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1.
Nat Commun ; 15(1): 6103, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030231

RESUMO

While many countries employed digital contact tracing to contain the spread of SARS-CoV-2, the contribution of cospace-time interaction (i.e., individuals who shared the same space and time) to transmission and to super-spreading in the real world has seldom been systematically studied due to the lack of systematic sampling and testing of contacts. To address this issue, we utilized data from 2230 cases and 220,878 contacts with detailed epidemiological information during the Omicron outbreak in Beijing in 2022. We observed that contact number per day of tracing for individuals in dwelling, workplace, cospace-time interactions, and community settings could be described by gamma distribution with distinct parameters. Our findings revealed that 38% of traced transmissions occurred through cospace-time interactions whilst control measures were in place. However, using a mathematical model to incorporate contacts in different locations, we found that without control measures, cospace-time interactions contributed to only 11% (95%CI: 10%-12%) of transmissions and the super-spreading risk for this setting was 4% (95%CI: 3%-5%), both the lowest among all settings studied. These results suggest that public health measures should be optimized to achieve a balance between the benefits of digital contact tracing for cospace-time interactions and the challenges posed by contact tracing within the same setting.


Assuntos
COVID-19 , Busca de Comunicante , SARS-CoV-2 , Busca de Comunicante/métodos , Humanos , COVID-19/transmissão , COVID-19/epidemiologia , SARS-CoV-2/isolamento & purificação , China/epidemiologia , Surtos de Doenças , Modelos Teóricos
2.
Plant Physiol Biochem ; 213: 108860, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936070

RESUMO

Drought is one of the most common environmental stressors that severely threatens plant growth, development, and productivity. B2 (2,4-dichloroformamide cyclopropane acid), a novel plant growth regulator, plays an essential role in drought adaptation, significantly enhancing the tolerance of Carex breviculmis seedlings. Its beneficial effects include improved ornamental value, sustained chlorophyll content, increased leaf dry weight, elevated relative water content, and enhanced root activity under drought conditions. B2 also directly scavenges hydrogen peroxide and superoxide anion contents while indirectly enhancing the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase) to detoxify reactive oxygen species (ROS) oxidative damage. Transcriptome analysis demonstrated that B2 activates drought-responsive transcription factors (AP2/ERF-ERF, WRKY, and mTERF), leading to significant upregulation of genes associated with phenylpropanoid biosynthesis (HCT, POD, and COMT). Additionally, these transcription factors were found to suppress the degradation of starch. B2 regulates phytohormone signaling related-genes, leading to an increase in abscisic acid contents in drought-stressed plants. Collectively, these findings offer new insights into the intricate mechanisms underlying C. breviculmis' resistance to drought damage, highlighting the potential application of B2 for future turfgrass establishment and management with enhanced drought tolerance.


Assuntos
Secas , Reguladores de Crescimento de Plantas , Espécies Reativas de Oxigênio , Amido , Espécies Reativas de Oxigênio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Amido/metabolismo , Amido/biossíntese , Regulação da Expressão Gênica de Plantas , Transdução de Sinais , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Propanóis/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Resistência à Seca
3.
Chem Biol Interact ; 398: 111107, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38866309

RESUMO

Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.


Assuntos
Aminoácidos de Cadeia Ramificada , Benzeno , Ácidos Graxos , Oxirredução , Animais , Benzeno/toxicidade , Aminoácidos de Cadeia Ramificada/metabolismo , Ácidos Graxos/metabolismo , Oxirredução/efeitos dos fármacos , Camundongos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Masculino , Camundongos Endogâmicos C57BL , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/efeitos dos fármacos
4.
Emerg Infect Dis ; 30(7): 1434-1437, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38916639

RESUMO

We investigated Alongshan virus infection in reindeer in northeastern China. We found that 4.8% of the animals were viral RNA-positive, 33.3% tested positive for IgG, and 19.1% displayed neutralizing antibodies. These findings suggest reindeer could serve as sentinel animal species for the epidemiologic surveillance of Alongshan virus infection.


