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1.
Dalton Trans ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38841816

ABSTRACT

The burgeoning interest in the field of molecular magnetism is to perceive the high magnetic anisotropy in different geometries of metal complexes and hence to draw a magneto-structural correlation. Despite a handful of examples to exemplify the magnetic anisotropy in various coordination geometries of mononuclear complexes, the magnetic anisotropies for two different coordination geometries are underexplored. Employing an appropriate synthetic strategy utilizing the ligand LH2 [2,2'-{(1E,1'E)-pyridine2,6-diyl-bis(methaneylylidine)}-bis(azaneylylidine)diphenol] and cobalt halide salts in a 1 : 2 stoichiometric ratio in the presence of triethylamine allowed us to report a new family of dinuclear cobalt complexes [CoII2X2(L)(P)(Q)]·S with varying terminal halides [X = Cl, P = CH3CN, Q = H2O, S = H2O (1), X = Br, P = CH3CN, Q = H2O, S = H2O (2), X = I, P = CH3CN, and Q = CH3CN (3)]. All these complexes are characterized through single crystal X-ray crystallography, which reveals their crystallization in the monoclinic system P21/n space group with nearly identical structural features. These complexes share vital components, including Co(II) centers, a fully deprotonated ligand [L]2-, halide ions, and solvent molecules. The [L]2- ligand contains two Co(II) centers, where phenolate oxygen atoms bridge the Co(II) centers, forming a Co2O2 four-membered ring. Co1 demonstrates a distorted pentagonal-bipyramidal geometry with axial positions for solvent molecules, while Co2 displays a distorted tetrahedral geometry involving phenolate oxygen atoms and halide ions. Temperature-dependent dc magnetic susceptibility measurements were conducted on 1-3 within a range of 2 to 300 K at 1 kOe. The χmT vs. T plots exhibit similar trends, with χmT values at 300 K higher than the spin-only value, signifying a significant orbital contribution. As the temperature decreases, χmT decreases smoothly in all the complexes; however, no clear saturation at low temperatures is observed. Field-dependent magnetization measurements indicate a rapid increase below 20 kOe, with no hysteresis and a low magnetic blocking temperature. DFT and CASSCF/NEVPT2 theoretical calculations were performed to perceive the magnetic interaction and single-ion anisotropies of Co(II) ions in various ligand-field environments.

2.
Gland Surg ; 13(5): 775-780, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38845830

ABSTRACT

Background: Thyroglossal duct cyst (TGDC) is a common congenital neck mass that is the most frequent cause of neck swelling in children. The traditional open Sistrunk procedure for TGDC often leaves a visible scar on the neck. Therefore, it is essential to consider the impact of neck scarring on the quality of life for children and adolescents. Our study aimed to assess the safety and efficacy of robotic TGDC resection using the bilateral axillo-breast approach (BABA) in adolescents. Case Description: A 16-year-old female patient presented with a neck mass (no pain or redness) that had been present for 3 years. The palpable neck mass moved with swallowing and there was no history of other significant medical conditions. An ultrasound scan of the neck indicated a weak hypoechoic area in the thyrohyoid region measuring 29 mm × 20 mm. Additionally, the ultrasonography of the thyroid gland showed no obvious abnormalities. A computer tomography (CT) scan confirmed a low-density lesion on the right hyoid bone, measuring 27 mm × 18 mm × 26 mm, consistent with a TGDC. We successfully performed a BABA robotic TGDC resection on the 16-year-old female adolescent who had a strong desire for scar-free surgery. Conclusions: BABA robotic TGDC resection could achieve the same surgical effect as conventional open surgery while providing better cosmetic outcomes, which are essential for the physical and mental well-being of teenagers. Therefore, BABA robotic TGDC resection may be a safe and feasible treatment option with excellent cosmetic results in adolescents.

