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1.
ACS Appl Mater Interfaces ; 16(37): 49069-49082, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39236665

RESUMO

Transdermal drug delivery systems are highly appealing as a convenient drug delivery manner applicable to a wide variety of drugs. While most delivery relies on only passive diffusion and suffers low transdermal efficiencies. Ultrasound motivation promotes drug transdermal penetration but still calls for improvement, because only a thin proportion of the ultrasound energy is applied on the drug delivery patch and most ultrasound energy is wasted in deeper portions of biotissues. In this work, we develop a transdermal patch for enhanced drug delivery. The combination of microsized air pockets and the piezoelectric soft structure enable the conversion of an intended proportion of ultrasound energy into electric energy. The intensified drug flow and synergistic ultrasound pressure and electric field function simultaneously to enhance drug transdermal delivery. The delivery efficacy is related to the power of the ultrasound motivation, the size of the microscopic air pockets, and the chemical structure of the drug molecules. The temperature of the patch within the delivery process remains in the safe range, and the mild temperature elevation causes color changes of the thermochromic patch, used to indicate effective ultrasound-patch matching. A model delivery patch for pain release is constructed, and animal experiments indicate that the drug blood concentrations are 100% higher than the delivery using only ultrasound and even more remarkably enhanced when compared to only electric-field-motivated delivery or static delivery without external motivations.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Microbolhas , Animais , Adesivo Transdérmico , Pele/metabolismo , Camundongos , Ondas Ultrassônicas
2.
Life Sci ; 357: 123078, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39332489

RESUMO

BACKGROUND: The role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is multifaceted, paradoxically promoting both cell survival and cell death across multiple organs. However, its impact on lung homeostasis remains elusive. Here, we investigate the function of DNA-PKcs in mouse lungs, aiming to elucidate its role for lung abnormalities associated with DNA-PKcs deficiency. MATERIALS AND METHODS: Histological assessment and immunohistochemistry were used to reveal the pathological changes of the lungs in DNA-PKcs-deficient mice. Transcriptomic analysis identified differentially expressed genes and pathways in DNA-PKcs-deficient lungs. Furthermore, mitochondrial dysfunction induced by DNA-PKcs deficiency was investigated by qPCR and immunoblotting. Mouse primary lung fibroblasts were used to evaluate the potential therapeutic effect of inhibiting mitochondrial fission with Mdivi-1. KEY FINDINGS: In DNA-PKcs-deficient mouse lungs, we observed pathological changes including alveolar septal thickening, capillary congestion and hemorrhage, along with lung cell proliferation. Transcriptome analysis revealed an upregulation of the reactive oxygen species (ROS) biosynthesis process and the apoptotic signaling pathway caused by DNA-PKcs deficiency. Further investigations demonstrated that DNA-PKcs deficiency led to mitochondrial dysfunction and increased oxidative stress, along with increased cell apoptosis in the mouse lungs. Notably, we detected enhanced phosphorylation of the mitochondrial fission protein DRP1 in DNA-PKcs-deficient mouse lungs. Intriguingly, inhibiting mitochondrial fission using Mdivi-1 suppressed cell death in primary mouse lung fibroblasts with siRNA-mediated DNA-PKcs knockdown. SIGNIFICANCE: Our study provides insights into the crucial role of DNA-PKcs in sustaining lung homeostasis via the maintenance of mitochondrial functionality and provides a therapeutic strategy targeting mitochondrial fission against DNA-PKcs deficiency-associated lung diseases.

