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1.
JACC Basic Transl Sci ; 9(3): 303-318, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38559623

RESUMO

Most congenital heart defect (CHD) cases are attributed to nongenetic factors; however, the mechanisms underlying nongenetic factor-induced CHDs are elusive. Maternal diabetes is one of the nongenetic factors, and this study aimed to determine whether impaired mitochondrial fusion contributes to maternal diabetes-induced CHDs and if mitochondrial fusion activators, teriflunomide and echinacoside, could reduce CHD incidence in diabetic pregnancy. We demonstrated maternal diabetes-activated FoxO3a increases miR-140 and miR-195, which in turn represses Mfn1 and Mfn2, leading to mitochondrial fusion defects and CHDs. Two mitochondrial fusion activators are effective in preventing CHDs in diabetic pregnancy.

2.
Funct Integr Genomics ; 24(2): 53, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38453820

RESUMO

Hepatocellular carcinoma (HCC) is one of the malignancies with the worst prognosis worldwide, in the occurrence and development of which glycolysis plays a central role. This study uncovered a mechanism by which ZNF692 regulates ALDOA-dependent glycolysis in HCC cells. RT-qPCR and western blotting were used to detect the expression of ZNF692, KAT5, and ALDOA in HCC cell lines and a normal liver cell line. The influences of transfection-induced alterations in the expression of ZNF692, KAT5, and ALDOA on the functions of HepG2 cells were detected by performing MTT, flow cytometry, Transwell, cell scratch, and colony formation assays, and the levels of glucose and lactate were determined using assay kits. ChIP and luciferase reporter assays were conducted to validate the binding of ZNF692 to the KAT5 promoter, and co-IP assays to detect the interaction between KAT5 and ALDOA and the acetylation of ALDOA. ZNF692, KAT5, and ALDOA were highly expressed in human HCC samples and cell lines, and their expression levels were positively correlated in HCC. ZNF692, ALDOA, or KAT5 knockdown inhibited glycolysis, proliferation, invasion, and migration and promoted apoptosis in HepG2 cells. ZNF692 bound to the KAT5 promoter and promoted its activity. ALDOA acetylation levels were elevated in HCC cell lines. KAT5 bound to ALDOA and catalyzed ALDOA acetylation. ALDOA or KAT5 overexpression in the same time of ZNF692 knockdown, compared to ZNF692 knockdown only, stimulated glycolysis, proliferation, invasion, and migration and reduced apoptosis in HepG2 cells. ZNF692 promotes the acetylation modification and protein expression of ALDOA by catalyzing KAT5 transcription, thereby accelerating glycolysis to drive HCC cell development.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Células Hep G2 , Glicólise , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Frutose-Bifosfato Aldolase/genética , Frutose-Bifosfato Aldolase/metabolismo
3.
J Phys Chem Lett ; 15(13): 3619-3626, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38530255

RESUMO

The light-harvesting (LH) and reaction center (RC) core complex of purple bacterium Roseiflexus castenholzii, B880-B800-RC, are different from those of the typical photosynthetic unit, (B850-B800)x-B880-RC. To investigate the excitation flowing dynamics in this unique complex, two-dimensional electronic spectroscopy is employed. The obtained time constants for the exciton relaxation in B880, exciton relaxation in B800, B800 → B880 energy transfer (EET), and B880 → closed RC EET are 43 fs, 177 fs, 1.9 ps, and 205 ps, respectively. These time constants result in an overall EET efficiency similar to that of the typical photosynthetic unit. Analysis of the oscillatory signals reveals that while several vibronic coherences are involved in the exciton relaxation process, only one prominent vibronic coherence, with a frequency of 27 cm-1 and coupled to the B880 electronic transition, may contribute to the B800 → B880 EET process.