3.
Article in English | MEDLINE | ID: mdl-38818581

ABSTRACT

Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(5): 481-485, 2024 May 15.
Article in Chinese | MEDLINE | ID: mdl-38802908

ABSTRACT

OBJECTIVES: To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation (PMV) due to different primary diseases. METHODS: A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022. According to the primary disease, they were divided into respiratory disease (RD) group, central nervous system (CNS) group, neuromuscular disease (NMD) group, and other disease group. The four groups were compared in terms of general information, treatment, and outcome. RESULTS: There were significant differences among the four groups in age, body weight, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, Pediatric Risk of Mortality III (PRISM Ⅲ) score, analgesic and sedative treatment, nutrition supply, rehabilitation treatment, tracheotomy, successful ventilator weaning, and outcomes (P<0.05). Compared with the RD group, the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment, and the CNS group had a significantly higher proportion of children receiving tracheotomy (P<0.008). Compared with the other disease group, the CNS group and the NMD group had significantly lower PELOD-2 and PRISM III scores, and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged (P<0.008). CONCLUSIONS: There are differences in clinical characteristics among children receiving PMV due to different etiologies. Most children in the RD group have a younger age, and children in the CNS group have a relatively good prognosis.


Subject(s)
Neuromuscular Diseases , Respiration, Artificial , Humans , Male , Female , Retrospective Studies , Child, Preschool , Infant , Neuromuscular Diseases/therapy , Neuromuscular Diseases/etiology , Child , Central Nervous System Diseases/etiology , Central Nervous System Diseases/therapy , Respiratory Tract Diseases/therapy , Respiratory Tract Diseases/etiology
5.
J Plant Physiol ; 299: 154276, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38801806

ABSTRACT

Ginsenoside F1 has high medicinal values, which is a kind of rare triterpene saponin isolated from Panax plants. The extremely low content of ginsenoside F1 in herbs has limited its research and application in medical field. In this work, we constructed a pathway in tobacco for the biosynthesis of ginsenoside F1 by metabolic engineering. Four enzyme genes (PnDDS, CYP716A47, CYP716S1 and UGT71A56) isolated from Panax notoginseng were introduced into tobacco. Thus, a biosynthetic pathway for ginsenoside F1 synthesis was artificially constructed in tobacco cells; moreover, the four exogenous genes could be expressed in the roots, stems and leaves of transgenic plants. Consequently, ginsenoside F1 and its precursors were successfully synthesized in the transgenic tobacco, compared with Panax plants, the content of ginsenoside F1 in transgenic tobacco was doubled. In addition, accumulation of ginsenoside F1 and its precursors in transgenic tobacco shows organ specificity. Based on these results, a new approach was established to produce rare ginsenoside F1; meanwhile, such strategy could also be employed in plant hosts for the heterologous synthesis of other important or rare natural products.

6.
J Agric Food Chem ; 72(22): 12607-12617, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38785045

ABSTRACT

To explore the roles of loops around active pocket in the reuteran type 4,6-α-glucanotransferase (StGtfB) from S. thermophilus, they were individually or simultaneously replaced with those of an isomalto/maltopolysaccharides type 4,6-α-glucanotransferase from L. reuteri. StGtfB with the replaced loops A1, A2 (A1A2) and A1, A2, B (A1A2B), respectively, showed 1.41- and 0.83-fold activities of StGtfB. Two mutants reduced crystallinity and increased starch disorder at 2, 4, and 8 U/g more than StGtfB and increased DP ≤ 5 short branches of starch by 38.01% at 2 U/g, much more than StGtfB by 4.24%. A1A2B modified starches had the lowest retrogradation over 14 days. A1A2 modified starches had the highest percentage of slowly digestible fractions, ranging from 40.32% to 43.34%. StGtfB and its mutants bind substrates by hydrogen bonding and van der Waals forces at their nonidentical amino acid residues, suggesting that loop replacement leads to a different conformation and changes activity and product structure.


Subject(s)
Bacterial Proteins , Glycogen Debranching Enzyme System , Starch , Streptococcus thermophilus , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Streptococcus thermophilus/enzymology , Streptococcus thermophilus/genetics , Streptococcus thermophilus/chemistry , Streptococcus thermophilus/metabolism , Substrate Specificity , Starch/metabolism , Starch/chemistry , Glycogen Debranching Enzyme System/chemistry , Glycogen Debranching Enzyme System/metabolism , Glycogen Debranching Enzyme System/genetics , Catalytic Domain , Kinetics , Biocatalysis
7.
Materials (Basel) ; 17(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38793256

