Publications by authors named "Shan Huang"

558 Publications

Scale-dependent effects of niche specialisation: The disconnect between individual and species ranges.

Ecol Lett 2021 May 7. Epub 2021 May 7.

Senckenberg Biodiversity and Climate Research Centre (SBiK-F), Frankfurt, Germany.

One of the most general expectations of species range dynamics is that widespread species tend to have broader niches. However, it remains unclear how this relationship is expressed at different levels of biological organisation, which involve potentially distinctive processes operating at different spatial and temporal scales. Here, we show that range sizes of terrestrial non-volant mammals at the individual and species level show contrasting relationships with two ecological niche dimensions: diet and habitat breadth. While average individual home range size appears to be mainly shaped by the interplay of diet niche breadth and body mass, species geographical range size is primarily related to habitat niche breadth but not to diet niche breadth. Our findings suggest that individual home range size is shaped by the trade-off between energetic requirements, movement capacity and trophic specialisation, whereas species geographical range size is related to the ability to persist under various environmental conditions.
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http://dx.doi.org/10.1111/ele.13759DOI Listing
May 2021

Self-assembled nanomaterials for biosensing and therapeutics: recent advances and challenges.

Analyst 2021 May;146(9):2807-2817

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, China.

Self-assembled nanomaterials (SANs) exhibit designable biofunctions owing to their tunable nanostructures and modifiable surface. Various constituent units and multi-dimensional structures of SANs provide unlimited possibilities for numerous applications. This review emphasizes the recent development of SANs in the fields of biosensing, bioimaging, and nano-drug engineering. The unit type, design concepts, material advantages, assembly driving force, nanostructure effects, drug loading performance, etc. are discussed and summarized. Finally, we briefly summarize how to assemble unique nanomaterials and point out the key challenges in this field.
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http://dx.doi.org/10.1039/d1an00077bDOI Listing
May 2021

Anorectal Mucosal Melanoma in the Era of Immune Checkpoint Inhibition: Should We Change Our Surgical Management Paradigm?

Dis Colon Rectum 2021 May;64(5):555-562

1 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 2 New York Medical College at Metropolitan Hospital, New York, New York 3 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: The advent of immune checkpoint inhibition therapy has dramatically improved survival in patients with skin melanoma. Survival outcomes after resection of anorectal melanoma treated with immune checkpoint inhibition have not been reported.

Objective: This study aimed to compare survival outcomes following surgical resection of anorectal melanoma between patients who received immune checkpoint inhibition and patients who did not.

Design: This study is a retrospective analysis of data from a prospectively maintained database.

Setting: This study was conducted at a comprehensive cancer center.

Patients: Patients who underwent surgery for anorectal melanoma between 2006 and 2017 were included. They were stratified according to the use of immune checkpoint inhibition.

Main Outcome Measures: The primary outcomes measured were overall and disease-specific survival.

Results: Of the 47 patients included in the analysis, 29 (62%) received immune checkpoint inhibition therapy. Twenty-two (76%) of the 29 patients received immune checkpoint inhibition after detection of metastasis or disease progression rather than in the neoadjuvant or adjuvant setting. Overall survival did not differ significantly between patients who received immune checkpoint inhibition therapy and patients who did not (median, 52 and 20 months; 5-year rate, 41% vs 35%; p = 0.25). Disease-specific survival also did not differ significantly. Our analysis did not identify any clinical or pathological features associated with response to immune checkpoint inhibition therapy or with survival.

Limitations: This study was limited by its relatively small sample and retrospective design and by the heterogeneous treatment regimen in the immune checkpoint inhibition group.

Conclusions: Immune checkpoint inhibition therapy by itself does not appear to improve survival in patients who undergo resection or excision of anorectal melanoma. Combinations of immune checkpoint inhibition with other therapeutic modalities warrant further investigation. See Video Abstract at http://links.lww.com/DCR/B499. MELANOMA DE LA MUCOSA ANORRECTAL EN LA ERA DE LOS INHIBIDORES DEL PUNTO DE CONTROL INMUNOLÓGICO: ¿DEBEMOS DE CAMBIAR NUESTRO PARADIGMA DEL MANEJO QUIRÚRGICO: El advenimiento de la terapia de los inhibidores del punto de control inmunológico, han mejorado dramáticamente la supervivencia en pacientes con melanoma de piel. No se han informado los resultados de supervivencia después de la resección del melanoma anorrectal, tratado con inhibidores del punto de control inmunológico.Comparar los resultados de supervivencia después de la resección quirúrgica de melanoma anorrectal entre pacientes que recibieron y no recibieron inhibidores del punto de control inmunológico.Análisis retrospectivo de una base de datos mantenida prospectivamente.Centro oncológico integral.Pacientes que se sometieron a cirugía por melanoma anorrectal entre 2006 y 2017. Los pacientes fueron estratificados según el uso de inhibidores del punto de control inmunológico.Supervivencia global y específica de la enfermedad.De los 47 pacientes incluidos en el análisis, 29 (62%) recibieron terapia de inhibidores del punto de control inmunológico. Veintidós (76%) de los 29 pacientes recibieron inhibidores del punto de control inmunológico después de la detección de metástasis o progresión de la enfermedad, en vez de administración adyuvante o neoadyuvante. La supervivencia global no varió significativamente entre los pacientes que recibieron o no recibieron terapia de inhibidores del punto de control inmunológico (mediana, 52 y 20 meses, respectivamente; tasa a 5 años, 41% frente a 35%, respectivamente; p = 0,25). La supervivencia específica de la enfermedad tampoco varió significativamente. Nuestro análisis no identificó ninguna característica clínica o patológica, asociada con la respuesta a la terapia de inhibidores del punto de control inmunológico o con la supervivencia.Muestra relativamente pequeña y diseño retrospectivo. Régimen de tratamiento heterogéneo en el grupo de inhibidores del punto de control inmunológico.La terapia por sí sola, de inhibidores del punto de control inmunológico, no parece mejorar la supervivencia en pacientes que se someten a resección o escisión de melanoma anorrectal. Las combinaciones de inhibidores del punto de control inmunológico con otras modalidades terapéuticas, merecen una mayor investigación. Consulte Video Resumen en http://links.lww.com/DCR/B499. (Traducción-Dr. Fidel Ruiz Healy).
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http://dx.doi.org/10.1097/DCR.0000000000001872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097722PMC
May 2021

