Publications by authors named "Lina Lu"

184 Publications

Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2.

Cell Discov 2021 Jun 15;7(1):44. Epub 2021 Jun 15.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

The presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here, we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole-genome represents a large number of potential co-mutations. In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5'UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly attenuated the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.
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http://dx.doi.org/10.1038/s41421-021-00282-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203788PMC
June 2021

Docking-based generation of antibodies mimicking Cry1A/1B protein binding sites as potential insecticidal agents against diamondback moth (Plutella xylostella).

Pest Manag Sci 2021 Jun 6. Epub 2021 Jun 6.

Key Lab of Food Quality and Safety of Jiangsu Province-State Key Laboratory Breeding Base, Key Laboratory of Control Technology and Standard for Agro-product Safety and Quality, Ministry of Agriculture, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing, P. R. China.

Background: Broad use of insecticidal Cry proteins from Bacillus thuringiensis in biopesticides and transgenic crops has resulted in cases of practical field resistance, highlighting the need for novel approaches to insect control. Previously we described an anti-Cry1Ab idiotypic-antibody (B12-scFv) displaying toxicity against rice leafroller (Cnaphalocrocis medinalis) larvae, supporting the potential of antibodies for pest control. The goal of the present study was to generate insecticidal antibodies against diamondback moth (Plutella xylostella) larvae.

Results: Four genetically engineered antibodies (GEAbs) were designed in silico from B12-scFv using three-dimensional (3D) structure and docking predictions to alkaline phosphatase (ALP) as a Cry1Ac receptor in P. xylostella. Among these GEAbs, the GEAb-dV antibody consisting of two light chains had overlapping binding sites with Cry1A and Cry1B proteins and displayed high binding affinity to P. xylostella midgut brush border membrane (BBM) proteins. Proteins in BBM identified by pull-down assays as binding to GEAb-dV included an ABC transporter and V-ATPase subunit A protein. Despite lacking the α-helical structures in Cry1A that are responsible for pore formation, ingestion of GEAb-dV disrupted the P. xylostella larval midgut epithelium and resulted in toxicity. Apoptotic genes were activated in gut cells upon treatment with GEAb-dV .

Conclusion: This study describes the first insecticidal GEAb targeting P. xylostella by mimicking Cry proteins. Data support that GEAb-dV toxicity is associated to activation of intracellular cell death pathways, in contrast to pore-formation associated toxicity of Cry proteins. This work provides a foundation for the design of novel insecticidal antibodies for insect control.
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http://dx.doi.org/10.1002/ps.6499DOI Listing
June 2021

A deep learning system for detecting diabetic retinopathy across the disease spectrum.

Nat Commun 2021 05 28;12(1):3242. Epub 2021 May 28.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai, 200233, China.

Retinal screening contributes to early detection of diabetic retinopathy and timely treatment. To facilitate the screening process, we develop a deep learning system, named DeepDR, that can detect early-to-late stages of diabetic retinopathy. DeepDR is trained for real-time image quality assessment, lesion detection and grading using 466,247 fundus images from 121,342 patients with diabetes. Evaluation is performed on a local dataset with 200,136 fundus images from 52,004 patients and three external datasets with a total of 209,322 images. The area under the receiver operating characteristic curves for detecting microaneurysms, cotton-wool spots, hard exudates and hemorrhages are 0.901, 0.941, 0.954 and 0.967, respectively. The grading of diabetic retinopathy as mild, moderate, severe and proliferative achieves area under the curves of 0.943, 0.955, 0.960 and 0.972, respectively. In external validations, the area under the curves for grading range from 0.916 to 0.970, which further supports the system is efficient for diabetic retinopathy grading.
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http://dx.doi.org/10.1038/s41467-021-23458-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163820PMC
May 2021

Biosynthesis of Polydatin in .

J Agric Food Chem 2021 Jun 21;69(21):5917-5925. Epub 2021 May 21.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

Polydatin, with better structural stability and biological activities than resveratrol, is mainly extracted from the traditional Chinese medicinal plant . In this study, based on the transcriptome analysis of , we identified the key glycosyltransferase of resveratrol and achieved the biosynthesis of polydatin from glucose by incorporation with the resveratrol biosynthesis module, UDP-glucose supply module, and glycosyltransferase expression module. Through metabolic engineering and fermentation optimization, the production of polydatin reached 545 mg/L, and the dry cell weight was 27.83 mg/g DCW, which was about twice that of extracted from the root (11.404 mg/g DCW). Therefore, it is possible to replace the production mode of polydatin from plant extraction to microbial chassis in the future.
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http://dx.doi.org/10.1021/acs.jafc.1c01557DOI Listing
June 2021

Chromosome-level genome of Himalayan yew provides insights into the origin and evolution of the paclitaxel biosynthetic pathway.

Mol Plant 2021 Jul 2;14(7):1199-1209. Epub 2021 May 2.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin 300308, China.

Taxus, commonly known as yew, is a well-known gymnosperm with great ornamental and medicinal value. In this study, by assembling a chromosome-level genome of the Himalayan yew (Taxus wallichiana) with 10.9 Gb in 12 chromosomes, we revealed that tandem duplication acts as the driving force of gene family evolution in the yew genome, resulting in the main genes for paclitaxel biosynthesis, i.e. those encoding the taxadiene synthase, P450s, and transferases, being clustered on the same chromosome. The tandem duplication may also provide genetic resources for the nature to sculpt the core structure of taxoids at different positions and subsequently establish the complex pathway of paclitaxel by neofunctionalization. Furthermore, we confirmed that there are two genes in the cluster encoding isoenzymes of a known enzyme in the paclitaxel biosynthetic pathway. The reference genome of the Himalayan yew will serve as a platform for decoding the complete biosynthetic pathway of paclitaxel and understanding the chemodiversity of taxoids in gymnosperms.
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http://dx.doi.org/10.1016/j.molp.2021.04.015DOI Listing
July 2021

Optic disc morphology and peripapillary atrophic changes in diabetic children and adults without diabetic retinopathy or visual impairment.

Acta Ophthalmol 2021 May 5. Epub 2021 May 5.

Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, National Clinical Research Center for Eye Diseases, Shanghai Key laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To investigate the changes in optic disc morphology and peripapillary atrophy (PPA) in diabetic children and adults without diabetic retinopathy (DR) or visual impairment (VI).

