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1.
iScience ; 27(5): 109745, 2024 May 17.
Article En | MEDLINE | ID: mdl-38706839

Zeolite-encaged metal nanoparticles (NPs) catalysts are emerging as a new frontier owing to their superior ability to stabilize the structure and catalytic performance in the thermal and environmental catalytic reaction. However, the pore size below 2 nm of the conventional zeolites usually limits the accessibility of metal active sites. Herein, Co-Cu NPs of about 2.5-3.5 nm were uniformly encapsulated in the intracrystalline mesoporous Silicalite-1 (S-1) through alkali-treatment ligand-assisted strategy. The obtained sample (termed CoxCu1-x@HS-1) exhibited efficient activity and stability in the ammonia borane hydrolysis with the highest TOF value of 21.46 molH2·molMe-1·min-1. UV-vis DRS spectra indicated that intracrystalline mesopores have greatly improved the openness and accessibility of the active sites, thus improving their catalytic performance. The introduction of Cu regulates the electronic properties of Co, further increasing hydrogen production activity. This research creates new prospects to design other high-performance hierarchical porous zeolite-confined metal/metal oxide catalysts.

2.
Inorg Chem ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38743640

Enzyme immobilization within metal-organic frameworks (MOFs) is a promising solution to avoid denaturation and thereby utilize the desirable properties of enzymes outside of their native environments. The biomimetic mineralization strategy employs biomacromolecules as nucleation agents to promote the crystallization of MOFs in water at room temperature, thus overcoming pore size limitations presented by traditional postassembly encapsulation. Most biomimetic crystallization studies reported to date have employed zeolitic imidazole frameworks (ZIFs). Herein, we expand the library of MOFs suitable for biomimetic mineralization to include zinc(II) MOFs incorporating functionalized terephthalic acid linkers and study the catalytic performance of the enzyme@MOFs. Amine functionalization of terephthalic acids is shown to accelerate the formation of crystalline MOFs enabling new enzyme@MOFs to be synthesized. The structure and morphology of the enzyme@MOFs were characterized by PXRD, FTIR, and SEM-EDX, and the catalytic potential was evaluated. Increasing the linker length while retaining the amino moiety gave rise to a family of linkers; however, MOFs generated with the 2,2'-aminoterephthalic acid linker displayed the best catalytic performance. Our data also illustrate that the pH of the reaction mixture affects the crystal structure of the MOF and that this structural transformation impacts the catalytic performance of the enzyme@MOF.

3.
Article En | MEDLINE | ID: mdl-38710592

BACKGROUND AND AIM: The study aims to introduce a novel indicator, effective withdrawal time (WTS), which measures the time spent actively searching for suspicious lesions during colonoscopy and to compare WTS and the conventional withdrawal time (WT). METHODS: Colonoscopy video data from 472 patients across two hospitals were retrospectively analyzed. WTS was computed through a combination of artificial intelligence (AI) and manual verification. The results obtained through WTS were compared with those generated by the AI system. Patients were categorized into four groups based on the presence of polyps and whether resections or biopsies were performed. Bland Altman plots were utilized to compare AI-computed WTS with manually verified WTS. Scatterplots were used to illustrate WTS within the four groups, among different hospitals, and across various physicians. A parallel box plot was employed to depict the proportions of WTS relative to WT within each of the four groups. RESULTS: The study included 472 patients, with a median age of 55 years, and 57.8% were male. A significant correlation with manually verified WTS (r = 0.918) was observed in AI-computed WTS. Significant differences in WTS/WT among the four groups were revealed by the parallel box plot (P < 0.001). The group with no detected polyps had the highest WTS/WT, with a median of 0.69 (interquartile range: 0.40, 0.97). WTS patterns were found to be varied between the two hospitals and among senior and junior physicians. CONCLUSIONS: A promising alternative to traditional WT for quality control and training assessment in colonoscopy is offered by AI-assisted computation of WTS.

4.
Cell Death Discov ; 10(1): 212, 2024 May 02.
Article En | MEDLINE | ID: mdl-38697996

The escalating threat of bone-related diseases poses a significant challenge to human health. Mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs), as inherent cell-secreted natural products, have emerged as promising treatments for bone-related diseases. Leveraging outstanding features such as high biocompatibility, low immunogenicity, superior biological barrier penetration, and extended circulating half-life, MSC-EVs serve as potent carriers for microRNAs (miRNAs), long no-code RNAs (lncRNAs), and other biomolecules. These cargo molecules play pivotal roles in orchestrating bone metabolism and vascularity through diverse mechanisms, thereby contributing to the amelioration of bone diseases. Additionally, engineering modifications enhance the bone-targeting ability of MSC-EVs, mitigating systemic side effects and bolstering their clinical translational potential. This review comprehensively explores the mechanisms through which MSC-EVs regulate bone-related disease progression. It delves into the therapeutic potential of MSC-EVs as adept drug carriers, augmented by engineered modification strategies tailored for osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, and osteosarcoma. In conclusion, the exceptional promise exhibited by MSC-EVs positions them as an excellent solution with considerable translational applications in clinical orthopedics.

