Publications by authors named "Feng Xu"

3,358 Publications

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Normalization of tumor vasculature: A potential strategy to increase the efficiency of immune checkpoint blockades in cancers.

Int Immunopharmacol 2022 Jun 25;110:108968. Epub 2022 Jun 25.

Department of General Surgery, Shengjing Hospital of China Medical University, No.36.Sanhao stress, Shenyang 110004, Liaoning Province, China. Electronic address:

Immune checkpoint inhibitors (ICIs) eliminate tumor cells by reactivating CD8 + T cells using the cytotoxic effects of the immune system. However, in this process, tumor angiogenic factors and abnormal formation of tumor blood vessels are not conducive to the treatment of ICIs. In the tumor microenvironment (TME), proangiogenic factors prevent dendritic cell maturation, reduce T cell infiltration, and recruit inhibitory immune cells such as regulatory T (Treg) cells. Abnormal tumor blood vessels also prevent immune cells and chemotherapy drugs from reaching the target effectively and lead to poor perfusion and severe hypoxia of the tumor. Treatment with antiangiogenic inhibitors can block the transmission of abnormal angiogenesis signals and promote the normalization of tumor vasculature. Therefore, the combination of antiangiogenic inhibitors and ICIs is used in clinical therapy. Combination therapy has been proven theoretically feasible in preclinical trials, and many clinical trials have been completed to confirm its safety and efficacy.
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http://dx.doi.org/10.1016/j.intimp.2022.108968DOI Listing
June 2022

Thinned peach polyphenols alleviate obesity in high fat mice by affecting gut microbiota.

Food Res Int 2022 Jul 18;157:111255. Epub 2022 Apr 18.

College of Food and Pharmaceutical Sciences, Zhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, Ningbo University, Ningbo 315800, China. Electronic address:

The aim of this study was to explore the anti-obesity activity of thinned peach polyphenols (TPP) and their effects on gut microbiota. An obese mouse model was established using a high-fat diet, and high-throughput sequencing was used to analyze changes in gut microbiota in mice fed with TPP. The results showed that dietary TPP reduced body weight, promoted appetite, reduced liver injury, and reduced levels of TC, TG, LDL-C, ASL and ALT while increasing HDL-C. TPP also enhanced the richness and diversity of gut microbiota in later stages of feeding. Composition and correlation analysis indicated that TPP increased probiotics (such as Alistipes, Akkermansia, Klebsiella, Bacteroides) which negatively correlate with obesity. TPP also reduced the numbers of harmful bacteria (including Helicobacter, Anaeroplasma), which positively correlate with obesity. Probiotics and harmful bacteria cluster independently and the two groups affect each other negatively. These results suggest that TPP reduced obesity by affecting the composition of the gut microbiota in mice. TPP can therefore be used as an ingredient in food to prevent the development of obesity.
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http://dx.doi.org/10.1016/j.foodres.2022.111255DOI Listing
July 2022

Differential Responses of Primary Astrocytes under Hyperthermic Temperatures.

IEEE Trans Biomed Eng 2022 Jun 27;PP. Epub 2022 Jun 27.

Astrocyte is the most abundant cells in brain and plays critical roles in brain homeostasis and functions. Although hyperthermia (or fever) is a common symptom in patients, its influence on astrocyte viability, morphology, and functions remains elusive. Here we developed an in vitro astrocyte culture system capable of precisely controlling culture temperature to study astrocyte responses under clinically-relevant hyperthermic temperatures (38 ∼ 41°C). We found that hyperthermia in this temperature range does not alter cell morphology, but significantly affects cell viability, activation and functions. Specifically, high-hyperthermia (40°C and 41°C) causes irreversible and permanent damages to astrocytes and compromises their normal viability and functionalities repairing damaged neural tissue, recycling neurotransmitters, and promoting brain development, while mild-hyperthermia (38°C and 39°C) induces astrocyte activation and cytokine secretion without significant decreases in cell viability. This study sheds new insights into our understanding of various fever-associated symptoms, enabling the future development of astrocyte-targeted therapy to treat brain diseases via hyperthermia.
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http://dx.doi.org/10.1109/TBME.2022.3186509DOI Listing
June 2022

Catastrophic atrial tachycardia-induced cardiomyopathy in a teenager treated by extracorporeal membrane oxygenation and stereotactic arrhythmia radioablation.

Eur Heart J 2022 Jun 27. Epub 2022 Jun 27.

Department of Cardiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 600713, Sichuan Province, China.

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http://dx.doi.org/10.1093/eurheartj/ehac325DOI Listing
June 2022

Different Roles of the Left and Right Ventrolateral Prefrontal Cortex in Cognitive Reappraisal: An Online Transcranial Magnetic Stimulation Study.

Front Hum Neurosci 2022 10;16:928077. Epub 2022 Jun 10.

Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, China.

