Publications by authors named "Yi Zhu"

1,470 Publications

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High-throughput proteomic sample preparation using pressure cycling technology.

Nat Protoc 2022 Aug 5. Epub 2022 Aug 5.

Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.

High-throughput lysis and proteolytic digestion of biopsy-level tissue specimens is a major bottleneck for clinical proteomics. Here we describe a detailed protocol of pressure cycling technology (PCT)-assisted sample preparation for proteomic analysis of biopsy tissues. A piece of fresh frozen or formalin-fixed paraffin-embedded tissue weighing ~0.1-2 mg is placed in a 150 μL pressure-resistant tube called a PCT-MicroTube with proper lysis buffer. After closing with a PCT-MicroPestle, a batch of 16 PCT-MicroTubes are placed in a Barocycler, which imposes oscillating pressure to the samples from one atmosphere to up to ~3,000 times atmospheric pressure. The pressure cycling schemes are optimized for tissue lysis and protein digestion, and can be programmed in the Barocycler to allow reproducible, robust and efficient protein extraction and proteolysis digestion for mass spectrometry-based proteomics. This method allows effective preparation of not only fresh frozen and formalin-fixed paraffin-embedded tissue, but also cells, feces and tear strips. It takes ~3 h to process 16 samples in one batch. The resulting peptides can be analyzed by various mass spectrometry-based proteomics methods. We demonstrate the applications of this protocol with mouse kidney tissue and eight types of human tumors.
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http://dx.doi.org/10.1038/s41596-022-00727-1DOI Listing
August 2022

Induction chemotherapy of modified docetaxel, cisplatin, 5-fluorouracil for laryngeal preservation in locally advanced hypopharyngeal squamous cell carcinoma.

Head Neck 2022 Sep;44(9):2018-2029

Department of Radiation Oncology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China.

Background: Previous studies have investigated the value of induction chemotherapy (IC) in organ preservation strategies for head and neck cancers. This study evaluated the effectiveness of sequential IC with radiotherapy as a laryngeal preservation strategy for locally advanced hypopharyngeal carcinoma (LAHSCC).

Methods: One hundred and forty-two consecutive patients with LAHSCC were retrospectively analyzed who received three IC regimens from 2015 to 2019.

Results: In the TP (docetaxel plus cisplatin), TPF (TP plus 5-fluorouracil), and TPX (TP plus capecitabine) IC groups, there were 51, 29, and 62 patients, respectively. The primary tumor objective response rates were 51%, 55.2%, and 71%, and the 3-year survival rates with preserved larynx were 36.6%, 31.8%, and 51.2%, respectively (p = 0.03). There was no difference in overall survival and the adverse events were tolerable.

Conclusions: The TPX regimen displayed good efficacy and safety, indicating its potential as a therapeutic IC regimen for LAHSCC.
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http://dx.doi.org/10.1002/hed.27119DOI Listing
September 2022

The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma.

Head Neck 2022 Sep;44(9):2009-2017

Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Background: For patients with less chemosensitive neck nodes, poor prognosis after chemoradiotherapy (CRT) could be predicted and neck dissection is needed.

Methods: Ninety-two N2/3 hypopharyngeal carcinoma patients were retrospectively studied. According to response after induction chemotherapy (ICT), patients were treated with neck dissection followed by concurrent CRT (CCRT) (group 1), surgery plus postoperative CRT (group 2), or CCRT for primary and regional sites (group 3).

Results: Overall survival and disease-free survival rates of group 1 were significantly higher than group 2 (p = 0.038, p = 0.031) and group 3 (both p = 0.018). Regional control rate of group 1 was significantly higher than group 3 (p = 0.041). There were no significant differences between groups 1 and 2 regarding local and regional control (p = 0.746, p = 0.302).

Conclusions: Neck dissection followed by CCRT is the best choice for patients with responsive primary but nonresponsive nodes.
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http://dx.doi.org/10.1002/hed.27106DOI Listing
September 2022

Cellular senescence: a key therapeutic target in aging and diseases.

J Clin Invest 2022 Aug;132(15)

Robert and Arlene Kogod Center on Aging, and.

Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop a characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary senescence and disrupts tissue homeostasis, resulting in loss of tissue repair and regeneration. The use of transgenic mouse models in which SnCs can be genetically ablated has established a key role for SnCs in driving aging and age-related disease. Importantly, senotherapeutics have been developed to pharmacologically eliminate SnCs, termed senolytics, or suppress the SASP and other markers of senescence, termed senomorphics. Based on extensive preclinical studies as well as small clinical trials demonstrating the benefits of senotherapeutics, multiple clinical trials are under way. This Review discusses the role of SnCs in aging and age-related diseases, strategies to target SnCs, approaches to discover and develop senotherapeutics, and preclinical and clinical advances of senolytics.
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http://dx.doi.org/10.1172/JCI158450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337830PMC
August 2022

Coix Seed-Based Milk Fermented With Improves Lipid Metabolism and Gut Microbiota in Mice Fed With a High-Fat Diet.

Front Nutr 2022 12;9:921255. Epub 2022 Jul 12.

Plant Protection and Plant Quarantine Station of Guizhou Province, Guiyang, China.

