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1.
Cell Death Differ ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879723

RESUMO

N4-acetylcytidine (ac4C), a conserved but recently rediscovered RNA modification on tRNAs, rRNAs and mRNAs, is catalyzed by N-acetyltransferase 10 (NAT10). Lysine acylation is a ubiquitous protein modification that controls protein functions. Our latest study demonstrates a NAT10-dependent ac4C modification, which occurs on the polyadenylated nuclear RNA (PAN) encoded by oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), can induce KSHV reactivation from latency and activate inflammasome. However, it remains unclear whether a novel lysine acylation occurs in NAT10 during KSHV reactivation and how this acylation of NAT10 regulates tRNAs ac4C modification. Here, we showed that NAT10 was lactylated by α-tubulin acetyltransferase 1 (ATAT1), as a writer at the critical domain, to exert RNA acetyltransferase function and thus increase the ac4C level of tRNASer-CGA-1-1. Mutagenesis at the ac4C site in tRNASer-CGA-1-1 inhibited its ac4C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNASer-CGA-1-1 ac4C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac4C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases.

2.
Cell Death Dis ; 15(6): 409, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862475

RESUMO

Low glucose is a common microenvironment for rapidly growing solid tumors, which has developed multiple approaches to survive under glucose deprivation. However, the specific regulatory mechanism remains largely elusive. In this study, we demonstrate that glucose deprivation, while not amino acid or serum starvation, transactivates the expression of DCAF1. This enhances the K48-linked polyubiquitination and proteasome-dependent degradation of Rheb, inhibits mTORC1 activity, induces autophagy, and facilitates cancer cell survival under glucose deprivation conditions. This study identified DCAF1 as a new cellular glucose sensor and uncovered new insights into mechanism of DCAF1-mediated inactivation of Rheb-mTORC1 pathway for promoting cancer cell survival in response to glucose deprivation.


Assuntos
Sobrevivência Celular , Glucose , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteína Enriquecida em Homólogo de Ras do Encéfalo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/genética , Glucose/metabolismo , Linhagem Celular Tumoral , Autofagia , Ubiquitinação , Transdução de Sinais , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Células HEK293 , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética
3.
Dalton Trans ; 53(24): 10261-10269, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829195

RESUMO

The second near-infrared window (NIR-II) in the range of 1000-1400 nm is ideal for in vivo imaging and sensing through reduced scattering, absorption, and autofluorescence. However, there are only a few nanophosphor systems with emission in the NIR-II region. Here, we report on Mn5+-doped Ba5(PO4)3Cl nanoparticles (BPCl:Mn5+ NPs, d < 50 nm) toward NIR-II temperature sensing. BPCl:Mn5+ NPs are made by a two-step (hydrothermal and anion exchange) method. XRD, SEM, and TEM results showed that the as-prepared BPCl:Mn5+ NPs show high crystallinity, uniform size, and sphere-like morphology. The nanoparticles exhibit a broad excitation band of 500-850 nm and a temperature-sensitive peak emission at 1175 nm in the NIR-II range. NIR-II temperature sensing by 1E emission intensity is demonstrated with good linear fitting (R2 = 0.9895), high sensitivity (2.30% at 373 K), and good repeatability (99.0%). Thus, our study provides a path to develop a new NIR-II thermometer based on tetrahedral Mn(V) coordination.