3.
bioRxiv ; 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39314394

RESUMO

Neurofeedback concurrent with mindfulness meditation may reveal meditation effects on the brain and facilitate improved mental health outcomes. Here, we systematically reviewed EEG and fMRI studies of mindfulness meditation with neurofeedback (mbNF) and followed PRISMA guidelines. We identified 10 fMRI reports, consisting of 177 unique participants, and 9 EEG reports, consisting of 242 participants. Studies of fMRI focused primarily on downregulating the default-mode network (DMN). Although studies found decreases in DMN activations during neurofeedback, there is a lack of evidence for transfer effects, and the majority of studies did not employ adequate controls, e.g. sham neurofeedback. Accordingly, DMN decreases may have been confounded by general task-related deactivation. EEG studies typically examined alpha, gamma, and theta frequency bands, with the most robust evidence supporting the modulation of theta band activity. Both EEG and fMRI mbNF have been implemented with high fidelity in clinical populations. However, the mental health benefits of mbNF have not been established. In general, mbNF studies would benefit from sham-controlled RCTs, as well as clear reporting (e.g. CRED-NF).

4.
Bioorg Chem ; 151: 107675, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39126868

RESUMO

Rho-associated coiled-coil kinase (ROCK) is involved in multiple cellular activities regulating the actin cytoskeleton, such as cell morphology, adhesion, and migration. The inhibition of ROCK is a feasible strategy to suppress breast cancer metastasis. Herein, based on Belumosudil, a series of pyrazolo[1,5-a]pyrimidine derivatives as selective ROCK2 inhibitors were designed and synthesized. Through systematic investigation of SARs, the piperazine analog 7u was identified with optimum ROCK2 inhibitory activity (IC50 = 36.8 nM) and excellent selectivity over the isoform protein ROCK1 (>250-fold). Intriguingly, upon treatment with 7u, the arrangement of the MDA-MB-231 cytoskeleton was affected accompanied by the alteration of morphology. Furthermore, cell scratch and transwell assays indicated that 7u inhibited MDA-MB-231 cell migration and invasion in a dose-dependent manner. Ultimately, the binding model of 7u with ROCK2 well accounted for the superior activities of 7u as a promising ROCK2 inhibitor with the potential application in breast cancer metastasis treatment.


Assuntos
Antineoplásicos , Neoplasias da Mama , Movimento Celular , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases , Pirazóis , Pirimidinas , Quinases Associadas a rho , Humanos , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Movimento Celular/efeitos dos fármacos , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Feminino , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Descoberta de Drogas , Simulação de Acoplamento Molecular
5.
J Colloid Interface Sci ; 678(Pt A): 42-52, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39180847

RESUMO

Photodynamic therapy (PDT) and catalytic therapy were promising treatment modes, but tumor hypoxia and poor catalytic activity severely limited their efficacies. Herein, using a porphyrin metal-organic framework (PCN-224) as nanocarrier, a platinum/palladium (Pt/Pd) dual-modified PCN-224 nanoprobe (PCN-224-Pt@Pd) with strong peroxidase (POD)/catalase (CAT)-like activities was developed, achieving photothermal-promoted PDT/catalytic therapy. Compared with single ultrasmall Pt modifying, CAT-like activity of Pt/Pd dual-modifying increased oxygen concentration from 6.24 to 9.35 mg/L, which improved singlet oxygen (1O2) yield from 63.8 % to 82.9 %. Moreover, POD-like activity of Pt/Pd dual-modifying significantly accelerated hydroxyl radicals (·OH) generation. Importantly, PCN-224-Pt@Pd possessed near-infrared II (NIR-II) photothermal effect with a high efficiency (55.6 %), which further promoted ·OH production. Under combined therapy of PCN-224-Pt@Pd, the cell survival rate greatly reduced to 5.8 %, and the tumors were cured, suggesting NIR-II photothermal-enhanced PDT/catalytic therapy.

