Publications by authors named "Chunxia Li"

252 Publications

mmBCFA C17iso ensures endoplasmic reticulum integrity for lipid droplet growth.

J Cell Biol 2021 Nov 8;220(11). Epub 2021 Oct 8.

Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, Yunnan, China.

In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.
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http://dx.doi.org/10.1083/jcb.202102122DOI Listing
November 2021

Biodegradable Upconversion Nanoparticles Induce Pyroptosis for Cancer Immunotherapy.

Nano Lett 2021 10 30;21(19):8281-8289. Epub 2021 Sep 30.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

Pyroptosis, which is a mode of programmed cell death, has proven effective for cancer therapy. However, efficient pyroptosis inducers for tumor treatment are limited. This study proposes biodegradable KZrF:Yb/Er upconversion nanoparticles (ZrNPs) as pyroptosis inducers for cancer immunotherapy. ZrNPs, which are similar to ion reservoirs, can be dissolved inside cancer cells and release high amounts of K and [ZrF] ions, resulting a surge in intracellular osmolarity and homeostasis imbalance. This further induces an increase in reactive oxygen species (ROS), caspase-1 protein activation, gasdermin D (GSDMD) cleavage, and interleukin-1β (IL-1β) maturity, and results in cytolysis. In vivo tests confirm that ZrNPs-induced pyroptosis exhibits superior antitumor immunity activity confirmed by enhanced dendritic cells (DCs) maturity and frequency of effector-memory T cells, as well as observably inhibiting tumor growth and pulmonary metastasis. This work is believed to extend the biomedical applications of upconversion nanomaterials and deepen the understanding of intrinsic immunomodulatory activity of nanomaterials.
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http://dx.doi.org/10.1021/acs.nanolett.1c02790DOI Listing
October 2021

COVID-19 Home Quarantine Accelerated the Progression of Myopia in Children Aged 7 to 12 Years in China.

Invest Ophthalmol Vis Sci 2021 08;62(10):37

Department of Ophthalmology, Shanghai TCM-Integrated Hospital, Shanghai University of TCM, Shanghai, China.

Purpose: To investigate the effect of home quarantine during the COVID-19 pandemic on myopia progression in children and its associated factors.

Methods: Myopic children aged 7 to 12 years with regular follow-up visits every half a year from April 2019 to May 2020 were included. Cycloplegic refraction was measured at baseline and at two follow-up visits. The first follow-up visit (visit 1) was conducted before the COVID-19 home quarantine, whereas the second (visit 2) was four months after the home quarantine. Myopia progression at visits 1 and 2 were compared. Factors associated with changes in myopia progression were tested with a multiple regression analysis.

Results: In total, 201 myopic children were enrolled. There was a significantly greater change in spherical equivalent at visit 2 (-0.98 ± 0.52 D) than at visit 1 (-0.39 ± 0.58 D; P < 0.001). Students were reported to have spent more time on digital devices for online learning (P < 0.001) and less time on outdoor activities (P < 0.001) at visit 2 than at visit 1. Children using television and projectors had significantly less myopic shift than those using tablets and mobile phones (P < 0.001). More time spent on digital screens (β = 0.211, P < 0.001), but not less time on outdoor activities (β = -0.106, P = 0.110), was associated with greater myopia progression at visit 2.

Conclusions: Changes in behavior and myopic progression were found during the COVID-19 home quarantine. Myopic progression was associated with digital screen use for online learning, but not time spent on outdoor activities. The projector and television could be better choices for online learning.
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http://dx.doi.org/10.1167/iovs.62.10.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411864PMC
August 2021

Application of multivariate statistical analysis and network pharmacology to explore the mechanism of Danggui Liuhuang Tang in treating perimenopausal syndrome.

J Ethnopharmacol 2021 Aug 21:114543. Epub 2021 Aug 21.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address:

Ethnopharmacological Relevance: Danggui Liuhuang Tang (DGLHT), first recorded in "Lan-Shi-Mi-Cang" (written in 1276 AD), is a famous classical formula. In 2018, it was listed in the Catalogue of Ancient Classic and Famous Prescriptions (First Batch) formulated by the National Administration of Traditional Chinese Medicine and the National Medical Products Administration. Perimenopausal syndrome (PMS) refers to a series of syndromes with autonomic nervous system dysfunction and neuropsychological symptoms. The treatment of PMS demands non-hormonal drugs. Natural products are considered to be effective substitutes for the treatment of PMS. It is reported that DGLHT has not only good therapeutic effects but also higher safety and fewer side effects in the treatment of PMS. However, the mechanism of DGLHT in treating PMS is not clear.

Aim Of The Study: To explore the chemical basis and the mechanism of DGLHT in treating PMS.

Materials And Methods: Multivariate statistical analysis was used to analyze the difference of components in supernatant before and after compatibility of DGLHT based on LC-MS data. The qualitative analysis was performed on the precipitate formed in the decocting process using LC-MS while the quantitative analysis on the potential markers using LC-UV. Then, the potential markers were analyzed by network pharmacology. The regulatory effect of DGLHT on FSH, P and E were carried out in PMS rats.

Results: Five potential markers, epiberberine, coptisine, palmatine, berberine and baicalin, were screened from the analysis of compounds in the supernatant. Four complexes, composed of potential marker monomers, were identified in the sediment, including two that have not been reported. The key targets of potential markers include TNF, NOS3, EGFR, ESR1, PTGS2, AR, CDC42 and RPS6KB1. The top signaling pathways include the cGMP-PKG signaling pathway, PI3K-Akt signaling pathway and estrogen signaling pathway. DGLHT could call back the hormone levels of P and E in PMS rats.

