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1.
Plant Cell ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723161

RESUMO

The conserved microRNA (miRNA) miR408 enhances photosynthesis and compromises stress tolerance in multiple plants, but the cellular mechanism underlying its function remains largely unclear. Here, we show that in Arabidopsis (Arabidopsis thaliana), the transcript encoding the blue copper protein PLANTACYANIN (PCY) is the primary target for miR408 in vegetative tissues. PCY is preferentially expressed in the guard cells, and PCY is associated with the endomembrane surrounding individual chloroplasts. We found that the MIR408 promoter is suppressed by multiple abscisic acid (ABA)-responsive transcription factors, thus allowing PCY to accumulate under stress conditions. Genetic analysis revealed that PCY elevates reactive oxygen species (ROS) levels in the guard cells, promotes stomatal closure, reduces photosynthetic gas exchange, and enhances drought resistance. Moreover, the miR408-PCY module is sufficient to rescue the growth and drought tolerance phenotypes caused by gain- and loss-of-function of MYB44, an established positive regulator of ABA responses, indicating that the miR408-PCY module relays ABA signaling for regulating ROS homeostasis and drought resistance. These results demonstrate that miR408 regulates stomatal movement to balance growth and drought resistance, providing a mechanistic understanding of why miR408 is selected during land plant evolution and insights into the long-pursued quest of breeding drought-tolerant and high-yielding crops.

2.
N Engl J Med ; 385(15): 1355-1371, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34496194

RESUMO

BACKGROUND: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Hospitalização/estatística & dados numéricos , Vacina de mRNA-1273 contra 2019-nCoV , Ad26COVS1 , Idoso , Idoso de 80 Anos ou mais , Vacina BNT162 , COVID-19/epidemiologia , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estados Unidos/epidemiologia
3.
Small ; : e2311456, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497893

RESUMO

Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.

4.
Plant Cell ; 33(5): 1506-1529, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-33616669

RESUMO

Light-dependent seed germination is a vital process for many seed plants. A decisive event in light-induced germination is degradation of the central repressor PHYTOCHROME INTERACTING FACTOR 1 (PIF1). The balance between gibberellic acid (GA) and abscisic acid (ABA) helps to control germination. However, the cellular mechanisms linking PIF1 turnover to hormonal balancing remain elusive. Here, employing far-red light-induced Arabidopsis thaliana seed germination as the experimental system, we identified PLANTACYANIN (PCY) as an inhibitor of germination. It is a blue copper protein associated with the vacuole that is both highly expressed in mature seeds and rapidly silenced during germination. Molecular analyses showed that PIF1 binds to the miR408 promoter and represses miR408 accumulation. This in turn posttranscriptionally modulates PCY abundance, forming the PIF1-miR408-PCY repression cascade for translating PIF1 turnover to PCY turnover during early germination. Genetic analysis, RNA-sequencing, and hormone quantification revealed that PCY is necessary and sufficient to maintain the PIF1-mediated seed transcriptome and the low-GA-high-ABA state. Furthermore, we found that PCY domain organization and regulation by miR408 are conserved features in seed plants. These results revealed a cellular mechanism whereby PIF1-relayed external light signals are converted through PCY turnover to internal hormonal profiles for controlling seed germination.


Assuntos
Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Germinação , Luz , Metaloproteínas/metabolismo , MicroRNAs/metabolismo , Sementes/crescimento & desenvolvimento , Transdução de Sinais , Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Sequência Conservada , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Inativação Gênica , Genes de Plantas , Germinação/genética , Giberelinas/metabolismo , MicroRNAs/genética , Modelos Biológicos , Filogenia , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , Ligação Proteica/efeitos da radiação , Plântula/efeitos da radiação , Sementes/genética , Transdução de Sinais/efeitos da radiação , Vacúolos/metabolismo , Vacúolos/efeitos da radiação
5.
Plant Cell ; 33(3): 581-602, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955485

