Publications by authors named "Lan Ma"

442 Publications

Kinetics and Mass Yields of Aqueous Secondary Organic Aerosol from Highly Substituted Phenols Reacting with a Triplet Excited State.

Environ Sci Technol 2021 Apr 14. Epub 2021 Apr 14.

Department of Land, Air, and Water Resources, University of California, Davis, California 95616, United States.

Biomass burning emits large amounts of phenols, which can partition into cloud/fog drops and aerosol liquid water (ALW) and react to form aqueous secondary organic aerosol (aqSOA). Triplet excited states of organic compounds (C*) are likely oxidants, but there are no rate constants with highly substituted phenols that have high Henry's law constants () and are likely important in ALW. To address this gap, we investigated the kinetics of six highly substituted phenols with the triplet excited state of 3,4-dimethoxybenzaldehyde. Second-order rate constants at pH 2 are all fast, (2.6-4.6) × 10 M s, while values at pH 5 are 2-5 times smaller. Rate constants are reasonably described by a quantitative structure-activity relationship with phenol oxidation potentials, allowing rate constants of other phenols to be predicted. Triplet-phenol kinetics are unaffected by ammonium sulfate, sodium chloride, galactose (a biomass-burning sugar), or Fe(III). In contrast, ammonium nitrate increases the rate of phenol loss by making hydroxyl radicals, while Cu(II) inhibits phenol decay. Mass yields of aqueous SOA from triplet reactions are large and range from 59 to 99%. Calculations using our data along with previous oxidant measurements indicate that phenols with high can be an important source of aqSOA in ALW, with C* typically the dominant oxidant.
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http://dx.doi.org/10.1021/acs.est.1c00575DOI Listing
April 2021

The treatment of integrated traditional Chinese and Western medicine to cure severe immune thrombocytopenia in a patient in a minimally conscious state: a case report.

Ann Palliat Med 2021 Mar;10(3):3483-3490

Panzhihua University, Affiliated Hospital of Panzhihua University, Panzhihua, China.

Immune thrombocytopenia is a common complication in patients in a minimally conscious state (MCS). MCS patients are prone to pulmonary infection for the reasons of long-term bed rest and tracheotomy etc., which leads to frequent immune thrombocytopenia. At present, there is no specific treatment for immune thrombocytopenia. Moreover, the cost of routine treatment is high, and clinicians need to consider different drug combinations, side effects, and the risk of drug dependence when selecting treatments. Here, we report a case of a patient in a MCS who developed immune thrombocytopenia after tracheotomy and long-term bed laying in October 2015. The patient's platelet count declined continuously, and by December 2015, she was in a critical condition, with a platelet count of less than 20×109/L. The patient firstly received routine treatment, however, this could only temporarily prevent the drop in platelets. Following a series of explorations, the patient was treated with a combination of traditional Chinese and Western medicine, which included treatment and preventive measures. For treatment, the patient was given roxithromycin dispersible administration tablets and a self-made preparation of peanut red skin, which could quickly cure the immune thrombocytopenia. Preventive measures included the addition of ursodeoxycholic acid capsules, silybin capsules, and a traditional Chinese medicine preparation. As shown by laboratory examination results, the patient's platelet count has stayed around a normal level since March 2016, and she now has normal liver and kidney function. This outcome evidence that combined traditional Chinese and Western medicine could effectively cure immune thrombocytopenia and prevent its recurrence. Moreover, the cost of the treatment was lower and there were fewer side effects than routine treatment, and at the same time, the method of treatment was simple and convenient. Our practical experience may provide a valuable clue for the treatment of immune thrombocytopenia.
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http://dx.doi.org/10.21037/apm-21-307DOI Listing
March 2021

Influence of post-traumatic status on health-related quality of life among survivors 10 years after the Wenchuan earthquake in China.

Ann Palliat Med 2021 Mar;10(3):3059-3066

Health and Wellness School, Panzhihua University, Panzhihua, China.

Background: China is a country with frequent earthquakes. Beichuan was the epicenter of what was later called the Wenchuan earthquake, which caused nearly 80% of the houses in the area to collapse, with 8,605 people killed and 9,693 people missing. The aim of our study was to explore the prevalence of post-traumatic stress disorder (PTSD) and its influence on health-related quality of life (HRQOL) among the survivors 10 years after the 2008 Wenchuan earthquake in China.

Methods: A total of 610 survivors from Leigu town in Beichuan County were investigated by a systematic sampling method. Post-traumatic status, HRQOL, and demographic sources were measured by the PTSD Checklist Civilian Version (PCL-C), 36-item Health Survey Short Form (SF-36), and self-questionnaire, respectively.

Results: Ten years after the Wenchuan earthquake, the prevalence of PTSD for survivors was 1.6%. There were significant negative correlations between survivors' SF-36 scores and the scores of PCL-C. Higher scores in post-traumatic status were associated with a higher rate of poor physical HRQOL, which was lower than the mean score [adjusted odds ratio (OR) 1/4 0.96 per SD increase, P 1/4 0.001] and mental HRQOL (adjusted OR 1/4 0.93 per SD increase, P 1/4 0.001). The independent contribution of post-traumatic status to the risk for poor physical and mental HRQOL was 4.9% and 18.7% respectively.

Conclusions: As time has elapsed, the incidence of PTSD has gradually declined after the Wenchuan earthquake. Post-traumatic status was found to influence the health related quality of life of survivors.
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http://dx.doi.org/10.21037/apm-21-309DOI Listing
March 2021

Effects of continuous positive airway pressure treatment in obstructive sleep apnea patients with atrial fibrillation: A meta-analysis.

Medicine (Baltimore) 2021 Apr;100(15):e25438

Department of Cardiology, First Affiliated Hospital of Zhejiang Chinese Medical University.