ABSTRACT

The experimental and numerical simulation analysis of a TiAl alloy by laser metal deposition technology is presented in this paper. The research examines the macroscopic morphology, microstructure, and mechanical properties of samples as laser power varies. It also delves into how the temperature field and residual stress evolve under different laser powers. The results reveal that the microstructure of samples is mainly composed of α2-Ti3Al phase and a γ-TiAl phase and that the details of the microstructure are significantly affected by laser power. As laser power increases, coarse lamellar structure content increases, corresponding to a decrease in α2 phase content. The deposited layer hardness ranges from 550 HV to 600 HV, and the average deposition layer hardness decreases with increased laser power. Simulation results predict the molten pool's size, temperature, and residual stresses. A significant increase in the molten pool size is observed when the laser power exceeds 1000 W, and the measured molten pool depths correspond closely to simulation predictions. However, significant tensile stresses are generated in the deposition layer due to high cooling rates, mainly in the x direction. Cracks are observed on the surface of the deposition layer at all laser powers.

8.
Macromol Rapid Commun ; : e2400251, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813898

ABSTRACT

Core-shell tecto dendrimers (CSTDs) with excellent physicochemical properties and good tumor penetration and gene transfection efficiency have been demonstrated to have the potential to replace high-generation dendrimers in biomedical applications. However, their characterization and related biological properties of CSTDs for enhanced tumor penetration and gene delivery still lack in-depth investigation. Herein, we attempted to design three types of dual-responsive CSTDs for thorough physicochemical characterization and investigation of their tumor penetration and gene delivery efficiency. Three types of CSTDs were prepared through phenylborate ester bonds of phenylboronic acid (PBA)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and monose (galactose, glucose or mannose)-conjugated G3 PAMAM dendrimers as shells and thoroughly characterized via NMR and other techniques. We show that the produced CSTDs displayed strong correlation signals between the PBA and monose protons and similar hydrodynamic diameters, and possess dual reactive oxygen species- and pH-responsivenesses. The dual-responsive CSTDs were proven to have structure-dependent tumor penetration property and gene delivery efficiency in terms of small interference RNA for gene silencing and plasmid DNA for gene editing, thus revealing a great potential for different biomedical applications. This article is protected by copyright. All rights reserved.

9.
Front Surg ; 11: 1368493, 2024.
Article in English | MEDLINE | ID: mdl-38533091

ABSTRACT

Objective: Chronic hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) results in poor neurological outcomes and cognitive deficits. Currently, the main treatments for chronic hydrocephalus include ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS); however, the optimal treatment for chronic hydrocephalus after aSAH remains controversial. Method: The records of 82 patients were retrospectively analyzed, and the patients were divided into VPS and LPS groups based on surgical methods. The efficacy, shunt successful rate and complications were compared. The assessments of treatment efficacy included the Evans index score (EIS), Keifer's hydrocephalus score (KHS), Mini-Mental State Examination (MMSE) score and functional independence measure (FIM). Patients were followed up for three months to observe the postoperative curative effects and complications. Results: The rate of shunt obstruction was significantly higher in the LPS group than that in the VPS group (p < 0.05), and the shunt successful rate was significantly higher in the VPS group than that in the LPS group (p < 0.05). The total rate of complications was 24.4% for LPS and 39% for VPS. The improvements in EIS, KHS, MMSE, and FIM within each group after the shunt were significantly different compared to those before shunt (p < 0.05). Compared to those in the LPS group, the improvements in EIS, KHS, MMSE, and FIM were significantly different in the VPS group after shunt (p < 0.05). Conclusion: Compared with LPS, VPS in the treatment for chronic hydrocephalus after aSAH had greater therapeutic efficacy, as indicated by improved radiological outcomes, improved shunt successful rate, improved clinical outcomes, and improved quality of life. Therefore, we believe that VPS is the preferred treatment option for chronic hydrocephalus after aSAH, while LPS should only be used as an alternative to VPS.