Methods: This cross-sectional study included two groups of subjects. One group included 91 children with type 1 diabetes mellitus (T1DM) and 86 healthy children, and the other group included 444 adults with T2DM and 442 healthy controls. The optic disc parameters including major and minor axis lengths, optic disc ovality (ODO), optic disc tilt, optic disc area and β-PPA area were analysed in all subjects. Optic disc rotation and the Bergmeister papilla were analysed only in children. Patients with diabetes and healthy controls were compared in each group of the study population.

Results: In both groups, patients with diabetes and healthy controls were matched for age, sex and axial length (AL). Among the children, β-PPA area was significantly smaller in those with diabetes (0.29 ± 0.43 mm ) than in the healthy controls (0.46 ± 0.58 mm , p < 0.05). Multiple linear regression analysis showed that diagnosis of DM was negatively associated with β-PPA area. Longer AL and higher body mass index (BMI) were positively associated with β-PPA area. Among adults, ODO was significantly larger in those with diabetes (1.14 ± 0.09) than in healthy controls (1.12 ± 0.06, p < 0.05). Multiple linear regression analysis showed that the BMI and DM were potential risk factors affecting ODO.

Conclusion: Hyperglycaemia had different effects on the optic disc in children and adults. Unlike in healthy controls, hyperglycaemia had an impact on the peripapillary tissue in children and on optic disc shape in adults before DR and VI development.
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http://dx.doi.org/10.1111/aos.14885DOI Listing
May 2021

Andersen's utilization model for cataract surgical rate and empirical evidence from economically-developing areas.

BMC Ophthalmol 2021 Feb 26;21(1):107. Epub 2021 Feb 26.

Shanghai Eye Diseases Prevention & Treatment Center / Shanghai Eye Hospital, No. 380 Kang Ding Road, Shanghai, 200000, China.

Background: Un-operated cataract is the leading cause of vision loss worldwide, responsible for 33% of visual impairment, and half of global blindness. The study aimed to build a fast evaluation method utilizing Andersen's utilization framework and identify predictors of cataract surgical rate in sub-Saharan Africa and China.

Methods: The study was a cross-over ecological epidemiology study with a total of 19 countries in sub-Saharan Africa, and 31 provinces in China. Information was extracted from public data and published studies. Linear regression and structural equation modeling with Bootstrap were used to analyze predictors of CSR and their pathways to impact in sub-Saharan Africa and China separately.

Results: Cataract surgical resources in sub-Saharan Africa were linearly correlated with CSR (β = 0.74, 95% CI: 0.09, 0.91), while GDP/P didn't impact cataract surgical resources (β = 0.29, 95% CI: - 0.12, 0.75). In China, residents' average ability to pay was confirmed as the mediator between GDP/P and CSR (p = 0.32, RMSEA = 0.07; β = 0.77, 95% CI: 0.25, 0.90; β = 0.89, 95% CI: 0.82, 0.93).

Conclusions: In sub-Saharan Africa, CSR is determined by health care provision. Local economic development may not directly influence CSR. Therefore, international assistance aimed to providing free cataract surgery directly is crucial. In China, CSR is determined principally by health care demand (ability to pay). To increase CSR in underserved areas of China, ability to pay must be enhanced through social insurance, and reduced surgical fees.
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http://dx.doi.org/10.1186/s12886-021-01858-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908707PMC
February 2021

The origin and evolution of the diosgenin biosynthetic pathway in yam.

Plant Commun 2021 Jan 2;2(1):100079. Epub 2020 Jun 2.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

Diosgenin, mainly produced by species, is a traditional precursor of most hormonal drugs in the pharmaceutical industry. The mechanisms that underlie the origin and evolution of diosgenin biosynthesis in plants remain unclear. After sequencing the whole genome of , we revealed the evolutionary trajectory of the diosgenin biosynthetic pathway in and demonstrated the biosynthesis of diosgenin in a yeast cell factory. First, we found that P450 gene duplication and neo-functionalization, driven by positive selection, played important roles in the origin of the diosgenin biosynthetic pathway. Subsequently, we found that the enrichment of diosgenin in the yam lineage was regulated by CpG islands, which evolved to regulate gene expression in the diosgenin pathway and balance the carbon flux between the biosynthesis of diosgenin and starch. Finally, by integrating genes from plants, animals, and yeast, we heterologously synthesized diosgenin to 10 mg/l in genetically-engineered yeast. Our study not only reveals the origin and evolutionary mechanisms of the diosgenin biosynthetic pathway in , but also introduces an alternative approach for the production of diosgenin through synthetic biology.
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http://dx.doi.org/10.1016/j.xplc.2020.100079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816074PMC
January 2021

Congenital Short-Bowel Syndrome: Clinical and Genetic Presentation in China.

JPEN J Parenter Enteral Nutr 2020 Jul 28. Epub 2020 Jul 28.

Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Congenital short-bowel syndrome (CSBS) is a rare disorder characterized by retardation of intestinal development. However, it is still not well recognized at present. In this study, the etiological, clinical, and genetic characteristics of CSBS in China were analyzed.

Methods: Nine infants with CSBS were recruited. Full-thickness biopsy findings were evaluated by histopathology. Whole-exome sequencing was performed to identify mutations in patients and their family members. All patients were followed up at >1 year of age.

Results: Six of 9 infants had malrotation, and 2 patients had intestinal atresia. The average total small-bowel length was 51.7 (40-75) cm. Coxsackie and adenovirus receptor-like membrane protein (CLMP) mutations were found in 5 patients and were related to decreases in ileal goblet cells and mucous secretion. Among these 5 patients, 3 shared the same mutation (c. 206G>A p.R69H), 1 patient had an exon 3-5 deletion, and 1 patient had the C.655T>G, p.Cys219Gly, and C.389-2A>C. Another case carried a loss-of-function mutation in filamin A (FLNA). In the other 3 patients, no pathogenic mutations in genes related to intestinal development were found. The rate of catheter-related bloodstream infection was 4.3 per 1000 catheter days, and intestinal failure-associated liver disease (IFALD) was 77.8%. The median follow-up duration was 24.1 months. Eight patients were weaned off parenteral nutrition (PN). Six patients still exhibited malnutrition during follow-up.

Conclusions: Infants with CSBS often need long-term PN and remain at risk of SBS-related complications. CLMP and FLNA mutations are associated with CSBS in the Chinese population.
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http://dx.doi.org/10.1002/jpen.1974DOI Listing
July 2020

Long-term outcomes of various pediatric short bowel syndrome in China.

