Publications by authors named "Li Duan"

357 Publications

Neurophysiologic Complexity in Children Increases with Developmental Age and Is Reduced by General Anesthesia.

Anesthesiology 2021 Sep 7. Epub 2021 Sep 7.

Background: Neurophysiologic complexity in the cortex has been shown to reflect changes in the level of consciousness in adults but remains incompletely understood in the developing brain. This study aimed to address changes in cortical complexity related to age and anesthetic state transitions. This study tested the hypotheses that cortical complexity would (1) increase with developmental age and (2) decrease during general anesthesia.

Methods: This was a single-center, prospective, cross-sectional study of healthy (American Society of Anesthesiologists physical status I or II) children (n = 50) of age 8 to 16 undergoing surgery with general anesthesia at Michigan Medicine. This age range was chosen because it reflects a period of substantial brain network maturation. Whole scalp (16-channel), wireless electroencephalographic data were collected from the preoperative period through the recovery of consciousness. Cortical complexity was measured using the Lempel-Ziv algorithm and analyzed during the baseline, premedication, maintenance of general anesthesia, and clinical recovery periods. The effect of spectral power on Lempel-Ziv complexity was analyzed by comparing the original complexity value with those of surrogate time series generated through phase randomization that preserves power spectrum.

Results: Baseline spatiotemporal Lempel-Ziv complexity increased with age (yr; slope [95% CI], 0.010 [0.004, 0.016]; P < 0.001); when normalized to account for spectral power, there was no significant age effect on cortical complexity (0.001 [-0.004, 0.005]; P = 0.737). General anesthesia was associated with a significant decrease in spatiotemporal complexity (median [25th, 75th]; baseline, 0.660 [0.620, 0.690] vs. maintenance, 0.459 [0.402, 0.527]; P < 0.001), and spatiotemporal complexity exceeded baseline levels during postoperative recovery (0.704 [0.642, 0.745]; P = 0.009). When normalized, there was a similar reduction in complexity during general anesthesia (baseline, 0.913 [0.887, 0.923] vs. maintenance 0.851 [0.823, 0.877]; P < 0.001), but complexity remained significantly reduced during recovery (0.873 [0.840, 0.902], P < 0.001).

Conclusions: Cortical complexity increased with developmental age and decreased during general anesthesia. This association remained significant when controlling for spectral changes during anesthetic-induced perturbations in consciousness but not with developmental age.

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http://dx.doi.org/10.1097/ALN.0000000000003929DOI Listing
September 2021

Correction: FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation.

Cell Death Dis 2021 Aug 26;12(9):808. Epub 2021 Aug 26.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.

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http://dx.doi.org/10.1038/s41419-021-04096-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390478PMC
August 2021

Exosomes as Targeted Delivery Platform of CRISPR/Cas9 for Therapeutic Genome Editing.

Chembiochem 2021 Aug 21. Epub 2021 Aug 21.

Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, SAR, P. R. China.

Therapeutic genome editing harnesses the power of genome editing tools to correct erroneous genes associated with disease pathology. To bring the CRISPR/Cas9 tool from the bench to the bedside, a critical hurdle is the safe and efficient delivery of this nucleic acid tool to the desired type of cells in patients. This review discusses the use of natural carriers, extracellular vesicles (EVs), in particular exosomes, to fill the gap. Exosomes are lipid-containing nanovesicle released by various types of cells to mediate cell-cell communications. Their inherent long-distance transportation capability, biocompatibility, and engineerability have made EVs potential vehicles for delivering therapeutic drugs. We summarize the recent progress of harnessing exosomes as delivery vehicles for the CRISPR/Cas system to achieve therapeutic gene editing for disease treatment, with a focus on various strategies to achieve selective delivery to a particular type of cell and efficient packaging of the genome editing tools in the vesicles. Critical issues and possible solutions in the design and engineering of the targeting vehicles are highlighted. Taken together, we demonstrate EV/exosome-mediated packaging of the nucleic acid/protein tools and the cell/tissue-targeted delivery to be a viable way towards the clinical translation of the CRISPR/Cas9 technology.
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http://dx.doi.org/10.1002/cbic.202100359DOI Listing
August 2021

FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation.

Cell Death Dis 2021 Aug 9;12(8):780. Epub 2021 Aug 9.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.

FANCI is an essential component of Fanconi anemia pathway, which is responsible for the repair of DNA interstrand cross-links (ICLs). As an evolutionarily related partner of FANCD2, FANCI functions together with FANCD2 downstream of FA core complex. Currently, growing evidences showed that the essential role of FA pathway in male fertility. However, the underlying mechanisms for FANCI in regulating spermatogenesis remain unclear. In the present study, we found that the male Fanci mice were sterile and exhibited abnormal spermatogenesis, including massive germ cell apoptosis in seminiferous tubules and dramatically decreased number of sperms in epididymis. Besides, FANCI deletion impaired maintenance of undifferentiated spermatogonia. Further investigation indicated that FANCI was essential for FANCD2 foci formation and regulated H3K4 and H3K9 methylation on meiotic sex chromosomes. These findings elucidate the role and mechanism of FANCI during spermatogenesis in mice and provide new insights into the etiology and molecular basis of nonobstructive azoospermia.
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http://dx.doi.org/10.1038/s41419-021-04034-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353022PMC
August 2021

[Research Progress of Biodegradable Vascular Stent].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Jul;45(4):410-415

College of Chemistry and Chemical Engineering, University of South China, Hengyang, 421000.

