Publications by authors named "Sen Wang"

490 Publications

Multivariant ligands stabilize anionic solvent-oriented α-CsPbX nanocrystals at room temperature.

Nanoscale 2021 Feb 24. Epub 2021 Feb 24.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China. and University of Science and Technology of China, Hefei, 230026, People's Republic of China.

Cubic phase CsPbX3 nanocrystals (NCs) are promising candidates for optoelectronic applications. However, their chemical stability heavily depends on the dynamic ionic surface. In this work, based on the interdependency of the ligands and the reaction solvent, a protocol is developed for high-quality α-CsPbX3 under ambient conditions. Utilizing this method, the size and full width at half maximum of CsPbX3 NCs can be simply tuned via changing the cationic ligands or reaction solvent, such as CH3Cl, CH2Cl2, or toluene. One remarkable result is the synthesis of cubic CsPbI3 NCs, for which large-scale syntheses have not been reported in the literature except for our method, due to significant phase transition at room temperature. Another result is that we have realized ultrasmall sized CsPbCl3 NCs with emission at 385 nm for the first time. Furthermore, the elimination of reaction solvent (such as ODE, DMSO, DMF) in our protocol reduces the purification-induced surface ligand loss and the irreversible phase transition to a nonfluorescent phase. Our CsPbX3 NCs show near-perfect photoluminescence quantum yield (PL QY) and long-term stability in the presence of moisture. Further characterization demonstrates that all the ligands, whether the initial paired X type or the degenerated hybrid L-X type, remain perfectly passivating on the defect sites throughout.
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http://dx.doi.org/10.1039/d0nr08697eDOI Listing
February 2021

A microbial gene catalog of anaerobic digestion from full-scale biogas plants.

Gigascience 2021 Jan;10(1)

Biogas Institute of Ministry of Agricultural and Rural Affairs, Section 4-13, Renmin South Road, Chengdu 610041, China.

Background: Biogas production with anaerobic digestion (AD) is one of the most promising solutions for both renewable energy production and resolving the environmental problem caused by the worldwide increase in organic waste. However, the complex structure of the microbiome in AD is poorly understood.

Findings: In this study, we constructed a microbial gene catalog of AD (22,840,185 genes) based on 1,817 Gb metagenomic data derived from digestate samples of 56 full-scale biogas plants fed with diverse feedstocks. Among the gene catalog, 73.63% and 2.32% of genes were taxonomically annotated to Bacteria and Archaea, respectively, and 57.07% of genes were functionally annotated with KEGG orthologous groups. Our results confirmed the existence of core microbiome in AD and showed that the type of feedstock (cattle, chicken, and pig manure) has a great influence on carbohydrate hydrolysis and methanogenesis. In addition, 2,426 metagenome-assembled genomes were recovered from all digestate samples, and all genomes were estimated to be ≥80% complete with ≤10% contamination.

Conclusions: This study deepens our understanding of the microbial composition and function in the AD process and also provides a huge number of reference genome and gene resources for analysis of anaerobic microbiota.
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http://dx.doi.org/10.1093/gigascience/giaa164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842101PMC
January 2021

Socioeconomic Deprivation Index Is Associated With Psychiatric Disorders: An Observational and Genome-wide Gene-by-Environment Interaction Analysis in the UK Biobank Cohort.

Biol Psychiatry 2020 Nov 26. Epub 2020 Nov 26.

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Background: Psychiatric disorders are among the largest and fastest-growing categories of the global disease burden. However, limited effort has been made to further elucidate associations between socioeconomic factors and psychiatric disorders from a genetic perspective.

Methods: We randomly divided 501,882 participants in the UK Biobank cohort with socioeconomic Townsend deprivation index (TDI) data into a discovery cohort and a replication cohort. For both cohorts, we first conducted regression analyses to evaluate the associations between the TDI and common psychiatric disorders or traits, including anxiety, bipolar disorder, self-harm, and depression (based on self-reported depression and Patient Health Questionnaire scores). We then performed a genome-wide gene-by-environment interaction study using PLINK 2.0 with the TDI as an environmental factor to explore interaction effects.

Results: In the discovery cohort, significant associations were observed between the TDI and psychiatric disorders (p < 4.00 × 10), including anxiety (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.07-1.10), bipolar disorder (OR = 1.42, 95% CI = 1.36-1.48), self-harm (OR = 1.21, 95% CI = 1.19-1.23), self-reported depression (OR = 1.22, 95% CI = 1.20-1.24), and Patient Health Questionnaire scores (β = .07, SE = 0.004). We observed similar significant associations in the replication cohort. In addition, multiple candidate loci were identified by the genome-wide gene-by-environment interaction study, including rs10886438 at 10q26.11 (GRK5) (p = 5.72 × 10) for Patient Health Questionnaire scores and rs162553 at 2p22.2 (CYP1B1) (p = 2.25 × 10) for self-harm.

Conclusions: Our findings suggest the relevance of the TDI to psychiatric disorders. The genome-wide gene-by-environment interaction study identified several candidate genes interacting with the TDI, providing novel clues for understanding the biological mechanism of associations between the TDI and psychiatric disorders.
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http://dx.doi.org/10.1016/j.biopsych.2020.11.019DOI Listing
November 2020

Transcriptome-wide association study identifies susceptibility genes for rheumatoid arthritis.

Arthritis Res Ther 2021 01 22;23(1):38. Epub 2021 Jan 22.

School of Public Health, Xi'an Jiaotong University Health Science Center; Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, No.76, Yan Ta West Road, Xi'an, 710061, People's Republic of China.

