C-terminal fragment N580-L700, and its C-terminal S6-containing fragment L296-D343 interacts with the PKD2 N-terminal A594X. TACAN inhibits the function of the PKD2 channel by physical interaction. The complex of PKD2 with TACAN, but not PKD2 alone, confers mechanosensitivity.


Assuntos
Rim Policístico Autossômico Dominante , Peixe-Zebra , Animais , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Canais Iônicos/genética , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/metabolismo , Rim/metabolismo , Mamíferos/metabolismo
18.
Plant Biotechnol J ; 21(9): 1873-1886, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37323119

RESUMO

Salicylic acid (SA) is an essential plant hormone that plays critical roles in basal defence and amplification of local immune responses and establishes resistance against various pathogens. However, the comprehensive knowledge of the salicylic acid 5-hydroxylase (S5H) in rice-pathogen interaction is still elusive. Here, we reported that three OsS5H homologues displayed salicylic acid 5-hydroxylase activity, converting SA into 2,5-dihydroxybenzoic acid (2,5-DHBA). OsS5H1, OsS5H2, and OsS5H3 were preferentially expressed in rice leaves at heading stage and responded quickly to exogenous SA treatment. We found that bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) strongly induced the expression of OsS5H1, OsS5H2, and OsS5H3. Rice plants overexpressing OsS5H1, OsS5H2, and OsS5H3 showed significantly decreased SA contents and increased 2,5-DHBA levels, and were more susceptible to bacterial blight and rice blast. A simple single guide RNA (sgRNA) was designed to create oss5h1oss5h2oss5h3 triple mutants through CRISPR/Cas9-mediated gene mutagenesis. The oss5h1oss5h2oss5h3 exhibited stronger resistance to Xoo than single oss5h mutants. And oss5h1oss5h2oss5h3 plants displayed enhanced rice blast resistance. The conferred pathogen resistance in oss5h1oss5h2oss5h3 was attributed to the significantly upregulation of OsWRKY45 and pathogenesis-related (PR) genes. Besides, flg22-induced reactive oxygen species (ROS) burst was enhanced in oss5h1oss5h2oss5h3. Collectively, our study provides a fast and effective approach to generate rice varieties with broad-spectrum disease resistance through OsS5H gene editing.


Assuntos
Oryza , Xanthomonas , Resistência à Doença/genética , Sistemas CRISPR-Cas , RNA Guia de Sistemas CRISPR-Cas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo , Mutação/genética , Oryza/metabolismo , Doenças das Plantas/microbiologia , Regulação da Expressão Gênica de Plantas
19.
Plant Biotechnol J ; 21(4): 819-838, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36597711

RESUMO

Plant architecture and stress tolerance play important roles in rice breeding. Specific leaf morphologies and ideal plant architecture can effectively improve both abiotic stress resistance and rice grain yield. However, the mechanism by which plants simultaneously regulate leaf morphogenesis and stress resistance remains elusive. Here, we report that SRL10, which encodes a double-stranded RNA-binding protein, regulates leaf morphology and thermotolerance in rice through alteration of microRNA biogenesis. The srl10 mutant had a semi-rolled leaf phenotype and elevated sensitivity to high temperature. SRL10 directly interacted with catalase isozyme B (CATB), and the two proteins mutually increased one other's stability to enhance hydrogen peroxide (H2 O2 ) scavenging, thereby contributing to thermotolerance. The natural Hap3 (AGC) type of SRL10 allele was found to be present in the majority of aus rice accessions, and was identified as a thermotolerant allele under high temperature stress in both the field and the growth chamber. Moreover, the seed-setting rate was 3.19 times higher and grain yield per plant was 1.68 times higher in near-isogenic line (NIL) carrying Hap3 allele compared to plants carrying Hap1 allele under heat stress. Collectively, these results reveal a new locus of interest and define a novel SRL10-CATB based regulatory mechanism for developing cultivars with high temperature tolerance and stable yield. Furthermore, our findings provide a theoretical basis for simultaneous breeding for plant architecture and stress resistance.


Assuntos
Oryza , Termotolerância , Termotolerância/genética , Oryza/metabolismo , Catalase/genética , Catalase/metabolismo , Isoenzimas/metabolismo , Melhoramento Vegetal , Grão Comestível , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo
20.
Phys Rev Lett ; 131(17): 176401, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37955469

RESUMO

The disorder systems host three types of fundamental quantum states, known as the extended, localized, and critical states, of which the critical states remain being much less explored. Here we propose a class of exactly solvable models which host a novel type of exact mobility edges (MEs) separating localized states from robust critical states, and propose experimental realization. Here the robustness refers to the stability against both single-particle perturbation and interactions in the few-body regime. The exactly solvable one-dimensional models are featured by a quasiperiodic mosaic type of both hopping terms and on-site potentials. The analytic results enable us to unambiguously obtain the critical states which otherwise require arduous numerical verification including the careful finite size scalings. The critical states and new MEs are shown to be robust, illustrating a generic mechanism unveiled here that the critical states are protected by zeros of quasiperiodic hopping terms in the thermodynamic limit. Further, we propose a novel experimental scheme to realize the exactly solvable model and the new MEs in an incommensurate Rydberg Raman superarray. This Letter may pave a way to precisely explore the critical states and new ME physics with experimental feasibility.

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