FABP5 Deficiency Impairs Mitochondrial Function and Aggravates Pathological Cardiac Remodeling and Dysfunction.

Cardiovasc Toxicol 2021 Apr 30. Epub 2021 Apr 30.

Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.

Fatty acid-binding protein 5 (FABP5) is an important member of the FABP family and plays a vital role in the metabolism of fatty acids. However, few studies have examined the role of FABP5 in pathological cardiac remodeling and heart failure. The aim of this study was to explore the role of FABP5 in transverse aortic constriction (TAC)-induced pathological cardiac remodeling and dysfunction in mice. Quantitative RT-PCR (qRT-PCR) and western blotting (WB) analysis showed that the levels of FABP5 mRNA and protein, respectively, were upregulated in hearts of the TAC model. Ten weeks after TAC in FABP5 knockout and wild type control mice, echocardiography, histopathology, qRT-PCR, and WB demonstrated that FABP5 deficiency aggravated cardiac injury (both cardiac hypertrophy and fibrosis) and dysfunction. In addition, transmission electron microscopy, ATP detection, and WB revealed that TAC caused severe impairment to mitochondria in the hearts of FABP5-deficient mice compared with that in control mice. When FABP5 was downregulated by siRNA in primary mouse cardiac fibroblasts, FABP5 silencing increased oxidative stress, reduced mitochondrial respiration, and increased the expression of myofibroblast activation marker genes in response to treatment with transforming growth factor-β. Our findings demonstrate that FABP5 deficiency aggravates cardiac pathological remodeling and dysfunction by damaging cardiac mitochondrial function.
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http://dx.doi.org/10.1007/s12012-021-09653-2DOI Listing
April 2021

Clinical exome sequencing identifies novel compound heterozygous mutations of the gene in primary infertile women with fertilization failure.

Gynecol Endocrinol 2021 Apr 27:1-6. Epub 2021 Apr 27.

Department of Medical Genetics, Linyi People's Hospital, Linyi, PR China.

Objective: The genetic basis of fertilization failure after intracytoplasmic sperm injection (ICSI) is largely unknown and the aim of this study is to investigate the genetic causes of fertilization failure in primary infertile women.

Methods: Six affected women diagnosed with infertility and fertilization failure were recruited. The genetically pathogenic factor of their fertilization failures were investigated by clinical exome sequencing. One hundred healthy controls were verified by Sanger sequencing.

Results: Novel compound heterozygous mutations c.625G > T and c.759-2A > G of in one affected individual were revealed by clinical exome sequencing. Trios analysis of the mutations represented an autosomal recessive pattern. The nonsense mutation c.625G > T (p.Glu209*) indicated the truncation of the WEE2 protein and c.759-2A > G was predicted to affect the splicing.

Conclusions: The novel variants extend the spectrum of mutations, which promotes the prognostic value of testing for mutations in infertile women with fertilization failure.
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http://dx.doi.org/10.1080/09513590.2021.1916458DOI Listing
April 2021

Cognitive Behavioral Therapy for Autism Spectrum Disorders: A Systematic Review.

Pediatrics 2021 May;147(5)

Contributed equally as co-first authors.

Context: In several studies, authors have reported on cognitive behavioral therapy (CBT) for children and adolescents with autism spectrum disorders (ASDs), but inconsistent treatment effectiveness was revealed from these studies.

Objective: To evaluate the effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD by using a meta-analytic approach.

Data Sources: Data sources included PubMed, Embase, and the Cochrane Library.

Study Selection: We selected randomized controlled trials (RCTs) in which authors reported effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD from database inception to May 2019.

Data Extraction: For each study, 2 authors extracted data on the first author's surname, publication year, country, sample size, mean age, CBT target, intervention, outcome measurement, follow-up duration, and investigated outcomes.

Results: Forty-five RCTs and 6 quasi RCTs of 2485 children and adolescents with ASDs were selected for the final meta-analysis. There was no significant difference between CBT and control for symptoms related to ASD based on self-reported outcomes (standard mean difference: -0.09; 95% confidence interval: -0.42 to 0.24; = .593), whereas CBT significantly improved the symptoms related to ASD based on informant-reported outcomes, clinician-rated outcomes, and task-based outcomes. Moreover, the pooled standard mean differences indicated that CBT has no significant effect on symptoms of social-emotional problems based on self-reported outcomes.

Limitations: The quality of included studies was low to modest, significant heterogeneity among the included studies for all investigated outcomes was detected, and publication bias was inevitable.

Conclusions: These findings indicate that CBT may significantly improve the symptoms of ASD and social-emotional problems in children or adolescents with ASD.
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http://dx.doi.org/10.1542/peds.2020-049880DOI Listing
May 2021

Relationship between Artificial Intelligence-Based General Anesthetics and Postoperative Cognitive Dysfunction.