RESUMO

Plants possess unique primary cell walls made of complex polysaccharides that play critical roles in determining intrinsic cell and organ size. How genes responsible for synthesizing and modifying the polysaccharides in the cell wall are regulated by microRNAs (miRNAs) to control plant size remains largely unexplored. Here we identified 23 putative cell wall-related miRNAs, termed as CW-miRNAs, in Arabidopsis thaliana and characterized miR775 as an example. We showed that miR775 post-transcriptionally silences GALT9, which encodes an endomembrane-located galactosyltransferase belonging to the glycosyltransferase 31 family. Over-expression of miR775 and deletion of GALT9 led to significantly enlarged leaf-related organs, primarily due to increased cell size. Monosaccharide quantification, confocal Raman imaging, and immunolabeling combined with atomic force microscopy revealed that the MIR775A-GALT9 circuit modulates pectin levels and the elastic modulus of the cell wall. We also showed that MIR775A is directly repressed by the transcription factor ELONGATED HYPOCOTYL5 (HY5). Genetic analysis confirmed that HY5 is a negative regulator of leaf size that acts through the HY5-MIR775A-GALT9 repression cascade to control pectin levels. These findings demonstrate that miR775-regulated cell wall remodeling is an integral determinant of intrinsic leaf size in A. thaliana. Studying other CW-miRNAs would provide more insights into cell wall biology.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Parede Celular/metabolismo , Galactosiltransferases/metabolismo , Pectinas/metabolismo , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Arabidopsis/genética , Galactosiltransferases/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética
6.
Biomed Eng Online ; 23(1): 31, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468262

RESUMO

BACKGROUND: Ultrasound three-dimensional visualization, a cutting-edge technology in medical imaging, enhances diagnostic accuracy by providing a more comprehensive and readable portrayal of anatomical structures compared to traditional two-dimensional ultrasound. Crucial to this visualization is the segmentation of multiple targets. However, challenges like noise interference, inaccurate boundaries, and difficulties in segmenting small structures exist in the multi-target segmentation of ultrasound images. This study, using neck ultrasound images, concentrates on researching multi-target segmentation methods for the thyroid and surrounding tissues. METHOD: We improved the Unet++ to propose PA-Unet++ to enhance the multi-target segmentation accuracy of the thyroid and its surrounding tissues by addressing ultrasound noise interference. This involves integrating multi-scale feature information using a pyramid pooling module to facilitate segmentation of structures of various sizes. Additionally, an attention gate mechanism is applied to each decoding layer to progressively highlight target tissues and suppress the impact of background pixels. RESULTS: Video data obtained from 2D ultrasound thyroid serial scans served as the dataset for this paper.4600 images containing 23,000 annotated regions were divided into training and test sets at a ratio of 9:1, the results showed that: compared with the results of U-net++, the Dice of our model increased from 78.78% to 81.88% (+ 3.10%), the mIOU increased from 73.44% to 80.35% (+ 6.91%), and the PA index increased from 92.95% to 94.79% (+ 1.84%). CONCLUSIONS: Accurate segmentation is fundamental for various clinical applications, including disease diagnosis, treatment planning, and monitoring. This study will have a positive impact on the improvement of 3D visualization capabilities and clinical decision-making and research in the context of ultrasound image.


Assuntos
Imageamento Tridimensional , Glândula Tireoide , Glândula Tireoide/diagnóstico por imagem , Projetos de Pesquisa , Tecnologia , Processamento de Imagem Assistida por Computador
7.
Pain Med ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652573

RESUMO

BACKGROUND: There is a close association between diet and abdominal pain, however, relationship between inflammatory diet and characteristics of abdominal pain has not been characterized yet. METHODS: This study analyzed baseline data from the UK Biobank, 3-item DHQ-Abdominal Pain Questionnaire (DHQ-3Q) which including abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, and data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Energy-adjusted Dietary Inflammatory Index (E-DII), constructed based on 26 or 27 nutrients, was analyzed using continuous or categorical methods. Logistic regression and restricted cubic spline analyses examined the association between E-DII and abdominal pain. RESULTS: In UK Biobank, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.12 (95% CI 1.02-1.24; p = 0.022), 1.05 (95% CI 1.00-1.09; p = 0.030), 1.26 (95% CI 1.17-1.36; p < 0.001), and 1.10 (95% CI 1.00-1.20; p = 0.044) for chronic abdominal pain, abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, respectively. In NHANES, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.46 (95% CI 1.20-1.77; p < 0.001), 1.75 (95% CI 1.20-2.60; p = 0.005), 1.45 (95% CI 1.14-1.87; p = 0.003), and 1.18 (95% CI 0.82-1.72; p = 0.380) for abdominal pain in the past year, upper left abdominal pain, upper middle abdominal pain, and upper right abdominal pain. Additionally, there was a nonlinear correlation between E-DII score and DHQ-3Q (p nonlinear <0.001). CONCLUSION: Following a pro-inflammatory diet is linked to a higher likelihood of experiencing abdominal pain, as well as increased severity and frequency of such pain. Therefore, further longitudinal studies are necessary to investigate this relationship.