Conclusion: DGLHT active ingredients, epiberberine, coptisine, palmatine, berberine and baicalin contribute a lot to the therapeutic effect. And DGLHT takes effect by regulating hormones secreted by the ovary.
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http://dx.doi.org/10.1016/j.jep.2021.114543DOI Listing
August 2021

Autophagic elimination of ribosomes during spermiogenesis provides energy for flagellar motility.

Dev Cell 2021 Aug;56(16):2313-2328.e7

Department of Neurology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

How autophagy initiation is regulated and what the functional significance of this regulation is are unknown. Here, we characterized the role of yeast Vac8 in autophagy initiation through recruitment of PIK3C3-C1 to the phagophore assembly site (PAS). This recruitment is dependent on the palmitoylation of Vac8 and on its middle ARM domains for binding PIK3C3-C1. Vac8-mediated anchoring of PIK3C3-C1 promotes PtdIns3P generation at the PAS and recruitment of the PtdIns3P binding protein Atg18-Atg2. The mouse homolog of Vac8, ARMC3, is conserved and functions in autophagy in mouse testes. Mice lacking ARMC3 have normal viability but show complete male infertility. Proteomic analysis indicated that the autophagic degradation of cytosolic ribosomes was blocked in ARMC3-deficient spermatids, which caused low energy levels of mitochondria and motionless flagella. These studies uncovered a function of Vac8/ARMC3 in PtdIns3-kinase anchoring at the PAS and its physical significance in mammalian spermatogenesis with a germ tissue-specific autophagic function.
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http://dx.doi.org/10.1016/j.devcel.2021.07.015DOI Listing
August 2021

Synergistic Effect of Active Sites and a Multiple-Micropore System for a Metal-Organic Framework Exhibiting High Separation of CO/CH and CH/CH.

Inorg Chem 2021 Aug 25;60(16):12151-12157. Epub 2021 Jul 25.

Institute of Molecular Sciences and Engineering, Shandong University, Qingdao 266237, People's Republic of China.

Efficient gas separation and purification play a vital role in the current advanced development of industry, and the application of MOF adsorbents in this area with highly technical materials shows obvious advantages. On the basis of reticular chemistry, the 4-c lvt MOF adsorbent [CuDTTA]·3DMF·CHCN has been constructed (CuDTTA; HDTTA = 2,5-bis(1-1,2,4-triazol-1-yl)terephthalic acid). CuDTTA reveals a multiple-micropore system and high-density active sites decorated on the channel surfaces, which are conducive to its extraordinary selectivity of CO/CH and CH/CH (29 and 166, 1:1). In combination with an analysis of values, CuDTTA possesses the synergistic effect of size sieving and abundant functional sites, significantly improving the gas adsorption and separation performance. Meanwhile, the results also reveal that functional sites have a stronger binding affinity toward CH with respect to CO. Such a conclusion renders CuDTTA to be a promising adsorbent material for industrial applications.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01370DOI Listing
August 2021

Protein lysine crotonylation: past, present, perspective.

Cell Death Dis 2021 07 14;12(7):703. Epub 2021 Jul 14.

West China Second University Hospital, State Key Laboratory of Biotherapy, and Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, 610041, Chengdu, China.

Lysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon-carbon π-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation. In this review, we discussed the regulation of lysine crotonylation by enzymatic and non-enzymatic mechanisms, the recognition of substrate proteins, the physiological functions of lysine crotonylation and its cross-talk with other types of modification. The tools and methods for prediction and detection of lysine crotonylation were also described.
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http://dx.doi.org/10.1038/s41419-021-03987-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280118PMC
July 2021

Effect of folic acid combined with pravastatin on arteriosclerosis in elderly hypertensive patients with lacunar infarction.

Medicine (Baltimore) 2021 Jul;100(28):e26540

Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China.

Abstract: This study aimed to assess the effect of folic acid combined with pravastatin on atherosclerosis-related indexes in elderly patients with hypertension complicated with lacunar cerebral infarction.A total of 134 elderly hypertensive patients with lacunar cerebral infarction were randomly divided into 3 groups using the random number table method. Group A, the folic acid group, had 45 cases and received low-dose folic acid (0.8 mg/d) treatment on the basis of antihypertensive treatment. Group B, the pravastatin group, had 45 cases and received pravastatin (20 mg/d) treatment on the basis of antihypertensive treatment. Group C, the folic acid combined with the pravastatin group, had 44 cases. Members of this group received pravastatin (20 mg/d) and low-dose folic acid (0.8 mg/d) based on antihypertensive treatment. Levels of folic acid, homocysteine (Hcy), tumor necrosis factor alpha (TNF-a), matrix metallopeptidase 9 (MMP-9), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were measured by ELISA before treatment in all 3 groups. Carotid intima-media thickness (IMT) was measured using ultrasound, and systolic and diastolic blood pressure were measured with a mercury column. After 8 weeks of treatment, the levels of folic acid, Hcy, TNF-a, MMP-9, TC, LDL-C, and systolic and diastolic blood pressure were compared among the 3 groups. IMT levels were measured at 12 weeks of treatment.After 8 weeks of treatment, compared with group B, patients in groups A and C had folic acid levels significantly higher than baseline levels, with significantly lower Hcy levels (both P < .05). Patients in group C presented significantly decreased TNF-a, MMP-9, TC, and LDL-C levels and systolic and diastolic blood pressure after 8 weeks of treatment, compared with those in groups A and B (both P < .05). These patients also showed significantly decreased IMT levels compared with those in the other groups (P < .05).Low-dose folic acid combined with pravastatin in elderly patients with lacunar cerebral infarction can reduce the level of homocysteine, improve the degree of carotid atherosclerosis, protect vascular endothelium, and reduce blood lipids and blood pressure, presenting better benefits than pravastatin alone.
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http://dx.doi.org/10.1097/MD.0000000000026540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284717PMC
July 2021

