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1.
Neural Regen Res ; 16(1): 143-149, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788469

RESUMO

Veins are easy to obtain, have low immunogenicity, and induce a relatively weak inflammatory response. Therefore, veins have the potential to be used as conduits for nerve regeneration. However, because of the presence of venous valves and the great elasticity of the venous wall, the vein is not conducive to nerve regeneration. In this study, a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats. Compared with rats given the vein graft alone, rats given the tissue engineered nerve graft had an improved sciatic static index, and a higher amplitude and shorter latency of compound muscle action potentials. Furthermore, rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone. However, the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation. In summary, although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects, it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects. This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2016-x9-07) on September 7, 2016.

2.
Ann Lab Med ; 41(1): 68-76, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829581

RESUMO

BACKGROUND: Using commutable external quality assessment (EQA) materials is important for monitoring successful harmonization efforts. We assessed the commutability of four human serum pool (HSP) preparations to identify candidate EQA materials for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity measurement. METHODS: One set each of 85 clinical samples (CSs) was collected for ALT and AST activity measurement. The 15 candidate EQA materials included four types of HSP preparations (A to D): materials A, C, and D contained human original recombinant (HOR) aminotransferases; materials B was mixed leftover samples. The CSs and 15 candidate EQA materials were analyzed using seven routine assays, and the ln-transformed results were analyzed in 21 assay pairs. Commutability was assessed using Deming regression, with a 95% prediction interval (CLSI approach) and the difference in bias with an error component model (International Federation of Clinical Chemistry and Laboratory Medicine [IFCC] approach). RESULTS: For ALT, all materials were commutable for 14-21 assay pairs according to the CLSI and IFCC approaches. For AST, B01-03 showed commutability for 14-21 assay pairs, and C01-03 and D01-03 showed commutability for no less than 10 assay pairs according to the two approaches. A01-06 were commutable for 9-16 assay pairs according to the CLSI approach, but for 6-9 assay pairs according to the IFCC approach. CONCLUSIONS: Mixed leftover samples showed desirable commutability characteristics as candidate EQA materials for routine aminotransferase activity measurements. Human serum bases supplemented with HOR were commutable for most routine ALT activity measurements.

3.
Methods Mol Biol ; 2187: 131-145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32770505

RESUMO

The traditional methods to study lipid rafts and their association with membrane proteins are based mainly on the isolation of a detergent-resistant membrane by biochemical fractionation. However, the use of detergents may induce lipid segregation and/or redistribution of membrane proteins during the process of sample preparation. Here, we describe a detergent-free method to study the glycolipid and growth factor receptor interaction and their association with lipid rafts. This method combines the biochemical and immunoblotting tools with confocal microscopic imaging, which allows for evaluation and verification of the membrane protein interaction and association with the lipid rafts components in a multifaceted manner.

4.
Methods Mol Biol ; 2182: 179-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32894496

RESUMO

Antimicrobial susceptibilities testing is used for evaluating and monitoring the resistance of bacteria to antimicrobial agents. Here we describe three commonly used methods for testing susceptibility to antimicrobial agents in Salmonella, including the disk diffusion method, the broth microdilution method, and the agar dilution method.

5.
Talanta ; 221: 121421, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076058

RESUMO

Two-dimensional Cd-MOF/Tb3+ (Cd-MOF = [Cd (µ-2,3-pdc) (H2O)3]n (2,3-pdc = 2,3-pyridine dicarboxylic acid)) fluorescent nanosheets with the thickness of 1.4 nm were successfully synthesized by a simple solution route with subsequent ultrasonic exfoliation at room temperature. It was found that as-obtained Cd-MOF/Tb3+ ultrathin nanosheets could be homogeneously dispersed in aqueous system to form a sol with excellent stability. Also, the fluorescence intensity of nanosheets remarkably increased to almost 12 times higher than that of Cd-MOF/Tb3+ microsheets before exfoliation. Further investigations uncovered that the above strong fluorescence of Cd-MOF/Tb3+ nanosheets could be highly sensitively quenched by Cefixime antibiotic in aqueous solution without interference from other antibiotics, amino acids and pesticides. Hence, the as-obtained ultrathin Cd-MOF/Tb3+ nanosheets could be prepared as a highly selective and sensitive fluorescence probe for the detection of Cefixime in aqueous system. Compared with the bulk Cd-MOF/Tb3+ sensor, the Cd-MOF/Tb3+ ultrathin nanosheets sensor exhibited a far lower detection limit down to 26.7 nM for CFX. Also, the as-obtained nanosheets sensor presented satisfactory recovery ranging from 98.07% to 103.01% and acceptable repeatability (RSD < 6.29%, n = 6) for the detection of CFX in domestic water. Furthermore, the sensing mechanism studies revealed that the high selection of the present fluorescent probe for detection of CFX should be attributed to the cooperation of the photoinduced electron transfer and the inner filter effect.

