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1.
Nature ; 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39443804

RESUMO

Capture of CO2 from the air offers a promising approach to addressing climate change and achieving carbon neutrality goals1,2. However, the development of a durable material with high capacity, fast kinetics and low regeneration temperature for CO2 capture, especially from the intricate and dynamic atmosphere, is still lacking. Here a porous, crystalline covalent organic framework (COF) with olefin linkages has been synthesized, structurally characterized and post-synthetically modified by the covalent attachment of amine initiators for producing polyamines within the pores. This COF (termed COF-999) can capture CO2 from open air. COF-999 has a capacity of 0.96 mmol g-1 under dry conditions and 2.05 mmol g-1 under 50% relative humidity, both from 400 ppm CO2. This COF was tested for more than 100 adsorption-desorption cycles in the open air of Berkeley, California, and found to fully retain its performance. COF-999 is an exceptional material for the capture of CO2 from open air as evidenced by its cycling stability, facile uptake of CO2 (reaches half capacity in 18.8 min) and low regeneration temperature (60 °C).

2.
Nature ; 619(7970): 563-571, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37407812

RESUMO

Whereas progress has been made in the identification of neural signals related to rapid, cued decisions1-3, less is known about how brains guide and terminate more ethologically relevant decisions in which an animal's own behaviour governs the options experienced over minutes4-6. Drosophila search for many seconds to minutes for egg-laying sites with high relative value7,8 and have neurons, called oviDNs, whose activity fulfills necessity and sufficiency criteria for initiating the egg-deposition motor programme9. Here we show that oviDNs express a calcium signal that (1) dips when an egg is internally prepared (ovulated), (2) drifts up and down over seconds to minutes-in a manner influenced by the relative value of substrates-as a fly determines whether to lay an egg and (3) reaches a consistent peak level just before the abdomen bend for egg deposition. This signal is apparent in the cell bodies of oviDNs in the brain and it probably reflects a behaviourally relevant rise-to-threshold process in the ventral nerve cord, where the synaptic terminals of oviDNs are located and where their output can influence behaviour. We provide perturbational evidence that the egg-deposition motor programme is initiated once this process hits a threshold and that subthreshold variation in this process regulates the time spent considering options and, ultimately, the choice taken. Finally, we identify a small recurrent circuit that feeds into oviDNs and show that activity in each of its constituent cell types is required for laying an egg. These results argue that a rise-to-threshold process regulates a relative-value, self-paced decision and provide initial insight into the underlying circuit mechanism for building this process.


Assuntos
Tomada de Decisões , Drosophila melanogaster , Oviposição , Animais , Feminino , Sinalização do Cálcio , Tomada de Decisões/fisiologia , Drosophila melanogaster/anatomia & histologia , Drosophila melanogaster/fisiologia , Vias Neurais , Neurônios/metabolismo , Oviposição/fisiologia , Terminações Pré-Sinápticas/metabolismo , Desempenho Psicomotor
3.
Nature ; 589(7843): 577-581, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33239786

RESUMO

Choosing a mate is one of the most consequential decisions a female will make during her lifetime. A female fly signals her willingness to mate by opening her vaginal plates, allowing a courting male to copulate1,2. Vaginal plate opening (VPO) occurs in response to the male courtship song and is dependent on the mating status of the female. How these exteroceptive (song) and interoceptive (mating status) inputs are integrated to regulate VPO remains unknown. Here we characterize the neural circuitry that implements mating decisions in the brain of female Drosophila melanogaster. We show that VPO is controlled by a pair of female-specific descending neurons (vpoDNs). The vpoDNs receive excitatory input from auditory neurons (vpoENs), which are tuned to specific features of the D. melanogaster song, and from pC1 neurons, which encode the mating status of the female3,4. The song responses of vpoDNs, but not vpoENs, are attenuated upon mating, accounting for the reduced receptivity of mated females. This modulation is mediated by pC1 neurons. The vpoDNs thus directly integrate the external and internal signals that control the mating decisions of Drosophila females.