5.
Molecules ; 29(9)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38731439

The production of peanut oil in the industrial sector necessitates the utilization of diverse raw materials to generate consistent batches with stable flavor profiles, thereby leading to an increased focus on understanding the correlation between raw materials and flavor characteristics. In this study, sensory evaluations, headspace solid-phase micro-extraction gas chromatography mass spectrometry (HS-SPME-GC-MS), odor activity value (OAV) calculations, and correlation analysis were employed to investigate the flavors and main contributing amino acids of hot-pressed oils derived from different peanut varieties. The results confirmed that the levels of alcohols, aldehydes, and heterocyclic compounds in peanut oil varied among nine different peanut varieties under identical processing conditions. The OAVs of 25 key aroma compounds, such as methylthiol, 3-ethyl-2,5-dimethylpyrazine, and 2,3-glutarone, exceeded a value of 1. The sensory evaluations and flavor content analysis demonstrated that pyrazines significantly influenced the flavor profile of the peanut oil. The concentrations of 11 amino acids showed a strong correlation with the levels of pyrazines. Notably, phenylalanine, lysine, glutamic acid, arginine, and isoleucine demonstrated significant associations with both pyrazine and nut flavors. These findings will provide valuable insights for enhancing the sensory attributes of peanut oil and selecting optimal raw peanuts for its production.


Amino Acids , Arachis , Gas Chromatography-Mass Spectrometry , Odorants , Peanut Oil , Amino Acids/analysis , Amino Acids/chemistry , Arachis/chemistry , Odorants/analysis , Peanut Oil/chemistry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/chemistry , Flavoring Agents/chemistry , Flavoring Agents/analysis , Pyrazines/chemistry , Pyrazines/analysis , Solid Phase Microextraction , Taste , Hot Temperature
6.
J Immunother Cancer ; 12(4)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38688579

BACKGROUND: Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date. METHODS: We evaluated the CMV infection status of patients with GBM's tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro. RESULTS: We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model. CONCLUSIONS: These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.


Cytomegalovirus , Glioblastoma , Humans , Glioblastoma/immunology , Glioblastoma/virology , Glioblastoma/pathology , Mice , Cytomegalovirus/immunology , Animals , Cytomegalovirus Infections/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Brain Neoplasms/immunology , Tumor Microenvironment/immunology , RNA-Seq , Female , Male , Single-Cell Gene Expression Analysis
8.
Prev Med Rep ; 41: 102722, 2024 May.
Article En | MEDLINE | ID: mdl-38646072

Background: To describe the past, present and future burden of pancreatitis in older adults, and to explore cross-national inequalities across socio-demographic index (SDI). Methods: Data on pancreatitis in older adults, including mortality and disability-adjusted life years (DALYs) rates, were collected from the Global Burden of Disease (GBD) 2019 study. Temporal trends were measured using joinpoint analyses and predicted using a Bayesian age-period-cohort model. Additionally, the unequal distribution of the burden of pancreatitis in older adults was quantified. Results: From 1990 to 2019, the number of deaths and DALYs due to pancreatitis in older adults has been increasing annually. However, in most regions of the world, age-standardized death rates (ASDR) and age-standardized DALYs rates have been declining. The burden of pancreatitis in older adults was highest in low SDI region, primarily affecting the population aged 65-74, with a greater burden on males than females. Furthermore, from 1990 to 2019, absolute and relative cross-national inequalities in pancreatitis among older adults have remained largely unchanged. It is projected that in the next 11 years, the number of deaths in older adults due to pancreatitis will continue to increase, but the ASDR is expected to decline. Conclusion: Over the past 30 years, the ASDR and age-standardized DALYs rate of pancreatitis in older adults have shown a decline globally, but the absolute burden continues to increase. Cross-national health inequalities persist. Therefore, it is necessary to develop targeted intervention measures and enhance awareness among this vulnerable population regarding the risk factors associated with pancreatitis.