The ventrolateral prefrontal cortex (VLPFC) plays a pivotal role in cognitive reappraisal. Previous studies suggested a functional asymmetry of the bilateral VLPFC, but the evidence is still insufficient during cognitive reappraisal. In this study, we conducted an online single-pulse transcranial magnetic stimulation (spTMS) to investigate the causal and distinct roles of the left and right VLPFC in reappraisal. Participants were instructed to reappraise (down-regulate) or attend to pictures depicting social exclusion scenarios while the spTMS was applied over the left or right VLPFC of the participants' brains. The results showed that spTMS of either the left or the right VLPFC would increase reappraisal difficulty. Meanwhile, the outcome of reappraisal (measured by self-reported negative feelings) significantly deteriorated when the right (but not the left) VLPFC was temporally interrupted by spTMS, while the verbal fluency during oral reporting of the reappraisal strategy was significantly reduced when the left VLPFC was interrupted by spTMS. Taken together, these findings provide causal evidence for the involvement of left and right VLPFC with distinct roles: while the left VLPFC is responsible for the linguistic especially semantic process of generating and selecting appraisals according to the goal of emotion regulation, the right VLPFC plays a critical role in inhibiting inappropriate negative emotions and thoughts generated by the effective scenarios. These findings deepen our understanding of the neurocognitive mechanism of emotion regulation.
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http://dx.doi.org/10.3389/fnhum.2022.928077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226322PMC
June 2022

A green and rapid analytical method for determination of kitasamycin in animal feedstuffs by ultra-high performance liquid chromatography tandem mass spectrometry.

J Chromatogr A 2022 Jun 6;1676:463203. Epub 2022 Jun 6.

Ningbo Academy of Agricultural Sciences, Ningbo, 315040, PR China. Electronic address:

A rapid, simple, highly efficiency analytical method for detecting kitasamycin A1, A4, A5, and A13 in different feedstuffs was successfully developed by combining enhanced matrix removal (EMR) lipid cartridge and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). After extraction with acetonitrile, the sample supernatants were directly passed through the EMR lipid cartridge. Then, the cartridge was rinsed and eluted with acetonitrile and methanol, respectively, followed by UHPLC-MS/MS analysis with positive mode using multiple reaction monitoring. Optimized pretreatment procedure without solvent conversion, multiple nitrogen drying steps and activated cartridge before loading, and no significant interference were found during the analysis of different types of animal feedstuffs. Excellent sensitivity (Limit of quantification, LOQ) of kitasamycin A1, A4, A5, and A13 was 1.1-2.0 µg/kg. Satisfactory recoveries of kitasamycin A1, A4, A5, and A13 in different feedstuffs were from 74.0% to 98.8%, with the relative standard deviations (RSDs) below 10.4%, and good linear correlation coefficient (r)>0.9990 in the matrix matched standard curve range of 0.02-50.0 µg/L. Results demonstrated that the developed method exhibited excellent linearity, accuracy, precision, sensitivity, and the feasibility of using this method in kitasamycin determination of animal feedstuffs. The method was evaluated using the greenness analysis method through Eco-Scale assessment tool.
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http://dx.doi.org/10.1016/j.chroma.2022.463203DOI Listing
June 2022

Reconstruction of the Genome-Scale Metabolic Model of and Its Application in the Overproduction of Erythromycin.

Metabolites 2022 Jun 1;12(6). Epub 2022 Jun 1.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, China.

is considered to be an effective host for erythromycin. However, little is known about the regulation in terms of its metabolism. To develop an accurate model-driven strategy for the efficient production of erythromycin, a genome-scale metabolic model (iJL1426) was reconstructed for the industrial strain. The final model included 1426 genes, 1858 reactions, and 1687 metabolites. The accurate rates of the growth predictions for the 27 carbon and 31 nitrogen sources available were 92.6% and 100%, respectively. Moreover, the simulation results were consistent with the physiological observation and C metabolic flux analysis obtained from the experimental data. Furthermore, by comparing the single knockout targets with earlier published results, four genes coincided within the range of successful knockouts. Finally, iJL1426 was used to guide the optimal addition strategy of n-propanol during industrial erythromycin fermentation to demonstrate its ability. The experimental results showed that the highest erythromycin titer was 1442.8 μg/mL at an n-propanol supplementation rate of 0.05 g/L/h, which was 45.0% higher than that without n-propanol supplementation, and the erythromycin-specific synthesis rate was also increased by 30.3%. Therefore, iJL1426 will lead to a better understanding of the metabolic capabilities and, thus, is helpful in a systematic metabolic engineering approach.
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http://dx.doi.org/10.3390/metabo12060509DOI Listing
June 2022

[Research progress of in-hospital mortality risk model in patients with acute myocardial infarction].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2022 May;34(5):550-555

Department of Emergency, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.

The incidence of in-hospital death in acute myocardial infarction (AMI) is high, which seriously threatens the life and health of patients. At present, many countries and regions have established a variety of objective assessment models for predicting the in-hospital mortality of patients with AMI, providing important decision-making support for patients with different risk levels when formulating treatment plans. With the rise of artificial intelligence, many new modeling methods also show certain advantages over the traditional models. This article systematically introduces the commonly used and newly constructed risk prediction models for in-hospital mortality of AMI, in order to provide help for medical staff to assist decision-making in clinical practice, and provide reference for the establishment of a safe and more effective risk prediction model in the future.
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http://dx.doi.org/10.3760/cma.j.cn121430-20220328-00117DOI Listing
May 2022

Deep learning with weak annotation from diagnosis reports for detection of multiple head disorders: a prospective, multicentre study.

Lancet Digit Health 2022 Jun 17. Epub 2022 Jun 17.