6.
Schizophr Res ; 270: 358-365, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38968807

RESUMO

BACKGROUND: Individuals with schizophrenia (SZ) and auditory hallucinations (AHs) display a distorted sense of self and self-other boundaries. Alterations of activity in midline cortical structures such as the prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) during self-reference as well as in the superior temporal gyrus (STG) have been proposed as neuromarkers of SZ and AHs. METHODS: In this randomized, participant-blinded, sham-controlled trial, 22 adults (18 males) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication-resistant AHs received one session of real-time fMRI neurofeedback (NFB) either from the STG (n = 11; experimental group) or motor cortex (n = 11; control group). During NFB, participants were instructed to upregulate their STG activity by attending to pre-recorded sentences spoken in their own voice and downregulate it by ignoring unfamiliar voices. Before and after NFB, participants completed a self-reference task where they evaluated if trait adjectives referred to themselves (self condition), Abraham Lincoln (other condition), or whether adjectives had a positive valence (semantic condition). FMRI activation analyses of self-reference task data tested between-group changes after NFB (self>semantic, post>pre-NFB, experimental>control). Analyses were pre-masked within a self-reference network. RESULTS: Activation analyses revealed significantly (p < 0.001) greater activation increase in the experimental, compared to the control group, after NFB within anterior regions of the self-reference network (mPFC, ACC, superior frontal cortex). CONCLUSIONS: STG-NFB was associated with activity increase in the mPFC, ACC, and superior frontal cortex during self-reference. Modulating the STG is associated with activation changes in other, not-directly targeted, regions subserving higher-level cognitive processes associated with self-referential processes and AHs psychopathology in SZ. CLINICALTRIALS: GOV: Rt-fMRI Neurofeedback and AH in Schizophrenia; https://clinicaltrials.gov/study/NCT03504579.


Assuntos
Alucinações , Imageamento por Ressonância Magnética , Neurorretroalimentação , Esquizofrenia , Lobo Temporal , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Esquizofrenia/terapia , Masculino , Feminino , Adulto , Projetos Piloto , Neurorretroalimentação/métodos , Alucinações/fisiopatologia , Alucinações/diagnóstico por imagem , Alucinações/terapia , Alucinações/etiologia , Lobo Temporal/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Método Simples-Cego , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/terapia , Pessoa de Meia-Idade , Autoimagem , Adulto Jovem
7.
J Orthop Surg (Hong Kong) ; 32(2): 10225536241258336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910029

RESUMO

Background: To observe the activation strategies of the ankle muscles using surface electromyography (sEMG) during single-leg standing (SLS) and both-leg standing (BLS) on flat ground (FG), soft mat (SM), and BOSU ball (BB) surfaces. Methods: Thirty healthy young adults participated in the study. The muscle activities of the tibialis anterior (TA) and gastrocnemius medial (GM) were measured on the three surfaces during SLS and BLS. Electromyographic evaluations of the TA and GM were recorded during maximum voluntary isometric contractions (MVIC). Muscle activation was evaluated using MVIC%, and muscle co-contraction was evaluated using the co-contraction index (CI). Results: A statistically significant increase was observed in the MVIC% of the TA, GM, and CI on the three surfaces during SLS compared to BLS, except for the comparison of CI on BB between SLS and BLS (t = -1.35, p = 0.19). The MVIC% of the TA and GM during SLS and BLS on BB was significantly increased in comparison with FG and SM. The CI during BLS on BB increased compared to FG (t = 3.19, p < 0.01) and SM (t = 4.64, p < 0.01). The CI during BLS on SM (t = -1.46, p = 0.15) decreased when compared to FG but without statistical significance. Conclusions: SLS and unstable surfaces can induce greater muscle activation, and SLS can have a greater influence on ankle muscles.


Assuntos
Eletromiografia , Músculo Esquelético , Posição Ortostática , Humanos , Masculino , Músculo Esquelético/fisiologia , Adulto Jovem , Feminino , Adulto , Articulação do Tornozelo/fisiologia , Contração Isométrica/fisiologia , Tornozelo/fisiologia , Equilíbrio Postural/fisiologia
8.
Nat Commun ; 15(1): 4495, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802410

RESUMO

Unified visual perception requires integration of bottom-up and top-down inputs in the primary visual cortex (V1), yet the organization of top-down inputs in V1 remains unclear. Here, we used optogenetics-assisted circuit mapping to identify how multiple top-down inputs from higher-order cortical and thalamic areas engage V1 excitatory and inhibitory neurons. Top-down inputs overlap in superficial layers yet segregate in deep layers. Inputs from the medial secondary visual cortex (V2M) and anterior cingulate cortex (ACA) converge on L6 Pyrs, whereas ventrolateral orbitofrontal cortex (ORBvl) and lateral posterior thalamic nucleus (LP) inputs are processed in parallel in Pyr-type-specific subnetworks (Pyr←ORBvl and Pyr←LP) and drive mutual inhibition between them via local interneurons. Our study deepens understanding of the top-down modulation mechanisms of visual processing and establishes that V2M and ACA inputs in L6 employ integrated processing distinct from the parallel processing of LP and ORBvl inputs in L5.