8.
BMC Vet Res ; 20(1): 199, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745195

RESUMO

BACKGROUND: Rectal temperature (RT) is an important index of core temperature, which has guiding significance for the diagnosis and treatment of pet diseases. OBJECTIVES: Development and evaluation of an alternative method based on machine learning to determine the core temperatures of cats and dogs using surface temperatures. ANIMALS: 200 cats and 200 dogs treated between March 2022 and May 2022. METHODS: A group of cats and dogs were included in this study. The core temperatures and surface body temperatures were measured. Multiple machine learning methods were trained using a cross-validation approach and evaluated in one retrospective testing set and one prospective testing set. RESULTS: The machine learning models could achieve promising performance in predicting the core temperatures of cats and dogs using surface temperatures. The root mean square errors (RMSE) were 0.25 and 0.15 for cats and dogs in the retrospective testing set, and 0.15 and 0.14 in the prospective testing set. CONCLUSION: The machine learning model could accurately predict core temperatures for companion animals of cats and dogs using easily obtained body surface temperatures.


Assuntos
Temperatura Corporal , Aprendizado de Máquina , Animais , Gatos/fisiologia , Cães/fisiologia , Estudos Retrospectivos , Masculino , Feminino , Estudos Prospectivos
9.
Aging Clin Exp Res ; 36(1): 138, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935236

RESUMO

BACKGROUND: Body weight has been recognized as a driving factor of osteoarthritis. Few studies had investigated the association between weight status across adulthood and risk of osteoarthritis (OA). This study investigates the association of weight change patterns across adulthood (lasting at least 25 years) with the risk of OA from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. METHODS: The study assessed the relationship between weight change across adulthood and OA in 7392 individuals aged > 50 spanning a minimum of 25 years. Multivariate linear regression analyses were utilized to detect the association between weight change patterns and self-reported OA. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between absolute weight change and OA risk. RESULTS: From 10 years ago to survey, the risk of OA was 1.34-fold (95% CI 1.07-1.68) in people changed from obese to non-obese, 1.61-fold (95% CI 1.29-2.00) in people change from non-obese to obese, and 1.82-fold (95% CI 1.49-2.22) in stable obese people compared with people who were at stable normal weight. Similar patterns were also observed at age 25 years to baseline and age 25 years to 10 years before the baseline. The dose-response association of RCS found a U-shaped relationship between absolute weight change and OA risk. CONCLUSIONS: The study suggests that weight patterns across adulthood are associated with the risk of OA. These findings stressed important to maintain a normal weight throughout adulthood, especially to prevent ignored weight gain in early adulthood to reduce OA risk later.


Assuntos
Inquéritos Nutricionais , Obesidade , Osteoartrite , Humanos , Masculino , Osteoartrite/epidemiologia , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Obesidade/epidemiologia , Obesidade/complicações , Idoso , Aumento de Peso/fisiologia , Adulto , Peso Corporal
10.
PLoS Genet ; 17(8): e1009770, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34460822