Assuntos
Anticorpos Antivirais , Rena , Animais , Rena/virologia , China/epidemiologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Infecções por Bunyaviridae/veterinária , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/virologia , RNA Viral , Imunoglobulina G/sangue
5.
Sci Total Environ ; 946: 174300, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38936707

RESUMO

Microplastics (MPs) have been found in the air, human nasal cavity, and lung, suggesting that the respiratory tract is one of the important exposure routes for MPs. The lung is a direct target organ for injury from inhaled MPs, but data on lung injury from longer-term exposure to environmental doses of MPs are limited, and the mechanisms remain unclear. Here, C57BL/6 J mice were treated with 5 µm polystyrene (PS)-MPs by intratracheal instillation (0.6, 3, and 15 mg/kg) for 60 days to establish MPs exposure model. We found that PS-MPs lead to increased collagen fibers and decreased lung barrier permeability and lung function in lung tissue. Mechanistically, the abundance of gram-negative bacteria in the pulmonary flora increased after inhalation of PS-MPs, causing lipopolysaccharide (LPS) release. The expression of Toll-like receptor 4 (TLR4), the key receptor of LPS, was increased, and ferroptosis occurred in lung tissue cells. Further in vitro intervention experiments were performed, pulmonary flora/TLR4-induced imbalance of lung iron homeostasis is an important mechanism of PS-MPs-induced lung injury. Our study provides new evidence for lung injury caused by environmental doses of MPs and strategies to prevent it through longer-term dynamic observation.


Assuntos
Homeostase , Ferro , Pulmão , Camundongos Endogâmicos C57BL , Microplásticos , Poliestirenos , Receptor 4 Toll-Like , Animais , Poliestirenos/toxicidade , Camundongos , Pulmão/efeitos dos fármacos , Microplásticos/toxicidade , Receptor 4 Toll-Like/metabolismo , Homeostase/efeitos dos fármacos , Ferro/metabolismo , Lesão Pulmonar/induzido quimicamente , Exposição por Inalação/efeitos adversos
6.
Fish Shellfish Immunol ; 149: 109618, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729251

RESUMO

An eight-week feeding trial was designed to assess which component of commensal Bacillus siamensis LF4 can mitigate SBM-induced enteritis and microbiota dysbiosis in spotted seabass (Lateolabrax maculatus) based on TLRs-MAPKs/NF-кB signaling pathways. Fish continuously fed low SBM (containing 16 % SBM) and high SBM (containing 40 % SBM) diets were used as positive (FM group) and negative (SBM group) control, respectively. After feeding high SBM diet for 28 days, fish were supplemented with B. siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) or peptidoglycan (PGN) until 56 days. The results showed that a high inclusion of SBM in the diet caused enteritis, characterized with significantly (P < 0.05) decreased muscular thickness, villus height, villus width, atrophied and loosely arranged microvillus. Moreover, high SBM inclusion induced an up-regulation of pro-inflammatory cytokines and a down-regulation of occludin, E-cadherin, anti-inflammatory cytokines, apoptosis related genes and antimicrobial peptides. However, dietary supplementation with CW, LTA, and PGN of B. siamensis LF4 could effectively alleviate enteritis caused by a high level of dietary SBM. Additionally, CWP and PGN administration increased beneficial Cetobacterium and decreased pathogenic Plesiomonas and Brevinema, while dietary LTA decreased Plesiomonas and Brevinema, suggesting that CWP, LTA and PGN positively modulated intestinal microbiota in spotted seabass. Furthermore, CW, LTA, and PGN application significantly stimulated TLR2, TLR5 and MyD88 expressions, and inhibited the downstream p38 and NF-κB signaling. Taken together, these results suggest that LTA and PGN from B. siamensis LF4 could alleviate soybean meal-induced enteritis and microbiota dysbiosis in L. maculatus, and p38 MAPK/NF-κB pathways might be involved in those processes.


Assuntos
Ração Animal , Bacillus , Dieta , Disbiose , Enterite , Doenças dos Peixes , Microbioma Gastrointestinal , Glycine max , Lipopolissacarídeos , Peptidoglicano , Ácidos Teicoicos , Animais , Doenças dos Peixes/imunologia , Ração Animal/análise , Enterite/veterinária , Enterite/imunologia , Enterite/microbiologia , Disbiose/veterinária , Disbiose/imunologia , Bacillus/fisiologia , Bacillus/química , Microbioma Gastrointestinal/efeitos dos fármacos , Dieta/veterinária , Glycine max/química , Lipopolissacarídeos/farmacologia , Ácidos Teicoicos/farmacologia , Peptidoglicano/farmacologia , Peptidoglicano/administração & dosagem , Bass/imunologia , Probióticos/farmacologia , Probióticos/administração & dosagem , Suplementos Nutricionais/análise , Distribuição Aleatória
7.
Science ; 384(6696): 639-646, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38723095