Assuntos
Optogenética , Córtex Visual Primário , Animais , Córtex Visual Primário/fisiologia , Masculino , Tálamo/fisiologia , Vias Visuais/fisiologia , Neurônios/fisiologia , Córtex Visual/fisiologia , Giro do Cíngulo/fisiologia , Interneurônios/fisiologia , Percepção Visual/fisiologia , Camundongos , Feminino , Mapeamento Encefálico
9.
Nano Lett ; 24(23): 7055-7062, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38810105

RESUMO

Transparent passive cooling materials can cool targets environmentally without interfering with light transmission or visual information reception. They play a prominent role in solar cells and flexible display cooling. However, achieving potent transparent cooling remains challenging, because light transmission is accompanied by thermal energy. Here we propose to realize effective passive cooling in transparent materials via a microscale phase separation hydrogel film. The poly(N-isopropylacrylamide-co-acrylamide) hydrogel presents light transmittance of >96% and infrared emissivity as high as 95%. The microphase-separated structure affords a higher enthalpy of evaporation. The film is highly adhesive. In field applications, it reduces temperatures by 9.14 °C compared to those with uncovered photovoltaic panels and 7.68 °C compared to those for bare flexible light-emitting diode screens. Simulations indicate that energy savings of 32.76-51.65 MJ m-2 year-1 can be achieved in typical tropical monsoon climates and temperate continental climates. We expect this work to contribute to energy-efficient materials and a carbon-neutral society.

10.
J Neurosci ; 44(26)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38664013

RESUMO

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high-field 7 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals-yet, the present task posed only the most minimal (if any) "threat," with the cognitive tasks used being approximately as challenging as remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.


Assuntos
Imageamento por Ressonância Magnética , Memória de Curto Prazo , Substância Cinzenta Periaquedutal , Humanos , Substância Cinzenta Periaquedutal/fisiologia , Masculino , Feminino , Memória de Curto Prazo/fisiologia , Adulto , Imageamento por Ressonância Magnética/métodos , Adulto Jovem , Mapeamento Encefálico
11.
Heliyon ; 10(4): e24147, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420475

RESUMO

The flammable gas volatilized from the storage medium in the tank will burn and explode under the action of an accidental ignition source. Tank explosions formed by the explosive shock wave, explosive debris will not only cause their own damage, but also on the safe operation of adjacent tanks to form a threat. Therefore, in this paper, the vertical dome roof tank is taken as the research object, the criteria of brittle fracture failure of tank materials are constructed, and the multi-field coupling calculation model of tank detonation based on TNT equivalent method is established, taking into account the fluid properties inside and outside the tank, the structure of implosion tank and adjacent tank. By analyzing the full time domain process of gas detonation in tanks under different influence factors, the response to implosion damage of tanks and adjacent tanks under the action of explosion shock wave overpressure and debris was obtained. With the increase of the liquid level, the overpressure and deformation of the shock wave of the detonation tank and adjacent tank decrease, and the type and number of fragments decrease. With the increase of the volume of the tank, the overpressure and stress of the shock wave become larger, the strain rate of the tank becomes larger, and brittle failure is more likely to occur. The types and number of fragments formed increase, but detonation fragments are not formed when the tank is full. The research results in this paper provide a theoretical basis and calculation method for preventing and controlling tank implosion accidents, as well as tank design and tank spacing layout.

