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1.
Macromol Rapid Commun ; : e2400178, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683103

RESUMO

The investigation of chiral supramolecular stacking is of essential significance for the understanding of the origin of homochirality in nature. Unlike structurally well-defined amphiphilic liposomes, it remains unclear whether the solvophilic segments of the amphiphilic block copolymer play a decisive role in the construction of asymmetric superstructures. Herein, insights are presented into the stacking patterns and morphological regulation in azobenzene-containing block copolymer assemblies solely by modulating the solvophilic chain length. The solvophilic poly(methacrylic acid) (PMAA) segments of different molecular weights could cause multi-mode chirality inversions involving stacking transitions between intra-chain π-π stacking, inter-chain H- and J-aggregation. Furthermore, the length of the solvophilic PMAA also affects the morphology of the chiral supramolecular assemblies; rice grain-like micelles, worms, nanofibers, floccules, and lamellae can be prepared at different solvophilic-solvophobic balance. The comprehensive mechanism is collectively revealed by utilizing various measurement methods, such as including circular dichroism (CD), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD). This study highlights the critical importance of fully dissolved solvophilic segments for the chiroptical regulation of the aggregated core, providing new insights into the arrangement of chiral supramolecular structures in polymer systems.

2.
Sci Immunol ; 9(94): eadh2334, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669316

RESUMO

T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.


Assuntos
Neoplasias , Linfócitos T , Regulação para Cima , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Fosfolipases A/imunologia , Fosfolipases A/genética , Fosfolipases A2/imunologia , Linfócitos T/imunologia , Regulação para Cima/imunologia
3.
Angew Chem Int Ed Engl ; 63(17): e202401077, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38456382

RESUMO

Circularly polarized luminescence (CPL) plays a pivotal role in cutting-edge display and information technologies. Currently achieving precise color control and dynamic signal regulation in CPL still remains challenging due to the elusory relationship between fluorescence and chirality. Inspired by the natural mechanisms governing color formation and chiral interaction, we proposed an addition-subtraction principle theory to address this issue. Three fluorene-based polymers synthesized by Suzuki polycondensation with different electron-deficient monomers exhibit similar structures and UV/Vis absorption, but distinct fluorescence emissions due to intramolecular charge transfer. Based on this, precise-color CPL-active films are obtained through quantitative supramolecular co-assembly directed by addition principle. Particularly, an ideal white-emitting CPL film (CIE coordinates: (0.33, 0.33)) is facilely fabricated with a high quantum yield of 80.8 % and a dissymmetry factor (glum) of 1.4×10-2. Structural analysis reveals that the ordered stacking orientation favors higher glum. Furthermore, to address the dynamically regulated challenge, the comparable subtraction principle is proposed, involving a contactless chiral communication between excited and ground states. The representative system consisting of as-prepared fluorene-based polymers and chirality-selective absorption azobenzene (Azo)-containing polymers is constructed, achieving CPL weakening, reversal, and enhancement. Finally, a switchable quick response code is realized based on trans-cis isomerization of Azo moiety.

4.
Adv Sci (Weinh) ; 11(14): e2308371, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38311583

RESUMO

New insights are raised to interpret pathway complexity in the supramolecular assembly of chiral triarylamine tris-amide (TATA) monomer. In cosolvent systems, the monomer undergoes entirely different assembly processes depending on the chemical feature of the two solvents. Specifically, 1,2-dichloroethane (DCE) and methylcyclohexane (MCH) cosolvent trigger the cooperative growth of monomers with M helical arrangement, and hierarchical thin nanobelts are further formed. But in DCE and hexane (HE) combination, a different pathway occurs where monomers go through isodesmic growth to generate twisted nanofibers with P helical arrangement. Moreover, the two distinct assemblies exhibit opposite excited-state chirality. The driving force for both assemblies is the formation of intermolecular hydrogen bonds between amide moieties. However, the mechanistic investigation indicates that radical and neutral triarylamine species go through distinct assembly phases by changing solvent structures. The neutralization of radicals in MCH plays a critical role in pathway complexity, which significantly impacts the overall supramolecular assembly process, giving rise to inversed supramolecular helicity and distinct morphologies. This differentiation in pathways affected by radicals provides a new approach to manipulate chiral supramolecular assembly process by facile solvent-solute interactions.