4.
Proc Natl Acad Sci U S A ; 121(7): e2315476121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38319970

RESUMO

Marine photosynthetic dinoflagellates are a group of successful phytoplankton that can form red tides in the ocean and also symbiosis with corals. These features are closely related to the photosynthetic properties of dinoflagellates. We report here three structures of photosystem I (PSI)-chlorophylls (Chls) a/c-peridinin protein complex (PSI-AcpPCI) from two species of dinoflagellates by single-particle cryoelectron microscopy. The crucial PsaA/B subunits of a red tidal dinoflagellate Amphidinium carterae are remarkably smaller and hence losing over 20 pigment-binding sites, whereas its PsaD/F/I/J/L/M/R subunits are larger and coordinate some additional pigment sites compared to other eukaryotic photosynthetic organisms, which may compensate for the smaller PsaA/B subunits. Similar modifications are observed in a coral symbiotic dinoflagellate Symbiodinium species, where two additional core proteins and fewer AcpPCIs are identified in the PSI-AcpPCI supercomplex. The antenna proteins AcpPCIs in dinoflagellates developed some loops and pigment sites as a result to accommodate the changed PSI core, therefore the structures of PSI-AcpPCI supercomplex of dinoflagellates reveal an unusual protein assembly pattern. A huge pigment network comprising Chls a and c and various carotenoids is revealed from the structural analysis, which provides the basis for our deeper understanding of the energy transfer and dissipation within the PSI-AcpPCI supercomplex, as well as the evolution of photosynthetic organisms.


Assuntos
Antozoários , Dinoflagellida , Animais , Antozoários/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo , Dinoflagellida/metabolismo , Proliferação Nociva de Algas , Simbiose , Microscopia Crioeletrônica , Complexo de Proteína do Fotossistema I/metabolismo , Clorofila/metabolismo
5.
J Integr Plant Biol ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411333

RESUMO

Halorhodospira (Hlr.) halochloris is a triply extremophilic phototrophic purple sulfur bacterium, as it is thermophilic, alkaliphilic, and extremely halophilic. The light-harvesting-reaction center (LH1-RC) core complex of this bacterium displays an LH1-Qy transition at 1,016 nm, which is the lowest-energy wavelength absorption among all known phototrophs. Here we report the cryo-EM structure of the LH1-RC at 2.42 Å resolution. The LH1 complex forms a tricyclic ring structure composed of 16 αßγ-polypeptides and one αß-heterodimer around the RC. From the cryo-EM density map, two previously unrecognized integral membrane proteins, referred to as protein G and protein Q, were identified. Both of these proteins are single transmembrane-spanning helices located between the LH1 ring and the RC L-subunit and are absent from the LH1-RC complexes of all other purple bacteria of which the structures have been determined so far. Besides bacteriochlorophyll b molecules (B1020) located on the periplasmic side of the Hlr. halochloris membrane, there are also two arrays of bacteriochlorophyll b molecules (B800 and B820) located on the cytoplasmic side. Only a single copy of a carotenoid (lycopene) was resolved in the Hlr. halochloris LH1-α3ß3 and this was positioned within the complex. The potential quinone channel should be the space between the LH1-α3ß3 that accommodates the single lycopene but does not contain a γ-polypeptide, B800 and B820. Our results provide a structural explanation for the unusual Qy red shift and carotenoid absorption in the Hlr. halochloris spectrum and reveal new insights into photosynthetic mechanisms employed by a species that thrives under the harshest conditions of any phototrophic microorganism known.

6.
Phys Rev Lett ; 132(3): 035002, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38307082

RESUMO

We present the generation of x-ray pulses with average pulse energies up to one millijoule and rms pulse durations down to the femtosecond level. We have produced these intense and short pulses by employing the fresh-slice multistage amplification scheme with a transversely tilted electron beam in a free-electron laser. In this scheme, a short pulse is produced in the first stage and later amplified by fresh parts of the electron bunch in up to a total of four stages of amplification. Our implementation is efficient, since practically the full electron beam contributes to produce the x-ray pulse. Our implementation is also compact, utilizing only 32 m of undulator. The demonstration was done at Athos, the soft x-ray beamline of SwissFEL, which was designed with high flexibility to take full advantage of the multistage amplification scheme. It opens the door for scientific opportunities following ultrafast dynamics using nonlinear x-ray spectroscopy techniques or avoiding electronic damage when capturing structures with a single intense pulse via single-particle imaging.

