Publications by authors named "Shi Yan"

1,599 Publications

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Engineering the acyltransferase domain of epothilone polyketide synthase to alter the substrate specificity.

Microb Cell Fact 2021 Apr 21;20(1):86. Epub 2021 Apr 21.

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.

Background: Polyketide synthases (PKSs) include ketone synthase (KS), acyltransferase (AT) and acyl carrier protein (ACP) domains to catalyse the elongation of polyketide chains. Some PKSs also contain ketoreductase (KR), dehydratase (DH) and enoylreductase (ER) domains as modification domains. Insertion, deletion or substitution of the catalytic domains may lead to the production of novel polyketide derivatives or to the accumulation of desired products. Epothilones are 16-membered macrolides that have been used as anticancer drugs. The substrate promiscuity of the module 4 AT domain of the epothilone PKS (EPOAT4) results in production of epothilone mixtures; substitution of this domain may change the ratios of epothilones. In addition, there are two dormant domains in module 9 of the epothilone PKS. Removing these redundant domains to generate a simpler and more efficient assembly line is a desirable goal.

Results: The substitution of module 4 drastically diminished the activity of epothilone PKS. However, with careful design of the KS-AT linker and the post-AT linker, replacing EPOAT4 with EPOAT2, EPOAT6, EPOAT7 or EPOAT8 (specifically incorporating methylmalonyl-CoA (MMCoA)) significantly increased the ratio of epothilone D (4) to epothilone C (3) (the highest ratio of 4:3 = 4.6:1), whereas the ratio of 4:3 in the parental strain Schlegelella brevitalea 104-1 was 1.4:1. We also obtained three strains by swapping EPOAT4 with EPOAT3, EPOAT5, or EPOAT9, which specifically incorporate malonyl-CoA (MCoA). These strains produced only epothilone C, and the yield was increased by a factor of 1.8 compared to that of parental strain 104-1. Furthermore, mutations of five residues in the AT domain identified Ser310 as the critical factor for MMCoA recognition in EPOAT4. Then, the mutation of His308 to valine or tyrosine combined with the mutation of Phe310 to serine further altered the product ratios. At the same time, we successfully deleted the inactive module 9 DH and ER domains and fused the ΨKR domain with the KR domain through an ~ 25-residue linker to generate a productive and simplified epothilone PKS.

Conclusions: These results suggested that the substitution and deletion of catalytic domains effectively produces desirable compounds and that selection of the linkers between domains is crucial for maintaining intact PKS catalytic activity.
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http://dx.doi.org/10.1186/s12934-021-01578-3DOI Listing
April 2021

High-risk-pattern lung adenocarcinoma with epidermal growth factor receptor mutation is associated with distant metastasis risk and may benefit from adjuvant targeted therapy.

Interact Cardiovasc Thorac Surg 2021 Apr 21. Epub 2021 Apr 21.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China.

Objectives: This study aimed to evaluate the value of the high-risk-pattern histology (micropapillary and solid components) for predicting distant metastasis in lung adenocarcinoma and to determine the survival benefit with adjuvant targeted therapy for resected non-small cell lung cancer with high-risk-pattern histology.

Methods: Patients receiving surgery for non-small cell lung cancer were included in this retrospective study. Histological classification was performed according to 2015 World Health Organization classification. Tumours with micropapillary and solid components were defined as high-risk-pattern tumours. Univariable and multivariable Cox regression analyses were used for survival analysis. Adjuvant targeted therapy was alternative for patients with epidermal growth factor receptor (EGFR)-mutation and refusing adjuvant chemotherapy, and outcome was evaluated between 2 groups.

Results: The 514 patients (78 in high-risk group and 436 in low-risk group) were followed up for a median of 64 months. High-risk-pattern adenocarcinoma was significantly more common in male patients (P < 0.001) and in smokers (P < 0.001). Among patients with EGFR mutation (n = 164), the high-risk pattern was significantly associated with distant metastasis (P = 0.028) including brain metastasis (P = 0.022). In the 42 patients with high-risk pattern plus EGFR mutation, survival was significantly better after treatment with adjuvant targeted therapy than with chemotherapy (5-year overall survival: 56.4 ± 2.6 vs 44.7 ± 3.7 months, P = 0.011; 5-year disease-free survival: 54.0 ± 3.3 vs 41.9 ± 4.5 months, P = 0.006).

Conclusions: High-risk pattern is associated with distant metastasis in non-small cell lung cancer after surgery. Adjuvant targeted therapy may be superior to chemotherapy for treatment of patients with high-risk pattern and EGFR mutation.
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http://dx.doi.org/10.1093/icvts/ivab099DOI Listing
April 2021

Identification and functional analyses of host factors interacting with the 17-kDa protein of Barley yellow dwarf virus-GAV.

Sci Rep 2021 Apr 19;11(1):8453. Epub 2021 Apr 19.

College of Plant Protection, Henan Agricultural University, Zhengzhou, 450002, China.

Barley yellow dwarf viruses (BYDVs) cause significant economic losses on barley, wheat, and oats worldwide. 17-kDa protein (17K) of BYDVs plays a key role in viral infection in plants, whereas the underlying regulation mechanism of 17K in virus infection remains elusive. In this study, we determined that 17K of BYDV-GAV, the most common species found in China in recent years, was involved in viral pathogenicity. To identify the host factors interacting with 17K, the full length coding sequence of 17K was cloned into pGBKT7 to generate the bait plasmid pGBKT7-17K. 114 positive clones were identified as possible host factors to interact with 17K through screening a tobacco cDNA library. Gene ontology enrichment analysis showed that they were classified into 35 functional groups, involving three main categories including biological processes (BP), cellular components (CC), and molecular functions (MF). Kyoto Encyclopedia of Genes and Genome (KEGG) analysis indicated the acquired genes were assigned to 49 KEGG pathways. The majority of these genes were involved in glyoxylate and dicarboxylate metabolism, carbon fixation in photosynthetic organisms, and glycolysis/gluconeogenesis. The interactions between 17K and the 27 proteins with well-documented annotations were verified by conducting yeast two-hybrid assays and 12 of the 27 proteins were verified to interact with 17K. To explore the putative function of the 12 proteins in BYDV-GAV infection, the subcellular localization and expression alterations in the presence of BYDV-GAV were monitored. The results showed that, under the condition of BYDV-GAV infection, RuBisCo, POR, and PPD5 were significantly up-regulated, whereas AEP and CAT1 were significantly down-regulated. Our findings provide insights into the 17K-mediated BYDV-GAV infection process.
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http://dx.doi.org/10.1038/s41598-021-87836-1DOI Listing
April 2021

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA): Early diagnosis, treatment and outcomes.