Objective: To identify rheumatoid arthritis (RA)-associated susceptibility genes and pathways through integrating genome-wide association study (GWAS) and gene expression profile data.

Methods: A transcriptome-wide association study (TWAS) was conducted by the FUSION software for RA considering EBV-transformed lymphocytes (EL), transformed fibroblasts (TF), peripheral blood (NBL), and whole blood (YBL). GWAS summary data was driven from a large-scale GWAS, involving 5539 autoantibody-positive RA patients and 20,169 controls. The TWAS-identified genes were further validated using the mRNA expression profiles and made a functional exploration.

Results: TWAS identified 692 genes with P values < 0.05 for RA. CRIPAK (P = 0.01293, P = 0.00038, P = 0.02839, P = 0.0978), MUT (P = 0.00377, P = 0.00076, P = 0.00778, P = 0.00096), FOXRED1 (P = 0.03834, P = 0.01120, P = 0.01280, P = 0.00583), and EBPL (P = 0.00806, P = 0.03761, P = 0.03540, P = 0.04254) were collectively expressed in all the four tissues/cells. Eighteen genes, including ANXA5, AP4B1, ATIC (P = 0.0113, downregulated expression), C12orf65, CMAH, PDHB, RUNX3 (P = 0.0346, downregulated expression), SBF1, SH2B3, STK38, TMEM43, XPNPEP1, KIAA1530, NUFIP2, PPP2R3C, RAB24, STX6, and TLR5 (P = 0.04665, upregulated expression), were validated with integrative analysis of TWAS and mRNA expression profiles. TWAS-identified genes functionally involved in endoplasmic reticulum organization, regulation of cytokine production, TNF signaling pathway, immune response-regulating signaling pathway, regulation of autophagy, etc. CONCLUSION: We identified multiple candidate genes and pathways, providing novel clues for the genetic mechanism of RA.
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http://dx.doi.org/10.1186/s13075-021-02419-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821659PMC
January 2021

Gene expression pattern analysis using dual-color RT-MLPA and integrative genome-wide association studies of eQTL for tuberculosis suscepitibility.

Respir Res 2021 Jan 20;22(1):23. Epub 2021 Jan 20.

Department of Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China.

Background: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood.

Methods: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases.

Results: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients.

Conclusion: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.
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http://dx.doi.org/10.1186/s12931-020-01612-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816316PMC
January 2021

Divergent improvement of two cultivated allotetraploid cotton species.

Plant Biotechnol J 2021 Jan 14. Epub 2021 Jan 14.

Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, Plant Precision Breeding Academy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

Interspecific genomic variation can provide a genetic basis for local adaptation and domestication. A series of studies have presented its role of interspecific haplotypes and introgressions in adaptive traits, but few studies have addressed their role in improving agronomic character. Two allotetraploid Gossypium species, Gossypium barbadense (Gb) and G. hirsutum (Gh) originating from the Americas, are cultivated independently. Here, through sequencing and the comparison of one GWAS panel in 229 Gb accessions and two GWAS panels in 491 Gh accessions, we found that most associated loci or functional haplotypes for agronomic traits were highly divergent, representing the strong divergent improvement between Gb and Gh. Using a comprehensive interspecific haplotype map, we revealed that six interspecific introgressions from Gh to Gb were significantly associated with the phenotypic performance of Gb, which could explain 5%-40% of phenotypic variation in yield and fibre qualities. In addition, three introgressions overlapped with six associated loci in Gb, indicating that these introgression regions were under further selection and stabilized during improvement. A single interspecific introgression often possessed yield-increasing potential but decreased fibre qualities, or the opposite, making it difficult to simultaneously improve yield and fibre qualities. Our study not only has proved the importance of interspecific functional haplotypes or introgressions in the divergent improvement of Gb and Gh, but also supports their potential value in further human-mediated hybridization or precision breeding.
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http://dx.doi.org/10.1111/pbi.13547DOI Listing
January 2021

Duet FeC and FeN Sites for HO Generation and Activation toward Enhanced Electro-Fenton Performance in Wastewater Treatment.

Environ Sci Technol 2021 Jan 8;55(2):1260-1269. Epub 2021 Jan 8.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, South Australia 5005, Australia.

Heterogeneous electro-Fenton (HEF) reaction has been considered as a promising process for real effluent treatments. However, the design of effective catalysts for simultaneous HO generation and activation to achieve bifunctional catalysis for O toward •OH production remains a challenge. Herein, a core-shell structural Fe-based catalyst (FeNC@C), with FeC and FeN nanoparticles encapsulated by porous graphitic layers, was synthesized and employed in a HEF system. The FeNC@C catalyst presented a significant performance in degradation of various chlorophenols at various conditions with an extremely low level of leached iron. Electron spin resonance and radical scavenging revealed that •OH was the key reactive species and Fe would play a role at neutral conditions. Experimental and density function theory calculation revealed the dominated role of FeC in HO generation and the positive effect of FeN sites on HO activation to form •OH. Meanwhile, FeNC@C was proved to be less pH dependence, high stability, and well-recycled materials for practical application in wastewater purification.
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http://dx.doi.org/10.1021/acs.est.0c06825DOI Listing
January 2021

Ultrasonic-Assisted Ionic Liquid Extraction of Two Biflavonoids from .

ACS Omega 2020 Dec 17;5(51):33113-33124. Epub 2020 Dec 17.

School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563003, China.