6.
Chem Pharm Bull (Tokyo) ; 68(10): 946-953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999146

RESUMO

In the present study, a novel cocrystal of felodipine (FEL) and ß-resorcylic acid (ßRA) was developed. We specially focused on the change of binding pattern with bovine serum albumin (BSA) induced by cocrystallization of FEL with ßRA. The solid characterizations and density functional theory (DFT) simulation verified that FEL-ßRA cocrystal formed in equimolar ratio (1 : 1 M ratio) through C=O…H-O hydrogen bond between C=O group in FEL and O-H group in ßRA. The binding interactions between FEL-ßRA system and BSA were studied using fluorescence spectral and molecular docking methods. Two guest molecule systems, including a physical mixture of FEL and ßRA and FEL-ßRA cocrystal were performed binding to BSA in molecular docking. According to the Kb and binding energy, the supramolecular form of FEL-ßRA system was retained during binding to BSA. Molecular docking simulation suggested that FEL and its cocrystal inserted into the subdomain IIIA (site II') of BSA. The interactions between FEL and BSA including hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429 and LEU452 residues. However, the size of supramolecular FEL-ßRA better matched that of active cavity of BSA; the cocrystal is closely bound to BSA through hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429, VAL432, LEU452 and ILE387 residues. This change on binding affinity of FEL to BSA induced by cocrystallization with ßRA provided theoretical basis to evaluate the transportation, distribution and metabolism of cocrystal drug.

7.
Food Funct ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001073

RESUMO

Previous researches have indicated that sleep plays a vital role in cognitive functions. Sleep deprivation (SD) causes learning and memory damage, which is associated with oxidative stress. This study was performed to investigate the neuroprotective effects of an extract of Abelmoschus manihot flower (EAM) against memory deficit induced by SD in mice. The SD model was evoked by multiple platform method for 5 days, successively. The learning and memory-improving effects of EAM were assessed by behavioral trials and the underlying mechanism was investigated by measuring the oxidative stress alteration. Our findings indicated that the SD-induced memory deficit and the EAM treatment improved the cognitive functions of mice in the object location recognition test and passive avoidance task. In addition, EAM effectively improved the activities of the antioxidant enzyme, decreased the content of malondialdehyde (MDA), and restored the protein expression of the brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and glutamate receptor 1 (GluR1) in brain tissues. In conclusion, EAM could improve the SD-evoked learning and memory impairments. The possible underlying mechanisms of EAM may be related to its antioxidant capacity and enhanced BDNF/TrkB/GluR1 levels in the hippocampal memory.

8.
Biomater Sci ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001076

RESUMO

Drug resistance and side effects are the two main problems of chemotherapy. In order to address these big challenges, p-PB@d-SiO2, which has the ability to co-deliver both the hydrophobic drug doxorubicin hydrochloride (DOX) and the hydrophilic drug ibuprofen (IBU), is constructed to achieve synergistic treatment. The drug-loaded nanoparticle consists of porous Prussian blue (p-PB) as the core and dendrimer-like SiO2 (d-SiO2) as the shell, which is further thiolated and coated with polyethylene glycol thiol (HS-PEG) to form the "Dual-Key-and-Lock" drug carrier p-PB@d-SiO2-SS-PEG. The locked drugs can only be released in the presence of cooperative triggers, i.e., a high glutathione concentration (the first key) and an acidic environment (the second key). The "dual key"-triggered release is much more significant in cancer lesions than in normal tissues, reducing side effects. Furthermore, cell viability experiments highlight the superior therapeutic efficacy of the dual-drug-loaded nanoparticles compared with the single-drug systems (60%, 73% and 86% vs. 56%, 68%, and 76% at 100, 200 and 500 µg mL-1, respectively). In vitro and in vivo experiments demonstrate the potential application of p-PB@d-SiO2-SS-PEG for dual-mode fluorescence and magnetic-resonance-imaging-guided chemo-photothermal therapy. The "Dual-Key-and-Lock" drug carrier system exhibits the "1 + 1 > 2" effect, demonstrating its excellent performance in synergy therapy for improved therapeutic efficiency and thereby reducing conventional drug resistance and side effects.