Eur J Obstet Gynecol Reprod Biol 2021 Apr 16;261:12-16. Epub 2021 Apr 16.

Department of Urology, Children's Medicine Affiliated to Chongqing Medical University, Chongqing, PR China; Paediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Centre for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Chongqing Key Laboratory of Paediatrics, Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, PR China. Electronic address:

Objective: To describe and summarize the early diagnosis, treatment and outcomes of obstructed hemivagina and ipsilateral renal anomaly (OHVIRA).

Methods: Data from patients with OHVIRA treated at the study centre over the last decade were analysed retrospectively, including demographic characteristics, symptoms, diagnosis, treatment and outcomes. Relevant published literature was also reviewed in this study.

Results: In total, 11 cases were diagnosed with OHVIRA over the study period, ranging in age from 3 to 14 years (median 11 years). Four cases were asymptomatic, four had abdominal pain and three had urinary symptoms. All 11 cases underwent vaginoplasty. Ureteral bladder re-implantation (n = 1), dysplastic nephrectomy (n = 1), separation of labia minora adhesions (n = 1), perineoplasty (n = 1) and urethroplasty (n = 1) were performed. Cases were followed up for 2 months to 8 years (median 5 years) with good follow-up outcomes.

Conclusions: Based on the cases in this study and the relevant literature, ultrasound appears to be an effective method for the diagnosis of OHVIRA. Experienced ultrasonographers are able to achieve a high corrected diagnosis rate. The differential diagnosis of OHVIRA should be considered by paediatric surgeons, urologists, emergency physicians and gynaecologists when they identify patients with didelphys uterus or renal agenesis. Early surgery can reduce the risk of potential genital tract infection and gynaecological complications.
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http://dx.doi.org/10.1016/j.ejogrb.2021.03.018DOI Listing
April 2021

Caregiver burden and its prevalence, measurement scales, predictive factors and impact: a review with an Asian perspective.

Singapore Med J 2021 04 16. Epub 2021 Apr 16.

Department of Family Medicine and Continuing Care, Singapore General Hospital, Singapore.

Caregiver burden is a well-recognised global phenomenon. The primary aim of this review is to summarise the prevalence of caregiver burden and its measurement scales, predictive factors and impact in Singapore. PubMed® and Scopus® databases were searched using the key terms 'caregiver', 'burden', 'stress', 'strain' and 'Singapore'. A total of 206 papers were retrieved and 20 were included. This review showed that a significant proportion of caregivers in Singapore experience caregiver burden. Caregiving experiences and outcomes are affected by cultural, behavioural and socioeconomic factors. Being a Malay caregiver appears to be a protective factor for caregiver burden, whereas having negative coping strategies and care recipients with functional, cognitive and behavioural impairments are positive risk factors. As for outcomes, caregiver burden is associated with poorer self-rated health and reduced quality of life. Multiple instruments have been used to measure caregiver burden, and the Zarit Burden Interview is the most widely used.
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http://dx.doi.org/10.11622/smedj.2021033DOI Listing
April 2021

miR-214 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice.

Front Neurosci 2021 26;15:649982. Epub 2021 Mar 26.

The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Background: Ischemic stroke induces neuronal cell death and causes brain dysfunction. Preventing neuronal cell death after stroke is key to protecting the brain from stroke damage. Nevertheless, preventative measures and treatment strategies for stroke damage are scarce. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathogenesis of central nervous system (CNS) disorders and may serve as potential therapeutic targets.

Methods: A photochemically induced thrombosis (PIT) mouse model was used as an ischemic stroke model. qRT-PCR was employed to assess changes in miRNAs in ischemic lesions of PIT-stroke mice and primary cultured neurons subjected to oxygen-glucose deprivation (OGD). 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate brain infarction tissues . TUNEL staining was employed to assess neuronal death . Neurological scores and motor coordination were investigated to evaluate stroke damage, including neurological deficits and motor function.

Results: and results demonstrated that levels of miR-124 were significantly decreased following stroke, whereas changes in death-associated protein kinase 1 (DAPK1) levels exhibited the converse pattern. DAPK1 was identified as a direct target of miR-124. N-methyl-D-aspartate (NMDA) and OGD-induced neuronal death was rescued by miR-124 overexpression. Upregulation of miR-124 levels significantly improved PIT-stroke damage, including the overall neurological function in mice.

Conclusion: We demonstrate the involvement of the miR-124/DAPK1 pathway in ischemic neuronal death. Our results highlight the therapeutic potential of targeting this pathway for ischemic stroke.
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http://dx.doi.org/10.3389/fnins.2021.649982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032895PMC
March 2021

Preparation of the peroxisome proliferator-activated receptor α polyclonal antibody: Its application in fatty liver hemorrhagic syndrome.