12.
J Colloid Interface Sci ; 658: 301-312, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38109817

RESUMO

Ultrasmall platinum (Pt) nanozymes are used for catalytic therapy and oxygen (O2)-dependent photodynamic therapy (PDT) by harnessing the dual-enzyme activities of catalase (CAT) and peroxidase (POD). However, their applications as nanocatalysts are limited due to their low catalytic activity. Herein, we constructed a photothermal-promoted bimetallic nanoplatform (AuNTP@Pt-IR808) by depositing ultrasmall Pt nano-islands and modifying 1-(5-Carboxypentyl)-2-(2-(3-(2-(1-(5-carboxypentyl)-3,3-dimethylindolin-2-ylidene)ethylidene)-2-chlorocyclohex-1-en-1-yl)vinyl)-3,3-dimethyl-3H-indol-1-ium bromide (IR808) on gold nanotetrapod (AuNTP) with CAT/POD activities to enhance PDT/catalytic therapy. In the tumor microenvironment, the ultrasmall Pt can catalyze endogenous hydrogen peroxide (H2O2) to produce O2, relieving tumor hypoxia and enhancing the PDT performance. Moreover, AuNTP integration into the bimetallic nanoplatform showed good electron transfer properties and promoted the POD activity of ultrasmall Pt. Importantly, AuNTP@Pt-IR808 possessed higher photothermal conversion performance than single AuNTPs, which enhanced photothermal therapy (PTT). It also accelerated the CAT/POD dual-enzyme activities, and promoted the generation of singlet oxygen (1O2) and hydroxyl radical (OH). By enhancing the performances of PTT/PDT/catalytic therapy, the developed AuNTP@Pt-IR808 nanoplatform demonstrated good antitumor efficacy against breast cancer.


Assuntos
Nanopartículas Metálicas , Neoplasias , Fotoquimioterapia , Humanos , Linhagem Celular Tumoral , Ouro/farmacologia , Ouro/uso terapêutico , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico , Oxigênio , Platina/farmacologia , Microambiente Tumoral , Nanopartículas/química
13.
Opt Lett ; 48(22): 5935-5938, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966756

RESUMO

We present the design and fabrication of an on-chip FBG interrogator based on arrayed waveguide grating (AWG) technology. The spectral overlap between adjacent channels in the integrated AWG is significantly enhanced through a combination approach involving the reduction of the output waveguide spacing and an increase in the input waveguide width. As a result of these design choices, our AWG demonstrates excellent spectral consistency, with spectral cross talk exceeding 30 dB. The interrogator seamlessly combining optical and circuitry components achieves full integration and enables a wide range of interrogation wavelengths, including C-band and L-band. With an interrogation range extending up to 80 nm, it theoretically has the capacity to simultaneously interrogate the wavelengths of 20 FBG sensors. Experimental findings demonstrate an absolute interrogation accuracy of less than 2 pm for the fully integrated interrogator. With its compact size, cost-effectiveness, exceptional precision, and ease of integration, the proposed interrogator holds a substantial promise for widespread application in the realm of FBG sensing.

14.
BMC Psychiatry ; 23(1): 757, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848857

RESUMO

BACKGROUND: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. METHODS: Adolescents (N = 90) with a current diagnosis of MDD ages 13-18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. DISCUSSION: Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. TRIAL REGISTRATION: This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495).


Assuntos
Transtorno Depressivo Maior , Atenção Plena , Neurorretroalimentação , Humanos , Adolescente , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Imageamento por Ressonância Magnética/métodos , Neurorretroalimentação/métodos , Giro do Cíngulo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos
15.
Nat Commun ; 14(1): 6658, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37863881

RESUMO

Apiose is a natural pentose containing an unusual branched-chain structure. Apiosides are bioactive natural products widely present in the plant kingdom. However, little is known on the key apiosylation reaction in the biosynthetic pathways of apiosides. In this work, we discover an apiosyltransferase GuApiGT from Glycyrrhiza uralensis. GuApiGT could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, and exhibits strict selectivity towards UDP-apiose. We further solve the crystal structure of GuApiGT, determine a key sugar-binding motif (RLGSDH) through structural analysis and theoretical calculations, and obtain mutants with altered sugar selectivity through protein engineering. Moreover, we discover 121 candidate apiosyltransferase genes from Leguminosae plants, and identify the functions of 4 enzymes. Finally, we introduce GuApiGT and its upstream genes into Nicotiana benthamiana, and complete de novo biosynthesis of a series of flavonoid apiosides. This work reports an efficient phenolic apiosyltransferase, and reveals mechanisms for its sugar donor selectivity.