Enhanced As(III) sequestration using nanoscale zero-valent iron modified by combination of loading and sulfidation: characterizations, performance, kinetics and mechanism.

Water Sci Technol 2021 Jun;83(12):2886-2900

College of Resource and Environmental Engineering, Wuhan University of Science and Technology, Wuhan 430081, China and Hubei Key Laboratory for Efficient Utilization and Agglomeration of Metallurgic Mineral Resources, Wuhan University of Science and Technology, Wuhan 430081, China E-mail:

Nanoscale zero-valent iron (nZVI) and sulfides have been confirmed to be effective in arsenic sequestration from aqueous solution. In this study, attapulgite supported and sulfide-modified nanoscale zero-valent iron ([email protected]) are synthesized to realize the superposition effect of enhanced arsenic sequestration. The results indicated that nZVI clusters were well disaggregated and the BET specific surface area increased from 19.61 m·g to 46.04 m·g of [email protected], resulting in an enhanced removal efficiency of arsenic from 51.4% to 65.1% at 20 min. The sulfides in [email protected] mainly exist as mackinawite (FeS) and this causes the spherical nanoparticles to exhibit a larger average particle size (94.6 nm) compared to bare nZVI (66.0 nm). In addition, [email protected] exhibited a prominent ability for arsenic sequestration over a wide pH range of 3.0-6.0. The presence of anions SO and Cl can enhance the arsenic removal whereas HCO inhibited it. The arsenic adsorption by [email protected] could be explained by the pseudo-second-order kinetic model and the Langmuir model, with the maximum adsorption capacity of 193.8 mg·g. The mechanism of As(III) sequestration by [email protected] involved multiple processes, mainly including precipitation conversion from FeS to AsS, surface-complexation adsorption and co-precipitation.
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http://dx.doi.org/10.2166/wst.2021.184DOI Listing
June 2021

Arterial Infusion Chemotherapy for Neoplastic Esophagogastric Anastomotic Strictures After Esophagectomy.

Front Oncol 2021 26;11:668593. Epub 2021 May 26.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer is a very difficult problem in clinical practice. We aim at to investigate the safety and feasibility of arterial infusion chemotherapy in treatment of neoplastic esophagogastric anastomotic strictures after esophagectomy.

Methods: From October 2014 to December 2019, 50 patients with Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer were assessed retrospectively. Preoperative dysphagia was grade III in 34 cases and grade IV in 16 cases. Thirty-eight patients had different degrees of dyspnea before surgery Twenty-five patients had intolerable (grade IV) dyspnea and airway stenting was undertaken before surgery. Thirteen patients had tolerable dyspnea that did not require airway stenting, and preoperative dyspnea was grade III.

Results: All patients were successfully treated with arterial infusion chemotherapy, no paraplegia or death occurred. The dysphagia grade of 50 patients after AIC was compared: one case had grade I, 40 cases had grade II, and nine cases had grade III. Thirteen patients had tolerable dyspnea that did not necessitate airway stenting. Dyspnea was classified as grade I in five cases and grade II in eight cases. After 1-3 courses of AIC, 50 patients were followed up for a complete response (eight cases), partial response (28) and stable disease (14 cases). Total objective effective rate (complete response+ partial response) and disease control rate(complete response + partial response + stable disease)were 72.0% and 100.0%, respectively. The median duration of follow-up was 8.5 months. One-year survival was 46.0%.

Conclusion: Arterial infusion chemotherapy is safe and efficacious treatment for Neoplastic esophagogastric anastomotic strictures after esophagectomy.
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http://dx.doi.org/10.3389/fonc.2021.668593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187754PMC
May 2021

Modified Laboratory Risk Indicator for Necrotizing Fasciitis (m-LRINEC) Score System in Diagnosing Necrotizing Fasciitis: A Nested Case-Control Study.

Infect Drug Resist 2021 4;14:2105-2112. Epub 2021 Jun 4.

Department of Orthopaedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei, People's Republic of China.

Aim: This study aims to present a modified Laboratory Risk Indicator for Necrotizing Fasciitis (m-LRINEC) scoring system and to evaluate its ability in discriminating necrotizing fasciitis (NF) from other severe soft-tissue infections.

Methods: Patients with NF diagnosed by surgical findings in our institution between January 2014 and December 2020 were included as the case group, matched by controls with severe soft-tissue infections other than NF in a ratio of 2:1, based on demographics, calendar time and immunosuppressant status. Patients' demographics, comorbidities and laboratory test results were extracted from medical records. Logistic regression analyses were used to determine the association with NF after adjustment for confounders, whereby m-LRINEC was developed. Receiver operating characteristics (ROC) curves and the area under the curve (AUC) were used to evaluate its discriminating ability.

