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1.
Angew Chem Int Ed Engl ; : e202404374, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726699

ABSTRACT

Strategies for discovery of high-performance electrocatalysts are important to advance clean energy technologies. Metastable phases such as low temperature or interfacial structures that are difficult to access in bulk may offer such catalytically active surfaces. We report here that the suboxide Zr3O, which is formed at Zr-ZrO2 interfaces but does not appear in the experimental Zr-O phase diagram exhibits outstanding oxygen reduction reaction (ORR) performance surpassing that of benchmark Pt/C and most transition metal-based catalysts. Addition of Fe3C nanoparticles to give a Zr-Zr3O-Fe3C/NC catalyst (NC = nitrogen-doped carbon) gives a half-wave potential (E1/2) of 0.914 V, outperforming Pt/C and showing only a 3 mV decrease after 20,000 electrochemical cycles. A zinc-air battery (ZAB) using this cathode material has a high power density of 241.1 mW cm-2 and remains stable for over 50 days of continuous cycling, demonstrating potential for practical applications. Zr3O demonstrates that interfacial or other phases that are difficult to stabilize may offer new directions for the discovery of high-performance electrocatalysts.

2.
Sci Adv ; 10(19): eade9520, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38718112

ABSTRACT

Fast collective motions are widely present in biomolecules, but their functional relevance remains unclear. Herein, we reveal that fast collective motions of backbone are critical to the water transfer of aquaporin Z (AqpZ) by using solid-state nuclear magnetic resonance (ssNMR) spectroscopy and molecular dynamics (MD) simulations. A total of 212 residue site-specific dipolar order parameters and 158 15N spin relaxation rates of the backbone are measured by combining the 13C- and 1H-detected multidimensional ssNMR spectra. Analysis of these experimental data by theoretic models suggests that the small-amplitude (~10°) collective motions of the transmembrane α helices on the nanosecond-to-microsecond timescales are dominant for the dynamics of AqpZ. The MD simulations demonstrate that these collective motions are critical to the water transfer efficiency of AqpZ by facilitating the opening of the channel and accelerating the water-residue hydrogen bonds renewing in the selectivity filter region.


Subject(s)
Aquaporins , Molecular Dynamics Simulation , Water , Water/chemistry , Aquaporins/chemistry , Aquaporins/metabolism , Protein Conformation, alpha-Helical , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Nuclear Magnetic Resonance, Biomolecular , Escherichia coli Proteins
3.
Sci Adv ; 10(20): eadn7012, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758788

ABSTRACT

The ocean, a vast hydrogen reservoir, holds potential for sustainable energy and water development. Developing high-performance electrocatalysts for hydrogen production under harsh seawater conditions is challenging. Here, we propose incorporating a protective V2O3 layer to modulate the microcatalytic environment and create in situ dual-active sites consisting of low-loaded Pt and Ni3N. This catalyst demonstrates an ultralow overpotential of 80 mV at 500 mA cm-2, a mass activity 30.86 times higher than Pt-C and maintains at least 500 hours in seawater. Moreover, the assembled anion exchange membrane water electrolyzers (AEMWE) demonstrate superior activity and durability even under demanding industrial conditions. In situ localized pH analysis elucidates the microcatalytic environmental regulation mechanism of the V2O3 layer. Its role as a Lewis acid layer enables the sequestration of excess OH- ions, mitigate Cl- corrosion, and alkaline earth salt precipitation. Our catalyst protection strategy by using V2O3 presents a promising and cost-effective approach for large-scale sustainable green hydrogen production.

4.
Mikrochim Acta ; 191(6): 316, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38724679

ABSTRACT

An ultra-sensitive photoelectrochemical (PEC) sensor based on perovskite composite was developed for the determination of alkaline phosphatase (ALP) in human serum. In contrast to CsPbBr3 or Y6 that generated anodic current, the heterojunction of CsPbBr3/Y6 promoted photocarriers to separate and generated cathodic photocurrent. Ascorbic acid (AA) was produced by ALP hydrolyzing L-ascorbic acid 2-phosphate trisodium salt (AAP), which can combine with the holes on the photoelectrode surface, accelerating the transmission of photogenerated carriers, leading to enhanced photocurrent intensity. Thus, the enhancement of PEC current was linked to ALP activity. The PEC sensor exhibits good sensitivity for detection of ALP owing to the unique photoelectric properties of the CsPbBr3/Y6 heterojunction. The detection limit of the sensor was 0.012 U·L-1 with a linear dynamic range of 0.02-2000 U·L-1. Therefore, this PEC sensing platform shows great potential for the development of different PEC sensors.