Assuntos
Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Preferência de Acasalamento Animal , Vias Neurais/citologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Animais , Vias Auditivas , Copulação , Corte , Feminino , Masculino , Optogenética , Vocalização Animal
4.
Nature ; 579(7797): 101-105, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32103180

RESUMO

Mating and egg laying are tightly cooordinated events in the reproductive life of all oviparous females. Oviposition is typically rare in virgin females but is initiated after copulation. Here we identify the neural circuitry that links egg laying to mating status in Drosophila melanogaster. Activation of female-specific oviposition descending neurons (oviDNs) is necessary and sufficient for egg laying, and is equally potent in virgin and mated females. After mating, sex peptide-a protein from the male seminal fluid-triggers many behavioural and physiological changes in the female, including the onset of egg laying1. Sex peptide is detected by sensory neurons in the uterus2-4, and silences these neurons and their postsynaptic ascending neurons in the abdominal ganglion5. We show that these abdominal ganglion neurons directly activate the female-specific pC1 neurons. GABAergic (γ-aminobutyric-acid-releasing) oviposition inhibitory neurons (oviINs) mediate feed-forward inhibition from pC1 neurons to both oviDNs and their major excitatory input, the oviposition excitatory neurons (oviENs). By attenuating the abdominal ganglion inputs to pC1 neurons and oviINs, sex peptide disinhibits oviDNs to enable egg laying after mating. This circuitry thus coordinates the two key events in female reproduction: mating and egg laying.


Assuntos
Copulação/fisiologia , Drosophila melanogaster/fisiologia , Vias Neurais/fisiologia , Oviposição/fisiologia , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Feminino , Gânglios Simpáticos/citologia , Masculino , Peptídeos/metabolismo , Células Receptoras Sensoriais/metabolismo , Abstinência Sexual/fisiologia
5.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38741271

RESUMO

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.


Assuntos
Infartos do Tronco Encefálico , Cerebelo , Imageamento por Ressonância Magnética , Vias Neurais , Ponte , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Ponte/diagnóstico por imagem , Ponte/fisiopatologia , Infartos do Tronco Encefálico/fisiopatologia , Infartos do Tronco Encefálico/diagnóstico por imagem , Idoso , Adulto , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem
6.
J Am Chem Soc ; 146(1): 89-94, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38109262

RESUMO

The synthesis of crystalline polyphenylene covalent organic frameworks (COFs) was accomplished by linking fluorinated tris(4-acetylphenyl)benzene building units using aldol cyclotrimerization. The structures of the two COFs, reported here, were confirmed by powder X-ray diffraction techniques, Fourier transform infrared, and solid-state 13C CP/MAS NMR spectroscopy. The results showed that the COFs were porous and chemically stable in corrosive, harsh environments for at least 1 week. Accordingly, postsynthetically modified derivatives of these COFs using primary amines showed CO2 uptake from air and flue gas.

7.
J Am Chem Soc ; 146(4): 2835-2844, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38236722

RESUMO

We have developed two series of amine-functionalized zirconium (Zr) metal-organic framework-808 (MOF-808), which were produced by postsynthetic modifications to have either amino acids coordinated to Zr ions (MOF-808-AAs) or polyamines covalently bound to the chloro-functionalized structure (MOF-808-PAs). These MOF variants were comprehensively characterized by liquid-state 1H nuclear magnetic resonance (NMR) measurements and potentiometric acid-base titration to determine the amounts of amines, energy-dispersive X-ray spectroscopy to assess the extent of covalent substitution by polyamines, powder X-ray diffraction analysis to verify the maintenance of the MOF crystallinity and structure after postsynthetic modifications, nitrogen sorption isotherm measurements to confirm retention of the porosity, and water sorption isotherm measurements to find the water uptake in the pores of each member of the series. Evaluation and testing of these compounds in direct air capture (DAC) of CO2 showed improved CO2 capture performance for the functionalized forms, especially under humid conditions: In dry conditions, the l-lysine- and tris(3-aminopropyl)amine-functionalized variants, termed as MOF-808-Lys and MOF-808-TAPA, exhibited the highest CO2 uptakes at 400 ppm, measuring 0.612 and 0.498 mmol g-1, and further capacity enhancement was achieved by introducing 50% relative humidity, resulting in remarkable uptakes of 1.205 and 0.872 mmol g-1 corresponding to 97 and 75% increase compared to the dry uptakes, respectively. The mechanism underlying the enhanced uptake efficiency was revealed by 13C solid-state NMR and temperature-programmed desorption measurements, indicating the formation of bicarbonate species, and therefore a stoichiometry of 1:1 CO2 to each amine site.