The aim of this study was to investigate the effects of coix seed-based milk (CSM) fermented with () on dyslipidemia and the composition of the intestinal microbiota in high fat diet (HFD)-fed mice. Changes in the body weight, serum lipid levels, activities of hepatic oxidative stress factors, expression of lipid-related genes, and composition of the intestinal microbiota of HFD-fed mice after supplementation with CSM were determined. The results showed that intake of CSM reduced the body weight gain as well as serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and increased the high-density lipoprotein cholesterol (HDL-C) levels in the mice. Meanwhile, supplementation with CSM could relieve liver oxidative stress, down-regulate the expression of genes related to lipid synthesis, and prevent liver fat accumulation in mice fed with HFD. The 16S rRNA sequencing of the intestinal microbiota showed that CSM regulated the gut microbiota community structure at different taxonomic levels, and reversed gut dysbiosis induced by HFD. The relative abundance of and which are negatively correlated with blood lipid levels were significantly increased by the intervention of CSM, while the relative abundance of , and which have positive correlation with blood lipid levels were significantly decreased. These results indicated that CSM might serve as a novel and promising dietary supplement for ameliorating hyperlipidemia and intestinal microbiota disorders caused by HFDs.
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http://dx.doi.org/10.3389/fnut.2022.921255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320324PMC
July 2022

[F]ROStrace detects oxidative stress in vivo and predicts progression of Alzheimer's disease pathology in APP/PS1 mice.

EJNMMI Res 2022 Jul 27;12(1):43. Epub 2022 Jul 27.

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Background: Oxidative stress is implicated in the pathogenesis of the most common neurodegenerative diseases, such as Alzheimer's disease (AD). However, tracking oxidative stress in the brain has proven difficult and impeded its use as a biomarker. Herein, we investigate the utility of a novel positron emission tomography (PET) tracer, [F]ROStrace, as a biomarker of oxidative stress throughout the course of AD in the well-established APP/PS1 double-mutant mouse model. PET imaging studies were conducted in wild-type (WT) and APP/PS1 mice at 3 different time points, representing early (5 mo.), middle (10 mo.), and advanced (16 mo.) life (n = 6-12, per sex). Semi-quantitation SUVRs of the plateau phase (40-60 min post-injection; SUVR) of ten brain subregions were designated by the Mirrione atlas and analyzed by Pmod. Statistical parametric mapping (SPM) was used to distinguish brain regions with elevated ROS in APP/PS1 relative to WT in both sexes. The PET studies were validated by ex vivo autoradiography and immunofluorescence with the parent compound, dihydroethidium.

Results: [F]ROStrace retention was increased in the APP/PS1 brain compared to age-matched controls by 10 mo. of age (p < 0.0001) and preceded the accumulation of oxidative damage in APP/PS1 neurons at 16 mo. (p < 0.005). [F]ROStrace retention and oxidative damages were higher and occurred earlier in female APP/PS1 mice as measured by PET (p < 0.001), autoradiography, and immunohistochemistry (p < 0.05). [F]ROStrace differences emerged midlife, temporally and spatially correlating with increased Aβ burden (r = 0.36; p = 0.0003), which was also greatest in the female brain (p < 0.001).

Conclusions: [F]ROStrace identifies increased oxidative stress and neuroinflammation in APP/PS1 female mice, concurrent with increased amyloid burden midlife. Differences in oxidative stress during this crucial time may partially explain the sexual dimorphism in AD. [F]ROStrace may provide a long-awaited tool to stratify at-risk patients who may benefit from antioxidant therapy prior to irreparable neurodegeneration.
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http://dx.doi.org/10.1186/s13550-022-00914-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329498PMC
July 2022

Enhanced inflammation and suppressed adaptive immunity in COVID-19 with prolonged RNA shedding.

Cell Discov 2022 Jul 25;8(1):70. Epub 2022 Jul 25.

Calibra Lab in DIAN Diagnostics, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, Zhejiang, China.

Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway, substantial suppression of diverse metabolites, activation of the complement system, suppressed cell migration, and enhanced viral replication. Furthermore, a ten-molecule learning model was established which could potentially predict viral RNA shedding period. In summary, this study uncovered enhanced inflammation and suppressed adaptive immunity in COVID-19 patients with prolonged viral RNA shedding, and proposed a multi-omic classifier for viral RNA shedding prediction.
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http://dx.doi.org/10.1038/s41421-022-00441-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311354PMC
July 2022

Global Trends and Research Hotspots of Exercise for Intervening Diabetes: A Bibliometric Analysis.

Front Public Health 2022 7;10:902825. Epub 2022 Jul 7.

Rehabilitation Therapy Center, Luoyang Orthopedic Hospital of Henan Province, Luoyang, China.

Background: Diabetes is a chronic metabolic disease characterized by hyperglycemia that often occurs in adults. Many studies have indicated that exercise is beneficial to the medical management of diabetes. Bibliometric analysis can help investigators to identify the current research concerns to guide future research directions. Nevertheless, the overview bibliometric analysis of this global research topic related to exercise and diabetes is lacking. The present bibliometric study aimed to investigate development trends and research hotspots of exercise and diabetes research and provide researchers with new perspectives in further studies.

Materials And Methods: The articles and reviews regarding exercise and diabetes between 2000 and 2020 were retrieved from the Web of Science Core Collection. The scientometrics analytical tool CiteSpace software was used to analyze the cooperation among countries/institutions/journals/authors, analysis of co-occurrence keywords, keywords bursts, and references.

Results: In all, 3,029 peer-reviewed papers were found with a persistently increased tendency over time. The most prolific country and institution were the USA (965) and Univ Alberta (76), respectively. Diabetes Care published most papers (178) and was the most co-cited journal (2,630). Riddell MC had the most publications (53), and Sigal RJ was the most influential author (503 cited times). Colberg et al.'s paper (co-citation counts: 183) showed the strongest citation bursts by the end of 2020, which was the most representative reference. The four research focuses were mellitus, exercise, physical activity, and glycemic control. The two frontiers trends were sedentary behavior and stress. The combination of aerobic and resistance training can effectively improve glycemic control, decrease HbA1c levels, enhance cardiorespiratory fitness, improve lipid levels, and decrease the demand for non-insulin antihyperglycemic agents.