Subject(s)
Alkaline Phosphatase , Ascorbic Acid , Electrochemical Techniques , Electrodes , Limit of Detection , Oxides , Photochemical Processes , Titanium , Alkaline Phosphatase/chemistry , Alkaline Phosphatase/blood , Alkaline Phosphatase/metabolism , Humans , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Ascorbic Acid/chemistry , Ascorbic Acid/blood , Ascorbic Acid/analogs & derivatives , Titanium/chemistry , Oxides/chemistry , Calcium Compounds/chemistry , Biosensing Techniques/methods
5.
BMC Plant Biol ; 24(1): 451, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789940

ABSTRACT

Root-knot nematodes (RKNs) infect host plants and obtain nutrients such as sugars for their own development. Therefore, inhibiting the nutrient supply to RKNs may be an effective method for alleviating root-knot nematode disease. At present, the pathway by which sucrose is unloaded from the phloem cells to giant cells (GCs) in root galls and which genes related to sugar metabolism and transport play key roles in this process are unclear. In this study, we found that sugars could be unloaded into GCs only from neighboring phloem cells through the apoplastic pathway. With the development of galls, the contents of sucrose, fructose and glucose in the galls and adjacent tissue increased gradually. SUT1, SUT2, SWEET7a, STP10, SUS3 and SPS1 may provide sugar sources for GCs, while STP1, STP2 and STP12 may transport more sugar to phloem parenchyma cells. At the early stage of Meloidogyne incognita infestation, the sucrose content in tomato roots and leaves increased, while the glucose and fructose contents decreased. SWEET7a, SPS1, INV-INH1, INV-INH2, SUS1 and SUS3 likely play key roles in root sugar delivery. These results elucidated the pathway of sugar unloading in tomato galls and provided an important theoretical reference for eliminating the sugar source of RKNs and preventing root-knot nematode disease.


Subject(s)
Plant Roots , Plant Tumors , Solanum lycopersicum , Tylenchoidea , Tylenchoidea/physiology , Animals , Solanum lycopersicum/parasitology , Solanum lycopersicum/metabolism , Plant Roots/parasitology , Plant Roots/metabolism , Plant Tumors/parasitology , Plant Diseases/parasitology , Sucrose/metabolism , Sugars/metabolism , Carbohydrate Metabolism
6.
Small ; : e2401053, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597730

ABSTRACT

Single-component electrocatalysts generally lead to unbalanced adsorption of OH- and urea during urea oxidation reaction (UOR), thus obtaining low activity and selectivity especially when oxygen evolution reaction (OER) competes at high potentials (>1.5 V). Herein, a cross-alignment strategy of in situ vertically growing Ni(OH)2 nanosheets on 2D semiconductor g-C3N4 is reported to form a hetero-structured electrocatalyst. Various spectroscopy measurements including in situ experiments indicate the existence of enhanced internal electric field at the interfaces of vertical Ni(OH)2 and g-C3N4 nanosheets, favorable for balancing adsorption of reaction intermediates. This heterojunction electrocatalyst shows high-selectivity UOR compared to pure Ni(OH)2, even at high potentials (>1.5 V) and large current density. The computational results show the vertical heterojunction could steer the internal electric field to increase the adsorption of urea, thus efficiently avoiding poisoning of strongly adsorbed OH- on active sites. A membrane electrode assembly (MEA)-based electrolyzer with the heterojunction anode could operate at an industrial-level current density of 200 mA cm-2. This work paves an avenue for designing high-performance electrocatalysts by vertical cross-alignments of active components.