9.
J Ovarian Res ; 13(1): 119, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998774

RESUMO

BACKGROUND: Wilms tumor 1 associated protein (WTAP) modulates other genes via transcriptional and post-transcriptional regulation, in particular, by acting as a N6-methyladenosine writer or binding to the 3'UTR of mRNA, and promotes a variety of tumuors. However, the roles and mechanisms of WTAP in ovarian cancer are unknown. RESULTS: In this study, using univariate Cox analysis and online CPTA analysis, we found that WTAP was a poor prognostic factor for ovarian cancer, and its protein expression level was higher in ovarian cancer than in normal tissue. Functionally, WTAP promoted the proliferation, invasion, and migration capability of ovarian cancer, according to the results of real time cellular analysis (RTCA), EdU cell proliferation assay, transwell assay. Subsequently, we identified a module containing 133 genes that were carefully related to WTAP expression through weighted gene co-expression network analysis (WGCNA). By calculating the hazard ratios of these genes and comparing their differences in the WTAP high-expression group and the low-expression group, we observed that there was a significant positive correlation between WTAP and two poor survival-related genes, family with sequence similarity 76 member A (FAM76A) and HBS1 like translational GTPase (HBS1L), which was also verified by quantitative real-time PCR in SKOV3 and A2780 cells. CONCLUSION: WTAP functions as an oncogenic factor that promotes the progression of ovarian cancer in which WTAP-HBS1L/FAM76A axis may be involved. Our study indicates the potential role of WTAP in prognostic biomarker and therapeutic target for ovarian cancer.

10.
Nat Commun ; 11(1): 4971, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009408

RESUMO

Assembly of different metal-organic framework (MOF) building blocks into hybrid MOF-on-MOF heterostructures is promising in chemistry and materials science, however the development of ternary MOF-on-MOF heterostructures with controllable architectural and compositional complexity is challenging. Here we report the synthesis of three types of ternary MOF-on-MOF heterostructures via a multiple selective assembly strategy. This strategy relies on the choice of one host MOF with more than one facet that can arrange the growth of a guest MOF, where the arrangement is site-selective without homogenous growth of guest MOF or homogenous coating of guest on host MOF. The growth of guest MOF on a selected site of host MOF in each step provides the opportunity to further vary the combinations of arrangements in multiple steps, leading to ternary MOF-on-MOF heterostructures with tunable complexity. The developed strategy paves the way towards the rational design of intricate and unprecedented MOF-based superstructures for various applications.

11.
12.
Nucleic Acids Res ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010163

RESUMO

RNA endowed with both protein-coding and noncoding functions is referred to as 'dual-function RNA', 'binary functional RNA (bifunctional RNA)' or 'cncRNA (coding and noncoding RNA)'. Recently, an increasing number of cncRNAs have been identified, including both translated ncRNAs (ncRNAs with coding functions) and untranslated mRNAs (mRNAs with noncoding functions). However, an appropriate database for storing and organizing cncRNAs is still lacking. Here, we developed cncRNAdb, a manually curated database of experimentally supported cncRNAs, which aims to provide a resource for efficient manipulation, browsing and analysis of cncRNAs. The current version of cncRNAdb documents about 2600 manually curated entries of cncRNA functions with experimental evidence, involving more than 2,000 RNAs (including over 1300 translated ncRNAs and over 600 untranslated mRNAs) across over 20 species. In summary, we believe that cncRNAdb will help elucidate the functions and mechanisms of cncRNAs and develop new prediction methods. The database is available at http://www.rna-society.org/cncrnadb/.