Conclusions: This study offers a scientific perspective on exercise and diabetes research and provides investigators with valuable information to detect the current research condition, hotspots, and emerging trends for further study.
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http://dx.doi.org/10.3389/fpubh.2022.902825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300903PMC
July 2022

A Cadaver Feasibility Study of Extradural Contralateral C7 Ventral Root Transfer Technique for Treating Upper Extremity Paralysis.

Spine (Phila Pa 1976) 2022 Jul 14. Epub 2022 Jul 14.

Department of Orthopedics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Study Design: A total of 6 formalin-fixed cadavers were included in the cadaver feasibility study.

Objective: To ascertain the anatomical feasibility of extradural contralateral C7 ventral root transfer technique by cervical posterior.

Summary Of Background Data: Upper limb spastic hemiplegia is a common sequela after stroke. In our previous study, we established a method by transferring contralateral C7 dorsal and ventral roots to the corresponding C7 dorsal and ventral roots on the affected side in the cervical posterior.

Methods: In the present study, six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. Experimental anastomosis in cadavers was conducted. The pertinent lengths of the extradural nerve roots were measured. The tissue structures surrounding regions between the extradural CC7 nerve roots and the vertebral artery were observed. The cervical MRI scans of 60 adults were used to measure the distance between the donor and recipient nerves.

Results: Experimental anastomosis showed that the distance between the donor and recipient nerves was approximately 1 cm; the short segment of the sural nerve needed bridging. The distance between both exit sites of the exit of the extradural dura mater was 33.57±1.55 mm. The length of the extradural CC7 ventral root was 22.00±0.98 mm. The ventral distance (vd) and the dorsal distance (dd) in males were 23.98±1.72 mm and 30.85±2.22 mm (P<0.05), while those in females were 23.28±1.51 mm and 30.03±2.16 mm, respectively. C7 vertebral transverse process, ligaments, and other soft tissues were observed between the vertebral artery and the extradural C7 nerve root.

Conclusion: Under the premise of less trauma, our study shows that the extradural contralateral C7 ventral root transfer technique, , in theory, yields better surgical results, including better recovery of motor function and complete preservation of sensory function.

Level Of Evidence: 5.
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http://dx.doi.org/10.1097/BRS.0000000000004367DOI Listing
July 2022

Association of sorting and assembly machinery component 50 homolog gene polymorphisms with nonalcoholic fatty liver disease susceptibility.

Medicine (Baltimore) 2022 Jul 22;101(29):e29958. Epub 2022 Jul 22.

College of Pharmacy, Xinjiang Medical University, Urumqi, China.

Background: Sorting and assembly machinery component 50 homolog (SAMM50) gene single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD), but with inconsistent results across the current evidence. The present work was schemed to explore the association between SAMM50 gene SNPs and NAFLD vulnerability via meta-analysis.

Methods: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang were retrieved for eligible literature previous to June 10, 2021. The odds ratios (ORs) of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals (95% CIs) were computed to evaluate the strength of the associations. The quality of included studies was assessed using Newcastle-Ottawa Scale (NOS).

Results: In total, 8 case-control studies encompassing 6297 NAFLD patients and 7306 disease-free controls in this meta-analysis. Ultimately, this analysis included 8, 6, and 5 studies for rs2143571, rs3761472, and rs738491 polymorphisms respectively. The pooled data revealed that the 3 polymorphisms had conspicuous associations with NAFLD susceptibility: rs2143571, A vs. G, OR=1.51, 95% CI, 1.37-1.66, P < .01; rs3761472, A vs. G, OR=1.50, 95% CI, 1.35-1.67, P < .01; rs738491, A vs. G, OR=1.51, 95% CI, 1.40-1.63, P < .01.

Conclusion: This meta-analysis suggests that rs2143571, rs3761472, and rs738491 polymorphisms of the SAMM50 gene are appreciably associated with augmented risk of NAFLD vulnerability. It will provide the latest evidence to support the susceptibility of SAMM50 gene polymorphisms and NAFLD, and provide strategies for the prevention and treatment of NAFLD.
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http://dx.doi.org/10.1097/MD.0000000000029958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302252PMC
July 2022

Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention.

Acta Pharm Sin B 2022 Jul 26;12(7):3063-3072. Epub 2022 Feb 26.

Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the -adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.
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http://dx.doi.org/10.1016/j.apsb.2022.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293664PMC
July 2022

COVID-19 Hospitalization Trends in Rural Versus Urban Areas in the United States.

Med Care Res Rev 2022 Jul 17:10775587221111105. Epub 2022 Jul 17.

University of Minnesota, Minneapolis, USA.

Since the summer of 2020, the rate of coronavirus cases in the United States has been higher in rural areas than in urban areas, raising concerns that patients with coronavirus disease 2019 (COVID-19) will overwhelm under-resourced rural hospitals. Using data from the University of Minnesota COVID-19 Hospitalization Tracking Project and the U.S. Department of Health and Human Services, we document disparities in COVID-19 hospitalization rates between rural and urban areas. We show that rural-urban differences in COVID-19 admission rates were minimal in the summer of 2020 but began to diverge in fall 2020. Rural areas had statistically higher hospitalization rates from September 2020 through early 2021, after which rural-urban admission rates re-converged. The insights in this article are relevant to policymakers as they consider the adequacy of hospital resources across rural and urban areas during the COVID-19 pandemic.
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http://dx.doi.org/10.1177/10775587221111105DOI Listing
July 2022

Association between Weitbrecht's Retinaculum Injury and Femoral Head Necrosis in Femoral Neck Fractures.