7.
Drug Des Devel Ther ; 18: 1053-1081, 2024.
Article in English | MEDLINE | ID: mdl-38585257

ABSTRACT

Methods: Related studies on PD and ferroptosis were searched in Web of Science Core Collection (WOSCC) from inception to 2023. VOSviewer, CiteSpace, RStudio, and Scimago Graphica were employed as bibliometric analysis tools to generate network maps about the collaborations between authors, countries, and institutions and to visualize the co-occurrence and trends of co-cited references and keywords. Results: A total of 160 original articles and reviews related to PD and ferroptosis were retrieved, produced by from 958 authors from 162 institutions. Devos David was the most prolific author, with 9 articles. China and the University of Melbourne had leading positions in publication volume with 84 and 12 publications, respectively. Current hot topics focus on excavating potential new targets for treating PD based on ferroptosis by gaining insight into specific molecular mechanisms, including iron metabolism disorders, lipid peroxidation, and imbalanced antioxidant regulation. Clinical studies aimed at treating PD by targeting ferroptosis remain in their preliminary stages. Conclusion: A continued increase was shown in the literature within the related field over the past decade. The current study suggested active collaborations among authors, countries, and institutions. Research into the pathogenesis and treatment of PD based on ferroptosis has remained a prominent topic in the field in recent years, indicating that ferroptosis-targeted therapy is a potential approach to halting the progression of PD.


Subject(s)
Ferroptosis , Parkinson Disease , Humans , Parkinson Disease/drug therapy , Antioxidants , China , Lipid Peroxidation
8.
Front Endocrinol (Lausanne) ; 15: 1343704, 2024.
Article in English | MEDLINE | ID: mdl-38586461

ABSTRACT

Background: To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing. Methods: A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value. Results: The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older. Conclusion: Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age.


Subject(s)
Captopril , East Asian People , Hyperaldosteronism , Humans , Adult , Middle Aged , Hyperaldosteronism/diagnosis , Aldosterone , Essential Hypertension/diagnosis , China/epidemiology
9.
JBMR Plus ; 8(5): ziae047, 2024 May.
Article in English | MEDLINE | ID: mdl-38665314

ABSTRACT

Emerging evidence indicates a complex interplay between skeletal muscle and cognitive function. Despite the known differences between muscle quantity and quality, which can be measured via computed tomography (CT), the precise nature of their associations with cognitive performance remain underexplored. To investigate the links between muscle size and density and cognitive impairment (CI) in the older adults with hip fractures, we conducted a post hoc, cross-sectional analysis within a prospective cohort study on 679 patients with hip fractures over 65. Mini-Mental State Examination (MMSE) and routine hip CT imaging were utilized to assess cognition function and muscle characteristics in older adults with hip fractures. The CT scans provided data on cross-sectional area and attenuation for the gluteus maximus (G.MaxM) and the combined gluteus medius and minimus (G.Med/MinM). Participants were categorized into CI and non-CI groups based on education levels and MMSE scores. Multivariate logistic regressions, propensity score (PS) methods, and subgroup analysis were employed to analyze associations and validate findings. This study included 123 participants (81.6 ± 6.8 years, 74% female) with CI and 556 participants (78.5 ± 7.7 years, 72% female) without. Compared to the non-CI group, muscle parameters, especially density, were significantly lower in the CI group. Specifically, G.Med/Min muscle density, but not size was robustly associated with CI (odds ratio (OR) = 0.77, 95% confidence interval = 0.62-0.96, P = 0.02), independent of other medical situations. Sensitivity analysis corroborated that G.Med/Min muscle density was consistently lower in the CI group than the non-CI group, as evidenced in the PS matched (P = 0.024) and weighted cohort (P = 0.033). Enhanced muscle parameters, particularly muscle density in the G.Med/MinM muscle, correlate with a lower risk of CI. Muscle density demonstrates a stronger association with cognitive performance than muscle size, highlighting its potential as a key focus in future cognitive health research.