Background: Obstructive sleep apnea (OSA) is correlated with atrial fibrillation (AF). Over the past decade, there has been an increasing interest in the relationship between OSA with continuous positive airway pressure (CPAP) and progression or recurrence of AF.

Methods: This investigation was an analysis of studies searched in the Cochrane Library, PubMed, EMBASE, EBSCO, OVID, and Web of Science databases from inception to July 2020 to evaluate the recurrence or progression of AF in CPAP users, CPAP nonusers, and patients without OSA.

Results: Nine studies with 14,812 patients were recruited. CPAP therapy reduced the risk of AF recurrence or progression by 63% in a random-effects model (24.8% vs 40.5%, risk ratio [RR] = 0.70, 95% confidence interval [CI] = 0.57-0.85, P = .035). Compared with non-OSA patients, AF recurrence or progression was much higher in CPAP nonusers (40.6% vs 21.1%, RR = 1.70, 95% CI = 1.19-2.43, P = .000). However, AF recurrence or progression in the CPAP group was similar to that in the non-OSA group (24.0% vs 21.1%, RR = 1.13, 95% CI = 0.87-1.47, P = .001). Begg correlation test and Egger regression test revealed no publication bias in this analysis.

Conclusions: OSA is a salient factor in the progression or recurrence of AF. CPAP therapy for OSA may contribute to reduction of AF in patients for whom radiofrequency ablation or direct current cardioversion is not performed.

Trial Registration: The protocol for this meta-analysis was registered on PROSPERO with a registration No. CRD42019135229.
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http://dx.doi.org/10.1097/MD.0000000000025438DOI Listing
April 2021

Honokiol exerts protective effects on neural myelin sheaths after compressed spinal cord injury by inhibiting oligodendrocyte apoptosis through regulation of ER-mitochondrial interactions.

J Spinal Cord Med 2021 Apr 8:1-10. Epub 2021 Apr 8.

Medical College, China Three Gorges University, Yichang, Hubei, People's Republic of China.

Objective: To investigate the effect of honokiol on demyelination after compressed spinal cord injury (CSCI) and it's possible mechanism.

Design: Animal experiment study.

Setting: Institute of Neuroscience of Chongqing Medical University.

Interventions: Total of 69 Sprague-Dawley (SD) rats were randomly divided into 3 groups: sham group (n=15), honokiol group (n=27) and vehicle group (n=27). After established CSCI model by a custom-made compressor successfully, the rats of sham group were subjected to the limited laminectomy without compression; the rats of honokiol group were subjected to CSCI surgery and intraperitoneal injection of 20 mg/kg honokiol; the rats of vehicle group were subjected to CSCI surgery and intraperitoneal injection of an equivalent volume of saline. The locomotor function of each group was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. The pathological changes of myelinated nerve fibers of spinal cord in 3 groups were detected by osmic acid staining and transmission electron microcopy (TME). Immunofluorescence and Western blot were used to research the experessions of active caspase-3, caspase-12, cytochrome C and myelin basic protein (MBP) respectively.

Results: In the vehicle group, the rats became paralyzed and spastic after injury, and the myelin sheath became swollen and broken down along with decreased number of myelinated nerve fibers. Western blot analysis manifested that active caspase-3, caspase-12 and cytochrome C began to increase 1 d after injury while the expression of MBP decreased gradually. After intervened with honokiol for 6 days, compared with the vehicle group, the locomotor function and the pathomorphological changes of myelin sheath of the CSCD rats were improved with obviously decreased expression of active caspase-3, caspase-12 and cytochrome C.

Conclusions: Honokiol may improve locomotor function and protect neural myelin sheat from demyelination via prevention oligodendrocytes (OLs) apoptosis through mediate endoplasmic reticulum (ER)-mitochondria pathway after CSCI.
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http://dx.doi.org/10.1080/10790268.2021.1890878DOI Listing
April 2021

Complete mitochondrial genome of (Burr, 1899).

Mitochondrial DNA B Resour 2021 Mar 11;6(3):831-832. Epub 2021 Mar 11.

The Key Laboratory of Zoological Systematics and Application, Hebei University, Baoding, China.

Species of have a long history as singing pets in China. The complete mitochondrial genome of (Burr, 1899) is 15,719 bp in size. It consists of 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and an A + T-rich region. The base composition of mitochondrial genome is A (34.7%), T (30.4%), G (12.0%), and C (22.9%), with an A + T bias (65.1%). Phylogenetic analyses based on the 13 PCGs showed that was sister to . The present genomic-level and male genitalia evidences support to restore the taxonomic status of .
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http://dx.doi.org/10.1080/23802359.2021.1884020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954433PMC
March 2021

Identification of New miRNA-mRNA Networks in the Development of Non-syndromic Cleft Lip With or Without Cleft Palate.

Front Cell Dev Biol 2021 1;9:631057. Epub 2021 Mar 1.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

To identify new microRNA (miRNA)-mRNA networks in non-syndromic cleft lip with or without cleft palate (NSCL/P). Overlapping differentially expressed miRNAs (DEMs) were selected from cleft palate patients (GSE47939) and murine embryonic orofacial tissues (GSE20880). Next, the target genes of DEMs were predicted by Targetscan, miRDB, and FUNRICH, and further filtered through differentially expressed genes (DEGs) from NSCL/P patients and controls (GSE42589), MGI, MalaCards, and DECIPHER databases. The results were then confirmed by experiments. NSCL/P lip tissues were obtained to explore the expression of miRNAs and their target genes. Let-7c-5p and miR-193a-3p were identified as DEMs, and their overexpression inhibited cell proliferation and promoted cell apoptosis. and were confirmed as targets of let-7c-5p and miR-193a-3p, respectively, and were involved in craniofacial development in mice. Negative correlation between miRNA and mRNA expression was detected in the NSCL/P lip tissues. They were also associated with the occurrence of NSCL/P based on the MGI, MalaCards, and DECIPHER databases. Let-7c-5p- and miR-193a-3p- networks may be involved in the development of NSCL/P.
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http://dx.doi.org/10.3389/fcell.2021.631057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957012PMC
March 2021

Identification of novel prognostic genes of triple-negative breast cancer using meta-analysis and weighted gene co-expressed network analysis.