4.
Cancer Imaging ; 24(1): 71, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863062

RESUMO

BACKGROUND: There is an urgent need to find a reliable and effective imaging method to evaluate the therapeutic efficacy of immunochemotherapy in advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the capability of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis based on different region of interest (ROI) selection methods for predicting treatment response to chemoimmunotherapy in advanced NSCLC. METHODS: Seventy-two stage III or IV NSCLC patients who received chemoimmunotherapy were enrolled in this study. IVIM and DKI were performed before treatment. The patients were classified as responders group and non-responders group according to the Response Evaluation Criteria in Solid Tumors 1.1. The histogram parameters of ADC, Dslow, Dfast, f, Dk and K were measured using whole tumor volume ROI and single slice ROI analysis methods. Variables with statistical differences would be included in stepwise logistic regression analysis to determine independent parameters, by which the combined model was also established. And the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of histogram parameters and the combined model. RESULTS: ADC, Dslow, Dk histogram metrics were significantly lower in the responders group than in the non-responders group, while the histogram parameters of f were significantly higher in the responders group than in the non-responders group (all P < 0.05). The mean value of each parameter was better than or equivalent to other histogram metrics, where the mean value of f obtained from whole tumor and single slice both had the highest AUC (AUC = 0.886 and 0.812, respectively) compared to other single parameters. The combined model improved the diagnostic efficiency with an AUC of 0.968 (whole tumor) and 0.893 (single slice), respectively. CONCLUSIONS: Whole tumor volume ROI demonstrated better diagnostic ability than single slice ROI analysis, which indicated whole tumor histogram analysis of IVIM and DKI hold greater potential than single slice ROI analysis to be a promising tool of predicting therapeutic response to chemoimmunotherapy in advanced NSCLC at initial state.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imagem de Difusão por Ressonância Magnética , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Imunoterapia/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Resultado do Tratamento , Adulto , Curva ROC
5.
Bioorg Med Chem ; 107: 117759, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795572

RESUMO

Small molecule drugs sourced from natural products are pivotal for novel therapeutic discoveries. However, their clinical deployment is often impeded by non-specific activity and severe adverse effects. This study focused on 3-fluoro-10-hydroxy-Evodiamine (F-OH-Evo), a potent derivative of Evodiamine, whose development is curtailed due to suboptimal tumor selectivity and heightened cytotoxicity. By harnessing the remarkable stability, specificity, and αvß3 integrin affinity of c(RGDFK), a novel prodrug by conjugating F-OH-Evo with cRGD was synthesized. This innovative prodrug substantially enhanced the tumor-specific targeting of F-OH-Evo and improved the anti-tumor activities. Among them, compound 3c demonstrated the best selective inhibitory activity toward U87 cancer cells in vitro. It selectively enterd U87 cells by binding to αvß3 integrin, releasing the parent molecule under the dual response of ROS and GSH to exert inhibitory activity on topo I. The results highlight the potential of cRGD-conjugated prodrugs in targeted cancer therapy. This approach signifies a significant advancement in developing safer and more effective chemotherapy drugs, emphasizing the role of prodrug strategies in overcoming the limitations of traditional cancer treatments.


Assuntos
Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Peptídeos Cíclicos , Pró-Fármacos , Quinazolinas , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/antagonistas & inibidores , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/síntese química , Relação Estrutura-Atividade , Quinazolinas/química , Quinazolinas/farmacologia
6.
Acta Biomater ; 182: 228-244, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38761962

RESUMO

Arsenic (As) poisoning has become a global public problem threatening human health. Chelation therapy (CT) is the preferred treatment for arsenic poisoning. Nevertheless, efficient and safe arsenic removal in vivo remains a daunting challenge due to the limitations of chelators, including weak affinity, poor cell membrane penetration, and short half-life. Herein, a mercapto-functionalized and size-tunable hierarchical porous Zr-MOF (UiO-66-TC-SH) is developed, which possesses abundant arsenic chemisorption sites, effective cell uptake ability, and long half-life, thereby efficiently removing toxic arsenic in vivo. Moreover, the strong binding affinity of UiO-66-TC-SH for arsenic reduces systemic toxicity caused by off-target effects. In animal trials, UiO-66-TC-SH decreases the blood arsenic levels of acute arsenic poisoning mice to a normal value within 48 h, and the efficacy is superior to clinical drugs 2,3-dimercaptopropanesulfonic acid sodium salt (DMPS). Meanwhile, UiO-66-TC-SH also significantly mitigates the arsenic accumulation in the metabolic organs of chronic arsenic poisoning mice. Surprisingly, UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates the side effects of arsenic drugs antitumor therapy. STATEMENT OF SIGNIFICANCE: Arsenic (As) contamination has become a global problem threatening public health. The present clinical chelation therapy (CT) still has some limitations, including the weak affinity, poor cell membrane permeability and short half-life of hydrophilic chelators. Herein, a metal-organic framework (MOF)-based multieffective arsenic removal strategy in vivo is proposed for the first time. Mercapto-functionalized and size-tunable hierarchical porous Zr-MOF nanoantidote (denoted as UiO-66-TC-SH) is accordingly designed and synthesized. After injection, UiO-66-TC-SH can form Zr-O-As bonds and As-S bonds with arsenic, thus enhancing arsenic adsorption capacity, cycling stability and systemic safety simultaneously. The acute arsenic poisoning model results indicate that UiO-66-TC-SH shows superior efficacy to the clinical drug sodium dimercaptopropanesulfonate (DMPS). More meaningfully, we find that UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates side effects of arsenic drugs anti-tumor therapy.