Int J Biol Macromol 2021 Apr 7;182:179-186. Epub 2021 Apr 7.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

Peroxisome proliferator-activated receptor α (PPARα) play a key role in the regulation of metabolic homeostasis, inflammation, cellular growth, and differentiation. To further explore the potential role of PPARα in the energy homeostasis of fatty liver hemorrhagic syndrome (FLHS), we reported the prokaryotic expression and purification of chicken PPARα subunit protein, and successfully prepared a polyclonal antibody against PPARα recombinant protein. The 987 bp PPARα subunit genes were cloned into the pEASY-T3 clone vector. Then the plasmid PCR products encoding 329 amino acids were ligated to pEASY-Blunt E2 vector and transformed into BL21 to induce expression. The recombinant PPARα subunit protein, containing His-tag, was purified by affinity column chromatography using Ni-NTA affinity column. Rabbit antiserum was generated by using the concentration of recombinant PPARα subunit protein as the antigen. The results of western blotting showed that the antiserum can specifically recognize chicken endogenous PPARα protein. Immunohistochemistry and immunofluorescence showed that the PPARα mainly existed in the nucleus of hepatocytes, renal epithelial cells and hypothalamic endocrine nerve cells. More importantly, western blotting and real-time quantitative PCR indicated that FLHS significantly decreased the expression of PPARα.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.018DOI Listing
April 2021

Cognitive leisure activity and all-cause mortality in older adults: a 4-year community-based cohort.

BMC Geriatr 2021 04 9;21(1):236. Epub 2021 Apr 9.

School of Public Health, Fudan University, Shanghai, 200032, China.

Background: Cognitive leisure activity, such as reading, playing mahjong or cards and computer use, is common among older adults in China. Previous studies suggest a negative correlation between cognitive leisure activity and cognitive impairment. However, the relationship between cognitive leisure activity and all-cause mortality has rarely been reported.

Objectives: This study aims to explore the relationships between cognitive leisure activity and all-cause mortality in a community-based older people cohort in China.

Methods: The current study sample comprised 4003 community residents aged ≥60 y who were enrolled in June 2015, and were followed up every year from 2015 to 2018. Reading, playing mahjong or cards and computer use were measured by questionnaires and summed into a cognitive leisure activity index (CLAI) score. Time-Dependent Cox Regression Model and Kaplan-Meier survival analysis were used to examine the association of cognitive leisure activity with all-cause mortality.

Results: During the 4-year follow-up of 4003 participants, 208 (5.2%) deaths were registered. Of all participants, 66.8, 26.7, 6.1 and 0.35% reported CLAI scores of 0, 1, 2 and 3, respectively. A strong association was noted between the CLA score and all-cause mortality (adjusted hazard ratio [HR] = 0.72, 95% confidence intervals [CI]: 0.54-0.97, P = 0.028). Stratified analysis suggested that a higher CLAI score was significantly associated with a decreased risk of all-cause mortality mainly among those who were male, aged ≥80 y, cognitively impaired, and not diagnosed with cancer (P < 0.05).

Conclusion: Cognitive leisure activity was positively associated with reduced risk of death from all cause among the older people in major city of China, which helped promote a comprehensive understanding of health characteristics at advanced ages.
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http://dx.doi.org/10.1186/s12877-021-02180-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033664PMC
April 2021

Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior.

Nano Lett 2021 Apr 8. Epub 2021 Apr 8.

Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.

The genetic heterogeneities in cancer cells pose challenges to achieving precise drug treatment in a widely applicable manner. Most single-cell gene analysis methods rely on cell lysis for gene extraction and identification, showing limited capacity to provide the correlation of genetic properties and real-time cellular behaviors. Here, we report a single living cell analysis nanoplatform that enables interrogating gene properties and drug resistance in millions of single cells. We designed a Domino-probe to identify intracellular target RNAs while releasing 10-fold amplified fluorescence signals. An on-chip addressable microwell-nanopore array was developed for enhanced electro-delivery of the Domino-probe and in situ observation of cell behaviors. The proof-of-concept of the system was validated in primary lung cancer cell samples, revealing the positive-correlation of the ratio of EGFR mutant cells with their drug susceptibilities. This platform provides a high-throughput yet precise tool for exploring the relationship between intracellular genes and cell behaviors at the single-cell level.
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http://dx.doi.org/10.1021/acs.nanolett.1c00199DOI Listing
April 2021

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Mar;24(3):141-160

Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing 100142, China.

Background: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).

Methods: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.

Results: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.

Conclusions: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.06DOI Listing
March 2021

Structure Analysis and Study of Biological Activities of Condensed Tannins from (L.) Lam and Their Effect on Fresh-Cut Lotus Roots.

Molecules 2021 Mar 4;26(5). Epub 2021 Mar 4.

School of Life Sciences, Xiamen University, Xiamen 361102, China.

(L.) Lam is a mangrove plant that spread in many parts of the world. Though mangrove plant polyphenols have been reported to exhibit many biological activities, little is known about mangrove plant tannins. To explore the application value of tannins from , analyses on the structure and biological activity of condensed tannins (CTs) from (L.) Lam were carried out. The results from C nuclear magnetic resonance (C-NMR) and reversed-phase, high-performance liquid chromatography (RP-HPLC) showed that the CTs were dominated by procyanidins, with a small quantity of prodelphinidins and propelargonidins; and that the monomeric constituents of tannins were catechin/epicatechin, gallocatechin/epigallocatechin and afzelechin/epiafzelechin. The CTs were reversible and mixed competitive inhibitors of tyrosinase and the 50% inhibiting concentration (IC) was estimated to be 123.90 ± 0.140 μg/mL. The antioxidant activities of CTs from leaves were evaluated, the IC for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid diammonium salt) (ABTS) scavenging activities were 88.81 ± 0.135 and 105.03 ± 0.130 μg/mL, respectively, and the ferric ion reducing antioxidant power (FRAP) value was 1052.27 ± 4.17 mgAAE/g. In addition, the results from fresh-keeping assays on fresh-cut lotus root reveal that CTs from had excellent effects on inhibiting the activities of polyphenol oxidase (PPO) and peroxidase (POD), protecting fresh-cut lotus root from the oxidation of total phenolics and malondialdehyde (MDA) content and slowing the increase in total phenol content (TPC) at 4 °C during the whole storage period. Therefore, CTs showed good effects against the browning of fresh-cut lotus root. Together, these results suggested that CTs are promising antibrowning agents for fresh-cut fruits.
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http://dx.doi.org/10.3390/molecules26051369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961348PMC
March 2021

Is SARS-CoV-2 vaccination safe and effective for elderly individuals with neurodegenerative diseases?