Biodegradable vascular stents have better biocompatibility than drug-eluting stents. The blood vessels are rebuilt and degraded after normal physiological functions are restored. Due to it will not stay in the body for a long time and the patients don't need taking anti-rejection drugs all the time, it becomes the focus of attention in the treatment of coronary heart disease. This article introduced the development history of biodegradable stents and reviewed the research status of several different materials of vascular stents (animals or humans) and pointed out the existing problems. And it also predicted the research direction of biodegradable vascular stents.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.04.013DOI Listing
July 2021

Impacts of bio-stimulants on pyrene degradation, prokaryotic community compositions, and functions.

Environ Pollut 2021 Jul 31;289:117863. Epub 2021 Jul 31.

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, PR China; State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, PR China. Electronic address:

Bio-stimulation of the indigenous microbial community is considered as an effective strategy for the bioremediation of polluted environments. This examination explored the near effects of various bio-stimulants on pyrene degradation, prokaryotic community compositions, and functions using 16S rRNA amplicon sequencing and qPCR. At first, the results displayed significant differences (p < 0.05) between the prokaryotic community structures of the control group, PYR (contains pyrene only), and bio-stimulants amended groups. Among the bio-stimulants, biochar, oxalic acid, salicylate, NPK, and ammonium sulfate augmented the pyrene degradation potential of microbial communities. Moreover, the higher abundance of genera, such as Flavobacterium, Hydrogenophaga, Mycobacterium, Rhodococcus, Flavihumibacter, Pseudomonas, Novosphingobium, etc., across the treatments indicated that these genera play a vital role in pyrene metabolism. Based on the higher abundance of GP-RHD and nidA genes, we speculated that Gram-positive prokaryotic communities are more competent in pyrene dissipation than Gram-negative. Furthermore, the marked abundance of nifH, and pqqC genes in the NPK and SA treatments, respectively, suggested that different bio-stimulants might enrich certain bacterial assemblages. Besides, the significant distinctions (p < 0.05) between the bacterial consortia of HA (humic acid) and SA (sodium acetate) groups from NPK, OX (oxalic acid), UR (urea), NH4, and SC (salicylate) groups also suggested that different bio-stimulants might induce distinct ecological impacts influencing the succession of prokaryotic communities in distinct directions. This work provides new insight into the bacterial degradation of pyrene using the bio-stimulation technique. It suggests that it is equally important to investigate the community structure and functions along with studying their impacts on degradation when devising a bio-stimulation technology.
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http://dx.doi.org/10.1016/j.envpol.2021.117863DOI Listing
July 2021

Light-induced osteogenic differentiation of BMSCs with graphene/TiO composite coating on Ti implant.

Colloids Surf B Biointerfaces 2021 Jul 20;207:111996. Epub 2021 Jul 20.

Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address:

Light-induced surface potential have been demonstrated as an effective bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation regulator. However, traditional bone repair implants almost were weak or no light-responsive. Fortunately, surface modification was a feasible strategy to realize its light functionalization for bone implants. Herein, a graphene oxide (GO)/titanium dioxide (TiO) nanodots composite coating on the surface of titanium (Ti) implant was constructed, and GO was reduced to reduced graphene oxide (rGO) with the method of UV-assisted photocatalytic reduction. After rGO deposited on the surface of TiO, a heterojunction formed at the interface of rGO and TiO. With visible light illumination, positive charges accumulated on the surface of rGO/TiO film, and performed as a positive surface potential change. The light-induced surface potential which was generated under proper light intensity is harmless to the cell adhesion and proliferation behavior, but presented a good BMSCs osteogenic differentiation promoting effect, and the activation of the voltage-gated calcium channels through surface potential and the promotion of the adsorption of osteogenic growth factors could be the reason. This work given a new insight of the modification for Ti implant with a light-induced surface potential, and shows potential application for bone regeneration on the clinical practice through light stimulation.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111996DOI Listing
July 2021

IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis.

J Cell Physiol 2021 Jul 23. Epub 2021 Jul 23.

Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic Engineering, Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University, Health Science Center), Shenzhen, China.

IRE1 is an important central regulator of unfolded protein response (UPR) in the endoplasmic reticulum (ER) because of its ability to regulate cell fate as a function of stress sensing. When misfolded proteins accumulated in chondrocytes ER, IRE1 disintegrates with BIP/GRP78 and undergoes dimer/oligomerization and transautophosphorylation. These two processes are mediated through an enzyme activity of IRE1 to activate endoribonuclease and generates XBP1 by unconventional splicing of XBP1 messenger RNA. Thereby promoting the transcription of UPR target genes and apoptosis. The deficiency of inositol-requiring enzyme 1α (IRE1α) in chondrocytes downregulates prosurvival factors XBP1S and Bcl-2, which enhances the apoptosis of chondrocytes through increasing proapoptotic factors caspase-3, p-JNK, and CHOP. Meanwhile, the activation of IRE1α increases chondrocyte viability and reduces cell apoptosis. However, the understanding of IRE1 responses and cell death fate remains controversial. This review provides updated data about the role IRE1 plays in chondrocytes and new insights about the potential efficacy of IRE1 regulation in cartilage repair and osteoarthritis treatment.
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http://dx.doi.org/10.1002/jcp.30537DOI Listing
July 2021

Decentralized Robust Portfolio Optimization Based on Cooperative-Competitive Multiagent Systems.