J Healthc Eng 2021 1;2021:5553029. Epub 2021 Apr 1.

Nankai University, Tianjin 300071, China.

Postoperative cognitive dysfunction (POCD) refers to the complications of the central nervous system before and after surgery in patients without mental disorders. Many studies have shown that surgical anesthesia may cause POCD, especially in elderly patients. This article aims to study the relationship between artificial intelligence-based general anesthetics and postoperative cognitive dysfunction. This article first describes and classifies artificial intelligence, introduces its realization method, machine learning algorithms, and briefly introduces the basic principles of regression and classification methods in machine learning; then, the principles and techniques of general anesthetics are proposed. The pathogenesis of postoperative cognitive dysfunction (POCD) is explained in detail. Finally, the effect of anesthetics on postoperative cognitive dysfunction is obtained from both inhaled anesthetics and intravenous anesthetics. The impact on postoperative cognitive function is explained. The experimental results in this article show that there is no statistically significant difference in the two groups of patients' age, gender ratio, body mass index, education level, preoperative comorbidities, and other general indicators. Through the use of EEG bispectral index monitors to monitor the depth of anesthesia and postoperative cognitive dysfunction, first, there was no obvious relationship between the occurrence of postoperative cognitive dysfunction at 1, 5, 10, and 50 days and discharge time. The comprehensive monitoring group can reduce the clinical dose of preventive medication and cis-atracurium and shorten the patient's recovery time, extubation time, and recovery time. In addition, it can also reduce the increase of serum protein S100 in elderly patients and reduce the incidence of early postoperative cognitive dysfunction.
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http://dx.doi.org/10.1155/2021/5553029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032528PMC
April 2021

Application of Multilayer Network Models in Bioinformatics.

Front Genet 2021 31;12:664860. Epub 2021 Mar 31.

Department of Radiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.

Multilayer networks provide an efficient tool for studying complex systems, and with current, dramatic development of bioinformatics tools and accumulation of data, researchers have applied network concepts to all aspects of research problems in the field of biology. Addressing the combination of multilayer networks and bioinformatics, through summarizing the applications of multilayer network models in bioinformatics, this review classifies applications and presents a summary of the latest results. Among them, we classify the applications of multilayer networks according to the object of study. Furthermore, because of the systemic nature of biology, we classify the subjects into several hierarchical categories, such as cells, tissues, organs, and groups, according to the hierarchical nature of biological composition. On the basis of the complexity of biological systems, we selected brain research for a detailed explanation. We describe the application of multilayer networks and chronological networks in brain research to demonstrate the primary ideas associated with the application of multilayer networks in biological studies. Finally, we mention a quality assessment method focusing on multilayer and single-layer networks as an evaluation method emphasizing network studies.
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http://dx.doi.org/10.3389/fgene.2021.664860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044439PMC
March 2021

Predicting nucleation using machine learning in the Ising model.

Phys Rev E 2021 Mar;103(3-1):033305

Department of Physics, Boston University, Boston, Massachusetts 02215, USA and Department of Physics, Clark University, Worcester, Massachusetts 01610, USA.

We use a convolutional neural network (CNN) and two logistic regression models to predict the probability of nucleation in the two-dimensional Ising model. The three methods successfully predict the probability for the nearest-neighbor Ising model for which classical nucleation is observed. The CNN outperforms the logistic regression models near the spinodal of the long-range Ising model, but the accuracy of its predictions decreases as the quenches approach the spinodal. An occlusion analysis suggests that this decrease is due to the vanishing difference between the density of the nucleating droplet and the background. Our results are consistent with the general conclusion that predictability decreases near a critical point.
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http://dx.doi.org/10.1103/PhysRevE.103.033305DOI Listing
March 2021

Recruitment of KMT2C/MLL3 to DNA damage sites mediates DNA damage responses and regulates PARP inhibitor sensitivity in cancer.

Cancer Res 2021 Apr 14. Epub 2021 Apr 14.

Department of Cancer Biology, Wake Forest University School of Medicine

When recruited to promoters, histone 3 lysine 4 (H3K4) methyltransferases KMT2 (KMT2A-D) activate transcription by opening chromatin through H3K4 methylation. Here we report that KMT2 mutations occur frequently in non-small cell lung cancer (NSCLC) and are associated with high mutation loads and poor survival. KMT2C regulated DNA damage responses (DDR) through direct recruitment to DNA damage sites by Ago2 and small noncoding DNA damage response RNA, where it mediates H3K4 methylation, chromatin relaxation, secondary recruitment of DDR factors, and amplification of DDR signals along chromatin. Furthermore, by disrupting homologous recombination (HR)-mediated DNA repair, KMT2C/D mutations sensitized NSCLC to Poly(ADP-Ribose) Polymerase inhibitors (PARPi), whose efficacy is unclear in NSCLC due to low BRCA1/2 mutation rates. These results demonstrate a novel, transcription-independent role of KMT2C in DDR and identify high-frequency KMT2C/D mutations as much-needed biomarkers for PARPi therapies in NSCLC and other cancers with infrequent BRCA1/2 mutations.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0688DOI Listing
April 2021

DDAH2 suppresses RLR-MAVS-mediated innate antiviral immunity by stimulating nitric oxide-activated, Drp1-induced mitochondrial fission.

Sci Signal 2021 Apr 13;14(678). Epub 2021 Apr 13.

Department of Immunology, School of Basic Medical Sciences; Advanced Innovation Center for Human Brain Protection, Beijing Key Laboratory for Cancer Invasion and Metastasis, Department of Oncology, Capital Medical University, Beijing 100069, China.