5.
Molecules ; 29(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276578

RESUMO

Soluble dietary fiber (SDF) benefits human health, and different extraction methods might modify the structure and functions of the SDFs. Radish is rich in dietary fiber. To assess the impact of various extraction techniques on the properties and functions of radish SDF, the SDFs were obtained from white radish pomace using alkaline, ultrasonic-assisted, and fermentation-assisted extraction methods. Analysis was conducted on the structure, physicochemical characteristics, thermal properties, and functional attributes of the SDFs. The study revealed that various extraction techniques can impact the monosaccharides composition and functionality of the SDFs. Compared with the other two extraction methods, the surface structures of SDFs obtained by fermentation-assisted extraction were looser and more porous, and the SDF had better water solubility and water/oil holding capacity. The adsorption capacities of glucose and cholesterol of the SDFs obtained from fermentation-assisted extraction were also improved. Wickerhamomyces anomalus YFJ252 seems the most appropriate strain to ferment white radish pomace to acquire SDF; the water holding, oil holding, glucose absorption capacity, and cholesterol absorption capacity at pH 2 and pH 7 have a 3.06, 1.65, 3.19, 1.27, and 1.83 fold increase than the SDF extracted through alkaline extraction method.


Assuntos
Raphanus , Humanos , Água , Glucose , Colesterol/química , Fibras na Dieta/análise
6.
Angew Chem Int Ed Engl ; 63(5): e202315686, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38085492

RESUMO

Unraveling the chirality transfer mechanism of polymer assemblies and controlling their handedness is beneficial for exploring the origin of hierarchical chirality and developing smart materials with desired chiroptical activities. However, polydisperse polymers often lead to an ambiguous or statistical evaluation of the structure-property relationship, and it remains unclear how the iterative number of repeating units function in the helicity inversion of polymer assemblies. Herein, we report the macroscopic helicity and dynamic manipulation of the chiroptical activity of supramolecular assemblies from discrete azobenzene-containing oligomers (azooligomers), together with the helicity inversion and morphological transition achieved solely by changing the iterative chain lengths. The corresponding assemblies also differ from their polydisperse counterparts in terms of thermodynamic properties, chiroptical activities, and morphological control.

7.
Med Oncol ; 41(1): 10, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070011

RESUMO

Cadherin epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an epithelial sheet or multicellular clusters. CELSR1 has been suggested to play a role in glioma, breast cancer, and chronic lymphocytic leukemia development; however, whether it has a role in the pathogenesis of ovarian cancer remains unknown. The aim of this study was to determine the role of CELSR1 in ovarian cancer and elucidate its underlying molecular mechanisms. By analyzing gene expression data downloaded from the Cancer Genome Atlas database, we found that CELSR1 expression was upregulated in ovarian cancer tissues compared to that in normal ovarian tissues. High CELSR1 expression levels were associated with poor prognosis in patients with ovarian cancer. Cell proliferation, scratch, and transwell assays revealed that CELSR1 promoted the proliferation, migration, and invasion of ovarian cancer cells in vitro. In addition, transcriptome sequencing analysis revealed that CELSR1 knockdown in T29H cells resulted in the dysregulation of the expression of 1320 genes. Further analysis revealed that genes involved in proliferation- and migration-associated signaling pathways were regulated by CELSR1. Our study demonstrates that CELSR1 is highly expressed in ovarian cancer cells and regulates their proliferation and migration, suggesting its potential as a diagnostic marker and therapeutic target.


