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1.
Nat Commun ; 15(1): 2988, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582884

RESUMO

Class I KNOTTED-like homeobox (KNOXI) genes are parts of the regulatory network that control the evolutionary diversification of leaf morphology. Their specific spatiotemporal expression patterns in developing leaves correlate with the degrees of leaf complexity between simple-leafed and compound-leafed species. However, KNOXI genes are not involved in compound leaf formation in several legume species. Here, we identify a pathway for dual repression of MtKNOXI function in Medicago truncatula. PINNATE-LIKE PENTAFOLIATA1 (PINNA1) represses the expression of MtKNOXI, while PINNA1 interacts with MtKNOXI and sequesters it to the cytoplasm. Further investigations reveal that UNUSUAL FLORAL ORGANS (MtUFO) is the direct target of MtKNOXI, and mediates the transition from trifoliate to pinnate-like pentafoliate leaves. These data suggest a new layer of regulation for morphological diversity in compound-leafed species, in which the conserved regulators of floral development, MtUFO, and leaf development, MtKNOXI, are involved in variation of pinnate-like compound leaves in M. truncatula.


Assuntos
Medicago truncatula , Proteínas de Plantas/metabolismo , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas
2.
Materials (Basel) ; 17(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38591509

RESUMO

In this paper, the damage monitoring investigation based on the remote bonding fiber Bragg grating sensing is performed on the aerospace aluminum alloy thin-walled structure with prefabricated damage. Firstly, an ultrasonic excitation-fiber Bragg gratings (UE-FBGs) sensing experimental platform is established for the simulation of defects monitoring, in which the sensors are placed at a certain distance from the bonding area. Secondly, different arrangements of exciters and receivers are utilized for the original signals and the damage signals. Subsequently, the raw signals are processed by filter and feature extraction in order to denoise the signals and acquire the parameters sensitive to the damage. Finally, an improved Reconstruction for Image Defects (RAPID) algorithm is used to locate and reconstruct the pre-existing damage. The results show that the proposed system improves the sensitivity of the FBG receiver signal and the accuracy of the damage imaging.

3.
J Mater Chem B ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623831

RESUMO

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

4.
Cancer ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578977

RESUMO

BACKGROUND: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T-cell therapy-associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy. METHODS: In total, 93 patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving humanized anti-CD19 CAR T cells were recruited from May 2016 to November 2022. Forty-five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab. RESULTS: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event-free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell-associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells. CONCLUSIONS: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS.

5.
J Hazard Mater ; 470: 134221, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38615651

RESUMO

Constructed wetlands (CWs) are a promising approach for treating acid mine drainage (AMD). However, the extreme acidity and high loads of heavy metals in AMD can easily lead to the collapse of CWs without proper pre-treatment. Therefore, it is considered essential to maintain efficient and stable performance for AMD treatment in CWs. In this study, pre-prepared attapulgite-soda residue (ASR) composites were used to improve the substrate of CWs. Compared with CWs filled with gravel (CWs-G), the removal efficiencies of sulfate and Fe, Mn, Cu, Zn Cd and Pb in CWs filled with ASR composites (CWs-ASR) were increased by 30% and 10-70%, respectively. These metals were mainly retained in the substrate in stable forms, such as carbonate-, Fe/Mn (oxide)hydroxide-, and sulfide-bound forms. Additionally, higher levels of photosynthetic pigments and antioxidant enzyme activities in plants, along with a richer microbial community, were observed in CWs-ASR than in CWs-G. The application of ASR composites alleviated the adverse effects of AMD stresses on wetland plants and microorganisms. In return, the increased bacteria abundance, particularly SRB genera (e.g., Thermodesulfovibrionia and Desulfobacca), promoted the formation of metal sulfides, enabling the saturated ASR adsorbed with metals to regenerate and continuously capture heavy metals. The synergistic adsorption of ASR composites and microbial sulfate reduction maintained the stable and efficient operation of CWs. This study contributes to the resource utilization of industrial alkaline by-products and promotes the breakthrough of new techniques for low-cost and passive treatment systems such as CWs.