9.
World Neurosurg ; 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38677647

BACKGROUND: Anaplastic oligodendroglioma (AOD) is a rare high-grade central nervous system tumor. The current research on prognostic prediction of AOD remains limited. This study aimed to identify prognostic factors and establish the nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with AOD. METHODS: Patients diagnosed with AOD between 1992 and 2020 were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. We performed univariate and multivariate Cox regression analyses to identify independent prognostic factors based on the training group. KM survival curves were used to compare the impact of various independent factors on patient prognosis. For OS and CSS, the nomograms were constructed, and verified by the validation group. C-index, ROC curves, calibration curves, and DCA were used to assess the discrimination, consistency and clinical value of the nomograms. RESULTS: A total of 1202 AOD patients were enrolled, being randomly divided into training (n=841) and validation (n=361) groups (7:3 ratio). Univariate and multivariate Cox analysis identified four significant independent factors (tumor site, age, surgery, chemotherapy). For OS and CSS, C-index were 0.731 (0.705-0.757) and 0.728 (0.701-0.754) in the training group, 0.688 (0.646-0.731) and 0.684 (0.639-0.729) in the validation group, respectively. ROC curves and Calibration curves showed good discrimination and consistency, respectively. In addition, the DCA curves showed the nomograms have good clinical benefits. CONCLUSIONS: We successfully established the nomograms to predict the OS and CSS for AOD patients. The nomograms showed good performance in prognostic prediction, assisting clinicians in evaluating patient prognosis and personalizing treatment plans.

10.
Immunology ; 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38634546

Allergic asthma is characterized by the polarization of Th2 cells and impaired immune regulation. Macrophages occupy the largest proportion of airway immune cells. This study aims to discover the mechanism that hinders the immune regulatory functions of airway macrophages. In this study, macrophages were isolated from cells in bronchoalveolar lavage fluids (BALF) collected from asthma patients and normal control (NC) subjects. The results indicated that macrophages occupied the largest portion of the cellular components in BALF. The frequency of IL-10+ macrophage was significantly lower in asthma patients than in NC subjects. The expression of IL-10 in macrophages of BALF was associated with the levels of asthma-related parameters. The immune-suppressive functions of BALF M0 cells were defective in asthma patients. The inducibility of IL-10 expression was impaired in BALF macrophages of asthma patients, which could be restored by exposing to CpG. In conclusion, the induction of IL-10 in macrophages of BALF in asthma patients was impaired, and it could be restored by exposure to CpG.

11.
Nurs Crit Care ; 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38639246

BACKGROUND: Pneumonia has a high incidence in traumatic brain injury (TBI) patients and lacks effective treatments. Early mobilization (EM) may be a potentially effective treatment. AIM: To explore the impact of EM on TBI-related pneumonia in the neurosurgical intensive care unit (NICU). METHOD: This study was a historical control study. 100 TBI patients who received EM intervention were prospectively included as the experimental group (EM cohort), and 250 TBI patients were retrospectively included as the control group. The propensity score matching (PSM) method was employed to balance baseline and minimize potential bias. The relationship between EM and TBI-related pneumonia was investigated by univariate and multivariate logistic regression, then further determined by subgroup analysis. The influence of other variables was excluded by interaction analyses. Finally, the effect of EM on the prognosis of TBI patients was analysed by comparing the Glasgow Coma Scale (GCS) and the hospital stay. RESULTS: After screening, 86 patients were included in the EM cohort and 199 patients were included in the control cohort. There were obvious differences between the two cohorts at baseline, and these differences were eliminated after PSM, when the incidence of pneumonia was significantly lower in the EM cohort than in the control cohort (35.0% vs. 61.9%, p < .001). Multivariate logistic regression showed that EM was an independent risk factor for TBI-related pneumonia and was significantly associated with a decreased incidence of pneumonia. This correlation was present in most subgroups and was not affected by other variables (p for interaction >.05). Patients in the EM cohort had shorter length of ICU stay (6 vs. 7 days, p = .017) and higher GCS at discharge (12 vs. 11, p = .010). CONCLUSION: EM is a safe and effective treatment for TBI patients in NICU, which can reduce the incidence of pneumonia, help to improve prognosis and shorten the length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Although the utilization rate of EM is low in TBI patients for various reasons, EM is still an effective method to prevent complications. Our study confirms that a scientific and detailed EM strategy can effectively reduce the incidence of pneumonia while ensuring the safety of TBI patients, which is worthy of further research and clinical application.