Assuntos
Caderinas , Neoplasias Ovarianas , Feminino , Humanos , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/metabolismo , Regulação para Cima
8.
Artigo em Inglês | MEDLINE | ID: mdl-38082670

RESUMO

Supernumerary robot limbs (SL) can expand the ability of users by increasing the number of degrees of freedom that they control. While several SLs have been designed and tested on human participants, the effect of the limb's appearance on the user's acceptance, embodiment and device usage is not yet understood. We developed a virtual reality platform with a three-arm avatar that enabled us to systematically investigate the effect of the supernumerary limb's appearance on their perception and motion control performance. A pilot study with 14 participants exhibited similar performance, workload and preference in human-like or robot-like appearance with a trend of preference for the robotic appearance.


Assuntos
Robótica , Realidade Virtual , Humanos , Projetos Piloto , Extremidades
9.
PLoS One ; 18(12): e0295274, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38055714

RESUMO

Error based motor learning can be driven by both sensory prediction error and reward prediction error. Learning based on sensory prediction error is termed sensorimotor adaptation, while learning based on reward prediction error is termed reward learning. To investigate the characteristics and differences between sensorimotor adaptation and reward learning, we adapted a visuomotor paradigm where subjects performed arm movements while presented with either the sensory prediction error, signed end-point error, or binary reward. Before each trial, perturbation indicators in the form of visual cues were presented to inform the subjects of the presence and direction of the perturbation. To analyse the interconnection between sensorimotor adaptation and reward learning, we designed a computational model that distinguishes between the two prediction errors. Our results indicate that subjects adapted to novel perturbations irrespective of the type of prediction error they received during learning, and they converged towards the same movement patterns. Sensorimotor adaptations led to a pronounced aftereffect, while adaptation based on reward consequences produced smaller aftereffects suggesting that reward learning does not alter the internal model to the same degree as sensorimotor adaptation. Even though all subjects had learned to counteract two different perturbations separately, only those who relied on explicit learning using reward prediction error could timely adapt to the randomly changing perturbation. The results from the computational model suggest that sensorimotor and reward learning operate through distinct adaptation processes and that only sensorimotor adaptation changes the internal model, whereas reward learning employs explicit strategies that do not result in aftereffects. Additionally, we demonstrate that when humans learn motor tasks, they utilize both learning processes to successfully adapt to the new environments.


Assuntos
Retroalimentação Sensorial , Desempenho Psicomotor , Humanos , Aprendizagem , Movimento , Recompensa , Adaptação Fisiológica
10.
Cell Death Dis ; 14(12): 846, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114473

RESUMO

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.


Assuntos
Neoplasias Esofágicas , Interleucina-6 , Humanos , Recidiva Local de Neoplasia , Tolerância a Radiação/fisiologia , Neoplasias Esofágicas/radioterapia
11.
Exp Cell Res ; 433(2): 113851, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37940066

RESUMO

BACKGROUND: Ovarian cancer has been a worldwide health burden for women and its progression is highly hypoxia-independent. Here, we investigated the exact mechanisms by which hypoxia contributes to the malignant progression of ovarian cancer. METHOD: MTT, transwell, colony formation, and scratch wound healing assays were carried out for cellular functions. The underlying mechanism by which hypoxia functions was explored by RNA-seq, enrichment analysis, western blotting, qRT-PCR, flow cytometry, ChIP, luciferase reporter, and ELISA. Finally, animal experiments including the xenograft model and tumor metastasis model were constructed to validate the role of SLC2A12 in vivo. RESULTS: Hypoxia treatment promoted the cell proliferation, mobility, and colony growth abilities of the two ovarian cancer cell lines HO-8910 and A2780. RNA-seq and enrichment analysis showed that SLC2A12 was hyper-expressed under hypoxia condition and it may be related to glutathione and lipid metabolism. Besides, the expression of SLC2A12 was negatively correlated with overall survival. Hypoxia suppressed ferroptosis by SLC2A12 because silencing SLC2A12 declined the cell viability of HO-8910 and A2780 cells under hypoxia conditions, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) breached that result and upregulated the expression of glutathione peroxidase 4 (GPX4). Moreover, hypoxia increased the expression of hypoxia inducible factor 1 A (HIF-1A), and the accumulated HIF-1A binds to hypoxia inducible factor 1 B (HIF1B) to form HIF-1 complex, then promoted the binding of hypoxic response elements (HRE) to SLC2A12 promoter by HIF-1/HRE signal. Subsequently, SLC2A12 regulated glutathione metabolism and in turn inhibited ferroptosis. The animal experiments indicated that silencing SLC2A12 could significantly inhibit tumor growth and metastasis in vivo. CONCLUSION: Hypoxia promoted ovarian cancer progression by upregulating SLC2A12 and then regulating glutathione metabolism to inhibit ferroptosis.