Ann Transl Med 2021 Feb;9(3):205

State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high rates of metastasis and recurrence. Conventional clinical treatments are ineffective for it as it lacks therapeutic biomarkers. Figuring out the biomarkers related to TNBC will be beneficial for its clinical treatment and prognosis.

Methods: Five independent datasets downloaded from the Gene Expression Omnibus database were merged to identify differentially expressed genes between TNBC and non-TNBC samples by using the MetaDE.ES method followed by mapping the differentially expressed genes into a protein-protein interaction network. Meanwhile, the weighted gene co-expressed network analysis (WGCNA) of The Cancer Genome Atlas data was performed to screen the hub genes. The gene functional analyses were conducted by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The correlation between gene expression level and patient overall survival was evaluated by survival analysis.

Results: A total of 11 differentially expressed genes (, , , , , , , , , , ) were obtained from the protein-protein interaction network with degree >10. WGCNA revealed 5 hub genes (, , , , ) that were significantly associated with TNBC. Cell cycle, oocyte meiosis, spliceosome were the pathways significantly enriched in these genes according to GO functionally annotated terms and KEGG pathways analysis. The Kaplan-Meier curves showed that the expression levels of , , were significantly associated with the survival time of TNBC patients (P<0.05).

Conclusions: A total of 16 genes significantly associated with TNBC were identified by bioinformatic analyses. Among these 16 genes, , , might be able to be used as biomarkers of TNBC.
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http://dx.doi.org/10.21037/atm-20-5989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940929PMC
February 2021

Zinc source differentiation in hydrothermal vent mollusks: Insight from Zn isotope ratios.

Sci Total Environ 2021 Jun 5;773:145653. Epub 2021 Feb 5.

School of Energy and Environment, Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon, Hong Kong, China; Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, China; Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou, 511458, China. Electronic address:

Hydrothermal vent represents an extreme environment where metal-enriched fluids are in contact with chemosymbiotic animals. In the present study, Zn isotopic compositions were determined in multiple tissues of three dominant hydrothermal vent mollusks (the mussel Bathymodiolus marisindicus and two gastropods Chrysomallon squamiferum and Gigantopelta aegis) collected from a hydrothermal vent field (Southwest Indian Ridge in the Indian Ocean). We found approximately 1.78‰ differences in the δZn values among the three vent mollusks despite of their similar range of Zn concentrations. The significant variation in the δZn values was considered to be indicative of different Zn uptake sources among the three species as a result of their morphological adaptations. Zinc uptake associated with symbiotic activities may be more relevant in the vent gastropods, whereas Zn uptake from hydrothermal fluids during filter-feeding may also play a role in the vent mussels. However, no significant difference in δZn values was observed among tissues of any of the mollusks, showing the absence of Zn isotope fractionation during internal Zn transport. Our results demonstrated that variable Zn uptake pathways existed among different hydrothermal vent mollusks and could be differentiated by determining the Zn isotopic compositions in their tissues. We also highlight that Zn isotope ratios can be used to track Zn sources to the vent mollusks.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145653DOI Listing
June 2021

[Wiedemann-Steiner syndrome due to novel nonsense variant of KMT2A gene in a case].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Feb;38(2):138-140

Shanxi Provincial Children's Hospital (Shanxi Maternal and Child Health Care Hospital), Taiyuan, Shanxi 030013, China.

Objective: To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity.

Methods: Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents.

Results: WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3).

Conclusion: The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200122-00046DOI Listing
February 2021

Id3 and Bcl6 Promote the Development of Long-Term Immune Memory Induced by Tuberculosis Subunit Vaccine.

Vaccines (Basel) 2021 Feb 5;9(2). Epub 2021 Feb 5.

Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.

Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging the immune memory induced by a tuberculosis (TB) subunit vaccine. To address this research gap, mice were treated with the () subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64-Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1 at 0, 2, and 4 weeks, respectively. Immune responses induced by the vaccine were examined at 25 weeks after last immunization. The results showed that adeno-associated virus-mediated IL-7 allowed the TB subunit vaccine to induce the formation of long-lived memory T cells. Meanwhile, IL-7 increased the expression of , , and -the three key transcription factors for the generation of long-lived memory T cells. The adjuvant effects of transcriptional factors, together with TB fusion protein MH/LT70 vaccination, showed that both Bcl6 and Id3 increased the production of antigen-specific antibodies and long-lived memory T cells, characterized by high proliferative potential of antigen-specific CD4 and CD8 T cells, and IFN-γ secretion in CD4 and CD8 T cells, respectively, after re-exposure to the same antigen. Overall, our study suggests that IL-7 and transcriptional factors Id3 and Bcl6 help the TB subunit vaccine to induce long-term immune memory, which contributes to providing immune protection against infection.
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http://dx.doi.org/10.3390/vaccines9020126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914852PMC
February 2021

Bimetallic oxide MnFeO modified carbon felt anode by drip coating: an effective approach enhancing power generation performance of microbial fuel cell.

Bioprocess Biosyst Eng 2021 Feb 8. Epub 2021 Feb 8.

National Key Laboratory of High-Efficiency Utilization of Coal and Green Chemical Engineering, Ningxia University, Yinchuan, 750021, People's Republic of China.