IEEE Trans Cybern 2021 Jul 14;PP. Epub 2021 Jul 14.

This article addresses decentralized robust portfolio optimization based on multiagent systems. Decentralized robust portfolio optimization is first formulated as two distributed minimax optimization problems in a Markowitz return-risk framework. Cooperative-competitive multiagent systems are developed and applied for solving the formulated problems. The multiagent systems are shown to be able to reach consensuses in the expected stock prices and convergence in investment allocations through both intergroup and intragroup interactions. Experimental results of the multiagent systems with stock data from four major markets are elaborated to substantiate the efficacy of multiagent systems for decentralized robust portfolio optimization.
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http://dx.doi.org/10.1109/TCYB.2021.3088884DOI Listing
July 2021

Ultrasound-Guided Percutaneous Laser Ablation of the Thyroid Gland in a Swine Model: Comparison of Ablation Parameters and Ablation Zone Dimensions.

Cardiovasc Intervent Radiol 2021 Jul 12. Epub 2021 Jul 12.

Interventional Radiology Service, Department of Radiology, Weill-Cornell Medical College, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Howard 118, New York 10065, T 212 639 2209, New York, NY, USA.

Background: To compare laser ablation (LA) zone dimensions at two predetermined energy parameters to cover a theoretical 10 mm zone + 2 mm margin in a thyroid swine model.

Methods: Approval of the Institutional Animal Care and Use Committee was obtained. After hydrodissection, an ultrasound-guided LA (Elesta Echolaser X4 with Orblaze technology, 1064 nm) was performed in the periphery of the thyroid in 10 swine. Two cohorts were established to ablate a region of 10mm diameter with 2mm margin based on manufacturer's ex vivo data (n= 5 at 3W/1400J and n= 5 at 3W/1800J). The ablation zone was measured on contrast-enhanced computed tomography (CT) and compared to the pathological specimen. Euthanasia was performed 48 hours following ablation.

Results: All ablations in the 3W/1800J group achieved a diameter of 12 mm ± 1 mm in three dimensions. In the 3W/1400J group, 1 ablation reached 12 mm ± 1 mm in 2 dimensions and 4 ablations reached this size in one dimension. Maximum diameter was higher in the 3W/1800J compared to the 3W/1400J group, both on histology (1.46 cm ± 0.05 vs. 1.1 cm ± 0.0, p< 0.01) and CT (1.52 cm ± 0.04 vs. 1.18 cm ± 0.04, p< 0.01). Similar results were obtained regarding volumes, both on histology (1.12 mL ± 0.13 vs. 0.57 mL ± 0.06, p< 0.01) and CT (1.24 mL ± 0.13 vs. 0.59 mL ± 0.07, p< 0.01). Histology showed coagulation necrosis and correlated well with CT measurements.

Conclusion: Optimal parameters to obtain a LA zone of 10 mm with 2 mm margin utilizing a single needle are 3W/1800J.
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http://dx.doi.org/10.1007/s00270-021-02915-0DOI Listing
July 2021

Effect of high-flow nasal cannula oxygen therapy in patients with chronic obstructive pulmonary disease: A meta-analysis.

J Clin Nurs 2021 Jul 9. Epub 2021 Jul 9.

Department of Respiratory and Critical Care Medicine, The Ninth People's Hospital of Chongqing, Chongqing, China.

Background: High-flow nasal cannula oxygen therapy reduces the arterial partial pressure of carbon dioxide and acute exacerbation but does not increase exercise capacity or decrease hospitalisation or mortality. The study aimed to test the hypothesis that in chronic obstructive pulmonary disease patients, the use of high-flow nasal cannula decreases arterial partial pressure of carbon dioxide and increases the partial pressure of oxygen and 6-min walking distance.

Methods: PubMed, Embase and the Cochrane library were searched for eligible studies published from database inception to November 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist). The primary outcomes were partial pressure of carbon dioxide and partial pressure of oxygen, and the secondary outcomes were transcutaneous partial pressure of carbon dioxide and 6-min walking distance.

Results: Nine studies (680 patients) were included. high-flow nasal cannula did not decrease partial pressure of carbon dioxide compared with the control interventions (mean difference = -0.81, 95% confidence interval: -2.68 to 1.06, p = .395; I  = 42.9%, p  = .105). high-flow nasal cannula decreased partial pressure of carbon dioxide compared with long-term oxygen therapy (mean difference = -3.25, 95% confidence interval: -5.65 to -0.85, p = .008; I  = 0%, p = .375); no difference was observed for the control modalities. high-flow nasal cannula resulted in better partial pressure of carbon dioxide compared with control interventions in hypoxemic patients (mean difference = -2.59, 95% confidence interval: -4.82 to -0.35, p = .023; I  = 32.5%, p  = .224), but not in other types of patients. high-flow nasal cannula did not increase partial pressure of oxygen compared with the control interventions (mean difference = 1.17, 95% confidence interval: -1.50 to 3.83, p = .390; I  = 0%, p  = .660). high-flow nasal cannula decreased transcutaneous carbon dioxide tension (transcutaneous partial pressure of carbon dioxide) compared with the control interventions (mean difference = 2.37, 95% confidence interval: 0.07-4.68, p = .044; I  = 8.7%, p = .295). high-flow nasal cannula increased 6-min walking distance compared with the control interventions (mean difference = 18.22, 95% confidence interval: 0.86-,35.57, p = .040; I  = 0%, p  = .918). The sensitivity analyses showed that the results were robust.