7.
Bioresour Technol ; 394: 130178, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072080

RESUMO

In this study, an anaerobic/intermittently-aerated moving bed biofilm reactor (AnIA-MBBR) was proposed to realize simultaneous nitrification and endogenous denitrifying phosphorus removal (SNEDPR) in treating low carbon-to-nitrogen (C/N) ratio wastewater. The effect of different intermittent aeration modes (short and long aeration) on nutrients' removal was investigated. With the C/N ratio around 3, the removal efficiencies of total nitrogen and phosphorus were 90% and 74%, 88% and 59%, respectively, for short aeration and long aeration. The different aeration time also altered the nutrients' degradation pathway, biofilm characteristics, microbial community, and functional metabolic pathways. The results confirmed the occurrence of aerobic denitrifiers, anoxic denitrifiers, phosphorus accumulating organisms, glycogen accumulating organisms in AnIA-MBBR systems and their synergistic performance induced the SNEDPR. These results indicated that the application of AnIA in MBBR systems was an effective strategy to achieve SNEDPR, providing better simultaneous removal performance of nitrogen and phosphorus from low C/N ratio wastewater.


Assuntos
Nitrificação , Purificação da Água , Águas Residuárias , Desnitrificação , Eliminação de Resíduos Líquidos/métodos , Esgotos , Fósforo/metabolismo , Nitrogênio/metabolismo , Carbono/metabolismo , Biofilmes , Anaerobiose , Reatores Biológicos
8.
Diabetes Metab Res Rev ; 40(1): e3706, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37545385

RESUMO

OBJECTIVE: To explore the difference in temperature recovery following cold stimulation between participants with and without diabetes mellitus (DM). MATERIALS AND METHODS: The participants without (control group; n = 25) and with (DM group; n = 26) DM were subjected to local cold stimulation (10º C for 90 s). The thermal images of their hands were continuously captured using a thermal camera within 7 min following cold stimulation, and the highest temperature of each fingertip was calculated. According to the temperature values at different timepoints, the temperature recovery curves were drawn, and the baseline temperature (T-base), initial temperature after cooling (T0), temperature decline amplitude (T-range), and area under the temperature recovery curve > T0 (S) were calculated. Finally, symmetry differences between the two groups were analysed. RESULTS: No statistical differences in the T-base, T0, and T-range were observed between the DM and control groups. After drawing the rewarming curve according to the temperature of the fingertips of the patients following cold stimulation, the S in the DM group was significantly lower than that in the control group (p < 0.05). Furthermore, the asymmetry of the base temperature of the hand was observed in the DM group. CONCLUSIONS: Following cold stimulation, the patients with DM exhibited a different rewarming pattern than those without DM. Thus, cold stimulation tests under infrared thermography may contribute to the early screening of diabetic peripheral neuropathy in future.


Assuntos
Diabetes Mellitus , Termografia , Humanos , Temperatura , Termografia/métodos , Temperatura Baixa , Reaquecimento , Temperatura Cutânea
9.
Am J Obstet Gynecol ; 230(2): 254.e1-254.e13, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37531989