The RIG-I-like receptor (RLR) signaling pathway is pivotal for innate immunity against invading viruses, and dysregulation of this molecular cascade has been linked to various diseases. Here, we identified dimethylarginine dimethylaminohydrolase 2 (DDAH2) as a potent regulator of the RLR-mediated antiviral response in human and mouse. Overexpression of DDAH2 attenuated RLR signaling, whereas loss of DDAH2 function enhanced RLR signaling and suppressed viral replication ex vivo and in mice. Upon viral infection, DDAH2 relocated to mitochondria, where it induced the production of nitric oxide (NO) and the activation of dynamin-related protein 1 (Drp1), which promoted mitochondrial fission and blocked the activation of innate immune responses mediated by mitochondrial antiviral signaling (MAVS). TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. Our study thus identifies a reciprocal inhibitory loop between the DDAH2-NO cascade and the RLR signaling pathway that fine-tunes the antiviral immune response.
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http://dx.doi.org/10.1126/scisignal.abc7931DOI Listing
April 2021

A brief note on the potential of homo-oligo-dsDNA and hetero-oligo-dsDNA based on their binder-free electrochemical characteristics on gold electrode.

Anal Chim Acta 2021 May 12;1157:338377. Epub 2021 Mar 12.

The State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China. Electronic address:

In this fundamental research, we found that homo-oligo based dsDNA holds potential electrochemical characteristics in comparison to hetero-oligo based dsDNA which can be exploited in voltammetric and impedimetric biosensors. We prepared a homo-oligo based dsDNA from 20 deoxyribonucleotides of adenine, guanine, cytosine, and thymine (A20, G20, C20, and T20 respectively) and a hetero-oligo based dsDNA from two partially complementary oligos (5'-TTT TTT CAT CTA TCA ACA TCA GTC TGA TAA GCT ATA GAA GC-3' and 5'-TTT TTT ATA GCT TTG ATA GA-3'. Electrochemical impedance spectroscopy in 1 mM 0.1 M K[Fe(CN)]/KCl showed that Au working electrode modified with hetero-oligo based dsDNA (Au/hetero-oligo-dsDNA) was more resistive toward charge transfer of Fe(CN) compared to Au working electrode modified with homo-oligo based dsDNA (Au/homo-oligo-dsDNA). Additionally, cyclic voltammetry and linear sweep voltammetry showed that Au/homo-oligo-dsDNA produced quantifiable anodic and cathodic peak currents which were not observed for Au/hetero-oligo-dsDNA. Nyquist and Bode plots derived from electrochemical impedance spectroscopy on three different electroactive areas (0.0705, 0.0747 and 0.0837 cm) of Au working electrode showed no significant change in the capacitive behavior of Au/homo-oligo-dsDNA and Au/hetero-oligo-dsDNA in a linear range of frequency (10-100 Hz).
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http://dx.doi.org/10.1016/j.aca.2021.338377DOI Listing
May 2021

3D printing Silk-Gelatin-Propanediol scaffold with enhanced osteogenesis properties through p-Smad1/5/8 activated Runx2 pathway.

J Biomater Sci Polym Ed 2021 Apr 8:1-13. Epub 2021 Apr 8.

Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan, 410073, PR China.

The application of 3D printing technology in tissue engineering has become increasingly important. However, due to the limitations of bio-ink, there are still some remaining problems. For example, the major challenge for ideal bio-ink is to maintain stable 3D structure and good biocompatibility in the meantime while conventional gels are week and nearly unprintable. So, the development of new bio-ink material with improved rheological and mechanical properties is highly demanded to avoid compromising biocompatibility for tissue engineering. Silk fibroin (SF), a natural degradable polymer, is considered to be a proper material for the preparation of bio-inks. We used SF, gelatin, and polyols as raw materials to fabricate bio-inks and scaffolds. We evaluated the rheological properties and printability of bio-inks with a rotational rheometer and a 3D printer. The scaffolds were prepared by crosslinking and freeze-drying technologies. The biocompatibility and osteoinductive functions of scaffolds were investigated by evaluating proliferation, osteogenic differentiation and related cell signaling of cultured MC3T3-E1 cells. The results showed that the scaffolds using SF, Gel and propanediol (PG) not only had good rheological properties and storage modulus, but also could better enhance osteogenic specific genes expression mediated by Smad1/5/8 and Runx2 pathways. What is more, morphological characterization showed that α-mem incubation could help scaffold form porous structure on its surface, which could shed a light on a new 3D bio-printed bone repair scaffold with both naturally emerged and CAD-designed porous structure. Our findings provide a potential biomaterial for the treatment of bone tissue regeneration.
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http://dx.doi.org/10.1080/09205063.2021.1912977DOI Listing
April 2021

Experimental investigation of quasi-static mode degradation in a high power large mode area fiber amplifier.

Opt Express 2021 Mar;29(6):7986-7997

In this work, quasi-static mode degradation in high power fiber amplifiers has been investigated experimentally. An increase of M from 1.3 to 2.6 with distortion of the beam profile is observed, which results in the signal spectra and backward light characterization departing from the traditional phenomena. The amplifier has been operated at the same input pump power of 705 W for nearly 2.2 hours to investigate the relationship between quasi-static mode degradation and photodarkening. The evolution of M factor/beam profile, mode correlation coefficient and output laser power at different working times indicate that the quasi-static mode degradation in the high power fiber amplifiers is dependent on photodarkening and evolves on the scale of tens of minutes. A visible green light has been injected to photobleach the gain fiber for 19 hours, which reveals that the quasi-static mode degradation has been suppressed simultaneously. To the best of our knowledge, this is the first detail report of photodarkening-induced quasi-static degradation in high power fiber amplifiers.
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http://dx.doi.org/10.1364/OE.415690DOI Listing
March 2021