10.
Hepatol Commun ; 8(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38551384

ABSTRACT

BACKGROUND: Alcohol-associated liver disease (ALD) is a major health care challenge worldwide with limited therapeutic options. Although mesenchymal stem/stromal cells (MSCs) represent a newly emerging therapeutic approach to treat ALD, thus far, there have been extensive efforts to try and enhance their efficacy, including genetically engineering MSCs. FGF21, an endocrine stress-responsive hormone, has been shown to regulate energy balance, glucose, and lipid metabolism and to enhance the homing of MSCs toward injured sites. Therefore, the purpose of this study was to investigate whether MSCs that overexpress FGF21 (FGF21-MSCs) improve the therapeutic effect of MSCs in treating ALD. METHODS: Human umbilical cord-derived MSCs served as the gene delivery vehicle for the FGF21 gene. Human umbilical cord-derived MSCs were transduced with the FGF21 gene using lentiviral vectors to mediate FGF21 overexpression. We utilized both chronic Lieber-DeCarli and Gao-binge models of ethanol-induced liver injury to observe the therapeutic effect of FGF21-MSCs. Liver injury was phenotypically evaluated by performing biochemical methods, histology, and inflammatory cytokine levels. RESULTS: Compared with MSCs alone, administration of MSCs overexpressing FGF21(FGF21-MSCs) treatment significantly enhanced the therapeutic effect of ALD in mice, as indicated by the alleviation of liver injury with reduced steatosis, inflammatory infiltration, oxidative stress, and hepatic apoptosis, and the promotion of liver regeneration. Mechanistically, FGF21 could facilitate the immunomodulatory function of MSCs on macrophages by setting metabolic commitment for oxidative phosphorylation, which enables macrophages to exhibit anti-inflammatory inclination. CONCLUSIONS: Our data elucidate that MSC modification by FGF21 could enhance their therapeutic effect in ALD and may help in the exploration of effective MSCs-based cell therapies for the treatment of ALD.


Subject(s)
Fibroblast Growth Factors , Liver Diseases, Alcoholic , Animals , Humans , Mice , Ethanol , Fibroblast Growth Factors/genetics , Liver Diseases, Alcoholic/therapy , Macrophages , Stromal Cells
11.
J Asian Nat Prod Res ; : 1-8, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38515328

ABSTRACT

Two new sesquiterpenoid glycosides, 8α (H)-eudesmane-1,3,11 (13)-triene-2-one -12-O-ß-D-glucopyranoside (1) and dmetelisproside B (2), together with ten known compounds (3-12) were isolated from calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF). Their structures were unambiguously elucidated through HR-ESI-MS, UV, IR, and NMR spectral data. Compounds 1, 10, and 12 exhibited DPPH scavenging ability with IC50 values of 33.69 ± 6.65, 6.29 ± 0.06, and 25.66 ± 3.06 µM, respectively. Additionally, 10 and 12 demonstrated weak α-glucosidase inhibition activity with IC50 values of 250.9 ± 6.60 and 347.6 ± 2.48 µM, respectively.

12.
Pediatr Neurol ; 154: 70-78, 2024 May.
Article in English | MEDLINE | ID: mdl-38552337

ABSTRACT

BACKGROUND: This study aimed to evaluate the effects of a nurse-led cognitive behavioral intervention for parents of children with epilepsy (CWE). METHODS: The study recruited 238 CWE from the neurology ward of Xiangya Hospital from March 2019 to August 2022. According to the interventions after discharge, the children and their parents were randomly divided into 117 parent-child dyads in the intervention group and 121 parent-child dyads in the control group. The seizure severity and treatment compliance in CWE as well as the parents' psychological states and satisfaction with the care provided by nurses were compared before and after intervention. RESULTS: The follow-up six months after discharge showed that the seizure frequency among CWE in the intervention group was significantly less than the controls (P = 0.048). Compared with the controls, the intervention group also reported fewer symptoms of anxiety and depression, better sleep quality, and more positive attitudes toward epilepsy, as well as higher nursing satisfaction (P < 0.001). The correlation analysis indicated the correlation of CWE's seizure severity was correlated with the compliance, parents' psychological states, and parents' satisfaction with the care provided by nurses. CONCLUSIONS: The adoption of the nurse-led cognitive behavioral intervention on parents of CWE can improve the parents' mental health status and their satisfaction with the nurses, which can have a positive association with the seizure severity of CWE. In light of this information, this nursing intervention may be a new method for the long-term disease management of CWE.