Assuntos
Ferroptose , Proteínas Facilitadoras de Transporte de Glucose , Neoplasias Ovarianas , Animais , Feminino , Humanos , Linhagem Celular Tumoral , Ferroptose/genética , Glutationa , Hipóxia , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Ovarianas/patologia , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo
12.
Angew Chem Int Ed Engl ; 62(50): e202314848, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37903725

RESUMO

Precise control over the chirality and morphologies of polymer assemblies, a remaining challenge for both chemists and materials scientists, is receiving ever-increasing attention in the recent years. Herein, we report the subtle manipulation of the achiral spacers from the chiral stereocenter to the azobenzene (Azo) unit, of which the chiroptical consistency or chiroptical inversion of self-assemblies could be successfully controlled and present "two-fold" odd-even effect. Furthermore, morphological transitions from 0D spherical micelles, 1D worms, and nanowires to 3D vesicles, spindle- and dumbbell-shaped vesicles were also unexpectedly found to exhibit odd-even correlations. These observations were collectively elucidated by mesomorphic properties, stacking modes, chiroptical dynamics, and stimuli-responsive behaviors. Negligible modifications to the spacer structures can enable remarkable modulation of supramolecular chirality and anisotropic topologies in polymer assemblies, which is of great significance for the design of complex chiral functional polymers.

13.
Angew Chem Int Ed Engl ; 62(52): e202312259, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37738071

RESUMO

The construction of chiral superstructures through the self-assembly of non-chiral polymers usually relies on the interplay of multiple non-covalent bonds, which is significantly limited by the memory ability of induced chirality. Although the introduction of covalent crosslinking can undoubtedly enhance the stability of chiral superstructures, the concurrent strong constraining effect hinders the application of chirality-smart materials. To address this issue, we have made a first attempt at the reversible fixation of supramolecular chirality by introducing dynamic covalent crosslinking into the chiral self-assembly of side-chain polymers. After chiral induction, the reversible [2+2] cycloaddition reaction of the cinnamate group in the polymer chains can be further controlled by light to manipulate inter-chain crosslinking and decrosslinking. Based on this photo-programmable and dynamic chiral fixation strategy, a novel pattern-embedded storage mechanism of chiral polymeric materials was established for the first time.

14.
Int J Pharm ; 644: 123301, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37572859

RESUMO

To prolong the absorption of the drug and achieve the effect of gastric retention, new brivaracetam tablets together with the characteristics of rapid swelling and sustained floating have been developed here. The tablets were optimized and prepared by direct compression techniques using Kollidon® SR and cross-linked polyvinylpyrrolidone (PVPP) XL as the matrix and disintegrant respectively, and carbomer 71G NF and polyethylene oxide (PEO) N60K as the gel materials to achieve sustained release effect. The characteristics of static expansion, floating time, drug release and dynamic swelling performance in vitro of the tablets were evaluated. The optimized formulations (F5 and F10) exhibited satisfactory swelling and floating properties, mechanical strength, and in vitro sustained-release characteristic with diffusion and matrix erosion mechanisms. X-ray images of beagle dogs showed that the tablet F5 could be retained in the stomach for more than 6 h. Furthermore, the pharmacokinetic studies in volunteers exhibited that the bioavailability of F5 and F10 was 95.70% (90% CI, 83.80%-109.28%) and 103.39% (90% CI, 87.61%-122.01%), respectively, relative to commercial tablets, with Tmax prolonged, demonstrating an excellent sustained-release effect. Therefore, the present system can reduce dosing frequency and improve patient compliance, which is expected to be a promising treatment option for epilepsy patients.