Results: There were 177 patients included, 59 in the NF group and 118 in the non-NF group. We added comorbid diabetes and kidney disease to the original LRINEC scoring system, used high-sensitivity C-reactive protein (HCRP) to replace the CRP and redefined the cut-off values for the other four variables, to develop the m-LRINEC system. The cut-off value for m-LRINEC was 17 points, with corresponding sensitivity of 93.2% and specificity of 86.9%, and the AUC was 0.935 (95% CI 0.892 to 0.977; <0.001).

Conclusion: The m-LRINEC scoring system shows a high sensitivity and specificity in discriminating NF from other severe soft-tissue infections. Patients with an m-LRINEC score of >17 points should have a high index of suspicion for the presence of NF. The validity of the m-LRINEC needs to be confirmed in studies with larger samples and better design.
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http://dx.doi.org/10.2147/IDR.S313321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187035PMC
June 2021

Immunogenicity and persistence of high-dose recombinant hepatitis B vaccine in adults infected with human immunodeficiency virus in China: A randomized, double-blind, parallel controlled trial.

Vaccine 2021 06 26;39(27):3582-3589. Epub 2021 May 26.

School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, Shanxi, China. Electronic address:

Objectives: To explore the immunogenicity and persistence of the 60 µg hepatitis B vaccine in adults infected with human immunodeficiency virus (HIV).

Methods: We conducted a randomised controlled trial for adults infected with HIV. A total of 182 patients were randomly allocated to receive 20 µg (IM20 group) or 60 µg (IM60 group) of recombinant hepatitis B vaccine at months 0, 1, and 6 to assess the immunogenicity and were followed-up from month 7 to 42 to assess long-term immunogenicity.

Results: Our data showed that the response rate and geometric mean concentration (GMC) of antibodies to hepatitis B surface antigen (anti-HBs) in the IM60 group at month 7 were higher than those in the IM20 group (P > 0.05). The GMC of anti-HBs among the two groups decreased rapidly during the follow-up period (P > 0.05). Survival analysis showed that 25% of patients with anti-HBs ≥ 10 mIU/mL were 20 months in the IM60 group and 9.3 months in the IM20 group.

Conclusion: The three-dose 60 µg hepatitis B vaccine showed partially better immunogenicity and persistence than the three-dose 20 µg vaccine.

Trial Registration: The trial was registered on clinicaltrials.gov, NCT03316807.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.044DOI Listing
June 2021

Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation.

Front Immunol 2021 7;12:680068. Epub 2021 May 7.

Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China.

Toll-like receptors (TLRs) play critical roles in regulating the abnormal activation of the immune cells resulting in the pathogenesis of inflammation and autoimmune diseases. Pyruvate kinase M2 (PKM2), which governs the last step of glycolysis, is involved in multiple cellular processes and pathological conditions. However, little is known about the involvement of PKM2 in regulating TLR-mediated inflammation and autoimmunity. Herein, we investigated the role of PKM2 in the activation of the TLR pathways and the pathogenesis of inflammation and autoimmune diseases. The activation of TLR4, TLR7 and TLR9 pathways was found to induce the up-regulation of PKM2 expression in macrophages, dendritic cells (DCs) and B cells. The over-expression of PKM2 promotes the activation of TLR4, TLR7 and TLR9 pathways while interference with the PKM2 expression or the addition of the PKM2 inhibitor (PKM-IN) markedly inhibited the activation of TLR4, TLR7 and TLR9 pathways. Mechanistically, PKM2 augmented the activation of TLR4, TLR7 and TLR9 pathways by promoting the activation of the proline-rich tyrosine kinase 2 (Pyk2). Intriguingly, the PKM2 inhibitor PKM2-IN significantly protected the mice from the endotoxic shock mediated by the TLR4-agonist LPS. Additionally, it alleviated the progression in the TLR7-agonist imiquimod-mediated lupus mice and spontaneous lupus MRL/ mice. Moreover, PKM2 expression was highly elevated in the monocytes, DCs and B cells from systemic lupus erythematous (SLE) patients compared with those from the healthy donors. Besides, the PKM2 expression level was positively correlated with the degree of activation of these immune cells. In summary, PKM2 contributed to TLR-mediated inflammation and autoimmunity and can be a valuable target to control inflammation and autoimmunity.
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http://dx.doi.org/10.3389/fimmu.2021.680068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138060PMC
May 2021

Noncovalent microarrays from synthetic amino-terminating glycans: Implications in expanding glycan microarray diversity and platform comparison.

Glycobiology 2021 Sep;31(8):931-946

Glycosciences Laboratory, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom.

Glycan microarrays have played important roles in detection and specificity assignment of glycan recognition by proteins. However, the size and diversity of glycan libraries in current microarray systems are small compared to estimated glycomes, and these may lead to missed detection or incomplete assignment. For microarray construction, covalent and noncovalent immobilization are the two types of methods used, but a direct comparison of results from the two platforms is required. Here we develop a chemical strategy to prepare lipid-linked probes from both naturally derived aldehyde-terminating and synthetic amino-terminating glycans that addresses the two aspects: expansion of sequence-defined glycan libraries and comparison of the two platforms. We demonstrate the specific recognition by plant and mammalian lectins, carbohydrate-binding modules and antibodies and the overall similarities from the two platforms. Our results provide new knowledge on unique glycan-binding specificities for the immune receptor Dectin-1 toward β-glucans and the interaction of rotavirus P[19] adhesive protein with mucin O-glycan cores.
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http://dx.doi.org/10.1093/glycob/cwab037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434801PMC
September 2021

Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients.