Institute for Brain and Cognitive Sciences, BNRist, Tsinghua University, Beijing, China; Department of Automation, BLBCI, Tsinghua University, Beijing, China. Electronic address:

Background: A large training dataset with high-quality annotations is necessary for building an accurate and generalisable deep learning system, which can be difficult and expensive to prepare in medical applications. We present a novel deep-learning-based system, requiring no annotator but weak annotation from a diagnosis report, for accurate and generalisable performance in detecting multiple head disorders from CT scans, including ischaemia, haemorrhage, tumours, and skull fractures.

Methods: Our system was developed on 104 597 head CT scans from the Chinese PLA General Hospital, with associated textual diagnosis reports. Without expert annotation, we used keyword matching on the reports to automatically generate disorder labels for each scan. The labels were inaccurate because of the unreliable annotator-free strategy and inexact because of scan-level annotation. We proposed RoLo, a novel weakly supervised learning algorithm, with a noise-tolerant mechanism and a multi-instance learning strategy to address these issues. RoLo was tested on retrospective (2357 scans from the Chinese PLA General Hospital), prospective (650 scans from the Chinese PLA General Hospital), cross-centre (1525 scans from the Brain Hospital of Hunan Province), cross-equipment (1484 scans from the Chinese PLA General Hospital), and cross-nation (CQ500 public dataset from India) test datasets. Four radiologists were tested on the prospective test dataset before and after viewing system recommendations to assess whether the system could improve diagnostic performance.

Findings: The area under the receiver operating characteristic curve for detecting the four disorder types was 0·976 (95% CI 0·976-0·976) for retrospective, 0·975 (0·974-0·976) for prospective, 0·965 (0·964-0·966) for cross-centre, and 0·971 (0·971-0·972) for cross-equipment test datasets, and 0·964 (0·964-0·966) for CQ500 (with only haemorrhage and fracture). The system achieved similar performance to four radiologists and helped to improve sensitivity and specificity by 0·109 (95% CI 0·086-0·131) and 0·022 (0·017-0·026), respectively.

Interpretation: Without expert annotated data, our system achieved accurate and generalisable performance for head disorder detection. The system improved the diagnostic performance of radiologists. Because of its accuracy and generalisability, our computer-aided diganostic system could be used in clinical practice to improve the accuracy and efficiency of radiologists in different hospitals.

Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.
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http://dx.doi.org/10.1016/S2589-7500(22)00090-5DOI Listing
June 2022

The role of anesthesiologists' perceived self-efficacy in anesthesia-related adverse events.

BMC Anesthesiol 2022 Jun 20;22(1):190. Epub 2022 Jun 20.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.

Background: Self-efficacy, as the vital determinant of behavior, influencing clinicians' situation awareness, work performance, and medical decision-making, might affect the incidence of anesthesia-related adverse events (ARAEs). This study was employed to evaluate the association between perceived self-efficacy level and ARAEs.

Methods: A cross-sectional study was performed in the form of an online self-completion questionnaire-based survey. Self-efficacy was evaluated via validated 4-point Likert scales. Internal reliability and validity of both scales were also estimated via Cronbach's alpha and validity analysis. According to the total self-efficacy score, respondents were divided into two groups: normal level group and high level group. Propensity score matching and multivariable logistic regression were employed to identify the relationship between self-efficacy level and ARAEs.

Results: The response rate of this study was 34%. Of the 1011 qualified respondents, 38% were women. The mean (SD) age was 35.30 (8.19) years. The Cronbach's alpha of self-efficacy was 0.92. The KMO (KMO and Bartlett's test) value of the scale was 0.92. ARAEs occurred in 178 (33.0%) of normal level self-efficacy group and 118 (25.0%) of high level self-efficacy group. Before adjustment, high level self-efficacy was associated with a decreased incidence of ARAEs (RR [relative risk], 0.76; 95% CI [confidence interval], 0.62-0.92). After adjustment, high level self-efficacy was also associated with a decreased incidence of ARAEs (aRR [adjusted relative risk], 0.63, 95% CI, 0.51-0.77). In multivariable logistic regression, when other covariates including years of experience, drinking, and the hospital ranking were controlled, self-efficacy level (OR [odds ratio], 0.62; 95% CI, 0.46-0.82; P = 0.001) was significantly correlated with ARAEs.

Conclusions: Our results found a clinically meaningful and statistically significant correlation between self-efficacy and ARAEs. These findings partly support medical educators and governors in enhancing self-efficacy construction in clinical practice and training.
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http://dx.doi.org/10.1186/s12871-022-01732-3DOI Listing
June 2022

Laminar regenerated cellulose membrane employed for high-performance photothermal-gating osmotic power harvesting.

Carbohydr Polym 2022 Sep 26;292:119657. Epub 2022 May 26.

Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, PR China. Electronic address:

Inspired by acute temperature sensors in the mammalian sensory system to seek comfortable living environment, we construct temperature sensing nanochannels that are tightly linked to photo gating to form photothermal controlled nanochannels membrane. This membrane arises from the composite of laminar regenerated cellulose (RC) membrane formed by dissolution and regeneration of cellulose in the novel superbase-derived ionic liquid and poly-l-lysine (PLL)-modified conical nanochannels polyethylene terephthalate (PET) substrate. FeO nanoparticles are introduced into RC membrane as gating modifiers, controlling ion flux and osmotic energy conversion. Nanochannels are activated upon photo, inducing temperature changes result in PLL molecule structure shifted from α-helix to β-sheet. The difference in the rectification ratio at different temperatures is associated with photothermal-dependent opening and closing, its maximum is 116.76. This system could deliver an output power of approximately 4.9 W/m in osmotic energy harvesting. Our results suggest a simple photothermal-gating ion transport principle in laminar RC membrane.
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http://dx.doi.org/10.1016/j.carbpol.2022.119657DOI Listing
September 2022

Bilateral epididymal giant leiomyoma: A case report.