Orthop Surg 2022 Jul 11. Epub 2022 Jul 11.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Objective: To investigate associations between femoral head necrosis (FHN) and injury to the retinaculum of Weitbrecht in patients with femoral neck fractures who had undergone initial trials of either closed reduction or direct open reduction.

Methods: This prospective observational study included 110 patients with displaced femoral neck fractures admitted to the Sixth People's Hospital Affiliated to Shanghai Jiaotong University and Shanghai Tongji Hospital between January 2008 and May 2017. Among these, 25 patients underwent initial closed reductions, and 85 patients underwent an open reduction directly. Watson-Jones anterolateral approach was used during the surgery for injury to the retinaculum of Weitbrecht, and FHN was assessed as a surgical outcome. The severity of injury to the retinaculum of Weitbrecht was evaluated using a scoring system developed by our surgical team. Follow-up was at least 24 months.

Results: The initial closed reduction treatment group had significantly higher total scores of injury to the retinaculum of Weitbrecht (6.24 ± 2.20 vs 4.62 ± 2.12, p = 0.009) compared to the open reduction group. High total scores were significantly associated with initial trials of closed reduction treatment, especially for the broken and released injury to the superior and anterior retinacula (both p = 0.01). Twenty-six patients experienced FHN postoperatively, with mean onset time of 19.42 ± 3.87 months. FHN was significantly associated with the severity of injury to the retinaculum of Weitbrecht (p < 0.001) at the superior, anterior, and inferior retinacula. FHN was significantly associated with injury to the retinaculum of Weitbrecht in females.

Conclusions: Femoral neck displacement in patients treated initially with closed reduction is associated with subsequent injury to the retinaculum of Weibrecht, which may lead to FHN. Severity of injury to the retinaculum of Weibrecht may be used as a biomarker to evaluate bone necrosis in patients with femoral neck fractures.
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http://dx.doi.org/10.1111/os.13378DOI Listing
July 2022

HDAC4 Inhibitors as Antivascular Senescence Therapeutics.

Oxid Med Cell Longev 2022 29;2022:3087916. Epub 2022 Jun 29.

State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau 999078, China.

Aging is an inevitable consequence of life, and during this process, the epigenetic landscape changes and reactive oxygen species (ROS) accumulation increases. Inevitably, these changes are common in many age-related diseases, including neurodegeneration, hypertension, and cardiovascular diseases. In the current research, histone deacetylation 4 (HDAC4) was studied as a potential therapeutic target in vascular senescence. HDAC4 is a specific class II histone deacetylation protein that participates in epigenetic modifications and deacetylation of heat shock proteins and various transcription factors. There is increasing evidence to support that HDAC4 is a potential therapeutic target, and developments in the synthesis and testing of HDAC4 inhibitors are now gaining interest from academia and the pharmaceutical industry.
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http://dx.doi.org/10.1155/2022/3087916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259336PMC
July 2022

Near-infrared light-assisted methanol oxidation reaction over the ferrous phosphide.

J Colloid Interface Sci 2022 Jul 1;626:599-607. Epub 2022 Jul 1.

Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 511443, PR China. Electronic address:

Ferrous phosphide (FeP) possesses both functions of near-infrared light (NIR) responsive and metal-support interactional behaviors, which will show great significance in photo-assisted electrocatalytic methanol oxidation reaction (MOR) areas. Hereby, we use FeP as the support to load Pt nanoparticles and investigate the performance of the as-obtained Pt-FeP for MOR. The results show that the synergistic effect of photocatalysis and electrocatalysis contributes to the high-performance MOR, especially under NIR irradiation. The as-obtained Pt-FeP also shows excellent photoelectric response performance and long-time stability of photo-electrocatalytic activity with the assistance of NIR illumination. The mass activities of the Pt-FeP catalysts with the assistance of NIR towards MOR is 2430.0 mA mg, 4.7 times superior to the dark condition (521.1 mA mg), which is obviously better than that of traditional electrocatalysts and some reported photo-electrocatalysts. The strong metal-support interaction between Pt and FeP together with NIR excited hot electrons from FeP result in the above superior photo-electrocatalytic methanol oxidation abilities. The present investigation offers a NIR-assisted electrocatalytic MOR strategy, which may be a feasible approach to further elevate the catalytic performance for MOR in photo-assisted direct methanol fuel cells (DMFCs).
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http://dx.doi.org/10.1016/j.jcis.2022.06.159DOI Listing
July 2022

Phenylbutyrate modulates polyamine acetylase and ameliorates Snyder-Robinson syndrome in a Drosophila model and patient cells.

JCI Insight 2022 Jul 8;7(13). Epub 2022 Jul 8.

Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Polyamine dysregulation plays key roles in a broad range of human diseases from cancer to neurodegeneration. Snyder-Robinson syndrome (SRS) is the first known genetic disorder of the polyamine pathway, caused by X-linked recessive loss-of-function mutations in spermine synthase. In the Drosophila SRS model, altered spermidine/spermine balance has been associated with increased generation of ROS and aldehydes, consistent with elevated spermidine catabolism. These toxic byproducts cause mitochondrial and lysosomal dysfunction, which are also observed in cells from SRS patients. No efficient therapy is available. We explored the biochemical mechanism and discovered acetyl-CoA reduction and altered protein acetylation as potentially novel pathomechanisms of SRS. We repurposed the FDA-approved drug phenylbutyrate (PBA) to treat SRS using an in vivo Drosophila model and patient fibroblast cell models. PBA treatment significantly restored the function of mitochondria and autolysosomes and extended life span in vivo in the Drosophila SRS model. Treating fibroblasts of patients with SRS with PBA ameliorated autolysosome dysfunction. We further explored the mechanism of drug action and found that PBA downregulates the first and rate-limiting spermidine catabolic enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1), reduces the production of toxic metabolites, and inhibits the reduction of the substrate acetyl-CoA. Taken together, we revealed PBA as a potential modulator of SAT1 and acetyl-CoA levels and propose PBA as a therapy for SRS and potentially other polyamine dysregulation-related diseases.
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http://dx.doi.org/10.1172/jci.insight.158457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310527PMC
July 2022

Parenting sense of competence and its predictors among primiparous women: a longitudinal study in China.

BMC Pregnancy Childbirth 2022 Jul 7;22(1):548. Epub 2022 Jul 7.

Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.

Background: Parenting sense of competence significantly affects the quality of parenting behaviours and healthy infant development. However, primiparous women without parenting experience may lack confidence and feel stress. This study aimed to explore the status of parenting sense of competence and identify its predictors among primiparous women.

Methods: A longitudinal study design was used. Primiparous women were recruited by using a convenience sample from two women's and children's hospitals in two cities in China. All primiparous women completed questionnaires on demographic characteristics, infant characteristics, family function, and parenting sense of competence at 1 month postpartum. At 3 months postpartum, each women's parenting sense of competence was re-assessed. Generalised linear regression was applied to identify the predictors of parenting sense of competence at 3 months postpartum.

Results: A total of 743 Chinese primiparous women were included in the analysis. The average parenting sense of competence score of the participants at 3 months postpartum was 70.18 (SD = 12.33). According to the generalised linear regression analysis, higher levels of parenting sense of competence at 3 months postpartum were significantly associated with older age (β = 0.13, P = 0.005), better family function (β = 0.37, P <  0.001), and higher levels of parenting sense of competence (β = 0.35, P <  0.001) at 1 month postpartum. In contrast, lower levels of parenting sense of competence at 3 months postpartum were associated with poorer self-rated economic status (β = - 0.16, P = 0.027), poorer infant health (β = - 0.26, P = 0.007), and mixed or formula feeding (β = - 0.11, P = 0.018) at 1 month postpartum.

Conclusions: Chinese primiparous women have a relatively good parenting sense of competence, but there is still room for improvement. Maternal age, economic status, family function, infant health, and feeding patterns were significant predictors. To improve their parenting sense of competence, more attention should be paid to primiparous women who are young, with poor economic status, having an unhealthy infant, and mixed or formula feeding. In addition, measures should also be taken during the early postpartum period to improve family function.
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http://dx.doi.org/10.1186/s12884-022-04881-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260977PMC
July 2022

STAT3-NAV2 axis as a new therapeutic target for rheumatoid arthritis via activating SSH1L/Cofilin-1 signaling pathway.

Signal Transduct Target Ther 2022 07 8;7(1):209. Epub 2022 Jul 8.

State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.

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http://dx.doi.org/10.1038/s41392-022-01050-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262938PMC
July 2022

MicroRNA-34a: A Novel Therapeutic Target in Fibrosis.

Front Physiol 2022 20;13:895242. Epub 2022 Jun 20.

Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Fibrosis can occur in many organs, and severe cases leading to organ failure and death. No specific treatment for fibrosis so far. In recent years, microRNA-34a (miR-34a) has been found to play a role in fibrotic diseases. MiR-34a is involved in the apoptosis, autophagy and cellular senescence, also regulates TGF-β1/Smad signal pathway, and negatively regulates the expression of multiple target genes to affect the deposition of extracellular matrix and regulate the process of fibrosis. Some studies have explored the efficacy of miR-34a-targeted therapies for fibrotic diseases. Therefore, miR-34a has specific potential for the treatment of fibrosis. This article reviews the important roles of miR-34a in fibrosis and provides the possibility for miR-34a as a novel therapeutic target in fibrosis.
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http://dx.doi.org/10.3389/fphys.2022.895242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250967PMC
June 2022

Low-Power Magnetic Resonance-Guided Focused Ultrasound Tumor Ablation upon Controlled Accumulation of Magnetic Nanoparticles by Cascade-Activated DNA Cross-Linkers.

ACS Appl Mater Interfaces 2022 Jul 5;14(28):31677-31688. Epub 2022 Jul 5.

Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising non-invasive surgical technique with spatial specificity and minimal off-target effects. Despite the expanding clinical applications, the major obstacles associated with MRgFUS still lie in low magnetic resonance imaging (MRI) sensitivity and safety issues. High ultrasound power is required to resist the energy attenuation during the delivery to the tumor site and may cause damage to the surrounding healthy tissues. Herein, a surface modification strategy is developed to simultaneously strengthen MRI and ultrasound ablation of MRgFUS by prolonging FeO nanoparticles' blood circulation and tumor-environment-triggered accumulation and retention at the tumor site. Specifically, reactive oxygen species-labile methoxy polyethylene glycol and pH-responsive DNA cross-linkers are modified on the surface of FeO nanoparticles, which can transform nanoparticles into aggregations through the cascade responsive reactions at the tumor site. Notably, DNA is selected as the pH-responsive cross-linker because of its superior biocompatibility as well as the fast and sensitive response to the weak acidity of 6.5-6.8, corresponding to the extracellular pH of tumor tissues. Due to the significantly enhanced delivery and retention amount of FeO nanoparticles at the tumor site, the MRI sensitivity was enhanced by 1.7-fold. In addition, the ultrasound power was lowered by 35% to reach a sufficient thermal ablation effect. Overall, this investigation demonstrates a feasible resolution to promote the MRgFUS treatment by enhancing the therapeutic efficacy and reducing the side effects, which will be helpful to guide the clinical practice in the future.
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http://dx.doi.org/10.1021/acsami.2c07235DOI Listing
July 2022

Studies of Evaluation Methods for Resistance to Fusarium Wilt Race 4 ( f. sp. ) in Cotton: Effects of Cultivar, Planting Date, and Inoculum Density on Disease Progression.