Conclusions: High-flow nasal cannula did not significantly decrease partial pressure of carbon dioxide or increase partial pressure of oxygen in chronic obstructive pulmonary disease patients, which is different from the previous meta-analysis, but it decreases transcutaneous partial pressure of carbon dioxide and increased 6-min walking distance.

Relevance To Clinical Practice: This meta-analysis shows that in patients with chronic obstructive pulmonary disease, high-flow nasal cannula improves both transcutaneous partial pressure of carbon dioxide and 6-min walking distance, suggesting the high-flow nasal cannula has benefits in the management of chronic obstructive pulmonary disease. Considering that the literature suggests no impact of high-flow nasal cannula on hospitalisation and mortality, the benefits of high-flow nasal cannula might be limited to the patients who survive the chronic obstructive pulmonary disease events. Still, the global impact of high-flow nasal cannula on the quality of life of patients with chronic obstructive pulmonary disease should be examined.
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http://dx.doi.org/10.1111/jocn.15957DOI Listing
July 2021

Integrated Analyses of the Gut Microbiota, Intestinal Permeability, and Serum Metabolome Phenotype in Rats with Alcohol Withdrawal Syndrome.

Appl Environ Microbiol 2021 08 26;87(18):e0083421. Epub 2021 Aug 26.

The Second Affiliated Hospital of Xinxiang Medical Universitygrid.412990.7Xinxiang Medical University, Henan Key Laboratory of Biological Psychiatry, grid.412990.7, Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.

The etiology of alcohol dependence is not completely understood. Increasing evidence reveals that gut microbiota dysbiosis is associated with certain psychiatric disorders, including alcoholism, through the "microbiota-gut-brain" axis. The aims of this study were to evaluate the effect of alcohol abuse on the gut microbiota, intestinal permeability and serum metabolic profile and to determine whether alcohol-induced alterations in gut microbiota are correlated with gut permeability and serum metabolic phenotype changes. 16S rRNA gene high-throughput sequencing and nontarget metabolomics techniques were applied in an alcohol-dependent rat model in the present study. The results showed that alcohol intake altered the composition and structure of the colonic microbiota, especially the relative abundances of commensal microbes in the families and , which were significantly decreased. Alcohol-dependent rats developed gut leakiness and a serum metabolic phenotype disorder. The valine, leucine and isoleucine biosynthesis pathways and arginine and proline metabolism pathways were obviously influenced by alcohol intake. Moreover, alcohol consumption disturbed the brain's neurotransmitter homeostasis. Regression analysis showed that alcohol-induced colonic microbiota dysbiosis was strongly associated with increased intestinal permeability and serum metabolic phenotype and neurotransmitter disorders. These results revealed that gut microbiota dysbiosis and serum metabolite alteration might be a cofactor for developing of alcohol dependence. Gut microbiota dysbiosis is associated with certain psychiatric disorders through the "microbiota-gut-brain" axis. Here, we revealed that alcohol consumption induced colonic microbiota dysbiosis, increased intestinal permeability, and altered the serum metabolic phenotype in rats, and there was a strong correlation between gut microbiota dysbiosis and serum metabolite disorders. Thus, gut microbiota dysbiosis and serum metabolite alteration may be a cofactor for development of alcohol dependence.
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http://dx.doi.org/10.1128/AEM.00834-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388829PMC
August 2021

Based on a Decision Tree Model for Exploring the Risk Factors of Smartphone Addiction Among Children and Adolescents in China During the COVID-19 Pandemic.

Front Psychiatry 2021 8;12:652356. Epub 2021 Jun 8.

Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.

Smartphone addiction has emerged as a major concern among children and adolescents over the past few decades and may be heightened by the outbreak of COVID-19, posing a threat to their physical and mental health. Then we aimed to develop a decision tree model as a screening tool for unrecognized smartphone addiction by conducting large sample investigation in mainland China. The data from cross-sectional investigation of smartphone addiction among children and adolescents in mainland China ( = 3,615) was used to build models of smartphone addiction by employing logistic regression, visualized nomogram, and decision tree analysis. Smartphone addiction was found in 849 (23.5%) of the 3,615 respondents. According to the results of logistic regression, nomogram, and decision tree analyses, Internet addiction, hours spend on smartphone during the epidemic, levels of clinical anxiety symptoms, fear of physical injury, and sex were used in predictive model of smartphone addiction among children and adolescents. The C-index of the final adjusted model of logistic regression was 0.804. The classification accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and AUC area of decision tree for detecting smartphone addiction were 87.3, 71.4, 92.1, 73.5, 91.4, and 0.884, respectively. It was found that the incidence of smartphone addiction among children and adolescents is significant during the epidemic. The decision tree model can be used to screen smartphone addiction among them. Findings of the five risk factors will help researchers and parents assess the risk of smartphone addiction quickly and easily.
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http://dx.doi.org/10.3389/fpsyt.2021.652356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217434PMC
June 2021

Nanoparticle Delivery of CRISPR/Cas9 for Genome Editing.

Front Genet 2021 12;12:673286. Epub 2021 May 12.

Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen Key Laboratory for Psychological Healthcare & Shenzhen Institute of Mental Health, Shenzhen, China.

The emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated system (Cas) gene-editing system represents a promising tool for genome manipulation. However, its low intracellular delivery efficiency severely compromises its use and potency for clinical applications. Nanocarriers, such as liposomes, polymers, and inorganic nanoparticles, have shown great potential for gene delivery. The remarkable development of nanoparticles as non-viral carriers for the delivery of the CRISPR/Cas9 system has shown great promise for therapeutic applications. In this review, we briefly summarize the delivery components of the CRISPR/Cas9 system and report on the progress of nano-system development for CRISPR/Cas9 delivery. We also compare the advantages of various nano-delivery systems and their applications to deliver CRISPR/Cas9 for disease treatment. Nano-delivery systems can be modified to fulfill the tasks of targeting cells or tissues. We primarily emphasize the novel exosome-based CRISPR/Cas9 delivery system. Overall, we review the challenges, development trends, and application prospects of nanoparticle-based technology for CRISPR/Cas9 delivery.
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http://dx.doi.org/10.3389/fgene.2021.673286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149999PMC
May 2021

LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA.

Cell Death Discov 2021 May 16;7(1):107. Epub 2021 May 16.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, 250012, Jinan, Shandong, China.

Granulosa cell (GC) is a critical somatic component of ovarian follicles to support oocyte development, while the regulatory role of long noncoding RNA (lncRNA) in GCs is largely unknown. Here, we identified a down-regulated lncRNA ZNF674-AS1 in GCs from patients with biochemical premature ovarian insufficiency (bPOI), and its expression correlates with serum levels of clinical ovarian reserve indicators. Functional experiments showed that ZNF674-AS1 is induced by energy stress, and regulates the proliferation and glycolysis of GCs, which possibly leads to follicular dysfunction. Mechanistically, low-expressed ZNF674-AS1 reduced the enzymatic activity of aldolase A (ALDOA), concomitant with promoting the association between ALDOA and v-ATPase to activate the lysosome localized AMP-activated protein kinase (AMPK). These findings identified a new lncRNA-ALDOA complex through which ZNF674-AS1 exerts its functions, expanding the understanding of epigenetic regulation of GCs function and POI pathogenesis.
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http://dx.doi.org/10.1038/s41420-021-00493-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124069PMC
May 2021

Recovery of consciousness and cognition after general anesthesia in humans.

Elife 2021 05 10;10. Epub 2021 May 10.

Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.

Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, just prior to the recovery of consciousness, frontal-parietal dynamics returned to baseline. Consistent with our hypothesis, cognitive reconstitution after anesthesia evolved over time. Contrary to our hypothesis, executive function returned first. Early engagement of prefrontal cortex in recovery of consciousness and cognition is consistent with global neuronal workspace theory.
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http://dx.doi.org/10.7554/eLife.59525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163502PMC
May 2021

The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial.

Anesth Analg 2021 07;133(1):233-242

From the Department of Anesthesiology.

Background: Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively.

Methods: This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups.

Results: Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration.

Conclusions: Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence.
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http://dx.doi.org/10.1213/ANE.0000000000005532DOI Listing
July 2021

Sex-based differences in fecal short-chain fatty acid and gut microbiota in irritable bowel syndrome patients.

J Dig Dis 2021 May;22(5):246-255

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.

Objective: To explore alterations in fecal short-chain fatty acids (SCFA) and gut microbiota in patients with diarrhea-predominant irritable bowel disease (IBS-D) and their relationships with clinical manifestations.

Methods: We recruited 162 patients with IBS-D and 66 healthy controls (HC). Their manifestations and psychological status were evaluated using the IBS severity scoring system and the Hospital Anxiety and Depression Scale (HADS). Colorectal visceral sensitivity was evaluated using a barostat. Systemic inflammation was evaluated using plasma cytokine levels. Fecal SCFA were quantified using ultra-performance liquid chromatography-tandem mass spectrometry, and fecal microbiota communities were analyzed using 16S rRNA sequencing.

Results: More men presented with IBS-D than women in our patient cohort. Patients with IBS-D had more severe manifestations, higher HADS score, and a higher rate of previous infectious enteritis than HC. Notably, female patients had significantly higher HADS scores than male patients. Male patients had significantly higher levels of plasma interleukin (IL)-12, fecal propionate and colorectal visceral sensitivity than male HC, while no differences were observed between female patients and female HC. Fecal acetate, butyrate and valerate correlated with the initial visceral sensory threshold, stressors, and IL-10 and IL-12 levels. The propionate-producing Prevotella 9 genus was significantly increased in male patients and positively correlated with fecal propionate.

Conclusion: Distinct sex-based differences in clinical manifestations, fecal SCFA and microbiota richness are found in Chinese patients with IBS-D, which may be used to diagnose dysbiosis in these patients.
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http://dx.doi.org/10.1111/1751-2980.12988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252430PMC
May 2021

Identification and Characterization of EvpQ, a Novel T6SS Effector Encoded on a Mobile Genetic Element in .

Front Microbiol 2021 11;12:643498. Epub 2021 Mar 11.