Asian J Surg 2022 Jun 15. Epub 2022 Jun 15.

Department of Urology, Jinhu County People's Hospital, Huaian City, 211600, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.05.153DOI Listing
June 2022

Effect of functional group and structure on hydrophobic properties of environment-friendly lignin-based composite coatings.

Int J Biol Macromol 2022 Jun 15;215:132-140. Epub 2022 Jun 15.

Key Laboratory of Pulp and Paper Science and Technology of Ministry of Education, State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, PR China. Electronic address:

Hydrophobic coatings are widely used in a variety of materials surfaces. However, it remains a great challenge for the non-toxic and environmentally-friendly production of hydrophobic coatings. Herein, two nano-scale spherical lignin/SiO composite particles are synthesized based on the electrostatic interaction and the steric hindrance effect inspired by the self-protection of straw. Introduction of positively charged quaternary ammonium enhances the possibility of electrostatic self-assembly between lignin and SiO for QAL/SiO, and access of super-long hydrophobic chains induces the formation of nano-sized particles for QALC/SiO. The coatings were fabricated by simply spraying on substrates and hydrophilic/hydrophobic properties were detected. The results show that the long hydrophobic chain can enhance the hydrophobic properties of lignin polymers (CA = 129°) and the spherical micro-nano structure is beneficial to improve the hydrophobic properties of the lignin/SiO composite (CA = 137°). Meanwhile, the hydrophobic coating has good self-cleaning performance. The excellent hydrophobic and self-cleaning properties are mainly benefited from the nano effect, reasonable hydrophilic/hydrophobic structure, and good dispersibility of spherical structure. This work not only provides a kind of lignin-based nano-scale waterproof coatings holding excellent properties in terms of cost, scalability, and robustness, but also has important significance for the high-value utilization of biomass resources.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.06.055DOI Listing
June 2022

Concealable physically unclonable function chip with a memristor array.

Sci Adv 2022 Jun 17;8(24):eabn7753. Epub 2022 Jun 17.

School of Integrated Circuits, Beijing Innovation Center for Future Chips (ICFC), Tsinghua University, Beijing 100084, China.

A physically unclonable function (PUF) is a creditable and lightweight solution to the mistrust in billions of Internet of Things devices. Because of this remarkable importance, PUF need to be immune to multifarious attack means. Making the PUF concealable is considered an effective countermeasure but it is not feasible for existing PUF designs. The bottleneck is finding a reproducible randomness source that supports repeatable concealment and accurate recovery of the PUF data. In this work, we experimentally demonstrate a concealable PUF at the chip level with an integrated memristor array and peripherals. The correlated filamentary switching characteristic of the hafnium oxide (HfO)-based memristor is used to achieve PUF concealment/recovery with SET/RESET operations efficiently. PUF recovery with a zero-bit error rate and remarkable attack resistance are achieved simultaneously with negligible circuit overhead. This concealable PUF provides a promising opportunity to build memristive hardware systems with effective security in the near future.
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http://dx.doi.org/10.1126/sciadv.abn7753DOI Listing
June 2022

A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis.

Cell Metab 2022 Jun 7. Epub 2022 Jun 7.

Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Hunan 410008, China. Electronic address:

Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.
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http://dx.doi.org/10.1016/j.cmet.2022.05.009DOI Listing
June 2022

Integrated screens uncover a cell surface tumor suppressor gene involved in Hippo pathway.

Proc Natl Acad Sci U S A 2022 Jun 15;119(25):e2121779119. Epub 2022 Jun 15.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Cell surface proteins play essential roles in various biological processes and are highly related to cancer development. They also serve as important markers for cell identity and targets for pharmacological intervention. Despite their great potentials in biomedical research, comprehensive functional analysis of cell surface proteins remains scarce. Here, with a de novo designed library targeting cell surface proteins, we performed in vivo CRISPR screens to evaluate the effects of cell surface proteins on tumor survival and proliferation. We found that loss markedly promoted tumor growth in vivo. Moreover, KIRREL was significantly enriched in a separate CRISPR screen based on a specific Hippo pathway reporter. Further studies revealed that KIRREL binds directly to SAV1 to activate the Hippo tumor suppressor pathway. Together, our integrated screens reveal a cell surface tumor suppressor involved in the Hippo pathway and highlight the potential of these approaches in biomedical research.
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http://dx.doi.org/10.1073/pnas.2121779119DOI Listing
June 2022

Dietary fiber ameliorates lead-induced gut microbiota disturbance and alleviates neuroinflammation.

J Sci Food Agric 2022 Jun 15. Epub 2022 Jun 15.

College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, People's Republic of China.