10.
BMC Oral Health ; 24(1): 471, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637799

ABSTRACT

OBJECT: This study aimed to investigate the changes in the translucency and color of four different multi-layered zirconia materials when the sintering temperature were inaccurate. MATERIALS AND METHODS: Two hundred zirconia samples (11 × 11 × 1.0 mm) of four multi-layered zirconia, Upcera TT-GT (UG), Upcera TT-ML (UM), Cercon xt ML (CX), and Lava Esthetic (LE), were divided into five subgroups according to the sintering temperature: L1 (5% lower temperature), L2 (2.5% lower temperature), R (recommended sintering temperature), H2 (2.5% higher temperature), H1 (5% higher temperature). After sintering, color coordinates were measured. Then the translucency parameter (TP) values, and the color differences (between the inaccurate sintering temperature and the recommended temperature) of each zirconia specimen were calculated. Statistical analysis was performed by using three-way ANOVA tests, the one-way ANOVA, and Tukey's post hoc test. RESULTS: Three-way ANOVA results showed that material type, sintering temperature, specimen section, and their interactions significantly influenced the TP values (except for the interactions of specimen section and sintering temperature) (P < .05). TP values of zirconia specimens were significantly different in the inaccurate sintering temperatures (P < .05), except for the cervical and body sections of UG group (P > .05). Compared with recommended sintering temperature, higher sintering temperature caused higher TP values for CX, but lower for LE. Three-way ANOVA results showed that material type, sintering temperature, and their interactions significantly influenced the ∆E00 values (P < .05). There were no significant differences in ∆E00 values of UM and CX groups at different inaccurate sintering temperatures, and were clinical imperception (except for UM-L1) (∆E00 < 1.25). ∆E00 values of all zirconia specimens showed clinically acceptable (∆E00 < 2.23). CONCLUSION: The deviations in sintering temperature significantly influenced the translucency and color of tested multi-layered zirconia. The trends of translucency in the multi-layered zirconia depended on material type and the color changes of all zirconia materials were clinically acceptable at inaccurate sintering temperatures.


Subject(s)
Ceramics , Zirconium , Humans , Temperature , Materials Testing , Surface Properties , Color
11.
Heliyon ; 10(7): e28606, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38571577

ABSTRACT

Hip fracture, increasing exponentially with age, is osteoporosis's most severe clinical consequence. Intertrochanteric fracture, one of the main types of hip fracture, is associated with higher mortality and morbidity. The current research hotspots lay in improving the treatment effect and optimizing the secondary stability after intertrochanteric fracture surgery. Cortex buttress reduction is a widely accepted method for treating intertrochanteric fracture by allowing the head-neck fragment to slide and rigidly contact the femoral shaft's cortex. Medial cortical support is considered a more effective option in treating young patients. However, osteo-degenerations features, including bone weakness and cortical thickness thinning, affect the performance of cortex support in geriatric intertrochanteric fracture treatment. Literature focusing on the age-specific difference in cortex performance in the fractured hip is scarce. We hypothesized that this osteo-19 degenerative feature affects the performance of cortex support in treating intertrochanteric fractures between the young and the elderly. We established twenty models for the old and the young with intertrochanteric fractures and performed static and dynamic simulations under one-legged stance and walking cycle conditions. The von Mises stress and displacement on the femur, proximal femoral nail anti-rotation (PFNA) implant, fracture plane, and the cutting volume of cancellous bone of the femur were compared. It was observed that defects in the anterior and posterior cortical bone walls significantly increase the stress on the PFNA implant, the displacement of the fracture surface, and cause a greater volume of cancellous bone to be resected. We concluded that ensuring the integrity and alignment of the anterior and posterior cortical bones is essential for elderly patients, and sagittal support is recommended. This finding suggests that the treatment method for intertrochanteric fracture may differ, considering the patient's age difference.

12.
Angew Chem Int Ed Engl ; : e202405498, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38651652

ABSTRACT

Three new nitrides La3MN5 (M=Cr, Mn, and Mo) have been synthesized using a high pressure azide route. These are the first examples of ternary Cs3CoCl5-type nitrides, and show that this (MN4)NLa3 antiperovskite structure type may be used to stabilise high oxidation-state transition metals in tetrahedral molecular [MN4]n- nitridometallate anions. Magnetic measurements confirm that Cr and Mo are in the M6+ state, but the M=Mn phase has an anomalously small paramagnetic moment and large cell volume. Neutron powder diffraction data are fitted using an anion-excess La3MnN5.30 model (space group I4/mcm, a=6.81587(9) Šand c=11.22664(18) Šat 200 K) in which Mn is close to the +7 state. Excess-anion incorporation into Cs3CoCl5-type materials has not been previously reported, and this or other substitution mechanisms may enable many other high oxidation state transition metal nitrides to be prepared.