Expert Rev Vaccines 2021 Apr 12:1-9. Epub 2021 Apr 12.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing China.

Introduction: Coronavirus Disease 2019 (COVID-19) poses a substantial threat to the lives of the elderly, especially those with neurodegenerative diseases, and vaccination against viral infections is recognized as an effective measure to reduce mortality. However, elderly patients with neurodegenerative diseases often suffer from abnormal immune function and take multiple medications, which may complicate the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Currently, there is no expert consensus on whether SARS-CoV-2 vaccines are suitable for patients with neurodegenerative diseases.

Areas Covered: We searched Pubmed to conduct a systematic review of published studies, case reports, reviews, meta-analyses, and expert guidelines on the impact of SARS-CoV-2 on neurodegenerative diseases and the latest developments in COVID-19 vaccines. We also summarized the interaction between vaccines and age-related neurodegenerative diseases. The compatibility of future SARS-CoV-2 vaccines with neurodegenerative diseases is discussed.

Expert Opinion: Vaccines enable the body to produce immunity by activating the body's immune response. The pathogenesis and treatment of neurodegenerative diseases is complex, and these diseases often involve abnormal immune function, which can substantially affect the safety and effectiveness of vaccines. In short, this article provides recommendations for the use of vaccine candidates in patients with neurodegenerative diseases.
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http://dx.doi.org/10.1080/14760584.2021.1911653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054494PMC
April 2021

[Current quality standards of cattle bile and sheep bile quality standards and discussion on related problems].

Zhongguo Zhong Yao Za Zhi 2021 Mar;46(6):1580-1584

National Institutes for Food and Drug Control Beijing 102629,China.

To analyze quality standards of cattle bile and sheep bile, and to discuss the related problems in the standards. The results showed that physical forms of the related medicinal materials of cattle bile and sheep bile were chaotic, and the technical methods adopted in the quality standards were generally backward. In addition, there were still problems that some medicinal material standards lacked necessary test items, which were especially obvious in the relevant medicinal material standards of sheep bile and brought difficulties to quality evaluation and control. We suggest that physical forms of cattle bile and sheep bile in quality standards should be determined, and inspection items should be completed. Based on mainstream analytical technology, some technical methods of these standards should be improved.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201214.301DOI Listing
March 2021

[Investigation on reproductive characteristics of Polygonatum cyrtonema].

Zhongguo Zhong Yao Za Zhi 2021 Mar;46(5):1079-1083

State Key Laboratory of Subtropical Silviculture,Zhejiang A&F University Hangzhou 311300,China.

The study is aimed to investigate the reproductive biology characteristics of Polygonatum cyrtonema, especially including phenology, flower bud differentiation, flowering timing, floral traits, pollen vigor and stigma receptivity. The results showed that P. cyrtonema forms inflorescence before the leaves spread. In the wild, P. cyrtonema is mainly pollinated by insects such as bumblebees, with a seed setting rate of 65.12%. The seed setting rate of indoor single plant isolation or self-pollination enclosed by parchment paper bag is 0, indicating that it is self-incompatible. In Lin'an city, seedlings begin to emerge from mid-March to early April(the temperature is higher than 7.5 ℃), buds begin to emerge from the end of March to mid-April, and then undergo the full bloom stage from mid-to-late April, and the final flowering stage from the end of April to mid-May. The whole flowering period lasts 36 to 45 days. There are obvious differences in the phenology of different provenances. The flowers come into bloom from the base to the top along the aboveground main axis, which usually contain 4-22 inflorescences with(2-) 4-10(-21) flowers per inflorescence. The flowering pe-riod for a single plant is 26-38 days. The single flower lasts about 20-25 days from budding to opening and withers 2 days after pollination, and then the ovary will gradually expand. If unpollinated, it will continue to bloom for 3-5 days and then wither. Flower development period is significantly related to pollen vigor and stigma remittance. The pollen viability is the highest when the flower is fully opened with anthers gathering on the stigma, and the receptivity is the strongest when the stigma protrudes out of the perianth and secretes mucus. The fruits and seeds ripen in October, and proper shading can ensure the smooth development and maturity of the seeds. This study provides a basis for the hybrid breeding and seed production of P. cyrtonema.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201223.101DOI Listing
March 2021

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Thorac Cancer 2021 Mar 30. Epub 2021 Mar 30.

Peking University Cancer Hospital, Beijing, China.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.
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http://dx.doi.org/10.1111/1759-7714.13942DOI Listing
March 2021

Dynamic changes in metabolic health status in Chinese adults: multiple population-based surveys in Shanghai, China.

J Diabetes Investig 2021 Mar 31. Epub 2021 Mar 31.

Department of NCDs prevention and control, Shanghai municipal center for disease control and prevention, 1380 Zhong Shan Xi Road, Shanghai, 200336, China.

Aims/introduction: Metabolic syndrome (MS) has been increasing worldwide. The secular change in MS components, however, remains unclear. This study aimed to examine the dynamic change in metabolic health status in Chinese adults.

Materials And Methods: Three population-based surveys using multistage stratified sampling were performed in Chinese aged 35-74 years in Shanghai in 2002-2003 (n=12,302), 2009 (n=7,400), and 2017 (n=19,023). MS was defined according to the Adult Treatment Panel III criteria for Asian-Americans. Generalized Estimating Equations and Cochran-Armitage Trend Test was used to assess the prevalence trend over the years.

Results: The prevalence of MS doubled in Chinese adults over the period (p for trend < 0.001). The largest increase occurred in younger men. Among MS components, the prevalence of high waist-circumference (HWC), high blood glucose (HBG) and high blood pressure (HBP) increased in all subjects, whereas the prevalence of high triglycerides (HTG) and low high-density lipoprotein cholesterol (LHC) increased in men but decreased in women. The increase in HBP contributed most to elevated MS, followed by HBG and HWC, resulting in the HBP-HBG-HWC the most common cluster of MS components. Metabolically unhealthy overweight also grew over the period.