RESUMO

Despite identifying El Niño events as a factor in dengue dynamics, predicting the oscillation of global dengue epidemics remains challenging. Here, we investigate climate indicators and worldwide dengue incidence from 1990 to 2019 using climate-driven mechanistic models. We identify a distinct indicator, the Indian Ocean basin-wide (IOBW) index, as representing the regional average of sea surface temperature anomalies in the tropical Indian Ocean. IOBW is closely associated with dengue epidemics for both the Northern and Southern hemispheres. The ability of IOBW to predict dengue incidence likely arises as a result of its effect on local temperature anomalies through teleconnections. These findings indicate that the IOBW index can potentially enhance the lead time for dengue forecasts, leading to better-planned and more impactful outbreak responses.


Assuntos
Dengue , Epidemias , Humanos , Modelos Climáticos , Dengue/epidemiologia , El Niño Oscilação Sul , Incidência , Oceano Índico , Temperatura Alta
8.
Environ Pollut ; 352: 124100, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38714232

RESUMO

Decabromodiphenyl ether (BDE-209) has been universally detected in environmental media and animals, but its damage to ovarian function and mechanism is still unclear, and melatonin has been shown to improve mammalian ovarian function. This study aimed to investigate the toxic effects of BDE-209 on the ovary and tried to improve ovarian function with melatonin. Herein, BDE-209 was administered orally to female SD rats for 60 days. Enzyme-linked immunosorbent assay, HE staining, transcriptome analysis, qPCR and immunohistochemical staining were used to explore and verify the potential mechanism. We found that BDE-209 exposure had effects on the ovary, as shown by abnormal changes in the estrous cycle, hormone levels and ovarian reserve function in rats, while increasing the proportion of collagen fibres in ovarian tissue. In terms of mechanism, cuproptosis, a form of cell death, was identified to play a crucial role in BDE-209-induced ovarian dysfunction, with the phenotype manifested as copper salt accumulation in ovary, downregulation of glutathione pathway metabolism and copper transfer molecule (ATP7A/B), and upregulation of FDX1, lipoic acid pathway (LIAS, LIPT1), pyruvate dehydrogenase complex components (DLAT, PDHB, PDHA1), and copper transfer molecule (SLC31A1). Furthermore, possible interventions were explored. Notably, a supplement with melatonin has a repair effect on the damage to ovarian function by reversing the gene expression of cuproptosis-involved molecules. Overall, this study revealed that cuproptosis is involved in BDE-209-induced ovarian damage and the beneficial effect of melatonin on ovarian copper damage, providing evidence for the prevention and control of female reproductive damage induced by BDE-209.


Assuntos
Éteres Difenil Halogenados , Melatonina , Ovário , Ratos Sprague-Dawley , Animais , Melatonina/farmacologia , Feminino , Éteres Difenil Halogenados/toxicidade , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ratos , Substâncias Protetoras/farmacologia , Poluentes Ambientais/toxicidade
9.
RSC Adv ; 14(15): 10687-10696, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38567341

RESUMO

Fe3Al is a good magnetic loss absorber for microwave absorption. However, due to the relatively high density and poor impedance matching ratio, the potential of Fe3Al cannot be fully released. Herein, a dielectric loss absorber of carbon nanotubes (CNTs) is coupled with Fe3Al to form Fe3Al/CNTs composite absorbers. CNTs are randomly tangled and coated on the surface of the Fe3Al flakes, forming a connecting conductive network. By carefully tuning the content of CNTs, the optimized Fe3Al/CNTs composite absorber with 1.5% of CNTs can combine both magnetic loss and dielectric loss mechanisms, thus achieving an impedance matching ratio close to 1 while keeping strong attenuation for enhanced microwave absorption. As a result, an effective absorption bandwidth (RL ≤ -10 dB) of 4.73 GHz at a thickness of 2 mm is achieved.