Front Plant Sci 2022 13;13:900131. Epub 2022 Jun 13.

Texas A&M AgriLife Research, Lubbock, TX, United States.

Fusarium wilt caused by f. sp. race 4 (FOV4) is an early season disease causing root rot, seedling wilt, and death. To develop an appropriate field evaluation method for resistance to FOV4 in cotton breeding, the objectives of this study were to investigate the effects of cultivar, planting date, and inoculum density on disease progression in 2020-2021. Results showed that the usual local mid-April planting had the lowest disease severity (DSR) or mortality rate (MR) in 2020 and 2021. DSR or MR increased at the late April and early May plantings in both years and reached the highest at the early May planting in 2020, while MR in 2021 was followed by a decrease in the late May planting and reached the highest in the mid-June planting. Local daily low temperatures between mid-April and mid-June were favorable for FOV4 infections, whereas daily high temperatures at 35°C or higher suppressed wilt severity. When seedlings at the 2-true leaf stage were inoculated with 10, 10, 10, and 10 conidia ml per plant in 2020, DSR was low but a linear relationship between inoculum density and DSR was observed. When a FOV4-infested soil supplemented with artificial inoculation was used, disease progression in three moderately susceptible or moderately resistant cultivars followed a linear model, while it followed a quadratic model in the highly susceptible Pima S-7 cultivar only. Among the other three cultivars, FM 2334GLT had the lowest DSR or MR except for one planting date in both years, followed by PHY 725 RF and Pima PHY 881 RF in ascending order, which were consistent with the difference in regression coefficients of the linear models. This study demonstrates that disease progression curves due to FOV4 can be used to compare responses to FOV4 infections among cotton genotypes in cotton breeding and genetic studies, regardless of planting date and inoculation method.
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http://dx.doi.org/10.3389/fpls.2022.900131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234752PMC
June 2022

Instructor-learner body coupling reflects instruction and learning.

NPJ Sci Learn 2022 Jun 28;7(1):15. Epub 2022 Jun 28.

Integrative Pain (iPain) Laboratory, School of Public Health, University of Haifa, Haifa, Israel.

It is widely accepted that nonverbal communication is crucial for learning, but the exact functions of interpersonal coordination between instructors and learners remain unclear. Specifically, it is unknown what role instructional approaches play in the coupling of physical motion between instructors and learners, and crucially, how such instruction-mediated Body-to-Body Coupling (BtBC) might affect learning. We used a video-based, computer-vision Motion Energy Analysis (MEA) to quantify BtBC between learners and instructors who used two different instructional approaches to teach psychological concepts. BtBC was significantly greater when the instructor employed a scaffolding approach than when an explanation approach was used. The importance of the instructional approach was further underscored by the fact that an increase in motion in the instructor was associated with boosted BtBC, but only during scaffolding; no such relationship between the instructor movements and BtBC was found during explanation interactions. Finally, leveraging machine learning approaches (i.e., support vector and logistic regression models), we demonstrated that both learning outcome and instructional approaches could be decoded based on BtBC. Collectively, these results show that the real-time interaction of teaching and learning bodies is important for learning and that the instructional approach matters, with possible implications for both in-person and online learning.
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http://dx.doi.org/10.1038/s41539-022-00131-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240028PMC
June 2022

self-assembly of polydopamine inside injectable hydrogels: antibacterial activity and photothermal therapy for superbug-infected wound healing.

Biomater Sci 2022 Jul 26;10(15):4126-4139. Epub 2022 Jul 26.

Key Laboratory of Photochemical conversion and Optoelectronic Material, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Inspired by the mussel foot proteins, polydopamine nanoparticles (PDA NPs) are often used to design hydrogel wound dressings due to their strong wet adhesion. However, additional antibiotics or nanometal bactericides are always required to enhance their poor antibacterial activity, which will cause drug resistance and toxic side effects. Herein, self-assembly confined PDA NPs (SC-PDA NPs, <50 nm) are employed as a freestanding antibacterial ingredient for constructing an ideal hydrogel wound dressing, which maintains relatively strong reducibility and size effect. Through a rapid gelation (within 10 s) strategy triggered by electrostatic complexation, an antibacterial hydrogel system is obtained, in which the self-assembly of the SC-PDA NPs continues, endowing the gel with outstanding antibacterial activity, especially against methicillin-resistant (MRSA, >99.9%). With the continuous self-assembly, the size of the PDA NPs increases (>200 nm), eventually giving the gel an efficient photothermal therapy effect. Moreover, the gel presents a relatively strong wet adhesion (63 kPa), superior biocompatibility and non-immunogenicity. This work offers innovative insights into the antibacterial mechanism of SC-PDA NPs and provides a novel design for constructing safe antibacterial hydrogel wound dressings, demonstrating great potential applications in superbug-infected wound healing.
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http://dx.doi.org/10.1039/d2bm00310dDOI Listing
July 2022

The Potential Diagnostic Value of Immune-Related Genes in Interstitial Fibrosis and Tubular Atrophy after Kidney Transplantation.