RESUMO

BACKGROUND: Hyperglycemia from pregestational diabetes mellitus induces neural tube defects in the developing fetus. Folate supplementation is the only effective way to prevent neural tube defects; however, some cases of neural tube defects are resistant to folate. Excess folate has been linked to higher maternal cancer risk and infant allergy. Therefore, additional interventions are needed. Understanding the mechanisms underlying maternal diabetes mellitus-induced neural tube defects can identify potential targets for preventing such defects. Despite not yet being in clinical use, growing evidence suggests that microRNAs are important intermediates in embryonic development and can serve as both biomarkers and drug targets for disease intervention. Our previous studies showed that maternal diabetes mellitus in vivo activates the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in the developing embryo and that a high glucose condition in vitro reduces microRNA-322 (miR-322) levels. IRE1α is an RNA endonuclease; however, it is unknown whether IRE1α targets and degrades miR-322 specifically or whether miR-322 degradation leads to neural tube defects via apoptosis. We hypothesize that IRE1α can inhibit miR-322 in maternal diabetes mellitus-induced neural tube defects and that restoring miR-322 expression in developing neuroepithelium ameliorates neural tube defects. OBJECTIVE: This study aimed to identify potential targets for preventing maternal diabetes mellitus-induced neural tube defects and to investigate the roles and relationship of a microRNA and an RNA endonuclease in mouse embryos exposed to maternal diabetes mellitus. STUDY DESIGN: To determine whether miR-322 reduction is necessary for neural tube defect formation in pregnancies complicated by diabetes mellitus, male mice carrying a transgene expressing miR-322 were mated with nondiabetic or diabetic wide-type female mice to generate embryos with or without miR-322 overexpression. At embryonic day 8.5 when the neural tube is not yet closed, embryos were harvested for the assessment of 3 miR-322 transcripts (primary, precursor, and mature miR-322), tumor necrosis factor receptor-associated factor 3 (TRAF3), and neuroepithelium cell survival. Neural tube defect incidences were determined in embryonic day 10.5 embryos when the neural tube should be closed if there is no neural tube defect formation. To identify which miR-322 transcript is affected by maternal diabetes mellitus and high glucose conditions, 3 miR-322 transcripts were assessed in embryos from dams with or without diabetes mellitus and in C17.2 mouse neural stem cells treated with different concentrations of glucose and at different time points. To determine whether the endonuclease IRE1α targets miR-322, small interfering RNA knockdown of IRE1α or overexpression of inositol-requiring transmembrane kinase/endoribonuclease 1α by DNA plasmid transfection was used to determine the effect of IRE1α deficiency or overexpression on miR-322 expression. RNA immunoprecipitation was performed to reveal the direct targets of inositol-requiring transmembrane kinase/endoribonuclease 1α. RESULTS: Maternal diabetes mellitus suppressed miR-322 expression in the developing neuroepithelium. Restoring miR-322 expression in the neuroepithelium blocked maternal diabetes mellitus-induced caspase-3 and caspase-8 cleavage and cell apoptosis, leading to a neural tube defect reduction. Reversal of maternal diabetes mellitus-inhibited miR-322 via transgenic overexpression prevented TRAF3 up-regulation in embryos exposed to maternal diabetes mellitus. Activated IRE1α acted as an endonuclease and degraded precursor miR-322, resulting in mature miR-322 reduction. CONCLUSION: This study supports the crucial role of the IRE1α-microRNA-TRAF3 circuit in the induction of neuroepithelial cell apoptosis and neural tube defect formation in pregnancies complicated by diabetes mellitus and identifies IRE1α and miR-322 as potential targets for preventing maternal diabetes mellitus-induced neural tube defects.


Assuntos
Diabetes Mellitus Experimental , Diabetes Gestacional , MicroRNAs , Defeitos do Tubo Neural , Gravidez em Diabéticas , Humanos , Gravidez , Masculino , Feminino , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Endorribonucleases/genética , Endorribonucleases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/patologia , Gravidez em Diabéticas/genética , Gravidez em Diabéticas/metabolismo , Diabetes Gestacional/genética , Glucose , Ácido Fólico , Inositol
10.
Biomed Opt Express ; 14(11): 5904-5920, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38021129