13.
J Neural Eng ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022663

RESUMO

BACKGROUND: At present, sEMG-based gesture recognition requires vast amounts of training data; otherwise, it is limited to a few gestures. This paper presents a novel dynamic energy model that decodes continuous hand actions by training small amounts of sEMG data. METHOD: The activation of forearm muscles can set the corresponding fingers in motion or state with movement trends. The moving fingers store kinetic energy, and the fingers with movement trends store potential energy. The kinetic energy and potential energy in each finger are dynamically allocated due to the adaptive-coupling mechanism of five-fingers in actual motion. Meanwhile, the sum of the two energies remains constant at a certain muscle activation. We regarded hand movements with the same direction of acceleration for five-finger as the same in energy mode and divided hand movements into ten energy modes. Independent component analysis and machine learning methods were used to model associations between sEMG signals and energy modes and expressed gestures by energy form adaptively. This theory imitates the self-adapting mechanism in actual tasks. Thus, ten healthy subjects were recruited, and three experiments mimicking activities of daily living were designed to evaluate the interface: (1) the expression of untrained gestures, (2) the decoding of the amount of single-finger energy, and (3) real-time control. RESULTS: (1) Participants completed the untrained hand movements (100 /100, p < 0.0001). (2) The interface performed better than chance in the experiment where participants pricked balloons with a needle tip (779 /1000, p < 0.0001). (3) In the experiment where participants punched a hole in the plasticine on the balloon, the success rate was over 95% (97.67±5.04 %, p <0.01). CONCLUSION: The model can achieve continuous hand actions with speed or force information by training small amounts of sEMG data, which reduces learning task complexity.

14.
J Sports Sci ; : 1-9, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33019892

RESUMO

This study aimed to examine whether changes in physical activity (PA) after an 8-week pedometer-based intervention would result in changes on motor competence through competence beliefs towards physical education (PE). The study also evaluated whether the hypothesized causal pathway differed by gender. Participants were 259 children (Mean age  = 10.88, SD =.78), randomly allocated to three intervention groups. Children's PA, competence beliefs towards PE, and motor competence were measured at pre- and post-tests. Significant relationships between PA and competence beliefs towards PE were found at pre- and post-tests. The magnitude of the relationship between competence beliefs towards PE and motor competence was larger at post-test than at pre-test (.33 vs.20). The structural invariance test suggested that the differences between boys and girls for the hypothesized models were insignificant (CMIN = 15.97, df = 12; p =.193). In general, the results suggest that changes on PA may cause changes in competence beliefs towards PE, which could result in changes on motor competence in middle to later childhood, regardless of gender. These data offer the possibility of using competence beliefs towards PE as a mediator in PA interventions designed to increase motor competence in childhood.

15.
Nanotechnology ; 31(50): 505603, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021226

RESUMO

There is keen interest for designing promising tungsten oxide (VI, WO3) films or coatings due to their wide applications in fields of energy, engineering, etc. Thus, this paper firstly introduce a novel convenient method of electrophoretic assembly technique (EAT) in an optimal stable suspension of isopropyl alcohol, PEG-1000 and polyethyleneimine for designing the promising anti-wetting functional WO3 (VI) films with relative rough structures and uniform distribution in mild conditions. The product possess a high crystallinity and pureness by x-ray powder diffraction analysis. The EAT dynamic behaviours of WO3 (VI) nanoparticles are investigated in detail. Moreover, obtained films shows excellent anti-wetting properties after suface modification, and the hydrophobic studies results demonstrate that product have a high static water CA of approximate 169° and keep nearly stable even after ultralong exposure time (360 d), and show outstanding properties of anti-soaking, impacting-proof, and moisture resistance even in high relative humidity (90%). These breakthroughs will substantially push forward the convenient processing of other anti-wetting functional coatings with wide potential applications.