Assuntos
Intoxicação por Arsênico , Arsênio , Estruturas Metalorgânicas , Zircônio , Animais , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Zircônio/química , Zircônio/farmacologia , Arsênio/farmacocinética , Camundongos , Intoxicação por Arsênico/tratamento farmacológico , Intoxicação por Arsênico/metabolismo , Humanos , Quelantes/química , Quelantes/farmacologia , Porosidade , Ácidos Ftálicos
7.
Microbiol Spectr ; 12(6): e0039024, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38727239

RESUMO

Alternaria alternata is a ubiquitous soil-borne fungus capable of causing diseases in a variety of plants and occasionally in humans. While populations of A. alternata from infected plants have received significant attention, relatively little is known about its soil populations, including its population genetic structure and antifungal susceptibilities. In addition, over the last two decades, greenhouses have become increasingly important for food and ornamental plant production throughout the world, but how greenhouses might impact microbial pathogens such as A. alternata populations remains largely unknown. Different from open crop fields, greenhouses are often more intensively cultivated, with each greenhouse being a relatively small and isolated space where temperature and humidity are higher than surrounding environments. Previous studies have shown that greenhouse populations of two common molds, Aspergillus fumigatus and A. alternata, within a small community in southwestern China were variably differentiated. However, the relative contribution of physical separation among local greenhouses to the large-scale population structure remains unknown. Here, we isolated strains of A. alternata from seven greenhouses in Shijiazhuang, northeast China. Their genetic diversity and triazole susceptibilities were analyzed and compared with each other and with 242 isolates from nine greenhouses in Kunming, southwest China. Results showed that the isolation of greenhouses located <1 km from each other locally contributed similarly to the overall genetic variation as that between the two distant geographic regions. In addition, our results indicate that greenhouses could be significant sources of triazole resistance, with greenhouses often differing in their frequencies of resistant strains to different triazoles. IMPORTANCE: Greenhouses have become increasingly important for food production and food security. However, our understanding of how greenhouses may contribute to genetic variations in soil microbial populations is very limited. In this study, we obtained and analyzed soil populations of the cosmopolitan fungal pathogen Alternaria alternata in seven greenhouses in Shijiazhuang, northeast China. Our analyses revealed high proportions of isolates being resistant to agricultural triazole fungicides and medical triazole drugs, including cross-resistance to both groups of triazoles. In addition, we found that greenhouse populations of A. alternata located within a few kilometers showed similar levels of genetic differentiation as those separated by over 2,000 km between northeast and southwest China. Our study suggests that greenhouse populations of this and potentially other fungal pathogens represent an important ecological niche and an emerging threat to food security and human health.


Assuntos
Alternaria , Antifúngicos , Variação Genética , Doenças das Plantas , Microbiologia do Solo , Alternaria/genética , China , Doenças das Plantas/microbiologia , Antifúngicos/farmacologia , Filogenia , Farmacorresistência Fúngica/genética , Triazóis/farmacologia
8.
Molecules ; 29(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731462

RESUMO

A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-ß-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.