12.
Carbohydr Polym ; 335: 122078, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38616098

Microbial polysaccharides (MPs) are biopolymers secreted by microorganisms such as bacteria and fungi during their metabolic processes. Compared to polysaccharides derived from plants and animals, MPs have advantages such as wide sources, high production efficiency, and less susceptibility to natural environmental influences. The most attractive feature of MPs lies in their diverse biological activities, such as antioxidative, anti-tumor, antibacterial, and immunomodulatory activities, which have demonstrated immense potential for applications in functional foods, cosmetics, and biomedicine. These bioactivities are precisely regulated by their sophisticated molecular structure. However, the mechanisms underlying this precise regulation are not yet fully understood and continue to evolve. This article presents a comprehensive review of the most representative species of MPs, including their fermentation and purification processes and their biomedical applications in recent years. In particular, this work presents an in-depth analysis into the structure-activity relationships of MPs across multiple molecular levels. Additionally, this review discusses the challenges and prospects of investigating the structure-activity relationships, providing valuable insights into the broad and high-value utilization of MPs.


Anti-Bacterial Agents , Antioxidants , Animals , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Biological Transport , Fermentation , Functional Food
13.
Foods ; 13(8)2024 Apr 22.
Article En | MEDLINE | ID: mdl-38672949

In this study, the effects of microwave treatment on protease activity, dough properties and protein quality in sprouted wheat were investigated. Microwave treatment led to a significant (p < 0.05) reduction in protease activity in sprouted wheat. Proteases with a pH optimum of 4.4 (cysteine proteinases) were more susceptible to microwave heating, which contributed mostly to protease inactivation. Significant improvements (p < 0.05) in the dough properties and gluten quality of sprouted wheat were observed, which are probably attributable to the synergistic effectiveness of protease inactivation and heat-induced gluten cross-linking. After microwave treatment, the decrease in the solubility and extractability of protein in sprouted wheat indicated protein polymerization, which was induced by intermolecular disulfide bond cross-linking. The changes in gliadin were less pronounced due to the relatively low temperature of the microwave treatment. The cross-linking in sprouted wheat that occurred after microwave treatment seemed to mainly involve glutenin, especially B/C low-molecular-weight glutenin subunits (B/C-LMW-GSs) in the range of 30-50 kD.

14.
Front Neurosci ; 18: 1330634, 2024.
Article En | MEDLINE | ID: mdl-38595970

Introduction: The tendon-sheath actuated bending-tip system (TAB) has been widely applied to long-distance transmission scenes due to its high maneuverability, safety, and compliance, such as in exoskeleton robots, rescue robots, and surgical robots design. Due to the suitability of operation in a narrow or tortuous environment, TAB has demonstrated great application potential in the area of minimally invasive surgery. However, TAB involves highly non-linear behavior due to hysteresis, creepage, and non-linear friction existing on the tendon routing, which is an enormous challenge for accurate control. Methods: Considering the difficulties in the precise modeling of non-linearity friction, this paper proposes a novel fuzzy control scheme for the Euler-Lagrange dynamics model of TAB for achieving tracking performance and providing accurate friction compensation. Finally, the asymptotic stability of the closed-loop system is proved theoretically and the effectiveness of the controller is verified by numerical simulation carried out in MATLAB/Simulink. Results: The desired angle can be reached quickly within 3 s by adopting the proposed controller without overshoot or oscillation in Tracking Experiment, demonstrating the regulation performance of the proposed control scheme. The proposed method still achieves the desired trajectory rapidly and accurately without steady-state errors in Varying-friction Experiment. The angle errors generated by external disturbances are < 1 deg under the proposed controller, which returns to zero in 2 s in Anti-disturbance Experiment. In contrast, comparative controllers take more time to be steady and are accompanied by oscillating and residual errors in all experiments. Discussion: The proposed method is model-free control and has no strict requirement for the dynamics model and friction model. It is proved that advanced tracking performance and real-time response can be guaranteed under the presence of unknown bounded non-linear friction and time-varying non-linear dynamics.

15.
Int J Biol Macromol ; : 131771, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38688792

Xyloglucan (XG), as a natural biopolymer, possesses a sound biocompatibility and an impressive biodegradability, which are usually featured with abundant hydroxyl groups available for the bioconjugation with a bioactive moiety, suggesting a promising or unique value possibly applied in the field of biomedicine. In this study, XG was extracted from Tamarind seeds and subjected to four regioselective oxidation methods to introduce carboxyl groups onto the XG molecules for a bioconjugation with collagen. Galactose oxidase and reducing end aldehyde group oxidation mainly resulted in a low carboxylate content at ∼0.34 mmol/g, whereas the primary and secondary hydroxyl group oxidations would lead to a high carboxyl content at ∼0.84 mmol/g. The number-average molar mass (Mn) and weight-average molar mass (Mw) of XG were 8.8 × 105 g/mol and 1.1 × 106 g/mol, respectively. The oxidized XGs were then subjected to a further biofunctionalization with the collagen through EDC/NHS coupling, which exhibited a degree of conjugation rate, ranged from 50 % to 72 %. The collagen-conjugated at the C6 position of XGs exhibited the highest cell viability recorded at 168 % in promoting cell growth and proliferation after 72 h of culture, surpassing that of pure collagen recorded at 138 %, which may indeed suggest a promising value in a biomedical application.