RESUMO

The eye color of birds, generally referring to the color of the iris, results from both pigmentation and structural coloration. Avian iris colors exhibit striking interspecific and intraspecific variations that correspond to unique evolutionary and ecological histories. Here, we identified the genetic basis of pearl (white) iris color in domestic pigeons (Columba livia) to explore the largely unknown genetic mechanism underlying the evolution of avian iris coloration. Using a genome-wide association study (GWAS) approach in 92 pigeons, we mapped the pearl iris trait to a 9 kb region containing the facilitative glucose transporter gene SLC2A11B. A nonsense mutation (W49X) leading to a premature stop codon in SLC2A11B was identified as the causal variant. Transcriptome analysis suggested that SLC2A11B loss of function may downregulate the xanthophore-differentiation gene CSF1R and the key pteridine biosynthesis gene GCH1, thus resulting in the pearl iris phenotype. Coalescence and phylogenetic analyses indicated that the mutation originated approximately 5,400 years ago, coinciding with the onset of pigeon domestication, while positive selection was likely associated with artificial breeding. Within Aves, potentially impaired SLC2A11B was found in six species from six distinct lineages, four of which associated with their signature brown or blue eyes and lack of pteridine. Analysis of vertebrate SLC2A11B orthologs revealed relaxed selection in the avian clade, consistent with the scenario that during and after avian divergence from the reptilian ancestor, the SLC2A11B-involved development of dermal chromatophores likely degenerated in the presence of feather coverage. Our findings provide new insight into the mechanism of avian iris color variations and the evolution of pigmentation in vertebrates.


Assuntos
Columbidae/genética , Cor de Olho/genética , Cor de Olho/fisiologia , Animais , Evolução Biológica , Evolução Molecular , Olho/metabolismo , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla , Genótipo , Proteínas Facilitadoras de Transporte de Glucose/genética , Iris/metabolismo , Mutação , Fenótipo , Filogenia , Pigmentação/genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-38122925

RESUMO

Crustacean hyperglycemic hormone (CHH) superfamily peptides constitute a group of neurohormones, including the crustacean hyperglycemic hormone (CHH), molt-inhibiting hormone (MIH), and gonad-inhibiting hormone (GIH) or vitellogenesis-inhibiting hormone (VIH), which reportedly play an essential role in regulating various biological activities by binding to their receptors in crustaceans. Although bioinformatics analyses have identified G protein-coupled receptors (GPCRs) as potential CHH receptors, no validation through binding experiments has been carried out. This study employed a eukaryotic expression system, HEK293T cell transient transfection, and ligand-receptor interaction tests to identify the GPCRs of CHHs in the mud crab Scylla paramamosain. We found that four GPCRs (Sp-GPCR-A34-A37) were activated by their corresponding CHHs (Sp-CHH1-v1, Sp-MIH, Sp-VIH) in a dose-dependent manner. Of these, Sp-GPCR-A34 was exclusively activated by Sp-VIH; Sp-GPCR-A35 was activated by Sp-CHH1-v1 and Sp-VIH, respectively; Sp-GPCR-A36 was activated by Sp-CHH1-v1 and Sp-MIH; Sp-GPCR-A37 was exclusively activated by Sp-MIH. The half-maximal effective concentration (EC50) values for all CHHs/GPCRs pairs (both Ca2+ and cAMP signaling) were in the nanomolar range. Overall, our study provided hitherto undocumented evidence of the presence of G protein-coupled receptors of CHH in crustaceans, providing the foothold for further studies on the signaling pathways of CHHs and their corresponding GPCRs.


Assuntos
Braquiúros , Hormônios de Invertebrado , Humanos , Animais , Braquiúros/metabolismo , Células HEK293 , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Peptídeos/química , Proteínas de Transporte/metabolismo , Hormônios de Invertebrado/genética , Hormônios de Invertebrado/metabolismo , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo
12.
Int J Biometeorol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607561

RESUMO

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 µg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 µg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

13.
Zhongguo Zhong Yao Za Zhi ; 49(3): 763-769, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621880

RESUMO

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.