Dietary fiber (DF) is a carbohydrate from the edible part of plants and has the functions of promoting gastrointestinal motility, regulating gut microbiota (GM), and improving health. Lead (Pb) is a non-essential toxic heavy metal that can accumulate in the environment over time and enter the body through the respiratory tract, skin, and gastrointestinal tract. Lead not only causes disturbances in GM, but also leads to loss of homeostasis of immune functions, causes neuronal damage and results in neuroinflammation. Scientific literature reported that DF had anti-inflammatory activity as a natural product. This review highlights the role of DF and its metabolic products in alleviating lead-induced neuroinflammation by inducing changes in the species and quantity of GM and regulating the immune system, providing a potential dietary protective strategy for lead-induced disease. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jsfa.12074DOI Listing
June 2022

Inhibition of Nitrosative Stress Attenuates Myocardial Injury and Improves Outcomes after Cardiac Arrest and Resuscitation.

Shock 2022 Jun 25;57(6):299-307. Epub 2022 May 25.

Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China.

Objectives: Nitrosative stress is widely involved in cell injury via inducing the nitration modification of a variety of proteins. This study aimed to investigate whether inhibition of nitrosative stress attenuated myocardial injury and improved outcomes in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR).

Methods: Adult male Wistar rats were subjected to asphyxia-induced cardiac arrest and subsequently resuscitation. One minute after return of spontaneous circulation (ROSC), rats were randomized and administered the nitrosative stress inhibitor, FeTMPyP (1 or 3 mg/kg), or normal saline as a placebo. 3-Nitrotyrosine (3-NT), mean arterial pressure (MAP), heart rate (HR), mortality, electrocardiogram (ECG), left ventricular ejection fraction (EF) and fractional shortening (FS), and levels of myocardial apoptosis were evaluated. The concentrations of lactate, creatine kinase MB isoenzyme (CK-MB), and angiotensin II (Ang II), were measured in blood samples.

Results: 3-NT level was significantly increased in the heart after ROSC. Administration of FeTMPyP (1 or 3 mg/kg) attenuated the increase of 3-NT in the myocardium. Inhibition of nitrosative stress improved survival and attenuated CA/CPR-induced reperfusion injury by maintaining the stability of MAP and HR, and reducing the accumulation of lactic acid. Post-cardiac arrest rats had higher serum CK-MB and Ang II than healthy rats, while EF and FS were lower in healthy rats. Inhibition of nitrosative stress not only alleviated ischemic heart injury but also reduced the occurrence of CA/CPR-induced of arrhythmias. Moreover, nitrosative stress mediated the upregulation of Cleaved caspase-3 and downregulation Bcl-2, which was abolished by FeTMPyP.

Conclusions: Inhibition of nitrosative stress is a novel molecular target to alleviate myocardial injury and improve outcomes in a rat model of CA/CPR.
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http://dx.doi.org/10.1097/SHK.0000000000001939DOI Listing
June 2022

Approaching intrinsic dynamics of MXenes hybrid hydrogel for 3D printed multimodal intelligent devices with ultrahigh superelasticity and temperature sensitivity.

Nat Commun 2022 Jun 14;13(1):3420. Epub 2022 Jun 14.

Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE), Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University (NPU), Xi'an, PR China.

Hydrogels are investigated broadly in flexible sensors which have been applied into wearable electronics. However, further application of hydrogels is restricted by the ambiguity of the sensing mechanisms, and the multi-functionalization of flexible sensing systems based on hydrogels in terms of cost, difficulty in integration, and device fabrication remains a challenge, obstructing the specific application scenarios. Herein, cost-effective, structure-specialized and scenario-applicable 3D printing of direct ink writing (DIW) technology fabricated two-dimensional (2D) transition metal carbides (MXenes) bonded hydrogel sensor with excellent strain and temperature sensing performance is developed. Gauge factor (GF) of 5.7 (0 - 191% strain) and high temperature sensitivity (-5.27% °C) within wide working range (0 - 80 °C) can be achieved. In particular, the corresponding mechanisms are clarified based on finite element analysis and the first use of in situ temperature-dependent Raman technology for hydrogels, and the printed sensor can realize precise temperature indication of shape memory solar array hinge.
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http://dx.doi.org/10.1038/s41467-022-31051-7DOI Listing
June 2022

Artificial intelligence-assisted colorimetric lateral flow immunoassay for sensitive and quantitative detection of COVID-19 neutralizing antibody.

Biosens Bioelectron 2022 Jun 8;213:114449. Epub 2022 Jun 8.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an, 710049, PR China. Electronic address:

Currently, vaccination is the most effective medical measure to improve group immunity and prevent the rapid spread of COVID-19. Since the individual difference of vaccine effectiveness is inevitable, it is necessary to evaluate the vaccine effectiveness of every vaccinated person to ensure the appearance of herd immunity. Here, we developed an artificial intelligent (AI)-assisted colorimetric polydopamine nanoparticle (PDA)-based lateral flow immunoassay (LFIA) platform for the sensitive and accurate quantification of neutralizing antibodies produced from vaccinations. The platform integrates PDA-based LFIA and a smartphone-based reader to test the neutralizing antibodies in serum, where an AI algorithm is also developed to accurately and quantitatively analyze the results. The developed platform achieved a quantitative detection with 160 ng/mL of detection limit and 625-10000 ng/mL of detection range. Moreover, it also successfully detected totally 50 clinical serum samples, revealing a great consistency with the commercial ELISA kit. Comparing with commercial gold nanoparticle-based LFIA, our PDA-based LFIA platform showed more accurate quantification ability for the clinical serum. Therefore, we envision that the AI-assisted PDA-based LFIA platform with sensitive and accurate quantification ability is of great significance for large-scale evaluation of vaccine effectiveness and other point-of-care immunoassays.
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http://dx.doi.org/10.1016/j.bios.2022.114449DOI Listing
June 2022

Pooled-Analysis of Association of Sievers Bicuspid Aortic Valve Morphology With New Permanent Pacemaker and Conduction Abnormalities After Transcatheter Aortic Valve Replacement.