8.
Biochem Biophys Res Commun ; 714: 149970, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38663097

RESUMO

Movement dynamics in the nucleus involve various biological processes, including DNA repair, which is crucial for cancer prevention. Changes in the movement of the components of the nucleus indicate the changes in movement dynamics in the nucleus. In Schizosaccharomyces pombe, the inner nuclear membrane protein Bqt4 plays an essential role in attaching telomeres to the nuclear envelope. We observed that the deletion of bqt4+ caused a significant decrease in the mean square displacement (MSD) calculated from the distance between the nucleolar center and spindle pole body (SPB), hereafter referred to as MSD(SPB-Nucleolus). The MSD(SPB-Nucleolus) decrease in bqt4Δ was microtubule-dependent. The Rap1-binding ability loss mutant, bqt4F46A, and nonspecific DNA-binding ability mutants, bqt43E-A, did not exhibit an MSD(SPB-Nucleolus) decrease compared to the WT. Moreover, the bqt43E-Arap1Δ double mutant and 1-262 amino acids truncated mutant bqt4ΔN (263-432), which does not have either Rap1-binding or nonspecific DNA-binding abilities, did not exhibit the MSD(SPB-Nucleolus) decrease to the same extent as bqt4Δ. These results suggest that the unknown function of Bqt4 in the C-terminal domain is essential for the maintenance of the pattern of relative movement between SPB and the nucleolus.


Assuntos
Nucléolo Celular , Proteínas de Ligação a DNA , Proteínas Nucleares , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Corpos Polares do Fuso , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Nucléolo Celular/metabolismo , Corpos Polares do Fuso/metabolismo , Mutação , Microtúbulos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Ligação Proteica
9.
Biochem Biophys Res Commun ; 733: 150724, 2024 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-39332155

RESUMO

3,3'-Diindolylmethane is recognized for its anti-cancer activities in various pathways, though its mechanism remains to be fully elucidated. Previous studies have shown that 3,3'-Diindolylmethane disturbed the localization of Cut11, a nuclear pore complex subunit in Schizosaccharomyces pombe. This study further reveals that in Schizosaccharomyces pombe, 3,3'-Diindolylmethane also disrupts other components of nuclear envelope, causing GFP-NLS leakage, making it evident that 3,3'-Diindolylmethane disrupts the nuclear envelope. 3,3'-Diindolylmethane also disturbs the localization of GFP-ADEL and Ost4, which are endoplasmic reticulum lumen proteins and membrane proteins respectively, suggesting the function of 3,3'-Diindolylmethane on endoplasmic reticulum disturbance. The nuclear envelope repairment, normal nuclear envelope physical properties, and lipid metabolism homeostasis are crucial for cell survival in the presence of 3,3'-Diindolylmethane. These findings provide new insights into the understanding and development of 3,3'-Diindolylmethane as an anti-cancer agent.


Assuntos
Retículo Endoplasmático , Indóis , Membrana Nuclear , Schizosaccharomyces , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/metabolismo , Indóis/farmacologia , Membrana Nuclear/metabolismo , Membrana Nuclear/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética
10.
Biochem Biophys Res Commun ; 736: 150864, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39461006