Assuntos
Fabaceae , Fabaceae/metabolismo , Plantas/metabolismo , Flavonoides/metabolismo , Glicosídeos/metabolismo , Nicotiana/genética , Nicotiana/metabolismo
16.
Nat Commun ; 14(1): 5969, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749089

RESUMO

Acetylation contributes to the bioactivity of numerous medicinally important natural products. However, little is known about the acetylation on sugar moieties. Here we report a saponin acetyltransferase from Astragalus membranaceus. AmAT7-3 is discovered through a stepwise gene mining approach and characterized as the xylose C3'/C4'-O-acetyltransferse of astragaloside IV (1). To elucidate its catalytic mechanism, complex crystal structures of AmAT7-3/1 and AmAT7-3A310G/1 are obtained, which reveal a large active pocket decided by a specific sequence AADAG. Combining with QM/MM computation, the regiospecificity of AmAT7-3 is determined by sugar positioning modulated by surrounding amino acids including #A310 and #L290. Furthermore, a small mutant library is built using semi-rational design, where variants A310G and A310W are found to catalyze specific C3'-O and C4'-O acetylation, respectively. AmAT7-3 and its variants are also employed to acetylate other bioactive saponins. This work expands the understanding of saponin acetyltransferases, and provide efficient catalytic tools for saponin acetylation.


Assuntos
Astragalus propinquus , Saponinas , Acetiltransferases/genética , Engenharia de Proteínas , Xilose
17.
bioRxiv ; 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37546889

RESUMO

The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, a process called allostasis. In support of allostasis, the brain continually models the internal state of the body, a process called interoception. Using published tract-tracing studies in non-human animals as a guide, we previously identified a large-scale system supporting allostasis and interoception in the human brain with functional magnetic resonance imaging (fMRI) at 3 Tesla. In the present study, we replicated and extended this system in humans using 7 Tesla fMRI (N = 91), improving the precision of subgenual and pregenual anterior cingulate topography as well as brainstem nuclei mapping. We verified over 90% of the anatomical connections in the hypothesized allostatic-interoceptive system observed in non-human animal research. We also identified functional connectivity hubs verified in tract-tracing studies but not previously detected using 3 Tesla fMRI. Finally, we demonstrated that individuals with stronger fMRI connectivity between system hubs self-reported greater interoceptive awareness, building on construct validity evidence from our earlier paper. Taken together, these results strengthen evidence for the existence of a whole-brain system supporting interoception in the service of allostasis and we consider the implications for mental and physical health.

18.
Heliyon ; 9(8): e18549, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37554773

RESUMO

When the buried pipeline is subjected to the external explosion load, stress and deformation will occur. When the stress and deformation value exceed a specific range, it will affect the normal use of the buried pipeline. In this paper, a multiphase coupled model of pipeline, soil and fluid within the pipeline is established. The penalty function coupling method is used to describe the load between soil and pipeline and the fluid within the pipeline. By specifying the boundary conditions of the coupled system, the multiphase coupled global solution variational principle function of the soil-pipe-fluid is derived. According to the established multiphase coupled calculation method, the numerical simulation analysis of the response of pipeline to external explosion is carried out. The maximum error of the experimental and numerical simulation results is about 5%, which verifies the accuracy of the multiphase coupled calculation method. The soil-pipeline-fluid multiphase coupled numerical calculation model is established to analyze the response of the buried pipeline under the external explosion load. The results show that during the explosion shock wave propagating in the soil, the peak value of the explosion pressure in different positions in the soil of the gas pipeline is greater than that of the oil pipeline. As for the structural response, the maximum radial displacement value of the oil pipeline is reduced by 3.83 mm compared with the gas pipeline, the maximum stress value is reduced by 3.75%. The maximum radial displacement value of the pipeline with a fluid velocity of 1.5 m/s is 2.65 mm larger than that of the pipeline with a fluid velocity of 1 m/s, and the maximum stress value is increased by 5.72%. The deformation resistance and explosion resistance of the oil pipeline are both stronger than that of the gas pipeline. The higher the fluid velocity, the weaker the pipeline's resistance to deformation and explosion will be.