Invest Ophthalmol Vis Sci 2021 04;62(4):23

Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, Tongji University, Shanghai, China.

Purpose: To investigate the association between serum uric acid (SUA) levels and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes.

Methods: This cross-sectional study evaluated 3481 patients with type 2 diabetes from four communities in China between 2016 and 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema evaluated by fundus photography and optical coherence tomography. Potential association between SUA and VTDR was examined using multivariable logistic regression. Sub-group analyses based on sex were constructed.

Results: A total of 305 participants had VTDR. Both higher SUA (odds ratio [OR], 1.22 per 100 µmol/L; 95% confidence interval [CI], 1.04-1.44; P = 0.013) and hyperuricemia (OR, 1.47; 95% CI, 1.07-2.04; P = 0.019) were positively associated with VTDR after adjustment for relevant covariates. Compared with those in the lowest SUA quartile, participants in the third (OR, 1.60; 95% CI, 1.07-2.39; P = 0.022) and fourth (OR, 2.05; 95% CI, 1.37-3.08; P = 0.001) sex-specific SUA quartiles showed a significantly increased risk of VTDR after adjustment. No sex-related difference was observed.

Conclusions: Higher SUA levels were associated with an increased risk of VTDR in patients with type 2 diabetes in both sexes, although females seemed to be more sensitive to high SUA than males. Prospective cohort studies are needed to verify SUA as a biomarker for predicting the risk of VTDR. Whether decreased SUA levels could decrease the risk of VTDR also requires further investigation.
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http://dx.doi.org/10.1167/iovs.62.4.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083112PMC
April 2021

Single-Atom Pd Nanozyme for Ferroptosis-Boosted Mild-Temperature Photothermal Therapy.

Angew Chem Int Ed Engl 2021 06 28;60(23):12971-12979. Epub 2021 Apr 28.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Photothermal therapy (PTT) is an extremely promising tumor therapeutic modality. However, excessive heat inevitably injures normal tissues near tumors, and the damage to cancer cells caused by mild hyperthermia is easily repaired by stress-induced heat shock proteins (HSPs). Thus, maximizing the PTT efficiency and minimizing the damage to healthy tissues simultaneously by adopting appropriate therapeutic temperatures is imperative. Herein, an innovative strategy is reported: ferroptosis-boosted mild PTT based on a single-atom nanozyme (SAzyme). The Pd SAzyme with atom-economical utilization of catalytic centers exhibits peroxidase (POD) and glutathione oxidase (GSHOx) mimicking activities, and photothermal conversion performance, which can result in ferroptosis featuring the up-regulation of lipid peroxides (LPO) and reactive oxygen species (ROS). The accumulation of LPO and ROS provides a powerful approach for cleaving HSPs, which enables Pd SAzyme-mediated mild-temperature PTT.
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http://dx.doi.org/10.1002/anie.202101924DOI Listing
June 2021

Isostructural Single- And Dual-Lanthanide Metal-Organic Frameworks Based On Substituent-Group-Modifying Tetracarboxylate Ligands for Ratiometric Temperature Sensing.

Inorg Chem 2021 Mar 4;60(6):4133-4143. Epub 2021 Mar 4.

Institute of Frontier and Interdisciplinarity Science and Institute of Molecular Sciences and Engineering, Shandong University, Qingdao 266237, China.

In this study, two substituent-group-modifying tetracarboxylate ligands, 2',5'-dimethoxy-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid (HTPTC-2OMe) and 2',5'-dimethyl-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid (HTPTC-2Me), with similar geometries were used as the organic linkers to construct isostructural lanthanide metal-organic frameworks (LnMOFs). The as-prepared LnTPTC-2OMe and LnTPTC-2Me were structurally elucidated by means of single-crystal and powder X-ray diffraction in addition to thermogravimetric analysis and were assessed as luminescence ratiometric thermometers by obtaining the temperature dependence of the luminescence behaviors. We found that both the single lanthanide EuTPTC-2OMe and the dual lanthanide EuTbTPTC-2Me exhibited a distinct S-type luminescence response to temperatures in the range from 313 to 473 K, and their ratiometric parameters can be understood on the basis of the classic Mott-Seitz model. Energy transfers from the ligand to Tb (or Eu) and from Tb to Eu in these two systems were investigated theoretically as well as with low-temperature (77 K) time-resolved photoluminescence spectroscopy, quantum yield, and lifetime analysis. Therefore, these two materials possess a good relative sensitivity, a small temperature uncertainty, and a favorable spectral repeatability in addition to a remarkable emission color change, enhancing their potential use for temperature measurement and in situ monitoring in microelectronics.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00310DOI Listing
March 2021

Embedding Red Emitters in the NbO-Type Metal-Organic Frameworks for Highly Sensitive Luminescence Thermometry over Tunable Temperature Range.

ACS Appl Mater Interfaces 2021 Mar 26;13(9):11078-11088. Epub 2021 Feb 26.

Department of Chemistry, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-0698, United States.