Assuntos
Compostos de Magnésio , Metais Pesados , Mineração , Compostos de Silício , Sulfatos , Poluentes Químicos da Água , Áreas Alagadas , Sulfatos/química , Metais Pesados/química , Adsorção , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismo , Compostos de Silício/química , Compostos de Magnésio/química , Ácidos/química , Oxirredução , Biodegradação Ambiental , Concentração de Íons de Hidrogênio
6.
Proc Natl Acad Sci U S A ; 121(15): e2318072121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38573966

RESUMO

As one of the most stunning biological nanostructures, the single-diamond (SD) surface discovered in beetles and weevils exoskeletons possesses the widest complete photonic bandgap known to date and is renowned as the "holy grail" of photonic materials. However, the synthesis of SD is difficult due to its thermodynamical instability compared to the energetically favoured bicontinuous double diamond and other easily formed lattices; thus, the artificial fabrication of SD has long been a formidable challenge. Herein, we report a bottom-up approach to fabricate SD titania networks via a one-pot cooperative assembly scenario employing the diblock copolymer poly(ethylene oxide)-block-polystyrene as a soft template and titanium diisopropoxide bis(acetylacetonate) as an inorganic precursor in a mixed solvent, in which the SD scaffold was obtained by kinetically controlled nucleation and growth in the skeletal channels of the diamond minimal surface formed by the polymer matrix. Electron crystallography investigations revealed the formation of tetrahedrally connected SD frameworks with the space group Fd [Formula: see text] m in a polycrystalline anatase form. A photonic bandgap calculation showed that the resulting SD structure has a wide and complete bandgap. This work solves the complex synthetic enigmas and offers a frontier in hyperbolic surfaces, biorelevant materials, next-generation optical devices, etc.

7.
Brain Res ; 1835: 148932, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38609032

RESUMO

Alzheimer's disease (AD) is a primary degenerative encephalopathy that first appeared as a decline in memory and learning skills. Over time, the condition's severity grew. Palmatine (Pal) alleviates Alzheimer's disease symptoms, which has neuroprotective benefits. Numerous investigations have demonstrated a close relationship among AD and gut structure changes. The aim of the research was investigating whether the improvement of Pal on AD is linked to regulating gut flora and autophagy. First, we used Aß1-40 to induce apoptosis in HT22 cells. After Pal treatment, apoptosis can be improved. Then, We used bilateral intracranial hippocampal injection of Aß1-40 for establishing the AD model, after treatment with Pal, the morris water maze experiment and eight-arm maze test demonstrated that Pal enhanced the AD rats' capacity for learning and memory, HE staining illustrated that Pal improved the morphological abnormalities of brain cells and gut tissue damage. Pal reduced the death of hippocampus neurons, as shown by Nissl staining. Pal substantially reduced Tau hyperphosphorylation and Aß accumulation in the brain, according to immunohistochemical labelling. Pal improved the expression of LC3, Beclin 1, AMPK, and suppressed the expression of mTOR and P62, as validated by RT-qPCR and immunofluorescence labelling. This suggests that Pal's treatment of AD may be associated with the control of the AMPK/mTOR autophagy signalling system. 16S rRNA sequencing and short-chain fatty acids (SCFAs) content detection analysis illustrated that Pal has the potential to enhance the content of SCFAs, reverse the alterations in gut microorganisms. It has been showed by the study that Pal could improve AD by activating autophagy signaling pathway and improving gut barrier changes.