Conclusions: Metabolic health status has been exacerbating in Chinese adults, and may increase burden of non-communicable diseases.
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http://dx.doi.org/10.1111/jdi.13556DOI Listing
March 2021

Feasibility and efficacy of modified fixed citrate concentration protocol using only commercial preparations in critically ill patients: a prospective cohort study with a historical control group.

BMC Anesthesiol 2021 Mar 30;21(1):96. Epub 2021 Mar 30.

Department of medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China.

Background: The cumbersome program and the shortage of commercial solution hindered the regular application of regional citrate anticoagulation (RCA). It is urgent to simplify the protocol using only commercial preparations. The aim of this study was to explore the feasibility and efficacy of the modified protocol for continuous veno-venous hemofiltration (CVVH) in unselected critically ill patients.

Methods: A prospective cohort study was conducted in 66 patients who received a new protocol combining fixed citrate concentration with modified algorithm for supplements (i.e., fixed protocol), and compared the efficacy, safety and convenience for this group to a historical control group with a traditional protocol (n = 64), where citrate was titrated according to the circuit ionized calcium concentration (i.e., titrated protocol). The convenience was defined as the demand for monitoring test and dose adjustment of any supplement.

Results: The filter lifespan was 63.2 ± 16.1 h in the fixed group and 51.9 ± 17.7 h in the titrated group, respectively. Kaplan-Meier survival analysis demonstrated longer circuit lifetime for fixed group (log-rank, p = 0.026). The incidence of circuit clotting was lower in the fixed protocol (15.2% vs. 29.7% in the titrated protocol, p = 0.047). Moreover, compared with the titrated group, patients with fixed protocol had less demand for monitoring test and dose adjustment of any supplement (the number of times per person per day) (3.3 [IQR 2.3-4.5] vs. 5.7 [IQR 3.3-6.9], p = 0.001 and 1.9 [IQR 0.5-2.7] vs. 6.3 [IQR 4.2-7.9], p < 0.001; respectively). No new onset bleeding complications occurred in all patients. The overall incidence of suspected citrate accumulation was 4.6% and there was no difference between the two groups (p = 0.969), yet a lower rate of metabolic alkalosis was found in the fixed group (3.0% vs. 14.1%, p = 0.024).

Conclusions: Our modified fixed citrate concentration protocol is feasible, safe and effective to enhance the circuit lifespan and the convenience of implementation while maintaining a similar safety when compared to the traditional protocol. Using only commercial preparations may be helpful for widespread application of RCA.

Trial Registration: Clinicaltrials.gov. NCT02663960 . Registered 26 January 2016.
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http://dx.doi.org/10.1186/s12871-021-01319-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008573PMC
March 2021

Rapid Characterization of Drugs in Biological Fluid and Seized Material Using Thermal-Assisted Carbon Fiber Ionization Mass Spectrometry.

J Am Soc Mass Spectrom 2021 Apr 28;32(4):969-976. Epub 2021 Mar 28.

Department of Forensic Toxicology, Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Shanghai 200063, China.

Developing a rapid, simple, and sensitive method to analyze drugs is critical to forensic research study because of the widespread occurrence of the matrix effect. Herein, we develop a method using thermal-assisted carbon fiber ionization mass spectrometry that can be used to directly analyze drugs in biological fluid. The key feature of this technique is that the biological samples such as urine and blood can be achieved online as precipitated protein on the carbon fiber tip and thermally desorbed by the metal ceramics heater, which can reduce the matrix effects and improve the sensitivity. Analytes including raw urine, blood, oral fluid, drink, tobacco tar, drug tablets, and paper cards can be rapidly identified and analyzed within a few minutes regardless of their physical variations. Due to its simplicity and noninvasive analysis, this method can be used for drugged driving analysis and to achieve point-of-care drug testing in clinical and forensic chemistry.
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http://dx.doi.org/10.1021/jasms.0c00472DOI Listing
April 2021

Wideband composite planar spiral antenna for generation of tunable angular momentum wave.

Opt Express 2021 Feb;29(3):3754-3763

In this paper, a composite planar spiral antenna consisting of an eight-arm equiangular spiral antenna and eight Archimedean spiral antennas has been designed to radiate electromagnetic wave carrying tunable angular momenta in a wide band. A tunable eight-way Wilkinson power divider network is used to offer three kinds of feeding modes for the equiangular spiral antenna, and thus the composite antenna can radiate the electromagnetic waves with angular momenta of the modes l=1, 2, and 3, respectively. The Archimedean spiral is introduced to improve the gain of the composite antenna in the case of the angular momentum of l=3. By analyzing axis ratio (AR) of the proposed antenna, the generated angular momentum of l=1 is spin angular momentum (SAM), and the angular momenta of both l=2 and 3 include SAM and orbital angular momentum (OAM). Simulated and measured results are given to demonstrate good performance including tunable modes, good purity and wide band.
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http://dx.doi.org/10.1364/OE.414163DOI Listing
February 2021

NOTCH signaling pathway is required for bovine early embryonic development.

Biol Reprod 2021 Mar 24. Epub 2021 Mar 24.

Laboratory of Mammalian Molecular Embryology, College of Animal Sciences, Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.

The NOTCH signaling pathway plays an important role in regulating various biological processes, including lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of the NOTCH pathway in early embryonic development is poorly understood, especially in large animals. Here, we show that the expression of genes encoding key transcripts of the NOTCH pathway is dynamic throughout early embryonic development. We also confirm the presence of active NOTCH1 and RBPJ. By using pharmacological and RNAi tools, we demonstrate that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator-RBPJ, whose deficiency also compromised the embryo quality. Indeed, both NOTCH1 and RBPJ knockdown cause a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres, suggesting a cell cycle arrest at mitosis. Importantly, RNA-seq analyses reveal that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression.
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http://dx.doi.org/10.1093/biolre/ioab056DOI Listing
March 2021

leaf extract prevents diabetic nephropathy through the suppression of tissue transglutaminase.

Exp Ther Med 2021 Apr 8;21(4):333. Epub 2021 Feb 8.