RESUMO

Medical image segmentation is a crucial step in developing medical systems, especially for assisting doctors in diagnosing and treating diseases. Currently, UNet has become the preferred network for most medical image segmentation tasks and has achieved tremendous success. However, due to the limitations of convolutional operation mechanisms, its ability to model long-range dependencies between features is limited. With the success of transformers in the computer vision (CV) field, many excellent models that combine transformers with UNet have emerged, but most of them have fixed receptive fields and a single feature extraction method. To address this issue, we propose a transformer-CNN interactive (TCI) feature extraction module and use it to construct TCI-UNet. Specifically, we improve the self-attention mechanism in transformers to enhance the guiding ability of attention maps for computational resource allocation. It can strengthen the network's ability to capture global contextual information from feature maps. Additionally, we introduce local multi-scale information to supplement feature information, allowing the network to focus on important local information while modeling global contextual information. This improves the network's capability to extract feature map information and facilitates effective interaction between global and local information within the transformer, enhancing the representational power of transformers. We conducted a large number of experiments on the LiTS-2017 and ISIC-2018 datasets to verify the effectiveness of our proposed method, with DCIE values of 93.81% and 88.22%, respectively. Through ablation experiments, we proved the effectiveness of the TCI module, and in comparison with other state-of-the-art (SOTA) networks, we demonstrated the superiority of TCI-UNet in accuracy and generalization.

11.
Nat Commun ; 14(1): 5069, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37604879

RESUMO

X-ray free-electron lasers (FELs) are state-of-the-art scientific tools capable to study matter on the scale of atomic processes. Since the initial operation of X-ray FELs more than a decade ago, several facilities with upgraded performance have been put in operation. Here we present the first lasing results of Athos, the soft X-ray FEL beamline of SwissFEL at the Paul Scherrer Institute in Switzerland. Athos features an undulator layout based on short APPLE-X modules providing full polarisation control, interleaved with small magnetic chicanes. This versatile configuration allows for many operational modes, giving control over many FEL properties. We show, for example, a 35% reduction of the required undulator length to achieve FEL saturation with respect to standard undulator configurations. We also demonstrate the generation of more powerful pulses than the ones obtained in typical undulators. Athos represents a fundamental step forward in the design of FEL facilities, creating opportunities in FEL-based sciences.

12.
J Biol Chem ; 299(8): 105057, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37468106

RESUMO

In wild-type phototrophic organisms, carotenoids (Crts) are primarily packed into specific pigment-protein complexes along with (Bacterio)chlorophylls and play important roles in the photosynthesis. Diphenylamine (DPA) inhibits carotenogenesis but not phototrophic growth of anoxygenic phototrophs and eliminates virtually all Crts from photocomplexes. To investigate the effect of Crts on assembly of the reaction center-light-harvesting (RC-LH) complex from the filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii, we generated carotenoidless (Crt-less) RC-LH complexes by growing cells in the presence of DPA. Here, we present cryo-EM structures of the Rfl. castenholzii native and Crt-less RC-LH complexes with resolutions of 2.86 Å and 2.85 Å, respectively. From the high-quality map obtained, several important but previously unresolved details in the Rfl. castenholzii RC-LH structure were determined unambiguously including the assignment and likely function of three small polypeptides, and the content and spatial arrangement of Crts with bacteriochlorophyll molecules. The overall structures of Crt-containing and Crt-less complexes are similar. However, structural comparisons showed that only five Crts remain in complexes from DPA-treated cells and that the subunit X (TMx) flanked on the N-terminal helix of the Cyt-subunit is missing. Based on these results, the function of Crts in the assembly of the Rfl. castenholzii RC-LH complex and the molecular mechanism of quinone exchange is discussed. These structural details provide a fresh look at the photosynthetic apparatus of an evolutionary ancient phototroph as well as new insights into the importance of Crts for proper assembly and functioning of the RC-LH complex.


Assuntos
Proteínas de Bactérias , Chloroflexi , Fotossíntese , Proteínas de Bactérias/metabolismo , Carotenoides/metabolismo , Chloroflexi/metabolismo , Complexos de Proteínas Captadores de Luz/química
13.
Biomed Opt Express ; 14(4): 1428-1444, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37078042

RESUMO

Convolutional neural networks have been increasingly employed in the field of medical image segmentation. Based on the idea that the human visual cortex differs in terms of the size of the receptive field and can sense the stimulus location, we propose the pyramid channel coordinate attention (PCCA) module to fuse multiscale features in the channel direction, aggregate local and global channel information, combine them with the location information in the spatial direction, and then integrate them into the existing semantic segmentation network. We conducted numerous experiments on the datasets, namely LiTS, ISIC-2018, and CX, and obtained state-of-the-art results.