State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

In this study, a hypothetical protein (ORF02740) secreted by was identified. We renamed the ORF02740 protein as EvpQ, which is encoded by a mobile genetic element (MGE) in genome. The gene is spaced by 513 genes from type VI secretion system (T6SS) gene cluster. Low GC content, three tRNA, and three transposase genes nearby define this MGE that localizes as a genomic island. Sequence analysis reveals that EvpQ shares a conserved domain of C70 family cysteine protease and shares 23.91% identity with T3SS effector AvrRpt2 of phytopathogenic Instead, EvpQ of is proved to be secreted at a T6SS-dependent manner, and it can be translocated into host cells. EvpQ is thereof a novel T6SS effector. Significantly decreased competitive index of Δ strain in blue gourami fish (0.53 ± 0.27 in head kidney and 0.44 ± 0.19 in spleen) indicates that EvpQ contributes to the pathogenesis of . At 8-, 18-, and 24-h post-subculture into DMEM, the transcription of was found to be negatively regulated by Fur and positively regulated by EsrC, and the steady-state protein levels of EvpQ are negatively controlled by RpoS. Our study lays a foundation for further understanding the pathogenic role of T6SS in edwardsiellosis.
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http://dx.doi.org/10.3389/fmicb.2021.643498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991086PMC
March 2021

Manipulation of the Nanoscale Presentation of Integrin Ligand Produces Cancer Cells with Enhanced Stemness and Robust Tumorigenicity.

Nano Lett 2021 04 25;21(7):3225-3236. Epub 2021 Mar 25.

Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, 999077, China.

Developing strategies for efficient expansion of cancer stem-like cells (CSCs) will help investigate the mechanism underlying tumorigenesis and cancer recurrence. Herein, we report a dynamic culture substrate tethered with integrin ligand-bearing magnetic nanoparticles via a flexible polymeric linker to enable magnetic manipulation of the nanoscale ligand tether mobility. The cancer cells cultured on the substrate with high ligand tether mobility develop into large semispherical colonies with CSCs features, which can be abrogated by magnetically restricting the ligand tether mobility. Mechanistically, the substrate with high ligand tether mobility suppresses integrin-mediated mechanotransduction and histone-related methylation, thereby enhancing cancer cell stemness. The culture-derived high-stemness cells can generate tumors both locally and at the distant lung and uterus much more efficiently than the low-stemness cells. We believe that this magnetic nanoplatform provides a promising strategy for investigating the dynamic interaction between CSCs and the microenvironment and establishing a cost-effective tumor spheroid model.
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http://dx.doi.org/10.1021/acs.nanolett.1c00501DOI Listing
April 2021

Screening and verification of hub genes involved in osteoarthritis using bioinformatics.

Exp Ther Med 2021 Apr 8;21(4):330. Epub 2021 Feb 8.

Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Hand and Foot Surgery Department, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University), Shenzhen, Guangdong 518000, P.R. China.

Osteoarthritis (OA) is one of the most common causes of disability and its development is associated with numerous factors. A major challenge in the treatment of OA is the lack of early diagnosis. In the present study, a bioinformatics method was employed to filter key genes that may be responsible for the pathogenesis of OA. From the Gene Expression Omnibus database, the datasets GSE55457, GSE12021 and GSE55325 were downloaded, which comprised 59 samples. Of these, 30 samples were from patients diagnosed with osteoarthritis and 29 were normal. Differentially expressed genes (DEGs) were obtained by downloading and analyzing the original data using bioinformatics. The Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed using the Database for Annotation, Visualization and Integrated Discovery online database. Protein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/proteins online database. BSCL2 lipid droplet biogenesis associated, seipin, FOS-like 2, activator protein-1 transcription factor subunit (FOSL2), cyclin-dependent kinase inhibitor 1A (CDKN1A) and kinectin 1 (KTN1) genes were identified as key genes by using Cytoscape software. Functional enrichment revealed that the DEGs were mainly accumulated in the ErbB, MAPK and PI3K-Akt pathways. Reverse transcription-quantitative PCR analysis confirmed a significant reduction in the expression levels of FOSL2, CDKN1A and KTN1 in OA samples. These genes have the potential to become novel diagnostic and therapeutic targets for OA.
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http://dx.doi.org/10.3892/etm.2021.9761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903481PMC
April 2021

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight.

Authors:

Elife 2021 Mar 9;10. Epub 2021 Mar 9.

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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http://dx.doi.org/10.7554/eLife.60060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943191PMC
March 2021

Interleukin 1 beta-induced chloride currents are important in osteoarthritis onset: an in vitro study.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar;53(4):400-409

Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Hand and Foot Surgery Department, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University), Shenzhen 518000, China.

Persistent hypotonic and inflammatory conditions in the joint cavity can lead to the loss of cartilage matrix and cell death, which are the important mechanisms of osteoarthritis (OA) onset. Previous studies have confirmed that the existence of a hypotonic environment is a red flag for inflammation, as hypotonic environment induces the opening of the chloride channel of the cell and promotes chloride ion efflux, which prompts the cell volume to increase. Chloride channels play an important role in the regulation of mineralization and chondrocyte death. Here, we reported that OA chondrocytes showed a significant increase of cell death rate and the imbalance of cartilage matrix catabolism. We found that the distribution of skeleton protein F-actin was disordered. In addition, the volume-sensitive chloride current of OA chondrocytes decreased significantly with the increase of the expression levels of inflammation-related proteins caspase-1, caspase-3, and NLRP3. Moreover, interleukin-1β (IL-1β) showed a potential to activate the chloride current of normal chondrocytes. These results indicate that IL-1β-induced chloride channel opening in chondrocytes may be closely related to the occurrence of OA. This chloride channel opening process may therefore be a potential target for the treatment of OA.
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http://dx.doi.org/10.1093/abbs/gmab010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996641PMC
March 2021

Glutamatergic Neurons in the Preoptic Hypothalamus Promote Wakefulness, Destabilize NREM Sleep, Suppress REM Sleep, and Regulate Cortical Dynamics.