16.
AAPS PharmSciTech ; 25(3): 58, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38472689

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.


Hydrocortisone , Printing, Three-Dimensional , Drug Liberation , Tablets/chemistry , Technology, Pharmaceutical/methods
17.
Neurosurg Rev ; 47(1): 118, 2024 Mar 16.
Article En | MEDLINE | ID: mdl-38491247

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.


Meningeal Neoplasms , Meningioma , Humans , Gene Expression Profiling , Meningioma/genetics , Single-Cell Gene Expression Analysis , DNA Copy Number Variations , Meningeal Neoplasms/genetics
18.
ACS Nano ; 18(11): 8125-8142, 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38451090

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of the articular cartilage and inflammation. Mesenchymal stem cells' (MSCs) transplantation in OA treatment is emerging, but its clinical application is still limited by the low efficiency in oriented differentiation. In our study, to improve the therapeutic efficiencies of MSCs in OA treatment by carbonic anhydrase IX (CA9) siRNA (siCA9)-based inflammation regulation and Kartogenin (KGN)-based chondrogenic differentiation, the combination strategy of MSCs and the nanomedicine codelivering KGN and siCA9 (AHK-CaP/siCA9 NPs) was used. In vitro results demonstrated that these NPs could improve the inflammatory microenvironment through repolarization of M1 macrophages to the M2 phenotype by downregulating the expression levels of CA9 mRNA. Meanwhile, these NPs could also enhance the chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating the pro-chondrogenic TGF-ß1, ACAN, and Col2α1 mRNA levels. Moreover, in an advanced OA mouse model, compared with BMSCs alone group, the lower synovitis score and OARSI score were found in the group of BMSCs plus AHK-CaP/siCA9 NPs, suggesting that this combination approach could effectively inhibit synovitis and promote cartilage regeneration in OA progression. Therefore, the synchronization of regulating the inflammatory microenvironment through macrophage reprogramming (CA9 gene silencing) and promoting MSCs oriented differentiation through a chondrogenic agent (KGN) may be a potential strategy to maximize the therapeutic efficiency of MSCs for OA treatment.


Cartilage, Articular , Mesenchymal Stem Cells , Osteoarthritis , Synovitis , Mice , Animals , Chondrogenesis , Nanomedicine , Osteoarthritis/drug therapy , Cell Differentiation , Inflammation/metabolism , Synovitis/metabolism , RNA, Messenger/metabolism
19.
Chem Commun (Camb) ; 60(32): 4354-4357, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38546230

Asymmetric synthesis of 3-sulfonylated 3-substituted oxindoles through the addition of sodium sulfinate salts to 3-bromo-3-substituted oxindoles has been achieved using chiral nickel complexes of N,N'-dioxides. This method facilitates the creation of diverse chiral sulfonyl oxindoles, several of which display promising anticancer properties. Notably, the catalyst demonstrates remarkable tolerance to water, crucial for maintaining enantioselectivity. Furthermore, the utilization of topographic steric maps of the catalysts offers valuable insights into the mechanism underlying enantioselection reversal.

20.
Int J Biol Macromol ; 265(Pt 1): 130900, 2024 Apr.
Article En | MEDLINE | ID: mdl-38499126

Nanocellulose-based biomaterials have gained significant attention in various fields, especially in medical and pharmaceutical areas, due to their unique properties, including non-toxicity, high specific surface area, biodegradability, biocompatibility, and abundant feasible and sophisticated strategies for functional modification. The biosafety of nanocellulose itself is a prerequisite to ensure the safe and effective application of biomaterials as they interact with living cells, tissues, and organs at the nanoscale. Potential residual endogenous impurities and exogenous contaminants could lead to the failure of the intended functionalities or even serious health complications if they are not adequately removed and assessed before use. This review summarizes the sources of impurities in nanocellulose that may pose potential hazards to their biosafety, including endogenous impurities that co-exist in the cellulosic raw materials themselves and exogenous contaminants caused by external exposure. Strategies to reduce or completely remove these impurities are outlined and classified as chemical, physical, biological, and combined methods. Additionally, key points that require careful consideration in the interpretation of the biosafety evaluation outcomes were discussed to ensure the safety and effectiveness of the nanocellulose-based biomaterials in medical applications.


Biocompatible Materials , Containment of Biohazards
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