Pediatr Surg Int 2021 Apr 4;37(4):495-502. Epub 2021 Jan 4.

Department of Pediatric Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: The goal of this study was to analyze long-term outcome of various pediatric short bowel syndrome (SBS) at an intestinal rehabilitation center in China.

Methods: One hundred and fifty-seven children with SBS were enrolled in this study from October 1988 to July 2019. Their long-term follow-up outcome was analyzed according to the age of disease onset, parenteral nutrition (PN) duration, and anatomic types of short bowel, respectively. The clinical characteristics, which included demographics, the length of residual small bowel, PN duration, PN dependence, SBS-related complications such as IF-related liver disease (IFALD), catheter-related bloodstream infection (CRBI), and mortality were compared among the groups.

Results: The main etiology for SBS were intestinal atresia, NEC, and volvulus. Five of 157 patients did not wean off PN. The incidence of IFALD and CRBI was 24.2 and 22.3%, respectively. Sixteen cases died because of infection and liver failure and eight patients lost to follow-up. The survival rate of the 157 patients was 84.7%. PN duration was longer in the infants and children group (284 ± 457 d vs. 110 ± 64 d, P = 0.021; R = 0.264, P = 0.001) and more patients did not wean off PN than in the neonates group (11.6% vs. 0, P = 0.001; R = 0.295, P < 0.001). Patients with PN with a duration of longer than 90 days had more CRBIs (30.6%, P = 0.025; R = 0.236, P = 0.003). Additionally, the rate of CRBI was higher in patients with stoma (30.0%, P = 0.032). There was no difference in mortality among the groups. In five PN dependence patients, none was SBS onset in neonates.

Conclusion: Pediatric patients with SBS could achieve favorable long-term survival and enteral autonomy. Different standards of SBS classification such as the age of disease onset, PN duration, and anatomic types of short bowel did not impact the overall mortality of pediatric SBS. Prolonged PN duration positively correlated with the age of disease onset and the incidence of CRBI. Patients with the complete continuity of intestinal tract suffered less from CRBI.
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http://dx.doi.org/10.1007/s00383-020-04797-8DOI Listing
April 2021

Quantitative Proteomics and Weighted Correlation Network Analysis of Tear Samples in Adults and Children With Diabetes and Dry Eye.

Transl Vis Sci Technol 2020 12 4;9(13). Epub 2020 Dec 4.

Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, China.

Purpose: Diabetics are more prone to suffer from dry eye (DE). The ages of diabetes are decreasing, so ocular surface status in younger generations is worthy of attention. We used tandem mass tag (TMT)-labeled proteomics and weighted correlation network analysis (WGCNA) to identify differentially expressed proteins in the tear proteome of adults and children with diabetic DE.

Methods: Study subjects were divided into six groups of 10, including three groups each for adults and children. The adult groups included diabetics with DE (A), diabetics without DE (B), and normal controls (C); the corresponding groups of children were identified as (D), (E), and (F). DE tests were performed on all subjects. We extracted total proteins and labeled them with TMTs for analysis. WGCNA was used to recognize hub genes.

Results: Tear film function was poorer in patients with diabetic DE. In adults, 1922 proteins were identified, and WGCNA analysis revealed three hub genes related to diabetic DE. For children, 2709 proteins were identified, and WGCNA analysis identified one hub gene related to diabetic DE. Kyoto Encyclopedia of Genes and Genomes analysis found similarities among metabolic pathways involved in differential expression of proteins in adult and child tear samples.

Conclusions: The pathogenesis of diabetic DE was highly similar in adults and children. The differentially expressed tear proteins in type 2 diabetes of adults and children was associated with inflammation, immune factors, and lipid metabolism.

Translational Relevance: Our findings found high similarities in the pathogenesis of diabetic DE in adults and children.
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http://dx.doi.org/10.1167/tvst.9.13.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718812PMC
December 2020

The associations of lens power with age, axial length and type 2 diabetes mellitus in Chinese adults aged 50 and above.

Eye Vis (Lond) 2020 Dec 1;7(1):57. Epub 2020 Dec 1.

Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai Eye Hospital, No.380 Kangding Road, Shanghai, 200040, China.

Background: To investigate the associations of lens power with age, axial length (AL), and Type 2 diabetes mellitus (DM) in Chinese adults aged 50 and above.

Methods: Random clustering sampling was used to identify adults aged 50 years and above in urban regions of Shanghai. The participants underwent a comprehensive ophthalmic examination including subjective refraction, autorefraction, and IOL-Master. The crystalline lens power was calculated using Bennett's formula.

Results: A total of 4177 adults were included. A linear decrease in lens power was observed both with age and with AL, followed by a stop of lens power loss after the age of 70 or when AL ≥ 25 mm, respectively. Participants with Type 2 DM presented higher lens power (0.43 diopter (D), p < 0.001) and thicker lens thickness (0.06 mm, p < 0.001). In multivariate regression models, there was a positive correlation between lens power and Type 2 DM when age < 75 years (p < 0.001) or AL < 25 mm (p < 0.001) after adjusting for other factors, while no significant association was found in participants aged ≥ 75 years (p = 0.122) or with AL ≥ 25 mm (p = 0.172).

Conclusions: The lens power in adults aged 50 and above exhibited two stages with age and with AL. Type 2 DM caused an increase in lens power, which was not seen in participants aged ≥ 75 years or with AL ≥ 25 mm.
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http://dx.doi.org/10.1186/s40662-020-00222-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706194PMC
December 2020

Upregulation of Sec22b plays a neuroprotective role in a rat model of traumatic brain injury via inducing protective autophagy.

Brain Res Bull 2021 Jan 10;166:29-36. Epub 2020 Nov 10.

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.