Front Cardiovasc Med 2022 26;9:884911. Epub 2022 May 26.

Department of Emergency Medicine and Chest Pain Center, Cheeloo College of Medicine, Qilu Hospital of Shandong University, Jinan, China.

Background: Studies on the association of Sievers bicuspid aortic valve (BAV) morphology with conduction disorders after transcatheter aortic valve replacement (TAVR) have not reached consensus.

Methods: We here performed a pooled-analysis to explore whether Sievers type 1 BAV morphology increased the risk of post-TAVR conduction abnormalities and permanent pacemaker implantation (PPI) compared to type 0. Systematic literature searches through EMBASE, Medline, and Cochrane databases were concluded on 1 December 2021. The primary endpoint was post-TAVR new PPI and pooled as risk ratios (RRs) and 95% confidence intervals (CIs). Conduction abnormalities as the secondary endpoint were the composites of post-TAVR PPI and/or new-onset high-degree of atrial-ventricle node block and left-bundle branch block. Studies that reported incidence of outcomes of interest in both type 1 and type 0 BAV morphology who underwent TAVR for aortic stenosis were included.

Results: Finally, nine studies were included. Baseline characteristics were generally comparable, but type 1 population was older with a higher surgical risk score compared to type 0 BAV morphology. In the pooled-analysis type 1 BAV had significantly higher risk of post-TAVR new-onset conduction abnormalities ( = 1.68, 95% 1.09-2.60, = 0.0195) and new PPI ( = 1.97, 95% 1.29-2.99, = 0.0016) compared to type 0. Random-effects univariate meta-regression indicated that no significant association between baseline characteristics and PPI.

Conclusion: Sievers type 1 BAV morphology was associated with increased risk of post-TAVR PPI and conduction abnormalities compared to type 0. Dedicated cohort is warranted to further validate our hypothesis.
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http://dx.doi.org/10.3389/fcvm.2022.884911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178076PMC
May 2022

Cycle Performance of Aerated Lightweight Concrete Windowed and Windowless Wall Panel from the Perspective of Lightweight Deep Learning.

Comput Intell Neurosci 2022 3;2022:3968607. Epub 2022 Jun 3.

College of Civil Engineering, Nanjing Tech University, Nanjing 211816, China.

This paper aims to explore the seismic mechanical properties of newly developed fabricated aerated lightweight concrete (ALC) wall panels to clarify the interaction mechanism between wall panels and structures. It first introduces the lightweight deep learning object detection algorithm and constructs a network model with faster operation speed based on the convolutional neural network. Secondly, combined with the deep learning object detection algorithm, the quasi-static loading system is adopted to conduct the repeated loading test on two fabricated ALC wall panels. Finally, the hysteresis load-displacement curve of each test is recorded. The experimental results show that the proposed deep learning algorithm greatly improves the operation speed and compresses the model size without reducing the accuracy. The lightweight deep learning algorithm is applied to the study of the slip performance of the wall plate. The pretightening force of the connecting screw characterizes the slip performance between the wall plate and the structural beam, thereby affecting the deformation response of the wall plate when the interstory displacement increases. The hysteresis curve of the ALC wall panel has obvious squeezing effect, indicating that the slip of the connector can unload part of the external load and delay the damage of the wall panel. The skeleton curve suggests that the fabricated windowless ALC wall panel has higher positive and negative initial stiffness and bearing capacity than the fabricated windowed wall panel. However, the degradation analysis of the stiffness curve reveals that the lateral stiffness deviation of the fabricated windowless ALC wall panel is more obvious. It confirms that the proposed connection method based on the lightweight deep learning model can improve the seismic performance of ALC wall panels and provide reference for the structural analysis of embedding fabricated ALC wall panels. This work shows the important practical value for exploring the application effect of embedded ALC wall panels.
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http://dx.doi.org/10.1155/2022/3968607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187431PMC
June 2022

KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma.

Cancer Cell Int 2022 Jun 10;22(1):211. Epub 2022 Jun 10.

Department of Urology, Clinical School of Medical College, Jinling Hospital, Nanjing University, Nanjing, China.

Background: Studies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it's urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC.

Methods: To systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results.

Results: The construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs).

Conclusions: Generally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.
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http://dx.doi.org/10.1186/s12935-022-02626-7DOI Listing
June 2022

Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells.