The anode electrode of microbial fuel cell (MFC) is the key component to determine its power generation performance because it is the habitat and electron transfer center of the electricity-producing microorganisms. Carbon-based anodes have been confirmed to improve MFC performance. Its large surface area, excellent conductivity and low cost make it very suitable for electrode materials used in MFC. However, the low biocompatibility and instability of common carbon-based materials restrict their practical application in MFC. In this work, a bimetal oxide MnFeO was prepared and used to modify carbon felt anode by a simple drop coating method. The influence of the amount of MnFeO material on the performance of MFC was systematically studied. The results showed that the power density of the carbon felt anode with a MnFeO modified amount of 1 mg/cm increased by 66.9% compared with the unmodified anode. Meanwhile, the MFC cycle using MnFeO modified anode was more stable. After 6 months of long-term operation, the power density reached 3836 mW/m. The anode modified by MnFeO has capacitance characteristics, good biocompatibility and fast electron transmission rate, which significantly improves the power generation performance of MFC. In addition, the use of a simple drop coating method to prepare electrodes can reduce the difficulty of electrode fabrication and the cost of MFC, laying a certain foundation for the industrialization of MFC.
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http://dx.doi.org/10.1007/s00449-021-02511-zDOI Listing
February 2021

Uterine pyruvate metabolic disorder induced by silica nanoparticles act through the pentose phosphate pathway.

J Hazard Mater 2021 Jan 24;412:125234. Epub 2021 Jan 24.

Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan 250001, China. Electronic address:

Silica nanoparticles (SiNPs) have drawn considerable attention due to their environmental health effects, while enhanced understanding of metabolic disorders has provided insight into related diseases. To investigate the impacts of SiNPs exposure on reproduction and reveal their pathogenic mechanisms, this study was designed and conducted from a metabolic perspective. First, fluorescein isothiocyanate (FITC)-SiNPs were chemically synthesized and applied to track SiNPs in vitro and in vivo. Next, 30 pregnant mice were intratracheally instilled with 1.25 mg of SiNPs/mouse, then sacrificed 24 h post-treatment. We found that SiNPs penetrated the trophoblast membrane, triggering apoptosis and inhibiting cell proliferation, invasion, and tube formation in a dose-dependent manner. Mechanistically, SiNPs dysregulated phosphofructokinase (Pfkl) and fructose-bisphosphatase 2 (Fbp2) and induced glucose depletion and pyruvate accumulation via the pentose phosphate pathway. Besides, the downregulation of caspase-3 suggested a causal relationship between pyruvate accumulation, pentose phosphate pathway activation, and cell apoptosis. Pfkl and Fbp2 was also dysregulated in vivo, and the uterine inflammation aggravated in a time-dependent manner. In conclusion, SiNPs triggered acute cytotoxicity and uterine inflammation by inducing glucose depletion and pyruvate overload in trophoblasts, which were mediated in part by Pfkl and Fbp2 via the pentose phosphate pathway.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125234DOI Listing
January 2021

[Effect of testosterone propionate on condition and prognosis of sepsis patients].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Dec;32(12):1450-1453

Department of Critical Care Medicine, Weinan Central Hospital, Weinan 714000, Shaanxi, China. Corresponding author: Shi Shaolin, Email:

Objective: To investigate the effect of testosterone propionate injection on the condition and prognosis of patients with sepsis.

Methods: The clinical data of 61 sepsis patients admitted to the department of intensive care medicine, Weinan Central Hospital from June 2009 to October 2019 were retrospectively analyzed. All patients were treated with anti-infection, control of infection sources, organ function support, nutrition enhancement and supportive treatment. On the basis of routine treatment, observation group was given 100 mg of testosterone propionate injection for deep intramuscular injection twice a week (twice in total), and control group was not given testosterone propionate injection. The general information and laboratory indexes before treatment were observed, and the testosterone, albumin, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) score after treatment, intensive care unit (ICU) hospitalization time, total hospitalization cost, mechanical ventilation time, 28-day all-cause mortality and other indicators of the patients in two groups were compared.

Results: There were no significant differences between the two groups in gender, age and other baseline data and laboratory indexes before treatment. After treatment, in observation group the testosterone (μg/L: 3.69±2.38 vs. 2.85±0.90) and albumin (g/L: 39.87±1.98 vs. 26.25±4.13) were significantly higher than those in control group. Total hospitalization expenses (ten thousand Yuan: 10.14±3.22 vs. 12.10±3.91), APACHE II (13.71±2.13 vs. 23.23±2.52), SOFA (4.45±1.57 vs. 9.97±2.65), ICU hospitalization time (days: 12.36±4.37 vs. 14.03±3.86) and mechanical ventilation time (days: 3.00±1.85 vs. 7.00±2.50) were significantly lower than those in control group (all P < 0.05), and the difference in 28-day all-cause mortality of two groups was not significant [3.2% (1/31) vs. 13.3% (4/30), P > 0.05].

Conclusions: Testosterone propionate injection can increase albumin level, shorten the time of mechanical ventilation, and improve the condition and prognosis of patients with sepsis.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200429-00611DOI Listing
December 2020

Deciphering the Subtype Differentiation History of SARS-CoV-2 Based on a New Breadth-First Searching Optimized Alignment Method Over a Global Data Set of 24,768 Sequences.

Front Genet 2020 11;11:591833. Epub 2021 Jan 11.

Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, China.