8.
Adv Mater ; : e2402005, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598862

RESUMO

The emerging sodium-ion batteries (SIBs) are one of the most promising candidates expected to complement lithium-ion batteries and diversify the battery market. However, the exploitation of cathode materials with high-rate performance and long-cycle stability for SIBs has remained one of the major challenges. To this end, an efficient approach to enhance rate and cycling performance by introducing an ordered bicontinuous porous structure into cathode materials of SIBs is demonstrated. Prussian blue analogues (PBAs) are selected because they are recognized as a type of most promising SIB cathode materials. Thanks to the presence of 3D continuous channels enabling fast Na+ ions diffusion as well as the intrinsic mechanical stability of bicontinuous architecture, the resultant PBAs exhibit excellent rate capability (80 mAh g-1 at 2.5 A g-1) and ultralong cycling life (>3000 circulations at 0.5 A g-1), reaching the top performance of the reported PBA-based cathode materials. This study opens a new avenue for boosting sluggish ion diffusion kinetics in electrodes of rechargeable batteries and also provides a new paradigm for solving the dilemma that electrodes' failure due to high-stress concentration upon ion storage.

9.
J Biomed Opt ; 29(4): 046008, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38659998

RESUMO

Significance: Optical imaging is a non-invasive imaging technology that utilizes near-infrared light, allows for the image reconstruction of optical properties like diffuse and absorption coefficients within the tissue. A recent trend is to use signal processing techniques or new light sources and expanding its application. Aim: We aim to develop the reflective optical imaging using the chaotic correlation technology with chaotic laser and optimize the quality and spatial resolution of reflective optical imaging. Approach: Scattering medium was measured using reflective configuration in different inhomogeneous regions to evaluate the performance of the imaging system. The accuracy of the recovered optical properties was investigated. The reconstruction errors of absorption coefficients and geometric centers were analyzed, and the feature metrics of the reconstructed images were evaluated. Results: We showed how chaotic correlation technology can be utilized for information extraction and image reconstruction. This means that a higher signal-to-noise ratio and image reconstruction of inhomogeneous phantoms under different scenarios successfully were achieved. Conclusions: This work highlights that the peak values of correlation of chaotic exhibit smaller reconstruction error and better reconstruction performance in optical imaging compared with reflective optical imaging with the continuous wave laser.


Assuntos
Processamento de Imagem Assistida por Computador , Lasers , Imagem Óptica , Imagens de Fantasmas , Espalhamento de Radiação , Imagem Óptica/métodos , Processamento de Imagem Assistida por Computador/métodos , Razão Sinal-Ruído , Dinâmica não Linear , Algoritmos , Desenho de Equipamento
10.
IEEE Trans Med Imaging ; PP2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526887

RESUMO

Dynamic effective connectivity (DEC) is the accumulation of effective connectivity in the time dimension, which can describe the continuous neural activities in the brain. Recently, learning DEC from functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data has attracted the attention of neuroinformatics researchers. However, the current methods fail to consider the gap between the fMRI and EEG modality, which can not precisely learn the DEC network from multimodal data. In this paper, we propose a multimodal causal adversarial network for DEC learning, named MCAN. The MCAN contains two modules: multimodal causal generator and multimodal causal discriminator. First, MCAN employs a multimodal causal generator with an attention-guided layer to produce a posterior signal and output a set of DEC networks. Then, the proposed method uses a multimodal causal discriminator to unsupervised calculate the joint gradient, which directs the update of the whole network. The experimental results on simulated data sets show that MCAN is superior to other state-of-the-art methods in learning the network structure of DEC and can effectively estimate the brain states. The experimental results on real data sets show that MCAN can better reveal abnormal patterns of brain activity and has good application potential in brain network analysis.

11.
Aging (Albany NY) ; 16(5): 4759-4777, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38461449

RESUMO

Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of ß-sitosterol, a major constituent of Ranunculus ternatus Thunb, in hepatic fibrosis and identifies its underlying mechanisms. After treatment with ß-sitosterol, CCL4-induced hepatic fibrosis was reversed in mice, while inflammatory and hepatic fibrosis indices were improved. Meanwhile, we explored the molecular mechanism of ß-sitosterol treatment for hepatic fibrosis and, based on RNA-seq results, found that the ameliorative effect of ß-sitosterol on hepatic fibrosis was associated with the MK3 and NF-κB signalling pathways. MK3, an important kinase in the MAPK pathway, plays a role in transmitting upstream and downstream signals, whereas the NF-κB signalling pathway has been shown to be associated with HSC activation. We verified the interaction between MK3 and IκB in HSC cells using endogenous Co-IP, whereas ß-sitosterol reduced the binding of MK3 to IκB and the activation of the NF-κB signalling pathway. Our findings reveal the mechanism of ß-sitosterol in the treatment of liver fibrosis, suggesting that ß-sitosterol may be a promising drug for the treatment of liver fibrosis and deserves further investigation.