Toxicol Appl Pharmacol 2022 Jun 7;449:116110. Epub 2022 Jun 7.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, China; Department of Biomedicine, School of Medicine, Guizhou University, Guiyang 550025, China; Hebei Province Key Lab of Research and Application on Microbial Diversity, College of Life Sciences, Hebei University, Baoding 071002, China; Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang 110122, China; Anhui Medical University, Hefei 230032, China; Academy of Military Medicines, Aceademy of Military Sciences, Beijing 100850, China. Electronic address:

Protein phosphorylation is the most common type of post-translational modification where serine, threonine or tyrosine are reversibly bound to the phosphate group of ATP in a reaction catalyzed by protein kinases. Phosphorylation plays an important role in regulation of cell homeostasis, including but not limited to signal perception and transduction, gene expression and function of proteins. Protein phosphorylation happens on a fast time scale and represents an energy-efficient way for the cell to adapt to exposure to chemical stressors. To understand the cascade of cellular signaling induced by exposure to chemicals, we have exposed HepG2 cells to three chemicals with different modes of action, namely, caffeine, coumarin, and quercetin in a concentration and time response manner. Significantly upregulated and downregulated phosphosites were screened to analyze the activation/deactivation of signaling pathways by protein kinases. In total, 69, 44 and 12 signaling pathways were found enriched in caffeine, coumarin and quercetin treated cells, respectively, of which 9 pathways were co-enriched with 11 jointly responded kinases. Among identified co-responded kinases, CDK1, MAPK1 and MAPK3 play important roles in cell cycle and insulin signaling pathways. Quantitative phosphoproteomics can sensitively distinguish the effects of different chemicals on cells, allowing the assessment of chemical safety through changes in substrates and metabolic pathways at the cellular level, which is important for the development of non-animal approaches for chemical safety assessment.
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http://dx.doi.org/10.1016/j.taap.2022.116110DOI Listing
June 2022

Promoting the healing of infected diabetic wound by an anti-bacterial and nano-enzyme-containing hydrogel with inflammation-suppressing, ROS-scavenging, oxygen and nitric oxide-generating properties.

Biomaterials 2022 Jul 22;286:121597. Epub 2022 May 22.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan, 030000, China; Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. Electronic address:

The diabetic wound is easily to develop into a chronic wound because of the extremely serious and complex inflammatory microenvironment including biofilm formation, over-expressed reactive oxygen species (ROS), hypoxia and insufficiency of nitric oxide (NO) synthesis. In this work, a multifunctional hydrogel was designed and prepared by crosslinking hydrophilic poly(PEGMA-co-GMA-co-AAm) (PPGA) polymers with hyperbranched poly-L-lysine (HBPL)-modified manganese dioxide (MnO) nanozymes. Pravastatin sodium, which is supposed to participate in the synthesis of NO, was further loaded to obtain the HMP hydrogel. The capabilities of this hydrogel in scavenging different types of ROS, generating O, killing broad spectrum bacteria, and protecting cells against oxidative stress were confirmed in vitro. The transcriptome analysis revealed that HBPL inhibited bacterial quorum sensing (QS) system, downregulated virulent genes, and interfered bacterial metabolism. The HBPL-crosslinked hydrogels killed up to 94.1%-99.5% of methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (E. coli) and Pseudomonas aeruginosa even at 10 CFU/mL. HBPL modification greatly increased the stability of MnO nanosheets in physiological environment. The MRSA-caused infection was effectively treated by the HBPL-crosslinked HMP hydrogel in vivo, and thereby the wound closure at inflammatory phase was promoted significantly. The treatment of HMP hydrogel reduced the ROS degree and relieved the inflammatory level significantly, accompanied by the decreased neutrophil infiltration and enhanced M2-type macrophage polarization in vivo. Significantly lower levels of inflammatory factors such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and chemokines-1 (CXCL-1), and higher levels of anti-inflammatory cytokines such as IL-4 and IL-10 were also confirmed. Moreover, the HMP hydrogel could promote the secretion of transforming growth factor-β (TGF-β) and stimulate neovascularization, and deposition of collagen with a thicker skin and epithelium structure.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121597DOI Listing
July 2022

NSF-Based Analysis of the Structural Stressing State of Trussed Steel and a Concrete Box Girder.

Materials (Basel) 2022 May 26;15(11). Epub 2022 May 26.

School of Transportation Science and Engineering, Harbin Institute of Technology, Harbin 150090, China.

This paper analyses the characteristics of the mechanical behavior of a trussed steel and concrete box beam under bending conditions based on the structural stressing state theory and the numerical shape function method. Firstly, the parametric generalized strain energy density was introduced to characterize the structural stressing state of trussed steel stud concrete box girders, and the strain energy density sum was plotted. Then the Mann-Kendall criterion was used to discriminate the leap point of the curve change and to redefine the structural failure load. By analyzing the strain and displacement, the existence of a sudden change in the structural response during the load-bearing process was again demonstrated. Afterwards, the numerical shape function method was used to extend the strain data, and further in-depth analyses of strain/stress fields and internal forces were carried out to show in detail the working characteristics of each under load. Through an in-depth analysis from different angles, the rationality of updating the failure load was verified. Finally, the effects of different structure parameters on the evolution of the structural stresses of the members were analyzed in a transversal comparison. The analysis results of the stress state of a steel-concrete truss structure reveal the working behavior characteristics of a steel-concrete truss structure from a new angle, which provides a reference for the design of a steel-concrete truss structure in the future.
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http://dx.doi.org/10.3390/ma15113785DOI Listing
May 2022

Application of Multi-Criteria Decision-Making Analysis to Rural Spatial Sustainability Evaluation: A Systematic Review.