SARS-CoV-2 has caused a worldwide pandemic. Existing research on coronavirus mutations is based on small data sets, and multiple sequence alignment using a global-scale data set has yet to be conducted. Statistical analysis of integral mutations and global spread are necessary and could help improve primer design for nucleic acid diagnosis and vaccine development. Here, we optimized multiple sequence alignment using a conserved sequence search algorithm to align 24,768 sequences from the GISAID data set. A phylogenetic tree was constructed using the maximum likelihood (ML) method. Coronavirus subtypes were analyzed via t-SNE clustering. We performed haplotype network analysis and t-SNE clustering to analyze the coronavirus origin and spread. Overall, we identified 33 sense, 17 nonsense, 79 amino acid loss, and 4 amino acid insertion mutations in full-length open reading frames. Phylogenetic trees were successfully constructed and samples clustered into subtypes. The COVID-19 pandemic differed among countries and continents. Samples from the United States and western Europe were more diverse, and those from China and Asia mainly contained specific subtypes. Clades G/GH/GR are more likely to be the origin clades of SARS-CoV-2 compared with clades S/L/V. Conserved sequence searches can be used to segment long sequences, making large-scale multisequence alignment possible, facilitating more comprehensive gene mutation analysis. Mutation analysis of the SARS-CoV-2 can inform primer design for nucleic acid diagnosis to improve virus detection efficiency. In addition, research into the characteristics of viral spread and relationships among geographic regions can help formulate health policies and reduce the increase of imported cases.
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http://dx.doi.org/10.3389/fgene.2020.591833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831388PMC
January 2021

Successful application of snare-kissing-catheter technique to implant leadless pacemaker in severely dilated right heart.

Pacing Clin Electrophysiol 2021 Jan 25. Epub 2021 Jan 25.

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, Xuhui District, China.

Implantation of leadless pacemaker is efficacy and safety compared with the traditional pacemaker in structurally normal hearts. However, delivery experience of leadless pacemaker in patients with severe right heart enlargement remains limited. We present the rare case of a patient with giant right heart and moderate to severe tricuspid regurgitation implanted with a leadless Micra transcatheter pacemaker system. The extension of the Micra delivery catheter can be improved by using a single-loop snare on the catheter proximal to appropriate right ventricle (RV) pacing position. The snare-kissing-catheter technique can aid in successful deployment in the setting of challenging right heart enlargement.
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http://dx.doi.org/10.1111/pace.14173DOI Listing
January 2021

Comparative research on nucleocapsid and spike glycoprotein as the rapid immunodetection targets of COVID-19 and establishment of immunoassay strips.

Mol Immunol 2021 03 9;131:6-12. Epub 2021 Jan 9.

Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen 518055 PR China; School of Life Science, Tsinghua University, Beijing 100084, PR China; Tsinghua-Berkeley Shenzhen Institute (TBSI), Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, PR China; Shenzhen Bay Laboratory, Shenzhen, PR China. Electronic address:

The SARS-CoV-2 virus responsible for coronavirus 2019 (COVID-19) poses a significant challenge to healthcare systems worldwide. According to the World Health Organization (WHO), the outbreak of COVID-19 has been a pandemic that infected more than 25.32 million people and caused more than 848.25 thousand deaths worldwide at the time of 1st September 2020. Despite governmental initiatives aimed to contain the spread of the disease, several countries are experiencing unmanageable increases in medical equipment and larger testing capacity. The current diagnosis based on nuclear acid requires specialized instruments, time-consuming, and laborious, the low-cost and convenient technologies were still urgently needed. Both spike and nucleocapsid are key structural proteins of COVID-19 with good immunogenicity, can serve as primary targets for immunoassay. After comparative research, we certified nucleocapsid antigen-monoclonal antibody (mAbs) system was more suitable for the COVID-19 immunodetection. Subsequently, we designed a rapid test strip based on it that can be used in large-scale screening of COVID-19 in population and more suitable for some remote and special needs areas were restricted by a medical condition or for quick and large quantities of screenings.
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http://dx.doi.org/10.1016/j.molimm.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833923PMC
March 2021

Berberine-releasing electrospun scaffold induces osteogenic differentiation of DPSCs and accelerates bone repair.

Sci Rep 2021 Jan 13;11(1):1027. Epub 2021 Jan 13.

Department of Cariology and Endodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 210093, China.

The repair of skeletal defects in maxillofacial region remains an intractable problem, the rising technology of bone tissue engineering provides a new strategy to solve it. Scaffolds, a crucial element of tissue engineering, must have favorable biocompatibility as well as osteoinductivity. In this study, we prepared berberine/polycaprolactone/collagen (BBR/PCL/COL) scaffolds with different concentrations of berberine (BBR) (25, 50, 75 and 100 μg/mL) through electrospinning. The influence of dosage on scaffold morphology, cell behavior and in vivo bone defect repair were systematically studied. The results indicated that scaffolds could release BBR stably for up to 27 days. Experiments in vitro showed that BBR/PCL/COL scaffolds had appropriate biocompatibility in the concentration of 25-75 μg/mL, and 50 and 75 μg/mL scaffolds could significantly promote osteogenic differentiation of dental pulp stem cells. Scaffold with 50 μg/mL BBR was implanted into the critical bone defect of rats to evaluate the ability of bone repair in vivo. It was found that BBR/PCL/COL scaffold performed more favorable than polycaprolactone/collagen (PCL/COL) scaffold. Overall, our study is the first to evaluate the capability of in vivo bone repair of BBR/PCL/COL electrospun scaffold. The results indicate that BBR/PCL/COL scaffold has prospective potential for tissue engineering applications in bone regeneration therapy.
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http://dx.doi.org/10.1038/s41598-020-79734-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806735PMC
January 2021

(-449 G/C) G allele is positively associated with leukoaraiosis in northeastern China: a double-blind, intergroup comparison, case-control study.