14.
Anal Chem ; 96(16): 6180-6185, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38593062

ABSTRACT

Chemical recycling is a promising approach to reduce plastic pollution. Timely and accurate size analysis of produced nanoplastics is necessary to monitor the process and assess the quality of chemical recycling. In this work, a sandwich-type microelectrode sensor was developed for the size assessment of nanoplastics. ß-Mercaptoethylamine was modified on the microelectrode to enhance its surface positive charge density. Polystyrene (PS) nanoplastics were captured on the sensor through electrostatic interactions. Ferrocene was used as an electrochemical beacon and attached to PS via hydrophobic interactions. The results show a nonlinear dependence of the sensor's current response on the PS particle size. The size resolving ability of the microelectrode is mainly attributed to the small size of the electrode and the resulting attenuation of the electric field strength. For mixed samples with different particle sizes, this method can provide accurate average particle sizes. Through an effective pretreatment process, the method can be applied to PS nanoplastics with different surface properties, ensuring its application in evaluating different chemical recycling methods.

15.
Vaccines (Basel) ; 12(3)2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38543968

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global public health crisis [...].

16.
J Phys Chem A ; 128(12): 2383-2392, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38479752

ABSTRACT

Calculating the thermal rate constants of elementary combustion reactions is of great importance in theoretical chemistry. Machine learning has become a powerful, data-driven method for predicting rate constants nowadays. Recently, the molecular similarity combined with the topological indices were proposed to represent the hydrogen abstraction reactions of alkane [J. Chem. Inf. Model. 2023, 63, 5097-5106], which are, however, not applicable to alkane cracking reactions, another important class of combustion reactions, due to the cleavage of the C-C bond. In this work, a new feature selection scheme is proposed to describe both bimolecular and unimolecular cracking reactions. Molecular descriptors are elaborately selected individually for both reactants and products from those generated by the open-source software RDKit. Machine learning models combined with these molecular descriptors are proven to have the ability to accurately predict rate constants of both the hydrogen abstraction reactions of alkanes by CH3 and the alkane cracking reactions. The average deviation of the XGB-FNN model for prediction is around 60% for the hydrogen abstraction reactions of alkanes and 100% for the alkane cracking reactions. It is expected that the descriptors proposed in this work can be applied to build machine learning models for other reactions.

17.
Angew Chem Int Ed Engl ; 63(19): e202401364, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38465572

ABSTRACT

The development of high-purity and high-energy-density green hydrogen through water electrolysis holds immense promise, but issues such as electrocatalyst costs and power consumption have hampered its practical application. In this study, we present a promising solution to these challenges through the use of a high-performance bifunctional electrocatalyst for energy-efficient hydrogen production via coupled hydrazine degradation. The biphasic metal nitrides with highly lattice-matched structures are deliberately constructed, forming an enhanced local electric field between the electron-rich Ni3N and electron-deficient Co3N. Additionally, Mn is introduced as an electric field engine to further activate electron redistribution. Our Mn@Ni3N-Co3N/NF bifunctional electrocatalyst achieves industrial-grade current densities of 500 mA cm-2 at 0.49 V without degradation, saving at least 53.3 % energy consumption compared to conventional alkaline water electrolysis. This work will stimulate the further development of metal nitride electrocatalysts and also provide new perspectives on low-cost hydrogen production and environmental protection.