Subject(s)
Epilepsy , Nurse's Role , Humans , Parents/psychology , Epilepsy/diagnosis , Seizures , Cognition
13.
PLoS One ; 19(3): e0300677, 2024.
Article in English | MEDLINE | ID: mdl-38502660

ABSTRACT

This study aims to integrate research in the field of aerobics and mental health through the visualization analysis method of the CiteSpace map, to clarify the impact of aerobics on mental health and stress levels. Firstly, based on the literature method, pieces of literature related to aerobics and mental health are searched and collected. Secondly, the visualization analysis method of the CiteSpace map is employed to summarize and analyze the contents of the literature, involving statistical analysis of the annual number of publications, analysis of author characteristics, and analysis of publishing institution characteristics. In addition, keyword co-occurrence analysis and keyword cluster analysis are also conducted in related research fields. Among them, the Log-Likelihood Ratio is used in keyword cluster analysis. Finally, the results are analyzed using the visualization analysis method of the CiteSpace map and the statistics-based comprehensive results. The results demonstrate that in the recent 20 years, the average annual number of articles in related fields exceeds 190. The high-yield authors are distributed in economically developed areas, and the cooperation among authors is scattered. In the keyword clustering results, a total of 77 cluster labels are obtained. The Q value of the clustering module is 0.89, and the average clustering profile silhouette (S) value is 0.92, indicating that the clustering structure is significant and the results are reasonable. The aerobics cluster contains the most closely related keywords, covering mental health and stress levels. Data analysis based on existing studies reveals that aerobics has a significant impact on mental health and stress levels. Individuals participating in aerobics show obvious improvement in mental health inventory (MHI) scores (t(100) = 4.32, p<0.05). Individuals participating in aerobics present a remarkable reduction in the questionnaire evaluation of stress levels (t(100) = -3.91, p<0.05). This study's results support aerobics' positive effects on mental health and stress levels.


Subject(s)
Data Analysis , Mental Health , Humans , Cluster Analysis , Health Facilities , Publishing
14.
Heliyon ; 10(4): e26208, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38434087

ABSTRACT

Background: The core competencies of nursing students have gradually become the focus of attention of nursing educators. Nursing skills competitions are an important form of educational and teaching activity in universities and the nursing track at the Shandong Provincial University Students' Medical Technical Skills Competition gives nursing students an opportunity to demonstrate their clinical skills and knowledge. This study aims to describe the organisation and procedures of the nursing track, analyse the competition results and explore the impact the competition has on the core competencies of the nursing students. This will provide new ideas for future nursing professional education. Methods: Statistical analysis of the competition results was performed as a means of understanding the current status of theoretical knowledge and clinical skills of nursing students in Shandong Province. The impact of the competition on the core competencies of participating students was analysed by distributing questionnaires to universities in Shandong Province that participated in the competition. Results: 14 universities with nursing programmes participated in the competition, including eight public universities and six private universities. 220 questionnaires were distributed to nursing students at the participating universities and 218 were ultimately included, demonstrating an efficiency rate of 99.09%. Conclusions: The 2022 nursing track included the addition of a comprehensive written examination as a means of judging the competencies of nursing students in Shandong Province from a variety of aspects. Skills competitions are effective for improving the core competencies of nursing students and they will become an important means for nursing educators to reform education and improve the core competencies of nursing students in the future.

15.
Eur Spine J ; 2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38431753

ABSTRACT

OBJECTIVE: To evaluate the correlation between dual-energy CT (DECT) virtual calcium free (VNCA), CT attenuation, the ratio and difference of VNCA to CT attenuation, and Pfirrmann grading of lumbar disc degeneration. METHODS: A retrospective analysis on 135 intervertebral discs from 30 patients who underwent DECT and MR. Discs was graded using the Pfirrmann system. ROIs on the sagittal plane assessed HU value, VNCA value, Rho value, Z value, R-VH value, and D-VH value. Correlation, grade differences, and multivariate regression models were assessed. Diagnostic performance and cut-off values were determined using AUC. RESULTS: VNCA (r = 0.589, P < 0.001), R-VH (r = 0.622, P < 0.001), and D-VH (r = 0.613, P < 0.001) moderately correlated with Pfirrmann grading. HU (r = 0.388, P < 0.001), Rho (r = 0.142, P = 0.102), and Z (r = -0.125, P = 0.153) showed a weak correlation. R-VH, D-VH, and VNCA had significantly higher correlation than HU. Statistically significant differences were observed in P values of VNCA, HU, R-VH, and D-VH in relative groups (P < 0.05), but not in Rho and Z values (P > 0.05). R-VH and D-VH had significant differences between Pfirrmann grades 1 and 2, and grades 2 and 3 (early stage) (P < 0.05). AUC readings of R-VH and D-VH (≥2, ≥3, ≥4) were higher. The multivariate model IVNCa + CT had the highest AUC. CONCLUSION: The new quantitative indices R-VH value and D-VH value of DECT have advantages over VNCA value and HU value in evaluating early-stage disc degeneration (≥2 grades, ≥3 grades). The multivariate model IVNCa + CT has the best AUC values for evaluating disc degeneration at all stages.