The intrinsic advantages of metal-organic frameworks (MOFs), including extraordinarily high porosities, tailorable architectures, and diverse functional sites, make the MOFs platforms for multifunctional materials. In this study, we synthesized two kinds of isostructural NbO-type Zn-based MOFs, where two structurally similar tetracarboxylate ligands, 5,5'-(pyrazine-2,5-diyl)diisophthalic acid (HPZDDI) and 5,5'-(pyridine-2,5-diyl)diisophthalic acid (HPDDI), with pyridine or pyrazine moieties, were employed as the organic linkers. By embedding the red-emitting cationic units of pyridinium hemicyanine dye 4-[p-(dimethylamino)styryl]-1-methylpyridinium (DSM) and trivalent europium ion (Eu), two types of composites, [email protected] and [email protected] and [email protected] and [email protected], were harvested and evaluated for use as potential ratiometric temperature probes. The temperature-responsive luminescence of these dual-emitting composites was investigated, and their representative features of relative sensitivity, temperature resolution, spectral repeatability, and luminescence color change were discussed. Importantly, compared with the DSM-incorporated composites, [email protected] and [email protected] show a much wider sensing temperature range and higher relative sensitivities, suggesting the performance of the composites can be engineered by elaborately combining the host and guest units. Given the rich choices of porous MOFs and emitting units, such a strategy can be useful in the design and preparation of multifunctional dual-emitting sensory materials.
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http://dx.doi.org/10.1021/acsami.1c00635DOI Listing
March 2021

Recent Advances in Hyperthermia Therapy-Based Synergistic Immunotherapy.

Adv Mater 2021 Jan 2;33(4):e2004788. Epub 2020 Dec 2.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

The past decades have witnessed hyperthermia therapy (HTT) as an emerging strategy against malignant tumors. Nanomaterial-based photothermal therapy (PTT) and magnetic hyperthermia (MHT), as highly effective and noninvasive treatment models, offer advantages over other strategies in the treatment of different types of tumors. However, both PTT and MHT cannot completely cure cancer due to recurrence and distal metastasis. In recent years, cancer immunotherapy has attracted widespread attention owing to its capability to activate the body's own natural defense to identify, attack, and eradicate cancer cells. Significant efforts have been devoted to studying the activated immune responses caused by hyperthermia-ablated tumors. In this article, the synergistic mechanism of HTT in immunotherapy, including immunogenic cell death and reversal of the immunosuppressive tumor microenvironment is discussed. The reports of the combination of HTT or HTT-based multimodal therapy with immunotherapy, including immunoadjuvant exploitation, immune checkpoint blockade therapy, and adoptive cellular immunotherapy are summarized. As highlighted, these strategies could achieve synergistically enhanced therapeutic outcomes against both primary tumors and metastatic lesions, prevent cancer recurrence, and prolong the survival period. Finally, current challenges and prospective developments in HTT-synergized immunotherapy are also reviewed.
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http://dx.doi.org/10.1002/adma.202004788DOI Listing
January 2021

Fetal teratogenicity in a rhesus macaque (Macaca mulatta): Association with the chronic maternal treatment of amitriptyline.

J Med Primatol 2021 02 5;50(1):75-78. Epub 2020 Dec 5.

Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.

Amitriptyline is a tricyclic antidepressant commonly prescribed in humans for pain and sleep disorders and in non-human primates for self-injurious behaviors. Here, we report a clinical case on the teratogenic effect of maternal-fetal amitriptyline exposure.
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http://dx.doi.org/10.1111/jmp.12499DOI Listing
February 2021

Recent Advances on Rare Earth Upconversion Nanomaterials for Combined Tumor Near-Infrared Photoimmunotherapy.

Front Chem 2020 6;8:596658. Epub 2020 Nov 6.

Institute of Frontier and Interdisciplinarity Science, Institute of Molecular Sciences and Engineering, Shandong University, Qingdao, China.

Cancer has been threatening the safety of human life. In order to treat cancer, many methods have been developed to treat tumor, such as traditional therapies like surgery, chemotherapy, radiotherapy, as well as new strategies like photodynamic therapy, photothermal therapy, sonodynamic therapy, and other emerging therapies. Although there are so many ways to treat tumors, these methods all face the dilemma that they are incapable to cope with metastasis and recurrence of tumors. The emergence of immunotherapy has given the hope to conquer the challenge. Immunotherapy is to use the body's own immune system to stimulate and maintain a systemic immune response to form immunological memory, resist the metastasis and recurrence of tumors. At the same time, immunotherapy can combine with other treatments to exhibit excellent antitumor effects. Upconversion nanoparticles (UCNPs) can convert near-infrared (NIR) light into ultraviolet and visible light, thus have good performance in bioimaging and NIR triggered phototherapy. In this review paper, we summarize the design, fabrication, and application of UCNPs-based NIR photoimmunotherapy for combined cancer treatment, as well as put forward the prospect of future development.
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http://dx.doi.org/10.3389/fchem.2020.596658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677576PMC
November 2020

Correction: Shi, H., et al. Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling. 2020, , 6357.

Int J Mol Sci 2020 Nov 23;21(22). Epub 2020 Nov 23.

Institute of Immunology and Molecular Medicine, Jining Medical University, Jining 272067, China.

The authors wish to make the following correction to this paper [...].
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http://dx.doi.org/10.3390/ijms21228850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700356PMC
November 2020

Japanese encephalitis (JE) mimicking acute ischemic stroke: A case report.

Medicine (Baltimore) 2020 Nov;99(45):e23071

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University.

Introduction: Japanese encephalitis (JE) is one of the most serious viral infectious diseases of the central nervous system in Asia. The clinical manifestations of it might be non-specific. We herein report a case of JE mimicking acute ischemic stroke.