Investigation on conformational variation and activity of trypsin affected by black phosphorus quantum dots via multi-spectroscopy and molecular modeling.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 26;256:119746. Epub 2021 Mar 26.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, College of Chemistry and Materials, Nanning Normal University, Nanning 530001, PR China. Electronic address:

Binding interaction between black phosphorus quantum dots (BPQDs) and trypsin was researched deeply to illustrate the variations on conformation and activity of trypsin affected by BPQDs via multi-spectroscopy and molecular modeling. Experimental results implied that inherent fluorescence of trypsin was quenched by BPQDs via static fluorescence quenching mode. BPQDs bound with trypsin to construct ground-state complex under the binding forces of van der Waal interaction and hydrophobic interaction, resulting in the conformational change of trypsin to be more hydrophilic and incompact. The result of molecular modeling indicated that BPQDs interacted with trypsin at its allosteric site and inhibited the activity of trypsin via non-competitive manner. Finally, BPQDs efficiently inhibited the digestion activity of trypsin on human serum albumin, human cervical carcinoma HeLa cells, and human lung adenocarcinoma A549 cells. This work not only explores the in-depth understanding on the influence of BPQDs on proteinases but also paves the way for further application of BPQDs on human beings for diseases treatments.
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http://dx.doi.org/10.1016/j.saa.2021.119746DOI Listing
July 2021

Application of Seq2Seq Models on Code Correction.

Front Artif Intell 2021 19;4:590215. Epub 2021 Mar 19.

Department of Computer Science, Boston University, Boston, MA, United States.

We apply various seq2seq models on programming language correction tasks on Juliet Test Suite for C/C++ and Java of Software Assurance Reference Datasets and achieve 75% (for C/C++) and 56% (for Java) repair rates on these tasks. We introduce pyramid encoder in these seq2seq models, which significantly increases the computational efficiency and memory efficiency, while achieving similar repair rate to their nonpyramid counterparts. We successfully carry out error type classification task on ITC benchmark examples (with only 685 code instances) using transfer learning with models pretrained on Juliet Test Suite, pointing out a novel way of processing small programming language datasets.
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http://dx.doi.org/10.3389/frai.2021.590215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017285PMC
March 2021

Advances in the Identification of Circular RNAs and Research Into circRNAs in Human Diseases.

Front Genet 2021 19;12:665233. Epub 2021 Mar 19.

Department of Radiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a closed-loop structure that are mainly produced by variable processing of precursor mRNAs (pre-mRNAs). They are widely present in all eukaryotes and are very stable. Currently, circRNA studies have become a hotspot in RNA research. It has been reported that circRNAs constitute a significant proportion of transcript expression, and some are significantly more abundantly expressed than other transcripts. CircRNAs have regulatory roles in gene expression and critical biological functions in the development of organisms, such as acting as microRNA sponges or as endogenous RNAs and biomarkers. As such, they may have useful functions in the diagnosis and treatment of diseases. CircRNAs have been found to play an important role in the development of several diseases, including atherosclerosis, neurological disorders, diabetes, and cancer. In this paper, we review the status of circRNA research, describe circRNA-related databases and the identification of circRNAs, discuss the role of circRNAs in human diseases such as colon cancer, atherosclerosis, and gastric cancer, and identify remaining research questions related to circRNAs.
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http://dx.doi.org/10.3389/fgene.2021.665233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017306PMC
March 2021

A Novel Method for Accurate Quantification of Split Glomerular Filtration Rate Using Combination of Tc-99m-DTPA Renal Dynamic Imaging and Its Plasma Clearance.

Dis Markers 2021 13;2021:6643586. Epub 2021 Mar 13.

The Second Hospital of Anhui Medical University, Hefei, China.

Purpose: To precisely quantify split glomerular filtration rate by Tc-99m-DTPA renal dynamic imaging and plasma clearance in order to increase its consistency among doctors.

Methods: Tc-99m-DTPA renal dynamic imaging was performed according to the conventional radionuclide renal dynamic imaging by five double-blinded doctors independently and automatically calculated split GFR, namely, gGFR. Moreover, the conventional radionuclide renal dynamic imaging was assessed to only outline the kidney, blank background, and automatically calculated split GFR, gGFR'. The total GFR value of patients, tGFR, was obtained by the double-plasma method. According to the formula, Precise GFR (pGFR) = gGFR'/(gGFR' + gGFR') × tGFR. The precise GFR value of the divided kidney, pGFR, was calculated. The Kendall's test was used to compare the consistency of gGFR and pGFR drawn by five physicians.

Results: According to Kendall's consistency test, Kendall's coefficient of concordance was 0.834, = 0.0001 using conventional method. The same five doctors used blank background again and the same standard Gates method to draw the kidneys, which automatically calculated gGFR'. Using input formula, the pGFR was calculated and Kendall's consistency test (Kendall's coefficient of concordance = 0.956, = 0.0001).

Conclusion: The combination of Tc-99m-DTPA renal dynamic imaging combined with the double-plasma method could achieve accurate split GFR, and because of the omission of influence factors, the consistency of pGFR obtained by different doctors using this method was significantly higher than that of conventional Tc-99m-DTPA renal dynamic imaging.
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http://dx.doi.org/10.1155/2021/6643586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984922PMC
March 2021

[Effect of combined treatment with acupuncture, moxibustion and medication on endometrial receptivity and expression of serum HOXA10 in polycystic ovary syndrome of kidney deficiency and blood stagnation].