RESUMO

3,3'-Diindolylmethane (DIM), a compound derived from natural fruits and vegetables, is widely recognized for its anti-cancer activity. However, its action mechanisms remain ambiguous. In this study, to study the molecular mechanism of 3,3'-Diindolylmethane, we identified a novel mutation in the gene of mitochondrial translation elongation factor EF-Ts (tsf1+), a key factor in mitochondrial protein translation, that conferred DIM resistance to Schizosaccharomyces pombe. The tsf1Δ also conferred DIM resistance. Decreased mitochondrial translation was found to be responsible for conferring DIM resistance to Schizosaccharomyces pombe, as the cells gained DIM resistance after treatment with chloramphenicol, a specific mitochondrial translation inhibitor. Notably, tsf1Δ conferred DIM resistance in the absence of either autophagy-related protein, Atg7, or nuclear envelope protein, Lem2, two proteins that have been reported to be required for cell survival in the presence of DIM. Overall, this study revealed novel biological functions of DIM and highlighted its potential as an anti-cancer agent.

11.
Respir Res ; 25(1): 360, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39369191

RESUMO

BACKGROUND: Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. METHODS: This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. RESULTS: Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). CONCLUSION: mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Hospedeiro Imunocomprometido , Unidades de Terapia Intensiva , Metagenômica , Infecções Respiratórias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Idoso , Metagenômica/métodos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Infecções Respiratórias/mortalidade , Líquido da Lavagem Broncoalveolar/microbiologia , Adulto , Estudos Retrospectivos , Índice de Gravidade de Doença , Antibacterianos/uso terapêutico
12.
Mol Pharm ; 21(1): 267-282, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38079527

RESUMO

Messenger ribonucleic acid (mRNA)-based gene therapy has great potential for cancer gene therapy. However, the effectiveness of mRNA in cancer therapy needs to be further improved, and the delivery efficiency and instability of mRNA limit the application of mRNA-based products. Both the delivery efficiency can be elevated by cell-penetrating peptide modification, and the immune response can be enhanced by tumor cell lysate stimulation, representing an advantageous strategy to expand the effectiveness of mRNA gene therapy. Therefore, it is vital to exploit a vector that can deliver high-efficiency mRNA with codelivery of tumor cell lysate to induce specific immune responses. We previously reported that DMP cationic nanoparticles, formed by the self-assembly of DOTAP and mPEG-PCL, can deliver different types of nucleic acids. DMP has been successfully applied in gene therapy research for various tumor types. Here, we encapsulated tumor cell lysates with DMP nanoparticles and then modified them with a fused cell-penetrating peptide (TAT-iRGD) to form an MLSV system. The MLSV system was loaded with encoded Bim mRNA, forming the MLSV/Bim complex. The average size of the synthesized MLSV was 191.4 nm, with a potential of 47.8 mV. The MLSV/mRNA complex promotes mRNA absorption through caveolin-mediated endocytosis, with a transfection rate of up to 68.6% in B16 cells. The MLSV system could also induce the maturation and activation of dendritic cells, obviously promoting the expression of CD80, CD86, and MHC-II both in vitro and in vivo. By loading the encoding Bim mRNA, the MLSV/Bim complex can inhibit cell proliferation and tumor growth, with inhibition rates of up to 87.3% in vitro. Similarly, the MLSV/Bim complex can inhibit tumor growth in vivo, with inhibition rates of up to 78.7% in the B16 subcutaneous tumor model and 63.3% in the B16 pulmonary metastatic tumor model. Our results suggest that the MLSV system is an advanced candidate for mRNA-based immunogene therapy.


Assuntos
Peptídeos Penetradores de Células , Melanoma , Nanopartículas Multifuncionais , Nanopartículas , Humanos , Melanoma/genética , Melanoma/terapia , Transfecção , Terapia Genética , Linhagem Celular Tumoral
13.
J Opt Soc Am A Opt Image Sci Vis ; 41(2): 349-354, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437349

RESUMO

A simple twin-core D-shape photonic crystal fiber sensor based on surface plasmon resonance (SPR) is designed for the measurement of refractive indices (RI). The twin-core D-shape structure enhances the SPR effect, and the M g F 2-Au dual-layer film narrows the linewidth in the loss spectrum, consequently improving both the sensitivity and figure of merit (FOM). The properties of the sensor are analyzed by the finite element method. In the RI range of 1.32-1.42, the maximum wavelength sensitivity, FOM, and resolution are 62,000 nm/RIU, 1281R I U -1, and 1.61×10-6, respectively.