, a traditional Chinese medicine, contains a variety of bioactive components, among which biflavonoids are the main active ingredients and have antioxidant, antitumor, and anti-inflammatory properties. In this study, ultrasonic-assisted ionic liquid extraction (UAILE) is used for the first time to extract two main biflavonoids (amentoflavone (AME) and hinokiflavone (HIN)) from . A high-performance liquid chromatography method is used for the simultaneous determination of AME and HIN in . Then, three novel ILs are synthesized for the first time by a one-step method using benzoxazole and three acids or acid salts as raw materials, and the structures of the synthesized ILs are characterized by elemental analysis, infrared spectroscopy, and NMR spectroscopy, as well as the thermal stability of the ILs is evaluated by thermogravimetric analysis. After screening the extraction effects of three benzoxazole ILs, three pyridine ILs, and three imidazole ILs, it is found that [Bpy]BF is the best and therefore selected as the extractant. The optimal extraction process is explored in terms of the yields of AME and HIN from by a single-factor experiments and response surface analysis. Under the optimal level of each influencing factor (IL concentration of 0.15 mol/L, solid-liquid ratio of 1:12 g/mL, ultrasonic power of 280 W, ultrasonic time of 30 min, and three extraction cycles), the extraction rates of AME and HIN from are 13.51 and 6.74 mg/g, respectively. Moreover, the recovery experiment of [Bpy]BF on the extraction of biflavonoids shows that the recovered IL can repeatedly extract targets six times and the extraction rate is about 90%, which indicates that the IL can be effectively reused. UAILE can effectively and selectively extract AME and HIN, laying the foundation for the application of .
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http://dx.doi.org/10.1021/acsomega.0c04723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774283PMC
December 2020

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway.

J Exp Clin Cancer Res 2021 Jan 5;40(1). Epub 2021 Jan 5.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.

Background: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism).

Methods: Through RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2'-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization.

Results: CircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo. CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7.

Conclusions: CircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.
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http://dx.doi.org/10.1186/s13046-020-01791-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784001PMC
January 2021

[Spatio-temporal Evolution and Population Exposure Risk to PM in the Guanzhong Area].

Huan Jing Ke Xue 2020 Dec;41(12):5245-5255

College of Land Engineering, Chang'an University, Xi'an 710054, China.

In recent years, atmospheric pollution represented by fine particulate matter PM pollution has seriously threatened human health. Therefore, it is important to identify the risk level of population exposure to PM. Based on PM remote sensing inversion data and population distribution, this study measured the risk level of population exposure to PM in the Guanzhong area. Furthermore, the methods of Theil-Sen Median trend analysis, Mann-Kendall test, and geo-spatial analysis were used to reveal the temporal and spatial characteristics of population exposures risk to PM in the Guanzhong area from 2000 to 2016. The results show that:①The years with heavy pollution and wide range in the Guanzhong area are 2006, 2007, and 2013, and the annual average concentration of PM exceeded 35 μg·m in more than 40% of the Guanzhong area. From 2000 to 2016, the spatial distribution range of PM in the Guanzhong area continued to expand, forming a continuous belt-shaped concentrated distribution area from the center to the northeast. ②More than 60% of the population in the Guanzhong area was exposed in the areas with annual average concentration of PM above 35 μg·m from 2000 to 2016, and the population exposure risk continued to increase, especially after 2011, the range of the high-risk area expanded dramatically. ③The pattern of population exposure risk to PM in the Guanzhong area was generally similar from 2000 to 2016. The areas with higher risk levels were mainly concentrated in the central Guanzhong area, forming a continuous belt-shaped distribution area from west to east. The areas with the highest value were distributed in the urban areas of several major cities, while the areas with the lowest value were mainly concentrated in the surrounding areas of Guanzhong.
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http://dx.doi.org/10.13227/j.hjkx.202004189DOI Listing
December 2020

Mid-term Results of Subtalar Arthroereisis with Talar-Fit Implant in Pediatric Flexible Flatfoot and Identifying the Effects of Adjunctive Procedures and Risk Factors for Sinus Tarsi Pain.

Orthop Surg 2021 Feb 17;13(1):175-184. Epub 2020 Dec 17.

Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai, China.

Objectives: To (i) report the mid-term outcomes of subtalar arthroereisis using Talar-Fit implant for the treatment of flexible flatfoot patients; (ii) compare clinical and radiographic outcomes between arthroereisis with and without adjunctive operative procedures to investigate the effects of adjuncts on the outcomes; and (iii) analyze the risk factors associated with sinus tarsi pain, which is the most common postoperative complication of arthroereisis.

Methods: Thirty-one flexible flatfoot children and adolescents (46 feet) treated with subtalar arthroereisis using Talar-Fit implant from June 2014 to May 2019 were retrospectively analyzed. The feet were divided into four treatment groups: (i) arthroereisis alone, (ii) arthroereisis with gastrocnemius recession, (iii) arthroereisis with Kidner procedure, and (iv) arthroereisis with gastrocnemius recession and Kidner procedure. Clinical function was evaluated based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score. The following angles were measured for radiographic evaluation: talar-first metatarsal angle, calcaneal pitch angle, and talar declination angle on the lateral view; and talar-first metatarsal angle, talocalcaneal angle, and anteroposterior talonavicular coverage angle on the anteroposterior (AP) view. The paired Student's t-test was used to compare the pre- and postoperative angular measurements and AOFAS scores. The Wilcoxon rank-sum test was undertaken to determine the outcome differences among four treatment groups. Multivariate logistic regression analysis was used to analyze risk factors for sinus tarsi pain. P value <0.05 is considered statistically significant.