Assuntos
Compostos Azo , Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Camundongos , Ratos , Animais , Dieta Hiperlipídica/efeitos adversos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/farmacologia , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Camundongos Endogâmicos C57BL , Fígado , Hepatopatia Gordurosa não Alcoólica/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Triglicerídeos/metabolismo , Peso Corporal , Trifosfato de Adenosina/farmacologia
14.
Am J Respir Cell Mol Biol ; 68(6): 625-637, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36848480

RESUMO

In idiopathic pulmonary fibrosis (IPF), the normal delicate lung architecture is replaced with rigid extracellular matrix (ECM) as a result of the accumulation of activated myofibroblasts and excessive deposition of ECM. Lamins have a role in fostering mechanosignaling from the ECM to the nucleus. Although there is a growing number of studies on lamins and associated diseases, there are no prior reports linking aberrations in lamins with pulmonary fibrosis. Here, we discovered, through analysis of RNA sequencing data, a novel isoform of lamin A/C that is more highly expressed in IPF compared with control lung. This novel LMNA (lamin A/C) splice variant includes retained introns 10 and 11 and exons 11 and 12 as documented by rapid amplification of cDNA ends. We found that this novel isoform is induced by stiff ECM. To better clarify the specific effects of this novel isoform of lamin A/C and how it may contribute to the pathogenesis of IPF, we transduced the lamin transcript into primary lung fibroblasts and alveolar epithelial cells and found that it impacts several biological effects, including cell proliferation, senescence, cell contraction, and the transition of fibroblasts to myofibroblasts. We also observed that type II epithelial cells and myofibroblasts in the IPF lung exhibited wrinkled nuclei, and this is notable because this has not been previously described and is consistent with laminopathy-mediated cellular effects.


Assuntos
Fibrose Pulmonar Idiopática , Lamina Tipo A , Humanos , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Pulmão/patologia , Fibrose Pulmonar Idiopática/patologia , Fibroblastos/metabolismo , Miofibroblastos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
15.
Appl Environ Microbiol ; 89(11): e0086723, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37850723

RESUMO

IMPORTANCE: Dinoflagellates are the most common phytoplankton group and account for more than 75% of harmful algal blooms in coastal waters. In recent decades, dinoflagellates seem to prevail in phosphate-depleted waters. However, the underlying acclimation mechanisms and competitive strategies of dinoflagellates in response to phosphorus deficiency are poorly understood, especially in terms of intracellular phosphorus modulation and recycling. Here, we focused on the response of intracellular phosphorus metabolism to phosphorus deficiency in the model dinoflagellate Karenia mikimotoi. Our work reveals the strong capability of K. mikimotoi to efficiently regulate intracellular phosphorus resources, particularly through membrane phospholipid remodeling and miRNA regulation of energy metabolism. Our research improved the understanding of intracellular phosphorus metabolism in marine phytoplankton and underscored the advantageous strategies of dinoflagellates in the efficient modulation of internal phosphorus resources to maintain active physiological activity and growth under unsuitable phosphorus conditions, which help them outcompete other species in coastal phosphate-depleted environments.


Assuntos
Dinoflagellida , Fósforo , Proliferação Nociva de Algas , Fitoplâncton , Fosfatos
16.
J Med Virol ; 95(3): e28672, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36916779

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered alphacoronavirus with zoonotic potential that causes diarrhea and vomiting mainly in piglets. Having emerged suddenly in 2017, the prevailing opinion is that the virus originated from HKU2, an alphacoronavirus whose primary host is bats, and at some unknown point achieved interspecies transmission via some intermediate. Here, we further explore the evolutionary history and possible cross-species transmission event for SADS-CoV. Coevolutionary analysis demonstrated that HKU2 may have achieved host switch via SADS-related (SADSr)-CoV, which was isolated from the genus Rhinolophus in 2017. SADS-CoV, HKU2, and SADSr-CoV share similar codon usage patterns and showed a lower tendency to use CpG, which may reflect a method of immune escape. The analyses of virus-host coevolution and recombination support SADSr-CoV is the direct source of SADS-CoV that may have undergone recombination events during its formation. Structure-based spike glycoprotein variance analysis revealed a more nuanced evolutionary pathway to receptor recognition for host switch. We did not find a possible positive selection site, and the dN/dS of the S gene was only 0.29, which indicates that the current SADS-CoV is slowly evolving. These results provide new insights that may help predict future cross-species transmission, and possibly surveil future zoonotic outbreaks and associated public health emergencies.