Neural Regen Res 2021 Aug;16(8):1592-1597

Department of Geriatrics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase (DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this double-blind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, SmaI restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2 (-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models (GG and CG), while 89.13% of healthy control subjects had dominant genetic models (CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls (P = 0.0002). The frequency of G alleles in the leukoaraiosis patients (71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower (χ = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes (Kruskal-Wallis H = 24.5955, P < 0.0001). In addition, the GG genotype of DDAH2 (-449 G/C) was more common in patients with leukoaraiosis. These findings suggest that the G allele of DDAH2 (-449 G/C) is a risk factor for leukoaraiosis morbidity and is correlated with high levels of asymmetric dimethylarginine. This study was approved by the Institutional Ethics Committee of The 2nd Affiliated Hospital of Harbin Medical University of China (approval No. KY2016-177) on July 28, 2016.
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http://dx.doi.org/10.4103/1673-5374.303037DOI Listing
August 2021

Long non-coding RNAs in recurrent ovarian cancer: Theranostic perspectives.

Cancer Lett 2021 Apr 8;502:97-107. Epub 2021 Jan 8.

Tsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, PR China; Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, PR China. Electronic address:

Nearly 70% of ovarian cancer (OC) patients experience recurrence within the first 2 years after initial treatment. Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a pivotal role in the pathogenesis of OC progression, resistance to therapy and recurrent OC (ROC). Transcriptome profiling studies have reported differential expression patterns of lncRNAs in OC which are related to increased cell invasion, metastasis and drug resistance. In this review, we highlighted the roles of lncRNAs in OC progression and outlined the potential molecular mechanisms by which lncRNAs impact on ROC. Recent advances using lncRNAs as potential biomarkers for screening, detection, prediction, response to therapy and as therapeutic targets are discussed.
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http://dx.doi.org/10.1016/j.canlet.2020.12.042DOI Listing
April 2021

Self-Assembly of Hollow Graphene Oxide Microcapsules Directed by Cavitation for Loading Hydrophobic Drugs.

ACS Appl Mater Interfaces 2021 Jan 6;13(2):2988-2996. Epub 2021 Jan 6.

Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.

Hollow graphene oxide microcapsules (GOMs) have been widely used in energy, electronics, catalysis, sensing, tissue engineering, and drug loading due to their unique properties. However, it is still a great challenge to prepare GOMs with high quality and in large quantity using a simple method. In this work, we obtained single-component GOMs using the liquid nitrogen cavitation effect, which directed the self-assembly of graphene oxide (GO) debris at the gas-liquid interface. This method avoids the introduction of additional components and removal of templates. The morphology of GOM with wrinkles on its surface was characterized by transmission electron microscopy and scanning electron microscopy. The abundant polar groups of GO microcapsules enabled them to easily disperse in water. Based on this, GOMs have good potential for loading hydrophobic drugs. Subsequently, we used GOMs as carriers to deliver a hydrophobic drug paclitaxel (PTX), which exhibited a good loading capacity. Moreover, PTX loaded GOMs showed excellent cytotoxicity to A549 and MDA-MB-231 cells. The GOMs also showed a pH-dependent drug release performance. Therefore, GOMs can be regarded as potential carriers for biomedical applications.
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http://dx.doi.org/10.1021/acsami.0c16550DOI Listing
January 2021

An immune-related risk gene signature predicts the prognosis of breast cancer.

Breast Cancer 2021 Jan 5. Epub 2021 Jan 5.

State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, People's Republic of China.

Background: Accurate prediction of the outcome of breast cancer remains as a challenge due to its heterogeneous nature. We aimed to construct an immune-related risk signature to predict the overall outcome of breast cancer using bioinformatic approaches.

Methods: In this study, transcriptome and survival data obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database were used to identify differentially expressed genes between breast cancer and normal samples. A regulatory network was constructed based on the immune-related prognostic genes and transcription factors screened from the differently expressed genes. The immune-related risk gene signature was obtained using the least absolute shrinkage and selection operator (LASSO) method and Cox regression model. The immune-related prognostic scores of breast cancer (IPSBC) calculated from the risk signature were used to group breast cancer patients by risk levels. The accuracy of IPSBC was evaluated by survival analysis and receiver operating characteristic curve analysis. The independency and the relationship of IPSBC with clinicopathological characteristics and abundance of tumor-infiltrated immune cells were also investigated.

Results: A total of 4296 differentially expressed genes between breast cancer and normal samples were identified, and a total of 13 prognostic immune-related genes were eventually selected as the risk gene signature, which was an independent prognostic factor of the overall survival of breast cancer. The IPSBC stratified breast cancer patients into low- and high-risk groups. Breast cancer patients in the high-risk group were associated with worse overall outcomes, more advanced stage and less abundance of tumor-infiltrated immune cells, including B cells, CD4 T cells, CD8 T cells, neutrophils, macrophages, and dendritic cells compared to low-risk group.

Conclusion: In this study, an immune-related gene signature of breast cancer was identified, which could be used as potential prognostic and therapeutic targets of breast cancer.
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http://dx.doi.org/10.1007/s12282-020-01201-0DOI Listing
January 2021

Pharmacological Inhibition of BAD Ser99 Phosphorylation Enhances the Efficacy of Cisplatin in Ovarian Cancer by Inhibition of Cancer Stem Cell-like Behavior.

ACS Pharmacol Transl Sci 2020 Dec 9;3(6):1083-1099. Epub 2020 Oct 9.

Tsinghua Berkeley Shenzhen Institute (TBSI), Shenzhen, 518000, China.