Results: The mean follow-up of the feet was 32.8 months (range, 10-71 months). The mean AOFAS score significantly improved from 55.5 ± 14.5 preoperatively to 86.3 ± 9.9 (P < 0.001). Comparison of radiographic outcomes showed that the lateral talar-first metatarsal angle decreased by a mean of 19.1° ± 11.9° (P < 0.001), the calcaneal pitch angle increased by a mean of 5.4° ± 3.4° (P < 0.001), the talar declination angle decreased by a mean of 14.8° ± 9.9° (P < 0.001), the AP talar-first metatarsal angle decreased by a mean of 15.6° ± 10.3° (P < 0.001), the AP talocalcaneal angle decreased by a mean of 7.2° ± 8.3° (P = 0.001), and the AP talonavicular coverage angle decreased by a mean of 20.4° ± 9.0° (P < 0.001). There were no statistically significant differences with regard to AOFAS score and all angle measurements on both the AP and lateral views among the four treatment groups. There was one dislocation case caused by a fall 6 weeks after surgery, which was treated nonoperatively. The incidence of sinus tarsi pain was 13% and logistic regression analysis indicated that patients with a longer distance from the tail end of the implant to the lateral calcaneal wall had 38.8% greater odds of developing sinus tarsi pain.

Conclusions: The mid-term clinical and radiographic results were satisfactory in patients who underwent the subtalar arthroereisis procedure using Talar-Fit implant, alone or in combination with other adjuncts, for the treatment of flexible flatfoot.
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http://dx.doi.org/10.1111/os.12864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862150PMC
February 2021

Associations of Lifestyle Factors With Cognition in Community-Dwelling Adults Aged 50 and Older: A Longitudinal Cohort Study.

Front Aging Neurosci 2020 9;12:601487. Epub 2020 Nov 9.

School of Public Health, Fudan University, Shanghai, China.

In the absence of an effective treatment to alter the progressive course of cognitive decline and dementia, identification of modifiable risk factors that could promote healthy cognitive aging has become a public health research priority. This study seeks to comprehensively determine the contemporaneous associations of a broad spectrum of time-varying modifiable lifestyle factors with age-related cognitive decline in a large population-based cohort of older adults. A total of 5,711 subjects aged 50 and older from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Repeated measures of lifestyle factors and cognitive performance were conducted in 2009-2010 and 2014-2015. Linear random slope models were used to evaluate the contemporaneous associations between time-varying lifestyle factors and cognitive performance. Person-mean centering method was used to disaggregate the between- and within-person effects in the time-varying lifestyle factors in the random slope models. We found that higher vegetable and fruit consumption, as well as higher level of physical activity were positively associated with all cognitive domains. Body mass index (BMI) was negatively associated with all cognitive domains, whereas waist-to-hip ratio (WHR) was negatively associated with verbal fluency score only. Sedentary time was negatively associated with digit span score but positively associated with verbal fluency score. The between-person effects seem to be more dominant than within-person effects. Overall, our findings suggest better management of multiple lifestyle factors may protect against cognitive decline in later life. Higher vegetable and fruit consumption and physical activity are protective, whereas obesity is detrimental to cognitive decline in older adults. This study underpins the development of multi-domain lifestyle recommendations to promote healthy cognitive aging.
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http://dx.doi.org/10.3389/fnagi.2020.601487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680821PMC
November 2020

Effects of substrate type on enhancing pollutant removal performance and reducing greenhouse gas emission in vertical subsurface flow constructed wetland.

J Environ Manage 2021 Feb 18;280:111674. Epub 2020 Nov 18.

College of Environmental Science and Engineering, Qingdao University, Qingdao, China. Electronic address:

Constructed wetlands (CWs), known as an alternative clean technology, have been widely used for sewage treatment. However, greenhouse gas (NO, CH and CO) emissions are the accompanying problem in CWs. To mitigate the net global warming potential (GWP) with the constant removal efficiency for contaminants is attracting wide attention recently. In this study, four CWs were established to explore the effects of substrate types (gravel, walnut shell, manganese ore and activated alumina) on contaminant removal and greenhouse gas emissions. CWs using manganese ore substrate with function of electronic exchange showed high removal efficiencies on COD (90.1%), TN (65.1%), TP (97.1%) and low greenhouse gas flux. The emission fluxes of NO, CH and CO were 0.07-0.20, 2.00-252.30 and 337.54-782.57 mg m h, respectively. Especially, the lowest average CH emission flux in the manganese ore CW was only 2.00 mg m h while those of NO in walnut shell CW was only 0.07 mg m h, which will make a significant contribution on the mitigation of GWP of CWs. High-throughput sequencing results indicated that microbial community diversity and richness changed significantly among different substrates. The high pmoA and low mcrA, caused by the introduction of manganese ore as substrate, also explained why there was little CH emission in CWs. Our study provided new insights into GWP mitigation and contaminant removal enhancement in CWs using optimal substrate.
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http://dx.doi.org/10.1016/j.jenvman.2020.111674DOI Listing
February 2021

Exogenous hydrogen sulfide inhibits apoptosis by regulating endoplasmic reticulum stress-autophagy axis and improves myocardial reconstruction after acute myocardial infarction.

Acta Biochim Biophys Sin (Shanghai) 2020 Dec;52(12):1325-1336

Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang 421001, China.