18.
Sci Rep ; 14(1): 6129, 2024 03 13.
Article in English | MEDLINE | ID: mdl-38480859

ABSTRACT

Cervical cancer is one of the most common gynecologic malignancies worldwide, necessitating the identification of novel biomarkers and therapeutic targets. This study aimed to investigate the significance of MKRN1 in cervical cancer and explore its potential as a diagnostic marker and therapeutic target. The results indicated that MKRN1 expression was up-regulated in cervical cancer tissues and correlated with advanced tumor stage, higher grade, and poor patient survival. Functional studies demonstrated that targeting MKRN1 effectively inhibited cell proliferation, migration, and invasion, highlighting its critical role in tumor progression and metastasis. Moreover, the knockdown of MKRN1 resulted in altered expression patterns of six transcription factor-encoding genes, revealing its involvement in gene regulation. Co-expression network analysis unveiled complex regulatory mechanisms underlying the effects of MKRN1 knockdown on gene expression. Furthermore, the results suggested that MKRN1 might serve as a diagnostic marker for personalized treatment strategies and a therapeutic target to inhibit tumor growth, metastasis, and overcome drug resistance. The development of MKRN1-targeted interventions might hold promise for advancing personalized medicine approaches in cervical cancer treatment. Further research is warranted to validate these findings, elucidate underlying mechanisms, and translate these insights into improved management and outcomes for cervical cancer patients.


Subject(s)
MicroRNAs , Uterine Cervical Neoplasms , Female , Humans , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Cervix Uteri/pathology , Gene Expression Regulation , Gene Expression Regulation, Neoplastic , HeLa Cells , Transcription Factors/metabolism , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism
19.
ACS Sens ; 9(3): 1331-1338, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38377515

ABSTRACT

Fuel cell gas sensors have emerged as promising advanced sensing devices owing to their advantageous features of low power consumption and cost-effectiveness. However, commercially available Pt/C electrodes pose significant challenges in terms of stability and accurate detection of low concentrations of target gases. Here, we introduce an efficient Cu-Pt/CrN-based fuel cell gas sensor, designed specifically for the ultrasensitive detection of hydrogen sulfide (H2S) at room temperature. Compared to the commercial Pt/C sensor, the Cu-Pt/CrN sensor exhibits excellent sensitivity (0.26 µA/ppm), with an increase in the selectivity by a factor of 2.5, and demonstrates good stability over a 2 month period. The enhanced sensing performance can be attributed to the modulation of the electronic arrangement of Pt by Cu, resulting in an augmentation of H2S adsorption. The Cu-Pt/CrN fuel cell gas sensor provides an opportunity for detecting parts per billion-level H2S in various applications.


Subject(s)
Gases , Hydrogen Sulfide , Temperature , Electrodes
20.
Biomater Sci ; 12(7): 1750-1760, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38375548

ABSTRACT

Diabetes mellitus (DM) is characterized by prolonged hyperglycemia, impaired vascularization, and serious complications, such as blindness and chronic diabetic wounds. About 25% of patients with DM are estimated to encounter impaired healing of diabetic wounds, often leading to lower limb amputation. Multiple factors are attributed to the non-healing of diabetic wounds, including hyperglycaemia, chronic inflammation, and impaired angiogenesis. It is imperative to develop more efficient treatment strategies to tackle healing difficulties in diabetic wounds. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising for diabetic wound healing considering their anti-inflammatory, pro-angiogenic and pro-proliferative activities. A histone deacetylase 7 (HDAC7)-derived 7-amino-acid peptide (7A) was shown to be highly effective for angiogenesis. However, it has never been investigated whether MSC-EVs are synergistic with 7A for the healing of diabetic wounds. Herein, we propose that MSC-EVs can be combined with 7A to greatly promote diabetic wound healing. The combination of EVs and 7A significantly improved the migration and proliferation of skin fibroblasts. Moreover, EVs alone significantly suppressed LPS-induced inflammation in macrophages, and notably, the combination treatment showed an even better suppression effect. Importantly, the in vivo study revealed that the combination therapy consisting of EVs and 7A in an alginate hydrogel was more efficient for the healing of diabetic wounds in rats than monotherapy using either EV or 7A hydrogels. The underlying mechanisms include suppression of inflammation, improvement of skin cell proliferation and migration, and enhanced collagen fiber disposition and angiogenesis in wounds. In summary, the MSC-EV-7A hydrogel potentially constitutes a novel therapy for efficient healing of chronic diabetic wounds.


Subject(s)
Diabetes Mellitus , Mesenchymal Stem Cells , Humans , Rats , Animals , Hydrogels/chemistry , Angiogenesis , Wound Healing , Inflammation
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