16.
Mol Ther ; 32(4): 1144-1157, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38310354

ABSTRACT

The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.


Subject(s)
Mesenchymal Stem Cells , Superoxide Dismutase , Mice , Humans , Animals , Cell Differentiation , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Adipocytes , Mesenchymal Stem Cells/metabolism
17.
Adv Mater ; 36(19): e2400310, 2024 May.
Article in English | MEDLINE | ID: mdl-38298099

ABSTRACT

Rapid-acting, convenient, and broadly applicable medical materials are in high demand for the treatment of extensive and intricate tissue injuries in extremely medical scarcity environment, such as battlefields, wilderness, and traffic accidents. Conventional biomaterials fail to meet all the high criteria simultaneously for emergency management. Here, a multifunctional hydrogel system capable of rapid gelation and in situ spraying, addressing clinical challenges related to hemostasis, barrier establishment, support, and subsequent therapeutic treatment of irregular, complex, and urgent injured tissues, is designed. This hydrogel can be fast formed in less than 0.5 s under ultraviolet initiation. The precursor maintains an impressively low viscosity of 0.018 Pa s, while the hydrogel demonstrates a storage modulus of 0.65 MPa, achieving the delicate balance between sprayable fluidity and the mechanical strength requirements in practice, allowing flexible customization of the hydrogel system for differentiated handling and treatment of various tissues. Notably, the interactions between the component of this hydrogel and the cell surface protein confer upon its inherently bioactive functionalities such as osteogenesis, anti-inflammation, and angiogenesis. This research endeavors to provide new insights and designs into emergency management and complex tissue injuries treatment.


Subject(s)
Biocompatible Materials , Hydrogels , Hydrogels/chemistry , Biocompatible Materials/chemistry , Humans , Animals , Viscosity , Mice , Osteogenesis/drug effects
18.
Chemistry ; 30(25): e202400088, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38407545

ABSTRACT

P2-type layered manganese-based oxides have attracted considerable interest as economical, cathode materials with high energy density for sodium-ion batteries (SIBs). Despite their potential, these materials still face challenges related to sluggish kinetics and structural instability. In this study, a composite cathode material, Na0.67Ni0.23Mn0.67V0.1O2@Na3V2O2(PO4)2F was developed by surface-coating P2-type Na0.67Ni0.23Mn0.67V0.1O2 with a thin layer of Na3V2O2(PO4)2F to enhance both the electrochemical sodium storage and material air stability. The optimized Na0.67Ni0.23Mn0.67V0.1O2@5wt %Na3V2O2(PO4)2F exhibited a high discharge capacity of 176 mA h g-1 within the 1.5-4.1 V range at a low current density of 17 mA g-1. At an increased current density of 850 mA g-1 within the same voltage window, it still delivered a substantial initial discharge capacity of 112 mAh g-1. These findings validate the significant enhancement of ion diffusion capabilities and rate performance in the P2-type Na0.67Ni0.33Mn0.67O2 material conferred by the composite cathode.