J Neurosci 2021 04 4;41(15):3462-3478. Epub 2021 Mar 4.

Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-5615

Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study, we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. We also demonstrate, for the first time, that activation of these preoptic glutamatergic neurons causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, decreases body temperature, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons can initiate, but not maintain, arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the hypothesis that the preoptic area causally contributes to the regulation of both sleep and wakefulness. Historically, the preoptic area of the hypothalamus has been considered a key site for sleep generation. However, emerging modeling and empirical data suggest that this region might play a dual role in sleep-wake control. We demonstrate that chemogenetic stimulation of preoptic glutamatergic neurons produces brief arousals that fragment sleep, persistently suppresses REM sleep, causes hypothermia, and shifts EEG patterns toward a "lighter" NREM sleep state. We propose that preoptic glutamatergic neurons can initiate, but not maintain, arousal from sleep and gate REM sleep generation, possibly to block REM-like intrusions during NREM-to-wake transitions. In contrast to the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic, we provide further evidence that preoptic neurons also generate wakefulness.
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http://dx.doi.org/10.1523/JNEUROSCI.2718-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051693PMC
April 2021

Administration of zoledronic acid alleviates osteoporosis in HIV patients by suppressing osteoclastogenesis via regulating RANKL expression.

Mol Med 2021 02 26;27(1):19. Epub 2021 Feb 26.

Department of Orthopedics, Third People's Hospital of Shenzhen, No. 29 Bulan Road, Longgang, Shenzhen, 518112, Guangdong, People's Republic of China.

Background: Osteoporosis is a common phenomenon in HIV patients on tenofovir treatment, but its underlying mechanisms remain to be explored.

Methods: Quantitative real-time PCR was performed to analyze the expression of miR-302, miR-101, miR-145 and osteoclast-specific genes in the serum of HIV patients treated with tenofovir and ZOL. ELISA was used to evaluate the expression of RANKL, SMAD3 and PRKACB in the serum of these patients. Luciferase assay was carried out to explore the inhibitory effects of miR-302, miR-101 and miR-145 on the expression of PRKACB, RANKL and SMAD3, respectively. Western blot was used to examine the expression of genes involved in NF‑κB and JNK signaling pathways.

Results: ZOL treatment significantly suppressed the expression of CTx and osteocalcin in HIV patients treated with tenofovir. The BMD loss of HIV patients treated with tenofovir was effectively hindered by ZOL treatment. Mechanistically, the expression of miR-302, miR-101, miR-145, RANKL, SMAD3 and PRKACB in the serum was remarkably activated by ZOL treatment. Luciferase assays showed that miR-302, miR-101 and miR-145 effectively suppressed the expression of PRKACB, RANKL and SMAD3, respectively, through binding to their 3' UTR. Furthermore, ZOL treatment notably restored the normal expression of osteoclast‑specific genes while activating NF‑κB and JNK signaling pathways.

Conclusion: The findings of this study demonstrated that administration of ZOL suppressed the expression of RANKL via modulating signaling pathways of miR-101-3p/RANKL, miR-302/PRKACB/RANKL and miR-145/SMAD3/RANKL. Furthermore, down-regulated expression of RANKL by ZOL treatment alleviated osteoporosis in HIV-positive subjects treated with tenofovir.
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http://dx.doi.org/10.1186/s10020-021-00276-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908730PMC
February 2021

Deletion of FGF9 in GABAergic neurons causes epilepsy.

Cell Death Dis 2021 02 19;12(2):196. Epub 2021 Feb 19.

Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.

Fibroblast growth factor 9 (FGF9) has long been assumed to modulate multiple biological processes, yet very little is known about the impact of FGF9 on neurodevelopment. Herein, we found that loss of Fgf9 in olig1 progenitor cells induced epilepsy in mice, with pathological changes in the cortex. Then depleting Fgf9 in different neural populations revealed that epilepsy was associated with GABAergic neurons. Fgf9 CKO in GABAergic neuron (CKO) mice exhibited not only the most severe seizures, but also the most severe growth retardation and highest mortality. Fgf9 deletion in CKO mice caused neuronal apoptosis and decreased GABA expression, leading to a GABA/Glu imbalance and epilepsy. The adenylate cyclase/cyclic AMP and ERK signaling pathways were activated in this process. Recombinant FGF9 proteoliposomes could significantly decrease the number of seizures. Furthermore, the decrease of FGF9 was commonly observed in serum of epileptic patients, especially those with focal seizures. Thus, FGF9 plays essential roles in GABAergic neuron survival and epilepsy pathology, which could serve as a new target for the treatment of epilepsy.
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http://dx.doi.org/10.1038/s41419-021-03478-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896082PMC
February 2021

3D printed gelatin/hydroxyapatite scaffolds for stem cell chondrogenic differentiation and articular cartilage repair.

Biomater Sci 2021 Apr 17;9(7):2620-2630. Epub 2021 Feb 17.

Department of Orthopedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China.