19.
ACS Appl Mater Interfaces ; 15(31): 37640-37648, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37491709

RESUMO

As a new-generation photoelectric material, perovskites have attracted researchers' attention due to their excellent optoelectronic properties. However, the existence of defects inevitably causes structural degradation and restricts their performance, which need to be further improved by post-treatment. At present, post-treatments mostly focus on non-contact treatments, which may constrain the effect since the influence on the perovskites caused by the direct contact is much more straightly. Therefore, we proposed an annealing strategy of straight manipulation in a solvent atmosphere with the assistance of polyimide (PI) tape for the perovskite post-treatment, due to the high heat resistance and less glue residual of this tape. It casts an influence on the perovskite directly, proving the possibility of the straight manipulation by operators, promoting the recrystallization of the perovskite grains and removing the impurity substance. The optimized Pb-free perovskite film exhibits a better X-ray sensitivity of 7.5 × 104 µC Gyair-1 cm-2 and a great detection limit of 47 nGyair s-1, which is comparable to advanced Pb-based perovskite X-ray detectors and all commercial ones. The new annealing strategy provides a facile, effective, and simple method to improve the perovskite quality, exhibiting the potential and harmlessness of the direct contact post-treatment, which paves the way for a broader application of perovskites.

20.
Sci Rep ; 13(1): 11307, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438450

RESUMO

The hydrological processes play an important role in stimulating fish spawning behavior. Changes in the natural hydrological processes will alter the populations and distribution of fish, which may have a negative impact on the native aquatic organisms. The aim of this study is to identify the alteration of the water rising process during the fish spawning period and to construct an ecological flow optimization model to restore the water rising conditions for fish reproduction. The Mann-Kendall test and the sliding t-test were used to detect the mutation year of the mean daily flow data sets in the fish spawning period in each monitoring year. Then the data sets can be divided into pre-altered and post-altered periods. The water rising process was characterized by the water rising processes count, the duration, the daily flow increase rate, the date of the water rising process, and the initial water rising flow. The changes in hydrological processes in the middle reaches of the Yangtze River were investigated by comparing the post-altered and pre-altered characteristic parameters. Furthermore, we integrated the statistical values of the five characteristic parameters in pre-altered into an ecological flow optimization model to simulate the natural water rising processes for the spawning of the Four Major Chinese Carps (FMCC) and Chinese Sturgeon (CS). The analysis showed that after the hydrological mutation year, the duration and the initial water rising flow in the FMCC spawning season were increased, with hydrological alteration degrees of 63.10% and 70.16%, respectively; however, the daily flow increase rate was significantly decreased, with hydrological alteration of 86.50%. During the CS spawning season, the water rising processes count and the initial water rising flow were dramatically altered parameters, with hydrological alteration degrees of 50.86% and 83.27%, respectively. The former parameter increased, but the latter decreased significantly in the post-altered period. To induce the spawning activity of FMCC and CS, appropriate ecological flows and hydrological parameters were proposed. These results showed that during the spawning seasons of FMCC and CS, the hydrological processes of the middle reaches of the Yangtze River changed significantly. Therefore, ecological flow must be ensured through ecological operation of upstream reservoirs to provide suitable spawning conditions in target fish spawning grounds.


Assuntos
Carpas , Movimentos da Água , Animais , Hidrologia , Comportamento Sexual Animal
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