Assuntos
NF-kappa B , Ranunculus , Camundongos , Animais , NF-kappa B/metabolismo , Ranunculus/metabolismo , Farmacologia em Rede , Cirrose Hepática/metabolismo , Perfilação da Expressão Gênica , Fígado/metabolismo
12.
Cleft Palate Craniofac J ; : 10556656241231119, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490217

RESUMO

OBJECTIVE: To compare the complementation of magnetic resonance imaging (MRI) to prenatal ultrasound (US) with prenatal US alone in detecting orofacial clefts in high-risk fetuses. DESIGN: A network meta-analysis. SETTING: Literature retrieval in PubMed, EMBASE, and Cochrane library, and meta-analysis based on STATA 14.0. PATIENTS: Fetuses were at high-risk for orofacial clefts. INTERVENTIONS: Prenatal US and the complementation of MRI to prenatal US. MAIN OUTCOME MEASURES: The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), and area under the curve (AUC). RESULTS: Thirteen studies involving 776 patients were included. Direct meta-analysis showed that the complementation of MRI to prenatal US did not differ from prenatal US in detecting orofacial clefts if the type of orofacial clefts was not distinguished. Subgroup analysis showed that the specificity of prenatal US for the detection of isolated cleft palate (CP) was lower than that of the complementation of MRI to prenatal US. Furthermore, network meta-analysis consistently suggested a comparable diagnostic value between prenatal US and the complementation of MRI to prenatal US. Moreover, subgroup analysis showed that the specificity of prenatal US was significantly lower than that of complementation of MRI to prenatal US for the detection of isolated CP. CONCLUSIONS: MRI is more accurate than ultrasound in detecting cleft palate. Therefore, MRI should be offered if there is a fetus with a possible or ultrasound diagnosis of cleft palate, especially if the evaluation of cleft palate is deemed unsatisfactory after careful evaluation of the images.

13.
J Orthop Surg Res ; 19(1): 169, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448971

RESUMO

OBJECTIVE: The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). METHODS: Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. RESULTS: The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). CONCLUSION: In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.


Assuntos
Antraquinonas , Produtos Biológicos , Curcumina , Emodina , Polifenóis , Gentamicinas/farmacologia , Cimentos Ósseos/farmacologia , Curcumina/farmacologia , Quercetina , Staphylococcus aureus , Antibacterianos/farmacologia , Produtos Biológicos/farmacologia
14.
Molecules ; 29(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38542841

RESUMO

Polysilsesquioxane (PSQ) microspheres have shown promise in many fields, but previous studies about porous PSQ microspheres are scarce. Herein, we fabricated novel micron-sized thiol-functional polysilsesquioxane (TMPSQ) microspheres with open and interconnected macropores by combining inverse suspension polymerization with two-step sol-gel and polymerization-induced phase separation processes, without using phase-separation-promoting additives or sacrificial templates. The chemical composition of the TMPSQ microspheres was confirmed using FTIR and Raman spectroscopy. The morphology of the TMPSQ microspheres was characterized using SEM and TEM. TGA was employed to test the thermal stability of the TMPSQ microspheres. Mercury intrusion porosimetry and nitrogen adsorption-desorption tests were performed to investigate the pore structure of the TMPSQ microspheres. The results showed that the TMPSQ microspheres had open and interconnected macropores with a pore size of 839 nm, and the total porosity and intraparticle porosity reached 70.54% and 43.21%, respectively. The mechanism of porous generation was proposed based on the morphological evolution observed using optical microscopy. The macropores were formed through the following four steps: phase separation (spinodal decomposition), coarsening, gelation, and evaporation of the solvent. The macropores can facilitate the rapid mass transfer between the outer and inner spaces of the TMPSQ microspheres. The TMPSQ microspheres are promising in various fields, such as catalyst supports and adsorbents.