14.
Minerva Pediatr (Torino) ; 75(2): 171-175, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27827526

RESUMO

BACKGROUND: The objective of the present study was to investigate the effect of pediatric ultrasound guided brachial plexus block anesthesia and to determine the optimal anesthetic drug dosage. METHODS: Ninety-seven children who required elective upper limb surgery were randomly divided into three groups: group A with 32 cases, group B with 35 cases and group C with 30 cases. All three groups of patients underwent ultrasound guided brachial plexus block anesthesia. To compare differences of anesthetic effect, group A received 0.30% ropivacaine, group B received 0.40% ropivacaine, and group C received 0.50% ropivacaine. RESULTS: The total volume was 24 mL in each group. The onset time of ulnar nerve block in Group A was significantly longer than in Group B and Group C (P<0.05); there were no significant differences in onset time of nerve block of the other nerves among the three groups (P>0.05). Block maintenance time in Group A was significantly less than in Group B and Group C (P<0.05). The effective rate of anesthesia of Group A was lower than in Group B and Group C and the differences were statistically significant (P<0.05). There was no significant difference in the incidence of anesthetic complications among the three groups (P>0.05). CONCLUSIONS: Pediatric ultrasound guided brachial plexus block anesthesia is safe and reliable. Ropivacaine used at 0.40% is the optimal lower-concentration anesthetic dosage.


Assuntos
Bloqueio do Plexo Braquial , Criança , Humanos , Ropivacaina , Anestésicos Locais , Ultrassonografia , Ultrassonografia de Intervenção
15.
Infect Drug Resist ; 15: 6343-6355, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337930

RESUMO

Purpose: Early diagnosis of refractory Mycoplasma pneumoniae pneumonia (RMPP) is challenging because of the lack of practical diagnostic imaging tools. Lung ultrasound (LUS) is an emerging tool for diagnosing childhood pneumonia. Hence, we evaluated the role of a nomogram combining LUS findings, clinical features, and laboratory indices in the early prediction of RMPP in children. Patients and Methods: We retrospectively analyzed 225 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to our hospital between Dec 2018 and Aug 2021. Logistic regression analysis incorporated LUS findings and clinical predictors into the nomogram. Ninety patients hospitalized from Sep 2021 to Dec 2021 were used for external validation of the prediction model. Receiver operating characteristics (ROC) and calibration curves were used to evaluate the performance of the nomogram in the early diagnosis of RMPP. Results: Ultimately, Consolidation size /BSA (odds ratio (OR) 1.015, 95% confidence interval (CI) 1.536-2.446), Pleural Effusion (OR 3.551, 95% CI 1.921-15.600), LDH (OR 1.044, 95% CI 1.006-1. 021) and CRP (OR 3.293, 95% CI 1.019-1.098) were independent risk factors for the development of RMPP. The prediction model was represented visually as a nomogram. The area under the ROC curve for the predictive nomogram was 0.955 (95% CI 0.919-0.978) in the training cohort and 0.916 (95% CI 0.838-0.964) in the validation cohort. The calibration curve is close to the diagonal. Conclusion: This is the first-time lung ultrasound was added to the predicted nomogram, which can more comprehensively assess the condition and more accurately predict the occurrence of RMPP early. Therefore, this nomogram can be widely used in the early diagnosis of RMPP, especially in primary care hospitals.