Department of Obstetrics and Gynecology, The Second Hospital, Jilin University, Changchun, Jilin 130041, P.R. China.

The present study aimed to investigate the preventive effects of leaf extract (GBE) against extracellular matrix (ECM) accumulation in a streptozotocin (STZ)-induced rat model of diabetic nephropathy (DN), and to determine its underlying molecular mechanism. , a rat model of DN was established by intraperitoneal injection of STZ, and the rats were subsequently administered GBE. The results demonstrated that GBE significantly decreased blood glucose, the urine protein excretion rate and ECM accumulation in DN rats. In addition, the development of DN significantly induced tissue transglutaminase (tTG) protein expression, which was detected by immunohistochemistry, western blotting and PCR analyses, while GBE administration decreased tTG expression in the diabetic kidney. , rat glomerular mesangial cells (HBZY-1 cells) cultured with high glucose were also treated with GBE. The concentrations of tTG, fibronectin, type IV collagen, transforming growth factor (TGF)-β and connective tissue growth factor (CTGF) were detected via ELISA. The results demonstrated that GBE notably decreased the concentration of these proteins, and tTG expression was positively associated with TGF-β. GBE also suppressed tTG expression of high glucose-treated HBZY-1 cells in a concentration-dependent manner. Furthermore, tTG protein expression was detected in high glucose-treated HBZY-1 cells transfected with small interfering RNA (siRNA) oligonucleotides against TGF-β and CTGF to investigate a possible mechanism of GBE-mediated inhibition of tTG. The results demonstrated that the tTG levels remained unchanged in CTGF siRNA-transfected cells, but were decreased in the GBE + CTGF siRNA group compared with the control siRNA group, suggesting that tTG may not be regulated by CTGF, and the inhibitory effect of GBE on tTG may not be associated with the direct inhibition of CTGF. However, tTG expression was decreased following the transfection with TGF-β siRNA, in which levels of tTG were similar compared with both the GBE group and GBE + TGF-β siRNA group, indicating that tTG may be regulated by TGF-β, and that the GBE-induced repression of tTG expression may be associated with the downregulation of TGF-β. Taken together, the results of the present study suggest that GBE prevented ECM accumulation by suppressing tTG expression in DN, which was predominantly mediated by TGF-β.
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http://dx.doi.org/10.3892/etm.2021.9764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903480PMC
April 2021

How COVID-19 lockdown and reopening affected daily steps: evidence based on 164,630 person-days of prospectively collected data from Shanghai, China.

Int J Behav Nutr Phys Act 2021 03 17;18(1):40. Epub 2021 Mar 17.

Shanghai Municipal Center for Disease Control and Prevention, 1380 West Zhongshan Road, Shanghai, 200336, China.

Background: COVID-19 lockdowns may lead to physical inactivity, a major risk factor for non-communicable diseases. This study aims to determine: 1) the trajectory in daily step counts before, during and after the lockdown in China, and 2) the characteristics associated with the trajectories.

Methods: From December 2019 to July 2020, smartphone-based step counts were continuously collected in 815 Chinese adults residing in Shanghai over 202 days across three phases: before, during, and after the lockdown. Participant characteristics were reported, and height, weight and body composition measured before the lockdown. A 'sharp' regression discontinuity design with cluster robust standard errors was used to test the effect of the lockdown and reopening on daily steps and a linear mixed model was used to examine the characteristics associated with trajectories during the observed period.

Results: Based on 164,630 person-days of data, we found a sharp decline in daily step counts upon the lockdown (24/01/2020) by an average of 3796 (SE = 88) steps, followed by a significant trend of increase by 34 steps/day (SE = 2.5; p < .001) until the end of the lockdown (22/03/2020). This increasing trend continued into the reopening phase at a slower rate of 5 steps per day (SE = 2.3; p = 0.029). Those who were older, married, university educated, insufficiently active, had an 'at risk' body composition, and those in the control group, were slower at recovering step counts during the lockdown, and those who were older, married, without university education and with an 'at risk' body composition recovered step counts at a slower pace after the reopening.

Conclusions: Despite later increases in step counts, COVID-19 lockdown led to a sustained period of reduced physical activity, which may have adverse health implications. Governments and health professionals around the world should continue to encourage and facilitate physical activity during the pandemic.
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http://dx.doi.org/10.1186/s12966-021-01106-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968558PMC
March 2021

Polarization conversion metasurface design based on characteristic mode rotation and its application into wideband and miniature antennas with a low radar cross section.

Opt Express 2021 Mar;29(5):6794-6809

In this paper, a characteristic mode rotation (CMR) method has been proposed to design a compact metasurface antenna with a low radar cross section (RCS) in a wideband. In the proposed CMR method, the incident wave dependent complex characteristic currents corresponding to the dominant characteristic modes solved by the characteristic mode method (CMM) are calculated. With the direction of the superposition of the complex characteristic currents orthogonal to that of the incident electric field in the CMR method, the metasurface subarray with wideband polarization conversion characteristic is designed. By arranging the metasurface subarray in a rotation way, a metasurface array with a compact size of 1.28λ×1.28λ is designed for wideband RCS reduction. A miniature circle patch antenna is integrated with the metasurface array to achieve not only good radiation performance but also low observability for the in-band and the out-of-band of the antenna. Simulated and measured results demonstrate that the proposed miniature metasurface antenna designed by the CMR method has a good broadside radiation pattern, a maximal gain of 10.75 dB, and a -10 dB RCS reduction characteristic in the wide band of 6∼20.7 GHz with a fractional band of 110%.
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http://dx.doi.org/10.1364/OE.416976DOI Listing
March 2021

Analysis of the social and clinical factors affecting the age of children when receiving surgery for hypospadias: a retrospective study of 1611 cases in a single center.

Asian J Androl 2021 Mar 12. Epub 2021 Mar 12.

Children's Hospital of Chongqing Medical University, Chongqing 400010, China.