Assuntos
Alphacoronavirus , Quirópteros , Infecções por Coronavirus , Doenças dos Suínos , Animais , Suínos , Alphacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Diarreia/veterinária , Doenças dos Suínos/epidemiologia
17.
MMWR Morb Mortal Wkly Rep ; 71(53): 1637-1646, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36921274

RESUMO

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 32% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 59% compared with no vaccination, 42% compared with monovalent vaccination only with last dose 5-7 months earlier, and 48% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.


Assuntos
COVID-19 , Humanos , Adulto , Adolescente , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2/genética , Eficácia de Vacinas , Serviço Hospitalar de Emergência , Hospitalização , RNA Mensageiro , Vacinas Combinadas
18.
Inorg Chem ; 62(41): 16965-16973, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37794771

RESUMO

Atomically precise alloy nanoclusters (NCs) inherit the advantages of homometal NC counterparts such as atomic stacking fashion, quantum confinement effect, and enriched catalytic active sites and simultaneously possess the advantageous physicochemical properties such as significantly enhanced photostability, ideal photosensitization efficiency, and favorable energy band structure. Nevertheless, elucidation of the roles of alloy NCs and alloy nanocrystals (NYs) in boosting solar water oxidation has so far not yet been reported owing to the deficiency of applicable alloy NC photosystems. Herein, utilizing the generic thermal-induced self-transformation of alloy NCs to alloy NYs, we comprehensively explore the photosensitization properties of glutathione (GSH)-capped alloy NCs (AgxAu1-x@GSH and CuxAu1-x@GSH) and the corresponding alloy NY (AgAu and CuAu) counterparts in solar water oxidation reaction. The results imply that photoelectrons of alloy NCs surpass the hot electrons over plasmonic alloy NYs in stimulating the PEC water oxidation reaction. The photoelectrons of alloy NCs demonstrate lower interfacial charge-transfer resistance, longer carrier lifetime, and a more enhanced photosensitization effect with respect to the plasmonic alloy NYs, contributing to the significantly boosted photoelectrochemical water oxidation activities. Moreover, we found that our result is universal.

19.
Inorg Chem ; 62(45): 18649-18659, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37903426

RESUMO

Transition-metal chalcogenide quantum dots (TMC QDs) show great promise in artificial photosynthesis for excellent light-harvesting capability. Nonetheless, TMC QDs have limitations of ultrafast charge recombination rate, sluggish carrier migration kinetics, and generic photocorrosion, retarding their widespread applications. To solve these obstacles, herein, we demonstrate the stimulation of charge migration over TMC QDs with the aid of nonconjugated insulating polymer and graphene (GR) for a versatile photoredox selective organic transformation. To this end, an ultrathin insulating polymer layer, i.e., poly(allylamine hydrochloride) (PAH), grafted on the GR framework, is electrostatically intercalated at the interface of TMCs QDs and the GR framework via a self-assembly for constructing TMC QDs/PAH/GR three-dimensional spatially multilayered heterostructures. In this well-defined nanoarchitecture, TMC QDs function as a light-harvesting antenna, GR as a terminal electron reservoir, and PAH as an intermediate interfacial charge relay mediator. We ascertain that the ultrathin PAH interim layer unexpectedly fosters the photoelectron migration from TMCs QDs to the GR framework in a tunable fashion, boosting the charge separation of TMCs QDs and resulting in significantly improved photoactivities toward anaerobic reduction of aromatic nitro compounds to amino derivatives and oxidation of alcohols to aldehydes under visible light. Photoredox catalysis mechanisms of such TMC QDs/PAH/GR photosystems are elucidated, and the active species in these photoredox organic conversion reactions are comprehensively determined. Our work would open new frontiers to finely modulate the charge transport of TMCs QDs via nonconjugated insulating polymers for solar energy conversion.

20.
BMC Gastroenterol ; 23(1): 424, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041073

RESUMO

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN. METHODS: In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model. RESULTS: The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN. CONCLUSIONS: AP is predictive of malignancy in patients with IPMN.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Pancreatite , Masculino , Feminino , Humanos , Carcinoma Ductal Pancreático/patologia , Pancreatite/complicações , Pancreatite/patologia , Estudos Retrospectivos , Doença Aguda , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/patologia , Neoplasias Pancreáticas/patologia
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