Assuntos
Povidona , Estômago , Animais , Cães , Preparações de Ação Retardada/farmacocinética , Administração Oral , Comprimidos , Edema
15.
Cell Rep ; 42(8): 112852, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37481718

RESUMO

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.


Assuntos
DNA , Proteínas de Membrana , Masculino , Humanos , Proteína Beclina-1 , Proteínas de Membrana/metabolismo , DNA/metabolismo , Nucleotidiltransferases/metabolismo , Fosfatidilinositol 3-Quinase , Autofagia
16.
PLoS One ; 18(7): e0288495, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37437095

RESUMO

The recent decades have witnessed the rise of digital media; as an essential informal way of environmental education, the internet has become an important source where public acquire environmental knowledge. The current study investigates the heterogeneous treatment effects of internet use on environmental knowledge across members of the Chinese population. Based on a nationwide survey in China, the propensity score approach, a series of statistical techniques that are often used in the counterfactual framework to understand the causal relationship between an intervention and an outcome, is employed to adjust for population heterogeneity and to estimate heterogeneous treatment effects. The findings reveal highly significant positive associations between internet access/use and environmental knowledge. More importantly, this study shows that individuals who are least likely to access the internet benefit most from the knowledge returns to internet access and use, indicating a positive outlook for the potential of the digital media to narrow the environmental knowledge gap.


Assuntos
Uso da Internet , Internet , Humanos , China , Escolaridade , População do Leste Asiático
17.
J Am Chem Soc ; 145(30): 16474-16487, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37382899

RESUMO

Controlling the secondary phase in chiral liquid-crystalline (LC) polymers is of great importance since it transfers and amplifies molecular information to the macroscopic properties. However, the chiral superstructures of the LC phase are determined exclusively by the inherent configuration of the parent chiral source. Here, we report the switchable supramolecular chirality of heteronuclear structures by the untraditional command between common chiral "sergeant" units and various achiral "soldier" units. Different chiral induction pathways between sergeants and soldiers were observed for copolymer assemblies with mesogenic and non-mesogenic soldier units, demonstrating the formation of a helical phase independent of the absolute configuration of the stereocenter. In the presence of non-mesogenic soldier units, the classical SaS (Sergeants and Soldiers) effect in the amorphous phase was observed; whereas in a full LC system, bidirectional command of sergeants was activated in response to the phase transition. Meanwhile, a full spectrum of morphological phase diagrams including spherical micelles, worms, nanowires, spindles, tadpoles, anisotropic ellipsoidal vesicles, and isotropic spherical vesicles were successfully achieved. Such spindles, tadpoles, and anisotropic ellipsoidal vesicles have rarely been obtained previously from chiral polymer systems.