During acute myocardial infarction, endoplasmic reticulum (ER) stress-induced autophagy and apoptosis have been shown as important pathogeneses of myocardial reconstruction. Importantly, hydrogen sulfide (H2S), as a third endogenous gas signaling molecule, exerts strong cytoprotective effect on anti-ER stress, autophagy regulation and antiapoptosis. Here, we showed that H2S treatment inhibits apoptosis by regulating ER stress-autophagy axis and improves myocardial reconstruction after acute myocardial infarction. We found that H2S intervention improved left ventricle function, reduced glycogen deposition in myocardial tissue mesenchyme, and inhibited apoptosis. Moreover, the expressions of fibrosis indicators (Col3a1 and Col1a2), ER stress-related proteins (CHOP and BIP/ERP78), autophagy-related proteins (Beclin and ATG5), apoptosis protein (Bax), as well as fibrosis protein Col4a3bp were all decreased after treatment with H2S. H2S administration also maintained MMP/TIMP balance. Mechanistically, H2S activated the PI3K/AKT signaling pathway. In addition, H2S treatment also reduced the expressions of ER stress-related proteins, autophagy-related proteins, and apoptins in in vitro experiments. Interestingly, activation of ER stress-autophagy axis could reverse the inhibitory effect of H2S on myocardial apoptosis. Altogether, these results suggested that exogenous H2S suppresses myocardial apoptosis by blocking ER stress-autophagy axis, which in turn reverses cardiac remodeling after myocardial infarction.
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http://dx.doi.org/10.1093/abbs/gmaa133DOI Listing
December 2020

Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression.

J Exp Clin Cancer Res 2020 Nov 17;39(1):246. Epub 2020 Nov 17.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu province, China.

Background: Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated.

Methods: RNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM).

Results: CircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model.

Conclusions: CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.
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http://dx.doi.org/10.1186/s13046-020-01758-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670601PMC
November 2020

Circular RNA TMEM87A promotes cell proliferation and metastasis of gastric cancer by elevating ULK1 via sponging miR-142-5p.

J Gastroenterol 2021 Feb 6;56(2):125-138. Epub 2020 Nov 6.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.

Background: Circular RNAs (circRNAs) act as vital regulators of gene expression in a variety of cancers. However, the role of circRNAs in gastric cancer (GC) remains largely unexplored. Herein, we identified that circTMEM87A sponges miR-142-5p to promote GC progression through up-regulating ULK1 expression.

Methods: The expression of circTMEM87A in GC was determined by RNA sequencing and quantitative real-time PCR (qRT-PCR). The effects of knockdown or exogenous expression of circTMEM87A on GC cell phenotypes were evaluated both in vitro and in vivo. The interacting miRNA of circTMEM87A was predicted by bioinformatics and confirmed by RNA pull-down, dual-luciferase reporter assay and fluorescence in situ hybridization (FISH). The mechanism by which circTMEM87A/miR-142-5p/ULK1 axis promotes GC was determined by western blot, GFP/mRFP-LC3 puncta analysis, transmission electron microscope (TEM).

Results: CircTMEM87A was dramatically elevated in GC tissues and cell lines, and high circTMEM87A expression was closely correlated with poor prognosis of GC patients. Knockdown of circTMEM87A suppressed cell growth, migration, invasion and induced apoptosis in vitro, as well as inhibited GC tumorigenicity and lung metastasis potential in vivo. Meanwhile, circTMEM87A overexpression had the opposite effects. Furthermore, we demonstrated that circTMEM87A could act as a sponge of miR-142-5p to regulate ULK1 expression and GC progression.

Conclusions: Our findings suggest that circTMEM87A functions as an oncogene through the miR-142-5p/ULK1 axis in GC. CircTMEM87A might be a prognostic biomarker as well as a promising therapeutic target for GC.
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http://dx.doi.org/10.1007/s00535-020-01744-1DOI Listing
February 2021

Development of a compact coaxial cusped periodic permanent magnet focusing system.

Rev Sci Instrum 2020 Oct;91(10):104703

Department of Engineering Physics, Tsinghua University, Beijing 100084, China.

To achieve the application of a periodic permanent magnet in high power microwave, a compact coaxial cusped periodic permanent magnet (CPPM) focusing system is constructed. The system consists of permanent magnets with different magnetization directions and soft magnets. Taking the required magnetic field performance and the effect of demagnetization into account, NdFeB and FeCoV are selected as the permanent and soft magnet materials. After the system is constructed, the magnetic field is measured. The results show that the guiding magnetic field strength and period of the CPPM are about 0.29 T and 26 mm, respectively, and the magnetic field distribution of measurement shows good agreement with the simulation results. However, there are some differences between the measurement and simulation results, and the differences are compared and analyzed here.
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http://dx.doi.org/10.1063/5.0025010DOI Listing
October 2020

Suppressive effects of RASAL2 on renal cell carcinoma via SOX2/ERK/p38 MAPK pathway.

Exp Ther Med 2020 Dec 6;20(6):151. Epub 2020 Oct 6.

Department of General Surgery, Shaanxi Friendship Hospital, Xi'an, Shaanxi 710068, P.R. China.