10.
Heliyon ; 10(7): e28769, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38590908

RESUMO

Objective: To investigate the effectiveness of a multimodal deep learning model in predicting tumor budding (TB) grading in rectal cancer (RC) patients. Materials and methods: A retrospective analysis was conducted on 355 patients with rectal adenocarcinoma from two different hospitals. Among them, 289 patients from our institution were randomly divided into an internal training cohort (n = 202) and an internal validation cohort (n = 87) in a 7:3 ratio, while an additional 66 patients from another hospital constituted an external validation cohort. Various deep learning models were constructed and compared for their performance using T1CE and CT-enhanced images, and the optimal models were selected for the creation of a multimodal fusion model. Based on single and multiple factor logistic regression, clinical N staging and fecal occult blood were identified as independent risk factors and used to construct the clinical model. A decision-level fusion was employed to integrate these two models to create an ensemble model. The predictive performance of each model was evaluated using the area under the curve (AUC), DeLong's test, calibration curve, and decision curve analysis (DCA). Model visualization Gradient-weighted Class Activation Mapping (Grad-CAM) was performed for model interpretation. Results: The multimodal fusion model demonstrated superior performance compared to single-modal models, with AUC values of 0.869 (95% CI: 0.761-0.976) for the internal validation cohort and 0.848 (95% CI: 0.721-0.975) for the external validation cohort. N-stage and fecal occult blood were identified as clinically independent risk factors through single and multivariable logistic regression analysis. The final ensemble model exhibited the best performance, with AUC values of 0.898 (95% CI: 0.820-0.975) for the internal validation cohort and 0.868 (95% CI: 0.768-0.968) for the external validation cohort. Conclusion: Multimodal deep learning models can effectively and non-invasively provide individualized predictions for TB grading in RC patients, offering valuable guidance for treatment selection and prognosis assessment.

12.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38612714

RESUMO

Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.


Assuntos
Arabidopsis , Ésteres , Compostos Heterocíclicos com 3 Anéis , Lactonas , Naftalenos , Simulação de Acoplamento Molecular , Ácidos Carboxílicos
13.
Gut Microbes ; 16(1): 2323227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38436067

RESUMO

Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus. Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.


Assuntos
Ácidos Graxos Monoinsaturados , Microbioma Gastrointestinal , Interleucina-5 , Animais , Camundongos , Camundongos Endogâmicos C57BL , Benzeno/toxicidade , Ácidos Graxos , Inflamação
14.
Adv Healthc Mater ; 13(16): e2303939, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38447111

RESUMO

Nanoplatforms with high Mn2+ coordination can display efficient T1 magnetic resonance imaging (MRI) contrast enhancement. Herein, an earth gravity-like method for enhanced interaction between Ferritin (Fn) and Mn2+ by the growth of platinum nanoparticles (PNs) in Fn's cage structure via a biomineralization method is first proposed. Fn has good biocompatibility and can provide a suitable growth site for PNs. PNs with negative charge have certain attraction to Mn2+ with positive charge, improving Fn's loading capacity of Mn2+ by attraction force; and thus, achieving efficient MRI contrast enhancement. In addition, PNs can be applied for efficient photothermal therapy (PTT) under near infrared ray (NIR) irradiation. Systemic delivery of this nanoplatform shows obvious MRI contrast enhancement and tumor progression inhibition after NIR irradiation, as well as no obvious side effects. Therefore, this nanoplatform has the potential to contribute to nanotheranostic for clinical transformation.


Assuntos
Meios de Contraste , Ferritinas , Imageamento por Ressonância Magnética , Manganês , Nanopartículas Metálicas , Terapia Fototérmica , Platina , Platina/química , Platina/farmacologia , Terapia Fototérmica/métodos , Animais , Imageamento por Ressonância Magnética/métodos , Ferritinas/química , Ferritinas/metabolismo , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Manganês/química , Humanos , Camundongos , Meios de Contraste/química , Raios Infravermelhos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Camundongos Nus
15.
Cryobiology ; 115: 104889, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38513998