Platinum-based chemotherapy has been the standard treatment for ovarian cancer patients for approximately four decades. However, the prognosis of patients with advanced ovarian carcinoma remains dismal, mainly attributed to both dose-limiting toxicities of cisplatin and the high rate of chemo-resistant disease recurrence. Herein, both patient-derived and experimentally generated cisplatin-sensitive and -resistant ovarian cancer cell line models were used to delineate BADSer99 phosphorylation as an actionable target in ovarian cancer. BADSer99 phosphorylation was negatively associated with cisplatin sensitivity in ovarian cancer, and the inhibition of BADSer99 phosphorylation by point mutation induced apoptosis and reduced cisplatin IC. In addition, BAD phosphorylation was also shown to be associated with cancer stem cell-like properties. Henceforth, a novel small molecule which inhibits BAD phosphorylation specifically at Ser99 (NPB) was utilized. NPB promoted apoptosis and reduced 3D growth of bulk cancer cells and inhibited cancer stem cell-like properties in both cisplatin-sensitive and -resistant ovarian cancer cells. The combination of cisplatin with NPB exhibited synergistic effects . NPB in combination with cisplatin also achieved an improved outcome compared to either monotreatment , including suppression of the cancer stem cell population, an effect not observed with cisplatin treatment. Furthermore, NPB exhibited strong synergistic effects with the AKT inhibitor AZD5363, and significantly reduced its IC in cells resistant to cisplatin treatment. These findings identify BADSer99 phosphorylation as an actionable and pharmacologically relevant target to improve outcomes of cisplatin treated ovarian cancer.
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http://dx.doi.org/10.1021/acsptsci.0c00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737213PMC
December 2020

The Projection From Ventral CA1, Not Prefrontal Cortex, to Nucleus Accumbens Core Mediates Recent Memory Retrieval of Cocaine-Conditioned Place Preference.

Front Behav Neurosci 2020 16;14:558074. Epub 2020 Nov 16.

The State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and the Institutes of Brain Science, Fudan University, Shanghai, China.

Drug-paired cues inducing memory retrieval by expressing drug-seeking behaviors present a major challenge to drug abstinence. How neural circuits coordinate for drug memory retrieval remains unclear. Here, we report that exposure of the training chamber where cocaine-conditioned place preference (CPP) was performed increased neuronal activity in the core of nucleus accumbens (AcbC), ventral CA1 (vCA1), and medial prefrontal cortex (mPFC), as shown by elevated pERK and c-Fos levels. Chemogenetic inhibition of neuronal activity in the vCA1 and AcbC, but not mPFC, reduced the time spent in the cocaine-paired compartment, suggesting that the vCA1 and AcbC are required for the retrieval of cocaine-CPP memory and are key nodes recruited for cocaine memory storage. Furthermore, chemogenetic inhibition of the AcbC-projecting vCA1 neurons, but not the AcbC-projecting mPFC neurons, decreased the expression of cocaine-CPP. Optogenetic inhibition of the vCA1-AcbC projection, but not the mPFC-AcbC projection, also reduced the preference for the cocaine-paired compartment. Taken together, the cue-induced natural recall of cocaine memory depends on vCA1-AcbC circuits. The connectivity from the vCA1 to the AcbC may store the information of the cue-cocaine reward association critically required for memory retrieval. These data thus provide insights into the neural circuit basis of retrieval of drug-related memory.
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http://dx.doi.org/10.3389/fnbeh.2020.558074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701212PMC
November 2020

Effects of probiotic litchi juice on immunomodulatory function and gut microbiota in mice.

Food Res Int 2020 11 12;137:109433. Epub 2020 Jun 12.

Sericultural & Argi-Food Research Institute, Guangdong Academy of Agricultural Sciences/Key Laboratory of Functional Foods, Ministry of Agriculture and Rural Affairs/Guangdong Key Laboratory of Agricultural Products Processing, No. 133 Yiheng Street., Dongguanzhuang Road, Tianhe District, Guangzhou 510610, China. Electronic address:

Development new functional foods containing probiotics had gained much attention during the past two decades. In this study, probiotic litchi juice was developed, and its effects on immunomodulatory function and gut microbiota were evaluated. Firstly, the litchi juice was fermented with Lactobacillus casei, which increased total phenolic, total flavone, and exopolysaccharide contents of the litchi juice. Hence, the immunomodulatory influence of fermented litchi juice (FL) was investigated in cyclophosphamide-induced mice. The results showed that FL enhanced immune organs indexes (spleen, thymus) and antioxidant capacity, improved the secretions of cytokines (IL-2, IL-6) and immunoglobulins (IgA, IgG, SIgA), and protected the intestinal tract. Finally, the effect of FL on gut microbiota was analyzed by high-throughput sequencing analysis. The changes in the relative abundance of dominant microbe were investigated at phylum and genus levels, respectively. After treatment with FL, the relative abundance of Firmicutes phylum was dramatically increased, as well as the genera of Faecalibaculum, Lactobacillus, and Akkermansia. These findings indicated that probiotic litchi juice could alleviate immune dysfunction and modify gut microbiota structure of mice, which provide a potential functional food to improve the host health.
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http://dx.doi.org/10.1016/j.foodres.2020.109433DOI Listing
November 2020

Graphene Oxide Quantum Dots-Induced Mineralization via the Reactive Oxygen Species-Dependent Autophagy Pathway in Dental Pulp Stem Cells.

J Biomed Nanotechnol 2020 Jun;16(6):965-974

As an important recycling and degradation system, autophagy is considered to be critical in regulating stem cell differentiation. It has been shown that graphene oxide quantum dots (GOQDs) are a robust biological labelling tool for stem cells with little cytotoxicity. In this study, we explored the role of autophagy in regulating the impact of GOQDs on the odontoblastic differentiation of DPSCs during autophagy. Western blotting and immunofluorescence staining were used to evaluate the autophagic activity of DPSCs. Quantitative PCR, alizarin red S staining, and alkaline phosphatase staining were used to examine DPSC odontoblastic differentiation. The impacts of ROS scavengers on autophagy induction and reactive oxygen species (ROS) levels were also measured. Lentiviral vectors carrying Beclin1 siRNA sequences, as well as autophagy inhibitors (3-MA and bafilomycin A1), were used to inhibit autophagy. Initial exposure to GOQDs increased autophagic activity and enhanced DPSC mineralization. Autophagy inhibition suppressed GOQD-induced odontoblastic differentiation. Moreover, GOQD treatment induced autophagy in a ROS-dependent manner. GOQDs promoted differentiation, which could be modulated via ROS-induced autophagy.
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http://dx.doi.org/10.1166/jbn.2020.2934DOI Listing
June 2020

A novel approach to efficient degradation of indole using co-immobilized horseradish peroxidase-syringaldehyde as biocatalyst.