Metastatic renal cell carcinoma (RCC) is associated with poor prognosis. Ras protein activator like 2 (RASAL2) protein has been previously demonstrated to serves as a tumor suppressor in a variety of malignancies. Therefore, the aim of the present study was to investigate the role of RASAL2 in RCC. Reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry were performed to measure mRNA and protein expression in RCC tissues, whilst immunofluorescence and western blotting were performed to evaluate protein expression in RCC cells. A Cell Counting Kit-8 and 5-bromo-2'-deoxyuridine staining were applied to determine cell viability, and Transwell assays were conducted to measure RCC cell invasion and migration. RASAL2 expression was identified to be downregulated in RCC tissues, which associate negatively with RCC pathological grade. Sox2 expression, in addition to ERK1/2 and p38 MAPK phosphorylation, were demonstrated to be increased in RCC tissues. In RCC cells, RASAL2 overexpression decreased the expression of Sox2 and the activation of ERK1/2 and p38 MAPK. Physiologically, RASAL2 overexpression decreased RCC cell viability, invasion and migration. The expression of metalloproteinase-2/9 and tissue inhibitor of metalloproteinase 1 were also identified to be decreased and increased by RASAL2 overexpression, respectively. By contrast, RASAL2 knockdown exerted opposite effects on RCC cells compared with those observed following RASAL2 overexpression. RASAL2 expression decreased RCC cell viability, migration and invasion, which was demonstrated to be associated with the inactivation of SOX2/ERK1/2/p38 MAPK signaling. These results suggest that RASAL2 may potentially serve as a potential target for the development of novel therapeutic intervention strategies against RCC.
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http://dx.doi.org/10.3892/etm.2020.9280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571372PMC
December 2020

Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity.

Immunity 2020 Dec 20;53(6):1202-1214.e6. Epub 2020 Oct 20.

Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

The mechanisms by which regulatory T (Treg) cells differentially control allergic and autoimmune responses remain unclear. We show that Treg cells in food allergy (FA) had decreased expression of transforming growth factor beta 1 (TGF-β1) because of interleukin-4 (IL-4)- and signal transducer and activator of transciription-6 (STAT6)-dependent inhibition of Tgfb1 transcription. These changes were modeled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependent retinoic acid receptor-related orphan receptor gamma t (ROR-γt) Treg cell differentiation. This dysregulation was rescued by treatment with Clostridiales species, which upregulated Tgfb1 expression in Treg cells. Biallelic deficiency precipitated fatal autoimmunity with intense autoantibody production and dysregulated T follicular helper and B cell responses. These results identify a privileged role of Treg cell-derived TGF-β1 in regulating allergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose- and microbiota-dependent manner.
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http://dx.doi.org/10.1016/j.immuni.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744401PMC
December 2020

Xanthohumol and Gossypol Are Promising Inhibitors against by In Vitro Culture via High-Throughput Screening of 133 Natural Products.

Vaccines (Basel) 2020 10 16;8(4). Epub 2020 Oct 16.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

Human babesiosis caused by is an emerging threat for severe illness and even death, with an increasing impact worldwide. Currently, the regimen of atovaquone and azithromycin is considered as the standard therapy for treating human babesiosis, which, however, may result in drug resistance and relapse, suggesting the necessity of developing new drugs to control . In this regard, natural products are promising candidates for drug design against due to their active therapeutic efficacy, lower toxicity, and fewer adverse reactions to host. Here, the potential inhibitors against B. microti were preliminarily screened from 133 natural products, and 47 of them were selected for further screening. Gossypol (Gp) and xanthohumol (Xn) were finally shown to effectively inhibit the growth of with IC values of 8.47 μm and 21.40 μm, respectively. The cytotoxicity results showed that Gp and Xn were non-toxic to erythrocytes at a concentration below 100 μm. Furthermore, both of them were confirmed to be non-toxic to different types of cells in previous studies. Our findings suggest the potential of Gp and Xn as effective drugs against infection.
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http://dx.doi.org/10.3390/vaccines8040613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711813PMC
October 2020

A CMM-Based Method of Control Point Position Calibration for Light Pen Coordinate Measuring System.

Sensors (Basel) 2020 Sep 29;20(19). Epub 2020 Sep 29.

State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China.

A light pen coordinate measuring system (LPCMS) is a kind of vision-based portable coordinate measuring technique. It implements coordinate measurement by analyzing the image of a light pen, which has several control points and a probe. The relative positions of control points need to be determined before measurement and serve as the measuring basis in LPCMS. How to accurately calibrate the relative positions of control points is the most important issue in system calibration. In this paper, a new method of control point position calibration based on a traditional coordinate measuring machine (CMM) is proposed. A light pen is fastened to the measuring arm of a CMM and performs accurate translational movement driven by the CMM. A camera is used to capture the images of control points at different positions, and the corresponding readings of the CMM are recorded at the same time. By establishing a separate coordinate system for each control point, the relative positions of the control points can be transformed to the differences of a series of translation vectors. Experiments show that the calibration repeatability of control point positions can reach 10 μm and the standard deviation of measurement of the whole LPCMS can reach 30 μm. A CMM is used to generate accurate translation, which provides a high accuracy basis of calibration. Through certain mathematical treatment, tremendous data acquired by moving the light pen to tens of thousands of different positions can be processed in a simple way, which can reduce the influence of random error. Therefore, the proposed method provides a high-accuracy solution of control point position calibration for LPCMS.
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http://dx.doi.org/10.3390/s20195592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583052PMC
September 2020

Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition.