Patient Concerns: A 52-year-old man presented with acute onset of left-sided limb weakness for 2 hours and a 5-year history of hypertension but with no fever or cold before the onset. Immediate cranial computed tomography scan showed small ischemic foci.

Diagnosis: Initial diagnosis revealed acute cerebral infarction as the symptoms mimicked stroke at onset. Furthermore, his symptoms progressed and magnetic resonance scan after 6 days of onset appeared negative on diffusion weighted imaging. Other etiologies were also then considered. Japanese encephalitis virus immunoglobulin M in the serum supported positive diagnosis of JE.

Interventions: The patient was given Ribavirin, and then his symptoms slowly improved.

Outcomes: Brain MRI on day 29 after the onset revealed high-intensity lesions in bilateral thalamus on diffusion weighted imaging. During the follow-up (at about 2 months after the onset), the patient's consciousness was clear but could not walk. At about 6 months after the onset, he could walk with parkinsonian features.

Conclusion: Diagnosis of JE that mimicked acute stroke at onset and with no fever can be challenging. Recognition of disease development, MRI and Japanese encephalitis virus immunoglobulinM findings are helpful in early definitive diagnosis.
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http://dx.doi.org/10.1097/MD.0000000000023071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647585PMC
November 2020

Toll-like Receptor 4 Inhibitor TAK-242 Improves Fulminant Hepatitis by Regulating Accumulation of Myeloid-Derived Suppressor Cell.

Inflammation 2021 Apr 20;44(2):671-681. Epub 2020 Oct 20.

Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, 272067, Shandong, China.

Fulminant hepatitis (FH) is an acute clinical disease with a poor prognosis and high mortality rate. The purpose of this study was to determine the protective effect of the Toll-like receptor 4 (TLR4) inhibitor TAK-242 on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced explosive hepatitis and explore in vivo and in vitro mechanisms. Mice were pretreated with TAK-242 for 3 h prior to LPS (10 μg/kg)/D-GalN (250 mg/kg) administration. Compared to the LPS/D-GalN group, the TAK-242 pretreatment group showed significantly prolonged survival, reduced serum alanine aminotransferase and aspartate aminotransferase levels, relieved oxidative stress, and reduced inflammatory interleukin (IL)-6, IL-12, and tumor necrosis factor-α levels. In addition, TAK-242 increased the accumulation of myeloid-derived suppressor cells (MDSCs). Next, mice were treated with an anti-Gr-1 antibody to deplete MDSCs, and adoptive transfer experiments were performed. We found that TAK-242 protected against FH by regulating MDSCs. In the in vitro studies, TAK-242 regulated the accumulation of MDSCs and promoted the release of immunosuppressive inflammatory cytokines. In addition, TAK-242 inhibited protein expression of nuclear factor-κB and mitogen-activated protein kinases. In summary, TAK-242 had a hepatoprotective effect against LPS/D-GalN-induced explosive hepatitis in mice. Its protective effect may be involved in suppressing inflammation, reducing oxidative stress, and increasing the proportion of MDSCs.
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http://dx.doi.org/10.1007/s10753-020-01366-yDOI Listing
April 2021

Genome-wide association analysis of sucrose concentration in soybean (Glycine max L.) seed based on high-throughput sequencing.

Plant Genome 2020 11 14;13(3):e20059. Epub 2020 Oct 14.

Key Laboratory of Soybean Biology and Breeding/Genetics, Chinese Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.

The sucrose concentration in soybean seed significantly affects the flavor of soybean-derived products. In this study, an association panel of 178 elite accessions and 33,149 single-nucleotide polymorphisms (SNPs) was utilized to identify quantitative trait nucleotides (QTNs) of sucrose concentration in soybean seeds by genome-wide association study (GWAS). Five QTNs (rs2688589, rs29026218, rs5926884, rs6886889, and rs10299216) distributed across five genomic regions in five chromosomes were identified in two or more locations by GWAS. A total of 60 candidate genes near the 200-kb flanking region of these five identified loci were identified. Three of these genes (Glyma.04G032600, Glyma.04G034600, and Glyma.11G092100) have been reported to be involved in the process of sugar biosynthesis. Based on gene-based association and haplotype analyses, a total of 35 SNPs from 10 genes associated with sucrose concentration were identified. Of them, Glyma.04G032600 was the only gene that has been reported to be related to sucrose content; the other nine genes were novel and may be associated with sucrose content. These beneficial alleles and candidate genes may be of great value in improving sucrose content in soybean seeds.
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http://dx.doi.org/10.1002/tpg2.20059DOI Listing
November 2020

Combination of Bronchial Arterial Infusion Chemotherapy plus Drug-Eluting Embolic Transarterial Chemoembolization for Treatment of Advanced Lung Cancer-A Retrospective Analysis of 23 Patients.

J Vasc Interv Radiol 2020 Oct 18;31(10):1645-1653. Epub 2020 Sep 18.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Rd., Zhengzhou 450052, China. Electronic address:

Purpose: To determine the efficacy and safety of the combination of bronchial arterial infusion (BAI) chemotherapy and transarterial chemoembolization with the use of drug-eluting embolic (DEE) particles in the treatment of unresectable advanced lung cancer.

Materials And Methods: A retrospective review was performed of 23 patients with unresectable lung cancer (stage III/IV) who received BAI chemotherapy and DEE chemoembolization. Treatment response was assessed by enhanced CT and evaluated on the basis of Response Evaluation Criteria In Solid Tumors at 30 d after the last combination treatment. Patients were followed up until death or March 15, 2020, whichever was first. Overall survival (OS) was estimated by Kaplan-Meier analysis, and factors associated with OS were evaluated by Cox proportional-hazards test.