We aimed to explore the associations between the age at which children undergo surgery for hypospadias and a range of social and clinical factors in a single center. Our aim was to promote the early surgical treatment of children with hypospadias. For a 6-year period, social and clinical data were collected from all children undergoing surgery to repair hypospadias in Children's Hospital of Chongqing Medical University (Chongqing, China), located in southwest of China. We analyzed the correlations between age at surgery and a range of social and clinical factors. A total of 1611 eligible cases were recruited, with a mean age of 54.3 months and a median age of 42 months: 234 cases (14.5%) were classified into a "timely operation" group, 419 (26.0%) cases into a "subtimely operation" group, and 958 (59.5%) cases into a "delayed operation" group. According to multivariate regression analyses, the higher the regional economic level, the closer the urethral opening to the perineum, and the higher the educational level of the guardians was, the younger the children were when they underwent the initial surgery for hypospadias; this was also the case for families without other children. Our subgroup analysis showed that the primary educational level of the guardians was a risk factor for subtimely surgery in their children (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.08-2.15, P < 0.05). A lower regional economic level (OR = 1.87, 95% CI: 1.26-2.78, P < 0.01), a lower educational level of the guardians (OR = 3.84, 95% CI: 2.31-6.41, P < 0.01), and an anterior-segment urethral opening (OR [vs middle hypospadias] = 2.07, 95% CI: 1.42-3.03; OR [vs posterior hypospadias] = 2.63, 95% CI: 1.75-3.95; P < 0.01) were all risk factors for delayed surgery in children.
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http://dx.doi.org/10.4103/aja.aja_11_21DOI Listing
March 2021

Harmonized and high-quality datasets of aerosol optical depth at a US continental site, 1997-2018.

Sci Data 2021 Mar 11;8(1):82. Epub 2021 Mar 11.

Pacific Northwest National Laboratory, Richland, WA, USA.

Aerosol optical depth (AOD) characterizes the aerosol burden in the atmosphere, while its wavelength dependence is a sign of particle size. Long-term records of wavelength-resolved AOD with high quality and suitable continuity are required for climate change assessment. Typically, climate-related studies use AOD products provided by several, and perhaps different, ground-based instruments. The measurements from these instruments often have different accuracy and temporal resolution. To preserve the advantages of these products (high quality) and to reduce their disadvantages (patchy records), we generate a merged dataset obtained from four instruments deployed at a US continental site in which a nearly-continuous AOD record is found at two wavelengths (500 and 870 nm) with high quality and high temporal resolution (1-min) for a 21-yr period (1997-2018). The combined dataset addresses: (1) varying data quality and resolution mismatch of the individual AOD records, and (2) the uncertainty of the merged AOD and its relevance for user-specified needs. The generated dataset will be beneficial for a wide range of applications including aerosol-radiation interactions.
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http://dx.doi.org/10.1038/s41597-021-00866-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952417PMC
March 2021

SIN3A Regulates Porcine Early Embryonic Development by Modulating Expression.

Front Cell Dev Biol 2021 22;9:604232. Epub 2021 Feb 22.

Laboratory of Mammalian Molecular Embryology, Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China.

SIN3A is the central scaffold protein of the SIN3/histone deacetylase (HDAC) transcriptional repressor complex. SIN3A participates in the mouse preimplantation development by fine-tuning expression. However, it remains unresolved if this functional significance of SIN3A was conserved in other mammals. Herein, RNA-seq results show a large amount of mRNA is present in oocytes and early embryos prior to embryonic genome activation and a low amount thereafter, suggesting a maternal origin of SIN3A in pigs, cattle, mice, and humans. Interestingly, immunofluorescence data show that SIN3A protein level peaks at four-cell stage in pigs compared with morula stage in cattle. SIN3A depletion in early embryos causes a developmental arrest at two-cell stage in pigs but does not affect bovine early embryonic development. In contrast with mouse data, SIN3A depletion results in only a slight decrease and even no difference in HDAC1 expression in porcine and bovine early embryos, respectively. In addition, HDAC1 knockdown does not cause two-cell block but leads to a reduced blastocyst rate. By using unbiased RNA-seq approach, we found that () transcript level is dramatically reduced. Moreover, CCNB1 knockdown results in a similar phenotype as SIN3A depletion. Injection of exogenous mRNA into SIN3A-depleted embryos could partly rescue embryonic development to pass two-cell stage. In conclusion, our results indicate SIN3A plays an essential role in porcine early embryonic development, which probably involves the regulation of expression.
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http://dx.doi.org/10.3389/fcell.2021.604232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937639PMC
February 2021

A novel charge derivatization-direct infusion mass spectrometry method for the quantitative analysis of C-C fatty acids in rubber seed oil-based biodiesel.

Talanta 2021 May 16;226:122107. Epub 2021 Jan 16.

Key Laboratory of Analytical Chemistry of the State Ethnic Affairs Commission, College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, 430074, People's Republic of China. Electronic address:

The free fatty acids that contain one to eight carbons (C-C) in biodiesel would affect the quality of biodiesel. It is still a matter of challenge to simultaneously determine the composition of C-C fatty acids in seed oil and seed oil-based biodiesel. Herein, a novel method of charge derivatization coupling with direct infusion mass spectrometry (CD-DIMS) was developed for the determination of the C-C fatty acids in biodiesels. A fixed-charge derivatization reagent, 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide (CMCT), was used to convert fatty acids into their cationic derivatives, which significantly improved the sensitivity and selectivity of detection. Good linearity was observed with the limits of detection (LODs) in the range of 0.0002-0.001 μg mL for the investigated fatty acids. The recovery was in the range of 85.1%-101.9% and the matrix effect was within the range of 75.5-93.2%. The developed method was carried out to analyze C-C fatty acids in rubber seed oil (RSO) and RSO-based biodiesels produced by different catalysts, including NaOH, TiO, and carbodiimide. It was also applied to the dynamic monitoring of C-C fatty acids in RSO and produced RSO biodiesels during the oxidation process. As results, formic acid, acetic acid, and propionic acid were detected in aged RSO and biodiesel samples. The contents of formic acid, acetic acid, and propionic acid all increased in aged RSO and biodiesels, but with different growth rates. These results demonstrated that the developed CD-DIMS method can provide a quick, accurate, and sensitive analysis of C-C fatty acids in seed oil and biodiesel samples.
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http://dx.doi.org/10.1016/j.talanta.2021.122107DOI Listing
May 2021

Membrane protein density determining membrane fusion revealed by dynamic fluorescence imaging.