Mol Ecol Resour 2021 Feb 21;21(2):478-494. Epub 2020 Oct 21.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Whole-genome duplication (WGD), contributing to evolutionary diversity and environmental adaptability, has been observed across a wide variety of eukaryotic groups, but not in molluscs. Molluscs are the second largest animal phylum in terms of species numbers, and among the organisms that have successfully adapted to the nonmarine realm through aquatic-terrestrial (A-T) transition. We assembled a chromosome-level reference genome for Achatina immaculata, a globally invasive species, and compared the genomes of two giant African snails (A. immaculata and Achatina fulica) to other available mollusc genomes. Macrosynteny, colinearity blocks, Ks peak and Hox gene clusters collectively suggested a WGD event in the two snails. The estimated WGD timing (~70 million years ago) was close to the speciation age of the Sigmurethra-Orthurethra (within Stylommatophora) lineage and the Cretaceous-Tertiary (K-T) mass extinction, indicating that the WGD may have been a common event shared by all Sigmurethra-Orthurethra species and conferred ecological adaptability allowing survival after the K-T extinction event. Furthermore, the adaptive mechanism of WGD in terrestrial ecosystems was confirmed by the presence of gene families related to the respiration, aestivation and immune defence. Several mucus-related gene families expanded early in the Stylommatophora lineage, and the haemocyanin and phosphoenolpyruvate carboxykinase families doubled during WGD, and zinc metalloproteinase genes were highly tandemly duplicated after WGD. This evidence suggests that although WGD may not have been the direct driver of the A-T transition, it played an important part in the terrestrial adaptation of giant African snails.
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http://dx.doi.org/10.1111/1755-0998.13261DOI Listing
February 2021

Synthesis of Dimethyl Octyl Aminoethyl Ammonium Bromide and Preparation of Antibacterial ABS Composites for Fused Deposition Modeling.

Polymers (Basel) 2020 Sep 28;12(10). Epub 2020 Sep 28.

Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.

Additive manufacturing (AM) demonstrates benefits in the high-precision production of devices with complicated structures, and the modification of materials for AM is an urgent need. To solve the bacterial infection of medical devices in their daily application, dimethyl octyl aminoethyl ammonium bromide (octyl-QDED), an organic antibacterial agent, was synthesized via the quaternary ammonium reaction. Then, the synthesized octyl-QDED was blended with acrylonitrile butadiene styrene (ABS) through the melt extrusion process to prepare antibacterial composite filaments for fused deposition modeling (FDM). The entire preparation processes were convenient and controllable. Characterizations of the structure and thermal stability of octyl-QDED confirmed its successful synthesis and application in the subsequent processes. The introduced maleic acid in the blending process acted as a compatibilizer, which improved the compatibility between the two phases. Characterizations of the rheological and mechanical properties proved that the addition of octyl-QDED made a slight difference to the comprehensive performance of the ABS matrix. When the content of octyl-QDED reached 3 phr, the composites showed excellent antibacterial properties. The prepared antibacterial composite filaments for FDM demonstrated great potential in medical and surgical areas.
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http://dx.doi.org/10.3390/polym12102229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600671PMC
September 2020

Challenges of PD-L1 testing in non-small cell lung cancer and beyond.

J Thorac Dis 2020 Aug;12(8):4541-4548

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

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http://dx.doi.org/10.21037/jtd-2019-itm-010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475552PMC
August 2020

Apolygus lucorum genome provides insights into omnivorousness and mesophyll feeding.

Mol Ecol Resour 2021 Jan 2;21(1):287-300. Epub 2020 Oct 2.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.

Apolygus lucorum (Miridae) is an omnivorous pest that occurs worldwide and is notorious for the serious damage it causes to various crops and substantial economic losses. Although some studies have examined the biological characteristics of the mirid bug, no reference genome is available in Miridae, limiting in-depth studies of this pest. Here, we present a chromosome-scale reference genome of A. lucorum, the first sequenced Miridae species. The assembled genome size was 1.02 Gb with a contig N50 of 785 kb. With Hi-C scaffolding, 1,016 Mb contig sequences were clustered, ordered and assembled into 17 large scaffolds with scaffold N50 length 68 Mb, each corresponding to a natural chromosome. Numerous transposable elements occur in this genome and contribute to the large genome size. Expansions of genes associated with omnivorousness and mesophyll feeding such as those related to digestion, chemosensory perception, and detoxification were observed in A. lucorum, suggesting that gene expansion contributed to its strong environmental adaptability and severe harm to crops. We clarified that a salivary enzyme polygalacturonase is unique in mirid bugs and has significantly expanded in A. lucorum, which may contribute to leaf damage from this pest. The reference genome of A. lucorum not only facilitates biological studies of Hemiptera as well as an understanding of the damage mechanism of mesophyll feeding, but also provides a basis on which to develop efficient control technologies for mirid bugs.
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http://dx.doi.org/10.1111/1755-0998.13253DOI Listing
January 2021

Characterization of the variable merozoite surface antigen (VMSA) gene family of Babesia orientalis.

Parasitol Res 2020 Nov 15;119(11):3639-3648. Epub 2020 Sep 15.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Due to its wide presence in apicomplexan parasites as well as high polymorphism and antigenic diversity, the variable merozoite surface antigen (VMSA) family in Babesia sp. has attracted increasing attention of researchers. Here, all the reported VMSA genes of Babesia spp. were obtained from GenBank, and multiple alignments were performed by using conserved regions to blast the Babesia orientalis genome database (unpublished data). Five MSA genes (named MSA-2a1, MSA-2a2, MSA-2c1, MSA-1, and MSA-2c2, respectively) were identified, sequenced, and cloned from B. orientalis, which were shown to encode proteins with open reading frames ranging in size from 266 (MSA-2c1) to 317 (MSA-1) amino acids. All the five proteins contain an MSA-2c superfamily conserved domain, with an identical signal peptide and glycosyl phosphatidyl inositol (GPI)-anchor for each of them. The five proteins were also predicted to contain B cell epitopes, with only three for BoMSA-2c1, the smallest protein in the BoVMSA family, while at least six for each of the others. Notably, BoMSA-2a1 has 2 identical copies, a specific phenomenon only present in B. orientalis. This research has determined the MSA genes of B. orientalis and provides a genetic basis for further research of functional genes in B. orientalis.
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http://dx.doi.org/10.1007/s00436-020-06877-zDOI Listing
November 2020

Exogenous Hydrogen Sulfide Ameliorates Diabetic Myocardial Fibrosis by Inhibiting Cell Aging Through SIRT6/AMPK Autophagy.