Cortical neuronal cell death following traumatic brain injury (TBI) evoked by the cortical impact is a significant factor that contributes to neurological deficits. In the current study, we harvested the injured area and perilesional area of the injured brain induced by TBI. We explored the functions of Sec22b, an apoptosis-promoting kinase, and a pivotal bridge builder of apoptotic signaling in the etiopathogenesis of an experimental rat model of TBI. We found that Sec22b was expressed in neurons in the injured cortical area, and the expression level significantly decreased after TBI, especially at 24 h. Administration of Sec22b overexpressed plasmid significantly ameliorated TBI-induced apoptosis, neurological deficits, and blood-brain barrier permeability, accompanied by the activation of autophagy. However, the administration of Sec22b knockdown resulted in the opposite eff ;ects. Altogether, these findings indicated that Sec22b plays a neuroprotective role after TBI, suggesting that Sec22b may be a potential therapeutic target for TBI. We speculated that this neuroprotective effect might be achieved by upregulating autophagy levels and required further studies to explore.
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http://dx.doi.org/10.1016/j.brainresbull.2020.11.004DOI Listing
January 2021

Synthesis of Ligustrazine from Acetaldehyde by a Combined Biological-Chemical Approach.

ACS Synth Biol 2020 11 6;9(11):2902-2908. Epub 2020 Nov 6.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.

Ligustrazine is an important active alkaloid in medicine and in the food industry. Here, we developed a combined biological-chemical approach to produce ligustrazine from acetaldehyde. First, we constructed a whole-cell biocatalytic system to produce the precursor acetoin from acetaldehyde by overexpressing formolase (FLS). Second, a two-step strategy was developed to enhance protein expression of FLS by codon usage optimization at the first 14 codons and the introduction of an overlapping gene before the start codon. Through expression optimization and directed evolution of FLS, we improved the titer of acetoin about 40 fold when the concentration of acetaldehyde was 1.5 M. Finally, after reaction conditions optimization, the titer of acetoin and ligustrazine reached 222 g L and 94 g L, with a 86.5% and 48% conversion rate from acetaldehyde, respectively. The developed one-pot synthesis for acetoin and ligustrazine is expected to be applied to industrial production in the future with the advantages of a green process, high efficiency, and low cost.
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http://dx.doi.org/10.1021/acssynbio.0c00113DOI Listing
November 2020

Micronutrient deficiencies in pediatric short bowel syndrome: a 10-year review from an intestinal rehabilitation center in China.

Pediatr Surg Int 2020 Dec 24;36(12):1481-1487. Epub 2020 Oct 24.

Division of Pediatric Gastroenterology and Nutrition; School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, No.1665, KongJiang Road, Shanghai, 200082, China.

Purpose: Vitamins and trace elements are essential nutrients for growth and intestinal adaptation in children with short bowel syndrome (SBS). This study aimed to assess micronutrients' status during and after weaning off PN in pediatric SBS.

Methods: This retrospective study evaluated the follow-up of 31 children with SBS between Jan 2010 and Sep 2019. Clinical data were reviewed from the patients' electric medical record. Serum electrolytes, trace elements, vitamin B12, vitamin D, and folate concentrations were collected before and after enteral autonomy.

Results: Thirty-one SBS cases were reviewed (median onset age 11 days after birth, 51.6% boys, mean PN duration 4 months, and mean residual small intestine length 58.2 cm). Median duration of follow-up was 10 months (interquartile range [IQR]: 4, 19). The common micronutrient deficiencies were zinc (51.6%), copper (38.7%), vitamin D (32.3%), and phosphorus (25.8%) after the transition to EN. The proportion of patients deficient in vitamin D decreased dramatically from 93.5% to 32.3% (P < 0.001), and serum concentrations of vitamin D increased significantly (27.4 ± 12.3 vs. 60.3 ± 32.9 nmol/l, P = 0.03) after achieving full enteral feeding more than 1 month. Additionally, serum magnesium levels significantly increased (0.76 ± 0.17 vs. 0.88 ± 0.14 mmol/l, P = 0.03). Hemoglobin levels elevated significantly after weaning off PN (104.3 ± 10.7 vs. 117.8 ± 13.7 g/l, P = 0.03).

Conclusions: Micronutrient deficiencies remain a common problem in pediatric SBS through intestinal rehabilitation. Therefore, we strongly recommend supplementation of more vitamin D and trace elements (zinc, copper, and phosphorus) under regular monitoring during long-term intestinal rehabilitation.
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http://dx.doi.org/10.1007/s00383-020-04764-3DOI Listing
December 2020

Effects of phycocyanin on pulmonary and gut microbiota in a radiation-induced pulmonary fibrosis model.

Biomed Pharmacother 2020 Dec 14;132:110826. Epub 2020 Oct 14.

Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, PR China. Electronic address:

Objective: Radiation pneumonia and fibrosis are major clinical complications of radiotherapy for thoracic tumor patients, and may significantly reduce survival and quality of life. At present, no safe and effective radiation protection measures have been approved for clinical use. Phycocyanin, a protein responsible for photosynthesis from Spirulina, has been shown to have a variety of biological activities and to be beneficial for a variety of diseases, including pulmonary fibrosis. However, the preventive and protective effects of phycocyanin on radiation-induced pulmonary fibrosis have not been studied.

Design: X-ray single dose irradiation was used on the chest of mice to prepare a mouse model of pulmonary fibrosis, from which the effect of phycocyanin on pulmonary histopathologic change, pulmonary fibrosis, the microbiota in lung and gut, LPS, TNF-α, and IL-6 at different time after irradiation were evaluated.

Results: Phycocyanin alleviated the radiation-induced lung injury and reduced the level of inflammatory factors. Thorax irradiation led to the disorder in microbiota of the lung and gut. The variation trend of the diversity of the two tissues was opposite, but that of the microbiota composition was similar. The phycocyanin intervention regulated the composition of the lung and gut microbiota, transformed them into normal state, and reduced the level of LPS, which significantly reduced the abundance of inflammation-related bacteria, and increased the abundance of probiotics that produce short-chain fatty acids.

Conclusion: Phycocyanin could regulate the radiation-induced disorder in lung and gut microbiota of mice, and reduce the radiation-induced lung inflammation and fibrosis.
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http://dx.doi.org/10.1016/j.biopha.2020.110826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556228PMC
December 2020

Origin and Evolution of Fusidane-Type Antibiotics Biosynthetic Pathway through Multiple Horizontal Gene Transfers.