16.
Med Sci Monit ; 26: e926526, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011734

RESUMO

BACKGROUND Postoperative delirium (POD) is a frequent complication in elderly patients, usually occurring within a few days after surgery. This study investigated the effect of lung-protective ventilation (LPV) on POD in elderly patients undergoing spinal surgery and the mechanism by which LPV suppresses POD. MATERIAL AND METHODS Seventy-one patients aged ≥65 years were randomized to receive LPV or conventional mechanical ventilation (MV), consisting of intermittent positive pressure ventilation following induction of anesthesia. The tidal volume in patients who received MV was 8 ml/kg predicted body weight (PBW), and the ventilation frequency was 12 times/min. The tidal volume in patients who received LPV was 6 ml/kg PBW, the positive end-expiratory pressure was 5 cmH2O, and the ventilation frequency was 15 times/min, with a lung recruitment maneuver performed every 30 min. Blood samples were collected immediately before anesthesia induction (T0), 10 min (T1) and 60 min (T2) after turning over, immediately after the operation (T3), and 15 min after extubation (T4) for blood gas analysis. Simultaneous cerebral oxygen saturation (rSO2) and cerebral desaturation were recorded. Preoperative and postoperative serum concentrations of interleukin (IL)-6, IL-10 and glial fibrillary acidic protein (GFAP) were measured by ELISA. POD was assessed by nursing delirium screening score. RESULTS Compared with the MV group, pH was lower and PaCO2 higher in the LPV group at T2. In addition PaO2, SaO2, and PaO2/FiO2 were higher at T1, and T4, and rSO2 was higher at T3, and T4 in the LPV than in the MV group (P<0.05 each). Postoperative serum GFAP and IL-6 were lower and IL-10 higher in the LPV group. The incidences of cerebral desaturation and POD were significantly lower in the LPV group (P<0.05). CONCLUSIONS LPV may reduce POD in elderly patients undergoing spinal surgery by inhibiting inflammation and improving cerebral oxygen metabolism.

17.
J Epidemiol ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33012776

RESUMO

BackgroundTo investigate the causal link between early-life exposures and long-term health consequences, we established the Tianjin Birth Cohort (TJBC), a large-scale prospective cohort in northern China.MethodsTJBC aims to enroll 10,000 families with follow-ups from pregnancy until children's six year-old. Pregnant women and their spouses were recruited through a three-tier antenatal healthcare system at early pregnancy, with follow-ups at mid-pregnancy, late pregnancy, delivery, 42 days after delivery, 6 months after delivery and each year until 6 year-old. Antenatal/neonatal examination, biological samples and questionnaires were collected.ResultsFrom August 2017 to January 2019, a total of 3,924 pregnant women has already been enrolled, and 1697 women have given birth. We observed the prevalence of gestational diabetes mellitus as 18.1%, anemia as 20.4%, and thyroid hypofunction as 2.0%. In singleton live births, 5.6% were preterm birth (PTB), 3.7% were low birth weight and 7.3% were macrosomia. Based on current data, we also identified maternal/paternal factors which increased the risk of PTB, including paternal age (OR, 1.07; 95% CI, 1.01-1.14 for each year increase), vaginal bleeding during pregnancy (OR, 2.82; 95% CI, 1.54-5.17) and maternal early-pregnancy BMI (OR, 1.08; 95% CI, 1.01-1.15 for each kg/m2 increase).ConclusionTJBC has the strength of collecting comprehensive maternal, paternal and childhood information. With a diverse range of biological samples, we are also engaging with emerging new technologies for multi-omics researches. The study would provide new insight into the causal link between macro/micro-environmental exposures of early life and short/long-term health consequences.

18.
FEBS Open Bio ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33015999

RESUMO

Clear cell renal cell carcinoma (ccRCC) exhibits high recurrence and metastasis rate. Although target therapy has significantly improved the prognosis of some ccRCC patients, the median survival rate remains poor. There thus remains a need for the identification of novel potential targets for diagnosis and therapy. Here, we screened differentially expressed genes (DEGs) between ccRCC and normal tissues through analyzing the TCGA database. We identified 55 up-regulated and 67 down-regulated genes associated with poor prognosis. GO and KEGG pathway analysis revealed that these genes were associated with glycometabolic process, complement, and coagulation cascades. In addition, the 8 down-regulated genes (HRG, FABP1, ALDOB, PCK1, HAO2, CASR, PLG, HMGCS2) and 2 up-regulated genes (SERPINE1, TYROBP) were filtered out. Finally, TYROBP was selected through repeated verification of various databases. High expression of TYROBP is associated with low survival rate in ccRCC, is closely related to immune cell infiltration, and is co-expressed with PD-1 and CTLA-4. In conclusion, TYROBP may have potential for diagnosis and treatment of ccRCC.