15.
Am J Pathol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537935

RESUMO

Unexplained recurrent spontaneous abortion (URSA) is a serious reproductive issue that affects women of childbearing age. Studies have shown a close association between disrupted circadian rhythm and impaired epithelial-mesenchymal transition (EMT) process in trophoblasts during URSA, although the underlying mechanism has not been elaborated. This study aims to investigate the regulatory relationship between circadian rhythm gene cryptochrome 2 (CRY2) and ferroptosis on the migratory ability of trophoblast cells. Cell proliferation experiments, wound healing assays, and expression of related markers were conducted to verify the EMT efforts. Trophoblastic ferroptosis was confirmed by the expressions of malondialdehyde, glutathione, mitochondrial membrane potential, divalent iron ions, and related genes. The results showed significant increased expression of CRY2 and decreased expression of brain and muscle ARNT-like protein 1 (BMAL1) in the URSA villous tissues, accompanied by iron-dependent oxidative changes and abnormal expression of ferroptosis-related proteins. It was observed that CRY2 and BMAL1 were co-localized and function as a feedback loop, which regulated the dynamic changes of EMT-related markers in trophoblast cells. CRY2 promoted trophoblastic ferroptosis, whereas BMAL1 had the opposite effect. Particularly, the ferroptosis inhibitor (ferrostatin-1) effectively reversed the trophoblastic ferroptosis and EMT inhibition caused by CRY2 overexpression. Collectively, these results suggest that CRY2 regulates trophoblastic ferroptosis and hinders cellular EMT and migratory ability by suppressing BMAL1 expression.

16.
Int Immunopharmacol ; 131: 111831, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38489969

RESUMO

BACKGROUND: Fibrin(ogen) deposition in the central nervous system (CNS) contributes to neuropathological injury; however, its role in ischemic stroke is unknown. In this study, we identified fibrinogen as a novel proinflammatory regulator of post-stroke neuroinflammation and revealed the neuro-protection effect of fibrin-derived γ377-395peptide in stroke. METHODS: Fibrinogen depletion and fibrinogen-derived γ377-395peptide treatment were performed 2 h after establishing a permanent middle cerebral artery occlusion (pMCAO) model. The infarction volume, neurological score, fibrin(ogen) deposition, and inflammatory response were evaluated 24 h after occlusion. Both in vivo and in vitro studies were conducted to assess the therapeutic potential of the γ377-395peptide in blocking the interactions between fibrin(ogen) and neutrophils. RESULTS: Fibrin(ogen) deposited in the infarct core promoted post-stroke inflammation and exacerbated neurological deficits in the acute phase after stroke onset. Reducing fibrinogen deposition resulted in a decrease in infarction volume, improved neurological scores, and reduced inflammation in the brain. Additionally, the presence of neutrophil accumulation near fibrin(ogen) deposits was observed in ischemic lesions, and the engagement of fibrin(ogen) by integrin receptor αMß2 promoted neutrophil activation and post-stroke inflammation. Finally, inhibiting fibrin(ogen)-mediated neutrophil activation using a fibrinogen-derived γ377-395peptide significantly attenuated neurological deficits. CONCLUSIONS: Fibrin(ogen) is a crucial regulator of post-stroke inflammation and contributes to secondary brain injury. The inflammation induced by fibrin(ogen) is primarily driven by neutrophils during acute ischemic stroke and can be ameliorated using the fibrin-derived γ377-395peptide. Targeting the fibrin(ogen)-mediated neuropathological process represents a promising approach for neuroprotective therapy after stroke while preserving its beneficial coagulation function.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Doenças Neuroinflamatórias , Inflamação/tratamento farmacológico , Inflamação/patologia , Fibrinogênio , Peptídeos , Fibrina , Acidente Vascular Cerebral/tratamento farmacológico , Infarto
17.
Adv Healthc Mater ; : e2303016, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431929

RESUMO

Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti-oxidation and anti-inflammatory potential. However, curcumin exhibits low solubility (<1 µg mL-1 ), poor tissue-targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide-oxalate-curcumin) nanoparticle (SeOC-NP) with dual-reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one-step synthetic strategy. The results confirmed that dual-ROS sensitive chemical moieties endowed SeOC-NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high-efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4-fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC-NP significantly enhanced the antioxidant activity and anti-inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro-inflammatory cytokines. In mouse colitis models, orally administered SeOC-NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS-responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.