16.
Commun Biol ; 5(1): 1039, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180527

RESUMO

SARS-CoV-2 infection causes COVID-19, a severe acute respiratory disease associated with cardiovascular complications including long-term outcomes. The presence of virus in cardiac tissue of patients with COVID-19 suggests this is a direct, rather than secondary, effect of infection. Here, by expressing individual SARS-CoV-2 proteins in the Drosophila heart, we demonstrate interaction of virus Nsp6 with host proteins of the MGA/MAX complex (MGA, PCGF6 and TFDP1). Complementing transcriptomic data from the fly heart reveal that this interaction blocks the antagonistic MGA/MAX complex, which shifts the balance towards MYC/MAX and activates glycolysis-with similar findings in mouse cardiomyocytes. Further, the Nsp6-induced glycolysis disrupts cardiac mitochondrial function, known to increase reactive oxygen species (ROS) in heart failure; this could explain COVID-19-associated cardiac pathology. Inhibiting the glycolysis pathway by 2-deoxy-D-glucose (2DG) treatment attenuates the Nsp6-induced cardiac phenotype in flies and mice. These findings point to glycolysis as a potential pharmacological target for treating COVID-19-associated heart failure.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , COVID-19 , Proteínas de Drosophila/metabolismo , Insuficiência Cardíaca , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Desoxiglucose/metabolismo , Drosophila/metabolismo , Glicólise , Insuficiência Cardíaca/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , SARS-CoV-2
17.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(4): 721-729, 2022 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-36008336

RESUMO

[Abstract]Automatic and accurate segmentation of lung parenchyma is essential for assisted diagnosis of lung cancer. In recent years, researchers in the field of deep learning have proposed a number of improved lung parenchyma segmentation methods based on U-Net. However, the existing segmentation methods ignore the complementary fusion of semantic information in the feature map between different layers and fail to distinguish the importance of different spaces and channels in the feature map. To solve this problem, this paper proposes the double scale parallel attention (DSPA) network (DSPA-Net) architecture, and introduces the DSPA module and the atrous spatial pyramid pooling (ASPP) module in the "encoder-decoder" structure. Among them, the DSPA module aggregates the semantic information of feature maps of different levels while obtaining accurate space and channel information of feature map with the help of cooperative attention (CA). The ASPP module uses multiple parallel convolution kernels with different void rates to obtain feature maps containing multi-scale information under different receptive fields. The two modules address multi-scale information processing in feature maps of different levels and in feature maps of the same level, respectively. We conducted experimental verification on the Kaggle competition dataset. The experimental results prove that the network architecture has obvious advantages compared with the current mainstream segmentation network. The values of dice similarity coefficient (DSC) and intersection on union (IoU) reached 0.972 ± 0.002 and 0.945 ± 0.004, respectively. This paper achieves automatic and accurate segmentation of lung parenchyma and provides a reference for the application of attentional mechanisms and multi-scale information in the field of lung parenchyma segmentation.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
18.
Comput Biol Med ; 148: 105942, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35964466

RESUMO

Automatic segmentation of skin lesions is beneficial for improving the accuracy and efficiency of melanoma diagnosis. However, due to variation in the size and shape of the lesion areas and the low contrast between the edges of the lesion and the normal skin tissue, this task is very challenging. The traditional convolutional neural network based on codec structure lacks the capability of multi-scale context information modeling and cannot realize information interaction of skip connections at the various levels, which limits the segmentation performance. Therefore, a new codec structure of skin lesion Transformer network (SLT-Net) was proposed and applied to skin lesion segmentation in this study. Specifically, SLT-Net used CSwinUnet as the codec to model the long-distance dependence between features and used the multi-scale context Transformer (MCT) as the skip connection to realize information interaction between skip connections across levels in the channel dimension. We have performed extensive experiments to verify the effectiveness and superiority of our proposed method on three public skin lesion datasets, including the ISIC-2016, ISIC-2017, and ISIC-2018. The DSC values on the three data sets reached 90.45%, 79.87% and 82.85% respectively, higher than most of the state-of-the-art methods. The excellent performance of SLT-Net on these three datasets proved that it could improve the accuracy of skin lesion segmentation, providing a new benchmark reference for skin lesion segmentation tasks. The code is available at https://github.com/FengKaili-fkl/SLT-Net.git.