9.
Nat Microbiol ; 9(6): 1566-1578, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38649411

RESUMO

The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homologue of eukaryotic ubiquitin-conjugating enzymes, which is either an E1-E2 fusion or a single E2. However, the functions of single E2s in CBASS remain elusive. Here, using biochemical, genetic, cryo-electron microscopy and mass spectrometry investigations, we discover that the E2 enzyme from Serratia marcescens regulates cGAS by imitating the ubiquitination cascade. This includes the processing of the cGAS C terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond and poly-cGASylation. The poly-cGASylation activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Thus, our findings reveal a unique regulatory role of E2 in CBASS.


Assuntos
Nucleotidiltransferases , Enzimas de Conjugação de Ubiquitina , Ubiquitinação , Enzimas de Conjugação de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/química , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/química , Transdução de Sinais , Nucleotídeos Cíclicos/metabolismo , Bacteriófagos/genética , Bacteriófagos/enzimologia , Ubiquitina/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Humanos , Microscopia Crioeletrônica , Imunidade Inata
10.
Nat Commun ; 15(1): 3084, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600059

RESUMO

Irrigation is a land management practice with major environmental impacts. However, global energy consumption and carbon emissions resulting from irrigation remain unknown. We assess the worldwide energy consumption and carbon emissions associated with irrigation, while also measuring the potential energy and carbon reductions achievable through the adoption of efficient and low-carbon irrigation practices. Currently, irrigation contributes 216 million metric tons of CO2 emissions and consumes 1896 petajoules of energy annually, representing 15% of greenhouse gas emissions and energy utilized in agricultural operations. Despite only 40% of irrigated agriculture relies on groundwater sources, groundwater pumping accounts for 89% of the total energy consumption in irrigation. Projections indicate that future expansion of irrigation could lead to a 28% increase in energy usage. Embracing highly efficient, low-carbon irrigation methods has the potential to cut energy consumption in half and reduce CO2 emissions by 90%. However, considering country-specific feasibility of mitigation options, global CO2 emissions may only see a 55% reduction. Our research offers comprehensive insights into the energy consumption and carbon emissions associated with irrigation, contributing valuable information that can guide assessments of the viability of irrigation in enhancing adaptive capacity within the agricultural sector.

11.
J Craniofac Surg ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687033

RESUMO

AIM: To investigate the clinical nursing effect of bispectral index (BIS) monitoring for paroxysmal sympathetic hyperactivity (PSH) patients in the neurosurgical intensive care unit (NICU). METHODS: From January 2022 to June 2023, a total of 30 patients with PSH secondary to moderate to severe craniocerebral injury in the NICU were monitored for BIS. The patients' paroxysmal sympathetic hyperactivity-assessment measure (PSH-AM) scores were recorded. PSH patients generally appear in 3 states: calm state, seizure state, and postmedication state. Thirty PSH patients' BIS values were recorded during the calm period, during the seizure state, and postmedication state, and these 3 different stages' BIS values were divided into groups A, B, and C, using the Kruskal-Wallis H test to compare groups. RESULTS: The Kruskal-Wallis H test yielded a value of H=22.599, P<0.001. H0 was rejected against the test standard of α=0.05, and the BIS values of groups A, B, and C differed. The BIS values of group A and group B differed after a pairwise comparison, and the difference was statistically significant (adjusted P=0.001). Group B and group C had different BIS values, and the difference was statistically significant (adjusted P=0.001); group A and Group C had no difference in BIS values, and the difference was not statistically significant (adjusted P=1.00). CONCLUSIONS: Taking BIS value as the nursing observation index for PSH patients can make nursing work more objective, reasonable, and accurate, reduce the inducing factors of PSH attack, further reduce the attack of PSH, save nursing resources, and help guide the safety assessment of sedative use.