Zhongguo Zhen Jiu 2020 Nov;40(11):1154-8

School of Acupuncture and Moxibustion, Fujian University of TCM.

Objective: To compare the clinical effect of the combined treatment of acupuncture, moxibustion, Chinese herbal medicine and western medication and simple western medication on polycystic ovary syndrome (PCOS) of kidney deficiency and blood stagnation pattern and explore the effect on endometrial receptivity and the expression of serum homeobox gene A10 (HOXA10).

Methods: A total of 60 patients with PCOS of kidney deficiency and blood stagnation pattern were randomized into a combined treatment group and a western medication group, 30 cases in each one. In the western medication group, on the fifth day of menstruation, clomiphene citrate tablets were taken orally, 50 mg each time, once daily, consecutively for 5 days. On the day when the follicle diameter was ≥ 18 mm, chorionic gonadotrophin for muscular injection, a dose of 10 000 U was given. Before sleep, the aspirin enteric-coated tablets were taken orally, 50 mg (except during menstruation). In the combined treatment group, on the base of the treatment as the western medication group, acupuncture and moxibustion were adopted and the Chinese herbal for tonifying the kidney and activating blood circulation was taken orally. The acupoints were Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Zigong (EX-CA 1), etc. Acupuncture was remained for 30 min each time, once every two days and discontinued during menstruation. Chinese herbal was given from the 3rd day of menstruation till the onset of the next menstruation, one dose each day. After consecutive treatment for 3 menstrual cycles in the two groups, the real-time polymerase chain reaction (RT-PCR) method was adopted to determine the expression of serum HOXA10 before and after treatment in the patients of the two groups. The endometrial thickness at ovulatory phase, uterine arterial flow 7 days after ovulation [including uterine arterial pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV)/end diastolic velocity (EDV), meaning S/D], pregnancy rate and the score of Chinese medicine symptoms before and after treatment were compared in the patients between the two groups.

Results: ① After treatment, the expression of serum HOXA10 was higher than that before treatment in the patients of the two groups (<0.01). The increase range in the combined treatment group was larger than the western medication group (<0.01). ② After treatment, the endometrial thickness at the ovulatory phase was increased in the patients of the two groups (<0.01). The increase range of the endometrial thickness in the combined treatment group was larger than the western medication group (<0.01). ③ The pregnancy rate was 46.7% (14/30) in the combined treatment group, higher than 26.7% (8/30) in the western medication group (<0.05). ④ After treatment, the bilateral uterine arterial PI, RI and S/D values, as well as TCM symptom score were all lower than those before treatment in the patients of the two groups (<0.01). The decrease range of each index in the combined treatment group was greater than the western medication group (<0.01, <0.05).

Conclusion: The combined treatment with acupuncture, moxibustion and medication effectively improves endometrial receptivity and uterine arterial flow in the patients with PCOS of kidney deficiency and blood stagnation pattern and increases pregnancy rate. The therapeutic effect is better than the simple western medication and its mechanism is probably related to the regulation of serum HOXA10 expression.
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http://dx.doi.org/10.13703/j.0255-2930.20191022-k0006DOI Listing
November 2020

[Effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome with different glucose tolerance status].

Zhongguo Zhen Jiu 2021 Feb;41(2):155-60

Department of TCM, Fujian Maternal and Child Health Hospital Affiliated to Fujian Medical University, Fuzhou 350001, China.

Objective: To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).

Methods: A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared.

Results: Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (<0.05), and NO was increased (<0.05) in the two groups; FPG, 2hPG, FINS and HOMA-IR after treatment were decreased in the IGT group (<0.05), the improvement of the above indexes in the IGT group was more significant than that in the NGT group (<0.05). After treatment, the serum levels of ADMD, ET-1 and MDA were decreased (<0.05), and NO was increased (<0.05) in the obese subgroup. In the IGT group, the improvement of serum ADMD, ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (<0.05). In the NGT group, the improvement of ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (<0.05).

Conclusion: Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.
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http://dx.doi.org/10.13703/j.0255-2930.20200110-k0007DOI Listing
February 2021

Altered integrity of hepatocyte tight junctions in rats with triptolide-induced cholestasis.

Chin J Nat Med 2021 Mar;19(3):188-194

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg·d) induced the occurrence of cholestasis in female Wistar rats, as evidenced by increased serum levels of γ-glutamyl transpeptidase (γ-GGT), alkaline phosphatase (ALP) and hepatic total bile acids (TBAs). In addition, the heptocyte polarity associated with the strcture of tight junctions (TJs) was disrupted in both rats and sandwich-cultured primary hepatocytes. Immunoblotting revealed decreased expression of the TJ-associated proteins occludin, claudin-1, and zonula occludens protein (ZO-1), and downregulated mRNA levels of these TJs was also detected by real-time PCR. An immunofluorescence analysis showed abnormal subcellular localization of occludin, claudin-1 and ZO-1, which was also confirmed by transmission electron microscopy. Moreover, the concentration of FITC-dextran, a marker of paracellular penetration, was found to increase rapidly in bile increased rapidly (within 6 minutes) after treatment with TP, which indicated the functional impairment of TJs. Taken together, these results suggest that the administration of TP for 28 consecutive days to rats could induce cholestatic injury in the liver, and the increased paracellular permeability might play an important role in these pathological changes.
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http://dx.doi.org/10.1016/S1875-5364(21)60020-1DOI Listing
March 2021

Regulating Work Function of [CaAlO]:4e Electrides Via Changing Solvated Electron Characters.

J Phys Chem Lett 2021 Apr 25;12(13):3274-3280. Epub 2021 Mar 25.

School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.