18.
Front Med (Lausanne) ; 10: 1190758, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228404

RESUMO

Background: Several clinical trials of corticosteroids have been carried out in the treatment of septic shock, however, the therapeutic effect of the most widely used hydrocortisone is still controversial, and no studies have directly compared hydrocortisone versus hydrocortisone plus fludrocortisone for patients with septic shock. Methods: Baseline characteristics and treatment regimens of patients with septic shock treated with hydrocortisone from the Medical Information Mart for Intensive Care-IV database were collected. Patients were divided into hydrocortisone treatment groups and hydrocortisone plus fludrocortisone treatment groups. The primary outcome was 90-day mortality, and secondary outcomes included 28-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Binomial Logistic regression analysis was performed to identify independent risk factors for mortality. Survival analysis was performed and Kaplan-Meier curves were drawn for patients in different treatment groups. Propensity score matching (PSM) analysis was performed to reduce bias. Results: Six hundred and fifty three patients were enrolled, of which 583 were treated with hydrocortisone alone, and 70 with hydrocortisone plus fludrocortisone. After PSM, 70 patients were included in each group. The proportion of patients with acute kidney injury (AKI) and the proportion of renal replacement therapy (RRT) treatment in the hydrocortisone plus fludrocortisone group were higher than those in the hydrocortisone alone group, and there was no significant difference in other baseline characteristics. Compared with hydrocortisone alone, hydrocortisone plus fludrocortisone did not reduce the 90-day mortality (after PSM, relative risk/RR = 1.07, 95%CI 0.75-1.51), 28-day mortality (after PSM, RR = 0.82, 95%CI 0.59-1.14) and in-hospital mortality (after PSM, RR = 0.79, 95%CI 0.57-1.11) of the enrolled patients, nor did it affect the length of hospital stay (after PSM, 13.9 days vs. 10.9 days, p = 0.34) and ICU stay (after PSM, 6.0 days vs. 3.7 days, p = 0.14), and the survival analysis showed no statistically significant difference in the corresponding survival time. After PSM, binomial Logistic regression analysis showed that SAPS II score was an independent risk factor for 28-day morality (OR = 1.04, 95%CI 1.02-1.06, p < 0.01) and in-hospital morality (OR = 1.04, 95%CI 1.01-1.06, p < 0.01), while hydrocortisone plus fludrocortisone was not an independent risk factor for 90-day mortality (OR = 0.88, 95%CI 0.43-1.79, p = 0.72), 28-day morality (OR = 1.50, 95%CI 0.77-2.91, p = 0.24), or in-hospital morality (OR = 1.58, 95%CI 0.81-3.09, p = 0.18). Conclusion: In the treatment of patients with septic shock, hydrocortisone plus fludrocortisone did not reduce 90-day mortality, 28-day mortality, and in-hospital mortality compared with hydrocortisone alone, and had no effect on the length of hospital stay and ICU stay.

19.
Front Bioeng Biotechnol ; 11: 1177151, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122851

RESUMO

Nanomaterial-based drug delivery systems (NBDDS) are widely used to improve the safety and therapeutic efficacy of encapsulated drugs due to their unique physicochemical and biological properties. By combining therapeutic drugs with nanoparticles using rational targeting pathways, nano-targeted delivery systems were created to overcome the main drawbacks of conventional drug treatment, including insufficient stability and solubility, lack of transmembrane transport, short circulation time, and undesirable toxic effects. Herein, we reviewed the recent developments in different targeting design strategies and therapeutic approaches employing various nanomaterial-based systems. We also discussed the challenges and perspectives of smart systems in precisely targeting different intravascular and extravascular diseases.

20.
Chem Sci ; 14(19): 5116-5124, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37206386

RESUMO

In nature, the communication of primary amino acids in the polypeptides influences molecular-level packing, supramolecular chirality, and the resulting protein structures. In chiral side-chain liquid crystalline polymers (SCLCPs), however, the hierarchical chiral communication between supramolecular mesogens is still determined by the parent chiral source due to the intermolecular interactions. Herein, we present a novel strategy to enable the tunable chiral-to-chiral communication in azobenzene (Azo) SCLCPs, in which the chiroptical properties are not dominated by the configurational point chirality but by the conformationally supramolecular chirality that emerged. The communication of dyads biases supramolecular chirality with multiple packing preference, thereby overruling the configurational chirality of the stereocenter. The chiral communication mechanism between the side-chain mesogens is revealed through the systematic study of the chiral arrangement at the molecular level, including mesomorphic properties, stacking modes, chiroptical dynamics and further morphological dimensions.

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