Front Pharmacol 2020 31;11:1150. Epub 2020 Jul 31.

Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, China.

Stress aging of myocardial cells participates in the mechanism of myocardial fibrosis (MF). Previous studies have shown that hydrogen sulfide (HS) can improve MF, however the specific internal mechanism remains still unclear. Therefore, this study aims to explore whether HS can improve myocardial cell aging induced by high glucose and myocardial fibrosis in diabetic rats by activating autophagy through SIRT6/AMPK. We observed that HG (high glucose, 33 mM) induced down-regulation of endogenous HS-producing enzyme CSE protein expression, increased cell senescence, down-regulation of autophagy-related proteins Beclin1, Atg5, Atg12, Atg16L1, and inhibition of SIRT6/AMPK signaling pathway in H9c2 cardiomyocytes. HS (NaHS: 400 μM) could up-regulate CSE protein expression, inhibit cell senescence, activate autophagy and SIRT6/AMPK signaling pathway. On the contrary, no above phenomena was achieved upon addition of CSE inhibitor PAG (dl-propargylglycine: mmol/L). In order to further elucidate the relationship between HS and SIRT6/AMPK signaling pathway, dorsomorphin dihydrochloride (Dor), an inhibitor of AMPK signaling pathway, was added to observe the reversal of HS's inhibitory effect on myocardial cell aging. At the same, streptozotocin (STZ; 40 mg/kg) was injected intraperitoneally to build an animal model of diabetic SD rats. The results showed that myocardial collagen fibers were significantly deposited, myocardial tissue senescent cells were significantly increased and the expression of CSE protein was down-regulated, while SIRT6/AMPK signaling pathway and cell autophagy were significantly inhibited. HS-treated (NaHS; 56 μmol/kg) could significantly reverse the above phenomenon. In conclusion, these findings suggest that exogenous HS can inhibit myocardial cell senescence and improve diabetic myocardial fibrosis by activating CSE and autophagy through SIRT6/AMPK signaling pathway.
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http://dx.doi.org/10.3389/fphar.2020.01150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438924PMC
July 2020

PUFA-synthase-specific PPTase enhanced the polyunsaturated fatty acid biosynthesis via the polyketide synthase pathway in .

Biotechnol Biofuels 2020 31;13:152. Epub 2020 Aug 31.

CAS Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Energy Genetics, Shandong Engineering Laboratory of Single Cell Oil, Qingdao Engineering Laboratory of Single Cell Oil, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, No.189 Songling Road, Laoshan District, Qingdao, 266101 Shandong China.

Background: Phosphopantetheinyl transferase (PPTase) can change the acyl-carrier protein (ACP) from an inactive apo-ACP to an active holo-ACP that plays a key role in fatty acids biosynthesis. Currently, the PPTase has been proved to be involved in the biosynthesis of polyunsaturated fatty acids (PUFAs) via a polyketide synthase (PKS) pathway in Thraustochytrids, while its characteristics are not clarified.

Results: Here, the heterologous PPTase gene () from bacteria was first co-expressed with the PKS system (-) from Thraustochytrid . Then, a new endogenous PPTase () in was identified by homologous alignment and its function was verified in . Moreover, the endogenous was then overexpressed in , and results showed that the production and proportion of PUFAs, especially docosahexaenoic acid (DHA), in the transformant SD116::PPT_A were increased by 35.5% and 17.6%, respectively. Finally, higher DHA and PUFA proportion (53.9% and 64.5% of TFA, respectively) were obtained in SD116::PPT_A using a cerulenin feeding strategy.

Conclusions: This study has illustrated a PUFAs-synthase-specific PPTase in PKS system and provided a new strategy to improve the PUFA production in Thraustochytrids.
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http://dx.doi.org/10.1186/s13068-020-01793-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457351PMC
August 2020

Optimizing Eicosapentaenoic Acid Production by Grafting a Heterologous Polyketide Synthase Pathway in the Thraustochytrid .

J Agric Food Chem 2020 Oct 1;68(40):11253-11260. Epub 2020 Sep 1.

CAS Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Energy Genetics, Shandong Engineering Laboratory of Single Cell Oil, Qingdao Engineering Laboratory of Single Cell Oil, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, Shandong, China.

Eicosapentaenoic acid (EPA) is an essential nutritional supplement for human health. The most prominent dietary source of EPA is fish oil, which is unsustainable because of the decline in fishery resources and serious environmental pollution. Alternatively, a heterologous polyketide synthase pathway for EPA biosynthesis was assembled in Thraustochytrid . A 2A peptide-based facile assembly platform that can achieve multigene expression as a polycistron was first established. The platform was then applied to express the EPA biosynthetic gene cluster from in . In the shake flask fermentation, the lipid and PUFA yields of the mutant were increased by 26.9 and 36.0%, respectively, and led to about 5-fold increase of the EPA yield. The final EPA titer reached 2.7 g/L in fed-batch fermentation. This study provides a novel metabolic engineering strategy to regulate the EPA ratio in microalgal oil for human nutritional supplementation.
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http://dx.doi.org/10.1021/acs.jafc.0c04299DOI Listing
October 2020