12.
Food Chem ; 451: 139458, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38670017

RESUMO

Ripening refers to the process of chemical change during the refinement of Keemun black tea (KBT) and is crucial in the formation of Keemun Congou black tea's quality. In this study, the aroma composition of KBT during the ripening was analyzed. Sensomics indicated that ripening strengthened the coconut and fatty aroma of KBT and contributed to the decrease of green aroma substances, resulting in a shift of the overall aroma type of KBT to an integrated aroma profile, which was consistent with sensory evaluation. Changes in fatty acid content and the results of in vitro addition simulation tests confirmed that heat causes highly degradation of fatty acids into fatty aroma volatiles, which is a key driver of the formation of "Keemun aroma" quality. This study revealed the mechanism behind the formation of KBT's integrated "Keemun aroma" quality and the mode of thermal degradation of major fatty acids.


Assuntos
Ácidos Graxos , Temperatura Alta , Odorantes , Compostos Orgânicos Voláteis , Odorantes/análise , Ácidos Graxos/metabolismo , Ácidos Graxos/química , Humanos , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Chá/química , Chá/metabolismo , Camellia sinensis/química , Camellia sinensis/metabolismo , Camellia sinensis/crescimento & desenvolvimento , Aromatizantes/química , Aromatizantes/metabolismo , Manipulação de Alimentos
13.
J Agric Food Chem ; 72(15): 8460-8475, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564364

RESUMO

Liver injury and progressive liver failure are severe life-threatening complications in sepsis, further worsening the disease and leading to death. Macrophages and their mediated inflammatory cytokine storm are critical regulators in the occurrence and progression of liver injury in sepsis, for which effective treatments are still lacking. l-Ascorbic acid 6-palmitate (L-AP), a food additive, can inhibit neuroinflammation by modulating the phenotype of the microglia, but its pharmacological action in septic liver damage has not been fully explored. We aimed to investigate L-AP's antisepticemia action and the possible pharmacological mechanisms in attenuating septic liver damage by modulating macrophage function. We observed that L-AP treatment significantly increased survival in cecal ligation and puncture-induced WT mice and attenuated hepatic inflammatory injury, including the histopathology of the liver tissues, hepatocyte apoptosis, and the liver enzyme levels in plasma, which were comparable to NLRP3-deficiency in septic mice. L-AP supplementation significantly attenuated the excessive inflammatory response in hepatic tissues of septic mice in vivo and in cultured macrophages challenged by both LPS and ATP in vitro, by reducing the levels of NLRP3, pro-IL-1ß, and pro-IL-18 mRNA expression, as well as the levels of proteins for p-I-κB-α, p-NF-κB-p65, NLRP3, cleaved-caspase-1, IL-1ß, and IL-18. Additionally, it impaired the inflammasome ASC spot activation and reduced the inflammatory factor contents, including IL-1ß and IL-18 in plasma/cultured superannuants. It also prevented the infiltration/migration of macrophages and their M1-like inflammatory polarization while improving their M2-like polarization. Overall, our findings revealed that L-AP protected against sepsis by reducing macrophage activation and inflammatory cytokine production by suppressing their activation in NF-κB and NLRP3 inflammasome signal pathways in septic liver.


Assuntos
Inflamassomos , Sepse , Camundongos , Animais , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Interleucina-18 , Ativação de Macrófagos , Transdução de Sinais , Fígado/metabolismo , Ácido Ascórbico , Sepse/complicações , Sepse/tratamento farmacológico , Lipopolissacarídeos/farmacologia
14.
Zhongguo Zhong Yao Za Zhi ; 49(3): 717-727, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621875