Acute injury of the articular cartilage can lead to chronic disabling conditions because of the limited self-repair capability of the cartilage. Implantation of stem cells at the injury site is a viable treatment, but requires a scaffold with a precisely controlled geometry and porosity in the 3D space, high biocompatibility, and the capability of promoting chondrogenic differentiation of the implanted stem cells. Here we report the development of gelatin/hydroxyapatite (HAP) hybrid materials by microextrusion 3D bioprinting and enzymatic cross-linking as the scaffold for human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). The scaffold supports the adhesion, growth, and proliferation of hUCB-MSCs and induces their chondrogenic differentiation in vitro. Doping HAP in the gelatin scaffold increases the fluidity of the hydrogel, improves the gelation kinetics and the rheological properties, and allows better control over 3D printing. Implanting the hUCB-MSC-laden scaffold at the injury site of the articular cartilage effectively repairs the cartilage defects in a pig model. Altogether, this work demonstrates the 3D printing of gelatin-based scaffold materials for hUCB-MSCs to repair cartilage defects as a potential treatment of articular cartilage injury.
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http://dx.doi.org/10.1039/d0bm02103bDOI Listing
April 2021

Engineering exosomes for targeted drug delivery.

Theranostics 2021 1;11(7):3183-3195. Epub 2021 Jan 1.

Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

Exosomes are cell-derived nanovesicles that are involved in the intercellular transportation of materials. Therapeutics, such as small molecules or nucleic acid drugs, can be incorporated into exosomes and then delivered to specific types of cells or tissues to realize targeted drug delivery. Targeted delivery increases the local concentration of therapeutics and minimizes side effects. Here, we present a detailed review of exosomes engineering through genetic and chemical methods for targeted drug delivery. Although still in its infancy, exosome-mediated drug delivery boasts low toxicity, low immunogenicity, and high engineerability, and holds promise for cell-free therapies for a wide range of diseases.
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http://dx.doi.org/10.7150/thno.52570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847680PMC
July 2021

Forecasting sensitive targets of the kynurenine pathway in pancreatic adenocarcinoma using mathematical modeling.

Cancer Sci 2021 Apr 20;112(4):1481-1494. Epub 2021 Feb 20.

Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic Engineering, Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University, Health Science Center), Shenzhen, China.

In this study, a new mathematical model was established and validated to forecast and define sensitive targets in the kynurenine pathway (Kynp) in pancreatic adenocarcinoma (PDAC). Using the Panc-1 cell line, genetic profiles of Kynp molecules were tested. qPCR data were implemented in the algorithm programming (fmincon and lsqnonlin function) to estimate 35 parameters of Kynp variables by Matlab 2017b. All tested parameters were defined as non-negative and bounded. Then, based on experimental data, the function of the fmincon equation was employed to estimate the approximate range of each parameter. These calculations were confirmed by qPCR and Western blot. The correlation coefficient (R) between model simulation and experimental data (72 hours, in intervals of 6 hours) of every variable was >0.988. The analysis of reliability and predictive accuracy depending on qPCR and Western blot data showed high predictive accuracy of the model; R was >0.988. Using the model calculations, kynurenine (x3, a6), GPR35 (x4, a8), NF-kβp105 (x7, a16), and NF-kβp65 (x8, a18) were recognized as sensitive targets in the Kynp. These predicted targets were confirmed by testing gene and protein expression responses. Therefore, this study provides new interdisciplinary evidence for Kynp-sensitive targets in the treatment of PDAC.
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http://dx.doi.org/10.1111/cas.14832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019197PMC
April 2021

High expression of MAPK-14 promoting the death of chondrocytes is an important signal of osteoarthritis process.

PeerJ 2021 15;9:e10656. Epub 2021 Jan 15.

Hand and Foot Surgery Department, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University), Shenzhen, Guangdong, China.

Background: Osteoarthritis (OA) is one of the most common degenerative diseases worldwide. Many researchers are studying the pathogenesis of OA, however, it is still unclear.

Methods: Screening and validation of OA relevant hub genes are an important part of exploring their potential molecular mechanism. Therefore, this study aims to explore and verify the mechanisms of hub genes in the OA by bioinformatics, qPCR, fluorescence and propidium iodide staining.

Results: Microarray datasets GSE43923, GSE55457 and GSE12021 were collected in the Gene Expression Omnibus (GEO), including 45 samples, which divided into 23 osteoarthritis knee joint samples and 22 samples of normal knee joint. Thereafter, 265 differentiallyexpressedgenes (DEGs) were identified in all, which divided into 199 upregulated genes and 66 downregulated genes. The hub genes MAPK-14, PTPRC, PTPN12 were upregulated, while B9D1 was downregulated. In order to further confirm the expression of screening differential genes in human chondrocytes, the human chondrocytes were extracted from a joint replacement surgery and stained with toluidine blue for identification. Compared with normal chondrocytes, OA chondrocytes had high expression of COL I protein and low expression of COL II protein. The expression levels of MAPK-14, PTPRC and PTPN12 in OA chondrocytes were significantly higher than the expression levels of B9D1 in normal chondrocytes. Moreover, the inflammatory necrosis of OA chondrocytes was increased compared with the normal chondrocytes by propidium iodide staining.

Conclusions: The high expression of MAPK-14 works as a promoter of chondrocytes death and an important signal of the osteoarthritis process.
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http://dx.doi.org/10.7717/peerj.10656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812924PMC
January 2021
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