14.
Eur Spine J ; 33(8): 2982-2996, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39007984

RESUMO

OBJECTIVES: To investigate potential of enhancing image quality, maintaining interobserver consensus, and elevating disease diagnostic efficacy through the implementation of deep learning-based reconstruction (DLR) processing in 3.0 T cervical spine fast magnetic resonance imaging (MRI) images, compared with conventional images. METHODS: The 3.0 T cervical spine MRI images of 71 volunteers were categorized into two groups: sagittal T2-weighted short T1 inversion recovery without DLR (Sag T2w-STIR) and with DLR (Sag T2w-STIR-DLR). The assessment covered artifacts, perceptual signal-to-noise ratio, clearness of tissue interfaces, fat suppression, overall image quality, and the delineation of spinal cord, vertebrae, discs, dopamine, and joints. Spanning canal stenosis, neural foraminal stenosis, herniated discs, annular fissures, hypertrophy of the ligamentum flavum or vertebral facet joints, and intervertebral disc degeneration were evaluated by three impartial readers. RESULTS: Sag T2w-STIR-DLR images exhibited markedly superior performance across quality indicators (median = 4 or 5) compared to Sag T2w-STIR sequences (median = 3 or 4) (p < 0.001). No statistically significant differences were observed between the two sequences in terms of diagnosis and grading (p > 0.05). The interobserver agreement for Sag T2w-STIR-DLR images (0.604-0.931) was higher than the other (0.545-0.853), Sag T2w-STIR-DLR (0.747-1.000) demonstrated increased concordance between reader 1 and reader 3 in comparison to Sag T2w-STIR (0.508-1.000). Acquisition time diminished from 364 to 197 s through the DLR scheme. CONCLUSIONS: Our investigation establishes that 3.0 T fast MRI images subjected to DLR processing present heightened image quality, bolstered diagnostic performance, and reduced scanning durations for cervical spine MRI compared with conventional sequences.


Assuntos
Vértebras Cervicais , Aprendizado Profundo , Imageamento por Ressonância Magnética , Espondilose , Humanos , Espondilose/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto , Feminino , Vértebras Cervicais/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Processamento de Imagem Assistida por Computador/métodos
15.
Sensors (Basel) ; 24(19)2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39409284

RESUMO

Terahertz spectroscopy systems, which integrate terahertz sources and detectors, have important applications in many fields such as materials science and security checking. Based on highly sensitive frequency up-conversion detection, large dynamic range spectral measurements in a terahertz region are reported. Our system realized the detection sensitivity at a 10 aJ level with a 2-(3-(4-hydroxystyryl)-5,5-dime-thylcyclohex-2-enylidene) malononitrile (OH1) crystal and a dynamic range up to seven orders. Based on this system, we verified the validity of the spectral measurement with tests which were conducted on monohydrate glucose, anhydrous glucose and mixed tablet samples with a thickness of 0.8 mm in 1~3 THz, respectively. Also, a mini coppery elbow tube with an inner diameter of 1 mm was used for the transmission of a terahertz wave to simulate some strip biological tissue samples. By allowing terahertz to transmit through this tube filled with 0.5 g glucose powder, we successfully obtained the absorption spectrum with a minimum transmittance at the absorption peak in the order of 10-4.

16.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125865

RESUMO

Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-ß-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear. In this study, Gaussian accelerated molecular dynamics (GaMD) simulation was employed to elucidate the inhibitory mechanisms of NDGA and AKBA on 5LOX. It was found that the orthosteric inhibitor NDGA was tightly bound in the protein's active pocket, occupying the active site and inhibiting the catalytic activity of the 5LOX enzyme through competitive inhibition. The binding of the allosteric inhibitor AKBA induced significant changes at the distal active site, leading to a conformational shift of residues 168-173 from a loop to an α-helix and significant negative correlated motions between residues 285-290 and 375-400, reducing the distance between these segments. In the simulation, the volume of the active cavity in the stable conformation of the protein was reduced, hindering the substrate's entry into the active cavity and, thereby, inhibiting protein activity through allosteric effects. Ultimately, Markov state models (MSM) were used to identify and classify the metastable states of proteins, revealing the transition times between different conformational states. In summary, this study provides theoretical insights into the inhibition mechanisms of 5LOX by AKBA and NDGA, offering new perspectives for the development of novel inhibitors specifically targeting 5LOX, with potential implications for anti-inflammatory drug development.