Genome Biol Evol 2020 10;12(10):1830-1840

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

Fusidane-type antibiotics represented by fusidic acid, helvolic acid, and cephalosporin P1 have very similar core structures, but they are produced by fungi belonging to different taxonomic groups. The origin and evolution of fusidane-type antibiotics biosynthetic gene clusters (BGCs) in different antibiotics producing strains remained an enigma. In this study, we investigated the distribution and evolution of the fusidane BGCs in 1,284 fungal genomes. We identified 12 helvolic acid BGCs, 4 fusidic acid BGCs, and 1 cephalosporin P1 BGC in Pezizomycotina fungi. Phylogenetic analyses indicated six horizontal gene transfer (HGT) events in the evolutionary trajectory of the BGCs, including 1) three transfers across Eurotiomycetes and Sordariomycetes classes; 2) one transfer between genera under Sordariomycetes class; and 3) two transfers within Aspergillus genus under Eurotiomycetes classes. Finally, we proposed that the ancestor of fusidane BGCs would be originated from the Zoopagomycota by ancient HGT events according to the phylogenetic trees of key enzymes in fusidane BGCs (OSC and P450 genes). Our results extensively clarify the evolutionary trajectory of fusidane BGCs by HGT among distantly related fungi and provide new insights into the evolutionary mechanisms of metabolic pathways in fungi.
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http://dx.doi.org/10.1093/gbe/evaa163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750971PMC
October 2020

Diagnostic Performance of LI-RADS Version 2018, LI-RADS Version 2017, and OPTN Criteria for Hepatocellular Carcinoma.

AJR Am J Roentgenol 2020 11 2;215(5):1085-1092. Epub 2020 Sep 2.

Department of Radiology, Weill Cornell Medical Center, 525 E 68th St, New York, NY 10065.

Liver Imaging Reporting and Data System (LI-RADS) was updated in 2018 (LI-RADS version 2018 [LI-RADSv2018]) to facilitate integration into the American Association for the Study of Liver Diseases 2018 clinical practice guidelines and involved changes in LR-5 categorization and threshold growth definitions. There are also differences between the criteria for LI-RADSv2018 LR-5 category and the criteria for Organ Procurement and Transplantation Network (OPTN) class 5. The objective of our study was to compare the diagnostic performances of LI-RADSv2018, LI-RADS version 2017 (LI-RADSv2017), and OPTN criteria for diagnosing hepatocellular carcinoma (HCC) on MRI. In this retrospective study, 122 patients with 159 observations were included who met LI-RADS criteria for at risk for HCC and had at least one hepatic observation on MRI performed between January 1, 2015, and January 1, 2018 and who had histopathology results ( = 104) or follow-up imaging ( = 55) as reference standards. Three abdominal radiologists assigned categories independently and in consensus using LI-RADSv2017, LI-RADSv2018, and OPTN criteria. Diagnostic performance was compared among the guidelines with a generalized estimating equation. Fourteen of 159 (8.8%) observations were assigned a different category according to LI-RADSv2018 compared with LI-RADSv2017. Eight of 31 (25.8%) LR-4 observations using v2017 were recategorized as LR-5 using v2018, and all eight were HCC. Six of 31 (19.4%) LR-4 observations based on v2017 were recategorized as LR-3 using v2018, and all six were non-HCCs. Seven of 114 (6.1%) observations not meeting OPTN class 5 criteria were LR-5 using v2018, and all seven were HCC. Sensitivity for HCC of LR-5 and LR-TIV+5 (i.e., LR-TIV [tumor in vein] definitely due to HCC) categories based on v2018 was significantly higher than that based on v2017 (63.9% vs 55.2%, respectively; = 0.008) without a difference in specificity (97.3% vs 97.3%; = 1.00). Sensitivity of LR-5 and LR-TIV+5 in LI-RADSv2018 was significantly higher than the sensitivity of class 5 in OPTN criteria (63.9% vs 53.6%; = 0.004) without a difference in specificity (97.3% vs 97.3%; = 1.00). Reader agreement was moderate for overall LIRADSv2017 and LI-RADSv2018 categories (κ = 0.504 and 0.561, respectively); substantial for LR-5 and LR-TIV+5 categories as diagnostic of HCC versus other categories for both v2017 and v2018 (κ = 0.758 and 0.802, respectively); and substantial for OPTN class 5 criteria (κ = 0.756). The diagnostic performance of LI-RADSv2018 is higher, with higher sensitivity and similar specificity, than the diagnostic performance of LI-RADSv2017 and OPTN criteria for HCC.
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http://dx.doi.org/10.2214/AJR.20.22772DOI Listing
November 2020

Synergistic selection of a Helicoverpa armigera cadherin fragment with Cry1Ac in different cells and insects.

Int J Biol Macromol 2020 Dec 24;164:3667-3675. Epub 2020 Aug 24.

Key Lab of Food Quality and Safety of Jiangsu Province-State Key Laboratory Breeding Base, Key Laboratory of Control Technology and Standard for Agro-product Safety and Quality, Ministry of Agriculture, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China. Electronic address:

The midgut cadherin fragments were extensively studied as Bt synergists in insects, while their synergistic selection modes with Bt toxins in different mechanisms of resistance or insects have never been determined. Here, a soluble Helicoverpa armigera cadherin fragment which corresponds to the Cry1Ac binding region (HaCad-TBR) was expressed in Escherichia coli and its synergism with Cry1Ac toxin in H. armigera and Plutella xylostella larvae as well as Sf9 cells expressing different cadherins was tested. HaCad-TBR exhibited higher synergism factor in P. xylostella larvae (4.84-fold) than in H. armigera larvae (2.45-fold). Among the cells expressing HaCad alleles, HaCad-TBR enhanced the Cry1Ac toxicity only in the cells expressing the mutant lacking the extracellular domain. Moreover, HaCad-TBR had a weak enhancement of Cry1Ac toxicity in Sf9 cells expressing the P. xylostella cadherin. Further researches revealed that the enhancement of toxicity in Sf9 cells was correlated with increased toxin binding. These results suggested that cadherin fragments which have high binding level with Cry1Ac are more likely to enhance toxin toxicity well against the cells or larvae where the cadherin has lower binding level with Cry1Ac, especially in the cases lacking the toxin binding domain.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.175DOI Listing
December 2020

Multifunctional Nanoparticles in Precise Cancer Treatment: Considerations in Design and Functionalization of Nanocarriers.