RESUMO

Transcriptome sequencing was employed to mine the simple sequence repeat(SSR) locus information of Saposhnikovia divaricata and design specific primers, which aimed to provide a basis for the research on the genetic diversity of S. divaricata germplasm resources. The seed purity, 1 000-seed weight, germination rate, and seed vigor were determined. MISA was used to obtain the SSR locus information from 12 606 unigene longer than 1 kb in the transcriptome database. Forty-three pairs of SSR primers designed in Primer 3 were used to analyze the polymorphism of 28 S. divaricata samples of different sources. The results showed that there were differences in the seed purity, 1 000-seed weight, germination rate, vigor, and seed length and width among S. divaricata samples of different sources. Particularly, the germination rate and seed vigor had significant differences, and HB-ZJK1, NMG-CF4, NMG-BT, NMG-HLE1, and NMG-CF2 had significantly higher 1 000-seed weight, germination rate, and seed vigor than the samples of other sources. Among the 86 233 unigene, 12 606(14.62%) unigene contained 15 958 SSR loci, with one SSR locus every 5 009 bp on average. The SSR loci were mainly single nucleotide and dinucleotide repeats, which were dominated by G/C and TC/AG, respectively. All the primers were screened by using 28 S. divaricata sample from different habitats, and the primers corresponding to the amplification products with clear bands and stable polymorphism were obtained. The clustering results of the biological characteristics and genetic diversity of the 28 S. divaricata samples were basically consistent, and the samples of the same origin(HB-AG1, HB-AG2, HB-ZJK1, and HB-ZJK2) generally gathered together and had close genetic relationship. The SSRs in S. divaricata transcriptome has high frequency, rich types, and high polymorphism, which provides candidate molecular markers for the germplasm identification, genetic map construction, and molecular-assisted breeding.


Assuntos
Apiaceae , Transcriptoma , Polimorfismo Genético , Repetições de Microssatélites/genética , Apiaceae/genética , Etiquetas de Sequências Expressas
15.
Emerg Infect Dis ; 30(4): 826-828, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38526372

RESUMO

In 2022, we assessed avian influenza A virus subtype H5N6 seroprevalence among the general population in Guangdong Province, China, amid rising numbers of human infections. Among the tested samples, we found 1 to be seropositive, suggesting that the virus poses a low but present risk to the general population.


Assuntos
Influenza Aviária , Influenza Humana , Animais , Humanos , Influenza Aviária/epidemiologia , Estudos Soroepidemiológicos , Influenza Humana/epidemiologia , China/epidemiologia , Aves
16.
mBio ; 15(3): e0335823, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38303107

RESUMO

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others' works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural protein 6 (NSP6) inhibits the production of ACE2-exos by affecting the protein level of ACE2 as well as tetraspanin-CD63 which is a key factor for exosome biogenesis. We further found that the protein stability of CD63 and ACE2 is maintained by the deubiquitination of proteasome 26S subunit, non-ATPase 12 (PSMD12). NSP6 interacts with PSMD12 and counteracts its function, consequently promoting the degradation of CD63 and ACE2. As a result, NSP6 diminishes the antiviral efficacy of ACE2-exos and facilitates the virus to infect healthy bystander cells. Overall, our study provides a valuable target for the discovery of promising drugs for the treatment of coronavirus disease 2019. IMPORTANCE: The outbreak of coronavirus disease 2019 (COVID-19) severely endangers global public health. The efficacy of vaccines and antibodies declined with the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants. Angiotensin-converting enzyme 2-containing exosomes (ACE2-exos) therapy exhibits a broad neutralizing activity, which could be used against various viral mutations. Our study here revealed that SARS-CoV-2 nonstructural protein 6 inhibited the production of ACE2-exos, thereby promoting viral infection to the adjacent bystander cells. The identification of a new target for blocking SARS-CoV-2 depends on fully understanding the virus-host interaction networks. Our study sheds light on the mechanism by which the virus resists the host exosome defenses, which would facilitate the study and design of ACE2-exos-based therapeutics for COVID-19.


Assuntos
COVID-19 , Exossomos , Humanos , COVID-19/metabolismo , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Exossomos/metabolismo , Peptidil Dipeptidase A/metabolismo , Antivirais/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Ligação Proteica
17.
Cell Death Discov ; 10(1): 51, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38272890