Talanta 2021 May 2;226:122091. Epub 2021 Feb 2.

State Key Laboratory of Electroanalytical Chemistry, Research Center of Biomembranomics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, PR China; University of Science and Technology of China, Hefei, Anhui, 230026, PR China; Laboratory for Marine Biology and Biotechnology, Qing Dao National Laboratory for Marine Science and Technology, Qingdao, Shandong, 266237, PR China. Electronic address:

Membrane fusion is fundamental to biological activity of cells, so disclosingits relevant mechanism is very important for understanding various cell functions. Although artificial model systems have been developed to uncover the mechanism of membrane fusion, key factors determining the mode of membrane fusion remain unclear. Based on the construction of different types of liposome vesicles, we used a dynamic fluorescence imaging method to investigate the effect of membrane protein distribution density on membrane fusion. Time-resolved imaging revealed that protein-free pure phospholipid vesicles themselves occurred full membrane fusion. Moreover, we prepared proteoliposomes with increasing protein-to-lipid ratio to better reflect the characteristic of membrane structure in vivo. Our data showed that pure phospholipid vesicles no longer fused with the proteoliposomes that in a higher protein proportion, indicating dense membrane proteins may hinder membrane fusion. A further comparative analysis of the interactions of pure phospholipid vesicles with the cell membrane / giant plasma membrane vesicles (GPMVs) / protein-free giant unilamellar vesicles (GUVs) confirmed the inhibitory effect of dense membrane proteins on membrane fusion. Our work demonstrates the membrane protein density influences the mode of membrane fusion and lays a foundation for constructing quasi-native membrane fusion models in vitro.
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http://dx.doi.org/10.1016/j.talanta.2021.122091DOI Listing
May 2021

Prediction of ipsilateral lateral cervical lymph node metastasis in papillary thyroid carcinoma: a combined dual-energy CT and thyroid function indicators study.

BMC Cancer 2021 Mar 4;21(1):221. Epub 2021 Mar 4.

Department of Radiology, Tianjin First Central Hospital, School of Medicine, Nankai University, No. 24 Fu Kang Road, Nan Kai District, Tianjin, 300192, China.

Background: Predicting the possibility of ipsilateral lateral cervical lymph node metastasis (ipsi-LLNM) was crucial to the operation plan for patients with papillary thyroid carcinoma (PTC). This study aimed to investigate the independent risk factors for ipsi-LLNM in PTC patients by combining dual-energy computed tomography (DECT) with thyroid function indicators.

Methods: We retrospectively enrolled 406 patients with a pathological diagnosis of PTC from Jan 2016 to Dec 2019. Ensure the DECT images were clear and the thyroid function indicators were complete. Univariate and multivariate logistic analyses explored the independent risk factors for ipsi-LLNM. To evaluate the cutoff value of each risk factor by using receiver operating characteristic (ROC) curves.

Results: A total of 406 patients with PTC were analyzed, including 128 with ipsi-LLNM and 278 without ipsi-LLNM. There were statistical differences of parameters between the two groups (P < .0001), including serum Tg, Anti-Tg, Anti-TPO, the volume of the primary lesion, calcification, extrathyroidal extension (ETE), and iodine concentration (IC) in the arterial and the venous phases. Independent risk factors for ipsi-LLNM included serum Tg, Anti-Tg, ETE, and IC in the arterial and the venous phases (P < .05). The combined application of the above independent risk factors can predict the possibility of ipsi-LLNM, with an AUC of 0.834. Ipsi-LLNM was more likely to occur when the following conditions were met: with ETE, Tg >  100.01 ng/mL, Anti-Tg >  89.43 IU/mL, IC in arterial phase > 3.4 mg/mL and IC in venous phase > 3.1 mg/mL.

Conclusions: The combined application of DECT quantitative parameters and thyroid function indicators can help clinicians accurately predict ipsi-LLNM before surgery, thereby assisting the individualized formulation of surgical procedures.
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http://dx.doi.org/10.1186/s12885-021-07951-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934388PMC
March 2021

regulates pathological cardiac hypertrophy via a β-catenin-dependent mechanism.

Am J Physiol Heart Circ Physiol 2021 04 26;320(4):H1634-H1645. Epub 2021 Feb 26.

The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development College of Life Sciences, Hunan Normal University, Changsha, China.

Wnt/β-catenin signaling plays a key role in pathological cardiac remodeling in adults. The identification of a tissue-specific Wnt/β-catenin interaction factor may provide a tissue-specific clinical targeting strategy. encodes the core interaction factor of Wnt/β-catenin. Two homologs ( and ) have been identified in mammals. Different from the ubiquitous expression profile of , is enriched in cardiac tissue. However, the role of in mammalian cardiac disease is yet to be elucidated. In this study, we found that was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios, and increased cell size. The canonical β-catenin/T-cell transcription factor 4 (TCF4) complex was abundant in -overexpressing transgenic (-TG) cardiac tissue, and the downstream genes of Wnt signaling, that is, , , and c-Myc, were upregulated. A tail vein injection of β-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodeling in -TG mice. Furthermore, in vivo downregulated during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that regulates pathological cardiac hypertrophy in a canonical Wnt/β-catenin-dependent manner, which may provide new clues for tissue-specific clinical treatment via targeting this pathway. In this study, we found that is associated with human pathological hypertrophy. Cardiac-specific overexpression of in mice spontaneously led to cardiac hypertrophy. Meanwhile, cardiac function was improved when expression of was interfered in hypertrophy-model mice. Our study is the first to present in vivo evidence demonstrating that regulates pathological cardiac hypertrophy in a canonical Wnt/β-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway.
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http://dx.doi.org/10.1152/ajpheart.00538.2020DOI Listing
April 2021