Assuntos
Melanoma , Dermatopatias , Dermoscopia , Humanos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação
19.
Front Endocrinol (Lausanne) ; 13: 875678, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957840

RESUMO

Background: Identification of the high risk population for osteoporosis and timely prevention are the best strategies at present. Detailed epidemiological investigation in a well-defined population is necessary to explore the population-based characteristics and risk factors of osteoporosis, thus to facilitate better prevention programs. Method: In this prospective cross-sectional study, 1423 questionnaires were given out to the urban residents (female ≥ 40 years of age, male ≥50 years) who lived in the 27 Elderly-Care Inns interspersed among the seven central urban areas of Beijing. All participants were voluntary and underwent routine physical examination and spine and hip BMD measurements using the DXA instrument. The study protocols were approved by the Medical Ethics Committee of Dongzhimen Hospital, Beijing University of Chinese Medicine (JDZX2015079). Results: Altogether 1407 participants fulfilled the survey. Among 359 men, the prevalence of osteoporosis, osteopenia, and normal BMD were 18.1%, 56.6%, and 25.3%, respectively; among 1048 women, the corresponding figures were 40.3%, 42.8%, and 16.9%, respectively. After adjustment of age and BMI, both hands grip strength, height loss over 3 cm, serum levels of ß-CTx, PINP, and OST were the independent risk factors for osteoporosis in both men and women; besides, familial Alzheimer's disease history in men; and history of steatohepatitis and fracture, serum levels of PTH and ALT, age of menarche, age of menopause, and duration of menstruation in women were also risk factors of osteoporosis. In both genders, the cost-effective method, which adopted both hands grip strength, height loss over 3 cm, and medical history, indicated a good predictive ability to evaluate the risk of osteoporosis (in men AUC=0.730, 95%CI=0.642~0.817; in women AUC=0.769, 95%CI=0.724~0.813). Conclusions: In the population of elderly Beijing urban residents in Elderly-Care Inns, the prevalence of osteoporosis in women is higher than that in men and increases with aging more rapidly; the prevalence of osteopenia in men is higher than in women. The cost-effective method, including both hands grip strength, height loss over 3 cm, and familial Alzheimer's disease history in men; fracture and steatohepatitis history as well as menstrual history in women is recommended in identifying the high-risk subjects for osteoporosis.


Assuntos
Doença de Alzheimer , Doenças Ósseas Metabólicas , Fígado Gorduroso , Fraturas Ósseas , Osteoporose , Absorciometria de Fóton/métodos , Idoso , Densidade Óssea , Estudos Transversais , Feminino , Fraturas Ósseas/epidemiologia , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Estudos Prospectivos , Inquéritos e Questionários , População Urbana
20.
Front Mol Neurosci ; 15: 843897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845609

RESUMO

Background: Epilepsy is a chronic brain disease that recurs during childhood, and more than half of adult epilepsy originates from childhood. Studies suggested that immunoglobulin G (IgG) glycosylation are closely related to neurological diseases. Here we analyzed the characteristics of the immunoglobulin glycosylation profile of children with epilepsy. Methods: Patients were recruited in Taian, Shandong Province from December 2019 to March 2020. Serum IgG glycome composition was analyzed by hydrophilic interaction liquid chromatography with ultra-high-performance liquid chromatography approach. Results: The proportion of fucosylated glycans in total IgG glycans was 93.72% in the epilepsy patients, which was significantly lower than that in the control group (94.94%). A lower level of total monogalactosylated and digalactosylated glycans were observed in the epilepsy patients group (30.76 and 40.14%) than that in the controls (36.17 and 42.69%). There was no significant difference between the two groups in bisected GlcNAc glycans and sialylated glycans. Conclusion: The decrease of core fucosylation and galactosylation may promote the inflammatory reaction of the body and participate in the occurrence of epilepsy in children.

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