19.
Cancer Med ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016643

RESUMO

BACKGROUND: AUF1 is one of the AU-rich binding proteins, which promotes rapid ARE-mRNA degradation. Recently, it has been reported that AUF1 is involved in regulating the antioxidant system because of its capacity to bind specifically to RNA containing oxidized bases and degrade oxidized RNA. Many antioxidant proteins have been reported to be overexpressed in colorectal cancer (CRC), however, the role of AUF1 in the progression of CRC has not been explored. METHODS: The expression level of AUF1 protein in human CRC cell lines and CRC tissues was detected by western blotting and immunohistochemistry (IHC. The effects of AUF1 knockdown on CRC cell proliferation, migration, invasion and changes in the signaling pathways were evaluated using a cell counting kit-8 (CCK-8), Transwell assays and western blotting. Subcutaneous xenograft tumor model was employed to further substantiate the role of AUF1 in CRC. RESULTS: AUF1 protein was upregulated in CRC tissues and CRC cells, and high expression of AUF1 was significantly associated with advanced AJCC stage (P = .001), lymph node metastasis (P = .007), distant metastasis (P = .038) and differentiation (P = .009) of CRC specimens. CRC patients with the high expression of AUF1 had an extremely poor prognosis. The knockdown of AUF1 suppressed CRC cell line proliferation, migration and invasion, inhibited CRC cells tumorigenesis and growth in nude mice, and reduced phosphorylated-ERK1/2 and phosphorylated AKT in CRC cells. CONCLUSION: Our findings demonstrate that AUF1 is probably involved in the progression of CRC via the activation of the ERK1/2 and AKT pathways. AU-rich RNA-binding factor 1 could be used as a novel prognostic biomarker and a potential therapeutic target for CRC.

20.
Acta Biomater ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007486

RESUMO

Emerging evidence suggests that dysfunctional macrophages can cause chronic inflammation and impair tissue regeneration in diabetic wounds. Therefore, improving macrophage behaviors and functions may improve therapeutic outcomes of current treatments in diabetic wounds. Herein, we present a sulfated chitosan (SCS)-doped Collagen type I (Col I/SCS) hydrogel as a candidate for diabetic wound treatments, and assess its efficacy using streptozocin (STZ)-induced diabetic wound model. Results showed that Col I/SCS hydrogel significantly improved wound closure rate, collagen deposition, and revascularization in diabetic wounds. Flow cytometry analysis and immunofluorescent staining analysis showed that the Col I/SCS hydrogel accelerated the resolution of excessive inflammation by reducing the polarization of M1-like macrophages in chronic diabetic wounds. In addition, ELISA analysis revealed that the Col I/SCS hydrogel reduced the production of pro-inflammatory interleukin (IL)-6 and increased the production of anti-inflammatory cytokines including IL-4 and transforming growth factor-beta 1 (TGF-ß1) during wound healing. Moreover, the Col I/SCS hydrogel enhanced the transdifferentiation of macrophages into fibroblasts, which enhanced the formation of collagen and the extracellular matrix (ECM) in wound tissue. We highlight a potential application of manipulating macrophages behaviors in the pathological microenvironment via materials strategy. STATEMENT OF SIGNIFICANCE: Improving the chronic inflammatory microenvironment of diabetic wounds by regulating macrophage behaviors has been of wide concern in recent years. We designed a Col I/SCS hydrogel based on Collagen type I and sulfated chitosan (SCS) without exogenous cells or cytokines, which could significantly improve angiogenesis and resolve chronic inflammation in diabetic wounds, and hence accelerate diabetic wound healing. The Col I/SCS hydrogel could facilitate the polarization of M1-to-M2 macrophages and activate the transdifferentiation of macrophages to fibroblasts. Additionally, the Col I/SCS hydrogel also equilibrated the content of pro-inflammatory and anti-inflammatory cytokines. This strategy may afford a new avenue to improve macrophage functions and accelerate diabetic chronic wound healing.

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