Int J Environ Res Public Health 2022 May 27;19(11). Epub 2022 May 27.

School of Architecture and Planning, Hunan University, Changsha 410082, China.

The rational allocation of spatial resources is an important factor to ensure the sustainable development of rural areas, and effective pre-emptive spatial evaluation is the prerequisite for identifying the predicament of rural resource allocation. Multi-criteria decision-making analysis has advantages in solving multi-attribute and multi-objective decision-making problems, and has been used in sustainability evaluation research in various disciplines in recent years. Previous studies have proved the value of spatial evaluation using multi-criteria decision analysis in guiding rural incremental development and inventory updates, but systematic reviews of the previous literature from a multidisciplinary perspective and studies of the implementation steps of the evaluation framework are lacking. In the current paper, the research is reviewed from the two levels of quantitative statistics and research content, and through vertical and horizontal comparisons based on three common operating procedures: standard formulation, weight distribution, and ranking and verification. Through the results, the application status and characteristics of the MCDA method in related research are determined, and five research foci in the future are proposed.
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http://dx.doi.org/10.3390/ijerph19116572DOI Listing
May 2022

Cellular Crosstalk in the Vascular Wall Microenvironment: The Role of Exosomes in Vascular Calcification.

Front Cardiovasc Med 2022 23;9:912358. Epub 2022 May 23.

Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China.

Vascular calcification is prevalent in aging, diabetes, chronic kidney disease, cardiovascular disease, and certain genetic disorders. However, the pathogenesis of vascular calcification is not well-understood. It has been progressively recognized that vascular calcification depends on the bidirectional interactions between vascular cells and their microenvironment. Exosomes are an essential bridge to mediate crosstalk between cells and organisms, and thus they have attracted increased research attention in recent years. Accumulating evidence has indicated that exosomes play an important role in cardiovascular disease, especially in vascular calcification. In this review, we introduce vascular biology and focus on the crosstalk between the different vessel layers and how their interplay controls the process of vascular calcification.
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http://dx.doi.org/10.3389/fcvm.2022.912358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168031PMC
May 2022

pH-sensitive carbon nanotubes graft polymethylacrylic acid self-assembly nanoplatforms for cellular drug release.

J Biomater Appl 2022 Jun 7:8853282221107156. Epub 2022 Jun 7.

Key Laboratory of Macromolecular Science of Shaanxi Province, School of chemistry and chemical engineering, 12401Shaanxi Normal University, Xi'an, China.

pH-Sensitive carbon nanotubes graft polymethylacrylic acid hybrids (CNTs--PMAA) were prepared through a three-step process, and self-assembled into core-shell micelle nanoparticles. The chemical structure of the hybrids were characterized by FTIR, H NMR and TGA. The critical micelle concentration (CMC) was measured by surface tension, and the value hinged on the Mn values or chain lengths of PMAA segments. The UV-vis transmittance, dynamical light scattering (DLS), and potential measurements indicated that the hybrid self-assembly exhibited pH-sensentive responsiveness. The self-assembly was used to load an anticancer drug, paclitaxel (PTX), with an encapsulation efficiency of 77%. The PTX-loaded hybrid drug preparations were applied for cancer-cellular drug release, finding that the release rate was dependent on pH environments, and faster in acidic media of pH < 6.8 than in pH 7.4. MTT and hemolysis assays manifested that the blank hybrid drug carriers were nontoxic and safe, whereas the PTX-loaded drug preparations possessed comparable and even higher anticancer activity in comparison with free PTX. Consequently, the developed hybrid drug nanocarriers can be used for cancer therapy as a promising candidate.
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http://dx.doi.org/10.1177/08853282221107156DOI Listing
June 2022

Conductive Hydrogel Conduits with Growth Factor Gradients for Peripheral Nerve Repair in Diabetics with Non-Suture Tape.

Adv Healthc Mater 2022 Jun 7:e2200755. Epub 2022 Jun 7.

Department of Chemical and Biological Engineering, Guangdong-Hong Kong-Macao Joint Laboratory for Intelligent Micro-Nano Optoelectronic Technology, William Mong Institute of Nano Science and Technology, and Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, P. R. China.

Diabetic patients suffer from peripheral nerve injury with slow and incomplete regeneration owing to hyperglycemia and microvascular complications. This study develops a graphene-based nerve guidance conduit by incorporating natural double network hydrogel and a neurotrophic concentration gradient with non-invasive treatment for diabetics. GelMA/silk fibroin double network hydrogel plays quadruple roles for rapid setting/curing, suitable mechanical supporting, good biocompatibility, and sustainable growth factor delivery. Meanwhile, graphene mesh can improve the toughness of conduit and enhance conductivity of conduit for regeneration. Here, novel silk tapes show quick and tough adhesion of wet tissue by dual mechanism to replace suture step. The in vivo results demonstrate that gradient concentration of netrin-1 in conduit have better performance than uniform concentration caused by chemotaxis phenomenon for axon extension, remyelination, and angiogenesis. Altogether, GelMA/silk graphene conduit with gradient netrin-1 and dry double-sided adhesive tape can significantly promote repairing of peripheral nerve injury and inhibit the atrophy of muscles for diabetics.
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http://dx.doi.org/10.1002/adhm.202200755DOI Listing
June 2022
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