19.
J Robot Surg ; 18(1): 88, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38386236

ABSTRACT

Transoral vestibular robotic thyroidectomy can really make the patient's body surface free of scar. This study aimed to compare the surgical and patient-related outcomes between the transoral vestibular robotic thyroidectomy and traditional low-collar incision thyroidectomy. The clinical data of 120 patients underwent transoral vestibular robotic thyroidectomy (TOVRT) or traditional low-collar incision thyroidectomy (TLCIT) were collected from May 2020 to October 2021. Propensity score matching analysis was used to minimize selection bias. All these patients were diagnosed with papillary thyroid carcinoma (PTC) through ultrasound-guided fine-needle aspiration prior to surgical intervention and surgical plan was tailored for each patient. An intraoperative recurrent laryngeal nerve (RLN) detection system was used in all patients, whose RLNs were identified and protected. We performed transoral vestibular robotic thyroidectomy with three intraoral incisions. Additional right axillary fold incisions were adopted occasionally to enhance fine reverse traction of tissue for radical tumor dissection. Clinical data including gender, age, tumor size, BMI, operation time, postoperative drainage volume and time, pain score, postoperative length of stay (LOS),number of lymph nodes removed, complications, and medical expense were observed and analyzed. Propensity score matching was used for 1:1 matching between the TOVRT group and the TLCIT group. All these patients accepted total thyroidectomy(or lobectomy) plus central lymph node dissection and all suffered from PTC confirmed by postoperative pathology. No conversion to open surgery happened in TOVRT group. The operative time of TOVRT group was longer than that of TLCIT group (P < 0.05). The postoperative drainage volume of TOVRT group was more than that of TLCIT group (P < 0.05). The drainage tube placement time of TOVRT group were longer than that of TLCIT group (P < 0.05). Significant differences were also found in intraoperative bleeding volume, pain score and medical expense between the two groups (P < 0.05). The incidence of perioperative common complications such as hypoparathyroidism and vocal cord paralysis in the two groups was almost identical (P > 0.05). However, there were some specific complications such as surgical area infection (one case), skin burn (one case), oral tear (two cases), and paresthesia of the lower lip and the chin (two cases) were found in TOVRT group. Obviously, the postoperative cosmetic effect of the TOVRT group was better than TLCIT group (P < 0.05). TOVRT is safe and feasible for low to moderate-risk PTC patients and is a potential alternative for patients who require no scar on their neck. Patients accepted TOVRT can get more satisfaction and have less psychologic injury caused by surgery.


Subject(s)
Neoplasms , Robotic Surgical Procedures , Humans , Thyroidectomy/adverse effects , Robotic Surgical Procedures/methods , Drainage , Cicatrix , Pain
20.
J Hepatol ; 80(6): 913-927, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38340812

ABSTRACT

BACKGROUND & AIMS: Treatments directly targeting fibrosis remain limited. Given the unique intrinsic features of macrophages and their capacity to engraft in the liver, we genetically engineered bone marrow-derived macrophages with a chimeric antigen receptor (CAR) to direct their phagocytic activity against hepatic stellate cells (HSCs) in multiple mouse models. This study aimed to demonstrate the therapeutic efficacy of CAR macrophages (CAR-Ms) in mouse models of fibrosis and cirrhosis and to elucidate the underlying mechanisms. METHODS: uPAR expression was studied in patients with fibrosis/cirrhosis and in murine models of liver fibrosis, including mice treated with carbon tetrachloride, a 5-diethoxycarbonyl-1, 4-dihydrocollidine diet, or a high-fat/cholesterol/fructose diet. The safety and efficacy of CAR-Ms were evaluated in vitro and in vivo. RESULTS: Adoptive transfer of CAR-Ms resulted in a significant reduction in liver fibrosis and the restoration of function in murine models of liver fibrosis. CAR-Ms modulated the hepatic immune microenvironment to recruit and modify the activation of endogenous immune cells to drive fibrosis regression. These CAR-Ms were able to recruit and present antigens to T cells and mount specific antifibrotic T-cell responses to reduce fibroblasts and liver fibrosis in mice. CONCLUSION: Collectively, our findings demonstrate the potential of using macrophages as a platform for CAR technology to provide an effective treatment option for liver fibrosis. CAR-Ms might be developed for treatment of patients with liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis is an incurable condition that afflicts millions of people globally. Despite the clear clinical need, therapies for liver fibrosis are limited. Our findings provide the first preclinical evidence that chimeric antigen receptor (CAR)-macrophages (CAR-Ms) targeting uPAR can attenuate liver fibrosis and cirrhosis. We show that macrophages expressing this uPAR CAR exert a direct antifibrotic effect and elicit a specific T-cell response that augments the immune response against liver fibrosis. These findings demonstrate the potential of using CAR-Ms as an effective cell-based therapy for the treatment of liver fibrosis.


Subject(s)
Disease Models, Animal , Liver Cirrhosis , Macrophages , Receptors, Chimeric Antigen , Animals , Mice , Macrophages/immunology , Macrophages/metabolism , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Liver Cirrhosis/therapy , Liver Cirrhosis/immunology , Humans , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/immunology , Male , Mice, Inbred C57BL , Female , Adoptive Transfer/methods
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