RESUMO

Chimeric antigen receptor (CAR) T-cell therapies are increasingly adopted as a commercially available treatment for hematologic and solid tumor cancers. As CAR-T therapies reach more patients globally, the cryopreservation and banking of patients' leukapheresis materials is becoming imperative to accommodate intra/inter-national shipping logistical delays and provide greater manufacturing flexibility. This study aims to determine the optimal temperature range for transferring cryopreserved leukapheresis materials from two distinct types of controlled rate freezing systems, Liquid Nitrogen (LN2)-based and LN2-free Conduction Cooling-based, to the ultracold LN2 storage freezer (≤-135 °C), and its impact on CAR T-cell production and functionality. Presented findings demonstrate that there is no significant influence on CAR T-cell expansion, differentiation, or downstream in-vitro function when employing a transfer temperature range spanning from -30 °C to -80 °C for the LN2-based controlled rate freezers as well as for conduction cooling controlled rate freezers. Notably, CAR T-cells generated from cryopreserved leukapheresis materials using the conduction cooling controlled rate freezer exhibited suboptimal performance in certain donors at transfer temperatures lower than -60 °C, possibly due to the reduced cooling rate of lower than 1 °C/min and extended dwelling time needed to reach the final temperatures within these systems. This cohort of data suggests that there is a low risk to transfer cryopreserved leukapheresis materials at higher temperatures (between -30 °C and -60 °C) with good functional recovery using either controlled cooling system, and the cryopreserved materials are suitable to use as the starting material for autologous CAR T-cell therapies.


Assuntos
Criopreservação , Imunoterapia Adotiva , Leucaférese , Linfócitos T , Criopreservação/métodos , Leucaférese/métodos , Humanos , Linfócitos T/citologia , Linfócitos T/imunologia , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos , Temperatura , Congelamento , Técnicas de Cultura de Células/métodos
16.
Small ; : e2400356, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389174

RESUMO

Nickel oxide (NiOx ) has been limited in use as a hole transport layer for its low conduction, surface defects, and redox reactions with the perovskite layer. To address these issues, the incorporation of zwitterion L-tryptophan (Trp) is proposed at the NiOx /Trp interface. The carboxyl group of Trp effectively passivates the surface positive defects of NiOx , thereby improving its optical and electrical properties. The ammonium group of Trp not only passivates negative defects but modulates the growth of the perovskite layer, resulting in an improved perovskite film quality. Furthermore, the Trp layer acts as a buffer layer, suppressing adverse interfacial reactions between the perovskite and NiOx . Consequently, perovskite solar cells with 1.56 and 1.68 eV absorbers achieve the champion power conversion efficiency (PCE) of 23.79% and 20.41%, respectively. Moreover, the unencapsulated devices demonstrate excellent long-term stability, retaining above 80% of the initial PCE value after 1600 h of storage in the air with a humidity of 50-60%.

17.
Science ; 383(6683): 659-666, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38330135

RESUMO

Secretory structures in terrestrial plants serve as reservoirs for a variety of secondary metabolites. Among these, the secretory cavity of the Rutaceae family is notable for containing essential oils with a wide range of applications. However, the molecular basis underlying secretory cavity development is unknown. Here, we reveal a molecular framework for Citrus oil gland formation. Using genetic mapping and genome editing, we demonstrated that this process requires LATE MERISTEM IDENTITY1 (LMI1), a key regulator of leaf serration. A conserved GCC box element of the LMI1 promoter recruits DORNROSCHEN-like (DRNL) for transcriptional activation. This DRNL-LMI1 cascade triggers MYC5 activation, facilitating the development of oil glands and the biosynthesis of essential oils. Our findings spotlight cis-regulatory divergence within leaf shape genes, propelling novel functional tissue formation.


Assuntos
Citrus , Óleos Voláteis , Proteínas de Plantas , Fatores de Transcrição , Tricomas , Citrus/genética , Citrus/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Óleos Voláteis/metabolismo , Tricomas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
18.
Eur Radiol ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38337068