Curr Top Med Chem 2020 ;20(27):2427-2441

School of Nuclear Science and Technology, Lanzhou University, Lanzhou, Gansu, China

Nanotechnology has revolutionized cancer treatment in both diagnosis and therapy. Since the initial application of nanoparticles (NPs) in cancer treatment, the main objective of nanotechnology was developing effective nanosystems with high selectivity and specificity for cancer treatment and diagnosis. To achieve this, different encapsulation and conjugation strategies along with surface functionalization techniques have been developed to synthesize anticancer drugs loaded NPs with effective targeting to specific tumor cells. The unique physicochemical attributes of NPs make them promising candidates for targeted drug delivery, localized therapies, sensing, and targeting at cellular levels. However, a nanosystem for localized and targeted cancer managements should overcome several biological barriers and biomedical challenges such as endothelial barriers, blood brain barrier, reticuloendothelial system, selective targeting, biocompatibility, acute/chronic toxicity, tumor-targeting efficacy. The NPs for in vivo applications encounter barriers at system, organ, and the cellular level. To overcome these barriers, different strategies during the synthesis and functionalization of NPs should be adapted. Pharmacokinetics and cellular uptake of NPs are largely associated with physicochemical attributes of NPs, morphology, hydrodynamic size, charge, and other surface properties. These properties can be adjusted during different phases of synthesis and functionalization of the NPs. This study reviews the advances in targeted cancer treatment and the parameters influencing the efficacies of NPs as therapeutics. Different strategies for overcoming the biological barriers at cellular, organ and system levels and biomedical challenges are discussed. Moreover, the applications of NPs in preclinical and clinical practice are reviewed.
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http://dx.doi.org/10.2174/1568026620666200825170030DOI Listing
July 2021

Variants in the Enteric Smooth Muscle Actin γ-2 Cause Pediatric Intestinal Pseudo-obstruction in Chinese Patients.

J Pediatr Gastroenterol Nutr 2021 01;72(1):36-42

Division of Pediatric Gastroenterology and Nutrition.

Objectives: Pediatric intestinal pseudo-obstruction (PIPO) is a severe gastrointestinal disorder occurring in children, leading to failure to thrive, malnutrition, and long-term parenteral nutrition dependence. Enteric smooth muscle actin γ-2 (ACTG2) variants have been reported to be related to the pathogenesis of PIPO. This study aimed to determine the presence of ACTG2 variants in Chinese PIPO patients.

Methods: Whole-exome sequencing was performed using samples from 39 recruited patients, whereas whole ACTG2 Sanger sequencing was performed using samples from 2 patients. Published data was reviewed to determine the number of pathogenic variants and the genotype related to ACTG2 variants in the Chinese population.

Results: A total of 21 Chinese probands were found to carry heterozygous missense variants of ACTG2, among which 20 were de novo. Fifteen probands had p.Arg257 variants (c.770G>A and c.769C>T), and the other 2 probands had c.533G>A (p.Arg178His) and c.443G>T (p.Arg148Leu) variants. Four probands had novel variants c.337C>T (p.Pro113Ser), c.588G>C (p.Glu196Asp), c.734A>G (p.Asp245Gly), and c.553G>T (p.Asp185Tyr).

Conclusions: Variants affecting codon 257 of ACTG2 protein sequence appeared to be frequent in both Chinese and Caucasian PIPO patients, whereas p.Arg178 variants were less common in Chinese patients compared with Caucasian patients. The 4 novel variants in ACTG2 were also found to be related to Chinese PIPO.
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http://dx.doi.org/10.1097/MPG.0000000000002897DOI Listing
January 2021

Alterations of gut microbiota and serum bile acids are associated with parenteral nutrition-associated liver disease.

J Pediatr Surg 2021 Apr 27;56(4):738-744. Epub 2020 Jun 27.

Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address:

Background: Parenteral nutrition-associated liver disease (PNALD) is a major complication of long-term parenteral nutrition (PN). The pathogenesis of PNALD remains unclear. We investigated the changes in taxonomic and functional composition of gut microbiota and serum bile acid levels in a rat model of PNALD.

Methods: Male 4-week-old Sprague Dawley rats received either total parenteral nutrition or standard chow with 0.9% saline for 7 days. The taxonomic composition of cecal microbiota and its functional composition associated with bile acid metabolism were measured.

Results: There were differences in taxonomic composition between the two groups. The abundance of the secondary bile acid biosynthesis pathway was higher in the TPN group (p < 0.05) with an increase in the percentage of bacteria expressing 7-alpha-hydroxysteroid dehydrogenase (p < 0.05). The abundance of enzymes associated with bile salt hydrolase was also higher (p < 0.05) in the TPN group. The TPN group showed a distinct bile acid profile characterized by a higher ratio of secondary bile acids to primary bile acids.

Conclusions: The alteration of bile acid-associated microbiota may lead to increased secondary bile acid production in a rat model of PNALD.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.06.035DOI Listing
April 2021

MicroRNA‑16‑5p regulates cell survival, cell cycle and apoptosis by targeting AKT3 in prostate cancer cells.

Oncol Rep 2020 Sep 9;44(3):1282-1292. Epub 2020 Jul 9.

Gansu Provincial Academic Institute for Medical Research, Lanzhou, Gansu 730050, P.R. China.

Prostate cancer (PCa) is a malignancy with the highest morbidity rate in 105 countries worldwide and was a major cause of cancer‑associated death in men in 2018. Accumulating evidence suggests that microRNAs (miRNAs/miRs) have important functions in the carcinogenesis of PCa, and may provide novel treatment targets. Previous studies have indicated that miR‑16‑5p is associated with PCa. However, the relevance and importance of miR‑16‑5p in PCa carcinogenesis are still not completely understood. In the current study, we aimed to investigate the role and mechanism of miR‑16‑5p in PCa carcinogenesis. The results showed that miR‑16‑5p was markedly downregulated in PCa cells, and MTS assay, colony formation, flow cytometric analyses demonstrated that miR‑16‑5p inhibited PCa cell survival, regulated cell cycle distribution and induced apoptosis. Moreover, luciferase reporter assay and western blot analysis showed that miR‑16‑5p directly targets AKT3 (AKT serine/threonine kinase 3), which is associated with PCa carcinogenesis, and the effects of the downregulation of AKT3 were similar to the effects of upregulation of miR‑16‑5p in PC‑3 cells. In conclusion, our data clarify that miR‑16‑5p has anticancer functions in PCa cells, and our findings provide experimental evidence to highlight the potential value of miR‑targeting treatment strategies for PCa.
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http://dx.doi.org/10.3892/or.2020.7682DOI Listing
September 2020

Genome-wide analysis of DNA methylation identifies S100A13 as an epigenetic biomarker in individuals with chronic (≥ 30 years) type 2 diabetes without diabetic retinopathy.