Results: Complete response, partial response, stable disease, and progressive disease were seen in 2, 16, 5, and 0 patients at 30 d after the last combination treatment, respectively; therefore, the overall response rate was 78.3% and the disease control rate was 100%. Preprocedure symptoms (hemoptysis in 7 patients and dyspnea in 10) resolved in all cases after combination therapy. Nineteen patients died during follow-up, and 4 survived. Median OS was 15.6 mo (95% confidence interval, 10.1-21.1 mo). On univariate analysis and multivariate analysis, tumor/node/metastasis staging was an independent risk factor for prognosis. There were no serious adverse events during the procedures.

Conclusions: The combination of BAI chemotherapy plus DEE chemoembolization appears to be a promising method for treatment of advanced lung cancer.
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http://dx.doi.org/10.1016/j.jvir.2020.06.007DOI Listing
October 2020

Colorectal Tumor Microenvironment-Activated Bio-Decomposable and Metabolizable Cu [email protected] Nanocomposites for Synergistic Oncotherapy.

Adv Mater 2020 Oct 18;32(43):e2004647. Epub 2020 Sep 18.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Rational design of tumor microenvironment (TME)-activated nanocomposites provides an innovative strategy to construct responsive oncotherapy. In colorectal cancer (CRC), the specific physiological features are the overexpressed endogenous H S and slightly acidic microenvironment. Here, a core-shell Cu [email protected] nanostructure for CRC "turn-on" therapy is reported. With CaCO responsive to pH decomposition and Cu O responsive to H S sulfuration, Cu [email protected] can be triggered "on" into the therapeutic mode by the colorectal TME. When the CaCO shell decomposes and releases calcium in acidic colorectal TME, the loss of protection from the CaCO shell exposes the Cu O core to be sulfuretted by H S to form metabolizable Cu S nanocrystals that gain remarkably strong near-infrared absorption. After modifying hyaluronic acid, Cu [email protected] can achieve synergistic CRC-targeted and TME-triggered photothermal/photodynamic/chemodynamic/calcium-overload-mediated therapy. Moreover, it is found that the generation of hyperthermia and oxidative stress from Cu [email protected] nanocomposites can efficiently reprogram the macrophages from the M2 phenotype to the M1 phenotype and initiate a vaccine-like immune effect after primary tumor removal, which further induces an immune-favorable TME and intense immune responses for anti-CD47 antibody to simultaneously inhibit CRC distant metastasis and recurrence by immunotherapy.
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http://dx.doi.org/10.1002/adma.202004647DOI Listing
October 2020

Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling.

Int J Mol Sci 2020 Sep 2;21(17). Epub 2020 Sep 2.

Institute of Immunology and Molecular Medicine, Jining Medical University, Jining 272067, China.

Invasive breast cancer is highly regulated by tumor-derived cytokines in tumor microenvironment. The development of drugs that specifically target cytokines are promising in breast cancer treatment. In this study, we reported that arctigenin, a bioactive compound from L., could decrease tumor-promoting cytokines GM-CSF, MMP-3, MMP-9 and TSLP in breast cancer cells. Arctigenin not only inhibited the proliferation, but also the invasion and stemness of breast cancer cells via decreasing GM-CSF and TSLP. Mechanistically, arctigenin decreased the promoter activities of GM-CSF and TSLP via reducing the nuclear translocation of NF-κB p65 which is crucial for the transcription of GM-CSF and TSLP. Furthermore, arctigenin-induced depletion of GM-CSF and TSLP inhibited STAT3 phosphorylation and β-catenin signaling resulting in decreased proliferation, invasion and stemness of breast cancer cells in vitro and in vivo. Our findings provide new insights into the mechanism by which tumor-promoting cytokines regulate breast cancer progression and suggest that arctigenin is a promising candidate for cytokine-targeted breast cancer therapy.
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http://dx.doi.org/10.3390/ijms21176357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503539PMC
September 2020

Supercrystallographic Reconstruction of 3D Nanorod Assembly with Collectively Anisotropic Upconversion Fluorescence.

Nano Lett 2020 10 9;20(10):7367-7374. Epub 2020 Sep 9.

Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China.

Constructing three-dimensional (3D) metamaterials from functional nanoparticles endows them with emerging collective properties tailored by the packing geometries. Herein, we report 3D supercrystals self-assembled from upconversion nanorods (NaYF:Yb,Er NRs), which exhibit both translational ordering of NRs and orientational ordering between constituent NRs in the superlattice (SL). The construction of 3D reciprocal space mappings (RSMs) based on synchrotron-based X-ray scattering measurements was developed to uncover the complex structure of such an assembly. That is, the two main orthogonal sets of hexagonal close-packing ()-like SLs share the [110] axis, and NRs within the SL possess orientational relationships of [120]//[100], [210]//[010], and [001]//[001]. Notably, these supercrystals containing well-aligned NRs exhibit collectively anisotropic upconversion fluorescence in two perpendicular directions. This study not only demonstrates novel crystalline superstructures and functionality of NR-based 3D assemblies but also offers a unique tool for deciphering a wide range of complex nanoparticle supercrystals.
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http://dx.doi.org/10.1021/acs.nanolett.0c02779DOI Listing
October 2020
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