Assuntos
Araquidonato 5-Lipoxigenase , Inibidores de Lipoxigenase , Cadeias de Markov , Simulação de Dinâmica Molecular , Araquidonato 5-Lipoxigenase/metabolismo , Araquidonato 5-Lipoxigenase/química , Inibidores de Lipoxigenase/farmacologia , Inibidores de Lipoxigenase/química , Humanos , Domínio Catalítico , Ligação Proteica , Masoprocol/farmacologia , Masoprocol/química , Conformação Proteica
17.
J Am Chem Soc ; 145(42): 22885-22889, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37844128

RESUMO

Although reticular chemistry has commonly utilized mutually embracing tetrahedral metal complexes as crossing points to generate three-dimensional molecularly woven structures, weaving in two dimensions remains largely unexplored. We report a new strategy to access 2D woven COFs by controlling the angle of the usually linear linker, resulting in the successful synthesis of a 2D woven pattern based on chain-link fence. The synthesis was accomplished by linking aldehyde-functionalized copper(I) bisphenanthroline complexes with bent 4,4'-oxydianiline building units. This results in the formation of a crystalline solid, termed COF-523-Cu, whose structure was characterized by spectroscopic techniques and electron and X-ray diffraction techniques to reveal a molecularly woven, twofold-interpenetrated chain-link fence. The present work significantly advances the concept of molecular weaving and its practice in the design of complex chemical structures.

18.
J Hum Genet ; 68(11): 769-775, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37491516

RESUMO

Acute necrotizing encephalopathy (ANE) is a rare disease that predominantly affects children and is associated with a high mortality rate. Here we report three cases of COVID-19-related ANE in children, with the mutation detection in two genes associated with mitochondrial dysfunction. The cases exhibited common ANE symptoms, such as fever, impaired consciousness, positive pathological reflex, increased cerebrospinal fluid protein, and multifocal and symmetric brain lesions identified through MRI. Using genotype-phenotype correlation analysis in trio-whole exome sequencing (WES), four potential pathogenic variants were identified in two genes associated with mitochondrial function (RANBP2 and MCCC2). Notably, MCCC2 was identified as being potentially associated with COVID-19-related ANE for the first time, and two of the four variants had not been previously reported. Our findings expand the clinical and mutation spectrum of COVID-19-related ANE in pediatric cases. The finding of these three new cases in our study further supports the previous hypothesis about the role of mitochondrial homeostatic imbalance in COVID-19-related ANE. It is essential to use genetic testing to identify this subset of patients with compromised mitochondrial function in order to improve patient management and prognosis.

19.
Opt Express ; 31(23): 38970-38976, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017987

RESUMO

The wide applications of terahertz (THz) wave technology in the ∼1-3 THz range has resulted in a surge in the demand for the performance improvement of THz wave detection technique. In this study, a frequency tunable, highly sensitive frequency upconversion detection based on a 2-(3-(4-hydroxystyryl)-5,5-dime-thylcyclohex-2-enylidene) malononitrile (OH1) crystal at room temperature is demonstrated. Moreover, to effectively increase the signal-to-noise ratio in the low frequency range, a beam isolation enhancer is proposed and its effect is verified. The minimum detectable THz pulse energy reaches about 100 aJ at 1.9 THz. The frequency tuning ranging from 1 to 3 THz. Sensitivity comparison with a 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) crystal system shows that OH1 is a more suitable nonlinear crystal in the 1-2.4 THz range.

20.
BMC Cancer ; 23(1): 858, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700255

RESUMO

BACKGROUND: Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS: Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS: Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS: The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Algoritmos , Curva ROC
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