Since electrides behave as electron donors in catalytic reactions and device substrates due to the anionic electrons localized in periodic interstitial spaces, their work functions (Φ) could be used as key indicators in describing the high electron-donating power. Taking the [CaAlO]:4e electride as an example, we here propose a new computational scheme of Φ and, further, characterize Φ of the bulk derivative structures of the electride for clarifying the relationship between structural characteristics and Φ. Results indicate that the external strain hardly affects Φ, but the interior heteroatom-doping and distortion bring about significant changes. All these unique variations of the bulk Φ are governed by the distribution and solvation character of anionic electrons in the cage conduction band states. The mechanism of regulating Φ revealed in this work may play a role in the rational design of electride-based catalysts and devices with a superior performance.
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http://dx.doi.org/10.1021/acs.jpclett.1c00180DOI Listing
April 2021

Development and validation for prognostic nomogram of epithelial ovarian cancer recurrence based on circulating tumor cells and epithelial-mesenchymal transition.

Sci Rep 2021 Mar 22;11(1):6540. Epub 2021 Mar 22.

Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

We aimed to determine the prognosis value of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal, and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan-Meier analysis among the training group (n = 114) and validation group (n = 38). By regression screening, both CTC counts (HR 1.187; 95% CI 1.098-1.752; p = 0.012) and M-CTC (HR 1.098; 95% CI 1.047-1.320; p = 0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites, and CA-125 were also selected (p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive values for the nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts (p = 0.0241), M-CTC (p = 0.0107), and the nomogram (p = 0.0021) were drawn with significant differences. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016.
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http://dx.doi.org/10.1038/s41598-021-86122-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985206PMC
March 2021

Increased Nuclear Transporter KPNA2 Contributes to Tumor Immune Evasion by Enhancing PD-L1 Expression in PDAC.

J Immunol Res 2021 1;2021:6694392. Epub 2021 Mar 1.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and is known for its high resistance and low response to treatment. Tumor immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Karyopherin alpha 2 (KPNA2), a member of the nuclear transporter family, is elevated in multiple human cancers and accelerates carcinogenesis. However, the specific role of KPNA2 in PDAC remains unclear. In this study, we found that expression of KPNA2 was significantly upregulated in PDAC compared to adjacent nontumor tissue and its high expression was correlated with poor survival outcome by analyzing the GEO datasets. Similar KPNA2 expression pattern was also found in both human patient samples and KPC mouse models through IHC staining. Although KPNA2 knockdown failed to impair the vitality and migration ability of PDAC cells , the tumor growth was significantly impeded and the expression of immune checkpoint ligand PD-L1 was reduced by silencing KPNA2. Furthermore, we uncovered that KPNA2 modulated the expression of PD-L1 by mediating nuclear translocation of STAT3. Collectively, our data suggested that KPNA2 has the potential to serve as a promising biomarker for diagnosis in PDAC.
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http://dx.doi.org/10.1155/2021/6694392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939744PMC
March 2021

Effects of transjugular intrahepatic portosystemic shunt using the Viatorr stent on hepatic reserve function in patients with cirrhosis.

World J Clin Cases 2021 Mar;9(7):1532-1542

Department of Gastroenterology, General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China.

Background: As transjugular intrahepatic portosystemic shunt (TIPS) creation alters the hemodynamic status of the portal system, whether reduced portal blood supply affects the synthetic reserve function of the liver has been the focus of clinical attention. Since the Viatorr stent entered the Chinese market in 2015, it has not yet been widely used in clinical practice. Further, unlike other countries, the main cause of liver cirrhosis in China is viral hepatitis. Therefore, use of the Viatorr stent to establish a TIPS channel in patients with liver cirrhosis with differing etiologies is of great clinical interest.

Aim: To investigate factors affecting changes in liver reserve function after TIPS Viatorr stent implantation.

Methods: Clinical data from 200 patients with cirrhotic portal hypertension who received TIPS treatment from March 2016 to March 2020 were analyzed retrospectively. The patients were divided into three groups (A-C), according to their disease etiology, with post-hepatitis, autoimmune, and alcoholic cirrhosis, respectively. Preoperative and postoperative liver and renal function and coagulation data, Child-Pugh grade, and model for end-stage liver disease (MELD) scores were collected. Statistical analyses were performed using the -test or chi-square test. The incidence and of hepatic encephalopathy and patient survival were calculated using Kaplan-Meier method.

Results: The surgical success rate was 100%, with mean portal pressure gradient (mmHg) decreasing from 25.5 ± 5.22 to 10.04 ± 2.76 ( = 45.80; < 0.001). After 24 mo, the cumulative incidence of hepatic encephalopathy in group A was significantly lower than that in group B/C, while the cumulative survival rate was significantly higher in group A than in group B/C ( < 0.05 for both). The Child-Pugh score for group A was 6.96 ± 1.21, which was significantly better than those of groups B (7.42 ± 0.99; = -2.44; = 0.016) and C (7.52 ± 1.12; = -2.67; = 0.009). Further, the MELD score for group A (9.62 ± 2.19) was significantly better than those for groups B (10.64 ± 1.90; = -2.92; = 0.004) and C (10.82 ± 2.01; = -3.29; = 0.001).

Conclusion: Insertion of 8 mm internal diameter Viatorr stent has no significant effects on liver reserve function. Changes of liver reserve function in the medium and long term may be related to the etiology and treatment of portal hypertension.
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http://dx.doi.org/10.12998/wjcc.v9.i7.1532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942045PMC
March 2021

Fasciculation score: a sensitive biomarker in amyotrophic lateral sclerosis.

Neurol Sci 2021 Mar 11. Epub 2021 Mar 11.