Clin Epigenetics 2020 06 3;12(1):77. Epub 2020 Jun 3.

Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.

Background: This study aimed to determine the epigenetic biomarkers of diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). This retrospective study is based on the Shanghai Xinjing community prevention and treatment administrative system of chronic diseases. The subjects enrolled herein were T2DM patients who had undergone long-term follow-up evaluation in the system. Two consecutive studies were conducted. In the discovery cohort, among 19 subjects who had developed DR with a DM duration < 3 years and 21 subjects without DR > 30 years after being diagnosed with DM, an Infinium Human Methylation 850 Beadchip was used to identify differential methylation regions (DMRs) and differential methylation sites (DMSs). The function of the genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis, and pathway network analysis. In the replication cohort, 87 DR patients with a short DM duration and 89 patients without DR over a DM duration > 20 years were compared to assess the association between DMSs and DR upon pyrosequencing.

Results: A total of 34 DMRs were identified. Genes containing DMSs with the top 5 highest beta value differences between DR and non-DR participants were located on chromosome 1 and were present in the S100A13 gene, which was associated with 71 GO terms. Two S100A13 gene sites, i.e., cg02873163 and cg11343894, displayed a good correlation with DR on pyrosequencing.

Conclusions: DMSs in the S100A13 gene may be potential biomarkers of DR.
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http://dx.doi.org/10.1186/s13148-020-00871-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268721PMC
June 2020

Odorranalectin modified PEG-PLGA/PEG-PBLG curcumin-loaded nanoparticle for intranasal administration.

Drug Dev Ind Pharm 2020 Jun 7;46(6):899-909. Epub 2020 May 7.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.

Curcumin (Cur) is a promising drug for neurological diseases. Nevertheless, the application of Cur has been limited due to its difficulty in penetrating blood-brain barrier (BBB). Intranasal drug delivery, a noninvasive alternative delivery of Cur, can effectively help Cur cross BBB and inert into central nervous system directly. Odorranalectin (OL) which is the smallest lectin can prolong the residence time of Cur in the nasal mucosa and promote cellular uptake. In this work, a nasal delivery system incorporating OL modified Cur-loaded nanoparticles (Cur-OL-NPs) was developed and expected to bypass BBB and promote the absorption of Cur. We conjugated OL to polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA), and combined polyethylene glycol-poly (γ-benzyl-L-glutamate) (PEG-PBLG) and OL-PEG-PLGA to prepare nanoparticles to improve the stability, bioavailability and targeting of Cur. Compared with unmodified NPs, increased efficiency of Cur-OL-NPs cellular uptake by Calu-3 cells had been obtained with no severe toxicity. Furthermore, pharmacokinetic studies also showed that Cur-OL-NPs had higher relative bioavailability. Thus, it is concluded that the results indicated that OL-NPs as carriers of Cur had a promising future in nasal drug delivery system.
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http://dx.doi.org/10.1080/03639045.2020.1762202DOI Listing
June 2020

Patients' perspectives on the barriers to referral after telescreening for diabetic retinopathy in communities.

BMJ Open Diabetes Res Care 2020 03;8(1)

Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center/Shanghai Eye Hospital, Shanghai, China

Objective: To understand the referral completion and explore the associated barriers to the referral after telescreening for diabetic retinopathy (DR) among people with vision-threatening DR (VTDR).

Research Design And Methods: All participants with VTDR after DR telescreening in the communities completed the self-reported questionnaires to assess referral completion and their perspectives on referral barriers. Sociodemographic characteristics and perceived barriers related to incomplete referrals were identified by conducting univariate analysis and multiple logistic regression model. The final model was then built to predict incomplete referral.

Results: Of the 3362 participants, 46.1% had incomplete referral. Old age and lower education level showed significant association with incomplete referral. Almost all participants had at least one barrier during the referral process. Knowledge-related and attitude-related barriers, including 'Too old to want any more treatment', 'Difficulty in getting time to referral', 'No serious illness requiring treatment at present', 'My eyes are okay', 'Distrust the recommended hospital' and 'Have not been diagnosed or treated before', and logistics-related barrier 'Mobility or transportation difficulties' showed significant association with incomplete referral.

Conclusions: The issue of incomplete referral after DR telescreening is serious among individuals with VTDR, particularly in the elder and low education level population. The negativity of knowledge-related and attitude-related factors might be more prominent than logistic barriers in predicting incomplete referral. Therefore, new strategies to improve the compliance with referral assist in optimizing the referral accessibility, and the ongoing educational support to improve the awareness of disease and increase the effectiveness of physician-patient communication.
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http://dx.doi.org/10.1136/bmjdrc-2019-000970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103829PMC
March 2020

Risk factors of parenteral nutrition-associated cholestasis in very-low-birthweight infants.

J Paediatr Child Health 2020 Nov 26;56(11):1785-1790. Epub 2020 Feb 26.

Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Aim: We aimed to explore risk factors associated with parenteral nutrition-associated cholestasis (PNAC) in very-low-birthweight (VLBW) infants.

Methods: VLBW infants receiving parenteral nutrition (PN) for at least 14 days were enrolled in a retrospective dual-centre study and divided into two groups chronologically: group A (2000-2007) and group B (2008-2015). The incidence of PNAC and related factors were investigated. We compared the differences between PNAC and non-PNAC groups. A multivariate binary logistic regression analysis was carried out to identify the potential risk factors of PNAC.

Results: A total of 387 VLBW infants (53 in group A and 334 in group B) were enrolled in the study. The total incidence of PNAC was 6.7%, 9.4% in group A and 6.3% in group B. The dosage of amino acid (P = 0.009), glucose (P = 0.006), PN calories (P = 0.021) and the ratio of glucose/fat (P = 0.014) were significantly higher in group B than in group A. Non-protein energy to nitrogen ratio (P = 0.017) was lower in group B. Birthweight was significantly lower in the PNAC group than in the non-PNAC group (P = 0.021). Subgroup analysis showed that gestational age and duration of PN were significantly different between the PNAC and non-PNAC groups (P < 0.05). Logistic regression showed that prolonged duration of PN (≥43 days) (odds ratio 3.155, 95% confidence interval 1.009-9.861, P = 0.048) was an independent risk factor of PNAC.