RESUMO

OBJECTIVES: We aimed to develop a multi-modality model to predict axillary lymph node (ALN) metastasis by combining clinical predictors with radiomic features from magnetic resonance imaging (MRI) and mammography (MMG) in breast cancer. This model might potentially eliminate unnecessary axillary surgery in cases without ALN metastasis, thereby minimizing surgery-related complications. METHODS: We retrospectively enrolled 485 breast cancer patients from two hospitals and extracted radiomics features from tumor and lymph node regions on MRI and MMG images. After feature selection, three random forest models were built using the retained features, respectively. Significant clinical factors were integrated with these radiomics models to construct a multi-modality model. The multi-modality model was compared to radiologists' diagnoses on axillary ultrasound and MRI. It was also used to assist radiologists in making a secondary diagnosis on MRI. RESULTS: The multi-modality model showed superior performance with AUCs of 0.964 in the training cohort, 0.916 in the internal validation cohort, and 0.892 in the external validation cohort. It surpassed single-modality models and radiologists' ALN diagnosis on MRI and axillary ultrasound in all validation cohorts. Additionally, the multi-modality model improved radiologists' MRI-based ALN diagnostic ability, increasing the average accuracy from 70.70 to 78.16% for radiologist A and from 75.42 to 81.38% for radiologist B. CONCLUSION: The multi-modality model can predict ALN metastasis of breast cancer accurately. Moreover, the artificial intelligence (AI) model also assisted the radiologists to improve their diagnostic ability on MRI. CLINICAL RELEVANCE STATEMENT: The multi-modality model based on both MRI and mammography images allows preoperative prediction of axillary lymph node metastasis in breast cancer patients. With the assistance of the model, the diagnostic efficacy of radiologists can be further improved. KEY POINTS: • We developed a novel multi-modality model that combines MRI and mammography radiomics with clinical factors to accurately predict axillary lymph node (ALN) metastasis, which has not been previously reported. • Our multi-modality model outperformed both the radiologists' ALN diagnosis based on MRI and axillary ultrasound, as well as single-modality radiomics models based on MRI or mammography. • The multi-modality model can serve as a potential decision support tool to improve the radiologists' ALN diagnosis on MRI.

19.
Nat Commun ; 15(1): 1476, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368459

RESUMO

Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-XL can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective BCL-2 inhibitor. However, its application has led to an emergence of resistant mutations, calling for drugs with an innovative mechanism of action. Herein we present cyclic peptides (CPs) with nanomolar-level binding affinities to BCL-2 or BCL-XL, and further reveal the structural and functional mechanisms of how these CPs target two proteins in a fashion that is remarkably different from traditional small-molecule inhibitors. In addition, these CPs can bind to the venetoclax-resistant clinical BCL-2 mutants with similar affinities as to the wild-type protein. Furthermore, we identify a single-residue discrepancy between BCL-2 D111 and BCL-XL A104 as a molecular "switch" that can differently engage CPs. Our study suggests that CPs may inhibit BCL-2 or BCL-XL by delicately modulating protein-protein interactions, potentially benefiting the development of next-generation therapeutics.


Assuntos
Antineoplásicos , Peptídeos Cíclicos , Peptídeos Cíclicos/farmacologia , Proteína bcl-X/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Apoptose , Linhagem Celular Tumoral
20.
Fish Shellfish Immunol ; 145: 109370, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216004

RESUMO

Live commensal Bacillus siamensis LF4 showed reparative potentials against high SM-induced negative effects, but whether its paraprobiotic (heat-killed B. siamensis, HKBS) and postbiotic (cell-free supernatant, CFS) forms had reparative functions and potential mechanisms are not yet known. In this study, the reparative functions of HKBS and CFS were investigated by establishing an injured model of spotted seabass (Lateolabrax maculatus) treated with dietary high soybean meal (SM). The results showed that HKBS and CFS effectively mitigated growth suppression, immune deficiency, and liver injury induced by dietary high SM. Simultaneously, HKBS and CFS application positively shaped intestinal microbiota by increased the abundance of beneficial bacteria (Fusobacteria, Firmicutes, Bacteroidota, and Cetobacterium) and decreased harmful bacteria (Proteobacteria and Plesiomonasare). Additionally, HKBS and CFS improved SM-induced intestinal injury by restoring intestinal morphology, upregulating the expression of tight junction proteins, anti-inflammatory cytokines, antimicrobial peptides, downregulating the expression of pro-inflammatory cytokines and apoptotic proteins. Furthermore, HKBS and CFS intervention significantly activated TLR2, TLR5 and MyD88 signaling, and eventually inhibited p38 and NF-κB pathways. In conclusion, paraprobiotic (HKBS) and postbiotic (CFS) from B. siamensis LF4 can improve growth, immunity, repair liver and intestinal injury, and shape intestinal microbiota in L. maculatus fed high soybean meal diet, and TLRs/p38 MAPK/NF-κB signal pathways might be involved in those processes. These results will serve as a base for future application of paraprobiotics and postbiotics to prevent and repair SM-induced adverse effects in fish aquaculture.


Assuntos
Bacillus , Bass , NF-kappa B , Animais , Farinha , Dieta , Fígado/metabolismo , Citocinas/metabolismo , Ração Animal/análise
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