J Immunol Res 2022 17;2022:7212852. Epub 2022 Jun 17.

Department of Hepato-Pancreato-Biliary Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China.

Background: Inflammation within areas of interstitial fibrosis and tubular atrophy (IF/TA) is associated with kidney allograft failure. The aim of this study was to reveal new diagnostic markers of IF/TA based on bioinformatics analysis.

Methods: Raw data of IF/TA samples after kidney transplantation and control samples after kidney transplantation were extracted from the Gene Expression Omnibus (GEO) database (GSE76882 and GSE120495 datasets), and genes that were differentially expressed between the two groups (DEGs) were screened. Gene Set Enrichment Analysis (GSEA), ESTIMATE and single sample GSEA (ssGSEA), least absolute shrinkage and selection operator (LASSO) regression analysis, and competing endogenous RNA (ceRNA) network were used to analyze the data.

Results: The results of GSEA revealed that multiple immune-related pathways were enriched in the IF/TA group, and subsequent immune landscape analysis also showed that the IF/TA group had higher immune and stromal scores and up to 15 types of immune cells occupied them, such as B cells, cytotoxic cells, and T cells. LASSO regression analysis selected 6 (including , , , , , and ) out of 14 DE-IRGs as diagnostic genes to construct a diagnostic model. Then, receiver operating characteristic (ROC) curve analysis showed the powerful diagnostic value of the model, and the area under the curve (AUC) of a single diagnostic gene was greater than 0.75. The results of ingenuity pathway analysis (IPA) also indicated that DEGs were involved in the immune system and kidney disease-related pathways. Finally, we found multiple miRNAs that could regulate diagnostic genes from the ceRNA network.

Conclusion: This study identified 6 IF/TA-related genes, which might be used as a new diagnosis model in the clinical practice.
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http://dx.doi.org/10.1155/2022/7212852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232312PMC
June 2022

Protocol on irradiation-dark photochemical deposition and characterization of metal nanoclusters on semiconductor support.

STAR Protoc 2022 09 15;3(3):101459. Epub 2022 Jun 15.

Research Center of Nano Science and Technology, College of Sciences, Shanghai University, Shanghai 200444, P. R. China.

Controlling the size and uniform dispersion of noble metal nanoclusters on the metal oxide based semiconductor are difficult due to the natural tendency for metal atoms to agglomerate. Here, we present the protocol for an "irradiation-dark" photochemical deposition to obtain uniform metal nanoclusters on semiconductor support, and the protocol for measuring the size and size distribution of metal nanoclusters. For complete details on the use and execution of this protocol, please refer to Wu et al. (2022).
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http://dx.doi.org/10.1016/j.xpro.2022.101459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213822PMC
September 2022

Modulation Spectral Signal Representation for Quality Measurement and Enhancement of Wearable Device Data: A Technical Note.

Sensors (Basel) 2022 Jun 17;22(12). Epub 2022 Jun 17.

Institut National de la Recherche Scientifique, University of Quebec, Montréal, QC H5A 1K6, Canada.

Wearable devices are burgeoning, and applications across numerous verticals are emerging, including human performance monitoring, at-home patient monitoring, and health tracking, to name a few. Off-the-shelf wearables have been developed with focus on portability, usability, and low-cost. As such, when deployed in highly ecological settings, wearable data can be corrupted by artifacts and by missing data, thus severely hampering performance. In this technical note, we overview a signal processing representation called the modulation spectrum. The representation quantifies the rate-of-change of different spectral magnitude components and is shown to separate signal from noise, thus allowing for improved quality measurement, quality enhancement, and noise-robust feature extraction, as well as for disease characterization. We provide an overview of numerous applications developed by the authors over the last decade spanning different wearable modalities and list the results obtained from experimental results alongside comparisons with various state-of-the-art benchmark methods. Open-source software is showcased with the hope that new applications can be developed. We conclude with a discussion on possible future research directions, such as context awareness, signal compression, and improved input representations for deep learning algorithms.
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http://dx.doi.org/10.3390/s22124579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229858PMC
June 2022

Phytoplankton community variation and ecological health assessment for impounded lakes along the eastern route of China's South-to-North Water Diversion Project.

J Environ Manage 2022 Sep 20;318:115561. Epub 2022 Jun 20.

Water Engineering and Management, Asian Institute of Technology, Pathum Thani, 12120, Thailand.

Interbasin water diversion projects have been proven to effectively alleviate water resource shortages in areas along water diversion lines, but few studies have focused on ecological health in impounded lakes compared with research on water quality and pollutants. Herein, monitoring data were collected during the nonwater diversion period (NWDP) and the water diversion period (WDP) from 2018 to 2019, and the index of biological integrity (IBI) method based on phytoplankton communities was used to evaluate the ecological health of the impounded lakes (Nansi Lake and Dongping Lake) along the eastern route of the South-to-North Water Diversion Project. The results demonstrated that water diversion improved the water quality of the impounded lakes during the WDP, especially total nitrogen and ammonia nitrogen. Meanwhile, the water diversion affected the phytoplankton community structure and diversity, and network analysis further revealed water diversion could be beneficial to the ecological health of impounded lakes. Furthermore, the P-IBI showed that the overall ecological health assessment was "good" during the WDP. Water diversion substantially improved the ecological health status and stability of the impounded lakes during the dry season. Finally, the direct correlations between the water quality parameters and the P-IBI were weak, and water quality parameters could indirectly affect the P-IBI by changing the phytoplankton community structure. These findings will enhance our understanding of the ecological health of the impounded lakes of the South-to-North Water Diversion Project. Furthermore, this study will provide a reference to support the ecosystem security of impounded lakes in other large water diversion projects.
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http://dx.doi.org/10.1016/j.jenvman.2022.115561DOI Listing
September 2022

Codon Optimization Using a Recurrent Neural Network.