Chemosphere 2021 Jan 23;262:128411. Epub 2020 Sep 23.

State Key Laboratory of High-efficiency Coal Utilization and Green Chemical Engineering, College of Chemistry & Chemical Engineering, Ningxia University, Yinchuan, 750021, PR China. Electronic address:

Biocatalytic degradation technology has received a great deal of attention in water treatment because of its advantages of high efficiency, environmental friendliness, and no secondary pollution. Herein, for the first time, horseradish peroxidase and mediator syringaldehyde were co-immobilized into functionalized calcium alginate composite beads grafted with glycidyl methacrylate and dopamine. The resultant biocatalyst of the co-immobilized horseradish peroxidase-syringaldehyde system has displayed excellent catalytic performance to degrade indole in water. The degradation rate of 100% was achieved in the presence of hydrogen peroxide even if the indole concentration was changing from 25 mg/L to 500 mg/L. If only the free enzyme was used under the identical water treatment conditions, the degradation of indole could hardly be observed even when the concentration of indole is low at 25 mg/L. This was attributed to the effective co-immobilization of the enzyme and the mediator so that the catalytic activity of horseradish peroxidase and the synergistic catalytic action of syringaldehyde could be fully developed. Furthermore, while the spherical catalyst was operated in succession and reused for four cycles in 50 mg/L indole solution, the degradation rate remained 91.8% due to its considerable reusability. This research demonstrated and provided a novel biocatalytic approach to degrade indole in water by the co-immobilized horseradish peroxidase-syringaldehyde system as biocatalyst.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128411DOI Listing
January 2021

In vitro and in vivo uterine metabolic disorders induced by silica nanoparticle through the AMPK signaling pathway.

Sci Total Environ 2021 Mar 21;762:143152. Epub 2020 Oct 21.

Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan 250001, China. Electronic address:

Exposure to silica nanoparticles (SiNPs) has been suggested to cause physical disorders, yet the effects of SiNPs on female reproduction have not been illustrated. This study was implemented to explore the reproductive toxicity of SiNPs on female and reveal its underlying mechanisms. Methodologically, the fluorescein isothiocyanate (FITC)-SiNPs were synthesized by coupling with FITC and then used to track the biodistribution of SiNPs in vitro and in vivo. In total, 30 mice were intratracheally injected 0.25 g of FITC-SiNPs, and 6 mice injected with the same volume of saline were used as controls. The results showed that SiNPs penetrated the cellular membrane, triggering apoptosis and inhibiting proliferation, tube formation, and invasion of trophoblast. Mechanistically, SiNPs was demonstrated to dysregulate Fbp2, Cpt1a, Scd1, and Pfkl, and further induced accumulation of pyruvate and fatty acid in mitochondria through the AMPK signaling pathway, which finally activated the Caspase-3-dependent apoptosis. Consistently, the similar alterations of these genes were detected in vivo, and the uterine inflammatory infiltration aggravated with the extension of the observation duration. These results suggested that SiNPs induced trophoblast apoptosis and uterine inflammation, and ultimately caused acute reproductive toxicity on female. The underlying mechanism might be explained by the dysregulation of Fbp2/Cpt1a/Pfkl/Scd1 axis, which promoted the overload of glucose and lipid through the AMPK signaling pathway. These findings were of great significance to guide a comprehensive understanding of the reproductive toxicity of SiNPs as well as the development of environmental standards.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143152DOI Listing
March 2021

Integrating GWAS and eQTL to predict genes and pathways for non-syndromic cleft lip with or without palate.

Oral Dis 2020 Oct 31. Epub 2020 Oct 31.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Objective: To explore susceptibility genes and pathways for non-syndromic cleft lip with or without cleft palate (NSCL/P).

Materials And Methods: Two genome-wide association studies (GWAS) datasets, including 858 NSCL/P cases and 1,248 controls, were integrated with expression quantitative trait loci (eQTL) dataset identified by Genotype-Tissue Expression (GTEx) project in whole-blood samples. The expression of the candidate genes in mouse orofacial development was inquired from FaceBase. Protein-protein interaction (PPI) network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to explore the underlying risk pathways.

Results: A total of 233 eQTL single-nucleotide polymorphisms (SNPs) in 432 candidate genes were identified to be associated with the risk of NSCL/P. One hundred and eighty-three susceptible genes were expressed in mouse orofacial development according to FaceBase. PPI network analysis highlighted that these genes involved in ubiquitin-mediated proteolysis (KCTD7, ASB1, UBOX5, ANAPC4) and DNA synthesis (XRCC3, RFC3, KAT5, RHNO1) were associated with the risk of NSCL/P. GO and KEGG pathway analyses revealed that the fatty acid metabolism pathway (ACADL, HSD17B12, ACSL5, PPT1, MCAT) played an important role in the development of NSCL/P.

Conclusions: Our results identified novel susceptibility genes and pathways associated with the development of NSCL/P.
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http://dx.doi.org/10.1111/odi.13699DOI Listing
October 2020

Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate.

J Cell Mol Med 2020 12 27;24(23):13669-13678. Epub 2020 Oct 27.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Although several genome-wide association studies (GWAS) of non-syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in-depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case-parent trios and another in-house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3' of SERTAD4, P = 6.44 × 10 ; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10 and 2.80 × 10 , respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10 ; rs2095293: intron of NR6A1, P = 2.98 × 10 ). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10 ). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down-regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.
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http://dx.doi.org/10.1111/jcmm.15878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754035PMC
December 2020