18.
J Cancer Res Clin Oncol ; 150(3): 147, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512406

RESUMO

OBJECTIVE: To construct a multi-region MRI radiomics model for predicting pathological complete response (pCR) in breast cancer (BCa) patients who received neoadjuvant chemotherapy (NACT) and provide a theoretical basis for the peritumoral microenvironment affecting the efficacy of NACT. METHODS: A total of 133 BCa patients who received NACT, including 49 with confirmed pCR, were retrospectively analyzed. The radiomics features of the intratumoral region, peritumoral region, and background parenchymal enhancement (BPE) were extracted, and the most relevant features were obtained after dimensional reduction. Then, combining different areas, multivariate logistic regression analysis was used to select the optimal feature set, and six different machine learning models were used to predict pCR. The optimal model was selected, and its performance was evaluated using receiver operating characteristic (ROC) analysis. SHAP analysis was used to examine the relationship between the features of the model and pCR. RESULTS: For signatures constructed using three individual regions, BPE provided the best predictions of pCR, and the diagnostic performance of the intratumoral and peritumoral regions improved after adding the BPE signature. The radiomics signature from the combination of all the three regions with the XGBoost machine learning algorithm provided the best predictions of pCR based on AUC (training set: 0.891, validation set: 0.861), sensitivity (training set: 0.882, validation set: 0.800), and specificity (training set: 0.847, validation set: 0.84). SHAP analysis demonstrated that LZ_log.sigma.2.0.mm.3D_glcm_ClusterShade_T12 made the greatest contribution to the predictions of this model. CONCLUSION: The addition of the BPE MRI signature improved the prediction of pCR in BCa patients who received NACT. These results suggest that the features of the peritumoral microenvironment are related to the efficacy of NACT.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , 60570 , Imageamento por Ressonância Magnética/métodos , Aprendizado de Máquina , Microambiente Tumoral
19.
Org Biomol Chem ; 22(15): 3068-3072, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38546264

RESUMO

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high Z-selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

20.
Heliyon ; 10(5): e26659, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449620

RESUMO

Background: The coexistence of autoimmune encephalitis (AE) with multiple neural auto-antibodies is of great clinical significance because overlying antibodies may cause superposition or variation of clinical syndrome, which increases the difficulty of diagnosis and treatment of the disease. To the best of our knowledge, the coexistence of anti-N-methyl d-aspartate Receptor (NMDAR) and anti-IgLON5 antibodies in AE has not been published previously. Case presentation: A 38-year-old female patient presented to our hospital due to headache and abnormal psychiatric behavior. Based on her clinical manifestations (psychiatric and behavioral abnormalities, involuntary limb movements, and sleep disorders) and laboratory assessment results (positive human leukocyte antigen (HLA)-DQB1*05:01 haplotype, anti-NMDAR, and anti-IgLON5 antibodies), she was diagnosed as AE with coexisting anti-NMDAR and anti-IgLON5 antibodies. After treatment with intravenous methylprednisolone and immunoglobulin, as well as plasmapheresis, her symptoms gradually improved with exception for the sleep disorders. Although oral prednisone acetate and mycophenolate mofetil were continued after discharge, her symptoms of sleep disorders did not improve at 6-month follow-up. Conclusion: This is the first case of AE co-existing with anti-NMDAR and anti-IgLON5 antibodies. Co-existence of neural auto-antibodies should be considered when patients present with overlapping or atypical symptoms. Special attention should be paid to the treatment of these patients as some anti-IgLON5 encephalitis patients may not benefit from immunotherapy treatment.

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