Conclusions: For VLBW infants, prolonged duration of PN is a risk factor for the development of PNAC. PNAC may be prevented by weaning off PN as early as possible in VLBW infants.
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http://dx.doi.org/10.1111/jpc.14826DOI Listing
November 2020

The role of ascorbic acid in rice leaf senescence and photo-carbon imbalance.

Funct Plant Biol 2020 02;47(3):263-278

Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, College of Life Sciences, South China Normal University, 510631, Guangzhou, China; and Corresponding author. Email:

Leaf senescence is an important factor that affects crop yield traits and is regulated by various factors. Here, we propose the photo-carbon imbalance hypothesis to explain the mechanism of rice leaf senescence. The main idea of this hypothesis is that carbon assimilation decreases faster than the absorption of light energy in photosynthesis during the late stages of rice growth, which ultimately results in leaf senescence. Our results indicate that endogenous ascorbic acid (Asc) plays an important role in leaf senescence by affecting the expression of senescence genes, thereby influencing photosynthetic capacity and consequently grain yield. The effects of exogenous Asc and methyl jasmonate (MeJA) on photosynthetic capability implied that the balance between photoreaction and carbon assimilation is regulated by exogenous antioxidants or accelerators of senescence. The results of the shading treatments indicated that shading will mitigate the photo-carbon imbalance and improve photosynthetic capacity, resulting in increased yields. Increasing antioxidant concentrations can enhance the reactive oxygen species (ROS) scavenging capacity, whereas shading reduces excess light energy, which may help to restore the photo-carbon balance.
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http://dx.doi.org/10.1071/FP19248DOI Listing
February 2020

Analysis of association between common variants of uncoupling proteins genes and diabetic retinopathy in a Chinese population.

BMC Med Genet 2020 02 6;21(1):25. Epub 2020 Feb 6.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (originally named"Shanghai First People's Hospital"), Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, National Clinical Research Center for Eye Diseases, No.100 Haining Road, Shanghai, 20080, China.

Background: The aim of this study was to explore the association between diabetic retinopathy (DR) and the variants of uncoupling proteins (UCPs) genes in a Chinese population of type 2 diabetes, in total and in patients of different glycemic status separately.

Methods: This case-control study included a total of 3107 participants from two datasets, among which 662 were DR patients (21.31%). Eighteen tag single nucleotide polymorphisms (SNPs) of UCP1, UCP2, and UCP3 were selected as genetic markers. TaqMan probes, Sequenom MassARRAY MALDI-TOF mass spectrometry platform and Affymetrix Genome-Wide Human SNP Array were used for genotyping. Online SHEsis software was used for association analysis. Bonferroni correction was used for multiple comparisons correction.

Results: Three SNPs of UCP1: rs7688743 (A allele, OR = 1.192, p = 0.013), rs3811787 (T allele, OR = 0.863, p = 0.023), and rs10011540 (G allele, OR = 1.368, p = 0.004) showed association with DR after the adjustment of glucose, but only rs10011540 was marginally significantly associated with DR when Bonferroni correction was strictly applied (p = 0.048). In patients with uncontrolled glucose, rs7688743 (A allele, p = 0.012, OR = 1.309), rs10011540 (G allele, p = 0.033, OR = 1.432), and rs3811787 (T allele, p = 0.022, OR = 0.811) were associated with DR, while in participants with well controlled glucose, the rs2734827 of UCP3 was associated with DR (A allele, p = 0.017, OR = 0.532). Rs3811787 of UCP1 showed a protective effect to sight threatening DR (T allele, p = 0.007, OR = 0.490), and the association existed after the adjustment for environmental factors and the correction. In patients with uncontrolled glucose, the rs3811787 of UCP1 (T allele, p = 0.017, OR = 0.467) and the rs591758 of UCP3 (C allele, p = 0.026, OR = 0.103) were associated with STDR. While in those with well controlled glucose, only the rs7688743 of UCP1 showed a protective effect (A allele, p = 0.024, OR = 0.049). None of the associations remain significant when Bonferroni correction was strictly applied (all p < 0.05).

Conclusions: The rs10011540 and rs3811787 of the UCP1 gene was marginally significantly associated with DR in Chinese type 2 diabetes patients. There might be different mechanisms of DR development in patients with different glycemic status.
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http://dx.doi.org/10.1186/s12881-020-0956-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006419PMC
February 2020

Thinner Average Choroidal Thickness Is a Risk Factor for the Onset of Diabetic Retinopathy.

Ophthalmic Res 2020 5;63(3):259-270. Epub 2020 Feb 5.

Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China,

Purpose: To analyze the relationships between choroidal thickness (CT) and diabetes mellitus (DM), diabetic retinopathy (DR), and DR severity in community residents diagnosed with type 2 DM, and to explore whether CT can improve the discriminatory ability of other risk factors to predict the incidence of DR.

Methods: A total of 1,250 type 2 DM residents and 1,027 healthy controls in Xinjing community of Shanghai participated a cross-sectional survey of eye diseases in 2016. CT was measured using swept-source optical coherence tomography. DR was classified according to the 2002 international clinical classification of DR. A total of 537 subjects with type 2 DM without DR at the 2016 survey were followed up in 2018 to investigate the 2-year incidence of DR. Receiver operating characteristic curve analysis was used to test the accuracy of different indicators in predicting the onset of DR.

Results: The central CT of the control, no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR, and PDR groups were 223.40, 216.22, 213.57, 211.91, 178.47, and 168.15 μm, respectively (p for trend <0.001), and the average CT (ACT) were 197.83, 186.94, 182.03, 178.00, 156.91, and 136.72 μm respectively (p for trend <0.001). Body mass index (BMI), DM duration, fasting blood glucose, glycosylated hemoglobin (HbA1C), and ACT were risk factors for 2-year DR incidence. For the onset of DR, as predicted by ACT, after tenfold cross validation the average area under the curve was 0.55 (p = 0.048). Addition of ACT did not improve the discriminatory ability of DM duration, BMI, glucose and HbA1C on the incidence of DR (Z = 0.48; p = 0.63).

Conclusions: As the severity of DR increased, the CT of community type 2 DM patients showed a significant downward trend compared with the healthy controls. Thinner ACT was found to be a risk factor for DR incidence, but it did not improve the discriminatory ability of other risk factors to predict the incidence of DR.
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http://dx.doi.org/10.1159/000504756DOI Listing
March 2021