J Comput Biol 2022 Jun 21. Epub 2022 Jun 21.

Department of Protein Engineering, and SysImmune, Inc., Redmond, Washington, USA.

Codon optimization of a DNA sequence can significantly increase efficiency of protein expression, reducing the cost to manufacture biologic pharmaceuticals. Although directed methods based on such factors as codon usage bias and GC nucleotide content are often used to optimize protein expression, undirected optimization using machine learning could further improve the process by capitalizing on undiscovered patterns that exist within real DNA sequences. To explore this hypothesis, Chinese hamster DNA sequences were used to train a recurrent neural network (RNN) model of codon optimization. The model was used to generate optimized DNA sequence based on an input amino acid sequence for the example receptor programmed death-ligand 1 and for an example monoclonal antibody. When RNN-optimized sequences were transfected transiently or stably into Chinese hamster ovary cells, the resulting protein expression was as high or higher than that produced by DNA sequences optimized by conventional algorithms.
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http://dx.doi.org/10.1089/cmb.2021.0458DOI Listing
June 2022

Representation Learning: Recommendation With Knowledge Graph Triple-Autoencoder.

Front Genet 2022 3;13:891265. Epub 2022 Jun 3.

School of Information Engineering, Yangzhou University, Yangzhou, China.

The last decades have witnessed a vast amount of interest and research in feature representation learning from multiple disciplines, such as biology and bioinformatics. Among all the real-world application scenarios, feature extraction from knowledge graph (KG) for personalized recommendation has achieved substantial performance for addressing the problem of information overload. However, the rating matrix of recommendations is usually sparse, which may result in significant performance degradation. The crucial problem is how to extract and extend features from additional side information. To address these issues, we propose a novel feature representation learning method for the recommendation in this paper that extends item features with knowledge graph via triple-autoencoder. More specifically, the comment information between users and items is first encoded as sentiment classification. These features are then applied as the input to the autoencoder for generating the auxiliary information of items. Second, the item-based rating, the side information, and the generated comment representations are incorporated into the semi-autoencoder for reconstructed output. The low-dimensional representations of this extended information are learned with the semi-autoencoder. Finally, the reconstructed output generated by the semi-autoencoder is input into a third autoencoder. A serial connection between the semi-autoencoder and the autoencoder is designed here to learn more abstract and higher-level feature representations for personalized recommendation. Extensive experiments conducted on several real-world datasets validate the effectiveness of the proposed method compared to several state-of-the-art models.
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http://dx.doi.org/10.3389/fgene.2022.891265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204654PMC
June 2022

[Role of ferroptosis in cerebellar injury of mice following lead exposure].

Wei Sheng Yan Jiu 2022 May;51(3):443-469

School of Public Health, North China University of Science and Technology, Tangshan 063210, China Laboratory Animal Center, North China University of Science and Technology, Tangshan 063210, China.

Objective: To investigate the role of ferroptosis in cerebellar injury of mice following lead exposure.

Methods: A total of forty SPF C57 mice were randomly divided into control group, low-dose lead exposure group, middle-dose lead exposure group and high-dose lead exposure group, with 10 mice in each group. Mice in three lead exposure groups were given 0.25, 0.50, 1.00 g/L lead acetate through drinking water for twelve weeks respectively. Lead concentration was detected by inductively coupled plasma mass spectrometer. The motor function was detected by beam walking test and open field test. Pathological changes of cerebellum in mice were observed by H&E staining. Western blotting was used to detect the protein expression of transferrin receptor-1(TFR-1), ferroportin(FPN-1), solute carrier family 7 member 11(SLC7 A11), glutathione peroxidase 4(GPX4), NF-E2-related factor 2(Nrf2) and heme oxygenase-1(HO-1).

Results: The lead concentration in cerebellum of mice in low lead group, medium lead group and high lead group were(1.05±0.11), (1.21±0.10) and(1.48±0.1) μg/g, respectively, which were significantly higher than that in the control group. The time to traverse the beam in low lead group, medium lead group and high lead group was 1.34, 1.64 and 2.02 folds of that in control group, respectively. Open field test showed that the central residence time and standing times of mice in low lead group, medium lead group and high lead group were significantly lower than that in control. Purkinje cells in the cerebellum of mice exposed to different doses of lead showed irregular arrangement, small cell bodies and deep staining, especially in the high lead group. The relative levels of iron in low lead group, medium lead group and high lead group was 1.77, 2.29 and 3.77 folds of that in control group, respectively. The content of MDA in cerebellum of mice in three lead exposure groups increased significantly, while the GHS decreased significantly. Compared with the control group, the expression of TFR-1 protein increased significantly in the lead exposure group, while the expression of FPN-1 protein decreased significantly only in the medium lead group and high lead group, which was 60% and 50% of the control group. Compared with the control group, the expressions of oxidative stress regulatory proteins SLC7 A11 and GPX4 in medium lead group and high lead group decreased significantly. Lead exposure significantly decreased the expression of Nrf2 and HO-1 protein in cerebellum, especially in high lead group.

Conclusion: In this experiment condition, lead may induce ferroptosis in cerebellum of mice, of which, Nrf2/HO-1 signaling pathway might be involved in, and then further result in motor dysfunction of mice.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2022.03.017DOI Listing
May 2022
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