RESUMO

Acute myeloid leukemia (AML) is caused by clonal disorders of hematopoietic stem cells. Differentiation therapy is emerging as an important treatment modality for leukemia, given its less toxicity and wider applicable population, but the arsenal of differentiation-inducing agents is still very limited. In this study, we adapted a competitive peptide phage display platform to search for candidate peptides that could functionally induce human leukemia cell differentiation. A monoclonal phage (P6) and the corresponding peptide (pep-P6) were identified. Both L- and D-chirality of pep-P6 showed potent efficiency in inducing AML cell line differentiation, driving their morphologic maturation and upregulating the expression of macrophage markers and cytokines, including CD11b, CD14, IL-6, IL-1ß, and TNF-α. In the THP-1 xenograft animal model, administration of D-pep-P6 was effective in inhibiting disease progression. Importantly, exposure to D-pep-P6 induced the differentiation of primary human leukemia cells isolated AML patients in a similar manner to the AML cell lines. Further mechanism study suggested that D-pep-P6 induced human leukemia cell differentiation by directly activating a TLR-2 signaling pathway. These findings identify a novel D-peptide that may promote leukemia differentiation therapy.

18.
Dalton Trans ; 53(7): 3296-3305, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38258948

RESUMO

It is of great importance to develop new broadband red phosphors since they have possible applications like plant cultivation, indoor lighting and non-destructive sensing. Herein, we report a series of Eu2+, Mn2+ activated NaSrSc(BO3)2 phosphors via a conventional solid-state reaction route. It has been found that both Mn2+ and Eu2+ solo-doped NaSrSc(BO3)2 show weak or no luminescence, while Eu2+, Mn2+ co-doped NaSrSc(BO3)2 exhibits wide-band absorption and intense deep-red emission at 680 nm with color purity of 89%. Analysis of the absorption, excitation and emission spectra of Eu2+, Mn2+ solo- and co-doped NaSrSc(BO3)2 indicates that this deep-red broadband emission originates from Eu2+ sensitization of the octahedron Mn2+ 4T1-6A1 transition. It was found that the photoionization process led by energetic similarity of the host band-gap and the Eu2+ lowest 5d excited state was mainly responsible for the vanished luminescence of Eu2+. The values of internal quantum efficiency (IQE) and absorption efficiency (AE) for the optimal NSSO:0.007Eu2+,0.05Mn2+ sample are 24.5% and 61.8%, respectively. This work could provide new insights into exploring novel Mn-activated deep-red luminescent materials.

19.
Asian J Psychiatr ; 92: 103884, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171225

RESUMO

Depression is a common mental disorder caused by the interaction of social, psychological, and biological factors. Treatments include psychotherapy, pharmacotherapy, and other therapies, but they have limitations. Particularly, the COVID-19 pandemic may have a negative impact on depressed people. Thus, developing more potential treatments for depression has currently been an urgent challenge. A growing number of studies have found that acupressure is effective in relieving the symptoms of depression. Thus, this study aimed to evaluate the efficacy and safety of acupressure in people with depression. English (PubMed, CENTRAL, EMBASE, APA PsycINFO, and CINAHL) and Chinese databases (CBM, CNKI, Wanfang, and VIP), ClinicalTrials.gov and Chinese Clinical Trial Registry were searched for randomized controlled trials (RCTs) on patients diagnosed with depression from study inception until March 31, 2023. Studies that compared acupressure with sham acupressure, conventional treatments (i.e., medication, usual care, etc.), and acupressure as an adjunct to conventional treatment for depression were included. The primary outcome was depression level measured using the Hamilton Depression Scale, Self-Rating Depression Scale, or Geriatric Depression Scale. A total of 19 RCTs involving 1686 participants were included. The pooled results showed that acupressure exhibited a significant beneficial effect on reducing the severity of depression compared with sham acupressure and served as an adjunct to conventional treatment, although the evidence level was moderate. Thus, acupressure may be a potential treatment for depression.


Assuntos
Acupressão , Terapia por Acupuntura , Transtornos Psicóticos , Humanos , Idoso , Depressão/terapia , Psicoterapia/métodos , Terapia por Acupuntura/métodos
20.
Eur J Med Chem ; 265: 116118, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181651

RESUMO

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.


Assuntos
Antineoplásicos , Neoplasias Esofágicas , Melfalan , gama-Globulinas , Humanos , Moduladores de Tubulina , Tubulina (Proteína)/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Relação Estrutura-Atividade , Benzotiazóis/farmacologia , Triazóis/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Polimerização , Estrutura Molecular
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