Department of Neurology, First Hospital, Shanxi Medical University, No.85, Jiefang South Street, Taiyuan, 030000, People's Republic of China.

Objective: The aim of our study was to elucidate the characteristic of fasciculation distributions in amyotrophic lateral sclerosis (ALS) using a fasciculation score (FS) of muscle ultrasound (MUS) and to compare the diagnostic values of three MUS fasciculation parameters in patients.

Methods: Thirty ALS patients, 16 ALS mimics, and 10 healthy subjects were involved. MUS of unilateral 10 muscles in each patient and needle electromyography (EMG) of total 204 muscles were performed to detect fasciculations and spontaneous activity respectively in ALS. Control groups underwent only MUS. Fasciculation was graded semiquantitatively with FS.

Results: Three hundred fifty muscles in ALS and 260 in controls were examined. The fasciculation detection rates, total FS, the number of muscles with fasciculation, and the total number of fasciculations in ALS were all significantly higher than those of controls (P < 0.001). ALS patients exhibited a multifocal continuous pattern of fasciculation in limbs, whereas there were few fasciculations in controls. Compared with other parameters, total FS had the largest area under the curve (AUC) (AUC = 0.899, P < 0.001) in ALS diagnosis. The detection rates of lower motor neuron (LMN) acute lesions by MUS (70.6%) and EMG (72.1%) were nearly the same, and a positive correlation between the FS and spontaneous activity grades (P < 0.001, r = 0.359) was proved.

Conclusions: ALS patients exhibited the multifocal continuous pattern of fasciculation in limbs. FS showed high sensitivity and specificity in differentiating ALS from non-ALS patients, and the optimal cut-off value was determined as 4. The combination of MUS and EMG can provide additional information about specific muscles.
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http://dx.doi.org/10.1007/s10072-021-05166-6DOI Listing
March 2021

MicroRNA-223-3p inhibits vascular calcification and the osteogenic switch of vascular smooth muscle cells.

J Biol Chem 2021 Feb 26:100483. Epub 2021 Feb 26.

Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. Electronic address:

Vascular calcification is the ectopic deposition of calcium hydroxyapatite minerals in arterial wall which involves the transdifferentiation of vascular smooth muscle cells (VSMCs) toward an osteogenic phenotype. However, the underlying molecular mechanisms regulating the VSMC osteogenic switch remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in vascular calcification. miRNA-seq transcriptome analysis identified miR-223-3p as a candidate miRNA in calcified mouse aortas. MiR-223-3p knockout aggravated calcification in both medial and atherosclerotic vascular calcification models. Further, RNA-seq transcriptome analysis verified JAK-STAT and PPAR signaling pathways were upregulated in both medial and atherosclerotic calcified aortas. Overlapping genes in these signaling pathways with predicted target genes of miR-223-3p derived from miRNA databases, we identified signal transducer and activator of transcription 3 (STAT3) as a potential target gene of miR-223-3p in vascular calcification. In vitro experiments showed that miR-223-3p blocked interleukin-6 (IL-6)/STAT3 signaling, thereby preventing the osteogenic switch and calcification of VSMCs. In contrast, overexpression of STAT3 diminished the effect of miR-223-3p. Taken together, the results indicate a protective role of miR-223-3p that inhibits both medial and atherosclerotic vascular calcification by regulating IL-6/STAT3 signaling mediated VSMC transdifferentiation.
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http://dx.doi.org/10.1016/j.jbc.2021.100483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039724PMC
February 2021

Sodium Fluoride-18 and Radium-223 Dichloride Uptake Colocalize in Osteoblastic Mouse Xenograft Tumors.

Cancer Biother Radiopharm 2021 Mar 25;36(2):133-142. Epub 2021 Feb 25.

Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Patients with osteoblastic bone metastases are candidates for radium-223 (RaCl) therapy and may undergo sodium fluoride-18 (F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. F-NaF has been shown to predict RaCl uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of F-NaF and RaCl in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. F-NaF and RaCl were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. F and Ra accumulated in proportional amounts in whole Hu09-H3 tumors ( = 0.82) and in microcalcified regions within these tumors ( = 0.87). Intratumor distributions of F and Ra were spatially congruent in these microcalcified regions. F-NaF and RaCl uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of F is predictive of Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered Ra dose and therapeutic effect.
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http://dx.doi.org/10.1089/cbr.2020.4068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994428PMC
March 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Identification and quantitative chemical analysis of betaines in different organic wastes and their bioconversion composts.

Bioresour Technol 2021 May 17;328:124857. Epub 2021 Feb 17.

College of Environmental and Resource Sciences, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Zhejiang University, Hangzhou 310058, China. Electronic address:

Global organic waste is increasing, bioconversion of organic waste arises because it can recover valuable nutrients and produce bioactive substances. Betaines are important bioactive substances in plants under environmental stress, but have received limited attention in vermicompost/larvae bioconversion compost. In this study, betaines in organic waste and vermicompost/larvae bioconversion compost were identified and quantified by HPLC-ESI-MS/MS. We observed the existence of glutamine betaine in all samples, which was first found in natural sources recently. Valine betaine was the highest among all detected betaines followed by GABA betaine, and both were rare in plants. The existence of tyrosine betaine in cow dung (CD) and vermicompost (CDV) was found, which was previously shown to be in fungi. Most importantly, we found larvae bioconversion could increase betaines by 5.56-99.75%, while vermicomposting decreased them. Bioconversion of larvae can effectively increase betaines in compost and can be used to produce potential novel functional organic fertilizers.
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http://dx.doi.org/10.1016/j.biortech.2021.124857DOI Listing
May 2021